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  1. Complement Activation in Arterial and Venous Thrombosis is Mediated by Plasmin

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    Jonathan H. Foley

    2016-03-01

    Full Text Available Thrombus formation leading to vaso-occlusive events is a major cause of death, and involves complex interactions between coagulation, fibrinolytic and innate immune systems. Leukocyte recruitment is a key step, mediated partly by chemotactic complement activation factors C3a and C5a. However, mechanisms mediating C3a/C5a generation during thrombosis have not been studied. In a murine venous thrombosis model, levels of thrombin–antithrombin complexes poorly correlated with C3a and C5a, excluding a central role for thrombin in C3a/C5a production. However, clot weight strongly correlated with C5a, suggesting processes triggered during thrombosis promote C5a generation. Since thrombosis elicits fibrinolysis, we hypothesized that plasmin activates C5 during thrombosis. In vitro, the catalytic efficiency of plasmin-mediated C5a generation greatly exceeded that of thrombin or factor Xa, but was similar to the recognized complement C5 convertases. Plasmin-activated C5 yielded a functional membrane attack complex (MAC. In an arterial thrombosis model, plasminogen activator administration increased C5a levels. Overall, these findings suggest plasmin bridges thrombosis and the immune response by liberating C5a and inducing MAC assembly. These new insights may lead to the development of strategies to limit thrombus formation and/or enhance resolution.

  2. Does plasmin have anticoagulant activity?

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    Jane Hoover-Plow

    2010-03-01

    Full Text Available Jane Hoover-PlowJoseph J Jacobs Center for Thrombosis and Vascular Biology, Departments of Cardiovascular Medicine and Molecular Cardiology, Lerner Research Institute Cleveland Clinic, Ohio, USAAbstract: The coagulation and fibrinolytic pathways regulate hemostasis and thrombosis, and an imbalance in these pathways may result in pathologic hemophilia or thrombosis. The plasminogen system is the primary proteolytic pathway for fibrinolysis, but also has important proteolytic functions in cell migration, extracellular matrix degradation, metalloproteinase activation, and hormone processing. Several studies have demonstrated plasmin cleavage and inactivation of several coagulation factors, suggesting plasmin may be not only be the primary fibrinolytic enzyme, but may have anticoagulant properties as well. The objective of this review is to examine both in vitro and in vivo evidence for plasmin inactivation of coagulation, and to consider whether plasmin may act as a physiological regulator of coagulation. While several studies have demonstrated strong evidence for plasmin cleavage and inactivation of coagulation factors FV, FVIII, FIX, and FX in vitro, in vivo evidence is lacking for a physiologic role for plasmin as an anticoagulant. However, inactivation of coagulation factors by plasmin may be useful as a localized anticoagulant therapy or as a combined thrombolytic and anticoagulant therapy.Keywords: thrombosis, anticoagulant, cardiovascular disease, plasminogen’s protease, blood

  3. Plasmin cleaves fibrinogen and the human complement proteins C3b and C5 in the presence of Leptospira interrogans proteins: A new role of LigA and LigB in invasion and complement immune evasion.

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    Castiblanco-Valencia, Mónica Marcela; Fraga, Tatiana Rodrigues; Pagotto, Ana Helena; Serrano, Solange Maria de Toledo; Abreu, Patricia Antonia Estima; Barbosa, Angela Silva; Isaac, Lourdes

    2016-05-01

    Plasminogen is a single-chain glycoprotein found in human plasma as the inactive precursor of plasmin. When converted to proteolytically active plasmin, plasmin(ogen) regulates both complement and coagulation cascades, thus representing an important target for pathogenic microorganisms. Leptospira interrogans binds plasminogen, which is converted to active plasmin. Leptospiral immunoglobulin-like (Lig) proteins are surface exposed molecules that interact with extracellular matrix components and complement regulators, including proteins of the FH family and C4BP. In this work, we demonstrate that these multifunctional molecules also bind plasminogen through both N- and C-terminal domains. These interactions are dependent on lysine residues and are affected by ionic strength. Competition assays suggest that plasminogen does not share binding sites with C4BP or FH on Lig proteins at physiological molar ratios. Plasminogen bound to Lig proteins is converted to proteolytic active plasmin in the presence of urokinase-type plasminogen activator (uPA). Lig-bound plasmin is able to cleave the physiological substrates fibrinogen and the complement proteins C3b and C5. Taken together, our data point to a new role of LigA and LigB in leptospiral invasion and complement immune evasion. Plasmin(ogen) acquisition by these versatile proteins may contribute to Leptospira infection, favoring bacterial survival and dissemination inside the host. Copyright © 2016. Published by Elsevier GmbH.

  4. Prostasin-dependent activation of epithelial Na+ channels by low plasmin concentrations

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    Svenningsen, Per; Uhrenholt, Torben R; Palarasah, Yaseelan

    2009-01-01

    by which plasmin stimulates ENaC activity. Cy3-labeled plasmin was found to bind to the surface of the mouse cortical collecting duct cell line, M-1. Binding depended on a glycosylphosphatidylinositol (GPI)-anchored protein. Biotin-label transfer showed that plasmin interacted with the GPI-anchored protein...... plasmin-stimulated ENaC current in monolayers of M-1 cells at low plasmin concentration (1-4 microg/ml). At a high plasmin concentration of 30 microg/ml, there was no difference between cell layers treated with or without PI-PLC. Knockdown of prostasin attenuated binding of plasmin to M1 cells and blocked...... labeling of M-1 cells. Pretreatment with plasmin abolished labeling of M-1 cells in a prostasin-dependent way. We conclude that, at low concentrations, plasmin interacts with GPI-anchored prostasin, which leads to cleavage of the gamma-subunit and activation of ENaC, while at higher concentrations, plasmin...

  5. Plasmin enzymatic activity in the presence of actin

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    Yusova E. I.

    2015-10-01

    Full Text Available Aim. To study the changes in the plasmin activity towards substrates with high and low molecular mass in the presence of actin. Methods. The proteins used for this investigation were obtained by affinity chromatography and gel-filtration. The plasmin enzymatic activity was determined by a turbidimetric assay and a chromogenic substrate-based assay. The enzyme linked immunosorbent assay and biotin-avidin-phosphatase system were used to study the interaction of plasminogen and its fragments with actin. Results. It was shown that G-actin causes 1.5-fold decrease in the rate of polymeric fibrin hydrolysis by plasmin and Glu-plasminogen activated by the tissue plasminogen activator. However, actin did not impede plasmin autolysis and had no influence on its amidase activity. We have studied an interaction of biotinylated Glu-plasminogen and its fragments (kringle 1-3, kringle 4 and mini-plasminogen with immobilized G-actin. Glu-plasminogen and kringle 4 had a high affinity towards actin (C50 is 113 and 117 nM correspondingly. Mini-plasminogen and kringe 4 did not bind to actin. A similar affinity of Glu-plasminogen and kringle 1-3 towards actin proves the involvement of the kringle 1-3 lysine-binding sites of the native plasminogen form in the actin interaction. Conclusions. Actin can modulate plasmin specificity towards high molecular mass substrates through its interaction with lysine-binding sites of the enzyme kringle domains. Actin inhibition of the fibrinolytic activity of plasmin is due to its competition with fibrin for thelysine binding sites of plasminogen/plasmin.

  6. Radioimmunoassay of an early plasmin degradation product of human fibrinogen, 'fragment A', and its clinical application

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    Takagi, K; Kawai, T [Jichi Medical School, Kawachi, Tochigi (Japan)

    1978-02-01

    Upon the plasmin digestion of human fibrinogen, an early cleavage product, which has been designated as fragment A, was isolated, and to study the action of plasmin in the circulation, radioimmunoassay for fragment A was carried out. This assay used rabbit immune serum obtained by injection of fragment A mixed with complete Freund's adjuvant, and fragment A was labelled with /sup 125/I using the Chloramin-T method. In 20 normal healthy donors its serum level was 3.57 +- 1.62..mu..g/ml (mean+-SD), and it was increased significantly in certain diseases, such as acute leukemias, candiovascular disorders, malignancies, renal failure, systemic lupus erythematosus and sepsis.

  7. Lens subluxation after plasmin and SF6 injections in rabbit eyes.

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    Wei-Chi Wu

    Full Text Available To investigate the rate of lens subluxation following plasmin and/or SF6 injections in eyes, and whether a subsequent elevated level of vascular endothelial growth factor (VEGF and vitreous tap would aggravate subluxation.Four groups of rabbits were used. Group 1 received an intravitreal injection (IVI of plasmin and SF6 in the right eye; group 2 received an IVI of plasmin in the right eye; group 3 received an IVI of SF6 in the right eye; and group 4 received an IVI of balanced salt solution in the right eye. After treatment, IVIs of VEGF were given and vitreous tap was performed three times, followed by clinical observation of lens subluxation and scanning electronic microscope evaluation of the zonular fibers.After IVIs of plasmin and SF6, and VEGF and vitreous tap had been performed one to three times, lens subluxation was noted in 0%, 43%, 71%, 71%, and 86% of the eyes in group 1. After IVIs of plasmin, VEGF, and vitreous tap had been performed one to three times, lens subluxation was noted in 11%, 22%, 44%, 44%, and 67% of the eyes in group 2. The eyes in group 3 and 4 did not show signs of lens subluxation after VEGF IVIs and vitreous tap. Histology confirmed zonular fiber damage in the eyes treated with plasmin.The incidence of lens subluxation increased following plasmin injections in the eyes, and this was aggravated by the subsequent high VEGF level in the eyes and vitreous tapping. Zonular fibers were disrupted following plasmin treatment. These effects should be kept in mind when using plasmin enzymes in patients with vitreoretinal abnormalities.

  8. Diagnosis of deep venous thrombosis by phlebography and 99Tcsup (m)-Plasmin

    International Nuclear Information System (INIS)

    Edenbrandt, C-M.; Nilsson, J.; Ohlin, P.

    1982-01-01

    One hundred and thirty-four patients admitted to the medical emergency ward due to suspect deep venous thrombosis (DVT) were examined. The uptake of intravenously injected porcine 99 Tcsup (m)-plasmin was estimated in both legs. Thereafter, phlebography was performed using a high osmolar contrast medium. All phlebographies were evaluated independently. All patients with negative phlebography were examined after 3-5 days. The plasmin test and phlebography were repeated when called for. The sensivity of the plasmin test was 100% and the specificity 51% when compared to phlebography. The extension of the DVT as demonstrated by the plasmin test was similar to that determined by phlebography. Post-phlebographic trombosis was very rare. It is concluded that 99 Tcsup (m)-plasmin test is a rapid method, convenient to the patient and well suitable as a screening test. The results indicate that a negative plasmin test excludes DVT while a positive test necessitates additional examination by phlebography. (Authors)

  9. The fibrinolytic mechanism of defibrotide: effect of defibrotide on plasmin activity.

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    Echart, Cinara L; Graziadio, Barbara; Somaini, Simona; Ferro, Laura I; Richardson, Paul G; Fareed, Jawed; Iacobelli, Massimo

    2009-12-01

    Fibrinolytic activity has been shown to be reduced in many vascular diseases, including hepatic veno-occlusive disease after stem cell transplantation, a microangiopathy characterized by sinusoidal endothelial cell injury. Defibrotide is a polydisperse oligonucleotide with antithrombotic, profibrinolytic, anti-ischemic, and antiadhesive properties. Numerous clinical studies have shown promising activity of defibrotide in the treatment and prevention of veno-occlusive disease, with minimal toxicity. In corollary laboratory studies, defibrotide has been shown to decrease plasminogen activator inhibitor-1, increase tissue plasminogen activator levels, and increase overall plasma fibrinolytic activity in patients. Plasmin, a potent and nonspecific serine protease, plays a pivotal role in fibrinolysis by virtue of its ability to effectively degrade fibrin clots. In this study, defibrotide increases the activity of plasmin in hydrolyzing its substrate in a dose-dependent and length-dependent manner. Similar concentration-dependent effects of defibrotide were observed when plasmin was generated by tissue plasminogen activator or urokinase activation of plasminogen. In contrast, defibrotide had no direct effect on the activation of plasminogen to plasmin. Defibrotide was also able to enhance the activity of plasmin in degrading fibrin clot formed from fibrinogen, plasminogen, and thrombin. This effect was also concentration-dependent and directly correlated with the enzymatic activity of plasmin. This study therefore demonstrates that defibrotide is capable of enhancing the activity of plasmin and so contributes to its fibrinolytic activity. Taken together, these results support the effect of defibrotide in restoring the fibrinolytic vascular phenotype, in microangiopathic conditions such as veno-occlusive disease.

  10. Contact thermography, 99mTc-plasmin scintimetry and 99mTc-plasmin scintigraphy as screening methods for deep venous thrombosis following major hip surgery

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    Christensen, S W; Wille-Jørgensen, P; Kjaer, L

    1987-01-01

    Fifty-six patients scheduled for total hip alloplasty were screened for deep venous thrombosis by means of 99mTc-plasmin scintimetry, 99mTc-plasmin scintigraphy and contact thermography. Investigations were performed on the seventh postoperative day, and a total of 112 legs were examined. Bilateral...

  11. Diagnosis of deep venous thrombosis by phlebography and /sup 99/Tcsup (m)-Plasmin

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    Edenbrandt, C.M.; Nilsson, J.; Ohlin, P. (County Hospital, Helsingborg (Sweden). Dept. of Medicine, Diagnostic Radiology and Clinical Physology)

    1982-01-01

    One hundred and thirty-four patients admitted to the medical emergency ward due to suspected deep venous thrombosis (DVT) were examined. The uptake of intravenously injected porcine /sup 99/Tcsup (m)-plasmin was estimated in both legs. Thereafter, phlebography was performed using a high osmolar contrast medium. All phlebographies were evaluated independently. All patients with negative phlebography were examined after 3-5 days. The plasmin test and phlebography were repeated when called for. The sensivity of the plasmin test was 100% and the specificity 51% when compared to phlebography. The extension of the DVT as demonstrated by the plasmin test was similar to that determined by phlebography. Post-phlebographic trombosis was very rare. It is concluded that /sup 99/Tcsup (m)-plasmin test is a rapid method, convenient to the patient and well suitable as a screening test. The results indicate that a negative plasmin test excludes DVT while a positive test necessitates additional examination by phlebography.

  12. Urinary plasmin activates collecting duct ENaC current in preeclampsia

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    Buhl, KB; Friis, Ulla Glenert; Svenningsen, Per

    2012-01-01

    In nephrotic syndrome, plasminogen is aberrantly filtered from plasma to the urinary space and activated along the tubular system. In vitro, plasmin increases ENaC current by proteolytic cleavage of the γ-subunit. It was hypothesized that preeclampsia is associated with plasmin-dependent ability...

  13. Concentraciones de activador tisular del plasminógeno e inhibidor del activador del plasminógeno en pacientes con homocistinuria clásica

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    SA Castañeda

    2001-07-01

    Full Text Available El objetivo de este estudio fue determinar las concentraciones de homocisteína (Hcy, inhibidor del activador del plasminógeno tipo 1 (PAI-1 y activador tisular del plasminógeno (tPA en pacientes con homocistinuria clásica, en familiares de éstos y en población control sana.

  14. Plasmin substrate binding site cooperativity guides the design of potent peptide aldehyde inhibitors.

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    Swedberg, Joakim E; Harris, Jonathan M

    2011-10-04

    Perioperative bleeding is a cause of major blood loss and is associated with increased rates of postoperative morbidity and mortality. To combat this, antifibrinolytic inhibitors of the serine protease plasmin are commonly used to reduce bleeding during surgery. The most effective and previously widely used of these is the broad range serine protease inhibitor aprotinin. However, adverse clinical outcomes have led to use of alternative serine lysine analogues to inhibit plasmin. These compounds suffer from low selectivity and binding affinity. Consequently, a concerted effort to discover potent and selective plasmin inhibitors has developed. This study used a noncombinatorial peptide library to define plasmin's extended substrate specificity and guide the design of potent transition state analogue inhibitors. The various substrate binding sites of plasmin were found to exhibit a higher degree of cooperativity than had previously been appreciated. Peptide sequences capitalizing on these features produced high-affinity inhibitors of plasmin. The most potent of these, Lys-Met(sulfone)-Tyr-Arg-H [KM(O(2))YR-H], inhibited plasmin with a K(i) of 3.1 nM while maintaining 25-fold selectivity over plasma kallikrein. Furthermore, 125 nM (0.16 μg/mL) KM(O(2))YR-H attenuated fibrinolysis in vitro with an efficacy similar to that of 15 nM (0.20 μg/mL) aprotinin. To date, this is the most potent peptide inhibitor of plasmin that exhibits selectivity against plasma kallikrein, making this compound an attractive candidate for further therapeutic development.

  15. Demonstration of 99mTc-labelled plasmin on the surface of ex vivo thrombi

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    Tengborn, L.; Hedner, U.; Rohlin, M.; Stahlberg, F.

    1982-01-01

    In an vitro system using the Chandler model for the preparation of in vitro thrombi trace amounts of porcine or human 99mTc-labelled plasmin was found to adsorb to the surface of a preformed thrombus. A radioactive lining of the thrombus could be demonstrated using autoradiography after addition of 99mTc-labelled plasmin in concentrations of 0.04 - 0.07 or 0.4 - 0.7 CTA u/thrombus made from 2 ml whole blood (0.035 - 0.35 microM). The same pattern was found for porcine as for human plasmin. The presence of tranexamic acid in concentrations of 3 to 12 mM did not affect the binding of plasmin indicating that the plasmin binding to fibrin was independent of the lysine binding sites. Furthermore alpha 2-antiplasmin was demonstrated on/in the thrombus also when no plasmin was present indicating a binding of alpha 2-antiplasmin to the thrombus. The plasmin bound to the thrombus was proteolytically inactive. In order to obtain thrombolysis most of the alpha 2-antiplasmin in the surrounding medium had to be neutralized

  16. Plasminogen Binding Proteins and Plasmin Generation on the Surface of Leptospira spp.: The Contribution to the Bacteria-Host Interactions

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    Monica L. Vieira

    2012-01-01

    Full Text Available Leptospirosis is considered a neglected infectious disease of human and veterinary concern. Although extensive investigations on host-pathogen interactions have been pursued by several research groups, mechanisms of infection, invasion and persistence of pathogenic Leptospira spp. remain to be elucidated. We have reported the ability of leptospires to bind human plasminogen (PLG and to generate enzimatically active plasmin (PLA on the bacteria surface. PLA-coated Leptospira can degrade immobilized ECM molecules, an activity with implications in host tissue penetration. Moreover, we have identified and characterized several proteins that may act as PLG-binding receptors, each of them competent to generate active plasmin. The PLA activity associated to the outer surface of Leptospira could hamper the host immune attack by conferring the bacteria some benefit during infection. The PLA-coated leptospires obstruct complement C3b and IgG depositions on the bacterial surface, most probably through degradation. The decrease of leptospiral opsonization might be an important aspect of the immune evasion strategy. We believe that the presence of PLA on the leptospiral surface may (i facilitate host tissue penetration, (ii help the bacteria to evade the immune system and, as a consequence, (iii permit Leptospira to reach secondary sites of infection.

  17. A link between interferon and augmented plasmin generation in exocrine gland damage in Sjögren's syndrome.

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    Gliozzi, Maria; Greenwell-Wild, Teresa; Jin, Wenwen; Moutsopoulos, Niki M; Kapsogeorgou, Efstathia; Moutsopoulos, Haralampos M; Wahl, Sharon M

    2013-02-01

    Sjögren's syndrome is an autoimmune disease that targets exocrine glands, but often exhibits systemic manifestations. Infiltration of the salivary and lacrimal glands by lymphoid and myeloid cells orchestrates a perpetuating immune response leading to exocrine gland damage and dysfunction. Th1 and Th17 lymphocyte populations and their products recruit additional lymphocytes, including B cells, but also large numbers of macrophages, which accumulate with disease progression. In addition to cytokines, chemokines, chitinases, and lipid mediators, macrophages contribute to a proteolytic milieu, underlying tissue destruction, inappropriate repair, and compromised glandular functions. Among the proteases enhanced in this local environment are matrix metalloproteases (MMP) and plasmin, generated by plasminogen activation, dependent upon plasminogen activators, such as tissue plasminogen activator (tPA). Not previously associated with salivary gland pathology, our evidence implicates enhanced tPA in the context of inflamed salivary glands revolving around lymphocyte-mediated activation of macrophages. Tracking down the mechanism of macrophage plasmin activation, the cytokines IFNγ and to a lesser extent, IFNα, via Janus kinase (JAK) and signal transducer and activator of transcription (STAT) activation, were found to be pivotal for driving the plasmin cascade of proteolytic events culminating in perpetuation of the inflammation and tissue damage, and suggesting intervention strategies to blunt irreversible tissue destruction. Published by Elsevier Ltd.

  18. Plasmin-dependent proteolysis of tissue factor pathway inhibitor in a mouse model of endotoxemia.

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    Lupu, C; Herlea, O; Tang, H; Lijnen, R H; Lupu, F

    2013-01-01

    The development of a procoagulant state in sepsis, owing to aberrant expression of tissue factor (TF) and a sharp decrease in the level of its major inhibitor, TF pathway inhibitor (TFPI), could lead to microthrombotic organ failure. The mechanism for the decline in TFPI activity in the lung could involve plasmin-mediated cleavage of the inhibitor. To investigate the effect of plasmin generation on lung-associated TFPI activity, in normal conditions and during infusion of endotoxin (lipopolysaccharide [LPS]) in mice. Plasmin generation and TFPI activity were assayed in the lungs of mice deficient in tissue-type plasminogen (Plg) activator (t-PA) or Plg, at 2 h after LPS or saline injection. The sharp loss of lung-associated TFPI activity at 2 h after LPS challenge paralleled the abrupt increase in plasmin generation. TFPI activity was significantly retained in both t-PA(-/-) and Plg(-/-) mice, which are unable to generate plasmin. The increased plasmin generation during the early stages of sepsis could cleave/inactivate TFPI and thus lead to thrombotic complications. © 2012 International Society on Thrombosis and Haemostasis.

  19. Purification and characterization of mutant miniPlasmin for thrombolytic therapy

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    Lin Xiaotao

    2013-01-01

    Full Text Available Abstract Background Previous animal studies by us and others have indicated that catheter-administered plasmin or its des-kringle derivatives may be more appropriate alternatives to plasminogen activators for treating thrombolytic diseases, since it has a very short serum half-life and therefore does not result in hemorrhaging. We have previously produced recombinant miniPlasmin (mPlasmin that was proven suitable for treating peripheral arterial occlusion in animal models. However, our previous results showed that non-specific cleavage at position K698 of mPlasmin during activation hindered the further development of this promising therapeutic candidate. In order to minimize or eliminate the non-specific cleavage problem, we performed saturation mutagenesis at the K698 position to develop a mutant form of mPlasmin for thrombolytic therapy. Methods We changed K698 to 16 other amino acids, with preferred E. coli codons. Each of these mutants were expressed in E. coli as inclusion bodies and then refolded, purified, and subsequently characterized by detailed kinetic assays/experiments/studies which identified highly active mutants devoid of non-specific cleavage. Results Activation studies indicated that at those conditions in which the wild type enzyme is cut at the non-specific position K698, the active mutants can be activated without being cleaved at this position. Conclusions From the above results, we selected two mutants, K698Q and K698N, as our lead candidates for further thrombolytic drug developments. The selected mutants are potentially better therapeutic candidates for thrombolytic therapy.

  20. PVD following plasmin but not hyaluronidase: implications for combination pharmacologic vitreolysis therapy.

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    Wang, Zhi-Liang; Zhang, Xi; Xu, Xun; Sun, Xiao-Dong; Wang, Fang

    2005-01-01

    To study whether intravitreal injection of plasmin + hyaluronidase safely induces posterior vitreous detachment (PVD). Rabbits were randomized into three groups: (A) 20 rabbits, intravitreal injection of plasmin 1 U + hyaluronidase 20 U in balanced salt solution (BSS) 0.1 mL into one eye; (B) 12 rabbits, plasmin alone; (C) 12 rabbits, hyaluronidase alone. The fellow eye of each rabbit was injected BSS 0.1 mL. In Group A, scanning electron microscopy (SEM) was done in four rabbits at 0.5 hour and in four rabbits at 1 hour. After 7 days, all the remaining 36 rabbits received electroretinography, SEM was examined in eight of each group, and immunohistochemistry was done in four of each group. SEM disclosed the eyes of Group A had complete PVD (8/8), Group B partial PVD (7/8), and Group C (8/8) and all the control eyes (24/24) no PVD after 7 days. Partial PVD was found in 4/4 at 0.5 hour and complete PVD was seen in 3/4 at 1 hour in Group A. Immunohistochemistry showed that the amounts of laminin and fibronectin in the vitreoretinal interface were decreased in Group A and B versus the control eyes (P 0.05). Electroretinography showed no changes in any group (P >0.05). Vitreous injection of plasmin + hyaluronidase induced complete PVD with no obvious toxicity. Plasmin induced partial PVD, but hyaluronidase had no effects.

  1. Plasmin digest of κ-casein as a source of antibacterial peptides.

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    Sedaghati, Marjaneh; Ezzatpanah, Hamid; Boojar, Masoud Mashhadi Akbar; Ebrahimi, Maryam Tajabadi; Aminafshar, Mehdi

    2014-05-01

    This study investigated the antibacterial properties of plasmin, the plasmin hydrolysis of bovine κ-casein and the fractions (named κC1, κC2, κC3, κC4, and κC5) liberated from it using RP-HPLC. The target bacteria were Escherichia coli, Staphylococcus aureus (pathogenic), Lactobacillus casei and Lactobacillus acidophilus (probiotic). Three peptides (kC1, kC3, and kC4) were found to have antibacterial activity, with κC3 peptide being the most active. The plasmin digest of bovine κ-casein proved to be stronger than any of its fractions in terms of antibacterial potential. Measurement of the minimum inhibitory concentration (MIC) showed that Gram-positive bacteria are generally more sensitive to antibacterial activity than Gram-negative bacteria. The MIC of nisin, as a bacteriocin peptide, was also measured. The three antibacterial peptides were identified using LC-Mass. The molecular mass of kC1, kC3, and kC4 corresponded to the f(17-21), f(22-24), and f(1-3) of bovine κ-casein, respectively. It was also found that the positive charge and hydrophobicity of a peptide are not key factors in antibacterial activity. On the whole, the present study demonstrated that the plasmin digest of κ-casein has a high antibacterial potential and can be considered as a natural antibacterial agent in the food chain.

  2. Inhibition of plasmin activity by tranexamic acid does not influence inflammatory pathways during human endotoxemia

    NARCIS (Netherlands)

    Renckens, Rosemarijn; Weijer, Sebastiaan; de Vos, Alex F.; Pater, Jennie M.; Meijers, Joost C.; Hack, C. Erik; Levi, Marcel; van der Poll, Tom

    2004-01-01

    Objective - Plasmin activates several proinflammatory pathways at the cellular level in vitro. Lipopolysaccharide (LPS) administration to healthy humans results in a rapid generation of plasmin activity, accompanied by activation of a number of inflammatory systems. Methods and Results - To

  3. Exogenous t-PA administration increases hippocampal mature BDNF levels. plasmin- or NMDA-dependent mechanism?

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    Marion Rodier

    Full Text Available Brain-derived neurotrophic factor (BDNF through TrkB activation is central for brain functioning. Since the demonstration that plasmin is able to process pro-BDNF to mature BDNF and that these two forms have opposite effects on neuronal survival and plasticity, a particular attention has been paid to the link between tissue plasminogen activator (tPA/plasmin system and BDNF metabolism. However, t-PA via its action on different N-methyl-D-aspartate (NMDA receptor subunits is also considered as a neuromodulator of glutamatergic transmission. In this context, the aim of our study was to investigate the effect of recombinant (rt-PA administration on brain BDNF metabolism in rats. In the hippocampus, we found that rt-PA (10 mg/kg administration induced a progressive increase in mature BDNF levels associated with TrkB activation. In order to delineate the mechanistic involved, plasmin activity was assessed and its inhibition was attempted using tranexamic acid (30 or 300 mg/kg, i.v. while NMDA receptors were antagonized with MK801 (0.3 or 3 mg/kg, i.p. in combination with rt-PA treatment. Our results showed that despite a rise in rt-PA activity, rt-PA administration failed to increase hippocampal plasmin activity suggesting that the plasminogen/plasmin system is not involved whereas MK801 abrogated the augmentation in mature BDNF levels observed after rt-PA administration. All together, our results show that rt-PA administration induces increase in hippocampal mature BDNF expression and suggests that rt-PA contributes to the control of brain BDNF synthesis through a plasmin-independent potentiation of NMDA receptors signaling.

  4. Concentraciones del activador tisular del plasminógeno y del inhibidor del activador del plasminógeno en pacientes con homocistinuria clásica

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    Beatriz Meneses

    2001-04-01

    Full Text Available El aumento moderado o severo de Homocisteína (Hcy en sangre y las alteraciones en el sistema fibrinolítico, se asocian con enfermedad vascular que afecta venas y arterias de todos los calibres. Los pacientes con homocistinuria clásica padecen con mucha frecuencia eventos tromboembólicos, que son su principal causa de mortalidad. El objetivo de este estudio fue determinar las concentraciones de Hcy, Inhibidor del Activador del Plasminógeno tipo 1 (PAI-1 y Activador tisular del Plasminógeno (tPA en pacientes con homocistinuria clásica, en familiares de éstos y en población control sana.

  5. Plasmin in urine from patients with type 2 diabetes and treatment-resistant hypertension activates ENaC in vitro

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    Buhl, Kristian B; Stolzenburg Oxlund, Christina; Friis, Ulla G

    2014-01-01

    diabetes mellitus (T2DM) and treatment-resistant hypertension excrete plasmin(ogen) in urine in proportion to albumin and that plasmin confers to urine the ability to activate ENaC. METHOD:: Patients (n = 113) with T2DM and resistant hypertension, defined as systolic blood pressure (SBP) more than 130 mm...... of plasmin in preurine may inappropriately activate ENaC in patients with type 2 diabetes and microalbuminuria. This may contribute to treatment-resistant hypertension.......BACKGROUND:: Aberrant filtration of plasminogen from plasma and subsequent activation to plasmin in the urinary space may activate proteolytically the epithelial sodium channel, ENaC. In conditions with chronic albuminuria, this may cause hypertension. It was hypothesized that patients with type 2...

  6. Plasmin in Nephrotic Urine Activates the Epithelial Sodium Channel

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    Svenningsen, Per; Bistrup, Claus; Friis, Ulla G

    2009-01-01

    stimulated amiloride-sensitive transepithelial sodium transport in M-1 cells and increased amiloride-sensitive whole-cell currents in Xenopus laevis oocytes heterologously expressing ENaC. Activation of ENaC by plasmin involved cleavage and release of an inhibitory peptide from the ENaC gamma subunit...

  7. Return to normal of sup(99m)Tc-plasmin test after deep venous thrombosis and its relationship to vessel wall fibrinolysis

    Energy Technology Data Exchange (ETDEWEB)

    Edenbrandt, C.M.; Hedner, U.; Tengborn, L.; Nilsson, J.; Ohlin, P.

    1986-08-01

    Fourteen patients with deep venous thrombosis (DVT) and a positive sup(99m)Tc-plasmin test were followed up to determine how soon a negative test was obtained. Localization and extension of the thrombi were determined by phlebography. Plasminogen activator activity in vein walls and local fibrinolytic activity after venous occlusion were measured in order to find out what the prerequisites for impaired thrombolysis are. The time required to obtain a negative sup(99m)Tc-plasmin test showed considerable variation, ranging from less than 1 week to more than 6 months. The sup(99m)Tc-plasmin test had returned to normal in 64% of the patients after 6 months. No relationship was found between vessel wall fibrinolysis and time to normalization. Instead, we found an association between the time to normalization of the sup(99m)Tc-plasmin test and the size of the thrombus, according to phlebography, as well as between the time to normalization of the sup(99m)Tc-plasmin test and the extension of leg points with a positive sup(99m)Tc-plasmin test at admission. The finding of abnormal sup(99m)Tc-plasmin test results more than 6 months after acute DVT is of practical importance and warrants caution when evaluating patients with symptoms and signs suggestive of acute recurrent DVT.

  8. Determinación de los parámetros cinéticos de la plasmina porcina y comparación con la humana = Porcine plasmin: determination of kinetic parameters and comparison with human plasmin

    Directory of Open Access Journals (Sweden)

    Arbeláez Ramírez, Luis Fernando

    2012-04-01

    Full Text Available El plasminógeno es el zimógeno de la plasmina, enzima relacionada con la disolución del coágulo sanguíneo. Estudios con plasminas de diferentes especies animales han demostrado mayor afinidad que la plasmina humana por sustratos análogos hechos exclusivamente para ella. Así lo confirman la activación y cinética del sistema plasminógeno/plasmina porcino, que hasta el presente no se habían determinado ni comparado con el humano. En este trabajo se utilizaron, para la purificación del plasminógeno, cromatografía de afinidad y cambio iónico; se utilizó urocinasa para la activación del plasminógeno a plasmina y se determinaron los parámetros cinéticos con el sustrato cromógeno S-2251. Los terminales-N se determinaron por el método de degradación de Edman. La plasmina porcina demostró mayor afinidad (Km por el sustrato que la plasmina humana, 1,55 y 5,3 mM respectivamente, mientras que la plasmina humana mostró mayor velocidad de conversión del sustrato a producto (0,1 UA/ seg que la porcina (0,033 UA/seg. Los terminales-N se diferenciaron en los aminoácidos 1 y 3, DPPDDY (porcino y EPLDDY (humano.

  9. An ibuprofen-antagonized plasmin inhibitor released by human endothelial cells.

    Science.gov (United States)

    Rockwell, W B; Ehrlich, H P

    1991-02-01

    Serum-free culture medium harvested from endothelial cell monolayer cultures derived from human scars and dermis was examined for inhibition of fibrinolysis using a fibrin plate assay. Human cultured fibroblasts and smooth muscle cells did not produce any detectable inhibitory activity. The inhibitor is spontaneously released from the cultured endothelial cells over time. In the fibrin plate assay of plasmin-induced fibrinolysis, one nonsteroidal antiinflammatory (NSAI) drug, ibuprofen, was demonstrated to antagonize the inhibition of fibrinolysis. The antagonistic activity of ibuprofen appears unrelated to its NSAI drug activity because other NSAI drugs such as indomethacin and tolmetin have minimal antagonistic activity. Heating the cultured endothelial cells to 42 degrees C stimulates greater release of the inhibitor in a shorter period of time. This plasmin inhibitor, which is produced by endothelial cells, may contribute to postburn vascular occlusion, leading to secondary progressive necrosis in burn-traumatized patients.

  10. Plasma levels of plasmin-antiplasmin-complexes are predictive for small abdominal aortic aneurysms expanding to operation-recommendable sizes

    DEFF Research Database (Denmark)

    Lindholt, Jes Sanddal; Jørgensen, B; Fasting, H

    2001-01-01

    Three proteolytic systems seem involved in the aneurysmal degradation of the aortic wall. Plasmin is a common activator of the systems and could thus be predictive for the progression of abdominal aortic aneurysms (AAAs).......Three proteolytic systems seem involved in the aneurysmal degradation of the aortic wall. Plasmin is a common activator of the systems and could thus be predictive for the progression of abdominal aortic aneurysms (AAAs)....

  11. Plasmin-driven fibrinolysis facilitates skin tumor growth in a gender-dependent manner

    DEFF Research Database (Denmark)

    Hald, Andreas; Eickhardt, Hanne; Maerkedahl, Rasmus Baadsgaard

    2012-01-01

    deficiency was due to thrombosis and lost patency of the tumor vasculature, resulting in tumor necrosis. The connection between plasmin-dependent fibrinolysis, vascular patency, and tumor growth was further substantiated as the effect of plasminogen deficiency on tumor growth could be reverted...

  12. Dimerized plasmin fragment D as a potential biomarker to predict successful catheter-directed thrombolysis therapy in acute deep vein thrombosis.

    Science.gov (United States)

    Luo, Chien-Ming; Wu, I-Hui; Chan, Chih-Yang; Chen, Yih-Sharng; Yang, Wei-Shiung; Wang, Shoei-Shen

    2015-10-01

    The value of dimerized plasmin fragment D in the clinical monitoring during the catheter-directed thrombolysis in patients with acute deep vein thrombosis is not known. Dimerized plasmin fragment D levels in 24 patients with acute deep vein thrombosis undergoing catheter-directed thrombolysis were prospectively evaluated. The plasma dimerized plasmin fragment D level was measured serially before and at every 12 h during catheter-directed thrombolysis for 24 h. Technical success was defined as restoration of patency and flow with less than 50% residual thrombus by surveillance rotational venography. Technical success was achieved in 79.2% (19 of 24) of the treated limbs after catheter-directed thrombolysis. In univariate analysis, there was significant elevation of the dimerized plasmin fragment D at 12th h after starting the catheter-directed thrombolysis (P fragment D to predict successful catheter-directed thrombolysis was determined as 18.4 µg/ml at the 12th h after starting the catheter-directed thrombolysis with sensitivity 0.8 and specificity 0.8 (P = 0.03). It was further validated in multivariate logistic regression analysis (odds ratio: 14.38; 95% CI: 1.22-169.20; P = 0.03). Catheter-directed thrombolysis is safe and effective for restoration of blood flow in patients with acute deep vein thrombosis. Dimerized plasmin fragment D value greater than 18.4 µg/ml at the 12th h after starting catheter-directed thrombolysis had a high predictive rate of greater than 50% lysis at the end of catheter-directed thrombolysis. © The Author(s) 2014.

  13. Mhp182 (P102) binds fibronectin and contributes to the recruitment of plasmin(ogen) to the Mycoplasma hyopneumoniae cell surface.

    Science.gov (United States)

    Seymour, Lisa M; Jenkins, Cheryl; Deutscher, Ania T; Raymond, Benjamin B A; Padula, Matthew P; Tacchi, Jessica L; Bogema, Daniel R; Eamens, Graeme J; Woolley, Lauren K; Dixon, Nicholas E; Walker, Mark J; Djordjevic, Steven P

    2012-01-01

    Mycoplasma hyopneumoniae is a major, economically damaging respiratory pathogen. Although M. hyopneumoniae cells bind plasminogen, the identification of plasminogen-binding surface proteins and the biological ramifications of acquiring plasminogen requires further investigation. mhp182 encodes a highly expressed 102 kDa protein (P102) that undergoes proteolytic processing to generate surface-located N-terminal 60 kDa (P60) and C-terminal 42 kDa (P42) proteins of unknown function. We show that recombinant P102 (rP102) binds plasminogen at physiologically relevant concentrations (K(D) ~ 76 nM) increasing the susceptibility of plasmin(ogen) to activation by tissue-specific plasminogen activator (tPA). Recombinant proteins constructed to mimic P60 (rP60) and P42 (rP42) also bound plasminogen at physiologically significant levels. M. hyopneumoniae surface-bound plasminogen was activated by tPA and is able to degrade fibrinogen, demonstrating the biological functionality of M. hyopneumoniae-bound plasmin(ogen) upon activation. Plasmin(ogen) was readily detected in porcine ciliated airways and plasmin levels were consistently higher in bronchoalveolar lavage fluid from M. hyopneumoniae-infected animals. Additionally, rP102 and rP42 bind fibronectin with K(D) s of 26 and 33 nM respectively and recombinant P102 proteins promote adherence to porcine kidney epithelial-like cells. The multifunctional binding ability of P102 and activation of M. hyopneumoniae-sequestered plasmin(ogen) by an exogenous activator suggests P102 plays an important role in virulence. © 2011 Blackwell Publishing Ltd.

  14. Determining Human Clot Lysis Time (in vitro with Plasminogen/Plasmin from Four Species (Human, Bovine, Goat, and Swine

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    Omaira Cañas Bermúdez

    2015-05-01

    Full Text Available Cardiovascular disease is the leading cause of death worldwide, including failures in the plasminogen/plasmin system which is an important factor in poor lysis of blood clots. This article studies the fibrinolytic system in four species of mammals, and it identifies human plasminogen with highest thrombolysis efficiency. It examines plasminogen from four species (human, bovine, goat, and swine and identifies the most efficient one in human clot lysis in vitro. All plasminogens were identically purified by affinity chromatography. Human fibrinogen was purified by fractionation with ethanol. The purification of both plasminogen and fibrinogen was characterized by one-dimensional SDS-PAGE (10%. Human clot formation in vitro and its dissolution by plasminogen/plasmin consisted of determining lysis time from clot formation to its dilution. Purification of proteins showed greater than 95% purity, human plasminogen showed greater ability to lyse clot than animal plasminogen. The article concludes that human plasminogen/plasmin has the greatest catalysis and efficiency, as it dissolves human clot up to three times faster than that of irrational species.

  15. Evaluation of Serum Fibrinogen, Plasminogen, α2-Anti-Plasmin, and Plasminogen Activator Inhibitor Levels (PAI and Their Correlation with Presence of Retinopathy in Patients with Type 1 DM

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    Sefika Burcak Polat

    2014-01-01

    Full Text Available Background. Diabetic retinopathy (DR is the leading cause of blindness in the world. Retinopathy can still progress despite optimal metabolic control. The aim of the study was to determine whether different degrees of DR (proliferative or nonproliferative were associated with abnormally modulated hemostatic parameters in patients with T1DM. Method. 52 T1DM patients and 40 healthy controls were enrolled in the study. Patients were subdivided into three categories. Group I was defined as those without retinopathy, group II with NPRP, and group III with PRP. We compared these subgroups with each other and the control group (Group IV according to the serum fibrinogen, plasminogen, alpha2-anti-plasmin (α2-anti-plasmin, and PAI. Results. We detected that PAI-1, serum fibrinogen, and plasminogen levels were similar between the diabetic and control groups (P=0.209, P=0.224, and P=0.244, resp., whereas α2-anti-plasmin was higher in Groups I, II, and III compared to the control group (P<0.01, P<0.05, and P<0.001, resp.. There was a positive correlation between serum α2-anti-plasmin and HbA1c levels (r=0,268, P=0.031. Conclusion. To our knowledge there is scarce data in the literature about α2-anti-plasmin levels in type 1 diabetes. A positive correlation between α2-anti-plasmin with HbA1c suggests that fibrinolytic markers may improve with disease regulation and better glycemic control.

  16. Anticoagulant and calcium-binding properties of high molecular weight derivatives of human fibrinogen (plasmin fragments Y)

    NARCIS (Netherlands)

    Nieuwenhuizen, W.; Voskuilen, M.; Hermans, J.

    1982-01-01

    The present study was undertaken as a step to delineate further the localization of the calcium-binding sites in fibrinogen and to assess the anticlotting properties of fibrinogen degradation products. To this purpose, fragments Y were prepared by plasmin digestion of human fibrinogen in the

  17. Gender affects skin wound healing in plasminogen deficient mice

    DEFF Research Database (Denmark)

    Rønø, Birgitte; Engelholm, Lars Henning; Lund, Leif Røge

    2013-01-01

    closure in female versus male plasmin deficient mice. Further studies showed that this gender effect could not be reversed by ovariectomy, suggesting that female sex-hormones did not mediate the accelerated skin wound healing in plasmin deficient female mice. Histological examination of healed wounds...... functional plasmin thus display decreased tumor growth in a variety of cancer models. Interestingly, this role of plasmin has, in regard to skin cancer, been shown to be restricted to male mice. It remains to be clarified whether gender also affects other phenotypic characteristics of plasmin deficiency...... or if this gender effect is restricted to skin cancer. To investigate this, we tested the effect of gender on plasmin dependent immune cell migration, accumulation of hepatic fibrin depositions, skin composition, and skin wound healing. Gender did not affect immune cell migration or hepatic fibrin accumulation...

  18. Simultaneous assay for plasmin and DNase using radiolabeled human fibroblasts on microcarriers

    International Nuclear Information System (INIS)

    Boswell, G.S.; Dimitrijevich, S.D.; Gracy, R.W.

    1989-01-01

    A critical step in tissue and wound repair is the removal of eschar--accumulation of denatured cellular and extracellular macromolecules. Enzymatic debridement using a combination of plasmin (fibrinolysin) and DNase has been successfully utilized on a variety of types of wounds. Monitoring the activity of these enzymes by measuring the rate of fibrinolysis, or by viscometric changes due to DNA hydrolysis, is exceedingly cumbersome, time consuming, and, at best, only semiquantitative. Although spectrophotometric assays using synthetic substrates offer several advantages, they do not allow extrapolation of the data to the more complex natural substrates encountered in vivo. We have, therefore, developed an in vitro radioisotopic assay for the simultaneous and quantitative measurement of the hydrolytic activity of both plasmin and DNase. Double labeled ([3H]thymidine, [14C]leucine) human dermal fibroblasts grown on microcarrier beads are utilized as sources of nucleic acid and protein substrates. The assay meets all the criteria of analytical validity, is sensitive and rapid, and is amenable to adaptation for analysis of other hydrolytic enzymes. The method offers a direct evaluation of the enzymatic debridement of wounds using actual human cellular substrates. Moreover, the microcarriers provide a greatly increased surface area for cell attachment and growth, are amenable to rapid separation from the cells by simple mechanical methods, and are ideally suited to analytical manipulations

  19. PEGylated DX-1000: Pharmacokinetics and Antineoplastic Activity of a Specific Plasmin Inhibitor

    Directory of Open Access Journals (Sweden)

    Laetitia Devy

    2007-11-01

    Full Text Available Novel inhibitors of the urokinase-mediated plasminogen (plg activation system are potentially of great clinical benefit as anticancer treatments. Using phage display, we identified DX-1000 a tissue factor pathway inhibitor-derived Kunitz domain protein which is a specific high-affinity inhibitor of plasmin (pin (Ki = 99 pM. When tested in vitro, DX-1000 blocks plasminmediated pro-matrix metal loproteinase-9 (proMMP-9 activation on cells and dose-dependently inhibits tube formation, while not significantly affecting hemostasis and coagulation. However, this low-molecular weight protein inhibitor (~ 7 kDa exhibits rapid plasma clearance in mice and rabbits, limiting its potential clinical use in chronic diseases. After site-specific PEGylation, DX-1000 retains its activity and exhibits a decreased plasma clearance. This PEGylated derivative is effective in vitro, as well as potent in inhibiting tumor growth of green fluorescent protein (GFP-labeled MDA-MB-231 cells. 4PEG-DX-1000 treatment causes a significant reduction of urokinase-type plasminogen activator (uPA and plasminogen expressions, a reduction of tumor proliferation, and vascularization. 4PEG-DX-1000 treatment significantly decreases the level of active mitogenactivated protein kinase (MAPK in the primary tumors and reduces metastasis incidence. Together, our results demonstrate the potential value of plasmin inhibitors as therapeutic agents for blocking breast cancer growth and metastasis.

  20. Can the activation of plasminogen/plasmin system of the host by metabolic products of Dirofilaria immitis participate in heartworm disease endarteritis?

    Science.gov (United States)

    González-Miguel, Javier; Morchón, Rodrigo; Carretón, Elena; Montoya-Alonso, José Alberto; Simón, Fernando

    2015-04-01

    Proliferative endarteritis is one of the key pathological mechanisms of cardiopulmonary dirofilariosis, a cosmopolitan parasitosis caused by Dirofilaria immitis affecting dogs and cats around the world. It has been shown that the excretory/secretory antigens from D. immitis adult worms (DiES) bind plasminogen (PLG) and activate fibrinolysis, which can lead to a survival mechanism for the parasite in its intravascular environment. However, overproduction of plasmin (final product of the route) has been related to pathological processes similar to those described in proliferative endarteritis. The aim of this study is to relate the appearance of this pathological condition with the activation of the PLG/plasmin system of the host by DiES. Cell proliferation through the crystal violet technique, cell migration by wound healing assay and degradation of the extracellular matrix by measuring collagen degradation and levels of matrix metalloproteinases were studied in an "in vitro" model using canine vascular endothelial and smooth muscle cells. These cells were treated with a mixture of DiES + PLG. Untreated cells, cells only stimulated with DiES or with PLG, or with a mixture of DiES + PLG + εACA (an inhibitor of the PLG-plasmin conversion) were employed as controls. In addition, the effect of DiES on the expression of the fibrinolytic activators tPA and uPA, the inhibitor PAI-1 and the PLG receptor Annexin A2 was analyzed in both types of cultures by western blot. Plasmin generated by DiES + PLG binding produced a significant increase in the cell proliferation and migration of the endothelial and smooth muscle cells, as well as an increase in the destruction of the extracellular matrix based on a further degradation of Type I Collagen and an increased level of matrix metalloproteinase-2. DiES also induce an increase in the expression of tPA and uPA in endothelial cells in culture, as well as a decrease in the expression of PAI-1 in both types of cells

  1. Comparison between 99Tcm-porcine plasmin and 99Tcm-labelled erythrocytes in diagnosis of deep vein thrombosis

    Energy Technology Data Exchange (ETDEWEB)

    Edenbrandt, C.M.; Dahlstroem, J.A.; Nilsson, J.; Ohlin, P.

    1984-06-01

    In 20 patients with suspect deep venous thrombosis (DVT), scintillation detector measurements were performed over each leg during the first 60 min after intravenous injection of 99Tcm-porcine plasmin. Thereafter, 99Tcm-labelled autologous erythrocytes were injected i.v. and repeat measurements were performed. Finally, scintillation camera images of both legs were obtained. Phlebography was used as a reference method. A close relationship was found between the scintillation detector measurements, both in patients with DVT (n . 11) and in patients without DVT (n . 9). Thus, 99Tcm-plasmin is not specifically bound to the thrombus. Rather the clinical utility of the test depends mainly on circulatory changes secondary to the thrombus. Scintillation camera images of 99Tcm-erythrocytes in the legs were not useful for diagnosis of DVT in the calves but showed a high specificity for DVT in the popliteal and femoral veins.

  2. Anticoagulant and calcium-binding properties of high molecular weight derivatives of human fibrinogen, produced by plasmin (fragments X)

    NARCIS (Netherlands)

    Nieuwenhuizen, W.; Gravesen, M.

    1981-01-01

    Early plasmin degradation products (X fragments) of human fibrinogen were prepared in the presence of calcium-ions or EGTA, and purified on Sepharose 6B-CL. X fragments were characterized with respect to amino-terminal amino acids, polypeptide-chain composition, anticlotting properties and

  3. Discovery and Evaluation of Anti-Fibrinolytic Plasmin Inhibitors Derived from 5-(4-Piperidyl)isoxazol-3-ol (4-PIOL)

    DEFF Research Database (Denmark)

    Schmidt, Thomas C.; Eriksson, Per-Olof; Gustafsson, David

    2017-01-01

    Inhibition of plasmin has been found to effectively reduce fibrinolysis and to avoid hemorrhage. This can be achieved by addressing its kringle 1 domain with the known drug and lysine analogue tranexamic acid. Guided by shape similarities toward a previously discovered lead compound, 5-(4-piperidyl...

  4. Endogenously generated plasmin at the vascular wall injury site amplifies lysine binding site-dependent plasminogen accumulation in microthrombi.

    Directory of Open Access Journals (Sweden)

    Tomasz Brzoska

    Full Text Available The fibrinolytic system plays a pivotal role in the regulation of hemostasis; however, it remains unclear how and when the system is triggered to induce thrombolysis. Using intra-vital confocal fluorescence microscopy, we investigated the process of plasminogen binding to laser-induced platelet-rich microthrombi generated in the mesenteric vein of transgenic mice expressing green fluorescent protein (GFP. The accumulation of GFP-expressing platelets as well as exogenously infused Alexa Fluor 568-labeled Glu-plasminogen (Glu-plg on the injured vessel wall was assessed by measuring the increase in the corresponding fluorescence intensities. Glu-plg accumulated in a time-dependent manner in the center of the microthrombus, where phosphatidylserine is exposed on platelet surfaces and fibrin formation takes place. The rates of binding of Glu-plg in the presence of ε-aminocaproic acid and carboxypeptidase B, as well as the rates of binding of mini-plasminogen lacking kringle domains 1-4 and lysine binding sites, were significantly lower than that of Glu-plg alone, suggesting that the binding was dependent on lysine binding sites. Furthermore, aprotinin significantly suppressed the accumulation of Glu-plg, suggesting that endogenously generated plasmin activity is a prerequisite for the accumulation. In spite of the endogenous generation of plasmin and accumulation of Glu-plg in the center of microthrombi, the microthrombi did not change in size during the 2-hour observation period. When human tissue plasminogen activator was administered intravenously, Glu-plg further accumulated and the microthrombi were lysed. Glu-plg appeared to accumulate in the center of microthrombi in the early phase of microthrombus formation, and plasmin activity and lysine binding sites were required for this accumulation.

  5. Gender affects skin wound healing in plasminogen deficient mice.

    Directory of Open Access Journals (Sweden)

    Birgitte Rønø

    Full Text Available The fibrinolytic activity of plasmin plays a fundamental role in resolution of blood clots and clearance of extravascular deposited fibrin in damaged tissues. These vital functions of plasmin are exploited by malignant cells to accelerate tumor growth and facilitate metastases. Mice lacking functional plasmin thus display decreased tumor growth in a variety of cancer models. Interestingly, this role of plasmin has, in regard to skin cancer, been shown to be restricted to male mice. It remains to be clarified whether gender also affects other phenotypic characteristics of plasmin deficiency or if this gender effect is restricted to skin cancer. To investigate this, we tested the effect of gender on plasmin dependent immune cell migration, accumulation of hepatic fibrin depositions, skin composition, and skin wound healing. Gender did not affect immune cell migration or hepatic fibrin accumulation in neither wildtype nor plasmin deficient mice, and the existing differences in skin composition between males and females were unaffected by plasmin deficiency. In contrast, gender had a marked effect on the ability of plasmin deficient mice to heal skin wounds, which was seen as an accelerated wound closure in female versus male plasmin deficient mice. Further studies showed that this gender effect could not be reversed by ovariectomy, suggesting that female sex-hormones did not mediate the accelerated skin wound healing in plasmin deficient female mice. Histological examination of healed wounds revealed larger amounts of fibrotic scars in the provisional matrix of plasmin deficient male mice compared to female mice. These fibrotic scars correlated to an obstruction of cell infiltration of the granulation tissue, which is a prerequisite for wound healing. In conclusion, the presented data show that the gender dependent effect of plasmin deficiency is tissue specific and may be secondary to already established differences between genders, such as skin

  6. The Complement Binding and Inhibitory Protein CbiA of Borrelia miyamotoi Degrades Extracellular Matrix Components by Interacting with Plasmin(ogen

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    Ngoc T. T. Nguyen

    2018-02-01

    Full Text Available The emerging relapsing fever spirochete Borrelia (B. miyamotoi is transmitted by ixodid ticks and causes the so-called hard tick-borne relapsing fever or B. miyamotoi disease (BMD. More recently, we identified a surface-exposed molecule, CbiA exhibiting complement binding and inhibitory capacity and rendering spirochetes resistant to complement-mediated lysis. To gain deeper insight into the molecular principles of B. miyamotoi-host interaction, we examined CbiA as a plasmin(ogen receptor that enables B. miyamotoi to interact with the serine protease plasmin(ogen. Recombinant CbiA was able to bind plasminogen in a dose-dependent fashion. Moreover, lysine residues appear to play a crucial role in the protein-protein interaction as binding of plasminogen was inhibited by the lysine analog tranexamic acid as well as increasing ionic strength. Of relevance, plasminogen bound to CbiA can be converted by urokinase-type plasminogen activator (uPa to active plasmin which cleaved both, the chromogenic substrate S-2251 and its physiologic substrate fibrinogen. Concerning the involvement of specific amino acids in the interaction with plasminogen, lysine residues located at the C-terminus are frequently involved in the binding as reported for various other plasminogen-interacting proteins of Lyme disease spirochetes. Lysine residues located within the C-terminal domain were substituted with alanine to generate single, double, triple, and quadruple point mutants. However, binding of plasminogen to the mutated CbiA proteins was not affected, suggesting that lysine residues distant from the C-terminus might be involved in the interaction.

  7. Yeast two-hybrid screening of proteins interacting with plasmin receptor subunit: C-terminal fragment of annexin A2.

    Science.gov (United States)

    Li, Qun; Laumonnier, Yves; Syrovets, Tatiana; Simmet, Thomas

    2011-11-01

    To identify proteins that interact with the C-terminal fragment of annexin A2 (A2IC), generated by plasmin cleavage of the plasmin receptor, a heterotetramer (AA2t) containing annexin A2. The gene that encodes the A2IC fragment was obtained from PCR-amplified cDNA isolated from human monocytes, and was ligated into the pBTM116 vector using a DNA ligation kit. The resultant plasmid (pBTM116-A2IC) was sequenced with an ABI PRISM 310 Genetic Analyzer. The expression of an A2IC bait protein fused with a LexA-DNA binding domain (BD) was determined using Western blot analysis. The identification of proteins that interact with A2IC and are encoded in a human monocyte cDNA library was performed using yeast two-hybrid screening. The DNA sequences of the relevant cDNAs were determined using an ABI PRISM BigDye terminator cycle sequencing ready reaction kit. Nucleotide sequence databases were searched for homologous sequences using BLAST search analysis (http://www.ncbi.nlm.nih.gov). Confirmation of the interaction between the protein LexA-A2IC and each of cathepsin S and SNX17 was conducted using a small-scale yeast transformation and X-gal assay. The yeast transformed with plasmids encoding the bait proteins were screened with a human monocyte cDNA library by reconstituting full-length transcription factors containing the GAL4-active domain (GAL4-AD) as the prey in a yeast two-hybrid approach. After screening 1×10(7) clones, 23 independent β-Gal-positive clones were identified. Sequence analysis and a database search revealed that 15 of these positive clones matched eight different proteins (SNX17, ProCathepsin S, RPS2, ZBTB4, OGDH, CCDC32, PAPD4, and actin which was already known to interact with annexin A2). A2IC A2IC interacts with various proteins to form protein complexes, which may contribute to the molecular mechanism of monocyte activation induced by plasmin. The yeast two-hybrid system is an efficient approach for investigating protein interactions.

  8. From fibrinolysis to the plasminogen-plasmin system and beyond: a remarkable growth of knowledge, with personal observations on the history of fibrinolysis.

    Science.gov (United States)

    Kwaan, Hau C

    2014-07-01

    Great advances have been made in our understanding of the fibrinolytic system from the initial discovery of proteolysis of fibrin by plasmin to the multifaceted and complex role of the plasminogen-plasmin (P-P) system. We now know that the P-P system is composed of several serine proteases and their inhibitors (serpins). This system is involved in many physiological functions, including embryogenesis, cell migration, and wound healing. They also play an important role in the pathogenesis of many diseases, including atherosclerosis, obesity, cancer, and even autoimmune disorders, and neuronal degeneration. Knowledge of their role in cancer enables their use as a prognostic factor. Therapeutic use of various forms of proteases derived from this system has been employed as thrombolytic agents. In addition, small molecules designed to inhibit many of the components of the P-P system are now available for clinical trial, aimed at treatment of these various disorders. The history of such remarkable development of our knowledge on fibrinolysis is reviewed in this article. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  9. Interplay between behavioural thermoregulation and immune response in mealworms.

    Science.gov (United States)

    Catalán, Tamara P; Niemeyer, Hermann M; Kalergis, Alexis M; Bozinovic, Francisco

    2012-11-01

    Since the preferential body temperature should positively correlate with physiological performance, behavioural fever should enhance an organism's immune response under an immune challenge. Here we have studied the preferential body temperature (T(p)) and its consequences on immune response performance after an immune challenge in larvae of Tenebrio molitor. We evaluated T(p) and immune responses of larvae following a challenge with various concentrations of lipopolysaccharide (LPS), and we studied the correlation between T(p) and two immune traits, namely antibacterial and phenoloxidase (PO) activities. Larvae that were immune challenged with higher LPS concentrations (C(50) and C(100)) preferred in average, warmer temperatures than did larvae challenged with lower concentrations (C(0) and C(25)). T(p) of C(25)-C(100) (challenged)-mealworms was 2.3°C higher than of C(0) (control) larvae. At lower LPS concentration immune challenge (C(0) and C(25)) antibacterial activity correlated positively with T(p), but at C(50) and C(100) correlation was lose. PO activity was higher at higher LPS concentration, but its magnitude of response did not correlate with T(p) Our data suggest that behavioural fever may have a positive effect on host performance by enhancing antibacterial response under a low pathogen load situation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Neutrophils are immune cells preferentially targeted by retinoic acid in elderly subjects

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    Minet-Quinard Régine

    2010-08-01

    Full Text Available Abstract Background The immune system gradually deteriorates with age and nutritional status is a major factor in immunosenescence. Of the many nutritional factors implicated in age-related immune dysfunction, vitamin A may be a good candidate, since vitamin A concentrations classically decrease during aging whereas it may possess important immunomodulatory properties via its active metabolites, the retinoic acids. This prompted us to investigate the immune response induced by retinoids in adults and elderly healthy subjects. Before and after oral supplementation with 13cis retinoic acid (0.5 mg/kg/day during 28 days, whole blood cells were phenotyped, and functions of peripheral blood mononuclear cells (PBMC and polymorphonuclear cells (PMN were investigated by flow cytometry and ELISA tests. Results In both young adults (n = 20, 25 ± 4 years and older subjects (n = 20, 65 ± 4 years, retinoic acid supplementation had no effect on the distribution of leukocyte subpopulations or on the functions of PBMC (Il-2 and sIl-2R production, membrane expression of CD25. Concerning PMN, retinoic acid induced an increase in both spontaneous migration and cell surface expression of CD11b in the two different age populations, whereas bactericidal activity and phagocytosis remained unchanged. Conclusions We demonstrated that retinoic acid induces the same intensity of immune response between adult and older subjects, and more specifically affects PMN functions, i.e. adhesion and migration, than PBMC functions.

  11. Immunization of networks with community structure

    International Nuclear Information System (INIS)

    Masuda, Naoki

    2009-01-01

    In this study, an efficient method to immunize modular networks (i.e. networks with community structure) is proposed. The immunization of networks aims at fragmenting networks into small parts with a small number of removed nodes. Its applications include prevention of epidemic spreading, protection against intentional attacks on networks, and conservation of ecosystems. Although preferential immunization of hubs is efficient, good immunization strategies for modular networks have not been established. On the basis of an immunization strategy based on eigenvector centrality, we develop an analytical framework for immunizing modular networks. To this end, we quantify the contribution of each node to the connectivity in a coarse-grained network among modules. We verify the effectiveness of the proposed method by applying it to model and real networks with modular structure.

  12. PREFERENTIAL SECRETION OF INDUCIBLE HSP70 BY VITILIGO MELANOCYTES UNDER STRESS

    Science.gov (United States)

    Mosenson, Jeffrey A.; Flood, Kelsey; Klarquist, Jared; Eby, Jonathan M.; Koshoffer, Amy; Boissy, Raymond E.; Overbeck, Andreas; C.Tung, Rebecca; Poole, I. Caroline Le

    2014-01-01

    SUMMARY Inducible HSP70 (HSP70i) chaperones peptides from stressed cells, protecting them from apoptosis. Upon extracellular release, HSP70i serves an adjuvant function, enhancing immune responses to bound peptides. We questioned whether HSP70i differentially protects control and vitiligo melanocytes from stress and subsequent immune responses. We compared expression of HSP70i in skin samples, evaluated the viability of primary vitiligo and control melanocytes exposed to bleaching phenols, and measured secreted HSP70i. We determined whether HSP70i traffics to melanosomes to contact immunogenic proteins by cell fractionation, western blotting, electron microscopy and confocal microscopy. Viability of vitiligo and control melanocytes was equally affected under stress. However, vitiligo melanocytes secreted increased amounts of HSP70i in response to MBEH, corroborating with aberrant HSP70i expression in patient skin. Intracellular HSP70i colocalized with melanosomes, and more so in response to MBEH in vitiligo melanocytes. Thus whereas either agent is cytotoxic to melanocytes, MBEH preferentially induces immune responses to melanocytes. PMID:24354861

  13. Genome-wide analysis of immune system genes by EST profiling

    Science.gov (United States)

    Giallourakis, Cosmas; Benita, Yair; Molinie, Benoit; Cao, Zhifang; Despo, Orion; Pratt, Henry E.; Zukerberg, Lawrence R.; Daly, Mark J.; Rioux, John D.; Xavier, Ramnik J.

    2013-01-01

    Profiling studies of mRNA and miRNA, particularly microarray-based studies, have been extensively used to create compendia of genes that are preferentially expressed in the immune system. In some instances, functional studies have been subsequently pursued. Recent efforts such as ENCODE have demonstrated the benefit of coupling RNA-Seq analysis with information from expressed sequence tags (ESTs) for transcriptomic analysis. However, the full characterization and identification of transcripts that function as modulators of human immune responses remains incomplete. In this study, we demonstrate that an integrated analysis of human ESTs provides a robust platform to identify the immune transcriptome. Beyond recovering a reference set of immune-enriched genes and providing large-scale cross-validation of previous microarray studies, we discovered hundreds of novel genes preferentially expressed in the immune system, including non-coding RNAs. As a result, we have established the Immunogene database, representing an integrated EST “road map” of gene expression in human immune cells, which can be used to further investigate the function of coding and non-coding genes in the immune system. Using this approach, we have uncovered a unique metabolic gene signature of human macrophages and identified PRDM15 as a novel overexpressed gene in human lymphomas. Thus we demonstrate the utility of EST profiling as a basis for further deconstruction of physiologic and pathologic immune processes. PMID:23616578

  14. Neutralisation of uPA with a monoclonal antibody reduces plasmin formation and delays skin wound healing in tPA-deficient mice

    DEFF Research Database (Denmark)

    Jögi, Annika; Rønø, Birgitte; Lund, Ida K

    2010-01-01

    Proteolytic degradation by plasmin and metalloproteinases is essential for epidermal regeneration in skin wound healing. Plasminogen deficient mice have severely delayed wound closure as have mice simultaneously lacking the two plasminogen activators, urokinase-type plasminogen activator (u......PA) and tissue-type plasminogen activator (tPA). In contrast, individual genetic deficiencies in either uPA or tPA lead to wound healing kinetics with no or only slightly delayed closure of skin wounds....

  15. TIPE2, a negative regulator of innate and adaptive immunity that maintains immune homeostasis.

    Science.gov (United States)

    Sun, Honghong; Gong, Shunyou; Carmody, Ruaidhri J; Hilliard, Anja; Li, Li; Sun, Jing; Kong, Li; Xu, Lingyun; Hilliard, Brendan; Hu, Shimin; Shen, Hao; Yang, Xiaolu; Chen, Youhai H

    2008-05-02

    Immune homeostasis is essential for the normal functioning of the immune system, and its breakdown leads to fatal inflammatory diseases. We report here the identification of a member of the tumor necrosis factor-alpha-induced protein-8 (TNFAIP8) family, designated TIPE2, that is required for maintaining immune homeostasis. TIPE2 is preferentially expressed in lymphoid tissues, and its deletion in mice leads to multiorgan inflammation, splenomegaly, and premature death. TIPE2-deficient animals are hypersensitive to septic shock, and TIPE2-deficient cells are hyper-responsive to Toll-like receptor (TLR) and T cell receptor (TCR) activation. Importantly, TIPE2 binds to caspase-8 and inhibits activating protein-1 and nuclear factor-kappaB activation while promoting Fas-induced apoptosis. Inhibiting caspase-8 significantly blocks the hyper-responsiveness of TIPE2-deficient cells. These results establish that TIPE2 is an essential negative regulator of TLR and TCR function, and its selective expression in the immune system prevents hyperresponsiveness and maintains immune homeostasis.

  16. In vitro assessment of Tc-99m labeled bovine thrombin and streptokinase-activated human plasmin: concise communication

    International Nuclear Information System (INIS)

    Wong, D.W.; Tanaka, T.; Mishkin, F.; Lee, T.

    1979-01-01

    Bovine thrombin and streptokinase-activated human plasmin have been labeled with Tc-99m using stannous reduction of pertechnetate under physiological conditions (pH 7.4). The binding efficiency of radiotechnetium to these enzymes is greater than 94%, with less than 5% of reduced but unbound Tc-99m (Sn) complex as assayed by ascending paper radiochromatography using ITLC silica gel plate. Free or unbound pertechnetate is less than 1%. In vitro enzymatic analyses of the Tc-99m-labeled enzymes demonstrate no evidence of protein denaturation or significant loss of enzymatic activity after labeling. Both labeled enzymes are biochemically active in vitro with their respective substrates

  17. Basic Evaluation of the Newly Developed "Lias Auto P-FDP" Assay and the Influence of Plasmin-α2 Plasmin Inhibitor Complex Values on Discrepancy in the Comparison with "Lias Auto D-Dimer Neo" Assay.

    Science.gov (United States)

    Kumano, Osamu; Ieko, Masahiro; Komiyama, Yutaka; Naito, Sumiyoshi; Yoshida, Mika; Takahashi, Nobuhiko; Ohmura, Kazumasa; Hayasaki, Junki; Hayakawa, Mineji

    2018-04-01

    Laboratory determination of fibrin/fibrinogen degradation products (FDP) levels, along with that of the D-dimer, is important for assessing the fibrinolytic situation. Recently, we developed a new FDP reagent "Lias Auto P-FDP", which can detect various FDP fragments. The purpose of this study was to evaluate the basic performance of the newly developed Lias Auto P-FDP and compare it with Lias Auto D-Dimer Neo assay. The within-run precision of Lias Auto P-FDP and Lias Auto D-Dimer was determined 20 times in low and high value controls. The between-day precision was evaluated five times a day for five days. The linearity study was performed by diluting high value samples for 2 - 10-fold and 2 - 8-fold. The comparative study was performed using 172 patient samples with elevated FDP values. For the discrepancy analysis, the samples were divided into three groups by the discrepancy percentage between the FDP and D-dimer values. The groups were defined as follows: lower discrepancy group, less than -20%; no discrepancy group, -20% to 20%; upper discrepancy group, more than 20%. The coefficient of variation % (CV%) in within-run and between-day precision were within 3.8% for both FDP and the D-dimer. The correlation coefficients were more than 0.999 and the linearity was high. In the comparative study, the values of FDP were higher than that of the D-dimer in all samples. The median FDP and D-dimer values of lower discrepancy, no discrepancy, and upper discrepancy groups were 11.8, 20.3, and 51.4, and 8.0, 11.3, and 13.1, respectively. FDP showed an increasing tendency but D-Dimer showed constant values. Thus, the possible cause of discrepancy between FDP and D-dimer values were the elevated FDP values. In addition, the values of plasmin-α2 plasmin inhibitor complex (PIC) in the upper discrepancy group were higher than that of the lower and no discrepancy groups, indicating progression of fibrinolysis. In this study, we evaluated the newly developed Lias Auto P

  18. Mycobacterium leprae-Infected Macrophages Preferentially Primed Regulatory T Cell Responses and Was Associated with Lepromatous Leprosy.

    Directory of Open Access Journals (Sweden)

    Degang Yang

    2016-01-01

    Full Text Available The persistence of Mycobacterium leprae (M. leprae infection is largely dependent on the types of host immune responses being induced. Macrophage, a crucial modulator of innate and adaptive immune responses, could be directly infected by M. leprae. We therefore postulated that M. leprae-infected macrophages might have altered immune functions.Here, we treated monocyte-derived macrophages with live or killed M. leprae, and examined their activation status and antigen presentation. We found that macrophages treated with live M. leprae showed committed M2-like function, with decreased interleukin 1 beta (IL-1beta, IL-6, tumor necrosis factor alpha (TNF-alpha and MHC class II molecule expression and elevated IL-10 and CD163 expression. When incubating with naive T cells, macrophages treated with live M. leprae preferentially primed regulatory T (Treg cell responses with elevated FoxP3 and IL-10 expression, while interferon gamma (IFN-gamma expression and CD8+ T cell cytotoxicity were reduced. Chromium release assay also found that live M. leprae-treated macrophages were more resistant to CD8+ T cell-mediated cytotoxicity than sonicated M. leprae-treated monocytes. Ex vivo studies showed that the phenotype and function of monocytes and macrophages had clear differences between L-lep and T-lep patients, consistent with the in vitro findings.Together, our data demonstrate that M. leprae could utilize infected macrophages by two mechanisms: firstly, M. leprae-infected macrophages preferentially primed Treg but not Th1 or cytotoxic T cell responses; secondly, M. leprae-infected macrophages were more effective at evading CD8+ T cell-mediated cytotoxicity.

  19. Mycobacterium leprae-Infected Macrophages Preferentially Primed Regulatory T Cell Responses and Was Associated with Lepromatous Leprosy.

    Science.gov (United States)

    Yang, Degang; Shui, Tiejun; Miranda, Jake W; Gilson, Danny J; Song, Zhengyu; Chen, Jia; Shi, Chao; Zhu, Jianyu; Yang, Jun; Jing, Zhichun

    2016-01-01

    The persistence of Mycobacterium leprae (M. leprae) infection is largely dependent on the types of host immune responses being induced. Macrophage, a crucial modulator of innate and adaptive immune responses, could be directly infected by M. leprae. We therefore postulated that M. leprae-infected macrophages might have altered immune functions. Here, we treated monocyte-derived macrophages with live or killed M. leprae, and examined their activation status and antigen presentation. We found that macrophages treated with live M. leprae showed committed M2-like function, with decreased interleukin 1 beta (IL-1beta), IL-6, tumor necrosis factor alpha (TNF-alpha) and MHC class II molecule expression and elevated IL-10 and CD163 expression. When incubating with naive T cells, macrophages treated with live M. leprae preferentially primed regulatory T (Treg) cell responses with elevated FoxP3 and IL-10 expression, while interferon gamma (IFN-gamma) expression and CD8+ T cell cytotoxicity were reduced. Chromium release assay also found that live M. leprae-treated macrophages were more resistant to CD8+ T cell-mediated cytotoxicity than sonicated M. leprae-treated monocytes. Ex vivo studies showed that the phenotype and function of monocytes and macrophages had clear differences between L-lep and T-lep patients, consistent with the in vitro findings. Together, our data demonstrate that M. leprae could utilize infected macrophages by two mechanisms: firstly, M. leprae-infected macrophages preferentially primed Treg but not Th1 or cytotoxic T cell responses; secondly, M. leprae-infected macrophages were more effective at evading CD8+ T cell-mediated cytotoxicity.

  20. In vitro assessment of Tc-99m labeled bovine thrombin and streptokinase-activated human plasmin: concise communication. [Iodine 125

    Energy Technology Data Exchange (ETDEWEB)

    Wong, D.W.; Tanaka, T.; Mishkin, F.; Lee, T.

    1979-09-01

    Bovine thrombin and streptokinase-activated human plasmin have been labeled with Tc-99m using stannous reduction of pertechnetate under physiological conditions (pH 7.4). The binding efficiency of radiotechnetium to these enzymes is greater than 94%, with less than 5% of reduced but unbound Tc-99m (Sn) complex as assayed by ascending paper radiochromatography using ITLC silica gel plate. Free or unbound pertechnetate is less than 1%. In vitro enzymatic analyses of the Tc-99m-labeled enzymes demonstrate no evidence of protein denaturation or significant loss of enzymatic activity after labeling. Both labeled enzymes are biochemically active in vitro with their respective substrates.

  1. Non-preferential Trading Clubs

    DEFF Research Database (Denmark)

    Raimondos-Møller, Pascalis; Woodland, Alan D.

    2006-01-01

    This paper examines the welfare implications of non-discriminatory tariff reforms by a subset of countries, which we term a non-preferential trading club. We show that there exist coordinated tariff reforms, accompanied by appropriate income transfers between the member countries, that unambiguou......This paper examines the welfare implications of non-discriminatory tariff reforms by a subset of countries, which we term a non-preferential trading club. We show that there exist coordinated tariff reforms, accompanied by appropriate income transfers between the member countries...

  2. Relação entre atividade de plasmina e frações de caseína durante o armazenamento do leite longa vida Relationship between plasmin activity and casein fractions during storage of UHT milk

    Directory of Open Access Journals (Sweden)

    Carlos Humberto Corassin

    2013-03-01

    Full Text Available Este estudo teve como objetivo correlacionar a atividade da plasmina e as concentrações de frações de caseína no leite longa vida (UAT produzido em usina de beneficiamento do Estado de São Paulo. O leite cru foi submetido à pasteurização (72-76 ºC, 15-20 segundos, seguida da esterilização por processo de injeção direta de vapor (132-136 ºC, 34 segundos, sendo homogeneizado e envasado assepticamente em embalagens cartonadas. Quatro lotes de UAT foram analisados para atividade de plasmina e frações de caseína após 10, 30, 60, 90 e 120 dias de armazenamento. A atividade de plasmina no leite longa vida aumentou durante o armazenamento, correlacionando-se negativamente com a concentração de αs1-caseína. A atividade da plasmina apresenta resistência à esterilização do leite pelo processo UAT e aumenta a proteólise do leite longa vida como consequência da degradação da αs1-caseína.The objective of this study was to correlate the plasmin activity and the concentrations of casein fractions in ultra-high-temperature (UHT milk manufactured in a dairy plant in the State of Sao Paulo, Brazil. Raw milk was pasteurized (72-76 ºC, 15-20 seconds, followed by direct steam injection into the milk (132-136 ºC, 34 seconds, then homogenized and aseptically packaged into cartons. Four replicates of the UHT milk were analyzed for the plasmin activity and casein fractions after 10, 30, 60, 90 and 120 days of storage. Plasmin activity significantly increased in the UHT milk during storage and was negatively correlated with the concentration of αs1-casein. Plasmin is resistant to milk sterilization by the UHT process, and increases proteolysis of the UHT milk as a consequence of αs1-casein degradation.

  3. Preferential sampling in veterinary parasitological surveillance

    Directory of Open Access Journals (Sweden)

    Lorenzo Cecconi

    2016-04-01

    Full Text Available In parasitological surveillance of livestock, prevalence surveys are conducted on a sample of farms using several sampling designs. For example, opportunistic surveys or informative sampling designs are very common. Preferential sampling refers to any situation in which the spatial process and the sampling locations are not independent. Most examples of preferential sampling in the spatial statistics literature are in environmental statistics with focus on pollutant monitors, and it has been shown that, if preferential sampling is present and is not accounted for in the statistical modelling and data analysis, statistical inference can be misleading. In this paper, working in the context of veterinary parasitology, we propose and use geostatistical models to predict the continuous and spatially-varying risk of a parasite infection. Specifically, breaking with the common practice in veterinary parasitological surveillance to ignore preferential sampling even though informative or opportunistic samples are very common, we specify a two-stage hierarchical Bayesian model that adjusts for preferential sampling and we apply it to data on Fasciola hepatica infection in sheep farms in Campania region (Southern Italy in the years 2013-2014.

  4. A generalized theory of preferential linking

    Science.gov (United States)

    Hu, Haibo; Guo, Jinli; Liu, Xuan; Wang, Xiaofan

    2014-12-01

    There are diverse mechanisms driving the evolution of social networks. A key open question dealing with understanding their evolution is: How do various preferential linking mechanisms produce networks with different features? In this paper we first empirically study preferential linking phenomena in an evolving online social network, find and validate the linear preference. We propose an analyzable model which captures the real growth process of the network and reveals the underlying mechanism dominating its evolution. Furthermore based on preferential linking we propose a generalized model reproducing the evolution of online social networks, and present unified analytical results describing network characteristics for 27 preference scenarios. We study the mathematical structure of degree distributions and find that within the framework of preferential linking analytical degree distributions can only be the combinations of finite kinds of functions which are related to rational, logarithmic and inverse tangent functions, and extremely complex network structure will emerge even for very simple sublinear preferential linking. This work not only provides a verifiable origin for the emergence of various network characteristics in social networks, but bridges the micro individuals' behaviors and the global organization of social networks.

  5. Comparing perceptual and preferential decision making.

    Science.gov (United States)

    Dutilh, Gilles; Rieskamp, Jörg

    2016-06-01

    Perceptual and preferential decision making have been studied largely in isolation. Perceptual decisions are considered to be at a non-deliberative cognitive level and have an outside criterion that defines the quality of decisions. Preferential decisions are considered to be at a higher cognitive level and the quality of decisions depend on the decision maker's subjective goals. Besides these crucial differences, both types of decisions also have in common that uncertain information about the choice situation has to be processed before a decision can be made. The present work aims to acknowledge the commonalities of both types of decision making to lay bare the crucial differences. For this aim we examine perceptual and preferential decisions with a novel choice paradigm that uses the identical stimulus material for both types of decisions. This paradigm allows us to model the decisions and response times of both types of decisions with the same sequential sampling model, the drift diffusion model. The results illustrate that the different incentive structure in both types of tasks changes people's behavior so that they process information more efficiently and respond more cautiously in the perceptual as compared to the preferential task. These findings set out a perspective for further integration of perceptual and preferential decision making in a single ramework.

  6. Preferential Attachment in Online Networks: Measurement and Explanations

    NARCIS (Netherlands)

    Kunegis, J; Blattner, M; Moser, C.

    2013-01-01

    We perform an empirical study of the preferential attachment phenomenon in temporal networks and show that on the Web, networks follow a nonlinear preferential attachment model in which the exponent depends on the type of network considered. The classical preferential attachment model for networks

  7. Loss of renal function causes premature aging of the immune system.

    Science.gov (United States)

    Betjes, Michiel G H; Meijers, Ruud W J; Litjens, Nicolle H R

    2013-01-01

    Uremia-associated immune deficiency is a well-known complication of loss of renal function and contributes significantly to the overall mortality and morbidity of patients with end-stage renal disease. Chronic inflammation and increased oxidative stress are underlying the uremia-associated immune deficiency. In this review, the differential impact of uremia on the cellular immune system is summarized. Virtually all immune cells studied show a combination of an activated status and loss of function. However, uremia preferentially decreases the number and function of lymphoid cells while myeloid cells show normal and/or elevated cell numbers with increased production of inflammatory cytokines and reactive oxygen species. These particular changes are compatible with immunological aging, which is characterized by loss of thymic function, attrition of telomeres and an expanded memory T cell population. Similar to aging in healthy individuals, the proinflammatory and potential cardiotoxic subsets of CD28(null) T cells and CD16(+) monocytes are increased. Epigenetically changed hematopoietic stem cells may be involved in immunological aging as specific DNA regions become hypermethylated. Proinflammatory T cells and monocytes persist after kidney transplantation, which constitutes a persistent cardiovascular risk factor. Possible therapeutic options to reverse or halt uremia-associated immunological aging are discussed. Premature aging of the immune system is a dominant feature in patients with end-stage renal failure, which corresponds to immunological aging in elderly healthy individuals, which is characterized by preferential loss of cells belonging to the lymphoid cell lineage, inflammation and expansion of proinflammatory immune cells. © 2013 S. Karger AG, Basel.

  8. Preferential flow occurs in unsaturated conditions

    Science.gov (United States)

    Nimmo, John R.

    2012-01-01

    Because it commonly generates high-speed, high-volume flow with minimal exposure to solid earth materials, preferential flow in the unsaturated zone is a dominant influence in many problems of infiltration, recharge, contaminant transport, and ecohydrology. By definition, preferential flow occurs in a portion of a medium – that is, a preferred part, whether a pathway, pore, or macroscopic subvolume. There are many possible classification schemes, but usual consideration of preferential flow includes macropore or fracture flow, funneled flow determined by macroscale heterogeneities, and fingered flow determined by hydraulic instability rather than intrinsic heterogeneity. That preferential flow is spatially concentrated associates it with other characteristics that are typical, although not defining: it tends to be unusually fast, to transport high fluxes, and to occur with hydraulic disequilibrium within the medium. It also has a tendency to occur in association with large conduits and high water content, although these are less universal than is commonly assumed. Predictive unsaturated-zone flow models in common use employ several different criteria for when and where preferential flow occurs, almost always requiring a nearly saturated medium. A threshold to be exceeded may be specified in terms of the following (i) water content; (ii) matric potential, typically a value high enough to cause capillary filling in a macropore of minimum size; (iii) infiltration capacity or other indication of incipient surface ponding; or (iv) other conditions related to total filling of certain pores. Yet preferential flow does occur without meeting these criteria. My purpose in this commentary is to point out important exceptions and implications of ignoring them. Some of these pertain mainly to macropore flow, others to fingered or funneled flow, and others to combined or undifferentiated flow modes.

  9. Preferential role restrictions

    CSIR Research Space (South Africa)

    Britz, K

    2013-07-01

    Full Text Available ., Pozzato, G.: ALC+T : a preferential exten- sion of description logics. Fundamenta Informaticae 96(3), 341–372 (2009) 15. Giordano, L., Olivetti, N., Gliozzi, V., Pozzato, G.: A minimal model semantics for nonmonotonic reasoning. In: Proc. JELIA. pp. 228...

  10. Modeling online social networks based on preferential linking

    International Nuclear Information System (INIS)

    Hu Hai-Bo; Chen Jun; Guo Jin-Li

    2012-01-01

    We study the phenomena of preferential linking in a large-scale evolving online social network and find that the linear preference holds for preferential creation, preferential acceptance, and preferential attachment. Based on the linear preference, we propose an analyzable model, which illustrates the mechanism of network growth and reproduces the process of network evolution. Our simulations demonstrate that the degree distribution of the network produced by the model is in good agreement with that of the real network. This work provides a possible bridge between the micro-mechanisms of network growth and the macrostructures of online social networks

  11. Preferential Affirmative Action.

    Science.gov (United States)

    Bell, Derrick A., Jr.

    1982-01-01

    Discusses the philosophical rationale for preferential affirmative action presented by Daniel C. Maguire in "A New American Justice." Maintains that self-interest bars present society's acceptance of Maguire's theories of justice, as demonstrated in negative reactions to the Harvard Law Review's affirmative action plan. (MJL)

  12. Concept model semantics for DL preferential reasoning

    CSIR Research Space (South Africa)

    Britz, K

    2011-07-01

    Full Text Available ., Olivetti, N., Gliozzi, V., Pozzato, G.: ALC +T : a preferential exten- sion of description logics. Fund. Informatica 96(3), 341{372 (2009) 7. Kraus, S., Lehmann, D., Magidor, M.: Nonmonotonic reasoning, preferential mod- els and cumulative logics. Arti...

  13. Determination of plasminogen/plasmin system components and indicators of lipoproteins oxidative modification under arterial hypertension

    Directory of Open Access Journals (Sweden)

    O. I. Yusova

    2018-02-01

    Full Text Available The present study was investigated of levels of oxidative modification of lipoproteins and content of plasminogen/plasmin system components – tissue-type plasminogen activator (t-PA and plasminogen activators inhibitor-1 (PAI-I, in patients with stage II arterial hypertension (AHT and resistant form. It was established that t-PA level in blood plasma of the patients is 2 times lower under stage II hypertension than normal and 2.5 times lower under resistant AHT. The inhibitor activity is 1.5 and 2 times higher consequently. It is concluded that patients with AHT have a decreased fibrinolytic potential, which can cause thrombotic states. Our evaluation showed a significant accumulation of products of lipid and protein oxidation, decrease of activity of antioxidant enzymes and changes of the activity of high density-lipoproteins-associated enzymes (decrease of paraoxonase-1 activity, increase of myeloperoxidase activity. Oxidized lipoproteins, t-PA and PAI-1 can be used as prognostic markers of development of complications and for evaluating the efficacy of therapy in patients with arterial hypertension.

  14. Preferential attachment in evolutionary earthquake networks

    Science.gov (United States)

    Rezaei, Soghra; Moghaddasi, Hanieh; Darooneh, Amir Hossein

    2018-04-01

    Earthquakes as spatio-temporal complex systems have been recently studied using complex network theory. Seismic networks are dynamical networks due to addition of new seismic events over time leading to establishing new nodes and links to the network. Here we have constructed Iran and Italy seismic networks based on Hybrid Model and testified the preferential attachment hypothesis for the connection of new nodes which states that it is more probable for newly added nodes to join the highly connected nodes comparing to the less connected ones. We showed that the preferential attachment is present in the case of earthquakes network and the attachment rate has a linear relationship with node degree. We have also found the seismic passive points, the most probable points to be influenced by other seismic places, using their preferential attachment values.

  15. Preferential attachment in the evolution of metabolic networks

    Directory of Open Access Journals (Sweden)

    Elofsson Arne

    2005-11-01

    Full Text Available Abstract Background Many biological networks show some characteristics of scale-free networks. Scale-free networks can evolve through preferential attachment where new nodes are preferentially attached to well connected nodes. In networks which have evolved through preferential attachment older nodes should have a higher average connectivity than younger nodes. Here we have investigated preferential attachment in the context of metabolic networks. Results The connectivities of the enzymes in the metabolic network of Escherichia coli were determined and representatives for these enzymes were located in 11 eukaryotes, 17 archaea and 46 bacteria. E. coli enzymes which have representatives in eukaryotes have a higher average connectivity while enzymes which are represented only in the prokaryotes, and especially the enzymes only present in βγ-proteobacteria, have lower connectivities than expected by chance. Interestingly, the enzymes which have been proposed as candidates for horizontal gene transfer have a higher average connectivity than the other enzymes. Furthermore, It was found that new edges are added to the highly connected enzymes at a faster rate than to enzymes with low connectivities which is consistent with preferential attachment. Conclusion Here, we have found indications of preferential attachment in the metabolic network of E. coli. A possible biological explanation for preferential attachment growth of metabolic networks is that novel enzymes created through gene duplication maintain some of the compounds involved in the original reaction, throughout its future evolution. In addition, we found that enzymes which are candidates for horizontal gene transfer have a higher average connectivity than other enzymes. This indicates that while new enzymes are attached preferentially to highly connected enzymes, these highly connected enzymes have sometimes been introduced into the E. coli genome by horizontal gene transfer. We speculate

  16. Conceptualization of preferential flow for hillslope stability assessment

    Science.gov (United States)

    Kukemilks, Karlis; Wagner, Jean-Frank; Saks, Tomas; Brunner, Philip

    2018-03-01

    This study uses two approaches to conceptualize preferential flow with the goal to investigate their influence on hillslope stability. Synthetic three-dimensional hydrogeological models using dual-permeability and discrete-fracture conceptualization were subsequently integrated into slope stability simulations. The slope stability simulations reveal significant differences in slope stability depending on the preferential flow conceptualization applied, despite similar small-scale hydrogeological responses of the system. This can be explained by a local-scale increase of pore-water pressures observed in the scenario with discrete fractures. The study illustrates the critical importance of correctly conceptualizing preferential flow for slope stability simulations. It further demonstrates that the combination of the latest generation of physically based hydrogeological models with slope stability simulations allows for improvement to current modeling approaches through more complex consideration of preferential flow paths.

  17. Normal modal preferential consequence

    CSIR Research Space (South Africa)

    Britz, K

    2012-12-01

    Full Text Available beyond the basic (propositional) KLM postulates, thereby making use of the additional expressivity provided by modal logic. In particular, we show that the additional constraints we impose on the preferential semantics ensure that the rule...

  18. Preferential Market Access, Foreign Aid and Economic Development

    DEFF Research Database (Denmark)

    Afesorgbor, Sylvanus Kwaku; Abreha, Kaleb Girma

    contributed to the economic development of the beneficiary countries. Focusing on the ACP countries over the period 1970-2009, we show that only the EU preferential scheme is effective in promoting exports and that market access plays a significant and economically large role in the development of beneficiary......Several studies highlight that exporters in developing countries face substantial trade costs. To reduce these costs, a few developed countries mainly Canada, the EU, Japan and the USA granted preferential market access to these exporters. We assess whether these preferential accesses have...

  19. Preferential effects of leptin on CD4 T cells in central and peripheral immune system are critically linked to the expression of leptin receptor

    Energy Technology Data Exchange (ETDEWEB)

    Kim, So Yong; Lim, Ju Hyun [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Choi, Sung Won [Department of Molecular Biology, School of Arts and Sciences (S.W.C), Cornell University, Ithaca, NY 18450 (United States); Kim, Miyoung; Kim, Seong-Tae [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Kim, Min-Seon; Cho, You Sook [Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-600 (Korea, Republic of); Chun, Eunyoung, E-mail: chun.eunyoung@gmail.com [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Lee, Ki-Young, E-mail: thylee@med.skku.ac.kr [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of)

    2010-04-09

    Leptin can enhance thymopoiesis and modulate the T-cell immune response. However, it remains controversial whether these effects correlate with the expression of leptin receptor, ObR. We herein addressed this issue by using in vivo animal models and in vitro culture systems. Leptin treatment in both ob/ob mice and normal young mice induced increases of CD4 SP thymocytes in thymus and CD4 T cells in the periphery. Interestingly, expression of the long form ObR was significantly restricted to DN, DP and CD4 SP, but not CD8 SP thymocytes. Moreover, in the reaggregated DP thymocyte cultures with leptin plus TSCs, leptin profoundly induced differentiation of CD4 SP but not CD8 SP thymocytes, suggesting that the effects of leptin on thymocyte differentiation might be closely related to the expression of leptin receptor in developing thymocytes. Surprisingly, ObR expression was markedly higher in peripheral CD4 T cells than that in CD8 T cells. Furthermore, leptin treatment with or without IL-2 and PHA had preferential effects on cell proliferation of CD4 T cells compared to that of CD8 T cells. Collectively, these data provide evidence that the effects of leptin on differentiation and proliferation of CD4 T cells might be closely related to the expression of leptin receptor.

  20. Preferential effects of leptin on CD4 T cells in central and peripheral immune system are critically linked to the expression of leptin receptor

    International Nuclear Information System (INIS)

    Kim, So Yong; Lim, Ju Hyun; Choi, Sung Won; Kim, Miyoung; Kim, Seong-Tae; Kim, Min-Seon; Cho, You Sook; Chun, Eunyoung; Lee, Ki-Young

    2010-01-01

    Leptin can enhance thymopoiesis and modulate the T-cell immune response. However, it remains controversial whether these effects correlate with the expression of leptin receptor, ObR. We herein addressed this issue by using in vivo animal models and in vitro culture systems. Leptin treatment in both ob/ob mice and normal young mice induced increases of CD4 SP thymocytes in thymus and CD4 T cells in the periphery. Interestingly, expression of the long form ObR was significantly restricted to DN, DP and CD4 SP, but not CD8 SP thymocytes. Moreover, in the reaggregated DP thymocyte cultures with leptin plus TSCs, leptin profoundly induced differentiation of CD4 SP but not CD8 SP thymocytes, suggesting that the effects of leptin on thymocyte differentiation might be closely related to the expression of leptin receptor in developing thymocytes. Surprisingly, ObR expression was markedly higher in peripheral CD4 T cells than that in CD8 T cells. Furthermore, leptin treatment with or without IL-2 and PHA had preferential effects on cell proliferation of CD4 T cells compared to that of CD8 T cells. Collectively, these data provide evidence that the effects of leptin on differentiation and proliferation of CD4 T cells might be closely related to the expression of leptin receptor.

  1. Early detection of preferential channeling in reverse electrodialysis

    NARCIS (Netherlands)

    Vermaas, David; Saakes, Michel; Nijmeijer, Dorothea C.

    2014-01-01

    Membrane applications often experience fouling, which prevent uniform flow distribution through the feed water compartments, i.e. preferential channeling may occur. This research shows the effect of preferential channeling on energy generation from mixing salt water and fresh water using reverse

  2. Monoclonal antibodies from rats immunized with fragment D of human fibrinogen

    International Nuclear Information System (INIS)

    Kennel, S.J.; Chen, J.P.; Lankford, P.K.; Foote, L.J.

    1981-01-01

    Fischer rats were immunized with fragment D (Fg-D) of human fibrinogen (Fg) to obtain antibody specific for neoantigens unique to this molecule. Absorption of serum with whole Fg indicated that some of the antibody produced reacted preferentially with Fg-D. Hybridoma cultures were prepared by fusion of immune rat spleen cells with mouse myeloma P3-X63-Ag8. Monoclonal antibodies obtained from these cultures fell into two classes: (a) Those reacting equally well with Fg and Fg-D. (b) Those reacting preferentially but not absolutely wth Fg-D. Antibody from hybridoma 104-14, a member of the first group had an affinity for Fg-D of 1.5 x 10 9 M -1 while antibodies from 106-59 and 106-71 (group 2) demonstrated much lower affinities of 1.0 x 10 7 and 4.7 x 10 6 M -1 , respectively. The cross reactivity of antibodies in the second group indicated that they react with protein conformations that are altered during production of Fg-D from Fg

  3. Dependence of plasmin-mediated degradation of platelet adhesive receptors on temperature and Ca2+

    International Nuclear Information System (INIS)

    Winters, K.J.; Eisenberg, P.R.; Jaffe, A.S.; Santoro, S.A.

    1990-01-01

    The effects of activation of plasminogen by streptokinase and tissue-type-plasminogen activator on platelet activation and the membrane glycoproteins (GPs) that mediate platelet adhesion and aggregation are not yet fully defined. To clarify effects on platelets during activation of plasminogen in vitro, we used monoclonal antibodies (MoAbs), flow cytometry, and platelets surface-labeled with 125 I to characterize changes in receptors for fibrinogen (GPIIb-IIIa), von Willebrand factor (GPIb), and collagen (GPIa-IIa). Activation of plasminogen in plasma with pharmacologic concentrations of plasminogen activators did not degrade GPIIb-IIIa or GPIb, and caused only a modest decrease in GPIa. In washed platelets GPIIb-IIIa was extensively degraded by plasmin at 37 degrees C in the absence of exogenous Ca 2+ , conditions that destabilize the IIb-IIIa complex. Degradation of GPIb in washed platelets displayed a similar although less-marked dependence on temperature and the absence of Ca 2+ . The binding of activation-specific MoAbs did not increase during activation of plasminogen in plasma. We conclude that during pharmacologic fibrinolysis, reported inhibition of platelet function in plasma is not due to degradation of platelet-adhesive receptors. In addition, platelet activation observed during thrombolytic therapy does not appear to be a direct consequence of plasminogen activation

  4. Preferential flow from pore to landscape scales

    Science.gov (United States)

    Koestel, J. K.; Jarvis, N.; Larsbo, M.

    2017-12-01

    In this presentation, we give a brief personal overview of some recent progress in quantifying preferential flow in the vadose zone, based on our own work and those of other researchers. One key challenge is to bridge the gap between the scales at which preferential flow occurs (i.e. pore to Darcy scales) and the scales of interest for management (i.e. fields, catchments, regions). We present results of recent studies that exemplify the potential of 3-D non-invasive imaging techniques to visualize and quantify flow processes at the pore scale. These studies should lead to a better understanding of how the topology of macropore networks control key state variables like matric potential and thus the strength of preferential flow under variable initial and boundary conditions. Extrapolation of this process knowledge to larger scales will remain difficult, since measurement technologies to quantify macropore networks at these larger scales are lacking. Recent work suggests that the application of key concepts from percolation theory could be useful in this context. Investigation of the larger Darcy-scale heterogeneities that generate preferential flow patterns at the soil profile, hillslope and field scales has been facilitated by hydro-geophysical measurement techniques that produce highly spatially and temporally resolved data. At larger regional and global scales, improved methods of data-mining and analyses of large datasets (machine learning) may help to parameterize models as well as lead to new insights into the relationships between soil susceptibility to preferential flow and site attributes (climate, land uses, soil types).

  5. Discovering Preferential Patterns in Sectoral Trade Networks.

    Science.gov (United States)

    Cingolani, Isabella; Piccardi, Carlo; Tajoli, Lucia

    2015-01-01

    We analyze the patterns of import/export bilateral relations, with the aim of assessing the relevance and shape of "preferentiality" in countries' trade decisions. Preferentiality here is defined as the tendency to concentrate trade on one or few partners. With this purpose, we adopt a systemic approach through the use of the tools of complex network analysis. In particular, we apply a pattern detection approach based on community and pseudocommunity analysis, in order to highlight the groups of countries within which most of members' trade occur. The method is applied to two intra-industry trade networks consisting of 221 countries, relative to the low-tech "Textiles and Textile Articles" and the high-tech "Electronics" sectors for the year 2006, to look at the structure of world trade before the start of the international financial crisis. It turns out that the two networks display some similarities and some differences in preferential trade patterns: they both include few significant communities that define narrow sets of countries trading with each other as preferential destinations markets or supply sources, and they are characterized by the presence of similar hierarchical structures, led by the largest economies. But there are also distinctive features due to the characteristics of the industries examined, in which the organization of production and the destination markets are different. Overall, the extent of preferentiality and partner selection at the sector level confirm the relevance of international trade costs still today, inducing countries to seek the highest efficiency in their trade patterns.

  6. Emergence of global preferential attachment from local interaction

    International Nuclear Information System (INIS)

    Li Menghui; Fan Ying; Wu Jinshan; Di Zengru; Gao Liang

    2010-01-01

    Global degree/strength-based preferential attachment is widely used as an evolution mechanism of networks. But it is hard to believe that any individual can get global information and shape the network architecture based on it. In this paper, it is found that the global preferential attachment emerges from the local interaction models, including the distance-dependent preferential attachment (DDPA) evolving model of weighted networks (Li et al 2006 New J. Phys. 8 72), the acquaintance network model (Davidsen et al 2002 Phys. Rev. Lett. 88 128701) and the connecting nearest-neighbor (CNN) model (Vazquez 2003 Phys. Rev. E 67 056104). For the DDPA model and the CNN model, the attachment rate depends linearly on the degree or vertex strength, whereas for the acquaintance network model, the dependence follows a sublinear power law. It implies that for the evolution of social networks, local contact could be more fundamental than the presumed global preferential attachment.

  7. Babassu aqueous extract (BAE as an adjuvant for T helper (Th1-dependent immune responses in mice of a Th2 immune response-prone strain

    Directory of Open Access Journals (Sweden)

    Nascimento Flavia RF

    2011-01-01

    Full Text Available Abstract Background The aqueous extract of a Brazilian palm-tree fruit - the babassu - (BAE exerts a clear immunostimulative activity in vivo. In the present work, the possibility that BAE can promote Th1 immune responses in mice of a Th2 immune response-prone strain - the BALB/c was investigated. BAE itself, and preparations consisting of Leishmania amazonensis promastigote extract (LE, adsorbed or not to Al(OH3, and in the presence or not of BAE, were used as immunogens. LE and Al(OH3 have been shown to preferentially elicit Th2 immune responses. Results The addition of BAE to LE-containing immunogenic preparations, adsorbed or not to Al(OH3, clearly promoted the in vitro production of interferon γ (IFN-γ, a major Th1-dependent cytokine, and not of interleukin (IL-4 (a Th2-dependent cytokine, by LE-stimulated splenocytes of immunized BALB/c mice. It also promoted the in vivo formation of IgG2a anti-LE antibodies. However, immunization with LE by itself led to an increased production of IL-4 by LE-stimulated splenocytes, and this production, albeit not enhanced, was not reduced by the addition of BAE to the immunogen. On the other hand, the IL-4 production by LE-stimulated splenocytes was significantly lower in mice immunized with a preparation containing Al(OH3-adsorbed LE and BAE than in mice immunized with the control preparation of Al(OH3-adsorbed LE without BAE. Moreover, an increased production of IFN-γ, and not of IL-4, was observed in the culture supernatants of splenocytes, from BAE-immunized mice, which were in vitro stimulated with BAE or which received no specific in vitro stimulus. No differences in IL-10 (an immunoregulatory cytokine levels in the supernatants of splenocytes from mice that were injected with BAE, in relation to splenocytes from control mice, were observed. The spontaneous ex vivo production of NO by splenocytes of mice that had been injected with BAE was significantly higher than the production of NO by

  8. Reverse preferential spread in complex networks

    Science.gov (United States)

    Toyoizumi, Hiroshi; Tani, Seiichi; Miyoshi, Naoto; Okamoto, Yoshio

    2012-08-01

    Large-degree nodes may have a larger influence on the network, but they can be bottlenecks for spreading information since spreading attempts tend to concentrate on these nodes and become redundant. We discuss that the reverse preferential spread (distributing information inversely proportional to the degree of the receiving node) has an advantage over other spread mechanisms. In large uncorrelated networks, we show that the mean number of nodes that receive information under the reverse preferential spread is an upper bound among any other weight-based spread mechanisms, and this upper bound is indeed a logistic growth independent of the degree distribution.

  9. Preferential reasoning for modal logics

    CSIR Research Space (South Africa)

    Britz, K

    2011-11-01

    Full Text Available Modal logic is the foundation for a versatile and well-established class of knowledge representation formalisms in artificial intelligence. Enriching modal logics with non-monotonic reasoning capabilities such as preferential reasoning as developed...

  10. Distributed network generation based on preferential attachment in ABS

    NARCIS (Netherlands)

    K. Azadbakht (Keyvan); N. Bezirgiannis (Nikolaos); F.S. de Boer (Frank)

    2017-01-01

    textabstractGeneration of social networks using Preferential Attachment (PA) mechanism is proposed in the Barabasi-Albert model. In this mechanism, new nodes are introduced to the network sequentially and they attach to the existing nodes preferentially where the preference can be based on the

  11. Preferential flow through intact soil cores: Effects of matrix head

    Energy Technology Data Exchange (ETDEWEB)

    Langner, H.W.; Gaber, H.M.; Wraith, J.M.; Huwe, B.; Inskeep, W.P.

    1999-12-01

    Continuous soil pores may act as pathways for preferential flow depending on their size and water status (filled or drained), the latter being largely controlled by the soil matrix head (h). The literature contains a wide range of proposed minimal pore sizes that may contribute to preferential flow. The objective of this study was to examine the relationship between h (and corresponding pore sizes) and preferential solute transport in a naturally structured soil. Tracer ({sup 3}H{sub 2}O and pentafluorobenzoic acid, [PFBA]) miscible displacement experiments were performed at several h values in intact soil cores (15-cm diameter, 30-cm length) using an apparatus especially suited to maintain constant h while collecting large effluent volumes. To test for the occurrence of preferential flow, observed breakthrough curves (BTCs) were evaluated for physical nonequilibrium (PNE) using a comparison between fitted local equilibrium (PNE) and PNE models. Fitting results of the observed BTCs indicated absence of PNE in all solute transport experiments at h {le} {minus}10 cm. Experiments at h {ge} {minus}5 cm consistently exhibited PNE conditions, indicating the presence of preferential flow. These results suggest that soil pores with effective radii of 150 {micro}m and smaller (water-filled at h = {minus}10 cm) do not contribute to preferential flow. Observed pore water velocities were not indicative of the presence or absence of preferential flow conditions. Continuous measurements of soil water content ({theta}) using time domain reflectometry (TDR) revealed that at h = {minus}10 cm, <2% of the soil volume had drained.

  12. 15 CFR 700.14 - Preferential scheduling.

    Science.gov (United States)

    2010-01-01

    ...) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE REGULATIONS DEFENSE PRIORITIES AND ALLOCATIONS SYSTEM Industrial Priorities § 700.14 Preferential scheduling. (a) A...

  13. Measles immune suppression: lessons from the macaque model.

    Directory of Open Access Journals (Sweden)

    Rory D de Vries

    Full Text Available Measles remains a significant childhood disease, and is associated with a transient immune suppression. Paradoxically, measles virus (MV infection also induces robust MV-specific immune responses. Current hypotheses for the mechanism underlying measles immune suppression focus on functional impairment of lymphocytes or antigen-presenting cells, caused by infection with or exposure to MV. We have generated stable recombinant MVs that express enhanced green fluorescent protein, and remain virulent in non-human primates. By performing a comprehensive study of virological, immunological, hematological and histopathological observations made in animals euthanized at different time points after MV infection, we developed a model explaining measles immune suppression which fits with the "measles paradox". Here we show that MV preferentially infects CD45RA(- memory T-lymphocytes and follicular B-lymphocytes, resulting in high infection levels in these populations. After the peak of viremia MV-infected lymphocytes were cleared within days, followed by immune activation and lymph node enlargement. During this period tuberculin-specific T-lymphocyte responses disappeared, whilst strong MV-specific T-lymphocyte responses emerged. Histopathological analysis of lymphoid tissues showed lymphocyte depletion in the B- and T-cell areas in the absence of apoptotic cells, paralleled by infiltration of T-lymphocytes into B-cell follicles and reappearance of proliferating cells. Our findings indicate an immune-mediated clearance of MV-infected CD45RA(- memory T-lymphocytes and follicular B-lymphocytes, which causes temporary immunological amnesia. The rapid oligoclonal expansion of MV-specific lymphocytes and bystander cells masks this depletion, explaining the short duration of measles lymphopenia yet long duration of immune suppression.

  14. Semantic foundation for preferential description logics

    CSIR Research Space (South Africa)

    Britz, K

    2011-12-01

    Full Text Available Description logics are a well-established family of knowledge representation formalisms in Artificial Intelligence. Enriching description logics with non-monotonic reasoning capabilities, especially preferential reasoning as developed by Lehmann...

  15. Soil properties and preferential solute transport at the field scale

    DEFF Research Database (Denmark)

    Koestel, J K; Minh, Luong Nhat; Nørgaard, Trine

    An important fraction of water flow and solute transport through soil takes place through preferential flow paths. Although this had been already observed in the nineteenth century, it had been forgotten by the scientific community until it was rediscovered during the 1970s. The awareness...... of the relevance of preferential flow was broadly re-established in the community by the early 1990s. However, since then, the notion remains widespread among soil scientists that the occurrence and strength of preferential flow cannot be predicted from measurable proxy variables such as soil properties or land...

  16. Regulation of aeroallergen immunity by the innate immune system: laboratory evidence for a new paradigm.

    Science.gov (United States)

    Horner, Anthony A

    2010-01-01

    Over the last decade, it has become increasingly clear that innate responses to microbes are mediated largely by toll-like receptors (TLRs), which recognize a diverse family of molecules produced by viruses, bacteria and fungi. This article will present evidence that TLRs also play a dominant role in innate responses to non-infectious immunostimulatory materials present in house dust extracts (HDEs) and the living environments they represent. However, our investigations challenge the commonly held view that microbial products in ambient air protect against the allergic march by promoting protective Th1 biased responses to inspired aeroallergens. Instead, all HDEs studied to date have preferentially promoted the development of Th2 biased airway hypersensitivities when used as adjuvants for intranasal (i.n.) vaccination. In contrast, daily low dose i.n. HDE delivery was found to promote the development of aeroallergen tolerance. This article will review these experimental findings as evidence to propose a new paradigm by which airborne TLR ligands and other stimulants of innate immunity may influence aeroallergen specific immunity and the genesis of allergic respiratory diseases.

  17. Intranasal immunization with protective antigen of Bacillus anthracis induces a long-term immunological memory response.

    Science.gov (United States)

    Woo, Sun-Je; Kang, Seok-Seong; Park, Sung-Moo; Yang, Jae Seung; Song, Man Ki; Yun, Cheol-Heui; Han, Seung Hyun

    2015-10-01

    Although intranasal vaccination has been shown to be effective for the protection against inhalational anthrax, establishment of long-term immunity has yet to be achieved. Here, we investigated whether intranasal immunization with recombinant protective antigen (rPA) of Bacillus anthracis induces immunological memory responses in the mucosal and systemic compartments. Intranasal immunization with rPA plus cholera toxin (CT) sustained PA-specific antibody responses for 6 months in lung, nasal washes, and vaginal washes as well as serum. A significant induction of PA-specific memory B cells was observed in spleen, cervical lymph nodes (CLNs) and lung after booster immunization. Furthermore, intranasal immunization with rPA plus CT remarkably generated effector memory CD4(+) T cells in the lung. PA-specific CD4(+) T cells preferentially increased the expression of Th1- and Th17-type cytokines in lung, but not in spleen or CLNs. Collectively, the intranasal immunization with rPA plus CT promoted immunologic memory responses in the mucosal and systemic compartments, providing long-term immunity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. A Negative Feedback Loop Between Autophagy and Immune Responses in Mycobacterium leprae Infection.

    Science.gov (United States)

    Ma, Yuelong; Zhang, Li; Lu, Jie; Shui, Tiejun; Chen, Jia; Yang, Jun; Yuan, Joanna; Liu, Yeqiang; Yang, Degang

    2017-01-01

    The obligate intracellular bacterium Mycobacterium leprae is the causative agent of leprosy and primarily infects macrophages, leading to irreversible nerve damage and deformities. So far, the underlying reasons allowing M. leprae to persist and propagate in macrophages, despite the presence of cellular immunity, are still a mystery. Here, we investigated the role of autophagy, a cellular process that degrades cytosolic materials and intracellular pathogens, in M. leprae infection. We found that live M. leprae infection of macrophages resulted in significantly elevated autophagy level. However, macrophages with high autophagy levels preferentially expressed lower levels of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, IL-12, and tumor necrosis factor-α, and preferentially primed anti-inflammatory T cells responses, characterized by high IL-10 and low interferon-γ, granzyme B, and perforin responses. These anti-inflammatory T cells could suppress further induction of autophagy, leading to improved survival of intracellular M. leprae in infected macrophages. Therefore, these data demonstrated that although autophagy had a role in eliminating intracellular pathogens, the induction of autophagy resulted in anti-inflammatory immune responses, which suppressed autophagy in a negative feedback loop and allowed the persistence of M. leprae.

  19. Defeasible modes of inference: A preferential perspective

    CSIR Research Space (South Africa)

    Britz, K

    2012-06-01

    Full Text Available . Hence UM = f(Mi; wj) j i 2 f1; 2g; j 2 f1; 2; 3; 4gg. We construct a preferential model (Definition 4) in which to check the satisfiability and truth of a few sentences. The purpose is to illustrate the semantics of our notion of defea- sibility... exceptional situations would the pile be on while the cooler is off, e.g. during a serious malfunction (states s7 and s8). In the preferential model P depicted above, one can check that s6 2 Jh^ p p f:hK: at s6 we have a hazardous situ- ation...

  20. Cytokine production in BALB/c mice immunized with radiation attenuated third stage larvae of the filarial nematode, Brugia pahangi

    International Nuclear Information System (INIS)

    Bancroft, A.J.; Devaney, E.; Grencis, R.K.; Else, K.J.

    1993-01-01

    BALB/c mice immunized with radiation-attenuated third stage larvae of the filarial nematode Brugia pahangi are strongly immune to challenge infection. Investigation of the profile of cytokines secreted by spleen cells from immune mice stimulated in vitro with either parasite Ag or with Con A revealed high levels of IL-5 and IL-9 and moderate levels of IL-4. In contrast, secretion of IFN-γ by spleen cells from immune animals was negligible. Spleen cells from control mice secreted low levels of all cytokines assayed. Levels of parasite-specific IgE were significantly elevated in immune animals and a peripheral blood eosinophilia was observed, which exhibited a biphasic distribution. Our results are consistent with the preferential expansion of Th2 cells in immune animals and provide the basis for dissecting the means by which radiation-attenuated larvae of filarial nematodes stimulate immunity. 5l refs., 3 figs., 3 tabs

  1. Current challenges in quantifying preferential flow through the vadose zone

    Science.gov (United States)

    Koestel, John; Larsbo, Mats; Jarvis, Nick

    2017-04-01

    In this presentation, we give an overview of current challenges in quantifying preferential flow through the vadose zone. A review of the literature suggests that current generation models do not fully reflect the present state of process understanding and empirical knowledge of preferential flow. We believe that the development of improved models will be stimulated by the increasingly widespread application of novel imaging technologies as well as future advances in computational power and numerical techniques. One of the main challenges in this respect is to bridge the large gap between the scales at which preferential flow occurs (pore to Darcy scales) and the scale of interest for management (fields, catchments, regions). Studies at the pore scale are being supported by the development of 3-D non-invasive imaging and numerical simulation techniques. These studies are leading to a better understanding of how macropore network topology and initial/boundary conditions control key state variables like matric potential and thus the strength of preferential flow. Extrapolation of this knowledge to larger scales would require support from theoretical frameworks such as key concepts from percolation and network theory, since we lack measurement technologies to quantify macropore networks at these large scales. Linked hydro-geophysical measurement techniques that produce highly spatially and temporally resolved data enable investigation of the larger-scale heterogeneities that can generate preferential flow patterns at pedon, hillslope and field scales. At larger regional and global scales, improved methods of data-mining and analyses of large datasets (machine learning) may help in parameterizing models as well as lead to new insights into the relationships between soil susceptibility to preferential flow and site attributes (climate, land uses, soil types).

  2. Atividade de plasmina e plasminogênio no leite longa vida com alta e baixa contagem de células somáticas durante o armazenamento Activity of plasmin and plasminogen in ultra high temperature milk with high and low somatic cell counts during storage

    Directory of Open Access Journals (Sweden)

    Carlos Humberto Corassin

    2010-12-01

    Full Text Available O objetivo deste estudo foi avaliar o efeito da contagem de células somáticas (CCS do leite na atividade de plasmina e plasminogênio durante o período de armazenamento do leite longa vida integral. Os leites crus foram categorizados em grupos de CCS de baixa (342.000-487.000 células mL-1 e alta contagem (603.000-808.000 células mL-1. Dois lotes de leite longa vida em cada categoria de CCS foram analisados para determinação de plasmina e plasminogênio após 10, 30, 60, 90 e 120 dias de armazenamento em temperatura ambiente. Para a fabricação do leite longa vida, o leite cru foi submetido à pasteurização rápida seguida da esterilização industrial do leite por injeção de vapor pelo método direto e embalagem asséptica do produto. A CCS não apresentou efeitos sobre as características físico-químicas do leite cru, e nem sobre a atividade de plasmina e plasminogênio nos leites cru e longa vida, armazenados por 120 dias. Entretanto, independentemente da CCS, a atividade de plasmina e plasminogênio aumentou no leite longa vida ao longo do armazenamento, indicando a possibilidade de aumento da proteólise no produto durante sua vida de prateleira.This study aimed to evaluate the effect of somatic cell counts (SCC in milk on plasmin and plasminogen activities of ultra high temperature (UHT milk during storage. Raw milks were categorized in SCC groups of low (342,000-487,000 cells mL-1 and high cells (603,000-808,000 cells mL-1. Two replicates of UHT milks within each SCC category were analyzed for plasmin and plasminogen activities after 10, 30, 60, 90 and 120 days of storage at room temperature. For manufacture of UHT milk, raw milk was pasteurized and sterilized by direct vapor injection process, followed by aseptic packaging. SCC had no effect on physical-chemical characteristics of raw milk, and on plasmin or plasminogen activities in raw and UHT milks during 120 days of storage. However, independently of the SCC in raw milk

  3. Genetic adaptation of the antibacterial human innate immunity network.

    Science.gov (United States)

    Casals, Ferran; Sikora, Martin; Laayouni, Hafid; Montanucci, Ludovica; Muntasell, Aura; Lazarus, Ross; Calafell, Francesc; Awadalla, Philip; Netea, Mihai G; Bertranpetit, Jaume

    2011-07-11

    Pathogens have represented an important selective force during the adaptation of modern human populations to changing social and other environmental conditions. The evolution of the immune system has therefore been influenced by these pressures. Genomic scans have revealed that immune system is one of the functions enriched with genes under adaptive selection. Here, we describe how the innate immune system has responded to these challenges, through the analysis of resequencing data for 132 innate immunity genes in two human populations. Results are interpreted in the context of the functional and interaction networks defined by these genes. Nucleotide diversity is lower in the adaptors and modulators functional classes, and is negatively correlated with the centrality of the proteins within the interaction network. We also produced a list of candidate genes under positive or balancing selection in each population detected by neutrality tests and showed that some functional classes are preferential targets for selection. We found evidence that the role of each gene in the network conditions the capacity to evolve or their evolvability: genes at the core of the network are more constrained, while adaptation mostly occurred at particular positions at the network edges. Interestingly, the functional classes containing most of the genes with signatures of balancing selection are involved in autoinflammatory and autoimmune diseases, suggesting a counterbalance between the beneficial and deleterious effects of the immune response.

  4. Evaluation of local immune response to Fasciola hepatica experimental infection in the liver and hepatic lymph nodes of goats immunized with Sm14 vaccine antigen

    Directory of Open Access Journals (Sweden)

    Ricardo E Mendes

    2010-08-01

    Full Text Available Protection against Fasciola hepatica in goats immunized with a synthetic recombinant antigen from Schistosoma mansoni fatty acid-binding protein 14 (rSm14 was investigated by assessing worm burdens, serum levels of hepatic enzymes, faecal egg count and hepatic damage, which was evaluated using gross and microscopic morphometric observation. The nature of the local immune response was assessed by examining the distribution of CD2+, CD4+, CD8+ and γ´+ T lymphocytes along with IgG+, IL-4+ and IFN-γ+ cells in the liver and hepatic lymph nodes (HLN. The goats used consisted of group 1 (unimmunized and uninfected, group 2 [infected control - immunized with Quillaia A (Quil A] and group 3 (immunized with rSm14 in Quil A and infected, each containing seven animals. Immunization with rSm14 in Quil A adjuvant induced a reduction in gross hepatic lesions of 56.6% (p < 0.001 and reduced hepatic and HLN infiltration of CD2+, CD4+, CD8+ and γ´+ T lymphocytes as well as IL-4+ and IFN-γ+ cells (p < 0.05. This is the first report of caprine immunization against F. hepatica using a complete rSm14 molecule derived from S. mansoni. Immunization reduced hepatic damage and local inflammatory infiltration into the liver and HLN. However, considering that Quil A is not the preferential/first choice adjuvant for Sm14 immunization, further studies will be undertaken using the monophosphoryl lipid A-based family of adjuvants during clinical trials to facilitate anti-Fasciolavaccine development.

  5. Affecting factors of preferential flow in the forest of the Three Gorges area, Yangtze River

    Institute of Scientific and Technical Information of China (English)

    CHENG Jinhua; ZHANG Hongjiang; HE Fan; QI Shenglin; SUN Yanhong; ZHANG Youyan; SHI Yuhu

    2007-01-01

    In order to study the factors affecting preferential flow,a 2.9 m-long,2.6 m-deep soil profile was dug in the Quxi watershed,Yangtze River.To analyze the influence of rainfall on preferential flow,the preferential flow process was observed when the rainfalls were recorded.Soil physical and infiltration characteristics were also measured to study their effect on preferential flow.The results showed that the rainfall amount that could cause preferential flow was over 26 mm.There are four types of rainfall in the Three Gorges area,namely gradually dropping rain,even rain,sudden rain and peak rain.Preferential flow process was found to be relevant to the rainfall process.It was determined that with different rainfall types,preferential flow appeared at different times,occurring first in peak rain,followed by sudden rain,gradually dropping rain,and then even rain.Preferential flow would appear when the rainfall intensity was over 0.075 mm/min.In the studied area,the coarse soil particles increased with the soil depth,and for the deeper soil layer,the coarse particles promote the formation of preferential flow.Preferential flow accelerates the steady infiltration rate in the 83-110 cm soil horizon,and the quickly moving water in this horizon also enhanced the further formation and development of preferential flow.

  6. Spreading dynamics of an e-commerce preferential information model on scale-free networks

    Science.gov (United States)

    Wan, Chen; Li, Tao; Guan, Zhi-Hong; Wang, Yuanmei; Liu, Xiongding

    2017-02-01

    In order to study the influence of the preferential degree and the heterogeneity of underlying networks on the spread of preferential e-commerce information, we propose a novel susceptible-infected-beneficial model based on scale-free networks. The spreading dynamics of the preferential information are analyzed in detail using the mean-field theory. We determine the basic reproductive number and equilibria. The theoretical analysis indicates that the basic reproductive number depends mainly on the preferential degree and the topology of the underlying networks. We prove the global stability of the information-elimination equilibrium. The permanence of preferential information and the global attractivity of the information-prevailing equilibrium are also studied in detail. Some numerical simulations are presented to verify the theoretical results.

  7. Preferential ascus discharge during cross maturation in Sordaria brevicollis.

    Science.gov (United States)

    MacDonald, D J; Bond, D J

    1974-02-01

    Crosses involving spore color mutants of Sordaria brevicollis all showed a decline in the frequency of second division asymmetric asci (2:2:2:2's) as the cross matured. This decline was due to the preferential maturation and/or discharge of these asci. The proportion of spindle overlap and recombinational asci within the group did not change as shown by ascus dissection. The preferential discharge was also found to occur in two-point crosses where the asci did not contain wild-type spores.

  8. Numerical modeling of the effect of preferential flow on hillslope hydrology and slope stability

    NARCIS (Netherlands)

    Shao, W.

    2017-01-01

    The topic of this thesis is the quantification of the influence of preferential flow on landslide-triggering in potentially unstable slopes. Preferential flow paths (e.g., cracks, macropores, fissures, pipes, etc.) commonly exists in slopes. Flow velocities in preferential flow paths can be

  9. Recovery of the immune system after exercise.

    Science.gov (United States)

    Peake, Jonathan M; Neubauer, Oliver; Walsh, Neil P; Simpson, Richard J

    2017-05-01

    The notion that prolonged, intense exercise causes an "open window" of immunodepression during recovery after exercise is well accepted. Repeated exercise bouts or intensified training without sufficient recovery may increase the risk of illness. However, except for salivary IgA, clear and consistent markers of this immunodepression remain elusive. Exercise increases circulating neutrophil and monocyte counts and reduces circulating lymphocyte count during recovery. This lymphopenia results from preferential egress of lymphocyte subtypes with potent effector functions [e.g., natural killer (NK) cells, γδ T cells, and CD8 + T cells]. These lymphocytes most likely translocate to peripheral sites of potential antigen encounter (e.g., lungs and gut). This redeployment of effector lymphocytes is an integral part of the physiological stress response to exercise. Current knowledge about changes in immune function during recovery from exercise is derived from assessment at the cell population level of isolated cells ex vivo or in blood. This assessment can be biased by large changes in the distribution of immune cells between blood and peripheral tissues during and after exercise. Some evidence suggests that reduced immune cell function in vitro may coincide with changes in vivo and rates of illness after exercise, but more work is required to substantiate this notion. Among the various nutritional strategies and physical therapies that athletes use to recover from exercise, carbohydrate supplementation is the most effective for minimizing immune disturbances during exercise recovery. Sleep is an important aspect of recovery, but more research is needed to determine how sleep disruption influences the immune system of athletes. Copyright © 2017 the American Physiological Society.

  10. Genetic adaptation of the antibacterial human innate immunity network

    Directory of Open Access Journals (Sweden)

    Lazarus Ross

    2011-07-01

    Full Text Available Abstract Background Pathogens have represented an important selective force during the adaptation of modern human populations to changing social and other environmental conditions. The evolution of the immune system has therefore been influenced by these pressures. Genomic scans have revealed that immune system is one of the functions enriched with genes under adaptive selection. Results Here, we describe how the innate immune system has responded to these challenges, through the analysis of resequencing data for 132 innate immunity genes in two human populations. Results are interpreted in the context of the functional and interaction networks defined by these genes. Nucleotide diversity is lower in the adaptors and modulators functional classes, and is negatively correlated with the centrality of the proteins within the interaction network. We also produced a list of candidate genes under positive or balancing selection in each population detected by neutrality tests and showed that some functional classes are preferential targets for selection. Conclusions We found evidence that the role of each gene in the network conditions the capacity to evolve or their evolvability: genes at the core of the network are more constrained, while adaptation mostly occurred at particular positions at the network edges. Interestingly, the functional classes containing most of the genes with signatures of balancing selection are involved in autoinflammatory and autoimmune diseases, suggesting a counterbalance between the beneficial and deleterious effects of the immune response.

  11. Secretion of alpha 2-plasmin inhibitor is impaired by amino acid deletion in a small region of the molecule.

    Science.gov (United States)

    Toyota, S; Hirosawa, S; Aoki, N

    1994-02-01

    Alpha 2-plasmin inhibitor (alpha 2PI) deficiency Okinawa results from defective secretion of the inhibitor from the liver and appears to be a direct consequence of the deletion of Glu137 in the amino acid sequence of alpha 2PI. To examine the effects of replacing the amino acid occupying position 137 or deleting its neighboring amino acid on alpha 2PI secretion, we used oligonucleotide-directed mutagenesis of alpha 2PI cDNA to change the codon specifying Glu137 or delete a codon specifying its neighboring amino acid. The effects were determined by pulse-chase experiments and by enzyme-linked immunosorbent assay of media from transiently transfected COS-7 cells. Replacement of Glu137 with an amino acid other than Cys had little effect on alpha 2PI secretion. In contrast, deletion of an amino acid in a region spanning a sequence of less than 30 amino acids including positions 127 and 137 severely impaired the secretion. The results suggest that structural integrity of the region, rather than its component amino acids, is important for the intracellular transport and secretion of alpha 2PI.

  12. A Weighted Evolving Network with Community Size Preferential Attachment

    International Nuclear Information System (INIS)

    Zhuo Zhiwei; Shan Erfang

    2010-01-01

    Community structure is an important characteristic in real complex network. It is a network consists of groups of nodes within which links are dense but among which links are sparse. In this paper, the evolving network include node, link and community growth and we apply the community size preferential attachment and strength preferential attachment to a growing weighted network model and utilize weight assigning mechanism from BBV model. The resulting network reflects the intrinsic community structure with generalized power-law distributions of nodes' degrees and strengths.

  13. Protein-solvent preferential interactions, protein hydration, and the modulation of biochemical reactions by solvent components.

    Science.gov (United States)

    Timasheff, Serge N

    2002-07-23

    Solvent additives (cosolvents, osmolytes) modulate biochemical reactions if, during the course of the reaction, there is a change in preferential interactions of solvent components with the reacting system. Preferential interactions can be expressed in terms of preferential binding of the cosolvent or its preferential exclusion (preferential hydration). The driving force is the perturbation by the protein of the chemical potential of the cosolvent. It is shown that the measured change of the amount of water in contact with protein during the course of the reaction modulated by an osmolyte is a change in preferential hydration that is strictly a measure of the cosolvent chemical potential perturbation by the protein in the ternary water-protein-cosolvent system. It is not equal to the change in water of hydration, because water of hydration is a reflection strictly of protein-water forces in a binary system. There is no direct relation between water of preferential hydration and water of hydration.

  14. The Probabilistic Nature of Preferential Choice

    Science.gov (United States)

    Rieskamp, Jorg

    2008-01-01

    Previous research has developed a variety of theories explaining when and why people's decisions under risk deviate from the standard economic view of expected utility maximization. These theories are limited in their predictive accuracy in that they do not explain the probabilistic nature of preferential choice, that is, why an individual makes…

  15. Endocrine and Local IGF-I in the Bony Fish Immune System.

    Science.gov (United States)

    Franz, Anne-Constance; Faass, Oliver; Köllner, Bernd; Shved, Natallia; Link, Karl; Casanova, Ayako; Wenger, Michael; D'Cotta, Helena; Baroiller, Jean-François; Ullrich, Oliver; Reinecke, Manfred; Eppler, Elisabeth

    2016-01-26

    A role for GH and IGF-I in the modulation of the immune system has been under discussion for decades. Generally, GH is considered a stimulator of innate immune parameters in mammals and teleost fish. The stimulatory effects in humans as well as in bony fish often appear to be correlated with elevated endocrine IGF-I (liver-derived), which has also been shown to be suppressed during infection in some studies. Nevertheless, data are still fragmentary. Some studies point to an important role of GH and IGF-I particularly during immune organ development and constitution. Even less is known about the potential relevance of local (autocrine/paracrine) IGF-I within adult and developing immune organs, and the distinct localization of IGF-I in immune cells and tissues of mammals and fish has not been systematically defined. Thus far, IGF-I has been localized in different mammalian immune cell types, particularly macrophages and granulocytes, and in supporting cells, but not in T-lymphocytes. In the present study, we detected IGF-I in phagocytic cells isolated from rainbow trout head kidney and, in contrast to some findings in mammals, in T-cells of a channel catfish cell line. Thus, although numerous analogies among mammals and teleosts exist not only for the GH/IGF-system, but also for the immune system, there are differences that should be further investigated. For instance, it is unclear whether the primarily reported role of GH/IGF-I in the innate immune response is due to the lack of studies focusing on the adaptive immune system, or whether it truly preferentially concerns innate immune parameters. Infectious challenges in combination with GH/IGF-I manipulations are another important topic that has not been sufficiently addressed to date, particularly with respect to developmental and environmental influences on fish growth and health.

  16. Endocrine and Local IGF-I in the Bony Fish Immune System

    Directory of Open Access Journals (Sweden)

    Anne-Constance Franz

    2016-01-01

    Full Text Available A role for GH and IGF-I in the modulation of the immune system has been under discussion for decades. Generally, GH is considered a stimulator of innate immune parameters in mammals and teleost fish. The stimulatory effects in humans as well as in bony fish often appear to be correlated with elevated endocrine IGF-I (liver-derived, which has also been shown to be suppressed during infection in some studies. Nevertheless, data are still fragmentary. Some studies point to an important role of GH and IGF-I particularly during immune organ development and constitution. Even less is known about the potential relevance of local (autocrine/paracrine IGF-I within adult and developing immune organs, and the distinct localization of IGF-I in immune cells and tissues of mammals and fish has not been systematically defined. Thus far, IGF-I has been localized in different mammalian immune cell types, particularly macrophages and granulocytes, and in supporting cells, but not in T-lymphocytes. In the present study, we detected IGF-I in phagocytic cells isolated from rainbow trout head kidney and, in contrast to some findings in mammals, in T-cells of a channel catfish cell line. Thus, although numerous analogies among mammals and teleosts exist not only for the GH/IGF-system, but also for the immune system, there are differences that should be further investigated. For instance, it is unclear whether the primarily reported role of GH/IGF-I in the innate immune response is due to the lack of studies focusing on the adaptive immune system, or whether it truly preferentially concerns innate immune parameters. Infectious challenges in combination with GH/IGF-I manipulations are another important topic that has not been sufficiently addressed to date, particularly with respect to developmental and environmental influences on fish growth and health.

  17. Preferential aerosolization of bacteria in bioaerosols generated in vitro.

    Science.gov (United States)

    Perrott, P; Turgeon, N; Gauthier-Levesque, L; Duchaine, C

    2017-09-01

    Little is known about how bacteria are aerosolized in terms of whether some bacteria will be found in the air more readily than others that are present in the source. This report describes in vitro experiments to compare aerosolization rates (also known as preferential aerosolization) of Gram-positive and Gram-negative bacteria as well as rod- and coccus-shaped bacteria, using two nebulization conditions. A consortium of five bacterial species was aerosolized in a homemade chamber. Aerosols generated with a commercial nebulizer and a homemade bubble-burst aerosol generator were compared. Data suggest that Pseudomonas aeruginosa was preferentially aerosolized in comparison to Moraxella catarrhalis, Lactobacillus paracasei, Staphylococcus aureus and Streptococcus suis, independently of the method of aerosolization. Bacterial integrity of Strep. suis was more preserved compared to other bacteria studied as revealed with PMA-qPCR. We reported the design of an aerosol chamber and bubble-burst generator for the in vitro study of preferential aerosolization. In our setting, preferential aerosolization was influenced by bacterial properties instead of aerosolization mechanism. These findings could have important implications for predicting the composition of bioaerosols in various locations such as wastewater treatment plants, agricultural settings and health care settings. © 2017 The Society for Applied Microbiology.

  18. Immunological regulation of metabolism--a novel quintessential role for the immune system in health and disease.

    Science.gov (United States)

    Schaefer, Jeremy S; Klein, John R

    2011-01-01

    The hypothalamus-pituitary-thyroid (HPT) axis is an integrated hormone network that is essential for maintaining metabolic homeostasis. It has long been known that thyroid stimulating hormone (TSH), a central component of the HPT axis, can be made by cells of the immune system; however, the role of immune system TSH remains enigmatic and most studies have viewed it as a cytokine used to regulate immune function. Recent studies now indicate that immune system-derived TSH, in particular, a splice variant of TSHβ that is preferentially made by cells of the immune system, is produced by a subset of hematopoietic cells that traffic to the thyroid. On the basis of these and other findings, we propose the novel hypothesis that the immune system is an active participant in the regulation of basal metabolism. We further speculate that this process plays a critical role during acute and chronic infections and that it contributes to a wide range of chronic inflammatory conditions with links to thyroid dysregulation. This hypothesis, which is amenable to empirical analysis, defines a previously unknown role for the immune system in health and disease, and it provides a dynamic connection between immune-endocrine interactions at the organismic level.

  19. MHJ_0461 is a multifunctional leucine aminopeptidase on the surface of Mycoplasma hyopneumoniae.

    Science.gov (United States)

    Jarocki, Veronica M; Santos, Jerran; Tacchi, Jessica L; Raymond, Benjamin B A; Deutscher, Ania T; Jenkins, Cheryl; Padula, Matthew P; Djordjevic, Steven P

    2015-01-01

    Aminopeptidases are part of the arsenal of virulence factors produced by bacterial pathogens that inactivate host immune peptides. Mycoplasma hyopneumoniae is a genome-reduced pathogen of swine that lacks the genetic repertoire to synthesize amino acids and relies on the host for availability of amino acids for growth. M. hyopneumoniae recruits plasmin(ogen) onto its cell surface via the P97 and P102 adhesins and the glutamyl aminopeptidase MHJ_0125. Plasmin plays an important role in regulating the inflammatory response in the lungs of pigs infected with M. hyopneumoniae. We show that recombinant MHJ_0461 (rMHJ_0461) functions as a leucine aminopeptidase (LAP) with broad substrate specificity for leucine, alanine, phenylalanine, methionine and arginine and that MHJ_0461 resides on the surface of M. hyopneumoniae. rMHJ_0461 also binds heparin, plasminogen and foreign DNA. Plasminogen bound to rMHJ_0461 was readily converted to plasmin in the presence of tPA. Computational modelling identified putative DNA and heparin-binding motifs on solvent-exposed sites around a large pore on the LAP hexamer. We conclude that MHJ_0461 is a LAP that moonlights as a multifunctional adhesin on the cell surface of M. hyopneumoniae.

  20. Preferentially Cytotoxic Constituents of Andrographis paniculata and their Preferential Cytotoxicity against Human Pancreatic Cancer Cell Lines.

    Science.gov (United States)

    Lee, Sullim; Morita, Hiroyuki; Tezuka, Yasuhiro

    2015-07-01

    In the course of our search for anticancer agents based on a novel anti-austerity strategy, we found that the 70% EtOH extract of the crude drug Andrographis Herba (aerial parts of Andrographis paniculata), used in Japanese Kampo medicines, killed PANC-1 human pancreatic cancer cells preferentially in nutrient-deprived medium (NDM). Phytochemical investigation of the 70% EtOH extract led to the isolation of 21 known compounds consisting of six labdane-type diterpenes (11, 15, 17-19, 21), six flavones (5, 7, 10, 12, 14, 20), three flavanones (2, 6, 16), two sterols (3, 8), a fatty acid (1), a phthalate (4), a triterpene (9), and a monoterpene (13). Among them, 14-deoxy-11,12-didehydroandrographolide (17) displayed the most potent preferential cytotoxicity against PANC-1 and PSN-1 cells with PC50 values of 10.0 μM and 9.27 μM, respectively. Microscopical observation, double staining with ethidium bromide (EB) and acridine orange (AO), and flow cytometry with propidium iodide/annexin V double staining indicated that 14-deoxy-11,12-didehydroandrographolide (17) triggered apoptosis-like cell death in NDM with an amino acids and/or serum-sensitive mode.

  1. Preferential flow in water-repellent sandy soils : model development and lysimeter experiments

    NARCIS (Netherlands)

    Rooij, de G.H.

    1996-01-01


    When water enters a water-repellent topsoil, preferential flow paths develop and the flow bypasses a large part of the unsaturated zone. Therefore, preferential flow caused by water- repellency is expected to accelerate solute leaching to the groundwater. In soils with water-repellent

  2. Variation in the activities of late stage filaggrin processing enzymes, calpain-1 and bleomycin hydrolase, together with pyrrolidone carboxylic acid levels, corneocyte phenotypes and plasmin activities in non-sun-exposed and sun-exposed facial stratum corneum of different ethnicities.

    Science.gov (United States)

    Raj, N; Voegeli, R; Rawlings, A V; Summers, B; Munday, M R; Lane, M E

    2016-12-01

    Knowledge of the ethnic differences and effects of photodamage on the relative amounts of natural moisturizing factor (NMF) together with filaggrin processing enzymes in facial stratum corneum is limited. Our aim was to characterize the activities of calpain-1 (C-1), bleomycin hydrolase (BH) and the levels of pyrrolidone carboxylic acid (PCA) as a marker for total NMF levels and to relate them to plasmin activities and corneocyte maturation. Enzyme activities, PCA levels and corneocyte maturation were determined from facial tape strippings of photoexposed cheek and photoprotected post-auricular areas (PA) of healthy Caucasian (C), Black African (BA) and albino African (AA) female subjects living in South Africa. PCA concentration levels were of the order AA > BA > C subjects, and the highest activities of BH were present in the AA subjects. BH activities were greater on the photoexposed sites for the BA and C subjects, but they were only numerically elevated in the AA subjects. Photoprotected sites had an increase in C-1 activity in pigmented groups (C and BA), whereas in the AA subjects, the opposite was measured. Plasmin activities were greater on the cheek compared with the PA site for the AA and C subjects, but the activity was low in the BA subjects. In both test sites, the AA, but not the BA and C subjects, had smaller, parakeratotic and less mature corneocytes. Variation in PCA levels has been found for different ethnic groups in this study (AA > BA > C subjects). The values in the AA subjects are surprising as one might expect that the lack of pigmentation, and thereby increased photodamage, might lead to lower levels. Increased BH, but not C-1 activity, was observed in the AA subjects indicating that BH is associated with PCA production to a greater extent. Surprisingly, corneocyte maturation is still impaired with elevated PCA levels in AA subjects. The higher levels of plasmin and BH activities on the cheeks, especially for AA and C subjects, suggest

  3. Preferential Allele Expression Analysis Identifies Shared Germline and Somatic Driver Genes in Advanced Ovarian Cancer

    Science.gov (United States)

    Halabi, Najeeb M.; Martinez, Alejandra; Al-Farsi, Halema; Mery, Eliane; Puydenus, Laurence; Pujol, Pascal; Khalak, Hanif G.; McLurcan, Cameron; Ferron, Gwenael; Querleu, Denis; Al-Azwani, Iman; Al-Dous, Eman; Mohamoud, Yasmin A.; Malek, Joel A.; Rafii, Arash

    2016-01-01

    Identifying genes where a variant allele is preferentially expressed in tumors could lead to a better understanding of cancer biology and optimization of targeted therapy. However, tumor sample heterogeneity complicates standard approaches for detecting preferential allele expression. We therefore developed a novel approach combining genome and transcriptome sequencing data from the same sample that corrects for sample heterogeneity and identifies significant preferentially expressed alleles. We applied this analysis to epithelial ovarian cancer samples consisting of matched primary ovary and peritoneum and lymph node metastasis. We find that preferentially expressed variant alleles include germline and somatic variants, are shared at a relatively high frequency between patients, and are in gene networks known to be involved in cancer processes. Analysis at a patient level identifies patient-specific preferentially expressed alleles in genes that are targets for known drugs. Analysis at a site level identifies patterns of site specific preferential allele expression with similar pathways being impacted in the primary and metastasis sites. We conclude that genes with preferentially expressed variant alleles can act as cancer drivers and that targeting those genes could lead to new therapeutic strategies. PMID:26735499

  4. Fibrin accumulation secondary to loss of plasmin-mediated fibrinolysis drives inflammatory osteoporosis in mice.

    Science.gov (United States)

    Cole, Heather A; Ohba, Tetsuro; Nyman, Jeffry S; Hirotaka, Haro; Cates, Justin M M; Flick, Matthew J; Degen, Jay L; Schoenecker, Jonathan G

    2014-08-01

    Osteoporosis is a skeletal disorder characterized by low bone mass and increased bone fragility associated with aging, menopause, smoking, obesity, or diabetes. Persistent inflammation has been identified as an instigating factor in progressive bone loss. In addition to the role of fibrin in coagulation, inordinate fibrin deposition within a tissue matrix results in increased local inflammation. Given that fibrin accumulation is a hallmark of osteoporosis-related comorbidities, we undertook this study to test the hypothesis that persistent fibrin deposition causes inflammatory osteoporosis. Multiple imaging modalities, bone integrity metrics, and histologic analyses were employed to evaluate skeletal derangements in relation to fibrin deposition, circulating fibrinogen levels, and systemic markers of inflammation in mice that were plasminogen deficient and in plasminogen-deficient mice that were concomitantly either fibrinogen deficient or carrying a mutant form of fibrinogen lacking the αM β2 binding motif. Mice generated with a genetic deficit in the key fibrinolytic protease, plasmin, uniformly developed severe osteoporosis. Furthermore, the development of osteoporosis was fibrin(ogen) dependent, and the derangements in the bone remodeling unit were mechanistically tied to fibrin(ogen)-mediated activation of osteoclasts via activation of the leukocyte integrin receptor αM β2 on monocytes and secondary stimulation of osteoblasts by RANKL. Notably, the genetic elimination of fibrin(ogen) or the expression of a mutant form of fibrinogen retaining clotting function but lacking the αM β2 binding motif prevented the degenerative skeletal phenotypes, resulting in normal local and systemic cytokine levels. Taken together, these data reveal for the first time that fibrin promotes inflammation-driven systemic osteoporosis, which suggests a novel association between hemostasis, inflammation, and bone biology. Copyright © 2014 by the American College of Rheumatology.

  5. Using DC electrical resistivity tomography to quantify preferential flow in fractured rock environments

    CSIR Research Space (South Africa)

    May, F

    2011-09-01

    Full Text Available . This investigation aims to identify preferential flow paths in fractured rock environments. Time-lapse Electrical Resistivity Tomography (TLERT, Lund Imaging System), is regarded as a suitable method for identifying preferential water flow....

  6. Development and characterization of a model system to study amphibian immune responses to iridoviruses

    International Nuclear Information System (INIS)

    Gantress, Jennifer; Maniero, Gregory D.; Cohen, Nicholas; Robert, Jacques

    2003-01-01

    The recent realization that viruses within the family Iridoviridae may contribute to the worldwide decline in amphibians makes it urgent to understand amphibian antiviral immune defenses. We present evidence that establishes the frog Xenopus laevis as an important model with which to study anti-iridovirus immunity. Adults resist high doses of FV3 infection, showing only transitory signs of pathology. By contrast, naturally MHC class-I-deficient tadpoles are highly susceptible to FV3 infection. Monitoring of viral DNA by PCR indicates a preferential localization of FV3 DNA in the kidney, with the inbred MHC homozygous J strain appearing to be more susceptible. Clearance of virus as measured by detection of FV3 DNA and also the disappearance of pathological and behavioral symptoms of infection, acceleration of viral clearance, and detection of IgY anti-FV3 antibodies after a second injection of FV3 are all consistent with the involvement of both cellular and humoral adaptive antiviral immune responses

  7. Identification of Homophily and Preferential Recruitment in Respondent-Driven Sampling.

    Science.gov (United States)

    Crawford, Forrest W; Aronow, Peter M; Zeng, Li; Li, Jianghong

    2018-01-01

    Respondent-driven sampling (RDS) is a link-tracing procedure used in epidemiologic research on hidden or hard-to-reach populations in which subjects recruit others via their social networks. Estimates from RDS studies may have poor statistical properties due to statistical dependence in sampled subjects' traits. Two distinct mechanisms account for dependence in an RDS study: homophily, the tendency for individuals to share social ties with others exhibiting similar characteristics, and preferential recruitment, in which recruiters do not recruit uniformly at random from their network alters. The different effects of network homophily and preferential recruitment in RDS studies have been a source of confusion and controversy in methodological and empirical research in epidemiology. In this work, we gave formal definitions of homophily and preferential recruitment and showed that neither is identified in typical RDS studies. We derived nonparametric identification regions for homophily and preferential recruitment and showed that these parameters were not identified unless the network took a degenerate form. The results indicated that claims of homophily or recruitment bias measured from empirical RDS studies may not be credible. We applied our identification results to a study involving both a network census and RDS on a population of injection drug users in Hartford, Connecticut (2012-2013). © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Fitness networks for real world systems via modified preferential attachment

    Science.gov (United States)

    Shang, Ke-ke; Small, Michael; Yan, Wei-sheng

    2017-05-01

    Complex networks are virtually ubiquitous, and the Barabási and Albert model (BA model) has became an acknowledged standard for the modelling of these systems. The so-called BA model is a kind of preferential attachment growth model based on the intuitive premise that popularity is attractive. However, preferential attachment alone is insufficient to describe the diversity of complex networks observed in the real world. In this paper we first use the accuracy of a link prediction method, as a metric for network fitness. The link prediction method predicts the occurrence of links consistent with preferential attachment, the performance of this link prediction scheme is then a natural measure of the ;preferential-attachment-likeness; of a given network. We then propose several modification methods and modified BA models to construct networks which more accurately describe the fitness properties of real networks. We find that all features assortativity, degree distribution and rich-club formation can play significant roles for the network construction and eventual structure. Moreover, link sparsity and the size of a network are key factors for network reconstruction. In addition, we find that the structure of the network which is limited by geographic location (nodes are embedded in a Euclidean space and connectivity is correlated with distances) differs from other typical networks. In social networks, we observe that the high school contact network has similar structure as the friends network and so we speculate that the contact behaviours can reflect real friendships.

  9. Plasma centrifugation does not influence thrombin-antithrombin and plasmin-antiplasmin levels but determines platelet microparticles count.

    Science.gov (United States)

    Stępień, Ewa; Gruszczyński, Krzysztof; Kapusta, Przemysław; Kowalik, Artur; Wybrańska, Iwona

    2015-01-01

    Centrifugation is an essential step for plasma preparation to remove residual elements in plasma, especially platelets and platelet-derived microparticles (PMPs). Our working hypothesis was that centrifugation as a preanalytical step may influence some coagulation parameters. Healthy young men were recruited (N=17). For centrifugation, two protocols were applied: (A) the first centrifugation at 2500xg for 15 min and (B) at 2500xg for 20 min at room temperature with a light brake. In protocol (A), the second centrifugation was carried out at 2500xg for 15 min, whereas in protocol (B), the second centrifugation involved a 10 min spin at 13,000 x g. Thrombin-antithrombin (TAT) and plasmin-antiplasmin (PAP) complexes concentrations were determined by enzyme-linked immunosorbent assays. PMPs were stained with CD41 antibody and annexin V, and analyzed by flow cytometry method. Procoagulant activity was assayed by the Calibrated Automated Thrombogram method as a slope of thrombin formation (CAT velocity). Median TAT and PAP concentrations did not differ between the centrifugation protocols. The high speed centrifugation reduced the median (IQR) PMP count in plasma from 1291 (841-1975) to 573 (391-1010) PMP/µL (P=0.001), and CAT velocity from 2.01 (1.31-2.88) to 0.97 (0.82-1.73) nM/min (P=0.049). Spearman's rank correlation analysis showed correlation between TAT and PMPs in the protocol A plasma which was (rho=0.52, PCentrifugation protocols do not influence the markers of plasminogen (PAP) and thrombin (TAT) generation but they do affect the PMP count and procoagulant activity.

  10. Preferential adsorption of uranium ions in aqueous solutions by polymers

    International Nuclear Information System (INIS)

    Sakuragi, Masako; Ichimura, Kunihiro; Fujishige, Shoei; Kato, Masao

    1981-01-01

    Amidoxime fiber and triazine fiber were prepared by chemical modification of commercially available polyacrylonitril fiber. It was found that the Amidoxime fiber is efficient to adsorb uranium ions in the artificial sea water. The efficiency of the preferential adsorption decreases by treatment the material with an acid-or an alkaline-solution. The triazine fiber adsorbs uranium ions only in aqueous solutions of such uranyl acetate, in the absence of other ions. In the artificial sea water, it adsorbs other ions instead of uranium. The preferential adsorption of uranium ions was further investigated with a series of polystyrenesulfonamides. Among the polystyrene derivatives, those having carboxyl groups, derived from imino diacetic acid (PSt-Imi), β-alanine (PSt-Ala), glycine (PSt-Gly), and sarcosine (PSt-Sar) were qualified for further discussion. However, it was found that the amount of adsorption of uranium ions by PSt-Imi decreases with increasing the volume of the artificial sea water and/or the duration of the treatment. Taking into account the facts, the preferential adsorption of uranium ions by PSt-Imi in aqueous solution was discussed in detail. (author)

  11. TWO MEASURES OF THE DEPENDENCE OF PREFERENTIAL RANKINGS ON CATEGORICAL VARIABLES

    Directory of Open Access Journals (Sweden)

    Lissowski Grzegorz

    2017-06-01

    Full Text Available The aim of this paper is to apply a general methodology for constructing statistical methods, which is based on decision theory, to give a statistical description of preferential rankings, with a focus on the rankings’ dependence on categorical variables. In the paper, I use functions of description errors that are based on the Kemeny and Hamming distances between preferential orderings, but the proposed methodology can also be applied to other methods of estimating description errors.

  12. Growth of preferential attachment random graphs via continuous ...

    Indian Academy of Sciences (India)

    Preferential attachment processes have a long history dating back at least to Yule ... We remark that some connections to branching and continuous-time Markov ..... convenience, we provide a short proof of Lemma 2.1 in the general form in ...

  13. Estimating preferential flow in karstic aquifers using statistical mixed models.

    Science.gov (United States)

    Anaya, Angel A; Padilla, Ingrid; Macchiavelli, Raul; Vesper, Dorothy J; Meeker, John D; Alshawabkeh, Akram N

    2014-01-01

    Karst aquifers are highly productive groundwater systems often associated with conduit flow. These systems can be highly vulnerable to contamination, resulting in a high potential for contaminant exposure to humans and ecosystems. This work develops statistical models to spatially characterize flow and transport patterns in karstified limestone and determines the effect of aquifer flow rates on these patterns. A laboratory-scale Geo-HydroBed model is used to simulate flow and transport processes in a karstic limestone unit. The model consists of stainless steel tanks containing a karstified limestone block collected from a karst aquifer formation in northern Puerto Rico. Experimental work involves making a series of flow and tracer injections, while monitoring hydraulic and tracer response spatially and temporally. Statistical mixed models (SMMs) are applied to hydraulic data to determine likely pathways of preferential flow in the limestone units. The models indicate a highly heterogeneous system with dominant, flow-dependent preferential flow regions. Results indicate that regions of preferential flow tend to expand at higher groundwater flow rates, suggesting a greater volume of the system being flushed by flowing water at higher rates. Spatial and temporal distribution of tracer concentrations indicates the presence of conduit-like and diffuse flow transport in the system, supporting the notion of both combined transport mechanisms in the limestone unit. The temporal response of tracer concentrations at different locations in the model coincide with, and confirms the preferential flow distribution generated with the SMMs used in the study. © 2013, National Ground Water Association.

  14. Preferential acceleration in collisionless supernova shocks

    International Nuclear Information System (INIS)

    Hainebach, K.; Eichler, D.; Schramm, D.

    1979-01-01

    The preferential acceleration and resulting cosmic ray abundance enhancements of heavy elements (relative to protons) are calculated in the collisionless supernova shock acceleration model described by Eichler in earlier work. Rapidly increasing enhancements up to several tens times solar ratios are obtained as a function of atomic weight over charge at the time of acceleration. For material typical of hot phase interstellar medium, good agreement is obtained with the observed abundance enhancements

  15. Preferential selection based on degree difference in the spatial prisoner's dilemma games

    Science.gov (United States)

    Huang, Changwei; Dai, Qionglin; Cheng, Hongyan; Li, Haihong

    2017-10-01

    Strategy evolution in spatial evolutionary games is generally implemented through imitation processes between individuals. In most previous studies, it is assumed that individuals pick up one of their neighbors randomly to learn from. However, by considering the heterogeneity of individuals' influence in the real society, preferential selection is more realistic. Here, we introduce a preferential selection mechanism based on degree difference into spatial prisoner's dilemma games on Erdös-Rényi networks and Barabási-Albert scale-free networks and investigate the effects of the preferential selection on cooperation. The results show that, when the individuals prefer to choose the neighbors who have small degree difference with themselves to imitate, cooperation is hurt by the preferential selection. In contrast, when the individuals prefer to choose those large degree difference neighbors to learn from, there exists optimal preference strength resulting in the maximal cooperation level no matter what the network structure is. In addition, we investigate the robustness of the results against variations of the noise, the average degree and the size of network in the model, and find that the qualitative features of the results are unchanged.

  16. Preferential interactions and the effect of protein PEGylation

    DEFF Research Database (Denmark)

    Holm, Louise Stenstrup; Thulstrup, Peter Waaben; Kasimova, Marina Robertovna

    2015-01-01

    enthalpy was decreased to half the value for PEGylated lysozyme. The ratio between calorimetric and van't Hoff enthalpy suggests that our PEGylated lysozyme is a dimer. CONCLUSION/SIGNIFICANCE: The PEGylated model protein displayed similar stability responses to the addition of preferentially active...

  17. Elevational variation in body-temperature response to immune challenge in a lizard

    Directory of Open Access Journals (Sweden)

    Francisco Javier Zamora-Camacho

    2016-04-01

    Full Text Available Immunocompetence benefits animal fitness by combating pathogens, but also entails some costs. One of its main components is fever, which in ectotherms involves two main types of costs: energy expenditure and predation risk. Whenever those costs of fever outweigh its benefits, ectotherms are expected not to develop fever, or even to show hypothermia, reducing costs of thermoregulation and diverting the energy saved to other components of the immune system. Environmental thermal quality, and therefore the thermoregulation cost/benefit balance, varies geographically. Hence, we hypothesize that, in alpine habitats, immune-challenged ectotherms should show no thermal response, given that (1 hypothermia would be very costly, as the temporal window for reproduction is extremely small, and (2 fever would have a prohibitive cost, as heat acquisition is limited in such habitat. However, in temperate habitats, immune-challenged ectotherms might show a febrile response, due to lower cost/benefit balance as a consequence of a more suitable thermal environment. We tested this hypothesis in Psammodromus algirus lizards from Sierra Nevada (SE Spain, by testing body temperature preferred by alpine and non-alpine lizards, before and after activating their immune system with a typical innocuous pyrogen. Surprisingly, non-alpine lizards responded to immune challenge by decreasing preferential body-temperature, presumably allowing them to save energy and reduce exposure to predators. On the contrary, as predicted, immune-challenged alpine lizards maintained their body-temperature preferences. These results match with increased costs of no thermoregulation with elevation, due to the reduced window of time for reproduction in alpine environment.

  18. Altered tumor growth in vivo after immunization of mice with antitumor antibodies

    International Nuclear Information System (INIS)

    Gorczynski, R.M.; Kennedy, M.; Polidoulis, I.; Price, G.B.

    1984-01-01

    A comparison has been made between the growth patterns of two spontaneously appearing mammary adenocarcinomas in murine bone marrow radiation chimeras and in mice preimmunized with monoclonal antibodies (MAb) detecting embryo-associated antigenic determinants. A correlation was seen between the ability of the embryo-immunized chimeras to produce cytotoxic antibody to the tumors, as assessed by an antibody-dependent cellular cytotoxic assay, and the permissiveness of the mice for growth of a tumor transplant. In addition, mice deliberately preimmunized with cytotoxic MAb (antibody-dependent cellular cytotoxic assay) allowed more rapid growth specifically of that tumor earlier found to be most sensitive to the MAb used for immunization. By comparing the changing antigenic phenotype of tumor cells serially passaged through different immunized, nonimmunized mice, evidence was found suggesting that immunization could cause either antigen modulation of transferred tumor cells or a (transient) selective advantage to antigenically discrete subpopulations within the heterogeneous tumor population. Finally, a study has been made of the growth pattern of tumor cells transplanted into mice immunized with rabbit antibodies directed against the murine MAb. In this case, tumor growth was slowed preferentially for the tumor reactive with the specific MAb, and again, predictable changes in the antigenic spectrum of tumor cells harvested from these animals were observed. Our overall findings are interpreted in terms of the involvement of networks of antibodies reacting with embryo-associated antigens in the regulation of growth of the murine mammary adenocarcinomas studied

  19. Post-learning hippocampal dynamics promote preferential retention of rewarding events

    Science.gov (United States)

    Gruber, Matthias J.; Ritchey, Maureen; Wang, Shao-Fang; Doss, Manoj K.; Ranganath, Charan

    2016-01-01

    Reward motivation is known to modulate memory encoding, and this effect depends on interactions between the substantia nigra/ ventral tegmental area complex (SN/VTA) and the hippocampus. It is unknown, however, whether these interactions influence offline neural activity in the human brain that is thought to promote memory consolidation. Here, we used functional magnetic resonance imaging (fMRI) to test the effect of reward motivation on post-learning neural dynamics and subsequent memory for objects that were learned in high- or low-reward motivation contexts. We found that post-learning increases in resting-state functional connectivity between the SN/VTA and hippocampus predicted preferential retention of objects that were learned in high-reward contexts. In addition, multivariate pattern classification revealed that hippocampal representations of high-reward contexts were preferentially reactivated during post-learning rest, and the number of hippocampal reactivations was predictive of preferential retention of items learned in high-reward contexts. These findings indicate that reward motivation alters offline post-learning dynamics between the SN/VTA and hippocampus, providing novel evidence for a potential mechanism by which reward could influence memory consolidation. PMID:26875624

  20. Preferential Solvation of Silver (I) Bromate in Methanol-Dimethylsulfoxide Mixtures

    Science.gov (United States)

    Janardhanan, S.; Kalidas, C.

    1984-06-01

    The solubiltiy of silver bromate, the Gibbs transfer energy of Ag+ and BrO3- and the solvent transport number in methanol-dimethyl sulfoxide mixtures are reported. The solubility of silver bromate increases with addition of DMSO. The Gibbs energy of transfer of the silver ion (based on the ferrocene reference method) decreases, while that of the bromate ion becomes slightly negative with the addition of DMSO. The solvent transport number A passes through a maximum (⊿ = 1.0 at XDMSO = 0.65. From these results, it is concluded that the silver ion is preferentially solvated by DMSO whereas the bromate ion shows no preferential solvation.

  1. The Plasmin-Sensitive Protein Pls in Methicillin-Resistant Staphylococcus aureus (MRSA Is a Glycoprotein.

    Directory of Open Access Journals (Sweden)

    Isabelle Bleiziffer

    2017-01-01

    Full Text Available Most bacterial glycoproteins identified to date are virulence factors of pathogenic bacteria, i.e. adhesins and invasins. However, the impact of protein glycosylation on the major human pathogen Staphylococcus aureus remains incompletely understood. To study protein glycosylation in staphylococci, we analyzed lysostaphin lysates of methicillin-resistant Staphylococcus aureus (MRSA strains by SDS-PAGE and subsequent periodic acid-Schiff's staining. We detected four (>300, ∼250, ∼165, and ∼120 kDa and two (>300 and ∼175 kDa glycosylated surface proteins with strain COL and strain 1061, respectively. The ∼250, ∼165, and ∼175 kDa proteins were identified as plasmin-sensitive protein (Pls by mass spectrometry. Previously, Pls has been demonstrated to be a virulence factor in a mouse septic arthritis model. The pls gene is encoded by the staphylococcal cassette chromosome (SCCmec type I in MRSA that also encodes the methicillin resistance-conferring mecA and further genes. In a search for glycosyltransferases, we identified two open reading frames encoded downstream of pls on the SCCmec element, which we termed gtfC and gtfD. Expression and deletion analysis revealed that both gtfC and gtfD mediate glycosylation of Pls. Additionally, the recently reported glycosyltransferases SdgA and SdgB are involved in Pls glycosylation. Glycosylation occurs at serine residues in the Pls SD-repeat region and modifying carbohydrates are N-acetylhexosaminyl residues. Functional characterization revealed that Pls can confer increased biofilm formation, which seems to involve two distinct mechanisms. The first mechanism depends on glycosylation of the SD-repeat region by GtfC/GtfD and probably also involves eDNA, while the second seems to be independent of glycosylation as well as eDNA and may involve the centrally located G5 domains. Other previously known Pls properties are not related to the sugar modifications. In conclusion, Pls is a glycoprotein and

  2. Transcriptome-wide identification of preferentially expressed genes in the hypothalamus and pituitary gland

    Directory of Open Access Journals (Sweden)

    Jonny eSt-Amand

    2012-01-01

    Full Text Available To identify preferentially expressed genes in the central endocrine organs of the hypothalamus and pituitary gland, we generated transcriptome-wide mRNA profiles of the mouse hypothalamus, pituitary gland and parietal cortex using serial analysis of gene expression (SAGE. Total counts of SAGE tags for the hypothalamus, pituitary gland and parietal cortex were 165824, 126688 and 161045 tags, respectively. This represented 59244, 45151 and 55131 distinct tags, respectively. Comparison of these mRNA profiles revealed that 22 mRNA species, including three potential novel transcripts, were preferentially expressed in the hypothalamus. In addition to well-known hypothalamic transcripts, such as hypocretin, several genes involved in hormone function, intracellular transduction, metabolism, protein transport, steroidogenesis, extracellular matrix and brain disease were identified as preferentially expressed hypothalamic transcripts. In the pituitary gland, 106 mRNA species, including 60 potential novel transcripts, were preferentially expressed. In addition to well-known pituitary genes, such as growth hormone and thyroid stimulating hormone beta, a number of genes classified to function in transport, amino acid metabolism, intracellular transduction, cell adhesion, disulfide bond formation, stress response, transcription, protein synthesis and turnover, cell differentiation, the cell cycle and in the cytoskeleton and extracellular matrix were also preferentially expressed. In conclusion, the current study identified not only well-known hypothalamic and pituitary transcripts but also a number of new candidates likely to be involved in endocrine homeostatic systems regulated by the hypothalamus and pituitary gland.

  3. Transcriptome-wide identification of preferentially expressed genes in the hypothalamus and pituitary gland.

    Science.gov (United States)

    St-Amand, Jonny; Yoshioka, Mayumi; Tanaka, Keitaro; Nishida, Yuichiro

    2011-01-01

    To identify preferentially expressed genes in the central endocrine organs of the hypothalamus and pituitary gland, we generated transcriptome-wide mRNA profiles of the hypothalamus, pituitary gland, and parietal cortex in male mice (12-15 weeks old) using serial analysis of gene expression (SAGE). Total counts of SAGE tags for the hypothalamus, pituitary gland, and parietal cortex were 165824, 126688, and 161045 tags, respectively. This represented 59244, 45151, and 55131 distinct tags, respectively. Comparison of these mRNA profiles revealed that 22 mRNA species, including three potential novel transcripts, were preferentially expressed in the hypothalamus. In addition to well-known hypothalamic transcripts, such as hypocretin, several genes involved in hormone function, intracellular transduction, metabolism, protein transport, steroidogenesis, extracellular matrix, and brain disease were identified as preferentially expressed hypothalamic transcripts. In the pituitary gland, 106 mRNA species, including 60 potential novel transcripts, were preferentially expressed. In addition to well-known pituitary genes, such as growth hormone and thyroid stimulating hormone beta, a number of genes classified to function in transport, amino acid metabolism, intracellular transduction, cell adhesion, disulfide bond formation, stress response, transcription, protein synthesis, and turnover, cell differentiation, the cell cycle, and in the cytoskeleton and extracellular matrix were also preferentially expressed. In conclusion, the current study identified not only well-known hypothalamic and pituitary transcripts but also a number of new candidates likely to be involved in endocrine homeostatic systems regulated by the hypothalamus and pituitary gland.

  4. α-chymotrypsin in water-acetone and water-dimethyl sulfoxide mixtures: Effect of preferential solvation and hydration.

    Science.gov (United States)

    Sirotkin, Vladimir A; Kuchierskaya, Alexandra A

    2017-10-01

    We investigated water/organic solvent sorption and residual enzyme activity to simultaneously monitor preferential solvation/hydration of protein macromolecules in the entire range of water content at 25°C. We applied this approach to estimate protein destabilization/stabilization due to the preferential interactions of bovine pancreatic α-chymotrypsin with water-acetone (moderate-strength H-bond acceptor) and water-DMSO (strong H-bond acceptor) mixtures. There are three concentration regimes for the dried α-chymotrypsin. α-Chymotrypsin is preferentially hydrated at high water content. The residual enzyme activity values are close to 100%. At intermediate water content, the dehydrated α-chymotrypsin has a higher affinity for acetone/DMSO than for water. Residual enzyme activity is minimal in this concentration range. The acetone/DMSO molecules are preferentially excluded from the protein surface at the lowest water content, resulting in preferential hydration. The residual catalytic activity in the water-poor acetone is ∼80%, compared with that observed after incubation in pure water. This effect is very small for the water-poor DMSO. Two different schemes are operative for the hydrated enzyme. At high and intermediate water content, α-chymotrypsin exhibits preferential hydration. However, at intermediate water content, in contrast to the dried enzyme, the initially hydrated α-chymotrypsin possesses increased preferential hydration parameters. At low water content, no residual enzyme activity was observed. Preferential binding of DMSO/acetone to α-chymotrypsin was detected. Our data clearly demonstrate that the hydrogen bond accepting ability of organic solvents and the protein hydration level constitute key factors in determining the stability of protein-water-organic solvent systems. © 2017 Wiley Periodicals, Inc.

  5. When and where does preferential flow matter - from observation to large scale modelling

    Science.gov (United States)

    Weiler, Markus; Leistert, Hannes; Steinbrich, Andreas

    2017-04-01

    Preferential flow can be of relevance in a wide range of soils and the interaction of different processes and factors are still difficult to assess. As most studies (including our own studies) focusing on the effect of preferential flow are based on relatively high precipitation rates, there is always the question how relevant preferential flow is under natural conditions, considering the site specific precipitation characteristics, the effect of the drying and wetting cycle on the initial soil water condition and shrinkage cracks, the site specific soil properties, soil structure and rock fragments, and the effect of plant roots and soil fauna (e.g. earthworm channels). In order to assess this question, we developed the distributed, process-based model RoGeR (Runoff Generation Research) to include a large number relevant features and processes of preferential flow in soils. The model was developed from a large number of process based research and experiments and includes preferential flow in roots, earthworm channels, along rock fragments and shrinkage cracks. We parameterized the uncalibrated model at a high spatial resolution of 5x5m for the whole state of Baden-Württemberg in Germany using LiDAR data, degree of sealing, landuse, soil properties and geology. As the model is an event based model, we derived typical event based precipitation characteristics based on rainfall duration, mean intensity and amount. Using the site-specific variability of initial soil moisture derived from a water balance model based on the same dataset, we simulated the infiltration and recharge amounts of all event classes derived from the event precipitation characteristics and initial soil moisture conditions. The analysis of the simulation results allowed us to extracts the relevance of preferential flow for infiltration and recharge considering all factors above. We could clearly see a strong effect of the soil properties and land-use, but also, particular for clay rich soils a

  6. Which key properties controls the preferential transport in the vadose zone under transient hydrological conditions

    Science.gov (United States)

    Groh, J.; Vanderborght, J.; Puetz, T.; Gerke, H. H.; Rupp, H.; Wollschlaeger, U.; Stumpp, C.; Priesack, E.; Vereecken, H.

    2015-12-01

    Understanding water flow and solute transport in the unsaturated zone is of great importance for an appropriate land use management strategy. The quantification and prediction of water and solute fluxes through the vadose zone can help to improve management practices in order to limit potential risk on our fresh water resources. Water related solute transport and residence time is strongly affected by preferential flow paths in the soil. Water flow in soils depends on soil properties and site factors (climate or experiment conditions, land use) and are therefore important factors to understand preferential solute transport in the unsaturated zone. However our understanding and knowledge of which on-site properties or conditions define and enhance preferential flow and transport is still poor and mostly limited onto laboratory experimental conditions (small column length and steady state boundary conditions). Within the TERENO SOILCan lysimeter network, which was designed to study the effects of climate change on soil functions, a bromide tracer was applied on 62 lysimeter at eight different test sites between Dec. 2013 and Jan. 2014. The TERENO SOILCan infrastructure offers the unique possibility to study the occurrence of preferential flow and transport of various soil types under different natural transient hydrological conditions and land use (crop, bare and grassland) at eight TERENO SOILCan observatories. Working with lysimeter replicates at each observatory allows defining the spatial variability of preferential transport and flow. Additionally lysimeters in the network were transferred within and between observatories in order to subject them to different rainfall and temperature regimes and enable us to relate the soil type susceptibility of preferential flow and transport not only to site specific physical and land use properties, but also to different transient boundary conditions. Comparison and statistical analysis between preferential flow indicators 5

  7. Hematopoietic Stem and Progenitor Cells as Effectors in Innate Immunity

    Directory of Open Access Journals (Sweden)

    Jennifer L. Granick

    2012-01-01

    Full Text Available Recent research has shed light on novel functions of hematopoietic stem and progenitor cells (HSPC. While they are critical for maintenance and replenishment of blood cells in the bone marrow, these cells are not limited to the bone marrow compartment and function beyond their role in hematopoiesis. HSPC can leave bone marrow and circulate in peripheral blood and lymph, a process often manipulated therapeutically for the purpose of transplantation. Additionally, these cells preferentially home to extramedullary sites of inflammation where they can differentiate to more mature effector cells. HSPC are susceptible to various pathogens, though they may participate in the innate immune response without being directly infected. They express pattern recognition receptors for detection of endogenous and exogenous danger-associated molecular patterns and respond not only by the formation of daughter cells but can themselves secrete powerful cytokines. This paper summarizes the functional and phenotypic characterization of HSPC, their niche within and outside of the bone marrow, and what is known regarding their role in the innate immune response.

  8. THE DISTRIBUTION OF PREFERENTIAL PATHS AND ITS RELATION TO THE SOIL CHARACTERISTICS IN THE THREE GORGES AREA, CHINA

    Institute of Scientific and Technical Information of China (English)

    Hongjiang ZHANG; Jinhua CHENG; Yuhu SHI; Yun CHENG

    2007-01-01

    To study the characteristics of the distribution of the preferential paths and the affecting factors in the Three Gorges area, four soil profiles were dug to observe the distribution of preferential paths in the Quxi watershed in the Yangtze River basin. The Morisita exponential test method was used to examine the distribution type of preferential paths. The physical properties and infiltration characteristics of the soil were also measured to evaluate their relationship to preferential paths. The results showed that in this area, preferential paths clustered and mainly distributed in the 80-100 cm soil layer, and along the interface between the weathered layer and semi-weathered layer. There were more non-capillary pores in the 83-110 cm layer than in the other layers. It can be derived that most non-capillary pores in this layer were preferential paths caused by geological processes and rotten plant roots. The percentage of coarse soil particles increased with the depth of the soil layer. In the deeper soil layer, the coarse soil particles helped the formation of preferential paths. The fastest steady infiltration rate was observed in the of 83-110cm layer, which is inferred to be due to the greater number of preferential paths.

  9. Tranexamic Acid Attenuates The Loss of Lung Barrier Function in a Rat Model of Polytrauma And Hemorrhage With Resuscitation.

    Science.gov (United States)

    Wu, Xiaowu; Dubick, Michael A; Schwacha, Martin G; Cap, Andrew P; Darlington, Daniel N

    2017-04-01

    Severe trauma, hemorrhage, and resuscitation can lead to a trauma-related acute lung injury that involves rapid infiltration of immune cells and platelets. This infiltration involves exymatic degradation of matrix proteins, including plasmin, and causes loss of barrier function. Since tranexamic acid (TXA) inhibits plasminogen/ plasmin binding to target substrates, it may attenuate loss of barrier function after severe trauma, hemorrhage, and resuscitation. Sprague-Dawley rats were subjected to polytrauma (laparotomy, and trauma to intestines, liver, right leg skeletal muscle, and right femur fracture), then bled 40% of their blood volume. One hour after completion of polytrauma and hemorrhage, resuscitation was begun with fresh whole blood (FWB) or FWB with prior bolus administration of TXA (10 mg/kg in 0.2 mL). Polytrauma, hemorrhage, and resuscitation with FWB led to an elevation in lung water content that was significantly reduced with TXA administration. Polytrauma and hemorrhage led to rise in the number of neutrophils/monocytes and platelets in the lungs, and a rise in myeloperoxidase (MPO), neutrophil elastase and complement C5a content. While resuscitation with FWB significantly reduced the cellular infiltrate and MPO, FWB/TXA further reduced the levels of neutrophil/monocytes, neutrophil elastase, and complement C5a. Polytrauma and hemorrhage led to rise in lung plasmin activity that was significantly reduced with either FWB or FWB/TXA resuscitation. Severe trauma and hemorrhage leads to increases in lung water content, and immune cell, platelets, MPO, elastase, and C5a content in lung tissue, all markers of inflammation and acute lung injury. The addition of TXA to FWB resuscitation markedly attenuated the rise in these parameters suggesting its utility in treating acute lung injury.

  10. Activation of pro-urokinase and plasminogen on human sarcoma cells

    DEFF Research Database (Denmark)

    Stephens, R W; Pöllänen, J; Tapiovaara, H

    1989-01-01

    from the cells with tranexamic acid, an analogue of lysine. The bound plasmin was the result of plasminogen activation on the cell surface; plasmin activity was not taken up onto cells after deliberate addition of plasmin to the serum-containing medium. The cell surface plasmin formation was inhibited...

  11. PCSK9 at the crossroad of cholesterol metabolism and immune function during infections.

    Science.gov (United States)

    Paciullo, Francesco; Fallarino, Francesca; Bianconi, Vanessa; Mannarino, Massimo R; Sahebkar, Amirhossein; Pirro, Matteo

    2017-09-01

    Sepsis, a complex and dynamic syndrome resulting from microbial invasion and immune system dysregulation, is associated with an increased mortality, reaching up to 35% worldwide. Cholesterol metabolism is often disturbed during sepsis, with low plasma cholesterol levels being associated with poor prognosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of the low-density lipoprotein receptor (LDLR), thus regulating intracellular and plasma cholesterol levels. PCSK9 is often upregulated during sepsis and might have a detrimental effect on immune host response and survival. Accordingly, PCSK9 reduces lipopolysaccharide uptake and clearance by human hepatocytes. Moreover, PCSK9 upregulation exacerbates organ dysfunction and tissue inflammation during sepsis, whereas a protective effect of PCSK9 deficiency has been documented in septic patients. Although a possible detrimental impact of PCSK9 on survival has been described, some beneficial effects of PCSK9 on immune response may be hypothesized. First, PCSK9 is associated with increased plasma cholesterol levels, which might be protective during sepsis. Second, PCSK9, by stimulating LDLR degradation and inhibiting reverse cholesterol transport (RCT), might promote preferential cholesterol accumulation in macrophages and other immune cells; these events might improve lipid raft composition and augment toll-like receptor function thus supporting inflammatory response. Hence, a more clear definition of the role of PCSK9 in septic states might provide additional insight in the understanding of the sepsis-associated immune dysregulation and enhance therapeutic outcomes. © 2017 Wiley Periodicals, Inc.

  12. Field investigation of preferential fissure flow paths with hydrochemical analysis of small-scale sprinkling experiments

    NARCIS (Netherlands)

    Krzeminska, D.M.; Bogaard, T.A.; Debieche, T.H.; Cervi, F.; Marc, V.; Malet, J.P.

    2014-01-01

    The unsaturated zone largely controls groundwater recharge by buffering precipitation while at the same time providing preferential flow paths for infiltration. The importance of preferential flow on landslide hydrology is recognised in the literature; however, its monitoring and quantification

  13. Estriol-induced fibrinolysis due to the activation of plasminogen to plasmin by nitric oxide synthesis in platelets.

    Science.gov (United States)

    Jana, Pradipta; Maiti, Smarajit; Kahn, Nighat N; Sinha, Asru K

    2015-04-01

    Estriol, an oestrogen, at 0.6 nmol/l was reported to inhibit ADP-induced platelet aggregation through nitric oxide synthesis. As nitric oxide has been reported to cause fibrinolysis due to the activation of plasminogen to plasmin, the role of estriol as a fibrinolytic agent was investigated. Also, the mechanism of estriol-induced nitric oxide synthesis in anucleated platelets was investigated. The estriol-induced lysis of platelet-rich plasma (PRP) clot was determined by photography of the clot lysis and by the assay of fibrin degradation products in the lysate and was obtained by SDS-PAGE. Nitric oxide was determined by methemoglobin method. The platelet membrane protein was isolated from the platelets by using Triton X-100 (0.05% v/v). The binding of estriol to the protein was determined by Scatchard plot by using an ELISA for estriol. Estriol at 0.6 nmol/l was found to lyse the clotted PRP due to fibrinolysis that produced fibrin degradation products in the lysate. The amino acid analysis of the platelet membrane protein, which resembles with nitric oxide synthase (NOS) activity, was activated nearly 10-fold over the control in the presence of estriol and was identified to be a human serum albumin precursor (Mr. 69 kDa) that binds to estriol with Kd1 of 6.0 × 10 mol/l and 39 ± 2 molecules of estriol bound the NOS molecule. The estriol-induced nitric oxide is capable of inducing fibrinolysis of the clotted PRP. The binding of estriol to platelet membrane NOS activated the enzyme in the absence of DNA in the platelet.

  14. Acute aerobic exercise induces a preferential mobilisation of plasmacytoid dendritic cells into the peripheral blood in man.

    Science.gov (United States)

    Brown, Frankie F; Campbell, John P; Wadley, Alex J; Fisher, James P; Aldred, Sarah; Turner, James E

    2018-05-31

    30 min of exercise cessation. These results show that there is a preferential mobilisation of plasmacytoid DCs during exercise. Given the functional repertoire of plasmacytoid DCs, which includes the production of interferons against viral and bacterial pathogens, these findings indicate that exercise may augment immune-surveillance by preferentially mobilising effector cells; these findings have general implications for the promotion of exercise for health, and specifically for the optimisation of DC harvest for cancer immunotherapy. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. The impact of preferential procurement in South African construction ...

    African Journals Online (AJOL)

    The impact of preferential procurement in South African construction industry. ... The outcome of this study shows that there are problems in the implementation of PPPFA during tendering and procurement processes and procedures for achieving success in government projects. Key words: HDIs, PPPFA, Policies, ...

  16. Formal requirements for exclusion of the preferential right to shares

    Directory of Open Access Journals (Sweden)

    Marjanski Vladimir

    2014-01-01

    Full Text Available A preferential subscription right to shares is a subjective property right of a shareholder based on which he or she has a preferential right of subscription to shares from a new issue in proportion to the number of fully paid-in shares of that class he or she holds on the date of adoption of the decision on issuing of shares compared with the total number of shares of that class. However, this right of a shareholder can be completely or partially excluded, if formal and substantial requirements for such exclusion are met. This paper focuses primarily on analysis of formal requirements for exclusion envisaged by the Serbian Law on Companies with a brief review of EU law and comparative law. According to the Serbian Law on Companies, there are three formal requirements for exclusion of a preferential subscription right: 1. shares are issued through the offer for which there is no obligation to publish a prospectus; 2. there is a written proposal for exclusion from the Board of Directors, or of the Supervisory Board if a company has a two-tier management system; 3. the exclusion is based on a decision of the General Meeting of the Joint-stock company. With regards formal requirements, the paper concentrates on several weaknesses of the Serbian Law on Companies which considerably undermine the position of the so-called small shareholders.

  17. Preferential and Non-Preferential Approaches to Trade Liberalization in East Asia: What Differences Do Utilization Rates and Reciprocity Make?

    OpenAIRE

    Menon, Jayant

    2013-01-01

    Previous studies on the impacts of free trade agreements (FTAs) in East Asia have assumed full utilization of preferences. The evidence suggests that this assumption is seriously in error, with the estimated uptake particularly low in East Asia. In this paper, we assume a more realistic utilization rate in estimating impacts. We find that actual utilization rates significantly diminish the benefits from preferential liberalization, but in a non-linear way. Reciprocity is an important motivati...

  18. Bioclogging in Porous Media: Preferential Flow Paths and Anomalous Transport

    Science.gov (United States)

    Holzner, M.; Carrel, M.; Morales, V.; Derlon, N.; Beltran, M. A.; Morgenroth, E.; Kaufmann, R.

    2016-12-01

    Biofilms are sessile communities of microorganisms held together by an extracellular polymeric substance that enables surface colonization. In porous media (e.g. soils, trickling filters etc.) biofilm growth has been shown to affect the hydrodynamics in a complex fashion at the pore-scale by clogging individual pores and enhancing preferential flow pathways and anomalous transport. These phenomena are a direct consequence of microbial growth and metabolism, mass transfer processes and complex flow velocity fields possibly exhibiting pronounced three-dimensional features. Despite considerable past work, however, it is not fully understood how bioclogging interacts with flow and mass transport processes in porous media. In this work we use imaging techniques to determine the flow velocities and the distribution of biofilm in a porous medium. Three-dimensional millimodels are packed with a transparent porous medium and a glucose solution to match the optical refractive index. The models are inoculated with planktonic wildtype bacteria and biofilm cultivated for 60 h under a constant flow and nutrient conditions. The pore flow velocities in the increasingly bioclogged medium are measured using 3D particle tracking velocimetry (3D-PTV). The three-dimensional spatial distribution of the biofilm within the pore space is assessed by imaging the model with X-Ray microtomography. We find that biofilm growth increases the complexity of the pore space, leading to the formation of preferential flow pathways and "dead" pore zones. The probability of persistent high and low velocity regions (within preferential paths resp. stagnant flow regions) thus increases upon biofilm growth, leading to an enhancement of anomalous transport. The structural data seems to indicate that the largest pores are not getting clogged and carry the preferential flow, whereas intricated structures develop in the smallest pores, where the flow becomes almost stagnant. These findings may be relevant for

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Innovation and nested preferential growth in chess playing behavior

    Science.gov (United States)

    Perotti, J. I.; Jo, H.-H.; Schaigorodsky, A. L.; Billoni, O. V.

    2013-11-01

    Complexity develops via the incorporation of innovative properties. Chess is one of the most complex strategy games, where expert contenders exercise decision making by imitating old games or introducing innovations. In this work, we study innovation in chess by analyzing how different move sequences are played at the population level. It is found that the probability of exploring a new or innovative move decreases as a power law with the frequency of the preceding move sequence. Chess players also exploit already known move sequences according to their frequencies, following a preferential growth mechanism. Furthermore, innovation in chess exhibits Heaps' law suggesting similarities with the process of vocabulary growth. We propose a robust generative mechanism based on nested Yule-Simon preferential growth processes that reproduces the empirical observations. These results, supporting the self-similar nature of innovations in chess are important in the context of decision making in a competitive scenario, and extend the scope of relevant findings recently discovered regarding the emergence of Zipf's law in chess.

  1. Preferential flow in the vadose zone and interface dynamics: Impact of microbial exudates

    Science.gov (United States)

    Li, Biting; Pales, Ashley R.; Clifford, Heather M.; Kupis, Shyla; Hennessy, Sarah; Liang, Wei-Zhen; Moysey, Stephen; Powell, Brian; Finneran, Kevin T.; Darnault, Christophe J. G.

    2018-03-01

    In the hydrological cycle, the infiltration process is a critical component in the distribution of water into the soil and in the groundwater system. The nonlinear dynamics of the soil infiltration process yield preferential flow which affects the water distribution in soil. Preferential flow is influenced by the interactions between water, soil, plants, and microorganisms. Although the relationship among the plant roots, their rhizodeposits and water transport in soil has been the subject of extensive study, the effect of microbial exudates has been studied in only a few cases. Here the authors investigated the influence of two artificial microbial exudates-catechol and riboflavin-on the infiltration process, particularly unstable fingered flow, one form of preferential flow. Flow experiments investigating the effects of types and concentrations of microbial exudates on unstable fingered flow were conducted in a two-dimensional tank that was filled with ASTM

  2. Solution thermodynamics and preferential solvation of sulfamethazine in (methanol + water) mixtures

    International Nuclear Information System (INIS)

    Delgado, Daniel R.; Almanza, Ovidio A.; Martínez, Fleming; Peña, María A.; Jouyban, Abolghasem; Acree, William E.

    2016-01-01

    Highlights: • Solubility of sulfamethazine (SMT) was measured in (methanol + water) mixtures. • SMT solubility was correlated with Jouyban–Acree model. • Gibbs energy, enthalpy, and entropy of dissolution of SMT were calculated. • Non-linear enthalpy–entropy relationship was observed for SMT. • Preferential solvation of SMT by methanol was analyzed by using the IKBI method. - Abstract: The solubility of sulfamethazine (SMT) in {methanol (1) + water (2)} co-solvent mixtures was determined at five different temperatures from (293.15 to 313.15) K. The sulfonamide exhibited its highest mole fraction solubility in pure methanol (δ 1 = 29.6 MPa 1/2 ) and its lowest mole fraction solubility in water (δ 2 = 47.8 MPa 1/2 ) at each of the five temperatures studied. The Jouyban–Acree model was used to correlate/predict the solubility values. The respective apparent thermodynamic functions Gibbs energy, enthalpy, and entropy of solution were obtained from the solubility data through the van’t Hoff and Gibbs equations. Apparent thermodynamic quantities of mixing were also calculated for this drug using values of the ideal solubility reported in the literature. A non-linear enthalpy–entropy relationship was noted for SMT in plots of both the enthalpy vs. Gibbs energy of mixing and the enthalpy vs. entropy of mixing. These plots suggest two different trends according to the slopes obtained when the composition of the mixtures changes. Accordingly, the mechanism for SMT transfer processes in water-rich mixtures from water to the mixture with 0.70 in mass fraction of methanol is entropy driven. Conversely, the mechanism is enthalpy driven in mixtures whenever the methanol composition exceeds 0.70 mol fraction. An inverse Kirkwood–Buff integral analysis of the preferential solvation of SMT indicated that the drug is preferentially solvated by water in water-rich mixtures but is preferentially solvated by methanol in methanol-rich mixtures.

  3. The fictional transition of the preferential orientation of yttria-stabilized zirconia thin films

    International Nuclear Information System (INIS)

    Lamas, J.S.; Leroy, W.P.; Depla, D.

    2012-01-01

    The fundamental study of the microstructural and textural evolution of yttria-stabilized zirconia (YSZ) thin films is of great importance given that the crystallographic properties are intimately related to their extrinsic or functional properties. In order to study these properties, YSZ thin films were obtained using dual magnetron sputtering. The results of a polar plot graph, based on X-ray diffraction (XRD) data, seem to indicate a transition from [200] out-of-plane preferential orientation to [111], indicating a dependence on composition and yttrium target–substrate (Y T–S) distance at low pressure. However, no transition is identified at high pressure, showing only [111] out-of-plane orientation, independent of composition and Y T–S distance. Scanning electron microscopy (SEM) indicates a tilt in the columnar structure of the film but no other microstructural change is in evidence, possibly related to the growth transition from [200] to [111]. Pole figures were used to clarify the texture transition in the YSZ thin films. These results indicate that there is indeed no transition in the preferential orientation of the films from [200] to [111] but a tilt of the [200] orientation towards the zirconium source. Detailed study using pole figures and SEM, clearly indicated that no growth zone transition was present and the effect is caused by geometrical configuration, contradicting expectations from standard θ/2θ XRD measurements. - Highlights: ► Study of the preferential orientation of Yttria-stabilized zirconia thin films ► Comparison of the preferential orientation at two different chamber pressures ► Correlation with the energy per adparticle and the extended structure zone model ► Use of pole figures analyses to clarify the change in the preferential orientation

  4. The fictional transition of the preferential orientation of yttria-stabilized zirconia thin films

    Energy Technology Data Exchange (ETDEWEB)

    Lamas, J.S., E-mail: Jerika.Lamas@UGent.be; Leroy, W.P.; Depla, D.

    2012-12-15

    The fundamental study of the microstructural and textural evolution of yttria-stabilized zirconia (YSZ) thin films is of great importance given that the crystallographic properties are intimately related to their extrinsic or functional properties. In order to study these properties, YSZ thin films were obtained using dual magnetron sputtering. The results of a polar plot graph, based on X-ray diffraction (XRD) data, seem to indicate a transition from [200] out-of-plane preferential orientation to [111], indicating a dependence on composition and yttrium target-substrate (Y T-S) distance at low pressure. However, no transition is identified at high pressure, showing only [111] out-of-plane orientation, independent of composition and Y T-S distance. Scanning electron microscopy (SEM) indicates a tilt in the columnar structure of the film but no other microstructural change is in evidence, possibly related to the growth transition from [200] to [111]. Pole figures were used to clarify the texture transition in the YSZ thin films. These results indicate that there is indeed no transition in the preferential orientation of the films from [200] to [111] but a tilt of the [200] orientation towards the zirconium source. Detailed study using pole figures and SEM, clearly indicated that no growth zone transition was present and the effect is caused by geometrical configuration, contradicting expectations from standard {theta}/2{theta} XRD measurements. - Highlights: Black-Right-Pointing-Pointer Study of the preferential orientation of Yttria-stabilized zirconia thin films Black-Right-Pointing-Pointer Comparison of the preferential orientation at two different chamber pressures Black-Right-Pointing-Pointer Correlation with the energy per adparticle and the extended structure zone model Black-Right-Pointing-Pointer Use of pole figures analyses to clarify the change in the preferential orientation.

  5. Regulation of allergic airway inflammation by adoptive transfer of CD4+ T cells preferentially producing IL-10.

    Science.gov (United States)

    Matsuda, Masaya; Doi, Kana; Tsutsumi, Tatsuya; Fujii, Shinya; Kishima, Maki; Nishimura, Kazuma; Kuroda, Ikue; Tanahashi, Yu; Yuasa, Rino; Kinjo, Toshihiko; Kuramoto, Nobuyuki; Mizutani, Nobuaki; Nabe, Takeshi

    2017-10-05

    Anti-inflammatory pharmacotherapy for asthma has mainly depended on the inhalation of glucocorticoids, which non-specifically suppress immune responses. If the anti-inflammatory cytokine interleukin (IL)-10 can be induced by a specific antigen, asthmatic airway inflammation could be suppressed when individuals are exposed to the antigen. The purpose of this study was to develop cellular immunotherapeutics for atopic diseases using IL-10-producing CD4 + T cells. Spleen cells isolated from ovalbumin (OVA)-sensitized mice were cultured with the antigen, OVA and growth factors, IL-21, IL-27 and TGF-β for 7 days. After the 7-day culture, the CD4 + T cells were purified using a murine CD4 magnetic beads system. When the induced CD4 + T cells were stimulated by OVA in the presence of antigen-presenting cells, IL-10 was preferentially produced in vitro. When CD4 + T cells were adoptively transferred to OVA-sensitized mice followed by intratracheal OVA challenges, IL-10 was preferentially produced in the serum and bronchoalveolar lavage fluid in vivo. IL-10 production coincided with the inhibition of eosinophilic airway inflammation and epithelial mucus plugging. Most of the IL-10-producing CD4 + T cells were negative for Foxp3 and GATA-3, transcription factors of naturally occurring regulatory T cells and Th2 cells, respectively, but double positive for LAG-3 and CD49b, surface markers of inducible regulatory T cells, Tr1 cells. Collectively, most of the induced IL-10-producing CD4 + T cells could be Tr1 cells, which respond to the antigen to produce IL-10, and effectively suppressed allergic airway inflammation. The induced Tr1 cells may be useful for antigen-specific cellular immunotherapy for atopic diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Preferential radiosensitization of G1 checkpoint--deficient cells by methylxanthines

    International Nuclear Information System (INIS)

    Russell, Kenneth J.; Wiens, Linda W.; Demers, G. William; Galloway, Denise A.; Le, Tiep; Rice, Glenn C.; Bianco, James A.; Singer, Jack W.; Groudine, Mark

    1996-01-01

    Purpose: To develop a checkpoint-based strategy for preferential radiosensitization of human tumors with deficient and/or mutant p53. Methods and Materials: A549 human lung adenocarcinoma cell lines differing in their expression of the p53 tumor suppressor gene were produced by transduction with the E6 oncogene from human papilloma virus type 16. The cells expressing E6 (E6+) lack a G1 arrest in response to ionizing radiation, are deficient in p53 and p21 expression, and exhibit a fivefold greater clonogenic survival following 10 Gy radiation. Results: Postirradiation incubation with millimolar concentrations of the methylxanthine pentoxifylline (PTX) results in preferential radiosensitization of the E6+ cells compared to the LXSN+ vector transduced controls. There is a threefold sensitization of the LXSN+ cells and a 15-fold sensitization of the E6+ cells, which results in equal clonogenic survival of the two lines. Flow cytometry reveals PTX abrogation of the radiation induced G2 arrest for both cell lines. PTX also prolongs G1 transit for both cell lines. Preliminary results are presented using a novel methylxanthine, lisofylline (LSF), which has similar cell cycle effects on G1 and G2 and achieves differential radiosensitization at micromolar concentrations that are sustainable in humans. Conclusions: This checkpoint-based strategy is a promising approach for achieving preferential radiosensitization of p53- tumors relative to p53+ normal tissues

  7. Cancer Immunotherapy and the Immune Response in Hodgkin Lymphoma

    Directory of Open Access Journals (Sweden)

    Christoph Renner

    2018-06-01

    Full Text Available Patients with classical Hodgkin lymphoma (cHL have an impaired cellular immune response as indicated by an anergic reaction against standard recall antigens and a diminished rejection reaction of allogeneic skin transplant. This clinical observation can be linked to the histopathological feature of cHL since the typical pattern of a cHL manifestation is characterized by sparse large CD30+ tumor-infiltrating Hodgkin–Reed–Sternberg (HRS cells that are surrounded by a dense inflammatory immune microenvironment with mixed cellularity. Despite this extensive polymorphous inflammatory infiltrate, there is only a poor antitumor immune response seen to the neoplastic HRS cells. This is primarily mediated by a high expression of PD-L1 and PD-L2 ligands on the HRS cell surface which in turn antagonizes the activity of programmed death-1 (PD-1 antigen-positive T cells. PD-L1/L2 overexpression is caused by gene amplification at the 9p24.1 locus and/or latent Epstein–Barr virus infection present in around 40% of cHL cases. The blockade of the PD-L1/L2–PD-1 pathway by monoclonal antibodies can restore local T cell activity and leads to impressive tumor responses, some of which are long lasting and eventually curative. Another feature of HRS cells is the high CD30 antigen expression. Monoclonal antibody technology allowed for the successful development of CD30-specific immunotoxins, bispecific antibodies, and reprogrammed autologous T cells with the first one already approved for the treatment of high risk or relapsed cHL. Altogether, the discovery of the described pathomechanism of immune suppression and the identification of preferential target antigens has rendered cHL to be a prime subject for the successful development of new immunotherapeutic approaches.

  8. How Medical Tourism Enables Preferential Access to Care: Four Patterns from the Canadian Context.

    Science.gov (United States)

    Snyder, Jeremy; Johnston, Rory; Crooks, Valorie A; Morgan, Jeff; Adams, Krystyna

    2017-06-01

    Medical tourism is the practice of traveling across international borders with the intention of accessing medical care, paid for out-of-pocket. This practice has implications for preferential access to medical care for Canadians both through inbound and outbound medical tourism. In this paper, we identify four patterns of medical tourism with implications for preferential access to care by Canadians: (1) Inbound medical tourism to Canada's public hospitals; (2) Inbound medical tourism to a First Nations reserve; (3) Canadian patients opting to go abroad for medical tourism; and (4) Canadian patients traveling abroad with a Canadian surgeon. These patterns of medical tourism affect preferential access to health care by Canadians by circumventing domestic regulation of care, creating jurisdictional tensions over the provision of health care, and undermining solidarity with the Canadian health system.

  9. Cell-Intrinsic Glycogen Metabolism Supports Early Glycolytic Reprogramming Required for Dendritic Cell Immune Responses.

    Science.gov (United States)

    Thwe, Phyu M; Pelgrom, Leonard; Cooper, Rachel; Beauchamp, Saritha; Reisz, Julie A; D'Alessandro, Angelo; Everts, Bart; Amiel, Eyal

    2017-09-05

    Dendritic cell (DC) activation by Toll-like receptor (TLR) agonists causes rapid glycolytic reprogramming that is required to meet the metabolic demands of their immune activation. Recent efforts in the field have identified an important role for extracellular glucose sourcing to support DC activation. However, the contributions of intracellular glucose stores to these processes have not been well characterized. We demonstrate that DCs possess intracellular glycogen stores and that cell-intrinsic glycogen metabolism supports the early effector functions of TLR-activated DCs. Inhibition of glycogenolysis significantly attenuates TLR-mediated DC maturation and impairs their ability to initiate lymphocyte activation. We further report that DCs exhibit functional compartmentalization of glucose- and glycogen-derived carbons, where these substrates preferentially contribute to distinct metabolic pathways. This work provides novel insights into nutrient homeostasis in DCs, demonstrating that differential utilization of glycogen and glucose metabolism regulates their optimal immune function. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Kinds and meaning of preferential credits for development of agriculture and rural areas

    Directory of Open Access Journals (Sweden)

    Antoni Mickiewicz

    2013-06-01

    Full Text Available The theme of the paper was of preferential credits granted in two periods, that means after Poland’s accession to the European Union (2004-2006 and in the period after introduction of new legal regulations (2007-2010. The institution responsible for realisation of preferential credits was Agency of Restructuring and Modernisation of Agriculture which delegated its rights to banks. The credit policy in first period of our functioning in the European Union relied on gradual ending old legal regulations, not compliant with EU standards and undertaking activities in adaptation of Polish agriculture to standards obeyed in EU-15 Member States. Directions of preferential credits granting were changed in 2007. There were introduced 7 credit lines which aim was improvement of production efficiency, better use of production base in agricultural farms and acceleration of agrarian changes. The biggest beneficiaries of structural pensions were young farmers and farmers who wanted to increase the size of their farms.

  11. Assessing preferential flow by simultaneously injecting nanoparticle and chemical tracers

    KAUST Repository

    Subramanian, S. K.; Li, Yan; Cathles, L. M.

    2013-01-01

    The exact manner in which preferential (e.g., much faster than average) flow occurs in the subsurface through small fractures or permeable connected pathways of other kinds is important to many processes but is difficult to determine, because most chemical tracers diffuse quickly enough from small flow channels that they appear to move more uniformly through the rock than they actually do. We show how preferential flow can be assessed by injecting 2 to 5 nm carbon particles (C-Dots) and an inert KBr chemical tracer at different flow rates into a permeable core channel that is surrounded by a less permeable matrix in laboratory apparatus of three different designs. When the KBr tracer has a long enough transit through the system to diffuse into the matrix, but the C-Dot tracer does not, the C-Dot tracer arrives first and the KBr tracer later, and the separation measures the degree of preferential flow. Tracer sequestration in the matrix can be estimated with a Peclet number, and this is useful for experiment design. A model is used to determine the best fitting core and matrix dispersion parameters and refine estimates of the core and matrix porosities. Almost the same parameter values explain all experiments. The methods demonstrated in the laboratory can be applied to field tests. If nanoparticles can be designed that do not stick while flowing through the subsurface, the methods presented here could be used to determine the degree of fracture control in natural environments, and this capability would have very wide ranging value and applicability.

  12. Linking soil moisture balance and source-responsive models to estimate diffuse and preferential components of groundwater recharge

    Directory of Open Access Journals (Sweden)

    M. O. Cuthbert

    2013-03-01

    Full Text Available Results are presented of a detailed study into the vadose zone and shallow water table hydrodynamics of a field site in Shropshire, UK. A conceptual model is presented and tested using a range of numerical models, including a modified soil moisture balance model (SMBM for estimating groundwater recharge in the presence of both diffuse and preferential flow components. Tensiometry reveals that the loamy sand topsoil wets up via preferential flow and subsequent redistribution of moisture into the soil matrix. Recharge does not occur until near-positive pressures are achieved at the top of the sandy glaciofluvial outwash material that underlies the topsoil, about 1 m above the water table. Once this occurs, very rapid water table rises follow. This threshold behaviour is attributed to the vertical discontinuity in preferential flow pathways due to seasonal ploughing of the topsoil and to a lower permeability plough/iron pan restricting matrix flow between the topsoil and the lower outwash deposits. Although the wetting process in the topsoil is complex, a SMBM is shown to be effective in predicting the initiation of preferential flow from the base of the topsoil into the lower outwash horizon. The rapidity of the response at the water table and a water table rise during the summer period while flow gradients in the unsaturated profile were upward suggest that preferential flow is also occurring within the outwash deposits below the topsoil. A variation of the source-responsive model proposed by Nimmo (2010 is shown to reproduce the observed water table dynamics well in the lower outwash horizon when linked to a SMBM that quantifies the potential recharge from the topsoil. The results reveal new insights into preferential flow processes in cultivated soils and provide a useful and practical approach to accounting for preferential flow in studies of groundwater recharge estimation.

  13. Predicting Alcohol, Cigarette, and Marijuana Use from Preferential Music Consumption

    Science.gov (United States)

    Oberle, Crystal D.; Garcia, Javier A.

    2015-01-01

    This study investigated whether use of alcohol, cigarettes, and marijuana may be predicted from preferential consumption of particular music genres. Undergraduates (257 women and 78 men) completed a questionnaire assessing these variables. Partial correlation analyses, controlling for sensation-seeking tendencies and behaviors, revealed that…

  14. Information filtering via preferential diffusion

    Science.gov (United States)

    Lü, Linyuan; Liu, Weiping

    2011-06-01

    Recommender systems have shown great potential in addressing the information overload problem, namely helping users in finding interesting and relevant objects within a huge information space. Some physical dynamics, including the heat conduction process and mass or energy diffusion on networks, have recently found applications in personalized recommendation. Most of the previous studies focus overwhelmingly on recommendation accuracy as the only important factor, while overlooking the significance of diversity and novelty that indeed provide the vitality of the system. In this paper, we propose a recommendation algorithm based on the preferential diffusion process on a user-object bipartite network. Numerical analyses on two benchmark data sets, MovieLens and Netflix, indicate that our method outperforms the state-of-the-art methods. Specifically, it can not only provide more accurate recommendations, but also generate more diverse and novel recommendations by accurately recommending unpopular objects.

  15. Preferential transport of isoproturon at a plot scale and a field scale tile-drained site

    Science.gov (United States)

    Zehe, Erwin; Flühler, Hannes

    2001-06-01

    Irrigation experiments using the tracers Brilliant Blue (BB) and Bromide (Br) were conducted on three plots of 1.4×1.4 m 2 (plot scale) and a field scale subsurface drained test site (900 m 2) to clarify mechanisms causing rapid transport of surface applied Isoproturon (IPU) during preferential flow events. One of the small plots (site 10) and the field scale test site are located on the same field. One day after irrigation of the plot scale sites the Br and IPU concentration in two vertical soil profiles as well as the macroporousity on separate profiles and hydraulic properties of single macropores were determined. During irrigation of the field scale test site discharge, soil moisture as well as the concentration of IPU and Br in the drainage outlet were measured. Preferential flow in deep penetrating earthworm burrows caused a fast breakthrough of IPU and Br into the tile drain (1.2 m depth) at the field scale site as well as leaching of IPU into the subsoil (>0.8 m) at site 10. The results suggest a hierarchy of preconditions for the occurrence of preferential flow events of which a sufficient number of deep penetrating macropores interconnected to the soil surface seems to be the most important one. Moreover there is evidence that facilitated transport of IPU attached to mobile soil particles occurred during the preferential flow events at the field scale site and site 10. The susceptibility for preferential flow as well as the susceptibility for facilitated transport appear to be intrinsic properties of the investigated soil.

  16. Telomerase and Tel1p Preferentially Associate with Short Telomeres in S. cerevisiae

    Science.gov (United States)

    Sabourin, Michelle; Tuzon, Creighton T.; Zakian, Virginia A.

    2009-01-01

    SUMMARY In diverse organisms, telomerase preferentially elongates short telomeres. We generated a single short telomere in otherwise wild-type (WT) S. cerevisiae cells. The binding of the positive regulators Ku and Cdc13p was similar at short and WT-length telomeres. The negative regulators Rif1p and Rif2p were present at the short telomere, although Rif2p levels were reduced. Two telomerase holoenzyme components, Est1p and Est2p, were preferentially enriched at short telomeres in late S/G2 phase, the time of telomerase action. Tel1p, the yeast ATM-like checkpoint kinase, was highly enriched at short telomeres from early S through G2 phase and even into the next cell cycle. Nonetheless, induction of a single short telomere did not elicit a cell-cycle arrest. Tel1p binding was dependent on Xrs2p and required for preferential binding of telomerase to short telomeres. These data suggest that Tel1p targets telomerase to the DNA ends most in need of extension. PMID:17656141

  17. Evidence for preferential flux flow at the grain boundaries of superconducting RF-quality niobium

    Science.gov (United States)

    Sung, Z.-H.; Lee, P. J.; Gurevich, A.; Larbalestier, D. C.

    2018-04-01

    The question of whether grain boundaries (GBs) in niobium can be responsible for lowered operating field (B RF) or quality factor (Q 0) in superconducting radio frequency (SRF) cavities is still controversial. Here, we show by direct DC transport across planar GBs isolated from a slice of very large-grain SRF-quality Nb that vortices can preferentially flow along the grain boundary when the external magnetic field lies in the GB plane. However, increasing the misalignment between the GB plane and the external magnetic field vector markedly reduces preferential flux flow along the GB. Importantly, we find that preferential GB flux flow is more prominent for a buffered chemical polished than for an electropolished bi-crystal. The voltage-current characteristics of GBs are similar to those seen in low angle grain boundaries of high temperature superconductors where there is clear evidence of suppression of the superconducting order parameter at the GB. While local weakening of superconductivity at GBs in cuprates and pnictides is intrinsic, deterioration of current transparency of GBs in Nb appears to be extrinsic, since the polishing method clearly affect the local GB degradation. The dependence of preferential GB flux flow on important cavity preparation and experimental variables, particularly the final chemical treatment and the angle between the magnetic field and the GB plane, suggests two more reasons why real cavity performance can be so variable.

  18. Common mycorrhizal networks amplify competition by preferential mineral nutrient allocation to large host plants.

    Science.gov (United States)

    Weremijewicz, Joanna; Sternberg, Leonel da Silveira Lobo O'Reilly; Janos, David P

    2016-10-01

    Arbuscular mycorrhizal (AM) fungi interconnect plants in common mycorrhizal networks (CMNs) which can amplify competition among neighbors. Amplified competition might result from the fungi supplying mineral nutrients preferentially to hosts that abundantly provide fixed carbon, as suggested by research with organ-cultured roots. We examined whether CMNs supplied (15) N preferentially to large, nonshaded, whole plants. We conducted an intraspecific target-neighbor pot experiment with Andropogon gerardii and several AM fungi in intact, severed or prevented CMNs. Neighbors were supplied (15) N, and half of the target plants were shaded. Intact CMNs increased target dry weight (DW), intensified competition and increased size inequality. Shading decreased target weight, but shaded plants in intact CMNs had mycorrhizal colonization similar to that of sunlit plants. AM fungi in intact CMNs acquired (15) N from the substrate of neighbors and preferentially allocated it to sunlit, large, target plants. Sunlit, intact CMN, target plants acquired as much as 27% of their nitrogen from the vicinity of their neighbors, but shaded targets did not. These results suggest that AM fungi in CMNs preferentially provide mineral nutrients to those conspecific host individuals best able to provide them with fixed carbon or representing the strongest sinks, thereby potentially amplifying asymmetric competition below ground. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  19. Statistical properties and attack tolerance of growing networks with algebraic preferential attachment

    International Nuclear Information System (INIS)

    Liu Zonghua; Lai Yingcheng; Ye Nong

    2002-01-01

    We consider growing networks with algebraic preferential attachment and address two questions: (1) what is the effect of temporal fluctuations in the number of new links acquired by the network? and (2) what is the network tolerance against random failures and intentional attacks? We find that the fluctuations generally have little effect on the network properties, although they lead to a plateau behavior for small degrees in the connectivity distribution. Formulas are derived for the evolution and distribution of the network connectivity, which are tested by numerical simulations. Numerical study of the effect of failures and attacks suggests that networks constructed under algebraic preferential attachment are more robust than scale-free networks

  20. Preferential Alignment of Hydroxyapatite Crystallites in Nanocomposites with Chemically Disintegrated Silk Fibroin

    International Nuclear Information System (INIS)

    Nemoto, Rei; Wang Li; Ikoma, Toshiyuki; Tanaka, Junzo; Senna, Mamoru

    2004-01-01

    Hydroxyapatite (HAp) nanocrystals were prepared at room temperature by a coprecipitation method from Ca(OH) 2 and H 3 PO 4 , in the presence of chemically disintegrated silk fibroin (SF). Adsorbed amounts of cations on SF and crystallinity of HAp in the composite were increased by the chemical disintegration of SF higher order structure. Preferential alignment of c-axis of HAp crystallites along the longitudinal direction of ca. 150nm SF fibril was observed. These changes due to disintegration of SF were discussed in terms of the chemical interaction between HAp and SF. The resulted composite with preferential alignment of HAp nanocrystals is a good candidate as a starting material for bone substitutes

  1. The effect of trees on preferential flow and soil infiltrability in an agroforestry parkland in semiarid Burkina Faso.

    Science.gov (United States)

    Bargués Tobella, A; Reese, H; Almaw, A; Bayala, J; Malmer, A; Laudon, H; Ilstedt, U

    2014-04-01

    Water scarcity constrains the livelihoods of millions of people in tropical drylands. Tree planting in these environments is generally discouraged due to the large water consumption by trees, but this view may neglect their potential positive impacts on water availability. The effect of trees on soil hydraulic properties linked to groundwater recharge is poorly understood. In this study, we performed 18 rainfall simulations and tracer experiments in an agroforestry parkland in Burkina Faso to investigate the effect of trees and associated termite mounds on soil infiltrability and preferential flow. The sampling points were distributed in transects each consisting of three positions: (i) under a single tree, (ii) in the middle of an open area, and (iii) under a tree associated with a termite mound. The degree of preferential flow was quantified through parameters based on the dye infiltration patterns, which were analyzed using image analysis of photographs. Our results show that the degree of preferential flow was highest under trees associated with termite mounds, intermediate under single trees, and minimal in the open areas. Tree density also had an influence on the degree of preferential flow, with small open areas having more preferential flow than large ones. Soil infiltrability was higher under single trees than in the open areas or under trees associated with a termite mound. The findings from this study demonstrate that trees have a positive impact on soil hydraulic properties influencing groundwater recharge, and thus such effects must be considered when evaluating the impact of trees on water resources in drylands. Trees in dryland landscapes increase soil infiltrability and preferential flow Termite mounds in association with trees further enhance preferential flow.

  2. Refinement by Rietveld method of a rolled sheet Al-Mg-Si 6063 alloy with preferential orientation

    International Nuclear Information System (INIS)

    Carrio, J.A.G.; Hattori, C.S.; Miranda, L.F.; Domingues Junior, N.I.; Lima, N.B.; Couto, A.A.; Aguiar, A.A.

    2010-01-01

    The Rietveld refinement of a sample with preferential orientation was accomplished using data of X ray diffraction of a rolled 6063 aluminum alloy. The refinement of the preferential orientation by spherical harmonic was accomplished using a symmetry of sample mmm (rolling) until the order of 8 and was compared with experimental pole figures. The four pole figures presented indicate a sharp texture of the planes (111), (200), (220) and (311). The calculated pole figures obtained from the refinement of the X ray diffraction spectrum can incur in mistakes of preferential orientation. This happens because the measure is restricted to the planes parallel to the surface without inference to the symmetry of the sample. (author)

  3. A summary of the theory of the preferential sputtering of alloys

    International Nuclear Information System (INIS)

    Kelly, R.; Harrison, D.E.

    1985-01-01

    Preferential sputtering of alloys arises from mass differences, chemical binding differences and bombardment-induced gibbsian segregation. The relations underlying the mass effect, the chemical binding effect and bombardment-induced gibbsian segregation in binary alloys are given. (Auth.)

  4. Preferential Price and Trade Tied Aid in Fiji: Implications on Price ...

    African Journals Online (AJOL)

    Pacific island countries (PICs) have been receiving the highest percapita aid .... dimension of the preferential price by examining the role of forecast price as an ..... Abbot, D and S. Pollard (2004) Hardship and Poverty in the Pacific, Asian.

  5. Origin of preferential flow and its controlling factors on emission potential using numerical simulations and lab experiments

    NARCIS (Netherlands)

    Baviskar, S.M.; Heimovaara, T.J.

    2015-01-01

    We believe the unsaturated and heterogeneous nature of landfills leads to the emergence of preferential pathways of water and dissolved compounds through the waste body. In this research we explore the origin of preferential flow in a porous media with a deterministic numerical model. In this model

  6. 19 CFR 10.233 - Articles eligible for preferential tariff treatment.

    Science.gov (United States)

    2010-04-01

    ... control of the customs authority of the intermediate country; (ii) Did not enter into the commerce of the... 19 Customs Duties 1 2010-04-01 2010-04-01 false Articles eligible for preferential tariff treatment. 10.233 Section 10.233 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND...

  7. Inert Carbon Nanoparticles for the Assessment of Preferential Flow in Saturated Dual-Permeability Porous Media

    KAUST Repository

    Yao, Chuanjin

    2017-06-07

    Knowledge of preferential flow in heterogeneous environments is essential for enhanced hydrocarbon recovery, geothermal energy extraction, and successful sequestration of chemical waste and carbon dioxide. Dual tracer tests using nanoparticles with a chemical tracer could indicate the preferential flow. A dual-permeability model with a high permeable core channel surrounded by a low permeable annulus was constructed and used to determine the viability of an inert carbon nanoparticle tracer for this application. A series of column experiments were conducted to demonstrate how this nanoparticle tracer can be used to implement the dual tracer tests in heterogeneous environments. The results indicate that, with the injection rate selected and controlled appropriately, nanoparticles together with a chemical tracer can assess the preferential flow in heterogeneous environments. The results also implement the dual tracer tests in heterogeneous environments by simultaneously injecting chemical and nanoparticle tracers.

  8. Ocular myasthenia gravis induced by human acetylcholine receptor ϵ subunit immunization in HLA DR3 transgenic mice.

    Science.gov (United States)

    Wu, Xiaorong; Tuzun, Erdem; Saini, Shamsher S; Wang, Jun; Li, Jing; Aguilera-Aguirre, Leopoldo; Huda, Ruksana; Christadoss, Premkumar

    2015-12-01

    Extraocular muscles (EOM) are preferentially involved in myasthenia gravis (MG) and acetylcholine receptor (AChR) antibody positive MG patients may occasionally present with isolated ocular symptoms. Although experimental autoimmune myasthenia gravis (EAMG) induced by whole AChR immunization closely mimics clinical and immunopathological aspects of MG, EOM are usually not affected. We have previously developed an EAMG model, which imitates EOM symptoms of MG by immunization of human leukocyte antigen (HLA) transgenic mice with α or γ-subunits of human AChR (H-AChR). To investigate the significance of the ϵ-subunit in ocular MG, we immunized HLA-DR3 and HLA-DQ8 transgenic mice with recombinant H-AChR ϵ-subunit expressed in Escherichia coli. HLA-DR3 transgenic mice showed significantly higher clinical ocular and generalized MG severity scores and lower grip strength values than HLA-DQ8 mice. H-AChR ϵ-subunit-immunized HLA-DR3 transgenic mice had higher serum anti-AChR antibody (IgG, IgG1, IgG2b, IgG2c and IgM) levels, neuromuscular junction IgG and complement deposit percentages than ϵ-subunit-immunized HLA-DQ8 transgenic mice. Control mice immunized with E. coli extract or complete Freund adjuvant (CFA) did not show clinical and immunopathological features of ocular and generalized EAMG. Lymph node cells of ϵ-subunit-immunized HLA-DR3 mice showed significantly higher proliferative responses than those of ϵ-subunit-immunized HLA-DQ8 mice, crude E. coli extract-immunized and CFA-immunized transgenic mice. Our results indicate that the human AChR ϵ-subunit is capable of inducing myasthenic muscle weakness. Diversity of the autoimmune responses displayed by mice expressing different HLA class II molecules suggests that the interplay between HLA class II alleles and AChR subunits might have a profound impact on the clinical course of MG. Copyright © 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  9. Effects of preferential concentration on direct radiation transmission in a turbulent duct flow

    Science.gov (United States)

    Villafane, Laura; Banko, Andrew; Kim, Ji Hoon; Elkins, Chris; Eaton, John

    2017-11-01

    Inertial particles in turbulent flows preferentially concentrate, giving rise to spatial and temporal fluctuations of particle number density that affect radiation transmission through the medium. Positive particle correlations enhance direct transmission when compared to the exponential attenuation predicted by the Beer's Law for randomly distributed particles. In the context of a particle based solar receiver, this work studies the effects of preferential concentration and optical depth on direct transmission through a particle laden turbulent duct flow. Time resolved measurements of transmission through the mixture were performed for various particle loadings and Reynolds numbers, thus varying particle correlation lengths, optical depth and concentration fluctuations. These measurements were made using a photodiode to record the transmission of a collimated laser beam along the wall bisector of the duct. A synchronized high-speed camera provided particle positions along most of the beam path. Average and fluctuating radiation transmission results are compared to predictions derived from the imaged number density fields and to simplified analytical models. Simplified models are able to capture the correct trends with varying loading and preferential concentration. This work is funded by the Department of Energy's National Nuclear Security Administration, Grant #DE-NA0002373-1.

  10. Current status of research on radiation hormesis in the immune system after low level radiation

    International Nuclear Information System (INIS)

    Liu Shuzheng

    1995-01-01

    The paper highlights the chief results of experimental studies recently carried out in the author's laboratory on the stimulatory effects of low level radiation on immunity. The intercellular relationship within the immune system after whole-body irradiation (WBI) with low doses of X- and gamma-rays was briefly outlined with the emphasis on the potential effect of low dose radiation (LDR) on the helper T cells which was thought to occupy a pivotal position in the process of immuno-stimulation. Data suggesting the facilitation by LDR of the signal transduction process within the T cells were presented. Some hypotheses prevailing in the literature for the explanation of the stimulatory effect of LDR were critically evaluated. Existing experimental data both from the literature and from the author's laboratory were analysed giving no strong support to the speculation of either the preferential deletion of the radiosensitive suppressor T subset or the increased apoptosis of the T cell 'precursors' in the thymus leading to secondary immunologic augmentation by low doses which stimulate immune functions. The possible influence of systemic changes, especially those in the neuroendocrine regulation, on the T cell potentiation following LDR was suggested. Finally the biological implications of the hermetic effects of LDR were discussed

  11. Motility and chemotaxis mediate the preferential colonization of gastric injury sites by Helicobacter pylori.

    Directory of Open Access Journals (Sweden)

    Eitaro Aihara

    2014-07-01

    Full Text Available Helicobacter pylori (H. pylori is a pathogen contributing to peptic inflammation, ulceration, and cancer. A crucial step in the pathogenic sequence is when the bacterium first interacts with gastric tissue, an event that is poorly understood in vivo. We have shown that the luminal space adjacent to gastric epithelial damage is a microenvironment, and we hypothesized that this microenvironment might enhance H. pylori colonization. Inoculation with 106 H. pylori (wild-type Sydney Strain 1, SS1 significantly delayed healing of acetic-acid induced ulcers at Day 1, 7 and 30 post-inoculation, and wild-type SS1 preferentially colonized the ulcerated area compared to uninjured gastric tissue in the same animal at all time points. Gastric resident Lactobacillus spp. did not preferentially colonize ulcerated tissue. To determine whether bacterial motility and chemotaxis are important to ulcer healing and colonization, we analyzed isogenic H. pylori mutants defective in motility (ΔmotB or chemotaxis (ΔcheY. ΔmotB (10(6 failed to colonize ulcerated or healthy stomach tissue. ΔcheY (10(6 colonized both tissues, but without preferential colonization of ulcerated tissue. However, ΔcheY did modestly delay ulcer healing, suggesting that chemotaxis is not required for this process. We used two-photon microscopy to induce microscopic epithelial lesions in vivo, and evaluated accumulation of fluorescently labeled H. pylori at gastric damage sites in the time frame of minutes instead of days. By 5 min after inducing damage, H. pylori SS1 preferentially accumulated at the site of damage and inhibited gastric epithelial restitution. H. pylori ΔcheY modestly accumulated at the gastric surface and inhibited restitution, but did not preferentially accumulate at the injury site. H. pylori ΔmotB neither accumulated at the surface nor inhibited restitution. We conclude that bacterial chemosensing and motility rapidly promote H. pylori colonization of injury sites

  12. Motility and Chemotaxis Mediate the Preferential Colonization of Gastric Injury Sites by Helicobacter pylori

    Science.gov (United States)

    Aihara, Eitaro; Closson, Chet; Matthis, Andrea L.; Schumacher, Michael A.; Engevik, Amy C.; Zavros, Yana; Ottemann, Karen M.; Montrose, Marshall H.

    2014-01-01

    Helicobacter pylori (H. pylori) is a pathogen contributing to peptic inflammation, ulceration, and cancer. A crucial step in the pathogenic sequence is when the bacterium first interacts with gastric tissue, an event that is poorly understood in vivo. We have shown that the luminal space adjacent to gastric epithelial damage is a microenvironment, and we hypothesized that this microenvironment might enhance H. pylori colonization. Inoculation with 106 H. pylori (wild-type Sydney Strain 1, SS1) significantly delayed healing of acetic-acid induced ulcers at Day 1, 7 and 30 post-inoculation, and wild-type SS1 preferentially colonized the ulcerated area compared to uninjured gastric tissue in the same animal at all time points. Gastric resident Lactobacillus spp. did not preferentially colonize ulcerated tissue. To determine whether bacterial motility and chemotaxis are important to ulcer healing and colonization, we analyzed isogenic H. pylori mutants defective in motility (ΔmotB) or chemotaxis (ΔcheY). ΔmotB (106) failed to colonize ulcerated or healthy stomach tissue. ΔcheY (106) colonized both tissues, but without preferential colonization of ulcerated tissue. However, ΔcheY did modestly delay ulcer healing, suggesting that chemotaxis is not required for this process. We used two-photon microscopy to induce microscopic epithelial lesions in vivo, and evaluated accumulation of fluorescently labeled H. pylori at gastric damage sites in the time frame of minutes instead of days. By 5 min after inducing damage, H. pylori SS1 preferentially accumulated at the site of damage and inhibited gastric epithelial restitution. H. pylori ΔcheY modestly accumulated at the gastric surface and inhibited restitution, but did not preferentially accumulate at the injury site. H. pylori ΔmotB neither accumulated at the surface nor inhibited restitution. We conclude that bacterial chemosensing and motility rapidly promote H. pylori colonization of injury sites, and thereby biases

  13. PAFit: A Statistical Method for Measuring Preferential Attachment in Temporal Complex Networks.

    Directory of Open Access Journals (Sweden)

    Thong Pham

    Full Text Available Preferential attachment is a stochastic process that has been proposed to explain certain topological features characteristic of complex networks from diverse domains. The systematic investigation of preferential attachment is an important area of research in network science, not only for the theoretical matter of verifying whether this hypothesized process is operative in real-world networks, but also for the practical insights that follow from knowledge of its functional form. Here we describe a maximum likelihood based estimation method for the measurement of preferential attachment in temporal complex networks. We call the method PAFit, and implement it in an R package of the same name. PAFit constitutes an advance over previous methods primarily because we based it on a nonparametric statistical framework that enables attachment kernel estimation free of any assumptions about its functional form. We show this results in PAFit outperforming the popular methods of Jeong and Newman in Monte Carlo simulations. What is more, we found that the application of PAFit to a publically available Flickr social network dataset yielded clear evidence for a deviation of the attachment kernel from the popularly assumed log-linear form. Independent of our main work, we provide a correction to a consequential error in Newman's original method which had evidently gone unnoticed since its publication over a decade ago.

  14. Preferential treatment and exemption policy impacts energy

    International Nuclear Information System (INIS)

    Doelle, R.R.

    1991-01-01

    This paper reports on the preferential treatment and exemption policy of the Federal Energy Regulatory Commission (FERC) for State and State Agencies which creates an anticompetitive and restraint of trade attitude in California against the development of alternative energy resources by the private sector when such development competes directly with state owned power generation under the State Water and Central Valley Water Projects, particularly in the area of water and power supply. The existing state water policy fails to address the effects of global warming and the adverse potential of the greenhouse effect in California, i.e. rising tides can seriously impact sea water intrusion problems of the San Francisco Bay-Delta Area by not only flooding agricultural lands in the Delta and Central Valley, but impacting the supply of water to large population areas in Southern and Northern California, especially when coupled with drought conditions. The California investigative research results herein reported demonstrates the fallacy of a preferential treatment and exemption policy in a free market economy, especially when such policy creates the potential for excessive state budget burdens upon the public in the face of questionable subsidies to special interest, i.e., allowing the resulting windfall profits to be passed onto major utilities and commingled at the expense of public interest so as to undermine the financial means for development of alternative energy resources. The cited Congressional and State Legislative Laws which provide the ways and means to resolve any energy or water resource problems are only as good as the enforcement and the commitment by the executive branch of government and the lawmakers to up-hold existing laws

  15. Geostatistical integration and uncertainty in pollutant concentration surface under preferential sampling

    Directory of Open Access Journals (Sweden)

    Laura Grisotto

    2016-04-01

    Full Text Available In this paper the focus is on environmental statistics, with the aim of estimating the concentration surface and related uncertainty of an air pollutant. We used air quality data recorded by a network of monitoring stations within a Bayesian framework to overcome difficulties in accounting for prediction uncertainty and to integrate information provided by deterministic models based on emissions meteorology and chemico-physical characteristics of the atmosphere. Several authors have proposed such integration, but all the proposed approaches rely on representativeness and completeness of existing air pollution monitoring networks. We considered the situation in which the spatial process of interest and the sampling locations are not independent. This is known in the literature as the preferential sampling problem, which if ignored in the analysis, can bias geostatistical inferences. We developed a Bayesian geostatistical model to account for preferential sampling with the main interest in statistical integration and uncertainty. We used PM10 data arising from the air quality network of the Environmental Protection Agency of Lombardy Region (Italy and numerical outputs from the deterministic model. We specified an inhomogeneous Poisson process for the sampling locations intensities and a shared spatial random component model for the dependence between the spatial location of monitors and the pollution surface. We found greater predicted standard deviation differences in areas not properly covered by the air quality network. In conclusion, in this context inferences on prediction uncertainty may be misleading when geostatistical modelling does not take into account preferential sampling.

  16. Preferential transfer of certain plasma membrane proteins onto T and B cells by trogocytosis.

    Directory of Open Access Journals (Sweden)

    Sandrine Daubeuf

    2010-01-01

    Full Text Available T and B cells capture antigens via membrane fragments of antigen presenting cells (APC in a process termed trogocytosis. Whether (and how a preferential transfer of some APC components occurs during trogocytosis is still largely unknown. We analyzed the transfer onto murine T and B cells of a large panel of fluorescent proteins with different intra-cellular localizations in the APC or various types of anchors in the plasma membrane (PM. Only the latter were transferred by trogocytosis, albeit with different efficiencies. Unexpectedly, proteins anchored to the PM's cytoplasmic face, or recruited to it via interaction with phosphinositides, were more efficiently transferred than those facing the outside of the cell. For proteins spanning the PM's whole width, transfer efficiency was found to vary quite substantially, with tetraspanins, CD4 and FcRgamma found among the most efficiently transferred proteins. We exploited our findings to set immunodiagnostic assays based on the capture of preferentially transferred components onto T or B cells. The preferential transfer documented here should prove useful in deciphering the cellular structures involved in trogocytosis.

  17. Surface morphology and preferential orientation growth of TaC crystals formed by chemical vapor deposition

    Energy Technology Data Exchange (ETDEWEB)

    Xiong Xiang, E-mail: Xiong228@sina.co [State Key Lab for Powder Metallurgy, Central South University, Changsha 410083 (China); Chen Zhaoke; Huang Baiyun; Li Guodong [State Key Lab for Powder Metallurgy, Central South University, Changsha 410083 (China); Zheng Feng [School of Material Science and Engineering, Central South University, Changsha 410083 (China); Xiao Peng; Zhang Hongbo [State Key Lab for Powder Metallurgy, Central South University, Changsha 410083 (China)

    2009-04-02

    TaC film was deposited on (002) graphite sheet by isothermal chemical vapor deposition using TaCl{sub 5}-Ar-C{sub 3}H{sub 6} mixtures, with deposition temperature 1200 {sup o}C and pressure about 200 Pa. The influence of deposition position (or deposition rate) on preferential orientation and surface morphology of TaC crystals were investigated by X-ray diffraction and scanning electron microscopy methods. The deposits are TaC plus trace of C. The crystals are large individual columns with pyramidal-shape at deposition rate of 32.4-37.3 {mu}m/h, complex columnar at 37.3-45.6 {mu}m/h, lenticular-like at 45.6-54.6 {mu}m/h and cauliflower-like at 54.6-77.3 {mu}m/h, with <001>, near <001>, <110> and no clear preferential orientation, respectively. These results agree in part with the preditions of the Pangarov's model of the relationship between deposition rate and preferential growth orientation. The growth mechanism of TaC crystals in <001>, near <001>, <111> and no clear preferential orientation can be fairly explained by the growth parameter {alpha} with Van der Drift's model, deterioration model and Meakin model. Furthermore, a nucleation and coalescence model is also proposed to explain the formation mechanism of <110> lenticular-like crystals.

  18. Preferential semantics for action specification in first-order modal action logic

    NARCIS (Netherlands)

    Broersen, Jan; Wieringa, Roelf J.

    In this paper we investigate preferential semantics for declarative specifications in a First Order Modal Action Logic. We address some well known problems: the frame problem, the qualification problem and the ramification problem. We incorporate the assumptions that are inherent to both the frame

  19. Preferential processing of self-relevant stimuli occurs mainly at the perceptual and conscious stages of information processing.

    Science.gov (United States)

    Tacikowski, P; Ehrsson, H H

    2016-04-01

    Self-related stimuli, such as one's own name or face, are processed faster and more accurately than other types of stimuli. However, what remains unknown is at which stage of the information processing hierarchy this preferential processing occurs. Our first aim was to determine whether preferential self-processing involves mainly perceptual stages or also post-perceptual stages. We found that self-related priming was stronger than other-related priming only because of perceptual prime-target congruency. Our second aim was to dissociate the role of conscious and unconscious factors in preferential self-processing. To this end, we compared the "self" and "other" conditions in trials where primes were masked or unmasked. In two separate experiments, we found that self-related priming was stronger than other-related priming but only in the unmasked trials. Together, our results suggest that preferential access to the self-concept occurs mainly at the perceptual and conscious stages of the stimulus processing hierarchy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Unified Model for Generation Complex Networks with Utility Preferential Attachment

    International Nuclear Information System (INIS)

    Wu Jianjun; Gao Ziyou; Sun Huijun

    2006-01-01

    In this paper, based on the utility preferential attachment, we propose a new unified model to generate different network topologies such as scale-free, small-world and random networks. Moreover, a new network structure named super scale network is found, which has monopoly characteristic in our simulation experiments. Finally, the characteristics of this new network are given.

  1. Skin Immunization Obviates Alcohol-Related Immune Dysfunction

    Directory of Open Access Journals (Sweden)

    Rhonda M. Brand

    2015-11-01

    Full Text Available Alcoholics suffer from immune dysfunction that can impede vaccine efficacy. If ethanol (EtOH-induced immune impairment is in part a result of direct exposure of immune cells to EtOH, then reduced levels of exposure could result in less immune dysfunction. As alcohol ingestion results in lower alcohol levels in skin than blood, we hypothesized that the skin immune network may be relatively preserved, enabling skin-targeted immunizations to obviate the immune inhibitory effects of alcohol consumption on conventional vaccines. We employed the two most common chronic EtOH mouse feeding models, the liver-damaging Lieber-DeCarli (LD and liver-sparing Meadows-Cook (MC diets, to examine the roles of EtOH and/or EtOH-induced liver dysfunction on alcohol related immunosuppression. Pair-fed mice were immunized against the model antigen ovalbumin (OVA by DNA immunization or against flu by administering the protein-based influenza vaccine either systemically (IV, IM, directly to liver (hydrodynamic, or cutaneously (biolistic, ID. We measured resulting tissue EtOH levels, liver stress, regulatory T cell (Treg, and myeloid-derived suppressor cell (MDSC populations. We compared immune responsiveness by measuring delayed-type hypersensitivity (DTH, antigen-specific cytotoxic T lymphocyte (CTL, and antibody induction as a function of delivery route and feeding model. We found that, as expected, and independent of the feeding model, EtOH ingestion inhibits DTH, CTL lysis, and antigen-specific total IgG induced by traditional systemic vaccines. On the other hand, skin-targeted vaccines were equally immunogenic in alcohol-exposed and non-exposed subjects, suggesting that cutaneous immunization may result in more efficacious vaccination in alcohol-ingesting subjects.

  2. Quantifying Preferential Flow and Seasonal Storage in an Unsaturated Fracture-Facial Domain

    Science.gov (United States)

    Nimmo, J. R.; Malek-Mohammadi, S.

    2012-12-01

    Preferential flow through deep unsaturated zones of fractured rock is hydrologically important to a variety of contaminant transport and water-resource issues. The unsaturated zone of the English Chalk Aquifer provides an important opportunity for a case study of unsaturated preferential flow in isolation from other flow modes. The chalk matrix has low hydraulic conductivity and stays saturated, owing to its fine uniform pores and the wet climate of the region. Therefore the substantial fluxes observed in the unsaturated chalk must be within fractures and interact minimally with matrix material. Price et al. [2000] showed that irregularities on fracture surfaces provide a significant storage capacity in the chalk unsaturated zone, likely accounting for volumes of water required to explain unexpected dry-season water-table stability during substantial continuing streamflow observed by Lewis et al. [1993] In this presentation we discuss and quantify the dynamics of replenishment and drainage of this unsaturated zone fracture-face storage domain using a modification of the source-responsive model of Nimmo [2010]. This model explains the processes in terms of two interacting flow regimes: a film or rivulet preferential flow regime on rough fracture faces, active on an individual-storm timescale, and a regime of adsorptive and surface-tension influences, resembling traditional diffuse formulations of unsaturated flow, effective mainly on a seasonal timescale. The modified model identifies hydraulic parameters for an unsaturated fracture-facial domain lining the fractures. Besides helping to quantify the unsaturated zone storage described by Price et al., these results highlight the importance of research on the topic of unsaturated-flow relations within a near-fracture-surface domain. This model can also facilitate understanding of mechanisms for reinitiation of preferential flow after temporary cessation, which is important in multi-year preferential flow through deep

  3. Maternal immunity enhances systemic recall immune responses upon oral immunization of piglets with F4 fimbriae.

    Science.gov (United States)

    Nguyen, Ut V; Melkebeek, Vesna; Devriendt, Bert; Goetstouwers, Tiphanie; Van Poucke, Mario; Peelman, Luc; Goddeeris, Bruno M; Cox, Eric

    2015-06-23

    F4 enterotoxigenic Escherichia coli (ETEC) cause diarrhoea and mortality in piglets leading to severe economic losses. Oral immunization of piglets with F4 fimbriae induces a protective intestinal immune response evidenced by an F4-specific serum and intestinal IgA response. However, successful oral immunization of pigs with F4 fimbriae in the presence of maternal immunity has not been demonstrated yet. In the present study we aimed to evaluate the effect of maternal immunity on the induction of a systemic immune response upon oral immunization of piglets. Whereas F4-specific IgG and IgA could be induced by oral immunization of pigs without maternal antibodies and by intramuscular immunization of pigs with maternal antibodies, no such response was seen in the orally immunized animals with maternal antibodies. Since maternal antibodies can mask an antibody response, we also looked by ELIspot assays for circulating F4-specific antibody secreting cells (ASCs). Enumerating the F4-specific ASCs within the circulating peripheral blood mononuclear cells, and the number of F4-specific IgA ASCs within the circulating IgA(+) B-cells revealed an F4-specific immune response in the orally immunized animals with maternal antibodies. Interestingly, results suggest a more robust IgA booster response by oral immunization of pigs with than without maternal antibodies. These results demonstrate that oral immunization of piglets with F4-specific maternal antibodies is feasible and that these maternal antibodies seem to enhance the secondary systemic immune response. Furthermore, our ELIspot assay on enriched IgA(+) B-cells could be used as a screening procedure to optimize mucosal immunization protocols in pigs with maternal immunity.

  4. U.S. Immunization program adult immunization activities and resources

    Science.gov (United States)

    Woods, LaDora O.; Bridges, Carolyn B.; Graitcer, Samuel B.; Lamont, Brock

    2016-01-01

    ABSTRACT Adults are recommended to receive vaccines based on their age, medical conditions, prior vaccinations, occupation and lifestyle. However, adult immunization coverage is low in the United States and lags substantially below Healthy People 2020 goals. To assess activities and resources designated for adult immunization programs by state and local health department immunization programs in the United States, we analyzed 2012 and 2013 data from the Centers for Disease Control and Prevention's (CDC) Program Annual Reports and Progress Assessments (PAPA) survey of CDC-funded immunization programs. Fifty-six of 64 funded US immunization programs' responses were included in the analysis. Eighty-two percent of (n = 46) programs reported having a designated adult immunization coordinator in 2012 and 73% (n = 41) in 2013. Of the 46 coordinators reported in 2012, 30% (n = 14) spent more than 50% of their time on adult immunization activities, and only 24% (n = 10) of the 41 adult coordinators in 2013 spent more than 50% of their time on adult immunization activities. In 2012, 23% (n = 13) of the 56 programs had a separate immunization coalition for adults and 68% (n = 38) included adult issues in their overall immunization program coalition. In 2013, 25% (n = 14) had a separate adult immunization coalition while 57% (n = 32) incorporated adult immunizations into their overall immunization program coalition. The results indicate substantial variation across the US in public health infrastructure to support adult immunizations. Continued assessment of adult immunization resources and activities will be important in improving adult immunization coverage levels though program support. With many programs having limited resources dedicated to improving adult immunization rates in the in US, efforts by the health departments to collaborate with providers and other partners in their jurisdictions to increase awareness, increase the use of proven strategies to improve

  5. Introduction to the Special Issue: Precarious Solidarity-Preferential Access in Canadian Health Care.

    Science.gov (United States)

    Reid, Lynette

    2017-06-01

    Systems of universal health coverage may aspire to provide care based on need and not ability to pay; the complexities of this aspiration (conceptual, practical, and ethical) call for normative analysis. This special issue arises in the wake of a judicial inquiry into preferential access in the Canadian province of Alberta, the Vertes Commission. I describe this inquiry and set out a taxonomy of forms of differential and preferential access. Papers in this special issue focus on the conceptual specification of health system boundaries (the concept of medical need) and on the normative questions raised by complex models of funding and delivery of care, where patients, providers, and services cross system boundaries.

  6. Preferential growth in FeCoV/Ti:N multilayers

    Energy Technology Data Exchange (ETDEWEB)

    Clemens, D.; Senthil Kumar, M.; Boeni, P.; Horisberger, M. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1997-09-01

    The preferential growth in Fe{sub 0.50}Co{sub 0.48}V{sub 0.02}/Ti:N multilayers was studied by X-ray diffraction. X-ray specular reflectometry and subsequent simulation of the spectra was used to extract information about the thickness and interface roughness of individual layers. The investigation gives structural information about the material combination and its potential for the use of neutron polarizers. (author) 2 figs., 1 tab., 2 refs.

  7. Preferential solvation of fluorenone and 4-hydroxyfluorenone in binary solvent mixtures

    International Nuclear Information System (INIS)

    Jozefowicz, Marek; Heldt, Janina R.

    2003-01-01

    Preferential solvation of fluorenone and 4-hydroxyfluorenone in binary solvent mixtures has been studied using steady-state spectroscopic measurements. This study concerns the solvent-induced shift of the absorption and fluorescence spectra of both molecules in two solvent mixtures, i.e., cyclohexane-tetrahydrofuran and cyclohexane-ethanol. The first system contains polar solute molecules, fluorenone and 4-hydroxyfluorenone, in a mixture of polar aprotic (tetrahydrofuran) and non-polar (cyclohexane) solvents. In the second solvents mixture, hydrogen bonding with solute molecules (ethanol) may occur. The results of spectroscopic measurements are analysed using theoretical models of Bakshiev, Mazurenko and Suppan which describe preferential solvation phenomena. In the case of cyclohexane-tetrahydrofuran mixtures, the deviation from linearity in the absorption and fluorescence solvatochromic shifts vs. the solution polarity is due to non-specific dipolar solvent-solute interactions. For cyclohexane-ethanol binary mixtures, both non-specific and specific (hydrogen bond and proton-relay tautomerization) interactions contribute to the observed solvatochromism

  8. Role of Interleukin-33 in Innate-Type Immune Cells in Allergy

    Directory of Open Access Journals (Sweden)

    Susumu Nakae

    2013-01-01

    Full Text Available Interleukin-33 (IL-33, a member of the IL-1 cytokine family, is preferentially and constitutively expressed in epithelial cells, and it is especially localized in the cells' nucleus. The nuclear IL-33 is released by necrotic cells after tissue injury and/or trauma, and subsequently provokes local inflammation as an alarmin, like high-mobility group box protein-1 (HMGB-1 and IL-1α. IL-33 mainly activates Th2 cells and such innate-type immune cells as mast cells, basophils, eosinophils and natural helper cells that express IL-33R (a heterodimer of IL-1 receptor-like 1 [IL-1RL1; also called ST2, T1, Der4, fit-1] and IL-1 receptor accessory protein [IL-1RAcP]. That activation causes the cells to produce Th2 cytokines, which contribute to host defense against nematodes. On the other hand, excessive and/or inappropriate production of IL-33 is also considered to be involved in the development of such disorders as allergy. In this review, we summarize current knowledge regarding the pathogenic roles of IL-33 in the development of allergic inflammation by focusing on its effects on innate-type immune cells.

  9. The membrane attack complex of complement contributes to plasmin-induced synthesis of platelet-activating factor by endothelial cells and neutrophils.

    Science.gov (United States)

    Lupia, Enrico; Del Sorbo, Lorenzo; Bergerone, Serena; Emanuelli, Giorgio; Camussi, Giovanni; Montrucchio, Giuseppe

    2003-08-01

    Thrombolytic agents, used to restore blood flow to ischaemic tissues, activate several enzymatic systems with pro-inflammatory effects, thus potentially contributing to the pathogenesis of ischaemia-reperfusion injury. Platelet-activating factor (PAF), a phospholipid mediator of inflammation, has been implicated in the pathogenesis of this process. We previously showed that the infusion of streptokinase (SK) induces the intravascular release of PAF in patients with acute myocardial infarction (AMI), and that cultured human endothelial cells (EC) synthesized PAF in response to SK and plasmin (PLN). In the present study, we investigated the role of the membrane attack complex (MAC) of complement in the PLN-induced synthesis of PAF. In vivo, we showed a correlation between the levels of soluble terminal complement components (sC5b-9) and the concentrations of PAF detected in blood of patients with AMI infused with SK. In vitro both EC and polymorphonuclear neutrophils (PMN), incubated in the presence of PLN and normal human serum, showed an intense staining for the MAC neoepitope, while no staining was detected when they were incubated with PLN in the presence of heat-inactivated normal human serum. Moreover, the insertion of MAC on EC and PMN plasmamembrane elicited the synthesis of PAF. In conclusion, our results elucidate the mechanisms involved in PAF production during the activation of the fibrinolytic system, showing a role for complement products in this setting. The release of PAF may increase the inflammatory response, thus limiting the beneficial effects of thrombolytic therapy. Moreover, it may have a pathogenic role in other pathological conditions, such as transplant rejection, tumoral angiogenesis, and septic shock, where fibrinolysis is activated.

  10. The influence of preferential flow on pressure propagation and landslide triggering of the Rocca Pitigliana landslide

    Science.gov (United States)

    Shao, Wei; Bogaard, Thom; Bakker, Mark; Berti, Matteo

    2016-12-01

    The fast pore water pressure response to rain events is an important triggering factor for slope instability. The fast pressure response may be caused by preferential flow that bypasses the soil matrix. Currently, most of the hydro-mechanical models simulate pore water pressure using a single-permeability model, which cannot quantify the effects of preferential flow on pressure propagation and landslide triggering. Previous studies showed that a model based on the linear-diffusion equation can simulate the fast pressure propagation in near-saturated landslides such as the Rocca Pitigliana landslide. In such a model, the diffusion coefficient depends on the degree of saturation, which makes it difficult to use the model for predictions. In this study, the influence of preferential flow on pressure propagation and slope stability is investigated with a 1D dual-permeability model coupled with an infinite-slope stability approach. The dual-permeability model uses two modified Darcy-Richards equations to simultaneously simulate the matrix flow and preferential flow in hillslopes. The simulated pressure head is used in an infinite-slope stability analysis to identify the influence of preferential flow on the fast pressure response and landslide triggering. The dual-permeability model simulates the height and arrival of the pressure peak reasonably well. Performance of the dual-permeability model is as good as or better than the linear-diffusion model even though the dual-permeability model is calibrated for two single pulse rain events only, while the linear-diffusion model is calibrated for each rain event separately. In conclusion, the 1D dual-permeability model is a promising tool for landslides under similar conditions.

  11. Immunization Information System and Informatics to Promote Immunizations: Perspective From Minnesota Immunization Information Connection.

    Science.gov (United States)

    Muscoplat, Miriam Halstead; Rajamani, Sripriya

    2017-01-01

    The vision for management of immunization information is availability of real-time consolidated data and services for all ages, to clinical, public health, and other stakeholders. This is being executed through Immunization Information Systems (IISs), which are population-based and confidential computerized systems present in most US states and territories. Immunization Information Systems offer many functionalities, such as immunization assessment reports, client follow-up, reminder/recall feature, vaccine management tools, state-supplied vaccine ordering, comprehensive immunization history, clinical decision support/vaccine forecasting and recommendations, data processing, and data exchange. This perspective article will present various informatics tools in an IIS, in the context of the Minnesota Immunization Information Connection.

  12. Study of a diffusion flamelet model, with preferential diffusion effects included

    NARCIS (Netherlands)

    Delhaye, S.; Somers, L.M.T.; Bongers, H.; Oijen, van J.A.; Goey, de L.P.H.; Dias, V.

    2005-01-01

    The non-premixed flamelet model of Peters [1] (model1), which does not include preferential diffusion effects is investigated. Two similar models are presented, but without the assumption of unity Lewis numbers. One of these models was derived by Peters & Pitsch [2] (model2), while the other one was

  13. A shark antibody heavy chain encoded by a nonsomatically rearranged VDJ is preferentially expressed in early development and is convergent with mammalian IgG.

    Science.gov (United States)

    Rumfelt, L L; Avila, D; Diaz, M; Bartl, S; McKinney, E C; Flajnik, M F

    2001-02-13

    In most vertebrate embryos and neonates studied to date unique antigen receptors (antibodies and T cell receptors) are expressed that possess a limited immune repertoire. We have isolated a subclass of IgM, IgM(1gj), from the nurse shark Ginglymostoma cirratum that is preferentially expressed in neonates. The variable (V) region gene encoding the heavy (H) chain underwent V-D-J rearrangement in germ cells ("germline-joined"). Such H chain V genes were discovered over 10 years ago in sharks but until now were not shown to be expressed at appreciable levels; we find expression of H(1gj) in primary and secondary lymphoid tissues early in life, but in adults only in primary lymphoid tissue, which is identified in this work as the epigonal organ. H(1gj) chain associates covalently with light (L) chains and is most similar in sequence to IgM H chains, but like mammalian IgG has three rather than the four IgM constant domains; deletion of the ancestral IgM C2 domain thus defines both IgG and IgM(1gj). Because sharks are the members of the oldest vertebrate class known to possess antibodies, unique or specialized antibodies expressed early in ontogeny in sharks and other vertebrates were likely present at the inception of the adaptive immune system.

  14. Depth resolution and preferential sputtering in depth profiling of sharp interfaces

    International Nuclear Information System (INIS)

    Hofmann, S.; Han, Y.S.; Wang, J.Y.

    2017-01-01

    Highlights: • Interfacial depth resolution from MRI model depends on sputtering rate differences. • Depth resolution critically depends on the dominance of roughness or atomic mixing. • True (depth scale) and apparent (time scale) depth resolutions are different. • Average sputtering rate approximately yields true from apparent depth resolution. • Profiles by SIMS and XPS are different but similar to surface concentrations. - Abstract: The influence of preferential sputtering on depth resolution of sputter depth profiles is studied for different sputtering rates of the two components at an A/B interface. Surface concentration and intensity depth profiles on both the sputtering time scale (as measured) and the depth scale are obtained by calculations with an extended Mixing-Roughness-Information depth (MRI)-model. The results show a clear difference for the two extreme cases (a) preponderant roughness and (b) preponderant atomic mixing. In case (a), the interface width on the time scale (Δt(16–84%)) increases with preferential sputtering if the faster sputtering component is on top of the slower sputtering component, but the true resolution on the depth scale (Δz(16–84%)) stays constant. In case (b), the interface width on the time scale stays constant but the true resolution on the depth scale varies with preferential sputtering. For similar order of magnitude of the atomic mixing and the roughness parameters, a transition state between the two extremes is obtained. While the normalized intensity profile of SIMS represents that of the surface concentration, an additional broadening effect is encountered in XPS or AES by the influence of the mean electron escape depth which may even cause an additional matrix effect at the interface.

  15. Depth resolution and preferential sputtering in depth profiling of sharp interfaces

    Energy Technology Data Exchange (ETDEWEB)

    Hofmann, S. [Max Planck Institute for Intelligent Systems (formerly MPI for Metals Research), Heisenbergstrasse 3, D-70569 Stuttgart (Germany); Han, Y.S. [Department of Physics, Shantou University, 243 Daxue Road, Shantou, 515063 Guangdong (China); Wang, J.Y., E-mail: wangjy@stu.edu.cn [Department of Physics, Shantou University, 243 Daxue Road, Shantou, 515063 Guangdong (China)

    2017-07-15

    Highlights: • Interfacial depth resolution from MRI model depends on sputtering rate differences. • Depth resolution critically depends on the dominance of roughness or atomic mixing. • True (depth scale) and apparent (time scale) depth resolutions are different. • Average sputtering rate approximately yields true from apparent depth resolution. • Profiles by SIMS and XPS are different but similar to surface concentrations. - Abstract: The influence of preferential sputtering on depth resolution of sputter depth profiles is studied for different sputtering rates of the two components at an A/B interface. Surface concentration and intensity depth profiles on both the sputtering time scale (as measured) and the depth scale are obtained by calculations with an extended Mixing-Roughness-Information depth (MRI)-model. The results show a clear difference for the two extreme cases (a) preponderant roughness and (b) preponderant atomic mixing. In case (a), the interface width on the time scale (Δt(16–84%)) increases with preferential sputtering if the faster sputtering component is on top of the slower sputtering component, but the true resolution on the depth scale (Δz(16–84%)) stays constant. In case (b), the interface width on the time scale stays constant but the true resolution on the depth scale varies with preferential sputtering. For similar order of magnitude of the atomic mixing and the roughness parameters, a transition state between the two extremes is obtained. While the normalized intensity profile of SIMS represents that of the surface concentration, an additional broadening effect is encountered in XPS or AES by the influence of the mean electron escape depth which may even cause an additional matrix effect at the interface.

  16. Balancing practicality and hydrologic realism: a parsimonious approach for simulating rapid groundwater recharge via unsaturated-zone preferential flow

    Science.gov (United States)

    Mirus, Benjamin B.; Nimmo, J.R.

    2013-01-01

    The impact of preferential flow on recharge and contaminant transport poses a considerable challenge to water-resources management. Typical hydrologic models require extensive site characterization, but can underestimate fluxes when preferential flow is significant. A recently developed source-responsive model incorporates film-flow theory with conservation of mass to estimate unsaturated-zone preferential fluxes with readily available data. The term source-responsive describes the sensitivity of preferential flow in response to water availability at the source of input. We present the first rigorous tests of a parsimonious formulation for simulating water table fluctuations using two case studies, both in arid regions with thick unsaturated zones of fractured volcanic rock. Diffuse flow theory cannot adequately capture the observed water table responses at both sites; the source-responsive model is a viable alternative. We treat the active area fraction of preferential flow paths as a scaled function of water inputs at the land surface then calibrate the macropore density to fit observed water table rises. Unlike previous applications, we allow the characteristic film-flow velocity to vary, reflecting the lag time between source and deep water table responses. Analysis of model performance and parameter sensitivity for the two case studies underscores the importance of identifying thresholds for initiation of film flow in unsaturated rocks, and suggests that this parsimonious approach is potentially of great practical value.

  17. Is there reciprocity in preferential trade agreements on services?

    OpenAIRE

    Marchetti, Juan; Roy, Martin; Zoratto, Laura

    2012-01-01

    Are market access commitments on services in Preferential Trade Agreements (PTAs) reciprocal or simply unilateral? If reciprocal, do concessions granted in services depend on concessions received from the trading partner in other services or in non-services areas as well? In this paper we investigate the presence of reciprocity in bilateral services agreements, by sub-sector, mode of supply and type of agreement (North-North, South-North, South-South). To do so, we use a database of concessio...

  18. Vascular endothelium as a target of immune response in renal transplant rejection

    Directory of Open Access Journals (Sweden)

    Giovanni ePiotti

    2014-10-01

    Full Text Available This review of clinical and experimental studies aims at analysing the interplay between graft endothelium and host immune system in renal transplantation, and how it affects the survival of the graft. Graft endothelium is indeed the first barrier between self and non-self that is encountered by host lymphocytes upon reperfusion of vascularised solid transplants. Endothelial cells express all the major sets of antigens that elicit host immune response, and therefore represent a preferential target in organ rejection.Some of the antigens expressed by endothelial cells are target of the antibody-mediated response, such as the AB0 blood group system, the HLA and MICA systems, and the endothelial cell-restricted antigens; for each of these systems, the mechanisms of interaction and damage of both preformed and de novo donor-specific antibodies are reviewed along with their impact on renal graft survival. Moreover the rejection process can force injured endothelial cells to expose cryptic self-antigens, toward which an auto-immune response mounts, overlapping to the allo-immune response in the damaging of the graft. Not only are endothelial cells a passive target of the host immune response, but also an active player in lymphocyte activation; therefore their interaction with allogenic T-cells is analysed on the basis of experimental in vitro and in vivo studies, according to the patterns of expression of the HLA class I and II and the co-stimulatory molecules specific for cytotoxic and helper T-cells.Finally, as the response that follows transplantation has proven to be not necessarily destructive, the factors that foster graft endothelium functioning in spite of rejection, and how they could be therapeutically harnessed to promote long-term graft acceptance, are described: accommodation that is resistance of endothelial cells to donor-specific antibodies, and endothelial cell ability to induce Foxp3+ Regulatory T-cells, that are crucial mediators of

  19. Stationary and nonstationary properties of evolving networks with preferential linkage

    International Nuclear Information System (INIS)

    Jezewski, W.

    2002-01-01

    Networks evolving by preferential attachment of both external and internal links are investigated. The rate of adding an external link is assumed to depend linearly on the degree of a preexisting node to which a new node is connected. The process of creating an internal link, between a pair of existing vertices, is assumed to be controlled entirely by the vertex that has more links than the other vertex in the pair, and the rate of creation of such a link is assumed to be, in general, nonlinear in the degree of the more strongly connected vertex. It is shown that degree distributions of networks evolving only by creating internal links display for large degrees a nonstationary power-law decay with a time-dependent scaling exponent. Nonstationary power-law behaviors are numerically shown to persist even when the number of nodes is not fixed and both external and internal connections are introduced, provided that the rate of preferential attachment of internal connections is nonlinear. It is argued that nonstationary effects are not unlikely in real networks, although these effects may not be apparent, especially in networks with a slowly varying mean degree

  20. Estimation of Airline Benefits from Avionics Upgrade under Preferential Merge Re-sequence Scheduling

    Science.gov (United States)

    Kotegawa, Tatsuya; Cayabyab, Charlene Anne; Almog, Noam

    2013-01-01

    Modernization of the airline fleet avionics is essential to fully enable future technologies and procedures for increasing national airspace system capacity. However in the current national airspace system, system-wide benefits gained by avionics upgrade are not fully directed to aircraft/airlines that upgrade, resulting in slow fleet modernization rate. Preferential merge re-sequence scheduling is a best-equipped-best-served concept designed to incentivize avionics upgrade among airlines by allowing aircraft with new avionics (high-equipped) to be re-sequenced ahead of aircraft without the upgrades (low-equipped) at enroute merge waypoints. The goal of this study is to investigate the potential benefits gained or lost by airlines under a high or low-equipped fleet scenario if preferential merge resequence scheduling is implemented.

  1. Imbalanced immune homeostasis in immune thrombocytopenia.

    Science.gov (United States)

    Yazdanbakhsh, Karina

    2016-04-01

    Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder resulting from low platelet counts caused by inadequate production as well as increased destruction by autoimmune mechanisms. As with other autoimmune disorders, chronic ITP is characterized by perturbations of immune homeostasis with hyperactivated effector cells as well as defective regulatory arm of the adaptive immune system, which will be reviewed here. Interestingly, some ITP treatments are associated with restoring the regulatory imbalance, although it remains unclear whether the immune system is redirected to a state of tolerance once treatment is discontinued. Understanding the mechanisms that result in breakdown of immune homeostasis in ITP will help to identify novel pathways for restoring tolerance and inhibiting effector cell responses. This information can then be translated into developing therapies for averting autoimmunity not only in ITP but also many autoimmune disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Immunizing Children

    Directory of Open Access Journals (Sweden)

    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.

  3. Modelling the Preferential Solvation of Ferulic Acid in {2-Propanol (1 + Water (2} Mixtures at 298.15 K

    Directory of Open Access Journals (Sweden)

    Abolghasem Jouyban 1,2, Fleming Martínez 3 *

    2017-12-01

    Full Text Available Background: Recently Haq et al. reported the equilibrium solubility in {2-propanol (1 + water (2} mixtures at several temperatures with some numerical correlation analysis. Nevertheless, no attempt was made to evaluate the preferential solvation of this compound by the solvents. Methods: Preferential solvation of ferulic acid in the saturated mixtures at 298.15 K was analyzed based on the inverse Kirkwood-Buff integrals as described in the literature. Results: Ferulic acid is preferentially solvated by water in water-rich mixtures (0.00 < x1 < 0.19 but preferentially solvated by 2-propanol in mixtures with composition 0.19 < x1 < 1.00. Conclusion: These results could be interpreted as a consequence of hydrophobic hydration around the non-polar groups of the solute in the former case (0.00 < x1 < 0.19. Moreover, in the last case (0.19 < x1 < 1.00, the observed trend could be a consequence of the acid behavior of ferulic acid in front to 2-propanol molecules because this cosolvent is more basic than water as described by the respective solvatochromic parameters.

  4. Dihydroartemisinin induces apoptosis preferentially via a Bim-mediated intrinsic pathway in hepatocarcinoma cells.

    Science.gov (United States)

    Qin, Guiqi; Zhao, ChuBiao; Zhang, Lili; Liu, Hongyu; Quan, Yingyao; Chai, Liuying; Wu, Shengnan; Wang, Xiaoping; Chen, Tongsheng

    2015-08-01

    This report is designed to dissect the detail molecular mechanism by which dihydroartemisinin (DHA), a derivative of artemisinin, induces apoptosis in human hepatocellular carcinoma (HCC) cells. DHA induced a loss of the mitochondrial transmemberane potential (ΔΨm), release of cytochrome c, activation of caspases, and externalization of phosphatidylserine indicative of apoptosis induction. Compared with the modest inhibitory effects of silencing Bax, silencing Bak largely prevented DHA-induced ΔΨm collapse and apoptosis though DHA induced a commensurable activation of Bax and Bak, demonstrating a key role of the Bak-mediated intrinsic apoptosis pathway. DHA did not induce Bid cleavage and translocation from cytoplasm to mitochondria and had little effects on the expressions of Puma and Noxa, but did increase Bim and Bak expressions and decrease Mcl-1 expression. Furthermore, the cytotoxicity of DHA was remarkably reduced by silencing Bim, and modestly but significantly reduced by silencing Puma or Noxa. Silencing Bim or Noxa preferentially reduced DHA-induced Bak activation, while silencing Puma preferentially reduced DHA-induced Bax activation, demonstrating that Bim and to a lesser extent Noxa act as upstream mediators to trigger the Bak-mediated intrinsic apoptosis pathway. In addition, silencing Mcl-1 enhanced DHA-induced Bak activation and apoptosis. Taken together, our data demonstrate a crucial role of Bim in preferentially regulating the Bak/Mcl-1 rheostat to mediate DHA-induced apoptosis in HCC cells.

  5. Beneficial Effect of Preferential Music on Exercise Induced Changes in Heart Rate Variability.

    Science.gov (United States)

    Archana, R; Mukilan, R

    2016-05-01

    Music is known to reduce pain, anxiety and fear in several stressful conditions in both males and females. Further, listening to preferred music enhances the endurance during running performance of women rather than listening to non-preferred music. In recent years Heart Rate Variability (HRV) has been used as an indicator of autonomic nervous activity. This study was aimed to assess the effectiveness of preferential music on HRV after moderate exercise. This was an experimental study done in 30 healthy students aged between 20-25 years, of either sex. HRV was measured at rest, 15 minutes of exercise only and 15 minutes of exercise with listening preferential music in same participants. Data was analysed by One-Way ANOVA and Tukey HSD Post-hoc Test. Statistical significance was taken to be a p-value of less than 0.05. Low frequency and high frequency component was significantly increased followed by only exercise. Music minimized increase in both high and low frequency component followed by exercise. However, only high frequency change was statistically significant. LF/HF ratio was significantly increased followed by only exercise. Music significantly minimized increase in LF/HF ratio. This study provides the preliminary evidence that listening to preferential music could be an effective method of relaxation, as indicated by a shift of the autonomic balance towards the parasympathetic activity among medical students.

  6. A Novel Preferential Diffusion Recommendation Algorithm Based on User’s Nearest Neighbors

    Directory of Open Access Journals (Sweden)

    Fuguo Zhang

    2017-01-01

    Full Text Available Recommender system is a very efficient way to deal with the problem of information overload for online users. In recent years, network based recommendation algorithms have demonstrated much better performance than the standard collaborative filtering methods. However, most of network based algorithms do not give a high enough weight to the influence of the target user’s nearest neighbors in the resource diffusion process, while a user or an object with high degree will obtain larger influence in the standard mass diffusion algorithm. In this paper, we propose a novel preferential diffusion recommendation algorithm considering the significance of the target user’s nearest neighbors and evaluate it in the three real-world data sets: MovieLens 100k, MovieLens 1M, and Epinions. Experiments results demonstrate that the novel preferential diffusion recommendation algorithm based on user’s nearest neighbors can significantly improve the recommendation accuracy and diversity.

  7. Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake.

    Science.gov (United States)

    Flavahan, William A; Wu, Qiulian; Hitomi, Masahiro; Rahim, Nasiha; Kim, Youngmi; Sloan, Andrew E; Weil, Robert J; Nakano, Ichiro; Sarkaria, Jann N; Stringer, Brett W; Day, Bryan W; Li, Meizhang; Lathia, Justin D; Rich, Jeremy N; Hjelmeland, Anita B

    2013-10-01

    Like all cancers, brain tumors require a continuous source of energy and molecular resources for new cell production. In normal brain, glucose is an essential neuronal fuel, but the blood-brain barrier limits its delivery. We now report that nutrient restriction contributes to tumor progression by enriching for brain tumor initiating cells (BTICs) owing to preferential BTIC survival and to adaptation of non-BTICs through acquisition of BTIC features. BTICs outcompete for glucose uptake by co-opting the high affinity neuronal glucose transporter, type 3 (Glut3, SLC2A3). BTICs preferentially express Glut3, and targeting Glut3 inhibits BTIC growth and tumorigenic potential. Glut3, but not Glut1, correlates with poor survival in brain tumors and other cancers; thus, tumor initiating cells may extract nutrients with high affinity. As altered metabolism represents a cancer hallmark, metabolic reprogramming may maintain the tumor hierarchy and portend poor prognosis.

  8. Self-potential monitoring of a thermal pulse advecting through a preferential flow path

    Science.gov (United States)

    Ikard, S. J.; Revil, A.

    2014-11-01

    There is a need to develop new non-intrusive geophysical methods to detect preferential flow paths in heterogeneous porous media. A laboratory experiment is performed to non-invasively localize a preferential flow pathway in a sandbox using a heat pulse monitored by time-lapse self-potential measurements. Our goal is to investigate the amplitude of the intrinsic thermoelectric self-potential anomalies and the ability of this method to track preferential flow paths. A negative self-potential anomaly (-10 to -15 mV with respect to the background signals) is observed at the surface of the tank after hot water is injected in the upstream reservoir during steady state flow between the upstream and downstream reservoirs of the sandbox. Repeating the same experiment with the same volume of water injected upstream, but at the same temperature as the background pore water, produces a negligible self-potential anomaly. The negative self-potential anomaly is possibly associated with an intrinsic thermoelectric effect, with the temperature dependence of the streaming potential coupling coefficient, or with an apparent thermoelectric effect associated with the temperature dependence of the electrodes themselves. We model the experiment in 3D using a finite element code. Our results show that time-lapse self-potential signals can be used to track the position of traveling heat flow pulses in saturated porous materials, and therefore to find preferential flow pathways, especially in a very permeable environment and in real time. The numerical model and the data allows quantifying the intrinsic thermoelectric coupling coefficient, which is on the order of -0.3 to -1.8 mV per degree Celsius. The temperature dependence of the streaming potential during the experiment is negligible with respect to the intrinsic thermoelectric coupling. However, the temperature dependence of the potential of the electrodes needs to be accounted for and is far from being negligible if the electrodes

  9. Preferential adsorption of polycarboxylate superplasticizers on cement and silica fume in ultra-high performance concrete (UHPC)

    International Nuclear Information System (INIS)

    Schröfl, Ch.; Gruber, M.; Plank, J.

    2012-01-01

    UHPC is fluidized particularly well when a blend of MPEG- and APEG-type PCEs is applied. Here, the mechanism for this behavior was investigated. Testing individual cement and micro silica pastes revealed that the MPEG-PCE disperses cement better than silica whereas the APEG-PCE fluidizes silica particularly well. This behavior is explained by preferential adsorption of APEG-PCE on silica while MPEG-PCEs exhibit a more balanced affinity to both cement and silica. Adsorption data obtained from individual cement and micro silica pastes were compared with those found for the fully formulated UHPC containing a cement/silica blend. In the UHPC formulation, both PCEs still exhibit preferential and selective adsorption similar as was observed for individual cement and silica pastes. Preferential adsorption of PCEs is explained by their different stereochemistry whereby the carboxylate groups have to match with the steric position of calcium ions/atoms situated at the surfaces of cement hydrates or silica.

  10. The dynamics of power laws : fitness and aging in preferential attachment trees

    NARCIS (Netherlands)

    Garavaglia, A.; van der Hofstad, R.W.; Woeginger, G.

    2017-01-01

    Continuous-time branching processes describe the evolution of a population whose individuals generate a random number of children according to a birth process. Such branching processes can be used to understand preferential attachment models in which the birth rates are linear functions. We are

  11. Impact of pharmacists providing immunizations on adolescent influenza immunization.

    Science.gov (United States)

    Robison, Steve G

    2016-01-01

    To determine if the Oregon law change in 2011 to allow pharmacists to immunize adolescents 11 to 17 years of age increased influenza immunizations or changed existing immunization venues. With the use of Oregon's ALERT Immunization Information System (IIS), 2 measures of impact were developed. First, the change in adolescent age 11-17 influenza immunizations before (2007-2010) and after (2011-2014) the pharmacy law change was evaluated against a reference cohort (aged 7-10) not affected by the law. Community pharmacies were also compared with other types of influenza immunization sites within one of the study influenza seasons (2013-2014). From 2007 to 2014, adolescent influenza immunizations at community pharmacies increased from 36 to 6372 per year. After the 2011 pharmacy law change, adolescents aged 11 to 17 were more likely to receive an influenza immunization compared with the reference population (odds ratio, 1.21; 95% CI, 1.19-1.22). Analysis of the 2013-2014 influenza season suggests that community pharmacies immunized a different population of adolescents than other providers. The 2011 change in Oregon law allowed pharmacists to increase the total of influenza immunizations given to adolescents. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  12. DDA/TDB liposomes containing soluble Leishmania major antigens induced a mixed Th1/Th2 immune response in BALB/c mice

    Directory of Open Access Journals (Sweden)

    Mansure Hojatizade

    2017-04-01

    Full Text Available Objective(s: Leishmaniasis is a complex parasitic disease that represents a major public health problem. Despite numerous attempts over the past decades, yet there is no effective vaccine against human leishmaniasis probably due to the lack of suitable adjuvants. In this study, a first generation liposomal-based Leishmania vaccine was developed using soluble Leishmania major antigens (SLA and á, Ü-trehalose6, 6'-dibehenat (TDB as an immunostimulatory adjuvant. In this liposome structure, the cationic lipid Dimethyldioctadecylammonium (DDA provides intrinsic adjuvant activity and cholesterol was added as a membrane stabilizer. Liposomes containing SLA were prepared.Materials and Methods: BALB/c mice were subcutaneously (sc immunized with Lip (DDA/TDB/CHOL-SLA+, Lip (DDA/TDB-SLA+, Lip (DDA-SLA+, Lip (DDA/CHOL-SLA+, SLA or Tris-HCl buffer. Immunization was done every two weeks for three weeks. The immunized mice were then challenged sc in the left footpad with 1×106 stationary phase L. major promastigotes (50 ìl, at 2 weeks after last booster injection.Results: mice immunized with any of the liposomal formulations containing SLA (Lip-SLA+, substantially increased footpad swelling and parasite loads of foot and spleen with no significant difference compared to Tris-HCl buffer or SLA alone. Lip-SLA+ formulations induced a mixed Th1/Th2 immune response characterized by IFN-ã and IL-4 production as well as high levels of IgG1 anti-Leishmania antibody. Conclusion: immunization with liposomes containing DDA and/or TDB in combination with SLA induces a mixed Th1/Th2 immune response and is not an appropriate strategy for preferential induction of a Th1 response and protection against leishmaniasis.

  13. Plasminogen-induced aggregation of PANC-1 cells requires conversion to plasmin and is inhibited by endogenous plasminogen activator inhibitor-1.

    Science.gov (United States)

    Deshet, Naamit; Lupu-Meiri, Monica; Espinoza, Ingrid; Fili, Oded; Shapira, Yuval; Lupu, Ruth; Gershengorn, Marvin C; Oron, Yoram

    2008-09-01

    PANC-1 cells express proteinase-activated receptors (PARs)-1, -2, and respond to their activation by transient elevation of cytosolic [Ca(2+)] and accelerated aggregation (Wei et al., 2006, J Cell Physiol 206:322-328). We studied the effect of plasminogen (PGN), an inactive precursor of the PAR-1-activating protease, plasmin (PN) on aggregation of pancreatic adenocarcinoma (PDAC) cells. A single dose of PGN time- and dose-dependently promoted PANC-1 cells aggregation in serum-free medium, while PN did not. PANC-1 cells express urokinase plasminogen activator (uPA), which continuously converted PGN to PN. This activity and PGN-induced aggregation were inhibited by the uPA inhibitor amiloride. PGN-induced aggregation was also inhibited by alpha-antiplasmin and by the PN inhibitor epsilon-aminocaproic acid (EACA). Direct assay of uPA activity revealed very low rate, markedly enhanced in the presence of PGN. Moreover, in PGN activator inhibitor 1-deficient PANC-1 cells, uPA activity and PGN-induced aggregation were markedly potentiated. Two additional human PDAC cell lines, MiaPaCa and Colo347, were assayed for PGN-induced aggregation. Both cell lines responded by aggregation and exhibited PGN-enhanced uPA activity. We hypothesized that the continuous conversion of PGN to PN by endogenous uPA is limited by PN's degradation and negatively controlled by endogenously produced PAI-1. Indeed, we found that PANC-1 cells inactivate PN with t1/2 of approximately 7 h, while the continuous addition of PN promoted aggregation. Our data suggest that PANC-1 cells possess intrinsic, PAI-1-sensitive mechanism for promotion of aggregation and differentiation by prolonged exposure to PGN and, possibly, additional precursors of PARs agonists.

  14. Hypoxia preferentially destroys GABAergic neurons in developing rat neocortex explants in culture

    NARCIS (Netherlands)

    Romijn, H. J.; Ruijter, J. M.; Wolters, P. S.

    1988-01-01

    The hypothesis that hypoxic ischemia before or during the human birth process preferentially destroys GABAergic nerve cells, particularly in the neocortex, was tested in a tissue culture model system. To that end, rat neocortex explants dissected from 6-day-old rat pups and cultured to a

  15. Waste streams that preferentially corrode 55-gallon steel storage drums

    International Nuclear Information System (INIS)

    Zirker, L.R.; Beitel, G.A.; Reece, C.M.

    1995-06-01

    When 55-gal steel drum waste containers fail in service, i.e., leak, corrode or breach, the standard fix has been to overpack the drum. When a drum fails and is overpacked into an 83-gal overpack drum, there are several negative consequences. Identifying waste streams that preferentially corrode steel drums is essential to the pollution prevention philosophy that ''an ounce of prevention is worth a pound of cure.'' It is essential that facilities perform pollution prevention measures at the front end of processes to reduce pollution on the back end. If these waste streams can be identified before they are packaged, the initial drum packaging system could be fortified or increased to eliminate future drum failures, breaches, clean-ups, and the plethora of other consequences. Therefore, a survey was conducted throughout the US Department of Energy complex for information concerning waste streams that have demonstrated preferential corrosion of 55-gal steel drums. From 21 site contacts, 21 waste streams were so identified. The major components of these waste streams include acids, salts, and solvent liquids, sludges, and still bottoms. The solvent-based waste streams typically had the shortest time to failure, 0.5 to 2 years. This report provides the results of this survey and research

  16. Epidemic propagation on adaptive coevolutionary networks with preferential local-world reconnecting strategy

    International Nuclear Information System (INIS)

    Song Yu-Rong; Jiang Guo-Ping; Gong Yong-Wang

    2013-01-01

    In the propagation of an epidemic in a population, individuals adaptively adjust their behavior to avoid the risk of an epidemic. Differently from existing studies where new links are established randomly, a local link is established preferentially in this paper. We propose a new preferentially reconnecting edge strategy depending on spatial distance (PR-SD). For the PR-SD strategy, the new link is established at random with probability p and in a shortest distance with the probability 1 − p. We establish the epidemic model on an adaptive network using Cellular Automata, and demonstrate the effectiveness of the proposed model by numerical simulations. The results show that the smaller the value of parameter p, the more difficult the epidemic spread is. The PR-SD strategy breaks long-range links and establishes as many short-range links as possible, which causes the network efficiency to decrease quickly and the propagation of the epidemic is restrained effectively. (general)

  17. Induction of antitumor immunity through xenoplacental immunization

    Directory of Open Access Journals (Sweden)

    Agadjanyan Michael G

    2006-05-01

    Full Text Available Abstract Historically cancer vaccines have yielded suboptimal clinical results. We have developed a novel strategy for eliciting antitumor immunity based upon homology between neoplastic tissue and the developing placenta. Placenta formation shares several key processes with neoplasia, namely: angiogenesis, activation of matrix metalloproteases, and active suppression of immune function. Immune responses against xenoantigens are well known to break self-tolerance. Utilizing xenogeneic placental protein extracts as a vaccine, we have successfully induced anti-tumor immunity against B16 melanoma in C57/BL6 mice, whereas control xenogeneic extracts and B16 tumor extracts where ineffective, or actually promoted tumor growth, respectively. Furthermore, dendritic cells were able to prime tumor immunity when pulsed with the placental xenoantigens. While vaccination-induced tumor regression was abolished in mice depleted of CD4 T cells, both CD4 and CD8 cells were needed to adoptively transfer immunity to naïve mice. Supporting the role of CD8 cells in controlling tumor growth are findings that only freshly isolated CD8 cells from immunized mice were capable of inducing tumor cell caspases-3 activation ex vivo. These data suggest feasibility of using xenogeneic placental preparations as a multivalent vaccine potently targeting not just tumor antigens, but processes that are essential for tumor maintenance of malignant potential.

  18. Integrated Circuit Immunity

    Science.gov (United States)

    Sketoe, J. G.; Clark, Anthony

    2000-01-01

    This paper presents a DOD E3 program overview on integrated circuit immunity. The topics include: 1) EMI Immunity Testing; 2) Threshold Definition; 3) Bias Tee Function; 4) Bias Tee Calibration Set-Up; 5) EDM Test Figure; 6) EMI Immunity Levels; 7) NAND vs. and Gate Immunity; 8) TTL vs. LS Immunity Levels; 9) TP vs. OC Immunity Levels; 10) 7805 Volt Reg Immunity; and 11) Seventies Chip Set. This paper is presented in viewgraph form.

  19. Oral immune therapy: targeting the systemic immune system via the gut immune system for the treatment of inflammatory bowel disease.

    Science.gov (United States)

    Ilan, Yaron

    2016-01-01

    Inflammatory bowel diseases (IBD) are associated with an altered systemic immune response leading to inflammation-mediated damage to the gut and other organs. Oral immune therapy is a method of systemic immune modulation via alteration of the gut immune system. It uses the inherit ability of the innate system of the gut to redirect the systemic innate and adaptive immune responses. Oral immune therapy is an attractive clinical approach to treat autoimmune and inflammatory disorders. It can induce immune modulation without immune suppression, has minimal toxicity and is easily administered. Targeting the systemic immune system via the gut immune system can serve as an attractive novel therapeutic method for IBD. This review summarizes the current data and discusses several examples of oral immune therapeutic methods for using the gut immune system to generate signals to reset systemic immunity as a treatment for IBD.

  20. Evidence of inflammatory immune signaling in chronic fatigue syndrome: A pilot study of gene expression in peripheral blood

    Directory of Open Access Journals (Sweden)

    Vernon Suzanne D

    2008-09-01

    Full Text Available Abstract Background Genomic profiling of peripheral blood reveals altered immunity in chronic fatigue syndrome (CFS however interpretation remains challenging without immune demographic context. The object of this work is to identify modulation of specific immune functional components and restructuring of co-expression networks characteristic of CFS using the quantitative genomics of peripheral blood. Methods Gene sets were constructed a priori for CD4+ T cells, CD8+ T cells, CD19+ B cells, CD14+ monocytes and CD16+ neutrophils from published data. A group of 111 women were classified using empiric case definition (U.S. Centers for Disease Control and Prevention and unsupervised latent cluster analysis (LCA. Microarray profiles of peripheral blood were analyzed for expression of leukocyte-specific gene sets and characteristic changes in co-expression identified from topological evaluation of linear correlation networks. Results Median expression for a set of 6 genes preferentially up-regulated in CD19+ B cells was significantly lower in CFS (p = 0.01 due mainly to PTPRK and TSPAN3 expression. Although no other gene set was differentially expressed at p Conclusion Dissection of blood microarray profiles points to B cell dysfunction with coordinated immune activation supporting persistent inflammation and antibody-mediated NK cell modulation of T cell activity. This has clinical implications as the CD19+ genes identified could provide robust and biologically meaningful basis for the early detection and unambiguous phenotyping of CFS.

  1. Impacto del síndrome metabólico en la resistencia a la recanalización arterial y en el pronóstico de los pacientes con oclusión aguda de la arteria cerebral media tratados con activador tisular del plasminógeno

    OpenAIRE

    Dorado Bouix, Laura

    2012-01-01

    La recanalización arterial precoz es un punto clave para alcanzar un buen pronóstico funcional tras un ictus isquémico. El síndrome metabólico (SM) podría jugar un papel en la evolución de los pacientes con ictus isquémico tratados con activador tisular del plasminógeno (tPA) por vía sistémica (a) por su asociación a un estado protrombótico que podría interferir en la recanalización arterial inducida por tPA y (b) porque varias de las alteraciones metabólicas que acompañan al SM podrían contr...

  2. Impact of preferential sampling on exposure prediction and health effect inference in the context of air pollution epidemiology.

    Science.gov (United States)

    Lee, A; Szpiro, A; Kim, S Y; Sheppard, L

    2015-06-01

    Preferential sampling has been defined in the context of geostatistical modeling as the dependence between the sampling locations and the process that describes the spatial structure of the data. It can occur when networks are designed to find high values. For example, in networks based on the U.S. Clean Air Act monitors are sited to determine whether air quality standards are exceeded. We study the impact of the design of monitor networks in the context of air pollution epidemiology studies. The effect of preferential sampling has been illustrated in the literature by highlighting its impact on spatial predictions. In this paper, we use these predictions as input in a second stage analysis, and we assess how they affect health effect inference. Our work is motivated by data from two United States regulatory networks and health data from the Multi-Ethnic Study of Atherosclerosis and Air Pollution. The two networks were designed to monitor air pollution in urban and rural areas respectively, and we found that the health analysis results based on the two networks can lead to different scientific conclusions. We use preferential sampling to gain insight into these differences. We designed a simulation study, and found that the validity and reliability of the health effect estimate can be greatly affected by how we sample the monitor locations. To better understand its effect on second stage inference, we identify two components of preferential sampling that shed light on how preferential sampling alters the properties of the health effect estimate.

  3. The effect of trees on preferential flow and soil infiltrability in an agroforestry parkland in semiarid Burkina Faso

    Science.gov (United States)

    Bargués Tobella, A.; Reese, H.; Almaw, A.; Bayala, J.; Malmer, A.; Laudon, H.; Ilstedt, U.

    2014-04-01

    Water scarcity constrains the livelihoods of millions of people in tropical drylands. Tree planting in these environments is generally discouraged due to the large water consumption by trees, but this view may neglect their potential positive impacts on water availability. The effect of trees on soil hydraulic properties linked to groundwater recharge is poorly understood. In this study, we performed 18 rainfall simulations and tracer experiments in an agroforestry parkland in Burkina Faso to investigate the effect of trees and associated termite mounds on soil infiltrability and preferential flow. The sampling points were distributed in transects each consisting of three positions: (i) under a single tree, (ii) in the middle of an open area, and (iii) under a tree associated with a termite mound. The degree of preferential flow was quantified through parameters based on the dye infiltration patterns, which were analyzed using image analysis of photographs. Our results show that the degree of preferential flow was highest under trees associated with termite mounds, intermediate under single trees, and minimal in the open areas. Tree density also had an influence on the degree of preferential flow, with small open areas having more preferential flow than large ones. Soil infiltrability was higher under single trees than in the open areas or under trees associated with a termite mound. The findings from this study demonstrate that trees have a positive impact on soil hydraulic properties influencing groundwater recharge, and thus such effects must be considered when evaluating the impact of trees on water resources in drylands.

  4. Impact of preferential sampling on exposure prediction and health effect inference in the context of air pollution epidemiology

    Science.gov (United States)

    Lee, A.; Szpiro, A.; Kim, S.Y.; Sheppard, L.

    2018-01-01

    Summary Preferential sampling has been defined in the context of geostatistical modeling as the dependence between the sampling locations and the process that describes the spatial structure of the data. It can occur when networks are designed to find high values. For example, in networks based on the U.S. Clean Air Act monitors are sited to determine whether air quality standards are exceeded. We study the impact of the design of monitor networks in the context of air pollution epidemiology studies. The effect of preferential sampling has been illustrated in the literature by highlighting its impact on spatial predictions. In this paper, we use these predictions as input in a second stage analysis, and we assess how they affect health effect inference. Our work is motivated by data from two United States regulatory networks and health data from the Multi-Ethnic Study of Atherosclerosis and Air Pollution. The two networks were designed to monitor air pollution in urban and rural areas respectively, and we found that the health analysis results based on the two networks can lead to different scientific conclusions. We use preferential sampling to gain insight into these differences. We designed a simulation study, and found that the validity and reliability of the health effect estimate can be greatly affected by how we sample the monitor locations. To better understand its effect on second stage inference, we identify two components of preferential sampling that shed light on how preferential sampling alters the properties of the health effect estimate. PMID:29576734

  5. Purification and characterization of tenerplasminin-1, a serine peptidase inhibitor with antiplasmin activity from the coral snake (Micrurus tener tener) venom.

    Science.gov (United States)

    Vivas, Jeilyn; Ibarra, Carlos; Salazar, Ana M; Neves-Ferreira, Ana G C; Sánchez, Elda E; Perales, Jonás; Rodríguez-Acosta, Alexis; Guerrero, Belsy

    2016-01-01

    A plasmin inhibitor, named tenerplasminin-1 (TP1), was isolated from Micrurus tener tener (Mtt) venom. It showed a molecular mass of 6542Da, similarly to Kunitz-type serine peptidase inhibitors. The amidolytic activity of plasmin (0.5nM) on synthetic substrate S-2251 was inhibited by 91% following the incubation with TP1 (1nM). Aprotinin (2nM) used as the positive control of inhibition, reduced the plasmin amidolytic activity by 71%. Plasmin fibrinolytic activity (0.05nM) was inhibited by 67% following incubation with TP1 (0.1nM). The degradation of fibrinogen chains induced by plasmin, trypsin or elastase was inhibited by TP1 at a 1:2, 1:4 and 1:20 enzyme:inhibitor ratio, respectively. On the other hand, the proteolytic activity of crude Mtt venom on fibrinogen chains, previously attributed to metallopeptidases, was not abolished by TP1. The tPA-clot lysis assay showed that TP1 (0.2nM) acts like aprotinin (0.4nM) inducing a delay in lysis time and lysis rate which may be associated with the inhibition of plasmin generated from the endogenous plasminogen activation. TP1 is the first serine protease plasmin-like inhibitor isolated from Mtt snake venom which has been characterized in relation to its mechanism of action, formation of a plasmin:TP1 complex and therapeutic potential as anti-fibrinolytic agent, a biological characteristic of great interest in the field of biomedical research. They could be used to regulate the fibrinolytic system in pathologies such as metastatic cancer, parasitic infections, hemophilia and other hemorrhagic syndromes, in which an intense fibrinolytic activity is observed. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. The multifaceted roles of Leptospira enolase.

    Science.gov (United States)

    Salazar, Natália; Souza, Matilde Costa Lima de; Biasioli, Amanda Gameiro; Silva, Ludmila Bezerra da; Barbosa, Angela Silva

    A previous study had demonstrated that Leptospira enolase is secreted extracellularly by a yet unknown mechanism and reassociates with the bacterial membrane. Surface-anchored leptospiral enolase displays plasminogen binding activity. In this work, we explored the consequences of this interaction and also assessed whether Leptospira enolase might display additional moonlighting functions by interacting with other host effector proteins. We first demonstrated that enolase-bound plasminogen is converted to its active form, plasmin. The protease plasmin targets human fibrinogen and vitronectin, but not the complement proteins C3b and C5. Leptospira enolase also acts as an immune evasion protein by interacting with the negative complement regulators C4b binding protein and factor H. Once bound to enolase, both regulators remain functional as cofactors of factor I, mediating cleavage of C4b and C3b. In conclusion, enolase may facilitate leptospiral survival and dissemination, thus contributing to bacterial virulence. The identification and characterization of moonlighting proteins is a growing field of bacterial pathogenesis, as these multifaceted proteins may represent potential future therapeutic targets to fight bacterial infections. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  7. Secapin, a bee venom peptide, exhibits anti-fibrinolytic, anti-elastolytic, and anti-microbial activities.

    Science.gov (United States)

    Lee, Kwang Sik; Kim, Bo Yeon; Yoon, Hyung Joo; Choi, Yong Soo; Jin, Byung Rae

    2016-10-01

    Bee venom contains a variety of peptide constituents that have various biological, toxicological, and pharmacological actions. However, the biological actions of secapin, a venom peptide in bee venom, remain largely unknown. Here, we provide the evidence that Asiatic honeybee (Apis cerana) secapin (AcSecapin-1) exhibits anti-fibrinolytic, anti-elastolytic, and anti-microbial activities. The recombinant mature AcSecapin-1 peptide was expressed in baculovirus-infected insect cells. AcSecapin-1 functions as a serine protease inhibitor-like peptide that has inhibitory effects against plasmin, elastases, microbial serine proteases, trypsin, and chymotrypsin. Consistent with these functions, AcSecapin-1 inhibited the plasmin-mediated degradation of fibrin to fibrin degradation products, thus indicating the role of AcSecapin-1 as an anti-fibrinolytic agent. AcSecapin-1 also inhibited both human neutrophil and porcine pancreatic elastases. Furthermore, AcSecapin-1 bound to bacterial and fungal surfaces and exhibited anti-microbial activity against fungi and gram-positive and gram-negative bacteria. Taken together, our data demonstrated that the bee venom peptide secapin has multifunctional roles as an anti-fibrinolytic agent during fibrinolysis and an anti-microbial agent in the innate immune response. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Linking soil moisture balance and source-responsive models to estimate diffuse and preferential components of groundwater recharge

    Science.gov (United States)

    Cuthbert, M.O.; Mackay, R.; Nimmo, J.R.

    2012-01-01

    Results are presented of a detailed study into the vadose zone and shallow water table hydrodynamics of a field site in Shropshire, UK. A conceptual model is developed and tested using a range of numerical models, including a modified soil moisture balance model (SMBM) for estimating groundwater recharge in the presence of both diffuse and preferential flow components. Tensiometry reveals that the loamy sand topsoil wets up via macropore flow and subsequent redistribution of moisture into the soil matrix. Recharge does not occur until near-positive pressures are achieved at the top of the sandy glaciofluvial outwash material that underlies the topsoil, about 1 m above the water table. Once this occurs, very rapid water table rises follow. This threshold behaviour is attributed to the vertical discontinuity in the macropore system due to seasonal ploughing of the topsoil, and a lower permeability plough/iron pan restricting matrix flow between the topsoil and the lower outwash deposits. Although the wetting process in the topsoil is complex, a SMBM is shown to be effective in predicting the initiation of preferential flow from the base of the topsoil into the lower outwash horizon. The rapidity of the response at the water table and a water table rise during the summer period while flow gradients in the unsaturated profile were upward suggest that preferential flow is also occurring within the outwash deposits below the topsoil. A variation of the source-responsive model proposed by Nimmo (2010) is shown to reproduce the observed water table dynamics well in the lower outwash horizon when linked to a SMBM that quantifies the potential recharge from the topsoil. The results reveal new insights into preferential flow processes in cultivated soils and provide a useful and practical approach to accounting for preferential flow in studies of groundwater recharge estimation.

  9. Characterization of the preferential movement of elements during sputtering of binary targets

    International Nuclear Information System (INIS)

    Davarya, F.

    1982-01-01

    The knowledge of the physics of ion bombardment effects has matured considerably during the last decade. This has generated an ever increasing number of new applications and the subsequent need for better understanding of the collisional interaction, especially in bombardment of multicomponent materials. This research investigates the near-surface composition changes due to the preferential movement of target elements in binary systems under ion bombardment. The Monte-Carlo code EVOLVE, which has been developed at the University of Maryland for ion transport studies, has been utilized for these investigations. The effects of differences in three key parameters, surface binding energy, displacement energy, and mass of target elements have been studied. It has been observed that in the absence of any binding energy differences, the effect of the mass difference of target elements is contrary to the previously commonly held belief that the lighter target elements tend to be preferentially implanted inward relative to the heavier elements. Cases are presented where preferential inward movement of the heavier elements were observed. Further studies were carried out using EVOLVE and it has been observed that the heavier elements, while having shorter path length relative to the lighter elements, have a longer projected penetration depth. Due to the lack of standard reference materials (SRM's) for studing ion bombardment effects, quantitative comparison of results obtained using different techniques has been unreliable. In an effort to help resolve this need, multilayered thin-film structures (prepared for SRM use) have been studied using both experimental techniques and computer simulaton. The characteristics of those structures which are useful for SMR application, such as layer thickness, layer periodicity, and interface widths are presented

  10. A Review on Preferential Oxidation of Carbon Monoxide in Hydrogen Rich Gases

    Directory of Open Access Journals (Sweden)

    A. Mishra

    2011-05-01

    Full Text Available In this review, recent works on the preferential oxidation of carbon monoxide in hydrogen rich gases for fuel cell applications are summarized. H2 is used as a fuel for polymer-electrolyte membrane fuel cell (PEMFC. It is produced by reforming of natural gas or liquid fuels followed by water gas shift reaction. The produced gas consists of H2, CO, and CO2. In which CO content is around 1%, which is highly poisonous for the Pt anode of the PEMFC so that further removal of CO is needed. Catalytic preferential oxidation of CO (CO-PROX is one of the most suitable methods of purification of H2 because of high CO conversion rate at low temperature range, which is preferable for PEMFC operating conditions. Catalysts used for COPROX are mainly noble metal based; gold based and base metal oxide catalysts among them Copper-Ceria based catalysts are the most appropriate due to its low cost, easy availability and result obtained by these catalysts are comparable with the conventional noble metal catalysts. Copyright © 2011 BCREC UNDIP. All rights reserved(Received: 22nd October 2010, Revised: 12nd January 2011, Accepted: 19th January 2011[How to Cite: A. Mishra, R. Prasad. (2011. A Review on Preferential Oxidation of Carbon Monoxide in Hydrogen Rich Gases. Bulletin of Chemical Reaction Engineering & Catalysis, 6 (1: 1-14. doi:10.9767/bcrec.6.1.191.1-14][How to Link / DOI: http://dx.doi.org/10.9767/bcrec.6.1.191.1-14 || or local:  http://ejournal.undip.ac.id/index.php/bcrec/article/view/191] | View in 

  11. Adaptation in the innate immune system and heterologous innate immunity.

    Science.gov (United States)

    Martin, Stefan F

    2014-11-01

    The innate immune system recognizes deviation from homeostasis caused by infectious or non-infectious assaults. The threshold for its activation seems to be established by a calibration process that includes sensing of microbial molecular patterns from commensal bacteria and of endogenous signals. It is becoming increasingly clear that adaptive features, a hallmark of the adaptive immune system, can also be identified in the innate immune system. Such adaptations can result in the manifestation of a primed state of immune and tissue cells with a decreased activation threshold. This keeps the system poised to react quickly. Moreover, the fact that the innate immune system recognizes a wide variety of danger signals via pattern recognition receptors that often activate the same signaling pathways allows for heterologous innate immune stimulation. This implies that, for example, the innate immune response to an infection can be modified by co-infections or other innate stimuli. This "design feature" of the innate immune system has many implications for our understanding of individual susceptibility to diseases or responsiveness to therapies and vaccinations. In this article, adaptive features of the innate immune system as well as heterologous innate immunity and their implications are discussed.

  12. Using Dye Tracer for Visualization of Preferential Flow at Macro- and Microscales

    Czech Academy of Sciences Publication Activity Database

    Kodešová, R.; Němeček, K.; Kodeš, V.; Žigová, Anna

    2012-01-01

    Roč. 11, č. 1 (2012), s. 287-295 ISSN 1539-1663 R&D Projects: GA ČR GA526/08/0434 Institutional research plan: CEZ:AV0Z30130516 Keywords : dye tracer * preferential flow * soil types * macro- and microsccale Subject RIV: DF - Soil Science Impact factor: 2.200, year: 2012

  13. 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...

  14. Preferential site occupancy of alloying elements in TiAl-based phases

    Energy Technology Data Exchange (ETDEWEB)

    Holec, David, E-mail: david.holec@unileoben.ac.at; Reddy, Rajeev K.; Klein, Thomas; Clemens, Helmut [Department of Physical Metallurgy and Materials Testing, Montanuniversität Leoben, Franz-Josef-Strasse 18, A-8700 Leoben (Austria)

    2016-05-28

    First principles calculations are used to study the preferential occupation of ternary alloying additions into the binary Ti-Al phases, namely, γ-TiAl, α{sub 2}-Ti{sub 3}Al, β{sub o}-TiAl, and B19-TiAl. While the early transition metals (TMs, group IVB, VB, and VIB elements) prefer to substitute for Ti atoms in the γ-, α{sub 2}-, and B19-phases, they preferentially occupy Al sites in the β{sub o}-TiAl. Si is, in this context, an anomaly, as it prefers to sit on the Al sublattice for all four phases. B and C are shown to prefer octahedral Ti-rich interstitial positions instead of substitutional incorporation. The site preference energy is linked with the alloying-induced changes of energy of formation, hence alloying-related (de)stabilisation of the phases. We further show that the phase-stabilisation effect of early TMs on β{sub o}-phase has a different origin depending on their valency. Finally, an extensive comparison of our predictions with available theoretical and experimental data (which is, however, limited mostly to the γ-phase) shows a consistent picture.

  15. An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode

    Science.gov (United States)

    Doni, Andrea; Musso, Tiziana; Morone, Diego; Bastone, Antonio; Zambelli, Vanessa; Sironi, Marina; Castagnoli, Carlotta; Cambieri, Irene; Stravalaci, Matteo; Pasqualini, Fabio; Laface, Ilaria; Valentino, Sonia; Tartari, Silvia; Ponzetta, Andrea; Maina, Virginia; Barbieri, Silvia S.; Tremoli, Elena; Catapano, Alberico L.; Norata, Giuseppe D.; Bottazzi, Barbara; Garlanda, Cecilia

    2015-01-01

    Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule and a key component of the humoral arm of innate immunity. In four different models of tissue damage in mice, PTX3 deficiency was associated with increased fibrin deposition and persistence, and thicker clots, followed by increased collagen deposition, when compared with controls. Ptx3-deficient macrophages showed defective pericellular fibrinolysis in vitro. PTX3-bound fibrinogen/fibrin and plasminogen at acidic pH and increased plasmin-mediated fibrinolysis. The second exon-encoded N-terminal domain of PTX3 recapitulated the activity of the intact molecule. Thus, a prototypic component of humoral innate immunity, PTX3, plays a nonredundant role in the orchestration of tissue repair and remodeling. Tissue acidification resulting from metabolic adaptation during tissue repair sets PTX3 in a tissue remodeling and repair mode, suggesting that matrix and microbial recognition are common, ancestral features of the humoral arm of innate immunity. PMID:25964372

  16. Measuring polio immunity to plan immunization activities.

    Science.gov (United States)

    Voorman, Arend; Lyons, Hil M

    2016-11-21

    The Global Polio Eradication Initiative is closer than ever to achieving a polio-free world. Immunization activities must still be carried out in non-endemic countries to maintain population immunity at levels which will stop poliovirus from spreading if it is re-introduced from still-infected areas. In areas where there is no active transmission of poliovirus, programs must rely on surrogate indicators of population immunity to determine the appropriate immunization activities, typically caregiver-reported vaccination history obtained from non-polio acute flaccid paralysis patients identified through polio surveillance. We used regression models to examine the relationship between polio vaccination campaigns and caregiver-reported polio vaccination history. We find that in many countries, vaccination campaigns have a surprisingly weak impact on these commonly used indicators. We conclude that alternative criteria and data, such as routine immunization indicators from vaccination records or household surveys, should be considered for planning polio vaccination campaigns, and that validation of such surrogate indicators is necessary if they are to be used as the basis for program planning and risk assessment. We recommend that the GPEI and similar organizations consider or continue devoting additional resources to rigorously study population immunity and campaign effectiveness in at-risk countries. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Proteolysis of plasminogen activator inhibitor-1 by Yersinia pestis remodulates the host environment to promote virulence.

    Science.gov (United States)

    Eddy, J L; Schroeder, J A; Zimbler, D L; Caulfield, A J; Lathem, W W

    2016-09-01

    Essentials Effect of plasminogen activator inhibitor (PAI)-1 on plague and its Y. pestis cleavage is unknown. An intranasal mouse model of infection was used to determine the role of PAI-1 in pneumonic plague. PAI-1 is cleaved and inactivated by the Pla protease of Y. pestis in the lung airspace. PAI-1 impacts both bacterial outgrowth and the immune response to respiratory Y. pestis infection. Click to hear Dr Bock discuss pathogen activators of plasminogen. Background The hemostatic regulator plasminogen activator inhibitor-1 (PAI-1) inactivates endogenous plasminogen activators and aids in the immune response to bacterial infection. Yersinia pestis, the causative agent of plague, produces the Pla protease, a virulence factor that is required during plague. However, the specific hemostatic proteins cleaved by Pla in vivo that contribute to pathogenesis have not yet been fully elucidated. Objectives To determine whether PAI-1 is cleaved by the Pla protease during pneumonic plague, and to define the impact of PAI-1 on Y. pestis respiratory infection in the presence or absence of Pla. Methods An intranasal mouse model of pneumonic plague was used to assess the levels of total and active PAI-1 in the lung airspace, and the impact of PAI-1 deficiency on bacterial pathogenesis, the host immune response and plasmin generation following infection with wild-type or ∆pla Y. pestis. Results We found that Y. pestis cleaves and inactivates PAI-1 in the lungs in a Pla-dependent manner. The loss of PAI-1 enhances Y. pestis outgrowth in the absence of Pla, and is associated with increased conversion of plasminogen to plasmin. Furthermore, we found that PAI-1 regulates immune cell recruitment, cytokine production and tissue permeability during pneumonic plague. Conclusions Our data demonstrate that PAI-1 is an in vivo target of the Pla protease in the lungs, and that PAI-1 is a key regulator of the pulmonary innate immune response. We conclude that the inactivation of PAI-1 by Y

  18. Targeted detection of in vivo endogenous DNA base damage reveals preferential base excision repair in the transcribed strand.

    Science.gov (United States)

    Reis, António M C; Mills, Wilbur K; Ramachandran, Ilangovan; Friedberg, Errol C; Thompson, David; Queimado, Lurdes

    2012-01-01

    Endogenous DNA damage is removed mainly via base excision repair (BER), however, whether there is preferential strand repair of endogenous DNA damage is still under intense debate. We developed a highly sensitive primer-anchored DNA damage detection assay (PADDA) to map and quantify in vivo endogenous DNA damage. Using PADDA, we documented significantly higher levels of endogenous damage in Saccharomyces cerevisiae cells in stationary phase than in exponential phase. We also documented that yeast BER-defective cells have significantly higher levels of endogenous DNA damage than isogenic wild-type cells at any phase of growth. PADDA provided detailed fingerprint analysis at the single-nucleotide level, documenting for the first time that persistent endogenous nucleotide damage in CAN1 co-localizes with previously reported spontaneous CAN1 mutations. To quickly and reliably quantify endogenous strand-specific DNA damage in the constitutively expressed CAN1 gene, we used PADDA on a real-time PCR setting. We demonstrate that wild-type cells repair endogenous damage preferentially on the CAN1 transcribed strand. In contrast, yeast BER-defective cells accumulate endogenous damage preferentially on the CAN1 transcribed strand. These data provide the first direct evidence for preferential strand repair of endogenous DNA damage and documents the major role of BER in this process.

  19. Immunizations challenge healthcare personnel and affects immunization rates.

    Science.gov (United States)

    Strohfus, Pamela K; Kim, Susan C; Palma, Sara; Duke, Russell A; Remington, Richard; Roberts, Caleb

    2017-02-01

    This study measured 1. medical office immunization rates and 2. health care personnel competency in managing vaccine practices before and after evidence-based immunization education was provided. This descriptive study compared 32 family medicine and pediatric offices and 178 medical assistants, licensed practical nurses, registered nurses, nurse practitioners, and physicians in knowledge-based testing pre-education, post-education, and 12-months post-education. Immunization rates were assessed before and 18-months post-education. Immunization rates increased 10.3% - 18months post-education; knowledge increased 7.8% - 12months post-education. Family medicine offices, licensed practical nurses, and medical assistants showed significant knowledge deficits before and 12-months post-education. All demographic groups scored less in storage/handling 12-months post-education. This study is one of the first studies to identify competency challenges in effective immunization delivery among medical assistants, licensed practical nurses, and family medicine offices. Formal and continuous education in immunization administration and storage/handling is recommended among these select groups. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. A rare subset of skin-tropic regulatory T cells expressing Il10/Gzmb inhibits the cutaneous immune response.

    Science.gov (United States)

    Ikebuchi, Ryoyo; Teraguchi, Shunsuke; Vandenbon, Alexis; Honda, Tetsuya; Shand, Francis H W; Nakanishi, Yasutaka; Watanabe, Takeshi; Tomura, Michio

    2016-10-19

    Foxp3 + regulatory T cells (Tregs) migrating from the skin to the draining lymph node (dLN) have a strong immunosuppressive effect on the cutaneous immune response. However, the subpopulations responsible for their inhibitory function remain unclear. We investigated single-cell gene expression heterogeneity in Tregs from the dLN of inflamed skin in a contact hypersensitivity model. The immunosuppressive genes Ctla4 and Tgfb1 were expressed in the majority of Tregs. Although Il10-expressing Tregs were rare, unexpectedly, the majority of Il10-expressing Tregs co-expressed Gzmb and displayed Th1-skewing. Single-cell profiling revealed that CD43 + CCR5 + Tregs represented the main subset within the Il10/Gzmb-expressing cell population in the dLN. Moreover, CD43 + CCR5 + CXCR3 - Tregs expressed skin-tropic chemokine receptors, were preferentially retained in inflamed skin and downregulated the cutaneous immune response. The identification of a rare Treg subset co-expressing multiple immunosuppressive molecules and having tissue-remaining capacity offers a novel strategy for the control of skin inflammatory responses.

  1. Immunization

    Science.gov (United States)

    ... a lot worse. Some are even life-threatening. Immunization shots, or vaccinations, are essential. They protect against ... B, polio, tetanus, diphtheria, and pertussis (whooping cough). Immunizations are important for adults as well as children. ...

  2. 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.

  3. Dynamic preferential allocation to arbuscular mycorrhizal fungi explains fungal succession and coexistence.

    Science.gov (United States)

    Bachelot, Benedicte; Lee, Charlotte T

    2018-02-01

    Evidence accumulates about the role of arbuscular mycorrhizal (AM) fungi in shaping plant communities, but little is known about the factors determining the biomass and coexistence of several types of AM fungi in a plant community. Here, using a consumer-resource framework that treats the relationship between plants and fungi as simultaneous, reciprocal exploitation, we investigated what patterns of dynamic preferential plant carbon allocation to empirically-defined fungal types (on-going partner choice) would be optimal for plants, and how these patterns depend on successional dynamics. We found that ruderal AM fungi can dominate under low steady-state nutrient availability, and competitor AM fungi can dominate at higher steady-state nutrient availability; these are conditions characteristic of early and late succession, respectively. We also found that dynamic preferential allocation alone can maintain a diversity of mutualists, suggesting that on-going partner choice is a new coexistence mechanism for mutualists. Our model can therefore explain both mutualist coexistence and successional strategy, providing a powerful tool to derive testable predictions. © 2017 by the Ecological Society of America.

  4. Cross-immunity among allogeneic tumors of rats immunized with solid tumors

    International Nuclear Information System (INIS)

    Ogasawara, Masamichi

    1979-01-01

    Several experiments were done for the study of cross-immunity among allogeneic rat tumors by immunization using gamma-irradiated or non-irradiated solid tumors. Each group of rats which were immunized with gamma-irradiation solid tumor inocula from ascites tumor cell line of tetra-ploid Hirosaki sarcoma, Usubuchi sarcoma or AH 130, showed an apparent resistance against the intraperitoneal challenge with Hirosaki sarcoma. A similar resistance was demonstrated in the case of the challenge with Usubuchi sarcoma into rats immunized with non-irradiated methylcholanthrene (MCA)-induced tumors. In using solid MCA tumors as immunogen and Hirosaki sarcoma as challenge tumor, it was also demonstrated in 2 out of 3 groups immunized with non-irradiated tumors. In the experiment of trying to induce cross-immunity between 2 MCA tumors by immunization with irradiated solid tumor only, the inhibitory effect on the growth was observed in the early stage in the treated groups as compared with the control one. From the above results, it may be considered that the immunization with irradiated solid tumors fromas cites cell lines and non-irradiated solid MCA tumors induced strong cross-immunity in general, but that the immunization with only irradiated solid MCA tumors induced weak cross-immunity commonly. (author)

  5. The effect of chemical anti-inhibitors on fibrinolytic enzymes and inhibitors

    DEFF Research Database (Denmark)

    Sidelmann, Johannes Jakobsen; Jespersen, J; Kluft, C

    1997-01-01

    proteases. We studied the influence of chemical anti-inhibitors (chloramine T, flufenamate, sodium lauryl sulfate, and methylamine) on fibrinolytic serine proteases and fibrinolytic enzyme inhibitors using the physiological substrate fibrin as plasmin substrate. Low concentrations of chloramine T (0.01 mmol......%) and plasminogen activators (apparent recovery > 200%). Sodium lauryl sulfate eliminates the major fibrinolytic enzyme inhibitors, but increases the activity of plasmin (apparent recovery > 200%) and plasminogen activator, urokinase type (apparent recovery 130%). Methylamine affects only plasmin inhibition. We...

  6. How do preferential flow features connect? Combining tracers and excavation to examine hillslope flow pathways on Vancouver Island, British Columbia, Canada.

    Science.gov (United States)

    Anderson, A. E.; Weiler, M.

    2005-12-01

    Preferential flow is a complex process that influences water flow and solute transport in soils at different scales. Many studies have advanced our understanding about the physical structures of preferential pathways and their effects on water flow and solute transport at the column and plot scale. However, we still know very little about how preferential flow features connect over large distances and how they influence water flow and solute transport at the hillslope and catchment scale. Working in a forested watershed on northeast Vancouver Island in British Columbia, Canada, we conducted several artificial tracer experiments under natural and steady state flow conditions to investigate how water and solutes move through a hillslope section above a road cutbank. After these ``black-box'' tracer experiments we applied a blue food dye and excavated the hillslope to visualize the stained flow pathways. Under natural conditions two of the largest preferential features transmitted water at rates up to 30 liters/min. When a NaCl tracer was applied 12 m upslope of the road cutbank one soil pipe transmitted 97% of the recovered tracer during two large storms. When tracer was applied 30 m upslope of the road a more diffused response was observed. For the steady-state conditions we pumped water into trenches excavated at 12 m and 30 m above the road and then applied NaCl during constant outflow. Pumping water into the 12 m trench produced flow from only two preferential features, but a response in all preferential features was observed when water was pumped into the 30 m trench. The detailed excavations showed that the largest preferential feature was connected to the lower trench by large soil pipes at the interface of the organic and mineral soil horizons that were connected by flow through the organic soil. Other cross sections between 12 and 30 m upslope revealed concentrated flow through coarse mineral soil, diffused flow through mineral and organic soil, flow along

  7. Preferential Pathway for Glycine Formation in Star-Forming Regions

    Science.gov (United States)

    Pilling, S.; Boechat-Roberty, H. M.; Baptista, L.; Santos A. C., F.

    Interstellar clouds, similar to that from which the solar system was formed, contain many organic molecules including aldehydes, acids, ketones, and sugars Ehrenfreund & Charnley (2000). Those organic compounds have important functions in terrestrial biochemistry and could also have been important in prebiotic synthesis. The simplest amino acid, glycine (NH2CH2COOH), was recently detected in the hot molecular cores Sgr B2(N-LMH), Orion KL, and W51 e1/e2 Kuan et al. (2003). The formic acid (HCOOH) and acetic acid(CH3COOH) have also been detected in those regions Liu et al. (2002), Remijan et al. (2004). The goal of this work is to study experimentally photoionization and photodissociation processes of glycine precursor molecules, acetic acid and formic acid to elucidate a possible preferentially in the glycine synthesis between ice and gas phase. The measurements were taken at the Brazilian Synchrotron Light Laboratory (LNLS), employing soft X-ray photons from a toroidal grating monochromator TGM) beamline (100 - 310 eV). The experimental set up consists of a high vacuum chamber with a Time-Of-Flight Mass Spectrometer (TOF-MS). Mass spectra were obtained using PhotoElectron PhotoIon Coincidence (PEPICO) technique. Kinetic energy distributions and abundances for each ionic fragment have been obtained from the analysis of the corresponding peak shapes in the mass spectra. Dissociative and non-dissociative photoionization cross sections for both molecules were also determined Boechat-Roberty, Pilling & Santos (2005). Due to the high photodissociation cross section of formic acid it is possible that in PDRs regions, just after molecules evaporation from the grains surface, it is almost destructed by soft X-rays, justifying the observed low abundance of HCOOH in gaseous phase Ehrenfreund et al. (2001). Acetic acid have shown to be more stable to the ionizing field, and its main outcomes from dissociation process were the reactive ionic fragments COOH+ and CH3CO+. To

  8. Microbial-immune cross-talk and regulation of the immune system.

    Science.gov (United States)

    Cahenzli, Julia; Balmer, Maria L; McCoy, Kathy D

    2013-01-01

    We are all born germ-free. Following birth we enter into a lifelong relationship with microbes residing on our body's surfaces. The lower intestine is home to the highest microbial density in our body, which is also the highest microbial density known on Earth (up to 10(12) /g of luminal contents). With our indigenous microbial cells outnumbering our human cells by an order of magnitude our body is more microbial than human. Numerous immune adaptations confine these microbes within the mucosa, enabling most of us to live in peaceful homeostasis with our intestinal symbionts. Intestinal epithelial cells not only form a physical barrier between the bacteria-laden lumen and the rest of the body but also function as multi-tasking immune cells that sense the prevailing microbial (apical) and immune (basolateral) milieus, instruct the underlying immune cells, and adapt functionally. In the constant effort to ensure intestinal homeostasis, the immune system becomes educated to respond appropriately and in turn immune status can shape the microbial consortia. Here we review how the dynamic immune-microbial dialogue underlies maturation and regulation of the immune system and discuss recent findings on the impact of diet on both microbial ecology and immune function. © 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd.

  9. Hamiltonian dynamics of preferential attachment

    International Nuclear Information System (INIS)

    Zuev, Konstantin; Papadopoulos, Fragkiskos; Krioukov, Dmitri

    2016-01-01

    Prediction and control of network dynamics are grand-challenge problems in network science. The lack of understanding of fundamental laws driving the dynamics of networks is among the reasons why many practical problems of great significance remain unsolved for decades. Here we study the dynamics of networks evolving according to preferential attachment (PA), known to approximate well the large-scale growth dynamics of a variety of real networks. We show that this dynamics is Hamiltonian, thus casting the study of complex networks dynamics to the powerful canonical formalism, in which the time evolution of a dynamical system is described by Hamilton’s equations. We derive the explicit form of the Hamiltonian that governs network growth in PA. This Hamiltonian turns out to be nearly identical to graph energy in the configuration model, which shows that the ensemble of random graphs generated by PA is nearly identical to the ensemble of random graphs with scale-free degree distributions. In other words, PA generates nothing but random graphs with power-law degree distribution. The extension of the developed canonical formalism for network analysis to richer geometric network models with non-degenerate groups of symmetries may eventually lead to a system of equations describing network dynamics at small scales. (paper)

  10. Modelling rapid subsurface flow at the hillslope scale with explicit representation of preferential flow paths

    Science.gov (United States)

    Wienhöfer, J.; Zehe, E.

    2012-04-01

    Rapid lateral flow processes via preferential flow paths are widely accepted to play a key role for rainfall-runoff response in temperate humid headwater catchments. A quantitative description of these processes, however, is still a major challenge in hydrological research, not least because detailed information about the architecture of subsurface flow paths are often impossible to obtain at a natural site without disturbing the system. Our study combines physically based modelling and field observations with the objective to better understand how flow network configurations influence the hydrological response of hillslopes. The system under investigation is a forested hillslope with a small perennial spring at the study area Heumöser, a headwater catchment of the Dornbirnerach in Vorarlberg, Austria. In-situ points measurements of field-saturated hydraulic conductivity and dye staining experiments at the plot scale revealed that shrinkage cracks and biogenic macropores function as preferential flow paths in the fine-textured soils of the study area, and these preferential flow structures were active in fast subsurface transport of artificial tracers at the hillslope scale. For modelling of water and solute transport, we followed the approach of implementing preferential flow paths as spatially explicit structures of high hydraulic conductivity and low retention within the 2D process-based model CATFLOW. Many potential configurations of the flow path network were generated as realisations of a stochastic process informed by macropore characteristics derived from the plot scale observations. Together with different realisations of soil hydraulic parameters, this approach results in a Monte Carlo study. The model setups were used for short-term simulation of a sprinkling and tracer experiment, and the results were evaluated against measured discharges and tracer breakthrough curves. Although both criteria were taken for model evaluation, still several model setups

  11. Our Immune System

    Science.gov (United States)

    Our Immune System A story for children with primary immunodeficiency diseases Written by Sara LeBien IMMUNE DEFICIENCY FOUNDATION A note ... who are immune deficient to better understand their immune system. What is a “ B-cell, ” a “ T-cell, ” ...

  12. Stability of the octameric structure affects plasminogen-binding capacity of streptococcal enolase.

    Directory of Open Access Journals (Sweden)

    Amanda J Cork

    Full Text Available Group A Streptococcus (GAS is a human pathogen that has the potential to cause invasive disease by binding and activating human plasmin(ogen. Streptococcal surface enolase (SEN is an octameric α-enolase that is localized at the GAS cell surface. In addition to its glycolytic role inside the cell, SEN functions as a receptor for plasmin(ogen on the bacterial surface, but the understanding of the molecular basis of plasmin(ogen binding is limited. In this study, we determined the crystal and solution structures of GAS SEN and characterized the increased plasminogen binding by two SEN mutants. The plasminogen binding ability of SENK312A and SENK362A is ~2- and ~3.4-fold greater than for the wild-type protein. A combination of thermal stability assays, native mass spectrometry and X-ray crystallography approaches shows that increased plasminogen binding ability correlates with decreased stability of the octamer. We propose that decreased stability of the octameric structure facilitates the access of plasmin(ogen to its binding sites, leading to more efficient plasmin(ogen binding and activation.

  13. Preferential emission of photon emulsion nuclei in high energy nuclear disintegration

    International Nuclear Information System (INIS)

    Sarkar, Subir; Bhattacharjee, B.; Goswami, T.D.

    1997-01-01

    In the present work an effort has been made to observe such preferential emission, if any, in the CNO group of photo emulsion nuclei. Here the angle between any two slow (β b = 3,4,5 and 6. Assuming the fragments to be emitted isotropically as expected from evaporation theory, possible angles between any two tracks are computed separately for disintegrating centres with the same number of N b

  14. Exploring the antecedents of preferential customer treatment by suppliers: a mixed methods approach

    NARCIS (Netherlands)

    Huttinger, Lisa; Schiele, Holger; Schröer, Dennis

    2014-01-01

    Purpose – This paper aims to understand the factors that influence a supplier’s choice to treat selected customers more preferentially than others. Suppliers often lack the resources to treat all their customers equally, instead having to make choices to treat some customers as preferred. Empirical

  15. Immunization Coverage

    Science.gov (United States)

    ... room/fact-sheets/detail/immunization-coverage","@context":"http://schema.org","@type":"Article"}; العربية 中文 français русский español ... Plan Global Health Observatory (GHO) data - Immunization More information on vaccines and immunization News 1 in 10 ...

  16. Development of magnetic nanoparticle based calorimetric assay for the detection of bovine mastitis in cow milk.

    Science.gov (United States)

    Chinnappan, Raja; Al Attas, Sana; Kaman, Wendy E; Bikker, Floris J; Zourob, Mohammed

    2017-04-15

    Mastitis in dairy cattle is an inflammatory reaction of the udder tissue. Mastitis increases plasmin levels, leading to an increased proteolysis of milk proteins such as casein, resulting in a significant decrease in milk quality and related dairy products. Due to its key-role in mastitis, we used plasmin proteolytic activity as a biomarker for the detection of mastitis in bovine mastitic milk. Inspired by earlier studies on protease activity using mastitic milk samples, we developed a simple colorimetric assay to distinguish mastitic milk from milk derived from healthy animals. The plasmin substrate coupled to magnetic nanoparticles form a black self-assembled monolayer on a gold sensor surface. In the presence of increased levels of plasmin, the substrate is cleaved and the peptide fragment attached to the magnetic beads, will be attracted by the magnet which is present under the sensor strips revealing the golden surface. We found the area of the golden color surface proportional to plasmin activity. The sensitivity of this method was determined to be 1 ng/ml of plasmin in vitro. Next, we tested the biosensor using mastitis positive milk of which infection is confirmed by bacterial cultures. This newly developed colorimetric biosensor has high potential in applications for the diagnosis of mastitis with potential spin offs to health, food and environmental sectors. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. 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

  18. Immune Evasion, Immunopathology and the Regulation of the Immune System

    Directory of Open Access Journals (Sweden)

    Bruno Faivre

    2013-02-01

    Full Text Available Costs and benefits of the immune response have attracted considerable attention in the last years among evolutionary biologists. Given the cost of parasitism, natural selection should favor individuals with the most effective immune defenses. Nevertheless, there exists huge variation in the expression of immune effectors among individuals. To explain this apparent paradox, it has been suggested that an over-reactive immune system might be too costly, both in terms of metabolic resources and risks of immune-mediated diseases, setting a limit to the investment into immune defenses. Here, we argue that this view neglects one important aspect of the interaction: the role played by evolving pathogens. We suggest that taking into account the co-evolutionary interactions between the host immune system and the parasitic strategies to overcome the immune response might provide a better picture of the selective pressures that shape the evolution of immune functioning. Integrating parasitic strategies of host exploitation can also contribute to understand the seemingly contradictory results that infection can enhance, but also protect from, autoimmune diseases. In the last decades, the incidence of autoimmune disorders has dramatically increased in wealthy countries of the northern hemisphere with a concomitant decrease of most parasitic infections. Experimental work on model organisms has shown that this pattern may be due to the protective role of certain parasites (i.e., helminths that rely on the immunosuppression of hosts for their persistence. Interestingly, although parasite-induced immunosuppression can protect against autoimmunity, it can obviously favor the spread of other infections. Therefore, we need to think about the evolution of the immune system using a multidimensional trade-off involving immunoprotection, immunopathology and the parasitic strategies to escape the immune response.

  19. Immunity's fourth dimension: approaching the circadian-immune connection.

    Science.gov (United States)

    Arjona, Alvaro; Silver, Adam C; Walker, Wendy E; Fikrig, Erol

    2012-12-01

    The circadian system ensures the generation and maintenance of self-sustained ~24-h rhythms in physiology that are linked to internal and environmental changes. In mammals, daily variations in light intensity and other cues are integrated by a hypothalamic master clock that conveys circadian information to peripheral molecular clocks that orchestrate physiology. Multiple immune parameters also vary throughout the day and disruption of circadian homeostasis is associated with immune-related disease. Here, we discuss the molecular links between the circadian and immune systems and examine their outputs and disease implications. Understanding the mechanisms that underlie circadian-immune crosstalk may prove valuable for devising novel prophylactic and therapeutic interventions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Vaccines (immunizations) - overview

    Science.gov (United States)

    Vaccinations; Immunizations; Immunize; Vaccine shots; Prevention - vaccine ... of the vaccine. VACCINE SCHEDULE The recommended vaccination (immunization) schedule is updated every 12 months by the ...

  1. Alternative Immune Systems

    Directory of Open Access Journals (Sweden)

    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.

  2. Estimation and upscaling of dual-permeability model parameters for the transport of E.coli D21g in soils with preferential flow

    Science.gov (United States)

    Dual-permeability models are increasingly used to quantify the transport of solutes and microorganisms in soils with preferential flow. An ability to accurately determine the model parameters and their variation with preferential pathway characteristics is crucial for predicting the transport of mi...

  3. Cyclosporin A preferentially attenuates skeletal slow-twitch muscle regeneration

    Directory of Open Access Journals (Sweden)

    Miyabara E.H.

    2005-01-01

    Full Text Available Calcineurin, a Ca2+/calmodulin-dependent phosphatase, is associated with muscle regeneration via NFATc1/GATA2-dependent pathways. However, it is not clear whether calcineurin preferentially affects the regeneration of slow- or fast-twitch muscles. We investigated the effect of a calcineurin inhibitor, cyclosporin A (CsA, on the morphology and fiber diameter of regenerating slow- and fast-twitch muscles. Adult Wistar rats (259.5 ± 9 g maintained under standard conditions were treated with CsA (20 mg/kg body weight, ip for 5 days, submitted to cryolesion of soleus and tibialis anterior (TA muscles on the 6th day, and then treated with CsA for an additional 21 days. The muscles were removed, weighed, frozen, and stored in liquid nitrogen. Cryolesion did not alter the body weight gain of the animals after 21 days of regeneration (P = 0.001 and CsA significantly reduced the body weight gain (15.5%; P = 0.01 during the same period. All treated TA and soleus muscles showed decreased weights (17 and 29%, respectively, P < 0.05. CsA treatment decreased the cross-sectional area of both soleus and TA muscles of cryoinjured animals (TA: 2108 ± 930 vs 792 ± 640 µm²; soleus: 2209 ± 322 vs 764 ± 439 m²; P < 0.001. Histological sections of both muscles stained with Toluidine blue revealed similar regenerative responses after cryolesion. In addition, CsA was able to minimize these responses, i.e., centralized nuclei and split fibers, more efficiently so in TA muscle. These results indicate that calcineurin preferentially plays a role in regeneration of slow-twitch muscle.

  4. Rapid runoff via shallow throughflow and deeper preferential flow in a boreal catchment underlain by frozen silt (Alaska, USA)

    Science.gov (United States)

    Koch, Joshua C.; Ewing, Stephanie A.; Striegl, Robert G.; McKnight, Diane M.

    2013-01-01

    In high-latitude catchments where permafrost is present, runoff dynamics are complicated by seasonal active-layer thaw, which may cause a change in the dominant flowpaths as water increasingly contacts mineral soils of low hydraulic conductivity. A 2-year study, conducted in an upland catchment in Alaska (USA) underlain by frozen, well-sorted eolian silt, examined changes in infiltration and runoff with thaw. It was hypothesized that rapid runoff would be maintained by flow through shallow soils during the early summer and deeper preferential flow later in the summer. Seasonal changes in soil moisture, infiltration, and runoff magnitude, location, and chemistry suggest that transport is rapid, even when soils are thawed to their maximum extent. Between June and September, a shift occurred in the location of runoff, consistent with subsurface preferential flow in steep and wet areas. Uranium isotopes suggest that late summer runoff erodes permafrost, indicating that substantial rapid flow may occur along the frozen boundary. Together, throughflow and deep preferential flow may limit upland boreal catchment water and solute storage, and subsequently biogeochemical cycling on seasonal to annual timescales. Deep preferential flow may be important for stream incision, network drainage development, and the release of ancient carbon to ecosystems

  5. Preferential lentiviral targeting of astrocytes in the central nervous system.

    Directory of Open Access Journals (Sweden)

    Michael Fassler

    Full Text Available The ability to visualize and genetically manipulate specific cell populations of the central nervous system (CNS is fundamental to a better understanding of brain functions at the cellular and molecular levels. Tools to selectively target cells of the CNS include molecular genetics, imaging, and use of transgenic animals. However, these approaches are technically challenging, time consuming, and difficult to control. Viral-mediated targeting of cells in the CNS can be highly beneficial for studying and treating neurodegenerative diseases. Yet, despite specific marking of numerous cell types in the CNS, in vivo selective targeting of astrocytes has not been optimized. In this study, preferential targeting of astrocytes in the CNS was demonstrated using engineered lentiviruses that were pseudotyped with a modified Sindbis envelope and displayed anti-GLAST IgG on their surfaces as an attachment moiety. Viral tropism for astrocytes was initially verified in vitro in primary mixed glia cultures. When injected into the brains of mice, lentiviruses that displayed GLAST IgG on their surface, exhibited preferential astrocyte targeting, compared to pseudotyped lentiviruses that did not incorporate any IgG or that expressed a control isotype IgG. Overall, this approach is highly flexible and can be exploited to selectively target astrocytes or other cell types of the CNS. As such, it can open a window to visualize and genetically manipulate astrocytes or other cells of the CNS as means of research and treatment.

  6. The twilight of immunity: emerging concepts in aging of the immune system.

    Science.gov (United States)

    Nikolich-Žugich, Janko

    2018-01-01

    Immunosenescence is a series of age-related changes that affect the immune system and, with time, lead to increased vulnerability to infectious diseases. This Review addresses recent developments in the understanding of age-related changes that affect key components of immunity, including the effect of aging on cells of the (mostly adaptive) immune system, on soluble molecules that guide the maintenance and function of the immune system and on lymphoid organs that coordinate both the maintenance of lymphocytes and the initiation of immune responses. I further address the effect of the metagenome and exposome as key modifiers of immune-system aging and discuss a conceptual framework in which age-related changes in immunity might also affect the basic rules by which the immune system operates.

  7. Inert Carbon Nanoparticles for the Assessment of Preferential Flow in Saturated Dual-Permeability Porous Media

    KAUST Repository

    Yao, Chuanjin; Zhao, Yushi; Lei, Guanglun; Steenhuis, Tammo S.; Cathles, Lawrence M.

    2017-01-01

    appropriately, nanoparticles together with a chemical tracer can assess the preferential flow in heterogeneous environments. The results also implement the dual tracer tests in heterogeneous environments by simultaneously injecting chemical and nanoparticle

  8. Lack of mucosal immune reconstitution during prolonged treatment of acute and early HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Saurabh Mehandru

    2006-12-01

    Full Text Available During acute and early HIV-1 infection (AEI, up to 60% of CD4(+ T cells in the lamina propria of the lower gastrointestinal (GI tract are lost as early as 2-4 wk after infection. Reconstitution in the peripheral blood during therapy with highly active antiretroviral therapy (HAART is well established. However, the extent of immune reconstitution in the GI tract is unknown.Fifty-four AEI patients and 18 uninfected control participants underwent colonic biopsy. Forty of the 54 AEI patients were followed after initiation of antiretroviral therapy (18 were studied longitudinally with sequential biopsies over a 3-y period after beginning HAART, and 22 were studied cross sectionally after 1-7 y of uninterrupted therapy. Lymphocyte subsets, markers of immune activation and memory in the peripheral blood and GI tract were determined by flow cytometry and immunohistochemistry. In situ hybridization was performed in order to identify persistent HIV-1 RNA expression. Of the patients studied, 70% maintained, on average, a 50%-60% depletion of lamina propria lymphocytes despite 1-7 y of HAART. Lymphocytes expressing CCR5 and both CCR5 and CXCR4 were persistently and preferentially depleted. Levels of immune activation in the memory cell population, CD45RO+ HLA-DR+, returned to levels seen in the uninfected control participants in the peripheral blood, but were elevated in the GI tract of patients with persistent CD4+ T cell depletion despite therapy. Rare HIV-1 RNA-expressing cells were detected by in situ hybridization.Apparently suppressive treatment with HAART during acute and early infection does not lead to complete immune reconstitution in the GI mucosa in the majority of patients studied, despite immune reconstitution in the peripheral blood. Though the mechanism remains obscure, the data suggest that there is either viral or immune-mediated accelerated T cell destruction or, possibly, alterations in T cell homing to the GI tract. Although clinically

  9. 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.

  10. A nonproliferating parvovirus vaccine vector elicits sustained, protective humoral immunity following a single intravenous or intranasal inoculation.

    Science.gov (United States)

    Palmer, Gene A; Brogdon, Jennifer L; Constant, Stephanie L; Tattersall, Peter

    2004-02-01

    An ideal vaccine delivery system would elicit persistent protection following a single administration, preferably by a noninvasive route, and be safe even in the face of immunosuppression, either inherited or acquired, of the recipient. We have exploited the unique life cycle of the autonomous parvoviruses to develop a nonproliferating vaccine platform that appears to both induce priming and continually boost a protective immune response following a single inoculation. A crippled parvovirus vector was constructed, based on a chimera between minute virus of mice (MVM) and LuIII, which expresses Borrelia burgdorferi outer surface protein A (OspA) instead of its coat protein. The vector was packaged into an MVM lymphotropic capsid and inoculated into naive C3H/HeNcr mice. Vaccination with a single vector dose, either intravenously or intranasally, elicited high-titer anti-OspA-specific antibody that provided protection from live spirochete challenge and was sustained over the lifetime of the animal. Both humoral and cell-mediated Th(1) immunity was induced, as shown by anti-OspA immunoglobulin G2a antibody and preferential gamma interferon production by OspA-specific CD4(+) T cells.

  11. Embryonic common snapping turtles (Chelydra serpentina) preferentially regulate intracellular tissue pH during acid-base challenges.

    Science.gov (United States)

    Shartau, Ryan B; Crossley, Dane A; Kohl, Zachary F; Brauner, Colin J

    2016-07-01

    The nests of embryonic turtles naturally experience elevated CO2 (hypercarbia), which leads to increased blood PCO2  and a respiratory acidosis, resulting in reduced blood pH [extracellular pH (pHe)]. Some fishes preferentially regulate tissue pH [intracellular pH (pHi)] against changes in pHe; this has been proposed to be associated with exceptional CO2 tolerance and has never been identified in amniotes. As embryonic turtles may be CO2 tolerant based on nesting strategy, we hypothesized that they preferentially regulate pHi, conferring tolerance to severe acute acid-base challenges. This hypothesis was tested by investigating pH regulation in common snapping turtles (Chelydra serpentina) reared in normoxia then exposed to hypercarbia (13 kPa PCO2 ) for 1 h at three developmental ages: 70% and 90% of incubation, and yearlings. Hypercarbia reduced pHe but not pHi, at all developmental ages. At 70% of incubation, pHe was depressed by 0.324 pH units while pHi of brain, white muscle and lung increased; heart, liver and kidney pHi remained unchanged. At 90% of incubation, pHe was depressed by 0.352 pH units but heart pHi increased with no change in pHi of other tissues. Yearlings exhibited a pHe reduction of 0.235 pH units but had no changes in pHi of any tissues. The results indicate common snapping turtles preferentially regulate pHi during development, but the degree of response is reduced throughout development. This is the first time preferential pHi regulation has been identified in an amniote. These findings may provide insight into the evolution of acid-base homeostasis during development of amniotes, and vertebrates in general. © 2016. Published by The Company of Biologists Ltd.

  12. Childhood immunization

    Science.gov (United States)

    Romain, Sandra; Schillaci, Michael A.

    2009-01-01

    ABSTRACT OBJECTIVE To examine childhood immunization levels relative to the number of family physicians, pediatricians, and public health nurses in Ontario. DESIGN Retrospective comparative analysis of publicly available data on immunization coverage levels and the relative number of family physicians, pediatricians, and public health nurses. SETTING Ontario. PARTICIPANTS Seven-year-old children, family physicians, pediatricians, and public health nurses in Ontario. MAIN OUTCOME MEASURES The association between immunization coverage levels and the relative number of family physicians, pediatricians, and public health nurses. RESULTS We found correlations between immunization coverage levels and the relative number (ie, per 1000 Ontario residents) of family physicians (ρ = 0.60) and pediatricians (ρ = 0.70) and a lower correlation with the relative number of public health nurses (ρ = 0.40), although none of these correlations was significant. A comparison of temporal trends illustrated that variation in the relative number of family physicians and pediatricians in Ontario was associated with similar variation in immunization coverage levels. CONCLUSION Increasing the number of family physicians and pediatricians might help to boost access to immunizations and perhaps other components of cost-saving childhood preventive care. PMID:19910599

  13. Immune-Modulating Perspectives for Low Frequency Electromagnetic Fields in Innate Immunity

    Directory of Open Access Journals (Sweden)

    Maria Manuela Rosado

    2018-03-01

    Full Text Available In recent years, the effects of electromagnetic fields (EMFs on the immune system have received a considerable interest, not only to investigate possible negative health impact but also to explore the possibility to favorably modulate immune responses. To generate beneficial responses, the immune system should eradicate pathogens while “respecting” the organism and tolerating irrelevant antigens. According to the current view, damage-associated molecules released by infected or injured cells, or secreted by innate immune cells generate danger signals activating an immune response. These signals are also relevant to the subsequent activation of homeostatic mechanisms that control the immune response in pro- or anti-inflammatory reactions, a feature that allows modulation by therapeutic treatments. In the present review, we describe and discuss the effects of extremely low frequency (ELF-EMF and pulsed EMF on cell signals and factors relevant to the activation of danger signals and innate immunity cells. By discussing the EMF modulating effects on cell functions, we envisage the use of EMF as a therapeutic agent to regulate immune responses associated with wound healing.

  14. Winning the competition for supplier resources: The role of preferential resource allocation from suppliers

    NARCIS (Netherlands)

    Pulles, Niels Jaring; Veldman, Jasper; Schiele, Holger

    2016-01-01

    Purpose This paper examines the competition between buying firms for the supplier’s competitive resources. The purpose of this paper is to examine how indirect capabilities – the ability to access external resources – can help in obtaining preferential resource allocation from suppliers.

  15. The Dynamics of Power laws: Fitness and Aging in Preferential Attachment Trees

    Science.gov (United States)

    Garavaglia, Alessandro; van der Hofstad, Remco; Woeginger, Gerhard

    2017-09-01

    Continuous-time branching processes describe the evolution of a population whose individuals generate a random number of children according to a birth process. Such branching processes can be used to understand preferential attachment models in which the birth rates are linear functions. We are motivated by citation networks, where power-law citation counts are observed as well as aging in the citation patterns. To model this, we introduce fitness and age-dependence in these birth processes. The multiplicative fitness moderates the rate at which children are born, while the aging is integrable, so that individuals receives a finite number of children in their lifetime. We show the existence of a limiting degree distribution for such processes. In the preferential attachment case, where fitness and aging are absent, this limiting degree distribution is known to have power-law tails. We show that the limiting degree distribution has exponential tails for bounded fitnesses in the presence of integrable aging, while the power-law tail is restored when integrable aging is combined with fitness with unbounded support with at most exponential tails. In the absence of integrable aging, such processes are explosive.

  16. CRISPR-Cas systems exploit viral DNA injection to establish and maintain adaptive immunity.

    Science.gov (United States)

    Modell, Joshua W; Jiang, Wenyan; Marraffini, Luciano A

    2017-04-06

    Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems provide protection against viral and plasmid infection by capturing short DNA sequences from these invaders and integrating them into the CRISPR locus of the prokaryotic host. These sequences, known as spacers, are transcribed into short CRISPR RNA guides that specify the cleavage site of Cas nucleases in the genome of the invader. It is not known when spacer sequences are acquired during viral infection. Here, to investigate this, we tracked spacer acquisition in Staphylococcus aureus cells harbouring a type II CRISPR-Cas9 system after infection with the staphylococcal bacteriophage ϕ12. We found that new spacers were acquired immediately after infection preferentially from the cos site, the viral free DNA end that is first injected into the cell. Analysis of spacer acquisition after infection with mutant phages demonstrated that most spacers are acquired during DNA injection, but not during other stages of the viral cycle that produce free DNA ends, such as DNA replication or packaging. Finally, we showed that spacers acquired from early-injected genomic regions, which direct Cas9 cleavage of the viral DNA immediately after infection, provide better immunity than spacers acquired from late-injected regions. Our results reveal that CRISPR-Cas systems exploit the phage life cycle to generate a pattern of spacer acquisition that ensures a successful CRISPR immune response.

  17. Immune oncology, immune responsiveness and the theory of everything.

    Science.gov (United States)

    Turan, Tolga; Kannan, Deepti; Patel, Maulik; Matthew Barnes, J; Tanlimco, Sonia G; Lu, Rongze; Halliwill, Kyle; Kongpachith, Sarah; Kline, Douglas E; Hendrickx, Wouter; Cesano, Alessandra; Butterfield, Lisa H; Kaufman, Howard L; Hudson, Thomas J; Bedognetti, Davide; Marincola, Francesco; Samayoa, Josue

    2018-06-05

    Anti-cancer immunotherapy is encountering its own checkpoint. Responses are dramatic and long lasting but occur in a subset of tumors and are largely dependent upon the pre-existing immune contexture of individual cancers. Available data suggest that three landscapes best define the cancer microenvironment: immune-active, immune-deserted and immune-excluded. This trichotomy is observable across most solid tumors (although the frequency of each landscape varies depending on tumor tissue of origin) and is associated with cancer prognosis and response to checkpoint inhibitor therapy (CIT). Various gene signatures (e.g. Immunological Constant of Rejection - ICR and Tumor Inflammation Signature - TIS) that delineate these landscapes have been described by different groups. In an effort to explain the mechanisms of cancer immune responsiveness or resistance to CIT, several models have been proposed that are loosely associated with the three landscapes. Here, we propose a strategy to integrate compelling data from various paradigms into a "Theory of Everything". Founded upon this unified theory, we also propose the creation of a task force led by the Society for Immunotherapy of Cancer (SITC) aimed at systematically addressing salient questions relevant to cancer immune responsiveness and immune evasion. This multidisciplinary effort will encompass aspects of genetics, tumor cell biology, and immunology that are pertinent to the understanding of this multifaceted problem.

  18. Sculpting humoral immunity through dengue vaccination to enhance protective immunity

    Directory of Open Access Journals (Sweden)

    Wayne eCrill

    2012-11-01

    Full Text Available Dengue viruses (DENV are the most important mosquito transmitted viral pathogens infecting humans. DENV infection produces a spectrum of disease, most commonly causing a self-limiting flu-like illness known as dengue fever; yet with increased frequency, manifesting as life-threatening dengue hemorrhagic fever (DHF. Waning cross-protective immunity from any of the four dengue serotypes may enhance subsequent infection with another heterologous serotype to increase the probability of DHF. Decades of effort to develop dengue vaccines are reaching the finishing line with multiple candidates in clinical trials. Nevertheless, concerns remain that imbalanced immunity, due to the prolonged prime-boost schedules currently used in clinical trials, could leave some vaccinees temporarily unprotected or with increased susceptibility to enhanced disease. Here we develop a DENV serotype 1 (DENV-1 DNA vaccine with the immunodominant cross-reactive B cell epitopes associated with immune enhancement removed. We compare wild-type (WT with this cross-reactivity reduced (CRR vaccine and demonstrate that both vaccines are equally protective against lethal homologous DENV-1 challenge. Under conditions mimicking natural exposure prior to acquiring protective immunity, WT vaccinated mice enhanced a normally sub-lethal heterologous DENV-2 infection resulting in DHF-like disease and 95% mortality in AG129 mice. However, CRR vaccinated mice exhibited redirected serotype-specific and protective immunity, and significantly reduced morbidity and mortality not differing from naïve mice. Thus, we demonstrate in an in vivo DENV disease model, that non-protective vaccine-induced immunity can prime vaccinees for enhanced DHF-like disease and that CRR DNA immunization significantly reduces this potential vaccine safety concern. The sculpting of immune memory by the modified vaccine and resulting redirection of humoral immunity provide insight into DENV vaccine induced immune

  19. Scale-free behavior of networks with the copresence of preferential and uniform attachment rules

    Science.gov (United States)

    Pachon, Angelica; Sacerdote, Laura; Yang, Shuyi

    2018-05-01

    Complex networks in different areas exhibit degree distributions with a heavy upper tail. A preferential attachment mechanism in a growth process produces a graph with this feature. We herein investigate a variant of the simple preferential attachment model, whose modifications are interesting for two main reasons: to analyze more realistic models and to study the robustness of the scale-free behavior of the degree distribution. We introduce and study a model which takes into account two different attachment rules: a preferential attachment mechanism (with probability 1 - p) that stresses the rich get richer system, and a uniform choice (with probability p) for the most recent nodes, i.e. the nodes belonging to a window of size w to the left of the last born node. The latter highlights a trend to select one of the last added nodes when no information is available. The recent nodes can be either a given fixed number or a proportion (αn) of the total number of existing nodes. In the first case, we prove that this model exhibits an asymptotically power-law degree distribution. The same result is then illustrated through simulations in the second case. When the window of recent nodes has a constant size, we herein prove that the presence of the uniform rule delays the starting time from which the asymptotic regime starts to hold. The mean number of nodes of degree k and the asymptotic degree distribution are also determined analytically. Finally, a sensitivity analysis on the parameters of the model is performed.

  20. Consequences of preferential flow in cracking clay soils for contamination-risk of shallow aquifers

    NARCIS (Netherlands)

    Oostindie, K.; Bronswijk, J.J.B.

    1995-01-01

    A method is presented to asses the contamination risk of aquifers covered with cracking clay soils, with special emphasis on preferential flow through shrinkage cracks. A water extraction area was divided into units with homogeneous soil types and hydrological conditions. For each unit, a

  1. Spatial connectivity in a highly heterogeneous aquifer: From cores to preferential flow paths

    Science.gov (United States)

    Bianchi, M.; Zheng, C.; Wilson, C.; Tick, G.R.; Liu, Gaisheng; Gorelick, S.M.

    2011-01-01

    This study investigates connectivity in a small portion of the extremely heterogeneous aquifer at the Macrodispersion Experiment (MADE) site in Columbus, Mississippi. A total of 19 fully penetrating soil cores were collected from a rectangular grid of 4 m by 4 m. Detailed grain size analysis was performed on 5 cm segments of each core, yielding 1740 hydraulic conductivity (K) estimates. Three different geostatistical simulation methods were used to generate 3-D conditional realizations of the K field for the sampled block. Particle tracking calculations showed that the fastest particles, as represented by the first 5% to arrive, converge along preferential flow paths and exit the model domain within preferred areas. These 5% fastest flow paths accounted for about 40% of the flow. The distribution of preferential flow paths and particle exit locations is clearly influenced by the occurrence of clusters formed by interconnected cells with K equal to or greater than the 0.9 decile of the data distribution (10% of the volume). The fraction of particle paths within the high-K clusters ranges from 43% to 69%. In variogram-based K fields, some of the fastest paths are through media with lower K values, suggesting that transport connectivity may not require fully connected zones of relatively homogenous K. The high degree of flow and transport connectivity was confirmed by the values of two groups of connectivity indicators. In particular, the ratio between effective and geometric mean K (on average, about 2) and the ratio between the average arrival time and the arrival time of the fastest particles (on average, about 9) are consistent with flow and advective transport behavior characterized by channeling along preferential flow paths. ?? 2011 by the American Geophysical Union.

  2. Preferential repair of nuclear matrix associated DNA in xeroderma pigmentosum complementation group C

    International Nuclear Information System (INIS)

    Mullenders, L.H.F.; Kesteren, A.C. van; Bussmann, C.J.M.; Zeeland, A.A. van; Natarajan, A.T.

    1984-01-01

    The distribution of ultraviolet-induced DNA repair patches in the genome of xeroderma pigmentosum cells of complementation group C was investigated by determining the molecular weight distribution of repair labeled DNA and prelabeled DNA in alkaline sucrose gradients after treatment with the dimer-specific endonuclease V of bacteriophage T 4 . The results suggest that DNA-repair synthesis in xeroderma pigmentosum cells of complementation group C occurs in localized regions of the genome. Analysis of the spatial distribution of ultraviolet-induced repair patches in DNA loops attached to the nuclear matrix revealed that in xeroderma pigmentosum cells of complementation group C repair patches are preferentially situated near the attachment sites of DNA loops at the nuclear matrix. In normal human fibroblasts the authors observed no enrichment of repair-labeled DNA at the nuclear matrix and repair patches appeared to be distributed randomly along the DNA loops. The enrichment of repair-labeled DNA at the nuclear matrix in xeroderma pigmentosum cells of complementation group C may indicate that the residual DNA-repair synthesis in these cells occurs preferentially in regions of the genome. (Auth.)

  3. Immune System Quiz

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Quiz: Immune System KidsHealth / For Kids / Quiz: Immune System Print How much do you know about your immune system? Find out by taking this quiz! About Us ...

  4. Convergent and Divergent Signaling in PAMP-Triggered Immunity and Effector-Triggered Immunity.

    Science.gov (United States)

    Peng, Yujun; van Wersch, Rowan; Zhang, Yuelin

    2018-04-01

    Plants use diverse immune receptors to sense pathogen attacks. Recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors localized on the plasma membrane leads to PAMP-triggered immunity (PTI). Detection of pathogen effectors by intracellular or plasma membrane-localized immune receptors results in effector-triggered immunity (ETI). Despite the large variations in the magnitude and duration of immune responses triggered by different PAMPs or pathogen effectors during PTI and ETI, plasma membrane-localized immune receptors activate similar downstream molecular events such as mitogen-activated protein kinase activation, oxidative burst, ion influx, and increased biosynthesis of plant defense hormones, indicating that defense signals initiated at the plasma membrane converge at later points. On the other hand, activation of ETI by immune receptors localized to the nucleus appears to be more directly associated with transcriptional regulation of defense gene expression. Here, we review recent progress in signal transductions downstream of different groups of plant immune receptors, highlighting the converging and diverging molecular events.

  5. Universal immunity to influenza must outwit immune evasion

    Directory of Open Access Journals (Sweden)

    Sergio Manuel Quinones-Parra

    2014-06-01

    Full Text Available Although an influenza vaccine has been available for 70 years, influenza virus still causes seasonal epidemics and worldwide pandemics. Currently available vaccines elicit strain-specific antibody responses to the surface haemagglutinin (HA and neuraminidase (NA proteins, but these can be ineffective against serologically-distinct viral variants and novel subtypes. Thus, there is a need for cross-protective or universal influenza vaccines to overcome the necessity for annual immunisation against seasonal influenza and to provide immunity to reduce the severity of infection with pandemic or outbreak viruses. It is well established that natural influenza infection can provide cross-reactive immunity that can reduce the impact of infection with distinct influenza type A strains and subtypes, including H1N1, H3N2, H2N2, H5N1 and H7N9. The key to generating universal influenza immunity via vaccination is to target functionally-conserved regions of the virus, which include epitopes on the internal proteins for cross-reactive T cell immunity or on the HA stem for broadly reactive antibody responses. In the wake of the 2009 H1N1 pandemic, broadly neutralizing antibodies have been characterized and isolated from convalescent and vaccinated individuals, inspiring development of new vaccination techniques to elicit such responses. Induction of influenza-specific T cell responses through vaccination has also been examined in clinical trials. Strong evidence is available from human and animal models of influenza to show that established influenza-specific T cell memory can reduce viral shedding and symptom severity. However, the published evidence also shows that CD8+ T cells can efficiently select immune escape mutants early after influenza virus infection. Here, we discuss universal immunity to influenza viruses mediated by both cross-reactive T cells and antibodies, the mechanisms of immune evasion in influenza, and how to counteract commonly occurring

  6. Immune regulation in gut and cord : opportunities for directing the immune system

    NARCIS (Netherlands)

    de Roock, S.

    2012-01-01

    The gut is an important organ for the immune system. Microbes and immune cells interact directly or via epithelial cells. Both TH17 and Treg cells mature in this environment. The composition of the microbiota has an important influence on the immune homeostasis. Influencing the immune system via the

  7. A conductivity study of preferential solvation of lithium ion in acetonitrile-dimethyl sulfoxide mixtures

    International Nuclear Information System (INIS)

    Mozhzhukhina, Nataliia; Longinotti, M. Paula; Corti, Horacio R.; Calvo, Ernesto J.

    2015-01-01

    The electrical mobility of LiPF 6 in acetonitrile–dimethyl sulfoxide (ACN–DMSO) mixtures, a potential electrolyte in oxygen cathodes of lithium-air batteries, has been studied using a very precise conductance technique, which allowed the determination of the infinite dilution molar conductivity and association constant of the salt in the whole composition range. In the search for preferential Li + ion solvation, we also measured the electrical conductivity of tetrabutylammonium hexafluorophosphate (TBAPF 6 ), a salt formed by a bulky cation, over the same composition range. The results show a qualitative change in the curvature of the LiPF 6 molar conductivity composition dependence for ACN molar fraction (x ACN ) ∼ 0.95, which was not observed for TBAPF 6 . The dependence of the measured Li/Li + couple potential with solvent composition also showed a pronounced change around the same composition. We suggest that these observations can be explained by Li + ion preferential solvation by DMSO in ACN–DMSO mixtures with very low molar fractions of DMSO

  8. Selection and characterization of camelid nanobodies towards urokinase-type plasminogen activator

    DEFF Research Database (Denmark)

    Kaczmarek, Jakub; Skottrup, Peter Durand

    2015-01-01

    Urokinase-type plasminogen activator (uPA) is a trypsin-like serine protease that plays a vital role in extracellular conversion of inactive plasminogen into catalytically active plasmin. Activated plasmin facilitates the release of several proteolytic enzymes, which control processes like perice...

  9. Angiostatin generating capacity and anti-tumour effects of D-penicillamine and plasminogen activators.

    NARCIS (Netherlands)

    Groot-Besseling, R. de; Ruers, T.J.M.; Lamers-Elemans, I.L.; Maass, C.N.; Waal, R.M.W. de; Westphal, J.R.

    2006-01-01

    BACKGROUND: Upregulation of endogenous angiostatin levels may constitute a novel anti-angiogenic, and therefore anti-tumor therapy. In vitro, angiostatin generation is a two-step process, starting with the conversion of plasminogen to plasmin by plasminogen activators (PAs). Next, plasmin excises

  10. Cytokine regulation of immune tolerance

    OpenAIRE

    Wu, Jie; Xie, Aini; Chen, Wenhao

    2014-01-01

    The immune system provides defenses against invading pathogens while maintaining immune tolerance to self-antigens. This immune homeostasis is harmonized by the direct interactions between immune cells and the cytokine environment in which immune cells develop and function. Herein, we discuss three non-redundant paradigms by which cytokines maintain or break immune tolerance. We firstly describe how anti-inflammatory cytokines exert direct inhibitory effects on immune cells to enforce immune ...

  11. Immunizations - diabetes

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000331.htm Immunizations - diabetes To use the sharing features on this page, please enable JavaScript. Immunizations (vaccines or vaccinations) help protect you from some ...

  12. Skin innate immune system

    Directory of Open Access Journals (Sweden)

    Berna Aksoy

    2013-06-01

    Full Text Available All multicellular organisms protect themselves from external universe and microorganisms by innate immune sytem that is constitutively present. Skin innate immune system has several different components composed of epithelial barriers, humoral factors and cellular part. In this review information about skin innate immune system and its components are presented to the reader. Innate immunity, which wasn’t adequately interested in previously, is proven to provide a powerfull early protection system, control many infections before the acquired immunity starts and directs acquired immunity to develop optimally

  13. Using the dye tracer for visualization of preferential flow in macro and micro-scale

    Czech Academy of Sciences Publication Activity Database

    Kodešová, R.; Němeček, K.; Kodeš, V.; Fér, M.; Jirků, V.; Nikodem, A.; Žigová, Anna; Jakšík, O.; Kočárek, M.

    2010-01-01

    Roč. 12, - (2010) ISSN 1029-7006. [European Geosciences Union General Assembly 2010. 02.05.2010-07.05.2010, Wienna] R&D Projects: GA ČR GA526/08/0434 Institutional research plan: CEZ:AV0Z30130516 Keywords : dye tracer * preferential flow * micromorphology Subject RIV: DF - Soil Science

  14. Kidney and innate immunity.

    Science.gov (United States)

    Wang, Ying-Hui; Zhang, Yu-Gen

    2017-03-01

    Innate immune system is an important modulator of the inflammatory response during infection and tissue injury/repair. The kidney as a vital organ with high energy demand plays a key role in regulating the disease related metabolic process. Increasing research interest has focused on the immune pathogenesis of many kidney diseases. However, innate immune cells such as dendritic cells, macrophages, NK cells and a few innate lymphocytes, as well as the complement system are essential for renal immune homeostasis and ensure a coordinated balance between tissue injury and regeneration. The innate immune response provides the first line of host defense initiated by several classes of pattern recognition receptors (PRRs), such as membrane-bound Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), together with inflammasomes responsible for early innate immune response. Although the innate immune system is well studied, the research on the detailed relationship between innate immunity and kidney is still very limited. In this review, we will focus on the innate immune sensing system in renal immune homeostasis, as well as the corresponding pathogenesis of many kidney diseases. The pivotal roles of innate immunity in renal injury and regeneration with special emphasis on kidney disease related immunoregulatory mechanism are also discussed. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  15. Childhood Immunization

    Science.gov (United States)

    ... lowest levels in history, thanks to years of immunization. Children must get at least some vaccines before ... child provide protection for many years, adults need immunizations too. Centers for Disease Control and Prevention

  16. Effects of Soil Compaction and Organic Carbon Content on Preferential Flow in Loamy Field Soils

    DEFF Research Database (Denmark)

    Soares, Antonio; Moldrup, Per; Vendelboe, Anders Lindblad

    2015-01-01

    Preferential flow and transport through macropores affects plant water use efficiency and enhances leaching of agrochemicals and the transport of colloids, thereby increasing the risk for contamination of groundwater resources. As part of the Danish Pesticide Leaching Assessment Program this study...

  17. [Immune system and tumors].

    Science.gov (United States)

    Terme, Magali; Tanchot, Corinne

    2017-02-01

    Despite having been much debated, it is now well established that the immune system plays an essential role in the fight against cancer. In this article, we will highlight the implication of the immune system in the control of tumor growth and describe the major components of the immune system involved in the antitumoral immune response. The immune system, while exerting pressure on tumor cells, also will play a pro-tumoral role by sculpting the immunogenicity of tumors cells as they develop. Finally, we will illustrate the numerous mechanisms of immune suppression that take place within the tumoral microenvironment which allow tumor cells to escape control from the immune system. The increasingly precise knowledge of the brakes to an effective antitumor immune response allows the development of immunotherapy strategies more and more innovating and promising of hope. Copyright © 2016. Published by Elsevier Masson SAS.

  18. 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

  19. 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

  20. 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.

  1. In defence of partisan justice - an ethical reflection on �the preferential option for the poor�

    Directory of Open Access Journals (Sweden)

    PJ Naude

    2007-09-01

    Full Text Available Can one defend a form of partisan justice? This question is answered in the affirmative in the light of two broad arguments:� The theological argument arises from the preferential option for the poor from Latin America, and the philosophical argument is derived from John Rawls�� notion of the least� advantaged representative person and assistance due to burdened societies in a global context. In closing, a number of important implications of such a partisan notion of both distributive and cultural justice are explicated. This article is developed in three sections. The first section briefly sketches a profile of the different theological arguments underlying a preferential option for the poor as particularly developed by Latin American liberation theologians, and later accepted in wider ecumenical circles.� In the second section, philosophical arguments for a position of �prioritarianism� which seems to support such �preferential option� are outlined.� This is attempted via a discussion of two influential books by well-known� American political philosopher , John Rawls, namely his A theory of justice (1973, and The law of peoples (1999.� Section three concludes the article by demonstrating the synergy between these theological and philosophical views, and by pointing out � in a provisional manner - the important consequences of such a �preferential� or �partisan� view for guiding ethical reflection on local and global socio-economic relations.

  2. A model of hydrological and mechanical feedbacks of preferential fissure flow in a slow-moving landslide

    Directory of Open Access Journals (Sweden)

    D. M. Krzeminska

    2013-03-01

    Full Text Available The importance of hydrological processes for landslide activity is generally accepted. However, the relationship between precipitation, hydrological responses and movement is not straightforward. Groundwater recharge is mostly controlled by the hydrological material properties and the structure (e.g., layering, preferential flow paths such as fissures of the unsaturated zone. In slow-moving landslides, differential displacements caused by the bedrock structure complicate the hydrological regime due to continuous opening and closing of the fissures, creating temporary preferential flow paths systems for infiltration and groundwater drainage. The consecutive opening and closing of fissure aperture control the formation of a critical pore water pressure by creating dynamic preferential flow paths for infiltration and groundwater drainage. This interaction may explain the seasonal nature of the slow-moving landslide activity, including the often observed shifts and delays in hydrological responses when compared to timing, intensity and duration of precipitation. The main objective of this study is to model the influence of fissures on the hydrological dynamics of slow-moving landslide and the dynamic feedbacks between fissures, hydrology and slope stability. For this we adapt the spatially distributed hydrological and slope stability model (STARWARS to account for geotechnical and hydrological feedbacks, linking between hydrological response of the landside and the dynamics of the fissure network and applied the model to the hydrologically controlled Super-Sauze landslide (South French Alps.

  3. Preferential production and transport of grass-derived pyrogenic carbon in NE-Australian savanna ecosystems

    Science.gov (United States)

    Saiz, Gustavo; Goodrick, Iain; Wurster, Christopher; Nelson, Paul N.; Wynn, Jonathan; Bird, Michael

    2017-12-01

    Understanding the main factors driving fire regimes in grasslands and savannas is critical to better manage their biodiversity and functions. Moreover, improving our knowledge on pyrogenic carbon (PyC) dynamics, including formation, transport and deposition, is fundamental to better understand a significant slow-cycling component of the global carbon cycle, particularly as these ecosystems account for a substantial proportion of the area globally burnt. However, a thorough assessment of past fire regimes in grass-dominated ecosystems is problematic due to challenges in interpreting the charcoal record of sediments. It is therefore critical to adopt appropriate sampling and analytical methods to allow the acquisition of reliable data and information on savanna fire dynamics. This study uses hydrogen pyrolysis (HyPy) to quantify PyC abundance and stable isotope composition (δ13C) in recent sediments across 38 micro-catchments covering a wide range of mixed C3/C4 vegetation in north Queensland, Australia. We exploited the contrasting δ13C values of grasses (i.e. C4; δ13C >-15‰) and woody vegetation (i.e. C3; δ13C <-24‰) to assess the preferential production and transport of grass-derived PyC in savanna ecosystems. Analyses were conducted on bulk and size-fractionated samples to determine the fractions into which PyC preferentially accumulates. Our data show that the δ13C value of PyC in the sediments is decoupled from the δ13C value of total organic carbon, which suggests that a significant component of PyC may be derived from incomplete grass combustion, even when the proportion of C4 grass biomass in the catchment was relatively small. Furthermore, we conducted 16 experimental burns that indicate that there is a comminution of PyC produced in-situ to smaller particles, which facilitates the transport of this material, potentially affecting its preservation potential. Savanna fires preferentially burn the grass understory rather than large trees, leading to

  4. Immunization coverage among Hispanic ancestry, 2003 National Immunization Survey.

    Science.gov (United States)

    Darling, Natalie J; Barker, Lawrence E; Shefer, Abigail M; Chu, Susan Y

    2005-12-01

    The Hispanic population is increasing and heterogeneous (Hispanic refers to persons of Spanish, Hispanic, or Latino descent). The objective was to examine immunization rates among Hispanic ancestry for the 4:3:1:3:3 series (> or = 4 doses diphtheria, tetanus toxoids, and pertussis vaccine; > or = 3 doses poliovirus vaccine; > or = 1 doses measles-containing vaccine; > or = 3 doses Haemophilus influenzae type b vaccine; and > or = 3 doses hepatitis B vaccine). The National Immunization Survey measures immunization coverage among 19- to 35-month-old U.S. children. Coverage was compared from combined 2001-2003 data among Hispanics and non-Hispanic whites using t-tests, and among Hispanic ancestry using a chi-square test. Hispanics were categorized as Mexican, Mexican American, Central American, South American, Puerto Rican, Cuban, Spanish Caribbean (primarily Dominican Republic), other, and multiple ancestry. Children of Hispanic ancestry increased from 21% in 1999 to 25% in 2003. These Hispanic children were less well immunized than non-Hispanic whites (77.0%, +/-2.1% [95% confidence interval] compared to 82.5%, +/-1.1% (95% CI) > in 2003). Immunization coverage did not vary significantly among Hispanics of varying ancestries (p=0.26); however, there was substantial geographic variability. In some areas, immunization coverage among Hispanics was significantly higher than non-Hispanic whites. Hispanic children were less well immunized than non-Hispanic whites; however, coverage varied notably by geographic area. Although a chi-square test found no significant differences in coverage among Hispanic ancestries, the range of coverage, 79.2%, +/-5.1% for Cuban Americans to 72.1%, +/-2.4% for Mexican descent, may suggest a need for improved and more localized monitoring among Hispanic communities.

  5. Plant innate immunity

    Indian Academy of Sciences (India)

    Plants are invaded by an array of pathogens of which only a few succeed in causing disease. The attack by others is countered by a sophisticated immune system possessed by the plants. The plant immune system is broadly divided into two, viz. microbial-associated molecular-patterns-triggered immunity (MTI) and ...

  6. Effects of long-term use of the preferential COX-2 inhibitor meloxicam on growing pigs

    NARCIS (Netherlands)

    Gorissen, Ben M C|info:eu-repo/dai/nl/372825788; Uilenreef, Joost J|info:eu-repo/dai/nl/30483095X; Bergmann, Willie|info:eu-repo/dai/nl/36275585X; Meijer, Ellen|info:eu-repo/dai/nl/375288015; van Rietbergen, Bert; van der Staay, Franz Josef|info:eu-repo/dai/nl/074262653; Weeren, P René van; Wolschrijn, Claudia F|info:eu-repo/dai/nl/271539496

    2017-01-01

    Meloxicam, a preferential COX-2 inhibitor, is a commonly used NSAID in pigs. Besides having potential side effects on the gastrointestinal tract, this type of drug might potentially affect osteogenesis and chondrogenesis, processes relevant to growing pigs. Therefore, the effects of long-term

  7. Immunization in pregnancy.

    Science.gov (United States)

    Gruslin, Andrée; Steben, Marc; Halperin, Scott; Money, Deborah M; Yudin, Mark H

    2009-11-01

    To review the evidence and provide recommendations on immunization in pregnancy. Outcomes evaluated include effectiveness of immunization, risks and benefits for mother and fetus. The Medline and Cochrane databases were searched for articles published up to June 2008 on the topic of immunization in pregnancy. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. Implementation of the recommendations in this guideline should result in more appropriate immunization of pregnant and breastfeeding women, decreased risk of contraindicated immunization, and better disease prevention. The quality of evidence reported in this document has been assessed using the evaluation of evidence criteria in the Report of the Canadian Task Force on Preventive Health Care (Table 1). (1) All women of childbearing age should be evaluated for the possibility of pregnancy before immunization. (III-A). (2) Health care providers should obtain a relevant immunization history from all women accessing prenatal care. (III-A). (3) In general, live and/or live-attenuated virus vaccines should not be administered during pregnancy, as there is a, largely theoretical, risk to the fetus. (II-3B). (4) Women who have inadvertently received immunization with live or live-attenuated vaccines during pregnancy should not be counselled to terminate the pregnancy because of a teratogenic risk. (II-2A). (5) Non-pregnant women immunized with a live or live-attenuated vaccine should be counselled to delay pregnancy for at least four weeks. (III-B). (6) Inactivated viral vaccines, bacterial vaccines, and toxoids can be used safely in pregnancy. (II-1A). (7) Women who are breastfeeding can still be immunized (passive-active immunization, live or killed

  8. The Immune System: Basis of so much Health and Disease: 3. Adaptive Immunity.

    Science.gov (United States)

    Scully, Crispian; Georgakopoulou, Eleni A; Hassona, Yazan

    2017-04-01

    The immune system is the body’s primary defence mechanism against infections, and disturbances in the system can cause disease if the system fails in defence functions (in immunocompromised people), or if the activity is detrimental to the host (as in auto-immune and auto-inflammatory states). A healthy immune system is also essential to normal health of dental and oral tissues. This series presents the basics for the understanding of the immune system; this article covers adaptive immunity. Clinical relevance: Dental clinicians need a basic understanding of the immune system as it underlies health and disease.

  9. [Characters of infiltration and preferential flow of black soil in Northeast China under different tillage patterns].

    Science.gov (United States)

    Li, Wen-Feng; Zhang, Xiao-Ping; Liang, Ai-Zhen; Shen, Yan; Shi, Xiu-Huan; Luo, Jin-Ming; Yang, Xue-Ming

    2008-07-01

    By using dye tracer and double-ring infiltrometer techniques, the characters of infiltration and preferential flow of black soil under no-tillage (NT) and fall moldboard plow (MP) were compared after six years continuous management. The results showed that the infiltration rate was higher under NT than under MP. When the infiltration reached steady, the infiltration rate and accumulative infiltration capacity under NT were 1.35 and 1.44 times as high as those under MP, respectively. The penetration depth of methylene blue reached a depth of 43 cm in NT soil, being 16 cm deeper than that in MP soil. Comparing with MP soil, NT soil had better development of pore structure and more biological pores, and presented better preferential flow character, which were of importance for water infiltration and soil and water conservation.

  10. Urine albumin is a superior predictor of preeclampsia compared to urine plasminogen in type I diabetes patients

    DEFF Research Database (Denmark)

    Nielsen, Lise Hald; Jensen, Boye L; Fuglsang, Jens

    2018-01-01

    Pregnant women with type I diabetes mellitus (T1DM) are at increased risk of developing preeclampsia (PE). Plasminogen is aberrantly filtrated from plasma into tubular fluid in PE patients and activated to plasmin. Plasmin activates the epithelial sodium channel in the collecting ducts potentially...

  11. Preferential solvation: dividing surface vs excess numbers.

    Science.gov (United States)

    Shimizu, Seishi; Matubayasi, Nobuyuki

    2014-04-10

    How do osmolytes affect the conformation and configuration of supramolecular assembly, such as ion channel opening and actin polymerization? The key to the answer lies in the excess solvation numbers of water and osmolyte molecules; these numbers are determinable solely from experimental data, as guaranteed by the phase rule, as we show through the exact solution theory of Kirkwood and Buff (KB). The osmotic stress technique (OST), in contrast, purposes to yield alternative hydration numbers through the use of the dividing surface borrowed from the adsorption theory. However, we show (i) OST is equivalent, when it becomes exact, to the crowding effect in which the osmolyte exclusion dominates over hydration; (ii) crowding is not the universal driving force of the osmolyte effect (e.g., actin polymerization); (iii) the dividing surface for solvation is useful only for crowding, unlike in the adsorption theory which necessitates its use due to the phase rule. KB thus clarifies the true meaning and limitations of the older perspectives on preferential solvation (such as solvent binding models, crowding, and OST), and enables excess number determination without any further assumptions.

  12. Short-ranged memory model with preferential growth

    Science.gov (United States)

    Schaigorodsky, Ana L.; Perotti, Juan I.; Almeira, Nahuel; Billoni, Orlando V.

    2018-02-01

    In this work we introduce a variant of the Yule-Simon model for preferential growth by incorporating a finite kernel to model the effects of bounded memory. We characterize the properties of the model combining analytical arguments with extensive numerical simulations. In particular, we analyze the lifetime and popularity distributions by mapping the model dynamics to corresponding Markov chains and branching processes, respectively. These distributions follow power laws with well-defined exponents that are within the range of the empirical data reported in ecologies. Interestingly, by varying the innovation rate, this simple out-of-equilibrium model exhibits many of the characteristics of a continuous phase transition and, around the critical point, it generates time series with power-law popularity, lifetime and interevent time distributions, and nontrivial temporal correlations, such as a bursty dynamics in analogy with the activity of solar flares. Our results suggest that an appropriate balance between innovation and oblivion rates could provide an explanatory framework for many of the properties commonly observed in many complex systems.

  13. 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.

  14. Immune system and melanoma biology: a balance between immunosurveillance and immune escape.

    Science.gov (United States)

    Passarelli, Anna; Mannavola, Francesco; Stucci, Luigia Stefania; Tucci, Marco; Silvestris, Francesco

    2017-12-01

    Melanoma is one of the most immunogenic tumors and its relationship with host immune system is currently under investigation. Many immunomodulatory mechanisms, favoring melanomagenesis and progression, have been described to interfere with the disablement of melanoma recognition and attack by immune cells resulting in immune resistance and immunosuppression. This knowledge produced therapeutic advantages, such as immunotherapy, aiming to overcome the immune evasion. Here, we review the current advances in cancer immunoediting and focus on melanoma immunology, which involves a dynamic interplay between melanoma and immune system, as well as on effects of "targeted therapies" on tumor microenvironment for combination strategies.

  15. Detection of preferential particle orientation in the atmosphere: Development of an alternative polarization lidar system

    International Nuclear Information System (INIS)

    Geier, Manfred; Arienti, Marco

    2014-01-01

    Increasing interest in polarimetric characterization of atmospheric aerosols has led to the development of complete sample-measuring (Mueller) polarimeters that are capable of measuring the entire backscattering phase matrix of a probed volume. These Mueller polarimeters consist of several moving parts, which limit measurement rates and complicate data analysis. In this paper, we present the concept of a less complex polarization lidar setup for detection of preferential orientation of atmospheric particulates. On the basis of theoretical considerations of data inversion stability and propagation of measurement uncertainties, an optimum optical configuration is established for two modes of operation (with either a linear or a circular polarized incident laser beam). The conceptualized setup falls in the category of incomplete sample-measuring polarimeters and uses four detection channels for simultaneous measurement of the backscattered light. The expected performance characteristics are discussed through an example of a typical aerosol with a small fraction of particles oriented in a preferred direction. The theoretical analysis suggests that achievable accuracies in backscatter cross-sections and depolarization ratios are similar to those with conventional two-channel configurations, while in addition preferential orientation can be detected with the proposed four-channel system for a wide range of conditions. - Highlights: • A theoretical study of a new four-channel lidar concept is offered. • Preferential particle orientation detection could be realized with minor device modifications. • The proposed configuration is optimized to balance inversion uncertainties. • Circular polarized beam is demonstrated to provide the best noise performance. • Operation with ultra-short pulses is proposed to quantify particle number density

  16. Personalized recommendation based on preferential bidirectional mass diffusion

    Science.gov (United States)

    Chen, Guilin; Gao, Tianrun; Zhu, Xuzhen; Tian, Hui; Yang, Zhao

    2017-03-01

    Recommendation system provides a promising way to alleviate the dilemma of information overload. In physical dynamics, mass diffusion has been used to design effective recommendation algorithms on bipartite network. However, most of the previous studies focus overwhelmingly on unidirectional mass diffusion from collected objects to uncollected objects, while overlooking the opposite direction, leading to the risk of similarity estimation deviation and performance degradation. In addition, they are biased towards recommending popular objects which will not necessarily promote the accuracy but make the recommendation lack diversity and novelty that indeed contribute to the vitality of the system. To overcome the aforementioned disadvantages, we propose a preferential bidirectional mass diffusion (PBMD) algorithm by penalizing the weight of popular objects in bidirectional diffusion. Experiments are evaluated on three benchmark datasets (Movielens, Netflix and Amazon) by 10-fold cross validation, and results indicate that PBMD remarkably outperforms the mainstream methods in accuracy, diversity and novelty.

  17. Emergency abdominal aortic aneurysm repair with a preferential endovascular strategy : Mortality and cost-effectiveness analysis

    NARCIS (Netherlands)

    Kapma, Marten R.; Groen, Henk; Oranen, Bjorn I.; van der Hilst, Christian S.; Tielliu, Ignace F.; Zeebregts, Clark J.; Prins, Ted R.; van den Dungen, Jan J.; Verhoeven, Eric L.

    2007-01-01

    Purpose: To assess mortality and treatment costs of a new management protocol with preferential use of emergency endovascular aneurysm repair (eEVAR) for acute abdominal aortic aneurysm (AAA). Methods: From September 2003 until February 2005, 49 consecutive patients (45 men; mean age 71 years) with

  18. Effects of long-term use of the preferential COX-2 inhibitor meloxicam on growing pigs

    NARCIS (Netherlands)

    Gorissen, B.M.C.; Uilenreef, J.J.; Bergmann, W.; Meijer, E.; van Rietbergen, B.; van der Staay, F.J.; van Weeren, P.R.; Wolschrijn, C.F.

    2017-01-01

    Meloxicam, a preferential COX-2 inhibitor, is a commonly used nSAID in pigs. Besides having potential side effects on the gastrointestinal tract, this type of drug might potentially affect osteogenesis and chondrogenesis, processes relevant to growing pigs. Therefore, the effects of long-term

  19. Immune System

    Science.gov (United States)

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  20. Preferential Trade Agreements and the Law and Politics of GATT Article XXIV

    DEFF Research Database (Denmark)

    Alavi, Amin

    2010-01-01

    The tasks Preferential Trade Agreements (PTAs) perform are expressed in their scope and covered issues, thus in order to be WTO compatible these aspects of PTAs should comply with the relevant WTO rules. This paper examines which aspects of PTAs can violate these rules and therefore can be challe...... be challenged before the WTO Dis-pute Settlement Body, who may initiate such cases and why there hasn´t been more cases dealing with this im-portant issue....

  1. Immune markers and correlates of protection for vaccine induced immune responses

    DEFF Research Database (Denmark)

    Thakur, Aneesh; Pedersen, Lasse Eggers; Jungersen, Gregers

    2012-01-01

    of an appropriate humoral response currently remain the best validated correlates of protective immunity after vaccination. Despite advancements in the field of immunology over the past few decades currently there are, however, no sufficiently validated immune correlates of vaccine induced protection against......-specific production of interferon-gamma (IFN-γ) has been promoted as a quantitative marker of protective cell-mediated immune responses over the past couple of decades. More recently, however, evidence from several infections has pointed towards the quality of the immune response, measured through increased levels...... of antigen-specific polyfunctional T cells capable of producing a triad of relevant cytokines, as a better correlate of sustained protective immunity against this type of infections. Also the possibilities to measure antigen-specific cytotoxic T cells (CTL) during infection or in response to vaccination...

  2. Preferential microRNA targeting revealed by in vivo competitive binding and differential Argonaute immunoprecipitation.

    Science.gov (United States)

    Werfel, Stanislas; Leierseder, Simon; Ruprecht, Benjamin; Kuster, Bernhard; Engelhardt, Stefan

    2017-09-29

    MicroRNAs (miRNAs) have been described to simultaneously inhibit hundreds of targets, albeit to a modest extent. It was recently proposed that there could exist more specific, exceptionally strong binding to a subgroup of targets. However, it is unknown, whether this is the case and how such targets can be identified. Using Argonaute2-ribonucleoprotein immunoprecipitation and in vivo competitive binding assays, we demonstrate for miRNAs-21, -199-3p and let-7 exceptional regulation of a subset of targets, which are characterized by preferential miRNA binding. We confirm this finding by analysis of independent quantitative proteome and transcriptome datasets obtained after miRNA silencing. Our data suggest that mammalian miRNA activity is guided by preferential binding of a small set of 3'-untranslated regions, thereby shaping a steep gradient of regulation between potential targets. Our approach can be applied for transcriptome-wide identification of such targets independently of the presence of seed complementary sequences or other predictors. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Weakened Immune Systems

    Science.gov (United States)

    ... Issues Health Issues Health Issues Conditions Injuries & Emergencies Vaccine Preventable Diseases ... Children > Safety & Prevention > Immunizations > Weakened Immune Systems Safety & Prevention ...

  4. On Modelling an Immune System

    OpenAIRE

    Monroy, Raúl; Saab, Rosa; Godínez, Fernando

    2004-01-01

    Immune systems of live forms have been an abundant source of inspiration to contemporary computer scientists. Problem solving strategies, stemming from known immune system phenomena, have been successfully applied to challenging problems of modern computing. However, research in artificial immune systems has overlooked establishing a coherent model of known immune system behaviour. This paper aims reports on an preliminary computer model of an immune system, where each immune system component...

  5. Effects of fine root length density and root biomass on soil preferential flow in forest ecosystems

    Directory of Open Access Journals (Sweden)

    Yinghu Zhang

    2015-04-01

    Full Text Available Aim of study: The study was conducted to characterize the impacts of plant roots systems (e.g., root length density and root biomass on soil preferential flow in forest ecosystems. Area of study: The study was carried out in Jiufeng National Forest Park, Beijing, China. Material and methods: The flow patterns were measured by field dye tracing experiments. Different species (Sophora japonica Linn,Platycladus orientalis Franco, Quercus dentata Thunbwere quantified in two replicates, and 12 soil depth were applied. Plant roots were sampled in the sieving methods. Root length density and root biomass were measured by WinRHIZO. Dye coverage was implied in the image analysis, and maximum depth of dye infiltration by direct measurement. Main results: Root length density and root biomass decreased with the increasing distance from soil surface, and root length density was 81.6% higher in preferential pathways than in soil matrix, and 66.7% for root biomass with respect to all experimental plots. Plant roots were densely distributed in the upper soil layers. Dye coverage was almost 100% in the upper 5-10 cm, but then decreased rapidly with soil depth. Root length density and root biomass were different from species: Platycladus orientalis Franco > Quercus dentata Thunb > Sophora japonica Linn. Research highlights: The results indicated that fine roots systems had strong effects on soil preferential flow, particularly root channels enhancing nutrition transport across soil profiles in forest dynamics.

  6. Cross-immunity between syngeneic tumors in mice immunized with gamma-irradiated ascites tumors

    International Nuclear Information System (INIS)

    Kudo, Hajime; Waga, Takashi; Sato, Tatsusuke; Ogasawara, Masamichi; Ito, Izumi

    1980-01-01

    C3H/He mice immunized repeatedly with irradiated (13,000 rads 60 Co) MM46 or MM48, both transplantable ascites mammary carcinomas of the same strain, were subcutaneously challenged with the identical or the different tumor. In mice immunized with irradiated MM46, the growth of challenges of not only MM46 but also MM48 was inhibited. On the other hand, in mice immunized with irradiated MM48, the growth of challenges of MM48 was inhibited, but the inhibition of the growth of MM46 was not observed. Cross-immunity, therefore, was shown by immunization with MM46 but not with MM48. These findings were considered to indicate that MM46 expressed cross-immunity against MM48 because of its high resistance to the irradiation, and that MM48 did not show cross-immunity to MM46 because of its low resistance to the irradiation. (author)

  7. The Major Players in Adaptive Immunity-Cell-mediated Immunity

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 14; Issue 6. The Major Players in Adaptive Immunity - Cell-mediated Immunity. Asma Ahmed Banishree Saha Anand Patwardhan Shwetha Shivaprasad Dipankar Nandi. General Article Volume 14 Issue 6 June 2009 pp 610-621 ...

  8. Leptin as immune mediator: Interaction between neuroendocrine and immune system.

    Science.gov (United States)

    Procaccini, Claudio; La Rocca, Claudia; Carbone, Fortunata; De Rosa, Veronica; Galgani, Mario; Matarese, Giuseppe

    2017-01-01

    Leptin is an adipocyte-derived hormone/cytokine that links nutritional status with neuroendocrine and immune functions. Initially described as an anti-obesity hormone, leptin has subsequently been shown to exert pleiotropic effects, being also able to influence haematopoiesis, thermogenesis, reproduction, angiogenesis, and more importantly immune homeostasis. As a cytokine, leptin can affect both innate and adaptive immunity, by inducing a pro-inflammatory response and thus playing a key role in the regulation of the pathogenesis of several autoimmune/inflammatory diseases. In this review, we discuss the most recent advances on the role of leptin as immune-modulator in mammals and we also provide an overview on its main functions in non-mammalian vertebrates. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Tritiated bovine fibrinogen labelled in fibrinopeptide A region

    International Nuclear Information System (INIS)

    Wegrzynowicz, Z.; Kloczewiak, M.; Kopec, M.

    1974-01-01

    The method is described for labelling of bovine fibrinogen with 3 H-AcOAc. Preparations labelled at pH 7.8 with 10 to 40 molar excess of 3 H-AcOAc were found to contain 8 to 13 moles of acetyl residues per mole of fibrinogen. The content of clottable protein and UV spectra were unchanged as compared with control unlabelled preprations. The rate of clotting with thrombin was only slightly affected. The investigations on distribution of 3 H in products of proteolysis of 3 H-fibrinogen by thrombin and plasmin demonstrated a preferential labelling of fibrinopeptide A, absence of radioactive tracer in fibrinopeptide B, significantly higher specific radioactivity of fragment E than that of fragment D. Incorporation of the label into fibrinopeptide A opens the possibility for application of 3 H-fibrinogen as a convenient substrate for selective investigations on the enzymatic phase of clotting. (author)

  10. Immunization Schedules for Adults

    Science.gov (United States)

    ... ACIP Vaccination Recommendations Why Immunize? Vaccines: The Basics Immunization Schedule for Adults (19 Years of Age and ... diseases that can be prevented by vaccines . 2018 Immunization Schedule Recommended Vaccinations for Adults by Age and ...

  11. Immunizations and African Americans

    Science.gov (United States)

    ... Data > Minority Population Profiles > Black/African American > Immunizations Immunizations and African Americans African American adults are less ... 19 to 35 months had comparable rates of immunization. African American women are as likely to have ...

  12. Instant Childhood Immunization Schedule

    Science.gov (United States)

    ... Recommendations Why Immunize? Vaccines: The Basics Instant Childhood Immunization Schedule Recommend on Facebook Tweet Share Compartir Get ... date. See Disclaimer for additional details. Based on Immunization Schedule for Children 0 through 6 Years of ...

  13. Origins of adaptive immunity.

    Science.gov (United States)

    Liongue, Clifford; John, Liza B; Ward, Alister

    2011-01-01

    Adaptive immunity, involving distinctive antibody- and cell-mediated responses to specific antigens based on "memory" of previous exposure, is a hallmark of higher vertebrates. It has been argued that adaptive immunity arose rapidly, as articulated in the "big bang theory" surrounding its origins, which stresses the importance of coincident whole-genome duplications. Through a close examination of the key molecules and molecular processes underpinning adaptive immunity, this review suggests a less-extreme model, in which adaptive immunity emerged as part of longer evolutionary journey. Clearly, whole-genome duplications provided additional raw genetic materials that were vital to the emergence of adaptive immunity, but a variety of other genetic events were also required to generate some of the key molecules, whereas others were preexisting and simply co-opted into adaptive immunity.

  14. Regulation of Mucosal Immune Responses – The Missing Link in IBD?

    Directory of Open Access Journals (Sweden)

    Charles O Elson

    1996-01-01

    Full Text Available Although the etiology of inflammatory bowel disease (IBD remains unknown, a major working hypothesis is that it represents a dysregulated immune response to common enteric bacterial antigens. Until recently there has been a relative dearth of experimental models to study this hypothesis. However, exciting developments in experimental models of colitis, including spontaneous, transgenic and knockout mice, now allow this and other hypotheses to be tested. The regulation of mucosal immune responses is not well understood in the normal animal, much less in those with chronic intestinal inflammation. Clearly the CD4 Th1 and Th2 pathways are important in the host response to microbial pathogens, and recent data indicate that the intestinal mucosa seems to be a site of preferential Th2 responses toward exogenous antigens. Deletion of certain cytokine genes involved in maintaining this Th1/Th2 balance (interleukin [IL]-2, IL-10 resulted in colitis, although deletion of others (IL-4, interferon-gamma that are also involved did not. Whether these cytokine gene deletions cause a dysregulation of the mucosal immune response has yet to be shown. However, the importance of regulation can be demonstrated in a model in which a normal CD4+ T cell subset (CD45Rbhigh is transferred into syngeneic severe combined immunodeficiency syndrome recipients. This results in a striking colitis over the ensuing weeks with chronic diarrhea and wasting of the animals. If the reciprocal CD4+ subset (CD45Rblow is co-transferred or if whole CD4+ T cells are transferred no colitis ensues. Therefore, T cells capable of causing colitis are present in normal animals but are prevented from doing so by immunoregulatory mechanisms. The antigens that drive the colitis in several of these models (IL-2 knockout mouse, human leukocyte antigen B27/β2M transgenic rat appear to be those of the normal enteric bacterial flora because germ-free animals do not get the disease. Spontaneously

  15. Network evolution by nonlinear preferential rewiring of edges

    Science.gov (United States)

    Xu, Xin-Jian; Hu, Xiao-Ming; Zhang, Li-Jie

    2011-06-01

    The mathematical framework for small-world networks proposed in a seminal paper by Watts and Strogatz sparked a widespread interest in modeling complex networks in the past decade. However, most of research contributing to static models is in contrast to real-world dynamic networks, such as social and biological networks, which are characterized by rearrangements of connections among agents. In this paper, we study dynamic networks evolved by nonlinear preferential rewiring of edges. The total numbers of vertices and edges of the network are conserved, but edges are continuously rewired according to the nonlinear preference. Assuming power-law kernels with exponents α and β, the network structures in stationary states display a distinct behavior, depending only on β. For β>1, the network is highly heterogeneous with the emergence of starlike structures. For β<1, the network is widely homogeneous with a typical connectivity. At β=1, the network is scale free with an exponential cutoff.

  16. Preferential emission into epsilon-near-zero metamaterial [Invited

    International Nuclear Information System (INIS)

    Galfsky, Tal; Sun, Zheng; Jacob, Zubin; Menon, Vinod M.

    2015-01-01

    We report the use of epsilon near zero (ENZ) metamaterial to control spontaneous emission from Zinc-Oxide (ZnO) excitons. The ENZ material consists of alternating layers of silver and alumina with subwavelength thicknesses, resulting in an effective medium where one of the components of the dielectric constant approach zero between 370nm-440nm wavelength range. Bulk ZnO with photoluminescence maximum in the ENZ regime was deposited via atomic layer deposition to obtain a smooth film with near field coupling to the ENZ metamaterial. Preferential emission from the ZnO layer into the metamaterial with suppression of forward emission by 90% in comparison to ZnO on silicon is observed. We attribute this observation to the presence of dispersionless plasmonic modes in the ENZ regime as shown by the results of theoretical modeling presented here. Integration of ENZ metamaterials with light emitters is an attractive platform for realizing a low threshold subwavelength laser

  17. Functional hierarchy underlies preferential connectivity disturbances in schizophrenia.

    Science.gov (United States)

    Yang, Genevieve J; Murray, John D; Wang, Xiao-Jing; Glahn, David C; Pearlson, Godfrey D; Repovs, Grega; Krystal, John H; Anticevic, Alan

    2016-01-12

    Schizophrenia may involve an elevated excitation/inhibition (E/I) ratio in cortical microcircuits. It remains unknown how this regulatory disturbance maps onto neuroimaging findings. To address this issue, we implemented E/I perturbations within a neural model of large-scale functional connectivity, which predicted hyperconnectivity following E/I elevation. To test predictions, we examined resting-state functional MRI in 161 schizophrenia patients and 164 healthy subjects. As predicted, patients exhibited elevated functional connectivity that correlated with symptom levels, and was most prominent in association cortices, such as the fronto-parietal control network. This pattern was absent in patients with bipolar disorder (n = 73). To account for the pattern observed in schizophrenia, we integrated neurobiologically plausible, hierarchical differences in association vs. sensory recurrent neuronal dynamics into our model. This in silico architecture revealed preferential vulnerability of association networks to E/I imbalance, which we verified empirically. Reported effects implicate widespread microcircuit E/I imbalance as a parsimonious mechanism for emergent inhomogeneous dysconnectivity in schizophrenia.

  18. Immunization Action Coalition

    Science.gov (United States)

    ... IAC | Contact | A-Z Index | Donate | Shop | SUBSCRIBE Immunization Action Coalition Favorites ACIP Recommendations Package Inserts Additional Immunization Resources Photos Adult Vaccination Screening Checklists Ask the ...

  19. Predicting Alcohol, Cigarette, and Marijuana Use From Preferential Music Consumption.

    Science.gov (United States)

    Oberle, Crystal D; Garcia, Javier A

    2015-01-01

    This study investigated whether use of alcohol, cigarettes, and marijuana may be predicted from preferential consumption of particular music genres. Undergraduates (257 women and 78 men) completed a questionnaire assessing these variables. Partial correlation analyses, controlling for sensation-seeking tendencies and behaviors, revealed that listening to conventional music (pop, country, and religious genres) was negatively correlated with cigarette smoking (p=.001) and marijuana use (pmusic (rap or hip-hop and soul or funk genres) was positively correlated with marijuana use (p=.004). The only significant predictor of alcohol use was country music, with which it was positively correlated (p=.04). This research suggests an especially harmful influence of energetic music on marijuana use. © The Author(s) 2015.

  20. Proteolytic activation of the epithelial sodium channel ENaC in preeclampsia examined with urinary exosomes

    DEFF Research Database (Denmark)

    Nielsen, Maria Ravn; Rytz, Mie; Frederiksen-Møller, Britta

    2015-01-01

    OBJECTIVES: Increased activity of the epithelial sodium channel (ENaC) in the kidneys may explain the coupling between proteinuria, edema, suppressed aldosterone and hypertension in preeclampsia. Preeclamptic women excrete plasminogen-plasmin in urine. In vitro, plasmin increases the activity...... as a positive control for the presence of collecting duct membrane. RESULTS: Urine plasmin-plasminogen/creatinine ratio was increased in the preeclampsia group (p... pregnancy and preeclampsia CONCLUSIONS: It is possible to examine collecting duct transport proteins in urine exosome from pregnant women including γ-ENaC, 2) Urine exosome fraction displays a variable pattern of γ-ENaC signal with a predominance of cleaved forms in both normal and preeclamptic women...

  1. Nutritional components regulate the gut immune system and its association with intestinal immune disease development.

    Science.gov (United States)

    Lamichhane, Aayam; Kiyono, Hiroshi; Kunisawa, Jun

    2013-12-01

    The gut is equipped with a unique immune system for maintaining immunological homeostasis, and its functional immune disruption can result in the development of immune diseases such as food allergy and intestinal inflammation. Accumulating evidence has demonstrated that nutritional components play an important role in the regulation of gut immune responses and also in the development of intestinal immune diseases. In this review, we focus on the immunological functions of lipids, vitamins, and nucleotides in the regulation of the intestinal immune system and as potential targets for the control of intestinal immune diseases. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  2. Immune Antibody Libraries: Manipulating The Diverse Immune Repertoire for Antibody Discovery.

    Science.gov (United States)

    Lim, Theam Soon; Chan, Soo Khim

    2016-01-01

    Antibody phage display is highly dependent on the availability of antibody libraries. There are several forms of libraries depending mainly on the origin of the source materials. There are three major classes of libraries, mainly the naïve, immune and synthetic libraries. Immune antibody libraries are designed to isolate specific and high affinity antibodies against disease antigens. The pre-exposure of the host to an infection results in the production of a skewed population of antibodies against the particular infection. This characteristic takes advantage of the in vivo editing machinery to generate bias and specific immune repertoire. The skewed but diverse repertoire of immune libraries has been adapted successfully in the generation of antibodies against a wide range of diseases. We envisage immune antibody libraries to play a greater role in the discovery of antibodies for diseases in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Effects of subsoil compaction on hydraulic properties and preferential flow in a Swedish clay soil

    DEFF Research Database (Denmark)

    Mossadeghi-Björklund, M; Arvidsson, J.; Keller, Thomas

    2016-01-01

    in saturated hydraulic conductivity, air permeability and number of macropores at the second site. At this site, the traffic also significantly reduced the strength of preferential flow, presumably due to compaction-induced disruption of macropore continuity. In apparent contrast, some previous studies have shown......Soil compaction by vehicular traffic modifies the pore structure and soil hydraulic properties. These changes potentially influence the occurrence of preferential flow, which so far has been little studied. Our aim was to study the effect of compaction on soil hydraulic and transport properties...... transport derived from non-reactive tracer breakthrough curves and measurements of saturated hydraulic conductivity (Ks) and air permeability at the field moisture content (Ka). Although the traffic treatment did not cause any compaction effects at one of the two sites, it did result in significant reductions...

  4. THE EFFECT OF PREFERENTIAL TRADE AREAS (PTAs IN THE PERSPECTIVE OF REGIONALISM: THE CASE OF ASEAN

    Directory of Open Access Journals (Sweden)

    Abdurrahman Al-Faqiih

    2016-03-01

    Full Text Available The issue of regionalism particularly in the matter of preferential trade area is not an old fashion debate, but it becomes a prominent feature and a popular tool for global trading system. However, it does not mean that the regionalism might always bring benefit for any actor especially in terms of every national interest in the region. This paper would elaborate the effect of preferential trade area (PTAs establishment on the economic interest of ASEAN countries member. Through literature study, this paper concludes that the PTAs produce many positive benefits for the ASEAN countries member. The flexibility of partnerships and coverage selection under PTAs has helped ASEAN solve the crisis and increase efficiency as well as stimulate the main goal of global fair trade by expanding economic linkages. Thus, it could be said that PTAs enhance the multilateralism under the WTO system

  5. Comments on possible preferential order-disorder in A-15 compounds based upon Nb

    International Nuclear Information System (INIS)

    Cox, D.E.

    1977-01-01

    The possible existence of preferential B-site disorder in A-15 compounds recently claimed on the basis of x-ray powder diffraction data but questioned from the viewpoint of known phase diagrams is examined for some Nb-based compounds of this type. It is concluded that x-ray powder data do not allow the determination of both order and compositional variables as suggested, and the latter must therefore be determined by some other method. (author)

  6. Immunity's ancient arms

    OpenAIRE

    Litman, Gary W.; Cannon, John P.

    2009-01-01

    Diverse receptors on two types of cell mediate adaptive immunity in jawed vertebrates. In the lamprey, a jawless vertebrate, immunity is likewise compartmentalized but the molecular mechanics are very different.

  7. [Stress and auto-immunity].

    Science.gov (United States)

    Delévaux, I; Chamoux, A; Aumaître, O

    2013-08-01

    The etiology of auto-immune disorders is multifactorial. Stress is probably a participating factor. Indeed, a high proportion of patients with auto-immune diseases report uncommon stress before disease onset or disease flare. The biological consequences of stress are increasingly well understood. Glucocorticoids and catecholamines released by hypothalamic-pituitary-adrenal axis during stress will alter the balance Th1/Th2 and the balance Th17/Treg. Stress impairs cellular immunity, decreases immune tolerance and stimulates humoral immunity exposing individuals to autoimmune disease among others. The treatment for autoimmune disease should include stress management. Copyright © 2012 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  8. The Immune Response of Maternally Immune Chicks to Vaccination ...

    African Journals Online (AJOL)

    The Immune Response of Maternally Immune Chicks to Vaccination with Newcastle Disease Virus. ... G A El-Tayeb, M Y El-Ttegani, I E Hajer, M A Mohammed ... This study was conducted to determine the persistence of maternally derived antibodies (MDA) to Newcastle disease virus (NDV) in newly hatched chicks and the ...

  9. Rebuilding immunity with Remune.

    Science.gov (United States)

    Whitfield, L

    1998-01-01

    Remune, an immune response therapy composed of inactivated HIV, is designed to enhance the immune system's ability to recognize and kill HIV proteins. Developed by Dr. Jonas Salk, researchers hope Remune's actions can alter the course of HIV infection and slow disease progression. Remune has gained Food and Drug Administration (FDA) approval to enter the critical Phase III trial stage. Two clinical trials are tracking Remune's immunogenicity (ability to provoke an immune response), its immunogenicity relative to dose level, and its effect on viral load. An ongoing trial, approved in February of 1996, enrolled 2,500 patients at 74 sites. The manufacturer, Immune Response Corporation (IRC), announced earlier this year that treatment with Remune induces an immune response to HIV that cross-reacts with different strains of the virus. This immune response is crucial for developing an effective worldwide treatment. Remune decreases levels of tumor necrosis factor alpha (TNF-a). IRC recently began a Phase I clinical trial in Great Britain that combines Remune with a protease inhibitor, two antiviral nucleoside analogues, and Interleukin-2. The trial is designed to determine the role that the drug may play in restoring immune response.

  10. Cross-immunity among allogeneic tumors in rats immunized with gamma-irradiated ascites tumors

    International Nuclear Information System (INIS)

    Sato, Tatsusuke; Suga, Michio; Kudo, Hajime; Waga, Takashi; Ogasawara, Masamichi

    1980-01-01

    Non-inbred rats of the Gifu strain were intraperitoneally challenged with Hirosaki sarcoma (Tetraploid type, 10 5 cells) after repeated immunization with gamma-irradiated (13,000 rads 60 Co) allogeneic non-viral tumors of ascites type (Tetraploid or diploid type of Hirosaki sarcoma, Usubuchi sarcoma or AH130). In rats immunized not only with the same tumor as the immunizing tumor but also with a different tumor, the growth of the challenge tumor was markedly inhibited as compared with the control in non-immunized rats. It is considered that these tumors retained common antigen(s) by the resistance to irradiation because of their form of ascites tumor. The marked cross-immunity in rats immunized with AH130 may be explained by the fact that gamma-irradiated AH130 cells were alive longer in the peritoneal cavity than other tumors on account of its high resistance to irradiation. (author)

  11. A cocaine context renews drug seeking preferentially in a subset of individuals.

    Science.gov (United States)

    Saunders, Benjamin T; O'Donnell, Elizabeth G; Aurbach, Elyse L; Robinson, Terry E

    2014-11-01

    Addiction is characterized by a high propensity for relapse, in part because cues associated with drugs can acquire Pavlovian incentive motivational properties, and acting as incentive stimuli, such cues can instigate and invigorate drug-seeking behavior. There is, however, considerable individual variation in the propensity to attribute incentive salience to reward cues. Discrete and localizable reward cues act as much more effective incentive stimuli in some rats ('sign-trackers', STs), than others ('goal-trackers', GTs). We asked whether similar individual variation exists for contextual cues associated with cocaine. Cocaine context conditioned motivation was quantified in two ways: (1) the ability of a cocaine context to evoke conditioned hyperactivity and (2) the ability of a context in which cocaine was previously self-administered to renew cocaine-seeking behavior. Finally, we assessed the effects of intra-accumbens core flupenthixol, a nonselective dopamine receptor antagonist, on context renewal. In contrast to studies using discrete cues, a cocaine context spurred greater conditioned hyperactivity, and more robustly renewed extinguished cocaine seeking in GTs than STs. In addition, cocaine context renewal was blocked by antagonism of dopamine receptors in the accumbens core. Thus, contextual cues associated with cocaine preferentially acquire motivational control over behavior in different individuals than do discrete cues, and in these individuals the ability of a cocaine context to create conditioned motivation for cocaine requires dopamine in the core of the nucleus accumbens. We speculate that different individuals may be preferentially sensitive to different 'triggers' of relapse.

  12. MMP9 is protective against lethal inflammatory mass lesions in the mouse colon

    DEFF Research Database (Denmark)

    Hald, Andreas; Rønø, Birgitte; Melander, Maria C

    2011-01-01

    of individual members of the MMP family in animal models have been shown to have little effect. It has been speculated that this results from a functional overlap between individual MMPs and (as-yet-unclassified) functional overlaps between MMPs and other protease systems. We here present genetic data showing......, enlarged mesenteric lymph nodes, decreased thymus size and altered populations of circulating immune cells. A time-course study provided evidence that the massive lymphoid hyperplasia and reactive changes were secondary to discrete fibrinous lesions also observed in mice only deficient for plasminogen (Plg......), the zymogen for plasmin. These data demonstrate a non-appreciated vital protective role for MMP9 in the absence of Plg....

  13. 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)

  14. Generating Billion-Edge Scale-Free Networks in Seconds: Performance Study of a Novel GPU-based Preferential Attachment Model

    Energy Technology Data Exchange (ETDEWEB)

    Perumalla, Kalyan S. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Alam, Maksudul [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2017-10-01

    A novel parallel algorithm is presented for generating random scale-free networks using the preferential-attachment model. The algorithm, named cuPPA, is custom-designed for single instruction multiple data (SIMD) style of parallel processing supported by modern processors such as graphical processing units (GPUs). To the best of our knowledge, our algorithm is the first to exploit GPUs, and also the fastest implementation available today, to generate scale free networks using the preferential attachment model. A detailed performance study is presented to understand the scalability and runtime characteristics of the cuPPA algorithm. In one of the best cases, when executed on an NVidia GeForce 1080 GPU, cuPPA generates a scale free network of a billion edges in less than 2 seconds.

  15. Immune system simulation online

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Lund, Ole; Castiglione, Filippo

    2011-01-01

    MOTIVATION: The recognition of antigenic peptides is a major event of an immune response. In current mesoscopic-scale simulators of the immune system, this crucial step has been modeled in a very approximated way. RESULTS: We have equipped an agent-based model of the immune system with immuno...

  16. 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.

  17. The cell-mediated immunity of Drosophila melanogaster: hemocyte lineages, immune compartments, microanatomy and regulation.

    Science.gov (United States)

    Honti, Viktor; Csordás, Gábor; Kurucz, Éva; Márkus, Róbert; Andó, István

    2014-01-01

    In the animal kingdom, innate immunity is the first line of defense against invading pathogens. The dangers of microbial and parasitic attacks are countered by similar mechanisms, involving the prototypes of the cell-mediated immune responses, the phagocytosis and encapsulation. Work on Drosophila has played an important role in promoting an understanding of the basic mechanisms of phylogenetically conserved modules of innate immunity. The aim of this review is to survey the developments in the identification and functional definition of immune cell types and the immunological compartments of Drosophila melanogaster. We focus on the molecular and developmental aspects of the blood cell types and compartments, as well as the dynamics of blood cell development and the immune response. Further advances in the characterization of the innate immune mechanisms in Drosophila will provide basic clues to the understanding of the importance of the evolutionary conserved mechanisms of innate immune defenses in the animal kingdom. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Preferential growth of short aligned, metallic-rich single-walled carbon nanotubes from perpendicular layered double hydroxide film.

    Science.gov (United States)

    Zhao, Meng-Qiang; Tian, Gui-Li; Zhang, Qiang; Huang, Jia-Qi; Nie, Jing-Qi; Wei, Fei

    2012-04-07

    Direct bulk growth of single-walled carbon nanotubes (SWCNTs) with required properties, such as diameter, length, and chirality, is the first step to realize their advanced applications in electrical and optical devices, transparent conductive films, and high-performance field-effect transistors. Preferential growth of short aligned, metallic-rich SWCNTs is a great challenge to the carbon nanotube community. We report the bulk preferential growth of short aligned SWCNTs from perpendicular Mo-containing FeMgAl layered double hydroxide (LDH) film by a facile thermal chemical vapor deposition with CH(4) as carbon source. The growth of the short aligned SWCNTs showed a decreased growth velocity with an initial value of 1.9 nm s(-1). Such a low growth velocity made it possible to get aligned SWCNTs shorter than 1 μm with a growth duration less than 15 min. Raman spectra with different excitation wavelengths indicated that the as-grown short aligned SWCNTs showed high selectivity of metallic SWCNTs. Various kinds of materials, such as mica, quartz, Cu foil, and carbon fiber, can serve as the substrates for the growth of perpendicular FeMoMgAl LDH films and also the growth of the short aligned SWCNTs subsequently. These findings highlight the easy route for bulk preferential growth of aligned metallic-rich SWCNTs with well defined length for further bulk characterization and applications. This journal is © The Royal Society of Chemistry 2012

  19. Immune System and Kidney Transplantation.

    Science.gov (United States)

    Shrestha, Badri Man

    2017-01-01

    The immune system recognises a transplanted kidney as foreign body and mounts immune response through cellular and humoral mechanisms leading to acute or chronic rejection, which ultimately results in graft loss. Over the last five decades, there have been significant advances in the understanding of the immune responses to transplanted organs in both experimental and clinical transplant settings. Modulation of the immune response by using immunosuppressive agents has led to successful outcomes after kidney transplantation. The paper provides an overview of the general organisation and function of human immune system, immune response to kidney transplantation, and the current practice of immunosuppressive therapy in kidney transplantation in the United Kingdom.

  20. Controlled surface chemistry of diamond/β-SiC composite films for preferential protein adsorption.

    Science.gov (United States)

    Wang, Tao; Handschuh-Wang, Stephan; Yang, Yang; Zhuang, Hao; Schlemper, Christoph; Wesner, Daniel; Schönherr, Holger; Zhang, Wenjun; Jiang, Xin

    2014-02-04

    Diamond and SiC both process extraordinary biocompatible, electronic, and chemical properties. A combination of diamond and SiC may lead to highly stable materials, e.g., for implants or biosensors with excellent sensing properties. Here we report on the controllable surface chemistry of diamond/β-SiC composite films and its effect on protein adsorption. For systematic and high-throughput investigations, novel diamond/β-SiC composite films with gradient composition have been synthesized using the hot filament chemical vapor deposition (HFCVD) technique. As revealed by scanning electron microscopy (SEM), the diamond/β-SiC ratio of the composite films shows a continuous change from pure diamond to β-SiC over a length of ∼ 10 mm on the surface. X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) was employed to unveil the surface termination of chemically oxidized and hydrogen treated surfaces. The surface chemistry of the composite films was found to depend on diamond/β-SiC ratio and the surface treatment. As observed by confocal fluorescence microscopy, albumin and fibrinogen were preferentially adsorbed from buffer: after surface oxidation, the proteins preferred to adsorb on diamond rather than on β-SiC, resulting in an increasing amount of proteins adsorbed to the gradient surfaces with increasing diamond/β-SiC ratio. By contrast, for hydrogen-treated surfaces, the proteins preferentially adsorbed on β-SiC, leading to a decreasing amount of albumin adsorbed on the gradient surfaces with increasing diamond/β-SiC ratio. The mechanism of preferential protein adsorption is discussed by considering the hydrogen bonding of the water self-association network to OH-terminated surfaces and the change of the polar surface energy component, which was determined according to the van Oss method. These results suggest that the diamond/β-SiC gradient film can be a promising material for biomedical applications which

  1. Reinfection immunity in schistosomiasis

    International Nuclear Information System (INIS)

    Kamiya, Haruo

    1987-01-01

    Schistosomiasis is one of the most important parasitic diseases in the world, especially in endemic areas of developing countries. This situation has prompted parasitologist to attempt intensive researches on immune mechanisms, especially those of reinfection immunity associated with eliminating challenge infection. The current knowledge of reinfection immunity against Schistosoma spp. infection was therefore reviewed briefly and discussed with special reference to our data on protective immune responses induced by radiation-attenuated cercarial infection. A recently developed technique of compressed organ autoradiography (COA) has contributed to assessing parasite attrition in immune animals following challenge infection. Our study using COA has demonstrated that major attrition of schistosomula from challenge infection occurs in the skin of CBA/Ca mice vaccinated with 20 Krad gamma radiation-attenuated cercariae of S. mansoni, while in both lungs and liver of similarly vaccinated guinea pig model. Furthermore, gamma-irradiation to cercariae affected their migration potential and surface-antigen profiles. The immunizing stimuli of gamma radiation-attenuated cercariae profoundly affected the expression of responsiveness in vaccinated animals. The change in antigenic profiles and migration potential of those vaccinating population was discussed in relation to the kinetics of reinfection immunity induced in vaccinated amimal models. These works might provide a base line data to develop a practical vaccine for schistosomiasis using defined antigens. It must be emphasized that these vaccines could serve as a practical prophylactic measure for schistosomiasis in the endemic areas, even if the vaccines fail to induce sterilizing immunity. (author). 141 refs

  2. A preferential coating technique for fabricating large, high quality optics

    International Nuclear Information System (INIS)

    Alcock, S.G.; Cockerton, S.

    2010-01-01

    A major challenge facing optic manufacturers is the fabrication of large mirrors (>1 m) with minimal residual slope errors (<0.5 μrad rms). We present a differential coating method with the potential to satisfy such exacting technical demands. Iterative cycles of measurement using the Diamond-NOM, followed by preferential deposition, were performed on a 1200 mm long, silicon mirror. The applied coatings were observed to reduce the optical slope and figure errors from 1.62 to 0.44 μrad rms, and from 208 to 13 nm rms, respectively. It is hoped that this research will lead to commercially available products, of direct benefit to the Synchrotron, Free Electron Laser, Astronomy, Space, and Laser communities, who all require state-of-the-art optics.

  3. Preferential Production and Transport of Grass-Derived Pyrogenic Carbon in NE-Australian Savanna Ecosystems

    Directory of Open Access Journals (Sweden)

    Gustavo Saiz

    2018-01-01

    Full Text Available Understanding the main factors driving fire regimes in grasslands and savannas is critical to better manage their biodiversity and functions. Moreover, improving our knowledge on pyrogenic carbon (PyC dynamics, including formation, transport and deposition, is fundamental to better understand a significant slow-cycling component of the global carbon cycle, particularly as these ecosystems account for a substantial proportion of the area globally burnt. However, a thorough assessment of past fire regimes in grass-dominated ecosystems is problematic due to challenges in interpreting the charcoal record of sediments. It is therefore critical to adopt appropriate sampling and analytical methods to allow the acquisition of reliable data and information on savanna fire dynamics. This study uses hydrogen pyrolysis (HyPy to quantify PyC abundance and stable isotope composition (δ13C in recent sediments across 38 micro-catchments covering a wide range of mixed C3/C4 vegetation in north Queensland, Australia. We exploited the contrasting δ13C values of grasses (i.e., C4; δ13C > −15‰ and woody vegetation (i.e., C3; δ13C < −24‰ to assess the preferential production and transport of grass-derived PyC in savanna ecosystems. Analyses were conducted on bulk and size-fractionated samples to determine the fractions into which PyC preferentially accumulates. Our data show that the δ13C value of PyC in the sediments is decoupled from the δ13C value of total organic carbon, which suggests that a significant component of PyC may be derived from incomplete grass combustion, even when the proportion of C4 grass biomass in the catchment was relatively small. Furthermore, we conducted 16 experimental burns that indicate that there is a comminution of PyC produced in-situ to smaller particles, which facilitates the transport of this material, potentially affecting its preservation potential. Savanna fires preferentially burn the grass understory rather than

  4. Immune response to uv-induced tumors: transplantation immunity and lymphocyte populations exhibiting anti-tumor activity

    International Nuclear Information System (INIS)

    Streeter, P.R.

    1985-01-01

    Ultraviolet light-induced murine skin tumors were analyzed for their ability to induce tumor-specific and cross-protective transplantation immunity in immunocompetent syngeneic mice. These studies revealed that progressor UV-tumors, like regressor UV-tumors, possess tumor-specific transplantation antigens. Cross-protective transplantation immunity to UV-tumors, however, was associated with sensitization to the serum used to culture the tumor lines rather than to cross-reactive or common determinants on UV-tumors. An analysis of the cytolytic activity of lymphocytes from the spleens of mice immunized with either regressor or progressor UV-tumors revealed a striking difference between the two immune splenocyte populations. From regressor tumor-immune animals, cytolytic T (Tc) lymphocytes with specificity for the immunizing tumor were found. However, the analysis of splenic lymphocytes from progressor tumor immune animals revealed no such effector cells. To more effectively examine those lymphocytes exhibiting cytolytic activity in vitro, T lymphocyte cloning technology was used as a means of isolating homogeneous lymphocyte populations with the effector activities described above. The mechanisms where NK cells and other nonspecific effector cells could be induced in tumor-immune animals are discussed in the context of class II restricted immune responses

  5. Neural circuitry and immunity

    Science.gov (United States)

    Pavlov, Valentin A.; Tracey, Kevin J.

    2015-01-01

    Research during the last decade has significantly advanced our understanding of the molecular mechanisms at the interface between the nervous system and the immune system. Insight into bidirectional neuroimmune communication has characterized the nervous system as an important partner of the immune system in the regulation of inflammation. Neuronal pathways, including the vagus nerve-based inflammatory reflex are physiological regulators of immune function and inflammation. In parallel, neuronal function is altered in conditions characterized by immune dysregulation and inflammation. Here, we review these regulatory mechanisms and describe the neural circuitry modulating immunity. Understanding these mechanisms reveals possibilities to use targeted neuromodulation as a therapeutic approach for inflammatory and autoimmune disorders. These findings and current clinical exploration of neuromodulation in the treatment of inflammatory diseases defines the emerging field of Bioelectronic Medicine. PMID:26512000

  6. Src Kinase becomes preferentially associated with the VEGFR, KDR/Flk-1, following VEGF stimulation of vascular endothelial cells

    Directory of Open Access Journals (Sweden)

    Wang Jing

    2002-12-01

    Full Text Available Abstract Background The cytoplasmic tyrosine kinase, Src, has been found to play a crucial role in VEGF (vascular endothelial growth factor – dependent vascular permeability involved in angiogenesis. The two main VEGFRs present on vascular endothelial cells are KDR/Flk-1 (kinase insert domain-containing receptor/fetal liver kinase-1 and Flt-1 (Fms-like tyrosine kinase-1. However, to date, it has not been determined which VEGF receptor (VEGFR is involved in binding to and activating Src kinase following VEGF stimulation of the receptors. Results In this report, we demonstrate that Src preferentially associates with KDR/Flk-1 rather than Flt-1 in human umbilical vein endothelial cells (HUVECs, and that VEGF stimulation resulted in an increase of Src activity associated with activated KDR/Flk-1. These findings were determined through immunoprecipitation-kinase experiments and coimmunoprecipitation studies, and were further confirmed by GST-pull-down assays and Far Western studies. However, Fyn and Yes, unlike Src, were found to associate preferentially with Flt-1. Conclusions Thus, Src preferentially associates with KDR/Flk-1, rather than with Flt-1, upon VEGF stimulation in endothelial cells. Our findings further highlight the potential significance of upregulated KDR/Flk-1-associated Src activity in the process of angiogenesis, and help to elucidate more clearly the specific roles and mechanisms involving Src family tyrosine kinase in VEGF-stimulated signal transduction events.

  7. The Immune System Game

    Science.gov (United States)

    Work, Kirsten A.; Gibbs, Melissa A.; Friedman, Erich J.

    2015-01-01

    We describe a card game that helps introductory biology students understand the basics of the immune response to pathogens. Students simulate the steps of the immune response with cards that represent the pathogens and the cells and molecules mobilized by the immune system. In the process, they learn the similarities and differences between the…

  8. Preferential solvation of ions in mixed solvents. 6: Univalent anions in aqueous organic solvents according to the inverse Kirkwood-Buff integral (IKBI) approach

    International Nuclear Information System (INIS)

    Marcus, Yizhak

    2007-01-01

    The inverse Kirkwood-Buff integral (IKBI) approach is applied to the preferential solvation of F - , Cl - , Br - , I - , and ClO 4 - in aqueous mixtures of the co-solvents (S) methanol (MeOH), ethanol (EtOH), t-butanol (t-BuOH), 1,2-ethanediol (EG), glycerol (Gly), acetone (Me 2 CO), acetonitrile (MeCN), formamide (FA), N,N-dimethylformamide (DMF), N,N,N',N',N'',N''-hexamethyl phosphoric triamide (HMPT), and dimethylsulfoxide (DMSO), as far as the relevant data exist in the literature. Fluoride anions are selectively solvated by the water up to large mole fractions (x S ≥ 0.4) of S = EtOH, t-BuOH, Me 2 CO, MeCN, and DMF, and up to lower contents (x S ∼ 0.1) of MeOH, EG, FA, and DMSO. The other anions are preferentially solvated by water to diminishing extent as their sizes become larger, and the largest ones show some preference for S in water-rich mixtures of MeOH and FA, whereas in aqueous Gly even chloride is preferentially solvated by the Gly. The competition between the co-solvent and the anion for the hydrogen bonds that water molecules donate is the main cause for the observed preferential solvation behaviour

  9. Immune mediated liver failure.

    Science.gov (United States)

    Wang, Xiaojing; Ning, Qin

    2014-01-01

    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capacity. Direct damage and immune-mediated liver injury are two major factors involved in this process. Increasing evidence has suggested the essential role of immune-mediated liver injury in the pathogenesis of liver failure. Here, we review the evolved concepts concerning the mechanisms of immune-mediated liver injury in liver failure from human and animal studies. Both innate and adaptive immunity, especially the interaction of various immune cells and molecules as well as death receptor signaling system are discussed. In addition, we highlight the concept of "immune coagulation", which has been shown to be related to the disease progression and liver injury exacerbation in HBV related acute-on-chronic liver failure.

  10. Arkansas community pharmacists' opinions on providing immunizations.

    Science.gov (United States)

    Pace, Anne C; Flowers, Schwanda K; Hastings, Jan K

    2010-10-01

    To determine community pharmacists' attitudes and knowledge on providing immunizations including perceived barriers to immunizing. The study also examined the percentage of Arkansas pharmacists providing immunizations and the utilization of student pharmacists. Survey. Arkansas community pharmacies from February to March 2009. Community pharmacists. Mailed survey. Perceived barriers to providing immunizations, pharmacists' attitudes regarding immunizations, number of immunization-certified pharmacists, immunization administration rates within the last year, and senior student pharmacists utilization. A total of 350 surveys were mailed, and 129 were returned. In all, 79% of the respondents believed administering immunizations has advanced or significantly advanced the profession. Being certified and attitude toward providing immunizations were correlated; 37% of the respondents held certification to immunize, of which 77% reported immunizing within the last year. Commonly reported barriers included time (76%) followed by reimbursement and legal liability. Only half the respondents realized fourth year student pharmacists could immunize and only 33% of certified pharmacists utilized student pharmacists to immunize. Pharmacists perceive many barriers to providing immunizations. Training student pharmacists to give immunizations may not result in them providing immunizations upon graduation. Additional education on overcoming potential barriers and using senior student pharmacists to administer immunizations is needed.

  11. Grandparental Child Care in Europe: Evidence for Preferential Investment in More Certain Kin

    Directory of Open Access Journals (Sweden)

    Mirkka Danielsbacka

    2011-01-01

    Full Text Available Theories of kin selection and parental investment predict stronger investment in children and grandchildren by women and maternal kin. Due to paternity uncertainty, parental and grandparental investments along paternal lineages are based on less certain genetic relatedness with the children and grandchildren. Additionally, the hypothesis of preferential investment (Laham, Gonsalkorale, and von Hippel, 2005 predicts investment to vary according to available investment options. Two previous studies have tested this hypothesis with small samples and conflicting results. Using the second wave of the large and multinational Survey of Health, Ageing and Retirement in Europe (SHARE, collected in 2006–07, we study the preferential investment hypothesis in contemporary Europe based on self-reported grandparental provision of child care. We predict that 1 maternal grandmothers provide most care for their grandchildren, followed by maternal grandfathers, paternal grandmothers and last by paternal grandfathers; 2 maternal grandfathers and paternal grandmothers provide equal amounts of care when the latter do not have grandchildren via a daughter; 3 women who have grandchildren via both a daughter and a son will look after the children of the daughter more; and 4 men who have grandchildren via both a daughter and a son will look after the children of the daughter more. Results support all four hypotheses and provide evidence for the continuing effects of paternity uncertainty in contemporary kin behavior.

  12. Immune Regulation by Self-Recognition

    DEFF Research Database (Denmark)

    Andersen, Mads Hald

    2015-01-01

    Circulating T cells that specifically target normal self-proteins expressed by regulatory immune cells were first described in patients with cancer, but can also be detected in healthy individuals. The adaptive immune system is distinguished for its ability to differentiate between self......-antigens and foreign antigens. Thus, it was remarkable to discover T cells that apparently lacked tolerance to important self-proteins, eg, IDO, PD-L1, and FoxP3, expressed in regulatory immune cells. The ability of self-reactive T cells to react to and eliminate regulatory immune cells can influence general immune...... reactions. This suggests that they may be involved in immune homeostasis. It is here proposed that these T cells should be termed antiregulatory T cells (anti-Tregs). The role of anti-Tregs in immune-regulatory networks may be diverse. For example, pro-inflammatory self-reactive T cells that react...

  13. Preferential processing of task-irrelevant beloved-related information and task performance: Two event-related potential studies.

    Science.gov (United States)

    Langeslag, Sandra J E; van Strien, Jan W

    2017-09-18

    People who are in love have better attention for beloved-related information, but report having trouble focusing on other tasks, such as (home)work. So, romantic love can both improve and hurt cognition. Emotional information is preferentially processed, which improves task performance when the information is task-relevant, but hurts task performance when it is task-irrelevant. Because beloved-related information is highly emotional, the effects of romantic love on cognition may resemble these effects of emotion on cognition. We examined whether beloved-related information is preferentially processed even when it is task-irrelevant and whether this hurts task performance. In two event-related potential studies, participants who had recently fallen in love performed a visuospatial short-term memory task. Task-irrelevant beloved, friend, and stranger faces were presented during maintenance (Study 1), or encoding (Study 2). The Early Posterior Negativity (EPN) reflecting early automatic attentional capturing and the Late Positive Potential (LPP) reflecting sustained motivated attention were largest for beloved pictures. Thus, beloved pictures are preferentially processed even when they are task-irrelevant. Task performance and reaction times did not differ between beloved, friend, and stranger conditions. Nevertheless, self-reported obsessive thinking about the beloved tended to correlate negatively with task performance, and positively with reaction times, across conditions. So, although task-irrelevant beloved-related information does not impact task performance, more obsessive thinking about the beloved might relate to poorer and slower overall task performance. More research is needed to clarify why people experience trouble focusing on beloved-unrelated tasks and how this negative effect of love on cognition could be reduced. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Receptor-isoform-selective insulin analogues give tissue-preferential effects

    DEFF Research Database (Denmark)

    Vienberg, Sara Gry; Bouman, Stephan D; Sørensen, Heidi

    2011-01-01

    The relative expression patterns of the two IR (insulin receptor) isoforms, +/- exon 11 (IR-B/IR-A respectively), are tissue-dependent. Therefore we have developed insulin analogues with different binding affinities for the two isoforms to test whether tissue-preferential biological effects can...... be attained. In rats and mice, IR-B is the most prominent isoform in the liver (> 95%) and fat (> 90%), whereas in muscles IR-A is the dominant isoform (> 95%). As a consequence, the insulin analogue INS-A, which has a higher relative affinity for human IR-A, had a higher relative potency [compared with HI...... (human insulin)] for glycogen synthesis in rat muscle strips (26%) than for glycogen accumulation in rat hepatocytes (5%) and for lipogenesis in rat adipocytes (4%). In contrast, the INS-B analogue, which has an increased affinity for human IR-B, had higher relative potencies (compared with HI...

  15. Immunization alters body odor.

    Science.gov (United States)

    Kimball, Bruce A; Opiekun, Maryanne; Yamazaki, Kunio; Beauchamp, Gary K

    2014-04-10

    Infections have been shown to alter body odor. Because immune activation accompanies both infection and immunization, we tested the hypothesis that classical immunization might similarly result in the alteration of body odors detectable by trained biosensor mice. Using a Y-maze, we trained biosensor mice to distinguish between urine odors from rabies-vaccinated (RV) and unvaccinated control mice. RV-trained mice generalized this training to mice immunized with the equine West Nile virus (WNV) vaccine compared with urine of corresponding controls. These results suggest that there are similarities between body odors of mice immunized with these two vaccines. This conclusion was reinforced when mice could not be trained to directly discriminate between urine odors of RV- versus WNV-treated mice. Next, we trained biosensor mice to discriminate the urine odors of mice treated with lipopolysaccharide (LPS; a general elicitor of innate immunological responses) from the urine of control mice. These LPS-trained biosensors could distinguish between the odors of LPS-treated mouse urine and RV-treated mouse urine. Finally, biosensor mice trained to distinguish between the odors of RV-treated mouse urine and control mouse urine did not generalize this training to discriminate between the odors of LPS-treated mouse urine and control mouse urine. From these experiments, we conclude that: (1) immunization alters urine odor in similar ways for RV and WNV immunizations; and (2) immune activation with LPS also alters urine odor but in ways different from those of RV and WNV. Published by Elsevier Inc.

  16. Immune dysfunction in cirrhosis

    Science.gov (United States)

    Sipeki, Nora; Antal-Szalmas, Peter; Lakatos, Peter L; Papp, Maria

    2014-01-01

    Innate and adaptive immune dysfunction, also referred to as cirrhosis-associated immune dysfunction syndrome, is a major component of cirrhosis, and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver function. During the evolution of the disease, acute decompensation events associated with organ failure(s), so-called acute-on chronic liver failure, and chronic decompensation with progression of liver fibrosis and also development of disease specific complications, comprise distinct clinical entities with different immunopathology mechanisms. Enhanced bacterial translocation associated with systemic endotoxemia and increased occurrence of systemic bacterial infections have substantial impacts on both clinical situations. Acute and chronic exposure to bacteria and/or their products, however, can result in variable clinical consequences. The immune status of patients is not constant during the illness; consequently, alterations of the balance between pro- and anti-inflammatory processes result in very different dynamic courses. In this review we give a detailed overview of acquired immune dysfunction and its consequences for cirrhosis. We demonstrate the substantial influence of inherited innate immune dysfunction on acute and chronic inflammatory processes in cirrhosis caused by the pre-existing acquired immune dysfunction with limited compensatory mechanisms. Moreover, we highlight the current facts and future perspectives of how the assessment of immune dysfunction can assist clinicians in everyday practical decision-making when establishing treatment and care strategies for the patients with end-stage liver disease. Early and efficient recognition of inappropriate performance of the immune system is essential for overcoming complications, delaying progression and reducing mortality. PMID:24627592

  17. Cross-serotype immunity induced by immunization with a conserved rhinovirus capsid protein.

    Directory of Open Access Journals (Sweden)

    Nicholas Glanville

    Full Text Available Human rhinovirus (RV infections are the principle cause of common colds and precipitate asthma and COPD exacerbations. There is currently no RV vaccine, largely due to the existence of ∼150 strains. We aimed to define highly conserved areas of the RV proteome and test their usefulness as candidate antigens for a broadly cross-reactive vaccine, using a mouse infection model. Regions of the VP0 (VP4+VP2 capsid protein were identified as having high homology across RVs. Immunization with a recombinant VP0 combined with a Th1 promoting adjuvant induced systemic, antigen specific, cross-serotype, cellular and humoral immune responses. Similar cross-reactive responses were observed in the lungs of immunized mice after infection with heterologous RV strains. Immunization enhanced the generation of heterosubtypic neutralizing antibodies and lung memory T cells, and caused more rapid virus clearance. Conserved domains of the RV capsid therefore induce cross-reactive immune responses and represent candidates for a subunit RV vaccine.

  18. Preferential Reduction of Circulating Innate Lymphoid Cells Type 2 in Patients with Common Variable Immunodeficiency with Secondary Complications Is Part of a Broader Immune Dysregulation.

    Science.gov (United States)

    Friedmann, David; Keller, Baerbel; Harder, Ina; Schupp, Jonas; Tanriver, Yakup; Unger, Susanne; Warnatz, Klaus

    2017-11-01

    Over a third of patients with common variable immunodeficiency (CVID) suffer from secondary complications like inflammatory organ disease, autoimmune manifestations, or lymphoproliferation contributing to increased morbidity and mortality in affected patients. Innate lymphoid cells (ILCs) have emerging roles in setting the milieu for physiological, but also pathological, immune responses and inflammation. We therefore sought to correlate the recently identified disturbed homeostasis of ILCs with alterations of the adaptive immune system in complex CVID patients (CVIDc). We quantified peripheral blood ILC and T helper cell subsets of 58 CVID patients by flow cytometry and compared the results to the clinical and immunological phenotype. Total ILCs were significantly reduced in peripheral blood of CVIDc patients compared to healthy individuals, but not to CVID patients who suffered only from infections (CVIDio). This reduction was mainly due to a decrease in ILC2s, while ILC3s were relatively increased in CVIDc compared to CVIDio patients. This alteration in ILC phenotype was more prominent in patients with an expansion of CD21 low B cells, but we could not detect an association of the altered ILC phenotype with a T H 1-shift among circulating CD4 T cells, which was also prominent in CVIDc patients. We confirm a relative shift in ILCs of CVIDc patients towards ILC3s which was associated with the expansion of CD21 low B cells, but not overtly with the relative expansion of T H 1-like T cells. Given the relative abundance of T H 1-like T cells compared to ILCs, these probably represent a more prominent source of the observed IFNγ-signature in CVIDc patients.

  19. Immune response at birth, long-term immune memory and 2 years follow-up after in-utero anti-HBV DNA immunization.

    Science.gov (United States)

    Fazio, V M; Ria, F; Franco, E; Rosati, P; Cannelli, G; Signori, E; Parrella, P; Zaratti, L; Iannace, E; Monego, G; Blogna, S; Fioretti, D; Iurescia, S; Filippetti, R; Rinaldi, M

    2004-03-01

    Infections occurring at the end of pregnancy, during birth or by breastfeeding are responsible for the high toll of death among first-week infants. In-utero DNA immunization has demonstrated the effectiveness in inducing specific immunity in newborns. A major contribution to infant immunization would be achieved if a vaccine proved able to be protective as early as at the birth, preventing the typical 'first-week infections'. To establish its potential for use in humans, in-utero DNA vaccination efficiency has to be evaluated for short- and long-term safety, protection at delivery, efficacy of boosts in adults and effective window/s for modulation of immune response during pregnancy, in an animal model suitable with human development. Here we show that a single intramuscular in-utero anti-HBV DNA immunization at two-thirds of pig gestation produces, at birth, antibody titers considered protective in humans. The boost of antibody titers in every animal following recall at 4 and 10 months demonstrates the establishment of immune memory. The safety of in-utero fetus manipulation is guaranteed by short-term (no fetus loss, lack of local alterations, at-term spontaneous delivery, breastfeeding) and long-term (2 years) monitoring. Treatment of fetuses closer to delivery results in immune ignorance without induction of tolerance. This result highlights the repercussion of selecting the appropriate time point when this approach is used to deliver therapeutic genes. All these findings illustrate the relevance of naked DNA-based vaccination technology in therapeutic efforts aimed to prevent the high toll of death among first-week infants.

  20. Ethics of Immunization

    NARCIS (Netherlands)

    Verweij, M.F.; Quah, S.R.; Cockerham, W.C.

    2017-01-01

    Collective immunization can be highly effective in protecting societies against infectious diseases, but policy decisions about both the character and the content of immunization policies require ethical justification. This article offers an overview of ethical aspects that should be taken into

  1. Agouron and immune response to commercialize remune immune-based treatment.

    Science.gov (United States)

    James, J S

    1998-06-19

    Agouron Pharmaceuticals agreed in June to collaborate with The Immune Response Corporation on the final development and marketing of an immune-based treatment for HIV. Remune, the vaccine developed by Dr. Jonas Salk, is currently in Phase III randomized trials with 2,500 patients, and the trials are expected to be completed in April 1999. Immune-based treatments have been difficult to test, as there is no surrogate marker, like viral load, to determine if the drug is working. Agouron agreed to participate in the joint venture after reviewing encouraging results from preliminary trials in which remune was taken in combination with highly active antiretroviral drugs.

  2. Separation of Enantiomers by Preferential Crystallization: Mathematical Modeling of a Coupled Crystallizer Configuration

    DEFF Research Database (Denmark)

    Chaaban, Joussef Hussein; Dam-Johansen, Kim; Skovby, Tommy

    2014-01-01

    A mathematical model describing the separation of enantiomers by simultaneous preferential crystallization in a coupled crystallizer configuration is developed. The model was validated against experimental data for a chemical model compound, the conglomerate forming system of asparagine monohydrate....... The racemic compound and the pure enantiomer can be separated simultaneously in each crystallizer, having sufficient enrichment of the pure enantiomer in the feed solution. The model can also be extended to represent a fully continuous separation process taking into account the continuous supply...

  3. The Scaffold Immune Microenvironment: Biomaterial-Mediated Immune Polarization in Traumatic and Nontraumatic Applications.

    Science.gov (United States)

    Sadtler, Kaitlyn; Allen, Brian W; Estrellas, Kenneth; Housseau, Franck; Pardoll, Drew M; Elisseeff, Jennifer H

    2017-10-01

    The immune system mediates tissue growth and homeostasis and is the first responder to injury or biomaterial implantation. Recently, it has been appreciated that immune cells play a critical role in wound healing and tissue repair and should thus be considered potentially beneficial, particularly in the context of scaffolds for regenerative medicine. In this study, we present a flow cytometric analysis of cellular recruitment to tissue-derived extracellular matrix scaffolds, where we quantitatively describe the infiltration and polarization of several immune subtypes, including macrophages, dendritic cells, neutrophils, monocytes, T cells, and B cells. We define a specific scaffold-associated macrophage (SAM) that expresses CD11b + F4/80 + CD11c +/- CD206 hi CD86 + MHCII + that are characteristic of an M2-like cell (CD206 hi ) with high antigen presentation capabilities (MHCII + ). Adaptive immune cells tightly regulate the phenotype of a mature SAM. These studies provide a foundation for detailed characterization of the scaffold immune microenvironment of a given biomaterial scaffold to determine the effect of scaffold changes on immune response and subsequent therapeutic outcome of that material.

  4. Pharmacists as immunizers: a survey of community pharmacists' willingness to administer adult immunizations.

    Science.gov (United States)

    Edwards, Nicholas; Gorman Corsten, Erin; Kiberd, Mathew; Bowles, Susan; Isenor, Jennifer; Slayter, Kathryn; McNeil, Shelly

    2015-04-01

    Adult immunization rates worldwide fall below desired targets. Pharmacists are highly accessible healthcare providers with the potential to increase immunization rates among adults by administering vaccines in their practice setting. To determine the attitudes of community-based Canadian pharmacists with respect to expanding their scope of practice to include administration of immunizations. An internet-based survey was emailed to community pharmacists across Canada. The survey was piloted through focus groups for qualitative feedback, tested for content validity, and test-retest reliability prior to dissemination. There were 495 responses to the survey. The majority (88 %) agreed that pharmacists as immunizers would increase public access, improve rates (84 %), and be acceptable to the public (72 %). However, only 68 % agreed that pharmacists should be permitted to immunize. The majority of respondents (90 %) agreed that certification in vaccine administration should be required for pharmacists to administer vaccines. Pharmacists identified education, reimbursement, and negative interactions with other providers as barriers to pharmacists administering vaccines. Canadian pharmacists are willing to expand their scope of practice to include immunization. However, implementation requires professional development and certification in vaccine administration.

  5. Partial immunity in murine by immunization with a toxoplasmic DNA ...

    African Journals Online (AJOL)

    arsenal

    2012-06-12

    Jun 12, 2012 ... vaccine can be effective in partial protection against this parasite. In this study ... that mice immunized by pcROP1 with or without alum produced high Th1 immune response compared .... antigen-specific antibodies, 96-well costar plates were coated .... vaccines against some protozoa, for example, malaria,.

  6. The Limits to Buying Stability in Tibet: Tibetan Representation and Preferentiality in China's Contemporary Public Employment System

    NARCIS (Netherlands)

    A.M. Fischer (Andrew Martín); A. Zenz (Adrian)

    2017-01-01

    textabstractBased on an entirely unexplored source of data, this paper analyses the evolution of Tibetan representation and preferentiality within public employment recruitment across all Tibetan areas from 2007 to 2015. While recruitment collapsed after the end of the job placement system (fenpei)

  7. Immune System Dysfunction in the Elderly.

    Science.gov (United States)

    Fuentes, Eduardo; Fuentes, Manuel; Alarcón, Marcelo; Palomo, Iván

    2017-01-01

    Human aging is characterized by both physical and physiological frailty that profoundly affects the immune system. In this context aging is associated with declines in adaptive and innate immunity established as immunosenescence. Immunosenescence is a new concept that reflects the age-associated restructuring changes of innate and adaptive immune functions. Thus elderly individuals usually present chronic low-level inflammation, higher infection rates and chronic diseases. A study of alterations in the immune system during aging could provide a potentially useful biomarker for the evaluation of immune senescence treatment. The immune system is the result of the interplay between innate and adaptive immunity, yet the impact of aging on this function is unclear. In this article the function of the immune system during aging is explored.

  8. Immunizations for Preterm Babies

    Science.gov (United States)

    ... Issues Health Issues Health Issues Conditions Injuries & Emergencies Vaccine Preventable Diseases ... Children > Safety & Prevention > Immunizations > Immunizations For Preterm Babies Safety & ...

  9. Immunizations: Active vs. Passive

    Science.gov (United States)

    ... Issues Health Issues Health Issues Conditions Injuries & Emergencies Vaccine Preventable Diseases ... Children > Safety & Prevention > Immunizations > Immunizations: Active vs. Passive Safety & ...

  10. The Biochemistry and Regulation of S100A10: A Multifunctional Plasminogen Receptor Involved in Oncogenesis

    Directory of Open Access Journals (Sweden)

    Patricia A. Madureira

    2012-01-01

    Full Text Available The plasminogen receptors mediate the production and localization to the cell surface of the broad spectrum proteinase, plasmin. S100A10 is a key regulator of cellular plasmin production and may account for as much as 50% of cellular plasmin generation. In parallel to plasminogen, the plasminogen-binding site on S100A10 is highly conserved from mammals to fish. S100A10 is constitutively expressed in many cells and is also induced by many diverse factors and physiological stimuli including dexamethasone, epidermal growth factor, transforming growth factor-α, interferon-γ, nerve growth factor, keratinocyte growth factor, retinoic acid, and thrombin. Therefore, S100A10 is utilized by cells to regulate plasmin proteolytic activity in response to a wide diversity of physiological stimuli. The expression of the oncogenes, PML-RARα and KRas, also stimulates the levels of S100A10, suggesting a role for S100A10 in pathophysiological processes such as in the oncogenic-mediated increases in plasmin production. The S100A10-null mouse model system has established the critical role that S100A10 plays as a regulator of fibrinolysis and oncogenesis. S100A10 plays two major roles in oncogenesis, first as a regulator of cancer cell invasion and metastasis and secondly as a regulator of the recruitment of tumor-associated cells, such as macrophages, to the tumor site.

  11. Immune Repertoire after Immunization As Seen by Next-Generation Sequencing and Proteomics

    Directory of Open Access Journals (Sweden)

    Martijn M. VanDuijn

    2017-10-01

    Full Text Available The immune system produces a diverse repertoire of immunoglobulins in response to foreign antigens. During B-cell development, VDJ recombination and somatic mutations generate diversity, whereas selection processes remove it. Using both proteomic and NGS approaches, we characterized the immune repertoires in groups of rats after immunization with purified antigens. Proteomics and NGS data on the repertoire are in qualitative agreement, but did show quantitative differences that may relate to differences between the biological niches that were sampled for these approaches. Both methods contributed complementary information in the characterization of the immune repertoire. It was found that the immune repertoires resulting from each antigen had many similarities that allowed samples to cluster together, and that mutated immunoglobulin peptides were shared among animals with a response to the same antigen significantly more than for different antigens. However, the number of shared sequences decreased in a log-linear fashion relative to the number of animals that share them, which may affect future applications. A phylogenetic analysis on the NGS reads showed that reads from different individuals immunized with the same antigen populated distinct branches of the phylogram, an indication that the repertoire had converged. Also, similar mutation patterns were found in branches of the phylogenetic tree that were associated with antigen-specific immunoglobulins through proteomics data. Thus, data from different analysis methods and different experimental platforms show that the immunoglobulin repertoires of immunized animals have overlapping and converging features. With additional research, this may enable interesting applications in biotechnology and clinical diagnostics.

  12. Solubility and preferential solvation of some n-alkyl-parabens in methanol + water mixtures at 298.15 K

    International Nuclear Information System (INIS)

    Cárdenas, Zaira J.; Jiménez, Daniel M.; Delgado, Daniel R.; Almanza, Ovidio A.; Jouyban, Abolghasem; Martínez, Fleming; Acree, William E.

    2017-01-01

    Highlights: • Parabens equilibrium solubility was determined in methanol + water binary mixtures at 298.15 K. • Solubility values were correlated with the Jouyban-Acree model. • Preferential solvation parameters were derived by using the IKBI method. • δx 1,3 values are negative in water-rich mixtures but positive in the other mixtures. - Abstract: Methyl, ethyl and propyl parabens equilibrium solubility was determined in (methanol + water) binary mixtures at 298.15 K. The mole fraction solubility of these compounds increased in 503 (from 2.40 × 10 −4 to 0.121), 1377 (from 9.86 × 10 −5 to 0.136) and 4597 (from 3.73 × 10 −5 to 0.171) times when passing from neat water to neat methanol, for methyl, ethyl and propyl parabens, respectively. All these solubility values were correlated with the Jouyban-Acree model. Preferential solvation parameters by methanol (δx 1,3 ) of these parabens were derived from their thermodynamic solution properties using the inverse Kirkwood-Buff integrals (IKBI) method. For all compounds δx 1,3 values are negative in water-rich mixtures but positive in mixtures with methanol mole fraction greater than 0.32. It is conjecturable that in the former case the hydrophobic hydration around non-polar groups of parabens plays a relevant role in the solvation. Besides, the preferential solvation of these solutes by methanol in mixtures of similar co-solvent compositions and in methanol-rich mixtures could be explained in terms of the higher basic behaviour of methanol.

  13. [Comparison of immune response after oral and intranasal immunization with recombinant Lactobacillus casei expressing ETEC F41].

    Science.gov (United States)

    Liu, Jiankui; Wei, Chunhua; Hou, Xilin; Wang, Guihua; Yu, Liyun

    2009-04-01

    In order to represent a promising strategy for mucosal vaccination, oral or intranasal immunization of Specific Pathogen Free (SPF) BALB/c mice were performed. The mucosal immunity, systemic immune and protective immune responses were compared after immunization with the recombinant Lactobacillus casei (L. casei) harboring enterotoxigenic Escherichia coli (ETEC) F41. The recombinant fusion proteins were detected by Western blot. Surface localization of the fusion protein was verified by immunofluorescence microscopy and flow cytometry. Six-week-old female SPF BALB/c mice (160 heads) were divided into 4 groups for immunization and control. Oral and intranasal immunization of mice was performed with the recombinant strain L. casei harboring pLA-F41 or pLA. For oral immunization, the mice were inoculated daily on days 0 to 4, 7 to 11, 21 to 25, and 49 to 53. A lighter schedule was used for nasal immunization (days 0 to 2, 7 to 9, 21 and 49). Specific anti-F41 IgG antibody in the serum and specific anti-F41 secret immunoglobulin A (sIgA) antibody in the lung, intestines, vagina fluid and feces of mice were detected by indirect ELISA. The mice orally or intranasally immunized with pLA-F41/L. casei and pLA/IL. casei were challenged with standard-type ETEC F41 (C83919) (2 x 10(3) LD50). Mice immunized with pLA-F41/L. casei could produce remarkable anti-F41 antibody level. More than 90% survived in oral immunization group whereas more than 85% survived in intranasal immunization group after challenged with C83919, all dead in the control group. Ninety percent of the pups survived in oral immunization group whereas 80% survived in intranasal immunization group after challenged with C83919, but only a 5% survival rate for pups that were either immunized with a control pLA vector or unimmunized. Oral or intranasal immunization with recombinant L. casei displaying ETEC F41 antigens on the surface induced effective and similar systemic and mucosal immune responses against the

  14. Broad blockade antibody responses in human volunteers after immunization with a multivalent norovirus VLP candidate vaccine: immunological analyses from a phase I clinical trial.

    Directory of Open Access Journals (Sweden)

    Lisa C Lindesmith

    2015-03-01

    Full Text Available Human noroviruses (NoVs are the primary cause of acute gastroenteritis and are characterized by antigenic variation between genogroups and genotypes and antigenic drift of strains within the predominant GII.4 genotype. In the context of this diversity, an effective NoV vaccine must elicit broadly protective immunity. We used an antibody (Ab binding blockade assay to measure the potential cross-strain protection provided by a multivalent NoV virus-like particle (VLP candidate vaccine in human volunteers.Sera from ten human volunteers immunized with a multivalent NoV VLP vaccine (genotypes GI.1/GII.4 were analyzed for IgG and Ab blockade of VLP interaction with carbohydrate ligand, a potential correlate of protective immunity to NoV infection and illness. Immunization resulted in rapid rises in IgG and blockade Ab titers against both vaccine components and additional VLPs representing diverse strains and genotypes not represented in the vaccine. Importantly, vaccination induced blockade Ab to two novel GII.4 strains not in circulation at the time of vaccination or sample collection. GII.4 cross-reactive blockade Ab titers were more potent than responses against non-GII.4 VLPs, suggesting that previous exposure history to this dominant circulating genotype may impact the vaccine Ab response. Further, antigenic cartography indicated that vaccination preferentially activated preexisting Ab responses to epitopes associated with GII.4.1997. Study interpretations may be limited by the relevance of the surrogate neutralization assay and the number of immunized participants evaluated.Vaccination with a multivalent NoV VLP vaccine induces a broadly blocking Ab response to multiple epitopes within vaccine and non-vaccine NoV strains and to novel antigenic variants not yet circulating at the time of vaccination. These data reveal new information about complex NoV immune responses to both natural exposure and to vaccination, and support the potential

  15. Immune response in the lungs following oral immunization with bacterial lysates of respiratory pathogens.

    OpenAIRE

    Ruedl, C; Frühwirth, M; Wick, G; Wolf, H

    1994-01-01

    We have investigated the local immune response of the BALB/c mouse respiratory tract after oral immunization with a bacterial lysate of seven common respiratory pathogens. After two immunization on five consecutive days, we examined the immunoglobulin (immunoglobulin G [IgG], IgM, and IgA) secretion rates of cells isolated from the lungs and compared them with those of spleen cells of orally immunized and nonimmunized animals by using a new test system based on time-resolved fluorescence. The...

  16. Development of immune organs and functioning in humans and test animals: Implications for immune intervention studies.

    Science.gov (United States)

    Kuper, C Frieke; van Bilsen, Jolanda; Cnossen, Hilde; Houben, Geert; Garthoff, Jossie; Wolterbeek, Andre

    2016-09-01

    A healthy immune status is mostly determined during early life stages and many immune-related diseases may find their origin in utero and the first years of life. Therefore, immune health optimization may be most effective during early life. This review is an inventory of immune organ maturation events in relation to developmental timeframes in minipig, rat, mouse and human. It is concluded that time windows of immune organ development in rodents can be translated to human, but minipig reflects the human timeframes better; however the lack of prenatal maternal-fetal immune interaction in minipig may cause less responsiveness to prenatal intervention. It is too early to conclude which immune parameters are most appropriate, because there are not enough comparative immune parameters. Filling these gaps will increase the predictability of results observed in experimental animals, and guide future intervention studies by assessing relevant parameters in the right corresponding developmental time frames. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Studies on the transfer of protective immunity with lymphoid cells from mice immune to malaria sporozoites

    International Nuclear Information System (INIS)

    Verhave, J.P.; Strickland, G.T.; Jaffe, H.A.; Ahmed, A.

    1978-01-01

    In an effort to understand the mechanisms involved in the protective immunity to malarial sporozoites, an A/J mouse/Plasmodium berghei model was studied. Protective immunity could consistently be adoptively transferred only by using sublethal irradiation of recipients (500 R); a spleen equivalent (100 x 10 6 ) of donor cells from immune syngeneic mice; and a small booster immunization (1 x 10 4 ) of recipients with irradiation-attenuated sporozoites. Recipient animals treated in this manner were protected from lethal challenge with 1 x 10 4 nonattenuated sporozoites. Immune and nonimmune serum and spleen cells from nonimmune animals did not protect recipient mice. Fewer immune spleen cells (50 x 10 6 ) protected some recipients. In vitro treatment of immune spleen cells with anti-theta sera and complement abolished their ability to transfer protection. This preliminary study suggests that protective sporozoite immunity can be transferred with cells, and that it is T cell dependent

  18. Self-recognition drives the preferential accumulation of promiscuous CD4+ T-cells in aged mice

    OpenAIRE

    Deshpande, Neha R; Parrish, Heather L; Kuhns, Michael S

    2015-01-01

    eLife digest The immune system's T cells help the body to recognize and destroy harmful pathogens, such as viruses and bacteria. T cells ?remember? immunity-inducing fragments, called antigens, from the pathogens they have encountered. This memory then allows the immune system to quickly fend off infections if those pathogens, or even related pathogens, invade again. Vaccines exploit the ability to form immunological memory by exposing the body to harmless forms of the pathogen, or even just ...

  19. [Effect of vitamine A on mice immune response induced by specific periodontal pathogenic bacteria-immunization].

    Science.gov (United States)

    Lin, Xiao-Ping; Zhou, Xiao-Jia; Liu, Hong-Li; DU, Li-Li; Toshihisa, Kawai

    2010-12-01

    The aim of this study was to investigate the effect of vitamine-A deficiency on the induction of specific periodontal pathogenic bacteria A. actinomycetetemcomitans(Aa) immunization. BALB/c mice were fed with vitamine A-depleted diet or control regular diet throughout the whole experiment period. After 2 weeks, immunized formalin-killed Aa to build immunized models, 6 weeks later, sacrificed to determine specific antibody-IgG, IgM and sub-class IgG antibody titers in serum, and concentration of IL-10, IFN-γ, TNF-α and RANKL in T cell supernatant were measured by ELISA and T cell proliferation was measured by cintilography. SPSS 11.5 software package was used for statistical analysis. The levels of whole IgG and IgM antibody which were immunized by Aa significantly elevated, non-immune group was unable to produce any antibody. Compared with Aa immunized+RD group, the level of whole IgG in Aa immunized+VAD group was significantly higher (Pvitamin-A diet can increase the immunized mice's susceptibility to periodontal pathogenic bacteria and trigger or aggravate immune inflammatory response. Adequate vitamin A is an important factor in maintaining body health. Supported by Natural Science Foundation of Liaoning Province (Grant No.20092139) and Science and Technology Program of Shenyang Municipality (Grant No.F10-149-9-32).

  20. Maternal immunization increases nestling energy expenditure, immune function, and fledging success in a passerine bird

    Directory of Open Access Journals (Sweden)

    Gary Burness

    2018-04-01

    Full Text Available Female birds transfer maternally derived antibodies (matAb to their nestlings, via the egg yolk. These antibodies are thought to provide passive protection, and allow nestlings to avoid the costs associated with mounting an innate immune response. To test whether there is an energetic benefit to nestlings from receiving matAb, we challenged adult female tree swallows (Tachycineta bicolor prior to clutch initiation with either lipopolysaccharide (LPS or saline (Control. Following hatching, one half of each female's nestlings were immunized on day 8 post-hatch with LPS or saline, and the 4-h post-immunization nestling metabolic rate (MR was measured. There was no difference in either LPS-reactive antibodies or total Ig levels between offspring of immunized and non-immunized mothers on day 6 or 14 post-hatch, possibly reflecting a relatively short half-life of matAbs in altricial birds. Additionally, we found no evidence that nestlings from LPS-immunized mothers could avoid the growth suppression that may result from activation of an inflammatory response. Unexpectedly, we found that control nestlings from LPS mothers had higher resting MR than control nestlings of control mothers. We attribute the increased MR to the costs associated with a general non-specific enhancement of immune function in nestlings from LPS-immunized mothers. Consistent with enhanced immune function, nestlings of immunized mothers had a more robust inflammatory response to phytohaemagglutinin and higher fledging success. Our results suggest that maternal antigen exposure pre-laying can result in increased fitness for both mothers and offspring, depending on food availability.

  1. Studies on cross-immunity among syngeneic tumors by immunization with gamma-irradiated tumor cells

    International Nuclear Information System (INIS)

    Ito, Izumi

    1977-01-01

    In order to clarify whether cross-immunity among 3-methyl-cholanthrene (MCA)-induced sarcomas in C3H/He mice can be established or not, transplantations of syngeneic tumors were carried out in mice immunized with gamma-irradiated (13,000 rad 60 Co) tumor cells and in those immunized with living tumor cells thereafter. The following results were obtained. By using immunizing procedure with only gamma-irradiated tumor cells, a pair of tumors originating from one and the same mouse showed cross-resistance to each other. However, no such evidence was seen among tumors originating from different mice. Cross-immunity among syngeneic tumors originating from different mice could be clearly observed, when immunizing procedure using living tumor cells was added after the treatment with gamma-irradiated tumor cells. It was considered that common antigenicity among MCA-induced sarcoma cells was decreased by gamma-irradiation and that individual differences of tumor antigenecity were shown distinctly under such conditions. (auth.)

  2. Barriers to Immunizations and Strategies to Enhance Immunization Rates in Adults with Autoimmune Inflammatory Diseases.

    Science.gov (United States)

    Kirchner, Elizabeth; Ruffing, Victoria

    2017-02-01

    For as long as there have been immunizations, there have been barriers to them. Immunization rates in the United States are below target. Rheumatologists and rheumatology practitioners need to understand the issues of immunizations in patients with autoimmune inflammatory disease to identify and overcome barriers to immunization. Several strategies for overcoming these barriers are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Cross-immunity among mammary carcinomas in C3H/HE mice immunized with gamma-irradiated tumor cells

    International Nuclear Information System (INIS)

    Waga, Takashi

    1980-01-01

    By immunization with gamma-irradiated (13,000 rad) tumor cells, cross-immunity between ascites mammary carcinomas and among solid mammary carcinomas in C3H/He mice was studied. The results were as follows: (1) Two ascites mammary carcinomas designated MM 46 (high vitality) and MM 48 (intermediate vitality) were used in this experiment. The immunization with the tumor of high vitality (MM 46) induced strong cross-immunity against the challenge of the tumor of intermediate vitality (MM 48). The immunization with the tumor of intermediate vitality (MM 48) induced weak cross-immunity against the challenge of the tumor of high vitality (MM 46). (2) Three solid mammary carcinomas designated MT 10 (intermediate vitality), MT 7 (high vitality) and MT X (the highest vitality) were used in this experiment. The immunization with the tumor of high vitality (MT 7) induced strong cross-immunity against the challenge of the tumor of intermediate vitality (MT 10), and induced moderate cross-immunity against the challenge of the tumor of the highest vitality (MT X). The immunization with the tumor of intermediate vitality (MT 10) induced moderate cross-immunity against the challenge of the tumor of high vitality (MT 7), but could not induce any cross-immunity against the challenge of the tumor of the highest vitality (MT X). (author)

  4. [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.

  5. The Concordance of Parent and Child Immunization.

    Science.gov (United States)

    Robison, Steve G; Osborn, Andrew W

    2017-05-01

    A substantial body of work has related survey-based parental vaccine hesitancy to noncompliant childhood immunization. However little attention has been paid to the connection between parents' own immunization behavior and the immunizations their children receive. Using the Oregon ALERT Immunization Information System, we identified adult caregiver-child pairs for children between 9 months and 17 years of age. The likelihood of adult-child concordance of influenza immunization per influenza season from 2010-2011 through 2014-2015 was assessed. The utility of adult immunization as a predictor was also assessed for other, noninfluenza recommended immunizations for children and adolescents. A total of 450 687 matched adult caregiver-child pairs were included in the study. The children of immunizing adults were 2.77 times more likely to also be immunized for seasonal influenza across all seasons (95% confidence interval, 2.74-2.79), with similar results applying within each season. Adult immunization status was also significantly associated with the likelihood of children and adolescents getting other noninfluenza immunizations, such as the human papillomavirus vaccine (HPV). When adults improved their own behavior from nonimmunizing to immunizing across influenza seasons, their children if not immunized in the previous season were 5.44 times (95% confidence interval, 5.35-5.53) more likely to become immunized for influenza. Children's likelihood of following immunization recommendations is associated with the immunization behavior of their parents. Encouraging parental immunization is a potential tool for increasing children's immunization rates. Copyright © 2017 by the American Academy of Pediatrics.

  6. Surface-Selective Preferential Production of Reactive Oxygen Species on Piezoelectric Ceramics for Bacterial Killing

    OpenAIRE

    Tan, Guoxin; Wang, Shuangying; Zhu, Ye; Zhou, Lei; Yu, Peng; Wang, Xiaolan; He, Tianrui; Chen, Junqi; Mao, Chuanbin; Ning, Chengyun

    2016-01-01

    Reactive oxygen species (ROS) can be used to kill bacterial cells, and thus the selective generation of ROS from material surfaces is an emerging direction in antibacterial material discovery. We found the polarization of piezoelectric ceramic causes the two sides of the disk to become positively and negatively charged, which translate into cathode and anode surfaces in an aqueous solution. Because of the microelectrolysis of water, ROS are preferentially formed on the cathode surface. Conseq...

  7. Characterization and quantification of preferential flow in fractured rock systems, using resistivity tomography

    CSIR Research Space (South Africa)

    May, F

    2010-11-01

    Full Text Available , N Jovanovic2 and A Rozanov1 University of Stellenbosch1 and Council for Scientific and Industrial Research (CSIR)2 Characterization and quantification of preferential flow in fractured rock systems, using resistivity tomography Introduction... of slow and fast flowing pathways. Materials and Methods TABLE 1 DATE, TIME AND WEATHER CONDITIONS DURING RESISTIVITY TOMOGRAPHY SURVEY Survey No. Date Start time End time Precipitation (mm) Description KB001 8/27/2010 12H00 13H40 0.0 Sunny KB002 8...

  8. Student pharmacists' perceptions of immunizations.

    Science.gov (United States)

    Kubli, Kara; McBane, Sarah; Hirsch, Jan D; Lorentz, Sarah

    2017-05-01

    The primary aim of this study was to explore changes in knowledge level, perceived importance and apprehension of immunizations by first year pharmacy students pre- vs. post-immunization education and training. First year pharmacy students at the University of California San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences (UC San Diego SSPPS) completed a pre- and post-immunization training course questionnaire. Knowledge base and perceived importance level of immunizations including hepatitis B, influenza, measles, mumps, rubella (MMR), varicella, tetanus, diphtheria, pertussis (Tdap), meningococcal and human papilloma virus (HPV) were assessed. In addition, apprehension of needle administration and fears regarding safety and efficacy were evaluated. Of 120 students, 85 (71%) completed pre- and post-course questionnaires for this study. Mean knowledge test scores increased from 56% pre-course to 83% post-course. Pre-course, 73% of participants considered immunizations as very important in preventing future disease outbreaks. Post-course, this percentage climbed to 94%. Prior to taking the course, 52% of students were apprehensive about administering injections; however, after completing the course this percentage declined to 33%. The majority of students who had been fearful prior to the course retained their fears of receiving needle injections. The proportion of students believing immunizations should be a personal choice, not mandatory, did not significantly change from pre-course (49%) to post-course (44%). The UC San Diego SSPPS immunization course increased student knowledge of immunization facts and the perceived importance of immunizations. However, a substantial portion of students retained apprehension about administering and receiving needle injections and the proportion believing immunizations should be a personal choice, almost half, did not change appreciably. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Estimation of Unsaturated Zone Traveltimes for Rainier Mesa and Shoshone Mountain, Nevada Test Site, Nevada, Using a Source-Responsive Preferential-Flow Model

    Science.gov (United States)

    Ebel, Brian A.; Nimmo, John R.

    2009-01-01

    zone takes place as preferential flow, faster than would be predicted by the coupled Richards' and advection-dispersion equations with hydraulic properties estimated by traditional means. At present the hydrologic community has not achieved consensus as to whether a modification of Richards' equation, or a fundamentally different formulation, would best quantify preferential flow. Where the fastest contaminant transport speed is what needs to be estimated, there is the possibility of simplification of the evaluation process. One way of doing so is by a two-step process in which the first step is to evaluate whether significant preferential flow and solute transport is possible for the media and conditions of concern. The second step is to carry out (a) a basic Richards' and advection-dispersion equation analysis if it is concluded that preferential flow is not possible or (b) an analysis that considers only the fastest possible preferential-flow processes, if preferential flow is possible. For the preferential-flow situation, a recently published model describable as a Source-Responsive Preferential-Flow (SRPF) model is an easily applied option. This report documents the application of this two-step process to flow through the thick unsaturated zones of Rainier Mesa and Shoshone Mountain in the Nevada Test Site. Application of the SRPF model involves distinguishing between continuous and intermittent water supply to preferential flow paths. At Rainier Mesa and Shoshone Mountain this issue is complicated by the fact that contaminant travel begins at a location deep in the subsurface, where there may be perched water that may or may not act like a continuous supply, depending on such features as the connectedness of fractures and the nature of impeding layers. We have treated this situation by hypothesizing both continuous and intermittent scenarios for contaminant transport to the carbonate aquifer and reporting estimation of the fastest speed for both of th

  10. Estimation of unsaturated zone traveltimes for Rainier Mesa and Shoshone Mountain, Nevada Test Site, Nevada, using a source-responsive preferential-flow model

    Energy Technology Data Exchange (ETDEWEB)

    Brian A. Ebel; John R. Nimmo

    2009-09-11

    unsaturated zone takes place as preferential flow, faster than would be predicted by the coupled Richards' and advection-dispersion equations with hydraulic properties estimated by traditional means. At present the hydrologic community has not achieved consensus as to whether a modification of Richards' equation, or a fundamentally different formulation, would best quantify preferential flow. Where the fastest contaminant transport speed is what needs to be estimated, there is the possibility of simplification of the evaluation process. One way of doing so is by a two-step process in which the first step is to evaluate whether significant preferential flow and solute transport is possible for the media and conditions of concern. The second step is to carry out (a) a basic Richards' and advection-dispersion equation analysis if it is concluded that preferential flow is not possible or (b) an analysis that considers only the fastest possible preferential-flow processes, if preferential flow is possible. For the preferential-flow situation, a recently published model describable as a Source-Responsive Preferential-Flow (SRPF) model is an easily applied option. This report documents the application of this two-step process to flow through the thick unsaturated zones of Rainier Mesa and Shoshone Mountain in the Nevada Test Site. Application of the SRPF model involves distinguishing between continuous and intermittent water supply to preferential flow paths. At Rainier Mesa and Shoshone Mountain this issue is complicated by the fact that contaminant travel begins at a location deep in the subsurface, where there may be perched water that may or may not act like a continuous supply, depending on such features as the connectedness of fractures and the nature of impeding layers. We have treated this situation by hypothesizing both continuous and intermittent scenarios for contaminant transport to the carbonate aquifer and reporting estimation of the fastest speed for

  11. Monkeys preferentially process body information while viewing affective displays.

    Science.gov (United States)

    Bliss-Moreau, Eliza; Moadab, Gilda; Machado, Christopher J

    2017-08-01

    Despite evolutionary claims about the function of facial behaviors across phylogeny, rarely are those hypotheses tested in a comparative context-that is, by evaluating how nonhuman animals process such behaviors. Further, while increasing evidence indicates that humans make meaning of faces by integrating contextual information, including that from the body, the extent to which nonhuman animals process contextual information during affective displays is unknown. In the present study, we evaluated the extent to which rhesus macaques (Macaca mulatta) process dynamic affective displays of conspecifics that included both facial and body behaviors. Contrary to hypotheses that they would preferentially attend to faces during affective displays, monkeys looked for longest, most frequently, and first at conspecifics' bodies rather than their heads. These findings indicate that macaques, like humans, attend to available contextual information during the processing of affective displays, and that the body may also be providing unique information about affective states. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  12. Preferential rifting of continents - A source of displaced terranes

    Science.gov (United States)

    Vink, G. E.; Morgan, W. J.; Zhao, W.-L.

    1984-01-01

    Lithospheric rifting, while prevalent in the continents, rarely occurs in oceanic regions. To explain this preferential rifting of continents, the total strength of different lithospheres is compared by integrating the limits of lithospheric stress with depth. Comparisons of total strength indicate that continental lithosphere is weaker than oceanic lithosphere by about a factor of three. Also, a thickened crust can halve the total strength of normal continental lithosphere. Because the weakest area acts as a stress guide, any rifting close to an ocean-continent boundary would prefer a continental pathway. This results in the formation of small continental fragments or microplates that, once accreted back to a continent during subduction, are seen as displaced terranes. In addition, the large crustal thicknesses associated with suture zones would make such areas likely locations for future rifting episodes. This results in the tendency of new oceans to open along the suture where a former ocean had closed.

  13. Simulation study of soil water and heat dynamics at two sites with significant preferential flow

    Science.gov (United States)

    Votrubova, J.; Vogel, T.; Dohnal, M.; Tesar, M.

    2012-04-01

    Numerical models based on two hydraulically contrasting flow domains coupled through a simple transfer formula have become a useful tool for modeling both water flow and associated substance transport in structured soils. A comparative numerical study focused on the preferential flow effects on the soil heat transport is presented. Sites located in two different headwater catchments were included. Experimental catchment Liz is situated in a forested mountain area of Sumava Mts. in the southern part of the Czech Republic (altitude: 830 m, mean annual temperature: 6.3°C, mean annual precipitation: 861 mm). Uhlirska catchment is located in the north-west of the Czech Republic in Jizera Mts. and is currently undergoing reforestation (altitude: 820 m, mean annual temperature: 4.6°C, mean annual precipitation: 1400 mm). Both sites are instrumented for monitoring of the relevant meteorological and hydrological variables, as well as the soil moisture and temperature distribution. Changes of the soil water content and temperature during vegetation season were simulated. Model performance was qualitatively evaluated and shown to replicate the field measurements. The soils' heat budgets and the preferential flow effect thereon was compared and analyzed.

  14. Preferential solvation, ion pairing, and dynamics of concentrated aqueous solutions of divalent metal nitrate salts

    Science.gov (United States)

    Yadav, Sushma; Chandra, Amalendu

    2017-12-01

    We have investigated the characteristics of preferential solvation of ions, structure of solvation shells, ion pairing, and dynamics of aqueous solutions of divalent alkaline-earth metal nitrate salts at varying concentration by means of molecular dynamics simulations. Hydration shell structures and the extent of preferential solvation of the metal and nitrate ions in the solutions are investigated through calculations of radial distribution functions, tetrahedral ordering, and also spatial distribution functions. The Mg2+ ions are found to form solvent separated ion-pairs while the Ca2+ and Sr2+ ions form contact ion pairs with the nitrate ions. These findings are further corroborated by excess coordination numbers calculated through Kirkwood-Buff G factors for different ion-ion and ion-water pairs. The ion-pairing propensity is found to be in the order of Mg(NO3) 2 lead to the presence of substantial dynamical heterogeneity in these solutions of strongly interacting ions. The current study helps us to understand the molecular details of hydration structure, ion pairing, and dynamics of water in the solvation shells and also of ion diffusion in aqueous solutions of divalent metal nitrate salts.

  15. Preferential heating of oxygen 5{sup +} ions by finite-amplitude oblique Alfvén waves

    Energy Technology Data Exchange (ETDEWEB)

    Maneva, Yana G.; Poedts, Stefaan [Centre for mathematical Plasma Astrophysics, KU Leuven, B-3001 Leuven (Belgium); Viñas, Adolfo [NASA Goddard Space Flight Center, Heliophysics Science Division, Greenbelt, 20771 MD (United States); Araneda, Jaime [Departamento de Física, Universidad de Concepción, Casilla 160 - C, Concepción (Chile)

    2016-03-25

    Minor ions in the fast solar wind are known to have higher temperatures and to flow faster than protons in the interplanetary space. In this study we combine previous research on parametric instability theory and 2.5D hybrid simulations to study the onset of preferential heating of Oxygen 5{sup +} ions by large-scale finite-amplitude Alfvén waves in the collisionless fast solar wind. We consider initially non-drifting isotropic multi-species plasma, consisting of isothermal massless fluid electrons, kinetic protons and kinetic Oxygen 5{sup +} ions. The external energy source for the plasma heating and energization are oblique monochromatic Alfvén-cyclotron waves. The waves have been created by rotating the direction of initial parallel pump, which is a solution of the multi-fluid plasma dispersion relation. We consider propagation angles θ ≤ 30°. The obliquely propagating Alfvén pump waves lead to strong diffusion in the ion phase space, resulting in highly anisotropic heavy ion velocity distribution functions and proton beams. We discuss the application of the model to the problems of preferential heating of minor ions in the solar corona and the fast solar wind.

  16. Enhanced thermoelectric properties of polycrystalline Bi2Te3 core fibers with preferentially oriented nanosheets

    Directory of Open Access Journals (Sweden)

    Min Sun

    2018-03-01

    Full Text Available Bi2Te3-based materials have been reported to be one of the best room-temperature thermoelectric materials, and it is a challenge to substantially improve their thermoelectric properties. Here novel Bi2Te3 core fibers with borosilicate glass cladding were fabricated utilizing a modified molten core drawing method. The Bi2Te3 core of the fiber was found to consist of hexagonal polycrystalline nanosheets, and polycrystalline nanosheets had a preferential orientation; in other words, the hexagonal Bi2Te3 lamellar cleavage more tended to be parallel to the symmetry axis of the fibers. Compared with a homemade 3-mm-diameter Bi2Te3 rod, the polycrystalline nanosheets’ preferential orientation in the 89-μm-diameter Bi2Te3 core increased its electrical conductivity, but deduced its Seebeck coefficient. The Bi2Te3 core exhibits an ultrahigh ZT of 0.73 at 300 K, which is 232% higher than that of the Bi2Te3 rod. The demonstration of fibers with oriented nano-polycrystalline core and the integration with an efficient fabrication technique will pave the way for the fabrication of high-performance thermoelectric fibers.

  17. Preferential solvation of ions in mixed solvents. 6: Univalent anions in aqueous organic solvents according to the inverse Kirkwood-Buff integral (IKBI) approach

    Energy Technology Data Exchange (ETDEWEB)

    Marcus, Yizhak [Department of Inorganic and Analytical Chemistry, Hebrew University of Jerusalem, Jerusalem 91904 (Israel)], E-mail: ymarcus@vms.huji.ac.il

    2007-10-15

    The inverse Kirkwood-Buff integral (IKBI) approach is applied to the preferential solvation of F{sup -}, Cl{sup -}, Br{sup -}, I{sup -}, and ClO{sub 4}{sup -} in aqueous mixtures of the co-solvents (S) methanol (MeOH), ethanol (EtOH), t-butanol (t-BuOH), 1,2-ethanediol (EG), glycerol (Gly), acetone (Me{sub 2}CO), acetonitrile (MeCN), formamide (FA), N,N-dimethylformamide (DMF), N,N,N',N',N'',N''-hexamethyl phosphoric triamide (HMPT), and dimethylsulfoxide (DMSO), as far as the relevant data exist in the literature. Fluoride anions are selectively solvated by the water up to large mole fractions (x{sub S} {>=} 0.4) of S = EtOH, t-BuOH, Me{sub 2}CO, MeCN, and DMF, and up to lower contents (x{sub S} {approx} 0.1) of MeOH, EG, FA, and DMSO. The other anions are preferentially solvated by water to diminishing extent as their sizes become larger, and the largest ones show some preference for S in water-rich mixtures of MeOH and FA, whereas in aqueous Gly even chloride is preferentially solvated by the Gly. The competition between the co-solvent and the anion for the hydrogen bonds that water molecules donate is the main cause for the observed preferential solvation behaviour.

  18. Preferential methanogenic biodegradation of short-chain n-alkanes by microbial communities from two different oil sands tailings ponds.

    Science.gov (United States)

    Mohamad Shahimin, Mohd Faidz; Foght, Julia M; Siddique, Tariq

    2016-05-15

    Oil sands tailings ponds harbor diverse anaerobic microbial communities capable of methanogenic biodegradation of solvent hydrocarbons entrained in the tailings. Mature fine tailings (MFT) from two operators (Albian and CNRL) that use different extraction solvents were incubated with mixtures of either two (n-pentane and n-hexane) or four (n-pentane, n-hexane, n-octane and n-decane) n-alkanes under methanogenic conditions for ~600 d. Microbes in Albian MFT began methane production by ~80 d, achieving complete depletion of n-pentane and n-hexane in the two-alkane mixture and their preferential biodegradation in the four-alkane mixture. Microbes in CNRL MFT preferentially metabolized n-octane and n-decane in the four-alkane mixture after a ~80 d lag but exhibited a lag of ~360 d before commencing biodegradation of n-pentane and n-hexane in the two-alkane mixture. 16S rRNA gene pyrosequencing revealed Peptococcaceae members as key bacterial n-alkane degraders in all treatments except CNRL MFT amended with the four-alkane mixture, in which Anaerolineaceae, Desulfobacteraceae (Desulfobacterium) and Syntrophaceae (Smithella) dominated during n-octane and n-decane biodegradation. Anaerolineaceae sequences increased only in cultures amended with the four-alkane mixture and only during n-octane and n-decane biodegradation. The dominant methanogens were acetoclastic Methanosaetaceae. These results highlight preferential n-alkane biodegradation by microbes in oil sands tailings from different producers, with implications for tailings management and reclamation. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Incomplete Early Childhood Immunization Series and Missing Fourth DTaP Immunizations; Missed Opportunities or Missed Visits?

    Science.gov (United States)

    Robison, Steve G

    2013-01-01

    The successful completion of early childhood immunizations is a proxy for overall quality of early care. Immunization statuses are usually assessed by up-to-date (UTD) rates covering combined series of different immunizations. However, series UTD rates often only bear on which single immunization is missing, rather than the success of all immunizations. In the US, most series UTD rates are limited by missing fourth DTaP-containing immunizations (diphtheria/tetanus/pertussis) due at 15 to 18 months of age. Missing 4th DTaP immunizations are associated either with a lack of visits at 15 to 18 months of age, or to visits without immunizations. Typical immunization data however cannot distinguish between these two reasons. This study compared immunization records from the Oregon ALERT IIS with medical encounter records for two-year olds in the Oregon Health Plan. Among those with 3 valid DTaPs by 9 months of age, 31.6% failed to receive a timely 4th DTaP; of those without a 4th DTaP, 42.1% did not have any provider visits from 15 through 18 months of age, while 57.9% had at least one provider visit. Those with a 4th DTaP averaged 2.45 encounters, while those with encounters but without 4th DTaPs averaged 2.23 encounters.

  20. Estatus de la concentración de homocisteina y de algunos componentes de la fibrinólisis: Eslabón trombogénico en la homocistinuria clásica

    Directory of Open Access Journals (Sweden)

    S. A. Castañeda

    2001-07-01

    Full Text Available El objetivo de este estudio fue determinar el estatus de las concentraciones de homociteína (Hcy, inhibidor del activador del plasminógeno tipo 1 (PAI-1 y activador tisular del plasminógeno (tPA en pacientes con homocistinuria clásica, en familiares de éstos y en una población control sana.

  1. The response dynamics of preferential choice.

    Science.gov (United States)

    Koop, Gregory J; Johnson, Joseph G

    2013-12-01

    The ubiquity of psychological process models requires an increased degree of sophistication in the methods and metrics that we use to evaluate them. We contribute to this venture by capitalizing on recent work in cognitive science analyzing response dynamics, which shows that the bearing information processing dynamics have on intended action is also revealed in the motor system. This decidedly "embodied" view suggests that researchers are missing out on potential dependent variables with which to evaluate their models-those associated with the motor response that produces a choice. The current work develops a method for collecting and analyzing such data in the domain of decision making. We first validate this method using widely normed stimuli from the International Affective Picture System (Experiment 1), and demonstrate that curvature in response trajectories provides a metric of the competition between choice options. We next extend the method to risky decision making (Experiment 2) and develop predictions for three popular classes of process model. The data provided by response dynamics demonstrate that choices contrary to the maxim of risk seeking in losses and risk aversion in gains may be the product of at least one "online" preference reversal, and can thus begin to discriminate amongst the candidate models. Finally, we incorporate attentional data collected via eye-tracking (Experiment 3) to develop a formal computational model of joint information sampling and preference accumulation. In sum, we validate response dynamics for use in preferential choice tasks and demonstrate the unique conclusions afforded by response dynamics over and above traditional methods. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Probiotics to Target the Intestinal and Vaginal Microbiota in HIV

    NARCIS (Netherlands)

    R.B.S. Hummelen (Ruben)

    2011-01-01

    textabstractThe human immunodeficiency virus (HIV) preferentially targets, infects and kills CD4+ lymphocytes, which are essential for initiating an immune response against invading micro-organisms. Ultimately the immune response becomes severely compromised and opportunistic infections and

  3. Preferential adsorption of NH3 gas molecules on MWCNT defect sites probed using in situ Raman spectroscopy

    CSIR Research Space (South Africa)

    Chimowa, George

    2017-06-01

    Full Text Available The preferential adsorption of NH(sub3) gas molecules on multi-walled carbon nanotubes (MWCNTs) was studied using in situ Raman spectroscopy. It was observed that the full widths at half maximum of the G band and the intensity ratio I(sub2D...

  4. Integration of HIV in the Human Genome: Which Sites Are Preferential? A Genetic and Statistical Assessment

    Science.gov (United States)

    Gonçalves, Juliana; Moreira, Elsa; Sequeira, Inês J.; Rodrigues, António S.; Rueff, José; Brás, Aldina

    2016-01-01

    Chromosomal fragile sites (FSs) are loci where gaps and breaks may occur and are preferential integration targets for some viruses, for example, Hepatitis B, Epstein-Barr virus, HPV16, HPV18, and MLV vectors. However, the integration of the human immunodeficiency virus (HIV) in Giemsa bands and in FSs is not yet completely clear. This study aimed to assess the integration preferences of HIV in FSs and in Giemsa bands using an in silico study. HIV integration positions from Jurkat cells were used and two nonparametric tests were applied to compare HIV integration in dark versus light bands and in FS versus non-FS (NFSs). The results show that light bands are preferential targets for integration of HIV-1 in Jurkat cells and also that it integrates with equal intensity in FSs and in NFSs. The data indicates that HIV displays different preferences for FSs compared to other viruses. The aim was to develop and apply an approach to predict the conditions and constraints of HIV insertion in the human genome which seems to adequately complement empirical data. PMID:27294106

  5. New Players in Immunity to Tuberculosis: The Host Microbiome, Lung Epithelium, and Innate Immune Cells

    Science.gov (United States)

    Gupta, Nancy; Kumar, Rakesh; Agrawal, Babita

    2018-01-01

    Tuberculosis (TB) is a highly contagious infection and devastating chronic disease, causing 10.4 million new infections and 1.8 million deaths every year globally. Efforts to control and eradicate TB are hampered by the rapid emergence of drug resistance and limited efficacy of the only available vaccine, BCG. Immunological events in the airways and lungs are of major importance in determining whether exposure to Mycobacterium tuberculosis (Mtb) results in successful infection or protective immunity. Several studies have demonstrated that the host microbiota is in constant contact with the immune system, and thus continually directs the nature of immune responses occurring during new infections. However, little is known about its role in the eventual outcome of the mycobacterial infection. In this review, we highlight the changes in microbial composition in the respiratory tract and gut that have been linked to the alteration of immune responses, and to the risk, prevention, and treatment of TB. In addition, we summarize our current understanding of alveolar epithelial cells and the innate immune system, and their interaction with Mtb during early infection. Extensive studies are warranted to fully understand the all-inclusive role of the lung microbiota, its interaction with epithelium and innate immune responses and resulting adaptive immune responses, and in the pathogenesis and/or protection from Mtb infection. Novel interventions aimed at influencing the microbiota, the alveolar immune system and innate immunity will shape future strategies of prevention and treatment for TB. PMID:29692778

  6. 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

  7. 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.

  8. Role of the immune system in pancreatic cancer progression and immune modulating treatment strategies.

    Science.gov (United States)

    Sideras, K; Braat, H; Kwekkeboom, J; van Eijck, C H; Peppelenbosch, M P; Sleijfer, S; Bruno, M

    2014-05-01

    Traditional chemotherapeutics have largely failed to date to produce significant improvements in pancreatic cancer survival. One of the reasons for the resilience of pancreatic cancer towards intensive treatment is that the cancer is capable of high jacking the immune system: during disease progression the immune system is converted from a system that attacks tumor cells into a support structure for the cancer, exerting trophic actions on the cancer cells. This turn-around of immune system action is achieved through mobilization and activation of regulatory T cells, myeloid derived suppressor cells, tumor-associated macrophages and fibroblasts, all of which suppress CD8 T cells and NK cells. This immune suppression occurs both through the expression of tolerance-inducing cell surface molecules, such as PD-L1, as well as through the production of "tolerogenic" cytokines, such as IL-10 and TGF-β. Based on the accumulating insight into the importance of the immune system for the outcome of pancreatic cancer patients multiple new immunotherapeutic approaches against pancreatic cancer are being currently tested in clinical trials. In this review we give an overview of both the immune escaping mechanisms of pancreatic cancer as well as the new immune related therapeutic strategies currently being tested in pancreatic cancer clinical trials. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Therapeutic potential of helminths in autoimmune diseases: helminth-derived immune-regulators and immune balance.

    Science.gov (United States)

    Wang, Meng; Wu, Linxiang; Weng, Rennan; Zheng, Weihong; Wu, Zhongdao; Lv, Zhiyue

    2017-08-01

    Helminths have accompanied human throughout history by releasing immune-evasion molecules that could counteract an aberrant immune response within the host. In the past decades, helminth infections are becoming less prevalent possibly due to the developed sanitation. Meanwhile, the incidence of autoimmune diseases is increasing, which cannot be exclusively explained by the changes of susceptibility genes. While the hygiene hypothesis casts light on the problem. The infections of helminths are believed to interact with and regulate human immunity with the byproduct of suppressing the autoimmune diseases. Thus, helminths are potential to treat or cure the autoimmune diseases. The therapeutic progresses and possible immune suppression mechanisms are illustrated in the review. The helminths that are studied most intensively include Heligmosomoides polygyrus, Hymenolepis diminuta, Schistosoma mansoni, Trichinella spiralis, and Trichuris suis. Special attentions are paid on the booming animal models and clinical trials that are to detect the efficiency of immune-modulating helminth-derived molecules on autoimmune diseases. These trials provide us with a prosperous clinical perspective, but the precise mechanism of the down-regulatory immune response remains to be clarified. More efforts are needed to be dedicated until these parasite-derived immune modulators could be used in clinic to treat or cure the autoimmune diseases under a standard management.

  10. Evaluation of lung immunity in chimpanzees

    International Nuclear Information System (INIS)

    Bice, D.E.; Harris, D.L.; Muggenburg, B.A.; Bowen, J.A.

    1980-01-01

    The effects of inhaled pollutants on the immune defenses in the lung can be studied in several animal species. To assure that the data obtained can be extrapolated to man, it is essential that the development of lung immunity is similar in the experimental animal selected and in humans. Because of the similarity of immune responses in chimpanzees and in humans, the development of immunity in the chimpanzee after lung immunization was evaluated. The results from the chimpanzees were qualitatively the same as those from previous studies in which single lung lobes of dogs were immunized. It was concluded that immunotoxicology data obtained in dogs can be used to estimate the effects of inhaled pollutants on the immune defense mechanism in the human lung

  11. 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.

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

    Science.gov (United States)

    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.

  13. Polio immunity and the impact of mass immunization campaigns in the Democratic Republic of the Congo.

    Science.gov (United States)

    Voorman, Arend; Hoff, Nicole A; Doshi, Reena H; Alfonso, Vivian; Mukadi, Patrick; Muyembe-Tamfum, Jean-Jacques; Wemakoy, Emile Okitolonda; Bwaka, Ado; Weldon, William; Gerber, Sue; Rimoin, Anne W

    2017-10-09

    In order to prevent outbreaks from wild and vaccine-derived poliovirus, maintenance of population immunity in non-endemic countries is critical. We estimated population seroprevalence using dried blood spots collected from 4893 children 6-59months olds in the 2013-2014 Demographic and Health Survey in the Democratic Republic of the Congo (DRC). Population immunity was 81%, 90%, and 70% for poliovirus types 1, 2, and 3, respectively. Among 6-59-month-old children, 78% reported at least one dose of polio in routine immunization, while only 15% had three doses documented on vaccination cards. All children in the study had been eligible for at least two trivalent oral polio vaccine campaigns at the time of enrollment; additional immunization campaigns seroconverted 5.0%, 14%, and 5.5% of non-immune children per-campaign for types 1, 2, and 3, respectively, averaged over relevant campaigns for each serotype. Overall polio immunity was high at the time of the study, though pockets of low immunity cannot be ruled out. The DRC still relies on supplementary immunization campaigns, and this report stresses the importance of the quality and coverage of those campaigns over their quantity, as well as the importance of routine immunization. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Non-specific immunization against babesiosis

    International Nuclear Information System (INIS)

    Cox, F.E.G.

    1980-01-01

    The rodent babesias, Babesia rodhaini and the less virulent B. microti, are useful models with which to study immunity to and immunization against babesiosis. In contrast with the difficulty in inducing specific immunity to these parasites it is comparatively easy to induce non-specific immunity by prior exposure to related and unrelated intra-erythrocytic protozoa, micro-organisms such as Mycobacterium bovis (BCG) and Corynebacterium parvum, microbial extracts and muramyl dipeptide. This non-specific immunity is long lasting and extremely effective. It is characterized by the facts that (a) it occurs early in the infection at the height of the first peak of parasitaemia, and (b) it involves the intra-erythrocytic death of the parasites. After the primary parasitaemia has resolved, some parasites continue to persist at a low level and when introduced into clean mice produce only low-level 'attenuated' infections in these. Non-specific immunity is not equally effective in all strains of mice. It is suggested that immunity to babesiosis, and infections caused by other intra-erythrocytic protozoa, involves two mechanisms, the first non-specific and the second specific. The actual balance between these two mechanisms varies from parasite to parasite and from host to host. An effective vaccine would have to be based on an understanding of the roles of non-specific immunity in the actual disease under consideration, and would ideally combine an adjuvant that would also stimulate non-specific immunity and an attenuated strain of parasite that would induce a specific response. (author)

  15. Immune Mechanisms in Myelodysplastic Syndrome

    DEFF Research Database (Denmark)

    Glenthøj, Andreas; Ørskov, Andreas Due; Hansen, Jakob Werner

    2016-01-01

    diseases are common in patients with MDS, fueling hypotheses of common etiological mechanisms. Both innate and adaptive immune pathways are overly active in the hematopoietic niche of MDS. Although supportive care, growth factors, and hypomethylating agents are the mainstay of MDS treatment, some patients......-especially younger low-risk patients with HLA-DR15 tissue type-demonstrate impressive response rates after immunosuppressive therapy. This is in contrast to higher-risk MDS patients, where several immune activating treatments, such as immune checkpoint inhibitors, are in the pipeline. Thus, the dual role of immune...... mechanisms in MDS is challenging, and rigorous translational studies are needed to establish the value of immune manipulation as a treatment of MDS....

  16. Melatonin: Buffering the Immune System

    Directory of Open Access Journals (Sweden)

    Juan M. Guerrero

    2013-04-01

    Full Text Available Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system. Despite the large number of reports implicating melatonin as an immunomodulatory compound, it still remains unclear how melatonin regulates immunity. While some authors argue that melatonin is an immunostimulant, many studies have also described anti-inflammatory properties. The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation. The clinical relevance of the multiple functions of melatonin under different immune conditions, such as infection, autoimmunity, vaccination and immunosenescence, is also reviewed.

  17. Melatonin: Buffering the Immune System

    Science.gov (United States)

    Carrillo-Vico, Antonio; Lardone, Patricia J.; Álvarez-Sánchez, Nuria; Rodríguez-Rodríguez, Ana; Guerrero, Juan M.

    2013-01-01

    Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system. Despite the large number of reports implicating melatonin as an immunomodulatory compound, it still remains unclear how melatonin regulates immunity. While some authors argue that melatonin is an immunostimulant, many studies have also described anti-inflammatory properties. The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation. The clinical relevance of the multiple functions of melatonin under different immune conditions, such as infection, autoimmunity, vaccination and immunosenescence, is also reviewed. PMID:23609496

  18. Immunity to community: what can immune pathways tell us about disease patterns in corals?

    Science.gov (United States)

    Mydlarz, L. D.; Fuess, L.; Pinzon, J. C.; Weil, E.

    2016-02-01

    Predicting species composition and abundances is one of the most fundamental questions in ecology. This question is even more pressing in marine ecology and coral reefs since communities are changing at a rapid pace due to climate-related changes. Increases in disease prevalence and severity are just some of the consequences of these environmental changes. Particularly in coral reef ecosystems, diseases are increasing and driving region-wide population collapses. It has become clear, however, that not all reefs or coral species are affected by disease equally. In fact, the Caribbean is a concentrated area for diseases. The patterns in which disease manifests itself on an individual reef are also proving interesting, as not all coral species are affected by disease equally. Some species are host to different diseases, but seem to successfully fight them reducing mortality. Other species are disproportionately infected on any given reef and experience high mortality due to disease. We are interested in the role immunity can play in directing these patterns and are evaluating coral immunity using several novel approaches. We exposed 4 species of corals with different disease susceptibilities to immune stimulators and quantified of coral immunity using a combination of full transcriptome sequencing and protein activity assays for gene to phenotype analysis. We also mapped gene expression changes onto immune pathways (i.e. melanin-cascade, antimicrobial peptide synthesis, complement cascade, lectin-opsonization) to evaluate expression of immune pathways between species. In our preliminary data we found many immune genes in the disease susceptible Orbicella faveolata underwent changes in gene expression opposite of the predictions and may disply `dysfunctional' patterns of expression. We will present expression data for 4 species of coral and assess how these transcriptional and protein immune responses are related to disease susceptibility in nature, thus scaling up

  19. 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.

  20. Are Preferential Trade Agreements with Non-trade Objectives a Stumbling Block for Multilateral Liberalization?

    OpenAIRE

    Nuno Limão

    2007-01-01

    In many preferential trade agreements (PTAs), countries exchange not only reductions in trade barriers but also cooperation in non-trade issues such as labour and environmental standards, intellectual property, etc. We provide a model of PTAs motivated by cooperation in non-trade issues and analyse its implications for global free trade and welfare. We find that such PTAs increase the cost of multilateral tariff reductions and thus cause a stumbling block to global free trade. This occurs bec...

  1. Heat and immunity: an experimental heat wave alters immune functions in three-spined sticklebacks (Gasterosteus aculeatus).

    Science.gov (United States)

    Dittmar, Janine; Janssen, Hannah; Kuske, Andra; Kurtz, Joachim; Scharsack, Jörn P

    2014-07-01

    Global climate change is predicted to lead to increased temperatures and more extreme climatic events. This may influence host-parasite interactions, immunity and therefore the impact of infectious diseases on ecosystems. However, little is known about the effects of rising temperatures on immune defence, in particular in ectothermic animals, where the immune system is directly exposed to external temperature change. Fish are ideal models for studying the effect of temperature on immunity, because they are poikilothermic, but possess a complete vertebrate immune system with both innate and adaptive immunity. We used three-spined sticklebacks ( Gasterosteus aculeatus) originating from a stream and a pond, whereby the latter supposedly were adapted to higher temperature variation. We studied the effect of increasing and decreasing temperatures and a simulated heat wave with subsequent recovery on body condition and immune parameters. We hypothesized that the immune system might be less active at low temperatures, but will be even more suppressed at temperatures towards the upper tolerable temperature range. Contrary to our expectation, we found innate and adaptive immune activity to be highest at a temperature as low as 13 °C. Exposure to a simulated heat wave induced long-lasting immune disorders, in particular in a stickleback population that might be less adapted to temperature variation in its natural environment. The results show that the activity of the immune system of an ectothermic animal species is temperature dependent and suggest that heat waves associated with global warming may immunocompromise host species, thereby potentially facilitating the spread of infectious diseases. © 2014 The Authors. Journal of Animal Ecology © 2014 British Ecological Society.

  2. Immune regulation by microbiome metabolites.

    Science.gov (United States)

    Kim, Chang H

    2018-03-22

    Commensal microbes and the host immune system have been co-evolved for mutual regulation. Microbes regulate the host immune system, in part, by producing metabolites. A mounting body of evidence indicates that diverse microbial metabolites profoundly regulate the immune system via host receptors and other target molecules. Immune cells express metabolite-specific receptors such as P2X 7 , GPR41, GPR43, GPR109A, aryl hydrocarbon receptor precursor (AhR), pregnane X receptor (PXR), farnesoid X receptor (FXR), TGR5 and other molecular targets. Microbial metabolites and their receptors form an extensive array of signals to respond to changes in nutrition, health and immunological status. As a consequence, microbial metabolite signals contribute to nutrient harvest from diet, and regulate host metabolism and the immune system. Importantly, microbial metabolites bidirectionally function to promote both tolerance and immunity to effectively fight infection without developing inflammatory diseases. In pathogenic conditions, adverse effects of microbial metabolites have been observed as well. Key immune-regulatory functions of the metabolites, generated from carbohydrates, proteins and bile acids, are reviewed in this article. © 2018 John Wiley & Sons Ltd.

  3. Anisotropic Negative Thermal Expansion Behavior of the As-Fabricated Ti-Rich and Equiatomic Ti-Ni Alloys Induced by Preferential Grain Orientation

    Science.gov (United States)

    Zhao, Zhong-Xun; Ma, Xiao; Cao, Shan-Shan; Ke, Chang-Bo; Zhang, Xin-Ping

    2018-03-01

    The present study focuses on the anisotropic negative thermal expansion (NTE) behaviors of Ti-rich (Ti54Ni46) and equiatomic Ti-Ni (Ti50Ni50) alloys fabricated by vacuum arc melting and without subsequent plastic deformation. Both alloys exhibit NTE responses in vertical and horizontal directions, and the total strains and CTEs of the NTE stage along the two mutually perpendicular measuring directions are obviously different, indicating obvious anisotropic NTE behavior of the alloys. Besides, the numerical differences between the starting temperature of NTE and austenitic transformation and between the finishing temperature of NTE and austenitic transformation are very small, which indicates that an apparent relationship exists between the NTE behavior and the phase transformation. The microstructure in the vertical cross sections shows obviously preferential orientation characteristics: Ti2Ni phases of both alloys grow along the vertical direction, and B19' martensite of Ti50Ni50 alloy has distinct preferential orientation, which results from a large temperature gradient between the top and the bottom of the button ingots during solidification. The microstructure with preferential orientation induces the anisotropic NTE behavior of the samples.

  4. Seeking a preferential option for the rural poor in Chile

    Directory of Open Access Journals (Sweden)

    Edward Dew

    2006-01-01

    Full Text Available From colonial times well into the twentieth century (and, unfortunately, even beyond the man/land relationship in Latin America has been markedly unjust. Small numbers of families have owned large tracts of the best land, while large numbers of poor families have struggled with tiny plots of marginal land or labored on the estates of the rich. Chile was no exception to this pattern. Thus, its experiment with land reform in the 1960s and 1970s, the setback of reform under the military in the 1970s and 1980s, and the resumption of reform under democrats in the 1990s, may provide lessons for the rest of Latin America. Is a preferential option for the rural poor still possible in a neoliberal economic system? In Chile, the answer is a qualified “yes”

  5. Balancing immune protection and immune pathology by CD8+ T cell responses to influenza infection

    Directory of Open Access Journals (Sweden)

    Susu eDuan

    2016-02-01

    Full Text Available Influenza A virus (IAV is a significant human pathogen causing annual epidemics and periodic pandemics. CD8+ cytotoxic T lymphocyte (CTL-mediated immunity contributes to clearance of virus-infected cells; CTL immunity targeting the conserved internal proteins of IAVs is a key protection mechanism when neutralizing antibodies are absent during heterosubtypic IAV infection. However, CTL infiltration into the airways, their cytotoxicity, and the effects of produced pro-inflammatory cytokines can cause severe lung tissue injury, thereby contributing to immunopathology. Studies have discovered complicated and exquisite stimulatory and inhibitory mechanisms that regulate CTL magnitude and effector activities during IAV infection. Here, we review the state of knowledge on the roles of IAV-specific CTLs in immune protection and immunopathology during IAV infection in animal models, highlighting the key findings of various requirements and constraints regulating the balance of immune protection and pathology involved in CTL immunity. We also discuss the evidence of cross-reactive CTL immunity as a positive correlate of cross-subtype protection during secondary IAV infection in both animal and human studies. We argue that the effects of CTL immunity on protection and immunopathology depend on multiple layers of host and viral factors, including complex host mechanisms to regulate CTL magnitude and effector activity, the pathogenic nature of the IAV, the innate response milieu, and the host historical immune context of influenza infection. Future efforts are needed to further understand these key host and viral factors, especially to differentiate those that constrain optimally effective CTL anti-viral immunity from those necessary to restrain CTL-mediated nonspecific immunopathology in the various contexts of IAV infection, in order to develop better vaccination and therapeutic strategies for modifying protective CTL immunity.

  6. Vitamin E, immunity, and infection

    Science.gov (United States)

    A normally functioning immune system is critical for the body to fight and eliminate invading pathogens from the environment. On the other hand, the immune system also protects the body from internal risks such as neoplasia growing within and autoimmune responses that attack self. The immune system ...

  7. Immune TB Antibody Phage Display Library as a Tool To Study B Cell Immunity in TB Infections.

    Science.gov (United States)

    Hamidon, Nurul Hamizah; Suraiya, Siti; Sarmiento, Maria E; Acosta, Armando; Norazmi, Mohd Nor; Lim, Theam Soon

    2018-03-01

    B cells and in particular antibodies has always played second fiddle to cellular immunity in regard to tuberculosis (TB). However, recent studies has helped position humoral immunity especially antibodies back into the foray in relation to TB immunity. Therefore, the ability to correlate the natural antibody responses of infected individuals toward TB antigens would help strengthen this concept. Phage display is an intriguing approach that can be utilized to study antibody-mediated responses against a particular infection via harvesting the B cell repertoire from infected individuals. The development of disease-specific antibody libraries or immune libraries is useful to better understand antibody-mediated immune responses against specific disease antigens. This study describes the generation of an immune single-chain variable fragment (scFv) library derived from TB-infected individuals. The immune library with an estimated diversity of 10 9 independent clones was then applied for the identification of monoclonal antibodies against Mycobacterium tuberculosis α-crystalline as a model antigen. Biopanning of the library isolated three monoclonal antibodies with unique gene usage. This strengthens the role of antibodies in TB immunity in addition to the role played by cellular immunity. The developed library can be applied against other TB antigens and aid antibody-derived TB immunity studies in the future.

  8. Persistent hepatitis virus infection and immune homeostasis

    OpenAIRE

    ZHOU Yun

    2014-01-01

    Homeostasis between the host and viruses is naturally maintained. On the one hand, the immune system activates the immune response to kill or eliminate viruses; on the other hand, the immune system controls the immune response to maintain immune homeostasis. The cause of persistent infections with hepatitis viruses such as HBV and HCV is that viral molecules damage the immune system of the host and their variants escape immune clearance. Long-term coexistence of the host and viruses is the pr...

  9. Artificial Immune Networks: Models and Applications

    Directory of Open Access Journals (Sweden)

    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.

  10. Immune memory in invertebrates.

    Science.gov (United States)

    Milutinović, Barbara; Kurtz, Joachim

    2016-08-01

    Evidence for innate immune memory (or 'priming') in invertebrates has been accumulating over the last years. We here provide an in-depth review of the current state of evidence for immune memory in invertebrates, and in particular take a phylogenetic viewpoint. Invertebrates are a very heterogeneous group of animals and accordingly, evidence for the phenomenon of immune memory as well as the hypothesized molecular underpinnings differ largely for the diverse invertebrate taxa. The majority of research currently focuses on Arthropods, while evidence from many other groups of invertebrates is fragmentary or even lacking. We here concentrate on immune memory that is induced by pathogenic challenges, but also extent our view to a non-pathogenic context, i.e. allograft rejection, which can also show forms of memory and can inform us about general principles of specific self-nonself recognition. We discuss definitions of immune memory and a number of relevant aspects such as the type of antigens used, the route of exposure, and the kinetics of reactions following priming. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Immunity to Babesia in mice I. Adoptive transfer of immunity to Babesia rodhaini with immune spleen cells and the effect of irradiation on the protection of immune mice

    NARCIS (Netherlands)

    Kuil, H.; Zivkovic, D.; Seinen, W.; Albers-van Bemmel, C.M.G.; Speksnijder, J.E.

    1984-01-01

    Immunisation of Balb/c mice against Babesia rodhaini by an amicarbalide- controlled infection resulted in a solid immunity which lasted for 216 days. With spleen cells of immune mice protection could be transferred both to naive mice pretreated with cyclophosphamide. Treatment of naive mice with

  12. Immune defense and host life history.

    Science.gov (United States)

    Zuk, Marlene; Stoehr, Andrew M

    2002-10-01

    Recent interest has focused on immune response in an evolutionary context, with particular attention to disease resistance as a life-history trait, subject to trade-offs against other traits such as reproductive effort. Immune defense has several characteristics that complicate this approach, however; for example, because of the risk of autoimmunity, optimal immune defense is not necessarily maximum immune defense. Two important types of cost associated with immunity in the context of life history are resource costs, those related to the allocation of essential but limited resources, such as energy or nutrients, and option costs, those paid not in the currency of resources but in functional or structural components of the organism. Resource and option costs are likely to apply to different aspects of resistance. Recent investigations into possible trade-offs between reproductive effort, particularly sexual displays, and immunity have suggested interesting functional links between the two. Although all organisms balance the costs of immune defense against the requirements of reproduction, this balance works out differently for males than it does for females, creating sex differences in immune response that in turn are related to ecological factors such as the mating system. We conclude that immune response is indeed costly and that future work would do well to include invertebrates, which have sometimes been neglected in studies of the ecology of immune defense.

  13. 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.

  14. VACCINES AND IMMUNIZATION: WORLD SITUATION

    Directory of Open Access Journals (Sweden)

    G.H. Brundtland

    2007-01-01

    Full Text Available The last issue of the report «vaccines and immunization: world situation» stresses considerable success in immunization at the global level since the mid 90 s — completely total eradication of poliomyelitis across the world, as well as the drastic reduction of the new measles and tetanus cases among mothers and newborns in some poor countries. The report also briefly describes the progress in the development and implementation of the new life saving vaccines, which may save millions of lives annually. The authors have explained some of the reasons, why the global community should invest in immunization, as well as the perspectives for the use of vaccines and immunization in future.Key words: vaccine, immunization, children.

  15. Carbohydrate Mimetic Peptides Augment Carbohydrate-Reactive Immune Responses in the Absence of Immune Pathology

    International Nuclear Information System (INIS)

    Hennings, Leah; Artaud, Cecile; Jousheghany, Fariba; Monzavi-Karbassi, Behjatolah; Pashov, Anastas; Kieber-Emmons, Thomas

    2011-01-01

    Among the most challenging of clinical targets for cancer immunotherapy are Tumor Associated Carbohydrate Antigens (TACAs). To augment immune responses to TACA we are developing carbohydrate mimetic peptides (CMPs) that are sufficiently potent to activate broad-spectrum anti-tumor reactivity. However, the activation of immune responses against terminal mono- and disaccharide constituents of TACA raises concerns regarding the balance between “tumor destruction” and “tissue damage”, as mono- and disaccharides are also expressed on normal tissue. To support the development of CMPs for clinical trial testing, we demonstrate in preclinical safety assessment studies in mice that vaccination with CMPs can enhance responses to TACAs without mediating tissue damage to normal cells expressing TACA. BALB/c mice were immunized with CMPs that mimic TACAs reactive with Griffonia simplicifolia lectin 1 (GS-I), and tissue reactivity of serum antibodies were compared with the tissue staining profile of GS-I. Tissues from CMP immunized mice were analyzed using hematoxylin and eosin stain, and Luxol-fast blue staining for myelination. Western blots of membranes from murine mammary 4T1 cells, syngeneic with BALB/c mice, were also compared using GS-I, immunized serum antibodies, and naive serum antibodies. CMP immunization enhanced glycan reactivities with no evidence of pathological autoimmunity in any immunized mice demonstrating that tissue damage is not an inevitable consequence of TACA reactive responses

  16. Carbohydrate Mimetic Peptides Augment Carbohydrate-Reactive Immune Responses in the Absence of Immune Pathology

    Energy Technology Data Exchange (ETDEWEB)

    Hennings, Leah; Artaud, Cecile; Jousheghany, Fariba; Monzavi-Karbassi, Behjatolah; Pashov, Anastas; Kieber-Emmons, Thomas, E-mail: tke@uams.edu [Winthrop P. Rockefeller Cancer Institute and Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States)

    2011-11-11

    Among the most challenging of clinical targets for cancer immunotherapy are Tumor Associated Carbohydrate Antigens (TACAs). To augment immune responses to TACA we are developing carbohydrate mimetic peptides (CMPs) that are sufficiently potent to activate broad-spectrum anti-tumor reactivity. However, the activation of immune responses against terminal mono- and disaccharide constituents of TACA raises concerns regarding the balance between “tumor destruction” and “tissue damage”, as mono- and disaccharides are also expressed on normal tissue. To support the development of CMPs for clinical trial testing, we demonstrate in preclinical safety assessment studies in mice that vaccination with CMPs can enhance responses to TACAs without mediating tissue damage to normal cells expressing TACA. BALB/c mice were immunized with CMPs that mimic TACAs reactive with Griffonia simplicifolia lectin 1 (GS-I), and tissue reactivity of serum antibodies were compared with the tissue staining profile of GS-I. Tissues from CMP immunized mice were analyzed using hematoxylin and eosin stain, and Luxol-fast blue staining for myelination. Western blots of membranes from murine mammary 4T1 cells, syngeneic with BALB/c mice, were also compared using GS-I, immunized serum antibodies, and naive serum antibodies. CMP immunization enhanced glycan reactivities with no evidence of pathological autoimmunity in any immunized mice demonstrating that tissue damage is not an inevitable consequence of TACA reactive responses.

  17. Immune genes undergo more adaptive evolution than non-immune system genes in Daphnia pulex

    Directory of Open Access Journals (Sweden)

    McTaggart Seanna J

    2012-05-01

    Full Text Available Abstract Background Understanding which parts of the genome have been most influenced by adaptive evolution remains an unsolved puzzle. Some evidence suggests that selection has the greatest impact on regions of the genome that interact with other evolving genomes, including loci that are involved in host-parasite co-evolutionary processes. In this study, we used a population genetic approach to test this hypothesis by comparing DNA sequences of 30 putative immune system genes in the crustacean Daphnia pulex with 24 non-immune system genes. Results In support of the hypothesis, results from a multilocus extension of the McDonald-Kreitman (MK test indicate that immune system genes as a class have experienced more adaptive evolution than non-immune system genes. However, not all immune system genes show evidence of adaptive evolution. Additionally, we apply single locus MK tests and calculate population genetic parameters at all loci in order to characterize the mode of selection (directional versus balancing in the genes that show the greatest deviation from neutral evolution. Conclusions Our data are consistent with the hypothesis that immune system genes undergo more adaptive evolution than non-immune system genes, possibly as a result of host-parasite arms races. The results of these analyses highlight several candidate loci undergoing adaptive evolution that could be targeted in future studies.

  18. Evaluation of mucosal and systemic immune responses elicited by GPI-0100- adjuvanted influenza vaccine delivered by different immunization strategies.

    Directory of Open Access Journals (Sweden)

    Heng Liu

    Full Text Available Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response. However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery often results in poor systemic immunity. In order to find an immunization strategy which satisfies the need for induction of both mucosal and systemic immunity, we compared local and systemic immune responses elicited by two mucosal immunizations, given either by the intranasal (IN or the intrapulmonary (IPL route, with responses elicited by a mucosal prime followed by a systemic boost immunization. The study was conducted in BALB/c mice and the vaccine formulation was an influenza subunit vaccine supplemented with GPI-0100, a saponin-derived adjuvant. While optimal mucosal antibody titers were obtained after two intrapulmonary vaccinations, optimal systemic antibody responses were achieved by intranasal prime followed by intramuscular boost. The latter strategy also resulted in the best T cell response, yet, it was ineffective in inducing nose or lung IgA. Successful induction of secretory IgA, IgG and T cell responses was only achieved with prime-boost strategies involving intrapulmonary immunization and was optimal when both immunizations were given via the intrapulmonary route. Our results underline that immunization via the lungs is particularly effective for priming as well as boosting of local and systemic immune responses.

  19. Evaluation of Mucosal and Systemic Immune Responses Elicited by GPI-0100- Adjuvanted Influenza Vaccine Delivered by Different Immunization Strategies

    Science.gov (United States)

    Liu, Heng; Patil, Harshad P.; de Vries-Idema, Jacqueline; Wilschut, Jan; Huckriede, Anke

    2013-01-01

    Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response. However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery often results in poor systemic immunity. In order to find an immunization strategy which satisfies the need for induction of both mucosal and systemic immunity, we compared local and systemic immune responses elicited by two mucosal immunizations, given either by the intranasal (IN) or the intrapulmonary (IPL) route, with responses elicited by a mucosal prime followed by a systemic boost immunization. The study was conducted in BALB/c mice and the vaccine formulation was an influenza subunit vaccine supplemented with GPI-0100, a saponin-derived adjuvant. While optimal mucosal antibody titers were obtained after two intrapulmonary vaccinations, optimal systemic antibody responses were achieved by intranasal prime followed by intramuscular boost. The latter strategy also resulted in the best T cell response, yet, it was ineffective in inducing nose or lung IgA. Successful induction of secretory IgA, IgG and T cell responses was only achieved with prime-boost strategies involving intrapulmonary immunization and was optimal when both immunizations were given via the intrapulmonary route. Our results underline that immunization via the lungs is particularly effective for priming as well as boosting of local and systemic immune responses. PMID:23936066

  20. Scanning the cell surface proteome of cancer cells and identification of metastasis-associated proteins using a subtractive immunization strategy

    DEFF Research Database (Denmark)

    Rasmussen, Nicolaj; Ditzel, Henrik J

    2009-01-01

    and technologically challenging, and no ideal method is currently available. Here, we describe a strategy that allows scanning of the entire cell surface and identification of molecules that exhibit altered expression between two cell types. Concurrently, this method gives rise to valuable reagents for further...... characterization of the identified proteins. The strategy is based on subtractive immunization of mice, and we used the two isogenic cell lines, NM-2C5 and M-4A4, derived from the MDA-MB-435 cancer cell line, as a model system. Although the two cell lines are equally tumorigenic, only M-4A4 has metastatic...... capabilities. Our results yielded a large panel of monoclonal antibodies (mAbs) that recognized cell surface markers preferentially or exclusively expressed on metastatic vs nonmetastatic cancer cells. Four mAbs and their corresponding antigens were further characterized. Importantly, analysis on an extended...

  1. Measuring the immune system: a comprehensive approach for the analysis of immune functions in humans.

    Science.gov (United States)

    Claus, Maren; Dychus, Nicole; Ebel, Melanie; Damaschke, Jürgen; Maydych, Viktoriya; Wolf, Oliver T; Kleinsorge, Thomas; Watzl, Carsten

    2016-10-01

    The immune system is essential to provide protection from infections and cancer. Disturbances in immune function can therefore directly affect the health of the affected individual. Many extrinsic and intrinsic factors such as exposure to chemicals, stress, nutrition and age have been reported to influence the immune system. These influences can affect various components of the immune system, and we are just beginning to understand the causalities of these changes. To investigate such disturbances, it is therefore essential to analyze the different components of the immune system in a comprehensive fashion. Here, we demonstrate such an approach which provides information about total number of leukocytes, detailed quantitative and qualitative changes in the composition of lymphocyte subsets, cytokine levels in serum and functional properties of T cells, NK cells and monocytes. Using samples from a cohort of 24 healthy volunteers, we demonstrate the feasibility of our approach to detect changes in immune functions.

  2. Alcohol, aging, and innate immunity.

    Science.gov (United States)

    Boule, Lisbeth A; Kovacs, Elizabeth J

    2017-07-01

    The global population is aging: in 2010, 8% of the population was older than 65 y, and that is expected to double to 16% by 2050. With advanced age comes a heightened prevalence of chronic diseases. Moreover, elderly humans fair worse after acute diseases, namely infection, leading to higher rates of infection-mediated mortality. Advanced age alters many aspects of both the innate and adaptive immune systems, leading to impaired responses to primary infection and poor development of immunologic memory. An often overlooked, yet increasingly common, behavior in older individuals is alcohol consumption. In fact, it has been estimated that >40% of older adults consume alcohol, and evidence reveals that >10% of this group is drinking more than the recommended limit by the National Institute on Alcohol Abuse and Alcoholism. Alcohol consumption, at any level, alters host immune responses, including changes in the number, phenotype, and function of innate and adaptive immune cells. Thus, understanding the effect of alcohol ingestion on the immune system of older individuals, who are already less capable of combating infection, merits further study. However, there is currently almost nothing known about how drinking alters innate immunity in older subjects, despite innate immune cells being critical for host defense, resolution of inflammation, and maintenance of immune homeostasis. Here, we review the effects of aging and alcohol consumption on innate immune cells independently and highlight the few studies that have examined the effects of alcohol ingestion in aged individuals. © Society for Leukocyte Biology.

  3. Cerebral Innate Immunity in Drosophila Melanogaster

    Directory of Open Access Journals (Sweden)

    Brian P. Leung

    2015-03-01

    Full Text Available Modeling innate immunity in Drosophila melanogaster has a rich history that includes ground-breaking discoveries in pathogen detection and signaling. These studies revealed the evolutionary conservation of innate immune pathways and mechanisms of pathogen detection, resulting in an explosion of findings in the innate immunity field. In D. melanogaster, studies have focused primarily on responses driven by the larval fat body and hemocytes, analogs to vertebrate liver and macrophages, respectively. Aside from pathogen detection, many recent mammalian studies associate innate immune pathways with development and disease pathogenesis. Importantly, these studies stress that the innate immune response is integral to maintain central nervous system (CNS health. Microglia, which are the vertebrate CNS mononuclear phagocytes, drive vertebrate cerebral innate immunity. The invertebrate CNS contains microglial-like cells-ensheathing glia and reticular glia-that could be used to answer basic questions regarding the evolutionarily conserved innate immune processes in CNS development and health. A deeper understanding of the relationship between D. melanogaster phagocytic microglial-like cells and vertebrate microglia will be key to answering basic and translational questions related to cerebral innate immunity.

  4. Aging changes in immunity

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/004008.htm Aging changes in immunity To use the sharing features ... cells and antibodies that destroy these harmful substances. AGING CHANGES AND THEIR EFFECTS ON THE IMMUNE SYSTEM ...

  5. Interstitial ultrasound ablation of tumors within or adjacent to bone: Contributions of preferential heating at the bone surface

    Science.gov (United States)

    Scott, Serena J.; Prakash, Punit; Salgaonkar, Vasant; Jones, Peter D.; Cam, Richard N.; Han, Misung; Rieke, Viola; Burdette, E. Clif; Diederich, Chris J.

    2013-02-01

    Preferential heating of bone due to high ultrasound attenuation may enhance thermal ablation performed with cathetercooled interstitial ultrasound applicators in or near bone. At the same time, thermally and acoustically insulating cortical bone may protect sensitive structures nearby. 3D acoustic and biothermal transient finite element models were developed to simulate temperature and thermal dose distributions during catheter-cooled interstitial ultrasound ablation near bone. Experiments in ex vivo tissues and tissue-mimicking phantoms were performed to validate the models and to quantify the temperature profiles and ablated volumes for various distances between the interstitial applicator and the bone surface. 3D patient-specific models selected to bracket the range of clinical usage were developed to investigate what types of tumors could be treated, applicator configurations, insertion paths, safety margins, and other parameters. Experiments show that preferential heating at the bone surface decreases treatment times compared to when bone is absent and that all tissue between an applicator and bone can be ablated when they are up to 2 cm apart. Simulations indicate that a 5-7 mm safety margin of normal bone is needed to protect (thermal dose tumors 1.0-3.8 cm (L) and 1.3-3.0 cm (D) near or within bone were ablated (thermal dose > 240 CEM43°C) within 10 min without damaging the nearby spinal cord, lungs, esophagus, trachea, or major vasculature. Preferential absorption of ultrasound by bone may provide improved localization, faster treatment times, and larger treatment zones in tumors in and near bone compared to other heating modalities.

  6. Immune responses to metastases

    International Nuclear Information System (INIS)

    Herberman, R.B.; Wiltrout, R.H.; Gorelik, E.

    1987-01-01

    The authors present the changes in the immune system in tumor-bearing hosts that may influence the development of progression of metastases. Included are mononuclear cell infiltration of metastases; alterations in natural resistance mediated by natural killer cells and macrophages; development of specific immunity mediated by T-lymphocytes or antibodies; modulation of tumor-associated antigen expression; and the down-regulation of the immune response to the tumor by several suppressor mechanisms; the augmentation of the immune response and its potential for therapeutic application; includes the prophylaxis of metastases formation by NK cells; the therapy of metastases by augmentation NK-, macrophage-, or T-lymphocyte-mediated responses by biological response modifiers; and the transfer of anticancer activity by cytoxic T-lymphocytes or immunoconjugates of monoclonal antibodies with specificity for tumors

  7. The Peptide Vaccine Combined with Prior Immunization of a Conventional Diphtheria-Tetanus Toxoid Vaccine Induced Amyloid β Binding Antibodies on Cynomolgus Monkeys and Guinea Pigs

    Directory of Open Access Journals (Sweden)

    Akira Yano

    2015-01-01

    Full Text Available The reduction of brain amyloid beta (Aβ peptides by anti-Aβ antibodies is one of the possible therapies for Alzheimer’s disease. We previously reported that the Aβ peptide vaccine including the T-cell epitope of diphtheria-tetanus combined toxoid (DT induced anti-Aβ antibodies, and the prior immunization with conventional DT vaccine enhanced the immunogenicity of the peptide. Cynomolgus monkeys were given the peptide vaccine subcutaneously in combination with the prior DT vaccination. Vaccination with a similar regimen was also performed on guinea pigs. The peptide vaccine induced anti-Aβ antibodies in cynomolgus monkeys and guinea pigs without chemical adjuvants, and excessive immune responses were not observed. Those antibodies could preferentially recognize Aβ40, and Aβ42 compared to Aβ fibrils. The levels of serum anti-Aβ antibodies and plasma Aβ peptides increased in both animals and decreased the brain Aβ40 level of guinea pigs. The peptide vaccine could induce a similar binding profile of anti-Aβ antibodies in cynomolgus monkeys and guinea pigs. The peptide vaccination could be expected to reduce the brain Aβ peptides and their toxic effects via clearance of Aβ peptides by generated antibodies.

  8. Season of birth shapes neonatal immune function

    DEFF Research Database (Denmark)

    Thysen, Anna Hammerich; Rasmussen, Morten Arendt; Kreiner-Møller, Eskil

    2016-01-01

    Birth season has been reported to be a risk factor for several immune-mediated diseases. We hypothesized that this association is mediated by differential changes in neonatal immune phenotype and function with birth season. We sought to investigate the influence of season of birth on cord blood...... immune cell subsets and inflammatory mediators in neonatal airways. Cord blood was phenotyped for 26 different immune cell subsets, and at 1 month of age, 20 cytokines and chemokines were quantified in airway mucosal lining fluid. Multivariate partial least squares discriminant analyses were applied...... to determine whether certain immune profiles dominate by birth season, and correlations between individual cord blood immune cells and early airway immune mediators were defined. We found a birth season-related fluctuation in neonatal immune cell subsets and in early-life airway mucosal immune function...

  9. Innate immunity in the pathogenesis of psoriasis.

    LENUS (Irish Health Repository)

    Sweeney, Cheryl M

    2011-12-01

    Psoriasis is a common, immune-mediated inflammatory skin disorder. T helper(h)1 and Th17 lymphocytes contribute to the pathogenesis of psoriasis through the release of inflammatory cytokines that promote further recruitment of immune cells, keratinocyte proliferation and sustained inflammation. The innate immune system is the first line of defence against infection and plays a crucial role in the initiation of the adaptive immune response. The presence of innate immune cells and their products in psoriatic skin plaques suggests a role for innate immunity in this disease. In addition, the innate immune system can direct the development of pathogenic Th cells in psoriasis. In this article, we will summarise the role of the innate immune system in psoriasis with particular emphasis on the role of cytokines, signalling pathways and cells of the innate immune system.

  10. Innate immunity in vertebrates: an overview.

    Science.gov (United States)

    Riera Romo, Mario; Pérez-Martínez, Dayana; Castillo Ferrer, Camila

    2016-06-01

    Innate immunity is a semi-specific and widely distributed form of immunity, which represents the first line of defence against pathogens. This type of immunity is critical to maintain homeostasis and prevent microbe invasion, eliminating a great variety of pathogens and contributing with the activation of the adaptive immune response. The components of innate immunity include physical and chemical barriers, humoral and cell-mediated components, which are present in all jawed vertebrates. The understanding of innate defence mechanisms in non-mammalian vertebrates is the key to comprehend the general picture of vertebrate innate immunity and its evolutionary history. This is also essential for the identification of new molecules with applications in immunopharmacology and immunotherapy. In this review, we describe and discuss the main elements of vertebrate innate immunity, presenting core findings in this field and identifying areas that need further investigation. © 2016 John Wiley & Sons Ltd.

  11. Immunizations for adult women.

    Science.gov (United States)

    Faubion, Stephanie S; Larkin, Lisa C

    2016-12-01

    Immunizations protect individual persons and contribute to public health by reducing morbidity and mortality associated with common infectious diseases. In this Practice Pearl, we review guidelines for adult immunizations and recent and potential changes in vaccines.

  12. Structure, function and expression on blood and bone marrow cells of the urokinase-type plasminogen activator receptor, uPAR

    DEFF Research Database (Denmark)

    Plesner, T; Behrendt, N; Ploug, M

    1997-01-01

    patients with the rare blood disease paroxysmal nocturnal hemoglobinuria (PNH) that fail to express glycosyl-phosphatidylinositol-anchored proteins including uPAR, show a very significantly reduced transmigration over an endothelial barrier. Cell-associated plasminogen activation by PNH......Several important functions have been assigned to the receptor for urokinase-type plasminogen activator, uPAR. As implied by the name, uPAR was first identified as a high affinity cellular receptor for urokinase plasminogen activator (uPA). It mediates the binding of the zymogen, pro......-uPA, to the plasma membrane where trace amounts of plasmin will initiate a series of events referred to as "reciprocal zymogen activation" where plasmin converts pro-uPA to the active enzyme, uPA, which in turn converts plasma membrane-associated plasminogen to plasmin. This is an efficient machinery to generate...

  13. Comparative assessment of immunization coverage of migrant children between national immunization program vaccines and non-national immunization program vaccines in East China.

    Science.gov (United States)

    Hu, Yu; Luo, Shuying; Tang, Xuewen; Lou, Linqiao; Chen, Yaping; Guo, Jing

    2015-01-01

    This study aimed to describe the disparities in immunization coverage between National Immunization Program (NIP) vaccines and non-NIP vaccines in Yiwu and to identify potential determinants. A face-to-face interview-based questionnaire survey among 423 migrant children born from 1 June 2010 to 31 May 2013 was conducted. Immunization coverage was estimated according to the vaccines scheduled at different age, the birth cohorts, and socio- demographic characteristics. Single-level logistic regression analysis was applied to identify the determinants of coverage of non-NIP vaccines. We found that NIP vaccines recorded higher immunization coverage compared with non-NIP vaccines (87.9100%- vs 0%-74.8%). Among the non-NIP vaccines, varicella vaccine (VarV) recorded the highest coverage of 85.4%, which was introduced in 1998; while 7-valent pneumococcal conjugate vaccine(PCV7) recorded the lowest coverage of 0% for primary series, which was introduced recently. Lower coverage rate of non-NIP vaccines was significantly associated with more siblings in household, shorter duration of living in the surveyed areas, lower family income, mother with a job, mother with poor awareness of vaccination, and mother with lower education level. We found the immunization coverage rate of non-NIP vaccines was significant lower than that of NIP vaccines. Expansion of NIP to include non-NIP vaccines can provide better protection against the vaccine preventable diseases through increased immunization coverage.

  14. Factors associated with maternal influenza immunization decision-making. Evidence of immunization history and message framing effects.

    Science.gov (United States)

    Frew, Paula M; Owens, Lauren E; Saint-Victor, Diane S; Benedict, Samantha; Zhang, Siyu; Omer, Saad B

    2014-01-01

    We examined pregnant women's intention to obtain the seasonal influenza vaccine via a randomized controlled study examining the effects of immunization history, message exposure, and sociodemographic correlates. Pregnant women ages 18-50 participated in a randomized message framing study from September 2011 through May 2012. Venue-based sampling was used to recruit racial and ethnic minority women throughout Atlanta, Georgia. Key outcomes were evaluated using bivariate and multivariate analyses. History of influenza immunization was positively associated with intent to immunize during pregnancy [OR=2.31, 90%CI: (1.06, 5.00)]. Significant correlates of intention to immunize included perceived susceptibility to influenza during pregnancy [OR=3.8, 90% CI: (1.75, 8.36)] and vaccine efficacy [OR=10.53, 90% CI: (4.34, 25.50)]. Single message exposure did not influence a woman's intent to vaccinate. Prior immunization, perceived flu susceptibility and perceived vaccine effectiveness promoted immunization intent among this population of pregnant minority women. Vaccine efficacy and disease susceptibility are critical to promoting immunization among women with no history of seasonal influenza immunization, while those who received the vaccine are likely to do so again. These findings provide evidence for the promotion of repeated exposure to vaccine messages emphasizing vaccine efficacy, normative support, and susceptibility to influenza.

  15. Gut immunity in Lepidopteran insects.

    Science.gov (United States)

    Wu, Kai; Yang, Bing; Huang, Wuren; Dobens, Leonard; Song, Hongsheng; Ling, Erjun

    2016-11-01

    Lepidopteran insects constitute one of the largest fractions of animals on earth, but are considered pests in their relationship with man. Key to the success of this order of insects is its ability to digest food and absorb nutrition, which takes place in the midgut. Because environmental microorganisms can easily enter Lepidopteran guts during feeding, the innate immune response guards against pathogenic bacteria, virus and microsporidia that can be devoured with food. Gut immune responses are complicated by both resident gut microbiota and the surrounding peritrophic membrane and are distinct from immune responses in the body cavity, which depend on the function of the fat body and hemocytes. Due to their relevance to agricultural production, studies of Lepidopteran insect midgut and immunity are receiving more attention, and here we summarize gut structures and functions, and discuss how these confer immunity against different microorganisms. It is expected that increased knowledge of Lepidopteran gut immunity may be utilized for pest biological control in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. 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.

  17. Immune regulation and CNS autoimmune disease

    DEFF Research Database (Denmark)

    Antel, J P; Owens, T

    1999-01-01

    The central nervous system is a demonstrated target of both clinical and experimental immune mediated disorders. Immune regulatory mechanisms operative at the levels of the systemic immune system, the blood brain barrier, and within the CNS parenchyma are important determinants of the intensity...... and duration of the tissue directed injury. Convergence of research, involving direct manipulation of specific cells and molecular mediators in animal models and in vitro analysis of human immune and neural cells and tissues, is providing increasing insight into the role of these immune regulatory functions...

  18. Preferential selection based on strategy persistence and memory promotes cooperation in evolutionary prisoner's dilemma games

    Science.gov (United States)

    Liu, Yuanming; Huang, Changwei; Dai, Qionglin

    2018-06-01

    Strategy imitation plays a crucial role in evolutionary dynamics when we investigate the spontaneous emergence of cooperation under the framework of evolutionary game theory. Generally, when an individual updates his strategy, he needs to choose a role model whom he will learn from. In previous studies, individuals choose role models randomly from their neighbors. In recent works, researchers have considered that individuals choose role models according to neighbors' attractiveness characterized by the present network topology or historical payoffs. Here, we associate an individual's attractiveness with the strategy persistence, which characterizes how frequently he changes his strategy. We introduce a preferential parameter α to describe the nonlinear correlation between the selection probability and the strategy persistence and the memory length of individuals M into the evolutionary games. We investigate the effects of α and M on cooperation. Our results show that cooperation could be promoted when α > 0 and at the same time M > 1, which corresponds to the situation that individuals are inclined to select their neighbors with relatively higher persistence levels during the evolution. Moreover, we find that the cooperation level could reach the maximum at an optimal memory length when α > 0. Our work sheds light on how to promote cooperation through preferential selection based on strategy persistence and a limited memory length.

  19. Dopamine D2 receptors preferentially regulate the development of light responses of the inner retina

    Science.gov (United States)

    Tian, Ning; Xu, Hong-ping; Wang, Ping

    2014-01-01

    Retinal light responsiveness measured via electroretinography undergoes developmental modulation and is thought to be critically regulated by both visual experience and dopamine. The primary goal of this study is to determine whether the dopamine D2 receptor regulates the visual experience-dependent functional development of the retina. Accordingly, we recorded electroretinograms from wild type mice and mice with a genetic deletion of the gene that encodes the dopamine D2 receptor raised under normal cyclic light conditions and constant darkness. Our results demonstrate that mutation of the dopamine D2 receptors preferentially increases the amplitude of the inner retinal light responses evoked by high intensity light measured as oscillatory potentials in adult mice. During postnatal development, all three major components of electroretinograms, the a-wave, b-wave and oscillatory potentials, increase with age. Comparatively, mutation of the dopamine D2 receptors preferentially reduces the age-dependent increase of b-waves evoked by low intensity light. Light deprivation from birth reduces the amplitude of b-waves and completely diminishes the increased amplitude of oscillatory potentials. Taken together, these results demonstrate that the dopamine D2 receptor plays an important role in the activity-dependent functional development of the mouse retina. PMID:25393815

  20. Dynamic visualization of dendritic cell-antigen interactions in the skin following transcutaneous immunization.

    Directory of Open Access Journals (Sweden)

    Teerawan Rattanapak

    Full Text Available Delivery of vaccines into the skin provides many advantages over traditional parenteral vaccination and is a promising approach due to the abundance of antigen presenting cells (APC residing in the skin including Langerhans cells (LC and dermal dendritic cells (DDC. However, the main obstacle for transcutaneous immunization (TCI is the effective delivery of the vaccine through the stratum corneum (SC barrier to the APC in the deeper skin layers. This study therefore utilized microneedles (MN and a lipid-based colloidal delivery system (cubosomes as a synergistic approach for the delivery of vaccines to APC in the skin. The process of vaccine uptake and recruitment by specific types of skin APC was investigated in real-time over 4 hours in B6.Cg-Tg (Itgax-EYFP 1 Mnz/J mice by two-photon microscopy. Incorporation of the vaccine into a particulate delivery system and the use of MN preferentially increased vaccine antigen uptake by a highly motile subpopulation of skin APC known as CD207⁺ DC. No uptake of antigen or any response to immunisation by LC could be detected.