The inhibitory receptor FcgammaRII reduces joint inflammation and destruction in experimental immune complex-mediated arthritides not only by inhibition of FcgammaRI/III but also by efficient clearance and endocytosis of immune complexes.

NARCIS (Netherlands)

Lent, P.L.E.M. van; Nabbe, K.C.A.M.; Boross, P.; Blom, A.B.; Roth, J.; Holthuysen, A.E.M.; Sloetjes, A.W.; Verbeek, S.; Berg, W.B. van den

2003-01-01

Studies of FcgammaRII-/- mice identified the inhibitory function of this receptor in joint inflammation and cartilage destruction induced with immune complexes (ICs). To extend our insight in the role of FcgammaRII in arthritis, we explored the role of FcgammaRII in the absence of activating

Formation, clearance, deposition, pathogenicity, and identification of biopharmaceutical-related immune complexes: review and case studies.

Science.gov (United States)

Rojko, Jennifer L; Evans, Mark G; Price, Shari A; Han, Bora; Waine, Gary; DeWitte, Mark; Haynes, Jill; Freimark, Bruce; Martin, Pauline; Raymond, James T; Evering, Winston; Rebelatto, Marlon C; Schenck, Emanuel; Horvath, Christopher

2014-06-01

Vascular inflammation, infusion reactions, glomerulopathies, and other potentially adverse effects may be observed in laboratory animals, including monkeys, on toxicity studies of therapeutic monoclonal antibodies and recombinant human protein drugs. Histopathologic and immunohistochemical (IHC) evaluation suggests these effects may be mediated by deposition of immune complexes (ICs) containing the drug, endogenous immunoglobulin, and/or complement components in the affected tissues. ICs may be observed in glomerulus, blood vessels, synovium, lung, liver, skin, eye, choroid plexus, or other tissues or bound to neutrophils, monocytes/macrophages, or platelets. IC deposition may activate complement, kinin, and/or coagulation/fibrinolytic pathways and result in a systemic proinflammatory response. IC clearance is biphasic in humans and monkeys (first from plasma to liver and/or spleen, second from liver or spleen). IC deposition/clearance is affected by IC composition, immunomodulation, and/or complement activation. Case studies are presented from toxicity study monkeys or rats and indicate IHC-IC deposition patterns similar to those predicted by experimental studies of IC-mediated reactions to heterologous protein administration to monkeys and other species. The IHC-staining patterns are consistent with findings associated with generalized and localized IC-associated pathology in humans. However, manifestations of immunogenicity in preclinical species are generally not considered predictive to humans. © 2014 by The Author(s).

A simple two-step purification procedure for the iC3b binding collectin conglutinin

DEFF Research Database (Denmark)

Krogh-Meibom, Thomas; Ingvartsen, Klaus Lønne; Tornoe, Ida

2010-01-01

Bovine conglutinin is a serum protein involved in innate immunity. It binds calcium dependently to iC3b, a product of the complement component C3 deposited on cell surfaces, immune complexes or artificial surfaces after complement activation. We here present a simple and efficient two-step proced...

Poly (I:C) enhances the anti-tumor activity of canine parvovirus NS1 protein by inducing a potent anti-tumor immune response.

Science.gov (United States)

Gupta, Shishir Kumar; Yadav, Pavan Kumar; Tiwari, A K; Gandham, Ravi Kumar; Sahoo, A P

2016-09-01

The canine parvovirus NS1 (CPV2.NS1) protein selectively induces apoptosis in the malignant cells. However, for an effective in vivo tumor treatment strategy, an oncolytic agent also needs to induce a potent anti-tumor immune response. In the present study, we used poly (I:C), a TLR3 ligand, as an adjuvant along with CPV2.NS1 to find out if the combination can enhance the oncolytic activity by inducing a potent anti-tumor immune response. The 4T1 mammary carcinoma cells were used to induce mammary tumor in Balb/c mice. The results suggested that poly (I:C), when given along with CPV2.NS1, not only significantly reduced the tumor growth but also augmented the immune response against tumor antigen(s) as indicated by the increase in blood CD4+ and CD8+ counts and infiltration of immune cells in the tumor tissue. Further, blood serum analysis of the cytokines revealed that Th1 cytokines (IFN-γ and IL-2) were significantly upregulated in the treatment group indicating activation of cell-mediated immune response. The present study reports the efficacy of CPV2.NS1 along with poly (I:C) not only in inhibiting the mammary tumor growth but also in generating an active anti-tumor immune response without any visible toxicity. The results of our study may help in developing CPV2.NS1 and poly (I: C) combination as a cancer therapeutic regime to treat various malignancies.

Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes

Science.gov (United States)

Monsalvo, Ana Clara; Batalle, Juan P.; Lopez, M. Florencia; Krause, Jens C.; Klemenc, Jennifer; Zea, Johanna; Maskin, Bernardo; Bugna, Jimena; Rubinstein, Carlos; Aguilar, Leandro; Dalurzo, Liliana; Libster, Romina; Savy, Vilma; Baumeister, Elsa; Aguilar, Liliana; Cabral, Graciela; Font, Julia; Solari, Liliana; Weller, Kevin P.; Johnson, Joyce; Echavarria, Marcela; Edwards, Kathryn M.; Chappell, James D.; Crowe, James E.; Williams, John V.; Melendi, Guillermina A.; Polack, Fernando P.

2010-01-01

Pandemic influenza viruses often cause severe disease in middle-aged adults without preexistent co-morbidities. The mechanism of illness associated with severe disease in this age group is not well understood1–10. Here, we demonstrate preexisting serum antibody that cross-reacts with, but does not protect against 2009 H1N1 influenza virus in middle-aged adults. Non-protective antibody is associated with immune complex(IC)-mediated disease after infection. High titers of serum antibody of low avidity for H1-2009 antigen, and low avidity pulmonary ICs against the same protein were detected in severely ill patients. Moreover, C4d deposition - a sensitive marker of complement activation mediated by ICs- was present in lung sections of fatal cases. Archived lung sections from adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a novel biological mechanism for the unusual age distribution of severe cases during influenza pandemics. PMID:21131958

Mechanisms and kinetics for platelet and neutrophil localization in immune complex nephritis

Energy Technology Data Exchange (ETDEWEB)

Johnson, R.J.; Alpers, C.E.; Pruchno, C.; Schulze, M.; Baker, P.J.; Pritzl, P.; Couser, W.G. (Univ. of Washington, Seattle (USA))

1989-11-01

We have previously reported that both neutrophils (PMNs) and platelets mediate proteinuria in a model of subendothelial immune complex (IC) nephritis (GN) in the rat. In order to understand the interaction of PMNs and platelets in this model, we quantitated the uptake of {sup 111}In-labelled platelets in glomeruli and correlated this with the number of PMNs observed histologically at 10 and 30 minutes, 1, 4 and 24 hours following induction of GN. Platelet accumulation was biphasic with a major peak at 10 minutes and a minor peak at four hours. Early platelet accumulation was complement dependent, and PMN-independent. PMN accumulation occurred after the initial platelet influx, peaking at one and four hours, was complement dependent, but was not affected by platelet depletion. Complement depletion significantly reduced proteinuria. This is the first documentation that platelet accumulation in glomeruli in IC GN is complement dependent. In addition, the enhancement of PMN-mediated injury by the platelet in this model does not involve effects of platelets on PMN localization, thus implying a functional interaction between these cells within the glomerulus.

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

DEFF Research Database (Denmark)

Petersen, Ivan; Baatrup, Gunnar; Brandslund, I

1986-01-01

Nine patients with active classical rheumatoid arthritis (ARA criteria) were studied with reference to circadian variation of immunological and clinical parameters. Complement-mediated solubilization (CMS) of immune complexes (IC) and the level of circulating IC were found to be inversely related...... with low CMS and increased IC levels in the morning, and vice versa in the afternoon. Bed rest and exercise did not influence these fluctuations. The C3d concentration in plasma was increased but showed no diurnal or circadian periodic fluctuations when the levels were corrected for fluctuations in plasma...... albumin concentration. Clinical assessment by means of pain score exhibited marked variations, with high scores in the morning, and lower in the daytime, whereas measurements of Ritchie's joint index showed no consistent pattern. The circadian variations in CMS, serum IC and clinical parameters indicate...

α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8.

LENUS (Irish Health Repository)

Bergin, David A

2010-12-01

Hereditary deficiency of the protein α-1 antitrypsin (AAT) causes a chronic lung disease in humans that is characterized by excessive mobilization of neutrophils into the lung. However, the reason for the increased neutrophil burden has not been fully elucidated. In this study we have demonstrated using human neutrophils that serum AAT coordinates both CXCR1- and soluble immune complex (sIC) receptor-mediated chemotaxis by divergent pathways. We demonstrated that glycosylated AAT can bind to IL-8 (a ligand for CXCR1) and that AAT-IL-8 complex formation prevented IL-8 interaction with CXCR1. Second, AAT modulated neutrophil chemotaxis in response to sIC by controlling membrane expression of the glycosylphosphatidylinositol-anchored (GPI-anchored) Fc receptor FcγRIIIb. This process was mediated through inhibition of ADAM-17 enzymatic activity. Neutrophils isolated from clinically stable AAT-deficient patients were characterized by low membrane expression of FcγRIIIb and increased chemotaxis in response to IL-8 and sIC. Treatment of AAT-deficient individuals with AAT augmentation therapy resulted in increased AAT binding to IL-8, increased AAT binding to the neutrophil membrane, decreased FcγRIIIb release from the neutrophil membrane, and normalization of chemotaxis. These results provide new insight into the mechanism underlying the effect of AAT augmentation therapy in the pulmonary disease associated with AAT deficiency.

Protective immunity against rock bream iridovirus (RBIV) infection and TLR3-mediated type I interferon signaling pathway in rock bream (Oplegnathus fasciatus) following poly (I:C) administration.

Science.gov (United States)

Jung, Myung-Hwa; Jung, Sung-Ju

2017-08-01

In this study, we evaluated the potential of poly (I:C) to induce antiviral status for protecting rock bream from RBIV infection. Rock bream injected with poly (I:C) at 2 days before infection (1.1 × 10 4 ) at 20 °C had significantly higher protection with RPS 13.4% and 33.4% at 100 and 200 μg/fish, respectively, through 100 days post infection (dpi). The addition of boost immunization with poly (I:C) at before/post infection at 20 °C clearly enhanced the level of protection showing 33.4% and 60.0% at 100 and 200 μg/fish, respectively. To investigate the development of a protective immune response, rock bream were re-infected with RBIV (1.1 × 10 7 ) at 200 dpi. While 100% of the previously unexposed fish died, 100% of the previously infected fish survived. Poly (I:C) induced TLR3 and Mx responses were observed at several sampling time points in the spleen, kidney and blood. Moreover, significantly high expression levels of IRF3 (2.9- and 3.1-fold at 1 d and 2 days post administration (dpa), respectively), ISG15 and PKR expression (5.4- and 10.2-fold at 2 dpa, respectively) were observed in the blood, but the expression levels were low in the spleen and kidney after poly (I:C) administration. Our results showed the induction of antiviral immune responses and indicate the possibility of developing long term preventive measures against RBIV using poly (I:C). Copyright © 2017 Elsevier Ltd. All rights reserved.

Persistence of Circulating Hepatitis C Virus Antigens-Specific Immune Complexes in Patients with Resolved HCV Infection.

Science.gov (United States)

Hu, Ke-Qin; Cui, Wei

2018-05-01

Our recent study indicated the possible presence of detectable hepatitis C virus antigens (HCV-Ags) after denaturation of sera with resolved HCV (R-HCV) infection. The present study determined and characterized persistent HCV-Ags-specific immune complexes (ICs) in these patients. Sixty-eight sera with R-HCV and 34 with viremic HCV (V-HCV) infection were tested for free and IC-bound HCV-Ags using HCV-Ags enzyme immunoassay (EIA), the presence of HCV-Ags-specific ICs by immunoprecipitation and Western blot (IP-WB), HCV ICs containing HCV virions using IP and HCV RNA RT-PCR, and correlation of HCV ICs with clinical presentation in these patients. Using HCV-Ags EIA, we found 57.4% of sera with R-HCV infection were tested positive for bound, but not free HCV-Ags. Using pooled or individual anti-HCV E1/E2, cAg, NS3, NS4b, and/or NS5a to precipitate HCV-specific-Ags, we confirmed persistent HCV-Ags ICs specific to various HCV structural and non-structural proteins not only in V-HCV infection, but also in R-HCV infection. Using IP and HCV RNA PCR, we then confirmed the presence of HCV virions within circulating ICs in V-HCV, but not in R-HCV sera. Multivariable analysis indicated significant and independent associations of persistent circulating HCV-Ags-specific ICs with both age and the presence of cirrhosis in patients with R-HCV infection. Various HCV-Ag-specific ICs, but not virions, persist in 57.4% of patients who had spontaneous or treatment-induced HCV clearance for 6 months to 20 years. These findings enriched our knowledge on HCV pathogenesis and support further study on its long-term clinical relevance, such as extrahepatic manifestation, transfusion medicine, and hepatocarcinogenesis.

Bombyx mori and Aedes aegypti form multi-functional immune complexes that integrate pattern recognition, melanization, coagulants, and hemocyte recruitment.

Science.gov (United States)

Phillips, Dennis R; Clark, Kevin D

2017-01-01

The innate immune system of insects responds to wounding and pathogens by mobilizing multiple pathways that provide both systemic and localized protection. Key localized responses in hemolymph include melanization, coagulation, and hemocyte encapsulation, which synergistically seal wounds and envelop and destroy pathogens. To be effective, these pathways require a targeted deposition of their components to provide protection without compromising the host. Extensive research has identified a large number of the effectors that comprise these responses, but questions remain regarding their post-translational processing, function, and targeting. Here, we used mass spectrometry to demonstrate the integration of pathogen recognition proteins, coagulants, and melanization components into stable, high-mass, multi-functional Immune Complexes (ICs) in Bombyx mori and Aedes aegypti. Essential proteins common to both include phenoloxidases, apolipophorins, serine protease homologs, and a serine protease that promotes hemocyte recruitment through cytokine activation. Pattern recognition proteins included C-type Lectins in B. mori, while A. aegypti contained a protein homologous to Plasmodium-resistant LRIM1 from Anopheles gambiae. We also found that the B. mori IC is stabilized by extensive transglutaminase-catalyzed cross-linking of multiple components. The melanization inhibitor Egf1.0, from the parasitoid wasp Microplitis demolitor, blocked inclusion of specific components into the IC and also inhibited transglutaminase activity. Our results show how coagulants, melanization components, and hemocytes can be recruited to a wound surface or pathogen, provide insight into the mechanism by which a parasitoid evades this immune response, and suggest that insects as diverse as Lepidoptera and Diptera utilize similar defensive mechanisms.

Serum and plasma fibronectin binds to complement reacted immune complexes primarily via Clq

DEFF Research Database (Denmark)

Baatrup, G; Svehag, S E

1986-01-01

The binding of fibronectin to human Clq, C3b, and complement-reacted immune complexes (IC) was investigated by enzyme-linked immunosorbent assays. Microplates were coated with BSA followed by incubation with rabbit-anti-BSA IgG or F(ab')2 fragments of rabbit anti-BSA. Incubation of the solid phase...... with serum at 37 degrees C caused attachment of Clq and C3b. Addition of EDTA to the serum inhibited the binding of C3b, but not Clq, whereas substitution of the anti-BSA IgG on the solid phase with the F(ab')2 fragments abrogated the Clq, but not the C3b binding. Fibronectin binding was observed after...

Differential trafficking of oxidized LDL and oxidized LDL immune complexes in macrophages: impact on oxidative stress.

Directory of Open Access Journals (Sweden)

Mohammed M Al Gadban

2010-09-01

Full Text Available Oxidized low-density lipoproteins (oxLDL and oxLDL-containing immune complexes (oxLDL-IC contribute to formation of lipid-laden macrophages (foam cells. It has been shown that oxLDL-IC are considerably more efficient than oxLDL in induction of foam cell formation, inflammatory cytokines secretion, and cell survival promotion. Whereas oxLDL is taken up by several scavenger receptors, oxLDL-IC are predominantly internalized through the FCgamma receptor I (FCgamma RI. This study examined differences in intracellular trafficking of lipid and apolipoprotein moieties of oxLDL and oxLDL-IC and the impact on oxidative stress.Fluorescently labeled lipid and protein moieties of oxLDL co-localized within endosomal and lysosomal compartments in U937 human monocytic cells. In contrast, the lipid moiety of oxLDL-IC was detected in the endosomal compartment, whereas its apolipoprotein moiety advanced to the lysosomal compartment. Cells treated with oxLDL-IC prior to oxLDL demonstrated co-localization of internalized lipid moieties from both oxLDL and oxLDL-IC in the endosomal compartment. This sequential treatment likely inhibited oxLDL lipid moieties from trafficking to the lysosomal compartment. In RAW 264.7 macrophages, oxLDL-IC but not oxLDL induced GFP-tagged heat shock protein 70 (HSP70 and HSP70B', which co-localized with the lipid moiety of oxLDL-IC in the endosomal compartment. This suggests that HSP70 family members might prevent the degradation of the internalized lipid moiety of oxLDL-IC by delaying its advancement to the lysosome. The data also showed that mitochondrial membrane potential was decreased and generation of reactive oxygen and nitrogen species was increased in U937 cell treated with oxLDL compared to oxLDL-IC.Findings suggest that lipid and apolipoprotein moieties of oxLDL-IC traffic to separate cellular compartments, and that HSP70/70B' might sequester the lipid moiety of oxLDL-IC in the endosomal compartment. This mechanism could

Clearing the complexity: immune complexes and their treatment in lupus nephritis

Directory of Open Access Journals (Sweden)

Catherine Toong

2011-01-01

Full Text Available Catherine Toong1, Stephen Adelstein1, Tri Giang Phan21Department of Clinical Immunology, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW, Australia; 2Immunology Program, Garvan Institute of Medical Research and St. Vincent’s Clinical School, University of New South Wales, Darlinghurst, NSW, AustraliaAbstract: Systemic lupus erythematosus (SLE is a classic antibody-mediated systemic autoimmune disease characterised by the development of autoantibodies to ubiquitous self-antigens (such as antinuclear antibodies and antidouble-stranded DNA antibodies and widespread deposition of immune complexes in affected tissues. Deposition of immune complexes in the kidney results in glomerular damage and occurs in all forms of lupus nephritis. The development of nephritis carries a poor prognosis and high risk of developing end-stage renal failure despite recent therapeutic advances. Here we review the role of DNA-anti-DNA immune complexes in the pathogenesis of lupus nephritis and possible new treatment strategies aimed at their control.Keywords: immune complex, systemic lupus erythematosus, nephritis, therapy

Hydrodynamic delivery of plasmid DNA encoding human Fc?R-Ig dimers blocks immune-complex mediated inflammation in mice

OpenAIRE

Shashidharamurthy, Rangaiah; Machiah, Deepa; Bozeman, Erica N.; Srivatsan, Sanjay; Patel, Jaina; Cho, Alice; Jacob, Joshy; Selvaraj, Periasamy

2011-01-01

Therapeutic use and function of recombinant molecules can be studied by the expression of foreign genes in mice. In this study, we have expressed human Fcgamma receptor ?Ig fusion molecules (Fc?R-Igs) in mice by administering Fc?R-Ig plasmid DNAs hydrodynamically and compared their effectiveness to purified molecules in blocking immune-complex (IC) mediated inflammation in mice. The concentration of hydrodynamically expressed Fc?R-Igs (CD16AF-Ig, CD32AR-Ig and CD32AH-Ig) reached a maximum of ...

Prenatal immune challenge in rats: Altered responses to dopaminergic and glutamatergic agents, prepulse inhibition of acoustic startle, and reduced route-based learning as a function of maternal body weight gain after prenatal exposure to Poly IC

OpenAIRE

Vorhees, Charles V.; Graham, Devon L.; Braun, Amanda A.; Schaefer, Tori L.; Skelton, Matthew R.; Richtand, Neil M.; Williams, Michael T.

2012-01-01

Prenatal maternal immune activation has been used to test the neurodevelopmental hypothesis of schizophrenia. Most of the data are in mouse models; far less is available for rats. We previously showed that maternal weight change in response to the immune activator polyinosinic-polycytidylic (Poly IC) in rats differentially affects offspring. Therefore, we treated gravid Harlan Sprague-Dawley rats i.p. on embryonic day 14 with 8 mg/kg of Poly IC or Saline. The Poly IC group was divided into th...

Dynamics of interaction between complement-fixing antibody/dsDNA immune complexes and erythrocytes. In vitro studies and potential general applications to clinical immune complex testing

International Nuclear Information System (INIS)

Taylor, R.P.; Horgan, C.; Hooper, M.; Burge, J.

1985-01-01

Soluble antibody/ 3 H-double-stranded PM2 DNA (dsDNA) immune complexes were briefly opsonized with complement and then allowed to bind to human erythrocytes (via complement receptors). The cells were washed and subsequently a volume of autologous blood in a variety of media was added, and the release of the bound immune complexes from the erythrocytes was studied as a function of temperature and time. After 1-2 h, the majority of the bound immune complexes were not released into the serum during blood clotting at either 37 degrees C or room temperature, but there was a considerably greater release of the immune complexes into the plasma of blood that was anticoagulated with EDTA. Similar results were obtained using various conditions of opsonization and also using complexes that contained lower molecular weight dsDNA. Thus, the kinetics of release of these antibody/dsDNA immune complexes differed substantially from the kinetics of release of antibody/bovine serum albumin complexes that was reported by others. Studies using the solution phase C1q immune complex binding assay confirmed that in approximately half of the SLE samples that were positive for immune complexes, there was a significantly higher level of detectable immune complexes in plasma vs. serum. Freshly drawn erythrocytes from some SLE patients exhibiting this plasma/serum discrepancy had IgG antigen on their surface that was released by incubation in EDTA plasma. Thus, the higher levels of immune complexes observed in EDTA plasma vs. serum using the C1q assay may often reflect the existence of immune complexes circulating in vivo bound to erythrocytes

Circulating immune complexes – reviewing the biological roles in ...

African Journals Online (AJOL)

Circulating immune complexes – reviewing the biological roles in human immune function and exercise. ... studies that have investigated CIC's following exercise and proposes that a comprehensive understanding and interpretation of immune system responses to exercise should take these complexes into consideration.

Immune Algorithm Complex Method for Transducer Calibration

Directory of Open Access Journals (Sweden)

YU Jiangming

2014-08-01

Full Text Available As a key link in engineering test tasks, the transducer calibration has significant influence on accuracy and reliability of test results. Because of unknown and complex nonlinear characteristics, conventional method can’t achieve satisfactory accuracy. An Immune algorithm complex modeling approach is proposed, and the simulated studies on the calibration of third multiple output transducers is made respectively by use of the developed complex modeling. The simulated and experimental results show that the Immune algorithm complex modeling approach can improve significantly calibration precision comparison with traditional calibration methods.

Studies on pathogenesis and treatment of experimental immune complex glomerulonephrtis.

NARCIS (Netherlands)

Fleuren, Gerard Johannes Maria

1976-01-01

Chapter 1. In this thesis an investigation into pathogenetic mechanisms of epimembranous immune complex depostion in the glomeruli was described. For this study we used two related models of experimental immune complex glemerulonephritis: the heterologous and the autologous immune complex

Radioimmunological determination of soluble immune complexes

Energy Technology Data Exchange (ETDEWEB)

Falck, P; Meffert, H; Diezel, W; Schmidt, E; Soennichsen, N [Humboldt-Universitaet, Berlin (German Democratic Republic). Bereich Medizin (Charite)

1979-04-01

Soluble immune complexes were determined in sera from patients with systemic lupus erythematosus, using /sup 125/I-labelled anti-Ig-antibody and plastics-fixed C1q (component of complement). The detection limit of the method is 0.1 ..mu..g of aggregated human IgG and the range is between 0.1 ..mu..g and 10 ..mu..g per 0.5 ml serum. In 58% of the sera tested an increase of the number of immune complexes was found.

Innate immune responses against rock bream iridovirus (RBIV) infection in rock bream (Oplegnathus fasciatus) following poly (I:C) administration.

Science.gov (United States)

Jung, Myung-Hwa; Jung, Sung-Ju

2017-12-01

Poly (I:C) showed promise as an immunoprotective agents in rock bream against rock bream iridovirus (RBIV) infection. In this study, we evaluated the time-dependent virus replication pattern and antiviral immune responses in RBIV-infected rock bream with and without poly (I:C) administration. In the poly (I:C)+virus-injected group, virus copy numbers were more than 18.9-, 24.0- and 479.2-fold lower than in the virus only injected group at 4 (4.73 × 10 4 and 8.95 × 10 5 /μl, respectively), 7 (3.67 × 10 5 and 8.81 × 10 6 /μl, respectively) and 10 days post infection (dpi) (1.26 × 10 5 and 6.02 × 10 7 /μl, respectively). Moreover, significantly high expression levels of TLR3 (8.6- and 7.7-fold, at 4 and 7 dpi, respectively) and IL1β (3.6-fold at 2 dpi) were observed in the poly (I:C)+virus-injected group, but the expression levels were not significantly in the virus-injected group. However, IL8 and TNFα expression levels showed no statistical significance in both groups. Mx, ISG15 and PKR were significantly highly expressed from 4 to 10 dpi in the virus-injected group. Nevertheless, in the poly (I:C)+virus-injected group, Mx and ISG15 expression were significantly expressed from 2 dpi. In summary, poly (I:C) administration in rock bream induces TLR3, IL1β, Mx and ISG15-mediated immune responses, which could be a critical factor for inhibition of virus replication. Copyright © 2017 Elsevier Ltd. All rights reserved.

A simple method for determining polymeric IgA-containing immune complexes.

Science.gov (United States)

Sancho, J; Egido, J; González, E

1983-06-10

A simplified assay to measure polymeric IgA-immune complexes in biological fluids is described. The assay is based upon the specific binding of a secretory component for polymeric IgA. In the first step, multimeric IgA (monomeric and polymeric) immune complexes are determined by the standard Raji cell assay. Secondly, labeled secretory component added to the assay is bound to polymeric IgA-immune complexes previously fixed to Raji cells, but not to monomeric IgA immune complexes. To avoid false positives due to possible complement-fixing IgM immune complexes, prior IgM immunoadsorption is performed. Using anti-IgM antiserum coupled to CNBr-activated Sepharose 4B this step is not time-consuming. Polymeric IgA has a low affinity constant and binds weakly to Raji cells, as Scatchard analysis of the data shows. Thus, polymeric IgA immune complexes do not bind to Raji cells directly through Fc receptors, but through complement breakdown products, as with IgG-immune complexes. Using this method, we have been successful in detecting specific polymeric-IgA immune complexes in patients with IgA nephropathy (Berger's disease) and alcoholic liver disease, as well as in normal subjects after meals of high protein content. This new, simple, rapid and reproducible assay might help to study the physiopathological role of polymeric IgA immune complexes in humans and animals.

Detection of circulating immune complexes in hepatitis by means of a new method employing /sup 125/I-antibody. Circulating immune complexes in hepatitis

Energy Technology Data Exchange (ETDEWEB)

Fresco, G F [Genoa Univ. (Italy). Dept. of Internal Medicine

1978-06-01

A new RIA method for the detection of circulating immune complexes and antibodies arising in the course of viral hepatitis is described. It involves the use of /sup 125/I-labeled antibodies and foresees the possibility of employing immune complex-coated polypropylene tubes. This simple and sensitive procedure takes into account the possibility that the immune complexes may be absorbed by the surface of polypropylene tubes during the period in which the serum remains there.

Integration of the immune system: a complex adaptive supersystem

Science.gov (United States)

Crisman, Mark V.

2001-10-01

Immunity to pathogenic organisms is a complex process involving interacting factors within the immune system including circulating cells, tissues and soluble chemical mediators. Both the efficiency and adaptive responses of the immune system in a dynamic, often hostile, environment are essential for maintaining our health and homeostasis. This paper will present a brief review of one of nature's most elegant, complex adaptive systems.

Effect of zymosan and poly (I:C) adjuvants on responses to microneedle immunization coated with whole inactivated influenza vaccine.

Science.gov (United States)

Shin, Ju-Hyung; Noh, Jin-Yong; Kim, Kwon-Ho; Park, Jae-Keun; Lee, Ji-Ho; Jeong, Seong Dong; Jung, Dae-Yoon; Song, Chang-Seon; Kim, Yeu-Chun

2017-11-10

Microneedles are the micrometer size devices used for the delivery of vaccines and biotherapeutics. In order to increase the vaccine efficacy and reduce the antigen dose, there is a significant need to find some adjuvants for the microneedle vaccination. In this study, zymosan, which is the cell wall preparation of Saccharomyces cerevisiae, or poly (I:C) was coated on a microneedle with inactivated influenza virus, and then immunized into BALB/c mouse to determine the immunogenicity, protection and synergetic effect between two adjuvants. As a result, the group administered with zymosan and vaccine antigen showed significantly stronger IgG response, HI titer and IgG subtypes without any adverse effects, compared to the group immunized with the vaccine antigen alone. Also, there were enhanced cellular immune responses in the group received adjuvant with vaccine antigen. In addition, they showed superior protection and lung viral reduction against lethal viral challenge. Taken together, this study confirms that zymosan can be used as an immunostimulant for microneedle vaccination. Copyright © 2017 Elsevier B.V. All rights reserved.

Nasal and skin delivery of IC31(®)-adjuvanted recombinant HSV-2 gD protein confers protection against genital herpes.

Science.gov (United States)

Wizel, Benjamin; Persson, Josefine; Thörn, Karolina; Nagy, Eszter; Harandi, Ali M

2012-06-19

Genital herpes caused by herpes simplex virus type 2 (HSV-2) remains the leading cause of genital ulcers worldwide. Given the disappointing results of the recent genital herpes vaccine trials in humans, development of novel vaccine strategies capable of eliciting protective mucosal and systemic immune responses to HSV-2 is urgently required. Here we tested the ability of the adjuvant IC31(®) in combination with HSV-2 glycoprotein D (gD) used through intranasal (i.n.), intradermal (i.d.), or subcutaneous (s.c.) immunization routes for induction of protective immunity against genital herpes infection in C57BL/6 mice. Immunization with gD plus IC31(®) through all three routes of immunization developed elevated gD-specific serum antibody responses with HSV-2 neutralizing activity. Whereas the skin routes promoted the induction of a mixed IgG2c/IgG1 isotype profile, the i.n. route only elicited IgG1 antibodies. All immunization routes were able to induce gD-specific IgG antibody responses in the vaginas of mice immunized with IC31(®)-adjuvanted gD. Although specific lymphoproliferative responses were observed in splenocytes from mice of most groups vaccinated with IC31(®)-adjuvanted gD, only i.d. immunization resulted in a significant splenic IFN-γ response. Further, immunization with gD plus IC31(®) conferred 80-100% protection against an otherwise lethal vaginal HSV-2 challenge with amelioration of viral replication and disease severity in the vagina. These results warrant further exploration of IC31(®) for induction of protective immunity against genital herpes and other sexually transmitted infections. Copyright © 2012 Elsevier Ltd. All rights reserved.

Deposition of idiotype-anti-idiotype immune complexes in renal glomeruli after polyclonal B cell activation

International Nuclear Information System (INIS)

Goldman, M.; Rose, L.M.; Hochmann, A.; Lambert, P.H.

1982-01-01

We investigated the possible role of idiotypic interactions in the pathogenesis of the glomerular lesions observed in mice undergoing polyclonal B cell activation. BALB/c mice were studied for the presence of renal deposits of T15 idiotype-anti-T15 idiotype-immune complexes (IC) after injection of bacterial lipopolysaccharides (LPS). The T15 idiotype is the major idiotype of BALB/c mice anti-phosphorylcholine (PC) antibodies, which are cross-reactive with the idiotype of the TEPC-15 myeloma protein. This model was used because T15 idiotype-anti-T15 idiotype IC have been detected in the circulation of BALB/c mice after polyclonal B cell activation. First, an idiotype-specific immunofluorescence technique allowed us to detect T15 idiotype-bearing immunoglobulins in glomeruli from day 6 to day 28 after LPS injection. Second, fluorescein isothiocyanate-conjugated TEPC-15 myeloma protein was found to localize in the glomeruli after in vivo injection 18 d after LPS administration. This renal localization was shown to be idiotype-specific and could be quantified in a trace-labeling experiment. Third, kidney-deposited immunoglobulins of mice injected with LPS were eluted, radiolabeled, and analyzed by radioimmunoassay. Both T15 idiotype-bearing immunoglobulins and anti-T15 idiotype antibodies were detected in the eluates, providing further evidence for a renal deposition of T15 idiotype-anti-T15 idiotype IC. Polyclonal B cell activation is likely to result in a simultaneous triggering of many idiotypic clones and of corresponding anti-idiotypic clones represented in the B cell repertoire. This could lead to the formation of a variety of idiotype-anti-idiotype IC that could participate in the development of glomerular lesions

Hydrodynamic delivery of plasmid DNA encoding human FcγR-Ig dimers blocks immune-complex mediated inflammation in mice.

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Shashidharamurthy, R; Machiah, D; Bozeman, E N; Srivatsan, S; Patel, J; Cho, A; Jacob, J; Selvaraj, P

2012-09-01

Therapeutic use and function of recombinant molecules can be studied by the expression of foreign genes in mice. In this study, we have expressed human Fcγ receptor-Ig fusion molecules (FcγR-Igs) in mice by administering FcγR-Ig plasmid DNAs hydrodynamically and compared their effectiveness with purified molecules in blocking immune-complex (IC)-mediated inflammation in mice. The concentration of hydrodynamically expressed FcγR-Igs (CD16A(F)-Ig, CD32A(R)-Ig and CD32A(H)-Ig) reached a maximum of 130 μg ml(-1) of blood within 24 h after plasmid DNA administration. The in vivo half-life of FcγR-Igs was found to be 9-16 days and western blot analysis showed that the FcγR-Igs were expressed as a homodimer. The hydrodynamically expressed FcγR-Igs blocked 50-80% of IC-mediated inflammation up to 3 days in a reverse passive Arthus reaction model. Comparative analysis with purified molecules showed that hydrodynamically expressed FcγR-Igs are more efficient than purified molecules in blocking IC-mediated inflammation and had a higher half-life. In summary, these results suggest that the administration of a plasmid vector with the FcγR-Ig gene can be used to study the consequences of blocking IC binding to FcγRs during the development of inflammatory diseases. This approach may have potential therapeutic value in treating IC-mediated inflammatory autoimmune diseases such as lupus, arthritis and autoimmune vasculitis.

SEU immune ICs for project Galileo

International Nuclear Information System (INIS)

Giddings, A.E.; Hewlett, F.W.; Treece, R.K.; Nichols, D.K.; Smith, L.S.; Zoutendyk, J.A.

1985-01-01

Tests showed that bipolar chips in the attitude control computer of the Galileo spacecraft would likely cause catastrophic mission failure due to single particle upset. This paper describes the design and testing of CMOS replacements which are speed compatible with the bipolar parts and are immune to upset by 165-MeV krypton ions

Systemic activation of the immune system in HIV infection: The role of the immune complexes (hypothesis).

Science.gov (United States)

Korolevskaya, Larisa B; Shmagel, Konstantin V; Shmagel, Nadezhda G; Saidakova, Evgeniya V

2016-03-01

Currently, immune activation is proven to be the basis for the HIV infection pathogenesis and a strong predictor of the disease progression. Among the causes of systemic immune activation the virus and its products, related infectious agents, pro-inflammatory cytokines, and regulatory CD4+ T cells' decrease are considered. Recently microbial translocation (bacterial products yield into the bloodstream as a result of the gastrointestinal tract mucosal barrier integrity damage) became the most popular hypothesis. Previously, we have found an association between immune complexes present in the bloodstream of HIV infected patients and the T cell activation. On this basis, we propose a significantly modified hypothesis of immune activation in HIV infection. It is based on the immune complexes' participation in the immunocompetent cells' activation. Immune complexes are continuously formed in the chronic phase of the infection. Together with TLR-ligands (viral antigens, bacterial products coming from the damaged gut) present in the bloodstream they interact with macrophages. As a result macrophages are transformed into the type II activated forms. These macrophages block IL-12 production and start synthesizing IL-10. High level of this cytokine slows down the development of the full-scale Th1-response. The anti-viral reactions are shifted towards the serogenesis. Newly synthesized antibodies' binding to viral antigens leads to continuous formation of the immune complexes capable of interacting with antigen-presenting cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

The immune complex CTA1-DD/IgG adjuvant specifically targets connective tissue mast cells through FcγRIIIA and augments anti-HPV immunity after nasal immunization.

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Fang, Y; Zhang, T; Lidell, L; Xu, X; Lycke, N; Xiang, Z

2013-11-01

We have previously reported that CTA1-DD/IgG immune complexes augment antibody responses in a mast cell-dependent manner following intranasal (IN) immunizations. However, from a safety perspective, mast cell activation could preclude clinical use. Therefore, we have extended these studies and demonstrate that CTA1-DD/IgG immune complexes administered IN did not trigger an anaphylactic reaction. Importantly, CTA1-DD/IgE immune complexes did not activate mast cells. Interestingly, only connective tissue, but not mucosal, mast cells could be activated by CTA1-DD/IgG immune complexes. This effect was mediated by FcγRIIIA, only expressed on connective tissue mast cells, and found in the nasal submucosa. FcγRIIIA-deficient mice had compromised responses to immunization adjuvanted by CTA1-DD/IgG. Proof-of-concept studies revealed that IN immunized mice with human papillomavirus (HPV) type 16 L1 virus-like particles (VLP) and CTA1-DD/IgG immune complexes demonstrated strong and sustained specific antibody titers in serum and vaginal secretions. From a mast cell perspective, CTA1-DD/IgG immune complexes appear to be safe and effective mucosal adjuvants.

The roles of complement receptors type 1 (CR1, CD35) and type 3 (CR3, CD11b/CD18) in the regulation of the immune complex-elicited respiratory burst of polymorphonuclear leukocytes in whole blood

DEFF Research Database (Denmark)

Nielsen, C H; Antonsen, S; Matthiesen, S H

1997-01-01

The binding of immune complexes (IC) to polymorphonuclear leukocytes (PMN) and the consequent respiratory burst (RB) were investigated in whole blood cell preparations suspended in 75% human serum, using flow cytometry. Blockade of the complement receptor (CR)1 receptor sites for C3b on whole blood...... cells using the monoclonal antibody (mAb) 3D9 resulted in a 1.9-fold increase in the IC-elicited PMN RB after 5 min of incubation, rising to 3.1-fold after 40 min. This enhancement was not due to increased IC deposition on PMN. Blockade of CR3 abrogated the mAb 3D9-induced rise in RB activity...

IC-tagged proteins are able to interact with each other and perform complex reactions when integrated into muNS-derived inclusions.

Science.gov (United States)

Brandariz-Nuñez, Alberto; Otero-Romero, Iria; Benavente, Javier; Martinez-Costas, Jose M

2011-09-20

We have recently developed a versatile tagging system (IC-tagging) that causes relocation of the tagged proteins to ARV muNS-derived intracellular globular inclusions. In the present study we demonstrate (i) that the IC-tag can be successfully fused either to the amino or carboxyl terminus of the protein to be tagged and (ii) that IC-tagged proteins are able to interact between them and perform complex reactions that require such interactions while integrated into muNS inclusions, increasing the versatility of the IC-tagging system. Also, our studies with the DsRed protein add some light on the structure/function relationship of the evolution of DsRed chromophore. Copyright © 2011 Elsevier B.V. All rights reserved.

Antigen Cross-Presentation of Immune Complexes

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Platzer, Barbara; Stout, Madeleine; Fiebiger, Edda

2014-01-01

The ability of dendritic cells (DCs) to cross-present tumor antigens has long been a focus of interest to physicians, as well as basic scientists, that aim to establish efficient cell-based cancer immune therapy. A prerequisite for exploiting this pathway for therapeutic purposes is a better understanding of the mechanisms that underlie the induction of tumor-specific cytotoxic T-lymphocyte (CTL) responses when initiated by DCs via cross-presentation. The ability of humans DC to perform cross-presentation is of utmost interest, as this cell type is a main target for cell-based immunotherapy in humans. The outcome of a cross-presentation event is guided by the nature of the antigen, the form of antigen uptake, and the subpopulation of DCs that performs presentation. Generally, CD8α+ DCs are considered to be the most potent cross-presenting DCs. This paradigm, however, only applies to soluble antigens. During adaptive immune responses, immune complexes form when antibodies interact with their specific epitopes on soluble antigens. Immunoglobulin G (IgG) immune complexes target Fc-gamma receptors on DCs to shuttle exogenous antigens efficiently into the cross-presentation pathway. This receptor-mediated cross-presentation pathway is a well-described route for the induction of strong CD8+ T cell responses. IgG-mediated cross-presentation is intriguing because it permits the CD8− DCs, which are commonly considered to be weak cross-presenters, to efficiently cross-present. Engaging multiple DC subtypes for cross-presentation might be a superior strategy to boost CTL responses in vivo. We here summarize our current understanding of how DCs use IgG-complexed antigens for the efficient induction of CTL responses. Because of its importance for human cell therapy, we also review the recent advances in the characterization of cross-presentation properties of human DC subsets. PMID:24744762

Obesity-Associated Autoantibody Production Requires AIM to Retain the Immunoglobulin M Immune Complex on Follicular Dendritic Cells

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Satoko Arai

2013-04-01

Full Text Available Natural immunoglobulin M (IgM is reactive to autoantigens and is believed to be important for autoimmunity. Blood pentameric IgM loaded with antigens forms a large immune complex (IC that contains various elements, including apoptosis inhibitor of macrophage (AIM. Here we demonstrate that this IgM-AIM association contributes to autoantibody production under obese conditions. In mice fed a high-fat diet, natural IgM increased through B cell TLR4 stimulation. AIM associated with IgM and protected AIM from renal excretion, increasing blood AIM levels along with the obesity-induced IgM augmentation. Meanwhile, the AIM association inhibited IgM binding to the Fcα/μ receptor on splenic follicular dendritic cells, thereby protecting the IgM IC from Fcα/μ receptor-mediated internalization. This supported IgM-dependent autoantigen presentation to B cells, stimulating IgG autoantibody production. Accordingly, in obese AIM-deficient (AIM−/− mice, the increase of multiple IgG autoantibodies observed in obese wild-type mice was abrogated. Thus, the AIM-IgM association plays a critical role in the obesity-associated autoimmune process.

Acute lung injury in rat caused by immunoglobulin A immune complexes.

OpenAIRE

Johnson, K J; Wilson, B S; Till, G O; Ward, P A

1984-01-01

Mouse IgG and IgA, with reactivity to dinitrophenol conjugated to carrier protein, have been isolated from myeloma proteins by means of a variety of affinity techniques. The IgA was predominantly in the dimeric form. The in vitro and in vivo biological activities of IgA-containing immune complexes were assessed in the rat. IgA-containing immune complexes were demonstrated, in a dose-dependent manner in vitro, to activate neutrophils and to generate O.-2. In addition, these immune complexes sh...

Prenatal immune challenge in rats: altered responses to dopaminergic and glutamatergic agents, prepulse inhibition of acoustic startle, and reduced route-based learning as a function of maternal body weight gain after prenatal exposure to poly IC.

Science.gov (United States)

Vorhees, Charles V; Graham, Devon L; Braun, Amanda A; Schaefer, Tori L; Skelton, Matthew R; Richtand, Neil M; Williams, Michael T

2012-08-01

Prenatal maternal immune activation has been used to test the neurodevelopmental hypothesis of schizophrenia. Most of the data are in mouse models; far less is available for rats. We previously showed that maternal weight change in response to the immune activator polyinosinic-polycytidylic acid (Poly IC) in rats differentially affects offspring. Therefore, we treated gravid Harlan Sprague-Dawley rats i.p. on embryonic day 14 with 8 mg/kg of Poly IC or Saline. The Poly IC group was divided into those that lost or gained the least weight, Poly IC (L), versus those that gained the most weight, Poly IC (H), following treatment. The study design controlled for litter size, litter sampling, sex distribution, and test experience. We found no effects of Poly IC on elevated zero maze, open-field activity, object burying, light-dark test, straight channel swimming, Morris water maze spatial acquisition, reversal, or shift navigation or spatial working or reference memory, or conditioned contextual or cued fear or latent inhibition. The Poly IC (H) group showed a significant decrease in the rate of route-based learning when visible cues were unavailable in the Cincinnati water maze and reduced prepulse inhibition of acoustic startle in females, but not males. The Poly IC (L) group exhibited altered responses to acute pharmacological challenges: exaggerated hyperactivity in response to (+)-amphetamine and an attenuated hyperactivity in response to MK-801. This model did not exhibit the cognitive, or latent inhibition deficits reported in Poly IC-treated rats but showed changes in response to drugs acting on neurotransmitter systems implicated in the pathophysiology of schizophrenia (dopaminergic hyperfunction and glutamatergic hypofunction). Copyright © 2012 Wiley Periodicals, Inc.

Focal glomerular immune complex deposition: possible role of periglomerular fibrosis/atubular glomeruli.

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Satoskar, Anjali A; Calomeni, Edward; Bott, Cherri; Nadasdy, Gyongyi M; Nadasdy, Tibor

2009-02-01

Consensus exists among renal pathologists that, in biopsies with immune complex glomerulonephritis, even a single glomerulus with open capillary loops may be sufficient for immunofluorescence and/or electron microscopy evaluation because immune complex deposition is a diffuse phenomenon. However, we have encountered renal biopsies with focal absence of immune complexes in glomeruli on either immunofluorescence or electron microscopy examination despite presence of open glomerular capillary loops. To evaluate renal biopsies with focal immune complex deposition and look for any subtle or unusual morphologic changes in the glomeruli (and in the biopsy in general). Native and transplant renal biopsies were reviewed. All biopsies had been triaged and processed according to our routine protocol for light microscopy, immunofluorescence, and electron microscopy examination. Of 2018 renal biopsies from December 2005 to December 2007, we found 10 such biopsies; 5 native and 5 transplant kidney biopsies. We found that the glomeruli with absent immune complex deposits had periglomerular fibrosis with open, albeit, wrinkled appearing capillary loops but no glomerular sclerosis. We hypothesize that these histologic features are indicative of nonfunctional glomeruli and may be associated with disconnection between the Bowman capsule and proximal tubule (atubular glomeruli). These glomeruli may not have effective filtration, despite some degree of circulation through the open capillary loops, and therefore are unable to accumulate immune complex deposits. If biopsies are small and only such glomeruli are available for immunofluorescence or electron microscopy examination, the absence of immune complex deposition in them should be evaluated carefully.

The deconvolution of complex spectra by artificial immune system

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Galiakhmetova, D. I.; Sibgatullin, M. E.; Galimullin, D. Z.; Kamalova, D. I.

2017-11-01

An application of the artificial immune system method for decomposition of complex spectra is presented. The results of decomposition of the model contour consisting of three components, Gaussian contours, are demonstrated. The method of artificial immune system is an optimization method, which is based on the behaviour of the immune system and refers to modern methods of search for the engine optimization.

Intraluminal Administration of Poly I:C Causes an Enteropathy That Is Exacerbated by Administration of Oral Dietary Antigen

Science.gov (United States)

Araya, Romina E.; Jury, Jennifer; Bondar, Constanza

2014-01-01

Systemic administration of polyinosinic:polycytidylic acid (poly I:C), mimics virally-induced activation of TLR3 signalling causing acute small intestine damage, but whether and how mucosal administration of poly I:C causes enteropathy is less clear. Our aim was to investigate the inflammatory pathways elicited after intraluminal administration of poly I:C and determine acute and delayed consequences of this locally induced immune activation. Intraluminal poly I:C induced rapid mucosal immune activation in C57BL/6 mice involving IFNβ and the CXCL10/CXCR3 axis, that may drive inflammation towards a Th1 profile. Intraluminal poly I:C also caused enteropathy and gut dysfunction in gliadin-sensitive NOD-DQ8 mice, and this was prolonged by concomitant oral administration of gliadin. Our results indicate that small intestine pathology can be induced in mice by intraluminal administration of poly I:C and that this is exacerbated by subsequent oral delivery of a relevant dietary antigen. PMID:24915573

Computational Strategies for Dissecting the High-Dimensional Complexity of Adaptive Immune Repertoires

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Enkelejda Miho

2018-02-01

Full Text Available The adaptive immune system recognizes antigens via an immense array of antigen-binding antibodies and T-cell receptors, the immune repertoire. The interrogation of immune repertoires is of high relevance for understanding the adaptive immune response in disease and infection (e.g., autoimmunity, cancer, HIV. Adaptive immune receptor repertoire sequencing (AIRR-seq has driven the quantitative and molecular-level profiling of immune repertoires, thereby revealing the high-dimensional complexity of the immune receptor sequence landscape. Several methods for the computational and statistical analysis of large-scale AIRR-seq data have been developed to resolve immune repertoire complexity and to understand the dynamics of adaptive immunity. Here, we review the current research on (i diversity, (ii clustering and network, (iii phylogenetic, and (iv machine learning methods applied to dissect, quantify, and compare the architecture, evolution, and specificity of immune repertoires. We summarize outstanding questions in computational immunology and propose future directions for systems immunology toward coupling AIRR-seq with the computational discovery of immunotherapeutics, vaccines, and immunodiagnostics.

Solubilization of immune complexes in complement factor deficient sera and the influence of temperature, ionic strength and divalent cations on the solubilization reaction

DEFF Research Database (Denmark)

Baatrup, Gunnar; Petersen, Ivan; Svehag, Svend-Erik

1984-01-01

The complement-mediated solubilization (CMS) of immune complexes (IC) and the initial kinetics (IKS) of this reaction in human sera depleted of or deficient in C2, C3, C8, factors B, P and I were investigated. Sera depleted of B or P and those lacking native C3 or factor I showed virtually no CMS......M. Chelation of Ca2+ in serum by Mg2+-ethylene glycol tetraacetic acid reduced the CMS capacity by up to 50% and the IKS was markedly retarded. Varying the Zn2+ or Mn2+ ion concentrations in serum influenced neither the IKS nor the CMS capacity....

Autoantibodies in autoimmune thyroid disease promote immune complex formation with self antigens and increase B cell and CD4+ T cell proliferation in response to self antigens

DEFF Research Database (Denmark)

Nielsen, Claus Henrik; Hegedüs, Laszlo; Leslie, Robert Graham Quinton

2004-01-01

's thyroiditis (HT), Graves' disease (GD) and healthy controls were incubated with human thyroglobulin (Tg) before adding normal peripheral blood mononuclear cells. The deposition of immunoglobulins and C3 fragments on B cells was then assessed. Inclusion of Tg in serum from HT patients promoted B cell capture......B cells are centrally involved as antigen-presenting cells in certain autoimmune diseases. To establish whether autoantibodies form immune complexes (IC) with self-antigens in autoimmune thyroid disease (AITD) and promote B cell uptake of self-antigen, sera from patients with Hashimoto...

Autoantibodies in autoimmune thyroid disease promote immune complex formation with self antigens and increase B cell and CD4+ T cell proliferation in response to self antigens

DEFF Research Database (Denmark)

Nielsen, Claus Henrik; Hegedüs, Laszlo; Leslie, Robert Graham Quinton

2004-01-01

B cells are centrally involved as antigen-presenting cells in certain autoimmune diseases. To establish whether autoantibodies form immune complexes (IC) with self-antigens in autoimmune thyroid disease (AITD) and promote B cell uptake of self-antigen, sera from patients with Hashimoto......'s thyroiditis (HT), Graves' disease (GD) and healthy controls were incubated with human thyroglobulin (Tg) before adding normal peripheral blood mononuclear cells. The deposition of immunoglobulins and C3 fragments on B cells was then assessed. Inclusion of Tg in serum from HT patients promoted B cell capture...

Immune complexes, gallium lung scans, and bronchoalveolar lavage in idiopathic interstitial pneumonitis-fibrosis

International Nuclear Information System (INIS)

Gelb, A.F.; Dreisen, R.B.; Epstein, J.D.; Silverthorne, J.D.; Bickel, Y.; Fields, M.; Border, W.A.; Taylor, C.R.

1983-01-01

We obtained results of lung immune complexes (LIC), circulating immune complexes (CIC), 48-hour gallium lung scans (scans), bronchoalveolar lavage (BAL), and pulmonary function tests in 20 patients with idiopathic interstitial pneumonitis-fibrosis. Sixteen patients had predominantly interstitial (13 cases UIP) and/or intraalveolar (3 cases DIP) cellular disease (group 1). Prior to corticosteroid therapy in group 1, scans were positive in 75 percent, CIC were elevated in 86 percent, LIC were present in 64 percent, and BAL was abnormal in 90 percent. Duration of follow-up after treatment was 3.5 +/- 1.0 year. In group 1 after treatment with corticosteroids in 13 patients and corticosteroids and penicillamine (three patients) and plasmapheresis (one patient), only four patients remain stable or improved. After corticosteroid therapy, elevated CIC returned to normal values despite progressive patient deterioration. In three patients, lung immune complexes were still detected after circulating immune complexes had returned to normal after corticosteroid therapy. In group 2 were four patients with fibrotic disease; scans and CIC were uniformly negative, LIC were weakly present in only one patient, and BAL was abnormal in all. Despite corticosteroid therapy, all have died or deteriorated. These results suggest that positive gallium lung scans, BAL, circulating immune complexes, and to a lesser extent, lung immune complexes are associated with the cellular phase of interstitial pneumonia, but do not reliably identify a corticosteroid-responsive group

Analysis of Power Transfer Efficiency of Standard Integrated Circuit Immunity Test Methods

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Hai Au Huynh

2015-01-01

Full Text Available Direct power injection (DPI and bulk current injection (BCI methods are defined in IEC 62132-3 and IEC 62132-4 as the electromagnetic immunity test method of integrated circuits (IC. The forward power measured at the RF noise generator when the IC malfunctions is used as the measure of immunity level of the IC. However, the actual power that causes failure in ICs is different from forward power measured at the noise source. Power transfer efficiency is used as a measure of power loss of the noise injection path. In this paper, the power transfer efficiencies of DPI and BCI methods are derived and validated experimentally with immunity test setup of a clock divider IC. Power transfer efficiency varies significantly over the frequency range as a function of the test method used and the IC input impedance. For the frequency range of 15 kHz to 1 GHz, power transfer efficiency of the BCI test was constantly higher than that of the DPI test. In the DPI test, power transfer efficiency is particularly low in the lower test frequency range up to 10 MHz. When performing the IC immunity tests following the standards, these characteristics of the test methods need to be considered.

Extracción de cobre desde soluciones clorhídricas con LIX 860N-IC y LIX 84-IC

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Navarro, Carlos María

2001-08-01

Full Text Available In this work, the extraction of copper from chloride solutions with two hydroxyoximes: 5- nonylsalicylaldoxime (LIX 860N-IC and 2-hydroxy-5-nonylacetophenona oxime (LIX 84-IC is discussed. The results showed that an increase in the acidity and an increase in the total concentration of chloride ions in the aqueous phase decreased significantly the extraction of copper as well as the extraction of iron for both extractants. This effect of the chloride ions can be explained by the formation of a series of chloro complexes of Cu(II and Fe(III in the aqueous phase. The effect of initial pH and total chloride concentration on the extraction of chloride by the organic phase suggests that LIX 860N-IC, and to a lesser extent LIX 84-IC, extract small amounts of the cationic complex, CuCl⁺. An increase in the concentration of chloride ions also produced a small decrease in the rate of copper extraction with both hydroxyoximes.

En este trabajo se discute el estudio de la extracción de cobre desde soluciones clorhídricas con dos hidroxioximas: 5-nonilsalicilaldoxima (LIX 860N-IC, y 2-hidroxi-5 nonilacetofenona oxima (LIX 84-IC. Los resultados indicaron que al aumentar la acidez o aumentar la concentración de cloruro en la fase acuosa se produce una significativa disminución en la extracción de cobre y hierro con ambas hidroxioximas. Este efecto del ion cloruro se explica por la formación de varios clorocomplejos de Cu(II y Fe(III en la solución acuosa. El efecto del pH y la concentración total de cloruro en la extracción de cloruro sugiere que el LIX 860N-IC, y en menor grado el LIX 84-IC extraen pequeñas cantidades del catión monovalente, CuCl⁺. Se determinó también que un aumento en la concentración de cloruro en la solución acuosa produce una leve disminución en la velocidad de extracción del cobre con ambas hidroxioximas.

Focal cerebral vasculitis associated with circulating immune complexes and brain irradiation

Energy Technology Data Exchange (ETDEWEB)

Groothuis, D.R.; Mikhael, M.A.

1986-06-01

In this report we describe a patient with a benign glioma treated with surgery and radiation. After a period of stability he developed subacute bacterial endocarditis, and deteriorated neurologically. Computed tomographic scans did not show recurrent tumor. An angiogram showed vasculitis restricted to the previously irradiated area. Secondary to subacute bacterial endocarditis was the presence of high levels of circulating immune complexes. His neurological status was unchanged after antibiotics, but improved after treatment with dexamethasone. We interpret the clinical course as an immune-complex-mediated vasculitis superimposed on a subclinical radiation vasculitis. This case supports the hypothesis that immune mechanisms may be involved in delayed radiation injury to the nervous system.

Focal cerebral vasculitis associated with circulating immune complexes and brain irradiation

International Nuclear Information System (INIS)

Groothuis, D.R.; Mikhael, M.A.

1986-01-01

In this report we describe a patient with a benign glioma treated with surgery and radiation. After a period of stability he developed subacute bacterial endocarditis, and deteriorated neurologically. Computed tomographic scans did not show recurrent tumor. An angiogram showed vasculitis restricted to the previously irradiated area. Secondary to subacute bacterial endocarditis was the presence of high levels of circulating immune complexes. His neurological status was unchanged after antibiotics, but improved after treatment with dexamethasone. We interpret the clinical course as an immune-complex-mediated vasculitis superimposed on a subclinical radiation vasculitis. This case supports the hypothesis that immune mechanisms may be involved in delayed radiation injury to the nervous system

Delivery route determines the presence of immune complexes on umbilical cord erythrocytes.

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de Lima, Andrés; Franco, Luis C; Sarmiento, Andrés; González, John M

2017-11-01

Umbilical cord blood offers a unique opportunity to study the basal level of immunoglobulin complexes. This study aims to determine the presence of immune complexes and complement deposition on erythrocytes from umbilical cord blood from normal, full-term pregnancies. In vitro pre-formed IgA, IgG, and IgM complexes were used as positive control for flow cytometry detection, and for C3d deposition. Blood samples (34) of umbilical cord blood taken from vaginal and cesarean deliveries were tested for the presence of immunoglobulin complexes. Fourteen samples from vaginal deliveries and 20 samples from cesarean deliveries were assessed. IgG and IgM complexes were detected on erythrocytes, whereas no IgA complexes or complement deposition was observed. Interestingly, the percentage of IgG complexes was higher on erythrocytes from vaginal delivery samples compared to those from cesarean deliveries. No other associations between immune complexes and other maternal or newborn variables were found. IgG and IgM complexes seem to be normally present on umbilical cord erythrocytes. Erythrocytes from vaginal deliveries have a higher percentage of IgG complexes present compared to that from cesarean deliveries. Since no C3d activity was detected, these complexes are non-pathological and should be part of the newborn's initial innate immune response.

Simulation of SEU transients in CMOS ICs

International Nuclear Information System (INIS)

Kaul, N.; Bhuva, B.L.; Kerns, S.E.

1991-01-01

This paper reports that available analytical models of the number of single-event-induced errors (SEU) in combinational logic systems are not easily applicable to real integrated circuits (ICs). An efficient computer simulation algorithm set, SITA, predicts the vulnerability of data stored in and processed by complex combinational logic circuits to SEU. SITA is described in detail to allow researchers to incorporate it into their error analysis packages. Required simulation algorithms are based on approximate closed-form equations modeling individual device behavior in CMOS logic units. Device-level simulation is used to estimate the probability that ion-device interactions produce erroneous signals capable of propagating to a latch (or n output node), and logic-level simulation to predict the spread of such erroneous, latched information through the IC. Simulation results are compared to those from SPICE for several circuit and logic configurations. SITA results are comparable to this established circuit-level code, and SITA can analyze circuits with state-of-the-art device densities (which SPICE cannot). At all IC complexity levels, SITAS offers several factors of 10 savings in simulation time over SPICE

Detection and isolation of cell-derived microparticles are compromised by protein complexes resulting from shared biophysical parameters.

Science.gov (United States)

György, Bence; Módos, Károly; Pállinger, Eva; Pálóczi, Krisztina; Pásztói, Mária; Misják, Petra; Deli, Mária A; Sipos, Aron; Szalai, Anikó; Voszka, István; Polgár, Anna; Tóth, Kálmán; Csete, Mária; Nagy, György; Gay, Steffen; Falus, András; Kittel, Agnes; Buzás, Edit I

2011-01-27

Numerous diseases, recently reported to associate with elevated microvesicle/microparticle (MP) counts, have also long been known to be characterized by accelerated immune complex (IC) formation. The goal of this study was to investigate the potential overlap between parameters of protein complexes (eg, ICs or avidin-biotin complexes) and MPs, which might perturb detection and/or isolation of MPs. In this work, after comprehensive characterization of MPs by electron microscopy, atomic force microscopy, dynamic light-scattering analysis, and flow cytometry, for the first time, we drive attention to the fact that protein complexes, especially insoluble ICs, overlap in biophysical properties (size, light scattering, and sedimentation) with MPs. This, in turn, affects MP quantification by flow cytometry and purification by differential centrifugation, especially in diseases in which IC formation is common, including not only autoimmune diseases, but also hematologic disorders, infections, and cancer. These data may necessitate reevaluation of certain published data on patient-derived MPs and contribute to correct the clinical laboratory assessment of the presence and biologic functions of MPs in health and disease.

Immunogenicity and safety of different injection routes and schedules of IC41, a Hepatitis C virus (HCV) peptide vaccine.

Science.gov (United States)

Firbas, Christa; Boehm, Thomas; Buerger, Vera; Schuller, Elisabeth; Sabarth, Nicolas; Jilma, Bernd; Klade, Christoph S

2010-03-11

An effective vaccine would be a significant progress in the management of chronic HCV infections. This study was designed to examine whether different application schedules and injection routes may enhance the immunogenicity of the HCV peptide vaccine IC41. In this randomized trial 54 healthy subjects received either subcutaneous (s.c.) or intradermal (i.d.) vaccinations weekly (16 injections) or every other week (8 injections). One group additionally received imiquimod, an activator of the toll-like receptor (TLR) 7. The T cell epitope-specific immune response to IC41 was assessed using [(3)H]-thymidine CD4+ T cell proliferation, interferon-gamma (IFN-gamma) CD8+ and CD4+ ELIspot and HLA-A*0201 fluorescence-activated cell sorting (FACS) tetramer-binding assays. More than 60% of vaccinees responded in the CD4+ T cell proliferation assay in all groups. An HLA-A*0201 FACS tetramer-binding assay and IFN-gamma CD8+ ELIspot class I response of more than 70% was induced in four and three groups, respectively. IC41 induced significant immunological responses in all groups with responder rates of up to 100%. Interestingly, topical imiquimod was not able to enhance immunogenicity but was associated with a lower immune response. Local injection site reactions were mostly transient. Intradermal injections caused more pronounced reactions compared to s.c., especially erythema and edema. Compared to a previous study intensified dosing and/or i.d. injections enhanced the response rates to the vaccine IC41 in three assays measuring T cell function. Immunization with IC41 was generally safe in this study. These results justify testing IC41 in further clinical trials with HCV-infected individuals.

Profiles of the N II 6584 A line over the giant H II regions IC 1318b and c, NGC 7000 and IC 5070. 2

Energy Technology Data Exchange (ETDEWEB)

Canto, J; Johnson, P G; Meaburn, J; Mikhail, J S; Terrett, D L; White, N J [Manchester Univ. (UK). Dept of Astronomy

1979-06-01

Previously (Paper I) large-scale splitting of the (N II) line was discovered over an area of IC 1318b. The motions of the ionized material have now been mapped over a much larger region of this nebula and also IC 1318c. The splitting reaches a maximum value of 53 km/s over the faintest regions of IC 1318b and occurs over an area approximately > 20 pc across. However, few split (N II) lines were found over IC 1318c, but the motions of this whole ionized and neutral complex have been shown to be closely related. Wind-driven flows along neutral and ionized shells are proposed to explain the observations. Similar measurements have also been made on either side of the dark lane separating NGC 7000 from IC 5070.

Design of a Low-Power, Small-Area AEC-Q100-Compliant SENT Transmitter in Signal Conditioning IC for Automotive Pressure and Temperature Complex Sensors in 180 Nm CMOS Technology

Science.gov (United States)

Rikhan, Behnam Samadpoor; Kim, Dong-Gyu; Lee, Dong-Soo; Rehman, Muhammad Riaz Ur; Abbasizadeh, Hamed; Asif, Muhammad; Lee, Minjae; Yang, Youngoo; Lee, Kang-Yoon

2018-01-01

In this paper, a low-power and small-area Single Edge Nibble Transmission (SENT) transmitter design is proposed for automotive pressure and temperature complex sensor applications. To reduce the cost and size of the hardware, the pressure and temperature information is processed with a single integrated circuit (IC) and transmitted at the same time to the electronic control unit (ECU) through SENT. Due to its digital nature, it is immune to noise, has reduced sensitivity to electromagnetic interference (EMI), and generates low EMI. It requires only one PAD for its connectivity with ECU, and thus reduces the pin requirements, simplifies the connectivity, and minimizes the printed circuit board (PCB) complexity. The design is fully synthesizable, and independent of technology. The finite state machine-based approach is employed for area efficient implementation, and to translate the proposed architecture into hardware. The IC is fabricated in 1P6M 180 nm CMOS process with an area of (116 μm × 116 μm) and 4.314 K gates. The current consumption is 50 μA from a 1.8 V supply with a total 90 μW power. For compliance with AEC-Q100 for automotive reliability, a reverse and over voltage protection circuit is also implemented with human body model (HBM) electro-static discharge (ESD) of +6 kV, reverse voltage of −16 V to 0 V, over voltage of 8.2 V to 16 V, and fabricated area of 330 μm × 680 μm. The extensive testing, measurement, and simulation results prove that the design is fully compliant with SAE J2716 standard. PMID:29757996

Soluble immune complexes shift the TLR-induced cytokine production of distinct polarized human macrophage subsets towards IL-10.

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Carmen A Ambarus

Full Text Available BACKGROUND: Costimulation of murine macrophages with immune complexes (ICs and TLR ligands leads to alternative activation. Studies on human myeloid cells, however, indicate that ICs induce an increased pro-inflammatory cytokine production. This study aimed to clarify the effect of ICs on the pro- versus anti-inflammatory profile of human polarized macrophages. MATERIALS AND METHODS: Monocytes isolated from peripheral blood of healthy donors were polarized for four days with IFN-γ, IL-4, IL-10, GM-CSF, M-CSF, or LPS, in the presence or absence of heat aggregated gamma-globulins (HAGGs. Phenotypic polarization markers were measured by flow cytometry. Polarized macrophages were stimulated with HAGGs or immobilized IgG alone or in combination with TLR ligands. TNF, IL-6, IL-10, IL-12, and IL-23 were measured by Luminex and/or RT-qPCR. RESULTS: HAGGs did not modulate the phenotypic polarization and the cytokine production of macrophages. However, HAGGs significantly altered the TLR-induced cytokine production of all polarized macrophage subsets, with the exception of MΦ(IL-4. In particular, HAGGs consistently enhanced the TLR-induced IL-10 production in both classically and alternatively polarized macrophages (M1 and M2. The effect of HAGGs on TNF and IL-6 production was less pronounced and depended on the polarization status, while IL-23p19 and IL-12p35 expression was not affected. In contrast with HAGGs, immobilized IgG induced a strong upregulation of not only IL-10, but also TNF and IL-6. CONCLUSION: HAGGs alone do not alter the phenotype and cytokine production of in vitro polarized human macrophages. In combination with TLR-ligands, however, HAGGs but not immobilized IgG shift the cytokine production of distinct macrophage subsets toward IL-10.

Mod 1 ICS TI Report: ICS Conversion of a 140% HPGe Detector

Energy Technology Data Exchange (ETDEWEB)

Bounds, John Alan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2016-07-05

This report evaluates the Mod 1 ICS, an electrically cooled 140% HPGe detector. It is a custom version of the ORTEC Integrated Cooling System (ICS) modified to make it more practical for us to use in the field. Performance and operating characteristics of the Mod 1 ICS are documented, noting both pros and cons. The Mod 1 ICS is deemed a success. Recommendations for a Mod 2 ICS, a true field prototype, are provided.

Application of fluorescent monocytes for probing immune complexes on antigen microarrays.

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Zoltán Szittner

Full Text Available Microarrayed antigens are used for identifying serum antibodies with given specificities and for generating binding profiles. Antibodies bind to these arrayed antigens forming immune complexes and are conventionally identified by secondary labelled antibodies.In the body immune complexes are identified by bone marrow derived phagocytic cells, such as monocytes. In our work we were looking into the possibility of replacing secondary antibodies with monocytoid cells for the generation of antibody profiles. Using the human monocytoid cell line U937, which expresses cell surface receptors for immune complex components, we show that cell adhesion is completely dependent on the interaction of IgG heavy chains and Fcγ receptors, and this recognition is susceptible to differences between heavy chain structures and their glycosylation. We also report data on a possible application of this system in autoimmune diagnostics.Compared to secondary antibodies, fluorescent monocytesas biosensors are superior in reflecting biological functions of microarray-bound antibodies and represent an easy and robust alternative for profiling interactions between serum proteins and antigens.

Detection of circulating immune complexes in breast cancer and melanoma by three different methods

Energy Technology Data Exchange (ETDEWEB)

Krapf, F; Renger, D; Fricke, M; Kemper, A; Schedel, I; Deicher, H

1982-08-01

By the simultaneous application of three methods, C1q-binding-test (C1q-BA), a two antibody conglutinin binding ELISA and a polyethylene-glycol 6000 precipitation with subsequent quantitative determination of immunoglobulins and complement factors in the redissolved precipitates (PPLaNT), circulating immune complexes could be demonstrated in the sera of 94% of patients with malignant melanoma and of 75% of breast cancer patients. The specific detection rates of the individual methods varied between 23% (C1q-BA) and 46% (PPLaNT), presumably due to the presence of qualitatively different immune complexes in the investigated sera. Accordingly, the simultaneous use of the afore mentioned assays resulted in an increased diagnostic sensitivity and a duplication of the predictive value. Nevertheless, because of the relatively low incidence of malignant diseases in the total population, and due to the fact that circulating immune complexes occur in other non-malignant diseases with considerable frequency, tests for circulating immune complexes must be regarded as less useful parameters in the early diagnostic of cancer.

Ultraviolet light-denatured DNA/anti-ultraviolet light-denatured DNA immune-complex nephritis in rabbits

International Nuclear Information System (INIS)

Sweny, P.

1980-01-01

Two groups of preimmunized rabbits were studied during a 3-month course of daily intravenous injections of uv DNA in amounts sufficient to neuralize circulating antibody. One group was given high-molecular-weight uv DNA, and the other group, US uv DNA. Rabbits receiving US uv DNA formed potentially more damaging immune complexes, since this group of animals developed greater rises in blood urea and greater falls in C3. Both groups of animals developed evidence of immune complex-mediated glomerular nephritis as evidenced by heavy granular deposits of IgG and C3 in the glomeruli. The results suggest that immune complexes formed with US uv DNA may be more nephrotoxic

Genes of the major histocompatibility complex highlight interactions of the innate and adaptive immune system

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Barbara Lukasch

2017-08-01

Full Text Available Background A well-functioning immune defence is crucial for fitness, but our knowledge about the immune system and its complex interactions is still limited. Major histocompatibility complex (MHC molecules are involved in T-cell mediated adaptive immune responses, but MHC is also highly upregulated during the initial innate immune response. The aim of our study was therefore to determine to what extent the highly polymorphic MHC is involved in interactions of the innate and adaptive immune defence and if specific functional MHC alleles (FA or heterozygosity at the MHC are more important. Methods To do this we used captive house sparrows (Passer domesticus to survey MHC diversity and immune function controlling for several environmental factors. MHC class I alleles were identified using parallel amplicon sequencing and to mirror immune function, several immunological tests that correspond to the innate and adaptive immunity were conducted. Results Our results reveal that MHC was linked to all immune tests, highlighting its importance for the immune defence. While all innate responses were associated with one single FA, adaptive responses (cell-mediated and humoral were associated with several different alleles. Discussion We found that repeated injections of an antibody in nestlings and adults were linked to different FA and hence might affect different areas of the immune system. Also, individuals with a higher number of different FA produced a smaller secondary response, indicating a disadvantage of having numerous MHC alleles. These results demonstrate the complexity of the immune system in relation to the MHC and lay the foundation for other studies to further investigate this topic.

Genes of the major histocompatibility complex highlight interactions of the innate and adaptive immune system.

Science.gov (United States)

Lukasch, Barbara; Westerdahl, Helena; Strandh, Maria; Winkler, Hans; Moodley, Yoshan; Knauer, Felix; Hoi, Herbert

2017-01-01

A well-functioning immune defence is crucial for fitness, but our knowledge about the immune system and its complex interactions is still limited. Major histocompatibility complex (MHC) molecules are involved in T-cell mediated adaptive immune responses, but MHC is also highly upregulated during the initial innate immune response. The aim of our study was therefore to determine to what extent the highly polymorphic MHC is involved in interactions of the innate and adaptive immune defence and if specific functional MHC alleles (FA) or heterozygosity at the MHC are more important. To do this we used captive house sparrows ( Passer domesticus ) to survey MHC diversity and immune function controlling for several environmental factors. MHC class I alleles were identified using parallel amplicon sequencing and to mirror immune function, several immunological tests that correspond to the innate and adaptive immunity were conducted. Our results reveal that MHC was linked to all immune tests, highlighting its importance for the immune defence. While all innate responses were associated with one single FA, adaptive responses (cell-mediated and humoral) were associated with several different alleles. We found that repeated injections of an antibody in nestlings and adults were linked to different FA and hence might affect different areas of the immune system. Also, individuals with a higher number of different FA produced a smaller secondary response, indicating a disadvantage of having numerous MHC alleles. These results demonstrate the complexity of the immune system in relation to the MHC and lay the foundation for other studies to further investigate this topic.

Circulating immune complexes and complement concentrations in patients with alcoholic liver disease

DEFF Research Database (Denmark)

Gluud, C; Jans, H

1982-01-01

A prospective evaluation of circulating immune complexes (CIC) and the activity of the complement system was undertaken in 53 alcoholic patients just before diagnostic liver biopsy. Circulating immune complexes were detected in 39% of patients with alcoholic steatosis (n = 26), 58% of patients...... with alcoholic hepatitis (n = 12), and 60% of patients with alcoholic cirrhosis (n = 15). No significant difference was found between the three group of patients. The activity of the complement system was within reference limits in the majority of patients and only slight differences were detected between...

The function of the Mediator complex in plant immunity.

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An, Chuanfu; Mou, Zhonglin

2013-03-01

Upon pathogen infection, plants undergo dramatic transcriptome reprogramming to shift from normal growth and development to immune response. During this rapid process, the multiprotein Mediator complex has been recognized as an important player to fine-tune gene-specific and pathway-specific transcriptional reprogramming by acting as an adaptor/coregulator between sequence-specific transcription factor and RNA polymerase II (RNAPII). Here, we review current understanding of the role of five functionally characterized Mediator subunits (MED8, MED15, MED16, MED21 and MED25) in plant immunity. All these Mediator subunits positively regulate resistance against leaf-infecting biotrophic bacteria or necrotrophic fungi. While MED21 appears to regulate defense against fungal pathogens via relaying signals from upstream regulators and chromatin modification to RNAPII, the other four Mediator subunits locate at different positions of the defense network to convey phytohormone signal(s). Fully understanding the role of Mediator in plant immunity needs to characterize more Mediator subunits in both Arabidopsis and other plant species. Identification of interacting proteins of Mediator subunits will further help to reveal their specific regulatory mechanisms in plant immunity.

Circulating immune complexes, immunoglobulin classes (IgG, IgA ...

African Journals Online (AJOL)

Objective:- To evaluate serum levels of circulating immune complexes (CICs), immunoglobulin classes (IgG, IgA and IgM) and Complement Components (C3c, C4 and Factor B) in Nigerians with Type 1 or Type 2 diabetes mellitus. Design:- Case control study. Setting:- University College Hospital, Ibadan, Oyo State, Nigeria.

Children and IC

Science.gov (United States)

... Cola, and Orange Crush, for example), Kool-Aid, chocolate, and many fruits, fruit juices and drinks (including ... Guideline IC Treatments IC Diet & Self Management Physical Therapy Antidepressants Antihistamines Pentosan Polysulfate Sodium Bladder Instillations Immunosuppresants ...

Immunity to transplantable nitrosourea-induced neurogenic tumors. III. Systemic adoptive transfer of immunity

International Nuclear Information System (INIS)

Shibuya, N.; Hochgeschwender, U.; Kida, Y.; Hochwald, G.M.; Thorbecke, G.J.; Cravioto, H.

1984-01-01

The effect of intravenously injected tumor immune spleen cells on growth of 3 X 10 5 gliosarcoma T 9 cells injected intradermally (ID) or intracerebrally (IC) into sublethally irradiated CDF rats was evaluated. Spleen cells from donor rats with sufficient immunity to reject 5 X 10 5 T 9 cells inhibited the growth of T 9 cells mixed with spleen cells in a ratio of 1:25 and injected ID, but could not act after intravenous transfer. However, donor rats which had rejected increasing T 9 challenge doses up to 1 X 10 7 cells produced immune spleen cells which, upon IV transfer, could inhibit growth of ID T 9 challenge but not of EB-679, an unrelated glioma, in recipient rats. Rejection of IC T 9 challenge was also obtained after IV transfer, in recipients of such ''hyperimmune'' spleen cells, but was less (60% maximum) than that noted after ID T 9 challenge (100% maximum). The removal of B cells from the transferred spleen cells did not affect the results, suggesting that the specific immunity was mediated by T cells. The authors conclude that the special immunological circumstances of tumors growing in the brain renders them less accessible to rejection by systemically transferred immune cells, but it is nevertheless possible to effect a significant incidence of rejection of syngeneic tumor growth in the brain by the intravenous transfer of hyperimmune spleen cells

Application of human erythrocytes to a radioimmune assay of immune complexes in serum. [Lupus erythematosus, type B hepatitis

Energy Technology Data Exchange (ETDEWEB)

Tsuda, F; Miyakawa, Y; Mayumi, M [Tokyo Metropolitan Lab. of Public Health (Japan)

1979-07-01

An immune adherence receptor exists on the surface of primate erythrocytes, and has been characterized as a receptor for the activated third component of complement (C3b). Human red blood cells (RCBs, blood group O) were applied to a sensitive determination of complement-fixing, soluble immune complexes in serum. The method involved the binding of immune complexes with RBCs in the presence of complement and the detection of cell-bound IgG molecules by radiolabelled anti-human IgG antibodies. Since the binding of RBCs with monomeric IgG was minimal, cell bound IgG molecules were taken as representing immune complexes. When aggregated human gammaglobulin (AHG) was used as a model of immune complexes, as little as 5 ..mu..g dissolved in 1 ml of normal human serum were detected. The binding of RBCs with AHG was inhibited in EDTA solution where the classical complement pathway could not be activated. The RBC radioimmune assay was successfully applied to the determination of soluble immune complexes in pathological serum samples obtained from the patients with systemic lupus erythematosus and those with fulminant Type B hepatitis. False-positive results by autoantibodies against RBCs could be excluded by a Coombs test and by comparing the binding in the presence of complement with that in EDTA solution. The ubiquitous availability of RBCs coupled with a high sensitivity would allow the RBC radioimmune assay to be used as a further method of determining immune complexes in the serum.

Men and IC

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... Bowel Syndrome Lupus Pelvic Floor Dysfunction Pudendal Neuralgia Sjogren’s Syndrome Vulvodynia Newly Diagnosed Toolkit IC Awareness Toolkit Know ... Bowel Syndrome Lupus Pelvic Floor Dysfunction Pudendal Neuralgia Sjogren’s Syndrome Vulvodynia Newly Diagnosed Toolkit IC Awareness Toolkit Know ...

General IC Symptoms

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... Bowel Syndrome Lupus Pelvic Floor Dysfunction Pudendal Neuralgia Sjogren’s Syndrome Vulvodynia Newly Diagnosed Toolkit IC Awareness Toolkit Know ... Bowel Syndrome Lupus Pelvic Floor Dysfunction Pudendal Neuralgia Sjogren’s Syndrome Vulvodynia Newly Diagnosed Toolkit IC Awareness Toolkit Know ...

Pregnancy and IC

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... have not already done so, try to identify foods, beverages, and supplements that are irritating to your bladder ... Other Medicines Over-the-counter Medicines Pain Management Management of IC ... Diet Food Diaries Least and Most Bothersome Foods IC-Friendly ...

Maximum-Entropy Models of Sequenced Immune Repertoires Predict Antigen-Antibody Affinity

DEFF Research Database (Denmark)

Asti, Lorenzo; Uguzzoni, Guido; Marcatili, Paolo

2016-01-01

The immune system has developed a number of distinct complex mechanisms to shape and control the antibody repertoire. One of these mechanisms, the affinity maturation process, works in an evolutionary-like fashion: after binding to a foreign molecule, the antibody-producing B-cells exhibit a high...... of an HIV-1 infected patient. The Pearson correlation coefficient between our scoring function and the IC50 neutralization titer measured on 30 different antibodies of known sequence is as high as 0.77 (p-value 10-6), outperforming other sequence- and structure-based models....

Vaccination of koalas (Phascolarctos cinereus) with a recombinant chlamydial major outer membrane protein adjuvanted with poly I:C, a host defense peptide and polyphosphazine, elicits strong and long lasting cellular and humoral immune responses.

Science.gov (United States)

Khan, Shahneaz Ali; Waugh, Courtney; Rawlinson, Galit; Brumm, Jacqui; Nilsson, Karen; Gerdts, Volker; Potter, Andrew; Polkinghorne, Adam; Beagley, Kenneth; Timms, Peter

2014-10-07

Chlamydial infections are wide spread in koalas across their range and a solution to this debilitating disease has been sought for over a decade. Antibiotics are the currently accepted therapeutic measure, but are not an effective treatment due to the asymptomatic nature of some infections and a low efficacy rate. Thus, a vaccine would be an ideal way to address this infectious disease threat in the wild. Previous vaccine trials have used a three-dose regimen; however this is very difficult to apply in the field as it would require multiple capture events, which are stressful and invasive processes for the koala. In addition, it requires skilled koala handlers and a significant monetary investment. To overcome these challenges, in this study we utilized a polyphosphazine based poly I:C and a host defense peptide adjuvant combined with recombinant chlamydial major outer membrane protein (rMOMP) antigen to induce long lasting (54 weeks) cellular and humoral immunity in female koalas with a novel single immunizing dose. Immunized koalas produced a strong IgG response in plasma, as well as at mucosal sites. Moreover, they showed high levels of C. pecorum specific neutralizing antibodies in the plasma as well as vaginal and conjunctival secretions. Lastly, Chlamydia-specific lymphocyte proliferation responses were produced against both whole chlamydial elementary bodies and rMOMP protein, over the 12-month period. The results of this study suggest that a single dose rMOMP vaccine incorporating a poly I:C, host defense peptide and polyphosphazine adjuvant is able to stimulate both arms of the immune system in koalas, thereby providing an alternative to antibiotic treatment and/or a three-dose vaccine regime. Copyright © 2014 Elsevier Ltd. All rights reserved.

FcγRIIIa expression on monocytes in rheumatoid arthritis: role in immune-complex stimulated TNF production and non-response to methotrexate therapy.

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Dawn L Cooper

Full Text Available OBJECTIVE: The expression of FcγRIIIa/CD16 may render monocytes targets for activation by IgG-containing immune complexes (IC. We investigated whether FcγRIIIa/CD16 was upregulated in rheumatoid arthritis (RA, associated with TNF production in response to IC-stimulation, and if this predicted response to methotrexate therapy. METHODS: FcγRIIIa/CD16 expression on CD14(low and CD14++ monocytes was measured by flow cytometry in healthy controls and RA patients (early and long-standing disease. Intracellular TNF-staining was carried out after in vitro LPS or heat-aggregated immunoglobulin (HAG activation. FcγRIIIa/CD16 expression pre- and post-steroid/methotrexate treatment was examined. RESULTS: Increased FcγRIIIa/CD16 expression on CD14++ monocytes in long-standing RA patients compared to controls was demonstrated (p = 0.002 with intermediate levels in early-RA patients. HAG-induced TNF-production in RA patients was correlated with the percentage of CD14++ monocytes expressing FcγRIIIa/CD16 (p<0.001. The percentage of CD14++ monocytes expressing FcγRIIIa/CD16 at baseline in early DMARD-naïve RA patients was negatively correlated with DAS28-ESR improvement 14-weeks post-methotrexate therapy (p = 0.003 and was significantly increased in EULAR non-responders compared to moderate (p = 0.01 or good responders (p = 0.003. FcγRIIIa/CD16 expression was not correlated with age, presence of systemic inflammation or autoantibody titers. CONCLUSION: Increased FcγRIIIa/CD16 expression on CD14++ monocytes in RA may result in a cell that has increased responsiveness to IC-stimulation. This monocyte subset may contribute to non-response to methotrexate therapy.

FcγRIIIa Expression on Monocytes in Rheumatoid Arthritis: Role in Immune-Complex Stimulated TNF Production and Non-Response to Methotrexate Therapy

Science.gov (United States)

Cooper, Dawn L.; Martin, Stephen G.; Robinson, James I.; Mackie, Sarah L.; Charles, Christopher J.; Nam, Jackie; Consortium, YEAR; Isaacs, John D.; Emery, Paul; Morgan, Ann W.

2012-01-01

Objective The expression of FcγRIIIa/CD16 may render monocytes targets for activation by IgG-containing immune complexes (IC). We investigated whether FcγRIIIa/CD16 was upregulated in rheumatoid arthritis (RA), associated with TNF production in response to IC-stimulation, and if this predicted response to methotrexate therapy. Methods FcγRIIIa/CD16 expression on CD14low and CD14++ monocytes was measured by flow cytometry in healthy controls and RA patients (early and long-standing disease). Intracellular TNF-staining was carried out after in vitro LPS or heat-aggregated immunoglobulin (HAG) activation. FcγRIIIa/CD16 expression pre- and post-steroid/methotrexate treatment was examined. Results Increased FcγRIIIa/CD16 expression on CD14++ monocytes in long-standing RA patients compared to controls was demonstrated (p = 0.002) with intermediate levels in early-RA patients. HAG-induced TNF-production in RA patients was correlated with the percentage of CD14++ monocytes expressing FcγRIIIa/CD16 (p<0.001). The percentage of CD14++ monocytes expressing FcγRIIIa/CD16 at baseline in early DMARD-naïve RA patients was negatively correlated with DAS28-ESR improvement 14-weeks post-methotrexate therapy (p = 0.003) and was significantly increased in EULAR non-responders compared to moderate (p = 0.01) or good responders (p = 0.003). FcγRIIIa/CD16 expression was not correlated with age, presence of systemic inflammation or autoantibody titers. Conclusion Increased FcγRIIIa/CD16 expression on CD14++ monocytes in RA may result in a cell that has increased responsiveness to IC-stimulation. This monocyte subset may contribute to non-response to methotrexate therapy. PMID:22235253

Immune-mediated steroid-responsive epileptic spasms and epileptic encephalopathy associated with VGKC-complex antibodies.

Science.gov (United States)

Suleiman, Jehan; Brenner, Tanja; Gill, Deepak; Troedson, Christopher; Sinclair, Adriane J; Brilot, Fabienne; Vincent, Angela; Lang, Bethan; Dale, Russell C

2011-11-01

Autoantibodies that bind to voltage-gated potassium-channel complex proteins (VGKC-complex antibodies) occur frequently in adults with limbic encephalitis presenting with cognitive impairment and seizures. Recently, VGKC-complex antibodies have been described in a few children with limbic encephalitis, and children with unexplained encephalitis presenting with status epilepticus. We report a case of infantile-onset epileptic spasms and developmental delay compatible with epileptic encephalopathy. Our patient was a female infant, aged 4 months at presentation. She had evidence of immune activation in the central nervous system with elevated cerebrospinal fluid neopterin and mirrored oligoclonal bands, which prompted testing for autoantibodies. VGKC-complex antibodies were elevated (201 pmol/L, normalVGKC-complex antibodies might represent a marker of immune therapy responsiveness in a subgroup of patients with infantile epileptic encephalopathy. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.

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

DEFF Research Database (Denmark)

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

1994-01-01

-binding to granulocytes (PMN), monocytes and lymphocytes was inhibited by up to 46%, 61% and 48%, respectively, depending on the incubation time and the IC-concentration tested. The E-mediated inhibition of the binding to PMN was found to correlate with the average numbers of CR1 per E during the initial 15 min...... to the findings for PMN, the difference between IC-binding to monocytes in the absence and presence of E increased progressively over the 90 min observation period, suggesting that different mechanisms are involved in the late-phase IC uptake by monocytes and PMN. Lymphocytes were heterogeneous with respect to IC...... binding, the main contributors being B cells. E initially inhibited and then later enhanced the IC binding to lymphocytes, suggesting that E promote B cell uptake of C3d,g-covered IC via CR2. Our findings, that E can restrict the IC uptake by circulating leucocytes, and that an IC-induced degranulation...

Increased immune complexes of hypocretin autoantibodies in narcolepsy.

Science.gov (United States)

Deloumeau, Aude; Bayard, Sophie; Coquerel, Quentin; Déchelotte, Pierre; Bole-Feysot, Christine; Carlander, Bertrand; Cochen De Cock, Valérie; Fetissov, Sergueï O; Dauvilliers, Yves

2010-10-13

Hypocretin peptides participate in the regulation of sleep-wake cycle while deficiency in hypocretin signaling and loss of hypocretin neurons are causative for narcolepsy-cataplexy. However, the mechanism responsible for alteration of the hypocretin system in narcolepsy-cataplexy and its relevance to other central hypersomnias remain unknown. Here we studied whether central hypersomnias can be associated with autoantibodies reacting with hypocretin-1 peptide present as immune complexes. Serum levels of free and dissociated (total) autoantibodies reacting with hypocretin-1 peptide were measured by enzyme-linked immunosorbent assay and analyzed with regard to clinical parameters in 82 subjects with narcolepsy-cataplexy, narcolepsy without cataplexy or idiopathic hypersomnia and were compared to 25 healthy controls. Serum levels of total but not free IgG autoantibodies against hypocretin-1 were increased in narcolepsy-cataplexy. Increased levels of complexed IgG autoantibodies against hypocretin-1 were found in all patients groups with a further increase in narcolepsy-cataplexy. Levels of total IgM hypocretin-1 autoantibodies were also elevated in all groups of patients. Increased levels of anti-idiotypic IgM autoantibodies reacting with hypocretin-1 IgG autoantibodies affinity purified from sera of subjects with narcolepsy-cataplexy were found in all three groups of patients. Disease duration correlated negatively with serum levels of hypocretin-1 IgG and IgM autoantibodies and with anti-idiotypic IgM autoantibodies. Central hypersomnias and particularly narcolepsy-cataplexy are characterized by higher serum levels of autoantibodies directed against hypocretin-1 which are present as immune complexes most likely with anti-idiotypic autoantibodies suggesting their relevance to the mechanism of sleep-wake cycle regulation.

Increased immune complexes of hypocretin autoantibodies in narcolepsy.

Directory of Open Access Journals (Sweden)

Aude Deloumeau

Full Text Available BACKGROUND: Hypocretin peptides participate in the regulation of sleep-wake cycle while deficiency in hypocretin signaling and loss of hypocretin neurons are causative for narcolepsy-cataplexy. However, the mechanism responsible for alteration of the hypocretin system in narcolepsy-cataplexy and its relevance to other central hypersomnias remain unknown. Here we studied whether central hypersomnias can be associated with autoantibodies reacting with hypocretin-1 peptide present as immune complexes. METHODOLOGY: Serum levels of free and dissociated (total autoantibodies reacting with hypocretin-1 peptide were measured by enzyme-linked immunosorbent assay and analyzed with regard to clinical parameters in 82 subjects with narcolepsy-cataplexy, narcolepsy without cataplexy or idiopathic hypersomnia and were compared to 25 healthy controls. PRINCIPAL FINDINGS: Serum levels of total but not free IgG autoantibodies against hypocretin-1 were increased in narcolepsy-cataplexy. Increased levels of complexed IgG autoantibodies against hypocretin-1 were found in all patients groups with a further increase in narcolepsy-cataplexy. Levels of total IgM hypocretin-1 autoantibodies were also elevated in all groups of patients. Increased levels of anti-idiotypic IgM autoantibodies reacting with hypocretin-1 IgG autoantibodies affinity purified from sera of subjects with narcolepsy-cataplexy were found in all three groups of patients. Disease duration correlated negatively with serum levels of hypocretin-1 IgG and IgM autoantibodies and with anti-idiotypic IgM autoantibodies. CONCLUSION: Central hypersomnias and particularly narcolepsy-cataplexy are characterized by higher serum levels of autoantibodies directed against hypocretin-1 which are present as immune complexes most likely with anti-idiotypic autoantibodies suggesting their relevance to the mechanism of sleep-wake cycle regulation.

Abundances of Planetary Nebulae IC 418, IC 2165 and NGC 5882

NARCIS (Netherlands)

Pottasch, [No Value; Bernard-Salas, J; Beintema, DA; Feibelman, WA

The ISO and IUE spectra of the elliptical nebulae NGC 5882, IC 418 and IC 2165 are presented. These spectra are combined with the spectra in the visual wavelength region to obtain a complete, extinction corrected, spectrum. The chemical composition of the nebulae is then calculated and compared to

CD1d-restricted IFN-γ-secreting NKT cells promote immune complex-induced acute lung injury by regulating macrophage-inflammatory protein-1α production and activation of macrophages and dendritic cells.

Science.gov (United States)

Kim, Ji Hyung; Chung, Doo Hyun

2011-02-01

Immune complex-induced acute lung injury (IC-ALI) has been implicated in various pulmonary disease states. However, the role of NKT cells in IC-ALI remains unknown. Therefore, we explored NKT cell functions in IC-ALI using chicken egg albumin and anti-chicken egg albumin IgG. The bronchoalveolar lavage fluid of CD1d(-/-) and Jα18(-/-) mice contained few Ly6G(+)CD11b(+) granulocytes, whereas levels in B6 mice were greater and were increased further by α-galactosyl ceramide. IFN-γ and MIP-1α production in the lungs was greater in B6 than CD1d(-/-) mice. Adoptive transfer of wild type (WT) but not IFN-γ-, MIP-1α-, or FcγR-deficient NKT cells into CD1d(-/-) mice caused recruitment of inflammatory cells to the lungs. Moreover, adoptive transfer of IFN-γR-deficient NKT cells enhanced MIP-1α production and cell recruitment in the lungs of CD1d(-/-) or CD1d(-/-)IFN-γ(-/-) mice, but to a lesser extent than WT NKT cells. This suggests that IFN-γ-producing NKT cells enhance MIP-1α production in both an autocrine and a paracrine manner. IFN-γ-deficient NKT cells induced less IL-1β and TNF-α production by alveolar macrophages and dendritic cells in CD1d(-/-) mice than did WT NKT cells. Taken together, these data suggest that CD1d-restricted IFN-γ-producing NKT cells promote IC-ALI by producing MIP-1α and enhancing proinflammatory cytokine production by alveolar macrophages and dendritic cells.

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

DEFF Research Database (Denmark)

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

1994-01-01

binding, the main contributors being B cells. E initially inhibited and then later enhanced the IC binding to lymphocytes, suggesting that E promote B cell uptake of C3d,g-covered IC via CR2. Our findings, that E can restrict the IC uptake by circulating leucocytes, and that an IC-induced degranulation...

Advances in analog and RF IC design for wireless communication systems

CERN Document Server

Manganaro, Gabriele

2013-01-01

Advances in Analog and RF IC Design for Wireless Communication Systems gives technical introductions to the latest and most significant topics in the area of circuit design of analog/RF ICs for wireless communication systems, emphasizing wireless infrastructure rather than handsets. The book ranges from very high performance circuits for complex wireless infrastructure systems to selected highly integrated systems for handsets and mobile devices. Coverage includes power amplifiers, low-noise amplifiers, modulators, analog-to-digital converters (ADCs) and digital-to-analog converters

Expression of an immunogenic Ebola immune complex in Nicotiana benthamiana.

Science.gov (United States)

Phoolcharoen, Waranyoo; Bhoo, Seong H; Lai, Huafang; Ma, Julian; Arntzen, Charles J; Chen, Qiang; Mason, Hugh S

2011-09-01

Filoviruses (Ebola and Marburg viruses) cause severe and often fatal haemorrhagic fever in humans and non-human primates. The US Centers for Disease Control identifies Ebola and Marburg viruses as 'category A' pathogens (defined as posing a risk to national security as bioterrorism agents), which has lead to a search for vaccines that could prevent the disease. Because the use of such vaccines would be in the service of public health, the cost of production is an important component of their development. The use of plant biotechnology is one possible way to cost-effectively produce subunit vaccines. In this work, a geminiviral replicon system was used to produce an Ebola immune complex (EIC) in Nicotiana benthamiana. Ebola glycoprotein (GP1) was fused at the C-terminus of the heavy chain of humanized 6D8 IgG monoclonal antibody, which specifically binds to a linear epitope on GP1. Co-expression of the GP1-heavy chain fusion and the 6D8 light chain using a geminiviral vector in leaves of N. benthamiana produced assembled immunoglobulin, which was purified by ammonium sulphate precipitation and protein G affinity chromatography. Immune complex formation was confirmed by assays to show that the recombinant protein bound the complement factor C1q. Size measurements of purified recombinant protein by dynamic light scattering and size-exclusion chromatography also indicated complex formation. Subcutaneous immunization of BALB/C mice with purified EIC resulted in anti-Ebola virus antibody production at levels comparable to those obtained with a GP1 virus-like particle. These results show excellent potential for a plant-expressed EIC as a human vaccine. © 2011 The Authors. Plant Biotechnology Journal © 2011 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

PF4-HIT antibody (KKO) complexes activate broad innate immune and inflammatory responses.

Science.gov (United States)

Haile, Lydia A; Rao, Roshni; Polumuri, Swamy K; Arepally, Gowthami M; Keire, David A; Verthelyi, Daniela; Sommers, Cynthia D

2017-11-01

Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication of heparin anticoagulation therapy resulting in thrombocytopenia frequently accompanied by thrombosis. Current evidence suggests that HIT is associated with antibodies developed in response to multi-molecular complexes formed by platelet factor 4 (PF4) bound to heparin or cell surface glycosaminoglycans. These antibody complexes activate platelets and monocytes typically through FcγRIIA receptors increasing the production of PF4, inflammatory mediators, tissue factor and thrombin. The influence of underlying events in HIT including complex-induced pro-inflammatory cell activation and structural determinants leading to local inflammatory responses are not fully understood. The stoichiometry and complex component requirements were determined by incubating fresh peripheral blood mononuclear cells (PBMC) with different concentrations of unfractionated heparin (H), low molecular weight heparin (LMWH), PF4- and anti-PF4-H complex antibodies (KKO). Cytokine mRNA or protein were measured by qRT-PCR or Meso Scale Discovery technology, respectively. Gene expression profile analysis for 594 genes was performed using Nanostring technology and analyzed using Ingenuity Pathway Analysis software. The data show that antibodies magnify immune responses induced in PBMCs by PF4 alone or in complex with heparin or LMWH. We propose that following induction of HIT antibodies by heparin-PF4 complexes, binding of the antibodies to PF4 is sufficient to induce a local pro-inflammatory response which may play a role in the progression of HIT. In vitro assays using PBMCs may be useful in characterizing local inflammatory and innate immune responses induced by HIT antibodies in the presence of PF4 and different sources of heparins. The findings and conclusions in this article are solely the responsibility of the authors and are not being formally disseminated by the Food and Drug Administration. Thus, they should not be

Complex role for the immune system in initiation and progression of pancreatic cancer.

Science.gov (United States)

Inman, Kristin S; Francis, Amanda A; Murray, Nicole R

2014-08-28

The immune system plays a complex role in the development and progression of pancreatic cancer. Inflammation can promote the formation of premalignant lesions and accelerate pancreatic cancer development. Conversely, pancreatic cancer is characterized by an immunosuppressive environment, which is thought to promote tumor progression and invasion. Here we review the current literature describing the role of the immune response in the progressive development of pancreatic cancer, with a focus on the mechanisms that drive recruitment and activation of immune cells at the tumor site, and our current understanding of the function of the immune cell types at the tumor. Recent clinical and preclinical data are reviewed, detailing the involvement of the immune response in pancreatitis and pancreatic cancer, including the role of specific cytokines and implications for disease outcome. Acute pancreatitis is characterized by a predominantly innate immune response, while chronic pancreatitis elicits an immune response that involves both innate and adaptive immune cells, and often results in profound systemic immune-suppression. Pancreatic adenocarcinoma is characterized by marked immune dysfunction driven by immunosuppressive cell types, tumor-promoting immune cells, and defective or absent inflammatory cells. Recent studies reveal that immune cells interact with cancer stem cells and tumor stromal cells, and these interactions have an impact on development and progression of pancreatic ductal adenocarcinoma (PDAC). Finally, current PDAC therapies are reviewed and the potential for harnessing the actions of the immune response to assist in targeting pancreatic cancer using immunotherapy is discussed.

Individual differences in maternal response to immune challenge predict offspring behavior: Contribution of environmental factors

Science.gov (United States)

Bronson, Stefanie L.; Ahlbrand, Rebecca; Horn, Paul S.; Kern, Joseph R.; Richtand, Neil M.

2011-01-01

Maternal infection during pregnancy elevates risk for schizophrenia and related disorders in offspring. Converging evidence suggests the maternal inflammatory response mediates the interaction between maternal infection, altered brain development, and behavioral outcome. The extent to which individual differences in the maternal response to immune challenge influence the development of these abnormalities is unknown. The present study investigated the impact of individual differences in maternal response to the viral mimic polyinosinic:polycytidylic acid (poly I:C) on offspring behavior. We observed significant variability in body weight alterations of pregnant rats induced by administration of poly I:C on gestational day 14. Furthermore, the presence or absence of maternal weight loss predicted MK-801 and amphetamine stimulated locomotor abnormalities in offspring. MK-801 stimulated locomotion was altered in offspring of all poly I:C treated dams; however, the presence or absence of maternal weight loss resulted in decreased and modestly increased locomotion, respectively. Adult offspring of poly I:C treated dams that lost weight exhibited significantly decreased amphetamine stimulated locomotion, while offspring of poly I:C treated dams without weight loss performed similarly to vehicle controls. Social isolation and increased maternal age predicted weight loss in response to poly I:C but not vehicle injection. In combination, these data identify environmental factors associated with the maternal response to immune challenge and functional outcome of offspring exposed to maternal immune activation. PMID:21255612

CLINICAL CASE OF TREATMENT WITH RIBOSOMAL COMPLEX IN CHILD WITH COMPROMISED IMMUNITY

Directory of Open Access Journals (Sweden)

A.A. Alekseeva

2011-01-01

Full Text Available The leading pathology in children is acute respiratory infections (ARI according to the expert data of WHO. The incidence of prolonged and recurrent types of ARI increases during recent years. Patients with these diseases subsequently form the group of children with compromised immunity. Immunogens and immunomodulators are the drugs of nonspecific prophylaxis which are used for the prevention of ARI. The group of bacterial immunomodulators is big but most well-studied systemic drug from this group is Ribomunyl. Ribosomal complex is effective and safe in pediatric practice. The article presents the clinical case of treatment with ribosomal complex in immunocompronised child with allergic pathology.Key words: children with compromised immunity, allergy, acute respiratory infections, treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (2: 211–215

PSMA-targeted polyinosine/polycytosine vector induces prostate tumor regression and invokes an antitumor immune response in mice.

Science.gov (United States)

Langut, Yael; Talhami, Alaa; Mamidi, Samarasimhareddy; Shir, Alexei; Zigler, Maya; Joubran, Salim; Sagalov, Anna; Flashner-Abramson, Efrat; Edinger, Nufar; Klein, Shoshana; Levitzki, Alexander

2017-12-26

There is an urgent need for an effective treatment for metastatic prostate cancer (PC). Prostate tumors invariably overexpress prostate surface membrane antigen (PSMA). We designed a nonviral vector, PEI-PEG-DUPA (PPD), comprising polyethylenimine-polyethyleneglycol (PEI-PEG) tethered to the PSMA ligand, 2-[3-(1, 3-dicarboxy propyl)ureido] pentanedioic acid (DUPA), to treat PC. The purpose of PEI is to bind polyinosinic/polycytosinic acid (polyIC) and allow endosomal release, while DUPA targets PC cells. PolyIC activates multiple pathways that lead to tumor cell death and to the activation of bystander effects that harness the immune system against the tumor, attacking nontargeted neighboring tumor cells and reducing the probability of acquired resistance and disease recurrence. Targeting polyIC directly to tumor cells avoids the toxicity associated with systemic delivery. PPD selectively delivered polyIC into PSMA-overexpressing PC cells, inducing apoptosis, cytokine secretion, and the recruitment of human peripheral blood mononuclear cells (PBMCs). PSMA-overexpressing tumors in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice with partially reconstituted immune systems were significantly shrunken following PPD/polyIC treatment, in all cases. Half of the tumors showed complete regression. PPD/polyIC invokes antitumor immunity, but unlike many immunotherapies does not need to be personalized for each patient. The potent antitumor effects of PPD/polyIC should spur its development for clinical use.

Simplified design of IC amplifiers

CERN Document Server

Lenk, John

1996-01-01

Simplified Design of IC Amplifiers has something for everyone involved in electronics. No matter what skill level, this book shows how to design and experiment with IC amplifiers. For experimenters, students, and serious hobbyists, this book provides sufficient information to design and build IC amplifier circuits from 'scratch'. For working engineers who design amplifier circuits or select IC amplifiers, the book provides a variety of circuit configurations to make designing easier.Provides basics for all phases of practical design.Covers the most popular forms for amplif

IC Treatment: Surgical Procedures

Science.gov (United States)

... Bowel Syndrome Lupus Pelvic Floor Dysfunction Pudendal Neuralgia Sjogren’s Syndrome Vulvodynia Newly Diagnosed Toolkit IC Awareness Toolkit Know ... Bowel Syndrome Lupus Pelvic Floor Dysfunction Pudendal Neuralgia Sjogren’s Syndrome Vulvodynia Newly Diagnosed Toolkit IC Awareness Toolkit Know ...

IC: Frequently Asked Questions

Science.gov (United States)

... Bowel Syndrome Lupus Pelvic Floor Dysfunction Pudendal Neuralgia Sjogren’s Syndrome Vulvodynia Newly Diagnosed Toolkit IC Awareness Toolkit Know ... Bowel Syndrome Lupus Pelvic Floor Dysfunction Pudendal Neuralgia Sjogren’s Syndrome Vulvodynia Newly Diagnosed Toolkit IC Awareness Toolkit Know ...

Reconstructing an ancestral mammalian immune supercomplex from a marsupial major histocompatibility complex.

Directory of Open Access Journals (Sweden)

Katherine Belov

2006-03-01

Full Text Available The first sequenced marsupial genome promises to reveal unparalleled insights into mammalian evolution. We have used the Monodelphis domestica (gray short-tailed opossum sequence to construct the first map of a marsupial major histocompatibility complex (MHC. The MHC is the most gene-dense region of the mammalian genome and is critical to immunity and reproductive success. The marsupial MHC bridges the phylogenetic gap between the complex MHC of eutherian mammals and the minimal essential MHC of birds. Here we show that the opossum MHC is gene dense and complex, as in humans, but shares more organizational features with non-mammals. The Class I genes have amplified within the Class II region, resulting in a unique Class I/II region. We present a model of the organization of the MHC in ancestral mammals and its elaboration during mammalian evolution. The opossum genome, together with other extant genomes, reveals the existence of an ancestral "immune supercomplex" that contained genes of both types of natural killer receptors together with antigen processing genes and MHC genes.

Circulating immune complexes and complement concentrations in patients with alcoholic liver disease

DEFF Research Database (Denmark)

Gluud, C; Jans, H

1982-01-01

A prospective evaluation of circulating immune complexes (CIC) and the activity of the complement system was undertaken in 53 alcoholic patients just before diagnostic liver biopsy. Circulating immune complexes were detected in 39% of patients with alcoholic steatosis (n = 26), 58% of patients...... with alcoholic hepatitis (n = 12), and 60% of patients with alcoholic cirrhosis (n = 15). No significant difference was found between the three group of patients. The activity of the complement system was within reference limits in the majority of patients and only slight differences were detected between...... the three groups. No significant differences were observed in liver biochemistry and complement concentrations in CIC-positive and CIC-negative patients. Detection of CIC in patients with alcoholic liver disease does not seem to be of any diagnostic value or play any pathogenic role. The high prevalence...

The risk for behavioural deficits is determined by the maternal immune response to prenatal immune challenge in a neurodevelopmental model.

Science.gov (United States)

Missault, S; Van den Eynde, K; Vanden Berghe, W; Fransen, E; Weeren, A; Timmermans, J P; Kumar-Singh, S; Dedeurwaerdere, S

2014-11-01

Schizophrenia is a highly disabling psychiatric disorder with a proposed neurodevelopmental basis. One mechanism through which genetic and environmental risk factors might act is by triggering persistent brain inflammation, as evidenced by long-lasting neuro-immunological disturbances in patients. Our goal was to investigate whether microglia activation is a neurobiological correlate to the altered behaviour in the maternal immune activation (MIA) model, a well-validated animal model with relevance to schizophrenia. A recent observation in the MIA model is the differential maternal body weight response to the immune stimulus, correlated with a different behavioural outcome in the offspring. Although it is generally assumed that the differences in maternal weight response reflect differences in cytokine response, this has not been investigated so far. Our aim was to investigate whether (i) the maternal weight response to MIA reflects differences in the maternal cytokine response, (ii) the differential behavioural phenotype of the offspring extends to depressive symptoms such as anhedonia and (iii) there are changes in chronic microglia activation dependent on the behavioural phenotype. Based on a dose-response study, MIA was induced in pregnant rats by injecting 4mg/kg Poly I:C at gestational day 15. Serum samples were collected to assess the amount of TNF-α in the maternal blood following MIA. MIA offspring were divided into weight loss (WL; n=14) and weight gain (WG; n=10) groups, depending on the maternal body weight response to Poly I:C. Adult offspring were behaviourally phenotyped for prepulse inhibition, locomotor activity with and without amphetamine and MK-801 challenge, and sucrose preference. Finally, microglia activation was scored on CD11b- and Iba1-immunohistochemically stained sections. Pregnant dams that lost weight following MIA showed increased levels of TNF-α compared to controls, unlike dams that gained weight following MIA. Poly I:C WL

Canine Distemper Virus (CDV) immune-stimulating complexes (iscoms), but not measles virus iscoms, protect dogs against CDV infection.

NARCIS (Netherlands)

P. de Vries (Petra); F.G.C.M. Uytdehaag (Fons); A.D.M.E. Osterhaus (Albert)

1988-01-01

textabstractThe potential of immune-stimulating complexes (iscoms), a novel form of antigenic presentation, for the induction of protective immunity against morbillivirus infection was shown by immunizing dogs with canine distemper virus (CDV) iscoms, which contained the fusion (F) protein and a

LD to IC

CERN Multimedia

Association du personnel

2010-01-01

LC to IC – Publication of posts: Following the publication of new LD to IC posts, we regret that a large number of post descriptions are not available in both CERN official languages, English and French. Consequently, the Staff Association has decided to provide assistance to those who need it with the translation of one or more posts of interest. To do this, please contact the Staff Association secretariat, tel. 72819 or 72761 or 74224.

Effect of isologous and autologous insulin antibodies on in vivo bioavailability and metabolic fate of immune-complexed insulin in Lou/M rats

International Nuclear Information System (INIS)

Arquilla, E.R.; McDougall, B.R.; Stenger, D.P.

1989-01-01

The in vivo bioavailability, distribution, and metabolic fate of 125I-labeled insulin complexed to isologous and autologous antibodies were studied in inbred Lou/M rats. There was an impaired bioavailability of the 125I-insulin bound to the isologous and autologous antibodies. Very little of the 125I-insulin in these immune complexes could bind to insulin receptors on hepatocytes or renal tubular cells and be degraded, because the amounts of 125I from degraded 125I-insulin in the blood or secreted into the stomach were markedly attenuated in both cases for at least 30 min after injection. There was a simultaneous accumulation of 125I-insulin immune complexes in the liver and the kidneys of Lou/M rats injected with 125I-insulin complexed with isologous antibodies or when insulin-immunized Lou/M rats were injected with 125I-insulin during the same interval. The impaired bioavailability of immune-complexed insulin and altered distribution of radioactivity due to the accumulation of immune complexes in the liver and kidney were also observed in previous experiments in which Lewis rats were injected with xenogenic guinea pig and homologous insulin antibodies. These observations are therefore submitted as evidence that the Lou/M rat is a valid model in which to study the bioavailability of insulin immune complexed to isologous, homologous, and xenogenic antibodies and the metabolic fate of the respective insulin-antibody immune complexes

One Problem, Many Solutions : Simple Statistical Approaches Help Unravel the Complexity of the Immune System in an Ecological Context

NARCIS (Netherlands)

Buehler, Deborah M.; Versteegh, Maaike A.; Matson, Kevin D.; Tieleman, Irene

2011-01-01

The immune system is a complex collection of interrelated and overlapping solutions to the problem of disease. To deal with this complexity, researchers have devised multiple ways to measure immune function and to analyze the resulting data. In this way both organisms and researchers employ many

Antigen detection in vivo after immunization with different presentation forms of rabies virus antigen: Involvement of marginal metallophilic macrophages in the uptake of immune-stimulating complexes

NARCIS (Netherlands)

Claassen, I.J.T.M.; Osterhaus, A.D.M.E.; Claassen, E.

1995-01-01

Several mechanisms have been postulated to explain the relatively high immunogenicity of antigens presented in immune-stimulating complexes (iscom). Their potency can in part be explained by the specific targeting of these structures to cells presenting antigens to the immune system. However, until

Antigen detection in vivo after immunization with different presentation forms of rabies virus antigen: involvement of marginal metallophilic macrophages in the uptake of immune-stimulating complexes.

NARCIS (Netherlands)

I.J.Th.M. Claassen (Ivo); A.D.M.E. Osterhaus (Albert); H.J.H.M. Claassen (Eric)

1995-01-01

textabstractSeveral mechanisms have been postulated to explain the relatively high immunogenicity of antigens presented in immune-stimulating complexes (iscom). Their potency can in part be explained by the specific targeting of these structures to cells presenting antigens to the immune system.

An immune stimulating complex (iscom) subunit rabies vaccine protects dogs and mice against street rabies challenge.

NARCIS (Netherlands)

M. Fekadu; J.H. Schaddock; J. Ekströ m; A.D.M.E. Osterhaus (Albert); D.W. Sanderlin; B. Sundquist; B. Morein (Bror)

1992-01-01

textabstractDogs and mice were immunized with either a rabies glycoprotein subunit vaccine incorporated into an immune stimulating complex (ISCOM) or a commercial human diploid cell vaccine (HDCV) prepared from a Pitman Moore (PM) rabies vaccine strain. Pre-exposure vaccination of mice with two

Susceptibility of Ae. aegypti (Diptera: Culicidae) to infection with epidemic (subtype IC) and enzootic (subtypes ID, IIIC, IIID) Venezuelan equine encephalitis complex alphaviruses.

Science.gov (United States)

Ortiz, Diana I; Kang, Wenli; Weaver, Scoti C

2008-11-01

To test the hypothesis that enzootic and epidemic Venezuelan equine encephalitis (VEE) complex alphaviruses can infect and be transmitted by Ae. aegypti, we conducted a series of experimental infection studies. One set of experiments tested the susceptibility of geographic strains of Ae. aegypti from Peru and Texas (U.S.A.) for epidemic (subtype IC) and enzootic (subtype ID) strains from Colombia/Venezuela, whereas the second set of experiments tested the susceptibility of Ae. aegypti from Iquitos, Peru, to enzootic VEE complex strains (subtypes ID, IIIC, and IIID) isolated in the same region, at different infectious doses. Experimental infections using artificial bloodmeals suggested that Ae. aegypti mosquitoes, particularly the strain from Iquitos, Peru, is moderately to highly susceptible to all of these VEE complex alphaviruses. The occurrence of enzootic VEE complex viruses circulating endemically in Iquitos suggests the possibility of a dengue-like transmission cycle among humans in tropical cities.

The oiling of ICS

International Nuclear Information System (INIS)

Hunter, S.

1993-01-01

The incident command system (ICS) works for oil spills. It should be the industry standard and some will argue that it already is. But there are a number of temptations to fiddle with it. Fueling these inclinations is the fundamental difference between oil spills and natural disasters: Oil spills make the perpetrator fix the problem - under heavy oversight. Add to this difference the public outcry that attends oil spills and the dual role of government as both helper and prosecutor. From these conditions emerge adaptations of ICS which both weaken and strengthen it. The benefits of ICS are diminished by deputy incident commanders who block unified commanders from access to section chiefs, over-zealous crisis managers who displace command post decisions or its information office, separate press offices with party line slants, government law enforcement activity mixed into spill response, nonstandard operations terminology and structure involving open-quotes containment and clean upclose quotes or open-quotes salvage,close quotes and the commingling of public and private response funds. ICS's application to oil spill response is strengthened by the use of trained unified commanders, deputy incident commanders who operate as staff rather than line, crisis managers who support on-scene objectives, joint information centers, and heavy involvement of skilled, prepared environmental assessment teams in the planning section who generate priorities, strategies, and (operationally coordinated) tactics. Technically, not all these points constitute alterations of ICS, but most do and the others come close. This mixed bag of strengthening and weakening tweaks to oil spill ICS provides an opportunity to take a new look at this faithful friend to the crisis responder

Unanticipated Mycobacterium tuberculosis complex culture inhibition by immune modulators, immune suppressants, a growth enhancer, and vitamins A and D: clinical implications.

Science.gov (United States)

Greenstein, Robert J; Su, Liya; Shahidi, Azra; Brown, William D; Clifford, Anya; Brown, Sheldon T

2014-09-01

The development of novel antibiotics to treat multidrug-resistant (MDR) tuberculosis is time-consuming and expensive. Multiple immune modulators, immune suppressants, anti-inflammatories, and growth enhancers, and vitamins A and D, inhibit Mycobacterium avium subspecies paratuberculosis (MAP) in culture. We studied the culture inhibition of Mycobacterium tuberculosis complex by these agents. Biosafety level two M. tuberculosis complex (ATCC 19015 and ATCC 25177) was studied in radiometric Bactec or MGIT culture. Agents evaluated included clofazimine, methotrexate, 6-mercaptopurine, cyclosporine A, rapamycin, tacrolimus, monensin, and vitamins A and D. All the agents mentioned above caused dose-dependent inhibition of the M. tuberculosis complex. There was no inhibition by the anti-inflammatory 5-aminosalicylic acid, which causes bacteriostatic inhibition of MAP. We conclude that, at a minimum, studies with virulent M. tuberculosis are indicated with the agents mentioned above, as well as with the thioamide 5-propothiouricil, which has previously been shown to inhibit the M. tuberculosis complex in culture. Our data additionally emphasize the importance of vitamins A and D in treating mycobacterial diseases. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Genome complexity in the coelacanth is reflected in its adaptive immune system

Science.gov (United States)

Saha, Nil Ratan; Ota, Tatsuya; Litman, Gary W.; Hansen, John; Parra, Zuly; Hsu, Ellen; Buonocore, Francesco; Canapa, Adriana; Cheng, Jan-Fang; Amemiya, Chris T.

2014-01-01

We have analyzed the available genome and transcriptome resources from the coelacanth in order to characterize genes involved in adaptive immunity. Two highly distinctive IgW-encoding loci have been identified that exhibit a unique genomic organization, including a multiplicity of tandemly repeated constant region exons. The overall organization of the IgW loci precludes typical heavy chain class switching. A locus encoding IgM could not be identified either computationally or by using several different experimental strategies. Four distinct sets of genes encoding Ig light chains were identified. This includes a variant sigma-type Ig light chain previously identified only in cartilaginous fishes and which is now provisionally denoted sigma-2. Genes encoding α/β and γ/δ T-cell receptors, and CD3, CD4, and CD8 co-receptors also were characterized. Ig heavy chain variable region genes and TCR components are interspersed within the TCR α/δ locus; this organization previously was reported only in tetrapods and raises questions regarding evolution and functional cooption of genes encoding variable regions. The composition, organization and syntenic conservation of the major histocompatibility complex locus have been characterized. We also identified large numbers of genes encoding cytokines and their receptors, and other genes associated with adaptive immunity. In terms of sequence identity and organization, the adaptive immune genes of the coelacanth more closely resemble orthologous genes in tetrapods than those in teleost fishes, consistent with current phylogenomic interpretations. Overall, the work reported described herein highlights the complexity inherent in the coelacanth genome and provides a rich catalog of immune genes for future investigations.

Massively Parallel RNA Sequencing Identifies a Complex Immune Gene Repertoire in the lophotrochozoan Mytilus edulis

Science.gov (United States)

Philipp, Eva E. R.; Kraemer, Lars; Melzner, Frank; Poustka, Albert J.; Thieme, Sebastian; Findeisen, Ulrike; Schreiber, Stefan; Rosenstiel, Philip

2012-01-01

The marine mussel Mytilus edulis and its closely related sister species are distributed world-wide and play an important role in coastal ecology and economy. The diversification in different species and their hybrids, broad ecological distribution, as well as the filter feeding mode of life has made this genus an attractive model to investigate physiological and molecular adaptations and responses to various biotic and abiotic environmental factors. In the present study we investigated the immune system of Mytilus, which may contribute to the ecological plasticity of this species. We generated a large Mytilus transcriptome database from different tissues of immune challenged and stress treated individuals from the Baltic Sea using 454 pyrosequencing. Phylogenetic comparison of orthologous groups of 23 species demonstrated the basal position of lophotrochozoans within protostomes. The investigation of immune related transcripts revealed a complex repertoire of innate recognition receptors and downstream pathway members including transcripts for 27 toll-like receptors and 524 C1q domain containing transcripts. NOD-like receptors on the other hand were absent. We also found evidence for sophisticated TNF, autophagy and apoptosis systems as well as for cytokines. Gill tissue and hemocytes showed highest expression of putative immune related contigs and are promising tissues for further functional studies. Our results partly contrast with findings of a less complex immune repertoire in ecdysozoan and other lophotrochozoan protostomes. We show that bivalves are interesting candidates to investigate the evolution of the immune system from basal metazoans to deuterostomes and protostomes and provide a basis for future molecular work directed to immune system functioning in Mytilus. PMID:22448234

The alternative complement pathway control protein H binds to immune complexes and serves their detection

International Nuclear Information System (INIS)

Nydegger, U.E.; Corvetta, A.; Spaeth, P.J.; Spycher, M.

1983-01-01

During solubilization of immune complexes C3b becomes fixed to the immunoglobulin part and serves as a receptor for the alternative complement pathway control protein H. The H-C3b immune complex interaction can be made detectable using 4% polyethyleneglycol to separate free from bound 125 I-H. Tetanus toxoid (Te)/anti-Te complexes kept soluble with fresh serum and containing 125 IU of specific antibody bound 18% of 125 I-H; when fresh serum was chelated with 10 mM EDTA, 125 I-H binding was only 5%. On sucrose density gradients, the H-binding material sedimented in the range of 12 to 30 S. In 36 serum samples from rheumatoid arthritis (RA) patients and in 12 serum samples from patients with systemic lupus erythematosus (SLE), 125 I-H binding was significantly elevated to 9.5 +/- 4.7% (mean +/- 1 SD) and 13.3 +/- 5.6%, respectively, while 125 I-H binding by 36 normal human sera was 4 +/- 2%. RA samples (17/36, 47%) and SLE samples (9/12, 75%) had H-binding values increased by more than 2 SD above the normal mean. The serum samples were also assessed for conglutinin- and C1q-binding activities; a significant correlation between H and C1q binding was observed (P less than 0.001); there was no correlation between H and conglutinin binding. Although binding to immune complexes through its interaction with C3b, H clearly detects a population of complexes other than conglutinin, thus expanding the possibilities of further characterizing pathological complexes

Ternary WD40 repeat-containing protein complexes: evolution, composition and roles in plant immunity

Directory of Open Access Journals (Sweden)

Jimi C. Miller

2016-01-01

Full Text Available Plants, like mammals, rely on their innate immune system to perceive and discriminate among the majority of their microbial pathogens. Unlike mammals, plants respond to this molecular dialogue by unleashing a complex chemical arsenal of defense metabolites to resist or evade pathogen infection. In basal or non-host resistance, plants utilize signal transduction pathways to detect non-self, damaged-self and altered-self-associated molecular patterns and translate these danger signals into largely inducible chemical defenses. The WD40 repeat (WDR-containing proteins Gβ and TTG1 are constituents of two independent ternary protein complexes functioning at opposite ends of a plant immune signaling pathway. Gβ and TTG1 are also encoded by single-copy genes that are ubiquitous in higher plants, implying the limited diversity and functional conservation of their respective complexes. In this review, we summarize what is currently known about the evolutionary history of these WDR-containing ternary complexes, their repertoire and combinatorial interactions, and their downstream effectors and pathways in plant defense.

The Implications Related to Different IC, Different Projects and Different Thinking Addressing the Common Core of IC

DEFF Research Database (Denmark)

Lindgren, Peter; Saghaug, Kristin Margrethe

2009-01-01

challenge the development of IC: - The IC at the organizational level seems to diminish when innovation gets highly dispersed and is operated outside the core of the organization - The attractiveness of the organization to different ICA, which is one fundament to sustainable and successful innovation, seems...... to fall when the IC at the organizational core level diminishes The objective of this paper is therefore to understand 1) How the IC at the organizational core level may continue to be developed, when at the same time innovation is taking place in dispersed groups and projects. 2) How to motivate...... the different ICA´s to bring learning and knowledge back to the core with the purpose to develop IC at the organizational core level....

Reduced Incidence of Slowly Progressive Heymann Nephritis in Rats Immunized With a Modified Vaccination Technique

Directory of Open Access Journals (Sweden)

Arpad Z. Barabas

2006-01-01

Full Text Available A slowly progressive Heymann nephritis (SPHN was induced in three groups of rats by weekly injections of a chemically modified renal tubular antigen in an aqueous medium. A control group of rats received the chemically unmodified version of the antigen in an aqueous solution. One group of SPHN rats were pre- and post-treated with weekly injections of IC made up of rKF3 and rarKF3 IgM antibody at antigen excess (MIC (immune complexes [ICs] containing sonicated ultracentrifuged [u/c] rat kidney fraction 3 [rKF3] antigen and IgM antibodies specific against the antigen, at slight antigen excess. One group of SPHN rats were post-treated with MIC 3 weeks after the induction of the disease and one group of SPHN animals received no treatment. The control group of rats received pre- and post-treatment with sonicated u/c rKF3.

Proliferative, necrotizing and crescentic immune complex-mediated glomerulonephritis in a cat

Directory of Open Access Journals (Sweden)

Carolyn Gross

2015-09-01

Full Text Available Case Summary A 5-year-old cat was examined for vomiting and anorexia of 2 days’ duration. Azotemia, hyperphosphatemia and hypoalbuminemia were the main biochemical findings. Serial analyses of the urine revealed isosthenuria, proteinuria and eventual glucosuria. Hyperechoic perirenal fat was detected surrounding the right kidney by ultrasonography. Histopathologic evaluation of ante-mortem ultrasound-guided needle biopsies of the right kidney was consistent with proliferative, necrotizing and crescentic glomerulonephritis with fibrin thrombi, proteinaceous and red blood cell casts, and moderate multifocal chronic-active interstitial nephritis. Owing to a lack of clinical improvement, the cat was eventually euthanized. Post-mortem renal biopsies were processed for light microscopy, transmission electron microscopy and immunofluorescence. This revealed severe focal proliferative and necrotizing glomerulonephritis with cellular crescent formation, podocyte injury and secondary segmental sclerosis. Ultrastructural analysis revealed scattered electron-dense deposits in the mesangium, and immunofluorescence demonstrated positive granular staining for λ light chains, consistent with immune complex-mediated glomerulonephritis. Severe diffuse acute tubular epithelial injury and numerous red blood cell casts were also seen. Relevance and novel information To our knowledge, this is the first report of naturally occurring proliferative, necrotizing and crescentic immune complex glomerulonephritis in a cat.

Irregular Dwarf Galaxy IC 1613

Science.gov (United States)

2005-01-01

Ultraviolet image (left) and visual image (right) of the irregular dwarf galaxy IC 1613. Low surface brightness galaxies, such as IC 1613, are more easily detected in the ultraviolet because of the low background levels compared to visual wavelengths.

Circulating Immune Complexes among Diabetic Children

Directory of Open Access Journals (Sweden)

George Nicoloff

2004-01-01

Full Text Available Insulin dependent diabetes mellitus (IDDM is an autoimmune disease associated with the presence of different types of autoantibodies. The presence of these antibodies and the corresponding antigens in the circulation leads to the formation of circulating immune complexes (CIC. CIC are known to persist in the blood for long periods of time. Such CIC following deposition in the small blood vessels have the potential to lead to microangiopathy with debilitating clinical consequences. The aim of our pilot study was to investigate whether a correlation exists between CIC and the development of microvascular complications in diabetic children. Isolation of a new glycoprotein complement inhibition factor (CIF from the parasitic plant Cuscuta europea seed, which appears to bind specifically to complement component C3 has provided an unique tool for the measurement of immune complexes by means of ELISA-type techniques (CIF-ELISA. We studied the levels of CIC (IgG, IgM and IgA in 58 diabetic children (mean age 12.28±4.04 years, diabetes duration 5.3±3.7 years, 29 of them had vascular complications (group 1 and the other 29 were without vascular complications (group 2. As controls, we studied sera samples from 21 healthy children (mean age 13.54±4.03 years. Sera from the diabetic patients showed statistically significant higher levels of CIC IgG ( p=0.03 than sera from the control group. In sera from group 1 values of CIC IgG showed statistically significant higher levels than controls (0.720±0.31 vs. 0.46±0.045; p=0.011 Sera from 59% of the patients were positive for CIC IgG, 36% for CIC IgM and 9% for CIC IgA. Among 26 patients with microalbuminuria, sera from 17/26 (65% were positive for CIC IgG, 8/26 (31% for CIC IgM and 2/26 (8% for CIC IgA. CIC IgG correlated with HbA1c (r=0.51; p=0.005 and microalbuminuria (r=0.42, p=0.033. CIC IgA correlated with age (r=0.44, p=0.03. CIC IgM correlated with the duration of diabetes (r=0.63, p=0.02. These

CRISPR-based immune systems of the Sulfolobales: complexity and diversity

DEFF Research Database (Denmark)

Garrett, Roger Antony; Shah, Shiraz Ali; Vestergaard, Gisle Alberg

2011-01-01

CRISPR (cluster of regularly interspaced palindromic repeats)/Cas and CRISPR/Cmr systems of Sulfolobus, targeting DNA and RNA respectively of invading viruses or plasmids are complex and diverse. We address their classification and functional diversity, and the wide sequence diversity of RAMP...... (repeat-associated mysterious protein)-motif containing proteins encoded in Cmr modules. Factors influencing maintenance of partially impaired CRISPR-based systems are discussed. The capacity for whole CRISPR transcripts to be generated despite the uptake of transcription signals within spacer sequences...... is considered. Targeting of protospacer regions of invading elements by Cas protein-crRNA (CRISPR RNA) complexes exhibit relatively low sequence stringency, but the integrity of protospacer-associated motifs appears to be important. Different mechanisms for circumventing or inactivating the immune systems...

Maximum-Entropy Models of Sequenced Immune Repertoires Predict Antigen-Antibody Affinity.

Directory of Open Access Journals (Sweden)

Lorenzo Asti

2016-04-01

Full Text Available The immune system has developed a number of distinct complex mechanisms to shape and control the antibody repertoire. One of these mechanisms, the affinity maturation process, works in an evolutionary-like fashion: after binding to a foreign molecule, the antibody-producing B-cells exhibit a high-frequency mutation rate in the genome region that codes for the antibody active site. Eventually, cells that produce antibodies with higher affinity for their cognate antigen are selected and clonally expanded. Here, we propose a new statistical approach based on maximum entropy modeling in which a scoring function related to the binding affinity of antibodies against a specific antigen is inferred from a sample of sequences of the immune repertoire of an individual. We use our inference strategy to infer a statistical model on a data set obtained by sequencing a fairly large portion of the immune repertoire of an HIV-1 infected patient. The Pearson correlation coefficient between our scoring function and the IC50 neutralization titer measured on 30 different antibodies of known sequence is as high as 0.77 (p-value 10-6, outperforming other sequence- and structure-based models.

Tech-X Corporation releases simulation code for solving complex problems in plasma physics : VORPAL code provides a robust environment for simulating plasma processes in high-energy physics, IC fabrications and material processing applications

CERN Multimedia

2005-01-01

Tech-X Corporation releases simulation code for solving complex problems in plasma physics : VORPAL code provides a robust environment for simulating plasma processes in high-energy physics, IC fabrications and material processing applications

The HyVac4 subunit vaccine efficiently boosts BCG-primed anti-mycobacterial protective immunity.

Directory of Open Access Journals (Sweden)

Rolf Billeskov

Full Text Available BACKGROUND: The current vaccine against tuberculosis (TB, BCG, has failed to control TB worldwide and the protective efficacy is moreover limited to 10-15 years. A vaccine that could efficiently boost a BCG-induced immune response and thus prolong protective immunity would therefore have a significant impact on the global TB-burden. METHODS/FINDINGS: In the present study we show that the fusion protein HyVac4 (H4, consisting of the mycobacterial antigens Ag85B and TB10.4, given in the adjuvant IC31® or DDA/MPL effectively boosted and prolonged immunity induced by BCG, leading to improved protection against infection with virulent M. tuberculosis (M.tb. Increased protection correlated with an increased percentage of TB10.4 specific IFNγ/TNFα/IL-2 or TNFα/IL-2 producing CD4 T cells at the site of infection. Moreover, this vaccine strategy did not compromise the use of ESAT-6 as an accurate correlate of disease development/vaccine efficacy. Indeed both CD4 and CD8 ESAT-6 specific T cells showed significant correlation with bacterial levels. CONCLUSIONS/SIGNIFICANCE: H4-IC31® can efficiently boost BCG-primed immunity leading to an increased protective anti-M.tb immune response dominated by IFNγ/TNFα/IL-2 or TNFα/IL2 producing CD4 T cells. H4 in the CD4 T cell inducing adjuvant IC31® is presently in clinical trials.

Enhanced urothelial expression of human chorionic gonadotropin beta (hCGβ) in bladder pain syndrome/interstitial cystitis (BPS/IC).

Science.gov (United States)

Schwalenberg, Thilo; Stolzenburg, Jens-Uwe; Ho, Thi Phuc; Mallock, Tobias; Hartenstein, Siegurd; Alexander, Henry; Zimmermann, Gerolf; Hohenfellner, Rudolf; Denzinger, Stefan; Burger, Maximilian; Horn, Lars-Christian; Neuhaus, Jochen

2012-06-01

Bladder pain syndrome/interstitial cystitis (BPS/IC) is associated with urothelial lesions. Pathomechanisms of urothelial damage and factors for urothelial restoration are unknown. hCG is a factor for cellular differentiation, angiogenesis and immune competence of the endometrium during pregnancy. Clinical observations demonstrate improvement of BPS/IC symptoms during pregnancy or during infertility treatment with hCG. Our research aims were to examine the expression of hCG and luteinizing hormone receptor (LHR) in the urothelium of BPS/IC patients and compare the levels of hCGβ with healthy controls. Bladder biopsies of BPS/IC (CLSM: n = 10; qPCR: n = 15); Tumour-free control tissue from cystectomies (n = 12). hCGα, hCGβ and LHR expression were examined by confocal laser scanning microscopy (CLSM), and hCGβ expression was quantified. hCGβ5 and hCGβ7 mRNA splice variants were quantified in real-time polymerase chain reaction. We found constitutive expression of hCGα, hCGβ and LHR in healthy controls. HCGβ was significantly upregulated in BPS/IC patients in CLSM. PCR analysis revealed higher levels of hCGβ7 than hCGβ5 in controls and BPS/IC patients. The constitutive expression of hCG and LHR speaks in favour for a functional signalling in urothelial cells without any association with either pregnancy or tumour. We show for the first time that hCGβ is upregulated in BPS/IC urothelium and that hCGβ7 is the dominant splice variant in those cells. Our findings imply a major role of hCG for urothelial integrity and a disturbance of hCG signalling in case of BPS/IC. We conclude that hCG could gain therapeutical relevance in the future.

Neutralized adenovirus-immune complexes can mediate effective gene transfer via an Fc receptor-dependent infection pathway.

Science.gov (United States)

Leopold, Philip L; Wendland, Rebecca L; Vincent, Theresa; Crystal, Ronald G

2006-10-01

Neutralization of adenovirus (Ad) by anti-Ad neutralizing antibodies in serum involves formation of Ad-immune complexes that prevent the virus from interacting with target cells. We hypothesized that Ad-immune complexes likely contain viable Ad vectors which, although no longer capable of gaining access to receptors on target cells, may be able to express transgenes in cells bearing Fc receptors for immunoglobulins, i.e., that antibody-based "neutralization" of Ad vectors may be circumvented by the Fc receptor pathway. To test this hypothesis, we expressed the Fcgamma receptor IIA (FcgammaR) in A549 lung epithelial cells or human dermal fibroblasts and evaluated gene transfer in the presence of human neutralizing anti-Ad serum. FcgammaR-expressing cells bound and internalized copious amounts of Ad, with a distinct population of internalized Ad trafficking to the nucleus. The dose-response curves for inhibition of gene transfer revealed that FcgammaR-expressing cells required a more-than-10-fold higher concentration of anti-Ad serum to achieve 50% inhibition of Ad-encoded beta-galactosidase expression compared with non-FcgammaR-expressing cells. The discrepancy between neutralization of Ad during infection of FcgammaR-expressing cells and neutralization of Ad during infection of non-FcgammaR-expressing cells occurred with either heat-inactivated or non-heat-inactivated sera, was blocked by addition of purified Fc domain protein, and did not require the cytoplasmic domain of FcgammaR, suggesting that immune complex internalization proceeded via endocytosis rather than phagocytosis. FcgammaR-mediated infection by Ad-immune complexes did not require expression of the coxsackie virus-Ad receptor (CAR) since similar data were obtained when CAR-deficient human dermal fibroblasts were engineered to express FcgammaR. However, interaction of the Ad penton base with cell surface integrins contributed to the difference in neutralization between FcgammaR-expressing and non

Protecting ICS Systems Within the Energy Sector from Cyber Attacks

Science.gov (United States)

Barnes, Shaquille

Advance persistent threat (APT) groups are continuing to attack the energy sector through cyberspace, which poses a risk to our society, national security, and economy. Industrial control systems (ICSs) are not designed to handle cyber-attacks, which is why asset owners need to implement the correct proactive and reactive measures to mitigate the risk to their ICS environments. The Industrial Control Systems Cyber Emergency Response Team (ICS-CERT) responded to 290 incidents for fiscal year 2016, where 59 of those incidents came from the Energy Sector. APT groups know how vulnerable energy sector ICS systems are and the destruction they can cause when they go offline such as loss of production, loss of life, and economic impact. Defending against APT groups requires more than just passive controls such as firewalls and antivirus solutions. Asset owners should implement a combination of best practices and active defense in their environment to defend against APT groups. Cyber-attacks against critical infrastructure will become more complex and harder to detect and respond to with traditional security controls. The purpose of this paper was to provide asset owners with the correct security controls and methodologies to help defend against APT groups.

Wafer level 3-D ICs process technology

CERN Document Server

Tan, Chuan Seng; Reif, L Rafael

2009-01-01

This book focuses on foundry-based process technology that enables the fabrication of 3-D ICs. The core of the book discusses the technology platform for pre-packaging wafer lever 3-D ICs. However, this book does not include a detailed discussion of 3-D ICs design and 3-D packaging. This is an edited book based on chapters contributed by various experts in the field of wafer-level 3-D ICs process technology. They are from academia, research labs and industry.

Integration of IC/EC systems in ITER

International Nuclear Information System (INIS)

Gassmann, T.; Beaumont, B.; Baruah, U.K.; Bonicelli, T.; Chiocchio, S.; Cox, D.; Darbos, C.; Decamps, H.; Denisov, G.; Henderson, M.; Kazarian, F.; Lamalle, P.U.; Mukherjee, A.; Rasmussen, D.; Saibene, G.; Sartori, R.; Sakamoto, K.; Tanga, A.

2010-01-01

The RF heating and current drive (H and CD) systems that are to be installed in ITER during the construction phase, are the electron cyclotron (EC) and ion cyclotron (IC) systems. They are complex assemblies of high voltage power supplies (HVPS), RF generators, transmission lines and antennas. Their design and integration are constrained by many interfaces, both internal, between the subsystems, and external, with the other ITER systems. In addition, some components must be compatible with a nuclear environment and are classified as Safety Important Component. This paper describes the processes implemented in ITER to ensure proper integration.

Curcumin prevents human dendritic cell response to immune stimulants

International Nuclear Information System (INIS)

Shirley, Shawna A.; Montpetit, Alison J.; Lockey, R.F.; Mohapatra, Shyam S.

2008-01-01

Curcumin, a compound found in the Indian spice turmeric, has anti-inflammatory and immunomodulatory properties, though the mechanism remains unclear. Dendritic cells (DCs) are important to generating an immune response and the effect of curcumin on human DCs has not been explored. The role curcumin in the DC response to bacterial and viral infection was investigated in vitro using LPS and Poly I:C as models of infection. CD14 + monocytes, isolated from human peripheral blood, were cultured in GM-CSF- and IL-4-supplemented medium to generate immature DCs. Cultures were incubated with curcumin, stimulated with LPS or Poly I:C and functional assays were performed. Curcumin prevents DCs from responding to immunostimulants and inducing CD4 + T cell proliferation by blocking maturation marker, cytokine and chemokine expression and reducing both migration and endocytosis. These data suggest a therapeutic role for curcumin as an immune suppressant

DMPD: Cytosolic DNA recognition for triggering innate immune responses. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 18280611 Cytosolic DNA recognition for triggering innate immune responses. Takaoka ...A, Taniguchi T. Adv Drug Deliv Rev. 2008 Apr 29;60(7):847-57. Epub 2007 Dec 31. (.png) (.svg) (.html) (.csml) Show Cytosol...ic DNA recognition for triggering innate immune responses. PubmedID 18280611 Title Cytosolic D

Standardization and application of the solid phase C1q radioimmunoassay using soluble tetanus toxoid-antitetanus immune complexes in sera of patients with chronic polyarthritis and Lupus erythematodes

International Nuclear Information System (INIS)

Menzel, E.J.; Steffen, C.; Smolen, J.

1982-01-01

Soluble tetanus-antitetanus immune complexes were prepared with affinity-chromatography and gel chromatography. Serial dilutions of these immune complex preparations were tested in a solid phase C1q radioimmunoassay. Soluble immune complexes as well as aggregated human gamma globulin of identical protein concentrations were comparatively investigated. Soluble immune complexes rendered a more sensitive standardization of RIA. According to these observations a relation between μg/ml equivalents of defined tetanus-antitetanus complexes and ng second antibody obtained in C1q-RIA was calculated. Upper limit of mean values and two standard deviations of ng second antibody obtained in investigations of 55 normal sera was designated as 1 unit immune complexes and regarded as border line of negative results. Multiplication of μg/ml immune complex equivalents of 1 unit led to a scale of 1 to 15 units, showing the area of positive results. According to these values a standardization curve was constructed allowing a conversion of ng-second antibody obtained in serum investigations into immune complex units equivalent to defined standard immune complexes. With this curve investigation results of 56 RA sera and 21 SLE sera were expressed in the range of units, making a distinct gradation of positive results and a clear cut separation of positive and negative results possible. SLE sera of patients in acute stage showed highly positive results. (orig.) [de

Standardization and application of the solid phase C1q radioimmunoassay using soluble tetanus toxoid-antitetanus immune complexes in sera of patients with chronic polyarthritis and Lupus erythematodes

Energy Technology Data Exchange (ETDEWEB)

Menzel, E J; Steffen, C; Smolen, J

1982-11-22

Soluble tetanus-antitetanus immune complexes were prepared with affinity-chromatography and gel chromatography. Serial dilutions of these immune complex preparations were tested in a solid phase C1q radioimmunoassay. Soluble immune complexes as well as aggregated human gamma globulin of identical protein concentrations were comparatively investigated. Soluble immune complexes rendered a more sensitive standardization of RIA. According to these observations a relation between ..mu..g/ml equivalents of defined tetanus-antitetanus complexes and ng second antibody obtained in C1q-RIA was calculated. Upper limit of mean values and two standard deviations of ng second antibody obtained in investigations of 55 normal sera was designated as 1 unit immune complexes and regarded as border line of negative results. Multiplication of ..mu..g/ml immune complex equivalents of 1 unit led to a scale of 1 to 15 units, showing the area of positive results. According to these values a standardization curve was constructed allowing a conversion of ng-second antibody obtained in serum investigations into immune complex units equivalent to defined standard immune complexes. With this curve investigation results of 56 RA sera and 21 SLE sera were expressed in the range of units, making a distinct gradation of positive results and a clear cut separation of positive and negative results possible. SLE sera of patients in acute stage showed highly positive results.

Unique structure of iC3b resolved at a resolution of 24 Å by 3D-electron microscopy.

Science.gov (United States)

Alcorlo, Martin; Martínez-Barricarte, Ruben; Fernández, Francisco J; Rodríguez-Gallego, César; Round, Adam; Vega, M Cristina; Harris, Claire L; de Cordoba, Santiago Rodríguez; Llorca, Oscar

2011-08-09

Activation of C3, deposition of C3b on the target surface, and subsequent amplification by formation of a C3-cleaving enzyme (C3-convertase; C3bBb) triggers the effector functions of complement that result in inflammation and cell lysis. Concurrently, surface-bound C3b is proteolyzed to iC3b by factor I and appropriate cofactors. iC3b then interacts with the complement receptors (CR) of the Ig superfamily, CR2 (CD21), CR3 (CD11b/CD18), and CR4 (CD11c/CD18) on leukocytes, down-modulating inflammation, enhancing B cell-mediated immunity, and targeting pathogens for clearance by phagocytosis. Using EM and small-angle X-ray scattering, we now present a medium-resolution structure of iC3b (24 Å). iC3b displays a unique conformation with structural features distinct from any other C3 fragment. The macroglobulin ring in iC3b is similar to that in C3b, whereas the TED (thioester-containing domain) domain and the remnants of the CUB (complement protein subcomponents C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domain have moved to locations more similar to where they were in native C3. A consequence of this large conformational change is the disruption of the factor B binding site, which renders iC3b unable to assemble a C3-convertase. This structural model also justifies the decreased interaction between iC3b and complement regulators and the recognition of iC3b by the CR of the Ig superfamily, CR2, CR3, and CR4. These data further illustrate the extraordinary conformational versatility of C3 to accommodate a great diversity of functional activities.

Immunization Strategies Producing a Humoral IgG Immune Response against Devil Facial Tumor Disease in the Majority of Tasmanian Devils Destined for Wild Release

Directory of Open Access Journals (Sweden)

Ruth Pye

2018-02-01

Full Text Available Devil facial tumor disease (DFTD is renowned for its successful evasion of the host immune system. Down regulation of the major histocompatabilty complex class I molecule (MHC-I on the DFTD cells is a primary mechanism of immune escape. Immunization trials on captive Tasmanian devils have previously demonstrated that an immune response against DFTD can be induced, and that immune-mediated tumor regression can occur. However, these trials were limited by their small sample sizes. Here, we describe the results of two DFTD immunization trials on cohorts of devils prior to their wild release as part of the Tasmanian Government’s Wild Devil Recovery project. 95% of the devils developed anti-DFTD antibody responses. Given the relatively large sample sizes of the trials (N = 19 and N = 33, these responses are likely to reflect those of the general devil population. DFTD cells manipulated to express MHC-I were used as the antigenic basis of the immunizations in both trials. Although the adjuvant composition and number of immunizations differed between trials, similar anti-DFTD antibody levels were obtained. The first trial comprised DFTD cells and the adjuvant combination of ISCOMATRIX™, polyIC, and CpG with up to four immunizations given at monthly intervals. This compared to the second trial whereby two immunizations comprising DFTD cells and the adjuvant combination ISCOMATRIX™, polyICLC (Hiltonol® and imiquimod were given a month apart, providing a shorter and, therefore, more practical protocol. Both trials incorporated a booster immunization given up to 5 months after the primary course. A key finding was that devils in the second trial responded more quickly and maintained their antibody levels for longer compared to devils in the first trial. The different adjuvant combination incorporating the RNAase resistant polyICLC and imiquimod used in the second trial is likely to be responsible. The seroconversion in the majority of

Immunization Strategies Producing a Humoral IgG Immune Response against Devil Facial Tumor Disease in the Majority of Tasmanian Devils Destined for Wild Release

Science.gov (United States)

Pye, Ruth; Patchett, Amanda; McLennan, Elspeth; Thomson, Russell; Carver, Scott; Fox, Samantha; Pemberton, David; Kreiss, Alexandre; Baz Morelli, Adriana; Silva, Anabel; Pearse, Martin J.; Corcoran, Lynn M.; Belov, Katherine; Hogg, Carolyn J.; Woods, Gregory M; Lyons, A. Bruce

2018-01-01

Devil facial tumor disease (DFTD) is renowned for its successful evasion of the host immune system. Down regulation of the major histocompatabilty complex class I molecule (MHC-I) on the DFTD cells is a primary mechanism of immune escape. Immunization trials on captive Tasmanian devils have previously demonstrated that an immune response against DFTD can be induced, and that immune-mediated tumor regression can occur. However, these trials were limited by their small sample sizes. Here, we describe the results of two DFTD immunization trials on cohorts of devils prior to their wild release as part of the Tasmanian Government’s Wild Devil Recovery project. 95% of the devils developed anti-DFTD antibody responses. Given the relatively large sample sizes of the trials (N = 19 and N = 33), these responses are likely to reflect those of the general devil population. DFTD cells manipulated to express MHC-I were used as the antigenic basis of the immunizations in both trials. Although the adjuvant composition and number of immunizations differed between trials, similar anti-DFTD antibody levels were obtained. The first trial comprised DFTD cells and the adjuvant combination of ISCOMATRIX™, polyIC, and CpG with up to four immunizations given at monthly intervals. This compared to the second trial whereby two immunizations comprising DFTD cells and the adjuvant combination ISCOMATRIX™, polyICLC (Hiltonol®) and imiquimod were given a month apart, providing a shorter and, therefore, more practical protocol. Both trials incorporated a booster immunization given up to 5 months after the primary course. A key finding was that devils in the second trial responded more quickly and maintained their antibody levels for longer compared to devils in the first trial. The different adjuvant combination incorporating the RNAase resistant polyICLC and imiquimod used in the second trial is likely to be responsible. The seroconversion in the majority of devils in these anti

SEM probe of IC radiation sensitivity

Science.gov (United States)

Gauthier, M. K.; Stanley, A. G.

1979-01-01

Scanning Electron Microscope (SEM) used to irradiate single integrated circuit (IC) subcomponent to test for radiation sensitivity can localize area of IC less than .03 by .03 mm for determination of exact location of radiation sensitive section.

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

Science.gov (United States)

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

2016-08-12

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

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

Science.gov (United States)

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

2016-01-01

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

Quantitative Multiplex Immunohistochemistry Reveals Myeloid-Inflamed Tumor-Immune Complexity Associated with Poor Prognosis

Directory of Open Access Journals (Sweden)

Takahiro Tsujikawa

2017-04-01

Full Text Available Here, we describe a multiplexed immunohistochemical platform with computational image processing workflows, including image cytometry, enabling simultaneous evaluation of 12 biomarkers in one formalin-fixed paraffin-embedded tissue section. To validate this platform, we used tissue microarrays containing 38 archival head and neck squamous cell carcinomas and revealed differential immune profiles based on lymphoid and myeloid cell densities, correlating with human papilloma virus status and prognosis. Based on these results, we investigated 24 pancreatic ductal adenocarcinomas from patients who received neoadjuvant GVAX vaccination and revealed that response to therapy correlated with degree of mono-myelocytic cell density and percentages of CD8+ T cells expressing T cell exhaustion markers. These data highlight the utility of in situ immune monitoring for patient stratification and provide digital image processing pipelines to the community for examining immune complexity in precious tissue sections, where phenotype and tissue architecture are preserved to improve biomarker discovery and assessment.

Scalable IC Platform for Smart Cameras

Directory of Open Access Journals (Sweden)

Harry Broers

2005-08-01

Full Text Available Smart cameras are among the emerging new fields of electronics. The points of interest are in the application areas, software and IC development. In order to reduce cost, it is worthwhile to invest in a single architecture that can be scaled for the various application areas in performance (and resulting power consumption. In this paper, we show that the combination of an SIMD (single-instruction multiple-data processor and a general-purpose DSP is very advantageous for the image processing tasks encountered in smart cameras. While the SIMD processor gives the very high performance necessary by exploiting the inherent data parallelism found in the pixel crunching part of the algorithms, the DSP offers a friendly approach to the more complex tasks. The paper continues to motivate that SIMD processors have very convenient scaling properties in silicon, making the complete, SIMD-DSP architecture suitable for different application areas without changing the software suite. Analysis of the changes in power consumption due to scaling shows that for typical image processing tasks, it is beneficial to scale the SIMD processor to use the maximum level of parallelism available in the algorithm if the IC supply voltage can be lowered. If silicon cost is of importance, the parallelism of the processor should be scaled to just reach the desired performance given the speed of the silicon.

Dicty_cDB: FC-IC0102 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available FC-IC (Link to library) FC-IC0102 (Link to dictyBase) - - - Contig-U16527-1 FC-IC01...02F (Link to Original site) FC-IC0102F 434 - - - - - - Show FC-IC0102 Library FC-IC (Link to library) Clone ...ID FC-IC0102 (Link to dictyBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U16527-1 Original site URL http://dict... (bits) Value N AB088483 |AB088483.1 Dictyostelium discoideum gene for gamete and mating-type specific prote...oducing significant alignments: (bits) Value AB088483_1( AB088483 |pid:none) Dictyostelium discoideum gmsA g

Investigations of immunoglobulins, circulating immune complexes and plasma free hemoglobin in cancer patients on 60Co gamma-ray therapy

International Nuclear Information System (INIS)

Horvath, M.; Rode, I.L.; Fekete, B.; Kiss, B.; Ringwald, G.

1981-01-01

32 patients with different tumours were irradiated by 60 Co gamma-rays. During therapy lasting for several weeks, changes in the content of immunoglobulin and of some other serum proteins, circulating immune complexes and plasma free hemoglobin were determined. Immunosuppression according to immunoglobulin content in serum was not produced by this type of radiation. Decrease in immune complex levels was a good prognostic sign. Low values of plasma hemoglobin content during treatment indicated that no erythrocyte membrane damage had been effected. (orig.) [de

Dynamical Competition of IC-Industry Clustering from Taiwan to China

Science.gov (United States)

Tsai, Bi-Huei; Tsai, Kuo-Hui

2009-08-01

Most studies employ qualitative approach to explore the industrial clusters; however, few research has objectively quantified the evolutions of industry clustering. The purpose of this paper is to quantitatively analyze clustering among IC design, IC manufacturing as well as IC packaging and testing industries by using the foreign direct investment (FDI) data. The Lotka-Volterra system equations are first adopted here to capture the competition or cooperation among such three industries, thus explaining their clustering inclinations. The results indicate that the evolution of FDI into China for IC design industry significantly inspire the subsequent FDI of IC manufacturing as well as IC packaging and testing industries. Since IC design industry lie in the upstream stage of IC production, the middle-stream IC manufacturing and downstream IC packing and testing enterprises tend to cluster together with IC design firms, in order to sustain a steady business. Finally, Taiwan IC industry's FDI amount into China is predicted to cumulatively increase, which supports the industrial clustering tendency for Taiwan IC industry. Particularly, the FDI prediction of Lotka-Volterra model performs superior to that of the conventional Bass model after the forecast accuracy of these two models are compared. The prediction ability is dramatically improved as the industrial mutualism among each IC production stage is taken into account.

Synthetic double-stranded RNAs are adjuvants for the induction of T helper 1 and humoral immune responses to human papillomavirus in rhesus macaques.

Directory of Open Access Journals (Sweden)

Christiane Stahl-Hennig

2009-04-01

Full Text Available Toll-like receptor (TLR ligands are being considered as adjuvants for the induction of antigen-specific immune responses, as in the design of vaccines. Polyriboinosinic-polyribocytoidylic acid (poly I:C, a synthetic double-stranded RNA (dsRNA, is recognized by TLR3 and other intracellular receptors. Poly ICLC is a poly I:C analogue, which has been stabilized against the serum nucleases that are present in the plasma of primates. Poly I:C(12U, another analogue, is less toxic but also less stable in vivo than poly I:C, and TLR3 is essential for its recognition. To study the effects of these compounds on the induction of protein-specific immune responses in an animal model relevant to humans, rhesus macaques were immunized subcutaneously (s.c. with keyhole limpet hemocyanin (KLH or human papillomavirus (HPV16 capsomeres with or without dsRNA or a control adjuvant, the TLR9 ligand CpG-C. All dsRNA compounds served as adjuvants for KLH-specific cellular immune responses, with the highest proliferative responses being observed with 2 mg/animal poly ICLC (p = 0.002 or 6 mg/animal poly I:C(12U (p = 0.001 when compared with immunization with KLH alone. Notably, poly ICLC -- but not CpG-C given at the same dose -- also helped to induce HPV16-specific Th1 immune responses while both adjuvants supported the induction of strong anti-HPV16 L1 antibody responses as determined by ELISA and neutralization assay. In contrast, control animals injected with HPV16 capsomeres alone did not develop substantial HPV16-specific immune responses. Injection of dsRNA led to increased numbers of cells producing the T cell-activating chemokines CXCL9 and CXCL10 as detected by in situ hybridization in draining lymph nodes 18 hours after injections, and to increased serum levels of CXCL10 (p = 0.01. This was paralleled by the reduced production of the homeostatic T cell-attracting chemokine CCL21. Thus, synthetic dsRNAs induce an innate chemokine response and act as adjuvants

Spatio-temporal regulation of Hsp90-ligand complex leads to immune activation.

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Yasuaki eTamura

2016-05-01

Full Text Available Hsp90 is the most abundant cytosolic HSP and is known to act as a molecular chaperone. We found that an Hsp90-cancer antigen peptide complex was efficiently cross-presented by human monocyte-derived dendritic cells and induced peptide-specific cytotoxic T lymphocytes. Furthermore, we observed that the internalized Hsp90-peptide complex was strictly sorted to the Rab5+, EEA1+ static early endosome and the Hsp90-chaperoned peptide was processed and bound to MHC class I molecules through a endosome-recycling pathway. We also found that extracellular Hsp90 complexed with CpG-A or self-DNA stimulates production of a large amount of IFN-α from pDCs via static early endosome targeting. Thus, extracellular Hsp90 can target the antigen or nucleic acid to a static early endosome by spatio-temporal regulation. Moreover, we showed that Hsp90 associates with and delivers TLR7/9 from the ER to early endosomes for ligand recognition. Hsp90 inhibitor, geldanamycin derivative inhibited the Hsp90 association with TLR7/9, resulting in inhibition IFN-α production, leading to improvement of SLE symptoms. Interstingly, we observed that serum Hsp90 is clearly increased in patients with active SLE compared with that in patients with inactive disease. Serum Hsp90 detected in SLE patients binds to self-DNA and/or anti-DNA Ab, thus leading to stimulation of pDCs to produce IFN-α. Thus, Hsp90 plays a crucial role in the pathogenesis of SLE and that an Hsp90 inhibitor will therefore provide a new therapeutic approach to SLE and other nucleic acid-related autoimmune diseases. We will discuss how spatio-temporal regulation of Hsp90-ligand complexes within antigen-presenting cells affects the innate immunity and adaptive immunity.

IC Associated Conditions

Science.gov (United States)

... Bowel Syndrome Lupus Pelvic Floor Dysfunction Pudendal Neuralgia Sjogren’s Syndrome Vulvodynia Newly Diagnosed Toolkit IC Awareness Toolkit Know ... Bowel Syndrome Lupus Pelvic Floor Dysfunction Pudendal Neuralgia Sjogren’s Syndrome Vulvodynia Click to learn more about these and ...

T cell immunity

OpenAIRE

Emel Bülbül Başkan

2013-01-01

Since birth, our immune system is constantly bombarded with self-antigens and foreign pathogens. To stay healthy, complex immune strategies have evolved in our immune system to maintain self-tolerance and to defend against foreign pathogens. Effector T cells are the key players in steering the immune responses to execute immune functions. While effector T cells were initially identified to be immune promoting, recent studies unraveled negative regulatory functions of effector T cells...

Modification of glomerular immune complex deposition in mice by activation of the reticuloendothelial system.

OpenAIRE

Barcelli, U; Rademacher, R; Ooi, Y M; Ooi, B S

1981-01-01

To determine the effect of activation of the reticuloendothelial system on the localization of immune complexes in the kidney, a model of passive serum sickness nephritis in the mouse was used, with activation of the reticuloendothelial system with Corynebacterium parvum. Groups of mice, control and C. parvum-treated animals, were injected with BSA-125I-anti-BSA complexes containing 3 mg 125I-anti-BSA. Blood was obtained at 5 min, at 3 h, and at 12 h, when the animals were killed. Blood conce...

Complex pattern of immune evasion in MSI colorectal cancer.

Science.gov (United States)

Ozcan, Mine; Janikovits, Jonas; von Knebel Doeberitz, Magnus; Kloor, Matthias

2018-01-01

Mismatch repair (MMR)-deficient cancers accumulate multiple insertion/deletion mutations at coding microsatellites (cMS), which give rise to frameshift peptide neoantigens. The high mutational neoantigen load of MMR-deficient cancers is reflected by pronounced anti-tumoral immune responses of the host and high responsiveness towards immune checkpoint blockade. However, immune evasion mechanisms can interfere with the immune response against MMR-deficient tumors. We here performed a comprehensive analysis of immune evasion in MMR-deficient colorectal cancers, focusing on HLA class I-mediated antigen presentation. 72% of MMR-deficient colorectal cancers of the DFCI database harbored alterations affecting genes involved in HLA class I-mediated antigen presentation, and 54% of these mutations were predicted to abrogate function. Mutations affecting the HLA class I transactivator NLRC5 were observed as a potential new immune evasion mechanism in 26% (6% abrogating) of the analyzed tumors. NLRC5 mutations in MMR-deficient cancers were associated with decreased levels of HLA class I antigen expression. In summary, the majority of MMR-deficient cancers display mutations interfering with HLA class I antigen presentation that reflect active immune surveillance and immunoselection during tumor development. Clinical studies focusing on immune checkpoint blockade in MSI cancer should account for the broad variety of immune evasion mechanisms as potential biomarkers of therapy success.

Circulating immune complexes in the serum in systemic lupus erythematosus and in carriers of hepatitis B antigen: quantitation by binding to radiolabeled Cl/sub q/

International Nuclear Information System (INIS)

Nydegger, U.E.; Lambert, P.H.; Gerber, H.; Miescher, P.A.

1974-01-01

A sensitive and reproducible procedure fr the detection of souble immune complexes in sera from patients with various immunopathological disorders is reported. Radiolabeled Clq is reacted with sera containing immune complexes. Separation of free from complex bound [ 125 I]Clq is achieved by selective precipitation with polyethylene glycol (PEG). The minimal amount of aggregated immunoglobulins thus detected is about 10 μg and that of soluble human IgG-anti-IgG complexes is about 3 μg of complexed antibody. Some immune complexes formed in large antigen excess (Ag 2 Ab) can still be detected by this radiolabeled Clq bining assay. In a second step, this radiolabeled Clq binding assay was applied to an experimental model of immune complex disease and was shown to be efficient for the detection of in vivo formed immune complexes. Finally, the technique could be applied to the study of sera from patients with systemic lupus erythematosus (SLE) or to carriers of the Hepatitis B antigen (HB-Ag). Particularly high values were seen in active disease, a finding which was confirmed by follow-up studies performed with four SLE patients. No increased [ 125 I]Clq binding was seen in 18 healthy carriers of the HB-Ag; whereas, sera from carriers with hepatitis appear to precipitate increased [ 125 I]Clq percentages: 7/24 cases with acute transient and 4/7 cases with chronic persistent hepatitis were found to increasingly bind [ 125 I]Clq. The results were also used for a correlative study of [ 125 I]Clq binding to IgG levels in the sera but increased [ 125 I]Clq binding could not be attributed to high serum IgG levels which are likely to account for the evaluation of immune complex diseases in human pathology. (U.S.)

Detection of immune-complex-dissociated nonstructural-1 antigen in patients with acute dengue virus infections

NARCIS (Netherlands)

P. Koraka (Penelope); C.P. Burghoorn-Maas; A. Falconar; T.E. Setiati (Tatty); K. Djamiatun; J. Groen (Jan); A.D.M.E. Osterhaus (Albert)

2003-01-01

textabstractAccurate and timely diagnosis of dengue virus (DEN) infections is essential for the differential diagnosis of patients with febrile illness and hemorrhagic fever. In the present study, the diagnostic value of a newly developed immune-complex dissociated nonstructural-1 (NS-1) antigen dot

Detection of immune-complex-dissociated nonstructural-1 antigen in patients with acute dengue virus infections.

NARCIS (Netherlands)

Koraka, P.; Burghoorn-Maas, C.P.; Falconar, A.; Setiati, T.E.; Djamiatun, K.; Groen, J.; Osterhaus, A.D.

2003-01-01

Accurate and timely diagnosis of dengue virus (DEN) infections is essential for the differential diagnosis of patients with febrile illness and hemorrhagic fever. In the present study, the diagnostic value of a newly developed immune-complex dissociated nonstructural-1 (NS-1) antigen dot blot

[Autoantibody formation against the antigens of the synaptonemal complex in the syngeneic immunization of male Mus musculus].

Science.gov (United States)

Dadashev, S Ia; Gorach, G G; Kolomiets, O L

1994-01-01

Male mice were immunized with the suspension of synaptonemal complexes (SC) isolated from mouse spermatocytes nuclei. The indirect immunofluorescent analysis showed the active binding of sera obtained from immunized mice to SC of mouse spermatocyte spreads. At early and mid-pachytene, SC can be clearly identified in 19 autosome bivalents and in sex chromosome bivalent. According to the electron microscopic analysis, all structural elements of SC bind antibodies. Metaphase chromosomes were not stained with the immune sera. Specificity of interaction between SC components and antibodies was confirmed in a series of control experiments. Analysis of sera obtained from mice after their syngeneic immunization with isolated SC fraction suggested that certain mouse SC components induce the formation of autoantibodies. This, in turn, suggests that these SC components are meiosis-specific.

Formation of infectious dengue virus-antibody immune complex in vivo in marmosets (Callithrix jacchus) after passive transfer of anti-dengue virus monoclonal antibodies and infection with dengue virus.

Science.gov (United States)

Moi, Meng Ling; Ami, Yasushi; Shirai, Kenji; Lim, Chang-Kweng; Suzaki, Yuriko; Saito, Yuka; Kitaura, Kazutaka; Saijo, Masayuki; Suzuki, Ryuji; Kurane, Ichiro; Takasaki, Tomohiko

2015-02-01

Infection with a dengue virus (DENV) serotype induces cross-reactive, weakly neutralizing antibodies to different dengue serotypes. It has been postulated that cross-reactive antibodies form a virus-antibody immune complex and enhance DENV infection of Fc gamma receptor (FcγR)-bearing cells. We determined whether infectious DENV-antibody immune complex is formed in vivo in marmosets after passive transfer of DENV-specific monoclonal antibody (mAb) and DENV inoculation and whether infectious DENV-antibody immune complex is detectable using FcγR-expressing cells. Marmosets showed that DENV-antibody immune complex was exclusively infectious to FcγR-expressing cells on days 2, 4, and 7 after passive transfer of each of the mAbs (mAb 4G2 and mAb 6B6C) and DENV inoculation. Although DENV-antibody immune complex was detected, contribution of the passively transferred antibody to overall viremia levels was limited in this study. The results indicate that DENV cross-reactive antibodies form DENV-antibody immune complex in vivo, which is infectious to FcγR-bearing cells but not FcγR-negative cells. © The American Society of Tropical Medicine and Hygiene.

Immunizing Children

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Geraldine Jody Macdonald

2014-11-01

Full Text Available This article addresses the complex contexts within which Canadian health professionals engage in immunizing children and focuses on the Canadian practice guidelines and current scientific evidence that direct Canadian health professional competencies. The article begins by presenting two current global vaccine initiatives and links these to immunization in Canada. A selected literature review identifies current best immunization practices. With the purpose of promoting quality improvement, three key Canadian immunization competencies for health professional are highlighted: communication with parents, including those who are experiencing vaccine hesitancy; administration of immunizing agents; and documentation of immunizations. Health professionals are encouraged to reflect on immunization competencies and ensure evidence-based practices underpin vaccine delivery in their primary care settings.

Solid-phase enzyme immunoassay or radioimmunoassay for the detection of immune complexes based on their recognition by conglutinin: conglutinin-binding test

International Nuclear Information System (INIS)

Casali, P.; Bossus, A.; Carpentier, N.A.; Lambert, P.H.

1977-01-01

Bovine conglutinin was used in a solid-phase assay for the detection of immune complexes. In a first step, the tested serum sample was incubated in polypropylene tubes coated with conglutinin to allow C3-coated immune complexes to bind to solid-phase conglutinin. In a second step, the conglutinin-bound complexes were detected using an enzyme-conjugated or radiolabelled anti-immunoglobulin antibody. The conglutinin-binding (KgB) test did not suffer from the interference of DNA, heparin or endotoxins. Its limit of sensitivity for aggregated IgG was 3 μg/ml undiluted human serum. Immune complexes prepared in vitro using tetanus toxoid, or DNA, and corresponding antibodies in human sera could be detected at various antigen/antibody ratios and at antibody concentrations lower than 8 μg/ml. The KgB test allowed for the detection of immune complexes in sera from patients with systemic lupus erythematosus, rheumatoid arthritis, idiopathic vasculitis, leprosy and leukemia. These sera were also tested using the 125 I-labelled Clq-binding activity (BA) test and the KgB test simultaneously, and a significant rank order correlation was observed. In patients with leukemia, a significant correlation was observed using three tests, KgB, 125 I-labelled Clq BA and Raji-cell radioimmunoassay (RIA). Therefore, the KgB test appears as a simple and reproducible method, utilizing a very stable reagent, with a sensitivity and specificity comparable to the other tests studied and allowing for clinical application. (author)

Conceptualising Intellectual Capital (IC) as Language Game and Power

DEFF Research Database (Denmark)

Jørgensen, Kenneth Mølbjerg

2006-01-01

Intellectual Capital (IC) can be viewed as knowledge about knowledge, knowledge creation and how such processes might be leveraged into value. Developing a critical understanding of IC requires a historical and contextual understanding of how IC has emerged and how IC is used. This paper, drawing...... this process of social construction. The paper concludes by proposing some methodological guidelines for conducting critical genealogical research on intellectual capital....

Complex Immune Evasion Strategies in Classical Hodgkin Lymphoma.

Science.gov (United States)

Wein, Frederik; Weniger, Marc A; Höing, Benedikt; Arnolds, Judith; Hüttmann, Andreas; Hansmann, Martin-Leo; Hartmann, Sylvia; Küppers, Ralf

2017-12-01

The cellular microenvironment in classical Hodgkin lymphoma (cHL) is dominated by a mixed infiltrate of inflammatory cells with typically only about 1% Hodgkin and Reed/Sternberg (HRS) tumor cells. T cells are usually the largest population of cells in the cHL microenvironment, encompassing T helper (Th) cells, regulatory T cells (Tregs), and cytotoxic T cells. Th cells and Tregs presumably provide essential survival signals for HRS cells. Tregs are also involved in rescuing HRS cells from antitumor immune responses. An understanding of the immune evasion strategies of HRS cells is not only relevant for a characterization of the pathophysiology of cHL but is also clinically relevant, given the current treatment approaches targeting checkpoint inhibitors. Here, we characterized the cHL-specific CD4 + T-cell infiltrate regarding its role in immune evasion. Global gene expression analysis of CD4 + Th cells and Tregs isolated from cHL lymph nodes and reactive tonsils revealed that Treg signatures were enriched in CD4 + Th cells of cHL. Hence, HRS cells may induce Treg differentiation in Th cells, a conclusion supported by in vitro studies with Th cells and cHL cell lines. We also found evidence for immune-suppressive purinergic signaling and a role of the inhibitory receptor-ligand pairs B- and T-cell lymphocyte attenuator-herpesvirus entry mediator and CD200R-CD200 in promoting immune evasion. Taken together, this study highlights the relevance of Treg induction and reveals new immune checkpoint-driven immune evasion strategies in cHL. Cancer Immunol Res; 5(12); 1122-32. ©2017 AACR . ©2017 American Association for Cancer Research.

JAK kinases are required for the bacterial RNA and poly I:C induced tyrosine phosphorylation of PKR

Science.gov (United States)

Bleiblo, Farag; Michael, Paul; Brabant, Danielle; Ramana, Chilakamarti V; Tai, TC; Saleh, Mazen; Parrillo, Joseph E; Kumar, Anand; Kumar, Aseem

2013-01-01

Discriminating the molecular patterns associated with RNA is central to innate immunity. The protein kinase PKR is a cytosolic sensor involved in the recognition of viral dsRNA and triggering interferon-induced signaling. Here, we identified bacterial RNA as a novel distinct pattern recognized by PKR. We show that the tyrosine phosphorylation of PKR induced by either bacterial RNA or poly I:C is impaired in mutant cells lacking TYK2, JAK1, or JAK2 kinases. PKR was found to be a direct substrate for the activated JAKs. Our results indicated that the double-stranded structures of bacterial RNA are required to fully activate PKR. These results suggest that bacterial RNA signaling is analogous in some respects to that of viral RNA and interferons and may have implications in bacterial immunity. PMID:23236554

Differential effectiveness of Serratia plymuthica IC1270-induced systemic resistance against hemibiotrophic and necrotrophic leaf pathogens in rice

Directory of Open Access Journals (Sweden)

Höfte Monica M

2009-01-01

Full Text Available Abstract Background Induced resistance is a state of enhanced defensive capacity developed by a plant reacting to specific biotic or chemical stimuli. Over the years, several forms of induced resistance have been characterized, including systemic acquired resistance, which is induced upon localized infection by an avirulent necrotizing pathogen, and induced systemic resistance (ISR, which is elicited by selected strains of nonpathogenic rhizobacteria. However, contrary to the relative wealth of information on inducible defense responses in dicotyledoneous plants, our understanding of the molecular mechanisms underlying induced resistance phenomena in cereal crops is still in its infancy. Using a combined cytomolecular and pharmacological approach, we analyzed the host defense mechanisms associated with the establishment of ISR in rice by the rhizobacterium Serratia plymuthica IC1270. Results In a standardized soil-based assay, root treatment with IC1270 rendered foliar tissues more resistant to the hemibiotrophic pathogen Magnaporthe oryzae, causal agent of the devastating rice blast disease. Analysis of the cytological and biochemical alterations associated with restriction of fungal growth in IC1270-induced plants revealed that IC1270 primes rice for enhanced attacker-induced accumulation of reactive oxygen species (ROS and autofluorescent phenolic compounds in and near epidermal cells displaying dense cytoplasmic granulation. Similar, yet more abundant, phenotypes of hypersensitively dying cells in the vicinity of fungal hyphae were evident in a gene-for-gene interaction with an avirulent M. oryzae strain, suggesting that IC1270-inducible ISR and R protein conditioned effector-triggered immunity (ETI target similar defense mechanisms. Yet, this IC1270-inducible ISR response seems to act as a double-edged sword within the rice defense network as induced plants displayed an increased vulnerability to the necrotrophic pathogens Rhizoctonia

Interaction of complement-solubilized immune complexes with CR1 receptors on human erythrocytes. The binding reaction

DEFF Research Database (Denmark)

Jepsen, H H; Svehag, S E; Jarlbaek, L

1986-01-01

showed no binding. IC solubilized in 50% human serum in the presence of autologous RBC bound rapidly to RBC-CR1, with maximal binding within less than 1 min at 37 degrees C. Release of CR1-bound IC under these conditions occurred slowly, requiring more than 30 min. Only binding of 'partially' solubilized...... of an intact classical pathway in preparing the IC for binding to RBC-CR1. C-solubilized IC could be absorbed to solid-phase conglutinin or antibody to C3c and C4c, and these ligands were able to inhibit the binding of solubilized IC to RBC. Heparin also exerted a marked, dose-dependent inhibitory effect...

Scrapie affects the maturation cycle and immune complex trapping by follicular dendritic cells in mice.

Directory of Open Access Journals (Sweden)

Gillian McGovern

2009-12-01

Full Text Available Transmissible spongiform encephalopathies (TSEs or prion diseases are infectious neurological disorders of man and animals, characterised by abnormal disease-associated prion protein (PrP(d accumulations in the brain and lymphoreticular system (LRS. Prior to neuroinvasion, TSE agents often accumulate to high levels within the LRS, apparently without affecting immune function. However, our analysis of scrapie-affected sheep shows that PrP(d accumulations within the LRS are associated with morphological changes to follicular dendritic cells (FDCs and tingible body macrophages (TBMs. Here we examined FDCs and TBMs in the mesenteric lymph nodes (MLNs of scrapie-affected mice by light and electron microscopy. In MLNs from uninfected mice, FDCs could be morphologically categorised into immature, mature and regressing forms. However, in scrapie-affected MLNs this maturation cycle was adversely affected. FDCs characteristically trap and retain immune complexes on their surfaces, which they display to B-lymphocytes. In scrapie-affected MLNs, some FDCs were found where areas of normal and abnormal immune complex retention occurred side by side. The latter co-localised with PrP(d plasmalemmal accumulations. Our data suggest this previously unrecognised morphology represents the initial stage of an abnormal FDC maturation cycle. Alterations to the FDCs included PrP(d accumulation, abnormal cell membrane ubiquitin and excess immunoglobulin accumulation. Regressing FDCs, in contrast, appeared to lose their membrane-attached PrP(d. Together, these data suggest that TSE infection adversely affects the maturation and regression cycle of FDCs, and that PrP(d accumulation is causally linked to the abnormal pathology observed. We therefore support the hypothesis that TSEs cause an abnormality in immune function.

Sporothrix schenckii Immunization, but Not Infection, Induces Protective Th17 Responses Mediated by Circulating Memory CD4+ T Cells

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Alberto García-Lozano

2018-06-01

Full Text Available Sporotrichosis is a chronic subcutaneous mycosis caused by the Sporothrix schenckii species complex and it is considered an emerging opportunistic infection in countries with tropical and subtropical climates. The host’s immune response has a main role in the development of this disease. However, it is unknown the features of the memory cellular immune response that could protect against the infection. Our results show that i.d. immunization in the ears of mice with inactivated S. schenckii conidia (iC combined with the cholera toxin (CT induces a cellular immune response mediated by circulating memory CD4+ T cells, which mainly produce interleukin 17 (IL-17. These cells mediate a strong delayed-type hypersensitivity (DTH reaction. Systemic and local protection against S. schenckii was mediated by circulating CD4+ T cells. In contrast, the infection induces a potent immune response in the skin mediated by CD4+ T cells, which have an effector phenotype that preferentially produce interferon gamma (IFN-γ and mediate a transitory DTH reaction. Our findings prove the potential value of the CT as a potent skin adjuvant when combined with fungal antigens, and they also have important implications for our better understanding of the differences between the memory immune response induced by the skin immunization and those induced by the infection; this knowledge enhances our understanding of how a protective immune response against a S. schenckii infection is developed.

Herd Immunity to Ebolaviruses Is Not a Realistic Target for Current Vaccination Strategies

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Stuart G. Masterson

2018-05-01

Full Text Available The recent West African Ebola virus pandemic, which affected >28,000 individuals increased interest in anti-Ebolavirus vaccination programs. Here, we systematically analyzed the requirements for a prophylactic vaccination program based on the basic reproductive number (R0, i.e., the number of secondary cases that result from an individual infection. Published R0 values were determined by systematic literature research and ranged from 0.37 to 20. R0s ≥ 4 realistically reflected the critical early outbreak phases and superspreading events. Based on the R0, the herd immunity threshold (Ic was calculated using the equation Ic = 1 − (1/R0. The critical vaccination coverage (Vc needed to provide herd immunity was determined by including the vaccine effectiveness (E using the equation Vc = Ic/E. At an R0 of 4, the Ic is 75% and at an E of 90%, more than 80% of a population need to be vaccinated to establish herd immunity. Such vaccination rates are currently unrealistic because of resistance against vaccinations, financial/logistical challenges, and a lack of vaccines that provide long-term protection against all human-pathogenic Ebolaviruses. Hence, outbreak management will for the foreseeable future depend on surveillance and case isolation. Clinical vaccine candidates are only available for Ebola viruses. Their use will need to be focused on health-care workers, potentially in combination with ring vaccination approaches.

The measurement of Ksub(IC) in single crystal SiC using the indentation method

International Nuclear Information System (INIS)

Henshall, J.L.; Brookes, C.A.

1985-01-01

The present work has concentrated on investigating the underlying fracture toughness behaviour of SiC single crystals. This material was chosen because of the commercial importance of the various polycrystalline forms of SiC and the relative ready availability of reasonably sized single crystals. This study has examined the feasibility of using the indentation technique to determine Ksub(IC) in SiC single crystals. This requires much more less complex experimentation and also affords the possibility of being able to use this method to study the orientation dependence of Ksub(IC) in a similar manner to that used to investigate anisotropy in indentation hardness behaviour. A single crystal of 6H-SiC was used for all the hardness and conventional Ksub(IC) results reported here. The particular polytype and orientation were determined using the Laue X-ray method. All the measurements were made under ambient conditions. Three-point bend tests, with a 6 mm span on single edge notched beams, SENB, orientated such that the plane of the notch was brace 112-bar0 brace and the crack propagation direction were used for the conventional Ksub(IC) tests. The hardness indentations were all made on one particular SENB test piece after it had been fractured. The results are discussed. (author)

Allergen-containing immune complexes used for immunotherapy of allergic asthma. Preparation of complexes and evaluation of their clinical performance in guinea pigs

DEFF Research Database (Denmark)

Poulsen, L K; Lundberg, L; Søndergaard, I

1989-01-01

Guinea pigs inbred for their ability to develop respiratory anaphylaxis to experimental antigens have been used for comparison of different forms of immunotherapy (IT). Passive, active and combined (immune complexes between antigen and specific IgG) IT were compared with placebo. The bronchial re...... groups surprisingly recovered their original sensitivity to inhalation of the antigen....

HER2-Targeted Polyinosine/Polycytosine Therapy Inhibits Tumor Growth and Modulates the Tumor Immune Microenvironment.

Science.gov (United States)

Zigler, Maya; Shir, Alexei; Joubran, Salim; Sagalov, Anna; Klein, Shoshana; Edinger, Nufar; Lau, Jeffrey; Yu, Shang-Fan; Mizraji, Gabriel; Globerson Levin, Anat; Sliwkowski, Mark X; Levitzki, Alexander

2016-08-01

The development of targeted therapies that affect multiple signaling pathways and stimulate antitumor immunity is greatly needed. About 20% of patients with breast cancer overexpress HER2. Small molecules and antibodies targeting HER2 convey some survival benefits; however, patients with advanced disease succumb to the disease under these treatment regimens, possibly because HER2 is not completely necessary for the survival of the targeted cancer cells. In the present study, we show that a polyinosine/polycytosine (pIC) HER2-homing chemical vector induced the demise of HER2-overexpressing breast cancer cells, including trastuzumab-resistant cells. Targeting pIC to the tumor evoked a number of cell-killing mechanisms, as well as strong bystander effects. These bystander mechanisms included type I IFN induction, immune cell recruitment, and activation. The HER2-targeted pIC strongly inhibited the growth of HER2-overexpressing tumors in immunocompetent mice. The data presented here could open additional avenues in the treatment of HER2-positive breast cancer. Cancer Immunol Res; 4(8); 688-97. ©2016 AACR. ©2016 American Association for Cancer Research.

JAK kinases are required for the bacterial RNA and poly I:C induced tyrosine phosphorylation of PKR

OpenAIRE

Bleiblo, Farag; Michael, Paul; Brabant, Danielle; Ramana, Chilakamarti V; Tai, TC; Saleh, Mazen; Parrillo, Joseph E; Kumar, Anand; Kumar, Aseem

2012-01-01

Discriminating the molecular patterns associated with RNA is central to innate immunity. The protein kinase PKR is a cytosolic sensor involved in the recognition of viral dsRNA and triggering interferon-induced signaling. Here, we identified bacterial RNA as a novel distinct pattern recognized by PKR. We show that the tyrosine phosphorylation of PKR induced by either bacterial RNA or poly I:C is impaired in mutant cells lacking TYK2, JAK1, or JAK2 kinases. PKR was found to be a direct substra...

Measuring IC following a semi-qualitative approach: An integrated framework

Directory of Open Access Journals (Sweden)

Chiara Verbano

2013-09-01

Full Text Available Purpose: Considering the different IC measures adopted in literature, the advantages of adopting semi-qualitative measures, and the lack of an agreed system for IC evaluation, the purpose of the paper is to analyse literature on IC measurement following a semi-qualitative approach, with the final intent to build an IC measurement framework. Design/methodology/approach: A literature review on IC measurement system, following a semi-qualitative approach, has been conducted and analysed, in order to re-organize and synthesize all items used in previous researches. Findings: An integrated framework emerged from this research and it constitutes an IC  measurement system, created gathering and integrating different items previously adopted in literature. Each of these variables has been organized in categories belonging to one of the three main components of IC: human capital, internal structural capital and relational capital. Originality/value: This research provides an integrated tool for IC evaluation, fostering toward a well agreed measurement system that is still lacking in literature. This framework could be interesting  not only for the academic world, which in the last two decades reveals increasing attention to IC, but also for the management of the companies, that with IC measurement can increase awareness of the firm’s value and develop internal auditing system to support the management of these assets. Moreover, it could be a useful instrument for the communication of IC value to the external stakeholders, as customers, suppliers and especially shareholders, and to investors and financial analysts.

Complex structure of type VI peptidoglycan muramidase effector and a cognate immunity protein

International Nuclear Information System (INIS)

Wang, Tianyu; Ding, Jinjing; Zhang, Ying; Wang, Da-Cheng; Liu, Wei

2013-01-01

The structure of the Tse3–Tsi3 complex associated with the bacterial type VI secretion system of P. aeruginosa has been solved and refined at 1.9 Å resolution. The structural basis of the recognition of the muramidase effector and its inactivation by its cognate immunity protein is revealed. The type VI secretion system (T6SS) is a bacterial protein-export machine that is capable of delivering virulence effectors between Gram-negative bacteria. The T6SS of Pseudomonas aeruginosa transports two lytic enzymes, Tse1 and Tse3, to degrade cell-wall peptidoglycan in the periplasm of rival bacteria that are competing for niches via amidase and muramidase activities, respectively. Two cognate immunity proteins, Tsi1 and Tsi3, are produced by the bacterium to inactivate the two antibacterial effectors, thereby protecting its siblings from self-intoxication. Recently, Tse1–Tsi1 has been structurally characterized. Here, the structure of the Tse3–Tsi3 complex is reported at 1.9 Å resolution. The results reveal that Tse3 contains a C-terminal catalytic domain that adopts a soluble lytic transglycosylase (SLT) fold in which three calcium-binding sites were surprisingly observed close to the catalytic Glu residue. The electrostatic properties of the substrate-binding groove are also distinctive from those of known structures with a similar fold. All of these features imply that a unique catalytic mechanism is utilized by Tse3 in cleaving glycosidic bonds. Tsi3 comprises a single domain showing a β-sandwich architecture that is reminiscent of the immunoglobulin fold. Three loops of Tsi3 insert deeply into the groove of Tse3 and completely occlude its active site, which forms the structural basis of Tse3 inactivation. This work is the first crystallographic report describing the three-dimensional structure of the Tse3–Tsi3 effector–immunity pair

Complex structure of type VI peptidoglycan muramidase effector and a cognate immunity protein

Energy Technology Data Exchange (ETDEWEB)

Wang, Tianyu [Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Ding, Jinjing; Zhang, Ying; Wang, Da-Cheng, E-mail: dcwang@ibp.ac.cn [Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Liu, Wei, E-mail: dcwang@ibp.ac.cn [The Third Military Medical University, Chongqing 400038 (China); Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China)

2013-10-01

The structure of the Tse3–Tsi3 complex associated with the bacterial type VI secretion system of P. aeruginosa has been solved and refined at 1.9 Å resolution. The structural basis of the recognition of the muramidase effector and its inactivation by its cognate immunity protein is revealed. The type VI secretion system (T6SS) is a bacterial protein-export machine that is capable of delivering virulence effectors between Gram-negative bacteria. The T6SS of Pseudomonas aeruginosa transports two lytic enzymes, Tse1 and Tse3, to degrade cell-wall peptidoglycan in the periplasm of rival bacteria that are competing for niches via amidase and muramidase activities, respectively. Two cognate immunity proteins, Tsi1 and Tsi3, are produced by the bacterium to inactivate the two antibacterial effectors, thereby protecting its siblings from self-intoxication. Recently, Tse1–Tsi1 has been structurally characterized. Here, the structure of the Tse3–Tsi3 complex is reported at 1.9 Å resolution. The results reveal that Tse3 contains a C-terminal catalytic domain that adopts a soluble lytic transglycosylase (SLT) fold in which three calcium-binding sites were surprisingly observed close to the catalytic Glu residue. The electrostatic properties of the substrate-binding groove are also distinctive from those of known structures with a similar fold. All of these features imply that a unique catalytic mechanism is utilized by Tse3 in cleaving glycosidic bonds. Tsi3 comprises a single domain showing a β-sandwich architecture that is reminiscent of the immunoglobulin fold. Three loops of Tsi3 insert deeply into the groove of Tse3 and completely occlude its active site, which forms the structural basis of Tse3 inactivation. This work is the first crystallographic report describing the three-dimensional structure of the Tse3–Tsi3 effector–immunity pair.

[Humoral immune diseases: Cutaneous vasculitis and auto-immune bullous dermatoses].

Science.gov (United States)

Wechsler, Janine

2018-02-01

Humoral immunity is the cause of multiple diseases related to antibodies (IgA, IgG, IgM) produced by the patient. Two groups of diseases are identified. The first group is related to circulating antigen-antibody complexes. The antigens are various. They are often unknown. These immune complexes cause a vascular inflammation due to the complement fixation. Consequently, this group is dominated by inflammatory vasculitis. In the second group, the pathology is due to the fixation in situ of antibodies to a target antigen of the skin that is no more recognized by the patient. This group is represented by the auto-immune bullous dermatoses. Copyright © 2017. Published by Elsevier Masson SAS.

Gut microbiota, immunity and disease: a complex relationship

Directory of Open Access Journals (Sweden)

Michele M Kosiewicz

2011-09-01

Full Text Available Our immune system has evolved to recognize and eradicate pathogenic microbes. However, we have a symbiotic relationship with multiple species of bacteria that occupy the gut and comprise the natural commensal flora or microbiota. The microbiota is critically important for the breakdown of nutrients, and also assists in preventing colonization by potentially pathogenic bacteria. In addition, the gut commensal bacteria appears to be critical for the development of an optimally functioning immune system. Various studies have shown that individual species of the microbiota can induce very different types of immune cells (e.g., Th17 cells, Foxp3+ regulatory T cells and responses, suggesting that the composition of the microbiota can have an important influence on the immune response. Although the microbiota resides in the gut, it appears to have a significant impact on the systemic immune response. Indeed, specific gut commensal bacteria have been shown to affect disease development in organs other than the gut, and depending on the species, have been found to have a wide range of effects on diseases from induction and exacerbation to inhibition and protection. In this review, we will focus on the role that the gut microbiota plays in the development and progression of inflammatory/autoimmune disease, and we will also touch upon its role in allergy and cancer.

"Kill" the messenger

DEFF Research Database (Denmark)

Nielsen, Christoffer Tandrup; Rasmussen, Niclas S; Heegaard, Niels H H

2016-01-01

Immune complex (IC) deposition in the glomerular basement membrane (GBM) is a key early pathogenic event in lupus nephritis (LN). The clarification of the mechanisms behind IC deposition will enable targeted therapy in the future. Circulating cell-derived microparticles (MPs) have been proposed......, may be essential for the deposition of ICs in kidneys and thus for the ensuing formation of MP-derived electron dense structures in the GBM, and immune activation in LN. This review focuses on the notion of targeting surface molecules on MPs as an entirely novel treatment strategy in LN. By targeting...

The defective nature of ice Ic and its implications for atmospheric science

Science.gov (United States)

Kuhs, W. F.; Hansen, T. C.

2009-04-01

The possible atmospheric implication of ice Ic (cubic ice) has already been suggested some time ago in the context of snow crystal formation [1]. New findings from air-borne measurements in cirrus clouds and contrails have put ice Ic into the focus of interest to understand the so-called "supersaturation puzzle" [2,3,4,5]. Our recent microstructural work on ice Ic [6,7] appears to be highly relevant in this context. We have found that ice Ic is characterized by a complex stacking fault pattern, which changes as a function of temperature as well as time. Indeed, from our own [8] and other group's work [9] one knows that (in contrast to earlier believe) ice Ic can form up to temperatures at least as high as 240K - thus in the relevant range for cirrus clouds. We have good preliminary evidence that the "cubicity" (which can be related to stacking fault probabilities) as well as the particle size of ice Ic are the relevant parameters for this correlation. The "cubicity" of stacking faulty ice Ic (established by diffraction) correlates nicely with the increased supersaturation at decreasing temperatures observed in cirrus clouds and contrails, a fact, which may be considered as further evidence for the presence of ice Ic. Moreover, the stacking faults lead to kinks in the outer shapes of the minute ice Ic crystals as seen by cryo scanning electron microscopy (cryo-SEM); these defective sites are likely to play some role in heterogeneous reactions in the atmosphere. The cryo-SEM work suggests that stacking-faulty ice Ic has many more active centres for such reactions than the usually considered thermodynamically stable form, ice Ih. [1] T Kobayashi & T Kuroda (1987) Snow Crystals. In: Morphology of Crystals (ed. I Sunagawa), Terra Scientific Publishing, Tokyo, pp.649-743. [2] DM Murphy (2003) Dehydration in cold clouds is enhanced by a transition from from cubic to hexagonal ice. Geophys.Res.Lett.,30, 2230, doi:10.1029/2003GL018566. [3] RS Gao & 19 other authors (2004

HI observations of the irregular galaxy IC 10

International Nuclear Information System (INIS)

Shostak, G.S.; Woerden, H. van

1983-01-01

The authors have made radio synthesis observations of the galaxy IC 10 with resolutions of 30 arcsec and 8 km/sec in the neutral hydrogen line using the Westerbork telescope. These confirm Shostak's (1974) result that, in the central region of IC 10, the velocity gradient is opposite to that later measured by single-dish in the outer regions. The suggestion by Cohen (1979) that the velocity gradient reversal is due to IC 10 being nearly face-on and warped is consistent with the new data. (Auth.)

Prenatal Immune Challenge in Mice Leads to Partly Sex-Dependent Behavioral, Microglial, and Molecular Abnormalities Associated with Schizophrenia

Directory of Open Access Journals (Sweden)

Chin W. Hui

2018-02-01

Full Text Available Epidemiological studies revealed that environmental factors comprising prenatal infection are strongly linked to risk for later development of neuropsychiatric disorders such as schizophrenia. Considering strong sex differences in schizophrenia and its increased prevalence in males, we designed a methodological approach to investigate possible sex differences in pathophysiological mechanisms. Prenatal immune challenge was modeled by systemic administration of the viral mimic polyinosinic-polycytidylic acid (Poly I:C to C57BL/6 mice at embryonic day 9.5. The consequences on behavior, gene expression, and microglia—brain immune cells that are critical for normal development—were characterized in male vs. female offspring at adulthood. The cerebral cortex, hippocampus, and cerebellum, regions where structural and functional alterations were mainly described in schizophrenia patients, were selected for cellular and molecular analyses. Confocal and electron microscopy revealed most pronounced differences in microglial distribution, arborization, cellular stress, and synaptic interactions in the hippocampus of male vs. female offspring exposed to Poly I:C. Sex differences in microglia were also measured under both steady-state and Poly I:C conditions. These microglial alterations were accompanied by behavioral impairment, affecting for instance sensorimotor gating, in males. Consistent with these results, increased expression of genes related to inflammation was measured in cerebral cortex and hippocampus of males challenged with Poly I:C. Overall, these findings suggest that schizophrenia's higher incidence in males might be associated, among other mechanisms, with an increased microglial reactivity to prenatal immune challenges, hence determining disease outcomes into adulthood.

Bio-medical CMOS ICs

CERN Document Server

Yoo, Hoi-Jun

2011-01-01

This book is based on a graduate course entitled, Ubiquitous Healthcare Circuits and Systems, that was given by one of the editors. It includes an introduction and overview to biomedical ICs and provides information on the current trends in research.

A microplate adaptation of the solid-phase C1q immune complex assay

International Nuclear Information System (INIS)

Hunt, J.S.; Kennedy, M.P.; Barber, K.E.; McGiven, A.R.

1980-01-01

A method has been developed for the detection of C1q binding immune complexes in serum in which microculture plates are used as the solid-phase matrix for adsorption of C1q. This micromethod used only one-tenth of the amount of both C1q and [ 125 I]antihuman immunoglobulin per test and enabled 7 times as many samples to be tested in triplicate in comparison with the number performed in duplicate by the standard tube assay. (Auth.)

Electrospinning of functional poly(methyl methacrylate) nanofibers containing cyclodextrin-menthol inclusion complexes

International Nuclear Information System (INIS)

Uyar, Tamer; Besenbacher, Flemming; Nur, Yusuf; Hacaloglu, Jale

2009-01-01

Electrospinning of nanofibers with cyclodextrin inclusion complexes (CD-ICs) is particularly attractive since distinct properties can be obtained by combining the nanofibers with specific functions of the CD-ICs. Here we report on the electrospinning of poly(methyl methacrylate) (PMMA) nanofibers containing cyclodextrin-menthol inclusion complexes (CD-menthol-ICs). These CD-menthol-IC functionalized nanofibers were developed with the purpose of producing functional nanofibers that contain fragrances/flavors with high temperature stability, and menthol was used as a model fragrance/flavor material. The PMMA nanofibers were electrospun with CD-menthol-ICs using three type of CD: α-CD, β-CD, and γ-CD. Direct pyrolysis mass spectrometry (DP-MS) studies showed that the thermal evaporation of menthol occurred over a very high and a broad temperature range (100-355 deg. C) for PMMA/CDmenthol-IC nanowebs, demonstrating the complexation of menthol with the CD cavity and its high temperature stability. Furthermore, as the size of CD cavity increased in the order α-CD β-CD>α-CD.

K/sub Ic/ and J/sub Ic/ of Westerly granite: effects of thickness and in-plane dimensions

International Nuclear Information System (INIS)

Schmidt, R.A.; Lutz, T.J.

1978-01-01

An investigation is described in which tensile properties, fracture toughness, and critical J integral are measured for Westerly granite, a rock that is widely used in rock mechanics studies. This was primarily a parameter sensitivity study in which the effects of specimen dimensions and testing techniques were assessed. It is hoped that this study will aid in establishing tentative standards and guidelines for fracture toughness testing of rock as well as indicate the feasibility of using a J integral fracture criterion for this material. ASTM standard specimen configurations of the compact and bend types were tested with compact specimens ranging in width from W = 25.4 mm to W = 406.4 mm (0.5T to 8T) and with thickness ranging from 13 mm to 100 mm. A series of 4T compact specimens were tested to assess the effects of thickness and fatigue precracking. Techniques are described that enable several values of K/sub Ic/, a complete J vs crack growth curve, and a J/sub Ic/ value to be obtained from each sample. Direct-pull tension tests on shaped specimens of Westerly granite are described which indicate a high degree of nonlinear, inelastic behavior. This fact raises questions about the use of LEFM, but the J/sub Ic/ data presented appear to validate the K/sub Ic/ measurements

FAM26F: An Enigmatic Protein Having a Complex Role in the Immune System.

Science.gov (United States)

Malik, Uzma; Javed, Aneela

2016-09-19

Mammalian immune system is a complex amalgam of diverse cellular and noncellular components such as cytokines, receptors and co-receptors. FAM26F (family with sequence similarity 26, member F) is a recently identified tetraspanin-like membrane glycoprotein which is predicted to make homophilic interactions and potential synapses between several immune cells including CD4 + , CD8 + , NK, dendritic cells and macrophages. Various whole transcriptome analyses have demonstrated the differential expression of FAM26F in several bacterial, viral and parasitic infections, in certain pathophysiological conditions such as liver and heart transplantation, and in various cancers. The complete understanding of transcriptional regulation of FAM26F is in its infancy however it is up regulated by various stimulants such as polyI:C, LPS, INF gamma and TNF alpha, and via various proposed pathways including TLR3, TLR4 IFN-β and Dectin-1. These pathways can merge in STAT1 activation. The synergistic expression of FAM26F on both NK-cells and myeloid dendritic cells is required to activate NK-cells against tumors via its cytoplasmic tail, thus emphasizing therapeutic potential of FAM26F for NK sensitive tumors. Current review provides a comprehensive basis to propose that FAM26F expression level is at least a hallmark for IFN-γ-lead immune responses and thus can proficiently be regarded as an early diagnostic marker. Future investigation dissecting the role of FAM26F in activation of various immune cell populations in local amplification by cell-cell contact is crucial to provide the missing link imperative for elucidating the relevance of this protein in immune responses.

Detection of Immune-Complex Dissociated Nonstructural-1 (NS-1) Antigen in Patients with Acute Dengue Virus Infections

NARCIS (Netherlands)

P. Koraka (Penelope); C.P. Burghoorn-Maas; A. Falconar; T.E. Setiati (Tatty); K. Djamiatun; J. Groen (Jan); A.D.M.E. Osterhaus (Albert)

2003-01-01

textabstractAccurate and timely diagnosis of dengue virus (DEN) infections is essential for the differential diagnosis of patients with febrile illness and hemorrhagic fever. In the present study, the diagnostic value of a newly developed immune-complex dissociated nonstructural-1 (NS-1) antigen dot

Phenotypic effects of maternal immune activation and early postnatal milieu in mice mutant for the schizophrenia risk gene neuregulin-1.

Science.gov (United States)

O'Leary, C; Desbonnet, L; Clarke, N; Petit, E; Tighe, O; Lai, D; Harvey, R; Waddington, J L; O'Tuathaigh, C

2014-09-26

Risk of schizophrenia is likely to involve gene × environment (G × E) interactions. Neuregulin 1 (NRG1) is a schizophrenia risk gene, hence any interaction with environmental adversity, such as maternal infection, may provide further insights into the basis of the disease. This study examined the individual and combined effects of prenatal immune activation with polyriboinosinic-polyribocytidilic acid (Poly I:C) and disruption of the schizophrenia risk gene NRG1 on the expression of behavioral phenotypes related to schizophrenia. NRG1 heterozygous (NRG1 HET) mutant breeding pairs were time-mated. Pregnant dams received a single injection (5mg/kg i.p.) of Poly I:C or vehicle on gestation day 9 (GD9). Offspring were then cross-fostered to vehicle-treated or Poly I:C-treated dams. Expression of schizophrenia-related behavioral endophenotypes was assessed at adolescence and in adulthood. Combining NRG1 disruption and prenatal environmental insult (Poly I:C) caused developmental stage-specific deficits in social behavior, spatial working memory and prepulse inhibition (PPI). However, combining Poly I:C and cross-fostering produced a number of behavioral deficits in the open field, social behavior and PPI. This became more complex by combining NRG1 deletion with both Poly I:C exposure and cross-fostering, which had a robust effect on PPI. These findings suggest that concepts of G × E interaction in risk of schizophrenia should be elaborated to multiple interactions that involve individual genes interacting with diverse biological and psychosocial environmental factors over early life, to differentially influence particular domains of psychopathology, sometimes over specific stages of development. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Current status of ITER I&C system as integration begins

Energy Technology Data Exchange (ETDEWEB)

Davis, William, E-mail: william.davis@iter.org [ITER Organisation, Route de Vinon-sur Verdon, CS 90 046, 13067 St. Paul Lez Durance Cedex (France); Wallander, Anders [ITER Organisation, Route de Vinon-sur Verdon, CS 90 046, 13067 St. Paul Lez Durance Cedex (France); Yonekawa, Izuru [Nippon Advanced Technology Ltd., 3129-45 Hibara Muramatsu, Tokai, Naka-gun, Ibaraki 319-1112 (Japan)

2016-11-15

Highlights: • The ITER I&C system is organisationally complicated and technically challenging. • Standard technologies for the ITER I&C systems have been selected. • Supply of non-standard technologies will cause serious issues. • Differing levels of design maturity of plant I&C systems is a serious challenge. • Systems are in the final stages of design and are being delivered to site. - Abstract: The ITER I&C system is organisationally complicated and technically challenging, and integrating its many sub-systems into a single coherent system is critical for the ITER project to meet its objectives. This paper explains the integration risks being faced now and anticipated in the near future. Standardisation initiatives by the ITER central team to mitigate these risks are described. The paper also presents the architecture of the ITER I&C system, the current status of design and manufacture key developments made in recent years, and the current and future activities of the central I&C teams. Finally, a short description is given of the plant I&C systems that will be delivered to ITER in the near future.

El contenido de los mensajes icónicos: El discurso icónico como totalidad (2)

OpenAIRE

Dr. Raymond Colle

1999-01-01

En el capítulo anterior, hemos hablado de los códigos icónicos de modo general, por cuanto tienen algunas características comunes, en particular el uso de figuras como factores de los significantes. Sin embargo, como lo hemos señalado al final, no todos se construyen ni articulan de la misma manera. Tal como las lenguas son muchas y los códigos lingüísticos se rigen por diferentes reglas -aunque sobre la base de fonemas unidos secuencialmente-, los códigos icónicos son también variados y regi...

CYLD Limits Lys63- and Met1-Linked Ubiquitin at Receptor Complexes to Regulate Innate Immune Signaling

Directory of Open Access Journals (Sweden)

Matous Hrdinka

2016-03-01

Full Text Available Innate immune signaling relies on the deposition of non-degradative polyubiquitin at receptor-signaling complexes, but how these ubiquitin modifications are regulated by deubiquitinases remains incompletely understood. Met1-linked ubiquitin (Met1-Ub is assembled by the linear ubiquitin assembly complex (LUBAC, and this is counteracted by the Met1-Ub-specific deubiquitinase OTULIN, which binds to the catalytic LUBAC subunit HOIP. In this study, we report that HOIP also interacts with the deubiquitinase CYLD but that CYLD does not regulate ubiquitination of LUBAC components. Instead, CYLD limits extension of Lys63-Ub and Met1-Ub conjugated to RIPK2 to restrict signaling and cytokine production. Accordingly, Met1-Ub and Lys63-Ub were individually required for productive NOD2 signaling. Our study thus suggests that LUBAC, through its associated deubiquitinases, coordinates the deposition of not only Met1-Ub but also Lys63-Ub to ensure an appropriate response to innate immune receptor activation.

PREFACE: 3rd International Conference on Mathematical Modeling in Physical Sciences (IC-MSQUARE 2014)

Science.gov (United States)

2015-01-01

The third International Conference on Mathematical Modeling in Physical Sciences (IC-MSQUARE) took place at Madrid, Spain, from Thursday 28 to Sunday 31 August 2014. The Conference was attended by more than 200 participants and hosted about 350 oral, poster, and virtual presentations. More than 600 pre-registered authors were also counted. The third IC-MSQUARE consisted of different and diverging workshops and thus covered various research fields where Mathematical Modeling is used, such as Theoretical/Mathematical Physics, Neutrino Physics, Non-Integrable Systems, Dynamical Systems, Computational Nanoscience, Biological Physics, Computational Biomechanics, Complex Networks, Stochastic Modeling, Fractional Statistics, DNA Dynamics, Macroeconomics etc. The scientific program was rather heavy since after the Keynote and Invited Talks in the morning, three parallel oral sessions and one poster session were running every day. However, according to all attendees, the program was excellent with high level of talks and the scientific environment was fruitful, thus all attendees had a creative time. We would like to thank the Keynote Speaker and the Invited Speakers for their significant contribution to IC-MSQUARE. We also would like to thank the Members of the International Advisory and Scientific Committees as well as the Members of the Organizing Committee.

Immunity by equilibrium.

Science.gov (United States)

Eberl, Gérard

2016-08-01

The classical model of immunity posits that the immune system reacts to pathogens and injury and restores homeostasis. Indeed, a century of research has uncovered the means and mechanisms by which the immune system recognizes danger and regulates its own activity. However, this classical model does not fully explain complex phenomena, such as tolerance, allergy, the increased prevalence of inflammatory pathologies in industrialized nations and immunity to multiple infections. In this Essay, I propose a model of immunity that is based on equilibrium, in which the healthy immune system is always active and in a state of dynamic equilibrium between antagonistic types of response. This equilibrium is regulated both by the internal milieu and by the microbial environment. As a result, alteration of the internal milieu or microbial environment leads to immune disequilibrium, which determines tolerance, protective immunity and inflammatory pathology.

5th International Conference on Mathematical Modeling in Physical Sciences (IC-MSquare 2016)

International Nuclear Information System (INIS)

Vagenas, Elias C.; Vlachos, Dimitrios S.

2016-01-01

The 5th International Conference on Mathematical Modeling in Physical Sciences (IC- MSQUARE) took place at Athens, Greece, from Monday, 23"t"h of May, to Thursday, 26"t"h of May 2016. The Conference was attended by more than 130 participants and hosted about 170 oral, poster, and virtual presentations while counted more than 500 pre-registered authors. The 5"t"h IC-MSQUARE consisted of different and diverging workshops and thus covered various research fields where Mathematical Modeling is used, such as Theoretical/Mathematical Physics, Neutrino Physics, Non-Integrable Systems, Dynamical Systems, Computational Nanoscience, Biological Physics, Computational Biomechanics, Complex Networks, Stochastic Modeling, Fractional Statistics, DNA Dynamics, Macroeconomics etc. The scientific program was rather heavy since after the Keynote and Invited Talks in the morning, three parallel oral and one poster session were running every day. However, according to all attendees, the program was excellent with high level talks and the scientific environment was fruitful, thus all attendees had a creative time. We would like to thank the Keynote Speaker and the Invited Speakers for their significant contribution to IC-MSQUARE. We also would like to thank the Members of the International Advisory and Scientific Committees as well as the Members of the Organizing Committee. (paper)

Immune Aspects of Female Infertility

Directory of Open Access Journals (Sweden)

Andrea Brazdova

2016-05-01

Full Text Available Immune infertility, in terms of reproductive failure, has become a serious health issue involving approximately 1 out of 5 couples at reproductive age. Semen that is defined as a complex fluid containing sperm, cellular vesicles and other cells and components, could sensitize the female genital tract. The immune rejection of male semen in the female reproductive tract is explained as the failure of natural tolerance leading to local and/or systemic immune response. Present active immune mechanism may induce high levels of anti-seminal/sperm antibodies. It has already been proven that iso-immunization is associated with infertility. Comprehensive studies with regards to the identification of antibody-targets and the determination of specific antibody class contribute to the development of effective immuno-therapy and, on the other hand, potential immuno-contraception, and then of course to complex patient diagnosis. This review summarizes the aspects of female immune infertility.

Making the MagIC (Magnetics Information Consortium) Web Application Accessible to New Users and Useful to Experts

Science.gov (United States)

Minnett, R.; Koppers, A.; Jarboe, N.; Tauxe, L.; Constable, C.; Jonestrask, L.

2017-12-01

Challenges are faced by both new and experienced users interested in contributing their data to community repositories, in data discovery, or engaged in potentially transformative science. The Magnetics Information Consortium (https://earthref.org/MagIC) has recently simplified its data model and developed a new containerized web application to reduce the friction in contributing, exploring, and combining valuable and complex datasets for the paleo-, geo-, and rock magnetic scientific community. The new data model more closely reflects the hierarchical workflow in paleomagnetic experiments to enable adequate annotation of scientific results and ensure reproducibility. The new open-source (https://github.com/earthref/MagIC) application includes an upload tool that is integrated with the data model to provide early data validation feedback and ease the friction of contributing and updating datasets. The search interface provides a powerful full text search of contributions indexed by ElasticSearch and a wide array of filters, including specific geographic and geological timescale filtering, to support both novice users exploring the database and experts interested in compiling new datasets with specific criteria across thousands of studies and millions of measurements. The datasets are not large, but they are complex, with many results from evolving experimental and analytical approaches. These data are also extremely valuable due to the cost in collecting or creating physical samples and the, often, destructive nature of the experiments. MagIC is heavily invested in encouraging young scientists as well as established labs to cultivate workflows that facilitate contributing their data in a consistent format. This eLightning presentation includes a live demonstration of the MagIC web application, developed as a configurable container hosting an isomorphic Meteor JavaScript application, MongoDB database, and ElasticSearch search engine. Visitors can explore the MagIC

Relationship between renal pathology and the size of circulating immune complexes in patients with systemic lupus erythematosus

International Nuclear Information System (INIS)

Wener, M.H.; Mannik, M.; Schwartz, M.M.; Lewis, E.J.

1987-01-01

Sera from 35 patients with biopsy-proven diffuse proliferative (WHO class IV) or membranous (WHO class V) lupus nephritis were analyzed for the presence and size of circulating immune complexes. Elevations of the C1q solid-phase assay (C1qSP) for immune complexes were found in sera from all patients with diffuse proliferative nephritis, with a mean +/- 1 SEM of 166.8 +/- 42.0 micrograms/AHG-equivalents/ml serum, and in 71.4% of the patients with membranous nephritis (83.1 +/- 26.7, p = 0.06). Using the WHO criteria for subclasses of membranous lupus nephritis, we also designated renal biopsies as nonproliferative (WHO classes Va and Vb) or proliferative (WHO classes IV and Vc). Employing the latter groupings, we observed significant differences between C1qSP results of patients with nonproliferative (30.3 +/- 8.8) and proliferative (172.8 +/- 36.8, p less than 0.001) lupus nephritis. These data suggest that the presence of C1q-binding material in serum is pathophysiologically related to proliferative glomerular lesions, and that levels of C1qSP binding reflect renal lesions in SLE patients. Sucrose density gradient ultracentrifugation was performed on each serum, and gradient fractions analyzed for C1qSP-binding and total IgG, using techniques to minimize losses of immune complexes. The predominant peak of C1qSP activity sedimented with the 6.6S monomeric IgG. The 6.6S C1q-binding IgG was increased only in 1 of 10 patients with membranous lupus nephritis without proliferative changes, and was elevated in 16 of 25 patients with proliferative lesions (WHO classes IV and Vc)

A prospective study of long-term results and the red blood cell immune adherence function following 131I treatment of Graves' disease

International Nuclear Information System (INIS)

Sun Zengjun; Ma Yuqin; Liu Junqing; Zhang Xia

2003-01-01

Objective: To observe the long-term curative effect and red blood cell immune function in patients with Graves' Disease (GD) after radioactive iodine ( 131 I) treatment. Methods: To observe the hyperthyroid symptoms, physical signs and to measure the concentration of FT3, FT4, FSH by radioimmunoassay, the percent of RBC-C 3b R-YR(%), RBC-IC-YR(%). Results: Patients with GD treated by 131 I after three month, these hyperthyroid symptoms, Physical signs are alleviated and even vanished in patients who were treated by 131 I after 1.5 years, RBC-C 3b R-YR(%) are normal in all patients, but RBC-IC-YR(%) are higher than before treatment with 131 I, then become lower after three months, treatment by 131 I but they were higher than those in normal group, when treated with 131 I after 1.5 years, RBC-IC-YR(%) are normal, the relationship between RBC-C 3b R-YR(%) and RBC-IC-YR(%) are positively interacted. Conclusion: The 131 I treatment produces a good rapid curative effect for GD patients, the disorder state of the red cell immune adherence system is rapidly corrected and this effect is unidirectional. So RBC-C 3b R-YR(%), RBC-IC-YR(%) are the useful predictors of GD remission and their relationship, RBC-IC-YR(%) are helpful in explaining the mechanism of radioactive iodine therapy and are the predictors of GD remission after 131 I treatment

Characterization of Peripheral Immune Cell Subsets in Patients with Acute and Chronic Cerebrovascular Disease: A Case-Control Study

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Peter Kraft

2015-10-01

Full Text Available Immune cells (IC play a crucial role in murine stroke pathophysiology. However, data are limited on the role of these cells in ischemic stroke in humans. We therefore aimed to characterize and compare peripheral IC subsets in patients with acute ischemic stroke/transient ischemic attack (AIS/TIA, chronic cerebrovascular disease (CCD and healthy volunteers (HV. We conducted a case-control study of patients with AIS/TIA (n = 116 or CCD (n = 117, and HV (n = 104 who were enrolled at the University Hospital Würzburg from 2010 to 2013. We determined the expression and quantity of IC subsets in the three study groups and performed correlation analyses with demographic and clinical parameters. The quantity of several IC subsets differed between the AIS/TIA, CCD, and HV groups. Several clinical and demographic variables independently predicted the quantity of IC subsets in patients with AIS/TIA. No significant changes in the quantity of IC subsets occurred within the first three days after AIS/TIA. Overall, these findings strengthen the evidence for a pathophysiologic role of IC in human ischemic stroke and the potential use of IC-based biomarkers for the prediction of stroke risk. A comprehensive description of IC kinetics is crucial to enable the design of targeted treatment strategies.

Chromatin Remodeling and Plant Immunity.

Science.gov (United States)

Chen, W; Zhu, Q; Liu, Y; Zhang, Q

Chromatin remodeling, an important facet of the regulation of gene expression in eukaryotes, is performed by two major types of multisubunit complexes, covalent histone- or DNA-modifying complexes, and ATP-dependent chromosome remodeling complexes. Snf2 family DNA-dependent ATPases constitute the catalytic subunits of ATP-dependent chromosome remodeling complexes, which accounts for energy supply during chromatin remodeling. Increasing evidence indicates a critical role of chromatin remodeling in the establishment of long-lasting, even transgenerational immune memory in plants, which is supported by the findings that DNA methylation, histone deacetylation, and histone methylation can prime the promoters of immune-related genes required for disease defense. So what are the links between Snf2-mediated ATP-dependent chromosome remodeling and plant immunity, and what mechanisms might support its involvement in disease resistance? © 2017 Elsevier Inc. All rights reserved.

Immune System and Disorders

Science.gov (United States)

Your immune system is a complex network of cells, tissues, and organs that work together to defend against germs. It ... t, to find and destroy them. If your immune system cannot do its job, the results can be ...

Alternative Immune Systems

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Luis Fernando Cadavid Gutierrez

2011-09-01

Full Text Available The immune system in animals is a complex network of molecules, cells and tissues that coordinately maintain the physiological and genetic integrity of the organism. Traditionally, two classes of immunity have been considered, the innate immunity and the adaptive immunity. The former is ancestral, with limited variability and low discrimination. The latter is highly variable, specific and limited to jawed vertebrates. Adaptive immunity is based on antigen receptors that rearrange somatically to generate a nearly unlimited diversity of molecules. Likely, this mechanism of somatic recombination arose as a consequence of a horizontal transfer of transposons and transposases from bacterial genomes in the ancestor of jawed vertebrates. The recent discovery in jawless vertebrates and invertebrates of alternative adaptive immune mechanisms, suggests during evolution different animal groups have found alternative solutions to the problem of immune recognition.

Interband cascade (IC) photovoltaic (PV) architecture for PV devices

Science.gov (United States)

Yang, Rui Q.; Tian, Zhaobing; Mishima, Tetsuya D.; Santos, Michael B.; Johnson, Matthew B.; Klem, John F.

2015-10-20

A photovoltaic (PV) device, comprising a PV interband cascade (IC) stage, wherein the IC PV stage comprises an absorption region with a band gap, the absorption region configured to absorb photons, an intraband transport region configured to act as a hole barrier, and an interband tunneling region configured to act as an electron barrier. An IC PV architecture for a photovoltaic device, the IC PV architecture comprising an absorption region, an intraband transport region coupled to the absorption region, and an interband tunneling region coupled to the intraband transport region and to the adjacent absorption region, wherein the absorption region, the intraband transport region, and the interband tunneling region are positioned such that electrons will flow from the absorption region to the intraband transport region to the interband tunneling region.

The Value of a Comparative Approach to Understand the Complex Interplay between Microbiota and Host Immunity

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Norma M. Morella

2017-09-01

Full Text Available The eukaryote immune system evolved and continues to evolve within a microbial world, and as such is critically shaped by—and in some cases even reliant upon—the presence of host-associated microbial species. There are clear examples of adaptations that allow the host to simultaneously tolerate and/or promote growth of symbiotic microbiota while protecting itself against pathogens, but the relationship between immunity and the microbiome reaches far beyond simple recognition and includes complex cross talk between host and microbe as well as direct microbiome-mediated protection against pathogens. Here, we present a broad but brief overview of how the microbiome is controlled by and interacts with diverse immune systems, with the goal of identifying questions that can be better addressed by taking a comparative approach across plants and animals and different types of immunity. As two key examples of such an approach, we focus on data examining the importance of early exposure on microbiome tolerance and immune system development and function, and the importance of transmission among hosts in shaping the potential coevolution between, and long-term stability of, host–microbiome associations. Then, by comparing existing evidence across short-lived plants, mouse model systems and humans, and insects, we highlight areas of microbiome research that are strong in some systems and absent in others with the hope of guiding future research that will allow for broad-scale comparisons moving forward. We argue that such an approach will not only help with identification of generalities in host–microbiome–immune interactions but also improve our understanding of the role of the microbiome in host health.

Considerations in applying on-line IC techniques to BWR's

International Nuclear Information System (INIS)

Kaleda, R.J.

1992-01-01

Ion-Chromatography (IC) has moved from its traditional role as a laboratory analytical tool to a real time, dynamic, on-line measurement device to follow ppb and sub-ppb concentrations of deleterious impurities in nuclear power plants. Electric Power Research Institute (EPRI), individual utilities, and industry all have played significant roles in effecting the transition. This paper highlights considerations and the evolution in current on-line Ion Chromatography systems. The first applications of on-line techniques were demonstrated by General Electric (GE) under EPRI sponsorship at Rancho Seco (1980), Calvert Cliffs, and McGuire nuclear units. The primary use was for diagnostic purposes. Today the on-line IC applications have been expanded to include process control and routine plant monitoring. Current on-line IC's are innovative in design, promote operational simplicity, are modular for simplified maintenance and repair, and use field-proven components which enhance reliability. Conductivity detection with electronic or chemical suppression and spectrometric detection techniques are intermixed in applications. Remote multi-point sample systems have addressed memory effects. Early applications measured ionic species in the part per billion range. Today reliable part per trillion measurements are common for on-line systems. Current systems are meeting the challenge of EPRI guideline requirements. Today's on-line IC's, with programmed sampling systems, monitor fluid streams throughout a power plant, supplying data that can be trended, stored and retrieved easily. The on-line IC has come of age. Many technical challenges were overcome to achieve today's IC

Polymer-free nanofibers from vanillin/cyclodextrin inclusion complexes: high thermal stability, enhanced solubility and antioxidant property.

Science.gov (United States)

Celebioglu, Asli; Kayaci-Senirmak, Fatma; İpek, Semran; Durgun, Engin; Uyar, Tamer

2016-07-13

Vanillin/cyclodextrin inclusion complex nanofibers (vanillin/CD-IC NFs) were successfully obtained from three modified CD types (HPβCD, HPγCD and MβCD) in three different solvent systems (water, DMF and DMAc) via an electrospinning technique without using a carrier polymeric matrix. Vanillin/CD-IC NFs with uniform and bead-free fiber morphology were successfully produced and their free-standing nanofibrous webs were obtained. The polymer-free CD/vanillin-IC-NFs allow us to accomplish a much higher vanillin loading (∼12%, w/w) when compared to electrospun polymeric nanofibers containing CD/vanillin-IC (∼5%, w/w). Vanillin has a volatile nature yet, after electrospinning, a significant amount of vanillin was preserved due to complex formation depending on the CD types. Maximum preservation of vanillin was observed for vanillin/MβCD-IC NFs which is up to ∼85% w/w, besides, a considerable amount of vanillin (∼75% w/w) was also preserved for vanillin/HPβCD-IC NFs and vanillin/HPγCD-IC NFs. Phase solubility studies suggested a 1 : 1 molar complexation tendency between guest vanillin and host CD molecules. Molecular modelling studies and experimental findings revealed that vanillin : CD complexation was strongest for MβCD when compared to HPβCD and HPγCD in vanillin/CD-IC NFs. For vanillin/CD-IC NFs, water solubility and the antioxidant property of vanillin was improved significantly owing to inclusion complexation. In brief, polymer-free vanillin/CD-IC NFs are capable of incorporating a much higher loading of vanillin and effectively preserve volatile vanillin. Hence, encapsulation of volatile active agents such as flavor, fragrance and essential oils in electrospun polymer-free CD-IC NFs may have potential for food related applications by integrating the particularly large surface area of NFs with the non-toxic nature of CD and inclusion complexation benefits, such as high temperature stability, improved water solubility and an enhanced

Preliminary I&C Design for LORELEI

International Nuclear Information System (INIS)

Korotkin, S.; Kaufman, Y.; Guttmann, E. B.; Levy, S.; Amidan, D.; Gdalyho, B.; Cahana, T.; Ellenbogen, A.; Arad, M.; Weiss, Y.; Sasson, A.; Ferry, L.; Bourrelly, F.; Cohen, Y.

2014-01-01

This document summarizes the preliminary I&C design for LORELEI experiment The preliminary design deals with considerations regarding appropriate safety and service instrumentation. The determined closed loop control rules for temperature and position will be implemented in the detailed design. The Computer Aided Operator Decisions System (CAODS) will be used for prediction of hot spot temperature and thickness of oxidation layer using Baker-Just correlation. The proposed hybrid simulation system comprising of both virtual and real hardware will be in-cooperated for LORELEI verification. It will perform both integration cold tests for a partial hardware loop and virtual tests for the final I&C design

Adopting De Novo Programming Approach on IC Design Service Firms Resources Integration

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James K. C. Chen

2014-01-01

Full Text Available The semiconductor industry has very important position in computer industry, ICT field, and new electronic technology developing. The IC design service is one of key factor of semiconductor industry development. There are more than 365 IC design service firms have been established around Hsinchu Science Park in Taiwan. Building an efficient planning model for IC design service firm resources integrating is very interest issue. This study aims to construct a planning model for IC design service firm implementation resources integration. This study uses the De Novo programming as an approach of criteria alternative to achieve optimal resource allocation on IC design firm. Results show the IC design service firm should conduct open innovation concept and utilizes design outsourcing obtains cost down and enhance IC design service business performance. This plan model of De Novo programming is not only for IC design service firm and also can apply to the other industrial implementation strategic alliance/integrating resource. This plan model is a universal model for the others industries field.

PREFACE: 4th International Conference on Mathematical Modeling in Physical Sciences (IC-MSquare2015)

Science.gov (United States)

Vlachos, Dimitrios; Vagenas, Elias C.

2015-09-01

The 4th International Conference on Mathematical Modeling in Physical Sciences (IC-MSQUARE) took place in Mykonos, Greece, from Friday 5th June to Monday 8th June 2015. The Conference was attended by more than 150 participants and hosted about 200 oral, poster, and virtual presentations. There were more than 600 pre-registered authors. The 4th IC-MSQUARE consisted of different and diverging workshops and thus covered various research fields where Mathematical Modeling is used, such as Theoretical/Mathematical Physics, Neutrino Physics, Non-Integrable Systems, Dynamical Systems, Computational Nanoscience, Biological Physics, Computational Biomechanics, Complex Networks, Stochastic Modeling, Fractional Statistics, DNA Dynamics, Macroeconomics etc. The scientific program was rather intense as after the Keynote and Invited Talks in the morning, three parallel oral and one poster session were running every day. However, according to all attendees, the program was excellent with a high quality of talks creating an innovative and productive scientific environment for all attendees. We would like to thank the Keynote Speaker and the Invited Speakers for their significant contribution to IC-MSQUARE. We also would like to thank the Members of the International Advisory and Scientific Committees as well as the Members of the Organizing Committee.

Electrospinning of functional poly(methyl methacrylate) nanofibers containing cyclodextrin-menthol inclusion complexes

Energy Technology Data Exchange (ETDEWEB)

Uyar, Tamer; Besenbacher, Flemming [Interdisciplinary Nanoscience Center (iNANO), Aarhus University, DK-8000, Aarhus C (Denmark); Nur, Yusuf; Hacaloglu, Jale [Department of Chemistry, Middle East Technical University, Ankara, 06530 (Turkey)], E-mail: tamer@inano.dk, E-mail: tamer@unam.bilkent.edu.tr

2009-03-25

Electrospinning of nanofibers with cyclodextrin inclusion complexes (CD-ICs) is particularly attractive since distinct properties can be obtained by combining the nanofibers with specific functions of the CD-ICs. Here we report on the electrospinning of poly(methyl methacrylate) (PMMA) nanofibers containing cyclodextrin-menthol inclusion complexes (CD-menthol-ICs). These CD-menthol-IC functionalized nanofibers were developed with the purpose of producing functional nanofibers that contain fragrances/flavors with high temperature stability, and menthol was used as a model fragrance/flavor material. The PMMA nanofibers were electrospun with CD-menthol-ICs using three type of CD: {alpha}-CD, {beta}-CD, and {gamma}-CD. Direct pyrolysis mass spectrometry (DP-MS) studies showed that the thermal evaporation of menthol occurred over a very high and a broad temperature range (100-355 deg. C) for PMMA/CDmenthol-IC nanowebs, demonstrating the complexation of menthol with the CD cavity and its high temperature stability. Furthermore, as the size of CD cavity increased in the order {alpha}-CD<{beta}-CD<{gamma}-CD, the thermal evolution of menthol shifted to higher temperatures, suggesting that the strength of interaction between menthol and the CD cavity is in the order {gamma}-CD>{beta}-CD>{alpha}-CD.

Motor SUS i životna sredina / IC engine and environment

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Zoran Građin

2002-03-01

Full Text Available Ekološki pokreti u svetu su sve aktivniji, zbog stvarne ugroženosti Zemlje Mnogobrojni su oblici i izvori zagađenja, a jedan od najvećih su motori sa unutrašnjim sagorevanjem, za koje se pretpostavlja da će još dugo dominirati kao pogonski agregati u mnogim oblastima primene. U vezi s tim moguće je delovati u dva smera: zamenom konvencionalnih goriva alternativnim i konstrukcionim izmenama na motorima radi smanjenja emisije i potrošnje goriva. Jedna od mogućnosti konstrukcionog poboljšanja motora je i smanjenje mehaničkih gubitaka, koji kod današnjih konstrukcija još uvek imaju znatan udeo u gubicima, pogotovo na parcijalnim režimima. Treba naglasiti da kompleksni problemi smanjenja potrošnje goriva i emisije izduvnih gasova motora (vozila mogu da se reše samo spregom razvoja automobilske i naftne industrije. / Ecological trends and movements in the modern world grow stronger and more active, due to a real danger of Earth pollution. One of the main sources of pollution are IC engines and their influence on environment is significant. However, conventional combustion engines still are and will be dominant powering systems for numerous future applications. Two solutions are possible answers to this problem: first, the replacement of conventional fuels by alternative ones and second, modifications on the IC engine design in order to decrease fuel emission and consumption. One of the solutions for the improvement of IC engine design is the modification of engine parts or their design, with great influence on the decrease of mechanical losses, especially on partial rating. Therefore, it is important to say that complex problems of engine (automotive decrease of fuel consumption and exhaust gas emission can be solved only by simultaneous development of oil and engine (automotive industry.

INTEGRATED QUANTITATIVE ASSESSMENT OF CHANGES IN NEURO-ENDOCRINE-IMMUNE COMPLEX AND METABOLISM IN RATS EXPOSED TO ACUTE COLD-IMMOBILIZATION STRESS

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Sydoruk O Sydoruk

2016-09-01

    Abstracts Background. It is known that the reaction of the neuroendocrine-immune complex to acute and chronic stress are different. It is also known about sex differences in stress reactions. Previously we have been carry out integrated quantitative estimation of neuroendocrine and immune responses to chronic restraint stress at male rats. The purpose of this study - to carry out integrated quantitative estimation of neuroendocrine, immune and metabolic responses to acute stress at male and female rats. Material and research methods. The experiment is at 58 (28 male and 30 female white rats Wistar line weighing 170-280 g (Mean=220 g; SD=28 g. The day after acute (water immersion restraint stress determined HRV, endocrine, immune and metabolic parameters as well as gastric mucosa injuries and comparing them with parameters of intact animals. Results. Acute cold-immobilization stress caused moderate injuries the stomach mucosa as erosions and ulcers. Among the metabolic parameters revealed increased activity Acid Phosphatase, Asparagine and Alanine Aminotranspherase as well as Creatinephosphokinase. It was also found to reduce plasma Testosterone as well as serum Potassium and Phosphate probably due to increased Parathyrine and Mineralocorticoid activity and Sympathotonic shift of sympatho-vagal balance. Integrated quantitative measure manifestations of Acute Stress as mean of modules of Z-Scores makes for 10 metabolic parameters 0,75±0,10 σ and for 8 neuro-endocrine parameters 0,40±0,07 σ. Among immune parameters some proved resistant to acute stress factors, while 10 significant suppressed and 12 activated. Integrated quantitative measure poststressory changes makes 0,73±0,08 σ. Found significant differences integrated status intact males and females, whereas after stress differences are insignificant. Conclusion. The approach to integrated quantitative assessment of neuroendocrine-immune complex and metabolism may be useful for testing the

Fundamental roles of the innate-like repertoire of natural antibodies in immune homeostasis

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Jaya eVas

2013-02-01

Full Text Available The composition of the early immune repertoire is biased with prominent expression of spontaneously arising B-cell clones that produce IgM with recurrent and often autoreactive binding specificities. Amongst these naturally-arising antibodies (NAbs are IgM antibodies that specifically recognize damaged and senescent cells, often via oxidation-associated neo-determinants. These NAbs are present from birth and can be further boosted by apoptotic cell challenge. Recent studies have shown that IgM NAb to apoptotic cells can enhance phagocytic clearance, as well as suppress pro-inflammatory responses induced via Toll-like receptors, and block pathogenic IgG-immune complex (IC-mediated inflammatory responses. Specific antibody effector functions appear to be involved, as these anti-inflammatory properties are dependent on IgM-mediated recruitment of the early recognition factors of complement. Clinical surveys have suggested that anti-AC IgM NAbs may modulate disease activity in some patients with autoimmune disease. In mechanistic studies, anti-AC NAbs were shown to act in dendritic cells by inhibition of the Mitogen Activated Protein Kinase (MAPK pathway, a primary signal transduction pathway that controls inflammatory responses. This immunomodulatory pathway has an absolute requirement for the induction of MAPK Phosphatase-1. Taken together, recent studies have elucidated the novel properties of a class of protective NAbs, which may directly blunt inflammatory responses through a primitive pathway for regulation of the innate immune system.

Background Complex angiographic lesions and clinic presentation in unstable angina. A prospective study

International Nuclear Information System (INIS)

LLuberas, R.; Mallo, D.; Pouso, J.; Artucio, C.; Korytnicki; Argon, L.; Besada, E.; Tavella, N.

2002-01-01

Background Complex angiography lesions and intracoronary thrombus have been identified in unstable angina.Braunwalds categorization has been accepted in the last years.Identifying severe clinical classes class III (angina at rest during the last 48 hours), class C (angina postinfarction) and class c (angina with maximum therapeutic). The main objective of this study was to determine independent associations of Braunwalds classes III, C and c: complex lesions, intracoronary thrombus, total occlusion and distal flux TIMI<3 of the responsible vessel. The secondary objectives were to analyze the angiographic features of the lesion and the responsible vessel. Aprospective study of 300 patients with diagnosed unstable angina, clustered according to Braunwalds clinis classification was done. The angiographic evaluation was performed identifying the responsible lesion and the presence of the complex lesion, intracoronary thrombus, total occlusion and distal flux TIMI<3 of the responsible vessel. A univariate analysis and a multivariate model of binary logistic regression were used. In the 300 patient population, 22 patients with normal coronaries(7.3%) were identified. The responsible lesion was identified in 243 out of the remaining 278 patients (87,4%). Class III was significantly associated with the complex lesion (OR=2.74, IC95%=1,27-5,9) and intracoronary thrombus (OR=2,82 IC95=1,2-6,6). Class C was significantly associated with intracoronary thrombus (OR=3.9),IC95%=1.53-10,0).Class III was and independent predictor for the presence of the complex lesion(OR=1.98, IC 95%=1,01-3,87) and intracoronary thrombus (OR=2,47 IC95%=1,14-5,37). Class C was and independent predictor for the complex lesion (OR=5,05,IC95%=2.25-11,3), infracoronary thrombus (OR=8,04, IC 95%=3,49-18,0), total occlusion (OR=6,49, IC95%=2,67-15,7) and distal flux TIMI<3(OR=3,96,IC 95%=1,87-8,4) There was no significant association between classes III, C and c and the responsible vessel, localization of

Development of an FPGA-Based Motion Control IC for Caving Machine

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Chiu-Keng Lai

2014-03-01

Full Text Available Since the Field Programmable Gate Arrays (FPGAs with high density are available nowadays, systems with complex functions can thus be realized by FPGA in a single chip while they are traditionally implemented by several individual chips. In this research, the control of stepping motor drives as well as motion controller is integrated and implemented on Altera Cyclone III FPGA; the resulting system is evaluated by applying it to a 3-axis caving machine which is driven by stepping motors. Finally, the experimental results of current regulation and motion control integrated in FPGA IC are shown to prove the validness.

PENGARUH IC TERHADAP KINERJA KEUANGAN PERUSAHAAN PERBANKAN PERIODE 2005-2007

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Subkhan -

2012-03-01

Full Text Available Tujuan dari penelitian ini adalah untuk meneliti pengaruh intellectual capital (IC perusahaan pada kinerja keuangan mereka. Penelitian ini menggunakan Public Framework dan data dari 57 sektor perbankan Indonesia yang tercatat antara tahun 2005 dan 2007 pada Indonesian Stock Exchange. Penelitian ini menggunakan partial least square (PLS untuk menganalisis data. 3 elemen IC dan kinerja perusahaan dites dalam penelitian ini. Hasilnya memperlihatkan bahwa IC dan kinerja keuangan mempunyai pengaruh yang signifikan, VACA mempunyai pengaruh yang signifikan terhadap kinerja keuangan, VAHU mempuyai pengaruh yang signifikan  terhadap kinerja keuangan, dan STVA mempunyai pengaruh yang signifikan terhadap kinerja keuangan. Abstract The objective of this study is to investigate the influence of firm’s intellectual capital (IC on their financial performance. This paper uses Public Framework and data from 57 Indonesian banking sectors listed between 2005 and 2007 on the Indonesian Stock Exchange. This study uses partial least square (PLS for data analysis. Three elements of IC and company performances are tested by this study. The results show that IC and financial performance have significant influence, VACA has significant influence to financial performance, VAHU has significant influence to financial performance, and STVA has significant influence to financial performance.Keywords: intellectual capital; financial performance

Increase in complement iC3b is associated with anti-inflammatory cytokine expression during late pregnancy in mice.

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Keigo Nakamura

Full Text Available Immunological tolerance between fetal allograft and mother is crucial for pregnancy establishment and maintenance; however, these mechanisms particularly those during the latter part of pregnancy have not been definitively elucidated. The aim of this study was to examine the presence and potential function of innate immunity characteristic to the middle to late pregnancy. We first characterized up-regulated proteins in decidua from day 11 pregnant (P11 mice using 2D-PAGE, followed by MALDI-TOF/MS analysis. These analyses identified increased complement component 3 (C3 and its derivatives in P11 decidua. We then found that in the decidual tissues, C3 mRNA increased on P15 and remained high on P19. C3 is converted to C3b and then iC3b by complement component factor I (Cfi and complement receptor 1-like protein (Crry, both of which were present in P19 placentas. In addition, iC3b proteins and its receptor CR3 (Cd11b/Cd18 in decidual and placental tissues increased toward the latter phase of pregnancy. Moreover, CR3 subunit CD11b protein was predominantly localized to spongiotrophoblast layer in the P19 placenta. Because iC3b is known to induce anti-inflammatory cytokine production, the analysis was extended to examine changes in pro- and anti-inflammatory cytokines, Il12, Il10, and Tgfb1. Il12 expression decreased in P15 and P19 placenta, while high mRNA expression of Il10 and Tgfb1 was found in P19 placental tissues. Furthermore, placental Il10 and Tgfb1 mRNAs were down-regulated when pregnant mice were treated with an anti-C3 antibody, detecting C3, C3b and iC3b. These results indicated that C3 derivatives, in particular, iC3b and its receptor CR3 were up-regulated at the fetal-maternal interface, and suggest that iC3b may regulate the placental expression of anti-inflammatory cytokines, IL10 and TGFB1, during the latter phase of pregnancy.

Allergen-containing immune complexes used for immunotherapy of allergic asthma. II. IgE and IgG immune response during and after hyposensitization of sensitized guinea pigs

DEFF Research Database (Denmark)

Poulsen, L K; Lundberg, L; Søndergaard, I

1991-01-01

In a previous study guinea pigs inbred for their ability to develop respiratory anaphylaxis to experimental antigens have been used for comparison of different forms of immunotherapy (IT). Passive, active and combined (immune complexes prepared from antigen and specific IgG) IT was compared...... response and clinical symptoms. Thus, the strong IgG response during immunotherapy may not be causally related to the outcome of treatment....

ICS logging solution for network-based attacks using Gumistix technology

Science.gov (United States)

Otis, Jeremy R.; Berman, Dustin; Butts, Jonathan; Lopez, Juan

2013-05-01

Industrial Control Systems (ICS) monitor and control operations associated with the national critical infrastructure (e.g., electric power grid, oil and gas pipelines and water treatment facilities). These systems rely on technologies and architectures that were designed for system reliability and availability. Security associated with ICS was never an inherent concern, primarily due to the protections afforded by network isolation. However, a trend in ICS operations is to migrate to commercial networks via TCP/IP in order to leverage commodity benefits and cost savings. As a result, system vulnerabilities are now exposed to the online community. Indeed, recent research has demonstrated that many exposed ICS devices are being discovered using readily available applications (e.g., ShodanHQ search engine and Google-esque queries). Due to the lack of security and logging capabilities for ICS, most knowledge about attacks are derived from real world incidents after an attack has already been carried out and the damage has been done. This research provides a method for introducing sensors into the ICS environment that collect information about network-based attacks. The sensors are developed using an inexpensive Gumstix platform that can be deployed and incorporated with production systems. Data obtained from the sensors provide insight into attack tactics (e.g., port scans, Nessus scans, Metasploit modules, and zero-day exploits) and characteristics (e.g., attack origin, frequency, and level of persistence). Findings enable security professionals to draw an accurate, real-time awareness of the threats against ICS devices and help shift the security posture from reactionary to preventative.

PELE-IC test problems

International Nuclear Information System (INIS)

Gong, E.Y.; Alexander, E.E.; McMaster, W.H.; Quinones, D.F.

1979-01-01

This report provides prospective users of the Lawrence Livermore Laboratory (LLL) fluid-structure interaction computer code, PELE-IC, a variety of test problems for verifying the code on CDC 7600 computer systems at facilities external to the LLL environment. The test problems have been successfully run on CDC 7600 computers at the LLL and Lawrence Berkeley Laboratory (LBL) computer centers

Non-clinical efficacy and safety of HyVac4:IC31 vaccine administered in a BCG prime-boost regimen.

Science.gov (United States)

Skeiky, Yasir A W; Dietrich, Jes; Lasco, Todd M; Stagliano, Katherine; Dheenadhayalan, Veerabadran; Goetz, Margaret Ann; Cantarero, Luis; Basaraba, Randall J; Bang, Peter; Kromann, Ingrid; McMclain, J Bruce; Sadoff, Jerald C; Andersen, Peter

2010-01-22

Despite the extensive success with the introduction of M. bovis Bacille Calmette-Guérin (BCG), tuberculosis (TB) remains a major global epidemic infecting between 8 and 9 million people annually with an estimated 1.7 million deaths each year. However, because of its demonstrated effectiveness against some of the most severe forms of childhood TB, it is now realized that BCG vaccination of newborns is unlikely to be replaced. Therefore, BCG or an improved BCG will continue to be used as a prime TB vaccine and there is a need to develop effective boost vaccines that would enhance and prolong the protective immunity induced by BCG prime immunization. We report on a heterologous booster approach using two highly immunogenic TB antigens comprising Ag85B and TB10.4 (HyVac4) delivered as a fusion molecule and formulated in the proprietary adjuvant IC31. This vaccine was found to be immunogenic and demonstrated greater protection in the more stringent guinea pig model of pulmonary tuberculosis than BCG alone when used in a prime/boost regimen. Significant difference in lung involvement was observed for all animals in the HyVac4 boosted group compared to BCG alone regardless of time to death or sacrifice. A vaccine toxicology study of the HyVac4:IC31 regimen was performed and it was judged safe to advance the vaccine into clinical trials. Therefore, all non-clinical data supports the suitability of HyVac4 as a safe, immunogenic, and effective vaccination in a prime-boost regimen with BCG.

DEMONSTRATION OF ELECTROCHEMICAL REMEDIATION TECHNOLOGIES-INDUCED COMPLEXATION

Energy Technology Data Exchange (ETDEWEB)

Barry L. Burks

2002-12-01

The Project Team is submitting this Topical Report on the results of its bench-scale demonstration of ElectroChemical Remediation Technologies (ECRTs) and in particular the Induced Complexation (ECRTs-IC) process for remediation of mercury contaminated soils at DOE Complex sites. ECRTs is an innovative, in-situ, geophysically based soil remediation technology with over 50 successful commercial site applications involving remediation of over two million metric tons of contaminated soils. ECRTs-IC has been successfully used to remediate 220 cu m of mercury-contaminated sediments in the Union Canal, Scotland. In that operation, ECRTs-IC reduced sediment total mercury levels from an average of 243 mg/kg to 6 mg/kg in 26 days of operation. The clean up objective was to achieve an average total mercury level in the sediment of 20 mg/kg.

Development of grouped icEEG for the study of cognitive processing

Directory of Open Access Journals (Sweden)

Cihan Mehmet Kadipasaoglu

2015-07-01

Full Text Available Invasive intracranial EEG (icEEG offers a unique opportunity to study human cognitive networks at an unmatched spatiotemporal resolution. To date, the contributions of icEEG have been limited to the individual-level analyses or cohorts whose data are not integrated in any way. Here we discuss how grouped approaches to icEEG overcome challenges related to sparse-sampling, correct for individual variations in response and provide statistically valid models of brain activity in a population. By the generation of whole-brain activity maps, grouped icEEG enables the study of intra and interregional dynamics between distributed cortical substrates exhibiting task-dependent activity. In this fashion, grouped icEEG analyses can provide significant advances in understanding the mechanisms by which cortical networks give rise to cognitive functions.

Using network properties to evaluate targeted immunization algorithms

Directory of Open Access Journals (Sweden)

Bita Shams

2014-09-01

Full Text Available Immunization of complex network with minimal or limited budget is a challenging issue for research community. In spite of much literature in network immunization, no comprehensive research has been conducted for evaluation and comparison of immunization algorithms. In this paper, we propose an evaluation framework for immunization algorithms regarding available amount of vaccination resources, goal of immunization program, and time complexity. The evaluation framework is designed based on network topological metrics which is extensible to all epidemic spreading model. Exploiting evaluation framework on well-known targeted immunization algorithms shows that in general, immunization based on PageRank centrality outperforms other targeting strategies in various types of networks, whereas, closeness and eigenvector centrality exhibit the worst case performance.

Novel vaccination approach for dengue infection based on recombinant immune complex universal platform.

Science.gov (United States)

Kim, Mi-Young; Reljic, Rajko; Kilbourne, Jacquelyn; Ceballos-Olvera, Ivonne; Yang, Moon-Sik; Reyes-del Valle, Jorge; Mason, Hugh S

2015-04-08

Dengue infection is on the rise in many endemic areas of the tropics. Vaccination remains the most realistic strategy for prevention of this potentially fatal viral disease but there is currently no effective vaccine that could protect against all four known serotypes of the dengue virus. This study describes the generation and testing of a novel vaccination approach against dengue based on recombinant immune complexes (RIC). We modelled the dengue RIC on the existing Ebola RIC (Phoolcharoen, et al. Proc Natl Acad Sci USA 2011;108(Dec (51)):20695) but with a key modification that allowed formation of a universal RIC platform that can be easily adapted for use for other pathogens. This was achieved by retaining only the binding epitope of the 6D8 ant-Ebola mAb, which was then fused to the consensus dengue E3 domain (cEDIII), resulting in a hybrid dengue-Ebola RIC (DERIC). We expressed human and mouse versions of these molecules in tobacco plants using a geminivirus-based expression system. Following purification from the plant extracts by protein G affinity chromatography, DERIC bound to C1q component of complement, thus confirming functionality. Importantly, following immunization of mice, DERIC induced a potent, virus-neutralizing anti-cEDIII humoral immune response without exogenous adjuvants. We conclude that these self-adjuvanting immunogens have the potential to be developed as a novel vaccine candidate for dengue infection, and provide the basis for a universal RIC platform for use with other antigens. Copyright © 2015 Elsevier Ltd. All rights reserved.

Extreme low-power mixed signal IC design

CERN Document Server

Tajalli, Armin

2010-01-01

This book describes a completely novel class of techniques for designing ultra-low-power integrated circuits (ICs). In many applications such as battery operated systems and battery-less (energy-scavenging) systems, power dissipation is a critical parameter. As a result, there is a growing demand for reducing the power (energy) consumption in ICs to extremely low levels, not achievable by using classical ""subthreshold CMOS"" techniques. This book introduces a new family of ""subthreshold circuits"" called ""source-coupled circuits"". This family of circuits can be used for implementing digita

Design Developing of IC- Model Using VHDL

International Nuclear Information System (INIS)

Inzar-Anas

2005-01-01

In present, the electronic design required to become simple, small and flexible. The physical dimension of IC and number of pin can be significantly reduced while the flexibility and compatibility of IC was not change. Implementation of VHDL(VHSIC Hardware Description Language) seem as a great progress in the design of digital circuit. By using this language designing of model can be more simple, flexible and efficient. This paper was purposed to introduce VHDL and its features. Sample in modeling to illustrate the advantage of VHDL will also be described. (author)

Sensitivity Study on Availability of I&C Components Using Bayesian Network

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Rahman Khalil Ur

2013-01-01

Full Text Available The objective of this study is to find out the impact of instrumentation and control (I&C components on the availability of I&C systems in terms of sensitivity analysis using Bayesian network. The analysis has been performed on I&C architecture of reactor protection system. The analysis results would be applied to develop I&C architecture which will meet the desire reliability features and save cost. RPS architecture unavailability P(x=0 and availability P(x=1 were estimated to 6.1276E-05 and 9.9994E-01 for failure (0 and perfect (1 states, respectively. The impact of I&C components on overall system risk has been studied in terms of risk achievement worth (RAW and risk reduction worth (RRW. It is found that circuit breaker failure (TCB, bi-stable processor (BP, sensor transmitter (TR, and pressure transmitter (PT have high impact on risk. The study concludes and recommends that circuit breaker bi-stable processor should be given more consideration while designing I&C architecture.

Structure of insoluble immune complexes as studied by spectroturbidimetry and dynamic light scattering

Science.gov (United States)

Khlebtsov, Boris N.; Burygin, Gennadii L.; Matora, Larisa Y.; Shchyogolev, Sergei Y.; Khlebtsov, Nikolai G.

2004-07-01

We describe two variants of a method for determining the average composition of insoluble immune complex particles (IICP). The first variant is based on measuring the specific turbidity (the turbidity per unit mass concentration of the dispersed substance) and the average size of IICP determined from dynamic light scattering (DLS). In the second variant, the wavelength exponent (i.e., the slope of the logarithmic turbidity spectrum) is used in combination with specific turbidity measurements. Both variants allow the average biopolymer volume fraction to be determined in terms of the average refractive index of IICP. The method is exemplified by two experimental antigen+antibody systems: (i) lipopolysaccharide-protein complex (LPPC) of Azospirillum brasilense Sp245+rabbit anti-LPPC; and (ii) human IgG (hIgG)+sheep anti-hIgG. Our measurements by the two methods for both types of systems gave, on the average, the same result: the volume fraction of the IICP biopolymers is about 30%; accordingly, the volume fraction of buffer solvent is 70%.

Development of brain injury criteria (BrIC).

Science.gov (United States)

Takhounts, Erik G; Craig, Matthew J; Moorhouse, Kevin; McFadden, Joe; Hasija, Vikas

2013-11-01

Rotational motion of the head as a mechanism for brain injury was proposed back in the 1940s. Since then a multitude of research studies by various institutions were conducted to confirm/reject this hypothesis. Most of the studies were conducted on animals and concluded that rotational kinematics experienced by the animal's head may cause axonal deformations large enough to induce their functional deficit. Other studies utilized physical and mathematical models of human and animal heads to derive brain injury criteria based on deformation/pressure histories computed from their models. This study differs from the previous research in the following ways: first, it uses two different detailed mathematical models of human head (SIMon and GHBMC), each validated against various human brain response datasets; then establishes physical (strain and stress based) injury criteria for various types of brain injury based on scaled animal injury data; and finally, uses Anthropomorphic Test Devices (ATDs) (Hybrid III 50th Male, Hybrid III 5th Female, THOR 50th Male, ES-2re, SID-IIs, WorldSID 50th Male, and WorldSID 5th Female) test data (NCAP, pendulum, and frontal offset tests) to establish a kinematically based brain injury criterion (BrIC) for all ATDs. Similar procedures were applied to college football data where thousands of head impacts were recorded using a six degrees of freedom (6 DOF) instrumented helmet system. Since animal injury data used in derivation of BrIC were predominantly for diffuse axonal injury (DAI) type, which is currently an AIS 4+ injury, cumulative strain damage measure (CSDM) and maximum principal strain (MPS) were used to derive risk curves for AIS 4+ anatomic brain injuries. The AIS 1+, 2+, 3+, and 5+ risk curves for CSDM and MPS were then computed using the ratios between corresponding risk curves for head injury criterion (HIC) at a 50% risk. The risk curves for BrIC were then obtained from CSDM and MPS risk curves using the linear relationship

Prion seeding activities of mouse scrapie strains with divergent PrPSc protease sensitivities and amyloid plaque content using RT-QuIC and eQuIC.

Directory of Open Access Journals (Sweden)

Sarah Vascellari

Full Text Available Different transmissible spongiform encephalopathy (TSE-associated forms of prion protein (e.g. PrP(Sc can vary markedly in ultrastructure and biochemical characteristics, but each is propagated in the host. PrP(Sc propagation involves conversion from its normal isoform, PrP(C, by a seeded or templated polymerization mechanism. Such a mechanism is also the basis of the RT-QuIC and eQuIC prion assays which use recombinant PrP (rPrP(Sen as a substrate. These ultrasensitive detection assays have been developed for TSE prions of several host species and sample tissues, but not for murine models which are central to TSE pathogenesis research. Here we have adapted RT-QuIC and eQuIC to various murine prions and evaluated how seeding activity depends on glycophosphatidylinositol (GPI anchoring and the abundance of amyloid plaques and protease-resistant PrP(Sc (PrP(Res. Scrapie brain dilutions up to 10(-8 and 10(-13 were detected by RT-QuIC and eQuIC, respectively. Comparisons of scrapie-affected wild-type mice and transgenic mice expressing GPI anchorless PrP showed that, although similar concentrations of seeding activity accumulated in brain, the heavily amyloid-laden anchorless mouse tissue seeded more rapid reactions. Next we compared seeding activities in the brains of mice with similar infectivity titers, but widely divergent PrP(Res levels. For this purpose we compared the 263K and 139A scrapie strains in transgenic mice expressing P101L PrP(C. Although the brains of 263K-affected mice had little immunoblot-detectable PrP(Res, RT-QuIC indicated that seeding activity was comparable to that associated with a high-PrP(Res strain, 139A. Thus, in this comparison, RT-QuIC seeding activity correlated more closely with infectivity than with PrP(Res levels. We also found that eQuIC, which incorporates a PrP(Sc immunoprecipitation step, detected seeding activity in plasma from wild-type and anchorless PrP transgenic mice inoculated with 22L, 79A and/or RML

Immune chromatography: a quantitative radioimmunological assay

International Nuclear Information System (INIS)

Davis, J.W.; Demetriades, M.; Bowen, J.M.

1984-01-01

Immune chromatography, a radioimmunological binding assay, employs paper chromatography to separate immune complexes from free antigen and antibodies. During chromatography free antigen and antibodies become distributed throughout the paper, while immune complexes remain near the bottoms of the strips. The chromatographic differences can be made quantitative by using either iodinated antigens or antibodies. Under these conditions nanogram quantities of antigen can be detected or antibodies in sera diluted several 1000-fold. The immune chromatography assay can also be performed as an indirect assay, since the paper strips are cut from nitrocellulose paper. In this case the immune components are absorbed by the paper during chromatography. Antigen is then detected with an iodinated second antibody. The indirect immune chromatography assay is particularly useful for identifying different sera that react with the same antigen. Reaction with the first serum before chromatography reduces the amount of antigen available to the second serum following chromatography. In addition to characterizing the immune chromatography procedure, we discuss the possible applications of chromatography assays for the quantitation of other types of molecular binding interactions. (Auth.)

Membrane attack complex of complement is not essential for immune mediated demyelination in experimental autoimmune neuritis.

Science.gov (United States)

Tran, Giang T; Hodgkinson, Suzanne J; Carter, Nicole M; Killingsworth, Murray; Nomura, Masaru; Verma, Nirupama D; Plain, Karren M; Boyd, Rochelle; Hall, Bruce M

2010-12-15

Antibody deposition and complement activation, especially membrane attack complex (MAC) formation are considered central for immune mediated demyelination. To examine the role of MAC in immune mediated demyelination, we studied experimental allergic neuritis (EAN) in Lewis rats deficient in complement component 6 (C6) that cannot form MAC. A C6 deficient Lewis (Lewis/C6-) strain of rats was bred by backcrossing the defective C6 gene, from PVG/C6- rats, onto the Lewis background. Lewis/C6- rats had the same C6 gene deletion as PVG/C6- rats and their sera did not support immune mediated haemolysis unless C6 was added. Active EAN was induced in Lewis and Lewis/C6- rats by immunization with bovine peripheral nerve myelin in complete Freund's adjuvant (CFA), and Lewis/C6- rats had delayed clinical EAN compared to the Lewis rats. Peripheral nerve demyelination in Lewis/C6- was also delayed but was similar in extent at the peak of disease. Compared to Lewis, Lewis/C6- nerves had no MAC deposition, reduced macrophage infiltrate and IL-17A, but similar T cell infiltrate and Th1 cytokine mRNA expression. ICAM-1 and P-selectin mRNA expression and immunostaining on vascular endothelium were delayed in Lewis C6- compared to Lewis rats' nerves. This study found that MAC was not required for immune mediated demyelination; but that MAC enhanced early symptoms and early demyelination in EAN, either by direct lysis or by sub-lytic induction of vascular endothelial expression of ICAM-1 and P-selectin. Copyright © 2010 Elsevier B.V. All rights reserved.

Artificial Immune Networks: Models and Applications

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Xian Shen

2008-06-01

Full Text Available Artificial Immune Systems (AIS, which is inspired by the nature immune system, has been applied for solving complex computational problems in classification, pattern rec- ognition, and optimization. In this paper, the theory of the natural immune system is first briefly introduced. Next, we compare some well-known AIS and their applications. Several representative artificial immune networks models are also dis- cussed. Moreover, we demonstrate the applications of artificial immune networks in various engineering fields.

Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) RNAs in the Porphyromonas gingivalis CRISPR-Cas I-C System.

Science.gov (United States)

Burmistrz, Michal; Rodriguez Martinez, Jose Ignacio; Krochmal, Daniel; Staniec, Dominika; Pyrc, Krzysztof

2017-12-01

The CRISPR-Cas (clustered regularly interspaced short palindromic repeat-CRISPR-associated protein) system is unique to prokaryotes and provides the majority of bacteria and archaea with immunity against nucleic acids of foreign origin. CRISPR RNAs (crRNAs) are the key element of this system, since they are responsible for its selectivity and effectiveness. Typical crRNAs consist of a spacer sequence flanked with 5' and 3' handles originating from repeat sequences that are important for recognition of these small RNAs by the Cas machinery. In this investigation, we studied the type I-C CRISPR-Cas system in Porphyromonas gingivalis , a human pathogen associated with periodontitis, rheumatoid arthritis, cardiovascular disease, and aspiration pneumonia. We demonstrated the importance of the 5' handle for crRNA recognition by the effector complex and consequently activity, as well as secondary trimming of the 3' handle, which was not affected by modifications of the repeat sequence. IMPORTANCE Porphyromonas gingivalis , a clinically relevant Gram-negative, anaerobic bacterium, is one of the major etiologic agents of periodontitis and has been linked with the development of other clinical conditions, including rheumatoid arthritis, cardiovascular disease, and aspiration pneumonia. The presented results on the biogenesis and functions of crRNAs expand our understanding of CRISPR-Cas cellular defenses in P. gingivalis and of horizontal gene transfer in bacteria. Copyright © 2017 American Society for Microbiology.

PREFACE: 2nd International Conference on Mathematical Modeling in Physical Sciences 2013 (IC-MSQUARE 2013)

Science.gov (United States)

2014-03-01

The second International Conference on Mathematical Modeling in Physical Sciences (IC-MSQUARE) took place at Prague, Czech Republic, from Sunday 1 September to Thursday 5 September 2013. The Conference was attended by more than 280 participants and hosted about 400 oral, poster, and virtual presentations while counted more than 600 pre-registered authors. The second IC-MSQUARE consisted of different and diverging workshops and thus covered various research fields where Mathematical Modeling is used, such as Theoretical/Mathematical Physics, Neutrino Physics, Non-Integrable Systems, Dynamical Systems, Computational Nanoscience, Biological Physics, Computational Biomechanics, Complex Networks, Stochastic Modeling, Fractional Statistics, DNA Dynamics, Macroeconomics. The scientific program was rather heavy since after the Keynote and Invited Talks in the morning, three parallel sessions were running every day. However, according to all attendees, the program was excellent with high level of talks and the scientific environment was fruitful, thus all attendees had a creative time. We would like to thank the Keynote Speaker and the Invited Speakers for their significant contribution to IC-MSQUARE. We also would like to thank the Members of the International Advisory and Scientific Committees as well as the Members of the Organizing Committee. Further information on the editors, speakers and committees is available in the attached pdf.

Mammalian Gut Immunity

Science.gov (United States)

Chassaing, Benoit; Kumar, Manish; Baker, Mark T.; Singh, Vishal; Vijay-Kumar, Matam

2016-01-01

The mammalian intestinal tract is the largest immune organ in the body and comprises cells from non-hemopoietic (epithelia, Paneth cells, goblet cells) and hemopoietic (macrophages, dendritic cells, T-cells) origin, and is also a dwelling for trillions of microbes collectively known as the microbiota. The homeostasis of this large microbial biomass is prerequisite to maintain host health by maximizing beneficial symbiotic relationships and minimizing the risks of living in such close proximity. Both microbiota and host immune system communicate with each other to mutually maintain homeostasis in what could be called a “love–hate relationship.” Further, the host innate and adaptive immune arms of the immune system cooperate and compensate each other to maintain the equilibrium of a highly complex gut ecosystem in a stable and stringent fashion. Any imbalance due to innate or adaptive immune deficiency or aberrant immune response may lead to dysbiosis and low-grade to robust gut inflammation, finally resulting in metabolic diseases. PMID:25163502

Mismatch and noise in modern IC processes

CERN Document Server

Marshall, Andrew

2009-01-01

Component variability, mismatch, and various noise effects are major contributors to design limitations in most modern IC processes. Mismatch and Noise in Modern IC Processes examines these related effects and how they affect the building block circuits of modern integrated circuits, from the perspective of a circuit designer.Variability usually refers to a large scale variation that can occur on a wafer to wafer and lot to lot basis, and over long distances on a wafer. This phenomenon is well understood and the effects of variability are included in most integrated circuit design with the use

30 CFR 57.22209 - Auxiliary fans (I-C mines).

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Auxiliary fans (I-C mines). 57.22209 Section 57... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22209 Auxiliary fans (I-C mines). Electric auxiliary fans shall be approved by MSHA under the applicable requirements of 30 CFR part 18...

Identification of signals that facilitate isoform specific nucleolar localization of myosin IC

Energy Technology Data Exchange (ETDEWEB)

Schwab, Ryan S.; Ihnatovych, Ivanna; Yunus, Sharifah Z.S.A.; Domaradzki, Tera [Department of Physiology and Biophysics, University at Buffalo—State University of New York, Buffalo, NY (United States); Hofmann, Wilma A., E-mail: whofmann@buffalo.edu [Department of Physiology and Biophysics, University at Buffalo—State University of New York, Buffalo, NY (United States)

2013-05-01

Myosin IC is a single headed member of the myosin superfamily that localizes to the cytoplasm and the nucleus, where it is involved in transcription by RNA polymerases I and II, intranuclear transport, and nuclear export. In mammalian cells, three isoforms of myosin IC are expressed that differ only in the addition of short isoform-specific N-terminal peptides. Despite the high sequence homology, the isoforms show differences in cellular distribution, in localization to nuclear substructures, and in their interaction with nuclear proteins through yet unknown mechanisms. In this study, we used EGFP-fusion constructs that express truncated or mutated versions of myosin IC isoforms to detect regions that are involved in isoform-specific localization. We identified two nucleolar localization signals (NoLS). One NoLS is located in the myosin IC isoform B specific N-terminal peptide, the second NoLS is located upstream of the neck region within the head domain. We demonstrate that both NoLS are functional and necessary for nucleolar localization of specifically myosin IC isoform B. Our data provide a first mechanistic explanation for the observed functional differences between the myosin IC isoforms and are an important step toward our understanding of the underlying mechanisms that regulate the various and distinct functions of myosin IC isoforms. - Highlights: ► Two NoLS have been identified in the myosin IC isoform B sequence. ► Both NoLS are necessary for myosin IC isoform B specific nucleolar localization. ► First mechanistic explanation of functional differences between the isoforms.

Study on Mine Emergency Mechanism based on TARP and ICS

Science.gov (United States)

Xi, Jian; Wu, Zongzhi

2018-01-01

By analyzing the experiences and practices of mine emergency in China and abroad, especially the United States and Australia, normative principle, risk management principle and adaptability principle of constructing mine emergency mechanism based on Trigger Action Response Plans (TARP) and Incident Command System (ICS) are summarized. Classification method, framework, flow and subject of TARP and ICS which are suitable for the actual situation of domestic mine emergency are proposed. The system dynamics model of TARP and ICS is established. The parameters such as evacuation ratio, response rate, per capita emergency capability and entry rate of rescuers are set up. By simulating the operation process of TARP and ICS, the impact of these parameters on the emergency process are analyzed, which could provide a reference and basis for building emergency capacity, formulating emergency plans and setting up action plans in the emergency process.

Plant-based oral tolerance to hemophilia therapy employs a complex immune regulatory response including LAP+CD4+ T cells

OpenAIRE

Wang, Xiaomei; Su, Jin; Sherman, Alexandra; Rogers, Geoffrey L.; Liao, Gongxian; Hoffman, Brad E.; Leong, Kam W.; Terhorst, Cox; Daniell, Henry; Herzog, Roland W.

2015-01-01

Coadministering FIX orally and systemically induces tolerance via complex immune regulation, involving tolerogenic dendritic and T-cell subsets.Induced CD4+CD25−LAP+ regulatory T cells with increased IL-10 and TGF-β expression and CD4+CD25+ regulatory T cells suppress antibody formation against FIX.

Prometheus Reactor I&C Software Development Methodology, for Action

Energy Technology Data Exchange (ETDEWEB)

T. Hamilton

2005-07-30

The purpose of this letter is to submit the Reactor Instrumentation and Control (I&C) software life cycle, development methodology, and programming language selections and rationale for project Prometheus to NR for approval. This letter also provides the draft Reactor I&C Software Development Process Manual and Reactor Module Software Development Plan to NR for information.

Large Eddy Simulations of Two-phase Turbulent Reactive Flows in IC Engines

Science.gov (United States)

Banaeizadeh, Araz; Schock, Harold; Jaberi, Farhad

2008-11-01

The two-phase filtered mass density function (FMDF) subgrid-scale (SGS) model is used for large-eddy simulation (LES) of turbulent spray combustion in internal combustion (IC) engines. The LES/FMDF is implemented via an efficient, hybrid numerical method. In this method, the filtered compressible Navier-Stokes equations in curvilinear coordinate systems are solved with a generalized, high-order, multi-block, compact differencing scheme. The spray and the FMDF are implemented with Lagrangian methods. The reliability and the consistency of the numerical methods are established for different IC engines and the complex interactions among mean and turbulent velocity fields, fuel droplets and combustion are shown to be well captured with the LES/FMDF. In both spark-ignition/direct-injection and diesel engines, the droplet size and velocity distributions are found to be modified by the unsteady, vortical motions generated by the incoming air during the intake stroke. In turn, the droplets are found to change the in-cylinder flow structure. In the spark-ignition engine, flame propagation is similar to the experiment. In the diesel engine, the maximum evaporated fuel concentration is near the cylinder wall where the flame starts, which is again consistent with the experiment.

Regulatory effects of intrinsic IL-10 in IgG immune complex-induced lung injury

DEFF Research Database (Denmark)

Shanley, T P; Schmal, H; Friedl, H P

1995-01-01

IL-10 has regulatory effects in vitro on cytokine production by activated macrophages. In the IgG immune complex model of lung injury, exogenously administered IL-10 has been shown to suppress in vivo formation of TNF-alpha, up-regulation of vascular ICAM-1, neutrophil recruitment, and ensuing lung....... Blocking of IL-10 by Ab resulted in a 52% increase in lung vascular permeability, a 56% increase in TNF-alpha activity in bronchoalveolar lavage fluids, and a 47 to 48% increase in bronchoalveolar lavage neutrophils and lung myeloperoxidase content. These findings suggest that IL-10 is an important natural...

In immune defense: redefining the role of the immune system in chronic disease.

Science.gov (United States)

Rubinow, Katya B; Rubinow, David R

2017-03-01

The recognition of altered immune system function in many chronic disease states has proven to be a pivotal advance in biomedical research over the past decade. For many metabolic and mood disorders, this altered immune activity has been characterized as inflammation, with the attendant assumption that the immune response is aberrant. However, accumulating evidence challenges this assumption and suggests that the immune system may be mounting adaptive responses to chronic stressors. Further, the inordinate complexity of immune function renders a simplistic, binary model incapable of capturing critical mechanistic insights. In this perspective article, we propose alternative paradigms for understanding the role of the immune system in chronic disease. By invoking allostasis or systems biology rather than inflammation, we can ascribe greater functional significance to immune mediators, gain newfound appreciation of the adaptive facets of altered immune activity, and better avoid the potentially disastrous effects of translating erroneous assumptions into novel therapeutic strategies.

Human innate responses and adjuvant activity of TLR ligands in vivo in mice reconstituted with a human immune system.

Science.gov (United States)

Cheng, Liang; Zhang, Zheng; Li, Guangming; Li, Feng; Wang, Li; Zhang, Liguo; Zurawski, Sandra M; Zurawski, Gerard; Levy, Yves; Su, Lishan

2017-10-27

TLR ligands (TLR-Ls) represent a class of novel vaccine adjuvants. However, their immunologic effects in humans remain poorly defined in vivo. Using a humanized mouse model with a functional human immune system, we investigated how different TLR-Ls stimulated human innate immune response in vivo and their applications as vaccine adjuvants for enhancing human cellular immune response. We found that splenocytes from humanized mice showed identical responses to various TLR-Ls as human PBMCs in vitro. To our surprise, various TLR-Ls stimulated human cytokines and chemokines differently in vivo compared to that in vitro. For example, CpG-A was most efficient to induce IFN-α production in vitro. In contrast, CpG-B, R848 and Poly I:C stimulated much more IFN-α than CpG-A in vivo. Importantly, the human innate immune response to specific TLR-Ls in humanized mice was different from that reported in C57BL/6 mice, but similar to that reported in nonhuman primates. Furthermore, we found that different TLR-Ls distinctively activated and mobilized human plasmacytoid dendritic cells (pDCs), myeloid DCs (mDCs) and monocytes in different organs. Finally, we showed that, as adjuvants, CpG-B, R848 and Poly I:C can all enhance antigen specific CD4 + T cell response, while only R848 and Poly I:C induced CD8 + cytotoxic T cells response to a CD40-targeting HIV vaccine in humanized mice, correlated with their ability to activate human mDCs but not pDCs. We conclude that humanized mice serve as a highly relevant model to evaluate and rank the human immunologic effects of novel adjuvants in vivo prior to testing in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chylous Ascites in a Patient with HIV/AIDS: A Late Complication of Mycobacterium avium Complex-Immune Reconstitution Inflammatory Syndrome

Directory of Open Access Journals (Sweden)

Imam H. Shaik

2014-01-01

Full Text Available Chylous ascites is very rare in HIV/AIDS and its association with Mycobacterium avium complex-immune reconstitution inflammatory syndrome (MAC-IRIS has been rarely reported. Here, we report a case of a young African-American male who developed chylous ascites as a late sequela to immune reconstitution inflammatory syndrome while on treatment for MAC. Antiretroviral drug-naive patients who start HAART in close proximity to the diagnosis of an opportunistic infection and have a rapid decline in HIV RNA level should be monitored for development of IRIS. Although the long term prognosis is poor, early diagnosis and treatment help to improve quality of life.

The Search for Wolf-Rayet Stars in IC10

Science.gov (United States)

Tehrani, Katie; Crowther, Paul; Archer, Isabelle

2017-11-01

We present a deep imaging and spectroscopic survey of the Local Group starburst galaxy IC10 using Gemini North/GMOS to unveil the global Wolf-Rayet population. It has previously been suggested that for IC10 to follow the WC/WN versus metallicity dependence seen in other Local Group galaxies, a large WN population must remain undiscovered. Our search revealed 3 new WN stars, and 5 candidates awaiting confirmation, providing little evidence to support this claim. We also compute an updated nebular derived metallicity of log(O/H)+12=8.40 +/- 0.04 for the galaxy using the direct method. Inspection of IC10 WR average line luminosities show these stars are more similar to their LMC, rather than SMC counterparts.

Safety and immunogenicity of H1/IC31®, an adjuvanted TB subunit vaccine, in HIV-infected adults with CD4+ lymphocyte counts greater than 350 cells/mm3: a phase II, multi-centre, double-blind, randomized, placebo-controlled trial.

Directory of Open Access Journals (Sweden)

Klaus Reither

Full Text Available Novel tuberculosis vaccines should be safe, immunogenic, and effective in various population groups, including HIV-infected individuals. In this phase II multi-centre, double-blind, placebo-controlled trial, the safety and immunogenicity of the novel H1/IC31 vaccine, a fusion protein of Ag85B-ESAT-6 (H1 formulated with the adjuvant IC31, was evaluated in HIV-infected adults.HIV-infected adults with CD4+ T cell counts >350/mm3 and without evidence of active tuberculosis were enrolled and followed until day 182. H1/IC31 vaccine or placebo was randomly allocated in a 5:1 ratio. The vaccine was administered intramuscularly at day 0 and 56. Safety assessment was based on medical history, clinical examinations, and blood and urine testing. Immunogenicity was determined by a short-term whole blood intracellular cytokine staining assay.47 of the 48 randomised participants completed both vaccinations. In total, 459 mild or moderate and 2 severe adverse events were reported. There were three serious adverse events in two vaccinees classified as not related to the investigational product. Local injection site reactions were more common in H1/IC31 versus placebo recipients (65.0% vs. 12.5%, p = 0.015. Solicited systemic and unsolicited adverse events were similar by study arm. The baseline CD4+ T cell count and HIV viral load were similar by study arm and remained constant over time. The H1/IC31 vaccine induced a persistent Th1-immune response with predominately TNF-α and IL-2 co-expressing CD4+ T cells, as well as polyfunctional IFN-γ, TNF-α and IL-2 expressing CD4+ T cells.H1/IC31 was well tolerated and safe in HIV-infected adults with a CD4+ Lymphocyte count greater than 350 cells/mm3. The vaccine did not have an effect on CD4+ T cell count or HIV-1 viral load. H1/IC31 induced a specific and durable Th1 immune response.Pan African Clinical Trials Registry (PACTR PACTR201105000289276.

Application of IC Card License for Road Transportation in Commercial Vehicles Supervision and Service

Directory of Open Access Journals (Sweden)

Li Weiwei

2016-01-01

Full Text Available IC card electronic license for road transport includes the IC card commercial vehicle’s certificate and IC card practitioner’s qualification certificate. In China, the IC card electronic license for road transport is the electronic ID card which must be carried by each commercial vehicles and practitioners. This paper briefly introduces the basic situation, data format and security keys architecture of IC card electronic license for road transportation of China. In order to strengthen the supervision and service of commercial vehicles, this paper puts forward the overall application framework of IC card electronic license for road transport. The application examples of IC card license in the supervision of passenger station, dangerous goods transport management, governance overload and logistics park and port area management are discussed. The practical application results show that the application of IC card electronic license for road transport is an important technical means to improve the supervision ability and service quality of the road transportation industry.

Complement's participation in acquired immunity

DEFF Research Database (Denmark)

Nielsen, Claus Henrik; Leslie, Robert Graham Quinton

2002-01-01

of the B cell receptor for antigen (BCR), a complex composed of the iC3b/C3d fragment-binding complement type 2 receptor (CR2, CD21) and its signaling element CD19 and the IgG-binding receptor FcgammaRIIb (CD32). The positive or negative outcome of signaling through this triad is determined by the context...

Mechanisms regulating skin immunity and inflammation.

Science.gov (United States)

Pasparakis, Manolis; Haase, Ingo; Nestle, Frank O

2014-05-01

Immune responses in the skin are important for host defence against pathogenic microorganisms. However, dysregulated immune reactions can cause chronic inflammatory skin diseases. Extensive crosstalk between the different cellular and microbial components of the skin regulates local immune responses to ensure efficient host defence, to maintain and restore homeostasis, and to prevent chronic disease. In this Review, we discuss recent findings that highlight the complex regulatory networks that control skin immunity, and we provide new paradigms for the mechanisms that regulate skin immune responses in host defence and in chronic inflammation.

ICECAP: an integrated, general-purpose, automation-assisted IC50/EC50 assay platform.

Science.gov (United States)

Li, Ming; Chou, Judy; King, Kristopher W; Jing, Jing; Wei, Dong; Yang, Liyu

2015-02-01

IC50 and EC50 values are commonly used to evaluate drug potency. Mass spectrometry (MS)-centric bioanalytical and biomarker labs are now conducting IC50/EC50 assays, which, if done manually, are tedious and error-prone. Existing bioanalytical sample preparation automation systems cannot meet IC50/EC50 assay throughput demand. A general-purpose, automation-assisted IC50/EC50 assay platform was developed to automate the calculations of spiking solutions and the matrix solutions preparation scheme, the actual spiking and matrix solutions preparations, as well as the flexible sample extraction procedures after incubation. In addition, the platform also automates the data extraction, nonlinear regression curve fitting, computation of IC50/EC50 values, graphing, and reporting. The automation-assisted IC50/EC50 assay platform can process the whole class of assays of varying assay conditions. In each run, the system can handle up to 32 compounds and up to 10 concentration levels per compound, and it greatly improves IC50/EC50 assay experimental productivity and data processing efficiency. © 2014 Society for Laboratory Automation and Screening.

Fast-Dissolving, Prolonged Release, and Antibacterial Cyclodextrin/Limonene-Inclusion Complex Nanofibrous Webs via Polymer-Free Electrospinning.

Science.gov (United States)

Aytac, Zeynep; Yildiz, Zehra Irem; Kayaci-Senirmak, Fatma; San Keskin, Nalan Oya; Kusku, Semran Ipek; Durgun, Engin; Tekinay, Turgay; Uyar, Tamer

2016-10-05

We have proposed a new strategy for preparing free-standing nanofibrous webs from an inclusion complex (IC) of a well-known flavor/fragrance compound (limonene) with three modified cyclodextrins (HPβCD, MβCD, and HPγCD) via electrospinning (CD/limonene-IC-NFs) without using a polymeric matrix. The experimental and computational modeling studies proved that the stoichiometry of the complexes was 1:1 for CD/limonene systems. MβCD/limonene-IC-NF released much more limonene at 37, 50, and 75 °C than HPβCD/limonene-IC-NF and HPγCD/limonene-IC-NF because of the greater amount of preserved limonene. Moreover, MβCD/limonene-IC-NF has released only 25% (w/w) of its limonene, whereas HPβCD/limonene-IC-NF and HPγCD/limonene-IC-NF released 51 and 88% (w/w) of their limonene in 100 days, respectively. CD/limonene-IC-NFs exhibited high antibacterial activity against E. coli and S. aureus. The water solubility of limonene increased significantly and CD/limonene-IC-NFs were dissolved in water in a few seconds. In brief, CD/limonene-IC-NFs with fast-dissolving character enhanced the thermal stability and prolonged the shelf life along with antibacterial properties could be quite applicable in food and oral care applications.

30 CFR 57.22203 - Main fan operation (I-C mines).

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Main fan operation (I-C mines). 57.22203... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22203 Main fan operation (I-C mines). Main fans shall be operated continuously while ore production is in progress. ...

Simultaneous detection of three lily viruses using Triplex IC-RT-PCR.

Science.gov (United States)

Zhang, Yubao; Wang, Yajun; Xie, Zhongkui; Yang, Guo; Guo, Zhihong; Wang, Le

2017-11-01

Viruses commonly infecting lily (Lilium spp.) include: Lily symptomless virus (LSV), Cucumber mosaic virus (CMV) and Lily mottle virus (LMoV). These viruses usually co-infect lilies causing severe economic losses in terms of quantity and quality of flower and bulb production around the world. Reliable and precise detection systems need to be developed for virus identification. We describe the development of a triplex immunocapture (IC) reverse transcription (RT) polymerase chain reaction (PCR) assay for the simultaneous detection of LSV, CMV and LMoV. The triplex IC-RT-PCR was compared with a quadruplex RT-PCR assay. Relative to the quadruplex RT-PCR, the specificity of the triplex IC-RT-PCR system for LSV, CMV and LMoV was 100% for field samples. The sensitivity of the triplex IC-RT-PCR system was 99.4%, 81.4% and 98.7% for LSV, CMV and LMoV, respectively. Agreement (κ) between the results obtained from the two tests was 0.968, 0.844 and 0.984 for LSV, CMV and LMoV, respectively. This is the first report of the simultaneous detection of LSV, CMV and LMoV in a triplex IC-RT-PCR assay. In particular we believe this convenient and reliable triplex IC-RT-PCR method could be used routinely for large-scale field surveys or crop health monitoring of lily. Copyright © 2017. Published by Elsevier B.V.

Low-Complexity Full-Diversity Detection in Two-User MIMO X Channels

KAUST Repository

Ismail, Amr

2014-01-26

Several interference cancellation (IC) schemes have been recently proposed to suppress multi-user interference for various network configurations (e.g., multiple access and X channels). However, most of these schemes trade-off diversity for implementation complexity or vice-versa. In this paper, we propose a full-diversity interference cancellation scheme in a multiple-input multiple-output (MIMO) X channel with two sources and two destinations while maintaining low decoding complexity. We provide sufficient conditions for a wide range of space-time block codes (STBCs) to achieve full-diversity gain under the so-called partial interference cancellation group decoding (PICGD) in the configuration of interest. A systematic construction is then proposed to achieve full-diversity. The constructed scheme is compared to recently proposed IC scheme in terms of performance and decoding complexity. Our IC scheme outperforms the recently proposed scheme in the case it provides higher transmission rate, while it loses slightly in the case of equal rates. In terms of decoding complexity, both schemes are equivalent.

Low-Complexity Full-Diversity Detection in Two-User MIMO X Channels

KAUST Repository

Ismail, Amr; Abediseid, Walid; Alouini, Mohamed-Slim

2014-01-01

Several interference cancellation (IC) schemes have been recently proposed to suppress multi-user interference for various network configurations (e.g., multiple access and X channels). However, most of these schemes trade-off diversity for implementation complexity or vice-versa. In this paper, we propose a full-diversity interference cancellation scheme in a multiple-input multiple-output (MIMO) X channel with two sources and two destinations while maintaining low decoding complexity. We provide sufficient conditions for a wide range of space-time block codes (STBCs) to achieve full-diversity gain under the so-called partial interference cancellation group decoding (PICGD) in the configuration of interest. A systematic construction is then proposed to achieve full-diversity. The constructed scheme is compared to recently proposed IC scheme in terms of performance and decoding complexity. Our IC scheme outperforms the recently proposed scheme in the case it provides higher transmission rate, while it loses slightly in the case of equal rates. In terms of decoding complexity, both schemes are equivalent.

Characterization of NF-κB Reporter U937 Cells and Their Application for the Detection of Inflammatory Immune-Complexes.

Directory of Open Access Journals (Sweden)

Csilla Kecse-Nagy

Full Text Available Our study tested the hypothesis that immunoglobulins differ in their ability to activate the nuclear factor-κB pathway mediated cellular responses. These responses are modulated by several properties of the immune complex, including the ratio of antibody isotypes binding to antigen. Immunoassays allow the measurement of antigen specific antibodies belonging to distinct immunoglobulin classes and subclasses but not the net biological effect of the combination of these antibodies. We set out to develop a biosensor that is suitable for the detection and characterization of antigen specific serum antibodies. We genetically modified the monocytoid U937 cell line carrying Fc receptors with a plasmid encoding NF-κB promoter-driven GFP. This clone, U937-NF-κB, was characterized with respect to FcR expression and response to solid-phase immunoglobulins. Human IgG3, IgG4 and IgG1 induced GFP production in a time- and dose-dependent manner, in this order of efficacy, while IgG2 triggered no activation at the concentrations tested. IgA elicited no response alone but showed significant synergism with IgG3 and IgG4. We confirmed the importance of activation via FcγRI by direct stimulation with monoclonal antibody and by competition assays. We used citrullinated peptides and serum from rheumatoid arthritis patients to generate immune complexes and to study the activation of U937-NF-κB, observing again a synergistic effect between IgG and IgA. Our results show that immunoglobulins have distinct pro-inflammatory potential, and that U937-NF-κB is suitable for the estimation of biological effects of immune-complexes, offering insight into monocyte activation and pathogenesis of antibody mediated diseases.

Studies on the pathogenesis of Aleutian disease of mink

International Nuclear Information System (INIS)

Mueller-Peddinghaus, R.; Meyer zu Schwabedissen, H.; Kalden, J.R.; Trautwein, G.; Ueberschaer, S.

1980-01-01

Aleutian disease (AD) of mink most closely resembles systemic lupus erythematosus (SLE) in man; both are immune complex disease. In experimental AD serum immune complexes are determined by the 125 J-C 1 q-binding test using human C 1 q. Mink (n = 12) infected intraperitoneally with Aleutian disease virus (ADV), grown in fetal mink kidney cells, developed during the course of infection a mean of 125 I-C 1 q serum binding equivalent to 3.62 +- 1.68 mg./ml. aggr. HGG. (aggregated human immunoglobulin). Sera of mink (n = 8) which were infected with ADV grown in L-cells showed a less marked 125 I-C 1 q binding with a mean equivalent to 2.52 +- 1.43 mg./ml. aggr. HGG. In contrast control animals (n = 8) treated with non-ADV-infected mink epidermal fibroblasts or Eagle's minimal essential medium substituted with fetal calf serum only bound 125 I-C 1 q equivalent to 1.02 +- 0.99 mg./ml. aggr. HGG. In mink infected with ADV propagated in fetal mink kidney cells a constant increase in the 125 I-C 1 q serum binding occurred from the 4th to the 7th and 13th week after ADV infection. Mink which were infected with ADV propagated in mouse L-cells exhibited a different pattern of the 125 I-C 1 q serum binding capacity with a sharp increase from the 4th to the 7th week, followed by a decline towards the 13th week post infection. The serum 125 I-C 1 q binding capacity of all experimental animal groups exhibited at different times of the experiment a significant correlation with the presence of hypergammaglobulinaemia and raised ADV-antibody titers. From the data obtained it appears that the 125 I-C 1 q binding test, utilizing human C 1 q, is a suitable method for the detection of circulating serum immune complexes in mink during the course of ADV-infection. (orig.) [de

Tsc2 Haploinsufficiency Has Limited Effects on Fetal Brain Cytokine Levels during Gestational Immune Activation

Directory of Open Access Journals (Sweden)

Dan Ehninger

2014-01-01

Full Text Available Dysregulated TSC/mTOR signaling may play a pathogenetic role in forms of syndromic autism, such as autism associated with tuberous sclerosis, a genetic disorder caused by heterozygous TSC1 or TSC2 mutations. Environmental risk factors, such as gestational viral infections, may, in some cases, also contribute to the pathogenesis of autism and related neuropsychiatric disorders. We have recently found that a heterozygous Tsc2 mutation and the poly I:C model of maternal immune activation (MIA interactively perturb fetal development and adult social behavior in mice, suggesting that these factors converge on shared pathways. TSC/mTOR signaling plays an important role in the modulation of immune responses, raising the possibility that the damage caused by MIA was greater in Tsc2+/− than in wildtype fetuses because of an exacerbated immune response in the mutants. Here, cytokine antibody arrays were employed to measure relative cytokine abundances in the fetal brain and the placenta during MIA. Cytokines were induced by gestational poly I:C but there was no obvious modulatory effect of Tsc2 haploinsufficiency. The data indicate that cytokine exposure during MIA is comparable in Tsc2 haploinsufficient and wildtype control fetuses, suggesting that downstream molecular and cellular processes may account for the interactive effects of Tsc2 haploinsufficiency and MIA.

Effect of IgG subclasses on in vivo bioavailability and metabolic fate of immune-complexed insulin in Lewis rats

International Nuclear Information System (INIS)

Arquilla, E.R.; Stenger, D.; McDougall, B.; Ulich, T.R.

1987-01-01

The bioavailability, distribution, and metabolic fate of 125 I-labeled insulin complexed to antibodies in guinea pig antiserum, purified guinea pig IgG1, IgG2, a mixture of IgG1 and IgG2, and homologous Lou/m rat antiserum were studied in inbred Lewis rats. 125 I-insulin complexed to purified guinea pig IgG2 antibodies was rapidly cleared from the blood and sequestered in increasing amounts with time in the liver. Large amounts of the 125 I-insulin complexed to guinea pig IgG1 antibodies remained in the blood for at least 30 min. The bioavailability of 125 I-insulin bound to IgG1 and IgG2 antibodies was inhibited for at least 30 min because significantly less was available for rapid binding to insulin receptors on hepatocytes and renal tubular cells and its subsequent rapid degradation. The bioavailability of 125 I-insulin was further decreased when bound to antibodies in native guinea pig antiserum or a mixture of IgG1 and IgG2 antibodies compared with the 125 I-insulin complexed to either purified IgG1 or IgG2 antibodies alone. The 125 I-insulin bound to antibodies in native guinea pig antiserum or a mixture of IgG1 and IgG2 antibodies was distributed in vivo in a manner reflecting the relative concentrations of the IgG1 and IgG2 antibodies present. The bioavailability, distribution, and metabolic fate of 125 I-insulin in immune complexes prepared with homologous Lou/m rat insulin antiserum was qualitatively similar to that observed with immune complexes prepared with guinea pig insulin antiserum. It appears that the Lewis rat can be used as an in vivo model to study the bioavailability,distribution,and metabolic fate of insulin bound to xenogenic or homologous insulin antibodies

Generic test platform for representative tests of safety I/C systems - 15546

International Nuclear Information System (INIS)

Fourestie, B.; Kuck, H.; Richter, J.; Rieche, S.; Waitz, M.

2015-01-01

In compliance with the IEC 61513 safety Instrumentation and Control (I/C) systems must be successfully validated in their final configuration prior to installation on site and commissioning. However the contingent need for modifications during system validation activities or subsequently during the commissioning phase may entail long and costly re-engineering of the I/C systems. With the view to ease these possible modifications, a Generic Test Platform has been developed by AREVA which allows combining a real I/C system subpart with an emulation server. This platform provides a faithful representation of the I/C System allowing crediting the validation test results carried out on this platform. (authors)

Toxoplasma gondii 70 kDa heat shock protein: systemic detection is associated with the death of the parasites by the immune response and its increased expression in the brain is associated with parasite replication.

Directory of Open Access Journals (Sweden)

Paulo Victor Czarnewski Barenco

Full Text Available The heat shock protein of Toxoplasma gondii (TgHSP70 is a parasite virulence factor that is expressed during T. gondii stage conversion. To verify the effect of dexamethasone (DXM-induced infection reactivation in the TgHSP70-specific humoral immune response and the presence of the protein in the mouse brain, we produced recombinant TgHSP70 and anti-TgHSP70 IgY antibodies to detect the protein, the specific antibody and levels of immune complexes (ICs systemically, as well as the protein in the brain of resistant (BALB/c and susceptible (C57BL/6 mice. It was observed higher TgHSP70-specific antibody titers in serum samples of BALB/c compared with C57BL/6 mice. However, the susceptible mice presented the highest levels of TgHSP70 systemically and no detection of specific ICs. The DXM treatment induced increased parasitism and lower inflammatory changes in the brain of C57BL/6, but did not interfere with the cerebral parasitism in BALB/c mice. Additionally, DXM treatment decreased the serological TgHSP70 concentration in both mouse lineages. C57BL/6 mice presented high expression of TgHSP70 in the brain with the progression of infection and under DXM treatment. Taken together, these data indicate that the TgHSP70 release into the bloodstream depends on the death of the parasites mediated by the host immune response, whereas the increased TgHSP70 expression in the brain depends on the multiplication rate of the parasite.

AGB stars as tracers to IC 1613 evolution.

Science.gov (United States)

Hashemi, S. A.; Javadi, A.; van Loon, J. Th.

We are going to apply AGB stars to find star formation history for IC 1613 galaxy; this a new and simple method that works well for nearby galaxies. IC 1613 is a Local Group dwarf irregular galaxy that is located at distance of 750 kpc, a gas rich and isolated dwarf galaxy that has a low foreground extinction. We use the long period variable stars (LPVs) that represent the very final stage of evolution of stars with low and intermediate mass at the AGB phase and are very luminous and cool so that they emit maximum brightness in near-infrared bands. Thus near-infrared photometry with using stellar evolutionary models help us to convert brightness to birth mass and age and from this drive star formation history of the galaxy. We will use the luminosity distribution of the LPVs to reconstruct the star formation history-a method we have successfully applied in other Local Group galaxies. Our analysis shows that the IC 1613 has had a nearly constant star formation rate, without any dominant star formation episode.

Two complex, adenovirus-based vaccines that together induce immune responses to all four dengue virus serotypes.

Science.gov (United States)

Holman, David H; Wang, Danher; Raviprakash, Kanakatte; Raja, Nicholas U; Luo, Min; Zhang, Jianghui; Porter, Kevin R; Dong, John Y

2007-02-01

Dengue virus infections can cause hemorrhagic fever, shock, encephalitis, and even death. Worldwide, approximately 2.5 billion people live in dengue-infested regions with about 100 million new cases each year, although many of these infections are believed to be silent. There are four antigenically distinct serotypes of dengue virus; thus, immunity from one serotype will not cross-protect from infection with the other three. The difficulties that hamper vaccine development include requirements of the natural conformation of the envelope glycoprotein to induce neutralizing immune responses and the necessity of presenting antigens of all four serotypes. Currently, the only way to meet these requirements is to use a mixture of four serotypes of live attenuated dengue viruses, but safety remains a major problem. In this study, we have developed the basis for a tetravalent dengue vaccine using a novel complex adenovirus platform that is capable of expressing multiple antigens de novo. This dengue vaccine is constructed as a pair of vectors that each expresses the premembrane and envelope genes of two different dengue virus serotypes. Upon vaccination, the vaccine expressed high levels of the dengue virus antigens in cells to mimic a natural infection and induced both humoral and cellular immune responses against multiple serotypes of dengue virus in an animal model. Further analyses show the humoral responses were indeed neutralizing against all four serotypes. Our studies demonstrate the concept of mimicking infections to induce immune responses by synthesizing dengue virus membrane antigens de novo and the feasibility of developing an effective tetravalent dengue vaccine by vector-mediated expression of glycoproteins of the four serotypes.

Prediction of fracture toughness K/sub Ic/ of steel from Charpy impact test results

Energy Technology Data Exchange (ETDEWEB)

Iwadate, Tadao; Tanaka, Yasuhiko; Takemata, Hiroyuki; Terashima, Shuhei

1986-08-01

This paper presents a method to predict the fracture toughness K/sub Ic/ and/or K/sub Id/ of steels using their Charpy impact test results and tensile properties. The fracture toughness, Charpy impact and tensile properties of 2 1/4 Cr-1Mo, ASTM A508 Cl.1, A508 Cl.2 A508 Cl.3 and A533 Gr.B Cl.1 steels were measured and analysed on the basis of the excess temperature (test temperature minus FATT) and Rolfe-Novak correlation. The relationship between K/sub Ic//K/sub Ic-us/ and the excess temperature, where K/sub Ic-us/ is the upper-shelf fracture toughness K/sub Ic/ predicted by Rolfe-Novak correlation, discloses that the K/sub Ic/ transition curves of several steels are representable by only one trend curve of K/sub Ic//K/sub Ic-us/ or K/sub Id//K/sub Id-us/ versus excess temperature relation. This curve is denoted as a ''master curve''. By using this curve, the fracture toughness of steel can be predicted using Charpy impact and tensile test results. By taking account of the scattering of both the fracture toughness and Charpy impact test results, the confidence limits of the master curve were also determined. Another approach to develop more general procedure of predicting the fracture toughness K/sub Ic/ is also discussed.

Protection against avian metapneumovirus subtype C in turkeys immunized via the respiratory tract with inactivated virus.

Science.gov (United States)

Cha, Ra Mi; Khatri, Mahesh; Sharma, Jagdev M

2011-01-10

Avian metapneumovirus subtype C (aMPV/C) causes a severe upper respiratory tract (URT) infection in turkeys. Turkeys were inoculated oculonasally with inactivated aMPV/C adjuvanted with synthetic double-stranded RNA polyriboinosinic polyribocytidylic acid (Poly IC). Immunized turkeys had elevated numbers of mucosal IgA+ cells in the URT and increased levels of virus-specific IgG and IgA in the lachrymal fluid and IgG in the serum. After 7 or 21 days post immunization, turkeys were challenged oculonasally with pathogenic aMPV/C. Immunized groups were protected against respiratory lesions induced by the challenge virus. Further, the viral copy number of the challenge virus in the URT were significantly lower in the immunized turkeys than in the unimmunized turkeys (P<0.05). These results showed that inactivated aMPV/C administered by the respiratory route induced protective immunity against pathogenic virus challenge. Copyright © 2010 Elsevier Ltd. All rights reserved.

Industry-Oriented Laboratory Development for Mixed-Signal IC Test Education

Science.gov (United States)

Hu, J.; Haffner, M.; Yoder, S.; Scott, M.; Reehal, G.; Ismail, M.

2010-01-01

The semiconductor industry is lacking qualified integrated circuit (IC) test engineers to serve in the field of mixed-signal electronics. The absence of mixed-signal IC test education at the collegiate level is cited as one of the main sources for this problem. In response to this situation, the Department of Electrical and Computer Engineering at…

30 CFR 57.22241 - Advance face boreholes (I-C mines).

Science.gov (United States)

2010-07-01

...) Boreholes shall be drilled in such a manner to insure that the advancing face will not accidently break into... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Advance face boreholes (I-C mines). 57.22241... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22241 Advance face boreholes (I-C mines...

PDC IC WELD FAILURE EVALUATION AND RESOLUTION

Energy Technology Data Exchange (ETDEWEB)

Korinko, P.; Howard, S.; Maxwell, D.; Fiscus, J.

2012-04-16

During final preparations for start of the PDCF Inner Can (IC) qualification effort, welding was performed on an automated weld system known as the PICN. During the initial weld, using a pedigree canister and plug, a weld defect was observed. The defect resulted in a hole in the sidewall of the canister, and it was observed that the plug sidewall had not been consumed. This was a new type of failure not seen during development and production of legacy Bagless Transfer Cans (FB-Line/Hanford). Therefore, a team was assembled to determine the root cause and to determine if the process could be improved. After several brain storming sessions (MS and T, R and D Engineering, PDC Project), an evaluation matrix was established to direct this effort. The matrix identified numerous activities that could be taken and then prioritized those activities. This effort was limited by both time and resources (the number of canisters and plugs available for testing was limited). A discovery process was initiated to evaluate the Vendor's IC fabrication process relative to legacy processes. There were no significant findings, however, some information regarding forging/anneal processes could not be obtained. Evaluations were conducted to compare mechanical properties of the PDC canisters relative to the legacy canisters. Some differences were identified, but mechanical properties were determined to be consistent with legacy materials. A number of process changes were also evaluated. A heat treatment procedure was established that could reduce the magnetic characteristics to levels similar to the legacy materials. An in-situ arc annealing process was developed that resulted in improved weld characteristics for test articles. Also several tack welds configurations were addressed, it was found that increasing the number of tack welds (and changing the sequence) resulted in decreased can to plug gaps and a more stable weld for test articles. Incorporating all of the process

PENGARUH MEKANISME CORPORATE GOVERNANCE TERHADAP PENGUNGKAPAN INTELLECTUAL CAPITAL: PADA PERUSAHAAN IC INTENSIVE

Directory of Open Access Journals (Sweden)

Dista Amalia Arifah

2012-12-01

Full Text Available Intangible asset proxied by Intellectual Capital has important role to drive companies values creation. Although many companies have applied corporate governance mechanism in order to have IC disclosure recognition, most of them do not focus on Intellectual Capital disclosure yet. The aim of this study is to analyze the influence of corporate governance mechanisms consisting of size of the board commissioners, the independence level of independent commissioner, the activities of independent commissioners, and audit committee on the intellectual capital disclosures of the companies listed in BEI in 2009 using intensive ICs category with the adding of kontrol variables. This study will provide an illustration on how the mechanisms of corporate governance practices and IC disclosure become a value creation source for the company. There are a total of 176 companies categorized as IC intensive. Using a purposive sampling method, 45 companies were selected as samples. The 2009 annual reports of the companies are used as secondary data source of this research. Furthermore, to get ICs disclosure data content analysis technique was used both for quantity and quality terms. The results indicate that audit committee is the only corporate governance mechanism that significantly affects the level of IC disclosures.

Dead-time free pixel readout architecture for ATLAS front-end IC

CERN Document Server

Einsweiler, Kevin F; Kleinfelder, S A; Luo, L; Marchesini, R; Milgrome, O; Pengg, F X

1999-01-01

A low power sparse scan readout architecture has been developed for the ATLAS pixel front-end IC. The architecture supports a dual discriminator and extracts the time over threshold (TOT) information along with a 2-D spatial address $9 of the hits associating them with a unique 7-bit beam crossing number. The IC implements level-1 trigger filtering along with event building (grouping together all hits in a beam crossing) in the end of column (EOC) buffer. The $9 events are transmitted over a 40 MHz serial data link with the protocol supporting buffer overflow handling by appending error flags to events. This mixed-mode full custom IC is implemented in 0.8 mu HP process to meet the $9 requirements for the pixel readout in the ATLAS inner detector. The circuits have been tested and the IC provides dead-time-less ambiguity free readout at 40 MHz data rate.

Relating illness complexity to reimbursement in CKD patients.

Science.gov (United States)

Bessette, Russell W; Carter, Randy L

2011-01-01

Despite significant investments of federal and state dollars to transition patient medical records to an all-electronic system, a chasm still exists between health care quality and payment for it. A major reason for this gap is the difficulty in evaluating health care outcomes based on claims data. Since both payers and patients may not appreciate how illness complexity impacts treatment outcomes, it is difficult to determine fair provider compensation. Chronic kidney disease (CKD) typifies these problems and is often associated with comorbidities that impact cost, health, and work productivity. Thus, the objective of this study was to evaluate an illness complexity score (ICS) based on a linear regression of select blood values that might assist in predicting average monthly reimbursements in CKD patients. A second objective was to compare the results of this ICS prediction to results obtained by prediction of average monthly reimbursement using CKD stage. A third objective was to analyze the relationship between the change in ICS, estimated glomerular filtration rate (eGFR), and CKD stage over time to average monthly reimbursement. We calculated parsimonious values for select variables associated with CKD patients and compared the ICS to ordinal staging of renal disease. Data from 177 de-identified patients over 13 months was collected, which included 15 blood chemistry observations along with complete claims data for all medical expenses. To test for the relationship between average blood chemistry values, stages of CKD, age, and average monthly reimbursement, we modeled an association through a linear regression function of age, eGFR, and the Z-scores calculated from average monthly values of phosphorus, parathyroid hormone, glucose, hemoglobin, bicarbonate, albumin, creatinine, blood urea nitrogen, potassium, calcium, sodium, alkaline phosphatase, alanine aminotransferase, and white blood cells. The results of our study demonstrated that the association

The basic circuit of the IC: tectothalamic neurons with different patterns of synaptic organization send different messages to the thalamus

Science.gov (United States)

Ito, Tetsufumi; Oliver, Douglas L.

2012-01-01

The inferior colliculus (IC) in the midbrain of the auditory system uses a unique basic circuit to organize the inputs from virtually all of the lower auditory brainstem and transmit this information to the medial geniculate body (MGB) in the thalamus. Here, we review the basic circuit of the IC, the neuronal types, the organization of their inputs and outputs. We specifically discuss the large GABAergic (LG) neurons and how they differ from the small GABAergic (SG) and the more numerous glutamatergic neurons. The somata and dendrites of LG neurons are identified by axosomatic glutamatergic synapses that are lacking in the other cell types and exclusively contain the glutamate transporter VGLUT2. Although LG neurons are most numerous in the central nucleus of the IC (ICC), an analysis of their distribution suggests that they are not specifically associated with one set of ascending inputs. The inputs to ICC may be organized into functional zones with different subsets of brainstem inputs, but each zone may contain the same three neuron types. However, the sources of VGLUT2 axosomatic terminals on the LG neuron are not known. Neurons in the dorsal cochlear nucleus, superior olivary complex, intermediate nucleus of the lateral lemniscus, and IC itself that express the gene for VGLUT2 only are the likely origin of the dense VGLUT2 axosomatic terminals on LG tectothalamic neurons. The IC is unique since LG neurons are GABAergic tectothalamic neurons in addition to the numerous glutamatergic tectothalamic neurons. SG neurons evidently target other auditory structures. The basic circuit of the IC and the LG neurons in particular, has implications for the transmission of information about sound through the midbrain to the MGB. PMID:22855671

Immunity booster

International Nuclear Information System (INIS)

Stefanescu, Ioan; Titescu, Gheorghe; Tamaian, Radu; Haulica, Ion; Bild, Walther

2002-01-01

The immunity booster is, according to its patent description, microbiologically pure water with an D/(D+H) isotopic concentration of 100 ppm, with physical-chemical characteristics similar to those of distilled water. It is obtained by sterilization of a mixture of deuterium depleted water, with a 25 ppm isotopic concentration, with distilled water in a volume ratio of 4:6. Unlike natural immunity boosters (bacterial agents as Bacillus Chalmette-Guerin, Corynebacterium parvum; lipopolysaccharides; human immunoglobulin) or synthetical products (levamysol; isoprinosyne with immunostimulating action), which cause hypersensitivity and shocks, thrill, fever, sickness and the immunity complex disease, the water of 100 ppm D/(D + H) isotopic concentration is a toxicity free product. The testing for immune reaction of the immunity booster led to the following results: - an increase of cell action capacity in the first immunity shielding stage (macrophages), as evidenced by stimulation of a number of essential characterizing parameters, as well as of the phagocytosis capacity, bactericide capacity, and opsonic capacity of serum; - an increase of the number of leucocyte particularly of the granulocyte in peripheral blood, produced especially when medullar toxic agents like caryolysine are used; - it hinders the effect of lowering the number of erythrocytes in peripheral blood produced by experimentally induced chronic inflammation; - an increase of nonspecific immunity defence capacity against specific bacterial aggression of both Gram-positive bacteria (Streptococcus pneumoniae 558 ) and of the Gram-negative ones (Klebsiella pneumoniae 507 ); - an increase of immunity - stimulating activity (proinflamatory), like that of levamisole as evidenced by the test of stimulation of experimentally induced inflammation by means of carrageenan. The following advantages of the immunity booster are stressed: - it is toxicity free and side effect free; - can be orally administrated as

The timing of the immune response in relation to virus growth determines the outcome of the LCM infection

DEFF Research Database (Denmark)

Thomsen, Allan Randrup; Volkert, M; Marker, O

1979-01-01

. The results showed a definite correlation between the brain virus titre at the time of the immune attack and the clinical outcome of the LCM infection. Furthermore, the results indicated that the extent of the extraneural infection is not unimportant but may affect the outcome of the infection through......In the present study earlier observations of a dual role of the immune response against lymphocytic choriomeningitis (LCM) virus were confirmed and extended. At different times after intracerebral (i.c.) inoculation of the virus, groups of immunosuppressed recipients were transplanted with primary...

Creating a FIESTA (Framework for Integrated Earth Science and Technology Applications) with MagIC

Science.gov (United States)

Minnett, R.; Koppers, A. A. P.; Jarboe, N.; Tauxe, L.; Constable, C.

2017-12-01

The Magnetics Information Consortium (https://earthref.org/MagIC) has recently developed a containerized web application to considerably reduce the friction in contributing, exploring and combining valuable and complex datasets for the paleo-, geo- and rock magnetic scientific community. The data produced in this scientific domain are inherently hierarchical and the communities evolving approaches to this scientific workflow, from sampling to taking measurements to multiple levels of interpretations, require a large and flexible data model to adequately annotate the results and ensure reproducibility. Historically, contributing such detail in a consistent format has been prohibitively time consuming and often resulted in only publishing the highly derived interpretations. The new open-source (https://github.com/earthref/MagIC) application provides a flexible upload tool integrated with the data model to easily create a validated contribution and a powerful search interface for discovering datasets and combining them to enable transformative science. MagIC is hosted at EarthRef.org along with several interdisciplinary geoscience databases. A FIESTA (Framework for Integrated Earth Science and Technology Applications) is being created by generalizing MagIC's web application for reuse in other domains. The application relies on a single configuration document that describes the routing, data model, component settings and external services integrations. The container hosts an isomorphic Meteor JavaScript application, MongoDB database and ElasticSearch search engine. Multiple containers can be configured as microservices to serve portions of the application or rely on externally hosted MongoDB, ElasticSearch, or third-party services to efficiently scale computational demands. FIESTA is particularly well suited for many Earth Science disciplines with its flexible data model, mapping, account management, upload tool to private workspaces, reference metadata, image

The commensal microbiota drives immune homeostasis

Directory of Open Access Journals (Sweden)

Marie-Claire eArrieta

2012-03-01

Full Text Available For millions of years, microbes have coexisted with eukaryotic cells at the mucosal surfaces of vertebrates in a complex, yet usually harmonious symbiosis. An ever-expanding number of reports describe how eliminating or shifting the intestinal microbiota has profound effects on the development and functionality of the mucosal and systemic immune systems. Here, we examine some of the mechanisms by which bacterial signals affect immune homeostasis. Focusing on the strategies that microbes use to keep our immune system healthy, as opposed to trying to correct the immune imbalances caused by dysbiosis, may prove to be a more astute and efficient way of treating immune-mediated disease.

The seroprevalence of human papillomavirus by immune status and by ethnicity in London

Directory of Open Access Journals (Sweden)

Harwood Catherine

2009-09-01

Full Text Available Abstract Background The natural history of cutaneous HPV is unclear and in particular, seroprevalence among individuals with different levels of immune function and ethnicity is unknown. As part of a study of cutaneous squamous cell carcinoma (SCC and HPV among organ transplant recipients (OTR from London, we investigated the seroprevalence and risk factors for 34 HPV types (detected using Luminex technology among 409 OTR patients without skin cancer (243 Caucasians and 166 non-Caucasians, 367 individuals with end stage renal failure on dialysis (222 Caucasians and 145 non-Caucasians and 152 immunocompetent (IC individuals without skin cancer (102 Caucasians and 50 non-Caucasians to compare the HPV seroprevalence in patients with differing immune status and ethnicity. In total, seroprevalence data from 928 individuals, all from London, was available. Results Overall, no difference between HPV seroprevalence by immune status was observed (P = 0.3 among Caucasian or among non-Caucasian individuals, with seroprevalence varying from 87% to 94% across different immune status and ethnic groups. Those individuals seropositive to multiple types of one genus were more likely to be seroreactive to multiple types of another genus, independent of immune status or ethnicity. Lower seroprevalence for gammaHPV 4, and to a lesser extent gammaHPV 48, were observed among OTR compared to IC and dialysis patients. Higher seroprevalence against antibodies to betaHPV 93 were detected more frequently in non-Caucasians than Caucasians whereas muHPV 1 and, to a lesser extent, gammaHPV 4 were found more frequently among Caucasians - these findings were independent of immune status. Within non-Caucasian subgroups, the seroprevalence of 8 HPV (alpha-mucosal HPV16 and 13, alpha-cutaneous HPV7 and 2, betaHPV8, 17, 23 and 38 was significantly (P Conclusion We did not observe major disturbance in antibody response between immunocompetent, dialysis and OTR individuals, but

Induction of complex immune responses and strong protection against retrovirus challenge by adenovirus-based immunization depends on the order of vaccine delivery.

Science.gov (United States)

Kaulfuß, Meike; Wensing, Ina; Windmann, Sonja; Hrycak, Camilla Patrizia; Bayer, Wibke

2017-02-06

In the Friend retrovirus mouse model we developed potent adenovirus-based vaccines that were designed to induce either strong Friend virus GagL 85-93 -specific CD8 + T cell or antibody responses, respectively. To optimize the immunization outcome we evaluated vaccination strategies using combinations of these vaccines. While the vaccines on their own confer strong protection from a subsequent Friend virus challenge, the simple combination of the vaccines for the establishment of an optimized immunization protocol did not result in a further improvement of vaccine effectivity. We demonstrate that the co-immunization with GagL 85-93 /leader-gag encoding vectors together with envelope-encoding vectors abrogates the induction of GagL 85-93 -specific CD8 + T cells, and in successive immunization protocols the immunization with the GagL 85-93 /leader-gag encoding vector had to precede the immunization with an envelope encoding vector for the efficient induction of GagL 85-93 -specific CD8 + T cells. Importantly, the antibody response to envelope was in fact enhanced when the mice were adenovirus-experienced from a prior immunization, highlighting the expedience of this approach. To circumvent the immunosuppressive effect of envelope on immune responses to simultaneously or subsequently administered immunogens, we developed a two immunizations-based vaccination protocol that induces strong immune responses and confers robust protection of highly Friend virus-susceptible mice from a lethal Friend virus challenge.

Relating illness complexity to reimbursement in CKD patients

Directory of Open Access Journals (Sweden)

Bessette RW

2011-09-01

Full Text Available Russell W Bessette1, Randy L Carter2,3 1Department of Health Sciences, Institute for Healthcare Informatics, 2Department of Biostatistics, 3Population Health Observatory, University at Buffalo, State University of New York, Buffalo, NY, USA Background: Despite significant investments of federal and state dollars to transition patient medical records to an all-electronic system, a chasm still exists between health care quality and payment for it. A major reason for this gap is the difficulty in evaluating health care outcomes based on claims data. Since both payers and patients may not appreciate how illness complexity impacts treatment outcomes, it is difficult to determine fair provider compensation. Objectives: Chronic kidney disease (CKD typifies these problems and is often associated with comorbidities that impact cost, health, and work productivity. Thus, the objective of this study was to evaluate an illness complexity score (ICS based on a linear regression of select blood values that might assist in predicting average monthly reimbursements in CKD patients. A second objective was to compare the results of this ICS prediction to results obtained by prediction of average monthly reimbursement using CKD stage. A third objective was to analyze the relationship between the change in ICS, estimated glomerular filtration rate (eGFR, and CKD stage over time to average monthly reimbursement. Methods: We calculated parsimonious values for select variables associated with CKD patients and compared the ICS to ordinal staging of renal disease. Data from 177 de-identified patients over 13 months was collected, which included 15 blood chemistry observations along with complete claims data for all medical expenses. To test for the relationship between average blood chemistry values, stages of CKD, age, and average monthly reimbursement, we modeled an association through a linear regression function of age, eGFR, and the Z-scores calculated from average

Development of an ASD IC for the Micro Pixel Chamber

CERN Document Server

Orito, R; Kubo, H; Miuchi, K; Nagayoshi, T; Okada, Y; Takada, A; Takeda, A; Tanimori, T; Ueno, M

2004-01-01

A new amplifier-shaper-discriminator (ASD) chip was designed and manufactured for the Micro Pixel Chamber ($\\mu$-PIC). The design of this ASD IC is based on the ASD IC (TGC-ASD) for the Thin Gap Chamber in the LHC Atlas Experiment. The decay time constant of the preamplifier is 5-times longer than that of the TGC-ASD, and some other modifications have been made in order to improve the signal-to-noise ratio of the $\\mu$-PIC. The ASD IC uses SONY Analog Master Slice bipolar technology. The IC contains 4 channels in a QFP48 package. The decay time constant of the preamplifier is 80 ns and its gain is approximately 0.8 V/pC. The output from the preamplifier is received by a shaper (main-amplifier) with a gain of 7. A baseline restoration circuit is incorporated in the main-amplifier, and the current used for the baseline restoration is 5-times smaller than that of the TGC-ASD. The threshold voltage for the discriminator section is common to the 4 channels and their digital output level is LVDS-compatible. The ASD...

Impact of Pharmacist Immunization Authority on Seasonal Influenza Immunization Rates Across States.

Science.gov (United States)

Drozd, Edward M; Miller, Laura; Johnsrud, Michael

2017-08-01

The goal of this study was to investigate the impact on immunization rates of policy changes that allowed pharmacists to administer influenza immunizations across the United States. Influenza immunization rates across states were compared before and after policy changes permitting pharmacists to administer influenza immunizations. The study used Behavioral Risk Factor Surveillance System (BRFSS) survey data on influenza immunization rates between 2003 and 2013. Logistic regression models were constructed and incorporated adjustments for the complex sample design of the BRFSS to predict the likelihood of a person receiving an influenza immunization based on various patient health, demographic, and access to care factors. Overall, as states moved to allow pharmacists to administer influenza immunizations, the odds that an adult resident received an influenza immunization rose, with the effect increasing over time. The average percentage of people receiving influenza immunizations in states was 35.1%, rising from 32.2% in 2003 to 40.3% in 2013. The policy changes were associated with a long-term increase of 2.2% to 7.6% in the number of adults aged 25 to 59 years receiving an influenza immunization (largest for those aged 35-39 years) and no significant change for those younger or older. These findings suggest that pharmacies and other nontraditional settings may offer accessible venues for patients when implementing other public health initiatives. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The H II regions of IC 1613

International Nuclear Information System (INIS)

Hodge, P.; Lee, M.G.; Gurwell, M.

1990-01-01

Narrow-band CCD H-alpha imaging of the Local Group irregular galaxy IC 1613 has revealed a total of 77 H II regions, five of which are complexes of several smaller emission regions. Positions, H-alpha luminosities, and sizes of these objects are tabulated. The H-alpha luminosity function has the same shape as that for more luminous galaxies, following a power law with an exponent of -1.6. The faintest H II regions are at the low-luminosity end of the generally observed luminosity function for H II regions in galaxies, with fluxes of only 10 to the 35th erg/sec. The size distribution has an exponential shape, as for other galaxies, with a size scale of 56 pc. The morphologies of different H II regions are discussed and compared to those in other galaxies. Published radio continuum maps compare well with the H-alpha emission distribution. The distribution of H I is also similar in the central areas to the H II with, however, a tendency for the H II regions to lie to one side of H I peaks. 31 refs

Understanding the function and dysfunction of the immune system in lung cancer: the role of immune checkpoints.

Science.gov (United States)

Karachaliou, Niki; Cao, Maria Gonzalez; Teixidó, Cristina; Viteri, Santiago; Morales-Espinosa, Daniela; Santarpia, Mariacarmela; Rosell, Rafael

2015-06-01

Survival rates for metastatic lung cancer, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), are poor with 5-year survivals of less than 5%. The immune system has an intricate and complex relationship with tumorigenesis; a groundswell of research on the immune system is leading to greater understanding of how cancer progresses and presenting new ways to halt disease progress. Due to the extraordinary power of the immune system-with its capacity for memory, exquisite specificity and central and universal role in human biology-immunotherapy has the potential to achieve complete, long-lasting remissions and cures, with few side effects for any cancer patient, regardless of cancer type. As a result, a range of cancer therapies are under development that work by turning our own immune cells against tumors. However deeper understanding of the complexity of immunomodulation by tumors is key to the development of effective immunotherapies, especially in lung cancer.

Understanding the function and dysfunction of the immune system in lung cancer: the role of immune checkpoints

International Nuclear Information System (INIS)

Karachaliou, Niki; Cao, Maria Gonzalez; Teixidó, Cristina; Viteri, Santiago; Morales-Espinosa, Daniela; Santarpia, Mariacarmela; Rosell, Rafael

2015-01-01

Survival rates for metastatic lung cancer, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), are poor with 5-year survivals of less than 5%. The immune system has an intricate and complex relationship with tumorigenesis; a groundswell of research on the immune system is leading to greater understanding of how cancer progresses and presenting new ways to halt disease progress. Due to the extraordinary power of the immune system—with its capacity for memory, exquisite specificity and central and universal role in human biology—immunotherapy has the potential to achieve complete, long-lasting remissions and cures, with few side effects for any cancer patient, regardless of cancer type. As a result, a range of cancer therapies are under development that work by turning our own immune cells against tumors. However deeper understanding of the complexity of immunomodulation by tumors is key to the development of effective immunotherapies, especially in lung cancer

The integrated circuit IC EMP transient state disturbance effect experiment method investigates

International Nuclear Information System (INIS)

Li Xiaowei

2004-01-01

Transient state disturbance characteristic study on the integrated circuit, IC, need from its coupling path outset. Through cable (aerial) coupling, EMP converts to an pulse current voltage and results in the impact to the integrated circuit I/O orifice passing the cable. Aiming at the armament system construction feature, EMP effect to the integrated circuit, IC inside the system is analyzed. The integrated circuit, IC EMP effect experiment current injection method is investigated and a few experiments method is given. (authors)

Use of advanced commercial ICs (COTS) for space application

International Nuclear Information System (INIS)

Strobel, D.J.; Czajkowski, D.R.; Layton, P.; Shanken, S.

1999-01-01

A product line of space-qualified radiation-tolerant ICs based on a high-volume commercial-off-the-shelf (COTS) silicon has been developed. The basic results from over 300 lots of COTS silicon, assembled and screened to Class B and Class S requirements will be presented. Intelligent use of commercial ICs engineered to improve radiation performance, is effective in introducing advanced technology to new satellite systems. Space Electronics has introduced over 125 space-qualified microelectronics standard products, that are used on over 90 space projects. (authors)

Moving from irrelevant intellectual capital (IC) reporting to value-relevant IC disclosures: key learning points from the Danish experience

DEFF Research Database (Denmark)

Schaper, Stefan; Nielsen, Christian; Roslender, Robin

2017-01-01

, largely informed by an accounting perspective, towards IC-related disclosures. Design/methodology/approach – The paper draws on data obtained from 21 semi-structured interviews with respondents in 16 companies. The respondents were contacted following a genealogical exercise carried out on the 102...... with a recognised reporting vehicle such as the annual report, were also encountered. Research limitations/implications – The implications of this study are that timely, value-relevant IC disclosures and compliant reporting, primarily for accountability purposes, have the potential to coexist. In addition...... to the usual limitations of a semi-structured interview research design, respondents’ difficulties in clearly recalling events during the project after some 10-12 years is a further potential limitation. Additionally, the use of internet-based communication channels for disclosure purposes was in its infancy...

Half-Sandwich Ru(II and Os(II Bathophenanthroline Complexes Containing a Releasable Dichloroacetato Ligand

Directory of Open Access Journals (Sweden)

Pavel Štarha

2018-02-01

Full Text Available We report on the preparation and thorough characterization of cytotoxic half-sandwich complexes [Ru(η6-pcym(bphen(dca]PF6 (Ru-dca and [Os(η6-pcym(bphen(dca]PF6 (Os-dca containing dichloroacetate(1– (dca as the releasable O-donor ligand bearing its own cytotoxicity; pcym = 1-methyl-4-(propan-2-ylbenzene (p-cymene, bphen = 4,7-diphenyl-1,10-phenanthroline (bathophenanthroline. Complexes Ru-dca and Os-dca hydrolyzed in the water-containing media, which led to the dca ligand release (supported by 1H NMR and electrospray ionization mass spectra. Mass spectrometry studies revealed that complexes Ru-dca and Os-dca do not interact covalently with the model proteins cytochrome c and lysozyme. Both complexes exhibited slightly higher in vitro cytotoxicity (IC50 = 3.5 μM for Ru-dca, and 2.6 μM for Os-dca against the A2780 human ovarian carcinoma cells than cisplatin (IC50 = 5.9 μM, while their toxicity on the healthy human hepatocytes was found to be IC50 = 19.1 μM for Ru-dca and IC50 = 19.7 μM for Os-dca. Despite comparable cytotoxicity of complexes Ru-dca and Os-dca, both the complexes modified the cell cycle, mitochondrial membrane potential, and mitochondrial cytochrome c release by a different way, as revealed by flow cytometry experiments. The obtained results point out the different mechanisms of action between the complexes.

Immunization of Epidemics in Multiplex Networks

Science.gov (United States)

Zhao, Dawei; Wang, Lianhai; Li, Shudong; Wang, Zhen; Wang, Lin; Gao, Bo

2014-01-01

Up to now, immunization of disease propagation has attracted great attention in both theoretical and experimental researches. However, vast majority of existing achievements are limited to the simple assumption of single layer networked population, which seems obviously inconsistent with recent development of complex network theory: each node could possess multiple roles in different topology connections. Inspired by this fact, we here propose the immunization strategies on multiplex networks, including multiplex node-based random (targeted) immunization and layer node-based random (targeted) immunization. With the theory of generating function, theoretical analysis is developed to calculate the immunization threshold, which is regarded as the most critical index for the effectiveness of addressed immunization strategies. Interestingly, both types of random immunization strategies show more efficiency in controlling disease spreading on multiplex Erdös-Rényi (ER) random networks; while targeted immunization strategies provide better protection on multiplex scale-free (SF) networks. PMID:25401755

Immunization of epidemics in multiplex networks.

Science.gov (United States)

Zhao, Dawei; Wang, Lianhai; Li, Shudong; Wang, Zhen; Wang, Lin; Gao, Bo

2014-01-01

Up to now, immunization of disease propagation has attracted great attention in both theoretical and experimental researches. However, vast majority of existing achievements are limited to the simple assumption of single layer networked population, which seems obviously inconsistent with recent development of complex network theory: each node could possess multiple roles in different topology connections. Inspired by this fact, we here propose the immunization strategies on multiplex networks, including multiplex node-based random (targeted) immunization and layer node-based random (targeted) immunization. With the theory of generating function, theoretical analysis is developed to calculate the immunization threshold, which is regarded as the most critical index for the effectiveness of addressed immunization strategies. Interestingly, both types of random immunization strategies show more efficiency in controlling disease spreading on multiplex Erdös-Rényi (ER) random networks; while targeted immunization strategies provide better protection on multiplex scale-free (SF) networks.

Targeting of Escherichia coli F4 fimbriae to Fcgamma receptors enhances the maturation of porcine dendritic cells.

Science.gov (United States)

Devriendt, Bert; Verdonck, Frank; Summerfield, Artur; Goddeeris, Bruno M; Cox, Eric

2010-06-15

F4(+) enterotoxigenic Escherichia coli (ETEC) infections are an important cause of postweaning diarrhoea in piglets and an oral immunization of piglets with purified F4 fimbriae protects them from a subsequent F4(+) ETEC infection. However, oral immunization of suckling piglets is hampered due to the immature status of their immune system. Targeting of antigens to Fcgamma receptors (FcgammaR) on human and murine dendritic cells (DC) has been shown to enhance DC maturation and both humoral and cellular immune responses. To investigate the effect of F4 fimbriae incorporated in immune complexes (F4-IC) on porcine DC, we used porcine monocytic-derived DC (MoDC) as a model system. The results in this study demonstrate that FcgammaRI, II and III mRNA is expressed by porcine MoDC. Furthermore, we show that FcgammaRII and III are expressed on the cell surface and that F4-IC are internalized by MoDC via FcgammaR. This FcgammaR ligation induced a significantly enhanced expression of Major Histocompatibility complex (MHCII) class II and the costimulatory molecules CD80/86 and CD40 by MoDC compared with immature MoDC. Furthermore, the phagocytic capacity of F4-IC stimulated MoDC was reduced as evidenced by a reduced uptake of DQ-ovalbumin and FITC-dextran. In an allogenic and autologous mixed lymphocyte reaction, these F4-IC-activated MoDC showed an improved T cell stimulatory capacity in comparison with immature MoDC. The F4-IC induced DC maturation correlated with significant higher expression levels of several pro-inflammatory cytokines such as interleukine (IL) 1beta, IL-6 and Tumor necrosis factor alpha, the chemokine IL-8 and IL-12p40 in comparison with immature MoDC. Altogether, these results clearly demonstrate that FcgammaR engagement enhances the maturation of porcine MoDC, which may suggest that antigen targeting to FcgammaR on DC could improve vaccine design against infections. Copyright 2009 Elsevier B.V. All rights reserved.

Curating the innate immunity interactome.

LENUS (Irish Health Repository)

Lynn, David J

2010-01-01

The innate immune response is the first line of defence against invading pathogens and is regulated by complex signalling and transcriptional networks. Systems biology approaches promise to shed new light on the regulation of innate immunity through the analysis and modelling of these networks. A key initial step in this process is the contextual cataloguing of the components of this system and the molecular interactions that comprise these networks. InnateDB (http:\\/\\/www.innatedb.com) is a molecular interaction and pathway database developed to facilitate systems-level analyses of innate immunity.

Innovative Teaching of IC Design and Manufacture Using the Superchip Platform

Science.gov (United States)

Wilson, P. R.; Wilcock, R.; McNally, I.; Swabey, M.

2010-01-01

This paper describes how an intelligent chip architecture has allowed a large cohort of undergraduate (UG) students to be given effective practical insight into integrated circuit (IC) design by designing and manufacturing their own ICs. To achieve this, an efficient chip architecture, the "Superchip," was developed, which allows multiple student…

The most common friend first immunization

International Nuclear Information System (INIS)

Nian Fu-Zhong; Hu Cha-Sheng

2016-01-01

In this paper, a standard susceptible-infected-recovered-susceptible(SIRS) epidemic model based on the Watts–Strogatz (WS) small-world network model and the Barabsi–Albert (BA) scale-free network model is established, and a new immunization scheme — “the most common friend first immunization” is proposed, in which the most common friend’s node is described as being the first immune on the second layer protection of complex networks. The propagation situations of three different immunization schemes — random immunization, high-risk immunization, and the most common friend first immunization are studied. At the same time, the dynamic behaviors are also studied on the WS small-world and the BA scale-free network. Moreover, the analytic and simulated results indicate that the immune effect of the most common friend first immunization is better than random immunization, but slightly worse than high-risk immunization. However, high-risk immunization still has some limitations. For example, it is difficult to accurately define who a direct neighbor in the life is. Compared with the traditional immunization strategies having some shortcomings, the most common friend first immunization is effective, and it is nicely consistent with the actual situation. (paper)

STAR FORMATION ACROSS THE W3 COMPLEX

Energy Technology Data Exchange (ETDEWEB)

Román-Zúñiga, Carlos G.; Ybarra, Jason E.; Tapia, Mauricio [Instituto de Astronomía, Universidad Nacional Autónoma de México, Unidad Académica en Ensenada, Km 103 Carr. Tijuana–Ensenada, Ensenada 22860 (Mexico); Megías, Guillermo D. [Facultad de Física. Universidad de Sevilla. Dpto. Física Atómica, Molecular y Nuclear, Sevilla, E-41080 (Spain); Lada, Elizabeth A. [Astronomy Department, University of Florida, 211 Bryant Space Sciences Center, FL 32611 (United States); Alves, Joáo F. [Institute of Astronomy, University of Vienna, Türkenschanzstr. 17, A-1180 Vienna (Austria)

2015-09-15

We present a multi-wavelength analysis of the history of star formation in the W3 complex. Using deep, near-infrared ground-based images combined with images obtained with Spitzer and Chandra observatories, we identified and classified young embedded sources. We identified the principal clusters in the complex and determined their structure and extension. We constructed extinction-limited samples for five principal clusters and constructed K-band luminosity functions that we compare with those of artificial clusters with varying ages. This analysis provided mean ages and possible age spreads for the clusters. We found that IC 1795, the centermost cluster of the complex, still hosts a large fraction of young sources with circumstellar disks. This indicates that star formation was active in IC 1795 as recently as 2 Myr ago, simultaneous to the star-forming activity in the flanking embedded clusters, W3-Main and W3(OH). A comparison with carbon monoxide emission maps indicates strong velocity gradients in the gas clumps hosting W3-Main and W3(OH) and shows small receding clumps of gas at IC 1795, suggestive of rapid gas removal (faster than the T Tauri timescale) in the cluster-forming regions. We discuss one possible scenario for the progression of cluster formation in the W3 complex. We propose that early processes of gas collapse in the main structure of the complex could have defined the progression of cluster formation across the complex with relatively small age differences from one group to another. However, triggering effects could act as catalysts for enhanced efficiency of formation at a local level, in agreement with previous studies.

[Molecular dynamics of immune complex of photoadduct-containing DNA with Fab-Anti-DNA antibody fragment].

Science.gov (United States)

Akberova, N I; Zhmurov, A A; Nevzorova, T A; Litvinov, R I

2016-01-01

Antibodies to DNA play an important role in the pathogenesis of autoimmune diseases. The elucidation of structural mechanisms of both the antigen recognition and the interaction of anti-DNA antibodies with DNA will help to understand the role of DNA-containing immune complexes in various pathologies and can provide a basis for new treatment modalities. Moreover, the DNA-antibody complex is an analog of specific intracellular DNA-protein interactions. In this work, we used in silico molecular dynamic simulations of bimolecular complexes of the dsDNA segment containing the Fab fragment of an anti-DNA antibody to obtain the detailed thermodynamic and structural characteristics of dynamic intermolecular interactions. Using computationally modified crystal structure of the Fab-DNA complex (PDB ID: 3VW3), we studied the equilibrium molecular dynamics of the 64M-5 antibody Fab fragment associated with the dsDNA fragment containing the thymine dimer, the product of DNA photodamage. Amino acid residues that constitute paratopes and the complementary nucleotide epitopes for the Fab-DNA construct were identified. Stacking and electrostatic interactions were found to play the main role in mediating the most specific antibody-dsDNA contacts, while hydrogen bonds were less significant. These findings may shed light on the formation and properties of pathogenic anti-DNA antibodies in autoimmune diseases, such as systemic lupus erythematosus associated with skin photosensitivity and DNA photodamage.

Purification, crystallization and preliminary X-ray analysis of aminoglycoside-2′′-phosphotransferase-Ic [APH(2′′)-Ic] from Enterococcus gallinarum

International Nuclear Information System (INIS)

Byrnes, Laura J.; Badarau, Adriana; Vakulenko, Sergei B.; Smith, Clyde A.

2008-01-01

APH(2′′)-Ic is an enzyme that is responsible for high-level gentamicin resistance in E. gallinarum isolates. Crystals of the wild-type enzyme and three mutants have been prepared and a complete X-ray diffraction data set was collected to 2.15 Å resolution from an F108L crystal. Bacterial resistance to aminoglycoside antibiotics is primarily the result of deactivation of the drugs. Three families of enzymes are responsible for this activity, with one such family being the aminoglycoside phosphotransferases (APHs). The gene encoding one of these enzymes, aminoglycoside-2′′-phosphotransferase-Ic [APH(2′′)-Ic] from Enterococcus gallinarum, has been cloned and the wild-type protein (comprising 308 amino-acid residues) and three mutants that showed elevated minimum inhibitory concentrations towards gentamicin (F108L, H258L and a double mutant F108L/H258L) were expressed in Escherichia coli and subsequently purified. All APH(2′′)-Ic variants were crystallized in the presence of 14–20%(w/v) PEG 4000, 0.25 M MgCl 2 , 0.1 M Tris–HCl pH 8.5 and 1 mM Mg 2 GTP. The crystals belong to the monoclinic space group C2, with one molecule in the asymmetric unit. The approximate unit-cell parameters are a = 82.4, b = 54.2, c = 77.0 Å, β = 108.8°. X-ray diffraction data were collected to approximately 2.15 Å resolution from an F108L crystal at beamline BL9-2 at SSRL, Stanford, California, USA

Phospholipase C-β in immune cells.

Science.gov (United States)

Kawakami, Toshiaki; Xiao, Wenbin

2013-09-01

Great progress has recently been made in structural and functional research of phospholipase C (PLC)-β. We now understand how PLC-β isoforms (β1-β4) are activated by GTP-bound Gαq downstream of G protein-coupled receptors. Numerous studies indicate that PLC-βs participate in the differentiation and activation of immune cells that control both the innate and adaptive immune systems. The PLC-β3 isoform also interplays with tyrosine kinase-based signaling pathways, to inhibit Stat5 activation by recruiting the protein-tyrosine phosphatase SHP-1, with which PLC-β3 and Stat5 form a multi-molecular signaling platform, named SPS complex. The SPS complex has important regulatory roles in tumorigenesis and immune cell activation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pregnancy immunology: decidual immune cells.

Science.gov (United States)

Sanguansermsri, Donruedee; Pongcharoen, Sutatip

2008-01-01

Human pregnancy is a complex process. Placental development depends on the function of secretory molecules produced by placental trophoblast cells as well as by maternal uterine immune cells within the decidua. These decidual immune cells are T cells, natural killer cells, macrophages and dendritic cells. The interactions between the trophoblast cells and the maternal immune cells have an impact on the outcome of the pregnancy. Knowledge about the phenotypes and functions of the maternal immune cells in normal and pathological pregnancies including recurrent spontaneous abortions, preeclampsia and hydatidiform moles may improve our understanding of the immunobiology of the normal pregnancy as a whole and may provide approaches for improving the treatment of pathological pregnancies.

Insect Immunity: The Post-Genomic Era

OpenAIRE

Bangham, Jenny; Jiggins, Frank; Lemaitre, Bruno

2006-01-01

Insects have a complex and effective immune system, many components of which are conserved in mammals. But only in the last decade have the molecular mechanisms that regulate the insect immune response--and their relevance to general biology and human immunology--become fully appreciated. A meeting supported by the Centre National de la Récherche Scientifique (France) was held to bring together the whole spectrum of researchers working on insect immunity. The meeting addressed diverse aspects...

Transient SEU characterization of analog IC's for ESA's satellite

International Nuclear Information System (INIS)

Harboe-Soerensen, R.; Van Dooren, J.; Guerre, F.X.; Constans, H.; Berger, G.; Hajdas, W.

1999-01-01

Data analysis of four self switch-off power supply events in the SOHO satellite pointed strongly in the direction of being Cosmic Ray or Proton induced. Further analysis of the relevant power supply schematics identified a number of analog IC's capable of causing or contributing to such events. This paper concentrates on the testing aspects of these analog IC's and presents the results of a Single Event Effects (SEEs) test program. Ground testing, simulating the flight conditions, were carried out at both heavy ion and proton accelerators. (authors)

Classification of fMRI independent components using IC-fingerprints and support vector machine classifiers.

Science.gov (United States)

De Martino, Federico; Gentile, Francesco; Esposito, Fabrizio; Balsi, Marco; Di Salle, Francesco; Goebel, Rainer; Formisano, Elia

2007-01-01

We present a general method for the classification of independent components (ICs) extracted from functional MRI (fMRI) data sets. The method consists of two steps. In the first step, each fMRI-IC is associated with an IC-fingerprint, i.e., a representation of the component in a multidimensional space of parameters. These parameters are post hoc estimates of global properties of the ICs and are largely independent of a specific experimental design and stimulus timing. In the second step a machine learning algorithm automatically separates the IC-fingerprints into six general classes after preliminary training performed on a small subset of expert-labeled components. We illustrate this approach in a multisubject fMRI study employing visual structure-from-motion stimuli encoding faces and control random shapes. We show that: (1) IC-fingerprints are a valuable tool for the inspection, characterization and selection of fMRI-ICs and (2) automatic classifications of fMRI-ICs in new subjects present a high correspondence with those obtained by expert visual inspection of the components. Importantly, our classification procedure highlights several neurophysiologically interesting processes. The most intriguing of which is reflected, with high intra- and inter-subject reproducibility, in one IC exhibiting a transiently task-related activation in the 'face' region of the primary sensorimotor cortex. This suggests that in addition to or as part of the mirror system, somatotopic regions of the sensorimotor cortex are involved in disambiguating the perception of a moving body part. Finally, we show that the same classification algorithm can be successfully applied, without re-training, to fMRI collected using acquisition parameters, stimulation modality and timing considerably different from those used for training.

Studying Radiation Tolerant ICs for LHC

CERN Multimedia

Faccio, F; Snoeys, W; Campbell, M; Casas-cubillos, J; Gomes, P

2002-01-01

%title\\\\ \\\\In the recent years, intensive work has been carried out on the development of custom ICs for the readout electronics for LHC experiments. As far as radiation hardness is concerned, attention has been focussed on high total dose applications, mainly for the tracker systems. The dose foreseen in this inner region is estimated to be higher than 1~Mrad/year. In the framework of R&D projects (RD-9 and RD-20) and in the ATLAS and CMS experiments, the study of different radiation hard processes has been pursued and good contacts with the manufacturers have been established. The results of these studies have been discussed during the Microelectronics User Group (MUG) rad-hard meetings, and now some HEP groups are working to develop radiation hard ICs for the LHC experiments on some of the available rad-hard processes.\\\\ \\\\In addition, a lot of the standard commercial electronic components and ASICs which are planned to be installed near the LHC machine and in the detectors will receive total doses in ...

Trial of using antibodies as carriers of alkylating agents. Pt. 2. Evaluation of ability to form /sup 32/P-cyclophosphamide + immune antibody complexes with homologous antigen

Energy Technology Data Exchange (ETDEWEB)

Trzeciak, J; Felus, E; Nolewajka, E; Szaflarski, J; Dudziak, Z [Slaska Akademia Medyczna, Katowice (Poland)

1976-01-01

/sup 32/P-cyclophosphamide was found to combine with ..gamma..-globulin fractions of immune sera. Immune sera incubated with /sup 32/P-cyclophosphamide retained ability to react specifically with homologou antigen in vitro in the system: MN antigens of human erythrocytes + rabbit anti-MN antibody, and probably reacted selectively with target antigens in vivo in the system: antigens of guinea pig kidney tissue + rabbit antibodies against these antigens. Hemagglutination, passive hemagglutination and precipitation in agar gel tests were used in the experiments. Ability to combine of the immune antibody + /sup 32/P-cyclophosphamide complex with homologous antigens was evaluated by measurements of radioactivity of studied materials (erythrocyte agglutinates and organ homogenates). The results indicate feasibility of using immune antibodies as carriers of cytostatic agents.

Mathematical and Simulation Modelling of Moisture Diffusion Mechanism during Plastic IC Packages Disassembly

OpenAIRE

Peng Mou; Dong Xiang; Guanghong Duan

2013-01-01

Reuse of plastic IC packages disassembled from printed circuit boards (PCBs) has significant environmental benefits and economic value. The interface delamination caused by moisture diffusion is the main failure mode of IC packages during the disassembling process, which greatly reduces the reusability and reliability of disassembled IC packages. Exploring moisture diffusion mechanism is a prerequisite to optimize prebaking processes before disassembling that is an effective way to avoid the ...

SUPER-LUMINOUS TYPE Ic SUPERNOVAE: CATCHING A MAGNETAR BY THE TAIL

International Nuclear Information System (INIS)

Inserra, C.; Smartt, S. J.; Jerkstrand, A.; Fraser, M.; Wright, D.; Smith, K.; Chen, T.-W.; Kotak, R.; Nicholl, M.; Valenti, S.; Pastorello, A.; Benetti, S.; Bresolin, F.; Kudritzki, R. P.; Burgett, W. S.; Chambers, K. C.; Flewelling, H.; Botticella, M. T.; Ergon, M.; Fynbo, J. P. U.

2013-01-01

We report extensive observational data for five of the lowest redshift Super-Luminous Type Ic Supernovae (SL-SNe Ic) discovered to date, namely, PTF10hgi, SN2011ke, PTF11rks, SN2011kf, and SN2012il. Photometric imaging of the transients at +50 to +230 days after peak combined with host galaxy subtraction reveals a luminous tail phase for four of these SL-SNe. A high-resolution, optical, and near-infrared spectrum from xshooter provides detection of a broad He I λ10830 emission line in the spectrum (+50 days) of SN2012il, revealing that at least some SL-SNe Ic are not completely helium-free. At first sight, the tail luminosity decline rates that we measure are consistent with the radioactive decay of 56 Co, and would require 1-4 M ☉ of 56 Ni to produce the luminosity. These 56 Ni masses cannot be made consistent with the short diffusion times at peak, and indeed are insufficient to power the peak luminosity. We instead favor energy deposition by newborn magnetars as the power source for these objects. A semi-analytical diffusion model with energy input from the spin-down of a magnetar reproduces the extensive light curve data well. The model predictions of ejecta velocities and temperatures which are required are in reasonable agreement with those determined from our observations. We derive magnetar energies of 0.4 ∼ 51 erg) ∼ ej (M ☉ ) ∼< 8.6. The sample of five SL-SNe Ic presented here, combined with SN 2010gx—the best sampled SL-SNe Ic so far—points toward an explosion driven by a magnetar as a viable explanation for all SL-SNe Ic.

Immunization of epidemics in multiplex networks.

Directory of Open Access Journals (Sweden)

Dawei Zhao

Full Text Available Up to now, immunization of disease propagation has attracted great attention in both theoretical and experimental researches. However, vast majority of existing achievements are limited to the simple assumption of single layer networked population, which seems obviously inconsistent with recent development of complex network theory: each node could possess multiple roles in different topology connections. Inspired by this fact, we here propose the immunization strategies on multiplex networks, including multiplex node-based random (targeted immunization and layer node-based random (targeted immunization. With the theory of generating function, theoretical analysis is developed to calculate the immunization threshold, which is regarded as the most critical index for the effectiveness of addressed immunization strategies. Interestingly, both types of random immunization strategies show more efficiency in controlling disease spreading on multiplex Erdös-Rényi (ER random networks; while targeted immunization strategies provide better protection on multiplex scale-free (SF networks.

Inactivated probiotic Bacillus coagulans GBI-30 induces complex immune activating, anti-inflammatory, and regenerative markers in vitro

Science.gov (United States)

Jensen, Gitte S; Cash, Howard A; Farmer, Sean; Keller, David

2017-01-01

Objective The aim of this study was to document the immune activating and anti-inflammatory effects of inactivated probiotic Bacillus coagulans GBI-30, 6086 (Staimune™) cells on human immune cells in vitro. Methods In vitro cultures of human peripheral blood mononuclear cells (PBMC) from healthy blood donors were treated with inactivated B. coagulans GBI-30, 6086 cells for 24 hours. After incubation, the PBMC were stained with fluorochrome-labeled monoclonal antibodies for CD3, CD56, and CD69 to monitor cellular activation by flow cytometry. The culture supernatants were tested for cytokine profile using a 27-plex Luminex array, including pro- and anti-inflammatory cytokines, chemokines, and growth factors. Results Inactivated B. coagulans GBI-30, 6086 cells induced the CD69 early activation marker on CD3+ CD56− T lymphocytes, CD3+ CD56+ NKT cells, CD3−CD56+ NK cells, and also some cells within the CD3−CD56− non-T non-NK cell subset. Culture supernatants showed robust increases in the immune-activating cytokines IL-1β, IL-6, IL-17A, and TNF-α. IFN-γ levels were increased, along with three chemokines, MCP-1, MIP-1α, and MIP-1β. The two anti-inflammatory cytokines IL-1ra and IL-10 showed increases, as well as the G-CSF growth factor involved in repair and stem cell biology. In contrast, GM-CSF levels showed a mild decrease, showing a highly selective growth factor response. Conclusion The inactivated B. coagulans GBI-30, 6086 cells activated human immune cells and altered the production of both immune activating and anti-inflammatory cytokines and chemokines. Of special importance is the novel demonstration of a selective upregulation of the G-CSF growth factor involved in postinjury and postinflammation repair and regeneration. This suggests that important immunogenic cell wall components, such as lipoteichoic acid, are undamaged after the inactivation and retain the complex beneficial biological activities previously demonstrated for the cell walls

Inactivated probiotic Bacillus coagulans GBI-30 induces complex immune activating, anti-inflammatory, and regenerative markers in vitro.

Science.gov (United States)

Jensen, Gitte S; Cash, Howard A; Farmer, Sean; Keller, David

2017-01-01

The aim of this study was to document the immune activating and anti-inflammatory effects of inactivated probiotic Bacillus coagulans GBI-30, 6086 (Staimune™) cells on human immune cells in vitro. In vitro cultures of human peripheral blood mononuclear cells (PBMC) from healthy blood donors were treated with inactivated B. coagulans GBI-30, 6086 cells for 24 hours. After incubation, the PBMC were stained with fluorochrome-labeled monoclonal antibodies for CD3, CD56, and CD69 to monitor cellular activation by flow cytometry. The culture supernatants were tested for cytokine profile using a 27-plex Luminex array, including pro- and anti-inflammatory cytokines, chemokines, and growth factors. Inactivated B. coagulans GBI-30, 6086 cells induced the CD69 early activation marker on CD3 + CD56 - T lymphocytes, CD3 + CD56 + NKT cells, CD3 - CD56 + NK cells, and also some cells within the CD3 - CD56 - non-T non-NK cell subset. Culture supernatants showed robust increases in the immune-activating cytokines IL-1β, IL-6, IL-17A, and TNF-α. IFN-γ levels were increased, along with three chemokines, MCP-1, MIP-1α, and MIP-1β. The two anti-inflammatory cytokines IL-1ra and IL-10 showed increases, as well as the G-CSF growth factor involved in repair and stem cell biology. In contrast, GM-CSF levels showed a mild decrease, showing a highly selective growth factor response. The inactivated B. coagulans GBI-30, 6086 cells activated human immune cells and altered the production of both immune activating and anti-inflammatory cytokines and chemokines. Of special importance is the novel demonstration of a selective upregulation of the G-CSF growth factor involved in postinjury and postinflammation repair and regeneration. This suggests that important immunogenic cell wall components, such as lipoteichoic acid, are undamaged after the inactivation and retain the complex beneficial biological activities previously demonstrated for the cell walls from live B. coagulans GBI-30, 6086

Immunization of chickens with an agonistic monoclonal anti-chicken CD40 antibody-hapten complex: rapid and robust IgG response induced by a single subcutaneous injection.

Science.gov (United States)

Chen, Chang-Hsin; Abi-Ghanem, Daad; Waghela, Suryakant D; Chou, Wen-Ko; Farnell, Morgan B; Mwangi, Waithaka; Berghman, Luc R

2012-04-30

Producing diagnostic antibodies in chicken egg yolk represents an alternate animal system that offers many advantages including high productivity at low cost. Despite being an excellent counterpart to mammalian antibodies, chicken IgG from yolk still represents an underused resource. The potential of agonistic monoclonal anti-CD40 antibodies (mAb) as a powerful immunological adjuvant has been demonstrated in mammals, but not in chickens. We recently reported an agonistic anti-chicken CD40 mAb (designated mAb 2C5) and showed that it may have potential as an immunological adjuvant. In this study, we examined the efficacy of targeting a short peptide to chicken CD40 [expressed by the antigen-presenting cells (APCs)] in enhancing an effective IgG response in chickens. For this purpose, an immune complex consisting of one streptavidin molecule, two directionally biotinylated mAb 2C5 molecules, and two biotinylated peptide molecules was produced. Chickens were immunized subcutaneously with doses of this complex ranging from 10 to 90 μg per injection once, and relative quantification of the peptide-specific IgG response showed that the mAb 2C5-based complex was able to elicit a strong IgG response as early as four days post-immunization. This demonstrates that CD40-targeting antigen to chicken APCs can significantly enhance antibody responses and induce immunoglobulin isotype-switching. This immunization strategy holds promise for rapid production of hapten-specific IgG in chickens. Copyright © 2012 Elsevier B.V. All rights reserved.

Requirement for C-X-C chemokines (macrophage inflammatory protein-2 and cytokine-induced neutrophil chemoattractant) in IgG immune complex-induced lung injury

DEFF Research Database (Denmark)

Shanley, T P; Schmal, H; Warner, R L

1997-01-01

chemokines, macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC). Both mRNA and protein for MIP-2 and CINC appeared in a time-dependent manner after initiation of IgG immune complex deposition in lung. There exists a 69% homology between the amino acid sequences...... for these proteins, and we found cross-reactivity between polyclonal Abs raised to these chemokines. By purifying the blocking Abs using double affinity methods (with Ag-immobilized beads), this cross-reactivity was removed. Individually, anti-MIP-2 and anti-CINC Ab significantly reduced lung injury (as measured...... activity in BAL fluids collected 2 h after injury from animals undergoing immune complex deposition could be shown to be chiefly due to the combined contributions of MIP-2 (39%), CINC (28%), and C5a (21%). When either MIP-2 or CINC was blocked in vivo, up-regulation of Mac-1 expression on neutrophils...

Challenges in IC design for hearing aids

DEFF Research Database (Denmark)

Jørgensen, Ivan Harald Holger

2012-01-01

Designing modern hearing aids is a formidable challenge. The size of hearing aids is constantly decreasing, making them virtually invisible today. Still, as in all other modern electronics, more and more features are added to these devices driven by the development in modern IC technology....... The demands for performance and features at very low supply voltage and power consumption constantly prove a challenge to the physical design of hearing aids and not at least the design of the ICs for these. As a result of this all large hearing aid manufacturers use fully customized ASICs in their products...... to produce a competitive advantage. This presentation will give a brief insight into the hearing aid market and industry, a brief view of the historic development of hearing aids and an introduction to how a modern hearing is constructed showing the amplifier as the key component in the modern hearing aid...

Simulation of design dependent failure exposure levels for CMOS ICs

International Nuclear Information System (INIS)

Kaul, N.; Bhuva, B.L.; Rangavajjhala, V.; van der Molen, H.; Kerns, S.E.

1990-01-01

The total dose exposure of CMOS ICs introduces bias-dependent parameter shifts in individual devices. The bias dependency of individual parameter shifts of devices cause different designs to behave differently under identical testing conditions. This paper studies the effect of design and bias on the radiation tolerance of ICs and presents an automated design tool that produces different designs for a logic function, and presents important parameters of each design to circuit designer for trade off analysis

A combined thermodynamic cycle based on methanol dissociation for IC (internal combustion) engine exhaust heat recovery

International Nuclear Information System (INIS)

Fu, Jianqin; Liu, Jingping; Xu, Zhengxin; Ren, Chengqin; Deng, Banglin

2013-01-01

In this paper, a novel approach for exhaust heat recovery was proposed to improve IC (internal combustion) engine fuel efficiency and also to achieve the goal for direct usage of methanol as IC engine fuel. An open organic Rankine cycle system using methanol as working medium is coupled to IC engine exhaust pipe for exhaust heat recovery. In the bottom cycle, the working medium first undergoes dissociation and expansion processes, and is then directed back to IC engine as fuel. As the external bottom cycle and the IC engine main cycle are combined together, this scheme forms a combined thermodynamic cycle. Then, this concept was applied to a turbocharged engine, and the corresponding simulation models were built for both of the external bottom cycle and the IC engine main cycle. On this basis, the energy saving potential of this combined cycle was estimated by parametric analyses. Compared to the methanol vapor engine, IC engine in-cylinder efficiency has an increase of 1.4–2.1 percentage points under full load conditions, while the external bottom cycle can increase the fuel efficiency by 3.9–5.2 percentage points at the working pressure of 30 bar. The maximum improvement to the IC engine global fuel efficiency reaches 6.8 percentage points. - Highlights: • A combined thermodynamic cycle using methanol as working medium for IC engine exhaust heat recovery is proposed. • The external bottom cycle of exhaust heat recovery and IC engine working cycle are combined together. • IC engine fuel efficiency could be improved from both in-cylinder working cycle and external bottom cycle. • The maximum improvement to the IC engine global fuel efficiency reaches 6.8 percentage points at full load

Early nutrition and immunity - progress and perspectives

NARCIS (Netherlands)

Calder, Philip C.; Krauss-Etschmann, Susanne; de Jong, Esther C.; Dupont, Christophe; Frick, Julia-Stefanie; Frokiaer, Hanne; Heinrich, Joachim; Garn, Holger; Koletzko, Sibylle; Lack, Gideon; Mattelio, Gianluca; Renz, Harald; Sangild, Per T.; Schrezenmeir, Jürgen; Stulnig, Thomas M.; Thymann, Thomas; Wold, Agnes E.; Koletzko, Berthold

2006-01-01

The immune system exists to protect the host against pathogenic organisms and highly complex pathways of recognition, response, elimination and memory have evolved in order to fulfil this role. The immune system also acts to ensure tolerance to 'self', to food and other environmental components, and

IC3 Internet and Computing Core Certification Global Standard 4 study guide

CERN Document Server

Rusen, Ciprian Adrian

2015-01-01

Hands-on IC3 prep, with expert instruction and loads of tools IC3: Internet and Computing Core Certification Global Standard 4 Study Guide is the ideal all-in-one resource for those preparing to take the exam for the internationally-recognized IT computing fundamentals credential. Designed to help candidates pinpoint weak areas while there's still time to brush up, this book provides one hundred percent coverage of the exam objectives for all three modules of the IC3-GS4 exam. Readers will find clear, concise information, hands-on examples, and self-paced exercises that demonstrate how to per

PTF 12gzk—A rapidly declining, high-velocity type Ic radio supernova

Energy Technology Data Exchange (ETDEWEB)

Horesh, Assaf; Kulkarni, Shrinivas R. [Cahill Center for Astrophysics, California Institute of Technology, Pasadena, CA 91125 (United States); Corsi, Alessandra [Department of Physics, The George Washington University, 725 21st Street, NW, Washington, DC 20052 (United States); Frail, Dale A. [National Radio Astronomy Observatory, P.O. Box 0, Socorro, NM 87801 (United States); Cenko, S. Bradley [Department of Astronomy, University of California, Berkeley, CA 94720-3411 (United States); Ben-Ami, Sagi; Gal-Yam, Avishay; Yaron, Ofer; Arcavi, Iair; Ofek, Eran O. [Department of Particle Physics and Astrophysics, The Weizmann Institute of Science, Rehovot 76100 (Israel); Kasliwal, Mansi M. [Carnegie Institution for Science, Department of Terrestrial Magnetism, 5241 Broad Branch Road, Washington, DC 20008 (United States)

2013-11-20

Only a few cases of Type Ic supernovae (SNe) with high-velocity ejecta (≥0.2 c) have been discovered and studied. Here, we present our analysis of radio and X-ray observations of the Type Ic SN PTF 12gzk. The radio emission declined less than 10 days after explosion, suggesting SN ejecta expanding at high velocity (∼0.3 c). The radio data also indicate that the density of the circumstellar material (CSM) around the supernova is lower by a factor of ∼10 than the CSM around normal Type Ic SNe. PTF 12gzk may therefore be an intermediate event between a 'normal' SN Ic and a gamma-ray-burst-SN-like event. Our observations of this rapidly declining radio SN at a distance of 58 Mpc demonstrates the potential to detect many additional radio SNe, given the new capabilities of the Very Large Array (improved sensitivity and dynamic scheduling), which are currently missed, leading to a biased view of radio SNe Ic. Early optical discovery followed by rapid radio observations would provide a full description of the ejecta velocity distribution and CSM densities around stripped massive star explosions as well as strong clues about the nature of their progenitor stars.

PTF 12gzk—A rapidly declining, high-velocity type Ic radio supernova

International Nuclear Information System (INIS)

Horesh, Assaf; Kulkarni, Shrinivas R.; Corsi, Alessandra; Frail, Dale A.; Cenko, S. Bradley; Ben-Ami, Sagi; Gal-Yam, Avishay; Yaron, Ofer; Arcavi, Iair; Ofek, Eran O.; Kasliwal, Mansi M.

2013-01-01

Only a few cases of Type Ic supernovae (SNe) with high-velocity ejecta (≥0.2 c) have been discovered and studied. Here, we present our analysis of radio and X-ray observations of the Type Ic SN PTF 12gzk. The radio emission declined less than 10 days after explosion, suggesting SN ejecta expanding at high velocity (∼0.3 c). The radio data also indicate that the density of the circumstellar material (CSM) around the supernova is lower by a factor of ∼10 than the CSM around normal Type Ic SNe. PTF 12gzk may therefore be an intermediate event between a 'normal' SN Ic and a gamma-ray-burst-SN-like event. Our observations of this rapidly declining radio SN at a distance of 58 Mpc demonstrates the potential to detect many additional radio SNe, given the new capabilities of the Very Large Array (improved sensitivity and dynamic scheduling), which are currently missed, leading to a biased view of radio SNe Ic. Early optical discovery followed by rapid radio observations would provide a full description of the ejecta velocity distribution and CSM densities around stripped massive star explosions as well as strong clues about the nature of their progenitor stars.

Staphylococcus aureus innate immune evasion is lineage-specific: a bioinfomatics study.

Science.gov (United States)

McCarthy, Alex J; Lindsay, Jodi A

2013-10-01

Staphylococcus aureus is a major human pathogen, and is targeted by the host innate immune system. In response, S. aureus genomes encode dozens of secreted proteins that inhibit complement, chemotaxis and neutrophil activation resulting in successful evasion of innate immune responses. These proteins include immune evasion cluster proteins (IEC; Chp, Sak, Scn), staphylococcal superantigen-like proteins (SSLs), phenol soluble modulins (PSMs) and several leukocidins. Biochemical studies have indicated that genetic variants of these proteins can have unique functions. To ascertain the scale of genetic variation in secreted immune evasion proteins, whole genome sequences of 88 S. aureus isolates, representing 25 clonal complex (CC) lineages, in the public domain were analysed across 43 genes encoding 38 secreted innate immune evasion protein complexes. Twenty-three genes were variable, with between 2 and 15 variants, and the variants had lineage-specific distributions. They include genes encoding Eap, Ecb, Efb, Flipr/Flipr-like, Hla, Hld, Hlg, Sbi, Scin-B/C and 13 SSLs. Most of these protein complexes inhibit complement, chemotaxis and neutrophil activation suggesting that isolates from each S. aureus lineage respond to the innate immune system differently. In contrast, protein complexes that lyse neutrophils (LukSF-PVL, LukMF, LukED and PSMs) were highly conserved, but can be carried on mobile genetic elements (MGEs). MGEs also encode proteins with narrow host-specificities arguing that their acquisition has important roles in host/environmental adaptation. In conclusion, this data suggests that each lineage of S. aureus evades host immune responses differently, and that isolates can adapt to new host environments by acquiring MGEs and the immune evasion protein complexes that they encode. Cocktail therapeutics that targets multiple variant proteins may be the most appropriate strategy for controlling S. aureus infections. Copyright © 2013 Elsevier B.V. All rights

The Immune Epitope Database 2.0

DEFF Research Database (Denmark)

Hoof, Ilka; Vita, R; Zarebski, L

2010-01-01

The Immune Epitope Database (IEDB, www.iedb.org) provides a catalog of experimentally characterized B and T cell epitopes, as well as data on Major Histocompatibility Complex (MHC) binding and MHC ligand elution experiments. The database represents the molecular structures recognized by adaptive...... immune receptors and the experimental contexts in which these molecules were determined to be immune epitopes. Epitopes recognized in humans, nonhuman primates, rodents, pigs, cats and all other tested species are included. Both positive and negative experimental results are captured. Over the course...

CMOS Analog IC Design: Fundamentals

OpenAIRE

Bruun, Erik

2018-01-01

This book is intended for use as the main textbook for an introductory course in CMOS analog integrated circuit design. It is aimed at electronics engineering students who have followed basic courses in mathematics, physics, circuit theory, electronics and signal processing. It takes the students directly from a basic level to a level where they can start working on simple analog IC design projects or continue their studies using more advanced textbooks in the field. A distinct feature of thi...

EVIDENCE FOR AN INTERACTION IN THE NEAREST STARBURSTING DWARF IRREGULAR GALAXY IC 10

International Nuclear Information System (INIS)

Nidever, David L.; Slater, Colin T.; Bell, Eric F.; Ashley, Trisha; Simpson, Caroline E.; Ott, Jürgen; Johnson, Megan; Stanimirović, Snežana; Putman, Mary; Majewski, Steven R.; Jütte, Eva; Oosterloo, Tom A.; Burton, W. Butler

2013-01-01

Using deep 21 cm H I data from the Green Bank Telescope we have detected an ≳18.3 kpc long gaseous extension associated with the starbursting dwarf galaxy IC 10. The newly found feature stretches 1.°3 to the northwest and has a large radial velocity gradient reaching to ∼65 km s –1 lower than the IC 10 systemic velocity. A region of higher column density at the end of the extension that possesses a coherent velocity gradient (∼10 km s –1 across ∼26') transverse to the extension suggests rotation and may be a satellite galaxy of IC 10. The H I mass of IC 10 is 9.5 × 10 7 (d/805 kpc) 2 M ☉ and the mass of the new extension is 7.1 × 10 5 (d/805 kpc) 2 M ☉ . An IC 10-M31 orbit using known radial velocity and proper motion values for IC 10 show that the H I extension is inconsistent with the trailing portion of the orbit so that an M31-tidal or ram pressure origin seems unlikely. We argue that the most plausible explanation for the new feature is that it is the result of a recent interaction (and possible late merger) with another dwarf galaxy. This interaction could not only have triggered the origin of the recent starburst in IC 10, but could also explain the existence of previously found counter-rotating H I gas in the periphery of the IC 10 which was interpreted as originating from primordial gas infall

Sensitive and specific detection of Crimean-Congo Hemorrhagic Fever Virus (CCHFV)—Specific IgM and IgG antibodies in human sera using recombinant CCHFV nucleoprotein as antigen in μ-capture and IgG immune complex (IC) ELISA tests

Science.gov (United States)

Emmerich, Petra; Mika, Angela; von Possel, Ronald; Rackow, Anne; Liu, Yang; Schmitz, Herbert; Sherifi, Kurtesh; Halili, Barie; Jakupi, Xhevat; Berisha, Lindita; Ahmeti, Salih

2018-01-01

As the most widespread tick-borne arbovirus causing infections in numerous countries in Asia, Africa and Europe, Crimean-Congo Hemorrhagic Fever Virus (CCHFV, family Nairoviridae) was included in the WHO priority list of emerging pathogens needing urgent Research & Development attention. To ensure preparedness for potential future outbreak scenarios, reliable diagnostic tools for identification of acute cases as well as for performance of seroprevalence studies are necessary. Here, the CCHFV ortholog of the major bunyavirus antigen, the nucleoprotein (NP), was recombinantly expressed in E.coli, purified and directly labeled with horseradish peroxidase (HRP). Employing this antigen, two serological tests, a μ-capture ELISA for the detection of CCHFV-specific IgM antibodies (BLACKBOX CCHFV IgM) and an IgG immune complex (IC) ELISA for the detection of CCHFV-specific IgG antibodies (BLACKBOX CCHFV IgG), were developed. Test performance was evaluated and compared with both in-house gold standard testing by IgM/IgG indirect immunofluorescence (IIF) and commercially available ELISA tests (VectoCrimean-CHF-IgM/IgG, Vector-Best, Russia) using a serum panel comprising paired samples collected in Kosovo during the years 2013–2016 from 15 patients with an acute, RT-PCR-confirmed CCHFV infection, and 12 follow-up sera of the same patients collected approximately one year after having overcome the infection. Reliably detecting IgM antibodies in all acute phase sera collected later than day 4 after onset of symptoms, both IgM ELISAs displayed excellent diagnostic and analytical sensitivity (100%, 95% confidence interval (CI): 85.2%–100.0%). While both IgG ELISAs readily detected the high IgG titers present in convalescent patients approximately one year after having overcome the infection (sensitivity 100%, 95% CI: 73.5%–100.0%), the newly developed BLACKBOX CCHFV IgG ELISA was superior to the commercial IgG ELISA in detecting the rising IgG titers during the acute phase

2nd International Conference on Rheology and Modeling of Materials (IC-RMM2)

International Nuclear Information System (INIS)

2017-01-01

, nanomaterials, medical- and biomaterials, cosmetics, coatings, light metals, alloys, glasses, films, composites, hetero-modulus, hetero-viscous, hetero-plastic complex materials, petrochemicals and hybrid materials. Multidisciplinary applications of rheology and rheological modeling in material science and technology encountered in sectors like alloys, ceramics, glasses, thin films, polymers, clays, construction materials, energy, aerospace, automotive and marine industry. Rheology in food, chemistry, medicine, biosciences and environmental sciences are of particular interests. In accordance to the program of the conference ic-rmm2 and symposiums is-pim1 and isrfs1 we have received more than 250 inquires and registrations from different organizations. Finally more than 240 abstracts were accepted for presentation. From them 12 were PLENARY lectures and 112 ORAL presentation. Researchers from 41 countries of Asia, Europe, Africa, North and South America arrived to Miskolc-Lillafüred (Hungary) and participated in the events of the conference. Including co-authors, the research work of more than 700 scientists were presented in the SESSIONS and SYMPOSIUMS of ic-rmm2 conference. Prof. Dr. László A. Gömze chair, ic-rmm2 (paper)

2nd International Conference on Rheology and Modeling of Materials (IC-RMM2)

Science.gov (United States)

2017-01-01

, nanomaterials, medical- and biomaterials, cosmetics, coatings, light metals, alloys, glasses, films, composites, hetero-modulus, hetero-viscous, hetero-plastic complex materials, petrochemicals and hybrid materials. Multidisciplinary applications of rheology and rheological modeling in material science and technology encountered in sectors like alloys, ceramics, glasses, thin films, polymers, clays, construction materials, energy, aerospace, automotive and marine industry. Rheology in food, chemistry, medicine, biosciences and environmental sciences are of particular interests. In accordance to the program of the conference ic-rmm2 and symposiums is-pim1 and isrfs1 we have received more than 250 inquires and registrations from different organizations. Finally more than 240 abstracts were accepted for presentation. From them 12 were PLENARY lectures and 112 ORAL presentation. Researchers from 41 countries of Asia, Europe, Africa, North and South America arrived to Miskolc-Lillafüred (Hungary) and participated in the events of the conference. Including co-authors, the research work of more than 700 scientists were presented in the SESSIONS and SYMPOSIUMS of ic-rmm2 conference. Prof. Dr. László A. Gömze chair, ic-rmm2

Inefficient binding of IgM immune complexes to erythrocyte C3b-C4b receptors (CR1) and weak incorporation of C3b-iC3b into the complexes

DEFF Research Database (Denmark)

Kávai, M; Rasmussen, J M; Baatrup, G

1988-01-01

, but the binding was low (2-3%) when compared to the binding of the corresponding IgG-IC (50-60%). Solid phase IC were prepared by coating microwells with heat-aggregated bovine serum albumin (BSA) followed by incubation with rabbit IgM anti-BSA antibody. The IC were reacted with human serum at 37 degrees C....... The binding of C3b-iC3b was determined by use of biotinylated F(ab')2 antibodies to C3b-C3c and avidin-coupled alkaline phosphatase. The incorporation of C3b-iC3b into solid-phase IgM-IC increased when increasing amounts of IgM antibody were reacted with the antigen. The binding reaction was slow, reaching...

A Solder Based Self Assembly Project in an Introductory IC Fabrication Course

Science.gov (United States)

Rao, Madhav; Lusth, John C.; Burkett, Susan L.

2015-01-01

Integrated circuit (IC) fabrication principles is an elective course in a senior undergraduate and early graduate student's curriculum. Over the years, the semiconductor industry relies heavily on students with developed expertise in the area of fabrication techniques, learned in an IC fabrication theory and laboratory course. The theory course…

Electronic States of IC60BA and PC71BM

International Nuclear Information System (INIS)

Sheng Chun-Qi; Wang Peng; Shen Ying; Li Wen-Jie; Li Hong-Nian; Zhang Wen-Hua; Zhu Jun-Fa; Lai Guo-Qiao

2013-01-01

We investigate the electronic states of IC 60 BA and PC 71 BM using first-principles calculations and photoelectron spectroscopy (PES) measurements. The energy level structures for all possible isomers are reported and compared with those of C 60 , C 70 and PC 61 BM. The attachment of the side chains can raise the LUMO energies and decrease the HOMO-LUMO gaps, and thus helps to increase the power-conversion efficiency of bulk heterojunction solar cells. In the PES studies, we prepared IC 60 BA and PC 71 BM films on Si:H(111) substrates to construct adsorbate/substrate interfaces describable with the integer charge-transfer (ICT) model. Successful measurements then revealed that one of the most important material properties for an electron acceptor, the energy of the negative integer charge-transfer state (E ICT− ), is 4.31 eV below the vacuum level for PC 71 BM. The E ICT− of IC 60 BA is smaller than 4.14 eV

Infrared tip of the red giant branch and distances to the MAFFEI/IC 342 group

Energy Technology Data Exchange (ETDEWEB)

Wu, Po-Feng; Tully, R. Brent; Jacobs, Bradley A. [Institute for Astronomy, University of Hawaii, 2680 Woodlawn Drive, HI 96822 (United States); Rizzi, Luca [W. M. Keck Observatory, 65-1120 Mamalahoa Hwy, Kamuela, HI 96743 (United States); Dolphin, Andrew E. [Raytheon, 1151 East Hermans Road, Tucson, AZ 85756 (United States); Karachentsev, Igor D. [Special Astrophysical Observatory, Russian Academy of Sciences, Nizhnij Arkhyz, Karachai-Cherkessian Republic 369167 (Russian Federation)

2014-07-01

In this paper, we extend the use of the tip of the red giant branch (TRGB) method to near-infrared wavelengths from the previously used I-band, using the Hubble Space Telescope (HST) Wide Field Camera 3 (WFC3). Upon calibration of a color dependency of the TRGB magnitude, the IR TRGB yields a random uncertainty of ∼5% in relative distance. The IR TRGB methodology has an advantage over the previously used Advance Camera for Surveys F606W and F814W filter set for galaxies that suffer from severe extinction. Using the IR TRGB methodology, we obtain distances toward three principal galaxies in the Maffei/IC 342 complex, which are located at low Galactic latitudes. New distance estimates using the TRGB method are 3.45{sub −0.13}{sup +0.13} Mpc for IC 342, 3.37{sub −0.23}{sup +0.32} Mpc for Maffei 1, and 3.52{sub −0.30}{sup +0.32} Mpc for Maffei 2. The uncertainties are dominated by uncertain extinction, especially for Maffei 1 and Maffei 2. Our IR calibration demonstrates the viability of the TRGB methodology for observations with the James Webb Space Telescope.

3D analysis of the TCR/pMHCII complex formation in monkeys vaccinated with the first peptide inducing sterilizing immunity against human malaria.

Directory of Open Access Journals (Sweden)

Manuel A Patarroyo

Full Text Available T-cell receptor gene rearrangements were studied in Aotus monkeys developing high antibody titers and sterilizing immunity against the Plasmodium falciparum malaria parasite upon vaccination with the modified synthetic peptide 24112, which was identified in the Merozoite Surface Protein 2 (MSP-2 and is known to bind to HLA-DRbeta1*0403 molecules with high capacity. Spectratyping analysis showed a preferential usage of Vbeta12 and Vbeta6 TCR gene families in 67% of HLA-DRbeta1*0403-like genotyped monkeys. Docking of peptide 24112 into the HLA-DRbeta1*0401-HA peptide-HA1.7TCR complex containing the VDJ rearrangements identified in fully protected monkeys showed a different structural signature compared to nonprotected monkeys. These striking results show the exquisite specificity of the TCR/pMHCII complex formation needed for inducing sterilizing immunity and provide important hints for a logical and rational methodology to develop multiepitopic, minimal subunit-based synthetic vaccines against infectious diseases, among them malaria.

CMV immune evasion and manipulation of the immune system with aging.

Science.gov (United States)

Jackson, Sarah E; Redeker, Anke; Arens, Ramon; van Baarle, Debbie; van den Berg, Sara P H; Benedict, Chris A; Čičin-Šain, Luka; Hill, Ann B; Wills, Mark R

2017-06-01

Human cytomegalovirus (HCMV) encodes numerous proteins and microRNAs that function to evade the immune response and allow the virus to replicate and disseminate in the face of a competent innate and acquired immune system. The establishment of a latent infection by CMV, which if completely quiescent at the level of viral gene expression would represent an ultimate in immune evasion strategies, is not sufficient for lifelong persistence and dissemination of the virus. CMV needs to reactivate and replicate in a lytic cycle of infection in order to disseminate further, which occurs in the face of a fully primed secondary immune response. Without reactivation, latency itself would be redundant for the virus. It is also becoming clear that latency is not a totally quiescent state, but is characterized by limited viral gene expression. Therefore, the virus also needs immune evasion strategies during latency. An effective immune response to CMV is required or viral replication will cause morbidity and ultimately mortality in the host. There is clearly a complex balance between virus immune evasion and host immune recognition over a lifetime. This poses the important question of whether long-term evasion or manipulation of the immune response driven by CMV is detrimental to health. In this meeting report, three groups used the murine model of CMV (MCMV) to examine if the contribution of the virus to immune senescence is set by the (i) initial viral inoculum, (ii) inflation of T cell responses, (iii) or the balance between functionally distinct effector CD4+ T cells. The work of other groups studying the CMV response in humans is discussed. Their work asks whether the ability to make immune responses to new antigens is compromised by (i) age and HCMV carriage, (ii) long-term exposure to HCMV giving rise to an overall immunosuppressive environment and increased levels of latent virus, or (iii) adapted virus mutants (used as potential vaccines) that have the capacity to

Copper (II) and zinc (II) complexes with flavanone derivatives: Identification of potential cholinesterase inhibitors by on-flow assays.

Science.gov (United States)

Sarria, André Lucio Franceschini; Vilela, Adriana Ferreira Lopes; Frugeri, Bárbara Mammana; Fernandes, João Batista; Carlos, Rose Maria; da Silva, Maria Fátima das Graças Fernandes; Cass, Quezia Bezerra; Cardoso, Carmen Lúcia

2016-11-01

Metal chelates strongly influence the nature and magnitude of pharmacological activities in flavonoids. In recent years, studies have shown that a promising class of flavanone-metal ion complexes can act as selective cholinesterase inhibitors (ChEIs), which has led our group to synthesize a new series of flavanone derivatives (hesperidin, hesperetin, naringin, and naringenin) complexed to either copper (II) or zinc (II) and to evaluate their potential use as selective ChEIs. Most of the synthesized complexes exhibited greater inhibitory activity against acetylcholinesterase (AChE) than against butyrylcholinesterase (BChE). Nine of these complexes constituted potent, reversible, and selective ChEIs with inhibitory potency (IC 50 ) and inhibitory constant (K i ) ranging from 0.02 to 4.5μM. Copper complexes with flavanone-bipyridine derivatives afforded the best inhibitory activity against AChE and BChE. The complex Cu(naringin)(2,2'-bipyridine) (11) gave IC 50 and K i values of 0.012±0.002 and 0.07±0.01μM for huAChE, respectively, which were lower than the inhibitory values obtained for standard galanthamine (IC 50 =206±30.0 and K i =126±18.0μM). Evaluation of the inhibitory activity of this complex against butyrylcholinesterase from human serum (huBChE) gave IC 50 and K i values of 8.0±1.4 and 2.0±0.1μM, respectively. A Liquid Chromatography-Immobilized Capillary Enzyme Reactor by UV detection (LC-ICER-UV) assay allowed us to determine the IC 50 and K i values and the type of mechanism for the best inhibitors. Copyright © 2016 Elsevier Inc. All rights reserved.

Consciência icônica: o sentimento material do significado

Directory of Open Access Journals (Sweden)

Jeffrey C. Alexander

Full Text Available Resumo Neste ensaio seminal, Jeffrey Alexander apresenta algumas das bases de sua virada icônica. O giro analítico proposto se fundamenta em uma compreensão da materialidade como portadora de conteúdo estético e moral, o que é sintetizado na noção de consciência icônica: o processo em que um observador vincula a superfície estética de uma materialidade a uma determinada estrutura moral de valores sociais.

Endoplasmic reticulum chaperone glucose regulated protein 170-Pokemon complexes elicit a robust antitumor immune response in vivo.

Science.gov (United States)

Yuan, Bangqing; Xian, Ronghua; Wu, Xianqu; Jing, Junjie; Chen, Kangning; Liu, Guojun; Zhou, Zhenhua

2012-07-01

Previous evidence suggested that the stress protein grp170 can function as a highly efficient molecular chaperone, binding to large protein substrates and acting as a potent vaccine against specific tumors when purified from the same tumor. In addition, Pokemon can be found in almost all malignant tumor cells and is regarded to be a promising candidate for the treatment of tumors. However, the potential of the grp170-Pokemon chaperone complex has not been well described. In the present study, the natural chaperone complex between grp170 and the Pokemon was formed by heat shock, and its immunogenicity was detected by ELISPOT and (51)Cr-release assays in vitro and by tumor bearing models in vivo. Our results demonstrated that the grp170-Pokemon chaperone complex could elicit T cell responses as determined by ELISPOT and (51)Cr-release assays. In addition, immunized C57BL/6 mice were challenged with subcutaneous (s.c.) injection of Lewis cancer cells to induce primary tumors. Treatment of mice with the grp170-Pokemon chaperone complex also significantly inhibited tumor growth and prolonged the life span of tumor-bearing mice. Our results indicated that the grp170-Pokemon chaperone complex might represent a powerful approach to tumor immunotherapy and have significant potential for clinical application. Copyright © 2012 Elsevier GmbH. All rights reserved.

APPLICATTON OF SCTENTIF'IC PRINCIPLES IN MERINO SHEEP ...

African Journals Online (AJOL)

THE PRACTICAI- APPLICATTON OF SCTENTIF'IC PRINCIPLES IN MERINO SHEEP BREEDING. C.A. van der ..... There is, however, no practical evidence in this ... 1910" Comparison of three Australian merino strains for wool and body traits.

Assessment of complex water pollution with heavy metals and Pyrethroid pesticides on transcript levels of metallothionein and immune related genes.

Science.gov (United States)

Ghazy, Haneen A; Abdel-Razek, Mohamed A S; El Nahas, Abeer F; Mahmoud, Shawky

2017-09-01

Alteration of immunological function of an aquatic organism can be used as an indicator for evaluating the direct effect of exposure to pollutants. The aim of this work is to assess the impact of complex water pollution with special reference to Pyrethroid pesticides and heavy metals on mRNA transcript levels of Metallothionine and some immune related genes of Nile tilapia (Oreochromas Niloticus). Residues of six heavy metals and six Pyrethroid were assessed in water as well as fish tissues at three different sites of Lake Burullus, located at Northern Egypt. Variations of water physicochemical properties associated with different levels of heavy metals at the three different sections were recorded. Tissue residues of Fe, Mn and Zn, Cu, Ni exceed water levels in contrast to elevated water level of Pb. All assessed Pyrethroids are detected in fish tissue samples with higher concentration (3-42 folds) than that found in water samples especially Cypermethrin. Significant down-regulation of expression levels of metallothionein (MT) at the three sections of the lake was observed. The expression of immune related genes (IgM) and inflammatory cytokines (TNF, IL.8 and IL.1) were affected. IgM and TNF were significantly down-regulated at eastern and western section of the lake; meanwhile the expression of IL8 is down regulated at the three sections of the lack. IL1 was significantly up-regulated at eastern and middle sections. We conclude that, variable gene expression of MT and immune-related genes at the three sections of the lack impose different response to complex water pollution in relation to variable aquatic environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

EVN observations of the OH megamaser galaxies Mrk 231 and IC 694

NARCIS (Netherlands)

Klockner, HR; Baan, WA; Migenes,; Reid, MJ

2002-01-01

We present EVN observations of hydroxyl (OH) main-line emission in two megamaser sources Mrk 231 and IC 694. The observations indicate that the broad maser emission lines originate within the nuclear regions. A single 1667 MHz main-line feature is seen at the nucleus of IC 694. In Mrk 231 both

Physical Activities, Exercises, and Their Effects to the Immune System

OpenAIRE

Nurmasitoh, Titis

2015-01-01

Every systems in human body correlate to maintain homeostasis. One of those systems which contribute to maintain homeostasis is the immune system. The immune system defends physiological functions against foreign substances and cancer cells through a complex and multilayered mechanism. The ability to defend against foreign substances and abnormal cells is done by two types of immune system, which are Innate immune system and adaptive/acquired immune system. There are also certain factors that...

Membrane microdomains and the cytoskeleton constrain AtHIR1 dynamics and facilitate the formation of an AtHIR1-associated immune complex.

Science.gov (United States)

Lv, Xueqin; Jing, Yanping; Xiao, Jianwei; Zhang, Yongdeng; Zhu, Yingfang; Julian, Russell; Lin, Jinxing

2017-04-01

Arabidopsis hypersensitive-induced reaction (AtHIR) proteins function in plant innate immunity. However, the underlying mechanisms by which AtHIRs participate in plant immunity remain elusive. Here, using VA-TIRFM and FLIM-FRET, we revealed that AtHIR1 is present in membrane microdomains and co-localizes with the membrane microdomain marker REM1.3. Single-particle tracking analysis revealed that membrane microdomains and the cytoskeleton, especially microtubules, restrict the lateral mobility of AtHIR1 at the plasma membrane and facilitate its oligomerization. Furthermore, protein proximity index measurements, fluorescence cross-correlation spectroscopy, and biochemical experiments demonstrated that the formation of the AtHIR1 complex upon pathogen perception requires intact microdomains and cytoskeleton. Taken together, these findings suggest that microdomains and the cytoskeleton constrain AtHIR1 dynamics, promote AtHIR1 oligomerization, and increase the efficiency of the interactions of AtHIR1 with components of the AtHIR1 complex in response to pathogens, thus providing valuable insight into the mechanisms of defense-related responses in plants. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Effect of preparation processes and structural insight into the supermolecular system: Bisacodyl and β-cyclodextrin inclusion complex

International Nuclear Information System (INIS)

Li, Shanshan; Zhai, Yuanming; Yan, Jin; Wang, Lili; Xu, Kailin; Li, Hui

2016-01-01

In this study, β-cyclodextrin (β-CD) and bisacodyl were chosen as model host and guest molecule to explore the effect of preparation processes on the physicochemical properties of inclusion complexes (ICs) and to gain an insight into the structure of ICs. The influence of temperature and pH on complexation was studied by multiple temperature–pH phase solubility analysis. The most favorable conformation was predicted by molecular modeling using AutoDock. "1H nuclear magnetic resonance and rotating frame nuclear Overhauser effect spectroscopy further confirmed the structure. Moreover, bisacodyl·β-CD ICs in solid state were successfully prepared via three different procedures (co-crystallization, co-evaporation, and co-grinding) and fully characterized by several solid-state techniques, namely, Fourier transform infrared spectroscopy, X-ray powder diffraction, thermogravimetric analysis, differential scanning calorimetry, solid-state NMR spectroscopy, and scanning electron microscopy. It was found that acid solution and low temperature were unfavorable for formation of bisacodyl·β-CD. The pyridine moiety was suggested to be enclosed in the hydrophobic cavity of β-CD. The complexes prepared using co-crystallization showed properties similar to those prepared using co-evaporation. Moreover, ICs obtained by co-evaporation and co-grinding had higher loading efficiency, water solubility, and dissolution rate than ICs obtained by co-crystallization. - Highlights: • The structure of inclusion complex-bisacodyl·β-CD was determined. • Thermodynamic behaviors of complexation under different conditions were discussed. • Products from three different preparation methods were systemically compared. • Co-crystallization and co-evaporation produced similar complexes. • Co-evaporation and co-grinding had better effects than co-crystallization.

Effect of preparation processes and structural insight into the supermolecular system: Bisacodyl and β-cyclodextrin inclusion complex

Energy Technology Data Exchange (ETDEWEB)

Li, Shanshan [College of Chemical Engineering, Sichuan University, Chengdu 610065 (China); Zhai, Yuanming [Analytical and Testing Center, Sichuan University, Chengdu 610064 (China); Yan, Jin; Wang, Lili; Xu, Kailin [College of Chemical Engineering, Sichuan University, Chengdu 610065 (China); Li, Hui, E-mail: lihuilab@sina.com [College of Chemical Engineering, Sichuan University, Chengdu 610065 (China)

2016-01-01

In this study, β-cyclodextrin (β-CD) and bisacodyl were chosen as model host and guest molecule to explore the effect of preparation processes on the physicochemical properties of inclusion complexes (ICs) and to gain an insight into the structure of ICs. The influence of temperature and pH on complexation was studied by multiple temperature–pH phase solubility analysis. The most favorable conformation was predicted by molecular modeling using AutoDock. {sup 1}H nuclear magnetic resonance and rotating frame nuclear Overhauser effect spectroscopy further confirmed the structure. Moreover, bisacodyl·β-CD ICs in solid state were successfully prepared via three different procedures (co-crystallization, co-evaporation, and co-grinding) and fully characterized by several solid-state techniques, namely, Fourier transform infrared spectroscopy, X-ray powder diffraction, thermogravimetric analysis, differential scanning calorimetry, solid-state NMR spectroscopy, and scanning electron microscopy. It was found that acid solution and low temperature were unfavorable for formation of bisacodyl·β-CD. The pyridine moiety was suggested to be enclosed in the hydrophobic cavity of β-CD. The complexes prepared using co-crystallization showed properties similar to those prepared using co-evaporation. Moreover, ICs obtained by co-evaporation and co-grinding had higher loading efficiency, water solubility, and dissolution rate than ICs obtained by co-crystallization. - Highlights: • The structure of inclusion complex-bisacodyl·β-CD was determined. • Thermodynamic behaviors of complexation under different conditions were discussed. • Products from three different preparation methods were systemically compared. • Co-crystallization and co-evaporation produced similar complexes. • Co-evaporation and co-grinding had better effects than co-crystallization.

IC 3475: A stripped dwarf galaxy in the Virgo cluster

International Nuclear Information System (INIS)

Vigroux, L.; Thuan, T.X.; Vader, J.P.; Lachieze-Rey, M.

1986-01-01

We have obtained B and R CCD and H I observations of the Virgo dwarf galaxy IC 3475. The galaxy is remarkable for its very large diameter (approx.10 kpc for a Virgo distance modulus of 31) and is comparable in size to the large dwarfs discussed by Sandage and Binggeli. Its light profile is best fitted by an exponential law, characteristic of a dwarf Magellanic irregular galaxy. It possesses a central bar with many knots and inclusions concentrated toward the center of the galaxy. These knots and inclusions have the same color (B-Rapprox.1.5) as the rest of the galaxy and are best explained as intermediate-age (1--7 x 10 9 yr) star clusters such as those found in the Magellanic Clouds. Despite possessing the photometric structure of a dwarf Magellanic irregular galaxy, IC 3475 contains less than 5.3 x 10 6 M/sub sun/ of neutral hydrogen. Its hydrogen mass to blue light ratio is less than 0.01, approx.60 times less than the mean value observed for dwarf Magellanic irregulars. It is most likely that IC 3475, which is located near the core of the Virgo cluster, is a stripped dwarf galaxy. The very large size of the galaxy (its diameter is approx.1.8 times larger than that of ''normal'' dwarfs) appears to rule out evolution of IC 3475 from a normal dwarf irregular or to a normal dwarf elliptical

NKT cell self-reactivity: evolutionary master key of immune homeostasis?

DEFF Research Database (Denmark)

Navikas, Shohreh

2011-01-01

Complex immune responses have evolved to protect multicellular organisms against the invasion of pathogens. This has exerted strong developmental pressure for specialized functions that can also limit damage to self-tissue. Two arms of immunity, the innate and adaptive immune system, have evolved...... through evolution by higher vertebrates could be related to their central function as master regulators of immune homeostasis that in part is shared with regulatory T cells. Hypothetical views on how self-reactive NKT cells secure such a central role will also be proposed.......Complex immune responses have evolved to protect multicellular organisms against the invasion of pathogens. This has exerted strong developmental pressure for specialized functions that can also limit damage to self-tissue. Two arms of immunity, the innate and adaptive immune system, have evolved....... The recent finding of self-peptide reactivity of NKT cells in the context of CD1d, with capacity to regulate multiple autoimmune and inflammatory conditions, motivates the current proposal that self-reactive NKT cells might be the ancestral link between present NK and T cells. Their parallel selection...

Late effects of radiation on immune system; a review

International Nuclear Information System (INIS)

Sado, T.

1979-01-01

Lymphocytes are divided into 2 major classes: T and B lymphocytes (or cells). T cells are responsible for cell-mediated immune response, and B cells for humoral immune response or antibody formation. The possible immunological complications that might develop as the late manifestation of radiation effects include: lymphoid neoplasms, immune complex diseases, auto-aggressive immune reactions, and other degenerative diseases of immunological nature. The development of lymphoid neoplasma following the exposure to radiation was extensively studied with mice. Radiation-induced immunological compications would not contribute significantly to the life-shortening of exposed individuals. The extensive health survey of adult A-bomb survivors revealed little evidence of immunological complications such as rheumatoid arthritis, kidney diseases, paraproteinemia, etc. The young healthy adults who had received thymic irradiation during infancy for the treatment of enlarged thymus manifested higher incidence of illness with abnormal immunological features. Immune complex diseases, particularly the inter-capillary glomerulosclerosis of kidneys, develop as a result of earlier exposure to high dose of radiation. (Yamashita, S.)

The immune strategy and stress response of the Mediterranean species of the Bemisia tabaci complex to an orally delivered bacterial pathogen.

Directory of Open Access Journals (Sweden)

Chang-Rong Zhang

Full Text Available BACKGROUND: The whitefly, Bemisia tabaci, a notorious agricultural pest, has complex relationships with diverse microbes. The interactions of the whitefly with entomopathogens as well as its endosymbionts have received great attention, because of their potential importance in developing novel whitefly control technologies. To this end, a comprehensive understanding on the whitefly defense system is needed to further decipher those interactions. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a comprehensive investigation of the whitefly's defense responses to infection, via oral ingestion, of the pathogen, Pseudomonas aeruginosa, using RNA-seq technology. Compared to uninfected whiteflies, 6 and 24 hours post-infected whiteflies showed 1,348 and 1,888 differentially expressed genes, respectively. Functional analysis of the differentially expressed genes revealed that the mitogen associated protein kinase (MAPK pathway was activated after P. aeruginosa infection. Three knottin-like antimicrobial peptide genes and several components of the humoral and cellular immune responses were also activated, indicating that key immune elements recognized in other insect species are also important for the response of B. tabaci to pathogens. Our data also suggest that intestinal stem cell mediated epithelium renewal might be an important component of the whitefly's defense against oral bacterial infection. In addition, we show stress responses to be an essential component of the defense system. CONCLUSIONS/SIGNIFICANCE: We identified for the first time the key immune-response elements utilized by B. tabaci against bacterial infection. This study provides a framework for future research into the complex interactions between whiteflies and microbes.

Evaluation of accelerated test parameters for CMOS IC total dose hardness prediction

International Nuclear Information System (INIS)

Sogoyan, A.V.; Nikiforov, A.Y.; Chumakov, A.I.

1999-01-01

The approach to accelerated test parameters evaluation is presented in order to predict CMOS IC total dose behavior in variable dose-rate environment. The technique is based on the analytical model of MOSFET parameters total dose degradation. The simple way to estimate model parameter is proposed using IC's input-output MOSFET radiation test results. (authors)

EMERGING I&C TECHNOLOGIES UNDER THE SHIFTING REGULATORY ENVIRONMENT IN SOUTH KOREA

Directory of Open Access Journals (Sweden)

Gyunyoung eHeo

2015-04-01

Full Text Available The role of Probabilistic Safety Assessment (PSA has been supplementary and Risk-Informed Applications (RIAs based on the insight from PSA has also been utilized limitedly in the licensing process for Nuclear Power Plants (NPPs in South Korea. However, as the technical significance of PSA is getting increased, PSA has become a mandatory part of Safety Analysis Reports and Periodic Safety Review. It is worthwhile to highlight the role of emerging Instrumentation and Control (I&C technologies including human-machine interface (HMI in developing more credible and realistic PSA models. Particularly, it is expected that the information technology (i.e. software embedded in digital I&C can adjust over- and under conservatism in analyzing risk. In this study, authors proposed the cases which would be able to significantly reduce risk if advanced I&C supported by information technologies is applied. In regard, the several enabling techniques and their effects are proposed. In order to improve the commercial competitiveness of NPPs, the need of collaboration and synergetic outcome of I&C, HMI and PSA should be emphasized.

Emerging I&C Technologies Under the Shifting Regulatory Environment in South Korea

Energy Technology Data Exchange (ETDEWEB)

Heo, Gyunyoung [Department of Nuclear Engineering, Kyung Hee University, Youngin-si (Korea, Republic of); Seong, Poong Hyun; Kang, Hyun Gook, E-mail: hyungook@kaist.ac.kr [Department of Nuclear and Quantum Engineering, Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

2015-04-29

The role of probabilistic safety assessment (PSA) has been supplementary and risk-informed applications based on the insight from PSA have also been utilized limitedly in the licensing process for nuclear power plants (NPPs) in South Korea. However, as the technical significance of PSA is getting increased, PSA has become a mandatory part of Safety Analysis Reports and Periodic Safety Review. It is worthwhile to highlight the role of emerging instrumentation and control (I&C) technologies including human–machine interface (HMI) in developing more credible and realistic PSA models. Particularly, it is expected that the information technology (i.e., software) embedded in digital I&C can adjust over- and under conservatism in analyzing risk. In this study, authors proposed the cases which would be able to significantly reduce risk if advanced I&C supported by information technologies is applied. In regard, the several enabling techniques and their effects are proposed. In order to improve the commercial competitiveness of NPPs, the need of collaboration and synergetic outcome of I&C, HMI, and PSA should be emphasized.

The effect of maternal and paternal immune challenge on offspring immunity and reproduction in a cricket.

Science.gov (United States)

McNamara, K B; van Lieshout, E; Simmons, L W

2014-06-01

Trans-generational immune priming is the transmission of enhanced immunity to offspring following a parental immune challenge. Although within-generation increased investment into immunity demonstrates clear costs on reproductive investment in a number of taxa, the potential for immune priming to impact on offspring reproductive investment has not been thoroughly investigated. We explored the reproductive costs of immune priming in a field cricket, Teleogryllus oceanicus. To assess the relative importance of maternal and paternal immune status, mothers and fathers were immune-challenged with live bacteria or a control solution and assigned to one of four treatments in which one parent, neither or both parents were immune-challenged. Families of offspring were reared to adulthood under a food-restricted diet, and approximately 10 offspring in each family were assayed for two measures of immunocompetence. We additionally quantified offspring reproductive investment using sperm viability for males and ovary mass for females. We demonstrate that parental immune challenge has significant consequences for the immunocompetence and, in turn, reproductive investment of their male offspring. A complex interaction between maternal and paternal immune status increased the antibacterial immune response of male offspring. This increased immune response was associated with a reduction in son's sperm viability, implicating a trans-generational resource trade-off between investment into immunocompetence and reproduction. Our data also show that these costs are sexually dimorphic, as daughters did not demonstrate a similar increase in immunity, despite showing a reduction in ovary mass. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

STAR FORMATION ASSOCIATED WITH THE SUPERNOVA REMNANT IC443

International Nuclear Information System (INIS)

Xu Jinlong; Wang Junjie; Miller, Martin

2011-01-01

We have performed submillimeter and millimeter observations in CO lines toward supernova remnant (SNR) IC443. The CO molecular shell coincides well with the partial shell of the SNR detected in radio continuum observations. Broad emission lines and three 1720 MHz OH masers were detected in the CO molecular shell. The present observations have provided further evidence in support of the interaction between the SNR and the adjoining molecular clouds (MCs). The total mass of the MCs is 9.26 x 10 3 M sun . The integrated CO line intensity ratio (R I CO(3-2) /I CO(2-1) ) for the whole MC is between 0.79 and 3.40. The average value is 1.58, which is much higher than previous measurements of individual Galactic MCs. Higher line ratios imply that shocks have driven into the MCs. We conclude that high R I CO(3-2) /I CO(2-1) is identified as a good signature of the SNR-MC interacting system. Based on the IRAS Point Source Catalog and the Two Micron All Sky Survey near-infrared database, 12 protostellar object and 1666 young stellar object (YSO) candidates (including 154 classical T Tauri stars and 419 Herbig Ae/Be stars) are selected. In the interacting regions, the significant enhancement of the number of protostellar objects and YSOs indicates the presence of some recently formed stars. After comparing the characteristic timescales of star formation with the age of IC443, we conclude that the protostellar objects and YSO candidates are not triggered by IC443. For the age of the stellar winds shell, we have performed our calculation on the basis of a stellar wind shell expansion model. The results and analysis suggest that the formation of these stars may be triggered by the stellar winds of the IC443 progenitor.

Inhalable Andrographolide-β-cyclodextrin Inclusion Complexes for Treatment of Staphylococcus aureus Pneumonia by Regulating Immune Responses.

Science.gov (United States)

Zhang, Tongtong; Zhu, Lifei; Li, Miao; Hu, Yuzhen; Zhang, Erfeng; Jiang, Qingcheng; Han, Guang; Jin, Yiguang

2017-05-01

Bacterial pneumonia is a serious disease with high mortality if no appropriate and immediate therapy is available. Andrographolide (AG) is an anti-inflammatory agent extracted from a traditional Chinese herb andrographis paniculata. Oral AG tablets and pills are clinically applied for treatment of upper respiratory tract infections. However, the low solubility and bioavailability of AG lead to high doses and long-term therapy. Here we developed an andrographolide-β-cyclodextrin inclusion complex (AG-β-CD) for inhalation therapy of Staphylococcus aureus pneumonia. AG-β-CD was identified with X-ray diffraction and FT-IR. Surprisingly, both AG-β-CD and AG showed little in vitro anti-S. aureus activity. However, pulmonary delivery of AG, AG-β-CD, or penicillin had significant anti-S. aureus pneumonia effects. Leukocytes, neutrophils, white blood cells, total proteins, TNF-α, IL-6, NF-κB p65 expression, and bacterial colonies in the bronchoalveolar lavage fluids were detected. Pulmonary delivery of AG and AG-β-CD led to bacterial inhibition and inflammation alleviation by regulating immune responses, while penicillin only killed bacteria without significant immune regulation. Moreover, the antipneumonia activity of AG-β-CD was much higher than that of AG, probably resulting from locally accelerated AG dissolution due to β-CD inclusion. The aerodynamic diameter of AG-β-CD powders was 2.03 μm, suitable for pulmonary delivery. Inhalable AG-β-CD is a promising antibacterial and anti-inflammatory medicine for the treatment of S. aureus pneumonia by regulating immune responses, and the effect is enhanced by β-CD inclusion. AG and its formulations might be potent weapons against the resistant bacterial pneumonia due to their specific mechanism in the future.

Cholesterol level in the circulating immune complexes of subjects suffering from the remote aftereffects of acute radiation sickness

International Nuclear Information System (INIS)

Nikitin, G.Yu.; Barabanova, A.V.; Nadezhina, N.M.; Tertov, V.V.; Orekhov, A.N.

1994-01-01

The potentiaoity of coronary atherosclerosis was assessed from cholesterol levels in the ciculationg immune complexes (CIC) in 53 subjects who suffered acute radiation sickness in 1986 after the Chernobyl power plant accident. CIC cholesterol levels of the subjects who suffered 3-4 years before acute radiation sickness of the first-second degrees of severity were found elevated as against an adequately matched reference group. Thus, subjects who suffered the second degree of severity acute radiation sickness after the radiation exposure, from 3-4 years later a group at high risk of coronary atherosclerosis

Virtual design and qualification of IC backend structures

NARCIS (Netherlands)

Silfhout, van R.B.R.; Sluis, van der O.; Driel, van W.D.; Janssen, J.H.J.; Zhang, G.Q.

2006-01-01

For Integrated Circuit (IC) wafer backend development, process developers have to design robust backend structures that guarantee both functionality and reliability during waferfab processes, packaging, qualification tests and lifetime. Figure 1 shows a simplified diagram for the design (and

IC modelling in the IRSN EPR level 1 PSA

International Nuclear Information System (INIS)

Delache, J.

2012-01-01

Today in France, an EPR (European Pressurized Water Reactor) Unit is under construction at the Flamanville site. The creation authorization was granted in April 2007 and the plant commissioning is planned for 2012. The plant operator (EDF) provided for the construction license several PSA (Probabilistic Safety Assessment) studies. IRSN, as TSO (Technical Safety Organisation), wishes to dispose of the appropriate knowledge and tools for the independent verification of the operator studies and so developed its own model of PSA level 1. The goal is not to rebuild the plant operator PSA (with a full scope...) but to dispose of a simplified model able to clearly point out specific important issues. In the IRSN model a particular effort has recently been done on the Digital IC modelling. The IC (Instrumentation and Control) is modelled in the IRSN EPR PSA by using Fault Trees. Instead, EDF EPR PSA applies the COMPACT model to simplify the command and instrumentation logics. The IRSN model is more detailed in order to be more accurate in the global analysis of the Digital IC. For instance the communication ways between automates are considered as well as the failure of support systems. The model is still under development mainly in order to define the CCF (Common Cause Failure) which may be considered. (authors)

Optimizing velocities and transports for complex coastal regions and archipelagos

Science.gov (United States)

Haley, Patrick J.; Agarwal, Arpit; Lermusiaux, Pierre F. J.

2015-05-01

We derive and apply a methodology for the initialization of velocity and transport fields in complex multiply-connected regions with multiscale dynamics. The result is initial fields that are consistent with observations, complex geometry and dynamics, and that can simulate the evolution of ocean processes without large spurious initial transients. A class of constrained weighted least squares optimizations is defined to best fit first-guess velocities while satisfying the complex bathymetry, coastline and divergence strong constraints. A weak constraint towards the minimum inter-island transports that are in accord with the first-guess velocities provides important velocity corrections in complex archipelagos. In the optimization weights, the minimum distance and vertical area between pairs of coasts are computed using a Fast Marching Method. Additional information on velocity and transports are included as strong or weak constraints. We apply our methodology around the Hawaiian islands of Kauai/Niihau, in the Taiwan/Kuroshio region and in the Philippines Archipelago. Comparisons with other common initialization strategies, among hindcasts from these initial conditions (ICs), and with independent in situ observations show that our optimization corrects transports, satisfies boundary conditions and redirects currents. Differences between the hindcasts from these different ICs are found to grow for at least 2-3 weeks. When compared to independent in situ observations, simulations from our optimized ICs are shown to have the smallest errors.

Adaptive Immunity to Cryptococcus neoformans Infections

Directory of Open Access Journals (Sweden)

Liliane Mukaremera

2017-11-01

Full Text Available The Cryptococcus neoformans/Cryptococcus gattii species complex is a group of fungal pathogens with different phenotypic and genotypic diversity that cause disease in immunocompromised patients as well as in healthy individuals. The immune response resulting from the interaction between Cryptococcus and the host immune system is a key determinant of the disease outcome. The species C. neoformans causes the majority of human infections, and therefore almost all immunological studies focused on C. neoformans infections. Thus, this review presents current understanding on the role of adaptive immunity during C. neoformans infections both in humans and in animal models of disease.

A GRB and Broad-lined Type Ic Supernova from a Single Central Engine

Science.gov (United States)

Barnes, Jennifer; Duffell, Paul C.; Liu, Yuqian; Modjaz, Maryam; Bianco, Federica B.; Kasen, Daniel; MacFadyen, Andrew I.

2018-06-01

Unusually high velocities (≳0.1c) and correspondingly high kinetic energies have been observed in a subset of Type Ic supernovae (so-called “broad-lined Ic” supernovae; SNe Ic-BL), prompting a search for a central engine model capable of generating such energetic explosions. A clue to the explosion mechanism may lie in the fact that all supernovae that accompany long-duration gamma-ray bursts (GRBs) belong to the SN Ic-BL class. Using a combination of two-dimensional relativistic hydrodynamics and radiation transport calculations, we demonstrate that the central engine responsible for long GRBs can also trigger an SN Ic-BL. We find that a reasonable GRB engine injected into a stripped Wolf–Rayet progenitor produces a relativistic jet with energy ∼1051 erg, as well as an SN whose synthetic light curves and spectra are fully consistent with observed SNe Ic-BL during the photospheric phase. As a result of the jet’s asymmetric energy injection, the SN spectra and light curves depend on viewing angle. The impact of viewing angle on the spectrum is particularly pronounced at early times, while the viewing-angle dependence for the light curves (∼10% variation in bolometric luminosity) persists throughout the photospheric phase.

The Effects of Industry Type, Company Size and Performance on Chinese Companies’ IC Disclosure: A Research Note

Directory of Open Access Journals (Sweden)

Yi An

2011-09-01

Full Text Available This paper examines the effects of industry type, firm size and corporate performance on intellectual capital (IC disclosure among Chinese (mainland companies. It was found that industry type did not have a significant influence on IC reporting practices of Chinese firms; the larger firms generally reported more IC information than the relatively smaller firms; and there was a positive relationship between corporate performance and IC disclosure. This paper contributes to fairly limited literature regarding the associations between the level of IC disclosure and a variety of relevant impact factors, in particular in the Chinese mainland context. In addition, the findings of this research provide some references for policy-makers while developing an IC reporting framework applicable to the Chinese environment.

Viral subversion of the immune system

International Nuclear Information System (INIS)

Gillet, L.; Vanderplasschen, A.

2005-01-01

The continuous interactions between host and viruses during their co-evolution have shaped not only the immune system but also the countermeasures used by viruses. Studies in the last decade have described the diverse arrays of pathways and molecular targets that are used by viruses to elude immune detection or destruction, or both. These include targeting of pathways for major histocompatibility complex class I and class II antigen presentation, natural killer cell recognition, apoptosis, cytokine signalling, and complement activation. This paper provides an overview of the viral immune-evasion mechanisms described to date. It highlights the contribution of this field to our understanding of the immune system, and the importance of understanding this aspect of the biology of viral infection to develop efficacious and safe vaccines. (author)

Captive and free-living red knots Calidris canutus exhibit differences in non-induced immunity that suggest different immune strategies in different environments

NARCIS (Netherlands)

Buehler, Deborah M.; Piersma, Theunis; Tieleman, B. Irene

Experiments on captive animals, in which conditions can be controlled, are useful for examining complex biological phenomena such as immune function. Such experiments have increased our understanding of immune responses in the context of trade-offs and pathogen pressure. However, few studies have

CMOS analog integrated circuit design technology; CMOS anarogu IC sekkei gijutsu

Energy Technology Data Exchange (ETDEWEB)

Fujimoto, H.; Fujisawa, A. [Fuji Electric Co. Ltd., Tokyo (Japan)

2000-08-10

In the field of the LSI (large scale integrated circuit) in rapid progress toward high integration and advanced functions, CAD (computer-aided design) technology has become indispensable to LSI development within a short period. Fuji Electric has developed design technologies and automatic design system to develop high-quality analog ICs (integrated circuits), including power supply ICs. within a short period. This paper describes CMOS (complementary metal-oxide semiconductor) analog macro cell, circuit simulation, automatic routing, and backannotation technologies. (author)

Signaling Mechanisms in Pattern-Triggered Immunity (PTI)

KAUST Repository

Bigeard, Jean; Colcombet, Jean; Hirt, Heribert

2015-01-01

In nature, plants constantly have to face pathogen attacks. However, plant disease rarely occurs due to efficient immune systems possessed by the host plants. Pathogens are perceived by two different recognition systems that initiate the so-called pattern-triggered immunity (PTI) and effector-triggered immunity (ETI), both of which are accompanied by a set of induced defenses that usually repel pathogen attacks. Here we discuss the complex network of signaling pathways occurring during PTI, focusing on the involvement of mitogen-activated protein kinases. © 2015 The Author.

Psychosocial co-morbidities in Interstitial Cystitis/Bladder Pain syndrome (IC/BPS): A systematic review.

Science.gov (United States)

McKernan, Lindsey C; Walsh, Colin G; Reynolds, William S; Crofford, Leslie J; Dmochowski, Roger R; Williams, David A

2018-03-01

Psychosocial factors amplify symptoms of Interstitial Cystitis (IC/BPS). While psychosocial self-management is efficacious in other pain conditions, its impact on an IC/BPS population has rarely been studied. The objective of this review is to learn the prevalence and impact of psychosocial factors on IC/BPS, assess baseline psychosocial characteristics, and offer recommendations for assessment and treatment. Following PRISMA guidelines, primary information sources were PubMed including MEDLINE, Embase, CINAHL, and GoogleScholar. Inclusion criteria included: (i) a clearly defined cohort with IC/BPS or with Chronic Pelvic Pain Syndrome provided the IC/BPS cohort was delineated with quantitative results from the main cohort; (ii) all genders and regions; (iii) studies written in English from 1995 to April 14, 2017; (iv) quantitative report of psychosocial factors as outcome measures or at minimum as baseline characteristics. Thirty-four of an initial 642 articles were reviewed. Quantitative analyses demonstrate the magnitude of psychosocial difficulties in IC/BPS, which are worse than average on all measures, and fall into areas of clinical concern for 7 out of 10 measures. Meta-analyses shows mean Mental Component Score of the Short-Form 12 Health Survey (MCS) of 40.80 (SD 6.25, N = 2912), where <36 is consistent with severe psychological impairment. Averaged across studies, the population scored in the range seen in clinical depression (CES-D 19.89, SD 13.12, N = 564) and generalized anxiety disorder (HADS-A 8.15, SD 4.85, N = 465). The psychological impact of IC/BPS is pervasive and severe. Existing evidence of treatment is lacking and suggests self-management intervention may be helpful. © 2017 Wiley Periodicals, Inc.

Detection of copper ions using microcantilever immunosensors and enzyme-linked immunosorbent assay

International Nuclear Information System (INIS)

Zhao Hongwei; Xue Changguo; Nan Tiegui; Tan Guiyu; Li Zhaohu; Li, Qing X.; Zhang Qingchuan; Wang Baomin

2010-01-01

A sensitive and specific monoclonal antibody (designated as mAb6A9) recognizing a Cu(II)-ethylenediamine-N,N,N',N'-tetraacetic acid (EDTA) complex but not metal-free EDTA was obtained by using an 1-(4-aminobenzyl)-EDTA-Cu(II) complex covalently coupled to a carrier protein as an immunogen to immunize the Balb/c mice. A mAb6A9-modified microcantilever sensor (MCS) was developed. A bending response was found to occur at or below 1 ng mL -1 of Cu(II)-EDTA complex. An indirect competitive enzyme-linked immunosorbent assay (icELISA) was developed with mAb6A9. The icELISA had a half maximum inhibition concentration and working range of approximately 1.8 and 0.2-17 ng mL -1 , respectively. The icELISA showed cross-reactivity of 18.8%, 1.1% and less than 1% with bivalent cobalt, mercury and other metals, respectively. The icELISA and functionalized MCSs were utilized to analyze the content of copper in spiked tap water samples. The assay conditions were optimized. The results of icELISA and MCS correlated well with those obtained by graphite furnace atomic absorption spectrometry.

Tumoral immune-infiltrate (IF), PD-L1 expression and role of CD8/TIA-1 lymphocytes in localized osteosarcoma patients treated within protocol ISG-OS1.

Science.gov (United States)

Palmerini, Emanuela; Agostinelli, Claudio; Picci, Piero; Pileri, Stefano; Marafioti, Teresa; Lollini, Pier-Luigi; Scotlandi, Katia; Longhi, Alessandra; Benassi, Maria Serena; Ferrari, Stefano

2017-12-19

We hypothesized that immune-infiltrates were associated with superior survival, and examined a primary osteosarcoma tissue microarrays (TMAs) to test this hypothesis. 129 patients (pts) with localized osteosarcoma treated within protocol ISG-OS1 were included in the study. Clinical characteristics, expression of CD8, CD3, FOXP3, CD20, CD68/CD163 (tumor associated macrophage, TAM), Tia-1 (cytotoxic T cell), CD303 (plasmacytoid dendritic cells: pDC), Arginase-1 (myeloid derived suppressor cells: MDSC), PD-1 on immune-cells (IC), and PD-L1 on tumoral cells (TC) and IC were analysed and correlated with outcome. Most of the cases presented tumor infiltrating lymphocytes (TILs) (CD3+ 90%; CD8+ 86%). Tia-1 was detected in 73% of the samples. PD-L1 expression was found in 14% patients in IC and 0% in TC; 22% showed PD-1 expression in IC.With a median follow-up of 8 years (range 1-13), the 5-year overall survival (5-year OS) was 74% (95% CI 64-85). Univariate analysis showed better 5-year OS for: a) pts with a good histologic response to neoadjuvant chemotherapy (p = 0.0001); b) pts with CD8/Tia1 tumoral infiltrates (p = 0.002); c) pts with normal alkaline phosphatas (sALP) (p = 0.04). After multivariate analysis, histologic response (p = 0.007) and CD8/Tia1 infiltration (p = 0.01) were independently correlated with survival. In the subset of pts with CD8+ infiltrate, worse (p 0.02) OS was observed for PD-L1(IC)+ cases. Our findings support the hypothesis that CD8/Tia1 infiltrate in tumor microenvironment at diagnosis confers superior survival for pts with localized osteosarcoma, while PD-L1 expression is associated with worse survival.

C-reactive protein, Rheumatoid factor and circulatory immune complex as markers for monitoring treatment of infective endocarditis

International Nuclear Information System (INIS)

Alavi, S.M.; Ahmadi, F.; Nashibi, R.

2010-01-01

Objectives: To evaluate the diagnostic usefulness of serum C-reactive protein (CRP), rheumatoid factor (RF) and circulatory immune complex (CIC) determinations in monitoring the outcome of infective endocarditis (IE). Methodology: In this prospective analytic descriptive study CRP, RF and CIC were measured on admission and 4 weeks after initiation of standard antibiotic regimen in 30 hospitalized patients with IE in an educational hospital between 2006 and 2007 in Ahvaz a city south west Iran . Duke criteria were used for diagnosis of IE. CRP and RF were examined using quantitative neflometry (Binding site kit, UK) and CIC was detected by semi quantitative immune diffusion (Baharafshan SIRD kit, Iran). Data were evaluated using statistical analyses in SPSS (version 12, USA) software for windows. Results: The fall in serum C-reactive protein or RF was significant (P= 0.05). Only two of the 30 patients, who had elevated CRP, RF and CIC week four failed to response and one needed cardiac surgery. Conclusions: The C-reactive protein proved to be a good tool for monitoring the treatment of IE. Also RF proved useful in the assessment of patients with IE, but the value of CIC was negligible. (author)

PF-1355, a mechanism-based myeloperoxidase inhibitor, prevents immune complex vasculitis and anti-glomerular basement membrane glomerulonephritis.

Science.gov (United States)

Zheng, Wei; Warner, Roscoe; Ruggeri, Roger; Su, Chunyan; Cortes, Christian; Skoura, Athanasia; Ward, Jessica; Ahn, Kay; Kalgutkar, Amit; Sun, Dexue; Maurer, Tristan S; Bonin, Paul D; Okerberg, Carlin; Bobrowski, Walter; Kawabe, Thomas; Zhang, Yanwei; Coskran, Timothy; Bell, Sammy; Kapoor, Bhupesh; Johnson, Kent; Buckbinder, Leonard

2015-05-01

Small vessel vasculitis is a life-threatening condition and patients typically present with renal and pulmonary injury. Disease pathogenesis is associated with neutrophil accumulation, activation, and oxidative damage, the latter being driven in large part by myeloperoxidase (MPO), which generates hypochlorous acid among other oxidants. MPO has been associated with vasculitis, disseminated vascular inflammation typically involving pulmonary and renal microvasculature and often resulting in critical consequences. MPO contributes to vascular injury by 1) catabolizing nitric oxide, impairing vasomotor function; 2) causing oxidative damage to lipoproteins and endothelial cells, leading to atherosclerosis; and 3) stimulating formation of neutrophil extracellular traps, resulting in vessel occlusion and thrombosis. Here we report a selective 2-thiouracil mechanism-based MPO inhibitor (PF-1355 [2-(6-(2,5-dimethoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide) and demonstrate that MPO is a critical mediator of vasculitis in mouse disease models. A pharmacokinetic/pharmacodynamic response model of PF-1355 exposure in relation with MPO activity was derived from mouse peritonitis. The contribution of MPO activity to vasculitis was then examined in an immune complex model of pulmonary disease. Oral administration of PF-1355 reduced plasma MPO activity, vascular edema, neutrophil recruitment, and elevated circulating cytokines. In a model of anti-glomerular basement membrane disease, formerly known as Goodpasture disease, albuminuria and chronic renal dysfunction were completely suppressed by PF-1355 treatment. This study shows that MPO activity is critical in driving immune complex vasculitis and provides confidence in testing the hypothesis that MPO inhibition will provide benefit in treating human vasculitic diseases. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Complex multicellular functions at a unicellular eukaryote level: Learning, memory, and immunity.

Science.gov (United States)

Csaba, György

2017-06-01

According to experimental data, eukaryote unicellulars are able to learn, have immunity and memory. Learning is carried out in a very primitive form, and the memory is not neural but an epigenetic one. However, this epigenetic memory, which is well justified by the presence and manifestation of hormonal imprinting, is strong and permanent in the life of cell and also in its progenies. This memory is epigenetically executed by the alteration and fixation of methylation pattern of genes without changes in base sequences. The immunity of unicellulars is based on self/non-self discrimination, which leads to the destruction of non-self invaders and utilization of them as nourishment (by phagocytosis). The tools of learning, memory, and immunity of unicellulars are uniformly found in plasma membrane receptors, which formed under the effect of dynamic receptor pattern generation, suggested by Koch et al., and this is the basis of hormonal imprinting, by which the encounter between a chemical substance and the cell is specifically memorized. The receptors and imprinting are also used in the later steps of evolution up to mammals (including man) in each mentioned functions. This means that learning, memory, and immunity can be deduced to a unicellular eukaryote level.

Escaping deleterious immune response in their hosts: lessons from trypanosomatids

Directory of Open Access Journals (Sweden)

Anne eGeiger

2016-05-01

Full Text Available The Trypanosomatidae family includes the genera Trypanosoma and Leishmania, protozoan parasites displaying complex digenetic life cycles requiring a vertebrate host and an insect vector. Trypanosoma brucei gambiense, T. cruzi and Leishmania spp are important human pathogens causing Human African Trypanosomiasis (HAT or Sleeping Sickness, Chagas’ disease, and various clinical forms of Leishmaniasis, respectively. They are transmitted to humans by tsetse flies, triatomine bugs or sandflies and affect millions of people worldwide.In humans, extracellular African trypanosomes (T. brucei evade the hosts’ immune defences, allowing their transmission to the next host, via the tsetse vector. By contrast, T. cruzi and Leishmania sp. have developed a complex intracellular lifestyle, also preventing several mechanisms to circumvent the host’s immune response.This review seeks to set out the immune evasion strategies developed by the different trypanosomatids resulting from parasite-host interactions and, will focus on: clinical and epidemiological importance of diseases; life cycles: parasites-hosts-vectors; innate immunity: key steps for trypanosomatids in invading hosts; deregulation of antigen presenting cells; disruption of efficient specific immunity; and the immune responses used for parasite proliferation.

Escaping Deleterious Immune Response in Their Hosts: Lessons from Trypanosomatids

Science.gov (United States)

Geiger, Anne; Bossard, Géraldine; Sereno, Denis; Pissarra, Joana; Lemesre, Jean-Loup; Vincendeau, Philippe; Holzmuller, Philippe

2016-01-01

The Trypanosomatidae family includes the genera Trypanosoma and Leishmania, protozoan parasites displaying complex digenetic life cycles requiring a vertebrate host and an insect vector. Trypanosoma brucei gambiense, Trypanosoma cruzi, and Leishmania spp. are important human pathogens causing human African trypanosomiasis (HAT or sleeping sickness), Chagas’ disease, and various clinical forms of Leishmaniasis, respectively. They are transmitted to humans by tsetse flies, triatomine bugs, or sandflies, and affect millions of people worldwide. In humans, extracellular African trypanosomes (T. brucei) evade the hosts’ immune defenses, allowing their transmission to the next host, via the tsetse vector. By contrast, T. cruzi and Leishmania sp. have developed a complex intracellular lifestyle, also preventing several mechanisms to circumvent the host’s immune response. This review seeks to set out the immune evasion strategies developed by the different trypanosomatids resulting from parasite–host interactions and will focus on: clinical and epidemiological importance of diseases; life cycles: parasites–hosts–vectors; innate immunity: key steps for trypanosomatids in invading hosts; deregulation of antigen-presenting cells; disruption of efficient specific immunity; and the immune responses used for parasite proliferation. PMID:27303406

Computing fundamentals IC3 edition

CERN Document Server

Wempen, Faithe

2014-01-01

Kick start your journey into computing and prepare for your IC3 certification With this essential course book you'll be sending e-mails, surfing the web and understanding the basics of computing in no time. Written by Faithe Wempen, a Microsoft Office Master Instructor and author of more than 120 books, this complete guide to the basics has been tailored to provide comprehensive instruction on the full range of entry-level computing skills. It is a must for students looking to move into almost any profession, as entry-level computing courses have become a compulsory requirement in the modern w

Local and systemic tumor immune dynamics

Science.gov (United States)

Enderling, Heiko

Tumor-associated antigens, stress proteins, and danger-associated molecular patterns are endogenous immune adjuvants that can both initiate and continually stimulate an immune response against a tumor. In retaliation, tumors can hijack intrinsic immune regulatory programs that are intended to prevent autoimmune disease, thereby facilitating continued growth despite the activated antitumor immune response. In metastatic disease, this ongoing tumor-immune battle occurs at each site. Adding an additional layer of complexity, T cells activated at one tumor site can cycle through the blood circulation system and extravasate in a different anatomic location to surveil a distant metastasis. We propose a mathematical modeling framework that incorporates the trafficking of activated T cells between metastatic sites. We extend an ordinary differential equation model of tumor-immune system interactions to multiple metastatic sites. Immune cells are activated in response to tumor burden and tumor cell death, and are recruited from tumor sites elsewhere in the body. A model of T cell trafficking throughout the circulatory system can inform the tumor-immune interaction model about the systemic distribution and arrival of T cells at specific tumor sites. Model simulations suggest that metastases not only contribute to immune surveillance, but also that this contribution varies between metastatic sites. Such information may ultimately help harness the synergy of focal therapy with the immune system to control metastatic disease.

Macrophage Inducible C-Type Lectin As a Multifunctional Player in Immunity

Directory of Open Access Journals (Sweden)

Emmanuel C. Patin

2017-07-01

Full Text Available The macrophage-inducible C-type lectin (Mincle is an innate immune receptor on myeloid cells sensing diverse entities including pathogens and damaged cells. Mincle was first described as a receptor for the mycobacterial cell wall glycolipid, trehalose-6,6′-dimycolate, or cord factor, and the mammalian necrotic cell-derived alarmin histone deacetylase complex unit Sin3-associated protein 130. Upon engagement by its ligands, Mincle induces secretion of innate cytokines and other immune mediators modulating inflammation and immunity. Since its discovery more than 25 years ago, the understanding of Mincle’s immune function has made significant advances in recent years. In addition to mediating immune responses to infectious agents, Mincle has been linked to promote tumor progression, autoimmunity, and sterile inflammation; however, further studies are required to completely unravel the complex role of Mincle in these distinct host responses. In this review, we discuss recent findings on Mincle’s biology with an emphasis on its diverse functions in immunity.

Circulating immune complexes, immunoglobulin G, salivary proteins and salivary immunoglobulin A in patients with Sjögren's syndrome

Directory of Open Access Journals (Sweden)

Hadži-Mihailović Miloš

2009-01-01

Full Text Available Introduction. Sjögren's syndrome (SS is a chronic autoimmune disorder, with its major clinical manifestations resulting from changes in exocrine glands. Objective The aim of this study was to evaluate serum concentrations of circulating immune complexes (CIC and immunoglobulin G (IgG, and salivary proteins (SP and salivary immunoglobulin A (sIgA in 40 patients with SS, and to correlate these values among themselves, as well as with the unstimulated salivary flow rate (USFR and the duration of disease. Methods. The total of 40 patients were included in this research. CIC was determined using the solution of polyethylene glycol and IgG with the standard procedure of radial immunodiffusion. SP was investigated by the method of Lowry and sIgA was separated from the whole saliva using the method of immune chromatography. Results. The values of most of the studied parameters exceeded the normal range in a high degree: CIC 72.5%, IgG 70%, SP 80%. The concentrations of CIC were significantly higher in the patients with the duration of disease less than 10 years. With the decrease of USFR, the concentration of sIgA and IgG were increased with statistical significance. Conclusion The increased prevalence of abnormal values of CIC, IgG and SP indicate that the patients with SS have developed a higher level of immune reactivity. These results could be useful in diagnosis and disease activity monitoring.

A novel prototyping method for die-level monolithic integration of MEMS above-IC

International Nuclear Information System (INIS)

Cicek, Paul-Vahe; Zhang, Qing; Saha, Tanmoy; Mahdavi, Sareh; Allidina, Karim; Gamal, Mourad El; Nabki, Frederic

2013-01-01

This work presents a convenient and versatile prototyping method for integrating surface-micromachined microelectromechanical systems (MEMS) directly above IC electronics, at the die level. Such localized implementation helps reduce development costs associated with the acquisition of full-sized semiconductor wafers. To demonstrate the validity of this method, variants of an IC-compatible surface-micromachining MEMS process are used to build different MEMS devices above a commercial transimpedance amplifier chip. Subsequent functional assessments for both the electronics and the MEMS indicate that the integration is successful, validating the prototyping methodology presented in this work, as well as the suitability of the selected MEMS technology for above-IC integration. (paper)

PAMP INDUCED EXPRESSION OF IMMUNE RELEVANT GENES IN HEAD KIDNEY LEUKOCYTES OF RAINBOW TROUT (ONCORHYNCHUS MYKISS)

DEFF Research Database (Denmark)

Chettri, Jiwan Kumar; Holten-Andersen, Lars; Kania, Per Walter

mykiss) to different PAMPs mimicking bacterial (flagellin and LPS), viral (poly I:C) and fungal infections (zymosan and ß-glucan). Transcript of cytokines related to inflammation (IL-1ß, IL-6, IL-10 and TNF-a) were highly up-regulated following LPS exposure whereas flagellin or poly I:C induced merely...... of the invader. Phagocytic cells are known to initiate a respiratory burst following an exposure to the pathogen, but the underlying and associated specific elements are poorly elucidated in fish. The present study describes the differential response of head kidney leukocytes from rainbow trout (Oncorhynchus...... of LPS and zymosan became evident after 4 h exposure. This study suggests that rainbow trout leukocytes respond differently to viral, bacterial and fungal PAMPs, which may reflect activation of specific signaling cascades eventually leading to activation of different immune effector molecules....

Periods and light curves of 16 Cepheid variables in IC 1613 not completed by Baade

International Nuclear Information System (INIS)

Carlson, G.; Sandage, A.

1990-01-01

New periods and light curves are presented for 16 of the faintest Cepheids in IC 1613 which had not been finished by Baade. Magnitudes have been reduced to Freedman's new photometric scale. The P-L relation is extended to periods of 2 days using these new data. Comparison of the total Cepheid data now available in IC 1613 with the data in LMC shows no significant slope difference in the two P-L relations for periods of less than 10 days despite the lower metallicity of the young stars in IC 1613. Fifty new faint Cepheid candidates have been found in IC 1613 by blinking plates not used for this purpose by Baade. Most of these stars will have probable periods of less than 2 days, which will eventually permit an extension of the P-L relation in IC 1613 to fainter magnitudes when the photometry and period determinations are completed. 18 refs

Effects of Protein-Iron Complex Concentrate Supplementation on Iron Metabolism, Oxidative and Immune Status in Preweaning Calves

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Robert Kupczyński

2017-07-01

Full Text Available The objective of this study was to determine the effects of feeding protein-iron complex (PIC on productive performance and indicators of iron metabolism, hematology parameters, antioxidant and immune status during first 35 days of a calf’s life. Preparation of the complex involved enzymatic hydrolysis of milk casein (serine protease from Yarrowia lipolytica yeast. Iron chloride was then added to the hydrolyzate and lyophilizate. Calves were divided into treated groups: LFe (low iron dose 10 g/day calf of protein-iron complex, HFe (height iron dose 20 g/day calf, and control group. Dietary supplements containing the lower dose of concentrate had a significant positive effect on iron metabolism, while the higher dose of concentrate resulted in increase of total iron binding capacity (TIBC, saturation of transferrin and decrease of and unsaturated iron binding capacity (UIBC, which suggest iron overload. Additionally, treatment with the lower dose of iron remarkably increased the antioxidant parameters, mainly total antioxidant (TAS and glutathione peroxidase activity (GPx. Higher doses of PIC were related to lower total antioxidant status. IgG, IgM, insulin, glucose, TNFα and IGF-1 concentration did not change significantly in either group after supplementation. In practice, the use of protein-iron complex concentrate requires taking into account the iron content in milk replacers and other feedstuffs.

The time-dependence of the defective nature of ice Ic (cubic ice) and its implications for atmospheric science

Science.gov (United States)

Sippel, Christian; Koza, Michael M.; Hansen, Thomas C.; Kuhs, Werner F.

2010-05-01

The possible atmospheric implication of ice Ic (cubic ice) has already been suggested some time ago in the context of snow crystal formation [1]. New findings from air-borne measurements in cirrus clouds and contrails have put ice Ic into the focus of interest to understand the so-called "supersaturation puzzle" [2,3,4]. Our recent microstructural work on ice Ic [5,6] appears to be highly relevant in this context. We have found that ice Ic is characterized by a complex stacking fault pattern, which changes as a function of temperature as well as time. Indeed, from our own [7] and other group's work [8] one knows that (in contrast to earlier believe) ice Ic can form up to temperatures at least as high as 240K - thus in the relevant range for cirrus clouds. We have good preliminary evidence that the "cubicity" (which can be related to stacking fault probabilities) as well as the particle size of ice Ic are the relevant parameters for this correlation. The "cubicity" of stacking faulty ice Ic (established by diffraction) correlates nicely with the increased supersaturation at decreasing temperatures observed in cirrus clouds and contrails, a fact, which may be considered as further evidence for the presence of ice Ic. Recently, we have studied the time-dependency of the changes in both "cubicity" and particle size at various temperatures of relevance for cirrus clouds and contrails by in-situ neutron powder diffraction. The timescales over which changes occur (several to many hours) are similar to the life-time of cirrus clouds and contrails and suggest that the supersaturation situation may change within this time span in the natural environment too. Some accompanying results obtained by cryo-SEM (scanning electron microscopy) work will also be presented and suggest that stacking-faulty ice Ic has kinky surfaces providing many more active centres for heterogeneous reactions on the surface than in the usually assumed stable hexagonal form of ice Ih with its rather

Watching AGN feedback at its birth: HST observations of nascent outflow host IC860

Science.gov (United States)

Alatalo, Katherine

2016-10-01

IC860 is a nearby IR-luminous early-type spiral with a unique set of properties: it is a shocked, poststarburst galaxy that hosts an AGN-driven neutral wind and a compact core of molecular gas. IC860 can serve as a rosetta stone for the early stages of triggering AGN feedback. We propose to use WFC3 on HST to obtain NUV, optical and near-IR imaging of IC860. We will create a spatially-resolved history of star formation quenching through SED-fitting of 7 requested broadband filters, and compare the spatially resolved star formation histories to in different positions within the underlying stellar features (such as spiral structure) that might define a narrative of how star formation is quenching in IC860. These observations will also resolve the super-star cluster sites to trace the most recent star formation. Finally, these observations will trace the mass of the outflow by building an absorption map of the dust. IC860 presents a unique opportunity to study a galaxy at an early stage of transitioning from blue spiral to red early-type galaxy, that also hosts an AGN-driven neutral wind and a compact, turbulent molecular gas core.

The Commensal Microbiota Drives Immune Homeostasis

OpenAIRE

Arrieta, Marie-Claire; Finlay, Barton Brett

2012-01-01

For millions of years, microbes have coexisted with eukaryotic cells at the mucosal surfaces of vertebrates in a complex, yet usually harmonious symbiosis. An ever-expanding number of reports describe how eliminating or shifting the intestinal microbiota has profound effects on the development and functionality of the mucosal and systemic immune systems. Here, we examine some of the mechanisms by which bacterial signals affect immune homeostasis. Focusing on the strategies that microbes use t...

ICES IN THE QUIESCENT IC 5146 DENSE CLOUD

International Nuclear Information System (INIS)

Chiar, J. E.; Pendleton, Y. J.; Allamandola, L. J.; Ennico, K.; Greene, T. P.; Roellig, T. L.; Sandford, S. A.; Boogert, A. C. A.; Geballe, T. R.; Mason, R. E.; Keane, J. V.; Lada, C. J.; Tielens, A. G. G. M.; Werner, M. W.; Whittet, D. C. B.; Decin, L.; Eriksson, K.

2011-01-01

This paper presents spectra in the 2 to 20 μm range of quiescent cloud material located in the IC 5146 cloud complex. The spectra were obtained with NASA's Infrared Telescope Facility SpeX instrument and the Spitzer Space Telescope's Infrared Spectrometer. We use these spectra to investigate dust and ice absorption features in pristine regions of the cloud that are unaltered by embedded stars. We find that the H 2 O-ice threshold extinction is 4.03 ± 0.05 mag. Once foreground extinction is taken into account, however, the threshold drops to 3.2 mag, equivalent to that found for the Taurus dark cloud, generally assumed to be the touchstone quiescent cloud against which all other dense cloud and embedded young stellar object observations are compared. Substructure in the trough of the silicate band for two sources is attributed to CH 3 OH and NH 3 in the ices, present at the ∼2% and ∼5% levels, respectively, relative to H 2 O-ice. The correlation of the silicate feature with the E(J - K) color excess is found to follow a much shallower slope relative to lines of sight that probe diffuse clouds, supporting the previous results by Chiar et al.

Detection of immune complexes in sera of dogs with rheumatic and neoplastic diseases by 125I-Clq binding test

International Nuclear Information System (INIS)

Terman, D.S.; Moore, D.; Collins, J.; Johnston, B.; Person, D.; Templeton, J.; Poser, R.; Quinby, F.

1979-01-01

Some canine rheumatic and neoplastic diseases bear a striking clinical and serological resemblance to their counterparts in man. In the present study, human 125 I-Clq was employed in a radioimmunoassay for detection of immune complexes in sera of normal dogs and those with rheumatic and neoplastic diseases. Human 125 I-Clq showed binding of 16.7 +- 5.73% in a group of normal dog sera with binding of 32.5 +- 17.3% and 43.0 +- 16.0% in sera of dogs with rheumatic and neoplastic diseases. respectively. Human 125 I-Clq bound similar quantities of heat-aggregated canine and human gamma-globulin over a broad range of concentrations and human 125 I-Clq binding in canine sera was effectively inhibited by similar quantities of heat aggregated canine and human gamma-globulin. Seven of 12 dogs with elevated levels of Clq binding had active clinical and serological rheumatic disease (SLE or rheumatoid arthritis), while none of 7 dogs with values within the normal range had active clinical disease. All 5 dogs with widespread osteogenic sarcoma and all 4 dogs with high grade adenocarcinoma of the mammary gland had elevated Clq binding values while 2 animals with low grade malignancies without evident metastases did not. Thus, it appears that human 125 I-Clq may be employed to assay immune complexes in canine sera and may be a valuable technique for the study of dogs with various rheumatic and neoplastic diseases. (author)

Definition of intercultural competence (IC) in undergraduate students at a private university in the USA: A mixed-methods study.

Science.gov (United States)

Gierke, Lioba; Binder, Nadine; Heckmann, Mark; Odağ, Özen; Leiser, Anne; Kedzior, Karina Karolina

2018-01-01

Intercultural competence (IC) is an important skill to be gained from higher education. However, it remains unclear what IC means to students and what factors might influence their definitions of IC. The aim of the current study was to qualitatively assess how students at one higher education institution in the USA define IC and to quantitatively test for relationships among IC components and various demographic characteristics, including intercultural experience and study context. A further aim was to descriptively compare the IC definitions from the US sample with the definitions obtained from another sample of university students in Germany. A purposive sample of n = 93 undergraduate, second semester students at Dickinson College, USA, participated in the study by completing an online questionnaire. The qualitative data were content-analyzed to define the dimensions of IC. The quantitative data were cluster-analyzed to assess the multivariate relationships among the IC components and the demographic characteristics of the sample. The most important dimensions of IC were Knowledge, External Outcomes (interaction, communication), and Attitudes (respect, tolerance) according to the US sample. The most frequently chosen dimensions of IC differed between both samples: Knowledge was chosen by the sample in the USA while External Outcomes was chosen by the sample in Germany. Relative to the US sample, significantly more students chose Attitudes, External Outcomes, and Intrapersonal Skills in the sample in Germany. The relationships among IC components and demographic characteristics were only weak in the US sample. A person with IC was rated as Open-minded and Respectful by students who lived predominantly in the USA or Tolerant and Curious by those who lived outside the USA for at least six months. The current results suggest that students residing in two countries (USA or Germany) define IC using similar dimensions. However, IC definitions may depend on the

Analog IC Design at the University of Twente

NARCIS (Netherlands)

Nauta, Bram

2007-01-01

This article describes some recent research results from the IC Design group of the University of Twente, located in Enschede, The Netherlands. Our research focuses on analog CMOS circuit design with emphasis on high frequency and broadband circuits. With the trend of system integration in mind, we

30 CFR 57.22102 - Smoking (I-C mines).

Science.gov (United States)

2010-07-01

... Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22102 Smoking (I-C mines). (a...

Immune response of calves inoculated with proteins ofAnaplasma marginale bound to an immunostimulant complex

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Marcela Ribeiro Gasparini

Full Text Available Despite our current knowledge of the immunology, pathology, and genetics of Anaplasma marginale, prevention in cattle is currently based on old standbys, including live attenuated vaccines, antibiotic treatment, and maintaining enzootic stability in cattle herds. In the present study, we evaluated the use of an immunostimulant complex (ISCOMATRIX adjuvant, associated with a pool of recombinant major surface proteins (rMSP1a, rMSP1b, rMSP4 and rMSP5 to improve the humoral immune response triggered in calves mainly by IgG2. Ten calves were divided in three groups: 4 calves were inoculated with the ISCOMATRIX/rMSPs (G1; 2 calves were inoculated with ISCOMATRIX adjuvant (G2; and 4 calves received saline (G3. Three inoculations were administered at 21-day intervals. In G1, the calves showed significant increases in total IgG, IgG1 and IgG2 levels 21 days after the second inoculation, compared to the control group (p < 0.05, and G1 calves remained above the cut-off value 28 days after the third inoculation (p < 0.05. The post-immunized sera from calves in G1 reacted specifically for each of the rMSPs used. In conclusion, the ISCOMATRIX/rMSPs induced antigen-specific seroconversion in calves. Therefore, additional testing to explore the protection induced by rMSPs, both alone and in conjunction with proteins previously identified as subdominant epitopes, is warranted.

VizieR Online Data Catalog: Optical & Spitzer photometry in IC 1805 (Sung+, 2017)

Science.gov (United States)

Sung, H.; Bessell, M. S.; Chun, M.-Y.; Yi, J.; Naze, Y.; Lim, B.; Karimov, R.; Rauw, G.; Park, B.-G.; Hur, H.

2017-06-01

For a study of the IMF and the star-formation history of the young open cluster IC 1805, we obtained deep wide-field VRI and Hα images of IC 1805 using the CFH12K mosaic CCD camera of the CFHT on 2002 January 6 and 7. We also observed several regions in IC 1805, for a study of the reddening and massive star content, using the SITe 2000x800 CCD (Maidanak 2k CCD) and standard UBVRI filters of the AZT-22 1.5m telescope at the Maidanak Astronomical Observatory in Uzbekistan on 2003 August 18 and 2004 december 25,30. Later, we obtained additional images of the central region of IC 1805 with the Fairchild 486 CCD (SNUCam) and UBVI and Hα filters of the AZT-22 telescope on 2007 October 7 and 2009 January 19. The Spitzer mapping observations were performed on 2006 September 20 under program ID 20052 (PI: S. Wolff). For complete photometry of stars in the CFH12K FOV in 3.6 and 4.5um, we also downloaded and reduced the GLIMPSE360 data (AOR: 38753280, 38763264, 38769408, 38799104, 38798592, 38784512, PI: B. A. Whitney). MIPS scans of IC 1805 were obtained on 2005 August 31 and 2005 September 2 (PID 3234, PI: J. S. Greeves). The Chandra X-ray Observatory Observations of IC 1805 (ObsID: 7033, PI: L. Townley) were made on 2006 November 25. The total exposure time was about 79ks. The properties of 647 X-ray sources were published in Townsley+ (2014,J/ApJS/213/1). We searched for the optical and MIR counterparts of these X-ray sources with a matching radius of up to 1.5". (4 data files).

Inactivated probiotic Bacillus coagulans GBI-30 induces complex immune activating, anti-inflammatory, and regenerative markers in vitro

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Jensen GS

2017-08-01

Full Text Available Gitte S Jensen,1 Howard A Cash,2 Sean Farmer,2 David Keller2 1NIS Labs, Esplanade, Klamath Falls, OR, USA, 2Ganeden Biotech Inc., Landerbrook Drive Suite, Mayfield Heights, OH, USA Objective: The aim of this study was to document the immune activating and anti-inflammatory effects of inactivated probiotic Bacillus coagulans GBI-30, 6086 (Staimune™ cells on human immune cells in vitro.Methods: In vitro cultures of human peripheral blood mononuclear cells (PBMC from healthy blood donors were treated with inactivated B. coagulans GBI-30, 6086 cells for 24 hours. After incubation, the PBMC were stained with fluorochrome-labeled monoclonal antibodies for CD3, CD56, and CD69 to monitor cellular activation by flow cytometry. The culture supernatants were tested for cytokine profile using a 27-plex Luminex array, including pro- and anti-inflammatory cytokines, chemokines, and growth factors.Results: Inactivated B. coagulans GBI-30, 6086 cells induced the CD69 early activation marker on CD3+ CD56− T lymphocytes, CD3+ CD56+ NKT cells, CD3−CD56+ NK cells, and also some cells within the CD3−CD56− non-T non-NK cell subset. Culture supernatants showed robust increases in the immune-activating cytokines IL-1β, IL-6, IL-17A, and TNF-α. IFN-γ levels were increased, along with three chemokines, MCP-1, MIP-1α, and MIP-1β. The two anti-inflammatory cytokines IL-1ra and IL-10 showed increases, as well as the G-CSF growth factor involved in repair and stem cell biology. In contrast, GM-CSF levels showed a mild decrease, showing a highly selective growth factor response.Conclusion: The inactivated B. coagulans GBI-30, 6086 cells activated human immune cells and altered the production of both immune activating and anti-inflammatory cytokines and chemokines. Of special importance is the novel demonstration of a selective upregulation of the G-CSF growth factor involved in postinjury and postinflammation repair and regeneration. This suggests that

Shocked molecular hydrogen in the supernova remnant IC 443

International Nuclear Information System (INIS)

Burton, M.G.; Brand, P.W.J.L.; Webster, A.S.

1988-01-01

Emission from the υ = 1-0 S(1) line of molecular hydrogen has been mapped over a section of the supernova remnant IC 443. The emission originates in a sinuous ridge where the expanding shell of the SNR is interacting with a molecular cloud. The relative intensities of the 1-0 S(1), 1-0 S(0) and 2-1 S(1) lines at 2.1-2.2 μm were measured and found to be characteristic of shock-excitation of the gas. The ridge shows bright spots which are possibly density enhancements in the molecular cloud. The total luminosity of the molecular hydrogen lines in the mapped region is estimated to be about 1000 times the solar luminosity, making IC 443 one of the most luminous galactic molecular hydrogen sources yet detected. (author)

Some new results on shock chemistry in IC 443

International Nuclear Information System (INIS)

DeNoyer, L.K.; Frerking, M.A.

1981-01-01

We have made new observations of CO, 13 CO, SiO, SO, H 2 CO, HCO + , N 2 H + , CS, OCS, HCN, and OH in the shocked clouds of IC 443. At position IC 443 B, we find (a) the shocked CO is optically thin, (b) the HCO + /CO abundance ratio is 4--9 x 10 -4 , a tenfold enhancement over normal interstellar clouds, (c) HCN/CO = 1--3 x 10 -4 and CS/CO = 2--3 x 10 -4 , consistent with abundances found in ordinary clouds, (d) no enhancements of SO or SiO as occur in Orion KL, (e) optically thin preshock OH, confirming a hundredfold enhancement of OH/CO in the shock, and (f) an OH main line anomaly, with T/sub ex/(1667)>T/sub ex/(1665) in the shocked region

A remotely-controlled locomotive IC driven by electrolytic bubbles and wireless powering.

Science.gov (United States)

Hsieh, Jian-Yu; Kuo, Po-Hung; Huang, Yi-Chun; Huang, Yu-Jie; Tsai, Rong-Da; Wang, Tao; Chiu, Hung-Wei; Wang, Yao-Hung; Lu, Shey-Shi

2014-12-01

A batteryless remotely-controlled locomotive IC utilizing electrolytic bubbles as propelling force is realized in 0.35 μm CMOS technology. Without any external components, such as magnets and on-board coils, the bare IC is wirelessly powered and controlled by a 10 MHz ASK modulated signal with RS232 control commands to execute movement in four moving directions and with two speeds. The receiving coil and electrolysis electrodes are all integrated on the locomotive chip. The experiment successfully demonstrated that the bare IC moved on the surface of an electrolyte with a speed up to 0.3 mm/s and change moving directions according to the commands. The total power consumptions of the chip are 207.4 μW and 180 μ W while the output electrolysis voltages are 2 V and 1.3 V, respectively.

Two additions to the Jacea-Lepteranthus complex: parallel adaptation in the enigmatic species Centaurea subtilis and <i>C. exarata

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Hilpold, A.

2009-12-01

Full Text Available Centaurea subtilis from south east Italy and <i>C. exarata from south west Iberia were classified in the Acrolophus- Phalolepis group and therein in section Maculosae. A molecular survey based on ITS sequence data indicates that both species should rather be placed in the Jacea-Lepteranthus group instead. This placement is consistent with the chromosome number of the two species, which is x = 11 like the rest of species of the Jacea-Lepteranthus group, and differs from the x = 9 of the other taxa included in sect. Maculosae. These results confi rm previous suggestions on the unnaturality of sect. Maculosae. Centaurea exarata and <i>C. subtilis are quite different from the other species of Jacea-Lepteranthus in some striking morphological characters, which we hypothesize to be the result of parallel adaptation to dryer climates. The lack of competitors for pollination might be a good explanation for the partial or even total loss of showy flowers in these two species.

[es] Centaurea subtilis del sureste de Italia y <i>C. exarata del suroeste de la Península Ibérica fueron clasificadas anteriormente en el grupo Acrolophus-Phalolepis y dentro de él en la sect. Maculosae. Una revisión molecular basada en secuencias de la región ITS indica que ambas deberían clasificarse en el grupo Jacea-Lepteranthus. Este cambio es coherente con el número cromosómico de las dos especies, que tienen x = 11 como el resto de las especies del grupo Jacea-Lepteranthus y no x = 9 como las especies del grupo Acrolophus-Phalolepis. Estos resultados confirman advertencias anteriores sobre el carácter artificial de la sect. Maculosae. Centaurea exarata y <i>C. subtilis son bastante diferentes de las otras especies de Jacea-Lepteranthus en algunos caracteres morfológicos importantes, resultado, según nuestra hipótesis, de adaptaciones a

Archean crustal growth of the Imataca complex, Amazonian craton: Evidence from U-Pb-Sm-Nd and Rb-Sr geochronology

International Nuclear Information System (INIS)

Tassinari, C.C.G.; Teixeira, W; Nutman, A.P; Szabo, G.; Mondin, M.; Sato, K; Santos, A.P; Siso, C.S

2001-01-01

The Archean Imataca Complex (IC), NW Amazonian Craton, forms a ENE-trending, fault-bounded block adjacent to the Paleoproterozoic Maroni-Itacai as magmatic arc (2.2 2.0 Ga) (Tassinari and Macambira, 1999). The IC rocks are complexely deformed, exhibiting elongated and symmetrical domes and thrusts combined with isoclinal folds. Transcurrent faults are also important, like the Guri Fault System - a zone of multiple faulting, shearing and mylonitization along the southeastern edge of the IC. In a pre-Pangean reconstruction using paleomagnetic data from rocks of the African counterpart, the Guri System is contiguous to the Sassandra (Ivory coast) and Zednes (Mauritaine) faults, in agreement also with the comparable geologic evolution between the NW Amazonian and the West Africa cratons, during the Archean and Late-Paleoproterozoic. The IC mainly composed of medium- to high grade quartz-feldspathic paragneiss, exhibits extensive mortar, augen, flaser and mylonitic textures. Calc-alkaline gneiss and granitoid rocks of igneous protolith are also present in the IC, as well as dolomitic marbles, orthopyroxene and magnetite quartzites, and BIFs that include huge ore deposits of Algoma type. Moreover, migmatite injections and anatexis (devoid of metasedimentary components) are widespread in the western part of Complex, the largest migmatite mass centered in Cerro La Ceiba. This paper reports zircon U-Pb SHRIMP, Sm-Nd and Rb-Sr isotopic data of different IC rocks in order to investigate their age and geological evolution within the tectonic framework of the Amazonian Craton (au)

mTOR at the Transmitting and Receiving Ends in Tumor Immunity.

Science.gov (United States)

Guri, Yakir; Nordmann, Thierry M; Roszik, Jason

2018-01-01

Cancer is a complex disease and a leading cause of death worldwide. Immunity is critical for cancer control. Cancer cells exhibit high mutational rates and therefore altered self or neo-antigens, eliciting an immune response to promote tumor eradication. Failure to mount a proper immune response leads to cancer progression. mTOR signaling controls cellular metabolism, immune cell differentiation, and effector function. Deregulated mTOR signaling in cancer cells modulates the tumor microenvironment, thereby affecting tumor immunity and possibly promoting carcinogenesis.

Spitzer Observations Of IC 2118

Science.gov (United States)

2010-09-01

Micron All-Sky Survey ( 2MASS ; Skrutskie et al. 2006) photometric data in an effort to segregate YSOs from background galaxies. While one previously known T...Spectral Typea Other names IRAS 04591−0856 05 01 30.2 −08 52 14 . . . HHL 17, G13 2MASS 05020630−0850467 05 02 06.3 −08 50 47 M2 IV . . . RXJ 0502.4−0744b...05 02 20.8 −07 44 10 . . . 2MASS 05022084−0744099 2MASS 05060574−0646151c 05 06 05.7 −06 46 15 G8: (May not be a member of IC 2118; see Kun et al

Early gene Broad complex plays a key role in regulating the immune response triggered by ecdysone in the Malpighian tubules of Drosophila melanogaster.

Science.gov (United States)

Verma, Puja; Tapadia, Madhu G

2015-08-01

In insects, humoral response to injury is accomplished by the production of antimicrobial peptides (AMPs) which are secreted in the hemolymph to eliminate the pathogen. Drosophila Malpighian tubules (MTs), however, are unique immune organs that show constitutive expression of AMPs even in unchallenged conditions and the onset of immune response is developmental stage dependent. Earlier reports have shown ecdysone positively regulates immune response after pathogenic challenge however, a robust response requires prior potentiation by the hormone. Here we provide evidence to show that MTs do not require prior potentiation with ecdysone hormone for expression of AMPs and they respond to ecdysone very fast even without immune challenge, although the different AMPs Diptericin, Cecropin, Attacin, Drosocin show differential expression in response to ecdysone. We show that early gene Broad complex (BR-C) could be regulating the IMD pathway by activating Relish and physically interacting with it to activate AMPs expression. BR-C depletion from Malpighian tubules renders the flies susceptible to infection. We also show that in MTs ecdysone signaling is transduced by EcR-B1 and B2. In the absence of ecdysone signaling the IMD pathway associated genes are down regulated and activation and translocation of transcription factor Relish is also affected. Copyright © 2015 Elsevier Ltd. All rights reserved.

Immune mechanisms and immuno therapy of thyroid cancer

International Nuclear Information System (INIS)

Samuel, A.M.

1999-01-01

In recent years the role of immune mechanisms in the induction and progress of cancer has been established. The importance of oncogenes, growth suppressor genes, gene regulation immune surveillance and the interactions of the various components of the immune system in the pathogenesis and progress of cancers is being extensively studied. In fact, the newer concepts of using immune reactions as a modality of therapy is being explored in conjunction with the treatments for cancer. The increased hope and enthusiasm for tumor immunotherapy is in a large part due to animal studies and a better understanding about surface antigens on tumors, major histocompatibility complex molecules, adhesion molecules, cytokines and a variety of newly discovered molecules which play a role in immune interactions

NKT cell self-reactivity: evolutionary master key of immune homeostasis?

Science.gov (United States)

Issazadeh-Navikas, Shohreh

2012-04-01

Complex immune responses have evolved to protect multicellular organisms against the invasion of pathogens. This has exerted strong developmental pressure for specialized functions that can also limit damage to self-tissue. Two arms of immunity, the innate and adaptive immune systems, have evolved for quick, non-specific immune responses to pathogens and more efficient, long-lasting ones upon specific recognition of recurrent pathogens. Specialized cells have arisen as the sentinels of these functions, including macrophages, natural killer (NK), and T and B-lymphocytes. Interestingly, a population of immune cells that can exert both of these complex functions, NKT cells, not only share common functions but also exhibit shared cell surface markers of cells of both arms of the immune system. These features, in combination with sophisticated maintenance of immune homeostasis, will be discussed. The recent finding of self-peptide reactivity of NKT cells in the context of CD1d, with capacity to regulate multiple autoimmune and inflammatory conditions, motivates the current proposal that self-reactive NKT cells might be the ancestral link between present NK and T cells. Their parallel selection through evolution by higher vertebrates could be related to their central function as master regulators of immune homeostasis that in part is shared with regulatory T cells. Hypothetical views on how self-reactive NKT cells secure such a central role will also be proposed.

Intellectual Capital (IC Analysis and The Effect to Financial Performance in PT Kalasuba Indonesia (KSI

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Dwi Ermayanti Susilo

2016-10-01

Full Text Available Financial Performance (FP is one of the important things for a company to know the development of the company. One important thing that influences FP is the Intellectual Capital (IC. Research was conducted to get the best IC analysis in order to get success and fulfill the daily human needs which always increases. Therefore, it had research problem ‘how was the components of IC affecting the FP of PT Kalasuba Indonesia (KSI, and the objective is to explore the IC components in affecting the FP. It was interesting to be explored because it had unique characteristics, which consist of spiritual knowledge, attitude, discipline, management knowledge and managerial experience, as well as skill and capabilities, in which the first three points were different from the rest. It used qualitative analysis method as the instrument. It was done by collecting the data through observation and was analyzed using the Robbins theory. It can be concluded that those five IC has important effect in increasing FP of PT KSI and keeping it stable.

Characterization of DNA antigens from immune complexes deposited in the skin of patients with systemic lupus erythematosus

Institute of Scientific and Technical Information of China (English)

曾凡钦; 尹若菲; 谭国珍; 郭庆; 许德清

2004-01-01

Background Skin lesions are common manifestations in systemic lupus erythematosus (SLE). It is still unknown what the definite pathogenesis of skin involvement was and whether DNA participated in it. Our study was designed to explore the pathogenetic role and nature of nuclear antigen (DNA) deposited in the skin lesions of patients with SLE.Methods Thirty skin samples from patients with SLE and 2 normal skin samples were studied. Extracellular DNA was evaluated by indirect immunofluorescence methods. The deposited immune complexes were extracted by cryoprecipitation, and DNA was then isolated with phenol and chloroform. DNA fragment sizes were detected by agarose gel electrophoresis. Finally, 8 different probes were used to analyze the origin of these DNA molecules using Dot hybridization.Results Extracellular DNA staining was found only in skin lesions, mainly those located in the basement membrane zone, vascular wall, and hair follicle wall. Normal skin and non-lesion SLE skin showed no fluorescence at locations outside the nuclei. There were no differences in the rate and intensity of extracellular DNA staining when comparing active phase to remission phase patients. No relationship was found between extracellular DNA and circulating anti-dsDNA antibodies. Deposited DNA fragments clustered into four bands of somewhat discrete sizes: 20 000 bp, 1300 bp, 800-900 bp, 100-200 bp. Small sized fragments (100-200 bp) were positively correlated with disease activity (P<0.05, r=0.407). Dot hybridization showed significant homology of the various extracellular DNA fragments examined with human genomic DNA, but not with DNA from the microorganisms and viruses we examined. There were also homologies between DNA samples from different individuals.Conclusions DNA and its immune complexes may contribute to the pathogenesis of skin lesions in SLE. These DNA molecules range in size from 100 bp to 20 kb and may be endogenous in origin.

Monitoring System for Slope Stability under Rainfall by using MEMS Acceleration Sensor IC tags

International Nuclear Information System (INIS)

Murakami, S; Dairaku, A; Komine, H; Saito, O; Sakai, N; Isizawa, T; Maruyama, I

2013-01-01

Real-time warning system for slope failure under rainfall is available to disaster prevention and mitigation. Monitoring of multi-point and wireless measurements is effective because it is difficult to conclude the most dangerous part in a slope. The purpose of this study is to propose a method of monitoring system with multi-point and wireless measurements for a slope stability using MEMS acceleration sensor IC tags. MEMS acceleration sensor IC tag is an acceleration sensor microminiaturized by a technology of Micro Electro Mechanical Systems on board IC tag. Especially, low cost of the sensor will yield to the realization of the system. In order to investigate the applicability of the proposed system, a large-scale model test of artificial slope subjected to rainfall has been performed. MEMS acceleration sensor IC tags has been located on the slope and ground acceleration caused by forced vibration has been measured until the model slope collapses. The experimental results show that the MEMS acceleration sensor IC tag is comfortably available under rainfall, the characteristics of ground accelerations varies with changing the condition of the slope subjected to rainfall, and the proposed method can be applied to a real-time monitoring system for slope failure under rainfall.

Solid-phase enzyme immunoassay or radioimmunoassay for the detection of immune complexes based on their recognition by conglutinin: conglutinin-binding test. A comparative study with /sup 125/I-labelled Clq binding and Raji-cell RIA tests

Energy Technology Data Exchange (ETDEWEB)

Casali, P; Bossus, A; Carpentier, N A; Lambert, P H [Hopital Cantonal Geneve (Switzerland)

1977-01-01

Bovine conglutinin was used in a solid-phase assay for the detection of immune complexes. In a first step, the tested serum sample was incubated in polypropylene tubes coated with conglutinin to allow C3-coated immune complexes to bind to solid-phase conglutinin. In a second step, the conglutinin-bound complexes were detected using an enzyme-conjugated or radiolabelled anti-immunoglobulin antibody. The conglutinin-binding (KgB) test did not suffer from the interference of DNA, heparin or endotoxins. Its limit of sensitivity for aggregated IgG was 3 ..mu..g/ml undiluted human serum. Immune complexes prepared in vitro using tetanus toxoid, or DNA, and corresponding antibodies in human sera could be detected at various antigen/antibody ratios and at antibody concentrations lower than 8 ..mu..g/ml. The KgB test allowed for the detection of immune complexes in sera from patients with systemic lupus erythematosus, rheumatoid arthritis, idiopathic vasculitis, leprosy and leukemia. These sera were also tested using the /sup 125/I-labelled Clq-binding activity (BA) test and the KgB test simultaneously, and a significant rank order correlation was observed. In patients with leukemia, a significant correlation was observed using three tests, KgB, /sup 125/I-labelled Clq BA and Raji-cell radioimmunoassay (RIA). Therefore, the KgB test appears as a simple and reproducible method, utilizing a very stable reagent, with a sensitivity and specificity comparable to the other tests studied and allowing for clinical application.

Regulation of TGFβ in the immune system: an emerging role for integrins and dendritic cells.

Science.gov (United States)

Worthington, John J; Fenton, Thomas M; Czajkowska, Beata I; Klementowicz, Joanna E; Travis, Mark A

2012-12-01

Regulation of an immune response requires complex crosstalk between cells of the innate and adaptive immune systems, via both cell-cell contact and secretion of cytokines. An important cytokine with a broad regulatory role in the immune system is transforming growth factor-β (TGF-β). TGF-β is produced by and has effects on many different cells of the immune system, and plays fundamental roles in the regulation of immune responses during homeostasis, infection and disease. Although many cells can produce TGFβ, it is always produced as an inactive complex that must be activated to bind to the TGFβ receptor complex and promote downstream signalling. Thus, regulation of TGFβ activation is a crucial step in controlling TGFβ function. This review will discuss how TGFβ controls diverse immune responses and how TGFβ function is regulated, with a focus on recent work highlighting a critical role for the integrin αvβ8 expressed by dendritic cells in activating TGFβ. Copyright © 2012 Elsevier GmbH. All rights reserved.

Nutrition, immune function and health of dairy cattle.

Science.gov (United States)

Ingvartsen, K L; Moyes, K

2013-03-01

The large increase in milk yield and the structural changes in the dairy industry have caused major changes in the housing, feeding and management of the dairy cow. However, while large improvements have occurred in production and efficiency, the disease incidence, based on veterinary records, does not seem to be improved. Earlier reviews have covered critical periods such as the transition period in the cow and its influence on health and immune function, the interplay between the endocrine system and the immune system and nutrition and immune function. Knowledge on these topics is crucial for our understanding of disease risk and our effort to develop health and welfare improving strategies, including proactive management for preventing diseases and reducing the severity of diseases. To build onto this the main purpose of this review will therefore be on the effect of physiological imbalance (PI) on immune function, and to give perspectives for prevention of diseases in the dairy cow through nutrition. To a large extent, the health problems during the periparturient period relate to cows having difficulty in adapting to the nutrient needs for lactation. This may result in PI, a situation where the regulatory mechanisms are insufficient for the animals to function optimally leading to a high risk of a complex of digestive, metabolic and infectious problems. The risk of infectious diseases will be increased if the immune competence is reduced. Nutrition plays a pivotal role in the immune response and the effect of nutrition may be directly through nutrients or indirectly by metabolites, for example, in situations with PI. This review discusses the complex relationships between metabolic status and immune function and how these complex interactions increase the risk of disease during early lactation. A special focus will be placed on the major energetic fuels currently known to be used by immune cells (i.e. glucose, non-esterified fatty acids, beta

Metabolic immune restraints: implications for anticancer vaccines.

Science.gov (United States)

Mocellin, Simone

2010-01-01

Metabolic immune restraints belong to a highly complex network of molecular mechanisms underlying the failure of naturally occurring and therapeutically induced immune responses against cancer. In the light of the disappointing results yielded so far with anticancer vaccines in the clinical setting, the dissection of the cascade of molecular events leading to tumor immune escape appears the most promising way to develop more effective immunotherapeutic strategies. Here we review the significant advances recently made in the understanding of the tumor-specific metabolic features that contribute to keep malignant cells from being recognized and destroyed by immune effectors. These mechanistic insights are fostering the development of rationally designed therapeutics aimed to revert the immunosuppressive circuits and thus to enhance the effectiveness of anticancer vaccines.

Epstein-Barr virus-encoded EBNA2 alters immune checkpoint PD-L1 expression by downregulating miR-34a in B-cell lymphomas.

Science.gov (United States)

Anastasiadou, Eleni; Stroopinsky, Dina; Alimperti, Stella; Jiao, Alan L; Pyzer, Athalia R; Cippitelli, Claudia; Pepe, Giuseppina; Severa, Martina; Rosenblatt, Jacalyn; Etna, Marilena P; Rieger, Simone; Kempkes, Bettina; Coccia, Eliana M; Sui, Shannan J Ho; Chen, Christopher S; Uccini, Stefania; Avigan, David; Faggioni, Alberto; Trivedi, Pankaj; Slack, Frank J

2018-06-26

Cancer cells subvert host immune surveillance by altering immune checkpoint (IC) proteins. Some Epstein-Barr virus (EBV)-associated tumors have higher Programmed Cell Death Ligand, PD-L1 expression. However, it is not known how EBV alters ICs in the context of its preferred host, the B lymphocyte and in derived lymphomas. Here, we found that latency III-expressing Burkitt lymphoma (BL), diffuse large B-cell lymphomas (DLBCL) or their EBNA2-transfected derivatives express high PD-L1. In a DLBCL model, EBNA2 but not LMP1 is sufficient to induce PD-L1. Latency III-expressing DLBCL biopsies showed high levels of PD-L1. The PD-L1 targeting oncosuppressor microRNA miR-34a was downregulated in EBNA2-transfected lymphoma cells. We identified early B-cell factor 1 (EBF1) as a repressor of miR-34a transcription. Short hairpin RNA (shRNA)-mediated knockdown of EBF1 was sufficient to induce miR-34a transcription, which in turn reduced PD-L1. MiR-34a reconstitution in EBNA2-transfected DLBCL reduced PD-L1 expression and increased its immunogenicity in mixed lymphocyte reactions (MLR) and in three-dimensional biomimetic microfluidic chips. Given the importance of PD-L1 inhibition in immunotherapy and miR-34a dysregulation in cancers, our findings may have important implications for combinatorial immunotherapy, which include IC inhibiting antibodies and miR-34a, for EBV-associated cancers.

A SPECTROSCOPICALLY NORMAL TYPE Ic SUPERNOVA FROM A VERY MASSIVE PROGENITOR

International Nuclear Information System (INIS)

Valenti, Stefano; Pastorello, Andrea; Benetti, Stefano; Cappellaro, Enrico; Tomasella, Lina; Turatto, Massimo; Taubenberger, Stefan; Aramyan, Levon; Botticella, Maria Teresa; Fraser, Morgan; Smartt, Stephen J.; Magill, Lindsay; Kotak, Rubina; Wright, Darryl E.; Elias-Rosa, Nancy; Ergon, Mattias; Sollerman, Jesper; Magnier, Eugene; Price, Paul A.

2012-01-01

We present observations of the Type Ic supernova (SN Ic) 2011bm spanning a period of about one year. The data establish that SN 2011bm is a spectroscopically normal SN Ic with moderately low ejecta velocities and with a very slow spectroscopic and photometric evolution (more than twice as slow as SN 1998bw). The Pan-STARRS1 retrospective detection shows that the rise time from explosion to peak was ∼40 days in the R band. Through an analysis of the light curve and the spectral sequence, we estimate a kinetic energy of ∼7-17 foe and a total ejected mass of ∼7-17 M ☉ , 5-10 M ☉ of which is oxygen and 0.6-0.7 M ☉ is 56 Ni. The physical parameters obtained for SN 2011bm suggest that its progenitor was a massive star of initial mass 30-50 M ☉ . The profile of the forbidden oxygen lines in the nebular spectra shows no evidence of a bi-polar geometry in the ejected material.

Stress Voiding in IC Interconnects - Rules of Evidence for Failure Analysts

Energy Technology Data Exchange (ETDEWEB)

FILTER, WILLIAM F.

1999-09-17

Mention the words ''stress voiding'', and everyone from technology engineer to manager to customer is likely to cringe. This IC failure mechanism elicits fear because it is insidious, capricious, and difficult to identify and arrest. There are reasons to believe that a damascene-copper future might be void-free. Nevertheless, engineers who continue to produce ICs with Al-alloy interconnects, or who assess the reliability of legacy ICs with long service life, need up-to-date insights and techniques to deal with stress voiding problems. Stress voiding need not be fearful. Not always predictable, neither is it inevitable. On the contrary, stress voids are caused by specific, avoidable processing errors. Analytical work, though often painful, can identify these errors when stress voiding occurs, and vigilance in monitoring the improved process can keep it from recurring. In this article, they show that a methodical, forensics approach to failure analysis can solve suspected cases of stress voiding. This approach uses new techniques, and patiently applies familiar ones, to develop evidence meeting strict standards of proof.

LES of Gas Exchange in IC Engines

Directory of Open Access Journals (Sweden)

Mittal V.

2013-10-01

Full Text Available As engine technologies become increasingly complex and engines are driven to new operating points, understanding transient phenomena is important to ensure reliable engine operation. Unlike Reynolds Averaged Navier-Stokes (RANS studies that only provide cycle-averaged information, Large Eddy Simulation (LES studies are capable of simulating cycle-to-cycle dynamics. In this work, a finite difference based structured methodology for LES of IC engines is presented. This structured approach allows for an efficient mesh generation process and provides potential for higher order numerical accuracy. An efficient parallel scalable block decomposition is done to overcome the challenges associated with the low ratio of fluid elements to overall mesh elements. The motion of the valves and piston is handled using a dynamic cell blanking approach and the Arbitrary Lagrangian Eulerian (ALE method, respectively. Modified three-dimensional Navier-Stokes Characteristic Boundary Conditions (NSCBC are used in the simulation to prescribe conditions in the manifolds. The accuracy of the simulation framework is validated using various canonical configurations. Flow bench simulations of an axisymmetric configuration and an actual engine geometry are done with the LES methodology. Simulations of the gas exchange in an engine under motored conditions are also performed. Overall, good agreement is obtained with experiments for all the cases. Therefore, this framework can be used for LES of engine simulations. In the future, reactive LES simulations will be performed using this framework.

mTOR at the Transmitting and Receiving Ends in Tumor Immunity

Directory of Open Access Journals (Sweden)

Yakir Guri

2018-03-01

Full Text Available Cancer is a complex disease and a leading cause of death worldwide. Immunity is critical for cancer control. Cancer cells exhibit high mutational rates and therefore altered self or neo-antigens, eliciting an immune response to promote tumor eradication. Failure to mount a proper immune response leads to cancer progression. mTOR signaling controls cellular metabolism, immune cell differentiation, and effector function. Deregulated mTOR signaling in cancer cells modulates the tumor microenvironment, thereby affecting tumor immunity and possibly promoting carcinogenesis.

Vitamin D and neonatal immune function.

LENUS (Irish Health Repository)

Clancy, N

2013-05-01

Vitamin D deficiency is widespread in the neonatal and paediatric population of northern latitudes, particularly in children of African, Middle Eastern and Asian ethnicity. This is associated with diminished immune function and increases the risk of Th1 autoimmune diseases like type 1 diabetes. Epidermiological studies have also shown a link between vitamin D deficiency in children and a more severe course of illness with lower respiratory tract infection or Respiratory Syncitial Virus (RSV) bronchiolitis. The mechanism by which vitamin D enhances immunity is complex. It acts through the innate immune system by inducing antimicrobial peptides in epithelial cells, neutrophils and macrophages. The role of Vitamin D in neonatal and paediatric immunomodulation requires further study.

Feeding Our Immune System: Impact on Metabolism

Directory of Open Access Journals (Sweden)

Isabelle Wolowczuk

2008-01-01

Full Text Available Endogenous intestinal microflora and environmental factors, such as diet, play a central role in immune homeostasis and reactivity. In addition, microflora and diet both influence body weight and insulin-resistance, notably through an action on adipose cells. Moreover, it is known since a long time that any disturbance in metabolism, like obesity, is associated with immune alteration, for example, inflammation. The purpose of this review is to provide an update on how nutrients-derived factors (mostly focusing on fatty acids and glucose impact the innate and acquired immune systems, including the gut immune system and its associated bacterial flora. We will try to show the reader how the highly energy-demanding immune cells use glucose as a main source of fuel in a way similar to that of insulin-responsive adipose tissue and how Toll-like receptors (TLRs of the innate immune system, which are found on immune cells, intestinal cells, and adipocytes, are presently viewed as essential actors in the complex balance ensuring bodily immune and metabolic health. Understanding more about these links will surely help to study and understand in a more fundamental way the common observation that eating healthy will keep you and your immune system healthy.

Physical IC debug ─ backside approach and nanoscale challenge

Directory of Open Access Journals (Sweden)

U. Kerst

2008-05-01

Full Text Available Physical analysis for IC functionality in submicron technologies requires access through chip backside. Based upon typical global backside preparation with 50–100 µm moderate silicon thickness remaining, a state of the art of the analysis techniques available for this purpose is presented and evaluated for functional analysis and layout pattern resolution potential. A circuit edit technique valid for nano technology ICs, is also presented that is based upon the formation of local trenches using the bottom of Shallow Trench Isolation (STI as endpoint for Focused Ion Beam (FIB milling. As a derivative from this process, a locally ultra thin silicon device can be processed, creating a back surface as work bench for breakthrough applications of nanoscale analysis techniques to a fully functional circuit through chip backside. Several applications demonstrate the power and potential of this new approach.

ASD IC for the thin gap chambers in the LHC Atlas experiment

International Nuclear Information System (INIS)

Sasaki, Osamu; Yoshida, Mitsuhiro

1999-01-01

An amplifier-shaper-discriminator (ASD) chip was designed and built for Thin Gap Chambers in the forward muon trigger system of the LHC Atlas experiment. The ASD IC uses SONY Analog Master Slice bipolar technology. The IC contains 4 channels in a QFP48 package. The gain of its first stage (preamplifier) is approximately 0.8V/pC and output from the preamplifier is received by a shaper (main-amplifier) with a gain of 7. The baseline restoration circuit is incorporated in the main-amplifier. The threshold voltage for discriminator section is common to the 4 channels and their digital output level is LVDS-compatible. The IC also has analog output of the preamplifier. The equivalent noise charge at input capacitance of 150 pF is around 7,500 electrons. The power dissipation with LDVS outputs (100 Omega load) is 59mW/ch

ASD IC for the thin gap chambers in the LHC ATLAS experiment

CERN Document Server

Sasaki, O

1998-01-01

An amplifier-shaper-discriminator (ASD) chip was designed and built for Thin Gap Chambers in the forward muon trigger system of the LHC ATLAS experiment. The ASD IC uses SONY Analog Master Slice bipolar technology. The IC contains 4 $9 channels in a QFP48 package. The gain of its first stage (preamplifier) is approximately 0.8 V/pC and output from the preamplifier is received by a shaper (main-amplifier) with a gain of 7. The baseline restoration circuit is $9 incorporated in the main-amplifier. The threshold voltage for the discriminator section is common to the 4 channels and their digital output level is LVDS-compatible. The IC also has analog output for the preamplifier. The equivalent $9 noise charge at input capacitance of 150 pF is around 7500 electrons. The power dissipation with LDVS outputs (100 Omega load) is 59 mW/ch. (8 refs).

ASD IC for the thin gap chambers in the LHC ATLAS Experiment

CERN Document Server

Sasaki, O

1999-01-01

An amplifier-shaper-discriminator (ASD) chip was designed and built for Thin Gap Chambers in the forward muon trigger system of the LHC Atlas experiment. The ASD IC uses SONY Analog Master Slice bipolar technology. The IC contains 4 channels in a QFP48 package. The gain of its first stage (preamplifier) is approximately 0.8 V/pC and output from the preamplifier is received by a shaper (main-amplifier) with a gain of 7. The baseline restoration circuit is incorporated in the main-amplifier. The threshold voltage for discriminator section is common to the 4 channels and their digital output level is LVDS- compatible. The IC also has analog output of the preamplifier. The equivalent noise charge at input capacitance of 150 pF is around 7500 electrons. The power dissipation with LDVS outputs (100 Omega load) is 59 mW/ch.

AREVA advanced safety IC solutions and licensing experience for new nuclear builds and modernization projects - 15545

International Nuclear Information System (INIS)

Fourestie, B.; Pickelmann, J.; Richter, S.; Hilsenkopf, P.; Paris, P.

2015-01-01

Regulatory requirements for the Instrumentation and Control (IC) for Nuclear Power Plants have become significantly more stringent during the last 10 years in the areas of software development and qualification, traceability, diversity, or seismic requirements for instance, and with the introduction of new standards (such as the IEC 62566, or the IEC 62003). Based on a large and comprehensive experience gained from projects in several regulatory environments and different plant types (including non-OEM plants), AREVA has developed and adapted its processes and products to provide state-of-the-art IC solutions in full compliance with the regulatory demands and requirements in terms of robustness (independence, defense-in-depth, diversity and cyber-security). In this paper we present the safety IC platforms developed by AREVA. These platforms include TELEPERM XS as the computerized safety IC platform for class 1 system implementation, the Qualified Display System (QDS) for safety classified screen-based interface, and UNICORN as fully diverse analog safety IC platform for backup systems

Use of radioimmune assay in investigating reagents to be used in the immunocytochemical localization of hepatitis B surface antigen in immune complexes in the kidney of patients with membranous nephropathy and Australia antigenaemia

Energy Technology Data Exchange (ETDEWEB)

Wolfe-Coote, S [South African Medical Research Council, Tygerberg (South Africa). Inst. for Electron Microscopy

1983-09-01

Radioimmune assay (RIA) was used to investigate the effect of fixatives on antigenicity of the hepatitis B surface antigen (HBsAg) and the effect of pronase on the elution of antibody (Ab) from the HBsAg-Ab complex. The effect of pronase on Ab elution was also tested on sections of kidney from a patient with the immune complex disease systemic lupus erythematosus (SLE). Immunoglobulin G (IgG) was located in pronase treated and untreated sections using the indirect immunoperoxidase technique. Glutareldehyde was shown to be the fixative of choice for studies involving HBsAg. All fixatives were shown to have less effect on antigenicity at 4/sup 0/C than at room temperature. Osmium tetroxide reduced antigenicity to one-third, even at 4/sup 0/C. RIA and SLE kidney section studies showed that Ab was eluted from immune complexes by pronase. Pre-fixation of the antigen (Ag) by glutaraldehyde appears to have no effect on the final elution, although fixation after pronase treatment seemed to enhance the elution effects. The availability of an RIA kit with HBsAg- and Ab-coated beads was of great assistance in evaluating reagents to be used in immunoperoxidase studies of HBsAg in immune complexes of patients with membranous nephropathy and Australia antigenaemia.