Sample records for controls ephrin shedding

  1. Cytoplasmic relaxation of active Eph controls ephrin shedding by ADAM10.

    Directory of Open Access Journals (Sweden)

    Peter W Janes


    Full Text Available Release of cell surface-bound ligands by A-Disintegrin-And-Metalloprotease (ADAM transmembrane metalloproteases is essential for signalling by cytokine, cell adhesion, and tyrosine kinase receptors. For Eph receptor ligands, it provides the switch between cell-cell adhesion and repulsion. Ligand shedding is tightly controlled by intrinsic tyrosine kinase activity, which for Eph receptors relies on the release of an inhibitory interaction of the cytoplasmic juxtamembrane segment with the kinase domain. However, a mechanism linking kinase and sheddase activities had remained elusive. We demonstrate that it is a membrane-proximal localisation of the latent kinase domain that prevents ephrin ligand shedding in trans. Fluorescence lifetime imaging microscopy and electron tomography reveal that activation extends the Eph receptor tyrosine kinase intracellular domain away from the cell membrane into a conformation that facilitates productive association with ADAM10. Accordingly, EphA3 mutants with constitutively-released kinase domains efficiently support shedding, even when their kinase is disabled. Our data suggest that this phosphorylation-activated conformational switch of EphA3 directly controls ADAM-mediated shedding.

  2. EphrinA/EphA-induced ectodomain shedding of neural cell adhesion molecule regulates growth cone repulsion through ADAM10 metalloprotease. (United States)

    Brennaman, Leann H; Moss, Marcia L; Maness, Patricia F


    EphrinA/EphA-dependent axon repulsion is crucial for synaptic targeting in developing neurons but downstream molecular mechanisms remain obscure. Here, it is shown that ephrinA5/EphA3 triggers proteolysis of the neural cell adhesion molecule (NCAM) by the metalloprotease a disintegrin and metalloprotease (ADAM)10 to promote growth cone collapse in neurons from mouse neocortex. EphrinA5 induced ADAM10 activity to promote ectodomain shedding of polysialic acid-NCAM in cortical neuron cultures, releasing a ~ 250 kDa soluble fragment consisting of most of its extracellular region. NCAM shedding was dependent on ADAM10 and EphA3 kinase activity as shown in HEK293T cells transfected with dominant negative ADAM10 and kinase-inactive EphA3 (K653R) mutants. Purified ADAM10 cleaved NCAM at a sequence within the E-F loop of the second fibronectin type III domain (Leu(671) -Lys(672) /Ser(673) -Leu(674) ) identified by mass spectrometry. Mutations of NCAM within the ADAM10 cleavage sequence prevented EphA3-induced shedding of NCAM in HEK293T cells. EphrinA5-induced growth cone collapse was dependent on ADAM10 activity, was inhibited in cortical cultures from NCAM null mice, and was rescued by WT but not ADAM10 cleavage site mutants of NCAM. Regulated proteolysis of NCAM through the ephrin5/EphA3/ADAM10 mechanism likely impacts synapse development, and may lead to excess NCAM shedding when disrupted, as implicated in neurodevelopmental disorders such as schizophrenia. PSA-NCAM and ephrinA/EphA3 coordinately regulate inhibitory synapse development. Here, we have found that ephrinA5 stimulates EphA3 kinase and ADAM10 activity to promote PSA-NCAM cleavage at a site in its second FNIII repeat, which regulates ephrinA5-induced growth cone collapse in GABAergic and non-GABAergic neurons. These findings identify a new regulatory mechanism which may contribute to inhibitory connectivity.

  3. Eph:ephrin-B1 forward signaling controls fasciculation of sensory and motor axons. (United States)

    Luxey, Maëva; Jungas, Thomas; Laussu, Julien; Audouard, Christophe; Garces, Alain; Davy, Alice


    Axon fasciculation is one of the processes controlling topographic innervation during embryonic development. While axon guidance steers extending axons in the accurate direction, axon fasciculation allows sets of co-extending axons to grow in tight bundles. The Eph:ephrin family has been involved both in axon guidance and fasciculation, yet it remains unclear how these two distinct types of responses are elicited. Herein we have characterized the role of ephrin-B1, a member of the ephrinB family in sensory and motor innervation of the limb. We show that ephrin-B1 is expressed in sensory axons and in the limb bud mesenchyme while EphB2 is expressed in motor and sensory axons. Loss of ephrin-B1 had no impact on the accurate dorso-ventral innervation of the limb by motor axons, yet EfnB1 mutants exhibited decreased fasciculation of peripheral motor and sensory nerves. Using tissue-specific excision of EfnB1 and in vitro experiments, we demonstrate that ephrin-B1 controls fasciculation of axons via a surround repulsion mechanism involving growth cone collapse of EphB2-expressing axons. Altogether, our results highlight the complex role of Eph:ephrin signaling in the development of the sensory-motor circuit innervating the limb.

  4. Ephrin-B1 controls the columnar distribution of cortical pyramidal neurons by restricting their tangential migration. (United States)

    Dimidschstein, Jordane; Passante, Lara; Dufour, Audrey; van den Ameele, Jelle; Tiberi, Luca; Hrechdakian, Tatyana; Adams, Ralf; Klein, Rüdiger; Lie, Dieter Chichung; Jossin, Yves; Vanderhaeghen, Pierre


    Neurons of the cerebral cortex are organized in layers and columns. Unlike laminar patterning, the mechanisms underlying columnar organization remain largely unexplored. Here, we show that ephrin-B1 plays a key role in this process through the control of nonradial steps of migration of pyramidal neurons. In vivo gain of function of ephrin-B1 resulted in a reduction of tangential motility of pyramidal neurons, leading to abnormal neuronal clustering. Conversely, following genetic disruption of ephrin-B1, cortical neurons displayed a wider lateral dispersion, resulting in enlarged ontogenic columns. Dynamic analyses revealed that ephrin-B1 controls the lateral spread of pyramidal neurons by limiting neurite extension and tangential migration during the multipolar phase. Furthermore, we identified P-Rex1, a guanine-exchange factor for Rac3, as a downstream ephrin-B1 effector required to control migration during the multipolar phase. Our results demonstrate that ephrin-B1 inhibits nonradial migration of pyramidal neurons, thereby controlling the pattern of cortical columns.

  5. EphrinB1/EphB3b Coordinate Bidirectional Epithelial-Mesenchymal Interactions Controlling Liver Morphogenesis and Laterality

    DEFF Research Database (Denmark)

    Cayuso, Jordi; Dzementsei, Aliaksandr; Fischer, Johanna C


    and adjacent lateral plate mesoderm (LPM), resulting in asymmetric positioning of the zebrafish liver. EphrinB1 in hepatoblasts regulates directional migration and mediates interactions with the LPM, where EphB3b controls polarity and movement of the LPM. EphB3b in the LPM concomitantly repels hepatoblasts...

  6. Variable combinations of specific ephrin ligand/Eph receptor pairs control embryonic tissue separation.

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    Nazanin Rohani


    Full Text Available Ephrins and Eph receptors are involved in the establishment of vertebrate tissue boundaries. The complexity of the system is puzzling, however in many instances, tissues express multiple ephrins and Ephs on both sides of the boundary, a situation that should in principle cause repulsion between cells within each tissue. Although co-expression of ephrins and Eph receptors is widespread in embryonic tissues, neurons, and cancer cells, it is still unresolved how the respective signals are integrated into a coherent output. We present a simple explanation for the confinement of repulsion to the tissue interface: Using the dorsal ectoderm-mesoderm boundary of the Xenopus embryo as a model, we identify selective functional interactions between ephrin-Eph pairs that are expressed in partial complementary patterns. The combined repulsive signals add up to be strongest across the boundary, where they reach sufficient intensity to trigger cell detachments. The process can be largely explained using a simple model based exclusively on relative ephrin and Eph concentrations and binding affinities. We generalize these findings for the ventral ectoderm-mesoderm boundary and the notochord boundary, both of which appear to function on the same principles. These results provide a paradigm for how developmental systems may integrate multiple cues to generate discrete local outcomes.

  7. Variable combinations of specific ephrin ligand/Eph receptor pairs control embryonic tissue separation. (United States)

    Rohani, Nazanin; Parmeggiani, Andrea; Winklbauer, Rudolf; Fagotto, François


    Ephrins and Eph receptors are involved in the establishment of vertebrate tissue boundaries. The complexity of the system is puzzling, however in many instances, tissues express multiple ephrins and Ephs on both sides of the boundary, a situation that should in principle cause repulsion between cells within each tissue. Although co-expression of ephrins and Eph receptors is widespread in embryonic tissues, neurons, and cancer cells, it is still unresolved how the respective signals are integrated into a coherent output. We present a simple explanation for the confinement of repulsion to the tissue interface: Using the dorsal ectoderm-mesoderm boundary of the Xenopus embryo as a model, we identify selective functional interactions between ephrin-Eph pairs that are expressed in partial complementary patterns. The combined repulsive signals add up to be strongest across the boundary, where they reach sufficient intensity to trigger cell detachments. The process can be largely explained using a simple model based exclusively on relative ephrin and Eph concentrations and binding affinities. We generalize these findings for the ventral ectoderm-mesoderm boundary and the notochord boundary, both of which appear to function on the same principles. These results provide a paradigm for how developmental systems may integrate multiple cues to generate discrete local outcomes.

  8. Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells. (United States)

    Defourny, Jean; Poirrier, Anne-Lise; Lallemend, François; Mateo Sánchez, Susana; Neef, Jakob; Vanderhaeghen, Pierre; Soriano, Eduardo; Peuckert, Christiane; Kullander, Klas; Fritzsch, Bernd; Nguyen, Laurent; Moonen, Gustave; Moser, Tobias; Malgrange, Brigitte


    Hearing requires an optimal afferent innervation of sensory hair cells by spiral ganglion neurons in the cochlea. Here we report that complementary expression of ephrin-A5 in hair cells and EphA4 receptor among spiral ganglion neuron populations controls the targeting of type I and type II afferent fibres to inner and outer hair cells, respectively. In the absence of ephrin-A5 or EphA4 forward signalling, a subset of type I projections aberrantly overshoot the inner hair cell layer and invade the outer hair cell area. Lack of type I afferent synapses impairs neurotransmission from inner hair cells to the auditory nerve. By contrast, radial shift of type I projections coincides with a gain of presynaptic ribbons that could enhance the afferent signalling from outer hair cells. Ephexin-1, cofilin and myosin light chain kinase act downstream of EphA4 to induce type I spiral ganglion neuron growth cone collapse. Our findings constitute the first identification of an Eph/ephrin-mediated mutual repulsion mechanism responsible for specific sorting of auditory projections in the cochlea.

  9. EphrinB2 controls vessel pruning through STAT1-JNK3 signaling (United States)

    Salvucci, Ombretta; Ohnuki, Hidetaka; Maric, Dragan; Hou, Xu; Li, Xuri; Yoon, Sung Ok; Segarra, Marta; Eberhart, Charles G.; Acker-Palmer, Amparo; Tosato, Giovanna


    Angiogenesis produces primitive vascular networks that need pruning to yield hierarchically organized and functional vessels. Despite the critical importance of vessel pruning to vessel patterning and function, the mechanisms regulating this process are not clear. Here we show that EphrinB2, a well-known player in angiogenesis, is an essential regulator of endothelial cell death and vessel pruning. This regulation depends upon phosphotyrosine-EphrinB2 signaling repressing JNK3 activity via STAT1. JNK3 activation causes endothelial cell death. In the absence of JNK3, hyaloid vessel physiological pruning is impaired, associated with abnormal persistence of hyaloid vessels, defective retinal vasculature and microphthalmia. This syndrome closely resembles human persistent hyperplastic primary vitreus (PHPV), attributed to failed involution of hyaloid vessels. Our results provide evidence that EphrinB2/STAT1/JNK3 signaling is essential for vessel pruning, and that defects in this pathway may contribute to PHPV. PMID:25807892

  10. Eph/ephrins mediated thymocyte-thymic epithelial cell interactions control numerous processes of thymus biology

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    Javier eGarcia-Ceca


    Full Text Available Numerous studies emphasize the relevance of thymocyte-thymic epithelial cell (TECs interactions for the functional maturation of intrathymic T lymphocytes. The tyrosine kinase receptors Ephs (Erythropoietin-producing hepatocyte kinases and their ligands, ephrins (Eph receptor interaction proteins, are molecules known to be involved in the regulation of numerous biological systems in which cell-to-cell interactions are particularly relevant. In the last years, we and other authors have demonstrated the importance of these molecules in the thymic functions and the T-cell development. In the present report, we review data on the effects of Ephs and ephrins, in the functional maturation of both thymic epithelial microenvironment and thymocyte maturation as well as on their role in the lymphoid progenitor recruitment into the thymus.

  11. Control of rod shedding in the frog retina. (United States)

    Basinger, S F; Hollyfield, J G


    In all vertebrate species examined thus far, rod outer segment shedding follows a cyclic pattern in which the outer segment tips are shed shortly after the onset of light. Work in the rat retina suggests that rod shedding may follow a circadian rhythm which is controlled by one or more circadian oscillators. Our results in the frog retina are significantly different in that: rod shedding can be driven by the onset of light or other environmental cues; shedding does not persist in constant darkness; shedding is unaffected in frogs with chronic unilateral or bilateral optic nerve section; and shedding will rapidly phase shift to the time of light onset on a wide variety of diurnal cycles. Thus, rod shedding in the frog retina does not appear to be a classical circadian rhythm.

  12. Pou3f4-mediated regulation of ephrin-b2 controls temporal bone development in the mouse.

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    Steven Raft

    Full Text Available The temporal bone encases conductive and sensorineural elements of the ear. Mutations of POU3F4 are associated with unique temporal bone abnormalities and X-linked mixed deafness (DFNX2/DFN3. However, the target genes and developmental processes controlled by POU3F4 transcription factor activity have remained largely uncharacterized. Ephrin-B2 (Efnb2 is a signaling molecule with well-documented effects on cell adhesion, proliferation, and migration. Our analyses of targeted mouse mutants revealed that Efnb2 loss-of-function phenocopies temporal bone abnormalities of Pou3f4 hemizygous null neonates: qualitatively identical malformations of the stapes, styloid process, internal auditory canal, and cochlear capsule were present in both mutants. Using failed/insufficient separation of the stapes and styloid process as a quantitative trait, we found that single gene Efnb2 loss-of-function and compound Pou3f4/Efnb2 loss-of-function caused a more severe phenotype than single gene Pou3f4 loss-of-function. Pou3f4 and Efnb2 gene expression domains overlapped at the site of impending stapes-styloid process separation and at subcapsular mesenchyme surrounding the cochlea; at both these sites, Efnb2 expression was attenuated in Pou3f4 hemizygous null mutants relative to control. Results of immunoprecipitation experiments using chromatin isolated from nascent middle ear mesenchyme supported the hypothesis of a physical association between Pou3f4 and specific non-coding sequence of Efnb2. We propose that Efnb2 is a target of Pou3f4 transcription factor activity and an effector of mesenchymal patterning during temporal bone development.

  13. Circadian control sheds light on fungal bioluminescence. (United States)

    Oliveira, Anderson G; Stevani, Cassius V; Waldenmaier, Hans E; Viviani, Vadim; Emerson, Jillian M; Loros, Jennifer J; Dunlap, Jay C


    Bioluminescence, the creation and emission of light by organisms, affords insight into the lives of organisms doing it. Luminous living things are widespread and access diverse mechanisms to generate and control luminescence [1-5]. Among the least studied bioluminescent organisms are phylogenetically rare fungi-only 71 species, all within the ∼ 9,000 fungi of the temperate and tropical Agaricales order-are reported from among ∼ 100,000 described fungal species [6, 7]. All require oxygen [8] and energy (NADH or NADPH) for bioluminescence and are reported to emit green light (λmax 530 nm) continuously, implying a metabolic function for bioluminescence, perhaps as a byproduct of oxidative metabolism in lignin degradation. Here, however, we report that bioluminescence from the mycelium of Neonothopanus gardneri is controlled by a temperature-compensated circadian clock, the result of cycles in content/activity of the luciferase, reductase, and luciferin that comprise the luminescent system. Because regulation implies an adaptive function for bioluminescence, a controversial question for more than two millennia [8-15], we examined interactions between luminescent fungi and insects [16]. Prosthetic acrylic resin "mushrooms," internally illuminated by a green LED emitting light similar to the bioluminescence, attract staphilinid rove beetles (coleopterans), as well as hemipterans (true bugs), dipterans (flies), and hymenopterans (wasps and ants), at numbers far greater than dark control traps. Thus, circadian control may optimize energy use for when bioluminescence is most visible, attracting insects that can in turn help in spore dispersal, thereby benefitting fungi growing under the forest canopy, where wind flow is greatly reduced.

  14. Regulation of endothelial migration and proliferation by ephrin-A1. (United States)

    Wiedemann, Elisa; Jellinghaus, Stefanie; Ende, Georg; Augstein, Antje; Sczech, Ronny; Wielockx, Ben; Weinert, Sönke; Strasser, Ruth H; Poitz, David M


    Endothelial migration and proliferation are fundamental processes in angiogenesis and wound healing of injured or inflamed vessels. The present study aimed to investigate the regulation of the Eph/ephrin-system during endothelial proliferation and the impact of the ligand ephrin-A1 on proliferation and migration of human umbilical venous (HUVEC) and arterial endothelial cells (HUAEC). Endothelial cells that underwent contact inhibition showed a massive induction of ephrin-A1. In contrast, an injury to a confluent endothelial layer, associated with induction of migration and proliferation, showed reduced ephrin-A1 levels. In addition, reducing ephrin-A1 expression by siRNA led to increased proliferation, whereas the overexpression of ephrin-A1 led to decreased proliferative activity. Due to the fact that wound healing is a combination of proliferation and migration, migration was investigated in detail. First, classical wound-healing assays showed increased wound closure in both ephrin-A1 silenced and overexpressing cells. Live-cell imaging enlightened the underlying differences. Silencing of ephrin-A1 led to a faster but more disorientated migration. In contrast, ephrin-A1 overexpression did not influence velocity of the cells, but the migration was more directed in comparison to the controls. Additional analysis of EphA2-silenced cells showed similar results in terms of proliferation and migration compared to ephrin-A1 silenced cells. Detailed analysis of EphA2 phosphorylation on ligand-dependent phospho-site (Y588) and autonomous activation site (S897) revealed a distinct phosphorylation pattern. Furthermore, the endothelial cells ceased to migrate when they came in contact with an ephrin-A1 coated surface. Using a baculoviral-mediated expression system, ephrin-A1 silencing and overexpression was shown to modulate the formation of focal adhesions. This implicates that ephrin-A1 is involved in changes of the actin cytoskeleton which explains the alterations in


    Coate, Thomas M.; Wirz, Jacqueline A.; Copenhaver, Philip F.


    We have investigated whether reverse signaling via a GPI-linked ephrin controls the behavior of migratory neurons in vivo. During the formation of the enteric nervous system (ENS) in the moth Manduca, ~300 neurons (EP cells) migrate onto the midgut via bilaterally paired muscle bands but avoid adjacent midline regions. As they migrate, the EP cells express a single ephrin ligand (MsEphrin; a GPI-linked ligand), while the midline cells express the corresponding Eph receptor (MsEph). Blocking endogenous MsEphrin-MsEph receptor interactions in cultured embryos resulted in aberrant midline crossing by the neurons and their processes. In contrast, activating endogenous MsEphrin on the EP cells with dimeric MsEph-Fc constructs inhibited their migration and outgrowth, supporting a role for MsEphrin-dependent reverse signaling in this system. In short-term cultures, blocking endogenous MsEph receptors allowed filopodia from the neurons’ growth cones to invade the midline, whereas activating neuronal MsEphrin led to filopodial retraction. MsEphrin-dependent signaling may therefore guide the migratory enteric neurons by restricting the orientation of their leading processes. Knocking down MsEphrin expression in the EP cells with morpholino antisense oligonucleotides also induced aberrant midline crossing, consistent with the effects of blocking endogenous MsEphrin-MsEph interactions. Unexpectedly, this treatment enhanced the overall extent of migration, indicating that MsEphrin-dependent signaling may also modulate the general motility of the EP cells. These results demonstrate that MsEphrin-MsEph receptor interactions normally prevent midline crossing by migratory neurons within the developing ENS, an effect that is most likely mediated by reverse signaling through this GPI-linked ephrin ligand. PMID:18400884

  16. Nociceptor-expressed ephrin-B2 regulates inflammatory and neuropathic pain

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    Kullander Klas


    Full Text Available Abstract Background EphB receptors and their ephrin-B ligands play an important role in nervous system development, as well as synapse formation and plasticity in the adult brain. Recent studies show that intrathecal treatment with EphB-receptor activator ephrinB2-Fc induced thermal hyperalgesia and mechanical allodynia in rat, indicating that ephrin-B2 in small dorsal root ganglia (DRG neurons and EphB receptors in the spinal cord modulate pain processing. To examine the role of ephrin-B2 in peripheral pain pathways, we deleted ephrin-B2 in Nav1.8+ nociceptive sensory neurons with the Cre-loxP system. Sensory neuron numbers and terminals were examined using neuronal makers. Pain behavior in acute, inflammatory and neuropathic pain models was assessed in the ephrin-B2 conditional knockout (CKO mice. We also investigated the c-Fos expression and NMDA receptor NR2B phosphorylation in ephrin-B2 CKO mice and littermate controls. Results The ephrin-B2 CKO mice were healthy with no sensory neuron loss. However, pain-related behavior was substantially altered. Although acute pain behavior and motor co-ordination were normal, inflammatory pain was attenuated in ephrin-B2 mutant mice. Complete Freund's adjuvant (CFA-induced mechanical hyperalgesia was halved. Formalin-induced pain behavior was attenuated in the second phase, and this correlated with diminished tyrosine phosphorylation of N-methyl-D-aspartic acid (NMDA receptor subunit NR2B in the dorsal horn. Thermal hyperalgesia and mechanical allodynia were significantly reduced in the Seltzer model of neuropathic pain. Conclusions Presynaptic ephrin-B2 expression thus plays an important role in regulating inflammatory pain through the regulation of synaptic plasticity in the dorsal horn and is also involved in the pathogenesis of some types of neuropathic pain.

  17. EphrinB3 restricts endogenous neural stem cell migration after traumatic brain injury. (United States)

    Dixon, Kirsty J; Mier, Jose; Gajavelli, Shyam; Turbic, Alisa; Bullock, Ross; Turnley, Ann M; Liebl, Daniel J


    Traumatic brain injury (TBI) leads to a series of pathological events that can have profound influences on motor, sensory and cognitive functions. Conversely, TBI can also stimulate neural stem/progenitor cell proliferation leading to increased numbers of neuroblasts migrating outside their restrictive neurogenic zone to areas of damage in support of tissue integrity. Unfortunately, the factors that regulate migration are poorly understood. Here, we examine whether ephrinB3 functions to restrict neuroblasts from migrating outside the subventricular zone (SVZ) and rostral migratory stream (RMS). We have previously shown that ephrinB3 is expressed in tissues surrounding these regions, including the overlying corpus callosum (CC), and is reduced after controlled cortical impact (CCI) injury. Our current study takes advantage of ephrinB3 knockout mice to examine the influences of ephrinB3 on neuroblast migration into CC and cortex tissues after CCI injury. Both injury and/or ephrinB3 deficiency led to increased neuroblast numbers and enhanced migration outside the SVZ/RMS zones. Application of soluble ephrinB3-Fc molecules reduced neuroblast migration into the CC after injury and limited neuroblast chain migration in cultured SVZ explants. Our findings suggest that ephrinB3 expression in tissues surrounding neurogenic regions functions to restrict neuroblast migration outside the RMS by limiting chain migration.

  18. Vortex shedding noise control in idling circular saws using air ejection at the teeth (United States)

    Yanagimoto, K.; Mote, C. D.; Ichimiya, R.


    Aerodynamically induced noise from an idling circular saw can be very intense. The purpose of the present investigation is noise reduction through vortex shedding control in idling circular saws. Reduction of aerodynamic noise in idling circular saws may be possible by controlling the shed vortices and flow structures in the space between teeth, based on the earlier observations.

  19. Control of Vortex Shedding at Moderate Reynolds Numbers

    Institute of Scientific and Technical Information of China (English)

    邵传平; 鄂学全; 魏庆鼎; 朱凤荣


    The suppression method of vortex shedding from a circular cylinder has been studied experimentally in the Reynoldsnumber range from 300 to 1600. The test is performed in a water channel. The model cylinder is 1 cm in diameter and 38cm in length. A row of small rods of 0. 18 cm in diameter and 1.5 cm in length are perpendicularly connected to the surfaceof the model cylinder and distributed along the meridian. The distance between the neighboring rods and the angle of attackof the rods can be changed so that the suppression effect on vortex shedding can be adjusted. The results show that vortexshedding can be suppressed effectively if the distance between the neighboring rods is smaller than 3 times and the cylinderdiameter and the angle of attack is in the range of 30°≤β < 90°.

  20. EphrinB3 blocks EphB3 dependence receptor functions to prevent cell death following traumatic brain injury. (United States)

    Theus, M H; Ricard, J; Glass, S J; Travieso, L G; Liebl, D J


    Eph receptor tyrosine kinases and their membrane-bound ligands, ephrins, have a variety of roles in the developing and adult central nervous system that require direct cell-cell interactions; including regulating axon path finding, cell proliferation, migration and synaptic plasticity. Recently, we identified a novel pro-survival role for ephrins in the adult subventricular zone, where ephrinB3 blocks Eph-mediated cell death during adult neurogenesis. Here, we examined whether EphB3 mediates cell death in the adult forebrain following traumatic brain injury and whether ephrinB3 infusion could limit this effect. We show that EphB3 co-labels with microtubule-associated protein 2-positive neurons in the adult cortex and is closely associated with ephrinB3 ligand, which is reduced following controlled cortical impact (CCI) injury. In the complete absence of EphB3 (EphB3(-/-)), we observed reduced terminal deoxynucleotidyl transferase-dUTP nick end labeling (TUNEL), and functional improvements in motor deficits after CCI injury as compared with wild-type and ephrinB3(-/-) mice. We also demonstrated that EphB3 exhibits dependence receptor characteristics as it is cleaved by caspases and induces cell death, which is not observed in the presence of ephrinB3. Following trauma, infusion of pre-clustered ephrinB3-Fc molecules (eB3-Fc) into the contralateral ventricle reduced cortical infarct volume and TUNEL staining in the cortex, dentate gyrus and CA3 hippocampus of wild-type and ephrinB3(-/-) mice, but not EphB3(-/-) mice. Similarly, application of eB3-Fc improved motor functions after CCI injury. We conclude that EphB3 mediates cell death in the adult cortex through a novel dependence receptor-mediated cell death mechanism in the injured adult cortex and is attenuated following ephrinB3 stimulation.

  1. EphrinA4 mimetic peptide targeted to EphA binding site impairs the formation of long-term fear memory in lateral amygdala. (United States)

    Dines, M; Lamprecht, R


    Fear conditioning leads to long-term fear memory formation and is a model for studying fear-related psychopathologies conditions such as phobias and posttraumatic stress disorder. Long-term fear memory formation is believed to involve alterations of synaptic efficacy mediated by changes in synaptic transmission and morphology in lateral amygdala (LA). EphrinA4 and its cognate Eph receptors are intimately involved in regulating neuronal morphogenesis, synaptic transmission and plasticity. To assess possible roles of ephrinA4 in fear memory formation we designed and used a specific inhibitory ephrinA4 mimetic peptide (pep-ephrinA4) targeted to EphA binding site. We show that this peptide, composed of the ephrinA4 binding domain, interacts with EphA4 and inhibits ephrinA4-induced phosphorylation of EphA4. Microinjection of the pep-ephrinA4 into rat LA 30 min before training impaired long- but not short-term fear conditioning memory. Microinjection of a control peptide derived from a nonbinding E helix site of ephrinA4, that does not interact with EphA, had no effect on fear memory formation. Microinjection of pep-ephrinA4 into areas adjacent to the amygdala had no effect on fear memory. Acute systemic administration of pep-ephrinA4 1 h after training also impaired long-term fear conditioning memory formation. These results demonstrate that ephrinA4 binding sites in LA are essential for long-term fear memory formation. Moreover, our research shows that ephrinA4 binding sites may serve as a target for pharmacological treatment of fear and anxiety disorders.

  2. Ephrin-A3 reverse signaling regulates hippocampal neuronal damage and astrocytic glutamate transport after transient global ischemia. (United States)

    Yang, Jinshan; Luo, Xiang; Huang, Xiaojiang; Ning, Qin; Xie, Minjie; Wang, Wei


    Increasing evidence indicates that the Eph receptors and their ephrin ligands are involved in the regulation of interactions between neurons and astrocytes. Moreover, astrocytic ephrin-A3 reverse signaling mediated by EphA4 receptors is necessary for controlling the abundance of glial glutamate transporters. However, the role of ephrin-A3 reverse signaling in astrocytic function and neuronal death under ischemic conditions remains unclear. In the present study, we found that the EphA4 receptor and its ephrin-A3 ligand, which were distributed in neurons and astrocytes, respectively, in the hippocampus showed a coincident up-regulation of protein expression in the early stage of ischemia. Application of clustered EphA4 decreased the expressions of astrocytic glutamate transporters together with astrocytic glutamate uptake capacity through activating ephrin-A3 reverse signaling. In consequence, neuronal loss was aggravated in the CA1 region of the hippocampus accompanied by impaired hippocampus-dependent spatial memory when clustered EphA4 treatment was administered prior to transient global ischemia. These findings indicate that EphA4-mediated ephrin-A3 reverse signaling is a crucial mechanism for astrocytes to control glial glutamate transporters and prevent glutamate excitotoxicity under pathological conditions. Astrocytic ephrin-A3 reverse signaling mediated by EphA4 receptor is necessary for controlling the abundance of glial glutamate transporters under physiological conditions. However, the role of ephrin-A3 reverse signaling in astrocytic function and neuronal death under ischemic conditions remains unclear. We found EphA4-mediated ephrin-A3 reverse signaling to be a crucial mechanism for astrocytes to control glial glutamate transporters and protect hippocampal neurons from glutamate excitotoxicity under ischemic conditions, this cascade representing a potential therapeutic target for stroke.

  3. EphA/ephrin A reverse signaling promotes the migration of cortical interneurons from the medial ganglionic eminence. (United States)

    Steinecke, André; Gampe, Christin; Zimmer, Geraldine; Rudolph, Judith; Bolz, Jürgen


    Inhibitory interneurons control the flow of information and synchronization in the cerebral cortex at the circuit level. During embryonic development, multiple subtypes of cortical interneurons are generated in different regions of the ventral telencephalon, such as the medial and caudal ganglionic eminence (MGE and CGE), as well as the preoptic area (POA). These neurons then migrate over long distances towards their cortical target areas. Diverse families of diffusible and cell-bound signaling molecules, including the Eph/ephrin system, regulate and orchestrate interneuron migration. Ephrin A3 and A5, for instance, are expressed at the borders of the pathway of MGE-derived interneurons and prevent these cells from entering inappropriate regions via EphA4 forward signaling. We found that MGE-derived interneurons, in addition to EphA4, also express ephrin A and B ligands, suggesting Eph/ephrin forward and reverse signaling in the same cell. In vitro and in vivo approaches showed that EphA4-induced reverse signaling in MGE-derived interneurons promotes their migration and that this effect is mediated by ephrin A2 ligands. In EphA4 mutant mice, as well as after ephrin A2 knockdown using in utero electroporation, we found delayed interneuron migration at embryonic stages. Thus, besides functions in guiding MGE-derived interneurons to the cortex through forward signaling, here we describe a novel role of the ephrins in driving these neurons to their target via reverse signaling.

  4. Dishevelled mediates ephrinB1 signalling in the eye field through the planar cell polarity pathway. (United States)

    Lee, Hyun-Shik; Bong, Yong-Sik; Moore, Kathryn B; Soria, Kathleen; Moody, Sally A; Daar, Ira O


    An important step in retinal development is the positioning of progenitors within the eye field where they receive the local environmental signals that will direct their ultimate fate. Recent evidence indicates that ephrinB1 functions in retinal progenitor movement, but the signalling pathway is unclear. We present evidence that ephrinB1 signals through its intracellular domain to control retinal progenitor movement into the eye field by interacting with Xenopus Dishevelled (Xdsh), and by using the planar cell polarity (PCP) pathway. Blocking Xdsh translation prevents retinal progeny from entering the eye field, similarly to the morpholino-mediated loss of ephrinB1 (ref. 2). Overexpression of Xdsh can rescue the phenotype induced by loss of ephrinB1, and this rescue (as well as a physical association between Xdsh and ephrinB1) is completely dependent on the DEP (Dishevelled, Egl-10, Pleckstrin) domain of Xdsh. Similar gain- and loss-of-function experiments suggest that Xdsh associates with ephrinB1 and mediates ephrinB1 signalling through downstream members of the PCP pathway during eye field formation.


    Coate, Thomas M.; Swanson, Tracy L.; Copenhaver, Philip F.


    Reverse signaling via GPI-linked Ephrins may help control cell proliferation and outgrowth within the nervous system, but the mechanisms underlying this process remain poorly understood. In the embryonic enteric nervous system (ENS) of the moth Manduca sexta, migratory neurons forming the enteric plexus (EP cells) express a single Ephrin ligand (GPI-linked MsEphrin), while adjacent midline cells that are inhibitory to migration express the cognate receptor (MsEph). Knocking down MsEph receptor expression in cultured embryos with antisense morpholino oligonucleotides allowed the EP cells to cross the midline inappropriately, consistent with the model that reverse signaling via MsEphrin mediates a repulsive response in the ENS. Src family kinases have been implicated in reverse signaling by type-A Ephrins in other contexts, and MsEphrin colocalizes with activated forms of endogenous Src in the leading processes of the EP cells. Pharmacological inhibition of Src within the developing ENS induced aberrant midline crossovers, similar to the effect of blocking MsEphrin reverse signaling. Hyperstimulating MsEphrin reverse signaling with MsEph-Fc fusion proteins induced the rapid activation of endogenous Src specifically within the EP cells, as assayed by Western blots of single embryonic gut explants and by whole-mount immunostaining of cultured embryos. In longer cultures, treatment with MsEph-Fc caused a global inhibition of EP cell migration and outgrowth, an effect that was prevented by inhibiting Src activation. These results support the model that MsEphrin reverse signaling induces the Src-dependent retraction of EP cell processes away from the enteric midline, thereby helping to confine the neurons to their appropriate pathways. PMID:19295147

  6. Cell-specific information processing in segregating populations of Eph receptor ephrin-expressing cells

    DEFF Research Database (Denmark)

    Jørgensen, Claus; Sherman, Andrew; Chen, Ginny I


    Cells have self-organizing properties that control their behavior in complex tissues. Contact between cells expressing either B-type Eph receptors or their transmembrane ephrin ligands initiates bidirectional signals that regulate cell positioning. However, simultaneously investigating how...... information is processed in two interacting cell types remains a challenge. We implemented a proteomic strategy to systematically determine cell-specific signaling networks underlying EphB2- and ephrin-B1-controlled cell sorting. Quantitative mass spectrometric analysis of mixed populations of EphB2......- and ephrin-B1-expressing cells that were labeled with different isotopes revealed cell-specific tyrosine phosphorylation events. Functional associations between these phosphotyrosine signaling networks and cell sorting were established with small interfering RNA screening. Data-driven network modeling...

  7. Genetic factors controlling wool shedding in a composite Easycare sheep flock. (United States)

    Matika, O; Bishop, S C; Pong-Wong, R; Riggio, V; Headon, D J


    Historically, sheep have been selectively bred for desirable traits including wool characteristics. However, recent moves towards extensive farming and reduced farm labour have seen a renewed interest in Easycare breeds. The aim of this study was to quantify the underlying genetic architecture of wool shedding in an Easycare flock. Wool shedding scores were collected from 565 pedigreed commercial Easycare sheep from 2002 to 2010. The wool scoring system was based on a 10-point (0-9) scale, with score 0 for animals retaining full fleece and 9 for those completely shedding. DNA was sampled from 200 animals of which 48 with extreme phenotypes were genotyped using a 50-k SNP chip. Three genetic analyses were performed: heritability analysis, complex segregation analysis to test for a major gene hypothesis and a genome-wide association study to map regions in the genome affecting the trait. Phenotypes were treated as a continuous or binary variable and categories. High estimates of heritability (0.80 when treated as a continuous, 0.65-0.75 as binary and 0.75 as categories) for shedding were obtained from linear mixed model analyses. Complex segregation analysis gave similar estimates (0.80 ± 0.06) to those above with additional evidence for a major gene with dominance effects. Mixed model association analyses identified four significant (P wool shedding, demonstrated the possibility of a single putative dominant gene controlling this trait and identified four SNPs that may be in partial linkage disequilibrium with gene(s) controlling shedding.

  8. Model-based control of vortex shedding at low Reynolds numbers (United States)

    Illingworth, Simon J.


    Model-based feedback control of vortex shedding at low Reynolds numbers is considered. The feedback signal is provided by velocity measurements in the wake, and actuation is achieved using blowing and suction on the cylinder's surface. Using two-dimensional direct numerical simulations and reduced-order modelling techniques, linear models of the wake are formed at Reynolds numbers between 45 and 110. These models are used to design feedback controllers using {H}_∞ loop-shaping. Complete suppression of shedding is demonstrated up to Re = 110—both for a single-sensor arrangement and for a three-sensor arrangement. The robustness of the feedback controllers is also investigated by applying them over a range of off-design Reynolds numbers, and good robustness properties are seen. It is also observed that it becomes increasingly difficult to achieve acceptable control performance—measured in a suitable way—as Reynolds number increases.

  9. Gliosis after traumatic brain injury in conditional ephrinB2-knockout mice

    Institute of Scientific and Technical Information of China (English)

    LIU Ling; CHEN Xiao-lin; YANG Jian-kai; REN Ze-guang; WANG Shuo


    Background In response to the injury of the central nervous system (CNS),the astrocytes upregulate the expression of glial fibrillary acidic protein (GFAP),which largely contributes to the reactive gliosis after brain injury.The regulatory mechanism of this process is still not clear.In this study,we aimed to compare the ephrin-B2 deficient mice with the wild type ones with regard to gliosis after traumatic brain injury.Methods We generated ephrin-B2 knockout mice specifically in CNS astrocytes.Twelve mice from this gene-knockout strain were randomly selected along with twelve mice from the wild type littermates.In both groups,a modified controlled cortical impact injury model was applied to create a closed traumatic brain injury.Twenty-eight days after the injury,Nissl staining and GFAP immunofluorescence staining were used to compare the brain atrophy and GFAP immunoreactivity between the two groups.All the data were analyzed by t-test for between-group comparison.Results We successfully set up the conditional ephrin-B2 knockout mice strain,which was confirmed by genotyping and ephrin-B2/GFAP double staining.These mice developed normally without apparent abnormality in general appearance.Twenty-eight days following brain injury,histopathology revealed by immunohistochemistry showed different degrees of cerebral injuries in both groups.Compared with wild-type group,the ephrin-B2 knockout group exhibited less brain atrophy ratio for the injured hemispheres (P=0.005) and hippocampus (P=0.027).Also the wild-type group demonstrated greater GFAP immunoreactivity increment within hippocampal regions (P=0.008).Conclusions The establishment of conditional ephrin-B2 knockout mice provides us with a new way to explore the role of ephrin-B2 in astrocytes.Our findings revealed less atrophy and GFAP immunoreactivity in the knockout mice strain after traumatic brain injury,which implied ephrin-B2 could be one of the promoters to upregulate gliosis following brain injury.

  10. EphB/EphrinB receptors and Wnt signaling in colorectal cancer.

    NARCIS (Netherlands)

    Clevers, J.C.; Batlle, E.


    Eph receptors and their ephrin ligands mediate cell repulsion during embryonic development. In the intestinal epithelium, EphB receptors are Wnt signaling target genes that control cell compartmentalization along the crypt axis. Recent findings have shown that this family of receptors are key

  11. PI3K contributed to modulation of spinal nociceptive information related to ephrinBs/EphBs.

    Directory of Open Access Journals (Sweden)

    Li-Na Yu

    Full Text Available There is accumulating evidence to implicate the importance of EphBs receptors and ephrinBs ligands were involved in modulation of spinal nociceptive information. However, the downstream mechanisms that control this process are not well understood. In the present study, we investigated whether phosphatidylinositol 3-kinase (PI3K, as the downstream effectors, participates in modulation of spinal nociceptive information related to ephrinBs/EphBs. Intrathecal injection of ephrinB1-Fc produced a dose- and time-dependent thermal and mechanical hyperalgesia, accompanied by the increase of spinal PI3K-p110γ, phosphorylation of AKT (p-AKT and c-Fos expression. Pre-treatment with PI3K inhibitor wortmannin or LY294002 prevented activation of spinal AKT induced by ephrinB1-Fc. Inhibition of spinal PI3K signaling dose-dependently prevented and reversed pain behaviors and spinal c-Fos protein expression induced by intrathecal injection of ephrinB1-Fc. Inhibition of EphBs receptors by intrathecal injection of EphB1-Fc reduced formalin-induced inflammation and chronic constrictive injury-induced neuropathic pain behaviors accompanied by decreased expression of spinal PI3K,p-AKT and c-Fos protein. Furthermore, pre-treatment with PI3K inhibitor wortmannin or LY294002 prevented ephrinB1-Fc-induced ERK activation in spinal. These data demonstrated that PI3K and PI3K crosstalk to ERK signaling contributed to modulation of spinal nociceptive information related to ephrinBs/EphBs.

  12. Thermal control of rod outer segment length and shedding in a fish, Fundulus zebrinus. (United States)

    Allen, D M


    The effects of temperature on rod outer segment (ROS) length and membrane shedding were studied in a cyprinodont fish, Fundulus zebrinus. After 30 days in 14L/10D cyclic light and 17 degrees C, ROS length averaged 41.2 microns. Fish were then exposed to 7, 17 or 27 degrees C for 10 and 25 days before being sampled 5 hr before and 1-4 hr after light onset. In 7 degrees C ROS shortened to 83.5% of initial controls within 10 days, then only 4.1% further, to 79.4% by day 25 (34.4, 32.7 microns). ROS length did not change significantly in fish remaining at 17 degrees C (39.7 and 40.7 microns at day 10 and 25) or in fish moved to 27 degrees C (41.7 and 41.6 microns). Phagosomes were most numerous in 7 degrees C and least numerous in 17 degrees C, but varied in overall size among the largest phagosomes being more common after light onset. After light onset at day 25, the estimated volume per phagosome was 1.14, 4.73 and 5.75 microns 3 in 7, 17 and 27 degrees C. Total phagosome volume per 100 microns RPE at 27 degrees C was generally double that at 17 degrees C. Apparently, in F. zebrinus, the number of disks shed from ROS is adjusted during thermal acclimation to stabilize ROS length.

  13. Ephrin-A3 and ephrin-A4 contribute to microglia-induced angiogenesis in brain endothelial cells. (United States)

    Li, Ying; Liu, Dong-Xin; Li, Mei-Yang; Qin, Xiao-Xue; Fang, Wen-Gang; Zhao, Wei-Dong; Chen, Yu-Hua


    The association of microglia with brain vasculature during development and the reduced brain vascular complexity in microglia-deficient mice suggest the role of microglia in cerebrovascular angiogenesis. However, the underlying molecular mechanism remains unclear. Here, using an in vitro angiogenesis model, we found the culture supernatant of BV2 microglial cells significantly enhanced capillary-like tube formation and migration of brain microvascular endothelial cells (BMECs). The expression of angiogenic factors, ephrin-A3 and ephrin-A4, were specifically upregulated in BMECs exposed to BV2-derived culture supernatant. Knockdown of ephrin-A3 and ephrin-A4 in BMECs by siRNA significantly attenuated the enhanced angiogenesis and migration of BMECs induced by BV2 supernatant. Our further results indicated that the ability of BV2 supernatant to promote endothelial angiogenesis was caused by the soluble tumor necrosis factor α (TNF-α) released from BV2 microglial cells. Moreover, the upregulations of ephrin-A3 and ephrin-A4 in BMECs in response to BV2 supernatant were effectively abolished by neutralization antibody against TNF-α and TNF receptor 1, respectively. The present study provides evidence that microglia upregulates endothelial ephrin-A3 and ephrin-A4 to facilitate in vitro angiogenesis of brain endothelial cells, which is mediated by microglia-released TNF-α.

  14. Interaction between EphrinB1 and CNK1 Found to Play Role in Tumor Progression | Poster (United States)

    By Nancy Parrish, Staff Writer The family of proteins known as ephrins plays a critical role in a variety of biological processes. In a recent article in the Journal of Biological Chemistry, Hee Jun Cho, Ph.D., and colleagues report on the interaction between proteins CNK1 and ephrinB1 that promotes cell movement. Their findings may have an important implication in developing new therapeutics for reducing metastases in certain cancers. “Eph and ephrin signaling has become an area of intense interest due to the influence these molecules exert on the control of cell adhesion and cell movement,” Cho said. “This signaling affects the formation of tissues during development and has been shown to play an instructive role in angiogenesis, as well as tumor cell invasion.”

  15. Ephrin-B2 is differentially expressed in the intestinal epithelium in Crohn's disease and contributes to accelerated epithelial wound healing in vitro

    Institute of Scientific and Technical Information of China (English)

    Christian Hafner; Michael Landthaler; Thomas Vogt; Stefanie Meyer; Thomas Langmann; Gerd Schmitz; Frauke Bataille; Ilja Hagen; Bernd Becker; Alexander Roesch; Gerhard Rogler


    AIM: Eph receptor tyrosine kinases and their membrane bound receptor-like ligands, the ephrins, represent a bi-directional cell-cell contact signaling system that directs epithelial movements in development. The meaning of this system in the adult human gut is unknown. We investigated the Eph/ephrin mRNA expression in the intestinal epithelium of healthy controls and patients with inflammatory bowel disease (IBD).METHODS: mRNA expression profiles of all Eph/ephrin family members in normal small intestine and colon were established by real-time RT-PCR. In addition, differential expression in IBD was investigated by cDNA array technology, and validated by both real-time RT-PCR and immunohistochemistry. Potential effects of enhanced EphB/ephrin-B signaling were analyzed in an in vitro IEC-6 cell scratch wound model.RESULTS: Human adult intestinal mucosa exhibits a complex pattern of Eph receptors and ephrins. Beside the known prominent co-expression of EphA2 and ephrinA1,we found abundantly co-expressed EphB2 and ephrin-B1/2.Interestingly, cDNA array data, validated by real-time PCR and immunohistochemistry, showed upregulation of ephrin-B2 in both perilesional and lesional intestinal epithelial cells of IBD patients, suggesting a role in epithelial homeostasis. Stimulation of ephrin-B signaling in ephrinB1/2 expressing rat IEC-6-cells with recombinant EphB1Fc resulted in a significant dose-dependent acceleration of wound closure. Furthermore, fluorescence microscopy showed that EphB1-Fc induced coordinated migration of wound edge cells is associated with enhanced formation of lamellipodial protrusions into the wound, increased actin stress fiber assembly and production of laminin at the wound edge.CONCLUSION: EphB/ephrin-B signaling might represent a novel protective mechanism that promotes intestinal epithelial wound healing, with potential impact on epithelial restitution in IBD.

  16. Control of a coupled map lattice model for vortex shedding in the wake of a cylinder

    Indian Academy of Sciences (India)

    G Balasubramanian; D J Olinger; M A Demetriou


    The flow behind a vibrating flexible cable at low Reynolds numbers can exhibit complex wake structures such as lace-like patterns, vortex dislocations and frequency cells. These structures have been observed in experiments and numerical simulations, and are predicted by a previously developed low-order coupled map lattice (CML). The discrete (in time and space) CML models consist of a series of diffusively coupled circle map oscillators along the cable span. Motivated by a desire to modify the complex wake patterns behind flexible vibrating cables, we have studied the addition of control terms into the highly efficient CML models and explored the resulting dynamics. Proportional, adaptive proportional and discontinuous non-linear (DNL) control methods were used to derive the control laws. The first method employed occasional proportional feedback. The adaptive method used spatio-temporal feedback control. The DNL method used a discontinuous feedback linearization procedure, and the controller was designed for the resulting linearized system using eigenvalue assignment. These techniques were applied to a modeled vortex dislocation structure in the wake of a vibrating cable in uniform freestream flow. Parallel shedding patterns were achieved for a range of forcing frequency-forcing amplitude combinations studied to validate the control theory. The adaptive proportional and DNL methods were found to be more effective than the proportional control method due to the incorporation of a spatially varying feedback gain across the cylinder span. The DNL method was found to be the most efficient controller of the low-order CML model. The required control level across the cable span was correlated to the 1/1 lock-on behavior of the temporal circle map.

  17. Ephrin signalling in the developing nervous system. (United States)

    Klein, Rüdiger; Kania, Artur


    Ephrin ligands and their Eph receptors hold our attention since their link to axon guidance almost twenty years ago. Since then, they have been shown to be critical for short distance cell-cell interactions in the nervous system. The interest in their function has not abated, leading to ever-more sophisticated studies generating as many surprising answers about their function as new questions. We discuss recent insights into their functions in the developing nervous system, including neuronal progenitor sorting, stochastic cell migration, guidance of neuronal growth cones, topographic map formation, as well as synaptic plasticity.

  18. Numerical study of wingtip shed vorticity reduction by wing Boundary Layer Control (United States)

    Posada, Jose Alejandro

    Wingtip vortex reductions have been obtained by Boundary Layer Control application to an AR=1.5 rectangular wing using a NACA 0012 airfoil. If wingtip shed vorticity could be reduced significantly, then so would induced drag resulting in improved cruise fuel economy. Power savings would be even more impressive at low flight speed or in climb. A two dimensional wing produces lift without wingtip vorticity. Its bound vorticity, Gamma, equals the contour integral of the boundary layer vorticity gamma or Gamma = ∮gamma · dl. Where the upper and lower boundary layers meet at the cusped TE, their local static pressure pu=pl then the boundary layer outer edge inviscid velocity Vupper=Vlower and gammalower=-gamma upper. This explains the 2-D wing self cancellation of the upper and lower surface boundary layer vorticity when they meet upon shedding at the trailing edge. In finite wings, the presence of spanwise pressure gradients near the wing tips misaligns gammalower and gammaupper at the wingtip TE preventing the upper and lower surface boundary layers from completely canceling each other. To prevent them from generating wing tip vortices, the local boundary layers need to be captured in suction slots. Once vorticity is captured, it can be eliminated by viscous mixing prior to venting over board. The objective of this dissertation was to use a commercial Computational Fluid Dynamics code (Fluent) to search for the best configuration to locate BLC suction slots to capture non-parallel boundary layer vorticity prior to shedding near the wingtips. The configuration selected for running the simulations was tested by trying to duplicate a 3D wing for which sufficient experimental and computational models by others are available. The practical case selected was done by Chow et al in the 32 x 48 in. low speed wind tunnel at the Fluid Mechanics Laboratory of NASA Ames Research Center, and computationally analyzed by Dacles-Mariani et al, and Khim and Rhee. The present

  19. Ephrin B2/EphB4 pathway in hepatic stellate cells stimulates Erk-dependent VEGF production and sinusoidal endothelial cell recruitment (United States)

    Das, Amitava; Shergill, Uday; Thakur, Lokendra; Sinha, Sutapa; Urrutia, Raul; Mukhopadhyay, Debabrata


    Chemotaxis signals between hepatic stellate cells (HSC) and sinusoidal endothelial cells (SEC) maintain hepatic vascular homeostasis and integrity and also regulate changes in sinusoidal structure in response to liver injury. Our prior studies have demonstrated that the bidirectional chemotactic signaling molecules EphrinB2 and EphB4 are expressed in HSC. The aim of our present study was to explore whether and how the EphrinB2/EphB4 system in HSC could promote SEC recruitment, which is essential for sinusoidal structure and remodeling. Stimulation of human HSC (hHSC) with chimeric agonists (2 μg/ml) of either EphrinB2 or EphB4 (EphrinB2 Fc or EphB4 Fc, respectively) significantly increased VEGF mRNA levels in hHSC as assessed by quantitative PCR, with respective small interfering RNAs for EphrinB2 and EphB4 inhibiting this increase (P < 0.05, n = 3). EphrinB2 agonist-induced increase in VEGF mRNA levels in hHSC was associated with increased phosphorylation of Erk and was significantly blocked by U0126 (20 μM), an inhibitor of MEK, which is a kinase upstream from Erk (P < 0.05, n = 3). The EphB4 agonist also significantly increased human VEGF promoter activity (P < 0.05, n = 3) as assessed by promoter reporter luciferase assay in transfected LX2-HSC. This was associated with upregulation of the vasculoprotective transcription factor, Kruppel-like factor 2 (KLF2). In Boyden chamber assays, conditioned media from hHSC stimulated with agonists of EphrinB2 or EphB4 increased SEC chemotaxis in a VEGF-dependent manner, compared with control groups that included basal media with agonists of EphrinB2, EphB4, or HSC-conditioned media from HSC in absence of agonist stimulation (P < 0.05, n = 3). EphB4 expression was detected in situ within liver sinusoidal vessels of rats after carbon tetrachloride-induced liver injury. In summary, activation of the EphrinB2/EphB4 signaling pathway in HSC promotes chemotaxis of SEC through a pathway that involves Erk, KLF2, and VEGF. These

  20. Pro-neurotrophins secreted from retinal ganglion cell axons are necessary for ephrinA-p75NTR-mediated axon guidance

    Directory of Open Access Journals (Sweden)

    Broom Emma R


    Full Text Available Abstract Background Retinotectal map formation develops via topographically specific guidance and branching of retinal axons in their target area. This process is controlled, in part, by reverse signalling of ephrinAs expressed on retinal axons. As glycosylphosphatidylinositol-anchored molecules, ephrinAs require transmembrane co-receptors to exert this function, for which the two neurotrophin receptors, p75NTR and TrkB, were recently proposed. Results We show here that the ligands for these receptors, the brain-derived neurotrophic factor precursor (proBDNF and its processed form, BDNF, respectively, control the branching of retinal axons antagonistically, which they mediate by inducing the corresponding neurotrophin receptor-ephrinA complexes. Moreover, scavenging proneurotrophins, by adding antibodies specific for the pro-domain of proBNDF or a soluble extracellular domain of p75NTR, abolish repellent ephrinA reverse signalling in the stripe assay. Conclusions This indicates that retinal cells secrete proneurotrophins, inducing the ephrinA-p75NTR interaction and enabling repellent axon guidance. The antagonistic functions of proBDNF and BDNF raise the possibility that topographic branching is controlled by local control of processing of proneurotrophins.

  1. Effects of Porphyromonas gingivalis lipopolysaccharide on osteoblast-osteoclast bidirectional EphB4-EphrinB2 signaling. (United States)

    Zhang, Yi; Wang, Xi-Chao; Bao, Xing-Fu; Hu, Min; Yu, Wei-Xian


    In bone remodeling, the Eph family is involved in regulating the process of osteoclast and osteoblast coordination in order to maintain bone homeostasis. In this study, the effects of Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) on the osteoblast-osteoclast bidirectional EphB4-EphrinB2 signaling were investigated. An osteoblast-osteoclast co-culture system was achieved successfully. Hence, direct contact and communication between osteoblasts and osteoclasts was permitted. Regarding the protein expression and gene expression of EphB4 and EphrinB2, it was shown that Pg-LPS increased the expression of EphB4 while inhibiting the expression of EphrinB2. Therefore, the results indicate that, when treated with Pg-LPS, the EphB4 receptor on osteoblasts and the EphrinB2 ligand on osteoclasts may generate bidirectional anti-osteoclastogenic and pro-osteoblastogenic signaling into respective cells and potentially facilitate the transition from bone resorption to bone formation. This study may contribute to the control of osteoblast differentiation and bone formation at remodeling, and possibly also modeling, sites.

  2. Pericardial patch angioplasty heals via an Ephrin-B2 and CD34 positive cell mediated mechanism.

    Directory of Open Access Journals (Sweden)

    Xin Li

    Full Text Available OBJECTIVE: Pericardial patches are commonly used in vascular surgery to close arteriotomies. The mechanism of early healing after patch implantation is still not well defined. We used a rat aortic patch model to assess pericardial patch healing and examined Ephrin-B2, a marker of arterial identity, expression within the post-implantation patch. We also determined whether endothelial progenitor cells (EPC are associated with early patch healing in the arterial environment. METHODS: Wistar rats (200-250 grams underwent infrarenal aortic arteriotomy and then closure via bovine or porcine pericardial patch angioplasty. Control groups included subcutaneously implanted patches. Patches were harvested at 0-30 days and analyzed by histology, immunohistochemistry, immunofluorescence and Western blot as well as quantitative PCR. RESULTS: Prior to implantation, pericardial patches are largely composed of collagen and are acellular. Following arterial implantation, increasing numbers of CD68-positive cells as well as Ephrin-B2 and CD34 dual-positive cells are found within both bovine and porcine pericardial patches, whereas the infiltrating cells are negative for vWF and α-actin. Porcine patches have a luminal monolayer of cells at day 7, compared to bovine patches that have fewer luminal cells. Subcutaneously implanted patches do not attract Ephrin-B2/CD34-positive cells. By day 30, both bovine and porcine pericardial patches develop a neointima that contains Ephrin-B2, CD34, and VEGFR2-positive cells. CONCLUSION: Both CD68-positive and Ephrin-B2 and CD34 dual-positive cells infiltrate the pericardial patch early after implantation. Arteriotomy closure via pericardial patch angioplasty shows patch adaptation to the arterial environment that may involve a foreign body response as well as localization of EPC. Arterial remodeling of pericardial patches support endothelialization and may represent a paradigm of healing of scaffolds used for tissue engineering.

  3. Control of wake and vortex shedding behind a porous circular obstacle by exerting an external magnetic field

    Energy Technology Data Exchange (ETDEWEB)

    Bovand, M. [Department of Mechanical Engineering, Ferdowsi University of Mashhad, P.O. Box 91775-1111, Mashhad (Iran, Islamic Republic of); Rashidi, S., E-mail: [Department of Mechanical Engineering, Ferdowsi University of Mashhad, P.O. Box 91775-1111, Mashhad (Iran, Islamic Republic of); Dehghan, M. [Faculty of Mechanical Engineering, Semnan University, P.O. 35131-19111, Semnan (Iran, Islamic Republic of); Esfahani, J.A. [Department of Mechanical Engineering, Ferdowsi University of Mashhad, P.O. Box 91775-1111, Mashhad (Iran, Islamic Republic of); Valipour, M.S. [Faculty of Mechanical Engineering, Semnan University, P.O. 35131-19111, Semnan (Iran, Islamic Republic of)


    In this article the finite volume method (FVM) is carried out to simulate the flow around and through a two-dimensional porous cylinder. An external magnetic field is used to control the wake behind the bluff body and also to suppress the vortex shedding phenomena. The Darcy–Brinkman–Forchheimer model has been used for modeling the flow in the porous medium. Effects of Stuart (N), Reynolds (Re) and Darcy (Da) numbers on the flow behavior have been investigated. The results show that the critical Stuart number for suppress vortex shedding decreases with increasing the Darcy numbers. Also, the Stuart number for disappearance the re-circulating wake increases with increased Reynolds number for both porous and solid cylinders. - Highlights: • The formation and shedding of wakes behind a porous bluff-body are investigated. • Effects of a magnetic field on controlling the wake formation is explored. • Roles of Darcy, Reynolds and Stuart numbers on the flow behavior are analyzed. • Flow patterns change with Reynolds number and Darcy numbers. • The critical Stuart number decreases with increased Darcy numbers.

  4. Attenuation of eph receptor kinase activation in cancer cells by coexpressed ephrin ligands.

    Directory of Open Access Journals (Sweden)

    Giulia Falivelli

    Full Text Available The Eph receptor tyrosine kinases mediate juxtacrine signals by interacting "in trans" with ligands anchored to the surface of neighboring cells via a GPI-anchor (ephrin-As or a transmembrane segment (ephrin-Bs, which leads to receptor clustering and increased kinase activity. Additionally, soluble forms of the ephrin-A ligands released from the cell surface by matrix metalloproteases can also activate EphA receptor signaling. Besides these trans interactions, recent studies have revealed that Eph receptors and ephrins coexpressed in neurons can also engage in lateral "cis" associations that attenuate receptor activation by ephrins in trans with critical functional consequences. Despite the importance of the Eph/ephrin system in tumorigenesis, Eph receptor-ephrin cis interactions have not been previously investigated in cancer cells. Here we show that in cancer cells, coexpressed ephrin-A3 can inhibit the ability of EphA2 and EphA3 to bind ephrins in trans and become activated, while ephrin-B2 can inhibit not only EphB4 but also EphA3. The cis inhibition of EphA3 by ephrin-B2 implies that in some cases ephrins that cannot activate a particular Eph receptor in trans can nevertheless inhibit its signaling ability through cis association. We also found that an EphA3 mutation identified in lung cancer enhances cis interaction with ephrin-A3. These results suggest a novel mechanism that may contribute to cancer pathogenesis by attenuating the tumor suppressing effects of Eph receptor signaling pathways activated by ephrins in trans.

  5. Attenuation of Eph Receptor Kinase Activation in Cancer Cells by Coexpressed Ephrin Ligands (United States)

    Falivelli, Giulia; Lisabeth, Erika Mathes; de la Torre, Elena Rubio; Perez-Tenorio, Gizeh; Tosato, Giovanna; Salvucci, Ombretta; Pasquale, Elena B.


    The Eph receptor tyrosine kinases mediate juxtacrine signals by interacting “in trans” with ligands anchored to the surface of neighboring cells via a GPI-anchor (ephrin-As) or a transmembrane segment (ephrin-Bs), which leads to receptor clustering and increased kinase activity. Additionally, soluble forms of the ephrin-A ligands released from the cell surface by matrix metalloproteases can also activate EphA receptor signaling. Besides these trans interactions, recent studies have revealed that Eph receptors and ephrins coexpressed in neurons can also engage in lateral “cis” associations that attenuate receptor activation by ephrins in trans with critical functional consequences. Despite the importance of the Eph/ephrin system in tumorigenesis, Eph receptor-ephrin cis interactions have not been previously investigated in cancer cells. Here we show that in cancer cells, coexpressed ephrin-A3 can inhibit the ability of EphA2 and EphA3 to bind ephrins in trans and become activated, while ephrin-B2 can inhibit not only EphB4 but also EphA3. The cis inhibition of EphA3 by ephrin-B2 implies that in some cases ephrins that cannot activate a particular Eph receptor in trans can nevertheless inhibit its signaling ability through cis association. We also found that an EphA3 mutation identified in lung cancer enhances cis interaction with ephrin-A3. These results suggest a novel mechanism that may contribute to cancer pathogenesis by attenuating the tumor suppressing effects of Eph receptor signaling pathways activated by ephrins in trans. PMID:24348920

  6. Ephrin-B3 decreases the survival of adult rat spinal cord-derived neural stem/progenitor cells in vitro and after transplantation into the injured rat spinal cord. (United States)

    Fan, Xin Yan Susan; Mothe, Andrea J; Tator, Charles H


    Although transplantation of neural stem/progenitor cells (NSPC) encourages regeneration and repair after spinal cord injury (SCI), the survival of transplanted NSPC is limited. Ephrin-B3 has been shown to reduce the death of endogenous NSPC in the subventricular zone of the mouse brain without inducing uncontrolled proliferation. Due to similarities in the environment of the brain and spinal cord, we hypothesized that ephrin-B3 might reduce the death of both transplanted and endogenous spinal cord-derived NSPC. Both normal and injured (26 g clip compression) spinal cords were examined. Ephrin-B3-Fc was tested, and Fc fragments and phosphate-buffered saline (PBS) were used as controls. We found that EphA4 receptors were expressed by spinal cord-derived NSPC and expressed in the normal and injured rat spinal cord (higher expression in the latter). In vitro, ephrin-B3-Fc did not significantly reduce the survival of NSPC except at 1 μg/mL (Pinjured spinal cord compared with the infusion of PBS (Pinjured spinal cord, the infusion of either ephrin-B3-Fc or Fc fragments alone caused a 20-fold reduction in the survival of transplanted NSPC (P<0.001). Thus, after SCI, ephrin-B3-Fc and Fc fragments are toxic to transplanted NSPC.

  7. Assessing EphA2 and Ephrin-A as Novel Diagnostic and Prognostic Biomarkers of Prostate Cancer (United States)


    October 2015 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012...currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE October 2015 2. REPORT TYPE Annual 3. DATES...prostate biopsy and prostatectomy at our institution. We will correlate their levels of EphA2 and ephrin-A1 mRNA as well as staining of phosphorylated

  8. Distinctive Structure of the EphA3/Ephrin-A5 Complex Reveals a Dual Mode of Eph Receptor Interaction for Ephrin-A5.

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    Garry Jason Forse

    Full Text Available The Eph receptor tyrosine kinase/ephrin ligand system regulates a wide spectrum of physiological processes, while its dysregulation has been implicated in cancer progression. The human EphA3 receptor is widely upregulated in the tumor microenvironment and is highly expressed in some types of cancer cells. Furthermore, EphA3 is among the most highly mutated genes in lung cancer and it is also frequently mutated in other cancers. We report the structure of the ligand-binding domain of the EphA3 receptor in complex with its preferred ligand, ephrin-A5. The structure of the complex reveals a pronounced tilt of the ephrin-A5 ligand compared to its orientation when bound to the EphA2 and EphB2 receptors and similar to its orientation when bound to EphA4. This tilt brings an additional area of ephrin-A5 into contact with regions of EphA3 outside the ephrin-binding pocket thereby enlarging the size of the interface, which is consistent with the high binding affinity of ephrin-A5 for EphA3. This large variation in the tilt of ephrin-A5 bound to different Eph receptors has not been previously observed for other ephrins.

  9. Inhibition of gap junction communication at ectopic Eph/ephrin boundaries underlies craniofrontonasal syndrome.

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    Alice Davy


    Full Text Available Mutations in X-linked ephrin-B1 in humans cause craniofrontonasal syndrome (CFNS, a disease that affects female patients more severely than males. Sorting of ephrin-B1-positive and -negative cells following X-inactivation has been observed in ephrin-B1(+/- mice; however, the mechanisms by which mosaic ephrin-B1 expression leads to cell sorting and phenotypic defects remain unknown. Here we show that ephrin-B1(+/- mice exhibit calvarial defects, a phenotype autonomous to neural crest cells that correlates with cell sorting. We have traced the causes of calvarial defects to impaired differentiation of osteogenic precursors. We show that gap junction communication (GJC is inhibited at ectopic ephrin boundaries and that ephrin-B1 interacts with connexin43 and regulates its distribution. Moreover, we provide genetic evidence that GJC is implicated in the calvarial defects observed in ephrin-B1(+/- embryos. Our results uncover a novel role for Eph/ephrins in regulating GJC in vivo and suggest that the pleiotropic defects seen in CFNS patients are due to improper regulation of GJC in affected tissues.

  10. Heterogeneous shedding of Escherichia coli O157 in cattle and its implications for control

    NARCIS (Netherlands)

    Matthews, L.; Low, J.C.; Gally, D.L.; Pearce, M.C.; Mellor, D.J.; Heesterbeek, J.A.P.; Chase-Topping, M.; Naylor, S.W.; Shaw, D.J.; Reid, S.W.J.; Gunn, G.J.; Woolhouse, M.E.J.


    Identification of the relative importance of within- and between-host variability in infectiousness and the impact of these heterogeneities on the transmission dynamics of infectious agents can enable efficient targeting of control measures. Cattle, a major reservoir host for the zoonotic pathogen E

  11. Ephrin-a4 is involved in retinal neovascularization by regulating the VEGF signaling pathway. (United States)

    Du, Wei; Yu, Wenzhen; Huang, Lvzhen; Zhao, Min; Li, Xiaoxin


    Retinal neovascularization (NV) is a major cause of blindness. Recent research suggests that factors other than VEGF participate in this process. This study aimed to determine the role of ephrin-A4 in retinal NV. The expression and effect of ephrin-A4 was investigated in a mouse model of oxygen-induced retinopathy (OIR) and the RF/6A retina endothelial cell line. Ephrin-A4 expression and VEGF signaling pathway phosphorylation were determined by PCR, immunohistochemistry, and western blot analyses. ShRNA was used to silence ephrin-A4 in vitro and in vivo. Retinal flat mounts and tube formation assays were performed to evaluate ephrin-A4 function in the NV process in vivo and in vitro. Ephrin-A4 was overexpressed in the retina of OIR mice and in RF/6A and RPE cells after CoCl₂ stimulation. In vitro, Ephrin-A4/Fc treatment significantly increased the tube number of RF/6A cells on a membrane preparation and the phosphorylation levels of VEGR2, Akt1, and ERK1/2 in RF/6A cells. Moreover, ephrin-A4 knockout markedly suppressed pathologic neovascularization in vivo and inhibited the proliferation and tube formation capacity of RF/6A cells in vitro. Furthermore, in the absence of ephrin-A4, the phosphorylation of VEGFR2, Akt1, and ERK1/2 was defective under VEGF₁₆₅ stimulation, and the proangiogenic function of VEGF₁₆₅ was also compromised. This study suggests that ephrin-A4 plays an important role in retinal NV and is a potential target against retinal NV. The proangiogenic function of ephrin-A4 may be linked to its crucial role in the VEGF signaling pathway.

  12. The role of Ephs, Ephrins, and growth factors in Kaposi sarcoma and implications of EphrinB2 blockade


    Scehnet, Jeffrey S.; Ley, Eric J.; Krasnoperov, Valery; Liu, Ren; Manchanda, Parmeet K.; Sjoberg, Eric; Kostecke, Anna P.; Gupta, Sachin; Kumar, S. Ram; Gill, Parkash S.


    Kaposi sarcoma (KS) is associated with human herpesvirus (HHV)-8 and is dependent on the induction of vascular endothelial growth factors (VEGFs). VEGF regulates genes that provide arterial or venous identity to endothelial cells, such as the induction of EphrinB2, which phenotypically defines arterial endothelial cells and pericytes, and represses EphB4, which defines venous endothelial cells. We conducted a comprehensive analysis of the Eph receptor tyrosine kinases to determine which membe...

  13. Two key residues in ephrinB3 are critical for its use as an alternative receptor for Nipah virus.

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    Oscar A Negrete


    Full Text Available EphrinB2 was recently discovered as a functional receptor for Nipah virus (NiV, a lethal emerging paramyxovirus. Ephrins constitute a class of homologous ligands for the Eph class of receptor tyrosine kinases and exhibit overlapping expression patterns. Thus, we examined whether other ephrins might serve as alternative receptors for NiV. Here, we show that of all known ephrins (ephrinA1-A5 and ephrinB1-B3, only the soluble Fc-fusion proteins of ephrinB3, in addition to ephrinB2, bound to soluble NiV attachment protein G (NiV-G. Soluble NiV-G bound to cell surface ephrinB3 and B2 with subnanomolar affinities (Kd = 0.58 nM and 0.06 nM for ephrinB3 and B2, respectively. Surface plasmon resonance analysis indicated that the relatively lower affinity of NiV-G for ephrinB3 was largely due to a faster off-rate (K(off = 1.94 x 10(-3 s(-1 versus 1.06 x 10(-4 s(-1 for ephrinB3 and B2, respectively. EphrinB3 was sufficient to allow for viral entry of both pseudotype and live NiV. Soluble ephrinB2 and B3 were able to compete for NiV-envelope-mediated viral entry on both ephrinB2- and B3-expressing cells, suggesting that NiV-G interacts with both ephrinB2 and B3 via an overlapping site. Mutational analysis indicated that the Leu-Trp residues in the solvent exposed G-H loop of ephrinB2 and B3 were critical determinants of NiV binding and entry. Indeed, replacement of the Tyr-Met residues in the homologous positions in ephrinB1 with Leu-Trp conferred NiV receptor activity to ephrinB1. Thus, ephrinB3 is a bona fide alternate receptor for NiV entry, and two residues in the G-H loop of the ephrin B-class ligands are critical determinants of NiV receptor activity.

  14. The pineal gland does not control rod outer segment shedding and phagocytosis in the rat retina and pigment epithelium. (United States)

    Tamai, M; Teirstein, P; Goldman, A; O'Brien, P; Chader, G


    Diurnal patterns of retinal outer segment shedding and phagocytosis by the pigment epithelium were examined in pinealectomized, superior-cervical-ganglionectomized, and sham-operated rats. Phagocytosis was quantitatively similar in all groups. Sharp increases in the number of large phagosomes were observed soon after lights were turned on in the tree sets of animals. Pinealectomized animals kept in constant darkness over a 24 hr period also exhibited normal shedding patterns. Our results suggest that the pineal does not exert a major influence on the daily rhythms of shedding and phagocytosis observed in the retina-pigment epithelium unit.

  15. EphrinA5 suppresses colon cancer development by negatively regulating epidermal growth factor receptor stability. (United States)

    Wang, Tong-Hong; Chang, Junn-Liang; Ho, Jar-Yi; Wu, Hsiao-Chun; Chen, Tse-Ching


    Colon cancer is one of the most common human cancers worldwide. Owing to its aggressiveness and lethality, it is necessary to determine the mechanisms regulating the carcinogenesis of colon cancer. EphrinA5 has been reported to act as a putative tumor suppressor in glioma; however, little is known concerning the role of this protein in the context of colon cancer. To elucidate the biological significance of ephrinA5 in colon cancer, we examined ephrinA5 and epidermal growth factor receptor (EGFR) expression profiles in both colon cancer and normal tissues, using immunohistochemistry on a 96-spot tissue microarray. Gain-of-function and loss-of-function experiments were performed on the human colon cancer cell lines SW480 and WiDr to determine the biological effects of ephrinA5 in relation to cell proliferation, survival, and migration. It was found that ephrinA5 mRNA and protein levels were significantly reduced in colon cancer as compared with normal colon tissue specimens. EphrinA5 expression was also negatively associated with tumor differentiation and clinical stage. In colon cancer cell line models, ephrinA5 exerted an inhibitory effect on EGFR by promoting c-Cbl-mediated EGFR ubiquitination and degradation. EphrinA5 did not affect the transcriptional regulation of EGFR mRNA expression in colon cancer cells. Expression of ephrinA5 suppressed colon cancer cell proliferation, migration, and chemotherapeutic resistance. In conclusion, ephrinA5 inhibited colon cancer progression by promoting c-Cbl-mediated EGFR degradation. Our findings identify a novel mechanism that could be utilized to improve the therapeutic efficiency of EGFR-targeting strategies.

  16. Divergent roles for Eph and Ephrin in Avian Cranial Neural Crest

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    Burke Robert D


    Full Text Available Abstract Background As in other vertebrates, avian hindbrain neural crest migrates in streams to specific branchial arches. Signalling from Eph receptors and ephrins has been proposed to provide a molecular mechanism that guides the cells restricting them to streams. In mice and frogs, cranial neural crest express a combination of Eph receptors and ephrins that appear to exclude cells from adjacent tissues by forward and reverse signalling. The objective of this study was to provide comparative data on the distribution and function of Eph receptors and ephrins in avian embryos. Results To distinguish neural crest from bordering ectoderm and head mesenchyme, we have co-labelled embryos for Eph or ephrin RNA and a neural crest marker protein. Throughout their migration avian cranial neural crest cells express EphA3, EphA4, EphA7, EphB1, and EphB3 and move along pathways bordered by non-neural crest cells expressing ephrin-B1. In addition, avian cranial neural crest cells express ephrin-B2 and migrate along pathways bordered by non-neural crest cells expressing EphB2. Thus, the distribution of avian Eph receptors and ephrins differs from those reported in other vertebrates. In stripe assays when explanted cranial neural crest were given the choice between FN or FN plus clustered ephrin-B1 or EphB2 fusion protein, the cells strongly localize to lanes containing only FN. This preference is mitigated in the presence of soluble ephrin-B1 or EphB2 fusion protein. Conclusion These findings show that avian cranial neural crest use Eph and ephrin receptors as other vertebrates in guiding migration. However, the Eph receptors are expressed in different combinations by neural crest destined for each branchial arch and ephrin-B1 and ephrin-B2 appear to have opposite roles to those reported to guide cranial neural crest migration in mice. Unlike many of the signalling, specification, and effector pathways of neural crest, the roles of Eph receptors and ephrins

  17. Expression of the tyrosine kinase receptor EphA5 and its ligand ephrin-A5 during mouse spinal cord development%酪氨酸激酶受体EphA5及其配体ephrin-A5在小鼠脊髓发育过程中的表达

    Institute of Scientific and Technical Information of China (English)

    Christopher P. WASHBURN; Margaret A. COOPER; 周仁平


    Objectives To study the expression patterns of two Eph family molecules, the receptor EphA5, and the ligand ephrin-A5, during spinal cord development. Methods The receptor expression was analyzed using beta-galactosidase knockin mice, and affinity ligand probe binding. The ligand expression was assessed using two different affinity probes, and knockout mouse tissues as controls. Results EphA5 was expressed in the ventral spinal cord, while ephrin-A5 was located in the dorsolateral regions of the spinal cord throughout development. Conclusions These results show that EphA5 and ephrin-A5 are expressed over broad developmental stages and may play important roles in establishing the dorsoventral organization of the spinal cord.%目的 研究两个Eph家族分子,EphA5受体及其配体ephrin-A5,在脊髓发育过程中的表达方式.方法 β-半乳糖苷酶基因敲入小鼠和配体亲和探针分析受体的表达,两种不同的亲和探针分析配体的表达,基因敲除小鼠作为对照.结果 在发育过程中,EphA5表达于脊髓腹侧,而eprin-A5表达于脊髓背侧.结论 EphA5和ephrin-A5在多个脊髓发育阶段都有表达,他们可能在脊髓背腹侧组织结构的建立过程中发挥重要作用.

  18. Transsynaptic EphB/Ephrin-B signaling regulates growth of presynaptic boutons required for classical conditioning. (United States)

    Li, Wei; Zheng, Zhaoqing; Keifer, Joyce


    Learning-related presynaptic remodeling has been documented in only a few systems, and its molecular mechanisms are largely unknown. Here we describe a role for the bidirectional EphB/ephrin-B signaling system in structural plasticity of presynaptic nerve terminals using an in vitro model of classical conditioning. Conditioning or BDNF application induced significant growth of auditory nerve presynaptic boutons that convey the conditioned stimulus to abducens motor neurons. Interestingly, bouton enlargement occurred only for those synapses apposed to motor neuron dendrites rather than to somata. Phosphorylation of ephrin-B1, but not EphB2, was induced by both conditioning and BDNF application and was inhibited by postsynaptic injections of ephrin-B antibody. Finally, suppression of postsynaptic ephrin-B function inhibited presynaptic bouton enlargement that was rescued by activation of EphB2 by ephrin-B1-Fc. These data provide evidence for ephrin-B-induced EphB2 forward signaling in presynaptic structural plasticity during classical conditioning. They also reveal a functional interaction between BDNF/TrkB and the Eph/ephrin signaling systems in the coordination of presynaptic and postsynaptic modifications during conditioning.

  19. ephrin ligands and Eph receptors show regionally restricted expression in the developing palate and tongue

    Directory of Open Access Journals (Sweden)

    Guilherme Machado Xavier


    Full Text Available The Eph family receptor-interacting (ephrin ligands and erythropoietin-producing hepatocellular carcinoma (Eph receptors constitute the largest known family of receptor tyrosine kinases. Ephrin ligands and their receptors form an important cell communication system with widespread roles in normal physiology and disease pathogenesis. In order to investigate potential roles of the ephrin-Eph system during palatogenesis and tongue development, we have characterized the cellular mRNA expression of family members EphrinA1-A3, EphA1–A8 and EphrinB2, EphB1, EphB4 during murine embryogenesis between embryonic day 13.5–16.5 using radioactive in situ hybridization. With the exception of EphA6 and ephrinA3, all genes were regionally expressed during the process of palatogenesis, with restricted and often overlapping domains. Transcripts were identified in the palate epithelium, localized at the tip of the palatal shelves, in the mesenchyme and also confined to the medial epithelium seam. Numerous Eph transcripts were also identified during tongue development. In particular, EphA1 and EphA2 demonstrated a highly restricted and specific expression in the tongue epithelium at all stages examined, whereas EphA3 was strongly expressed in the lateral tongue mesenchyme. These results suggest regulatory roles for ephrin-EphA signaling in development of the murine palate and tongue.

  20. Aberrant EphB/ephrin-B expression in experimental gastric lesions and tumor cells (United States)

    Uchiyama, Shintaro; Saeki, Noritaka; Ogawa, Kazushige


    AIM: To determine whether the expression profiles of EphB receptor and ephrin-B ligand can be used as markers for dysplastic/oncogenic transformation in gastric mucosa. METHODS: The protein expression and localization of EphB and ephrin-B in normal, ulcerated regenerating, and dysplastic gastric mucosa were examined in a rat experimental model by immunolabeling, and mRNA expression was assessed in four human gastric carcinoma cell lines by reverse transcription-polymerase chain reaction. RESULTS: Ephrin-B- and EphB-expressing regions were divided along the pit-gland axis in normal gastric units. EphB2 was transiently upregulated in the experimental ulcer, and its expression domain extended to gastric pits and/or the luminal surface where ephrin-B-expressing pit cells reside. EphB2, B3, and B4 and ephrin-B1 were coexpressed in the experimental gastric dysplasia, and more than one ligand-receptor pair was highly expressed in each of the gastric carcinoma cell lines. CONCLUSION: Robust and stable coexpression of EphB and ephrin-B is a feature common to experimentally induced gastric dysplasia and human gastric carcinoma cell lines as compared to normal gastric and ulcerated regenerating epithelia. Thus, EphB/ephrin-B may be a useful marker combination for dysplastic/oncogenic transformation in gastric cancer. PMID:25593460

  1. Advances of EphrinBs/EphBs signaling pathway in the nociceptive process%EphrinBs/EphBs信号通路与疼痛研究进展

    Institute of Scientific and Technical Information of China (English)

    姜黎珊; 郁丽娜; 严敏


    Background Ephs is the largest subfamily of receptor tyrosine kinases (RTKs) in the human genome,which binds to the ligand,Ephrins,to regulate many development processes,including tissue-border formation,re-angiogenesis,axon guidance,and synaptic plasticity.Recent studies indicate that EphrinBs/EphBs signaling regulates the nociceptive process.Objective Here we retrospectively summarized the mechanism of EphrinBs/EphBs signaling pathway in regulating the process of pain. Content A great deal of studies have shown that EphrinBs/EphBs signaling pathway modulates the development of nociceptive process through upregulating the excitability of nociceptive dorsal root ganglia and wide dynamic range neurons in spinal dorsal horn,producing central sensitization,and activating the downstream mitogen-activated protein kinase (MAPKs) pathway.Trend Clarifying the downstream mechanism of EphrinBs/EphBs signaling pathway in the nociceptive process will be helpful helpful to find a new potential target for the treatment of pain.%背景 Ephs受体是人类基因组中受体型酪氨酸蛋白激酶(receptor tyrosine kinase,RTKs)中最大的亚家族,与其配体Ephrins结合参与组织边缘形成、血管再生、轴突导向及突触可塑性等诸多生长发育过程.近年来研究发现EphrinBs/EphBs 信号系统参与调控了疼痛的发生和维持.目的 回顾和总结EphrinBs/EphBs调控疼痛的机制.内容 大量研究证明EphrinBs/EphBs信号系统的激活可能通过上调伤害性脊神经节和脊髓后角的广动力范围型神经元兴奋性,诱导中枢致敏,以及活化下游丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPKs)通路参与了伤害性信息的调制.趋向 明晰EphrinBs/EphBs信号系统参与疼痛过程的下游机制,有助于发现临床上治疗疼痛的新靶点.

  2. Vortex shedding in high Reynolds number axisymmetric bluff-body wakes: Local linear instability and global bleed control (United States)

    Sevilla, A.; Martínez-Bazán, C.


    In the present work we study the large-scale helical vortex shedding regime in the wake of an axisymmetric body with a blunt trailing edge at high Reynolds numbers, both experimentally and by means of local, linear, and spatiotemporal stability analysis. In the instability analysis we take into account the detailed downstream evolution of the basic flow behind the body base. The study confirms the existence of a finite region of absolute instability for the first azimuthal number in the near field of the wake. Such instability is believed to trigger the large-scale helical vortex shedding downstream of the recirculating zone. Inhibition of vortex shedding is examined by blowing a given flow rate of fluid through the base of the slender body. The extent of the locally absolute region of the flow is calculated as a function of the bleed coefficient, Cb=qb/(πR2u∞), where qb is the bleed flow rate, R is the radius of the base, and u∞ is the incident free-stream velocity. It is shown that the basic flow becomes convectively unstable everywhere for a critical value of the bleed coefficient of Cb*˜0.13, such that no self-excited regime is expected for Cb>Cb*. In addition, we report experimental results of flow visualizations and hot-wire measurements for increasing values of the bleed coefficient. When a sufficient amount of base bleed is applied, flow visualizations indicate that vortex shedding is suppressed and that the mean flow becomes axisymmetric. The critical bleed coefficient predicted by linear instability analysis is shown to fall within the experimental values in the range of Reynolds numbers analyzed here.

  3. Middle East respiratory syndrome coronavirus (MERS-CoV viral shedding in the respiratory tract: an observational analysis with infection control implications

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    Ziad A. Memish


    Conclusions: Contacts cleared MERS-CoV earlier than ill patients. This finding could be related to the types of sample as well as the types of patient studied. More ill patients with significant comorbidities shed the virus for a significantly longer time. The results of this study could have critical implications for infection control guidance and its application in healthcare facilities handling positive cases.

  4. Lithocholic acid is an Eph-ephrin ligand interfering with Eph-kinase activation.

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    Carmine Giorgio

    Full Text Available Eph-ephrin system plays a central role in a large variety of human cancers. In fact, alterated expression and/or de-regulated function of Eph-ephrin system promotes tumorigenesis and development of a more aggressive and metastatic tumour phenotype. In particular EphA2 upregulation is correlated with tumour stage and progression and the expression of EphA2 in non-transformed cells induces malignant transformation and confers tumorigenic potential. Based on these evidences our aim was to identify small molecules able to modulate EphA2-ephrinA1 activity through an ELISA-based binding screening. We identified lithocholic acid (LCA as a competitive and reversible ligand inhibiting EphA2-ephrinA1 interaction (Ki =  49 µM. Since each ephrin binds many Eph receptors, also LCA does not discriminate between different Eph-ephrin binding suggesting an interaction with a highly conserved region of Eph receptor family. Structurally related bile acids neither inhibited Eph-ephrin binding nor affected Eph phosphorylation. Conversely, LCA inhibited EphA2 phosphorylation induced by ephrinA1-Fc in PC3 and HT29 human prostate and colon adenocarcinoma cell lines (IC(50  = 48 and 66 µM, respectively without affecting cell viability or other receptor tyrosine-kinase (EGFR, VEGFR, IGFR1β, IRKβ activity. LCA did not inhibit the enzymatic kinase activity of EphA2 at 100 µM (LANCE method confirming to target the Eph-ephrin protein-protein interaction. Finally, LCA inhibited cell rounding and retraction induced by EphA2 activation in PC3 cells. In conclusion, our findings identified a hit compound useful for the development of molecules targeting ephrin system. Moreover, as ephrin signalling is a key player in the intestinal cell renewal, our work could provide an interesting starting point for further investigations about the role of LCA in the intestinal homeostasis.

  5. Optimal load shedding and restoration (United States)

    Xu, Ding

    Load shedding is an emergency control action in power systems that can save systems from a wide-area blackout. Underfrequency load shedding, steady state load shedding, and voltage load shedding are widely used in power systems. These methods utilize either the steady state model or a simplified dynamic model to represent a power systems. In this dissertation, a general optimal load shedding method that considers both the dynamic process and load distribution is proposed. The unfavorable load shedding is then formulated as an optimization problem with the objective function of cost minimization. This objective function is subjected to system, security, and operation constraints. The entire problem becomes a question of optimization with differential and nonlinear equations as constraints. To solve this problem, discretization is used to change the differential equations into algebraic equations. The original problem is thus reformulated as an optimization problem and can be solved by a standard mathematical program. The general idea is then applied to traditional power systems, deregulated power systems, power systems with distributed generation, and load restoration. In the traditional power system, the method shows that governor action, generation dynamic, disturbance location, and economic factors can be taken into consideration. In the deregulated power system, two power market models are developed and incorporated into the load shedding scheme. In power systems with multiple distributed generations, the different cases of disturbances are analyzed and models of different distributed generation developed. The general idea is then applied. Finally, the load restoration problem is studied, and it is proposed that an optimization method be applied to it. This dissertation provides a comprehensive solution for load shedding problem in power systems. The models developed in this research can also be used to study other power system problems.

  6. Erythropoietin promotes bone formation through EphrinB2/EphB4 signaling. (United States)

    Li, C; Shi, C; Kim, J; Chen, Y; Ni, S; Jiang, L; Zheng, C; Li, D; Hou, J; Taichman, R S; Sun, H


    Recent studies have demonstrated that erythropoietin (EPO) has extensive nonhematopoietic biological functions. However, little is known about how EPO regulates bone formation, although several studies suggested that EPO can affect bone homeostasis. In this study, we investigated the effects of EPO on the communication between osteoclasts and osteoblasts through the ephrinB2/EphB4 signaling pathway. We found that EPO slightly promotes osteoblastic differentiation with the increased expression of EphB4 in ST2 cells. However, EPO increased the expression of Nfatc1 and ephrinB2 but decreased the expression of Mmp9 in RAW264.7 cells, resulting in an increase of ephrinB2-expressing osteoclasts and a decrease in resorption activity. The stimulation of ephrinB2/EphB4 signaling via ephrinB2-Fc significantly promoted EPO-mediated osteoblastic differentiation in ST2 cells. EphB4 knockdown through EphB4 shRNA inhibited EPO-mediated osteoblastic phenotypes. Furthermore, in vivo assays clearly demonstrated that EPO efficiently induces new bone formation in the alveolar bone regeneration model. Taken together, these results suggest that ephrinB2/EphB4 signaling may play an important role in EPO-mediated bone formation.

  7. A Voltage Instability-Avoidable Control Method for Load Shedding%一种防止电压失稳的切负荷控制方法

    Institute of Scientific and Technical Information of China (English)

    李鹏; 郝治国; 张保会; 舒进; 薄志谦


    Based on the two-node equivalent model of power network and voltage instability index, the control scheme for load shedding, which takes the prevention of voltage instability into account, is researched. The equivalent load model is used to calculate the sensibility of voltage instability index to load; the position to shed the load is chosen by comprehensively considering the control ability and effectiveness of load node; taking the voltage stability margin as objective, the amount of the load to be shed is calculated;finally, on this basis a scheme for centralized load shedding control system is constructed, and cooperating with the monitoring of voltage instability reasonable control measures are drawn up to prevent voltage instability. Simulation results of typical power system show that the proposed scheme can effectively head off the voltage deterioration of power system,keep voltage stability margin and voltage level of power system. The algorithm of the proposed load shedding control algorithm is simple and adaptable.%从电力网络2节点等值模型及电压不稳定指标出发研究防止电压失稳的切负荷控制方案.利用节点等值模型计算电压不稳定指标对负荷的灵敏度;综合考虑负荷节点控制能力及有效性来选择切负荷地点;并以保持电压稳定裕度为目标来计算切负荷量;最后基于此构建了集中式优化切负荷控制系统方案,与电压不稳定监视功能相配合,制定合理的控制措施,防止电压失稳.基于典型系统的仿真结果表明该方案能有效地阻止系统电压持续恶化,维持系统电压稳定裕度及电压水平.所提算法简单,有很好的适应性.

  8. Effect of HSV-2 Suppressive Therapy on Genital Tract HIV-1 RNA Shedding among Women on HAART: A Pilot Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    A. E. Nijhawan


    Full Text Available Background. The role of suppressive HSV therapy in women coinfected with HSV-2 and HIV-1 taking highly active antiretroviral therapy (HAART is unclear. Methods. 60 women with HIV-1/HSV-2 coinfection on HAART with plasma HIV-1 viral load (PVL ≤75 copies/mL were randomized to receive acyclovir (N=30 or no acyclovir (N=30. PVL, genital tract (GT HIV-1, and GT HSV were measured every 4 weeks for one year. Results. Detection of GT HIV-1 was not significantly different in the two arms (OR 1.23, P=0.67, although this pilot study was underpowered to detect this difference. When PVL was undetectable, the odds of detecting GT HIV were 0.4 times smaller in the acyclovir arm than in the control arm, though this was not statistically significant (P=0.07. The odds of detecting GT HSV DNA in women receiving acyclovir were significantly lower than in women in the control group, OR 0.38, P<0.05. Conclusions. Chronic suppressive therapy with acyclovir in HIV-1/HSV-2-positive women on HAART significantly reduces asymptomatic GT HSV shedding, though not GT HIV shedding or PVL. PVL was strongly associated with GT HIV shedding, reinforcing the importance of HAART in decreasing HIV sexual transmission.

  9. The SHED-IT community trial study protocol: a randomised controlled trial of weight loss programs for overweight and obese men

    Directory of Open Access Journals (Sweden)

    Young Myles D


    Full Text Available Abstract Background Obesity is a major cause of preventable death in Australia with prevalence increasing at an alarming rate. Of particular concern is that approximately 68% of men are overweight/obese, yet are notoriously difficult to engage in weight loss programs, despite being more susceptible than women to adverse weight-related outcomes. There is a need to develop and evaluate obesity treatment programs that target and appeal to men. The primary aim of this study is to evaluate the efficacy of two relatively low intensity weight loss programs developed specifically for men. Methods and Design The study design is an assessor blinded, parallel-group randomised controlled trial that recruited 159 overweight and obese men in Newcastle, Australia. Inclusion criteria included: BMI 25-40 (kg/m2; no participation in other weight loss programs during the study; pass a health-screening questionnaire and pre-exercise risk assessment; available for assessment sessions; access to a computer with e-mail and Internet facilities; and own a mobile phone. Men were recruited to the SHED-IT (Self-Help, Exercise and Diet using Internet Technology study via the media and emails sent to male dominated workplaces. Men were stratified by BMI category (overweight, obese class I, obese class II and randomised to one of three groups: (1 SHED-IT Resources - provision of materials (DVD, handbooks, pedometer, tape measure with embedded behaviour change strategies to support weight loss; (2 SHED-IT Online - same materials as SHED-IT Resources plus access to and instruction on how to use the study website; (3 Wait-list Control. The intervention programs are three months long with outcome measures taken by assessors blinded to group allocation at baseline, and 3- and 6-months post baseline. Outcome measures include: weight (primary outcome, % body fat, waist circumference, blood pressure, resting heart rate, objectively measured physical activity, self-reported dietary

  10. Receptor-binding domain of ephrin-A1: production in bacterial expression system and activity. (United States)

    Nekrasova, O V; Sharonov, G V; Tikhonov, R V; Kolosov, P M; Astapova, M V; Yakimov, S A; Tagvey, A I; Korchagina, A A; Bocharova, O V; Wulfson, A N; Feofanov, A V; Kirpichnikov, M P


    Eph receptor tyrosine kinases and their ligands, the ephrins, perform an important regulatory function in tissue organization, as well as participate in malignant transformation of cells. Ephrin-A1, a ligand of A class Eph receptors, is a modulator of tumor growth and progression, and the mechanism of its action needs detailed investigation. Here we report on the development of a system for bacterial expression of an ephrin-A1 receptor-binding domain (eA1), a procedure for its purification, and its renaturation with final yield of 50 mg/liter of culture. Functional activity of eA1 was confirmed by immunoblotting, laser scanning confocal microscopy, and flow cytometry. It is shown that monomeric non-glycosylated receptor-binding domain of ephrin-A1 is able to activate cellular EphA2 receptors, stimulating their phosphorylation. Ligand eA1 can be used to study the features of ephrin-A1 interactions with different A class Eph receptors. The created expression cassette is suitable for the development of ligands with increased activity and selectivity and experimental systems for the delivery of cytotoxins into tumor cells that overexpress EphA2 or other class A Eph receptors.

  11. Berberine inhibits the proliferation and migration of breast cancer ZR-75-30 cells by targeting Ephrin-B2. (United States)

    Ma, Weina; Zhu, Man; Zhang, Dongdong; Yang, Liu; Yang, Tianfeng; Li, Xin; Zhang, Yanmin


    Berberine, a plant-derived compound isolated from Coptis chinensis used in traditional Chinese medicine, has been shown to possess anti-cancer properties. However, no study has shown that berberine could target ephrin-B2, which plays a critical role in cell proliferation and migration. The aim of this study is to investigate the effect of berberine on cancer cell growth and migration, through the regulation of ephrin-B2 and downstream signaling molecules. In this study, a high ephrin-B2-expressing cell membrane chromatography method was developed to investigate 48 crude extracts from traditional Chinese medicine that could act on ephrin-B2. Cell proliferative and wound-healing assays were used to study the effect of berberine on cancer cell growth and migration. The mechanism of berberine was investigated using western blot. Berberine was isolated from C. chinensis extracts and showed activity on the HEK293/ephrin-B2 cell membrane chromatography column. Berberine showed a greater inhibitory effect in high-expressing ephrin-B2 cells (HEK293/ephrin-B2 cells) than in normal HEK293 cells, and decreased the expression of ephrin-B2 and its PDZ binding proteins, which indicates that ephrin-B2 is a target of berberine. Furthermore, berberine downregulates the phosphorylation of VEGFR2 and downstream signaling members (AKT and Erk1/2), which in turn downregulates the expression of MMP2 and MMP9. The above data confirm the inhibitory effects of berberine on ZR-75-30 cell proliferation and cell migration. Overall, our studies demonstrate that berberine inhibits cell growth and migration by targeting ephrin-B2. Copyright © 2016 Elsevier GmbH. All rights reserved.

  12. EphB–ephrin-B2 interactions are required for thymus migration during organogenesis (United States)

    Foster, Katie E.; Gordon, Julie; Cardenas, Kim; Veiga-Fernandes, Henrique; Makinen, Taija; Grigorieva, Elena; Wilkinson, David G.; Blackburn, C. Clare; Richie, Ellen; Manley, Nancy R.; Adams, Ralf H.; Kioussis, Dimitris; Coles, Mark C.


    Thymus organogenesis requires coordinated interactions of multiple cell types, including neural crest (NC) cells, to orchestrate the formation, separation, and subsequent migration of the developing thymus from the third pharyngeal pouch to the thoracic cavity. The molecular mechanisms driving these processes are unclear; however, NC-derived mesenchyme has been shown to play an important role. Here, we show that, in the absence of ephrin-B2 expression on thymic NC-derived mesenchyme, the thymus remains in the cervical area instead of migrating into the thoracic cavity. Analysis of individual NC-derived thymic mesenchymal cells shows that, in the absence of ephrin-B2, their motility is impaired as a result of defective EphB receptor signaling. This implies a NC-derived cell-specific role of EphB–ephrin-B2 interactions in the collective migration of the thymic rudiment during organogenesis. PMID:20616004

  13. Dynamic Optimization for Vortex Shedding Suppression

    Directory of Open Access Journals (Sweden)

    Bonis Ioannis


    Full Text Available Flows around structures exhibiting vortex shedding induce vibrations that can potentially damage the structure. A way to avoid it is to suppress vortex shedding by controlling the wake. Wake control of laminar flow behind a rotating cylinder is formulated herein as a dynamic optimization problem. Angular cylinder speed is the manipulated variable that is adjusted to suppress vortex shedding by minimizing lift coefficient variation. The optimal angular speed is assumed to be periodic like wake formation. The control problem is solved for different time horizons tH. The impact of tH to control is evaluated and the need for feedback is assessed.

  14. Ephrin-B reverse signaling induces expression of wound healing associated genes in IEC-6 intestinal epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Christian Hafner; Stefanie Meyer; Ilja Hagen; Bernd Becker; Alexander Roesch; Michael Landthaler; Thomas Vogt


    AIM: Eph receptors and ephrin ligands play a pivotal role in development and tissue maintenance. Since previous data have indicated an involvement of ephrin-B2 in epithelial healing, we investigated the gene expression and downstream signaling pathways induced by ephrin-B mediated cell-cell signaling in intestinal epithelial cells.METHODS: Upon stimulation of ephrin-B pathways in IFC-6 cells with recombinant rat EphB1-Fc, gene expression was analyzed by Affymetrix(R) rat genome 230 high density arrays at different time points. Differentially expressed genes were confirmed by real-time RT-PCR. In addition, MAP kinase pathways and focal adhesion kinase (FAK) activation downstream of ephrin-B were investigated by immunoblotting and fluorescence microscopy.RESULTS: Stimulation of the ephrin-B reverse signaling pathway in IEC-6 cells induces predominant expression of genes known to be involved into wound healing/cell migration, antiapoptotic pathways, host defense and inflammation. Cox-2, c-Fos, Egr-1, Egr-2, and MCP-1 were found among the most significantly regulated genes.Furthermore, we show that the expression of repairrelated genes is also accompanied by activation of the ERK1/2 MAP kinase pathway and FAK, two key regulators of epithelial restitution.CONCLUSION: Stimulation of the ephrin-B reverse signaling pathway induces a phenotype characterized by upregulation of repair-related genes, which may partially be mediated by ERK1/2 pathways.

  15. Expression of S100A4, ephrin-A1 and osteopontin in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Rud Ane


    Full Text Available Abstract Background The metastasis-promoting protein S100A4 induces expression of ephrin-A1 and osteopontin in osteosarcoma cell lines. The aim of this study was to investigate S100A4-mediated stimulation of ephrin-A1 and osteopontin in non-small cell lung cancer (NSCLC cell lines, and to characterize the expression of these biomarkers in primary tumor tissue from NSCLC patients. Methods Four NSCLC cell lines were treated with extracellular S100A4, and ephrin-A1 and osteopontin expression was analyzed by real time RT-PCR and Western blotting. Immunohistochemical staining for S100A4, ephrin-A1 and osteopontin was performed on tissue microarrays containing primary tumor samples from a cohort of 217 prospectively recruited NSCLC patients, and associations with clinicopathological parameters were investigated. Results S100A4 induced ephrin-A1 mRNA and protein expression in adenocarcinoma, but not in squamous carcinoma cell lines, whereas the level of osteopontin was unaffected by S100A4 treatment. In primary tumors, moderate or strong immunoreactivity was observed in 57% of cases for cytoplasmic S100A4, 46% for nuclear S100A4, 86% for ephrin-A1 and 77% for osteopontin. Interestingly, S100A4 expression was associated with ephrin-A1 also in vivo, but there was no association between S100A4 and osteopontin. Expression levels of S100A4 and ephrin-A1 were significantly higher in adenocarcinomas compared to other histological subtypes, and S100A4-positive tumors were smaller and more differentiated than tumors without expression. Conclusions Our findings suggest that S100A4, ephrin-A1 and osteopontin are involved in the biology of NSCLC, and further investigation of their potential use as biomarkers in NSCLC is warranted.

  16. Eph/ephrin-B-mediated cell-to-cell interactions govern MTS20(+) thymic epithelial cell development. (United States)

    Montero-Herradón, Sara; García-Ceca, Javier; Sánchez Del Collado, Beatriz; Alfaro, David; Zapata, Agustín G


    Thymus development is a complex process in which cell-to-cell interactions between thymocytes and thymic epithelial cells (TECs) are essential to allow a proper maturation of both thymic cell components. Although signals that control thymocyte development are well known, mechanisms governing TEC maturation are poorly understood, especially those that regulate the maturation of immature TEC populations during early fetal thymus development. In this study, we show that EphB2-deficient, EphB2LacZ and EphB3-deficient fetal thymuses present a lower number of cells and delayed maturation of DN cell subsets compared to WT values. Moreover, deficits in the production of chemokines, known to be involved in the lymphoid seeding into the thymus, contribute in decreased proportions of intrathymic T cell progenitors (PIRA/B(+)) in the mutant thymuses from early stages of development. These features correlate with increased proportions of MTS20(+) cells but fewer MTS20(-) cells from E13.5 onward in the deficient thymuses, suggesting a delayed development of the first epithelial cells. In addition, in vitro the lack of thymocytes or the blockade of Eph/ephrin-B-mediated cell-to-cell interactions between either thymocytes-TECs or TECs-TECs in E13.5 fetal thymic lobes coursed with increased proportions of MTS20(+) TECs. This confirms, for the first time, that the presence of CD45(+) cells, corresponding at these stages to DN1 and DN2 cells, and Eph/ephrin-B-mediated heterotypic or homotypic cell interactions between thymocytes and TECs, or between TECs and themselves, contribute to the early maturation of MTS20(+) TECs.

  17. Shedding of cell membrane-bound proteoglycans. (United States)

    Nam, Eon Jeong; Park, Pyong Woo


    Membrane-bound proteoglycans function primarily as coreceptors for many glycosaminoglycan (GAG)-binding ligands at the cell surface. The majority of membrane-bound proteoglycans can also function as soluble autocrine or paracrine effectors as their extracellular domains, replete with all GAG chains, are enzymatically cleaved and released from the cell surface by ectodomain shedding. In particular, the ectodomain shedding of syndecans, a major family of cell surface heparan sulfate proteoglycans, is an important posttranslational mechanism that modulates diverse pathophysiological processes. Syndecan shedding is a tightly controlled process that regulates the onset, progression, and resolution of various infectious and noninfectious inflammatory diseases. This review describes methods to induce and measure the shedding of cell membrane-bound proteoglycans, focusing on syndecan shedding as a prototypic example.

  18. Ephrin-A3 promotes and maintains slow muscle fiber identity during postnatal development and reinnervation. (United States)

    Stark, Danny A; Coffey, Nathan J; Pancoast, Hannah R; Arnold, Laura L; Walker, J Peyton D; Vallée, Joanne; Robitaille, Richard; Garcia, Michael L; Cornelison, D D W


    Each adult mammalian skeletal muscle has a unique complement of fast and slow myofibers, reflecting patterns established during development and reinforced via their innervation by fast and slow motor neurons. Existing data support a model of postnatal "matching" whereby predetermined myofiber type identity promotes pruning of inappropriate motor axons, but no molecular mechanism has yet been identified. We present evidence that fiber type-specific repulsive interactions inhibit innervation of slow myofibers by fast motor axons during both postnatal maturation of the neuromuscular junction and myofiber reinnervation after injury. The repulsive guidance ligand ephrin-A3 is expressed only on slow myofibers, whereas its candidate receptor, EphA8, localizes exclusively to fast motor endplates. Adult mice lacking ephrin-A3 have dramatically fewer slow myofibers in fast and mixed muscles, and misexpression of ephrin-A3 on fast myofibers followed by denervation/reinnervation promotes their respecification to a slow phenotype. We therefore conclude that Eph/ephrin interactions guide the fiber type specificity of neuromuscular interactions during development and adult life.

  19. Axo-Glia Interaction Preceding CNS Myelination Is Regulated by Bidirectional Eph-Ephrin Signaling

    Directory of Open Access Journals (Sweden)

    Cecilie Linneberg


    Full Text Available In the central nervous system, myelination of axons is required to ensure fast saltatory conduction and for survival of neurons. However, not all axons are myelinated, and the molecular mechanisms involved in guiding the oligodendrocyte processes toward the axons to be myelinated are not well understood. Only a few negative or positive guidance clues that are involved in regulating axo-glia interaction prior to myelination have been identified. One example is laminin, known to be required for early axo-glia interaction, which functions through α6β1 integrin. Here, we identify the Eph-ephrin family of guidance receptors as novel regulators of the initial axo-glia interaction, preceding myelination. We demonstrate that so-called forward and reverse signaling, mediated by members of both Eph and ephrin subfamilies, has distinct and opposing effects on processes extension and myelin sheet formation. EphA forward signaling inhibits oligodendrocyte process extension and myelin sheet formation, and blocking of bidirectional signaling through this receptor enhances myelination. Similarly, EphB forward signaling also reduces myelin membrane formation, but in contrast to EphA forward signaling, this occurs in an integrin-dependent manner, which can be reversed by overexpression of a constitutive active β1-integrin. Furthermore, ephrin-B reverse signaling induced by EphA4 or EphB1 enhances myelin sheet formation. Combined, this suggests that the Eph-ephrin receptors are important mediators of bidirectional signaling between axons and oligodendrocytes. It further implies that balancing Eph-ephrin forward and reverse signaling is important in the selection process of axons to be myelinated.

  20. Ephrin-A1-mediated dopaminergic neurogenesis and angiogenesis in a rat model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Xuefeng Jing

    Full Text Available Cells of the neural stem cell lineage in the adult subventricular zone (SVZ respond to brain insult by increasing their numbers and migrating through the rostral migratory stream. However, in most areas of the brain other than the SVZ and the subgranular zone of the dentate gyrus, such a regenerative response is extremely weak. Even these two neurogenic regions do not show extensive regenerative responses to repair tissue damage, suggesting the presence of an intrinsic inhibitory microenvironment (niche for stem cells. In the present study, we assessed the effects of injection of clustered ephrin-A1-Fc into the lateral ventricle of rats with unilateral nigrostriatal dopamine depletion. Ephrin-A1-Fc clustered by anti-IgG(Fc antibody was injected stereotaxically into the ipsilateral lateral ventricle of rats with unilateral nigrostriatal lesions induced by 6-hydroxydopamine, and histologic analysis and behavioral tests were performed. Clustered ephrin-A1-Fc transformed the subventricular niche, increasing bromodeoxyuridine-positive cells in the subventricular area, and the cells then migrated to the striatum and differentiated to dopaminergic neurons and astrocytes. In addition, clustered ephrin-A1-Fc enhanced angiogenesis in the striatum on the injected side. Along with histologic improvements, behavioral derangement improved dramatically. These findings indicate that the subventricular niche possesses a mechanism for regulating both stem cell and angiogenic responses via an EphA-mediated signal. We conclude that activation of EphA receptor-mediated signaling by clustered ephrin-A1-Fc from within the lateral ventricle could potentially be utilized in the treatment of neurodegenerative diseases such as Parkinson's disease.

  1. Repetitive grooming and sensorimotor abnormalities in an ephrin-A knockout model for Autism Spectrum Disorders. (United States)

    Wurzman, Rachel; Forcelli, Patrick A; Griffey, Christopher J; Kromer, Lawrence F


    EphA receptors and ephrin-A ligands play important roles in neural development and synaptic plasticity in brain regions where expression persists into adulthood. Recently, EPHA3 and EPHA7 gene mutations were linked with Autism Spectrum Disorders (ASDs) and developmental neurological delays, respectively. Furthermore, deletions of ephrin-A2 or ephrin-A3, which exhibit high binding affinity for EphA3 and EphA7 receptors, are associated with subtle deficits in learning and memory behavior and abnormalities in dendritic spine morphology in the cortex and hippocampus in mice. To better characterize a potential role for these ligands in ASDs, we performed a comprehensive behavioral characterization of anxiety-like, sensorimotor, learning, and social behaviors in ephrin-A2/-A3 double knockout (DKO) mice. The predominant phenotype in DKO mice was repetitive and self-injurious grooming behaviors such as have been associated with corticostriatal circuit abnormalities in other rodent models of neuropsychiatric disorders. Consistent with ASDs specifically, DKO mice exhibited decreased preference for social interaction in the social approach assay, decreased locomotor activity in the open field, increased prepulse inhibition of acoustic startle, and a shift towards self-directed activity (e.g., grooming) in novel environments, such as marble burying. Although there were no gross deficits in cognitive assays, subtle differences in performance on fear conditioning and in the Morris water maze resembled traits observed in other rodent models of ASD. We therefore conclude that ephrin-A2/-A3 DKO mice have utility as a novel ASD model with an emphasis on sensory abnormalities and restricted, repetitive behavioral symptoms.

  2. Dissecting the roles of Ephrin-A3 in malignant peripheral nerve sheath tumor by TALENs. (United States)

    Wang, Zhengguang; Liu, Zhendong; Liu, Bo; Liu, Gengyan; Wu, Song


    Malignant peripheral nerve sheath tumor (MPNST) is a rare and aggressive soft tissue sarcoma for which effective treatments have not yet been established due to poor understanding of its pathogenesis. Our previous study indicated that miR-210-mediated Ephrin-A3 (EFNA3) promotion of proliferation and invasion of MPNST cells plays an important role in MPNST tumorigenesis and progression. The purpose of the present study was to further investigate the roles of EFNA3 in MPNST. Constructed transcription activator-like effector nucleases (TALENs) and lentiviral vectors were transfected into MPNST ST88-14 (NF1 wild-type) and sNF96.2 (NF1 mutant type) cell lines to obtain gain- and loss-of-function cell lines for the EFNA3 function study. The results showed that the knockout of ENFA3 increased cellular viability and invasiveness of the MPNST cells. However, the adhesion ability of MPNST cells was enhanced or inhibited when EFNA3 was overexpressed or knocked out, respectively. It was also observed that knockout of EFNA3 significantly decreased the expression of phosphorylated FAK (p-FAK) and the tumor necrosis factor α (TNF-α) compared to that in the control cells, yet the expression of phosphatidylinositol 3-kinase (PI3K), GTPase, integrins, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1α (HIF-α) increased significantly. Inversely, overexpression of EFNA3 significantly increased the expression of p-FAK and TNF-α compared to that in the control cells, yet the expression of PI3K, GTPase, integrins, VEGF and HIF-α decreased significantly. The results indicated that EFNA3 serves as a tumor suppressor in MPNST cells and it may play a critical role in the focal adhesion kinase (FAK) signaling and VEGF-associated tumor angiogenesis pathway. These findings may not only facilitate the better understanding of MPNST pathogenesis, but also suggest EFNA3 as a promising target for MPNST treatment.

  3. Adaptive load shedding and regional protection

    Energy Technology Data Exchange (ETDEWEB)

    Ford, J.J.; Ledwich, G. [School of Engineering Systems, Queensland University of Technology, Brisbane, Qld 4001 (Australia); Bevrani, H. [Department of Electrical and Computer Engineering, University of Kurdistan Sanandaj, Kurdistan (Iran)


    The requirement for improved efficiency whilst maintaining system security necessitates the development of improved system analysis approaches and the development of advanced emergency control technologies. Load shedding is a type of emergency control that is designed to ensure system stability by curtailing system load to match generation supply. This paper presents a new adaptive load shedding scheme that provides emergency protection against excess frequency decline, whilst minimizing the risk of line overloading. The proposed load shedding scheme uses the local frequency rate information to adapt the load shedding behaviour to suit the size and location of the experienced disturbance. The proposed scheme is tested in simulation on a 3-region, 10-generator sample system and shows good performance. (author)

  4. Tumor necrosis factor (TNF) receptor shedding controls thresholds of innate immune activation that balance opposing TNF functions in infectious and inflammatory diseases

    DEFF Research Database (Denmark)

    Xanthoulea, Sofia; Pasparakis, Manolis; Kousteni, Stavroula


    ensues at the cost of disbalanced inflammatory reactions that lead to pathology. Mutant mice exhibit spontaneous hepatitis, enhanced susceptibility to endotoxic shock, exacerbated TNF-dependent arthritis, and experimental autoimmune encephalomyelitis. These results introduce a new concept for receptor...... shedding as a mechanism setting up thresholds of cytokine function to balance resistance and susceptibility to disease. Assessment of p55TNFR shedding may thus be of prognostic value in infectious, inflammatory, and autoimmune diseases....

  5. Study on the intelligent control system of the black fungus in the shed%棚栽黑木耳智能控制系统的研究

    Institute of Scientific and Technical Information of China (English)

    陈庆文; 纪彬; 周丽丽


    Using the sensor technology, SCM and PLC technology, ventilation, shading, spray cleaning method, the design is suitable in greenhouse cultivation of Auricularia auricula intelligent control system, the system can be in inside and outside greenhouse environmental parameters monitoring and experimental sunshade, side roller, spray, water curtain, ventilation in a variety of ways to ensure that shed environment suitable for black fungus growth process requirements.%利用传感技术、单片机和 PLC 技术,以通风、遮阳、喷淋等方式,设计适用于棚栽黑木耳的智能控制系统,本系统可对大棚内外环境、参数进行监测,采用遮阳、侧卷帘、外喷淋、水帘、通风等多种方式确保棚内环境适于黑木耳生长。

  6. Expression of EphB4 and EphrinB2 in retinoblastoma and their significance%视网膜母细胞瘤中EphB4和EphrinB2的表达及意义

    Institute of Scientific and Technical Information of China (English)

    耿祥娥; 赵玉斌; 张少华; 吕杰; 徐治伟; 王金清


    目的 探讨EphB4和EphrinB2的蛋白在视网膜母细胞瘤中的表达及其意义.方法 应用免疫组织化学SP法测定10例正常视网膜组织和40例视网膜母细胞瘤标本中EphB4和EphrinB2的表达水平,分析其与性别、临床分期、分化程度和视神经浸润的关系.结果(1)EphB4和EphrinB2蛋白表达的阳性率,在正常视网膜组织中分别为5%和2.5%,40例视网膜母细胞瘤标本中分别为77.5%和67.5%.EphB4和EphrinB2在视网膜母细胞瘤组织中的阳性率与显著高于正常视网膜组织中的阳性率(P<0.05).(2)EphB4和EphrinB2的蛋白在视网膜母细胞瘤的阳性表达率与肿瘤组织的临床分期、分化程度及视神经浸润显著相关(P<0.05).(3)EphB4和EphrinB2的蛋白在视网膜母细胞瘤组织中的阳性表达显著相关(P<0.05).结论 EphB4和EphrinB2可能在视网膜母细胞瘤的发生和发展过程中起重要作用,可作为评价视网膜母细胞瘤的浸润及预后的标志物.%Objective To investigate the protein expressions of EphB4 and EphrinB2 in retinoblastoma and to study their significance.Methods The expression of EphB4 and EphrinB2 was examined immunohistochemistrically by SP method in tissues of 10 normal retina and 40 patients with retinoblastoma and to study their relationship with gender,clinical stage,differentiation and optic nerve infiltration.Results 1.The protein expression of EphB4 and EphrinB2 observed in the normal tissues of retina was 5% and 2.5% respectively.In the 40 retinoblastoma cases,the positive rate of them was 77.5% and 67.5% respectively.The positive rate of EphB4 and EphrinB2 in retinoblastoma was higher than that in the normal retina(P<0.05).2.The positive expression of EphB4 and EphrinB2 protein were associated with clinical stage,differentiation and optic nerve infiltration(P<0.05).3.The positive expression of EphB4 and EphrinB2 protein in retinoblastoma was positively correlated(P<0.05).Conclusions Eph

  7. Regional Regulation of Purkinje Cell Dendritic Spines by Integrins and Eph/Ephrins. (United States)

    Heintz, Tristan G; Eva, Richard; Fawcett, James W


    Climbing fibres and parallel fibres compete for dendritic space on Purkinje cells in the cerebellum. Normally, climbing fibres populate the proximal dendrites, where they suppress the multiple small spines typical of parallel fibres, leading to their replacement by the few large spines that contact climbing fibres. Previous work has shown that ephrins acting via EphA4 are a signal for this change in spine type and density. We have used an in vitro culture model in which to investigate the ephrin effect on Purkinje cell dendritic spines and the role of integrins in these changes. We found that integrins α3, α5 and β4 are present in many of the dendritic spines of cultured Purkinje cells. pFAK, the main downstream signalling molecule from integrins, has a similar distribution, although the intenstity of pFAK staining and the percentage of pFAK+ spines was consistently higher in the proximal dendrites. Activating integrins with Mg2+ led to an increase in the intensity of pFAK staining and an increase in the proportion of pFAK+ spines in both the proximal and distal dendrites, but no change in spine length, density or morphology. Blocking integrin binding with an RGD-containing peptide led to a reduction in spine length, with more stubby spines on both proximal and distal dendrites. Treatment of the cultures with ephrinA3-Fc chimera suppressed dendritic spines specifically on the proximal dendrites and there was also a decrease of pFAK in spines on this domain. This effect was blocked by simultaneous activation of integrins with Mn2+. We conclude that Eph/ephrin signaling regulates proximal dendritic spines in Purkinje cells by inactivating integrin downstream signalling.

  8. Erythropoietin Promotes Bone Formation through EphrinB2/EphB4 Signaling


    Li, C; Shi, C.; Kim, J; Chen, Y.; Ni, S.; Jiang, L.; Zheng, C.; Li, D; J. Hou; Taichman, R. S.; Sun, H


    Recent studies have demonstrated that erythropoietin (EPO) has extensive nonhematopoietic biological functions. However, little is known about how EPO regulates bone formation, although several studies suggested that EPO can affect bone homeostasis. In this study, we investigated the effects of EPO on the communication between osteoclasts and osteoblasts through the ephrinB2/EphB4 signaling pathway. We found that EPO slightly promotes osteoblastic differentiation with the increased expression...

  9. Eph–ephrin bidirectional signalling: A promising approach for osteoporosis treatment

    Directory of Open Access Journals (Sweden)

    Wu Liang


    Full Text Available Osteoporosis is a common disease characterised by low bone density and brittle bone due to osteoblast–osteoclast uncoupling. The cellular and molecular mechanisms responsible for osteoblast–osteoclast coupling lead to the identification of novel therapeutic targets. The increasing evidence for a role for Eph–ephrin signalling in biological processes, including cell–cell interactions, cell morphology, cell migration, angiogenesis, cancer and bone homeostasis, identifies new molecular pathways and potentially novel therapeutic targets for the treatment of diseases. Recent studies suggest that the interactions between Eph and ephrin play critical roles in bone cell differentiation and patterning by exerting dimorphic effects on osteoblast and osteoclast differentiation, resulting in the intriguing coupling of bone resorption and bone formation. These findings suggest that interventions targeting osteoblast–osteoclast coupling by the regulation of the Eph–ephrin bidirectional signalling according to its biological effects, which results in inhibiting osteoclastic resorption and promoting osteoblastic formation, may be a promising approach for osteoporosis prevention and treatment in the near future.

  10. A novel, potent, and specific ephrinA1-based cytotoxin against EphA2 receptor expressing tumor cells. (United States)

    Wykosky, Jill; Gibo, Denise M; Debinski, Waldemar


    We have previously shown that the EphA2 receptor tyrosine kinase is overexpressed in glioblastoma multiforme (GBM) and represents a novel, attractive therapeutic target for the treatment of brain tumors. Here, we have developed an EphA2-targeted agent, ephrinA1-PE38QQR, a novel cytotoxin composed of ephrinA1, a ligand for EphA2, and PE38QQR, a mutated form of Pseudomonas aeruginosa exotoxin A. EphrinA1-PE38QQR showed potent and dose-dependent killing of GBM cells overexpressing the EphA2 receptor in cell viability and clonogenic survival assays, with an average IC(50) of approximately 10(-11) mol/L. The conjugate was also highly effective in killing breast and prostate cancer cells overexpressing EphA2. The cytotoxic effect of ephrinA1-PE38QQR was specific, as it was neutralized by an excess of EphA2 ligands. Moreover, normal human endothelial cells and breast cancer cells that do not overexpress EphA2, as well as GBM cells that have down-regulated EphA2, were not susceptible to the cytotoxin. EphrinA1-PE38QQR-mediated cytotoxicity induced caspase-dependent apoptosis, which was, however, not responsible for cell death in response to the conjugate. In addition, the conjugate elicited no changes in the activity of survival pathways such as phosphoinositide 3-kinase, measured by AKT phosphorylation. This is the first attempt to create a cytotoxic therapy using any of the ephrin ligands of either class (A or B) conjugated to a bacterial toxin. EphrinA1-PE38QQR is very potent and specific, produces cell death that is caspase independent, and forms the basis for the further development of clinically applicable EphA2-targeted cytotoxins.

  11. Breakdown of interlocking domains may contribute to formation of membranous globules and lens opacity in ephrin-A5(-/-) mice. (United States)

    Biswas, Sondip; Son, Alexander; Yu, Qili; Zhou, Renping; Lo, Woo-Kuen


    Ephrin-A5, a ligand of the Eph family of receptor tyrosine kinases, plays a key role in lens fiber cell packing and cell-cell adhesion, with approximately 87% of ephrin-A5(-/-) mice develop nuclear cataracts. Here, we investigated the extensive formation of light-scattering globules associated with breakdown of interlocking protrusions during lens opacification in ephrin-A5(-/-) mice. Lenses from wild-type (WT) and ephrin-A5(-/-) mice between 2 and 21 weeks old were studied with light and electron microscopy, immunofluorescence labeling, freeze-fracture TEM and filipin cytochemistry for membrane cholesterol detection. Lens opacities with various densities were first observed in ephrin-A5(-/-) mice at around 60 days old. Dense cataracts in the mutant lenses were seen primarily in the nuclear region surrounded by transparent cortices from all eyes examined. We confirmed that a majority of nuclear cataracts were dislocated posteriorly and ruptured the thinner posterior lens capsule. SEM analysis indicated that numerous interlocking protrusions and wavy ridge-and-valley membrane surfaces in deep cortical and nuclear fibers did not cause lens opacity in both transparent ephrin-A5(-/-) and WT mice. In contrast, abundant isolated membranous globules of approximately 1000 nm in size were distributed randomly along the intact fiber cells during early stage of all ephrin-A5(-/-) cataracts examined. A further examination using both SEM and TEM revealed that isolated globules were generated from the disintegrated interlocking protrusions originally located along the corners of hexagonal fiber cells. Freeze-fracture TEM further revealed the association of square-array aquaporin junctions with both isolated globules and interlocking membrane domains. This study reports for the first time that disrupted interlocking protrusions are the source of numerous large membranous globules that contribute to light scattering and nuclear cataracts in the ephrin-A5(-/-) mice. Our results

  12. Deregulated ephrin-B2 expression in the mammary gland interferes with the development of both the glandular epithelium and vasculature and promotes metastasis formation. (United States)

    Haldimann, Mirjam; Custer, Domenica; Munarini, Nadia; Stirnimann, Christoph; Zürcher, Gisela; Rohrbach, Valeria; Djonov, Valentin; Ziemiecki, Andrew; Andres, Anne-Catherine


    Eph receptor tyrosine kinases and their membrane-bound ephrin ligands play key roles during morphogenesis and adult tissue homeostasis. Receptor-ligand interactions result in forward and reverse signalling from the receptor and ligand respectively. To delineate the role(s) of forward and reverse signalling in mammary gland biology we have established transgenic mice exhibiting mammary epithelial-specific overexpression of either the native ephrin-B2 or a dominant negative ephrin-B2 mutant incapable of reverse signalling. During pregnancy and lactation overexpression of the native ephrin-B2 resulted in precocious differentiation, whereas overexpression of mutated ephrin-B2 caused delayed epithelial differentiation and in disturbed tissue architecture. Both transgenes affected also mammary vascularisation. Whereas ephrin-B2 induced superfluous but organised capillaries, mutant ephrin-B2 overexpression resulted in an irregular vasculature with blind-ending capillaries. Mammary tumours were not observed in either transgenic line, however, the crossing with NeuT transgenic animals revealed that mutated ephrin-B2 expression significantly accelerated tumour growth and imposed a metastatic phenotype.

  13. EphrinA1 stimulates cell attachment and inhibits cell aggregation through the EphA receptor pathway in human endometrial carcinoma-derived Ishikawa cells. (United States)

    Fujii, Haruko; Fujiwara, Hiroshi; Horie, Akihito; Suginami, Ko; Sato, Yukiyasu; Konishi, Ikuo


    Recently, the Eph-ephrinA system was proposed to contribute to the initial interaction between the maternal endometrial epithelium and embryonic trophectoderm. Since the Eph-ephrin interaction can induce adhesive and/or repulsive forces into the cells, we examined the possible role of this system in functional changes in endometrial epithelial cells using endometrial carcinoma-derived Ishikawa cells. The expressions of EphA1, A2 and A4 on Ishikawa cells were examined by RT-PCR and western blotting analyses. The effects of recombinant ephrinA1 on Ishikawa cells were also examined by western blot analysis and cell attachment and aggregation assays. EphA1, A2 and A4 were expressed on Ishikawa cells. Recombinant ephrinA1 bound to the surfaces of Ishikawa cells and induced phosphorylation of EphA2 and A4. In bovine serum albumin-blocked nitrocellulose-coated dishes, Ishikawa cells remained floating and aggregated with each other. Under these conditions, immobilized ephrinA1 promoted Ishikawa cell attachment with increased tyrosine phosphorylation in focal adhesion kinase. In addition, immobilized ephrinA1 reversibly inhibited Ishikawa cell aggregation. Gene-reduction of EphA1, A2 and A4 by siRNAs attenuated the inhibitory effects of ephrinA1 on cell aggregation, confirming that ephrinA1 affects Ishikawa cell functions through Eph-ephrinA interaction. This study demonstrated that the Eph-ephrinA system can promote cell attachment along with intercellular dissociation in Ishikawa cells. These findings suggest that this system can induce functional changes in endometrial epithelial cells.

  14. Ephrin-B2 and EphB2 regulation of astrocyte-meningeal fibroblast interactions in response to spinal cord lesions in adult rats. (United States)

    Bundesen, Liza Q; Scheel, Tracy Aber; Bregman, Barbara S; Kromer, Lawrence F


    The present study provides the first evidence that signaling occurs between B-ephrins and EphB receptors in the adult CNS in response to injury. Specifically, our combined histological and biochemical data indicate that two members of the B-class of ephrins and Eph receptors, ephrin-B2 and EphB2, are expressed by astrocytes and meningeal fibroblasts, respectively, in the adult spinal cord. In response to thoracic spinal cord transection lesions, ephrin-B2 and EphB2 protein levels exhibit an initial decrease (1 d after lesion), followed by a significant increase by day 14. Immunohistochemical data indicate that ephrin-B2 is expressed by reactive CNS astrocytes, and EphB2 is present on fibroblasts invading the lesion site from the adjacent meninges. During the first 3 d after injury, there is intermingling of ephrin-B2-expressing reactive astrocytes at the lesion surface with EphB2-containing fibroblasts that is concurrent with bidirectional activation (phosphorylation) of ephrin-B2 and EphB2. By 7 d, both cell types are establishing restricted cellular domains containing dense networks of cells and interweaving processes. This astroglial-meningeal fibroblast scar is fully developed by day 14 when there is strict segregation of ephrin-B2-expressing astrocytes from EphB2-positive meningeal fibroblasts. These morphological changes are concomitant with a simultaneous decrease in ephrin-B2 and EphB2 activation. These observations provide strong evidence that cell contact-mediated bidirectional signaling between ephrin-B2 on reactive astrocytes and EphB2 on meningeal fibroblasts is an early event in the cellular cascades that result in the development of the glial scar and the exclusion of meningeal fibroblasts from the injured spinal cord.

  15. Ephrin-A2 and-A3 are negative regulators of the regenerative potential of Müller cells

    Institute of Scientific and Technical Information of China (English)

    Zhu Ruilin; Cho Kin-Sang; Chen Dong Feng; Yang Liu


    Background In a previous study,we demonstrated that ephrin-A2 and-A3 negatively regulate the growth of neural progenitor cells in the central nervous system.Adult mice deficient in ephrin-A2 and-A3 (A2-/-A3-/-) displayed active ongoing neurogenesis throughout the brain,and mice deficient in ephrin-A3 alone showed increased proliferation of ciliary epithelium derived retinal stem cells.This study aimed to detect that the increase in proliferation and neurogenic potential of Müller cells is influenced by the absence of ephrin-A2 and-A3.Methods We assessed the retinal and Müller cell expression of ephrin-As and their receptor and neural progenitor cell markers by immunostaining and real-time PCR.We cultured purified primary Müller cells derived from wild-type and A2-/-A3-/-mice in a defined culture medium that enables trans-differentiation of Müller cells into retinal neurons.To evaluate proliferating Müller cells in vivo,we injected 5'-ethylnyl-2'-deoxiuridine (EdU) intraperitoneally to adult mice.Results Expression of ephrin-A2/A3 and their receptor EphA4 were detected in the retinas of adult mice,with EphA4 expression particularly enriched in Müller cells.Müller cells of A2-/-A3-/-mice exhibited significantly elevated expression of retinal progenitor cell markers,Pax6 and Chx10,when compared with those from wild-type mice.Moreover,a higher percentage of Müller cells of A2-/-A3-/-mice trans-differentiated and became recoverin+ and β-Ⅲ-tublin+ in the culture than those from wild type mice.Strikingly,an increased number of EdU+ retinal cells was detected in the retinas of adult A2-/-A3-/-mice as compared with wild-type mice.Conclusions Ephrin-A2 and-A3 are negative regulators of the proliferative and neurogenic potentials of Müller cells.Manipulating ephrin-A signaling may thus represent a novel strategy for stimulating neuroregeneration from endogenous progenitors to participate in retinal repair in case of disease or damage.

  16. Ephrin-B-dependent thymic epithelial cell-thymocyte interactions are necessary for correct T cell differentiation and thymus histology organization: relevance for thymic cortex development. (United States)

    Cejalvo, Teresa; Munoz, Juan J; Tobajas, Esther; Fanlo, Lucía; Alfaro, David; García-Ceca, Javier; Zapata, Agustín


    Previous analysis on the thymus of erythropoietin-producing hepatocyte kinases (Eph) B knockout mice and chimeras revealed that Eph-Eph receptor-interacting proteins (ephrins) are expressed both on T cells and thymic epithelial cells (TECs) and play a role in defining the thymus microenvironments. In the current study, we have used the Cre-LoxP system to selectively delete ephrin-B1 and/or ephrin-B2 in either thymocytes (EfnB1(thy/thy), EfnB2(thy/thy), and EfnB1(thy/thy)EfnB2(thy/thy) mice) or TECs (EfnB1(tec/tec), EfnB2(tec/tec), and EfnB1(tec/tec)EfnB2(tec/tec) mice) and determine the relevance of these Eph ligands in T cell differentiation and thymus histology. Our results indicate that ephrin-B1 and ephrin-B2 expressed on thymocytes play an autonomous role in T cell development and, expressed on TECs, their nonautonomous roles are partially overlapping. The effects of the lack of ephrin-B1 and/or ephrin-B2 on either thymocytes or TECs are more severe and specific on thymic epithelium, contribute to the cell intermingling necessary for thymus organization, and affect cortical TEC subpopulation phenotype and location. Moreover, ephrin-B1 and ephrin-B2 seem to be involved in the temporal appearance of distinct cortical TECs subsets defined by different Ly51 levels of expression on the ontogeny.

  17. Phthalate SHEDS-HT runs (United States)

    U.S. Environmental Protection Agency — Inputs and outputs for SHEDS-HT runs of DiNP, DEHP, DBP. This dataset is associated with the following publication: Moreau, M., J. Leonard, K. Phillips, J. Campbell,...

  18. Cooperative signaling between Slit2 and Ephrin-A1 regulates a balance between angiogenesis and angiostasis. (United States)

    Dunaway, Charlene M; Hwang, Yoonha; Lindsley, Craig W; Cook, Rebecca S; Wu, Jane Y; Boothby, Mark; Chen, Jin; Brantley-Sieders, Dana M


    Slit proteins induce cytoskeletal remodeling through interaction with roundabout (Robo) receptors, regulating migration of neurons and nonneuronal cells, including leukocytes, tumor cells, and endothelium. The role of Slit2 in vascular remodeling, however, remains controversial, with reports of both pro- and antiangiogenic activity. We report here that cooperation between Slit2 and ephrin-A1 regulates a balance between the pro- and antiangiogenic functions of Slit2. While Slit2 promotes angiogenesis in culture and in vivo as a single agent, Slit2 potently inhibits angiogenic remodeling in the presence of ephrin-A1. Slit2 stimulates angiogenesis through mTORC2-dependent activation of Akt and Rac GTPase, the activities of which are inhibited in the presence of ephrin-A1. Activated Rac or Akt partially rescues vascular assembly and motility in costimulated endothelium. Taken together, these data suggest that Slit2 differentially regulates angiogenesis in the context of ephrin-A1, providing a plausible mechanism for the pro- versus antiangiogenic functions of Slit2. Our results suggest that the complex roles of Slit-Robo signaling in angiogenesis involve context-dependent mechanisms.

  19. EphrinA5 Signaling Is Required for the Distinctive Targeting of Raphe Serotonin Neurons in the Forebrain (United States)

    Muzerelle, Aude


    Serotonin (5-HT) neurotransmission in the brain relies on a widespread axon terminal network originating from the hindbrain raphe nuclei. These projections are topographically organized such that the dorsal (DR), and median raphe (MnR) nuclei have different brain targets. However, the guidance molecules involved in this selective targeting in development are unknown. Here, we show the implication of ephrinA5 signaling in this process. We find that the EphA5 gene is selectively expressed in a subset of 5-HT neurons during embryonic and postnatal development. Highest coexpression of EphA5 and the 5-HT marker Tph2 is found in the DR, with lower coexpression in the MnR, and hardly any colocalization of the caudal raphe in the medulla. Accordingly, ephrinA induced a dose-dependent collapse response of 5-HT growth cones cultured from rostral but not caudal raphe. Ectopic expression of ephrinA3, after in utero electroporation in the amygdala and piriform cortex, repelled 5-HT raphe fiber ingrowth. Conversely, misplaced DR 5-HT axons were found in ephrin A5 knockout mice in brain regions that are normally only targeted by MnR 5-HT axons. This causes an overall increase in the density of 5-HT innervation in the ventromedial hypothalamus, the suprachiasmatic nucleus, and the olfactory bulb. All these brain areas have high expression of ephrinAs at the time of 5-HT fiber ingrowth. Present results show for the first time the role of a guidance molecule for the region-specific targeting of raphe neurons. This has important implications to understand how functional parsing of central 5-HT neurons is established during development. PMID:28197551

  20. Shedding Light on Trust

    Directory of Open Access Journals (Sweden)

    Lesley Gill


    Full Text Available New Zealand Human Resource Development practitioners interviewed in earlier research indicates that building “trust” is necessary if training efforts in the area of Emotional Intelligence are to be successful.  Yet, trust is often not defined clearly by those working in the field of HRD.  To establish a definition of trust that provides HRD practitioners with direction in the design of training programs, a large group conversation utilizing the “World Café” process was undertaken, after which EI training practitioners wrote reflections on the nature of trust.  Experienced EI Trainers tended to define trust in terms of the outcome produced in training, which was the readiness of participants to talk.  Defining trust in this way has the advantage of involving a low level of inference.  Trainers also identified actions within their control that could stimulate greater readiness amongst training participants about their experiences to trainers and other learners. The aim of the article is to provide a practice-based definition of trust that can inform HRD practitioners working in the field of Emotional Intelligence.

  1. EphrinA1-targeted nanoshells for photothermal ablation of prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Andre M Gobin


    Full Text Available Andre M Gobin, James J Moon, Jennifer L WestDepartment of Bioengineering, Rice University, Houston, TX, USAAbstract: Gold-coated silica nanoshells are a class of nanoparticles that can be designed to possess strong absorption of light in the near infrared (NIR wavelength region. When injected intravenously, these nanoshells have been shown to accumulate in tumors and subsequently mediate photothermal treatment, leading to tumor regression. In this work, we sought to improve their specificity by targeting them to prostate tumor cells. We report selective targeting of PC-3 cells with nanoshells conjugated to ephrinA1, a ligand for EphA2 receptor that is overexpressed on PC-3 cells. We demonstrate selective photo-thermal destruction of these cells upon application of the NIR laser.Keywords: nanoshell, near infrared, photothermal treatment, prostate cancer

  2. EPH/ephrin profile and EPHB2 expression predicts patient survival in breast cancer (United States)

    Husa, Anna-Maria; Magić, Željana; Larsson, Malin; Fornander, Tommy; Pérez-Tenorio, Gizeh


    The EPH and ephrins function as both receptor and ligands and the output on their complex signaling is currently investigated in cancer. Previous work shows that some EPH family members have clinical value in breast cancer, suggesting that this family could be a source of novel clinical targets. Here we quantified the mRNA expression levels of EPH receptors and their ligands, ephrins, in 65 node positive breast cancer samples by RT-PCR with TaqMan® Micro Fluidics Cards Microarray. Upon hierarchical clustering of the mRNA expression levels, we identified a subgroup of patients with high expression, and poor clinical outcome. EPHA2, EPHA4, EFNB1, EFNB2, EPHB2 and EPHB6 were significantly correlated with the cluster groups and particularly EPHB2 was an independent prognostic factor in multivariate analysis and in four public databases. The EPHB2 protein expression was also analyzed by immunohistochemistry in paraffin embedded material (cohort 2). EPHB2 was detected in the membrane and cytoplasmic cell compartments and there was an inverse correlation between membranous and cytoplasmic EPHB2. Membranous EPHB2 predicted longer breast cancer survival in both univariate and multivariate analysis while cytoplasmic EPHB2 indicated shorter breast cancer survival in univariate analysis. Concluding: the EPH/EFN cluster analysis revealed that high EPH/EFN mRNA expression is an independent prognostic factor for poor survival. Especially EPHB2 predicted poor breast cancer survival in several materials and EPHB2 protein expression has also prognostic value depending on cell localization. PMID:26870995

  3. Crab shedding-system designs



    There are as many ways to build and arrange crab shedding setups as there are people who make them. The following drawings are suggestions based on the experiencesof successful shedders. You may find changes that suit your operation better. (8pp.)

  4. Immunohistochemical study in dural arteriovenous fistula and possible role of ephrin-B2 for development of dural arteriovenous fistula

    Institute of Scientific and Technical Information of China (English)

    Wuttipong Tirakotai 王宝隆; BIAN Liu-guan 卞留贯; Helmut Bertalanffy; Siegfried Bien; Ulrich Sure


    Background Although there were several clinical and experimental studies discussing the pathogenesis of dural arteriovenous fistula (DAVF), the pathological process leading to intracranial DAVF so far remains unknown. In this study, we investigated the expression of vascular growth factors in order to elucidate the possible role of these factors for the development of DAVF and to study the biological activity of this uncommon lesion.Methods We examined the histological features, proliferative and angiogenic capacities of the tissue specimens obtained from 6 patients who underwent surgery at our institution. Immunohistochemical staining for vascular endothelial growth factor (VEGF), its receptors Flk-1 and Flt-1, ephrin-B2, MIB-1 and proliferating cell nuclear antigen (PCNA) was performed using standard immunohistochemical techniques. Results A positive immunostaining was found for all antibodies studied except MIB-1, whereas nuclear endothelial expression of PCNA was observed in only 3/6 cases. VEGF stained positive in all of the available specimens (6/6). Flk-1 showed a positive immunoreaction in only 2/6 cases and Flt-1 in 4/6 cases. Ephrin-B2 was expressed in the majority (5/6) of the cases.Conclusions These results support the hypothesis that DAVFs might be acquired dynamic vascular malformations with low biological activity. Vascular growth factors like VEGF and ephrin-B2 might play a pivotal role in the formation of DAVF.

  5. Eph/ephrin profiling in human breast cancer reveals significant associations between expression level and clinical outcome.

    Directory of Open Access Journals (Sweden)

    Dana M Brantley-Sieders

    Full Text Available Pre-clinical studies provide compelling evidence that Eph family receptor tyrosine kinases (RTKs and ligands promote cancer growth, neovascularization, invasion, and metastasis. Tumor suppressive roles have also been reported for the receptors, however, creating a potential barrier for clinical application. Determining how these observations relate to clinical outcome is a crucial step for translating the biological and mechanistic data into new molecularly targeted therapies. We investigated eph and ephrin expression in human breast cancer relative to endpoints of overall and/or recurrence-free survival in large microarray datasets. We also investigated protein expression in commercial human breast tissue microarrays (TMA and Stage I prognostic TMAs linked to recurrence outcome data. We found significant correlations between ephA2, ephA4, ephA7, ephB4, and ephB6 and overall and/or recurrence-free survival in large microarray datasets. Protein expression in TMAs supported these trends. While observed no correlation between ephrin ligand expression and clinical outcome in microarray datasets, ephrin-A1 and EphA2 protein co-expression was significantly associated with recurrence in Stage I prognostic breast cancer TMAs. Our data suggest that several Eph family members are clinically relevant and tractable targets for intervention in human breast cancer. Moreover, profiling Eph receptor expression patterns in the context of relevant ligands and in the context of stage may be valuable in terms of diagnostics and treatment.

  6. WSS25 inhibits Dicer, downregulating microRNA-210, which targets Ephrin-A3, to suppress human microvascular endothelial cell (HMEC-1) tube formation. (United States)

    Xiao, Fei; Qiu, Hong; Zhou, Ling; Shen, Xiaokun; Yang, Liping; Ding, Kan


    WSS25 is a sulfated polysaccharide that inhibits angiogenesis. However, the mechanism underlying the regulation of angiogenesis by WSS25 is not well understood. Using microRNA (miRNA) microarray analysis, a total of 25 miRNAs were found to be upregulated and 12 (including miR-210) downregulated by WSS25 in human microvascular endothelial cells (HMEC-1). Interestingly, Dicer, a key enzyme for miRNA biosynthesis, was downregulated by WSS25 in HMEC-1 cells. Further studies indicated that HMEC-1 cell tube formation and miR-210 expression were suppressed while Ephrin-A3 expression was enhanced by the silencing of Dicer. In contrast, HMEC-1 cell tube formation and miR-210 expression were induced while Ephrin-A3 expression was suppressed by Dicer overexpression. Moreover, miR-210 was downregulated while Ephrin-A3 was upregulated by WSS25 in HMEC-1 cells. HMEC-1 cell migration and tube formation were arrested, while Ephrin-A3 expression was augmented by anti-miR-210. In addition, HMEC-1 cell tube formation was significantly attenuated or augmented when Ephrin-A3 was overexpressed or silenced, respectively. Nevertheless, the tube formation blocked by WSS25 could be partially rescued by manipulation of Dicer, miR-210 and Ephrin-A3. These results suggest a new pathway whereby WSS25 inhibits angiogenesis via suppression of Dicer, leading to downregulation of miR-210 and upregulation of Ephrin-A3.

  7. EphrinA4 plays a critical role in α4 and αL mediated survival of human CLL cells during extravasation (United States)

    Trinidad, Eva M.; García, Dolores; Soler, Gloria; Ortuño, Francisco J.; Zapata, Agustín G.; Alonso, Luis M.


    A role of endothelial cells in the survival of CLL cells during extravasation is presently unknown. Herein we show that CLL cells but not normal B cells can receive apoptotic signals through physical contact with TNF-α activated endothelium impairing survival in transendothelial migration (TEM) assays. In addition, the CLL cells of patients having lymphadenopathy (LApos) show a survival advantage during TEM that can be linked to increased expression of α4 and αL integrin chains. Within this context, ephrinA4 expressed on the surface of CLL cells sequestrates integrins and inactivates them resulting in reduced adhesion and inhibition of apoptotic/survival signals through them. In agreement, ephrinA4 silencing resulted in increased survival of CLL cells of LApos patients but not LA neg patients. Similarly was observed when a soluble ephrinA4 isoform was added to TEM assays strongly suggesting that accumulation of this isoform in the serum of LApos patients could contribute to CLL cells dissemination and survival in vivo. In supporting, CLL lymphadenopathies showed a preferential accumulation of apoptotic CLL cells around high endothelial venules lacking ephrinA4. Moreover, soluble ephrinA4 isolated from sera of patients increased the number and viability of CLL cells recovered from the lymph nodes of adoptively transferred mice. Finally, we present evidence suggesting that soluble ephrinA4 mediated survival during TEM could enhance a transcellular TEM route of the CLL cells. Together these findings point to an important role of ephrinA4 in the nodal dissemination of CLL cells governing extravasation and survival. PMID:27374180

  8. Targeted delivery of let-7a microRNA encapsulated ephrin-A1 conjugated liposomal nanoparticles inhibit tumor growth in lung cancer

    Directory of Open Access Journals (Sweden)

    Lee HY


    Full Text Available Hung-Yen Lee,1,2 Kamal A Mohammed,1,3 Fredric Kaye,4 Parvesh Sharma,5 Brij M Moudgil,5 William L Clapp,6 Najmunnisa Nasreen1,3 1Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine in the College of Medicine, 2Biomaterials Center, Department of Materials Sciences and Engineering, 3North Florida/South Georgia Veterans Health System, Malcom Randall VA Medical Center, 4Division of Hematology and Oncology, Department of Medicine in the College of Medicine, 5Particle Engineering Research Center and Department of Materials Science and Engineering, 6Renal Pathology, Surgical Pathology, University of Florida, Gainesville, FL, USA Abstract: MicroRNAs (miRs are small noncoding RNA sequences that negatively regulate the expression of target genes by posttranscriptional repression. miRs are dysregulated in various diseases, including cancer. let-7a miR, an antioncogenic miR, is downregulated in lung cancers. Our earlier studies demonstrated that let-7a miR inhibits tumor growth in malignant pleural mesothelioma (MPM and could be a potential therapeutic against lung cancer. EphA2 (ephrin type-A receptor 2 tyrosine kinase is overexpressed in most cancer cells, including MPM and non-small-cell lung cancer (NSCLC cells. Ephrin-A1, a specific ligand of the EphA2 receptor, inhibits cell proliferation and migration. In this study, to enhance the delivery of miR, the miRs were encapsulated in the DOTAP (N-[1-(2.3-dioleoyloxypropyl]-N,N,N-trimethyl ammonium/Cholesterol/DSPE (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[cyanur(polyethylene glycol-2000]-PEG (polyethylene glycol-cyanur liposomal nanoparticles (LNP and ephrin-A1 was conjugated on the surface of LNP to target receptor EphA2 on lung cancer cells. The LNP with an average diameter of 100 nm showed high stability, low cytotoxicity, and high loading efficiency of precursor let-7a miR and ephrin-A1. The ephrin-A1 conjugated LNP (ephrin-A1–LNP and let-7a miR encapsulated LNP

  9. Shedding light on walking in the dark: the effects of reduced lighting on the gait of older adults with a higher-level gait disorder and controls

    Directory of Open Access Journals (Sweden)

    Gruendlinger Leor


    Full Text Available Abstract Objective To study the effects of reduced lighting on the gait of older adults with a high level gait disorder (HLGD and to compare their response to that of healthy elderly controls. Methods 22 patients with a HLGD and 20 age-matched healthy controls were studied under usual lighting conditions (1000 lumens and in near darkness (5 lumens. Gait speed and gait dynamics were measured under both conditions. Cognitive function, co-morbidities, depressive symptoms, and vision were also evaluated. Results Under usual lighting conditions, patients walked more slowly, with reduced swing times, and increased stride-to-stride variability, compared to controls. When walking under near darkness conditions, both groups slowed their gait. All other measures of gait were not affected by lighting in the controls. In contrast, patients further reduced their swing times and increased their stride-to-stride variability, both stride time variability and swing time variability. The unique response of the patients was not explained by vision, mental status, co-morbidities, or the values of walking under usual lighting conditions. Conclusion Walking with reduced lighting does not affect the gait of healthy elderly subjects, except for a reduction in speed. On the other hand, the gait of older adults with a HLGD becomes more variable and unsteady when they walk in near darkness, despite adapting a slow and cautious gait. Further work is needed to identify the causes of the maladaptive response among patients with a HLGD and the potential connection between this behavior and the increased fall risk observed in these patients.

  10. GRIP1 Binds to ApoER2 and EphrinB2 to Induce Activity-Dependent AMPA Receptor Insertion at the Synapse

    Directory of Open Access Journals (Sweden)

    Sylvia Pfennig


    Full Text Available Regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA receptor trafficking in response to neuronal activity is critical for synaptic function and plasticity. Here, we show that neuronal activity induces the binding of ephrinB2 and ApoER2 receptors at the postsynapse to regulate de novo insertion of AMPA receptors. Mechanistically, the multi-PDZ adaptor glutamate-receptor-interacting protein 1 (GRIP1 binds ApoER2 and bridges a complex including ApoER2, ephrinB2, and AMPA receptors. Phosphorylation of ephrinB2 in a serine residue (Ser-9 is essential for the stability of such a complex. In vivo, a mutation on ephrinB2 Ser-9 in mice results in a complete disruption of the complex, absence of ApoER2 downstream signaling, and impaired activity-induced and ApoER2-mediated AMPA receptor insertion. Using compound genetics, we show the requirement of this complex for long-term potentiation (LTP. Together, our findings uncover a cooperative ephrinB2 and ApoER2 signaling at the synapse, which serves to modulate activity-dependent AMPA receptor dynamic changes during synaptic plasticity.

  11. Asymptomatic Herpes Simplex Virus Shedding in STI Patients

    Institute of Scientific and Technical Information of China (English)

    叶兴东; 颜景兰; 朱慧兰; 张莉; 佟菊贞


    Objective: This study examined Herpes Simplex Virus(HSV) subclinical shedding in the genital tract of patients withgenital herpes (GH) or non-gonoccal urethritis (NGU). Method: Swabs were collected after exposure to rash andgenital tract during GH relapse or remission on a weekly basisfor four to six weeks. NGU patients with negative chlamydiaand mycoplasma tests were also swabbed for a similarduration. All swabs underwent HSV DNA detection withquantitative PCR. Result: There was a significant difference in the rate ofasymptomatic HSV shedding in urinary tracts comparing GHand the control group and comparing NGU and the controlgroup (P<0.05). The rate of HSV shedding was 22%, 9.8%and 3.3% for GH, NGU and control groups respectively. Therate of HSV shedding was 21.7% (20/92) for patients withactive GH and 23% for those in remission. The HSV positiverate was significantly higher in the group with patients whohad more than six relapses within one year compared to thegroup of patients with less than six GH relapses. Conclusion: There is HSV subclinical shedding in theirgenital tract during active GH and remission. SubclinicalHSV shedding is more common in patients with more than sixGH relapses per year compared to GH patients with fewerrelapses. Approximately 9.9% of NGU patients with negativechlamydia, mycoplasma testing was found to have subclinicalHSV infection.

  12. Shedding of immature germ cells. (United States)

    Ariagno, J; Curi, S; Mendeluk, G; Grinspon, D; Repetto, H; Chenlo, P; Pugliese, N; Sardi, M; Blanco, A M


    The immature germ cells (IGC) constitute the highest percentage (90%) of nonsperm cells (NSpC) in ejaculates from fertile or infertile men. The objective of this study was to evaluate IGC concentration and the IGC/(IGC + Sp) ratio, in normozoospermia and dispermia. Normozoospermia from men with proven fertility (NPF). nonproven fertility (NNPF). dispermia (D) and semen samples with excessive shedding of immature germ cells (GI 1.7 x 10(6) to 5 x 10(6) IGC/mL and GII > 5.0 x 10(6) IGC/mL) were used in this study. The mean value +2 SD for the NNPF (1.7 x 10(6)/mL) and the value proposed by WHO (5 x 10(6)/mL) were employed to define GI and GII groups. IGC concentration is statistically different in the studied groups. The IGC/Sp ratio showed a significant difference only between the NNPF and the D. When comparing semen parameters (Sp/ejaculate. grade (a) motility and morphology) there was a highly significant difference between NNPF and GI and GII: no difference was found between GI and GII. While studying 200 cases of dispermias 83% showed a high shedding of immature germ cells. The cytological study of nonsperm cells and the count and identification of the immature germ cells could be used to evaluate the dispermic disorders.

  13. Diffusion-Controlled Rotation of Triptycene in a Metal–Organic Framework (MOF) Sheds Light on the Viscosity of MOF-Confined Solvent (United States)


    Artificial molecular machines are expected to operate under conditions of very low Reynolds numbers with inertial forces orders of magnitude smaller than viscous forces. While these conditions are relatively well understood in bulk fluids, opportunities to assess the role of viscous forces in confined crystalline media are rare. Here we report one such example of diffusion-controlled rotation in crystals and its application as a probe for viscosity of MOF-confined solvent. We describe the preparation and characterization of three pillared paddlewheel MOFs, with 9,10-bis(4-pyridylethynyl)triptycene 3 as a pillar and molecular rotator, and three axially substituted dicarboxylate linkers with different lengths and steric bulk. The noncatenated structure with a bulky dicarboxylate linker (UCLA-R3) features a cavity filled by 10 molecules of N,N-dimethylformamide (DMF). Solid-state 2H NMR analysis performed between 293 and 343 K revealed a fast 3-fold rotation of the pillar triptycene group with the temperature dependence consistent with a site exchange process determined by rotator-solvent interactions. The dynamic viscosity of the MOF-confined solvent was estimated to be 13.3 N·s/m2 (or Pa·s), which is 4 orders of magnitude greater than that of bulk DMF (8.2 × 10–4 N·s/m2), and comparable to that of honey. PMID:27725958

  14. Capacity building in indigenous men's groups and sheds across Australia. (United States)

    Southcombe, Amie; Cavanagh, Jillian; Bartram, Timothy


    This article presents an investigation into capacity building, at the community level, in Aboriginal and Torres Strait Islander Men's Groups and Sheds. As safe men's spaces, Men's Groups and Sheds represent an ever-growing social, and health and well-being community service across Australia. The study is qualitative and employs 'yarning circles' (focus groups), semi-structured interviews and observations to gather data from 15 Groups/Sheds involving 45 men from urban, regional and remote communities. We found that capacity building is primarily about securing relationships between Group Leaders/Shed Co-ordinators and Government services. Capacity building establishes links to services such as Centrelink, Medicare, Department of Housing, Probation and Control, and positive outcomes such as Indigenous men securing housing and Centrelink payments. Capacity building results in better health outcomes and, educates and empowers men to improve their social, cultural, emotional and economic well-being. It helps men to better connect with family and community. The current research paves the way for countries worldwide to explore the conceptual and empirical approach of capacity building applicable to other Indigenous [and non-Indigenous] Men's Groups/Sheds. We recommend feasibilities studies, on approaches to capacity building in Indigenous Groups/Sheds, be carried out within urban, regional and remote regions across the country. © The Author (2014). Published by Oxford University Press. All rights reserved. For Permissions, please email:

  15. The soluble extracellular domain of EphB4 (sEphB4) antagonizes EphB4-EphrinB2 interaction, modulates angiogenesis, and inhibits tumor growth


    Kertesz, Nathalie; Krasnoperov, Valery; Reddy, Ramachandra; Leshanski, Lucy; Kumar, S. Ram; Zozulya, Sergey; Gill, Parkash S.


    The receptor tyrosine kinase EphB4 and its ligand EphrinB2 play a crucial role in vascular development during embryogenesis. The soluble monomeric derivative of the extracellular domain of EphB4 (sEphB4) was designed as an antagonist of EphB4/EphrinB2 signaling. sEphB4 blocks activation of EphB4 and EphrinB2; suppresses endothelial cell migration, adhesion, and tube formation in vitro; and inhibits the angiogenic effects of various growth factors (VEGF and bFGF) in vivo. sEphB4 also inhibits ...

  16. Automatic load shedding in multiarea elastic power systems

    Energy Technology Data Exchange (ETDEWEB)

    Di Caprio, U.; Marconato, R.


    A procedure for the design of automatic load shedding in an elastic multiarea power system is proposed. Assuming that the power-frequency transfer functions of the various areas are similar, and that the interconnection network can be approximated by a purely reactive network, separate specifications can be given with regard to the control of the mean-frequency transient and that of the interarea electromechanical oscillations. While the first determines the total load to be shed, the second determines its optimal subdivision in order to maximize the stability margin in the large.

  17. Ud af hjemløshed?

    DEFF Research Database (Denmark)

    Pico Geerdsen, Lars; Koch-Nielsen, Inger; Vinther, Henrik

    Hjemløshed er ofte forbundet med en række problemer som misbrug, psykisk sygdom, vold i parforholdet, ringe arbejdsmarkedstilknytning og levevilkår, kriminalitet, gæld og manglende sociale netværk. Det er alle problemer, der kan udløse hjemløshed og potentielt fastholde personer i en hjemløshedst...

  18. A dual role of EphB1/ephrin-B3 reverse signaling on migrating striatal and cortical neurons originating in the preoptic area: should I stay or go away ?

    Directory of Open Access Journals (Sweden)

    Judith eRudolph


    Full Text Available During embryonic development the preoptic area (POA gives rise to two populations of neurons which are generated at the same time, cortical interneurons and striatal cells. POA-derived cortical interneurons take a superficial path and avoid the developing striatum when they migrate to their target region. We found that EphB1, which is expressed in the striatal anlage, prevents cortical interneurons from entering the striatum via ephrin-B3 reverse signaling. In contrast, for striatal neurons which also express ephrin-B3, EphB1 acts as a stop signal. This dual role of EphB1 is due to differences in ephrin-B3 reverse signaling cascades. For striatal neurons, binding of EphB1 to ephrin-B3 reduces endogenously high levels of pSrc and pFAK, which then causes the cells to stop migration. In contrast, in cortical interneurons EphB1-ephrin-B3 reverse signaling leads to phosphorylation of Src and FAK which then mediates repulsion. Consistent with these in vitro findings, in an ephrin-B3 knockout mouse line, we discovered misrouted cortical interneurons in the striatum and an over-migration of striatal neurons in their target region. Thus, EphB1/ephrin-B3 reverse signaling has a different impact on two sets of neurons which are generated at the same time and place: it can act as a repulsive cue for migrating neurons or it can terminate neuronal migration, a novel role of the Eph/ephrin system.

  19. Vortex Shedding From a Flexible Hydrofoil


    Dreyer, Matthieu; Farhat, Mohamed


    Video of vortex shedding in the wake of a Naca0009 hydrofoil made of polyoxymethylene type C (POM C). This video was submitted as part of the Gallery of Fluid Motion 2011 which is showcase of fluid dynamics videos.

  20. Vortex shedding by a Savonius rotor (United States)

    Botrini, M.; Beguier, C.; Chauvin, A.; Brun, R.


    A series of flow visualizations was performed to characterize the wake vortices of a Savonius rotor. The trials were undertaken in an attempt to account for discrepancies between theoretical and experimentally-derived power coefficients. The Savonius examined was two-bladed with a center offset. All tests were made in a water tunnel. Dye injection provided the visualization, and average velocities and velocity fluctuations were measured using a laser Doppler anemometer. A system of three vortices was found to be periodically shed by the rotor. Flow velocity fluctuation intensity peaked as a vortex was shed. The vortex shedding alternated from blade to blade, so that one was shed from a blade moving upstream.

  1. Ephrin-Bs Drive Junctional Downregulation and Actin Stress Fiber Disassembly to Enable Wound Re-epithelialization. (United States)

    Nunan, Robert; Campbell, Jessica; Mori, Ryoichi; Pitulescu, Mara E; Jiang, Wen G; Harding, Keith G; Adams, Ralf H; Nobes, Catherine D; Martin, Paul


    For a skin wound to successfully heal, the cut epidermal-edge cells have to migrate forward at the interface between scab and healthy granulation tissue. Much is known about how lead-edge cells migrate, but very little is known about the mechanisms that enable active participation by cells further back. Here we show that ephrin-B1 and its receptor EphB2 are both upregulated in vivo, just for the duration of repair, in the first 70 or so rows of epidermal cells, and this signal leads to downregulation of the molecular components of adherens and tight (but not desmosomal) junctions, leading to loosening between neighbors and enabling shuffle room among epidermal cells. Additionally, this signaling leads to the shutdown of actomyosin stress fibers in these same epidermal cells, which may act to release tension within the wound monolayer. If this signaling axis is perturbed, then disrupted healing is a consequence in mouse and man.

  2. Arterial identity of endothelial cells is controlled by local cues. (United States)

    Othman-Hassan, K; Patel, K; Papoutsi, M; Rodriguez-Niedenführ, M; Christ, B; Wilting, J


    The ephrins and their Eph receptors comprise the largest family of receptor tyrosine kinases. Studies on mice have revealed an important function of ephrin-B2 and Eph-B4 for the development of the arterial and venous vasculature, respectively, but the mechanisms regulating their expression have not been studied yet. We have cloned a chick ephrin-B2 cDNA probe. Expression was observed in endothelial cells of extra- and intraembryonic arteries and arterioles in all embryos studied from day 2 (stage 10 HH, before perfusion of the vessels) to day 16. Additionally, expression was found in the somites and neural tube in early stages, and later also in the smooth muscle cells of the aorta, parts of the Müllerian duct, dosal neural tube, and joints of the limbs. We isolated endothelial cells from the internal carotid artery and the vena cava of 14-day-old quail embryos and grafted them separately into day-3 chick embryos. Reincubation was performed until day 6 and the quail endothelial cells were identified with the QH1 antibody. The grafted arterial and venous endothelial cells expressed ephrin-B2 when they integrated into the lining of arteries. Cells that were not integrated into vessels, or into vessels other than arteries, were ephrin-B2-negative. The studies show that the expression of the arterial marker ephrin-B2 is controlled by local cues in arterial vessels of older embryos. Physical forces or the media smooth muscle cells may be involved in this process.

  3. Shedding Light on Laser Welding

    NARCIS (Netherlands)

    Aalderink, B.J.; Aalderink, Benno; Aarts, Ronald G.K.M.; Jonker, Jan B.; Meijer, J.


    Nd:YAG laser welding is often used in industry to obtain high quality joints. This however does not mean that monitoring or control of this process is common practice. A few commercial products are available but none of these systems can be used for monitoring the laser welding process of aluminium.

  4. Developing of the EV charging and parking shed of BIPV

    Institute of Scientific and Technical Information of China (English)

    Wu Shaobo; Wei Chuanchuan; Yu Jiang


    Building-integrated photovoltaic (BIPV) is an important application way of solar photovoltaic power. The electric vehicle (EV) charging and parking shed of BIPV is the regeneration energy intellectual integration demonstration application system collection of photovoltaic (PV) grid power,PV off-grid power,EV charging and parking shed,and any part of the functions and their combination will be engaged in practical application on demand. The paper describes the PV shed system structure and design in detail with the present of its actual photos. The shed is 50 m long and 5.5 m wide and capable of parking 18 cars. Under the control of system intellectual con-troller,the power produced by PV from sunlight will charge the parking EV car prior to charging the storage bat-tery,charging the storage battery prior to grid power,grid power at last,and charge the EV by utility grid when it is a cloudy or rainy day.

  5. Smallpox vaccine, ACAM2000: Sites and duration of viral shedding and effect of povidone iodine on scarification site shedding and immune response. (United States)

    Pittman, Phillip R; Garman, Patrick M; Kim, Sung-Han; Schmader, Trevor J; Nieding, William J; Pike, Jason G; Knight, Ryan; Johnston, Sara C; Huggins, John W; Kortepeter, Mark G; Korman, Lawrence; Ranadive, Manmohan; Quinn, Xiaofei; Meyers, Mitchell S


    The U.S. Department of Defense vaccinates personnel deployed to high-risk areas with the vaccinia virus (VACV)-based smallpox vaccine. Autoinoculations and secondary and tertiary transmissions due to VACV shedding from the vaccination site continue to occur despite education of vaccinees on the risks of such infections. The objectives of this study were to investigate, in naïve smallpox vaccinees, (a) whether the vaccination site can remain contagious after the scab separates and (b) whether the application of povidone iodine ointment (PIO) to the vaccination site inactivates VACV without affecting the immune response. These objectives were tested in 60 individuals scheduled to receive smallpox vaccine. Thirty individuals (control) did not receive PIO; 30 subjects (treatment) received PIO starting on post-vaccination day 7. Counter to current dogma, this study showed that VACV continues to shed from the vaccination site after the scab separates. Overall viral shedding levels in the PIO group were significantly lower than those in the control group (p=0.0045), and PIO significantly reduced the duration of viral shedding (median duration 14.5 days and 21 days in the PIO and control groups, respectively; p=0.0444). At least 10% of control subjects continued to shed VACV at day 28, and 3.4% continued to shed the virus at day 42. PIO reduced the proportion of subjects shedding virus from the vaccination site from day 8 until days 21-23 compared with control subjects. Groups did not differ significantly in the proportion of subjects mounting an immune response, as measured by neutralizing antibodies, IgM, IgG, and interferon-gamma enzyme-linked immunospot assay. When applied to the vaccination site starting on day 7, PIO reduced viral shedding without altering the immune response. The use of PIO in addition to a semipermeable dressing may reduce the rates of autoinoculation and contact transmission originating from the vaccination site in smallpox-vaccinated individuals.

  6. Global evaluation of Eph receptors and ephrins in lung adenocarcinomas identifies EphA4 as an inhibitor of cell migration and invasion. (United States)

    Saintigny, Pierre; Peng, Shaohua; Zhang, Li; Sen, Banibrata; Wistuba, Ignacio I; Lippman, Scott M; Girard, Luc; Minna, John D; Heymach, John V; Johnson, Faye M


    The Eph family of receptors is the largest family of receptor tyrosine kinases, but it remains poorly studied in lung cancer. We aimed to systematically explore the human Eph receptors and their ligands, the ephrins, in lung adenocarcinoma. The prognostic impact of Eph receptor and ephrin gene expression was analyzed using 2 independent cohorts of lung adenocarcinoma. Gene expression profiles in lung adenocarcinoma compared with normal adjacent lung were studied in 3 independent cohorts and in cell lines. Gene expression profiles were validated with quantitative polymerase chain reaction (qPCR) and Western blotting in cell lines. Functional studies to assess the role of Eph receptor A4 (EphA4) were carried out in vitro. The biological effects of EphA4 in lung cancer cell lines were assayed following overexpression and knockdown. Of the 11 Eph receptors and 8 ephrins analyzed, only EphA4 and ephrin A1 gene expression were consistently associated with an improved outcome in patients with lung adenocarcinoma. Expression levels of EphA4 by microarray correlated well with expression levels measured by qPCR and Western blotting. EphA4 overexpression reduced cell migration and invasion but did not affect cell cycle, apoptosis, or drug sensitivity. Surprisingly, EphA4 was expressed at higher levels in cancer compared with non-cancer tissues and cell lines. EphA4 gene expression is associated with an improved outcome in patients with resected lung adenocarcinoma, possibly by affecting cancer cell migration and invasion.

  7. MicroRNA-210 Modulates Endothelial Cell Response to Hypoxia and Inhibits the Receptor Tyrosine Kinase Ligand Ephrin-A3*S⃞ (United States)

    Fasanaro, Pasquale; D'Alessandra, Yuri; Di Stefano, Valeria; Melchionna, Roberta; Romani, Sveva; Pompilio, Giulio; Capogrossi, Maurizio C.; Martelli, Fabio


    MicroRNAs (miRNAs) are small non-protein-coding RNAs that function as negative gene expression regulators. In the present study, we investigated miRNAs role in endothelial cell response to hypoxia. We found that the expression of miR-210 progressively increased upon exposure to hypoxia. miR-210 overexpression in normoxic endothelial cells stimulated the formation of capillary-like structures on Matrigel and vascular endothelial growth factor-driven cell migration. Conversely, miR-210 blockade via anti-miRNA transfection inhibited the formation of capillary-like structures stimulated by hypoxia and decreased cell migration in response to vascular endothelial growth factor. miR-210 overexpression did not affect endothelial cell growth in both normoxia and hypoxia. However, anti-miR-210 transfection inhibited cell growth and induced apoptosis, in both normoxia and hypoxia. We determined that one relevant target of miR-210 in hypoxia was Ephrin-A3 since miR-210 was necessary and sufficient to down-modulate its expression. Moreover, luciferase reporter assays showed that Ephrin-A3 was a direct target of miR-210. Ephrin-A3 modulation by miR-210 had significant functional consequences; indeed, the expression of an Ephrin-A3 allele that is not targeted by miR-210 prevented miR-210-mediated stimulation of both tubulogenesis and chemotaxis. We conclude that miR-210 up-regulation is a crucial element of endothelial cell response to hypoxia, affecting cell survival, migration, and differentiation. PMID:18417479

  8. Eph/ephrin signaling maintains the boundary of dorsal forerunner cell cluster during morphogenesis of the zebrafish embryonic left-right organizer (United States)

    Zhang, Junfeng; Jiang, Zheng; Liu, Xingfeng


    The Kupffer's vesicle (KV) is the so-called left-right organizer in teleost fishes. KV is formed from dorsal forerunner cells (DFCs) and generates asymmetrical signals for breaking symmetry of embryos. It is unclear how DFCs or KV cells are prevented from intermingling with adjacent cells. In this study, we show that the Eph receptor gene ephb4b is highly expressed in DFCs whereas ephrin ligand genes, including efnb2b, are expressed in cells next to the DFC cluster during zebrafish gastrulation. ephb4b knockdown or mutation and efnb2b knockdown cause dispersal of DFCs, a smaller KV and randomization of laterality organs. DFCs often dynamically form lamellipodium-like, bleb-like and filopodium-like membrane protrusions at the interface, which attempt to invade but are bounced back by adjacent non-DFC cells during gastrulation. Upon inhibition of Eph/ephrin signaling, however, the repulsion between DFCs and non-DFC cells is weakened or lost, allowing DFCs to migrate away. Ephb4b/Efnb2b signaling by activating RhoA activity mediates contact and repulsion between DFCs and neighboring cells during gastrulation, preventing intermingling of different cell populations. Therefore, our data uncover an important role of Eph/ephrin signaling in maintaining DFC cluster boundary and KV boundary for normal left-right asymmetrical development. PMID:27287807

  9. Itaalia maalikooli shedöövrid

    Index Scriptorium Estoniae


    I8. detsembrist Rüütelkonna hoones näitus "Itaalia maalikooli shedöövreid Eesti Kunstimuuseumi kogust" sarjast "Kadrioru lossi aarded", mis kajastab ka teoste restaureerimist ja uurimistööd. Maali "Püha Joosepi surm" ümberatribueerimisest XVII sajandi Veneetsia meistrile Giovanni Battista Piazzettale

  10. Shedding further light on late globalization

    DEFF Research Database (Denmark)

    Turcan, Romeo V.


    In his opening essay on ‘What and/or Who is Late’, Nikhilesh Dholakia delineated inter alia “stage-setting contexts” or levels of analysis which could shed light on the phenomenon of late globalization, including its causes and effects. Indeed, these, especially the effects in contemporary contex...

  11. Incidence of Latent Virus Shedding during Space Flight (United States)

    Mehta, Satish K.; Cohrs, Randall J.; Gilden, Donald H.; Tyring, Stephen K.; Ott, C. Mark; Pierson, Duane L.


    Measurements of immune parameters of both cellular and innate immunity indicate alterations in immune function in astronauts. Immune changes are due to stress and perhaps other factors associated with launch, flight, and landing phases. Medical relevance of observed changes is not known. The reactivation of latent viruses has been identified as an important in vivo indicator of clinically relevant immune changes. The polymerase chain reaction (PCR) was used to detect the presence of specific viral DNA in body fluids. Initial studies demonstrated Epstein-Barr virus (EBV) reactivation during all 3 mission phases. EBV is shed in saliva following reactivation from B-cells. Incidence of EBV in saliva was higher than control subjects during all 3 mission phases. However, quantitative PCR revealed 10-fold higher levels of EBV DNA present in saliva collected during flight than found in pre- and post flight specimens. To determine if other latent viruses showed similar effects, cytomegalovirus (CMV), another herpes virus, shed in urine following reactivation was studied. A very low incidence (less than 2%) of CMV in urine is found in healthy, lowstressed individuals. However, 25-50% of astronauts shed CMV in their urine before, during, or after flight. Our studies are now focused on varicella-zoster virus (VZV), the etiological agent of chicken-pox during childhood and shingles later in life. We demonstrated reactivation of VZV and shedding of the virus during and after spaceflight in saliva of astronauts with no sign of active infection or symptoms. The maximum shedding of VZV occurred during the flight phase and diminishes rapidly during the first five days after landing. We have utilized the same PCR assay for VZV in a clinical study of shingles patients. Generally, shingles patients shed much more VZV in saliva than astronauts. However, the VZV levels in astronauts overlap with the lower range of VZV numbers in shingles patients. Saliva from shingles patients and

  12. Ephrin-Bs Drive Junctional Downregulation and Actin Stress Fiber Disassembly to Enable Wound Re-epithelialization

    Directory of Open Access Journals (Sweden)

    Robert Nunan


    Full Text Available For a skin wound to successfully heal, the cut epidermal-edge cells have to migrate forward at the interface between scab and healthy granulation tissue. Much is known about how lead-edge cells migrate, but very little is known about the mechanisms that enable active participation by cells further back. Here we show that ephrin-B1 and its receptor EphB2 are both upregulated in vivo, just for the duration of repair, in the first 70 or so rows of epidermal cells, and this signal leads to downregulation of the molecular components of adherens and tight (but not desmosomal junctions, leading to loosening between neighbors and enabling shuffle room among epidermal cells. Additionally, this signaling leads to the shutdown of actomyosin stress fibers in these same epidermal cells, which may act to release tension within the wound monolayer. If this signaling axis is perturbed, then disrupted healing is a consequence in mouse and man.

  13. Phosphotyrosine profiling identifies ephrin receptor A2 as a potential therapeutic target in esophageal squamous-cell carcinoma. (United States)

    Syed, Nazia; Barbhuiya, Mustafa A; Pinto, Sneha M; Nirujogi, Raja Sekhar; Renuse, Santosh; Datta, Keshava K; Khan, Aafaque Ahmad; Srikumar, Kotteazeth; Prasad, T S Keshava; Kumar, M Vijaya; Kumar, Rekha Vijay; Chatterjee, Aditi; Pandey, Akhilesh; Gowda, Harsha


    Esophageal squamous-cell carcinoma (ESCC) is one of the most common malignancies in Asia. Currently, surgical resection of early-stage tumor is the best available treatment. However, most patients present late when surgery is not an option. Data suggest that chemotherapy regimens are inadequate for clinical management of advanced cancer. Targeted therapy has emerged as one of the most promising approaches to treat several malignancies. A prerequisite for developing targeted therapy is prior knowledge of proteins and pathways that drive proliferation in malignancies. We carried out phosphotyrosine profiling across four different ESCC cell lines and compared it to non-neoplastic Het-1A cell line to identify activated tyrosine kinase signaling pathways in ESCC. A total of 278 unique phosphopeptides were identified across these cell lines. This included several tyrosine kinases and their substrates that were hyperphosphorylated in ESCC. Ephrin receptor A2 (EPHA2), a receptor tyrosine kinase, was hyperphosphorylated in all the ESCC cell lines used in the study. EPHA2 is reported to be oncogenic in several cancers and is also known to promote metastasis. Immunohistochemistry-based studies have revealed EPHA2 is overexpressed in nearly 50% of ESCC. We demonstrated EPHA2 as a potential therapeutic target in ESCC by carrying out siRNA-based knockdown studies. Knockdown of EPHA2 in ESCC cell line TE8 resulted in significant decrease in cell proliferation and invasion, suggesting it is a promising therapeutic target in ESCC that warrants further evaluation.

  14. 76 FR 66220 - Automatic Underfrequency Load Shedding and Load Shedding Plans Reliability Standards (United States)


    ... differentiation in requirements based on entity size, though it provides the opportunity for planning coordinators... type of load shedding (i.e., automatic and manual) should not overlap. 49. There are no requirements in...

  15. Superhydrophobic porous networks for enhanced droplet shedding (United States)

    Liu, Yahua; Wang, Zuankai


    Recent research has shown that the use of submillimeter-scale tapered post arrays could generate the so-called pancake bouncing, which is characterized by the fast shedding of impinging drops from the surface in a pancake shape without undergoing the retraction stage as observed on conventional superhydrophobic surfaces. Despite this exciting discovery, the fabrication of this unique superhydrophobic surface with tapered post arrays involves complex processes, hindering its wide applications in practical sectors. Here, we report on the facile strategy to prepare a new hierarchical multilayered superhydrophobic surface directly from commercially available porous matrix that allows for efficient drop shedding. Further study shows that the enhanced drop mobility observed on such a surface is attributed to the synergistic cooperation of hierarchical structures endowing an adequate energy storage and effective energy release. The facile fabrication of superhydrophobic surface with enhanced drop mobility may find many practical applications including anti-icing, dropwise condensation and self-cleaning.

  16. Effect of steady rotation on low Reynolds number vortex shedding behind a circular cylinder (United States)

    Satish, Paluri; Patwardhan, Saurabh S.; Ramesh, O. N.


    In this paper control of oblique vortex shedding in the wake behind a straight circular cylinder is explored experimentally and computationally. Towards this, steady rotation of the cylinder about its axis is used as a control device. Some limited studies are also performed with a stepped circular cylinder, where at the step the flow is inevitably three-dimensional irrespective of the rotation rate. When there is no rotation, the vortex shedding pattern is three dimensional as described in many previous studies. With a non-zero rotation rate, it is demonstrated experimentally as well as numerically that the shedding pattern becomes more and more two-dimensional. At sufficiently high rotation rates, the vortex shedding is completely suppressed.

  17. On Load Shedding in Complex Event Processing



    Complex Event Processing (CEP) is a stream processing model that focuses on detecting event patterns in continuous event streams. While the CEP model has gained popularity in the research communities and commercial technologies, the problem of gracefully degrading performance under heavy load in the presence of resource constraints, or load shedding, has been largely overlooked. CEP is similar to "classical" stream data management, but addresses a substantially different class of queries. Thi...

  18. CAD Instructor Designs Eco-Friendly Shed (United States)

    Schwendau, Mark


    Dissatisfied with the options offered by big box stores--and wanting to save some money and go as green as possible--the author puts his design and construction skills to good use. In this article, he shares how he designed and built an eco-friendly shed. He says he is very pleased with the results of working with his own design, reducing waste,…

  19. CAD Instructor Designs Eco-Friendly Shed (United States)

    Schwendau, Mark


    Dissatisfied with the options offered by big box stores--and wanting to save some money and go as green as possible--the author puts his design and construction skills to good use. In this article, he shares how he designed and built an eco-friendly shed. He says he is very pleased with the results of working with his own design, reducing waste,…

  20. Biology and biogenesis of shed microvesicles. (United States)

    Tricarico, Christopher; Clancy, James; D'Souza-Schorey, Crislyn


    The ability of cells to transmit bioactive molecules to recipient cells and the extracellular environment is a fundamental requirement for both normal physiology and disease pathogenesis. It has traditionally been thought that soluble factors released from cells were responsible for this cellular signaling but recent research has revealed a fundamental role for microvesicles in this process. Microvesicles are heterogeneous membrane-bound sacs that are shed from the surface of cells into the extracellular environment in a highly regulated process. They are shed following the selective incorporation of a host of molecular cargo including multiple types of proteins and nucleic acids. In addition to providing new insight into the etiology of complex human diseases, microvesicles also show great promise as a tool for advanced diagnosis and therapy as we move forward into a new age of personalized medicine. Here we review current status of the rapidly evolving field of microvesicle biology, highlighting critical regulatory roles for several small GTPases in the biology and biogenesis of shed microvesicles.

  1. Kinetics of viral shedding provide insights into the epidemiology of viral hemorrhagic septicemia in Pacific herring (United States)

    Hershberger, Paul K.; Gregg, Jacob L.; Winton, James R.; Grady, Courtney; Collins, Rachael


    Losses from infectious diseases are an important component of natural mortality among marine fish species, but factors controlling the ecology of these diseases and their potential responses to anthropogenic changes are poorly understood. We used viral hemorrhagic septicemia virus (VHSV) and a laboratory stock of Pacific herring Clupea pallasii to investigate the kinetics of viral shedding and its effect on disease transmission and host mortality. Outbreaks of acute disease, accompanied by mortality and viral shedding, were initiated after waterborne exposure of herring to concentrations of VHSV as low as 101 plaque-forming units (pfu) ml–1. Shed virus in flow-through tanks was first detected 4 to 5 d post-exposure, peaked after 6 to 10 d, and was no longer detected after 16 d. Shedding rates, calculated from density, flow and waterborne virus titer reached 1.8 to 5.0 × 108 pfu fish–1 d–1. Onset of viral shedding was dose-dependent and preceded initial mortality by 2 d. At 21 d, cumulative mortality in treatment groups ranged from 81 to 100% and was dependent not on challenge dose, but on the kinetics and level of viral shedding by infected fish in the tank. Possible consequences of the viral shedding and disease kinetics are discussed in the context of epizootic initiation and perpetuation among populations of wild Pacific herring.

  2. Disturbed Expression of EphB4, but Not EphrinB2, Inhibited Bone Regeneration in an In Vivo Inflammatory Microenvironment

    Directory of Open Access Journals (Sweden)

    Li-Li Shen


    Full Text Available The important role of ephrinB2-EphB4 signaling pathway in bone remodeling has been well established. However, it is still unclear whether this bidirectional signaling also has effects on the regenerative processes of bone defects created in an inflammatory microenvironment. In this study, an experimental animal model of bone defects treated with lentiviruses was prepared and an inflammatory microenvironment was established. Expression levels of bone marker genes were monitored in the newly formed bone tissue using quantitative reverse transcriptase polymerase chain reaction and western blot. Immunohistochemical (IHC staining and histomorphometric analysis were also performed to evaluate bone healing processes. Compared with the pLenti6.3-ctrl group, the pLenti6.3-ephb4siRNA group exhibited lower expression levels of bone formation marker genes and a higher level of NFATc1 in the new bone tissue. In addition, the newly formed bone was thinner and the number of giant osteoclasts was higher in the pLenti6.3-ephb4siRNA group than that in the pLenti6.3-ctrl group. In contrast, there was no significant difference between the pLenti6.3-efnb2siRNA group and the pLenti6.3-ctrl group. In conclusion, EphB4 plays an irreplaceable role in bone regeneration in an inflammatory microenvironment, whereas the functional loss of ephrinB2 can be effectively compensated, most possibly by other ephrins with similar chemical structures.

  3. Positively charged polymers modulate the fate of human mesenchymal stromal cells via ephrinB2/EphB4 signaling

    Directory of Open Access Journals (Sweden)

    Ilenia De Luca


    Full Text Available Understanding the mechanisms by which mesenchymal stromal cells (MSCs interact with the physical properties (e.g. topography, charge, ζ-potential, and contact angle of polymeric surfaces is essential to design new biomaterials capable of regulating stem cell behavior. The present study investigated the ability of two polymers (pHM1 and pHM3 with different positive surface charge densities to modulate the differentiation of MSCs into osteoblast-like phenotype via cell-cell ephrinB2/EphB4 signaling. Although pHM1 promoted the phosphorylation of EphB4, leading to cell differentiation, pHM3, characterized by a high positive surface charge density, had no significant effect on EphB4 activation or MSCs differentiation. When the MSCs were cultured on pHM1 in the presence of a forward signaling blocking peptide, the osteoblast differentiation was compromised. Our results demonstrated that the ephrinB2/EphB4 interaction was required for MSCs differentiation into an osteoblast-like phenotype and that the presence of a high positive surface charge density altered this interaction.

  4. The effect of ephrin-A1 on resistance to Photofrin-mediated photodynamic therapy in esophageal squamous cell carcinoma cells. (United States)

    Yang, Pei-Wen; Chiang, Tzu-Hsuan; Hsieh, Ching-Yueh; Huang, Ya-Chuan; Wong, Li-Fan; Hung, Mien-Chie; Tsai, Jui-Chang; Lee, Jang-Ming


    Esophageal squamous cell carcinoma (ESCC), the most prevalent cell type of esophageal cancer, remains a dismal disease with poor prognosis. Photodynamic therapy (PDT) is a minimally invasive treatment option for early esophageal cancer. To explore possible factors involved in resistance to PDT in esophageal cancer cells, we selected PDT-resistant subcell lines by repeated treatment of CE48T/VGH (CE48T) ESCC cells with Photofrin-PDT and then analyzed the global gene modulations in the PDT-resistant cells by whole-genome microarray. More than 700 genes reached a fold change greater than 1.5 in each of the PDT-resistant cells compared to parental cells. Among these genes, both tumor necrosis factor (TNF) and EFNA1 genes were significantly upregulated in resistant cell lines. However, they were significantly downregulated in Photofrin-PDT-treated cells compared to untreated cells. The observations made in the microarray analysis were further confirmed by quantitative PCR. We observed that recombinant tumor necrosis factor alpha (TNF-α) activated the gene expression of EFNA1 at both the messenger RNA (mRNA) level and the protein level in CE48T cells. Functional analysis showed that when incubated with oligomeric and monomeric ephrin-A1 simultaneously, ESCC cells became significantly resistant to Photofrin-PDT. Functional analysis further suggested that transmembrane and soluble ephrin-A1 may cooperate to enhance resistance to Photofrin-PDT in ESCC cells.

  5. Zika viral dynamics and shedding in rhesus and cynomolgus macaques (United States)

    Osuna, Christa E; Lim, So-Yon; Deleage, Claire; Griffin, Bryan D; Stein, Derek; Schroeder, Lukas T; Omange, Robert Were; Best, Katharine; Luo, Ma; Hraber, Peter T; Andersen-Elyard, Hanne; Ojeda, Erwing Fabian Cardozo; Huang, Scott; Vanlandingham, Dana L; Higgs, Stephen; Perelson, Alan S; Estes, Jacob D; Safronetz, David; Lewis, Mark G; Whitney, James B


    Infection with Zika virus has been associated with serious neurological complications and fetal abnormalities. However, the dynamics of viral infection, replication and shedding are poorly understood. Here we show that both rhesus and cynomolgus macaques are highly susceptible to infection by lineages of Zika virus that are closely related to, or are currently circulating in, the Americas. After subcutaneous viral inoculation, viral RNA was detected in blood plasma as early as 1 d after infection. Viral RNA was also detected in saliva, urine, cerebrospinal fluid (CSF) and semen, but transiently in vaginal secretions. Although viral RNA during primary infection was cleared from blood plasma and urine within 10 d, viral RNA was detectable in saliva and seminal fluids until the end of the study, 3 weeks after the resolution of viremia in the blood. The control of primary Zika virus infection in the blood was correlated with rapid innate and adaptive immune responses. We also identified Zika RNA in tissues, including the brain and male and female reproductive tissues, during early and late stages of infection. Re-infection of six animals 45 d after primary infection with a heterologous strain resulted in complete protection, which suggests that primary Zika virus infection elicits protective immunity. Early invasion of Zika virus into the nervous system of healthy animals and the extent and duration of shedding in saliva and semen underscore possible concern for additional neurologic complications and nonarthropod-mediated transmission in humans. PMID:27694931

  6. Numerical simulation of icing, deicing, and shedding (United States)

    Wright, W. B.; Dewitt, K. J.; Keith, T. G., Jr.


    An algorithm has been developed to numerically model the concurrent phenomena of two-dimensional transient heat transfer, ice accretion, ice shedding and ice trajectory which arise from the use of electrothermal pad. The Alternating Direction Implicit method is used to simultaneously solve the heat transfer and accretion equations occurring in the multilayered body covered with ice. In order to model the phase change between ice and water, a technique was used which assumes a phase for each node. This allows the equations to be linearized such that a direct solution is possible. This technique requires an iterative procedure to find the correct phase at each node. The computer program developed to find this solution has been integrated with the NASA-Lewis flow/trajectory code LEWICE.

  7. Anti-Ephrin Type-B Receptor 2 (EphB2) and Anti-Three Prime Histone mRNA EXonuclease 1 (THEX1) Autoantibodies in Scleroderma and Lupus (United States)

    Azzouz, Doua F.; Martin, Gabriel V.; Arnoux, Fanny; Balandraud, Nathalie; Martin, Thierry; Dubucquoi, Sylvain; Hachulla, Eric; Farge-Bancel, Dominique; Tiev, Kiet; Cabane, Jean; Bardin, Nathalie; Chiche, Laurent; Martin, Marielle; Caillet, Eléonore C.; Kanaan, Sami B.; Harlé, Jean Robert; Granel, Brigitte; Diot, Elisabeth; Roudier, Jean; Auger, Isabelle; Lambert, Nathalie C.


    In a pilot ProtoArray analysis, we identified 6 proteins out of 9483 recognized by autoantibodies (AAb) from patients with systemic sclerosis (SSc). We further investigated the 6 candidates by ELISA on hundreds of controls and patients, including patients with Systemic Lupus Erythematosus (SLE), known for high sera reactivity and overlapping AAb with SSc. Only 2 of the 6 candidates, Ephrin type-B receptor 2 (EphB2) and Three prime Histone mRNA EXonuclease 1 (THEX1), remained significantly recognized by sera samples from SSc compared to controls (healthy or with rheumatic diseases) with, respectively, 34% versus 14% (P = 2.10−4) and 60% versus 28% (P = 3.10−8). Above all, EphB2 and THEX1 revealed to be mainly recognized by SLE sera samples with respectively 56%, (P = 2.10−10) and 82% (P = 5.10−13). As anti-EphB2 and anti-THEX1 AAb were found in both diseases, an epitope mapping was realized on each protein to refine SSc and SLE diagnosis. A 15-mer peptide from EphB2 allowed to identify 35% of SLE sera samples (N = 48) versus only 5% of any other sera samples (N = 157), including SSc sera samples. AAb titers were significantly higher in SLE sera (P<0.0001) and correlated with disease activity (p<0.02). We could not find an epitope on EphB2 protein for SSc neither on THEX1 for SSc or SLE. We showed that patients with SSc or SLE have AAb against EphB2, a protein involved in angiogenesis, and THEX1, a 3’-5’ exoribonuclease involved in histone mRNA degradation. We have further identified a peptide from EphB2 as a specific and sensitive tool for SLE diagnosis. PMID:27617966

  8. A systematic study of modulation of ADAM-mediated ectodomain shedding by site-specific O-glycosylation

    DEFF Research Database (Denmark)

    Goth, Christoffer K; Halim, Adnan; Khetarpal, Sumeet A;


    -glycosylation is often found and examples of crosstalk between shedding and O-glycosylation have been reported. Here, we systematically investigated the potential of site-specific O-glycosylation mediated by distinct polypeptide GalNAc-transferase (GalNAc-T) isoforms to coregulate ectodomain shedding mediated...... by the A Disintegrin And Metalloproteinase (ADAM) subfamily of proteases and in particular ADAM17. We analyzed 25 membrane proteins that are known to undergo ADAM17 shedding and where the processing sites included Ser/Thr residues within ± 4 residues that could represent O-glycosites. We used in vitro GalNAc-T enzyme...... and ADAM cleavage assays to demonstrate that shedding of at least 12 of these proteins are potentially coregulated by O-glycosylation. Using TNF-α as an example, we confirmed that shedding mediated by ADAM17 is coregulated by O-glycosylation controlled by the GalNAc-T2 isoform both ex vivo in isogenic cell...

  9. A New Optimal Under Frequency Load Shedding in Micro Grids in Presence of Wind Turbines by using ANFIS Networks

    Directory of Open Access Journals (Sweden)

    Habib Amooshahi


    Full Text Available The benefits of renewable energy have led to the high penetration of Distributed Generators (DG in the distribution systems. Besides the technical, economical and environmental benefits, Microgrids can operate in islanded (autonomous modes. Microgrids need an effective load shedding system for the control of system frequency and voltage profile in an autonomous operation mode. The generation uncertainty of wind turbines in microgrids is analyzed in this paper and a new load shedding criteria has been proposed. Reactive power balance is an important problem with considering short electrical distances in microgrids and considering this basic fact, the proposed load shedding method uses a combination of frequency and voltage criteria. The total load shedding amount is determined by using transient stability analysis. This method is implemented by using ANFIS network in microgrids. Simulation results show the effectiveness of the proposed load shedding method.

  10. Neural net based determination of generator-shedding requirements in electric power systems

    Energy Technology Data Exchange (ETDEWEB)

    Djukanovic, M. (Electrical Engineering Inst. ' Nikola Tesla' , Belgrade (Yugoslavia)); Sobajic, D.J.; Pao, Y.-H. (Case Western Reserve Univ., Cleveland, OH (United States). Dept. of Electrical Engineering and Applied Physics Case Western Reserve Univ., Cleveland, OH (United States). Dept. of Computer Engineering and Science AI WARE Inc., Cleveland, OH (United States))


    This paper presents an application of artificial neural networks (ANN) in support of a decision-making process by power system operators directed towards the fast stabilisation of multi-machine systems. The proposed approach considers generator shedding as the most effective discrete supplementary control for improving the dynamic performance of faulted power systems and preventing instabilities. The sensitivity of the transient energy function (TEF) with respect to changes in the amount of dropped generation is used during the training phase of ANNs to assess the critical amount of generator shedding required to prevent the loss of synchronism. The learning capabilities of neural nets are used to establish complex mappings between fault information and the amount of generation to be shed, suggesting it as the control signal to the power system operator. (author)

  11. Shedding light on restoring respiratory function after spinal cord injury

    Directory of Open Access Journals (Sweden)

    Warren J Alilain


    Full Text Available Loss of respiratory function is one of the leading causes of death following spinal cord injury. Because of this, much work has been done in studying ways to restore respiratory function following SCI - including pharmacological and regeneration strategies. With the emergence of new and powerful tools from molecular neuroscience, new therapeutically relevant alternatives to these approaches have become available, including expression of light sensitive proteins called channelrhodopsins. In this article we briefly review the history of various attempts to restore breathing after C2 hemisection, and focus on our recent work using the activation of light sensitive channels to restore respiratory function after experimental spinal cord injury. We also discuss how such light induced activity can help shed light on the inner workings of the central nervous system respiratory circuitry that controls diaphragmatic function.

  12. Coagulation-induced shedding of platelet glycoprotein VI mediated by factor Xa. (United States)

    Al-Tamimi, Mohammad; Grigoriadis, George; Tran, Huy; Paul, Eldho; Servadei, Patricia; Berndt, Michael C; Gardiner, Elizabeth E; Andrews, Robert K


    This study evaluated shedding of the platelet collagen receptor, glycoprotein VI (GPVI) in human plasma. Collagen or other ligands induce metalloproteinase-mediated GPVI ectodomain shedding, generating approximately 55-kDa soluble GPVI (sGPVI) and approximately 10-kDa platelet-associated fragments. In the absence of GPVI ligands, coagulation of platelet-rich plasma from healthy persons induced GPVI shedding, independent of added tissue factor, but inhibitable by metalloproteinase inhibitor, GM6001. Factor Xa (FXa) common to intrinsic and tissue factor-mediated coagulation pathways was critical for sGPVI release because (1) shedding was strongly blocked by the FXa-selective inhibitor rivaroxaban but not FIIa (thrombin) inhibitors dabigatran or hirudin; (2) Russell viper venom that directly activates FX generated sGPVI, with complete inhibition by enoxaparin (inhibits FXa and FIIa) but not hirudin; (3) impaired GPVI shedding during coagulation of washed platelets resuspended in FX-depleted plasma was restored by adding purified FX; and (4) purified FXa induced GM6001-inhibitable GPVI shedding from washed platelets. In 29 patients with disseminated intravascular coagulation, mean plasma sGPVI was 53.9 ng/mL (95% confidence interval, 39.9-72.8 ng/mL) compared with 12.5 ng/mL (95% confidence interval, 9.0-17.3 ng/mL) in thrombocytopenic controls (n = 36, P coagulation-induced GPVI shedding via FXa down-regulates GPVI under procoagulant conditions. FXa inhibitors have an unexpected role in preventing GPVI down-regulation.

  13. A Bankruptcy Problem Approach to Load-shedding in Multiagent-based Microgrid Operation (United States)

    Kim, Hak-Man; Kinoshita, Tetsuo; Lim, Yujin; Kim, Tai-Hoon


    A microgrid is composed of distributed power generation systems (DGs), distributed energy storage devices (DSs), and loads. To maintain a specific frequency in the islanded mode as an important requirement, the control of DGs’ output and charge action of DSs are used in supply surplus conditions and load-shedding and discharge action of DSs are used in supply shortage conditions. Recently, multiagent systems for autonomous microgrid operation have been studied. Especially, load-shedding, which is intentional reduction of electricity use, is a critical problem in islanded microgrid operation based on the multiagent system. Therefore, effective schemes for load-shedding are required. Meanwhile, the bankruptcy problem deals with dividing short resources among multiple agents. In order to solve the bankruptcy problem, division rules, such as the constrained equal awards rule (CEA), the constrained equal losses rule (CEL), and the random arrival rule (RA), have been used. In this paper, we approach load-shedding as a bankruptcy problem. We compare load-shedding results by above-mentioned rules in islanded microgrid operation based on wireless sensor network (WSN) as the communication link for an agent’s interactions. PMID:22163386

  14. Interaction between leading and trailing edge vortex shedding: effects of bluff body geometry (United States)

    Taylor, Zachary; Kopp, Gregory; Gurka, Roi


    Elongated bluff bodies are distinguished from shorter bluff bodies (e.g., circular cylinders) by the fact that they have separating-reattaching flow at the leading edge as well as having vortex shedding at the trailing edge. Engineering examples of these bodies include heat exchanger fins and long-span suspension bridges. We have performed experiments on elongated bluff bodies of varying geometry. These experiments have been performed at Reynolds numbers O(104) based on the thickness of the model. Both surface pressure measurements (using 512 simultaneously sampled pressure taps) and PIV are used to quantify the flow fields of these bodies. The leading edge separation angle is controlled by changing the leading edge geometry. It is observed that the size of the leading edge separation bubble increases with increasing leading edge separation angle. As the size of the leading edge separation bubble increases, it is shown to continually decrease the shedding frequency for a given elongation ratio. It is suggested that the shedding frequency is diminished because the trailing edge vortex shedding is affected by the structures being shed from the leading edge separation bubble. The implications of this competition between leading and trailing edge flows will be explored.

  15. A bankruptcy problem approach to load-shedding in multiagent-based microgrid operation. (United States)

    Kim, Hak-Man; Kinoshita, Tetsuo; Lim, Yujin; Kim, Tai-Hoon


    A microgrid is composed of distributed power generation systems (DGs), distributed energy storage devices (DSs), and loads. To maintain a specific frequency in the islanded mode as an important requirement, the control of DGs' output and charge action of DSs are used in supply surplus conditions and load-shedding and discharge action of DSs are used in supply shortage conditions. Recently, multiagent systems for autonomous microgrid operation have been studied. Especially, load-shedding, which is intentional reduction of electricity use, is a critical problem in islanded microgrid operation based on the multiagent system. Therefore, effective schemes for load-shedding are required. Meanwhile, the bankruptcy problem deals with dividing short resources among multiple agents. In order to solve the bankruptcy problem, division rules, such as the constrained equal awards rule (CEA), the constrained equal losses rule (CEL), and the random arrival rule (RA), have been used. In this paper, we approach load-shedding as a bankruptcy problem. We compare load-shedding results by above-mentioned rules in islanded microgrid operation based on wireless sensor network (WSN) as the communication link for an agent's interactions.

  16. Effect of Map-vaccination in ewes on body condition score, weight and Map-shedding. (United States)

    Hüttner, Klim; Krämer, Ulla; Kleist, Petra


    Vaccination against Mycobacterium avium subspecies paratuberculosis (Map) in sheep receives growing attention worldwide, particularly in countries with national Map control strategies. A field study was conducted, investigating the effect of GUDAIR on body condition, weight and Map-shedding in a professionally managed but largely Map-affected suffolk flock prior and after vaccination. For this, 80 ewes out of 1000 animals were randomly sampled. In the univariate analysis body condition scores of ewes twelve months after vaccination improved significantly compared to those sampled prior to vaccination. At the same time the rate of ewes shedding Map was reduced by 37%.

  17. Dynamic Magnetic Responsive Wall Array with Droplet Shedding-off Properties. (United States)

    Wang, Lei; Zhang, Miaoxin; Shi, Weiwei; Hou, Yongping; Liu, Chengcheng; Feng, Shile; Guo, Zhenyu; Zheng, Yongmei


    Directional control of droplets on a surface is an important issue for tasks of long-range liquid-transport, self-cleaning and water repellency. However, it is still challenging to control the structure motions in orientations so as to control the shedding-off of droplets. Herein, we report a novel dynamic magnetic responsive wall (DMRW) array on PDMS (polydimethylsiloxane)-based surface. The walls can easily tilt through the effect of the external magnet because of the magnetic material in the DMRW. The droplets can be shed off directionally on the surface. Particularly, with the shape recovery and flexible properties, it achieves simultaneous control of the tilt angles (0-60°) of DMRW for shedding-off of droplets with different volumes (1-15 μL) under magnetic action on DMRW. The mechanism of droplet shedding-off on DMRW is elucidated by theory of interfaces. It offers an insight into design of dynamic interface for water repellency. This strategy realizes the preparation of multifunctional, tunable and directional drive functions.

  18. Adaptive Tuning of Frequency Thresholds Using Voltage Drop Data in Decentralized Load Shedding

    DEFF Research Database (Denmark)

    Hoseinzadeh, Bakhtyar; Faria Da Silva, Filipe Miguel; Bak, Claus Leth


    Load shedding (LS) is the last firewall and the most expensive control action against power system blackout. In the conventional under frequency LS (UFLS) schemes, the load drop locations are already determined independently of the event location. Furthermore, the frequency thresholds of LS relays...

  19. Fly proof net shed for livestock: A novel concept of physical barrier for integrated management of Culicoides spp. (Diptera: Ceratopogonidae

    Directory of Open Access Journals (Sweden)

    B. W. Narladkar


    Full Text Available Aim: An age old and time tested technique of mosquito net requiring no energy, used by humans since prehistoric period was the inspiration behind this novel technique of fly proof net shed for livestock. With the aim to develop similar type of net shed for animals, which will protect them at night from biting of range of insects from Culicoides midges to mosquitoes, research was undertaken. Materials and Methods: Net shed with pitch roof (gable type was erected for use of livestock. The open inlet area was covered with 40 mesh size wire net. The roof at attic level was fitted with hurricane type of ventilator. Shed was used for animals at night hours only. vane anemometer was used for estimation of temperature and wind related parameters. Thermal humidity index (THI and air changes were calculated as per the standard formulas. Based on these parameters suitability of shed was judged. Results: It was observed that, due to netting of the shed population of Culicoides and other flies and incidences of their bites at night hours were considerably lowered. As a result, animals were found comfortable, and their body movements undertaken for wiping off these flies were significantly reduced from 196.50 to 22.16. All it accrued to increased milk yield to the tune of 18.97% in the net shed buffaloes as against control shed. Studies on suitability and comfort to animals were tested by estimating THI and air changes per hour in the net shed, which also revealed the estimates in comfortable regimen and ventilation, remained not much affected despite of netting. Other parameters studied for testing its more accuracy by taking other species of animals as kids, for them also, shed was found suitable through estimation of various physiological and behavioral parameters. Finally, the efficacy of shed was judged on the basis of cost effectiveness. Highly encouraging results on the above said parameters endorsed the effectiveness of the technique. Conclusion: A

  20. Application of active power sensitivity to frequency and voltage variations on load shedding

    Energy Technology Data Exchange (ETDEWEB)

    Girgis, Adly A. [Clemson University, 303 Riggs Hall, Clemson, SC 29634-0915 (United States); Mathure, Shruti [ITC Holdings, MI (United States)


    The occurrence of a large disturbance in a power system can lead to a decline in the system frequency and bus voltages due to a real and reactive power deficiency or due to the formation of islands with generation-load imbalance. Load shedding is an emergency control action that can prevent a blackout in the power system by relieving the overload in some parts of the system. This paper shows that rate of change of frequency can be utilized to determine the magnitude of generation-load imbalance, while the rate of change of voltage with respect to active power can be utilized to identify the sensitive bus for load shedding. The frequency, voltages and their rate of change can be obtained by means of measurements in real-time from various devices such as digital recorders or phasor measurement units or these parameters can be estimated from the voltage data by other means such as an optimal estimation method like Kalman filtering. The rate of change of system frequency, along with the equivalent system inertia may be used to estimate the magnitude of the disturbance prior to each load shedding step. The buses with a higher rate of change of voltage may be identified as the critical ones for load shedding and load can be first shed at these buses, depending on the change in the power flow at each bus. This application is tested on the IEEE 30 bus system and the preliminary results demonstrate that it is feasible to be used in load shedding to restore system voltage and frequency. (author)

  1. Systematic review of mucosal immunity induced by oral and inactivated poliovirus vaccines against virus shedding following oral poliovirus challenge.

    Directory of Open Access Journals (Sweden)

    Thomas R Hird

    Full Text Available Inactivated poliovirus vaccine (IPV may be used in mass vaccination campaigns during the final stages of polio eradication. It is also likely to be adopted by many countries following the coordinated global cessation of vaccination with oral poliovirus vaccine (OPV after eradication. The success of IPV in the control of poliomyelitis outbreaks will depend on the degree of nasopharyngeal and intestinal mucosal immunity induced against poliovirus infection. We performed a systematic review of studies published through May 2011 that recorded the prevalence of poliovirus shedding in stool samples or nasopharyngeal secretions collected 5-30 days after a "challenge" dose of OPV. Studies were combined in a meta-analysis of the odds of shedding among children vaccinated according to IPV, OPV, and combination schedules. We identified 31 studies of shedding in stool and four in nasopharyngeal samples that met the inclusion criteria. Individuals vaccinated with OPV were protected against infection and shedding of poliovirus in stool samples collected after challenge compared with unvaccinated individuals (summary odds ratio [OR] for shedding 0.13 (95% confidence interval [CI] 0.08-0.24. In contrast, IPV provided no protection against shedding compared with unvaccinated individuals (summary OR 0.81 [95% CI 0.59-1.11] or when given in addition to OPV, compared with individuals given OPV alone (summary OR 1.14 [95% CI 0.82-1.58]. There were insufficient studies of nasopharyngeal shedding to draw a conclusion. IPV does not induce sufficient intestinal mucosal immunity to reduce the prevalence of fecal poliovirus shedding after challenge, although there was some evidence that it can reduce the quantity of virus shed. The impact of IPV on poliovirus transmission in countries where fecal-oral spread is common is unknown but is likely to be limited compared with OPV.

  2. Systematic review of mucosal immunity induced by oral and inactivated poliovirus vaccines against virus shedding following oral poliovirus challenge. (United States)

    Hird, Thomas R; Grassly, Nicholas C


    Inactivated poliovirus vaccine (IPV) may be used in mass vaccination campaigns during the final stages of polio eradication. It is also likely to be adopted by many countries following the coordinated global cessation of vaccination with oral poliovirus vaccine (OPV) after eradication. The success of IPV in the control of poliomyelitis outbreaks will depend on the degree of nasopharyngeal and intestinal mucosal immunity induced against poliovirus infection. We performed a systematic review of studies published through May 2011 that recorded the prevalence of poliovirus shedding in stool samples or nasopharyngeal secretions collected 5-30 days after a "challenge" dose of OPV. Studies were combined in a meta-analysis of the odds of shedding among children vaccinated according to IPV, OPV, and combination schedules. We identified 31 studies of shedding in stool and four in nasopharyngeal samples that met the inclusion criteria. Individuals vaccinated with OPV were protected against infection and shedding of poliovirus in stool samples collected after challenge compared with unvaccinated individuals (summary odds ratio [OR] for shedding 0.13 (95% confidence interval [CI] 0.08-0.24)). In contrast, IPV provided no protection against shedding compared with unvaccinated individuals (summary OR 0.81 [95% CI 0.59-1.11]) or when given in addition to OPV, compared with individuals given OPV alone (summary OR 1.14 [95% CI 0.82-1.58]). There were insufficient studies of nasopharyngeal shedding to draw a conclusion. IPV does not induce sufficient intestinal mucosal immunity to reduce the prevalence of fecal poliovirus shedding after challenge, although there was some evidence that it can reduce the quantity of virus shed. The impact of IPV on poliovirus transmission in countries where fecal-oral spread is common is unknown but is likely to be limited compared with OPV.

  3. Insulation Characteristics of Bushing Shed at Cryogenic Temperature (United States)

    Kim, W. J.; Kim, Y. J.; Kim, S. H.


    In the development of high-Tc superconducting(HTS) devices, the bushing for HTS devices (HTS bushing) is the core technology, the need to because of supply high voltage to the cable or the winding of the transformer. The lower part of the bushing is exposed to the liquid nitrogen (LN2), and it has many sheds. In particular, the insulation body with sheds and electrical insulation at cryogenic temperature have attracted a great deal of interest from the view point of the size, weight and efficiency of bushing. This study has mainly investigated the shed and insulation body by comparing glass fiber reinforced plastics (GFRP) in LN2. We investigated the surface discharge characteristics according to insulating materials, width and height of the shed.

  4. Study Sheds Light on Safety of Driving with Epilepsy (United States)

    ... Study Sheds Light on Safety of Driving With Epilepsy Those who had longer seizures during driving tests ... SUNDAY, Dec. 4, 2016 (HealthDay News) -- People with epilepsy who experienced longer seizures during a simulated driving ...

  5. Oral shedding of herpes simplex virus type 2


    Wald, A; Ericsson, M.; Krantz, E; Selke, S; Corey, L


    Objectives: Herpes simplex virus (HSV) 1 and HSV-2 reactivate preferentially in the oral and genital area, respectively. We aimed to define frequency and characteristics associated with oral shedding of HSV-2.

  6. Vortex shedding effects in grid-generated turbulence (United States)

    Melina, G.; Bruce, P. J. K.; Vassilicos, J. C.


    The flow on the centerline of grid-generated turbulence is characterized via hot-wire anemometry for three grids with different geometry: a regular grid (RG60), a fractal grid (FSG17), and a single-square grid (SSG). Due to a higher value of the thickness t0 of its bars, SSG produces greater values of turbulence intensity Tu than FSG17, despite SSG having a smaller blockage ratio. However, the higher Tu for SSG is mainly due to a more pronounced vortex shedding contribution. The effects of vortex shedding suppression along the streamwise direction x are studied by testing a three-dimensional configuration, formed by SSG and a set of four splitter plates detached from the grid (SSG+SP). When vortex shedding is damped, the centerline location of the peak of turbulence intensity xpeak moves downstream and Tu considerably decreases in the production region. For FSG17 the vortex shedding is less intense and it disappears more quickly, in terms of x /xpeak , when compared to all the other configurations. When vortex shedding is attenuated, the integral length scale Lu grows more slowly in the streamwise direction, this being verified both for FSG17 and for SSG+SP. In the production region, there is a correlation between the vortex shedding energy and the skewness and the flatness of the velocity fluctuations. When vortex shedding is not significant, the skewness is highly negative and the flatness is much larger than 3. On the opposite side, when vortex shedding is prominent, the non-Gaussian behavior of the velocity fluctuations becomes masked.

  7. Subclinical Shed of Infectious Varicella zoster Virus in Astronauts (United States)

    Cohrs, Randall J.; Mehta, Satish K.; Schmid, D. Scott; Gilden, Donald H.; Pierson, Duane L.


    Aerosol borne varicella zoster virus (VZV) enters the nasopharynx and replicates in tonsillar T-cells, resulting in viremia and varicella (chickenpox). Virus then becomes latent in cranial nerve, dorsal root and autonomic nervous system ganglia along the entire neuraxis (1). Decades later, as cell-mediated immunity to VZV declines (4), latent VZV can reactivate to produce zoster (shingles). Infectious VZV is present in patients with varicella or zoster, but shed of infectious virus in the absence of disease has not been shown. We previously detected VZV DNA in saliva of astronauts during and shortly after spaceflight, suggesting stress induced subclinical virus reactivation (3). We show here that VZV DNA as well as infectious virus in present in astronaut saliva. VZV DNA was detected in saliva during and after a 13-day spaceflight in 2 of 3 astronauts (Fig. panel A). Ten days before liftoff, there was a rise in serum anti-VZV antibody in subjects 1 and 2, consistent with virus reactivation. In subject 3, VZV DNA was not detected in saliva, and there was no rise in anti-VZV antibody titer. Subject 3 may have been protected from virus reactivation by having zoster boost in cell-medicated immunity to VZV (2). No VZV DNA was detected in astronaut saliva months before spaceflight, or in saliva of 10 age/sex-matched healthy control subjects sampled on alternate days for 3 weeks (88 saliva samples). Saliva taken 2-6 days after landing from all 3 subjects was cultured on human fetal lung cells (Fig. panel B). Infectious VZV was recovered from saliva of subjects 1 and 2 on the second day after landing. Virus specificity was confirmed by antibody staining and DNA analysis which showed it to be VZV of European descent, common in the US (5). Further, both antibody staining and DNA PCR demonstrated that no HSV-1 was detected in any infected culture. This is the first report of infectious VZV shedding in the absence of clinical disease. Spaceflight presents a uniquely stressful

  8. Epstein-Barr virus shedding by astronauts during space flight (United States)

    Pierson, D. L.; Stowe, R. P.; Phillips, T. M.; Lugg, D. J.; Mehta, S. K.


    Patterns of Epstein-Barr virus (EBV) reactivation in 32 astronauts and 18 healthy age-matched control subjects were characterized by quantifying EBV shedding. Saliva samples were collected from astronauts before, during, and after 10 space shuttle missions of 5-14 days duration. At one time point or another, EBV was detected in saliva from each of the astronauts. Of 1398 saliva specimens from 32 astronauts, polymerase chain reaction analysis showed that 314 (23%) were positive for EBV DNA. Examination by flight phase showed that 29% of the saliva specimens collected from 28 astronauts before flight were positive for EBV DNA, as were 16% of those collected from 25 astronauts during flight and 16% of those collected after flight from 23 astronauts. The mean number of EBV copies from samples taken during the flights was 417 per mL, significantly greater (pEBV DNA with a frequency of 3.7% and mean number of EBV copies of 40 per mL of saliva. Ten days before flight and on landing day, titers of antibody to EBV viral capsid antigen were significantly (pEBV-specific antibody were consistent with EBV reactivation before, during, and after space flight.

  9. Correlates of HIV-1 genital shedding in Tanzanian women.

    Directory of Open Access Journals (Sweden)

    Clare Tanton

    Full Text Available BACKGROUND: Understanding the correlates of HIV shedding is important to inform strategies to reduce HIV infectiousness. We examined correlates of genital HIV-1 RNA in women who were seropositive for both herpes simplex virus (HSV-2 and HIV-1 and who were enrolled in a randomised controlled trial of HSV suppressive therapy (aciclovir 400 mg b.i.d vs. placebo in Tanzania. METHODOLOGY: Samples, including a cervico-vaginal lavage, were collected and tested for genital HIV-1 and HSV and reproductive tract infections (RTIs at randomisation and 6, 12 and 24 months follow-up. Data from all women at randomisation and women in the placebo arm during follow-up were analysed using generalised estimating equations to determine the correlates of cervico-vaginal HIV-1 RNA detection and load. PRINCIPAL FINDINGS: Cervico-vaginal HIV-1 RNA was detected at 52.0% of 971 visits among 482 women, and was independently associated with plasma viral load, presence of genital ulcers, pregnancy, bloody cervical or vaginal discharge, abnormal vaginal discharge, cervical ectopy, Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, an intermediate bacterial vaginosis score and HSV DNA detection. Similar factors were associated with genital HIV-1 RNA load. CONCLUSIONS: RTIs were associated with increased presence and quantity of genital HIV-1 RNA in this population. These results highlight the importance of integrating effective RTI treatment into HIV care services.

  10. Ebola Virus Shedding and Transmission: Review of Current Evidence. (United States)

    Vetter, Pauline; Fischer, William A; Schibler, Manuel; Jacobs, Michael; Bausch, Daniel G; Kaiser, Laurent


     The magnitude of the 2013-2016 Ebola virus disease outbreak in West Africa was unprecedented, with >28 500 reported cases and >11 000 deaths. Understanding the key elements of Ebola virus transmission is necessary to implement adequate infection prevention and control measures to protect healthcare workers and halt transmission in the community.  We performed an extensive PubMed literature review encompassing the period from discovery of Ebola virus, in 1976, until 1 June 2016 to evaluate the evidence on modes of Ebola virus shedding and transmission.  Ebola virus has been isolated by cell culture from blood, saliva, urine, aqueous humor, semen, and breast milk from infected or convalescent patients. Ebola virus RNA has been noted in the following body fluids days or months after onset of illness: saliva (22 days), conjunctiva/tears (28 days), stool (29 days), vaginal fluid (33 days), sweat (44 days), urine (64 days), amniotic fluid (38 days), aqueous humor (101 days), cerebrospinal fluid (9 months), breast milk (16 months [preliminary data]), and semen (18 months). Nevertheless, the only documented cases of secondary transmission from recovered patients have been through sexual transmission. We did not find strong evidence supporting respiratory or fomite-associated transmission. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail

  11. Dynamics of Persistent Oral Cytomegalovirus Shedding During Primary Infection in Ugandan Infants. (United States)

    Mayer, Bryan T; Matrajt, Laura; Casper, Corey; Krantz, Elizabeth M; Corey, Lawrence; Wald, Anna; Gantt, Soren; Schiffer, Joshua T


    Cytomegalovirus (CMV) infection occurs frequently in young children, who, when infected, are then a major source of transmission. Oral CMV shedding by 14 infants with primary infection was comprehensively characterized using quantitative polymerase chain reaction weekly for ≥9 months. Three phases of oral shedding were identified: expansion, transition, and clearance. Viral expansion occurred over a median of 7 weeks, with a median doubling time of 3 days. During the transition phase, expansion slowed over a median of 6 weeks before peak viral load was reached. Clearance was slow (22-day median half-life), and shedding did not resolve during observation for any infant. Mathematical modeling demonstrated that prolonged oral CMV expansion is explained by a low within-host reproduction number (median, 1.63) and a delayed immune response that only decreases the infected cell half-life by 44%. Thus, the prolonged oral CMV shedding observed during primary infection can be explained by slow viral expansion and inefficient immunologic control. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail

  12. Systematic review of influenza A(H1N1)pdm09 virus shedding: duration is affected by severity, but not age. (United States)

    Fielding, James E; Kelly, Heath A; Mercer, Geoffry N; Glass, Kathryn


    Duration of viral shedding following infection is an important determinant of disease transmission, informing both control policies and disease modelling. We undertook a systematic literature review of the duration of influenza A(H1N1)pdm09 virus shedding to examine the effects of age, severity of illness and receipt of antiviral treatment. Studies were identified by searching the PubMed database using the keywords 'H1N1', 'pandemic', 'pandemics', 'shed' and 'shedding'. Any study of humans with an outcome measure of viral shedding was eligible for inclusion in the review. Comparisons by age, degree of severity and antiviral treatment were made with forest plots. The search returned 214 articles of which 22 were eligible for the review. Significant statistical heterogeneity between studies precluded meta-analysis. The mean duration of viral shedding generally increased with severity of clinical presentation, but we found no evidence of longer shedding duration of influenza A(H1N1)pdm09 among children compared with adults. Shorter viral shedding duration was observed when oseltamivir treatment was administered within 48 hours of illness onset. Considerable differences in the design and analysis of viral shedding studies limit their comparison and highlight the need for a standardised approach. These insights have implications not only for pandemic planning, but also for informing responses and study of seasonal influenza now that the A(H1N1)pdm09 virus has become established as the seasonal H1N1 influenza virus.

  13. Synthetic sex pheromone attracts the leishmaniasis vector Lutzomyia longipalpis to experimental chicken sheds treated with insecticide

    Directory of Open Access Journals (Sweden)

    Brazil Reginaldo P


    Full Text Available Abstract Background Current strategies for controlling American visceral leishmaniasis (AVL have been unable to prevent the spread of the disease across Brazil. With no effective vaccine and culling of infected dogs an unpopular and unsuccessful alternative, new tools are urgently needed to manage populations of the sand fly vector, Lutzomyia longipalpis Lutz and Neiva (Diptera: Psychodidae. Here, we test two potential strategies for improving L. longipalpis control using the synthetic sand fly pheromone (±-9-methylgermacrene-B: the first in conjunction with spraying of animal houses with insecticide, the second using coloured sticky traps. Results Addition of synthetic pheromone resulted in greater numbers of male and female sand flies being caught and killed at experimental chicken sheds sprayed with insecticide, compared to pheromone-less controls. Furthermore, a ten-fold increase in the amount of sex pheromone released from test sheds increased the number of females attracted and subsequently killed. Treating sheds with insecticide alone resulted in a significant decrease in numbers of males attracted to sheds (compared to pre-spraying levels, and a near significant decrease in numbers of females. However, this effect was reversed through addition of synthetic pheromone at the time of insecticide spraying, leading to an increase in number of flies attracted post-treatment. In field trials of commercially available different coloured sticky traps, yellow traps caught more males than blue traps when placed in chicken sheds. In addition, yellow traps fitted with 10 pheromone lures caught significantly more males than pheromone-less controls. However, while female sand flies showed a preference for both blue and yellow pheromone traps sticky traps over white traps in the laboratory, neither colour caught significant numbers of females in chicken sheds, either with or without pheromone. Conclusions We conclude that synthetic pheromone could

  14. How do seal whiskers suppress vortex shedding (United States)

    Rinehart, Aidan; Flaherty, Justin; Bunjavick, Joseph; Shyam, Vikram; Zhang, Wei


    Certain seal whiskers possess a unique geometry that significantly reduces the vortex-induced vibration; which has attracted great attention to understand how the unique shape re-organizes the wake structure and its potential for passive flow control. The shape of the whiskers can be described as an elliptical cross-section that is lofted along the length of the whisker. Along the entire length of the whisker the ellipse varies in major and minor axis as well as angle of incidence with respect to the axis of the whisker. Of particular interest in this study is to identify what effect the angle of incidence has on the flow structure around the whisker, which has been overlooked in the past. The study will analyze the wake structure behind various scaled-up whisker models using particle image velocimitry (PIV). These whisker models share common geometry dimensions except for the angle of incidence. Flow conditions are created in a water channel and a wind tunnel, covering a wide range of Reynolds number (a few hundreds to thousands), similar to the ambient flow environment of seals and to the targeted aero-propulsion applications. This study will help address knowledge gaps in understanding of how certain geometry features of seal whiskers influence the wake and establish best practices for its application as effective passive flow control strategy.

  15. Proteolytic shedding of the macrophage scavenger receptor CD163 in multiple sclerosis

    DEFF Research Database (Denmark)

    Fabriek, Babs O; Møller, Holger J; Vloet, Rianka P M


    The scavenger receptor CD163 is selectively expressed on tissue macrophages and human monocytes. CD163 has been implicated to play a role in the clearance of hemoglobin and in the regulation of cytokine production by macrophages. Membrane CD163 can be cleaved by matrix metalloproteinases (MMP......) resulting in soluble CD163 (sCD163). In the present report the shedding of CD163 was investigated in multiple sclerosis (MS). An upregulation of plasma sCD163 and a down regulation of membrane CD163 in MS patients compared to healthy controls was observed. The levels of plasma sCD163 correlated with plasma...... MMP-9 levels in controls, but not in MS patients. Moreover, evidence was obtained for CD163-cleaving MMP activity in plasma of MS patients. Finally, the increased proteolytic shedding of CD163 correlated to reduced plasma levels of circulating inflammatory cytokines. Collectively, our results provide...

  16. Evaluation of Faecal Salmonella Shedding Among Dogs at Seven Animal Shelters across Texas. (United States)

    Leahy, A M; Cummings, K J; Rodriguez-Rivera, L D; Rankin, S C; Hamer, S A


    Estimates of prevalence of faecal Salmonella shedding among dogs in the United States have varied widely. Surveillance among shelter dogs has been limited, although dogs in animal shelters may be at elevated risk of Salmonella infection because of their previous exposure history as well as factors inherent to shelter environments. Our objectives were to estimate the prevalence of Salmonella shedding among shelter dogs across Texas, to identify risk factors for shedding and to characterize the isolates. Using a repeated cross-sectional study design, we collected faecal samples from dogs on two or three visits to each of seven Texas animal shelters between May 2013 and December 2014. Standard bacteriologic culture methods were used to isolate Salmonella from samples, and isolates were characterized via serotyping and anti-microbial susceptibility testing. The prevalence of faecal Salmonella shedding among sampled dogs was 4.9% (27/554), and within-shelter prevalence ranged from 1.9% to 8.3%. There was a marginal association (P = 0.09) between watery faecal samples and positive Salmonella status, as estimated by a logistic regression model that controlled for shelter as a random effect. However, over 60% of Salmonella-positive dogs had grossly normal faeces. Salmonella prevalence did not vary significantly by age group or sex. The most common serovars were Newport (22%) and Javiana (15%), both of which were widespread among shelters. Resistance to anti-microbial agents was uncommon. The prevalence of faecal Salmonella shedding among shelter dogs in Texas appears to be comparable to that seen among pet dogs in general. © 2016 Blackwell Verlag GmbH.

  17. Rac1 regulates platelet shedding of CD40L in abdominal sepsis. (United States)

    Hwaiz, Rundk; Rahman, Milladur; Zhang, Enming; Thorlacius, Henrik


    Matrix metalloproteinase-9 (MMP-9) regulates platelet shedding of CD40L in abdominal sepsis. However, the signaling mechanisms controlling sepsis-induced shedding of CD40L from activated platelets remain elusive. Rac1 has been reported to regulate diverse functions in platelets; we hypothesized herein that Rac1 might regulate platelet shedding of CD40L in sepsis. The specific Rac1 inhibitor NSC23766 (N6-[2-[[4-(diethylamino)-1-methylbutyl] amino]-6-methyl-4-pyrimidinyl]-2 methyl-4, 6-quinolinediamine trihydrochloride) was administered to mice undergoing cecal ligation and puncture (CLP). Levels of CD40L and MMP-9 in plasma, platelets, and neutrophils were determined by use of ELISA, western blot, and confocal microscopy. Platelet depletion abolished the CLP-induced increase in plasma levels of CD40L. Rac1 activity was significantly increased in platelets from septic animals. Administration of NSC23766 abolished the CLP-induced enhancement of soluble CD40L levels in the plasma. Moreover, Rac1 inhibition completely inhibited proteinase-activated receptor-4-induced surface mobilization and secretion of CD40L in isolated platelets. CLP significantly increased plasma levels of MMP-9 and Rac1 activity in neutrophils. Treatment with NSC23766 markedly attenuated MMP-9 levels in the plasma from septic mice. In addition, Rac1 inhibition abolished chemokine-induced secretion of MMP-9 from isolated neutrophils. Finally, platelet shedding of CD40L was significantly reduced in response to stimulation with supernatants from activated MMP-9-deficient neutrophils compared with supernatants from wild-type neutrophils, indicating a direct role of neutrophil-derived MMP-9 in regulating platelet shedding of CD40L. Our novel data suggest that sepsis-induced platelet shedding of CD40L is dependent on Rac1 signaling. Rac1 controls surface mobilization of CD40L on activated platelets and MMP-9 secretion from neutrophils. Thus, our findings indicate that targeting Rac1 signaling might be a

  18. Suppression of vortex shedding around a square cylinder using blowing

    Indian Academy of Sciences (India)

    Arun K Saha; Ankit Shrivastava


    Direct numerical simulation (DNS) of flow past a square cylinder at a Reynolds number of 100 has been carried out to explore the effect of blowing in the form of jet(s) on vortex shedding. Higher order spatial as well as temporal discretization has been employed for the discretization of governing equations. The varying number of jets, jet velocity profiles and different blowing velocities are studied to investigate the characteristics of vortex shedding. The parabolic velocity profile has been found to be more effective in suppressing the vortex shedding as compared to the uniform velocity. Complete suppression of vortex shedding along with remarkable reduction in drag coefficient has been achieved for both jet velocity profiles but at different velocities. The corresponding values for uniform and parabolic jet profiles are 0.87 and 0.6, respectively at a mass flux of 0.120. The study also reveals that there is considerable effect of the number of jets on the vortex shedding phenomena.

  19. An NF-κB--EphrinA5-Dependent Communication between NG2(+) Interstitial Cells and Myoblasts Promotes Muscle Growth in Neonates. (United States)

    Gu, Jin-Mo; Wang, David J; Peterson, Jennifer M; Shintaku, Jonathan; Liyanarachchi, Sandya; Coppola, Vincenzo; Frakes, Ashley E; Kaspar, Brian K; Cornelison, Dawn D; Guttridge, Denis C


    Skeletal muscle growth immediately following birth is critical for proper body posture and locomotion. However, compared with embryogenesis and adulthood, the processes regulating the maturation of neonatal muscles is considerably less clear. Studies in the 1960s predicted that neonatal muscle growth results from nuclear accretion of myoblasts preferentially at the tips of myofibers. Remarkably, little information has been added since then to resolve how myoblasts migrate to the ends of fibers. Here, we provide insight into this process by revealing a unique NF-κB-dependent communication between NG2(+) interstitial cells and myoblasts. NF-κB in NG2(+) cells promotes myoblast migration to the tips of myofibers through cell-cell contact. This occurs through expression of ephrinA5 from NG2(+) cells, which we further deduce is an NF-κB target gene. Together, these results suggest that NF-κB plays an important role in the development of newborn muscles to ensure proper myoblast migration for fiber growth.

  20. Ephrin-B2–Activated Peripheral Blood Mononuclear Cells From Diabetic Patients Restore Diabetes-Induced Impairment of Postischemic Neovascularization (United States)

    Broquères-You, Dong; Leré-Déan, Carole; Merkulova-Rainon, Tatiana; Mantsounga, Chris S.; Allanic, David; Hainaud, Patricia; Contrères, Jean-Olivier; Wang, Yu; Vilar, José; Virally, Marie; Mourad, Jean-Jacques; Guillausseau, Pierre-Jean; Silvestre, Jean-Sébastien; Lévy, Bernard I.


    We hypothesized that in vitro treatment of peripheral blood mononuclear cells (PB-MNCs) from diabetic patients with ephrin-B2/Fc (EFNB2) improves their proangiogenic therapeutic potential in diabetic ischemic experimental models. Diabetes was induced in nude athymic mice by streptozotocin injections. At 9 weeks after hyperglycemia, 105 PB-MNCs from diabetic patients, pretreated by EFNB2, were intravenously injected in diabetic mice with hindlimb ischemia. Two weeks later, the postischemic neovascularization was evaluated. The mechanisms involved were investigated by flow cytometry analysis and in vitro cell biological assays. Paw skin blood flow, angiographic score, and capillary density were significantly increased in ischemic leg of diabetic mice receiving EFNB2-activated diabetic PB-MNCs versus those receiving nontreated diabetic PB-MNCs. EFNB2 bound to PB-MNCs and increased the adhesion and transmigration of PB-MNCs. Finally, EFNB2-activated PB-MNCs raised the number of circulating vascular progenitor cells in diabetic nude mice and increased the ability of endogenous bone marrow MNCs to differentiate into cells with endothelial phenotype and enhanced their proangiogenic potential. Therefore, EFNB2 treatment of PB-MNCs abrogates the diabetes-induced stem/progenitor cell dysfunction and opens a new avenue for the clinical development of an innovative and accessible strategy in diabetic patients with critical ischemic diseases. PMID:22596048

  1. DXNN Platform: The Shedding of Biological Inefficiencies

    CERN Document Server

    Sher, Gene I


    In this paper I present a novel type of Topology and Weight Evolving Artificial Neural Network (TWEANN) system called Monolithic Discover & eXplore Neural Network (DXNN), a monolithic variant of the standard DXNN which utilized explicit modularity. Among the novel features presented in this paper is a simple and database friendly tuple based encoding of NNs, a 2 phase neuroevolutionary approach aimed at removing the need for speciation, a new "Targeted Tuning Phase" aimed at dealing with "the curse of dimensionality", and a new Random Intensity Mutation (RIM) method that removes the need for cross-over algorithms. I will discuss DXNN's mutation operators and its built in feature selection method that allows for the evolved system to expand, discover, and explore new sensors and actuators. I will then compare the DXNN platform to other state of the art TWEANNs on a control task, to demonstrate its superior ability to produce highly compact solutions faster than its competitors, and then perform oblation ex...

  2. Ephrin B2 is involved in Porphyromonas gingivalis infection-enhanced adhesion of THP-1 to human umbilical vein endothelial cells%肝配蛋白B2在牙龈卟啉单胞菌诱导单核细胞黏附人脐静脉内皮细胞中的作用

    Institute of Scientific and Technical Information of China (English)

    张彩霞; 宋洁; 徐杨; 吴娟; 孙卫斌; 李宽钰


    Objective To investigate the mechanisms of Porphyromonas gingivalis(Pg) infection-mediated enhancement of adhesion between monocytes THP-1 and human umbilical vein endothelial cells(HUVEC) by detecting the effect of erythropoietin producing hepatomocellular receptor interacting protein B2(Ephrin B2) and its receptors on the adhesion.Methods PgATCC33277 was cultured in an anaerobic jar,and THP-1 cells were infected with various concentrations of Pg at multiplicity of infection(MOI) of 1:100 for 8 and 24 h,respectively.The expression of Ephrin B2 receptor of THP-1 cells was detected.After removal of the free Pg,THP-1 cells were cocultured with HUVEC(overexpress of EphrinB2 or not) for 24 h to detect the expression of Ephrin B2 of HUVEC cells after additional cultivation for 23 h.Results The adhesion of THP-1 cells post infection by Pg to HUVEC was enhanced.The mRNA levels of Ephrin B2 receptors,including EphB3(5.169±0.152,P=0.005),EphB4(11.040± 1.195,P=0.001),and EphA4(4.976± 0.122,P=0.001) expressed by THP-1,and Ephrin B2(8.938±0.962,P=0.008) expressed by HUVEC were significantly elevated 24 h post infection of Pg.Over expression of Ephrin B2 in HUVEC promoted the adhesion of THP-1 to HUVEC.Conclusions Ephrin B2 and its receptors are involved in Pg infection mediated enhancement of the adhesion of THP-1 to HUVEC cells,suggesting that Ephrin B2 participates in the development of atherosclerosis.%目的 检测肝配蛋白B2 (erythropoietin producing hepatomocellular receptor interacting protein B2,Ephrin B2)及其受体在单核细胞THP-1黏附人脐静脉内皮细胞(human umbilical vein endothelial cell,HUVEC)中的作用,揭示牙龈卟啉单胞菌(Porphyromonas gingivalis,Pg)感染增强THP-1黏附HUVEC的分子机制.方法 应用厌氧罐培养Pg,以感染复数1∶100感染人单核细胞株THP-1,感染8和24 h后,收集部分样品分别用于检测THP-1细胞Ephrin B2及其受体表达水平的变化;其余样品与转染空载体或过表达Ephrin B2

  3. Stochastic oscillations induced by vortex shedding in wind

    DEFF Research Database (Denmark)

    Christensen, Claus


    As a fluid flows past a circular cylinder,vortices are shed alternately from each side at most values of the Reynolds number. Over a certain range of windspeeds, the periodicity in the wake is synchronized or captured by the mechanical system. The shedding abruptly deviates from the linear Strouhal...... dependence and stays constant at the mechanical natural frequency. This coupling between the velocity field and the motion of the mechanical system is referred to as the lock-in phenomenon. The lock-in phenomenon has importance in structural engineering for slightly damped slender structures exposed to wind...... are supported by experimental wind tunnel investigations. Department of Structural Engineering and Materials, DTUSeries R No 23 1997As a fluid flows past a circular cylinder, vortices are shed alternately from each side at most values of the Reynolds number. Over a certain range of windspeeds, the periodicity...

  4. A study on the frictional response of reptilian shed skin (United States)

    Abdel-Aal, H. A.; Vargiolu, R.; Zahouani, H.; El Mansori, M.


    Deterministic surfaces are constructs of which profile, topography and textures are integral to the function of the system they enclose. They are designed to yield a predetermined tribological response. Developing such entities relies on controlling the structure of the rubbing interface so that, not only the surface is of optimized topography, but also is able to self-adjust its tribological behaviour according to the evolution of sliding conditions. In seeking inspirations for such designs, many engineers are turning toward the biological world to study the construction and behaviour of bio-analogues, and to probe the role surface topography assumes in conditioning of frictional response. That is how a bio-analogue can self-adjust its tribological response to adapt to habitat constraints. From a tribological point of view, Squamate Reptiles, offer diverse examples where surface texturing, submicron and nano-scale features, achieves frictional regulation. In this paper, we study the frictional response of shed skin obtained from a snake (Python regius). The study employed a specially designed tribo-acoustic probe capable of measuring the coefficient of friction and detecting the acoustical behavior of the skin in vivo. The results confirm the anisotropy of the frictional response of snakes. The coefficient of friction depends on the direction of sliding: the value in forward motion is lower than that in the backward direction. Diagonal and side winding motion induces a different value of the friction coefficient. We discuss the origin of such a phenomenon in relation to surface texturing and study the energy constraints, implied by anisotropic friction, on the motion of the reptile.

  5. Distributed Load Shedding over Directed Communication Networks with Time Delays

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Tao; Wu, Di


    When generation is insufficient to support all loads under emergencies, effective and efficient load shedding needs to be deployed in order to maintain the supply-demand balance. This paper presents a distributed load shedding algorithm, which makes efficient decision based on the discovered global information. In the global information discovery process, each load only communicates with its neighboring load via directed communication links possibly with arbitrarily large but bounded time varying communication delays. We propose a novel distributed information discovery algorithm based on ratio consensus. Simulation results are used to validate the proposed method.

  6. On aerodynamic noise generation from vortex shedding in rotating blades (United States)

    Martin, B. T.; Bies, D. A.


    The interaction of the shed wakes of plates in a cascade with each following plate is investigated in a water tunnel and shown to provide an explanation for an observed very powerful aerodynamic noise source. In particular, the noise generation of an idling circular saw may be explained as due to the interaction of the wake shed by an upstream tooth with the leading edge of the following downstream tooth. When a vortex travelling downstream in the gullet between teeth encounters the leading edge of the downstream tooth it is deflected out of the gullet into the main stream. The associated impulses which the teeth encounter give rise to the radiated noise.

  7. The dynamics of herpesvirus and polyomavirus reactivation and shedding in healthy adults: a 14-month longitudinal study (United States)

    Ling, Paul D.; Lednicky, John A.; Keitel, Wendy A.; Poston, David G.; White, Zoe S.; Peng, RongSheng; Liu, Zhensheng; Mehta, Satish K.; Pierson, Duane L.; Rooney, Cliona M.; Vilchez, Regis A.; Smith, E. O'Brian; Butel, Janet S.


    Humans are infected with viruses that establish long-term persistent infections. To address whether immunocompetent individuals control virus reactivation globally or independently and to identify patterns of sporadic reactivation, we monitored herpesviruses and polyomaviruses in 30 adults, over 14 months. Epstein-Barr virus (EBV) DNA was quantitated in saliva and peripheral blood mononuclear cells (PBMCs), cytomegalovirus (CMV) was assayed in urine, and JC virus (JCV) and BK virus (BKV) DNAs were assayed in urine and PBMCs. All individuals shed EBV in saliva, whereas 67% had >or=1 blood sample positive for EBV. Levels of EBV varied widely. CMV shedding occurred infrequently but occurred more commonly in younger individuals (Por=40 years old (PEBV and JCV, but there was no correlation among shedding of EBV, CMV, and JCV (P>.50). Thus, adults independently control persistent viruses, which display discordant, sporadic reactivations.

  8. Characterization of the Lassa virus GP1 ectodomain shedding: implications for improved diagnostic platforms

    Directory of Open Access Journals (Sweden)

    Branco Luis M


    Full Text Available Abstract Background There is a significant requirement for the development and acquisition of reagents that will facilitate effective diagnosis, treatment, and prevention of Lassa fever. In this regard, detection of early markers of Lassa virus (LASV infection may improve diagnosis and ultimately successful treatment with antivirals. Characterization of LASV GP1 ectodomain shedding is an important step toward developing sensitive diagnostics to detect circulating levels of this viral glycoprotein in infected patient sera. Results Secretion of GP1 from mammalian cells expressing a native LASV GPC gene was not mediated by proteolytic cleavage, as determined by treatment with a panel of matrix metalloprotease (MMP inhibitors. The shedding of GP1 was also not the result of over-expression of GPC under the control of a strong intron-A containing CMV promoter, as the soluble component could be immunoprecipitated from supernatants of cells expressing low levels of GPC under the control of an intronless promoter. Cells transfected with GPC retained surface membrane-associated expression of GP1 as determined by immunofluorescence assay, in addition to secreting the glycoprotein. Secreted GP1 derived from GPC expression has a higher content of high mannose N-linked glycosylation than sGP1 expressed independently from the GP2 portion of the protein. Neither GP1 isoform contains sialylated N-glycans, O-linked carbohydrate chains, or galactose-β(1-4-N-acetylglucosamine commonly present in complex and hybrid N-glycan structures. Conclusion These results demonstrate the non-proteolytic secretory nature of GP1 shedding during expression of the arenaviral glycoprotein complex. This phenomenon parallels shedding of a secretory glycoprotein component in filovirus replication. The glycosylation pattern of soluble GP1 resulting from expression of GPC was different from that of a soluble GP1 construct (sGP1-RRAA-FLAG, highlighting the intricately orchestrated post

  9. Heritage Conservation in the "Back Shed" of the Learning City. (United States)

    Boshier, Roger


    Describes Back Shed, a group of New Zealand heritage conservationists who center their work in lifelong learning. Situates their activities in the context of the learning city, a community development concept that mobilizes learning resources across many sectors. Discusses heritage conservation as a process of meaning making. (Contains 29…

  10. The transmembrane domain of TACE regulates protein ectodomain shedding

    Institute of Scientific and Technical Information of China (English)

    Xiaojin Li; Liliana Pérez; Zui Pan; Huizhou Fan


    Numerous membrane proteins are cleaved by tumor necrosis factor-α converting enzyme (TACE), which causes the release of their ectodomains. An ADAM (a disintegrin and metalloprotease domain) family member, TACE contains several noncatalytic domains whose roles in ectodomain shedding have yet to be fully resolved. Here, we have explored the function of the transmembrane domain (TM) of TACE by coupling molecular engineering and functional analysis. A TM-free TACE construct that is anchored to the plasma membrane by a glycosylphosphatidylino-sitol (GPI)-binding polypeptide failed to restore shedding of transforming growth factor-α (TGF-α), tumor necrosis factor-α (TNF-α) and L-selectin in cells lacking endogenous TACE activity. Substitution of the TACE TM with that of the prolactin receptor or platelet-derived growth factor receptor (PDGFR) also resulted in severe loss of TGF-α shedding, but had no effects on the cleavage of TNF-α and L-selectin. Replacement of the TM in TGF-a with that of L-selectin enabled TGF-a shedding by the TACE mutants carrying the TM of prolactin receptor and PDGFR. Taken together, our observations suggest that anchorage of TACE to the lipid bilayer through a TM is required for efficient cleavage of a broad spectrum of substrates, and that the amino-acid sequence of TACE TM may play a role in regulatory specificity among TACE substrates.

  11. Weight-Loss Surgery Sheds Pounds Long Term (United States)

    ... page: Weight-Loss Surgery Sheds Pounds Long Term 10-year follow- ... 31, 2016 WEDNESDAY, Aug. 31, 2016 (HealthDay News) -- Weight-loss surgery helps people drop a significant amount of ...

  12. Shedding Phenomenon of Ventilated Partial Cavitation around an Underwater Projectile

    Institute of Scientific and Technical Information of China (English)

    WANG Yi-Wei; HUANG Chen-Guang; DU Te-Zhuan; WU Xian-Qian; FANG Xin; LIANG Nai-Gang; WEI Yan-Peng


    A new shedding phenomenon of ventilated partial cavitations is observed around an axisymmetric projectile in a horizontal launching experiment. The experiment system is established based on SHPB launching and high speed photography. A numerical simulation is carried out based on the homogeneous mixture approach, and its predicted evolutions of cavities are compared with the experimental results. The cavity breaks off by the interaction between the gas injection and the re-entry jet at the middle location of the projectile, which is obviously different from natural cavitation. The mechanism of cavity breaking and shedding is investigated, and the influences of important factors are also discussed.%A new shedding phenomenon of ventilated partial cavitations is observed around an axisymmetric projectile in a horizontal launching experiment.The experiment system is established based on SHPB launching and high speed photography.A numerical simulation is carried out based on the homogeneous mixture approach,and its predicted evolutions of cavities are compared with the experimental results.The cavity breaks off by the interaction between the gas injection and the re-entry jet at the middle location of the projectile,which is obviously different from natural cavitation.The mechanism of cavity breaking and shedding is investigated,and the influences of important factors are also discussed.

  13. Older Men as Learners: Irish Men's Sheds as an Intervention (United States)

    Carragher, Lucia; Golding, Barry


    To date, little attention has been placed on older men (aged 50+ years) as learners, with much of the literature on adult learning concerned with younger age-groups and issues around gender equity directed mainly at women. This article examines the impact of community-based men's sheds on informal and nonformal learning by older men in Ireland. It…


    A physically-based, Monte Carlo probabilistic model (SHEDS-Wood: Stochastic Human Exposure and Dose Simulation model for wood preservatives) has been applied to assess the exposure and dose of children to arsenic (As) and chromium (Cr) from contact with chromated copper arsenat...

  15. A Robust Load Shedding Strategy for Microgrid Islanding Transition

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Guodong [ORNL; Xiao, Bailu [ORNL; Starke, Michael R [ORNL; Ceylan, Oguzhan [ORNL; Tomsovic, Kevin [University of Tennessee, Knoxville (UTK)


    A microgrid is a group of interconnected loads and distributed energy resources. It can operate in either gridconnected mode to exchange energy with the main grid or run autonomously as an island in emergency mode. However, the transition of microgrid from grid-connected mode to islanded mode is usually associated with excessive load (or generation), which should be shed (or spilled). Under this condition, this paper proposes an robust load shedding strategy for microgrid islanding transition, which takes into account the uncertainties of renewable generation in the microgrid and guarantees the balance between load and generation after islanding. A robust optimization model is formulated to minimize the total operation cost, including fuel cost and penalty for load shedding. The proposed robust load shedding strategy works as a backup plan and updates at a prescribed interval. It assures a feasible operating point after islanding given the uncertainty of renewable generation. The proposed algorithm is demonstrated on a simulated microgrid consisting of a wind turbine, a PV panel, a battery, two distributed generators (DGs), a critical load and a interruptible load. Numerical simulation results validate the proposed algorithm.

  16. Fungal recognition enhances mannose receptor shedding through dectin-1 engagement. (United States)

    Gazi, Umut; Rosas, Marcela; Singh, Sonali; Heinsbroek, Sigrid; Haq, Imran; Johnson, Simon; Brown, Gordon D; Williams, David L; Taylor, Philip R; Martinez-Pomares, Luisa


    The mannose receptor (MR) is an endocytic type I membrane molecule with a broad ligand specificity that is involved in both hemostasis and pathogen recognition. Membrane-anchored MR is cleaved by a metalloproteinase into functional soluble MR (sMR) composed of the extracellular domains of intact MR. Although sMR production was initially considered a constitutive process, enhanced MR shedding has been observed in response to the fungal pathogen Pneumocystis carinii. In this work, we have investigated the mechanism mediating enhanced MR shedding in response to fungi. We show that other fungal species, including Candida albicans and Aspergillus fumigatus, together with zymosan, a preparation of the cell wall of Saccharomyces cerevisiae, mimic the effect of P. carinii on sMR production and that this effect takes place mainly through β-glucan recognition. Additionally, we demonstrate that MR cleavage in response to C. albicans and bioactive particulate β-glucan requires expression of dectin-1. Our data, obtained using specific inhibitors, are consistent with the canonical Syk-mediated pathway triggered by dectin-1 being mainly responsible for inducing MR shedding, with Raf-1 being partially involved. As in the case of steady-state conditions, MR shedding in response to C. albicans and β-glucan particles requires metalloprotease activity. The induction of MR shedding by dectin-1 has clear implications for the role of MR in fungal recognition, as sMR was previously shown to retain the ability to bind fungal pathogens and can interact with numerous host molecules, including lysosomal hydrolases. Thus, MR cleavage could also impact on the magnitude of inflammation during fungal infection.

  17. Adjoint sensitivity studies of loop current and eddy shedding in the Gulf of Mexico

    KAUST Repository

    Gopalakrishnan, Ganesh


    Adjoint model sensitivity analyses were applied for the loop current (LC) and its eddy shedding in the Gulf of Mexico (GoM) using the MIT general circulation model (MITgcm). The circulation in the GoM is mainly driven by the energetic LC and subsequent LC eddy separation. In order to understand which ocean regions and features control the evolution of the LC, including anticyclonic warm-core eddy shedding in the GoM, forward and adjoint sensitivities with respect to previous model state and atmospheric forcing were computed using the MITgcm and its adjoint. Since the validity of the adjoint model sensitivities depends on the capability of the forward model to simulate the real LC system and the eddy shedding processes, a 5 year (2004–2008) forward model simulation was performed for the GoM using realistic atmospheric forcing, initial, and boundary conditions. This forward model simulation was compared to satellite measurements of sea-surface height (SSH) and sea-surface temperature (SST), and observed transport variability. Despite realistic mean state, standard deviations, and LC eddy shedding period, the simulated LC extension shows less variability and more regularity than the observations. However, the model is suitable for studying the LC system and can be utilized for examining the ocean influences leading to a simple, and hopefully generic LC eddy separation in the GoM. The adjoint sensitivities of the LC show influences from the Yucatan Channel (YC) flow and Loop Current Frontal Eddy (LCFE) on both LC extension and eddy separation, as suggested by earlier work. Some of the processes that control LC extension after eddy separation differ from those controlling eddy shedding, but include YC through-flow. The sensitivity remains stable for more than 30 days and moves generally upstream, entering the Caribbean Sea. The sensitivities of the LC for SST generally remain closer to the surface and move at speeds consistent with advection by the high-speed core of

  18. Colonisation and shedding of Lawsonia intracellularis in experimentally inoculated rodents and in wild rodents on pig farms. (United States)

    Collins, A M; Fell, S; Pearson, H; Toribio, J-A


    Lawsonia intracellularis is an intracellular bacterium causing proliferative enteropathy in various animal species, and is considered an economically important pathogen of pigs. Rats and mice have been implicated as external vectors for a wide range of pig pathogens, including L. intracellularis. Previous studies have demonstrated L. intracellularis infection and proliferative enteropathy in rodents, but did not show the duration of shedding or the number of L. intracellularis shed by infected rodents, and therefore the infection risk that rodents pose to pigs. In this study, the number of L. intracellularis shed in the faeces and intestinal mucosa of wild rats trapped on pig farms was determined by a quantitative real time polymerase chain reaction assay. The prevalence of L. intracellularis in wild rats trapped on pig farms with endemic proliferative enteropathy (PE) was very high (≥ 70.6%), and large numbers of L. intracellularis were shed (10(10)/g of faeces) in a small proportion of wild rats. The duration of colonisation in laboratory rats and mice challenged with porcine isolates of L. intracellularis was also shown. Faecal shedding of L. intracellularis persisted for 14-21 days in rats and mice that were mildly affected with histological lesions of PE. The humoral immune response to L. intracellularis persisted for 40 days in both species. This study demonstrates that rodents may be an important reservoir of L. intracellularis on piggeries, and hence rodent control is important in disease eradication programs on pig farms.

  19. Matrix metalloproteinase-2 (MMP-2) generates soluble HLA-G1 by cell surface proteolytic shedding. (United States)

    Rizzo, Roberta; Trentini, Alessandro; Bortolotti, Daria; Manfrinato, Maria C; Rotola, Antonella; Castellazzi, Massimiliano; Melchiorri, Loredana; Di Luca, Dario; Dallocchio, Franco; Fainardi, Enrico; Bellini, Tiziana


    Human leukocyte antigen-G (HLA-G) molecules are non-classical HLA class I antigens with an important role in pregnancy immune regulation and inflammation control. Soluble HLA-G proteins can be generated through two mechanisms: alternative splicing and proteolytic release, which is known to be metalloprotease mediated. Among this class of enzymes, matrix metalloproteinases (MMPs) might be involved in the HLA-G1 membrane cleavage. Of particular interest are MMP-2 and MMP-9, which regulate the inflammatory process by cytokine and chemokine modulation. We evaluated the effect of MMP-9 and MMP-2 on HLA-G1 membrane shedding. In particular, we analyzed the in vitro effect of these two gelatinases on the secretion of HLA-G1 via proteolytic cleavage in 221-G1-transfected cell line, in JEG3 cell line, and in peripheral blood mononuclear cells. The results obtained by both cell lines showed the role of MMP-2 in HLA-G1 shedding. On the contrary, MMP-9 was not involved in this process. In addition, we identified three possible highly specific cleavage sites for MMP-2, whereas none were detected for MMP-9. This study suggests an effective link between MMP-2 and HLA-G1 shedding, increasing our knowledge on the regulatory machinery beyond HLA-G regulation in physiological and pathological conditions.

  20. Inhibitory role of TACE/ADAM17 cytotail in protein ectodomain shedding

    Institute of Scientific and Technical Information of China (English)

    Liliana; Pérez


    AIM:To determine if the cytotail of the principal sheddase tumor necrosis factor-α converting enzyme (TACE;ADAM17) controls protein ectodomain shedding.METHODS:Site-directed mutagenesis was performed to derive TACE variants. The resulting TACE expression plasmids with amino acid substitutions in the extracel-lular,cysteine-rich disintegrin domain (CRD) and/or deleted cytotail,along with an expression vector for the enhanced green fluorescence protein were transfected into shedding-defective M1 mutants stably expressing transmembrane L-selectin or transforming growth factor (TGF)-α. The expression levels of the TACE substrates at the cell surface were determined by flow cytometry. RESULTS:Consistent with published data,a single point mutation (C600Y) in the CRD led to shedding defi-ciency. However,removal of the cytotail from the C600Y TACE variant partially restored ectodomain cleavage of TGF-α and L-selectin. Cytotail-deleted mutants with any other substituting amino acid residues in place of Cys600 displayed similar function compared with tail-less C600Y TACE.CONCLUSION:The cytotail plays an inhibitory role,which becomes evident when it is removed from an enzyme with another mutation that affects the enzyme function.

  1. Technical note: concentration and composition of airborne aerobic bacteria inside an enclosed rabbit shed

    Directory of Open Access Journals (Sweden)

    S. Li


    Full Text Available Numerous studies have been conducted to analyse bacterial aerosols in animal houses, which is beneficial for the control of animal diseases. However, little information on aerosols in enclosed rabbit sheds was available. An FA-1 sampler was employed to collect air samples in an enclosed rabbit house in the Qingdao region of China. Concentration, composition, and aerodynamics of bacterial aerosols inside the enclosed rabbit shed were systematically analysed. The concentration of airborne bacteria inside the rabbit shed was 2.11-6.36×104 colony forming unit/m3 (CFU/m3. Seventeen species of bacteria belonging to eight genera were identified. Among these, there were 11 species belonging to 4 genera of gram-positive bacteria, and 6 species belonging to 4 genera of gram-negative bacteria. The dominant species of bacteria were, in descending order, Micrococcus luteus (49.4%, Staphylococcus epidermidis (25.5%, and Alcaligenes odorans (10.2%. A total of about 76.3% of airborne bacteria was distributed in stages C-F of the FA-1 sampler (that ranges from A to F, with aerodynamic radii <3.3 μm in diameter. These particulates could enter lower respiratory tracks and even alveoli, posing a potential threat to the health of both animals and breeders.

  2. Feeding of the probiotic bacterium Enterococcus faecium NCIMB 10415 differentially affects shedding of enteric viruses in pigs

    Directory of Open Access Journals (Sweden)

    Kreuzer Susanne


    Full Text Available Abstract Effects of probiotic bacteria on viral infections have been described previously. Here, two groups of sows and their piglets were fed with or without feed supplementation of the probiotic bacterium Enterococcus faecium NCIMB 10415. Shedding of enteric viruses naturally occurring in these pigs was analyzed by quantitative real-time RT-PCR. No differences between the groups were recorded for hepatitis E virus, encephalomyocarditis virus and norovirus. In contrast, astrovirus was exclusively detected in the non-supplemented control group. Rotavirus was shedded later and with lower amounts in the probiotic piglet group (p p p p p p 

  3. Increased Epstein-Barr virus in breast milk occurs with subclinical mastitis and HIV shedding. (United States)

    Sanosyan, Armen; Rutagwera, David G; Molès, Jean-Pierre; Bollore, Karine; Peries, Marianne; Kankasa, Chipepo; Mwiya, Mwiya; Tylleskär, Thorkild; Nagot, Nicolas; Van De Perre, Philippe; Tuaillon, Edouard


    Epstein-Barr virus (EBV) in breast milk and subclinical mastitis (SCM) are both associated with human immunodeficiency virus (HIV) shedding and possibly with postnatal HIV transmission. The objective of this nested case-control study was to investigate the interplay between SCM and EBV replication in breast milk of HIV-infected mothers.The relationships between EBV deoxyribonucleic acid (DNA) shedding, HIV-1 ribonucleic acid (RNA) level, and SCM were explored in breast milk samples of Zambian mothers participating in the ANRS 12174 trial. Mammary gland inflammation was defined as a breast milk sodium to potassium ratio (Na/K) greater than 0.6 and further subclassified as either "possible SCM" (Na/K ratio 0.6-1.0) or SCM (Na/K ratio ≥ 1.0). Breast milk interleukin 8 (IL-8) was measured as a surrogate marker of mammary gland inflammation.EBV DNA was detected in breast milk samples from 42 out of 83 (51%) participants and was associated with HIV-1 shedding in breast milk (P = 0.006). EBV DNA levels were higher in samples with SCM and "possible SCM" compared to non-SCM breast milk samples (P = 0.06; P = 0.007). An EBV DNA level of >200 copies/mL was independently associated with SCM and "possible SCM" (OR: 2.62; 95%: 1.13-6.10). In patients with SCM, higher EBV replication in the mammary gland was associated with a lower induction of IL-8 (P = 0.013). Resistance to DNase treatment suggests that EBV DNA in lactoserum is encapsidated.SCM and decreased IL-8 responses are associated with an increased EBV shedding in breast milk which may in turn facilitate HIV replication in the mammary gland.

  4. Calf-level risk factors for neonatal diarrhea and shedding of Cryptosporidium parvum in Ontario dairy calves. (United States)

    Trotz-Williams, Lise A; Wayne Martin, S; Leslie, Kenneth E; Duffield, Todd; Nydam, Daryl V; Peregrine, Andrew S


    . parvum oocysts had 5.3 (95% CI 4.4, 6.4) times the odds of diarrhea than non-shedding calves, controlling for other factors included in the final multivariable model. Furthermore, infected calves shedding more than 2.2 x 10(5) oocysts per gram of feces were more likely to scour than infected calves shedding lower numbers of oocysts (OR= 6.1, 95% CI 4.8, 7.8). The odds of diarrhea in calves shedding oocysts that had been allowed to remain with their dams for more than an hour were higher than the odds of diarrhea in shedding calves that had been separated from their dams within an hour after birth.

  5. rROP2 from Toxoplasma gondii as a potential vaccine against oocyst shedding in domestic cats

    Directory of Open Access Journals (Sweden)

    Dauton Luiz Zulpo

    Full Text Available Abstract The aim of the present study was to evaluate oocyst shedding in cats immunized by nasal route with T. gondii proteins ROP2. Twelve short hair cats (Felis catus were divided in three groups G1, G2 and G3 (n=4. Animals from G1 received 100 μg of rROP2 proteins plus 20 μg of Quil-A, G2 received 100 μg of BSA plus 20 μg of Quil-A, and the G3 only saline solution (control group. All treatments were done by intranasal route at days 0, 21, 42, and 63. The challenge was performed in all groups on day 70 with ≅ 800 tissue cysts of ME-49 strain by oral route. Animals from G1 shed less oocysts (86.7% than control groups. ELISA was used to detect anti-rROP2 IgG and IgA, however, there were no correlation between number of oocyst shedding by either IgG or IgA antibody levels. In the present work, in spite of lesser oocysts production in immunized group than control groups, it was not possible to associate the use of rROP2 via nostrils with protection against oocyst shedding. For the future, the use of either other recombinant proteins or DNA vaccine, in combination with rROP2 could be tested to try improving the efficacy of this kind of vaccine.

  6. Syndecan-4 shedding impairs macrovascular angiogenesis in diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ran; Xie, Jun; Wu, Han; Li, Guannan; Chen, Jianzhou; Chen, Qinhua; Wang, Lian; Xu, Biao, E-mail:


    Purpose: Syndecan-4 (synd4) is a ubiquitous heparan sulfate proteoglycan cell surface receptor that modulates cell proliferation, migration, mechanotransduction, and endocytosis. The extracellular domain of synd4 sheds heavily in acute inflammation, but the shedding of synd4 in chronic inflammation, such as diabetes mellitus (DM), is still undefined. We investigated the alterations of synd4 endothelial expression in DM and the influence of impaired synd4 signaling on angiogenesis in human umbilical vein endothelial cells (HUVECs), diabetic rats, synd4 null mice, and db/db mice. Material and methods: HUVECs were incubated with advanced glycation end products (AGEs). Western blot analysis was used to determine synd4 protein expression and ELISA was used to detect soluble synd4 fragments. The concentration of synd4 in the aortic endothelia of diabetic rats was detected by immunohistochemical staining. Aortic ring assays were performed to study the process of angiogenesis in the diabetic rats and in synd4 null and db/db mice. Recombinant adenoviruses containing the synd4 gene or null were constructed to enhance synd4 aortic expression in db/db mice. Results: Western blot analysis showed decreased expression of the synd4 extracellular domain in HUVECs, and ELISA detected increased soluble fragments of synd4 in the media. Synd4 endothelial expression in the aortas of diabetic rats was decreased. Aortic ring assay indicated impaired angiogenesis in synd4 null and db/db mice, which was partially reversed by synd4 overexpression in db/db mice. Conclusion: Synd4 shedding from vascular endothelial cells played an important role in the diabetes-related impairment of angiogenesis. -- Highlights: •Synd4 shedding from endothelial cells is accelerated under the stimulation of AGEs. •Extracellular domain of synd4 is diminished in the endothelium of DM rats. •Aortic rings of synd4 null mice showed impaired angiogenesis. •Overexpression of synd4 partly rescues macrovascular

  7. Vortex shedding noise of a cylinder with hairy flaps


    Kamps, L.; Geyer, T. F.; Sarradj, E.; Brücker, C.


    This study describes the modification of acoustic noise emitted from cylinders in a stationary subsonic flow for a cylinder equipped with flexible hairy flaps at the aft part as a passive way to manipulate the flow and acoustics. The study was motivated by the results from previous water tunnel measurements, which demonstrated that hairy flaps can modify the shedding cycle behind the cylinder and can reduce the wake deficit. In the present study, wind tunnel experiments were conducted on such...

  8. Birds shed RNA-viruses according to the pareto principle.

    Directory of Open Access Journals (Sweden)

    Mark D Jankowski

    Full Text Available A major challenge in disease ecology is to understand the role of individual variation of infection load on disease transmission dynamics and how this influences the evolution of resistance or tolerance mechanisms. Such information will improve our capacity to understand, predict, and mitigate pathogen-associated disease in all organisms. In many host-pathogen systems, particularly macroparasites and sexually transmitted diseases, it has been found that approximately 20% of the population is responsible for approximately 80% of the transmission events. Although host contact rates can account for some of this pattern, pathogen transmission dynamics also depend upon host infectiousness, an area that has received relatively little attention. Therefore, we conducted a meta-analysis of pathogen shedding rates of 24 host (avian - pathogen (RNA-virus studies, including 17 bird species and five important zoonotic viruses. We determined that viral count data followed the Weibull distribution, the mean Gini coefficient (an index of inequality was 0.687 (0.036 SEM, and that 22.0% (0.90 SEM of the birds shed 80% of the virus across all studies, suggesting an adherence of viral shedding counts to the Pareto Principle. The relative position of a bird in a distribution of viral counts was affected by factors extrinsic to the host, such as exposure to corticosterone and to a lesser extent reduced food availability, but not to intrinsic host factors including age, sex, and migratory status. These data provide a quantitative view of heterogeneous virus shedding in birds that may be used to better parameterize epidemiological models and understand transmission dynamics.

  9. Birds shed RNA-viruses according to the pareto principle. (United States)

    Jankowski, Mark D; Williams, Christopher J; Fair, Jeanne M; Owen, Jennifer C


    A major challenge in disease ecology is to understand the role of individual variation of infection load on disease transmission dynamics and how this influences the evolution of resistance or tolerance mechanisms. Such information will improve our capacity to understand, predict, and mitigate pathogen-associated disease in all organisms. In many host-pathogen systems, particularly macroparasites and sexually transmitted diseases, it has been found that approximately 20% of the population is responsible for approximately 80% of the transmission events. Although host contact rates can account for some of this pattern, pathogen transmission dynamics also depend upon host infectiousness, an area that has received relatively little attention. Therefore, we conducted a meta-analysis of pathogen shedding rates of 24 host (avian) - pathogen (RNA-virus) studies, including 17 bird species and five important zoonotic viruses. We determined that viral count data followed the Weibull distribution, the mean Gini coefficient (an index of inequality) was 0.687 (0.036 SEM), and that 22.0% (0.90 SEM) of the birds shed 80% of the virus across all studies, suggesting an adherence of viral shedding counts to the Pareto Principle. The relative position of a bird in a distribution of viral counts was affected by factors extrinsic to the host, such as exposure to corticosterone and to a lesser extent reduced food availability, but not to intrinsic host factors including age, sex, and migratory status. These data provide a quantitative view of heterogeneous virus shedding in birds that may be used to better parameterize epidemiological models and understand transmission dynamics.

  10. Shear driven droplet shedding and coalescence on a superhydrophobic surface (United States)

    Moghtadernejad, S.; Tembely, M.; Jadidi, M.; Esmail, N.; Dolatabadi, A.


    The interest on shedding and coalescence of sessile droplets arises from the importance of these phenomena in various scientific problems and industrial applications such as ice formation on wind turbine blades, power lines, nacelles, and aircraft wings. It is shown recently that one of the ways to reduce the probability of ice accretion on industrial components is using superhydrophobic coatings due to their low adhesion to water droplets. In this study, a combined experimental and numerical approach is used to investigate droplet shedding and coalescence phenomena under the influence of air shear flow on a superhydrophobic surface. Droplets with a size of 2 mm are subjected to various air speeds ranging from 5 to 90 m/s. A numerical simulation based on the Volume of Fluid method coupled with the Large Eddy Simulation turbulent model is carried out in conjunction with the validating experiments to shed more light on the coalescence of droplets and detachment phenomena through a detailed analysis of the aerodynamics forces and velocity vectors on the droplet and the streamlines around it. The results indicate a contrast in the mechanism of two-droplet coalescence and subsequent detachment with those related to the case of a single droplet shedding. At lower speeds, the two droplets coalesce by attracting each other with successive rebounds of the merged droplet on the substrate, while at higher speeds, the detachment occurs almost instantly after coalescence, with a detachment time decreasing exponentially with the air speed. It is shown that coalescence phenomenon assists droplet detachment from the superhydrophobic substrate at lower air speeds.

  11. Vortex Shedding from Tapered Cylinders at high Reynolds Numbers

    DEFF Research Database (Denmark)

    Johansson, Jens; Andersen, Michael Styrk; Christensen, Silas Sverre


    percent for strakes of circular cross section. The present paper argues that this height can be reduced for structures where the critical wind velocity for vortex shedding is in the Supercritical Reynolds number regime. The present investigations are aimed for suppressing VIV on offshore wind turbine......^5 (Supercritical). Results indicate that circular strakes with a diameter corresponding to 3 percent of the structures mean diameter can be used to efficiently reduce VIV in the Supercritical Reynolds number regime....

  12. A corrective load shedding scheme to mitigate voltage collapse

    Energy Technology Data Exchange (ETDEWEB)

    Echavarren, F.M.; Lobato, E.; Rouco, L. [School of Engineering, Universidad Pontificia Comillas, C/Alberto Aguilera, 23, 28015 Madrid (Spain)


    Voltage stability is concerned with the ability of a power system to maintain acceptable voltages at all buses. A measure of the power system voltage stability is the distance to the saddle node bifurcation of the power flow equations, which is called the load margin. When the power system load is very high, and/or there exists a large generation-demand imbalance in the power system areas the load margin to the saddle node bifurcation may be too low, and the power system may become close to voltage collapse. In case that active and reactive power generation resources in the importing areas are exhausted, corrective load shedding may become the last option. This paper presents a LP-based optimization load shedding algorithm to improve the load margin. The objective function consists of minimizing the total system demand decrease. First order sensitivities of the load margin with respect to the load to be shed are considered. The performance of the method is illustrated with a scenario of the Spanish power system. (author)

  13. HSV oropharyngeal shedding among HIV-infected children in Tanzania. (United States)

    Zuckerman, Richard; Manji, Karim; Matee, Mecky; Naburi, Helga; Bisimba, Jema; Martinez, Raquel; Wieland-Alter, Wendy; Kim, Faith; von Reyn, C Fordham; Palumbo, Paul


    Herpes simplex virus (HSV) oral shedding has not been studied among HIV-positive children in Africa. We sought to evaluate longitudinal oral HSV reactivation in HIV-positive and -negative children. Twenty HIV-positive antiretroviral-naive and 10 HIV-negative children aged 3-12 years in Tanzania were followed prospectively for 14 days. Oral swabs were collected daily and submitted for HSV DNA PCR analysis. Clinical data were collected via chart review and daily diaries. HSV DNA was detected in 10 (50%) of HIV-positive and 4 (40%) of HIV-negative children. Children who shed HSV had virus detected in a median of 21.4% of samples; shedding was intermittent. Median CD4 count among HIV-infected children was 667 cells/µL in those with positive HSV DNA and 886 cells/µL in those who were negative (p = 0.6). Of the HIV-positive children reporting prior sores, five (83%) had positive HSV swabs, whereas the one HIV-negative child with prior sores did not have a PCR-positive swab. HSV is detected frequently in children with and without HIV. HIV-infected children reporting oral sores have a high rate of HSV detection. Given the proven strong interactions between HIV and HSV, further study of co-infection with these viruses is warranted in children.

  14. Autotransfusion of shed mediastinal blood after open heart surgery

    Institute of Scientific and Technical Information of China (English)

    赵康丽; 许建屏; 胡盛寿; 吴清玉; 魏以桢; 刘迎龙


    Objective To determine the safety and effectiveness of autotransfusion of shed mediastinal blood after open heart surgery. Methods Sixty patients undergoing coronary artery bypass grafting (CABG) were selected randomly to receive either nonwashed shed mediastinal blood (Group 1, n=30) or banked blood (Group 2, n=30). Drainage and transfusion volume were determined after the operation. Hb, RBC, HCT and PLT were detected immediately before and after the operation, as well as 24 hours and 7 days after the operation. Data were analyzed using Fisher's exact test. A P0.05). In the two groups, no significant difference in the mean blood loss was observed during 24 hours after the operation (660±300 ml in Group 1 and 655±280 ml in Group 2, P>0.05). In Group 1, the mean volume autotransfused was 280±160 ml, and the patients required 360±80 ml banked blood compared with 660±120 ml in Group 2. In other words, the banked blood requirement in Group 1 was 40% lower. Conclusions Autotransfusion of shed mediastinal blood after an open heart operation is safe and effective.

  15. Laminar vortex shedding behind a cooled circular cylinder (United States)

    Trávníček, Zdeněk; Wang, An-Bang; Tu, Wen-Yun


    This paper addresses the functional demonstration of a hot air flow generator driven by convective heat transfer and the airflow behind a cooled circular cylinder in cross flow in the low velocity range. The wake flow was investigated experimentally using flow visualization, hot-wire anemometry, and laser Doppler anemometry. An evaluation of the free-stream velocity from the vortex shedding frequency was derived for the isothermal and non-isothermal cases and demonstrated using simple stroboscope measurements. The results confirm that cylinder cooling destabilizes the wake flow in air, i.e., the laminar steady regime can be changed into the vortex shedding regime, and the vortex shedding frequency increases as the cylinder temperature decreases. This thermal effect of cylinder cooling is consistent with its counterpart, the known effect of flow stabilization by cylinder heating. The effective temperature and effective Reynolds number concept have been further quantitatively evaluated, and the extension of their validity to the case of cooled cylinders has been confirmed.

  16. Ephrin B2受体对皮质脑梗死远隔部位血管发生和神经可塑性的影响%The Effects of Ephrin Receptor B2 on Angiogenesis and Neuroplasticity in Areas Remote From the Cortical Infarction

    Institute of Scientific and Technical Information of China (English)

    侯清华; 曾进胜


    脑梗死不仅是局部损伤,而且还会引起远隔缺血部位的继发性损伤,这种继发性损伤会阻碍神经功能的恢复.Ephrin B2受体(EphB2)在中枢神经系统发育和修复机制中起着重要作用.利用特异性抑制剂阻断脑内EphB2的作用,能促进实验性脑梗死后内源性神经干细胞增殖和迁移,改善神经功能,并可能影响远隔部位血管发生和神经可塑性,有望成为减轻脑梗死远隔部位损伤和促进神经功能恢复的新途径.

  17. Maintaining the Body's Immune System: Incidence of Latent Virus Shedding During Space Flight (United States)

    Pierson, Duane; Bloomberg, Jacob; Lee, Angie (Technical Monitor)


    Your body protects you from illness with its own security system - the immune system. This system keeps illness at bay not only by mounting a defense against foreign organisms, but also by controlling the population of bacteria and viruses that normally live in your body. But there's no need to panic: certain microbes can actually exist in your body without causing illness. Some bacteria are even beneficial - like the E. coli in the large intestine that are an important source of vitamin K. While viruses are not exactly considered beneficial, they can also inhabit the human body without causing immediate harm or infection. A good example is the herpes simplex virus type 1 (HSV1), more commonly known as cold sores or fever blisters. This virus infects 70 to 80 percent of all adults but remains latent much of the time. While latent, the virus within cells remains dormant. Activation of the dormant virus causes it to make copies of itself (known as replication) constantly detectable in body fluids such as urine or saliva in a process called shedding. When a person becomes sick or stressed, however, this weakened condition allows the virus to reactivate and multiply. These elevated levels may be enough to produce symptoms, but shedding can also occur without symptoms. This ability to shed without showing signs of infection, or asymptomatic shedding, is of great interest, as it increases the chances of infecting others. The stresses associated with space flight - adapting to microgravity, isolation from family and friends, living and working in a confined space, sleep deprivation, and busy schedules, to name but a few - may weaken astronauts' immune systems, leaving them at greater risk of viral reactivation. Members of the STS-107 crew will participate in this experiment, Incidence of Latent Viral Shedding in Space Flight, to help scientists understand how reactivation works in space, and at what level replication reaches before symptoms begin to show. This study also

  18. Vortex shedding noise reduction by single dielectric barrier discharge plasma actuators


    Al-Sadawi, L; Chong, TP


    An experimental study of active control of vortex shedding narrow band tonal noise from both blunt and rounded trailing edge of a profiled body at zero incidences was performed using Single Dielectric Barrier plasma actuators (DBD). Acoustics and flow measurements were carried out in an open jet, aerocoustic wind tunnel at Reynolds numbers ranging from 7x104 to 4x105. The noise results were obtained using single microphone, while both PIV and hot-wire were used for flow measurement in order t...

  19. The impact of load shedding on gender relations in heterosexual households in Mkoba north, Gweru, Zimbabwe: Implications for sustainable development

    Directory of Open Access Journals (Sweden)

    Manuku Mukoni


    Full Text Available This study explored the impact of load shedding on gender relations in heterosexual households. 20 couples were selected through judgmental sampling that was followed by network referencing; bringing the sample to 40 participants. Study was descriptive in nature. Questionnaires and interviews were used to collect data. Study reveals that load shedding have ripple effects in the social fabric of sustainable development through its impacts on gender relations. Load shedding is proving to be reproducing and maintaining gender relations of inequality, thus holding back sustainable development. Women are deprived control of areas that traditional belongs to them like the decision and control of energy use in the household giving men more power over women. Load shedding is increasing men’s time in the public sphere while women are tied more to the private sphere. For sustainable development to be achieved, household relationships should uphold the principles of sustainable development and gender equality is one of them. Empowerment of women and men in household energy uses will aid in opening up their ‘functioning space’. An understanding and appreciation of gender equality in the household will help men and women to be influential in the larger society leading to sustainable development.

  20. Enhancement of Voltage Stability of DC Smart Grid During Islanded Mode by Load Shedding Scheme (United States)

    Nassor, Thabit Salim; Senjyu, Tomonobu; Yona, Atsushi


    This paper presents the voltage stability of a DC smart grid based on renewable energy resources during grid connected and isolated modes. During the islanded mode the load shedding, based on the state of charge of the battery and distribution line voltage, was proposed for voltage stability and reservation of critical load power. The analyzed power system comprises a wind turbine, a photovoltaic generator, storage battery as controllable load, DC loads, and power converters. A fuzzy logic control strategy was applied for power consumption control of controllable loads and the grid-connected dual active bridge series resonant converters. The proposed DC Smart Grid operation has been verified by simulation using MATLAB® and PLECS® Blockset. The obtained results show the effectiveness of the proposed method.

  1. Characterization of shed medicinal leech mucus reveals a diverse microbiota

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    Brittany Maree Ott


    Full Text Available Microbial transmission through mucosal-mediated mechanisms is widespread throughout the animal kingdom. One example of this occurs with Hirudo verbana, the medicinal leech, where host attraction to shed conspecific mucus facilitates horizontal transmission of a predominant gut symbiont, the Gammaproteobacterium Aeromonas veronii. However, whether this mucus may harbor other bacteria has not been examined. Here, we characterize the microbiota of shed leech mucus through Illumina deep sequencing of the V3-V4 hypervariable region of the 16S rRNA gene. Additionally, Restriction Fragment Length Polymorphism (RFLP typing with subsequent Sanger Sequencing of a 16S rRNA gene clone library provided qualitative confirmation of the microbial composition. Phylogenetic analyses of full-length 16S rRNA sequences were performed to examine microbial taxonomic distribution. Analyses using both technologies indicate the dominance of the Bacteroidetes and Proteobacteria phyla within the mucus microbiota. We determined the presence of other previously described leech symbionts, in addition to a number of putative novel leech-associated bacteria. A second predominant gut symbiont, the Rikenella-like bacteria, was also identified within mucus and exhibited similar population dynamics to A. veronii, suggesting persistence in syntrophy beyond the gut. Interestingly, the most abundant bacterial genus belonged to Pedobacter, which includes members capable of producing heparinase, an enzyme that degrades the anticoagulant, heparin. Additionally, bacteria associated with denitrification and sulfate cycling were observed, indicating an abundance of these anions within mucus, likely originating from the leech excretory system. A diverse microbiota harbored within shed mucus has significant potential implications for the evolution of microbiomes, including opportunities for gene transfer and utility in host capture of a diverse group of symbionts.

  2. Vortex shedding noise of a cylinder with hairy flaps (United States)

    Kamps, Laura; Geyer, Thomas F.; Sarradj, Ennes; Brücker, Christoph


    This study describes the modification of acoustic noise emitted from cylinders in a stationary subsonic flow for a cylinder equipped with flexible hairy flaps at the aft part as a passive way to manipulate the flow and acoustics. The study was motivated by the results from previous water tunnel measurements, which demonstrated that hairy flaps can modify the shedding cycle behind the cylinder and can reduce the wake deficit. In the present study, wind tunnel experiments were conducted on such a modified cylinder and the results were compared to the reference case of a plain cylinder. The acoustic spectrum was measured using two microphones while simultaneously recording the flap motion. To further examine the flow structures in the downstream vicinity of the cylinder, constant temperature anemometry measurements as well as flow visualizations were also performed. The results show that, above a certain Reynolds number, the hairy flaps lead to a jump in the vortex shedding frequency. This phenomenon is similarly observed in the water flow experiments as a jump in the non-dimensional Strouhal number that is related to the change of the shedding cycle. This jump appears to be coupled to a resonant excitation of the flaps. The specific Reynolds number at which the jump occurs is higher in the present case, which is attributed to the lower added mass in air as compared with the one in water. The flow visualizations confirmed that such action of the flaps lead to a more slender elongated shape of the time-averaged separation bubble. In addition, the hairy flaps induce a noticeable reduction of the tonal noise as well as broadband noise as long as the flaps do not touch each other.

  3. Coordinated Scheme of Under-Frequency Load Shedding with Intelligent Appliances in a Cyber Physical Power System

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    Qi Wang


    Full Text Available The construction of a cyber physical system in a power grid provides more potential control strategies for the power grid. With the rapid employment of intelligent terminal equipment (e.g., smart meters and intelligent appliances in the environment of a smart grid, abundant dynamic response information could be introduced to support a secure and stable power system. Combining demand response technology with the traditional under-frequency load shedding (UFLS scheme, a new UFLS strategy-determining method involving intelligent appliances is put forward to achieve the coordinated control of quick response resources and the traditional control resources. Based on this method, intelligent appliances can be used to meet the regulatory requirements of system operation in advance and prevent significant frequency drop, thereby improving the flexibility and stability of the system. Time-domain simulation verifies the effectiveness of the scheme, which is able to mitigate frequency drop and reduce the amount of load shedding.

  4. Longitudinal prevalence and faecal shedding of Chlamydia pecorum in sheep. (United States)

    Yang, Rongchang; Jacobson, Caroline; Gardner, Graham; Carmichael, Ian; Campbell, Angus J D; Ryan, Una


    The prevalence and faecal shedding of Chlamydia spp. in sheep in Australia has not been well described. Two species-specific quantitative PCRs (qPCRs) targeting the chlamydial outer membrane protein cell surface antigen gene (ompA) were validated and used to determine the prevalence and faecal shedding of C. abortus and C. pecorum from faecal samples of lambs at three sampling times (weaning, post-weaning and pre-slaughter) from eight farms in South Australia, New South Wales, Victoria and Western Australia. A total of 3412 faecal samples were collected and screened from approximately 1189 lambs across the four states. C. abortus was not detected in any of the samples screened. The overall prevalence of C. pecorum was 1027/3412 (30.1%) and median bacterial concentrations at weaning, post-weaning and pre-slaughter were 1.8 × 10(7), 1.2 × 10(7) and 9.6 × 10(5)/g faeces, respectively. A subset of C. pecorum positive samples from each farm, (n = 48) was sequenced to confirm their identity. The present study demonstrates that C. pecorum is prevalent in Australian sheep, highlighting a need for further research on the impact of this bacterium on production.

  5. Association between nasal shedding and fever that influenza A (H3N2 induces in dogs

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    Oh Jinsik


    Full Text Available Abstract Background Avian origin canine influenza virus was reported in Korea. The dog to dog contact transmission of the avian origin canine influenza virus (CIV H3N2 and CIV H3N8 was shown by experimental contact transmission. This study was focused on viral excretion and fever in order to elucidate the epidemiological associations which might be helpful to control the disease transmissions in CIV outbreak in dogs. Methods An influenza seronegative 10-week-old Beagle dog was experimentally inoculated with the canine influenza virus A/canine/01/2007, subtype H3N2. Eight hours after inoculation, the infected dog was cohoused with seven uninfected Beagle dogs. Clinical signs including fever were recorded for 14 days post inoculation. Results The infected dog and four of seven contact dogs in the study showed clinical signs (sneezing, nasal discharge and coughing during the study. Viral shedding occurred in all of the animals tested and began on 1 to 6 DPI in dogs with clinical signs. Elevated body temperatures above 39.5°C (geometric mean temperature of 39.86°C±0.49 were observed in all symptomatic dogs. The mean viral titer during fever was 2.99 log EID50/ml, which was significantly higher than the viral titer detected in the non fever. Conclusions The data show that contact dogs with a canine influenza infected dog shed different levels of virus in their nasal excretions and demonstrate that clinical signs, including fever, significantly correlate with the viral shedding.

  6. The Role of Collaborative Learning on Training and Development Practices within the Australian Men's Shed Movement: A Study of Five Men's Sheds (United States)

    Cavanagh, Jillian; Southcombe, Amie; Bartram, Tim


    This study examines the role and impact of collaborative learning on training and development practices in Australian Men's Sheds. We use a case study approach, underpinned by Peters and Armstrong's theoretical framework of collaborative learning in adult education, to investigate five Men's Sheds. Semi-structured interviews were carried out with…

  7. Z-360, a novel therapeutic agent for pancreatic cancer, prevents up-regulation of ephrin B1 gene expression and phosphorylation of NR2B via suppression of interleukin-1 β production in a cancer-induced pain model in mice

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    Hori Yuko


    Full Text Available Abstract Background Z-360 is an orally active cholecystokinin-2 (CCK2/gastrin receptor antagonist currently under development as a therapeutic drug for pancreatic cancer. It was previously reported that Z-360 treatment in combination with gemcitabine prolonged the survival period in a lethal pancreatic cancer xenograft model in mice. In a phase Ib/IIa clinical study, Z-360 treatment displayed a trend of reduced pain in patients with advanced pancreatic cancer in combination with gemcitabine including analgesics such as opioids. Here, we investigated the mechanism of analgesic action of Z-360 in a severe cancer-induced pain model in mice, which is considered to be opioid-resistant, by examining ephrin B1 gene expression, N-methyl-D-aspartate receptor NR2B subunit phosphorylation, and interleukin-1β (IL-1β production. Results In a mouse model of cancer-induced pain, ephrin B1 gene expression in dorsal root ganglia (DRGs and the phosphorylation of NR2B in the spinal cord were induced. Z-360 treatment inhibited both ephrin B1 gene expression and the phosphorylation of NR2B. In addition, IL-1β production increased in the cancer-inoculated hind paw of mice, but could be suppressed by treatment with Z-360. Moreover, we observed that the CCK1 receptor antagonist devazepide similarly suppressed up-regulation of ephrin B1 gene expression and IL-1β production, and that the intraperitoneal injection of sulfated CCK-8 induced the production of IL-1β in the cancer-inoculated region. Conclusions We have identified a novel pain cascade, in which IL-1β production in cancer-inoculated regions induces ephrin B1 gene expression in DRGs and then ephrin B1 enhances the tyrosine phosphorylation of NR2B via Eph B receptor in the spinal cord. Notably, Z-360 relieves cancer-induced pain by preventing this pain cascade through the suppression of IL-1β production, likely via the blockade of CCK1 receptor. The pre-clinical results presented here support the analgesic

  8. Frequent genital HSV-2 shedding among women during labor in Soweto, South Africa. (United States)

    Perti, Tara; Nyati, Mandisa; Gray, Glenda; De Bruyn, Guy; Selke, Stacy; Magaret, Amalia; Huang, Meei-Li; Velaphi, Sithembiso; Corey, Lawrence; Wald, Anna


    Despite high herpes simplex virus type 2 (HSV-2) incidence and prevalence among women in Africa, we are unaware of published neonatal herpes reports. To assess neonatal HSV transmission potential in South Africa, we investigated the frequency of the strongest risk factors: HSV acquisition in late pregnancy and HSV shedding during labor. Women admitted in early labor to a hospital in Soweto underwent HSV serologic testing and genital swab collection for HSV PCR. HSV-2 seronegative women were assessed for seroconversion 4-6 weeks after delivery. Of 390 women enrolled, 229 (58.7%) were HSV-2 seropositive. Genital HSV-2 was detected in 17.2% of HSV-2 seropositive women, including 26 of 115 HIV-positive and 13 of 110 HIV-negative women (22.6% versus 11.8%; RR, 1.91; 95% CI, 1.04-3.53; P = 0.038), but in none of 161 HSV-2 seronegative women. Among the 91 HSV-2 seronegative women followed after delivery, none seroconverted. HSV-2 reactivation is common among South African women during labor, especially those with HIV coinfection. To determine the epidemiology of neonatal herpes in South Africa and to investigate whether the lack of reported cases is due to alterations in immune control or HSV-2 virulence, studies evaluating acutely ill neonates for HSV and studies of maternal HSV-2 shedding patterns are needed.

  9. Leaf Surface Wettability and Implications for Drop Shedding and Evaporation from Forest Canopies (United States)

    Konrad, W.; Ebner, M.; Traiser, C.; Roth-Nebelsick, A.


    Wettability and retention capacity of leaf surfaces are parameters that contribute to interception of rain, fog or dew by forest canopies. Contrary to common expectation, hydrophobicity or wettability of a leaf do not dictate the stickiness of drops to leaves. Crucial for the adhesion of drops is the contact angle hysteresis, the difference between leading edge contact angle and trailing edge contact angle for a running drop. Other parameters that are dependent on the static contact angle are the maximum volume of drops that can stick to the surface and the persistence of an adhering drop with respect to evaporation. Adaption of contact angle and contact angle hysteresis allow one to pursue different strategies of drop control, for example efficient water shedding or maximum retention of adhering water. Efficient water shedding is achieved if contact angle hysteresis is low. Retention of (isolated) large drops requires a high contact angle hysteresis and a static contact angle of 65.5°, while maximum retention by optimum spacing of drops necessitates a high contact angle hysteresis and a static contact angle of 111.6°. Maximum persistence with respect to evaporation is obtained if the static contact angle amounts to 77.5°, together with a high contact angle hysteresis. It is to be expected that knowledge of these parameters can contribute to the capacity of a forest to intercept water.

  10. γ-secretase directly sheds the survival receptor BCMA from plasma cells (United States)

    Laurent, Sarah A.; Hoffmann, Franziska S.; Kuhn, Peer-Hendrik; Cheng, Qingyu; Chu, Yuanyuan; Schmidt-Supprian, Marc; Hauck, Stefanie M.; Schuh, Elisabeth; Krumbholz, Markus; Rübsamen, Heike; Wanngren, Johanna; Khademi, Mohsen; Olsson, Tomas; Alexander, Tobias; Hiepe, Falk; Pfister, Hans-Walter; Weber, Frank; Jenne, Dieter; Wekerle, Hartmut; Hohlfeld, Reinhard; Lichtenthaler, Stefan F.; Meinl, Edgar


    Survival of plasma cells is regulated by B-cell maturation antigen (BCMA), a membrane-bound receptor activated by its agonist ligands BAFF and APRIL. Here we report that γ-secretase directly cleaves BCMA, without prior truncation by another protease. This direct shedding is facilitated by the short length of BCMA's extracellular domain. In vitro, γ-secretase reduces BCMA-mediated NF-κB activation. In addition, γ-secretase releases soluble BCMA (sBCMA) that acts as a decoy neutralizing APRIL. In vivo, inhibition of γ-secretase enhances BCMA surface expression in plasma cells and increases their number in the bone marrow. Furthermore, in multiple sclerosis, sBCMA levels in spinal fluid are elevated and associated with intracerebral IgG production; in systemic lupus erythematosus, sBCMA levels in serum are elevated and correlate with disease activity. Together, shedding of BCMA by γ-secretase controls plasma cells in the bone marrow and yields a potential biomarker for B-cell involvement in human autoimmune diseases. PMID:26065893

  11. Persistent parainfluenza virus shedding during isolation at the South Pole. (United States)

    Muchmore, H G; Parkinson, A J; Humphries, J E; Scott, E N; McIntosh, D A; Scott, L V; Cooney, M K; Miles, J A


    Persistent parainfluenza virus shedding in healthy young adults occurred throughout the 8 1/2-month winter isolation period at Amundsen-Scott South Pole Station during 1978. Two episodes of respiratory illness were observed after 10 and 29 weeks of complete social isolation. Throat swabs collected both routinely, and during each outbreak of respiratory illness, were directly inoculated into cell cultures. Parainfluenza virus types 1 and 3 were recovered from both symptomatic and asymptomatic subjects throughout the winter. No other viruses were obtained by these efforts. The presence of parainfluenza virus in these subjects long after the accepted incubation period for viral upper respiratory illness, and when the introduction of new virus to this community was impossible, suggests its persistence in man.

  12. Leading-edge vortex shedding from rotating wings

    CERN Document Server

    Kolomenskiy, Dmitry; Schneider, Kai


    The paper presents a numerical investigation of the leading-edge vortices generated by rotating triangular wings at Reynolds number $Re=250$. A series of three-dimensional numerical simulations have been carried out using a Fourier pseudo-spectral method with volume penalization. The transition from stable attachment of the leading-edge vortex to periodic vortex shedding is explored, as a function of the wing aspect ratio and the angle of attack. It is found that, in a stable configuration, the spanwise flow in the recirculation bubble past the wing is due to the centrifugal force, incompressibility and viscous stresses. For the flow outside of the bubble, an inviscid model of spanwise flow is presented.

  13. Vortex shedding from slender cones at low Reynolds numbers (United States)

    Papangelou, A.


    Wind-tunnel experiments on the flows created by a number of slightly tapered models of circular cross-section have shown the presence of spanwise cells (regions of constant shedding frequency) at Reynolds numbers of the order of 100. The experiments have also shown a number of other interesting features of these flows: the cellular flow configuration is dependent on the base Reynolds number and independent of the tip Reynolds number, the frequency jump between adjacent cells is a function of flow speed, taper angle and kinematic viscosity, but is constant along a cone's span, and the unsteady hot-wire anemometer signal is both amplitude and phase modulated. A mathematical model is proposed based on the complex Landau-Stuart equation with a spanwise diffusive coupling term. Numerical solutions of this equation have shown many of the qualitative features observed in the experiments.

  14. Nocturnal drainage wind characteristics in two converging air sheds

    Energy Technology Data Exchange (ETDEWEB)

    Gedayloo, T.; Clements, W.E.; Barr, S.; Archuleta, J.A.


    During the short experimental period in the Grants Basin of Northeastern New Mexico a survey was conducted on the complex meteorology of this area. Emphasis was placed on the nocturnal drainage flow because of the potential hazards to the populated areas of Milan and Grants from the effluents of the uranium mining and milling operation in this area. This investigation has shown that the nocturnal drainage flow patterns agree with the winds predicted on the basis of the complex terrain of the area. Because of the surface cooling at night (over 25/sup 0/C during summer and about 20/sup 0/C during winter), air from elevated surrounding areas flows to the low lying regions consequently setting up a nocturnal drainage flow. This regime exists over 60% of the time during summer months and over 65% of the time during winter months with a depth generally less than 200 m. In the San Mateo air shed the drainage flow is east northeast, and in the Ambrosia Lake air shed it is from northwest. The confluence of these two air flows contributes mainly to the drainage flow through the channel formed by La Ja Mesa and Mesa Montanosa. The analysis of data collected by the recording Flats Station confirms the prediction that although the area south of the channel region broadens considerably causing a reduction in flow speed, contributions from the southside of La Jara Mesa and Mesa Montanosa partly compensate for this reduction. The position of this recording station is 15 to 20 km from the populated towns of Milan and Grants. A drainage flow speed of approximately 2.2 m s/sup -1/ and the duration of over 11 hours as recorded by this station indicates that air from the San Mateo and Ambrosia Lake regions may be transported southwards to these population centers during a nocturnal period. In order to test this prediction, a series of multi-atmospheric tracer experiments were conducted in the Grants Basin.

  15. Consequence of temperature changes on cercarial shedding from Galba truncatula infected with Fasciola hepatica or Paramphistomum daubneyi

    Directory of Open Access Journals (Sweden)

    Rondelaud Daniel


    Full Text Available Experimental infections of Galba truncatula (two populations with Fasciola hepatica or Paramphistomum daubneyi were carried out to study the effect of water temperature changes (3 h at a mean of 12 °C every week on cercarial shedding during the patent period. The results were compared with those of control snails infected according to the same protocol and always maintained at 20 °C. Compared to controls, a significant increase in the number of cercariae-shedding snails, a significantly longer patent period and significantly greater cercarial production were noted in temperature-challenged snails, regardless of the type of digenean infection. In contrast, the number of incompletely formed metacercariae was significantly higher in temperature-challenged snails than in controls. Incompletely formed metacercariae of F. hepatica consisted of cysts whose colour remained whitish after shedding (25.4% for temperature-challenged snails or whose dome was flattened after encystment (74.6%. Those of P. daubneyi were totally dark brown or blackish after formation. These incomplete metacercariae might originate from young differentiating cercariae within the snail body (F. hepatica or from cercariae which died just after encystment (P. daubneyi. The use of regular temperature changes for snails infected with F. hepatica or P. daubneyi must be monitored carefully during collection of metacercariae to select completely formed cysts for infecting definitive hosts.

  16. Chemotherapy stimulates syndecan-1 shedding: a potentially negative effect of treatment that may promote tumor relapse. (United States)

    Ramani, Vishnu C; Sanderson, Ralph D


    In patients with multiple myeloma, the heparan sulfate proteoglycan syndecan-1 (CD138) is shed from the surface of tumor cells and accumulates in the serum and within the extracellular matrix of the bone marrow where it promotes tumor growth and metastasis. In the present study we discovered that commonly used anti-myeloma drugs stimulate syndecan-1 shedding both in vitro and in animals bearing myeloma tumors. Enhanced shedding is accompanied by increased syndecan-1 synthesis prior to drug induced tumor cell death. Addition of a caspase inhibitor blocks the drug-induced shedding of syndecan-1 in vitro indicating that shedding is linked to the onset of apoptosis. ADAM inhibitors or siRNA targeting ADAMs blocked drug-induced shedding suggesting that upregulation or activation of ADAMs is responsible for cleaving syndecan-1 from the tumor cell surface. These results reveal that myeloma chemotherapy stimulates synthesis and shedding of syndecan-1, a potentially negative side effect that may lead to the accumulation of high levels of syndecan-1 to establish a microenvironment that nurtures relapse and promotes tumor progression. Interestingly, we also found that chemotherapeutic drugs stimulated syndecan-1 shedding from pancreatic cancer cells as well, indicating that drug-induced shedding of syndecan-1 may occur in many cancer types. Overall, our results indicate that the use of metalloproteinase inhibitors (to inhibit syndecan-1 shedding) in combination with chemotherapy may represent a novel therapeutic strategy to prevent re-establishment of a microenvironment conducive for tumor relapse. © 2013.

  17. Analysis and Prediction of Ice Shedding for a Full-Scale Heated Tail Rotor (United States)

    Kreeger, Richard E.; Work, Andrew; Douglass, Rebekah; Gazella, Matthew; Koster, Zakery; Turk, Jodi


    When helicopters are to fly in icing conditions, it is necessary to consider the possibility of ice shed from the rotor blades. In 2013, a series of tests were conducted on a heated tail rotor at NASA Glenn's Icing Research Tunnel (IRT). The tests produced several shed events that were captured on camera. Three of these shed events were captured at a sufficiently high frame rate to obtain multiple images of the shed ice in flight that had a sufficiently long section of shed ice for analysis. Analysis of these shed events is presented and compared to an analytical Shedding Trajectory Model (STM). The STM is developed and assumes that the ice breaks off instantly as it reaches the end of the blade, while frictional and viscous forces are used as parameters to fit the STM. The trajectory of each shed is compared to that predicted by the STM, where the STM provides information of the shed group of ice as a whole. The limitations of the model's underlying assumptions are discussed in comparison to experimental shed events.

  18. Role of EphB4-EphrinB2 Bidirection-Signals in Angiogenesis and Prospect of Application of Traditional Chinese Medicine%酪氨酸激酶受体B4及其相关配体B2双向信号对血管生成的调节作用及中药应用展望

    Institute of Scientific and Technical Information of China (English)

    张静思; 胡雅琼; 高冬; 宋军


    Eph receptors and their ligands comprise the largest family of receptor tyrosine kinases (RTKs), which take part in various physiological and pathological processes. Eph-ephrin interactions mediate distinct forward and reverse signal pathway, especially the bi-directional signals of EphB4-ephrinB2 have attracted lots of attention. Studies on their function in vascular system may bring the scientific research and clinical treatment to a new era for the issue of angiogenesis. Traditional Chinese medicine ( TCM ) maintains human health by promoting blood circulation, removing blood stasis, eliminating phlegm, regulating and reinforcing the vital energy. TCM may also have angiogenic and anti-angiogenic effects. In recent years, with the evidences of bi-directional signals of EphB4-ephrinb2 and the application of TCM, scientists pay great attention on how TCM regulates the signal mechanism during the process of angiogenesis. Research has already reported that Xuefu Zhuyu decoction can up-regulate ephrinB2' gene expression during angiogenesis of endothelial cell, ECV304. On the basis of the relevant research, we believe TCM plays an important role in regulating angiogenic signals, especially, EphB4-ephrinB2.%Eph受体作为受体酪氨酸激酶家族(RTKs)最大的的亚群,在与配体ephrin相互作用中,形成颇具特色的正、负信号通路;尤其是EphB4-ephrinB2双向信号对血管生成的调节作用,为相关领域科研和临床治疗带来了新的希冀.中医药通过活血、祛瘀、理气、化痰、补益等多种治疗手段参与人体机能的调节,对血管生成同样具有促进和阻抑的双向作用.近年来随着国内外对EphB4-ephrinB2双向信号和中医药应用领域探索的进一步深入,中医药对血管生成信号机制调控作用受到越来越多的关注;有研究显示血府逐瘀汤在促内皮细胞ECV304血管新生中上调EphrinB2的基因表达,为中医药研究ephrinB2-EphB4及其双向信号提供了线索.

  19. Inhibiting avian influenza virus shedding using a novel RNAi antiviral vector technology: proof of concept in an avian cell model. (United States)

    Linke, Lyndsey M; Wilusz, Jeffrey; Pabilonia, Kristy L; Fruehauf, Johannes; Magnuson, Roberta; Olea-Popelka, Francisco; Triantis, Joni; Landolt, Gabriele; Salman, Mo


    Influenza A viruses pose significant health and economic threats to humans and animals. Outbreaks of avian influenza virus (AIV) are a liability to the poultry industry and increase the risk for transmission to humans. There are limitations to using the AIV vaccine in poultry, creating barriers to controlling outbreaks and a need for alternative effective control measures. Application of RNA interference (RNAi) techniques hold potential; however, the delivery of RNAi-mediating agents is a well-known obstacle to harnessing its clinical application. We introduce a novel antiviral approach using bacterial vectors that target avian mucosal epithelial cells and deliver (small interfering RNA) siRNAs against two AIV genes, nucleoprotein (NP) and polymerase acidic protein (PA). Using a red fluorescent reporter, we first demonstrated vector delivery and intracellular expression in avian epithelial cells. Subsequently, we demonstrated significant reductions in AIV shedding when applying these anti-AIV vectors prophylactically. These antiviral vectors provided up to a 10,000-fold reduction in viral titers shed, demonstrating in vitro proof-of-concept for using these novel anti-AIV vectors to inhibit AIV shedding. Our results indicate this siRNA vector technology could represent a scalable and clinically applicable antiviral technology for avian and human influenza and a prototype for RNAi-based vectors against other viruses.

  20. Emergency control

    Energy Technology Data Exchange (ETDEWEB)

    Di Caprio, U.


    The main trends in the development of techniques presently used for emergency control of electric power systems are illustrated, from load-shedding to islanding, generator control, automatic reclosure of circuits, reactive power control and auxiliary aids in the control centers. Methods for improving the design criteria are reviewed. 61 refs.

  1. Characterization of the Frictional Response of Squamata Shed Skin in Comparison to Human skin

    CERN Document Server

    Abdel-Aal, H A


    Deterministic surfaces are constructs of which profile, topography and textures are integral to the function of the system they enclose. They are designed to yield a predetermined rubbing response. Developing such entities relies on controlling the structure of the rubbing interface so that, not only the surface is of optimized topography, but also is able to self-adjust its behavior according to the evolution of sliding conditions. Inspirations for such designs are frequently encountered in natural species. In particular, and from a tribological point of view, Squamate Reptiles, offer diverse examples where surface texturing, submicron and nano-scale features, achieves frictional regulation. In this paper, we study the frictional response of shed skin obtained from a Python regius snake. The study employed a specially designed tribo-acoustic probe capable of measuring the coefficient of friction and detecting the acoustical behavior of the skin in vivo. The results confirm the anisotropy of the frictional re...

  2. Deposit Shedding in Biomass-Fired Boilers: Shear Adhesion Strength Measurements

    DEFF Research Database (Denmark)

    Laxminarayan, Yashasvi; Jensen, Peter Arendt; Wu, Hao


    a significant effect under the investigated conditions. Addition of compounds which increase the melt fraction of the ash dposit, typically by forming a eutectic system, increases the adhesion strength, whereas addition of inert compounds with a high melting point decreases the adhesion strength. Furthermore......Ash deposition on boiler surfaces is a major problem encountered in biomass combustion. Timely removal of ash deposits is essentialfor optimal boiler operation. In order to improve the understanding of deposit shedding in boilers, this study investigates the adhesion strength of biomass ash from...... off by an electrically controlled arm, and the corresponding adhesion strength was measured. The effect of sintering temperature, sintering time, deposit composition, thermal shocks on the deposit, and steel type was investigated. The results reveal that the adhesion strength of ash deposits...

  3. Cryogenic transmission electron microscopy nanostructural study of shed microparticles.

    Directory of Open Access Journals (Sweden)

    Liron Issman

    Full Text Available Microparticles (MPs are sub-micron membrane vesicles (100-1000 nm shed from normal and pathologic cells due to stimulation or apoptosis. MPs can be found in the peripheral blood circulation of healthy individuals, whereas elevated concentrations are found in pregnancy and in a variety of diseases. Also, MPs participate in physiological processes, e.g., coagulation, inflammation, and angiogenesis. Since their clinical properties are important, we have developed a new methodology based on nano-imaging that provides significant new data on MPs nanostructure, their composition and function. We are among the first to characterize by direct-imaging cryogenic transmitting electron microscopy (cryo-TEM the near-to-native nanostructure of MP systems isolated from different cell types and stimulation procedures. We found that there are no major differences between the MP systems we have studied, as most particles were spherical, with diameters from 200 to 400 nm. However, each MP population is very heterogeneous, showing diverse morphologies. We investigated by cryo-TEM the effects of standard techniques used to isolate and store MPs, and found that either high-g centrifugation of MPs for isolation purposes, or slow freezing to -80 °C for storage introduce morphological artifacts, which can influence MP nanostructure, and thus affect the efficiency of these particles as future diagnostic tools.

  4. CFTR Modulators: Shedding Light on Precision Medicine for Cystic Fibrosis (United States)

    Lopes-Pacheco, Miquéias


    Cystic fibrosis (CF) is the most common life-threatening monogenic disease afflicting Caucasian people. It affects the respiratory, gastrointestinal, glandular and reproductive systems. The major cause of morbidity and mortality in CF is the respiratory disorder caused by a vicious cycle of obstruction of the airways, inflammation and infection that leads to epithelial damage, tissue remodeling and end-stage lung disease. Over the past decades, life expectancy of CF patients has increased due to early diagnosis and improved treatments; however, these patients still present limited quality of life. Many attempts have been made to rescue CF transmembrane conductance regulator (CFTR) expression, function and stability, thereby overcoming the molecular basis of CF. Gene and protein variances caused by CFTR mutants lead to different CF phenotypes, which then require different treatments to quell the patients’ debilitating symptoms. In order to seek better approaches to treat CF patients and maximize therapeutic effects, CFTR mutants have been stratified into six groups (although several of these mutations present pleiotropic defects). The research with CFTR modulators (read-through agents, correctors, potentiators, stabilizers and amplifiers) has achieved remarkable progress, and these drugs are translating into pharmaceuticals and personalized treatments for CF patients. This review summarizes the main molecular and clinical features of CF, emphasizes the latest clinical trials using CFTR modulators, sheds light on the molecular mechanisms underlying these new and emerging treatments, and discusses the major breakthroughs and challenges to treating all CF patients. PMID:27656143

  5. Structural biology sheds light on the puzzle of genomic ORFans. (United States)

    Siew, Naomi; Fischer, Daniel


    Genomic ORFans are orphan open reading frames (ORFs) with no significant sequence similarity to other ORFs. ORFans comprise 20-30% of the ORFs of most completely sequenced genomes. Because nothing can be learnt about ORFans via sequence homology, the functions and evolutionary origins of ORFans remain a mystery. Furthermore, because relatively few ORFans have been experimentally characterized, it has been suggested that most ORFans are not likely to correspond to functional, expressed proteins, but rather to spurious ORFs, pseudo-genes or to rapidly evolving proteins with non-essential roles. As a snapshot view of current ORFan structural studies, we searched for ORFans among proteins whose three-dimensional structures have been recently determined. We find that functional and structural studies of ORFans are not as underemphasized as previously suggested. These recently determined structures correspond to ORFans from all Kingdoms of life, and include proteins that have previously been functionally characterized, as well as structural genomics targets of unknown function labeled as "hypothetical proteins". This suggests that many of the ORFans in the databases are likely to correspond to expressed, functional (and even essential) proteins. Furthermore, the recently determined structures include examples of the various types of ORFans, suggesting that the functions and evolutionary origins of ORFans are diverse. Although this survey sheds some light on the ORFan mystery, further experimental studies are required to gain a better understanding of the role and origins of the tens of thousands of ORFans awaiting characterization.

  6. Demand Response an Alternative Solution to Prevent Load Shedding Triggering

    Directory of Open Access Journals (Sweden)

    K. Mollah


    Full Text Available This paper investigates an alternative solution to prevent Load Shedding (LS triggering during underfrequency and proposes a new technique to restore the frequency during emergency events. Demand response (DR is considered as one of the most promising Smart Grid concepts that can be used to support the peak demand, whereas, LS is an existing last resort method during emergency grid situations. Both schemes aim to balance the load and generation in real-time and restore the frequency very quickly. This paper incorporates integrating Incentive based Demand Response (IDR with spinning reserve for smaller underfrequency events to manage the system peak demand. It also introduces a new frequency band for an Emergency Demand Response (EDR as an alternative inexpensive solution that can replace costly spinning reserves and help to prevent LS. An energy index factor is used to identify the consumption pattern of consumers to enable them to participate in IDR. An illustrative example of the performance of the proposed scheme on a modified 15 bus test system is shown. Simulation results on different scenarios confirm that the proposed method is effective to improve the frequency restoration process along with enabling participation of new services.

  7. Increased EBV Shedding in Astronaut Saliva During Spaceflight (United States)

    Pierson, D. L.; Stowe, R. P.; Phillips, T.; Lugg, D. J.; Mehta, S. K.


    Shedding of Epstein-Barr virus (EBV) by astronauts before, during, and after space shuttle missions was quantified. Of 1398 saliva specimens from 32 astronauts, 314 (23%) were positive for EBV DNA by PCR analysis. Of the saliva specimens collected before flight, 29% were positive for EBV DNA and of those collected during or after flight, 16% were EBV-positive. The number of EBV DNA copies from samples taken during the flight was 417+/-31, significantly higher (P EBV DNA with a frequency of 3.7% and a copy number of 40+/-2 per ml saliva. Ten days before flight and on landing day, antibody titers to EBV viral capsid antigen (VCA) were significantly (P < 0.05) higher than baseline levels. On landing day, urinary level of cortiso1 and catecholamines, and plasma levels of substance P and other neuropeptides, were increased over their preflight value. Results suggested that stress associated with spaceflight decreases cellular immunity and thereby leads to increased viral reactivation.

  8. Vortex Shedding in the Wake of a Dual Step Cylinder

    CERN Document Server

    Morton, Chris


    A dual-step cylinder is comprised of a large diameter cylinder (D) with low aspect ratio (L/D) attached co-axially to the mid-span of a small diameter cylinder (d). The fluid dynamics video presented in this investigation is used to illustrate the effect of aspect ratio on dual step cylinder wake development for Re = 2100, D/d = 2, and 0.2 < L/D < 3. In addition, the video provides visualization of such flow phenomena as interaction of spanwise vortices, development of streamwise vortex filaments, and formation of Kelvin-Helmholtz rollers. The experiments were performed in a water flume at the University of Waterloo. A hydrogen bubble flow visualization technique was employed to visualize vortical structures downstream of each cylinder model. High-resolution images of the flow were obtained with a high speed Photron camera and post-processed using Adobe Photoshop CS4. The results show a plethora of vortices developing in the wake of the dual step cylinder. For 1 < L/D < 3, spanwise vortex shedding...

  9. Hydrogen Bubbles as a Visualization Tool for Cylinder Shedding (United States)

    Sigurdson, Lorenz; Gilbert, Stuart


    We examine the behavior of hydrogen bubbles formed by electrolysis of water on a 2.54 mm cylindrical electrode in a water tunnel. The Reynolds Number based on cylinder diameter varies from 400 to 1100, and tunnel velocities range from 17 to 50 cm/s. At the lowest velocity buoyancy is a strong effect which inhibits accurate flow tracking by the bubbles. This effect largely disappears by 25 cm/s. As the tunnel velocity increases, bubble size decreases, reflected light for photography is reduced, and bubbles begin to track the von Karman vortex street vortex cores near the cylinder. The vortex cores have a sufficiently low pressure to capture the bubbles. Vortex street wavelength is seen to discretely increase as vortices proceed downstream. The location of this scale-change becomes nearer the cylinder as Re increases. Voids of bubbles occur in continuous linear downstream segments originating near the cylinder. They seem to be due to vortex modification in the wake similar to what other cylinder shedding researchers have found.

  10. Rotavirus vaccines: viral shedding and risk of transmission. (United States)

    Anderson, Evan J


    Rotavirus causes gastroenteritis in almost all children by 5 years of age. Immunity to rotavirus is incomplete, with potential for recurrent infections occurring throughout life. Live rotavirus vaccines have been developed for the protection of children from severe wildtype rotavirus infections. Transmission of vaccine virus strains from vaccinated children to unvaccinated contacts harbours the potential for herd immunity, but also the risk of vaccine-derived disease in immunocompromised contacts. A review of rotavirus vaccine prelicensure studies shows that viral shedding and transmission were higher with the old tetravalent rhesus rotavirus vaccine than with the current human attenuated monovalent rotavirus vaccine and the pentavalent bovine-human reassortant vaccine. Immunocompromised contacts should be advised to avoid contact with stool from the immunised child if possible, particularly after the first vaccine dose for at least 14 days. Since the risk of vaccine transmission and subsequent vaccine-derived disease with the current vaccines is much less than the risk of wildtype rotavirus disease in immunocompromised contacts, vaccination should be encouraged.

  11. Shear shedding of drops and the use of superhydrophobic surfaces in microgravity: PFC and ground based results (United States)

    Milne, Andrew; Amirfazli, Alidad

    In free fall, the absence of gravity poses many challenges for fluid handling systems. One such example of this is condensers. On earth, the condensed liquid is removed from the tilted condenser plate by gravity forced shedding. In microgravity, proposed solutions include the use of surfaces with gradients in wettability [1], the use of electrowetting [2], and shearing airflow [3]. In this talk, shear shedding results for a variety of surface (hydrophilic to superhydrophobic (extremely water repelling)) will be presented. Surface science and aerodynamics are used to reveal fundamental parameters controlling incipient motion for drops exposed to shearing airflow. It is found that wetting parameters such as contact angle and surface tension are very influential in determining the minimum required air velocity for drop shedding. Based on experimental results for drops of water and hexadecane (0.5-100 l) on PMMA, Teflon, and a superhydrophobic aluminum surface, an exponential function is proposed that relates the critical air velocity for shedding to the ratio of drop base length to projected area. The results for the water systems can be collapsed to a self similar curve by normalization, which also explains results from other researchers. Since shedding from superhydrophobic surfaces (SHS) is seen to be easier compared to other surfaces, the behaviour of SHS is also probed in this talk. SHS have space-based applications to shedding, self cleaning, anti-icing (spacecraft launch/re-entry), anti-fouling, fluid actuation, and decreased fluid friction. The mechanism for SHS is understood to be the existence of an air layer between large portions of the drop and solid. The first concrete visual evidence of this was gained performing a parabolic flight experiment with the ESA. Results of this experi-ment will be discussed, showing the extreme water repelling potential of SHS in microgravity, and demonstrating how the wetting behaviours seen (partial penetration, transition

  12. Community-based Men's Sheds: promoting male health, wellbeing and social inclusion in an international context. (United States)

    Cordier, Reinie; Wilson, Nathan J


    Males experience greater mortality and morbidity than females in most Western countries. The Australian and Irish National Male Health Policies aim to develop a framework to address this gendered health disparity. Men's Sheds have a distinct community development philosophy and are thus identified in both policies as an ideal location to address social isolation and positively impact the health and wellbeing of males who attend. The aim of this international cross-sectional survey was to gather information about Men's Sheds, the people who attend Men's Sheds, the activities at Men's Sheds, and the social and health dimensions of Men's Sheds. Results demonstrate that Men's Sheds are contributing a dual health and social role for a range of male subgroups. In particular, Men's Sheds have an outward social focus, supporting the social and mental health needs of men; health promotion and health literacy are key features of Men's Sheds. Men's Sheds have an important role to play in addressing the gendered health disparity that males face. They serve as an exemplar to health promotion professionals of a community development context where the aims of male health policy can be actualized as one part of a wider suite of global initiatives to reduce the gendered health disparity.

  13. Effects of decellularized matrices derived from periodontal ligament stem cells and SHED on the adhesion, proliferation and osteogenic differentiation of human dental pulp stem cells in vitro. (United States)

    Heng, Boon Chin; Zhu, Shaoyue; Xu, Jianguang; Yuan, Changyong; Gong, Ting; Zhang, Chengfei


    A major bottleneck to the therapeutic applications of dental pulp stem cells (DPSC) are their limited proliferative capacity ex vivo and tendency to undergo senescence. This may be partly due to the sub-optimal in vitro culture milieu, which could be improved by an appropriate extracellular matrix substratum. This study therefore examined decellularized matrix (DECM) from stem cells derived from human exfoliated deciduous teeth (SHED) and periodontal ligament stem cells (PDLSC), as potential substrata for DPSC culture. Both SHED-DECM and PDLSC-DECM promoted rapid adhesion and spreading of newly-seeded DPSC compared to bare polystyrene (TCPS), with vinculin immunocytochemistry showing expression of more focal adhesions by newly-adherent DPSC cultured on DECM versus TCPS. Culture of DPSC on SHED-DECM and PDLSC-DECM yielded higher proliferation of cell numbers compared to TCPS. The qRT-PCR data showed significantly higher expression of nestin by DPSC cultured on DECM versus the TCPS control. Osteogenic differentiation of DPSC was enhanced by culturing on PDLSC-DECM and SHED-DECM versus TCPS, as demonstrated by alizarin red S staining for mineralized calcium deposition, alkaline phosphatase assay and qRT-PCR analysis of key osteogenic marker expression. Hence, both SHED-DECM and PDLSC-DECM could enhance the ex vivo culture of DPSC under both non-inducing and osteogenic-inducing conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Replication and shedding kinetics of infectious hematopoietic necrosis virus in juvenile rainbow trout (United States)

    Wargo, Andrew R.; Scott, Robert J.; Kerr, Benjamin; Kurath, Gael


    Viral replication and shedding are key components of transmission and fitness, the kinetics of which are heavily dependent on virus, host, and environmental factors. To date, no studies have quantified the shedding kinetics of infectious hematopoietic necrosis virus (IHNV) in rainbow trout (Oncorhynchus mykiss), or how they are associated with replication, making it difficult to ascertain the transmission dynamics of this pathogen of high agricultural and conservation importance. Here, the replication and shedding kinetics of two M genogroup IHNV genotypes were examined in their naturally co-evolved rainbow trout host. Within host virus replication began rapidly, approaching maximum values by day 3 post-infection, after which viral load was maintained or gradually dropped through day 7. Host innate immune response measured as stimulation of Mx-1 gene expression generally followed within host viral loads. Shedding also began very quickly and peaked within 2 days, defining a generally uniform early peak period of shedding from 1 to 4 days after exposure to virus. This was followed by a post-peak period where shedding declined, such that the majority of fish were no longer shedding by day 12 post-infection. Despite similar kinetics, the average shedding rate over the course of infection was significantly lower in mixed compared to single genotype infections, suggesting a competition effect, however, this did not significantly impact the total amount of virus shed. The data also indicated that the duration of shedding, rather than peak amount of virus shed, was correlated with fish mortality. Generally, the majority of virus produced during infection appeared to be shed into the environment rather than maintained in the host, although there was more retention of within host virus during the post-peak period. Viral virulence was correlated with shedding, such that the more virulent of the two genotypes shed more total virus. This fundamental understanding of IHNV

  15. Replication and shedding kinetics of infectious hematopoietic necrosis virus in juvenile rainbow trout. (United States)

    Wargo, Andrew R; Scott, Robert J; Kerr, Benjamin; Kurath, Gael


    Viral replication and shedding are key components of transmission and fitness, the kinetics of which are heavily dependent on virus, host, and environmental factors. To date, no studies have quantified the shedding kinetics of infectious hematopoietic necrosis virus (IHNV) in rainbow trout (Oncorhynchus mykiss), or how they are associated with replication, making it difficult to ascertain the transmission dynamics of this pathogen of high agricultural and conservation importance. Here, the replication and shedding kinetics of two M genogroup IHNV genotypes were examined in their naturally co-evolved rainbow trout host. Within host virus replication began rapidly, approaching maximum values by day 3 post-infection, after which viral load was maintained or gradually dropped through day 7. Host innate immune response measured as stimulation of Mx-1 gene expression generally followed within host viral loads. Shedding also began very quickly and peaked within 2days, defining a generally uniform early peak period of shedding from 1 to 4days after exposure to virus. This was followed by a post-peak period where shedding declined, such that the majority of fish were no longer shedding by day 12 post-infection. Despite similar kinetics, the average shedding rate over the course of infection was significantly lower in mixed compared to single genotype infections, suggesting a competition effect, however, this did not significantly impact the total amount of virus shed. The data also indicated that the duration of shedding, rather than peak amount of virus shed, was correlated with fish mortality. Generally, the majority of virus produced during infection appeared to be shed into the environment rather than maintained in the host, although there was more retention of within host virus during the post-peak period. Viral virulence was correlated with shedding, such that the more virulent of the two genotypes shed more total virus. This fundamental understanding of IHNV shedding

  16. Acceleration of epithelial cell syndecan-1 shedding by anthrax hemolytic virulence factors

    Directory of Open Access Journals (Sweden)

    Chandhoke Vikas


    Full Text Available Abstract Background It has been recently reported that major pathogens Staphylococcus aureus and Pseudomonas aeruginosa accelerate a normal process of cell surface syndecan-1 (Synd1 ectodomain shedding as a mechanism of host damage due to the production of shedding-inducing virulence factors. We tested if acceleration of Synd1 shedding takes place in vitro upon treatment of epithelial cells with B. anthracis hemolysins, as well as in vivo during anthrax infection in mice. Results The isolated anthrax hemolytic proteins AnlB (sphingomyelinase and AnlO (cholesterol-binding pore-forming factor, as well as ClnA (B. cereus homolog of B. anthracis phosphatidyl choline-preferring phospholipase C cause accelerated shedding of Synd1 and E-cadherin from epithelial cells and compromise epithelial barrier integrity within a few hours. In comparison with hemolysins in a similar range of concentrations, anthrax lethal toxin (LT also accelerates shedding albeit at slower rate. Individual components of LT, lethal factor and protective antigen are inactive with regard to shedding. Inhibition experiments favor a hypothesis that activities of tested bacterial shedding inducers converge on the stimulation of cytoplasmic tyrosine kinases of the Syk family, ultimately leading to activation of cellular sheddase. Both LT and AnlO modulate ERK1/2 and p38 MAPK signaling pathways, while JNK pathway seems to be irrelevant to accelerated shedding. Accelerated shedding of Synd1 also takes place in DBA/2 mice challenged with Bacillus anthracis (Sterne spores. Elevated levels of shed ectodomain are readily detectable in circulation after 24 h. Conclusion The concerted acceleration of shedding by several virulence factors could represent a new pathogenic mechanism contributing to disruption of epithelial or endothelial integrity, hemorrhage, edema and abnormal cell signaling during anthrax infection.

  17. The toxicology of ion-shedding zinc oxide nanoparticles. (United States)

    Liu, Jia; Feng, Xiaoli; Wei, Limin; Chen, Liangjiao; Song, Bin; Shao, Longquan


    Zinc oxide nanoparticles (ZnO NPs) are nanomaterials that are widely used in many fields. ZnO NPs are ion-shedding particles, and zinc ions produce important and potent effects that differ from those of other metal or metal oxide NPs. Several studies have reported the toxicological effects of ZnO NPs administered via several different routes, including orally, dermally, by pulmonary absorption, intraperitoneally, and intravenously. Some potential routes for human exposure have produced various toxic effects in animal models. Moreover, several in vitro studies using a range of cell lines have reported the mechanisms underlying ZnO NP toxicity. Zinc ions play a very important role in ZnO NP toxicity, although the effects of the particulate form cannot be excluded. A crucial determinant of toxicity is the solubility of ZnO NPs, which is influenced by various factors, including the pH of the environment in tissues, cells, and organelles. In addition to the inflammatory responses and oxidative stress known to be induced by ZnO NPs, these NPs also exhibit some positive anti-inflammatory, anti-diabetic, and pro-coagulant effects at sub-toxic doses; these effects are probably induced by zinc ions, which are an essential element in cell homeostasis. It is highly likely that there are additional distinct mechanisms at sub-toxic doses and concentrations, which may be concealed or altered by the toxic effects observed at higher levels of ZnO NPs. Furthermore, many signaling pathway molecules associated with necrosis and apoptosis can be activated, leading to cell death. This review presents the status of ZnO NP toxicology and highlights areas requiring further investigation.

  18. Multi-frequency response of a cylinder subjected to vortex shedding and support motions

    Energy Technology Data Exchange (ETDEWEB)

    Vikestad, Kyrre


    This thesis deals with an experimental investigation of vortex induced vibrations of a circular cylinder. The purpose of the experiment was to identify the influence from a controlled disturbance of the cylinder motions on the response caused by vortex shedding. The cylinder investigated is 2 m long and the diameter is 10 cm. The cylinder is elastically mounted in an apparatus using springs, where the foundation of one of the springs can have a harmonic motion. The apparatus is placed on a carriage in a 25 m long towing tank. Towing velocities are varied between 0.140 m/s and 0.655 m/s corresponding to reduced velocity range from 2.8 to 13.2. The still water natural frequency is 0.497 Hz, and the natural frequency in air is 0.634 Hz. The cylinder is only able to oscillate in the cross-flow direction. The support motion frequency was varied between 0.26 Hz and 1.01 Hz, and the force motion amplitude was varied using 2, 4 and 6 cm support amplitudes. Three sets of experiments were carried out: (1) Still water oscillations due to harmonic support motion excitation, support amplitude and frequencies varied, (2) Towing tests with no support motion, the velocity is varied, (3) Combined excitation: Towing tests with support motion. All possible combinations of experiments (1) and (2) are carried out. The two first experiments provide reference values for the combined excitation experiments and for verification purposes. The results reveal the ability of the external disturbance to influence the vortex shedding process both regarding frequency and the resulting response amplitudes. Results for added mass, in-line drag and damping are also obtained. The work may be of use in deep water floating petroleum production. 81 refs., 73 figs., 6 tabs.

  19. Carbonate shedding and sedimentary cyclicities of a distally steepened carbonate ramp (Miocene, Great Bahama Bank) (United States)

    Betzler, C.; Pfeiffer, M.; Saxena, S.

    Depositional geometries as imaged in seismic lines, logging data, and quantitative petrographic data were used to analyse the slope and toe of slope deposits of the Miocene distally steepened carbonate ramp of Great Bahama Bank. The shedding pattern along the slope of this ramp is more complex than it is along the slope of the Pliocene-Pleistocene flat-topped carbonate platform. Compositional changes and compositional trends of periplatform sediments correlate with the positions of geophysically-defined sequence boundaries. Two types of depositional sequences occur. The first sequence is characterised by laterally traceable sequence-internal reflections, whereas the second type contains major intrasequential incisions. Erosional incisions and sedimentary infills of these canyons by turbidites formed during sea-level lowstands, as is indicated by the composition of the turbidites having a mixture of shallow-water and pelagic particles. Highstand turbidites are characterised by more extensive, laterally traceable geometries and by the occurrence of abundant shallow-water particles. In contrast to highstand turbidites shed from the Pliocene-Pleistocene flat-topped platform, shallow-water components in highstand turbidites of the Miocene ramp are of skeletal origin. The stacking pattern of the periplatform deposits is controlled by sea-level fluctuations. Four orders of sea-level changes are distinguished. Third-order cycles are delimited by sequence boundaries, and fourth (100,000a) order cycles govern the bundling of turbidites into packages. Fifth (40,000a) and sixth (23,000a) order cycles are recorded in the background sediments and resolvable with spectral analysis.

  20. Effectiveness of a commercial leptospiral vaccine on urinary shedding in naturally exposed sheep in New Zealand. (United States)

    Vallée, Emilie; Ridler, Anne L; Heuer, Cord; Collins-Emerson, Julie M; Benschop, Jackie; Wilson, Peter R


    L. borgpetersenii serovar Hardjo and L. interrogans serovar Pomona are endemic in New Zealand sheep. An effective vaccine and vaccination strategy would protect both humans and livestock. Four to 12 lambs were selected from each of eight farms (total=84, vaccinated group), while four to 16 lambs (total=98) served as unvaccinated controls. A commercial Hardjo/Pomona vaccine was given at 1-6 weeks of age, 5-11 weeks later and 33-67 weeks later on seven farms and at 18 weeks of age and 5 weeks later on the eighth farm. Vaccinates and controls were grazed together. Blood was regularly collected from the control group to assess flock exposure. Urine was collected from both groups 26-82 weeks after the second vaccination and tested by quantitative PCR. Seroprevalence in controls at the time of urine sampling ranged from 2.7 to 98.2% for Hardjo and from 0 to 54.1% for Pomona with seroconversion occurring 13 to 67 weeks after the second vaccination in all but one farm where exposure had happened by the time of vaccination. The shedding prevalence adjusted for clustering in farms was 45.1% [95% CI 17.6-72.7] (for an observed number of 50/98) in the control animals and 1.8% [95% CI 0.0-10.1] (for an observed number of 5/84) in the vaccinated animals. The vaccine was 100% effective on five farms where animals were vaccinated before 12 weeks of age and before natural exposure occurred, but the effectiveness was 80% [0-97] on one farm where the lambs were exposed before vaccination and 65% [9-87] to 80% [0-97] on one farm where the animals were fully vaccinated by 24 weeks of age. The overall vaccine effectiveness was 86.3% [63.6-94.8%] despite maternal antibodies in some flocks at first vaccination. Vaccination timing seemed to be crucial in achieving optimum reduction in shedding in urine in vaccinated sheep. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Eph-mediated tyrosine phosphorylation of citron kinase controls abscission (United States)

    Jungas, Thomas; Perchey, Renaud T.; Fawal, Mohamad; Callot, Caroline; Froment, Carine; Burlet-Schiltz, Odile; Besson, Arnaud


    Cytokinesis is the last step of cell division, culminating in the physical separation of daughter cells at the end of mitosis. Cytokinesis is a tightly regulated process that until recently was mostly viewed as a cell-autonomous event. Here, we investigated the role of Ephrin/Eph signaling, a well-known local cell-to-cell communication pathway, in cell division. We show that activation of Eph signaling in vitro leads to multinucleation and polyploidy, and we demonstrate that this is caused by alteration of the ultimate step of cytokinesis, abscission. Control of abscission requires Eph kinase activity, and Src and citron kinase (CitK) are downstream effectors in the Eph-induced signal transduction cascade. CitK is phosphorylated on tyrosines in neural progenitors in vivo, and Src kinase directly phosphorylates CitK. We have identified the specific tyrosine residues of CitK that are phosphorylated and show that tyrosine phosphorylation of CitK impairs cytokinesis. Finally, we show that, similar to CitK, Ephrin/Eph signaling controls neuronal ploidy in the developing neocortex. Our study indicates that CitK integrates intracellular and extracellular signals provided by the local environment to coordinate completion of cytokinesis. PMID:27551053

  2. Influence of thermal inhibitor position and temperature on vortex-shedding-driven pressure oscillations

    Institute of Scientific and Technical Information of China (English)

    Su Wanxing; Li Shipeng; Zhang Qiao; Li Junwei; Ye Qingqing; Wang Ningfei


    Vortex-acoustic coupling is one of the most important potential sources of combustion instability in solid rocket motors (SRMs).Based on the Von Karman Institute for Fluid Dynamics (VKI) experimental motor,the influence of the thermal inhibitor position and temperature on vortex-shedding-driven pressure oscillations is numerically studied via the large eddy simulation (LES)method.The simulation results demonstrate that vortex shedding is a periodic process and its accurate frequency can be numerically obtained.Acoustic modes could be easily excited by vortex shedding.The vortex shedding frequency and second acoustic frequency dominate the pressure oscillation characteristics in the chamber.Thermal inhibitor position and gas temperature have little effect on vortex shedding frequency,but have great impact on pressure oscillation amplitude.Pressure amplitude is much higher when the thermal inhibitor locates at the acoustic velocity anti-nodes.The farther the thermal inhibitor is to the nozzle head,the more vortex energy would be dissipated by the turbulence.Therefore,the vortex shedding amplitude at the second acoustic velocity antinode near 3/4L (L is chamber length) is larger than those of others.Besides,the natural acoustic frequencies increase with the gas temperature.As the vortex shedding frequency departs from the natural acoustic frequency,the vortex-acoustic feedback loop is decoupled.Consequently,both the vortex shedding and acoustic amplitudes decrease rapidly.

  3. Genetic relationship between wool shedding in ewe-lambs and ewes (United States)

    Interest in reducing labor costs related to shearing has led to the development of breeds that naturally shed their wool annually. This goal has been achieved by introducing hair-sheep genetics. These developments are relatively recent and thus the genetic underpinnings of wool shedding (WS) are not...

  4. A hybrid method for optimal load shedding and improving voltage stability

    Directory of Open Access Journals (Sweden)

    V. Tamilselvan


    Full Text Available In this paper, a hybrid method is proposed for reducing the amount of load shedding and voltage collapse. The hybrid method is the combination of Genetic Algorithm (GA and Neural Network (NN. The GA is used by two stages, one is to frame the optimization model and other stage is to generate data set for developing the NN based intelligent load shedding model. The appropriate buses for load shedding are selected based on the sensitivity of minimum eigenvalue of load flow Jacobian with respect to the load shed. The proposed method is implemented in MATLAB working platform and the performance is tested with 6 bus and IEEE 14 bus bench mark system. The result of the proposed hybrid method is compared with the GA based optimization algorithm. The comparison shows that, the proposed method ensures voltage stability with minimum loading shedding.

  5. EphA2 signaling following endocytosis: role of Tiam1. (United States)

    Boissier, Pomme; Chen, Jin; Huynh-Do, Uyen


    Eph receptors and their membrane-bound ligands, the ephrins, represent a complex subfamily of receptor tyrosine kinases (RTKs). Eph/ephrin binding can lead to various and opposite cellular behaviors such as adhesion versus repulsion, or cell migration versus cell-adhesion. Recently, Eph endocytosis has been identified as one of the critical steps responsible for such diversity. Eph receptors, as many RTKs, are rapidly endocytosed following ligand-mediated activation and traffic through endocytic compartments prior to degradation. However, it is becoming obvious that endocytosis controls signaling in many different manners. Here we showed that activated EphA2 are degraded in the lysosomes and that about 35% of internalized receptors are recycled back to the plasma membrane. Our study is also the first to demonstrate that EphA2 retains the capacity to signal in endosomes. In particular, activated EphA2 interacted with the Rho family GEF Tiam1 in endosomes. This association led to Tiam1 activation, which in turn increased Rac1 activity and facilitated Eph/ephrin endocytosis. Disrupting Tiam1 function with RNA interference impaired both ephrinA1-dependent Rac1 activation and ephrinA1-induced EphA2 endocytosis. In summary, our findings shed new light on the regulation of EphA2 endocytosis, intracellular trafficking and signal termination and establish Tiam1 as an important modulator of EphA2 signaling.

  6. Experimental Investigation on Cavitating Flow Shedding over an Axisymmetric Blunt Body

    Institute of Scientific and Technical Information of China (English)

    HU Changli; WANG Guoyu; HUANG Biao


    Nowadays, most researchers focus on the cavity shedding mechanisms of unsteady cavitating flows over different objects, such as 2D/3D hydrofoils, venturi-type section, axisymmetric bodies with different headforms, and so on. But few of them pay attention to the differences of cavity shedding modality under different cavitation numbers in unsteady cavitating flows over the same object. In the present study, two kinds of shedding patterns are investigated experimentally. A high speed camera system is used to observe the cavitating flows over an axisymmetric blunt body and the velocity fields are measured by a particle image velocimetry (PIV) technique in a water tunnel for different cavitation conditions. The U-type cavitating vortex shedding is observed in unsteady cavitating flows. When the cavitation number is 0.7, there is a large scale cavity rolling up and shedding, which cause the instability and dramatic fluctuation of the flows, while at cavitation number of 0.6, the detached cavities can be conjunct with the attached part to induce the break-off behavior again at the tail of the attached cavity, as a result, the final shedding is in the form of small scale cavity and keeps a relatively steady flow field. It is also found that the interaction between the re-entrant flow and the attached cavity plays an important role in the unsteady cavity shedding modality. When the attached cavity scale is insufficient to overcome the re-entrant flow, it deserves the large cavity rolling up and shedding just as that at cavitation number of 0.7. Otherwise, the re-entrant flow is defeated by large enough cavity to induce the cavity-combined process and small scale cavity vortexes shedding just as that of the cavitation number of 0.6. This research shows the details of two different cavity shedding modalities which is worthful and meaningful for the further study of unsteady cavitation.

  7. Patterns of human herpesvirus-8 oral shedding among diverse cohorts of human herpesvirus-8 seropositive persons. (United States)

    Bender Ignacio, Rachel A; Goldman, Jason D; Magaret, Amalia S; Selke, Stacy; Huang, Meei-Li; Gantt, Soren; Johnston, Christine; Phipps, Warren T; Schiffer, Joshua T; Zuckerman, Richard A; McClelland, R Scott; Celum, Connie; Corey, Larry; Wald, Anna; Casper, Corey


    Human herpesvirus-8 (HHV-8), the etiologic agent of Kaposi sarcoma (KS), establishes lifelong latent infection with periodic lytic replication ("shedding") at mucosal sites, especially the oropharynx. Patterns of HHV-8 shedding are not well understood, and require elucidation to better predict risk of HHV-8 related malignancies in those infected. We sought to characterize patterns of HHV-8 oropharyngeal shedding among diverse cohorts that enrolled HHV-8 seropositive persons. We quantified HHV-8 oral shedding using PCR among HHV-8 seropositive persons who collected at least 14 days of oral swabs in 22 studies on 3 continents. We excluded persons taking antivirals during sampling or any prior use of antiretrovirals in those who were HIV-infected. 248 participants were enrolled from the US, Peru, Cameroon, Uganda, and Kenya; 61 % were men, 58 % were HIV seropositive, and 16 % had KS. Overall, 3,123 of 10,557 samples (29.6 %) had HHV-8 detected. Quantity of virus shed was highly correlated with shedding rate, (ρ = 0.72, p < 0.0001). HHV-8 was detected in ≥1 sample in 55 % of participants with a median of 7 % of days in the US and Kenya, 0 % in Uganda and Peru, and 18 % in Cameroon. Median episode duration was three days, and episodes with high median quantity lasted longer (42 vs 3 days, p < 0.0001). In persons with multiple observations over time, 66 % of shedding rate variance was attributable to differences between individuals. In HHV-8 infected individuals from diverse settings, oral mucosal shedding rate, quantity, and duration were correlated; individual shedding was highly variable. Studies are needed to determine factors accounting for between-person variation and the relationship of HHV-8 shedding to development of associated diseases.

  8. Salmonella fecal shedding and immune responses are dose- and serotype- dependent in pigs.

    Directory of Open Access Journals (Sweden)

    Renata Ivanek

    Full Text Available Despite the public health importance of Salmonella infection in pigs, little is known about the associated dynamics of fecal shedding and immunity. In this study, we investigated the transitions of pigs through the states of Salmonella fecal shedding and immune response post-Salmonella inoculation as affected by the challenge dose and serotype. Continuous-time multistate Markov models were developed using published experimental data. The model for shedding had four transient states, of which two were shedding (continuous and intermittent shedding and two non-shedding (latency and intermittent non-shedding, and one absorbing state representing permanent cessation of shedding. The immune response model had two transient states representing responses below and above the seroconversion level. The effects of two doses [low (0.65×10(6 CFU/pig and high (0.65×10(9 CFU/pig] and four serotypes (Salmonella Yoruba, Salmonella Cubana, Salmonella Typhimurium, and Salmonella Derby on the models' transition intensities were evaluated using a proportional intensities model. Results indicated statistically significant effects of the challenge dose and serotype on the dynamics of shedding and immune response. The time spent in the specific states was also estimated. Continuous shedding was on average 10-26 days longer, while intermittent non-shedding was 2-4 days shorter, in pigs challenged with the high compared to low dose. Interestingly, among pigs challenged with the high dose, the continuous and intermittent shedding states were on average up to 10-17 and 3-4 days longer, respectively, in pigs infected with S. Cubana compared to the other three serotypes. Pigs challenged with the high dose of S. Typhimurium or S. Derby seroconverted on average up to 8-11 days faster compared to the low dose. These findings highlight that Salmonella fecal shedding and immune response following Salmonella challenge are dose- and serotype-dependent and that the detection of

  9. Profiling the gastrointestinal microbiota in response to Salmonella: low versus high Salmonella shedding in the natural porcine host. (United States)

    Bearson, Shawn M D; Allen, Heather K; Bearson, Bradley L; Looft, Torey; Brunelle, Brian W; Kich, Jalusa D; Tuggle, Christopher K; Bayles, Darrell O; Alt, David; Levine, Uri Y; Stanton, Thaddeus B


    Controlling Salmonella in the food chain is complicated by the ability of Salmonella to colonize livestock without causing clinical symptoms/disease. Salmonella-carrier animals are a significant reservoir for contamination of naïve animals, the environment, and our food supply. Salmonella carriage and shedding in pigs varies greatly both experimentally and on-farm. To investigate the dynamics between the porcine intestinal microbiota and Salmonella shedding, we temporally profiled the microbiota of pigs retrospectively classified as low and high Salmonella-shedders. Fifty-four piglets were collectively housed, fed and challenged with 10(9)Salmonella enterica serovar Typhimurium. Bacterial quantitation of Salmonella in swine feces was determined, and total fecal DNA was isolated for 16S rRNA gene sequencing from groups of high-shedder, low-shedder, and non-inoculated pigs (n=5/group; 15 pigs total). Analyses of bacterial community structures revealed significant differences between the microbiota of high-shedder and low-shedder pigs before inoculation and at 2 and 7 days post-inoculation (d.p.i.); microbiota differences were not detected between low-shedder and non-inoculated pigs. Because the microbiota composition prior to Salmonella challenge may influence future shedding status, the "will-be" high and low shedder phylotypes were compared, revealing higher abundance of the Ruminococcaceae family in the "will-be" low shedders. At 2d.p.i., a significant difference in evenness for the high shedder microbiota compared to the other two groups was driven by decreases in Prevotella abundance and increases in various genera (e.g. Catenibacterium, Xylanibacter). By 21 d.p.i., the microbial communities of high-shedder and low-shedder pigs were no longer significantly different from one another, but were both significantly different from non-inoculated pigs, suggesting a similar Salmonella-induced alteration in maturation of the swine intestinal microbiota regardless of

  10. Pregnancy Outcomes in Association with STDs including genital HSV-2 shedding in a South African Cohort Study. (United States)

    Moodley, Dhayendre; Sartorius, Benn; Madurai, Savithree; Chetty, Vani; Maman, Suzanne


    Genital herpes simplex virus-2 (HSV-2) shedding in pregnant women in association with neonatal herpes infection has been widely studied but there is limited evidence of its association with pregnancy outcomes. In this retrospective observational study, we included a subgroup of pregnant women who were enrolled in a randomized control behavioural intervention study that was conducted in South Africa in 2008-2010. In pregnancy, women had a HIV rapid test done and a genital swab taken to test for curable STIs and HSV-2 DNA. Subsequent visits were scheduled for 6, 10, 14 weeks and 9 months post-delivery. Pregnancy outcomes were documented at the 6-week or 10-week postpartum visit. Women were treated syndromically for curable STIs. Among 615 women included in this data analysis, 36.6% (n=225) tested HIV positive and 8.3% (n=51) tested positive for genital HSV-2 shedding during pregnancy. Women <24 years and HIV-1 seropositive women were 1.5 and 2.5 times more likely to test positive for HSV-2 genital shedding respectively. STI treatment records were available for 158/205 (77.1%) women; all 87 women with symptomatic STIs were treated the same day, and 50/71 (70.4%) asymptomatic women received treatment at the subsequent visit. Remaining 21 (29.6%) asymptomatic women did not receive treatment because they failed to return for antenatal follow-up. In a multivariable regression analysis, genital HSV-2 shedding, HIV-1, Neisseria gonorrhoea, Chlamydia trachomatis and Trichomanas vaginalis were not associated with preterm deliveries, still births and low birth weight. However with stratification by treatment for a STI, asymptomatic women who were not treated were 3.3 times more likely to deliver prematurely (33.3%; n=6/18) when compared to women who were treated during pregnancy (13.2%; n=15/114) (p=0.042). Genital HSV-2 shedding in pregnancy does not appear to alter pregnancy outcomes. Untreated curable STIs (T.vaginalis, C.trachomatis, N.gonorrhoea) were more likely

  11. Numerical simulation of terrain-induced vortex/wave shedding at the Hong Kong International Airport

    Directory of Open Access Journals (Sweden)

    Li Lei


    Full Text Available The present study aims at simulating the shedding of vortex/wave from a mountain nearby the Hong Kong International Airport using a computational fluid dynamics model by employing high resolution terrain data without smoothing. The successful simulation of this shedding would have an important application in the short-term forecasting of the chance of occurrence of terrain-induced windshear at an operating airport. Two typical cases of vortex/wave shedding are considered, namely, in neutral atmosphere associated with the passage of a typhoon, and in stably stratified atmosphere in spring-time easterly flow with continental origin. The model is found to successfully capture the salient features of the shedding. The simulated radial velocity fields of weather radar/LIDAR compare well with actual observations. In particular, the creation and the propagation of the vortex/wave through shedding from a mountain nearby the airport are captured well in the model simulation. The shedding periods are also reproduced. From the limited number of cases studied in this paper, it appears that the model has the capability of forecasting the occurrence of vortex/wave shedding by coupling with a mesoscale meteorological model.

  12. RhoB/ROCK mediates oxygen-glucose deprivation-stimulated syncytiotrophoblast microparticle shedding in preeclampsia. (United States)

    Han, Jian; Yang, Bo-Ping; Li, Yi-Lin; Li, Hong-Mei; Zheng, Xiu-Hui; Yu, Li-Li; Zhang, Qiong; Zheng, Ying-Ru; Yi, Ping; Li, Li; Guo, Jian-Xin; Zhou, Yuan-Guo


    Increased circulating syncytiotrophoblast microparticles (STBMs) are often associated with preeclampsia (PE) but the molecular mechanisms regulating STBM shedding remain elusive. Experimental evidence has shown that actin plays a key role in STBM shedding and that Rho/ROCK is important in regulating actin rearrangement. To investigate the role of RhoB/ROCK-regulated actin arrangement in STBM shedding in PE, chorionic villous explants were prepared from placenta of patients with normotensive or PE pregnancies and BeWo cells were fused to imitate syncytiotrophoblasts. The oxygen-glucose deprivation (OGD) conditions were applied to imitate the pathophysiology of PE in vitro. The results showed that RhoB and ROCK were activated in the preeclamptic placenta, accompanied by increased actin polymerization and decreased outgrowing microvilli. In villous tissue cultures or BeWo cells, OGD activated RhoB, ROCK1 and ROCK2 and promoted STBM shedding and actin stress fibers formation. In BeWo cells, RhoB overexpression activated ROCK1 and ROCK2, leading to F-actin redistribution and STBM shedding and the OGD-induced actin polymerization and STBM shedding could be reversed by RhoB or ROCK knockdown. These results reveal that RhoB and ROCK play a key role in PE by targeting STBM shedding through actin rearrangement and that RhoB/ROCK intervention may be a potential therapeutic strategy for PE.

  13. The Transition from Thick to Thin Plate Wake Physics: Whither Vortex Shedding? (United States)

    Rai, Man Mohan


    The near and very near wake of a flat plate with a circular trailing edge is investigated with data from direct numerical simulations. Computations were performed for six different combinations of the Reynolds numbers based on plate thickness (D) and boundary layer momentum thickness upstream of the trailing edge (theta). Unlike the case of the cylinder, these Reynolds numbers are independent parameters for the flat plate. The separating boundary layers are turbulent in all the cases investigated. One objective of the study is to understand the changes in the wake vortex shedding process as the plate thickness is reduced (increasing theta/D). The value of D varies by a factor of 16 and that of theta by approximately 5 in the computations. Vortex shedding is vigorous in the low theta/D cases with a substantial decrease in shedding intensity in the large theta/D cases. Other shedding characteristics are also significantly altered with increasing theta/D. A visualization of the shedding process in the different cases is provided and discussed. The basic shedding mechanism is explored in depth. The effect of changing theta/D on the time-averaged, near-wake velocity statistics is also discussed. A functional relationship between the shedding frequency and the Reynolds numbers mentioned above is obtained.

  14. Numerical simulation of terrain-induced vortex/wave shedding at the Hong Kong International Airport

    Energy Technology Data Exchange (ETDEWEB)

    Li, Lei; Zhang, Li-Jie; Mao, Hui [Shenzhen National Climate Observatory, Meteorological Bureau of Shenzhen Municipality (China); Chan, P.W. [Hong Kong Observatory (China)


    The present study aims at simulating the shedding of vortex/wave from a mountain nearby the Hong Kong International Airport using a computational fluid dynamics model by employing high resolution terrain data without smoothing. The successful simulation of this shedding would have an important application in the short-term forecasting of the chance of occurrence of terrain-induced windshear at an operating airport. Two typical cases of vortex/wave shedding are considered, namely, in neutral atmosphere associated with the passage of a typhoon, and in stably stratified atmosphere in spring-time easterly flow with continental origin. The model is found to successfully capture the salient features of the shedding. The simulated radial velocity fields of weather radar/LIDAR compare well with actual observations. In particular, the creation and the propagation of the vortex/wave through shedding from a mountain nearby the airport are captured well in the model simulation. The shedding periods are also reproduced. From the limited number of cases studied in this paper, it appears that the model has the capability of forecasting the occurrence of vortex/wave shedding by coupling with a mesoscale meteorological model. (orig.)

  15. Engineering Extreme Hydrophobic and Super Slippery Water Shedding Surfaces (United States)

    McHale, Glen


    The intrinsic water repellency of a material is fundamentally determined by its surface chemistry, but alone this does not determine the ability of a surface to shed water. Physical factors such as the surface texture/topography, rigidity/flexibility, granularity/porosity combined with the intrinsic wetting properties of the liquid with the surface and whether it is infused by a lubricating liquid are equally important. In this talk I will outline fundamental, but simple, ideas on the topographic enhancement of surface chemistry to create superhydrophobicity, the adhesion of particles to liquid-air interfaces to create liquid marbles, elastocapillarity to create droplet wrapping, and lubricant impregnated surfaces to create completely mobile droplets [1-3]. I will discuss how these ideas have their origins in natural systems and surfaces, such as Lotus leaves, galling aphids and the Nepenthes pitcher plant. I will show how we have applied these concepts to study the wetting of granular systems, such as sand, to understand extreme soil water repellency. I will argue that relaxing the assumption that a solid substrate is fixed in shape and arrangement, can lead to the formation of liquid marbles, whereby a droplet self-coats in a hydrophobic powder/grains. I will show that the concepts of wetting and porosity blur as liquids penetrate into a porous or granular substrate. I will also discuss how lubricant impregnated super slippery surfaces can be used to study a pure constant contact angle mode of droplet evaporation [4]. Finally, I will show dewetting of a surface is not simply a video reversal of wetting [5], and I will give an example of the use of perfect hydrophobicity using the Leidenfrost effect to create a new type of low friction mechanical and hear engine [6]. References: [1] Shirtcliffe, N. J., et al., An introduction to superhydrophobicity. Advances in Colloid and Interface Science, vol. 161, pp.124-138 (2010). [2] McHale, G. & Newton, M. I. Liquid

  16. Intrinsic repair protects cells from pore-forming toxins by microvesicle shedding. (United States)

    Romero, Matthew; Keyel, Michelle; Shi, Guilan; Bhattacharjee, Pushpak; Roth, Robyn; Heuser, John E; Keyel, Peter A


    Pore-forming toxins (PFTs) are used by both the immune system and by pathogens to disrupt cell membranes. Cells attempt to repair this disruption in various ways, but the exact mechanism(s) that cells use are not fully understood, nor agreed upon. Current models for membrane repair include (1) patch formation (e.g., fusion of internal vesicles with plasma membrane defects), (2) endocytosis of the pores, and (3) shedding of the pores by blebbing from the cell membrane. In this study, we sought to determine the specific mechanism(s) that cells use to resist three different cholesterol-dependent PFTs: Streptolysin O, Perfringolysin O, and Intermedilysin. We found that all three toxins were shed from cells by blebbing from the cell membrane on extracellular microvesicles (MVs). Unique among the cells studied, we found that macrophages were 10 times more resistant to the toxins, yet they shed significantly smaller vesicles than the other cells. To examine the mechanism of shedding, we tested whether toxins with engineered defects in pore formation or oligomerization were shed. We found that oligomerization was necessary and sufficient for membrane shedding, suggesting that calcium influx and patch formation were not required for shedding. However, pore formation enhanced shedding, suggesting that calcium influx and patch formation enhance repair. In contrast, monomeric toxins were endocytosed. These data indicate that cells use two interrelated mechanisms of membrane repair: lipid-dependent MV shedding, which we term 'intrinsic repair', and patch formation by intracellular organelles. Endocytosis may act after membrane repair is complete by removing inactivated and monomeric toxins from the cell surface.Cell Death and Differentiation advance online publication, 10 February 2017; doi:10.1038/cdd.2017.11.

  17. Hot-Wire Calibration at Low Velocities: Revisiting the Vortex Shedding Method

    Directory of Open Access Journals (Sweden)

    Sohrab S. Sattarzadeh


    Full Text Available The necessity to calibrate hot-wire probes against a known velocity causes problems at low velocities, due to the inherent inaccuracy of pressure transducers at low differential pressures. The vortex shedding calibration method is in this respect a recommended technique to obtain calibration data at low velocities, due to its simplicity and accuracy. However, it has mainly been applied in a low and narrow Reynolds number range known as the laminar vortex shedding regime. Here, on the other hand, we propose to utilize the irregular vortex shedding regime and show where the probe needs to be placed with respect to the cylinder in order to obtain unambiguous calibration data.

  18. Structural requirements for inducible shedding of the p55 tumor necrosis factor receptor

    DEFF Research Database (Denmark)

    Brakebusch, C; Varfolomeev, E E; Batkin, M


    Induced shedding of the p55 tumor necrosis factor receptor (p55-R) was previously shown to be independent of the amino acid sequence properties of the intracellular domain of this receptor. We now find it also independent of the sequence properties of the transmembrane domain and of the cysteine......-rich region that constitutes most of the extracellular domain of the receptor. The shedding is shown to depend solely on the sequence properties of a small region within the spacer that links the cysteine-rich region in the extracellular domain to the transmembrane domain. Detailed tests of effects......, however, by some mutations that seem to change the conformation of the spacer region. These findings suggest that a short amino acid sequence in the p55-R is essential and sufficient for its shedding and that the shedding is mediated either by a protease with limited sequence specificity or by several...

  19. Vortex shedding experiment with flat and curved bluff plates in water (United States)

    Reed, D.; Nesman, T.; Howard, P.


    Vortex shedding experiments were conducted in a water flow facility in order to simulate the strong discrete 4000-Hz vibration detected in the Space Shuttle Main Engine (SSME) which is thought to be associated with the SSME LOX inlet tee splitter vanes on the Main Injector. For the case of a flat vane with a blunt trailing edge excited by flow induced vortex shedding, lock-in with the first bending mode of the plate was observed. A curved vane displayed similar behavior, with the lock-in being a more discrete higher amplitude response. Aluminum vanes were employed to decouple the first vane bending mode from the vortex shedding mode. The application of an asymmetric 30-deg trailing edge bevel to both the flat and curved vanes was found to greatly reduce the strength of the shed vortices.

  20. Disease, parasite, and commensal prevalences for blue crab Callinectes sapidus at shedding facilities in Louisiana, USA. (United States)

    Rogers, Holly A; Taylor, Sabrina S; Hawke, John P; Schott, Eric J; Anderson Lively, Julie A


    Blue crab diseases, parasites, and commensals are not well studied in the Gulf of Mexico, and their prevalence rates have only been sporadically determined. Commercial soft shell shedding facilities in Louisiana experience high mortality rates of pre-molt crabs, and some of these deaths may be attributable to diseases or parasites. During the active shedding season in 2013, we determined the prevalence of shell disease, Vibrio spp., Lagenophrys callinectes, and Hematodinium perezi at 4 commercial shedding facilities along the Louisiana coast. We also detected Ameson michaelis and reo-like virus infections. Shell disease was moderately prevalent at rates above 50% and varied by shedding facility, collection month, and crab size. Vibrio spp. bacteria were prevalent in the hemolymph of 37% of the pre-molt crabs. Lagenophrys callinectes was highly prevalent in the pre-molt crabs, but because it is a commensal species, it may not cause high mortality rates. Hematodinium perezi was absent in all pre-molt crabs.


    National Research Council Canada - National Science Library

    M. Adela Valero; Miroslava Panova; Ana M. Comes; Roger Fons; Santiago Mas-Coma


    Using samples collected on the island of Corsica, a comparative study was done of the morphometry of Fasciola hepatica eggs shed by cattle and by naturally and experimentally infected murid rodents...

  2. An intelligent load shedding scheme using neural networks and neuro-fuzzy. (United States)

    Haidar, Ahmed M A; Mohamed, Azah; Al-Dabbagh, Majid; Hussain, Aini; Masoum, Mohammad


    Load shedding is some of the essential requirement for maintaining security of modern power systems, particularly in competitive energy markets. This paper proposes an intelligent scheme for fast and accurate load shedding using neural networks for predicting the possible loss of load at the early stage and neuro-fuzzy for determining the amount of load shed in order to avoid a cascading outage. A large scale electrical power system has been considered to validate the performance of the proposed technique in determining the amount of load shed. The proposed techniques can provide tools for improving the reliability and continuity of power supply. This was confirmed by the results obtained in this research of which sample results are given in this paper.

  3. Prevalence of human herpesvirus-8 salivary shedding in HIV increases with CD4 count. (United States)

    Gandhi, M; Koelle, D M; Ameli, N; Bacchetti, P; Greenspan, J S; Navazesh, M; Anastos, K; Greenblatt, R M


    Human herpesvirus-8 (HHV-8) is the etiologic agent of Kaposi's sarcoma (KS), which occurs in epidemic form in human immunodeficiency virus(HIV)-infected individuals. Saliva is the only mucosal fluid in which infectious HHV-8 has been identified, although factors associated with HHV-8 salivary shedding remain unclear. Our study performed PCR analysis for HHV-8 DNA in saliva (and other body fluids) in 66 HIV- and HHV-8-co-infected women without KS so that we could examine predictors for HHV-8 DNA detection. CD4 count was the most significant predictor of HHV-8 salivary shedding, with increased prevalence of HHV-8 salivary DNA at higher CD4 counts. The odds of salivary HHV8 shedding at CD4 counts > = 350 cells/microL was 63 times the odds of shedding at CD4 200. Analysis of these data suggests an increased potential for HHV-8 transmission early in HIV infection, with implications for HHV-8 prevention.

  4. Effect of valproic acid and injury on lesion size and endothelial glycocalyx shedding in a rodent model of isolated traumatic brain injury

    DEFF Research Database (Denmark)

    Jepsen, Cecilie Heerdegen; deMoya, Marc A; Perner, Anders;


    BACKGROUND: In isolated traumatic brain injury (TBI), little is known about the endothelial response and the effects of endothelial glycocalyx shedding. We have previously shown that treatment with valproic acid (VPA) improves outcomes following TBI and hemorrhagic shock.In this model, we...... hypothesized that severe isolated TBI would cause shedding of the endothelial glycocalyx, as measured by serum syndecan-1 (sSDC-1) levels. We further hypothesized that VPA treatment would reduce this response and reduce lesion size volume. METHODS: Forty Sprague-Dawley rats were allocated to TBI + VPA (n = 8......), TBI + saline vehicle control infusion (n = 8), sham + saline vehicle control infusion (n = 6), or sham + VPA (n = 8). TBI animals were subjected to severe controlled cortical impact and killed 6 hours after injury. VPA 300 mg/kg was given as an intravenous bolus 30 minutes after injury. Serum samples...

  5. Numerical Investigation on Vortex Shedding from a Hydrofoil with a Beveled Trailing Edge

    Directory of Open Access Journals (Sweden)

    Seung-Jae Lee


    study, we numerically investigated vortex shedding from various beveled trailing edges at a Reynolds number of 106. We then compared the numerical results with the experimental data, which show good agreement. We also conducted numerical simulations of wakes behind the hydrofoil at rest in periodically varying flows. Results reveal that vortex shedding is affected by the periodicity of a free-stream flow, as well as the trailing-edge shape.

  6. Modulation of statin-activated shedding of Alzheimer APP ectodomain by ROCK.

    Directory of Open Access Journals (Sweden)

    Steve Pedrini


    Full Text Available Statins are widely used cholesterol-lowering drugs that act by inhibiting HMGCoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. Recent evidence suggests that statin use may be associated with a decreased risk for Alzheimer disease, although the mechanisms underlying this apparent risk reduction are poorly understood. One popular hypothesis for statin action is related to the drugs' ability to activate alpha-secretase-type shedding of the alpha-secretase-cleaved soluble Alzheimer amyloid precursor protein ectodomain (sAPP(alpha. Statins also inhibit the isoprenoid pathway, thereby modulating the activities of the Rho family of small GTPases-Rho A, B, and C-as well as the activities of Rac and cdc42. Rho proteins, in turn, exert many of their effects via Rho-associated protein kinases (ROCKs. Several cell-surface molecules are substrates for activated alpha-secretase-type ectodomain shedding, and regulation of shedding typically occurs via activation of protein kinase C or extracellular-signal-regulated protein kinases, or via inactivation of protein phosphatase 1 or 2A. However, the possibility that these enzymes play a role in statin-stimulated shedding has been excluded, leading us to investigate whether the Rho/ROCK1 protein phosphorylation pathway might be involved.We found that both atorvastatin and simvastatin stimulated sAPP(alpha shedding from a neuroblastoma cell line via a subcellular mechanism apparently located upstream of endocytosis. A farnesyl transferase inhibitor also increased sAPP(alpha shedding, as did a dominant negative form of ROCK1. Most conclusively, a constitutively active ROCK1 molecule inhibited statin-stimulated sAPP(alpha shedding.Together, these data suggest that statins exert their effects on shedding of sAPP(alpha from cultured cells, at least in part, by modulation of the isoprenoid pathway and ROCK1.

  7. Concurrent oral shedding of feline calicivirus and feline herpesvirus 1 in cats with chronic gingivostomatitis. (United States)

    Lommer, M J; Verstraete, F J M


    Oral mucosal salivary samples were collected from 25 cats with chronic gingivostomatitis and 24 cats with periodontal disease. Viral culture and isolation of feline calicivirus and feline herpesvirus 1 were performed. Eighty-eight per cent of cats with chronic gingivostomatitis were shedding both viruses, compared to 21% of cats without chronic oral inflammatory disease. Cats with chronic gingivostomatitis are significantly more likely to concurrently shed both feline calicivirus and feline herpesvirus 1 than are cats with classical periodontal disease.

  8. Cylindrical shed construction: the shell roof on the Jamin factory at Oosterhout, Netherlands


    García García, Rafael; Valcarce Labrador, María Teresa


    The paper provides an overview of cylindrical shed reinforced concrete shells, a type of construction used primarily in industrial buildings. Like other types of shells, most cylindrical sheds were built between the end of World War II and the early nineteen sixties. The article reviews their characteristics and construction parameters based on contemporary studies and briefly documents some of the most prominent structures. The final chapter contains a detailed analysis of the design and con...

  9. Hot-Wire Calibration at Low Velocities: Revisiting the Vortex Shedding Method


    Sattarzadeh, Sohrab S.; Athanasia Kalpakli; Ramis Örlü


    The necessity to calibrate hot-wire probes against a known velocity causes problems at low velocities, due to the inherent inaccuracy of pressure transducers at low differential pressures. The vortex shedding calibration method is in this respect a recommended technique to obtain calibration data at low velocities, due to its simplicity and accuracy. However, it has mainly been applied in a low and narrow Reynolds number range known as the laminar vortex shedding regime. Here, on the other ha...

  10. An Ethernet LAN based distributed generation system load shedding strategy

    DEFF Research Database (Denmark)

    Wei, Mu; Chen, Zhe


    This paper firstly analyzes and compares various communication technologies, and proposes a communication system for a distributed generation system (DGS) with wind turbines. Then the paper presents a novel simulation method of considering the interactions between the communication system and power...... system, by using two software platforms: OPNET and EMTDC/PSCAD. A control method based on the communication technique has been designed to stabilize the DG system during power system disturbances. A case study is presented to demonstrate the effectiveness of the proposed communication system, simulation...... method and control strategy....

  11. Super-Shed Escherichia coli O157:H7 have potential for increased pathogen persistence and antibiotic resistance dissemination (United States)

    Cattle are primary reservoirs of Escherichia coli O157:H7 (O157), and super-shedding cattle shed O157 at greater than or equal to 10,000 colony-forming units/g feces. Host, bacteria, and/or the environment reportedly influence the super-shedding phenomenon. We recently demonstrated that a super-she...

  12. Genetic Algorithm Used for Load Shedding Based on Sensitivity to Enhance Voltage Stability (United States)

    Titare, L. S.; Singh, P.; Arya, L. D.


    This paper presents an algorithm to calculate optimum load shedding with voltage stability consideration based on sensitivity of proximity indicator using genetic algorithm (GA). Schur's inequality based proximity indicator of load flow Jacobian has been selected, which indicates system state. Load flow Jacobian of the system is obtained using Continuation power flow method. If reactive power and active rescheduling are exhausted, load shedding is the last line of defense to maintain the operational security of the system. Load buses for load shedding have been selected on the basis of sensitivity of proximity indicator. The load bus having large sensitivity is selected for load shedding. Proposed algorithm predicts load bus rank and optimum load to be shed on load buses. The algorithm accounts inequality constraints not only in present operating conditions, but also for predicted next interval load (with load shedding). Developed algorithm has been implemented on IEEE 6-bus system. Results have been compared with those obtained using Teaching-Learning-Based Optimization (TLBO), particle swarm optimization (PSO) and its variant.

  13. Power transfer capability assessment of transmission interfaces with SVC and load shedding systems

    Energy Technology Data Exchange (ETDEWEB)

    Pavlovsky, V. [DMCC-Engineering, Kiev (Ukraine). Inst. of Electrodynamics; Dolzhenitsa, Y. [DMCC Engineering, Kiev (Ukraine); Ushapovskiy, K. [National Power Co. Ukrenergo, Kiev (Ukraine)


    As a result of deregulation in the power industry, energy trade and markets are pushing transmission system operators to operate their systems closer to the edge of the power transfer capability. Voltage instability and inadequate reactive power support of generators is a key factor in most major outages around the world. The ideal way to control power systems is to avoid emergencies by reliable planning and secure operation of power systems. Therefore, the accurate calculation of the power transfer capability of transmission interfaces is an important task on the planning and operation stages. This paper discussed the issue of transfer capability assessment and monitoring for interfaces with static var compensator (SVC) and load shedding schemes. It also proposed a special measure, a distance to voltage instability point, to monitor transfer capability on-line. The distance may be observed by measurement of SVC output. The paper considered the problem of optimal SVC size selection and a new approach was proposed based on P-V curves analysis. The paper discussed the problem formulation and proposed approach. A case was also presented in order to demonstrate the proposed approach on the IPS Ukraine-Crimea interface. It was concluded that the proposed approach allows the optimal rating of SVC for increasing transfers capability of transmission corridors. 12 refs., 9 figs.

  14. Zika Virus Infection in Mice Causes Panuveitis with Shedding of Virus in Tears

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    Jonathan J. Miner


    Full Text Available Zika virus (ZIKV is an emerging flavivirus that causes congenital abnormalities and Guillain-Barré syndrome. ZIKV infection also results in severe eye disease characterized by optic neuritis, chorioretinal atrophy, and blindness in newborns and conjunctivitis and uveitis in adults. We evaluated ZIKV infection of the eye by using recently developed mouse models of pathogenesis. ZIKV-inoculated mice developed conjunctivitis, panuveitis, and infection of the cornea, iris, optic nerve, and ganglion and bipolar cells in the retina. This phenotype was independent of the entry receptors Axl or Mertk, given that Axl−/−, Mertk−/−, and Axl−/−Mertk−/− double knockout mice sustained levels of infection similar to those of control animals. We also detected abundant viral RNA in tears, suggesting that virus might be secreted from lacrimal glands or shed from the cornea. This model provides a foundation for studying ZIKV-induced ocular disease, defining mechanisms of viral persistence, and developing therapeutic approaches for viral infections of the eye.

  15. A self-learning coupled map lattice for vortex shedding in cable and cylinder wakes. (United States)

    Balasubramanian, G; Olinger, D J; Demetriou, M A


    A coupled map lattice (CML) with self-learning features is developed to model flow over freely vibrating cables and stationary cylinders at low Reynolds numbers. Coupled map lattices that combine a series of low-dimensional circle maps with a diffusion model have been used previously to predict qualitative features of these flows. However, the simple nature of these CML models implies that there will be unmodeled wake features if a detailed, quantitative comparison is made with laboratory or simulated wake flows. Motivated by a desire to develop an improved CML model, we incorporate self-learning features into a new CML that is first trained to precisely estimate wake patterns from a target numerical simulation. A new convective-diffusive map that includes additional wake dynamics is developed. The new self-learning CML uses an adaptive estimation scheme (multivariable least-squares algorithm). Studies of this approach are conducted using wake patterns from a Navier-Stokes solution (spectral element-based NEKTAR simulation) of freely vibrating cable wakes at Reynolds numbers Re=100. It is shown that the self-learning model accurately and efficiently estimates the simulated wake patterns. The self-learning scheme is then successfully applied to vortex shedding patterns obtained from experiments on stationary cylinders. This constitutes a first step toward the use of the self-learning CML as a wake model in flow control studies of laboratory wake flows.

  16. The seroprevalence and salivary shedding of herpesviruses in Behçet's syndrome and recurrent aphthous stomatitis

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    Noha Seoudi


    Full Text Available Background: Behçet's syndrome (BS is one of the multisystemic diseases that presents with oral ulceration and several other systemic manifestations including genital ulceration, folliculitis, erythema nodosum-like lesions, uveitis, and arthropathy. Ocular manifestation, central nervous system involvement, and gastrointestinal manifestation account for most of the complications of this disease, whereas orogenital ulceration and dermatological involvement affects the quality of life. The cause of the disease is not fully elucidated; however, herpesviruses have long been thought to play a pivotal role in the disease pathogenesis. Objective: To investigate the seroprevalence and salivary shedding of herpesviruses in BS. Method: The levels of specific immunoglobulin G in six different herpesviruses in serum samples collected from 54 BS, 28 healthy controls (HC, and 7 recurrent aphthous stomatitis (RAS patients were investigated. Salivary viral load was also quantified for these viruses in matched saliva samples using quantitative real-time polymerase chain reaction. Results: The BS had lower cytomegalovirus (CMV IgG level in comparison to HC (p=0.0226 and RAS (p=0.0450. There was statistically significant higher salivary shedding of Epstein-Barr virus (EBV in BS in comparison to HC (p=0.0052, but not RAS (p=0.3318. Conclusions: A high EBV shedding was observed in both BS and RAS and a lower level of CMV IgG was observed in BS only. The reason for the observed lower level of CMV IgG in BS is not clear. However, one explanation might be a defect in the cross-talk between innate and adaptive immune responses which was suggested by a previously described defect in the toll-like receptor 1 and 2 heterodimer formation and function, this being the initial receptor sensing of CMV.

  17. Mentoring at Men's Sheds: an international survey about a community approach to health and well-being. (United States)

    Cordier, Reinie; Wilson, Nathan J


    Men's Sheds are named within the Australian and Irish National Male Health Policies as an exemplar of male health and well-being and offer a range of formal and informal mentoring to counter the known consequences of social exclusion. The study aimed to report on whether Men's Sheds undertake mentoring programmes, and if so, who is being mentored; are mentors being trained, and if so by whom; and the perceived effectiveness of the mentoring programme. Furthermore, the study aimed to explore associations between sheds with a mentoring programme and factors that reflect an inclusive and a health-focused environment. All known Men's Sheds were invited to participate in the survey; of those, 324 (42.8%) Men's Sheds in Australia and 59 (48.0%) International sheds participated in the study between April and August 2012. Overall, 39.2% (n = 127) of Australian sheds and 23.7% (n = 14) of International sheds undertook formal mentoring. Youth was the most common group being mentored in both Australia (60.6%; n = 77) and Internationally (71.4%; n = 10). Over half of Australian shed co-ordinators rated their mentoring programme as moderately effective (52.8%; n = 67) and over a third as highly effective (36.2%; n = 46), while half of International shed co-ordinators rated theirs as highly effective (50.0%; n = 7). The findings from this paper support the notion that a large number of Men's Sheds offer formal mentoring programmes targeting a range of disadvantaged sub-populations, thus supporting social inclusion. Inter-generational mentoring is the most frequently occurring type of mentoring programme. While training mentors occurs at some sheds, the efficacy of this training and programme outcomes are unknown. A typology of shed types appears to be emerging based on a divergence of sheds with a more utilitarian focus and sheds that appear to embrace a health and well-being focus.

  18. Longitudinal study on oral shedding of herpes simplex virus 1 and varicella-zoster virus in individuals infected with HIV. (United States)

    van Velzen, Monique; Ouwendijk, Werner J D; Selke, Stacy; Pas, Suzan D; van Loenen, Freek B; Osterhaus, Albert D M E; Wald, Anna; Verjans, Georges M G M


    Primary herpes simplex virus 1 (HSV-1) and varicella-zoster virus (VZV) infection leads to a life-long latent infection of ganglia innervating the oral mucosa. HSV-1 and VZV reactivation is more common in immunocompromised individuals and may result in viral shedding in saliva. We determined the kinetics and quantity of oral HSV-1 and VZV shedding in HSV-1 and VZV seropositive individuals infected with HIV and to assess whether HSV-1 shedding involves reactivation of the same strain intra-individually. HSV-1 and VZV shedding was determined by real-time PCR of sequential daily oral swabs (n = 715) collected for a median period of 31 days from 22 individuals infected with HIV. HSV-1 was genotyped by sequencing the viral thymidine kinase gene. Herpesvirus shedding was detected in 18 of 22 participants. Shedding of HSV-1 occurred frequently, on 14.3% of days, whereas solely VZV shedding was very rare. Two participants shed VZV. The median HSV-1 load was higher compared to VZV. HSV-1 DNA positive swabs clustered into 34 shedding episodes with a median duration of 2 days. The prevalence, duration and viral load of herpesvirus shedding did not correlate with CD4 counts and HIV load. The genotypes of the HSV-1 viruses shed were identical between and within shedding episodes of the same person, but were different between individuals. One-third of the individuals shed an HSV-1 strain potentially refractory to acyclovir therapy. Compared to HSV-1, oral VZV shedding is rare in individuals infected with HIV. Recurrent oral HSV-1 shedding is likely due to reactivation of the same latent HSV-1 strain.

  19. Long-Term Shedding of Influenza Virus, Parainfluenza Virus, Respiratory Syncytial Virus and Nosocomial Epidemiology in Patients with Hematological Disorders.

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    Nicola Lehners

    Full Text Available Respiratory viruses are a cause of upper respiratory tract infections (URTI, but can be associated with severe lower respiratory tract infections (LRTI in immunocompromised patients. The objective of this study was to investigate the genetic variability of influenza virus, parainfluenza virus and respiratory syncytial virus (RSV and the duration of viral shedding in hematological patients. Nasopharyngeal swabs from hematological patients were screened for influenza, parainfluenza and RSV on admission as well as on development of respiratory symptoms. Consecutive swabs were collected until viral clearance. Out of 672 tested patients, a total of 111 patients (17% were infected with one of the investigated viral agents: 40 with influenza, 13 with parainfluenza and 64 with RSV; six patients had influenza/RSV or parainfluenza/RSV co-infections. The majority of infected patients (n = 75/111 underwent stem cell transplantation (42 autologous, 48 allogeneic, 15 autologous and allogeneic. LRTI was observed in 48 patients, of whom 15 patients developed severe LRTI, and 13 patients with respiratory tract infection died. Phylogenetic analysis revealed a variety of influenza A(H1N1pdm09, A(H3N2, influenza B, parainfluenza 3 and RSV A, B viruses. RSV A was detected in 54 patients, RSV B in ten patients. The newly emerging RSV A genotype ON1 predominated in the study cohort and was found in 48 (75% of 64 RSV-infected patients. Furthermore, two distinct clusters were detected for RSV A genotype ON1, identical RSV G gene sequences in these patients are consistent with nosocomial transmission. Long-term viral shedding for more than 30 days was significantly associated with prior allogeneic transplantation (p = 0.01 and was most pronounced in patients with RSV infection (n = 16 with a median duration of viral shedding for 80 days (range 35-334 days. Long-term shedding of respiratory viruses might be a catalyzer of nosocomial transmission and must be considered for

  20. Proteomics Approaches Shed New Light on Traditional Iranian Medicine (United States)

    Movahhed, Mina; Poursaleh, Zohreh


    Background: Until now, Iranian traditional medicine (ITM) had been extensively based on Iranian philosophy in theoretical approach in diagnosis and treatment, with doubts on academic medicine. Nevertheless, the diagnosis of temperaments, herbal standardization, and quality control had been with the obscurity of functional molecules and their action mechanisms. Proteomics is a potent board to the mechanistic investigation of ITM and has been comprehensively applied profile drug-regulated proteins. In this review, we assessed the application of this modern molecular biological method in the identification of temperaments and drug targets of ITM. Methods: All available studies related to proteomics in traditional medicine, alternative and complementary medicine, including books, journals, and other references were studied and assessed. Results: The present review showed the phenotypes of the various temperaments in healthy individuals, that is to say, same proteins with different dynamic properties. Therefore, the usefulness of proteomics seems authoritative to understand the means by which the molecular pathways protected in ITM. This might be also the key clinical viewpoint on this new approach for enabling the integration of Iranian traditional medicine and modern biological science and technology, as well for upholding the internationalization of ITM. Conclusion: Proteomics, as a powerful tool for systems biology, is an essential research methodology for understanding the mechanisms of traditional medicine. Further investigation on the applications of advanced proteomics in temperaments, herbal standardization, and quality control in ITM is recommended. PMID:27516684

  1. Duration of shedding of respiratory syncytial virus in a community study of Kenyan children

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    Ngama Mwanajuma


    Full Text Available Abstract Background Our understanding of the transmission dynamics of respiratory syncytial virus (RSV infection will be better informed with improved data on the patterns of shedding in cases not limited only to hospital admissions. Methods In a household study, children testing RSV positive by direct immunofluorescent antibody test (DFA were enrolled. Nasal washings were scheduled right away, then every three days until day 14, every 7 days until day 28 and every 2 weeks until a maximum of 16 weeks, or until the first DFA negative RSV specimen. The relationship between host factors, illness severity and viral shedding was investigated using Cox regression methods. Results From 151 families a total of 193 children were enrolled with a median age of 21 months (range 1-164 months, 10% infants and 46% male. The rate of recovery from infection was 0.22/person/day (95% CI 0.19-0.25 equivalent to a mean duration of shedding of 4.5 days (95%CI 4.0-5.3, with a median duration of shedding of 4 days (IQR 2-6, range 1-14. Children with a history of RSV infection had a 40% increased rate of recovery i.e. shorter duration of viral shedding (hazard ratio 1.4, 95% CI 1.01-1.86. The rate of cessation of shedding did not differ significantly between males and females, by severity of infection or by age. Conclusion We provide evidence of a relationship between the duration of shedding and history of infection, which may have a bearing on the relative role of primary versus re-infections in RSV transmission in the community.

  2. Life-long shedding of Puumala hantavirus in wild bank voles (Myodes glareolus). (United States)

    Voutilainen, Liina; Sironen, Tarja; Tonteri, Elina; Bäck, Anne Tuiskunen; Razzauti, Maria; Karlsson, Malin; Wahlström, Maria; Niemimaa, Jukka; Henttonen, Heikki; Lundkvist, Åke


    The knowledge of viral shedding patterns and viraemia in the reservoir host species is a key factor in assessing the human risk of zoonotic viruses. The shedding of hantaviruses (family Bunyaviridae) by their host rodents has widely been studied experimentally, but rarely in natural settings. Here we present the dynamics of Puumala hantavirus (PUUV) shedding and viraemia in naturally infected wild bank voles (Myodes glareolus). In a monthly capture-mark-recapture study, we analysed 18 bank voles for the presence and relative quantity of PUUV RNA in the excreta and blood from 2 months before up to 8 months after seroconversion. The proportion of animals shedding PUUV RNA in saliva, urine and faeces peaked during the first month after seroconversion, but continued throughout the study period with only a slight decline. The quantity of shed PUUV in reverse transcription quantitative PCR (RT-qPCR) positive excreta was constant over time. In blood, PUUV RNA was present for up to 7 months but both the probability of viraemia and the virus load declined with time. Our findings contradict the current view of a decline in virus shedding after the acute phase and a short viraemic period in hantavirus infection - an assumption widely adopted in current epidemiological models. We suggest the life-long shedding as a means of hantaviruses to survive over host population bottlenecks, and to disperse in fragmented habitats where local host and/or virus populations face temporary extinctions. Our results indicate that the kinetics of pathogens in wild hosts may differ considerably from those observed in laboratory settings.

  3. Inhibition of tumor vasculogenic mimicry and prolongation of host survival in highly aggressive gallbladder cancers by norcantharidin via blocking the ephrin type a receptor 2/focal adhesion kinase/paxillin signaling pathway.

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    Hui Wang

    Full Text Available Vasculogenic mimicry (VM is a newly-defined tumor microcirculation pattern in highly aggressive malignant tumors. We recently reported tumor growth and VM formation of gallbladder cancers through the contribution of the ephrin type a receptor 2 (EphA2/focal adhesion kinase (FAK/Paxillin signaling pathways. In this study, we further investigated the anti-VM activity of norcantharidin (NCTD as a VM inhibitor for gallbladder cancers and the underlying mechanisms. In vivo and in vitro experiments to determine the effects of NCTD on tumor growth, host survival, VM formation of GBC-SD nude mouse xenografts, and vasculogenic-like networks, malignant phenotypes i.e., proliferation, apoptosis, invasion and migration of GBC-SD cells. Expression of VM signaling-related markers EphA2, FAK and Paxillin in vivo and in vitro were examined by immunofluorescence, western blotting and real-time polymerase chain reaction (RT-PCR, respectively. The results showed that after treatment with NCTD, GBC-SD cells were unable to form VM structures when injecting into nude mouse, growth of the xenograft was inhibited and these observations were confirmed by facts that VM formation by three-dimensional (3-D matrix, proliferation, apoptosis, invasion, migration of GBC-SD cells were affected; and survival time of the xenograft mice was prolonged. Furthermore, expression of EphA2, FAK and Paxillin proteins/mRNAs of the xenografts was downregulated. Thus, we concluded that NCTD has potential anti-VM activity against human gallbladder cancers; one of the underlying mechanisms may be via blocking the EphA2/FAK/Paxillin signaling pathway.

  4. Presenilin mediates neuroprotective functions of ephrinB and brain-derived neurotrophic factor and regulates ligand-induced internalization and metabolism of EphB2 and TrkB receptors. (United States)

    Barthet, Gael; Dunys, Julie; Shao, Zhiping; Xuan, Zhao; Ren, Yimin; Xu, Jindong; Arbez, Nicolas; Mauger, Gweltas; Bruban, Julien; Georgakopoulos, Anastasios; Shioi, Junichi; Robakis, Nikolaos K


    Activation of EphB receptors by ephrinB (efnB) ligands on neuronal cell surface regulates important functions, including neurite outgrowth, axonal guidance, and synaptic plasticity. Here, we show that efnB rescues primary cortical neuronal cultures from necrotic cell death induced by glutamate excitotoxicity and that this function depends on EphB receptors. Importantly, the neuroprotective function of the efnB/EphB system depends on presenilin 1 (PS1), a protein that plays crucial roles in Alzheimer's disease (AD) neurodegeneration. Furthermore, absence of one PS1 allele results in significantly decreased neuroprotection, indicating that both PS1 alleles are necessary for full expression of the neuroprotective activity of the efnB/EphB system. We also show that the ability of brain-derived neurotrophic factor (BDNF) to protect neuronal cultures from glutamate-induced cell death depends on PS1. Neuroprotective functions of both efnB and BDNF, however, were independent of γ-secretase activity. Absence of PS1 decreases cell surface expression of neuronal TrkB and EphB2 without affecting total cellular levels of the receptors. Furthermore, PS1-knockout neurons show defective ligand-dependent internalization and decreased ligand-induced degradation of TrkB and Eph receptors. Our data show that PS1 mediates the neuroprotective activities of efnB and BDNF against excitotoxicity and regulates surface expression and ligand-induced metabolism of their cognate receptors. Together, our observations indicate that PS1 promotes neuronal survival by regulating neuroprotective functions of ligand-receptor systems.

  5. Shed urinary ALCAM is an independent prognostic biomarker of three-year overall survival after cystectomy in patients with bladder cancer (United States)

    Egloff, Shanna A. Arnold; Du, Liping; Loomans, Holli A.; Starchenko, Alina; Su, Pei-Fang; Ketova, Tatiana; Knoll, Paul B.; Wang, Jifeng; Haddad, Ahmed Q.; Fadare, Oluwole; Cates, Justin M.; Lotan, Yair; Shyr, Yu; Clark, Peter E.; Zijlstra, Andries


    Proteins involved in tumor cell migration can potentially serve as markers of invasive disease. Activated Leukocyte Cell Adhesion Molecule (ALCAM) promotes adhesion, while shedding of its extracellular domain is associated with migration. We hypothesized that shed ALCAM in biofluids could be predictive of progressive disease. ALCAM expression in tumor (n = 198) and shedding in biofluids (n = 120) were measured in two separate VUMC bladder cancer cystectomy cohorts by immunofluorescence and enzyme-linked immunosorbent assay, respectively. The primary outcome measure was accuracy of predicting 3-year overall survival (OS) with shed ALCAM compared to standard clinical indicators alone, assessed by multivariable Cox regression and concordance-indices. Validation was performed by internal bootstrap, a cohort from a second institution (n = 64), and treatment of missing data with multiple-imputation. While ALCAM mRNA expression was unchanged, histological detection of ALCAM decreased with increasing stage (P = 0.004). Importantly, urine ALCAM was elevated 17.0-fold (P cancer controls, correlated positively with tumor stage (P = 0.018), was an independent predictor of OS after adjusting for age, tumor stage, lymph-node status, and hematuria (HR, 1.46; 95% CI, 1.03–2.06; P = 0.002), and improved prediction of OS by 3.3% (concordance-index, 78.5% vs. 75.2%). Urine ALCAM remained an independent predictor of OS after accounting for treatment with Bacillus Calmette-Guerin, carcinoma in situ, lymph-node dissection, lymphovascular invasion, urine creatinine, and adjuvant chemotherapy (HR, 1.10; 95% CI, 1.02–1.19; P = 0.011). In conclusion, shed ALCAM may be a novel prognostic biomarker in bladder cancer, although prospective validation studies are warranted. These findings demonstrate that markers reporting on cell motility can act as prognostic indicators. PMID:27894096

  6. Shedding light on bioluminescence regulation in Vibrio fischeri. (United States)

    Miyashiro, Tim; Ruby, Edward G


    The bioluminescence emitted by the marine bacterium Vibrio fischeri is a particularly striking result of individual microbial cells co-ordinating a group behaviour. The genes responsible for light production are principally regulated by the LuxR-LuxI quorum-sensing system. In addition to LuxR-LuxI, numerous other genetic elements and environmental conditions control bioluminescence production. Efforts to mathematically model the LuxR-LuxI system are providing insight into the dynamics of this autoinduction behaviour. The Hawaiian squid Euprymna scolopes forms a natural symbiosis with V. fischeri, and utilizes the symbiont-derived bioluminescence for certain nocturnal behaviours, such as counterillumination. Recent work suggests that the tissue with which V. fischeri associates not only can detect bioluminescence but may also use this light to monitor the V. fischeri population. © 2012 Blackwell Publishing Ltd.

  7. Shedding light on ethylene metabolism in higher plants

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    Maria Aurineide Rodrigues


    Full Text Available Ethylene metabolism in higher plants is regulated by a wide array of endogenous and environmental factors. During most physiological processes, ethylene levels are mainly determined by a strict control of the rate-limiting biosynthetic steps responsible for the production of 1-aminocyclopropane-1-carboxylic acid (ACC and its subsequent conversion to ethylene. Responsible for these reactions, the key enzymes ACC synthase and ACC oxidase are encoded by multigene families formed by members that can be differentially regulated at the transcription and post-translational levels by specific developmental and environmental signals. Among the wide variety of environmental cues controlling plant ethylene production, light quality, duration and intensity have consistently been demonstrated to influence the metabolism of this plant hormone in diverse plant tissues, organs and species. Although still not completely elucidated, the mechanisms underlying the interaction between light signal transduction and ethylene evolution appears to involve a complex network that includes central transcription factors connecting multiple signaling pathways, which can be reciprocally modulated by ethylene itself, other phytohormones, and specific light wavelengths. Accumulating evidence has indicated particular photoreceptors as essential mediators in light-induced signaling cascades affecting ethylene levels. Therefore, this review specifically focuses on discussing the current knowledge of the potential molecular mechanisms implicated in the light-induced responses affecting ethylene metabolism during the regulation of developmental and metabolic plant responses. Besides presenting the state of the art in this research field, some overlooked mechanisms and future directions to elucidate the exact nature of the light-ethylene interplay in higher plants will also be compiled and discussed.

  8. Shedding Light on the Nature of Seminal Round Cells.

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    Gianpiero D Palermo

    Full Text Available In this investigation we assess the incidence of round cells (RCs in semen samples in our infertile patient population and their significance on intracytoplasmic sperm injection (ICSI cycle outcomes. We also evaluate the usefulness of RCs as indicators of bacterial infection and highlight the origin of this cell-type, as well as its role in the human ejaculate.In a prospective fashion, a total of 4,810 ejaculated samples were included in the study during a period of 24 months. RCs were characterized for white blood cell (WBC components versus exfoliated germ cells by testing for multiple markers of ploidy as well as protamine assays. Cases displaying ≥ 2 x 106/ml RCs were screened for bacteria. Raw specimens containing RC were processed by peroxidase and other leukocyte assays, specific stains for protamines were used to identify spermiogenic stage, aneuploidy (FISH assessment was carried out, and the presence of various Sertoli-cell cytoplasmic remnants was analyzed to identify and characterize immature germ cells. The effect of RC on clinical outcome was assessed in specimens used for ICSI.The average age of the men involved was 39.2 ± 7 years. Semen samples had a mean concentration of 40.7 ± 31 x 106/ml, motility of 42.6 ± 35%, and morphology of 2.3 ± 2%. RCs were identified in 261 specimens, representing a proportion of 5.4%. Men with RCs had comparable age but lower sperm concentration and morphology than the control group (P<0.001. The aneuploidy rate of 4.3% in RCs group was remarkably higher than the control group (2.3%; P<0.001. Sperm aneuploidy rate positively correlated with the number of RCs (P<0.001. Of 44 men, 17 of them in 18 cycles had up to 1.9 x 106/ml RCs without affecting fertilization and clinical pregnancy rates when compared to controls (n = 365 cycles. In 27 men undergoing 33 ICSI cycles with ≥ 2 x 106/ml RCs, the fertilization rate trended lower and the miscarriage rate was significantly increased (P = 0

  9. Quantitative profiling of the shedding rate of the three Marek's disease virus (MDV) serotypes reveals that challenge with virulent MDV markedly increases shedding of vaccinal viruses. (United States)

    Islam, Aminul; Walkden-Brown, Stephen W


    The shedding profile of Marek's disease virus serotype 1 (MDV1, virulent), serotype 2 (MDV2, vaccinal) and herpesvirus of turkeys (HVT, vaccinal) in commercial broiler chickens was determined by measuring the daily rate of production of feather dander from chickens housed in isolators and by quantifying the viral load of each of these serotypes in the dander using quantitative real-time PCR (qPCR). MDV1 and HVT viruses were detectable in dander filtered from isolator exhaust air from day 7 and MDV2 from day 12 after infection and thereafter until the end of the experiment at 61 days of age of the chickens. There was no difference in shedding rate among the three MDV1 isolates. Daily shedding of MDV1 increased sharply between days 7 and 28 and stabilized thereafter at about 10(9) virus copies per chicken per day, irrespective of vaccination status. Challenge with the three different MDV1 isolates markedly increased shedding of the vaccinal viruses HVT and MDV2 in dander by 38- and 75-fold, respectively. These results demonstrate the utility of qPCR for the differentiation and quantification of different MDV serotypes in feather dander and have significant implications for the routine monitoring of Marek's disease using qPCR assays of dust, for epidemiological modelling of the behaviour and spread of MDVs in chicken populations and for studies into the evolution of virulence in MDV1 in the face of blanket vaccination with imperfect vaccines that ameliorate disease but do not prevent infection and replication of virulent virus.

  10. An Experimental Study of the Effect of Vortex Shedding on Solar Collector Performance

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    Alaulddin Abdulqader Kadim


    Full Text Available In this work, the effect of vortex shedding on the solar collector performance of the parabolic trough solar collector (PTSC was estimated experimentally. The effect of structure oscillations due to wind vortex shedding on solar collector performance degradation was estimated. The performance of PTSC is evaluated by using the useful heat gain and the thermal instantaneous efficiency. Experimental work to simulate the vortex shedding excitation was done. The useful heat gain and the thermal efficiency of the parabolic trough collector were calculated from experimental measurements with and without vortex loading. The prototype of the collector was fabricated for this purpose. The effect of vortex shedding at different operation conditions was examined. The variation of angles of attack and wind velocity leads to different values of vortex loading coefficients and shedding frequencies. The relation between the dynamic characteristics and solar collector performance was evaluated. The finite element method was used to estimate the dynamic characteristic of the solar collector in addition to experimental work to evaluate the relation between the dynamic behavior of the collector and its performance.

  11. The Influence of Load Shedding on the Productivity of Hotel Staff in Cape Town, South Africa

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    Henriëtte STEENKAMP


    Full Text Available In South Africa, ESCOM is the country’s main electricity supplier. Since 2008, Eskom has implemented load shedding on an ongoing basis as a result of insufficient electricity supply to meet the demands of all its customers. Owing to the fact that many organisations across South Africa are depended on electricity in order to function, previous research studies show that the wide-spread impact of load shedding has had an adverse on the sustainability of many of these organisations. Among these organisations are those based in the hospitality industry – imperative in relation to the stimulation of the national economy; directly related to tourism. Albeit the aforementioned, the sustainability of organisations in the hospitality industry is also heavily dependent on the productivity of their employees. For this research study the influence of load shedding on the productivity of the staff in the hospitality industry was investigated within one particular hotel (Hotel X based in Cape Town. Empirical research was deployed, making use of a mixed methods approach to obtain both quantitative data and qualitative data from respondents. Stemming from the findings it was found that load shedding did have an adverse influence on the productivity of staff in Hotel X, despite the fact that affordable measures were put in place to mitigate the disruptions caused by load shedding. Moreover, the latter dispensation was found to have an inadvertently adverse influence on the overall sustainability of Hotel X on the long run.

  12. Estimating heritability of wool shedding in a cross-bred ewe population. (United States)

    Vargas Jurado, N; Leymaster, K A; Kuehn, L A; Lewis, R M


    Low wool prices and high production costs in sheep systems have resulted in the introduction of genotypes that shed wool into flocks to reduce shearing costs. Wool shedding occurs naturally in a few breeds and can be incorporated by cross-breeding. The opportunity to enhance shedding through selection depends on the extent of genetic variability present. Genetic and environmental parameters for wool shedding for ewes from a three-breed composite population were estimated using Bayesian inference. Data on 2025 cross-bred ewes, including 3345 wool shedding scores (WS) and 1647 breeding weight (BW) records, were analysed using bivariate and, for WS, univariate animal repeatability models. Breeding weight was included to account for possible selection bias. Breeding weight was moderately heritable and highly repeatable with means of 0.317 and 0.724, respectively. Under both models, WS was found to be moderately heritable and repeatable with means of 0.256 and 0.399, respectively. Based on a cumulative link model and contingency table analysis, age and reproductive activity influenced the extent of WS (p < 0.05). Given that WS is moderately heritable, selective gain in WS can be achieved.

  13. General relativistic considerations of the field shedding model of fast radio bursts (United States)

    Punsly, Brian; Bini, Donato


    Popular models of fast radio bursts (FRBs) involve the gravitational collapse of neutron star progenitors to black holes. It has been proposed that the shedding of the strong neutron star magnetic field (B) during the collapse is the power source for the radio emission. Previously, these models have utilized the simplicity of the Schwarzschild metric which has the restriction that the magnetic flux is magnetic `hair' that must be shed before final collapse. But neutron stars have angular momentum and charge and a fully relativistic Kerr-Newman solution exists in which B has its source inside of the event horizon. In this Letter, we consider the magnetic flux to be shed as a consequence of the electric discharge of a metastable collapsed state of a Kerr-Newman black hole. It has also been argued that the shedding model will not operate due to pair creation. By considering the pulsar death line, we find that for a neutron star with B = 1011-1013 G and a long rotation period, >1s this is not a concern. We also discuss the observational evidence supporting the plausibility of magnetic flux shedding models of FRBs that are spawned from rapidly rotating progenitors.

  14. Proper orthogonal decomposition analysis of vortex shedding behind a rotating circular cylinder

    Directory of Open Access Journals (Sweden)

    Dol Sharul Sham


    Full Text Available Turbulence studies were made in the wake of a rotating circular cylinder in a uniform free stream with the objective of describing the patterns of the vortex shedding up to suppression of the periodic vortex street at high velocity ratios, λ. The results obtained in the present study establish that shedding of Kármán vortices in a rotating circular cylinder-generated wake is modified by rotation of the cylinder. Alternate vortex shedding is highly visible when λ < 2.0 although the strength of the separated shear layers differ due to the rotation of the cylinder. The spectral density in the wakes indicate significant changes at λ = 2.0. The results indicate that the rotation of the cylinder causes significant disruption in the structure of the flow. Alternate vortex shedding is weak, distorted and close to being suppressed at λ = 2.0. It is clear that flow asymmetries will weaken vortex shedding, and when the asymmetries are significant enough, total suppression of a periodic street occurs. Particular attention was paid to the decomposition of the flow using Proper Orthogonal Decomposition (POD. By analyzing this decomposition with the help of Particle Image Velocimetry (PIV data, it was found that large scales contribute to the coherent motion. Vorticity structures in the modes become increasingly irregular with downstream distance, suggesting turbulent interactions are occurring at the more downstream locations, especially when the cylinder rotates.

  15. In Vitro Evaluation and Mechanism Analysis of the Fiber Shedding Property of Textile Pile Debridement Materials. (United States)

    Fu, Yijun; Xie, Qixue; Lao, Jihong; Wang, Lu


    Fiber shedding is a critical problem in biomedical textile debridement materials, which leads to infection and impairs wound healing. In this work, single fiber pull-out test was proposed as an in vitro evaluation for the fiber shedding property of a textile pile debridement material. Samples with different structural design (pile densities, numbers of ground yarns and coating times) were prepared and estimated under this testing method. Results show that single fiber pull-out test offers an appropriate in vitro evaluation for the fiber shedding property of textile pile debridement materials. Pull-out force for samples without back-coating exhibited a slight escalating trend with the supplement in pile density and number of ground yarn plies, while back-coating process significantly raised the single fiber pull-out force. For fiber shedding mechanism analysis, typical pull-out behavior and failure modes of the single fiber pull-out test were analyzed in detail. Three failure modes were found in this study, i.e., fiber slippage, coating point rupture and fiber breakage. In summary, to obtain samples with desirable fiber shedding property, fabric structural design, preparation process and raw materials selection should be taken into full consideration.

  16. Review of the Phenomenon of Ice Shedding from Wind Turbine Blades

    Directory of Open Access Journals (Sweden)

    H Xue


    Full Text Available Wind power is a sustainable source of energy. However, there are certain challenges to be  overcome. One of the operational challenges is the phenomenon of ice shedding. Icing happens on wind turbine blades in cold regions. When ice grows to a certain size, it separates from the wind turbine blades resulting in the phenomenon of ice shedding. This phenomenon is of significantly dangerous for equipment and personnel in the region. Ice shedding may happen either because of vibrations or bending in blades. However, it was noticed by operators at Nygårdsfjell wind park, Narvik, Norway that ice shedding is more probable to happen when blades are stopped and turned back on. This observation reveals the fact that bending of blades (from loaded to unloaded positions allows the ice to separate and hence result in ice shedding. This can be linked to the phenomenon of icing, mechanical and adhesive properties of ice. This paper reviews above in detail.

  17. Oral and systemic health correlates of HIV-1 shedding in saliva. (United States)

    Navazesh, M; Mulligan, R; Kono, N; Kumar, S K S; Nowicki, M; Alves, M; Mack, W J


    The relationship among oral and systemic health and HIV shedding in saliva is not well-understood. We hypothesized that oral and systemic health are associated with HIV shedding in saliva of HIV-infected women. Saliva from 127 participants enrolled in the Women's Interagency HIV Study (WIHS) was collected at repeated visits over a 5½-year study period (October 1998 through March 2004) and was evaluated for HIV-1 RNA. Demographic, lifestyle, and systemic and oral health characteristics were evaluated as possible correlates of salivary HIV-1 shedding. Multivariate models showed significantly increased risk of HIV-1 shedding in saliva as blood levels of CD4 cell counts decreased (p < 0.0001) and HIV RNA increased (p < 0.0001). Diabetes (p = 0.002) and a high proportion of gingival bleeding sites (p = 0.01) were associated with increased likelihood, while anti-retroviral therapy (p = 0.0003) and higher levels of stimulated saliva flow rates (p = 0.02) were associated with a lower likelihood of HIV-1 RNA shedding in saliva.

  18. Shedding Light on Neutrino Masses with Dark Forces

    CERN Document Server

    Batell, Brian; Shuve, Brian


    Heavy right-handed neutrinos (RHNs) provide the simplest explanation for the origin of light neutrino masses and mixings. If the RHN masses are at or below the weak scale, direct experimental discovery of these states is possible at accelerator experiments such as the LHC or new dedicated beam dump experiments; in such experiments, the RHN decays after traversing a macroscopic distance from the collision point. The experimental sensitivity to RHNs is significantly enhanced if there is a new "dark" gauge force connecting them to the Standard Model (SM), and detection of RHNs can be the primary discovery mode for the new dark force itself. We take the well-motivated example of a B-L gauge symmetry and analyze the sensitivity to displaced decays of the RHNs produced via the new gauge interaction in two experiments: the LHC and the proposed SHiP beam dump experiment. In the most favorable case in which the mediator can be produced on-shell and decays to RHNs, the sensitivity reach is controlled by the square of t...

  19. Skin shedding and tissue regeneration in African spiny mice (Acomys). (United States)

    Seifert, Ashley W; Kiama, Stephen G; Seifert, Megan G; Goheen, Jacob R; Palmer, Todd M; Maden, Malcolm


    Evolutionary modification has produced a spectrum of animal defence traits to escape predation, including the ability to autotomize body parts to elude capture. After autotomy, the missing part is either replaced through regeneration (for example, in urodeles, lizards, arthropods and crustaceans) or permanently lost (such as in mammals). Although most autotomy involves the loss of appendages (legs, chelipeds, antennae or tails, for example), skin autotomy can occur in certain taxa of scincid and gekkonid lizards. Here we report the first demonstration of skin autotomy in Mammalia (African spiny mice, Acomys). Mechanical testing showed a propensity for skin to tear under very low tension and the absence of a fracture plane. After skin loss, rapid wound contraction was followed by hair follicle regeneration in dorsal skin wounds. Notably, we found that regenerative capacity in Acomys was extended to ear holes, where the mice exhibited complete regeneration of hair follicles, sebaceous glands, dermis and cartilage. Salamanders capable of limb regeneration form a blastema (a mass of lineage-restricted progenitor cells) after limb loss, and our findings suggest that ear tissue regeneration in Acomys may proceed through the assembly of a similar structure. This study underscores the importance of investigating regenerative phenomena outside of conventional model organisms, and suggests that mammals may retain a higher capacity for regeneration than was previously believed. As re-emergent interest in regenerative medicine seeks to isolate molecular pathways controlling tissue regeneration in mammals, Acomys may prove useful in identifying mechanisms to promote regeneration in lieu of fibrosis and scarring.


    Institute of Scientific and Technical Information of China (English)

    LI Dan-yong; LIU Nan-sheng; LU Xi-yun; YIN Xie-zhen


    The objective of this study is to deal with unsteady force acting on a pitching foil in shear flow and to study the relation of the force characteristics with vortex shedding near the foil. The two-dimensional incompressible Navier-Stokes equations in the vorticity and stream-function formulation were solved with the fourth-order essentially compact finite difference schemes for the space derivatives and a fourth-order Runge-Kutta scheme for the time advancement. The force characteristics and vortex shedding of the pitching foil in shear flows were investigated. The effects of some typical factors, including the incoming flow shear, the oscillating frequency and amplitude, on the vortex shedding and force behavior were analyzed and discussed.

  1. Herpes Simplex [corrected] Virus Type 2 Shedding From Male Circumcision Wounds in Rakai, Uganda. (United States)

    Grabowski, Mary K; Kigozi, Godfrey; Gray, Ronald H; Armour, Benjamin; Manucci, Jordyn; Serwadda, David; Redd, Andrew D; Nalugoda, Fred; Patel, Eshan U; Wawer, Maria J; Quinn, Thomas C; Tobian, Aaron A R


    A prospective observational study of 176 men coinfected with human immunodeficiency virus and herpes simplex virus type 2 (HSV-2) was conducted to assess whether their sexual partners may be at an increased risk of HSV-2 from male circumcision (MC) wounds. Preoperative and weekly penile lavage samples were tested for penile HSV-2 shedding. Prevalence risk ratios (PRRs) were estimated using Poisson regression. Detectable penile HSV-2 shedding was present in 9.7% of men (17 of 176) before MC, compared with 12.9% (22 of 170) at 1 week (PRR, 1.33; 95% confidence interval [CI], .74-2.38) and 14.8% (23 of 155) at 2 weeks (PRR, 1.50; 95% CI, .86-2.62) after MC. HSV-2 shedding was lower among men with healed MC wounds (adjusted PRR, 0.62; 95% CI, .35-1.08). Men undergoing MC should be counseled on sexual abstinence and condom use.

  2. Dynamic Analysis of Overhead Power Lines after Ice-Shedding Using Finite Element Method (United States)

    Murín, Justín; Hrabovský, Juraj; Gogola, Roman; Janíček, František


    In this paper, the analysis of ice-shedding from ACSR conductors to its swing up height and vibration using Finite Element Method (FEM) is presented. For the numerical simulations the effective material properties of the ACSR conductor are calculated using the homogenisation method. Numerical analysis concerning vibration of one and triple-bundle conductors with icing for a whole range or on their certain parts are performed. The impact of ice-shedding to the mechanical tension in the conductors at the points of attachment is investigated and evaluated. Identification of the impact of ice-shedding from the ACSR conductors on its mechanical state may contribute to increasing the safety and quality of an electrical transmission system.

  3. Men with disabilities - A cross sectional survey of health promotion, social inclusion and participation at community Men's Sheds. (United States)

    Wilson, Nathan J; Cordier, Reinie; Parsons, Richard; Vaz, Sharmila; Buchanan, Angus


    The intersections between chronicity, disability and social inequality are well understood. Novel ways to counter the social determinants of health and disability are needed. Men's Sheds are a community space where men can participate in a range of shared activities and potentially experience a health and social benefits. This cross-sectional survey was conducted to inform future research by determining who attended Men's Sheds and the range of health, social, community, and educational activities undertaken there. This paper explores the membership of people with disabilities (PWD) at Men's Sheds and the factors that predict their membership. An online survey link was sent to all known Men's Sheds internationally in 2012. Data were analyzed using descriptive and inferential (univariate and multivariate) statistics. 32.2% of international sheds and 29% of Australian sheds specifically targeted the inclusion of PWD. 80% of these sheds have significantly more members with disabilities than sheds who do no target PWD. Factors associated with greater membership of PWD included the provision of transport, social outings and promoting occupational skills. PWD are being encouraged to join and are joining Men's Sheds. This is significant as the value of participation and inclusion toward better health and wellbeing is well known. Men's Sheds offer a community space where the social determinants of chronicity and disability can potentially be countered. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Shedding of foodborne pathogens by Caenorhabditis elegans in compost-amended and unamended soil. (United States)

    Anderson, Gary L; Kenney, Stephen J; Millner, Patricia D; Beuchat, Larry R; Williams, Phillip L


    A study was done to characterize the shedding of foodborne pathogenic bacteria by Caenorhabditis elegans, evaluate the persistence of worm populations cocultured with foodborne pathogens, and determine if C. elegans disperses ingested pathogens in soil as a result of shedding. Escherichia. coli O157:H7, Salmonella enterica serotype Poona, and Listeria monocytogenes, as well as E. coli OP50, a non-pathogenic strain, were studied. Synchronous populations of C. elegans were fed for 24 h on confluent lawns of nalidixic acid-adapted bacteria. C. elegans shed viable cells of ingested bacteria on tryptic soy agar supplemented with nalidixic acid (50 microg ml(-1)) (TSAN) throughout a 5-h post-feeding period. C. elegans persisted for up to 10 days by feeding on bacteria that had been shed and grew on TSAN. Eggs harvested from C. elegans cultured on shed foodborne pathogens had the same level of viability as those collected from C. elegans grown on shed E. coli OP50. After 6-7 days, 78%, 64%, 64%, and 76% of eggs laid by C. elegans that had fed on E. coli O157:H7, S. Poona, L. monocytogenes, and E. coli OP50, respectively, were viable. Worms fed on E. coli O157:H7 were inoculated into soil and soil amended with turkey manure compost. Populations of C. elegans persisted in compost-amended soil for at least 7 days but declined in unamended soil. E. coli O157:H7 was detected at 4 and 6 days post inoculation in compost-amended and unamended soil, and in unamended soil inoculated with E. coli OP50. Populations of E. coli O157:H7 in soil amended with turkey manure compost were significantly(alpha = 0.05) higher than those in unamended soil. Results indicate that C. elegans can act as a vector to disperse foodborne pathogens in soil, potentially resulting in increased risk of contaminating the surface of pre-harvest fruits and vegetables.

  5. N-glycosylation is required for matriptase-2 autoactivation and ectodomain shedding. (United States)

    Jiang, Jiang; Yang, Jianfeng; Feng, Ping; Zuo, Bin; Dong, Ningzheng; Wu, Qingyu; He, Yang


    Matriptase-2 is a hepatic membrane serine protease that regulates iron homeostasis. Defects in matriptase-2 cause iron deficiency anemia. In cells, matriptase-2 is synthesized as a zymogen. To date, how matriptase-2 expression and activation are regulated remains poorly understood. Here we expressed human matriptase-2 in HEK293 and hepatic BEL-7402, SMMC-7721, and QGY-7703 cells. By labeling cell surface proteins and Western analysis, we examined matriptase-2 cell surface expression, zymogen activation, and ectodomain shedding. Our results show that matriptase-2 was activated on the cell surface but not intracellularly. Activated matriptase-2 underwent ectodomain shedding, producing soluble fragments in the conditioned medium. By testing inactive mutants, R576A and S762A, we found that matriptase-2 activation and shedding were mediated by its own catalytic activity and that the one-chain form of matriptase-2 had little activity in ectodomain shedding. We made additional matriptase-2 mutants, N136Q, N184Q, N216Q, N338Q, N433Q, N453Q, and N518Q, in which each of the predicted N-glycosylation sites was mutated. All of these mutants were expressed on the cell surface. However, mutants N216Q, N453Q, and N518Q, but not the other mutants, had impaired zymogen activation and ectodomain shedding. Our results indicate that N-glycans at specific sites are critical for matriptase-2 activation. Together, these data provide new insights into the cell surface expression, zymogen activation, and ectodomain shedding of matriptase-2.

  6. Exploring the mechanisms of weight loss in the SHED-IT intervention for overweight men: a mediation analysis

    Directory of Open Access Journals (Sweden)

    Collins Clare E


    Full Text Available Abstract Background Statistical mediation analysis can be used to improve the design of obesity prevention and treatment programs by identifying the possible mechanisms through which an intervention achieved its effects. The aim of this study was to identify mediators of weight loss in an Internet-based weight-loss program specifically designed for overweight men. Methods The Self-Help, Exercise and Diet using Information Technology (SHED-IT program was a 3-month randomized controlled trial (Internet-based intervention group vs information only control group that was implemented in 2007 with baseline and 6-month follow-up assessment of weight, physical activity and dietary behaviors. Intention-to-treat and per-protocol mediation analyses were conducted using a product-of-coefficients test. Results Participants (N = 65 were overweight and obese male academic (n = 10 and non-academic (n = 27 staff and students (n = 28 from the University of Newcastle, Australia. Mean (SD age = 35.9 (11.1 years and mean (SD BMI = 30.6 (2.8. In the intention-to-treat analysis, both groups lost weight, but relative to the control group, the intervention did not have a statistically significant 'total effect' on weight, τ = -.507, p = .716 (95% CI = -3.277 to 2.263. In the per-protocol analysis, the intervention had a statistically significant 'total effect' on weight, τ = -4.487, p Conclusion Few studies have examined the mediators of weight loss in obesity treatment interventions. While none of the hypothesized mediators satisfied the criteria for mediation in the current study, there was some evidence to suggest that overweight men in the SHED-IT intervention reduced their fat intake over the study period. Future obesity treatment and prevention programs should explore behavioral mediators of weight loss using appropriate statistical methods. Trial Registration Australian New Zealand Clinical Trials Registry No: ANZCTRN12607000481471.

  7. Physicochemical Control of Adult Stem Cell Differentiation: Shedding Light on Potential Molecular Mechanisms (United States)


    skin [4], retina [5], pancreas [6], intestinal crypt [7], and liver [8] as well as in skeletal muscle [9]. Depending on the origin, these adult stem...and nuclear elements [126, 143]. This model has gained much attention due to the fact that it provides an architectural description of...Niemeyer, and H. J. Baker, “Isolation and characterization of multipotential mesenchymal stem cells from feline bone marrow,” Experi- mental

  8. Shedding the waters : institutional change and water control in the Lerma-Chapala Basin, Mexico

    NARCIS (Netherlands)

    Wester, P.


    Water resources development has led to water overexploitation in many river basins around the world. This is clearly the case in the Lerma-Chapala Basin in central Mexico, where excessive surface water use nearly resulted in the drying up of Lake Chapala, one of the world’s largest shallow lakes. It

  9. Shedding the waters : institutional change and water control in the Lerma-Chapala Basin, Mexico

    NARCIS (Netherlands)

    Wester, P.


    Water resources development has led to water overexploitation in many river basins around the world. This is clearly the case in the Lerma-Chapala Basin in central Mexico, where excessive surface water use nearly resulted in the drying up of Lake Chapala, one of the world’s largest shallow lakes. It

  10. Operational experience of load shedding and new requirements on frequency relays

    Energy Technology Data Exchange (ETDEWEB)

    Lindahl, S. [ASEA-ATOM AB, Vaesteraas (Sweden); Runvik, G. [Sydkraft AB, Malmoe (Sweden); Stranne, G. [ABB Network Partner AB (Sweden)


    This paper summarises experience and analysis of underfrequency load shedding and power generator islanding. Most power systems can withstand the loss of a single generating unit or a single transmission line. Simultaneous loss of several power system components may cause a severe deficit in active and reactive power. The action of overexcitation limiters on the remaining generators may further aggravate the situation. Such infrequent events may cause severe drop in system frequency and voltage magnitude. Frequency relays for load shedding and power generator islanding must operate correctly even if the system frequency decays and the voltage magnitude decays rapidly at the same time. (author)

  11. Suppression of vortex-shedding noise via derivative-free shape optimization (United States)

    Marsden, Alison L.; Wang, Meng; Dennis, J. E.; Moin, Parviz


    In this Letter we describe the application of a derivative-free optimization technique, the surrogate management framework (SMF), for designing the shape of an airfoil trailing edge which minimizes the noise of vortex shedding. Constraints on lift and drag are enforced within SMF using a filter. Several optimal shapes have been identified for the case of laminar vortex shedding with reasonable computational cost using several shape parameters, and results show a significant reduction in acoustic power. Physical mechanisms for noise reduction are discussed.

  12. Underfrequency Load Shedding for an Islanded Distribution System With Distributed Generators

    DEFF Research Database (Denmark)

    Mahat, Pukar; Chen, Zhe; Bak-Jensen, Birgitte


    Significant penetration of distributed generation in many distribution systems has opened an option of operating distribution systems in island mode for economical and technical reasons. However, balancing frequency of the islanded system is still an issue to be solved, especially when the demand...... exceeds the generation in the power island. This paper presents a strategy to shed an optimal number of loads in the island to stabilize the frequency. The load shedding strategy is based on frequency information, rate of change of frequency, customers' willingness to pay, and loads histories. Different...

  13. Induction of RAGE Shedding by Activation of G Protein-Coupled Receptors (United States)

    Metz, Verena V.; Kojro, Elzbieta; Rat, Dorothea; Postina, Rolf


    The multiligand Receptor for Advanced Glycation End products (RAGE) is involved in various pathophysiological processes, including diabetic inflammatory conditions and Alzheimes disease. Full-length RAGE, a cell surface-located type I membrane protein, can proteolytically be converted by metalloproteinases ADAM10 and MMP9 into a soluble RAGE form. Moreover, administration of recombinant soluble RAGE suppresses activation of cell surface-located RAGE by trapping RAGE ligands. Therefore stimulation of RAGE shedding might have a therapeutic value regarding inflammatory diseases. We aimed to investigate whether RAGE shedding is inducible via ligand-induced activation of G protein-coupled receptors (GPCRs). We chose three different GPCRs coupled to distinct signaling cascades: the V2 vasopressin receptor (V2R) activating adenylyl cyclase, the oxytocin receptor (OTR) linked to phospholipase Cβ, and the PACAP receptor (subtype PAC1) coupled to adenylyl cyclase, phospholipase Cβ, calcium signaling and MAP kinases. We generated HEK cell lines stably coexpressing an individual GPCR and full-length RAGE and then investigated GPCR ligand-induced activation of RAGE shedding. We found metalloproteinase-mediated RAGE shedding on the cell surface to be inducible via ligand-specific activation of all analyzed GPCRs. By using specific inhibitors we have identified Ca2+ signaling, PKCα/PKCβI, CaMKII, PI3 kinases and MAP kinases to be involved in PAC1 receptor-induced RAGE shedding. We detected an induction of calcium signaling in all our cell lines coexpressing RAGE and different GPCRs after agonist treatment. However, we did not disclose a contribution of adenylyl cyclase in RAGE shedding induction. Furthermore, by using a selective metalloproteinase inhibitor and siRNA-mediated knock-down approaches, we show that ADAM10 and/or MMP9 are playing important roles in constitutive and PACAP-induced RAGE shedding. We also found that treatment of mice with PACAP increases the amount of

  14. Calmodulin interacts with angiotensin-converting enzyme-2 (ACE2) and inhibits shedding of its ectodomain. (United States)

    Lambert, Daniel W; Clarke, Nicola E; Hooper, Nigel M; Turner, Anthony J


    Angiotensin-converting enzyme-2 (ACE2) is a regulatory protein of the renin-angiotensin system (RAS) and a receptor for the causative agent of severe-acute respiratory syndrome (SARS), the SARS-coronavirus. We have previously shown that ACE2 can be shed from the cell surface in response to phorbol esters by a process involving TNF-alpha converting enzyme (TACE; ADAM17). In this study, we demonstrate that inhibitors of calmodulin also stimulate shedding of the ACE2 ectodomain, a process at least partially mediated by a metalloproteinase. We also show that calmodulin associates with ACE2 and that this interaction is decreased by calmodulin inhibitors.

  15. Effect of a probiotic on prevention of diarrhea and Clostridium difficile and Clostridium perfringens shedding in foals

    DEFF Research Database (Denmark)

    Schoster, Angelika; Staempfli, H R; Abrahams, M


    BACKGROUND: Up to 60% of foals develop diarrhea within 6 months after birth. Preventive measures are limited but potentially probiotics could be used. OBJECTIVE: To evaluate the effect of a newly designed probiotic on the incidence of foal diarrhea in a randomized field trial. ANIMALS: Seventy......-two healthy neonatal foals. METHODS: Randomized, placebo-controlled field trial. Foals were administered a placebo or probiotic for 3 weeks and monitored for an additional week. A total of 3 fecal samples were taken from each foal at biweekly intervals. Statistical modeling was applied for comparison...... of incidence and duration of diarrhea and fecal shedding of Clostridium perfringens and Clostridium difficile between treatment and age groups. RESULTS: The overall incidence of diarrhea was 41 of 72 (59%) and did not differ (P = 0.37) between treatment groups. Foals treated with probiotics were more likely...

  16. The Gamma-Ray Burst ToolSHED is Open for Business (United States)

    Giblin, Timothy W.; Hakkila, Jon; Haglin, David J.; Roiger, Richard J.


    The GRB ToolSHED, a Gamma-Ray Burst SHell for Expeditions in Data-Mining, is now online and available via a web browser to all in the scientific community. The ToolSHED is an online web utility that contains pre-processed burst attributes of the BATSE catalog and a suite of induction-based machine learning and statistical tools for classification and cluster analysis. Users create their own login account and study burst properties within user-defined multi-dimensional parameter spaces. Although new GRB attributes are periodically added to the database for user selection, the ToolSHED has a feature that allows users to upload their own burst attributes (e.g. spectral parameters, etc.) so that additional parameter spaces can be explored. A data visualization feature using GNUplot and web-based IDL has also been implemented to provide interactive plotting of user-selected session output. In an era in which GRB observations and attributes are becoming increasingly more complex, a utility such as the GRB ToolSHED may play an important role in deciphering GRB classes and understanding intrinsic burst properties.

  17. Optimized Load Shedding Approach for Grid-Connected DC Microgrid Systems under Realistic Constraints

    Directory of Open Access Journals (Sweden)

    Leonardo Trigueiro dos Santos


    Full Text Available The microgrid system is an answer to the necessity of increasing renewable energy penetration and also works as a bridge for the future smart grid. Considering the microgrid system applied to commercial building equipped with photovoltaic sources, the usage of a DC microgrid architecture can improve the efficiency of the system, while ensuring robustness and reducing the overall energy cost. Given the power grid stress and the intermittency of the DC microgrid power production, backup power provision and load shedding operations may occur to stabilize the DC bus voltage. Based on the knapsack problem formulation, this paper presents a realistic optimization approach to shedding a building’s appliances, considering the priority of each appliance, and also considering a minimum amount of load that must be attended. The problem is solved by mixed integer linear programming and the CPLEX solver. The proposed architecture ensures critical load supply and voltage stabilization through the real-time operation of the operational algorithm allowing the load shedding optimization approach to be applied without compromising the robustness of the system. The results obtained by simulation prove that the DC microgrid is able to supply the building power network by applying the load shedding optimization program to overcome, mainly, the renewable energy intermittency.

  18. RSV-encoded NS2 promotes epithelial cell shedding and distal airway obstruction (United States)

    Liesman, Rachael M.; Buchholz, Ursula J.; Luongo, Cindy L.; Yang, Lijuan; Proia, Alan D.; DeVincenzo, John P.; Collins, Peter L.; Pickles, Raymond J.


    Respiratory syncytial virus (RSV) infection is the major cause of bronchiolitis in young children. The factors that contribute to the increased propensity of RSV-induced distal airway disease compared with other commonly encountered respiratory viruses remain unclear. Here, we identified the RSV-encoded nonstructural 2 (NS2) protein as a viral genetic determinant for initiating RSV-induced distal airway obstruction. Infection of human cartilaginous airway epithelium (HAE) and a hamster model of disease with recombinant respiratory viruses revealed that NS2 promotes shedding of infected epithelial cells, resulting in two consequences of virus infection. First, epithelial cell shedding accelerated the reduction of virus titers, presumably by clearing virus-infected cells from airway mucosa. Second, epithelial cells shedding into the narrow-diameter bronchiolar airway lumens resulted in rapid accumulation of detached, pleomorphic epithelial cells, leading to acute distal airway obstruction. Together, these data indicate that RSV infection of the airway epithelium, via the action of NS2, promotes epithelial cell shedding, which not only accelerates viral clearance but also contributes to acute obstruction of the distal airways. Our results identify RSV NS2 as a contributing factor for the enhanced propensity of RSV to cause severe airway disease in young children and suggest NS2 as a potential therapeutic target for reducing the severity of distal airway disease. PMID:24713657

  19. Prioritization of pesticides based on daily dietary exposure potential as determined from the SHEDS model (United States)

    A major pathway for exposure to many pesticides is through diet. The objectives were to rank pesticides by comparing their calculated daily dietary exposure as determined by EPA's Stochastic Human Exposure and Dose Simulation (SHEDS) to single pesticides for different age groups ...

  20. Relational Human Rights: Shed-DNA and the Identification of the Living Disappeared

    DEFF Research Database (Denmark)

    Vaisman, Noa


    forcibly abducted by the last military dictatorship in Argentina. They were raised by the perpetrators of the crime or their accomplices and kept unaware of their birth origins. TheCourt's deliberations focused on Guillermo's appeal of a lower-court decision to carry out an identity test based on his shed...

  1. Current Concepts for Genital Herpes Simplex Virus Infection: Diagnostics and Pathogenesis of Genital Tract Shedding (United States)

    Corey, Lawrence


    SUMMARY Herpes simplex virus 2 (HSV-2) is a DNA virus that is efficiently transmitted through intimate genital tract contact and causes persistent infection that cannot be eliminated. HSV-2 may cause frequent, symptomatic self-limited genital ulcers, but in most persons infection is subclinical. However, recent studies have demonstrated that the virus is frequently shed from genital surfaces even in the absence of signs or symptoms of clinical disease and that the virus can be transmitted during these periods of shedding. Furthermore, HSV-2 shedding is detected throughout the genital tract and may be associated with genital tract inflammation, which likely contributes to increased risk of HIV acquisition. This review focuses on HSV diagnostics, as well as what we have learned about the importance of frequent genital HSV shedding for (i) HSV transmission and (ii) genital tract inflammation, as well as (iii) the impact of HSV-2 infection on HIV acquisition and transmission. We conclude with discussion of future areas of research to push the field forward. PMID:26561565

  2. A probiotic is ineffective in reducing Salmonela shedding in orally-inoculated weaned pigs (United States)

    Salmonella shedding proximal to harvest is a significant issue for the swine and meat industries. Probiotic supplementation prior to transport, lairage, and harvest has been suggested as a possible intervention to reduce Salmonella carcass contamination. In this study, a bolus dose of probiotic pr...

  3. EPA's SHEDS-multimedia model: children's cumulative pyrethroid exposure estimates and evaluation against NHANES biomarker data (United States)

    The U.S. EPA's SHEDS-Multimedia model was applied to enhance the understanding of children's exposures and doses to multiple pyrethroid pesticides, including major contributing chemicals and pathways. This paper presents combined dietary and residential exposure estimates and cum...

  4. Flavobacterium psychrophilum, invasion into and shedding by rainbow trout Oncorhynchus mykiss

    DEFF Research Database (Denmark)

    Madetoja, J.; Nyman, P.; Wiklund, T.


    a long time period compared to the numbers of cells shed by Live fish. The results emphasise the importance of removing dead and moribund fish from rearing tanks in order to diminish the infection pressure against uninfected fish in commercial fish farms. In immunohistochemical examinations of organs...

  5. Dynamic Response of Rub Caused by a Shedding Annular Component Happening in a Steam Turbine

    Directory of Open Access Journals (Sweden)

    J. M. Chen


    Full Text Available Rub caused by a shedding annular component is a severe fault happening in a steam turbine, which could result in a long-term wearing effect on the shaft. The shafting abrasion defects shortened the service life and damaged the unit. To identify the fault in time, the dynamic response of rub caused by a shedding annular component was studied as follows: (I a rotor-bearing model was established based on the structural features of certain steam turbines; node-to-node contact constraint and penalty method were utilized to analyze the impact and friction; (II dynamic response of the rotor-bearing system and the shedding component was simulated with the development of rub after the component was dropping; (III fault features were extracted from the vibration near the bearing position by time-domain and frequency-domain analysis. The results indicate that the shedding annular component would not only rotate pivoting its axis but also revolve around the shaft after a period of time. Under the excitation of the contact force, the peak-peak vibration fluctuates greatly. The frequency spectrum contains two main components, that is, the working rotating frequency and revolving frequency. The same phenomenon was observed from the historical data in the field.

  6. Prioritization of pesticides based on daily dietary exposure potential as determined from the SHEDS model (United States)

    A major pathway for exposure to many pesticides is through diet. The objectives were to rank pesticides by comparing their calculated daily dietary exposure as determined by EPA's Stochastic Human Exposure and Dose Simulation (SHEDS) to single pesticides for different age groups ...

  7. Emergency Load Shedding Strategy Based on Sensitivity Analysis of Relay Operation Margin against Cascading Events

    DEFF Research Database (Denmark)

    Liu, Zhou; Chen, Zhe; Sun, Haishun Sun;


    In order to prevent long term voltage instability and induced cascading events, a load shedding strategy based on the sensitivity of relay operation margin to load powers is discussed and proposed in this paper. The operation margin of critical impedance backup relay is defined to identify the ru...... into account to compensate load shedding amount calculation. And the multi-agent technology is applied for the whole strategy implementation. A test system is built in real time digital simulator (RTDS) and has demonstrated the effectiveness of the proposed strategy.......In order to prevent long term voltage instability and induced cascading events, a load shedding strategy based on the sensitivity of relay operation margin to load powers is discussed and proposed in this paper. The operation margin of critical impedance backup relay is defined to identify...... the runtime emergent states of related system component. Based on sensitivity analysis between the relay operation margin and power system state variables, an optimal load shedding strategy is applied to adjust the emergent states timely before the unwanted relay operation. Load dynamics is also taken...

  8. General Relativistic Considerations of the Field Shedding Model of Fast Radio Bursts

    CERN Document Server

    Punsly, Brian


    Popular models of fast radio bursts (FRBs) involve the gravitational collapse of neutron star progenitors to black holes. It has been proposed that the shedding of the strong neutron star magnetic field ($B$) during the collapse is the power source for the radio emission. Previously, these models have utilized the simplicity of the Schwarzschild metric which has the restriction that the magnetic flux is magnetic "hair" that must be shed before final collapse. But, neutron stars have angular momentum and charge and a fully relativistic Kerr Newman solution exists in which $B$ has its source inside of the event horizon. In this letter, we consider the magnetic flux to be shed as a consequence of the electric discharge of a metastable collapsed state of a Kerr Newman black hole. It has also been argued that the shedding model will not operate due to pair creation. By considering the pulsar death line, we find that for a neutron star with $B = 10^{11} - 10^{13}$ G and a long rotation period, $>1$ s this is not a ...


    Energy Technology Data Exchange (ETDEWEB)

    Hirabayashi, Masatoshi [Research Associate, Colorado Center for Astrodynamics Research, Aerospace Engineering Sciences, University of Colorado Boulder (United States); Sánchez, Diego Paul [Senior Research Associate, Colorado Center for Astrodynamics Research, Aerospace Engineering Sciences, University of Colorado Boulder (United States); Scheeres, Daniel J., E-mail: [Richard Seebass Chair, Professor, Colorado Center for Astrodynamics Research, Aerospace Engineering Sciences, University of Colorado Boulder (United States)


    Surface shedding of an asteroid is a failure mode where surface materials fly off due to strong centrifugal forces beyond the critical spin period, while the internal structure does not deform significantly. This paper proposes a possible structure of an asteroid interior that leads to surface shedding due to rapid rotation rates. A rubble pile asteroid is modeled as a spheroid composed of a surface shell and a concentric internal core, the entire assembly called the test body. The test body is assumed to be uniformly rotating around a constant rotation axis. We also assume that while the bulk density and the friction angle are constant, the cohesion of the surface shell is different from that of the internal core. First, developing an analytical model based on limit analysis, we provide the upper and lower bounds for the actual surface shedding condition. Second, we use a Soft-sphere Discrete Element Method (SSDEM) to study dynamical deformation of the test body due to a quasi-static spin-up. In this paper we show the consistency of both approaches. Additionally, the SSDEM simulations show that the initial failure always occurs locally and not globally. In addition, as the core becomes larger, the size of lofted components becomes smaller. These results imply that if there is a strong core in a progenitor body, surface shedding is the most likely failure mode.

  10. Salmonella spp. fecal shedding detected by real-time PCR in competing endurance horses. (United States)

    Fielding, C Langdon; Meier, Chloe A; Magdesian, K Gary; Pusterla, Nicola


    Fecal shedding of Salmonella spp. was recently documented in 8% of endurance horses presented to equine referral centers for colic. Previous studies have documented fecal shedding of Salmonella spp. in as few as 0.8% of the general horse population, although horses with colic appear to be at higher risk. Fecal Salmonella spp. shedding before and after endurance horse competitions has not been evaluated. Fecal samples were collected from 204 horses during three separate 100 mile endurance competitions. Following incubation in selenite broth, 289 fecal samples were tested by real-time PCR analysis for Salmonella spp. Only one post-race sample (0.5% tested positive for Salmonella spp. in this study and no pre-race sample was available from this horse. Results suggest that fecal shedding of Salmonella spp. is uncommon in endurance horses during competitions. Further research is needed to confirm and identify the source of Salmonella spp. infection in endurance horses with colic requiring treatment at referral centers.

  11. Fatigue of threaded rods in cable anchorages due to Vortex shedding

    NARCIS (Netherlands)

    Maljaars, J.; Snijder, H.H.


    The 'Hovenring' is a bicycle roundabout flyover built as a signature bridge with a central steel pylon carrying a circular bridge deck suspended through stay-cables. Shortly after installation of the bridge, the stay-cables turned out to vibrate in the wind due to vortex shedding. These vibrations h

  12. Power System Stability Using Decentralized Under Frequency and Voltage Load Shedding

    DEFF Research Database (Denmark)

    Hoseinzadeh, Bakhtyar; Silva, Filipe Faria Da; Bak, Claus Leth


    of disturbance location. In this paper, to aim adaptive performance of the relays, the amount of load shed in each stage is determined proportional to the measured Rate of Change of Frequency (ROCOF). In order to localize the LS scheme close to the disturbance place, this scheme utilizes the voltage drop...

  13. The Time-Varying Characteristics of Overhead Electric Transmission Lines Considering the Induced-Ice-Shedding Effect

    Directory of Open Access Journals (Sweden)

    Kunpeng Ji


    Full Text Available More ice deposits accreted on conductors or ground wires may be shed off when an overhead electric transmission line is responding to shocks initiated by natural ice shedding. Ice shedding causes the global mass, stiffness, and damping of the tower-line system to vary with time, and the successive shedding effect beyond a trigger event has not been taken into account in previous studies due to the lack of an adequate ice detachment model. In this paper, the ice shedding effect induced by initial shocks was considered in finite element (FE analysis. An ice detachment criterion, in the way of user-defined element rupture subroutine, was implemented into the main commercial nonlinear FE program ADINA, making it possible to consider the induced-ice-shedding effect numerically. The incremental FE form of the system’s governing equations of motion is presented where the variations in the mass and stiffness matrices of the system are taken into consideration. Taking a transmission line section following natural ice shedding as a case study, the results indicate that neglecting successive ice shedding underestimates the adverse influence of natural ice shedding. The proposed method can help to improve the design and evaluation of transmission lines in cold regions and to ensure their mechanical security.

  14. Poliovirus shedding after the first and second doses of trivalent polio vaccines in newborns

    Directory of Open Access Journals (Sweden)

    Viramitha K. Rusmil


    Full Text Available Background The trivalent oral polio vaccine (tOPV produced by Bio Farma consists of three live, attenuated poliovirus serotypes (1, 2, and 3. The tOPV stimulates the formation of secretory IgA (sIgA on the intestinal wall and lumen. The existence of sIgA is considered giving immunity in the intestines, it could prevent the spread of viral replication and thus inhibit the transmission of the polio virus. Objective To determine the differences in shedding after each of the first two tOPV immunizations in newborns. Methods This one-way repeated measure study was conducted in newborns from three primary health centers in Bandung, West Java. After administering tOPV to newborns, we assessed the shedding of poliovirus in their stool specimens at 30 days after the first dose and 7 days after the second dose. Data was analyzed using McNemar test with 95% confidence intervals (CI to differentiate the shedding of poliovirus after the first and second doses. Results Of 150 children, 128 subjects completed the study. At 30 days after the first tOPV dose, 26 subjects (20.3% were negative for shedding of poliovirus in stool specimens. Of the 102 subjects who had poliovirus isolated from their stools, the serotypes comprised of polio 1: 10.9%, polio 2: 14.8%, polio 3: 45.3%, polio 1 and 3: 3.1%, polio 2 and 3: 4.7%, and polio 1,2, and 3: 0.8%. At 7 days after the second tOPV dose, there was a significant increase in subjects negative for shedding of poliovirus (78 subjects; 60.9%. Statistical analysis revealed significantly decreased shedding of poliovirus in stool specimens between the first and second doses of tOPV (P<0.05 . Conclusion There is a significantly decreased number of subjects with shedding of poliovirus in stool specimens 7 days after the second tOPV dose than at 30 days after the first tOPV dose

  15. Poliovirus shedding after the first and second doses of trivalent polio vaccines in newborns

    Directory of Open Access Journals (Sweden)

    Viramitha K. Rusmil


    Full Text Available Background The trivalent oral polio vaccine (tOPV produced by Bio Farma consists of three live, attenuated poliovirus serotypes (1, 2, and 3. The tOPV stimulates the formation of secretory IgA (sIgA on the intestinal wall and lumen. The existence of sIgA is considered giving immunity in the intestines, it could prevent the spread of viral replication and thus inhibit the transmission of the polio virus.Objective To determine the differences in shedding after each of the first two tOPV immunizations in newborns.Methods This one-way repeated measure study was conducted in newborns from three primary health centers in Bandung, West Java. After administering tOPV to newborns, we assessed the shedding of poliovirus in their stool specimens at 30 days after the first dose and 7 days after the second dose. Data was analyzed using McNemar test with 95% confidence intervals (CI to differentiate the shedding of poliovirus after the first and second doses.Results Of 150 children, 128 subjects completed the study. At 30 days after the first tOPV dose, 26 subjects (20.3% were negative for shedding of poliovirus in stool specimens. Of the 102 subjects who had poliovirus isolated from their stools, the serotypes comprised of polio 1: 10.9%, polio 2: 14.8%, polio 3: 45.3%, polio 1 and 3: 3.1%, polio 2 and 3: 4.7%, and polio 1,2, and 3: 0.8%. At 7 days after the second tOPV dose, there was a significant increase in subjects negative for shedding of poliovirus (78 subjects; 60.9%. Statistical analysis revealed significantly decreased shedding of poliovirus in stool specimens between the first and second doses of tOPV (P<0.05 .Conclusion There is a significantly decreased number of subjects with shedding of poliovirus in stool specimens 7 days after the second tOPV dose than at 30 days after the first tOPV dose.

  16. The Role of Shed PrP(c) in the Neuropathogenesis of HIV Infection. (United States)

    Megra, Bezawit W; Eugenin, Eliseo A; Berman, Joan W


    HIV-1 enters the CNS soon after peripheral infection and causes chronic neuroinflammation and neuronal damage that leads to cognitive impairment in 40-70% of HIV-infected people. The nonpathogenic cellular isoform of the human prion protein (PrP(c)) is an adhesion molecule constitutively expressed in the CNS. Previously, our laboratory showed that shed PrP(c) (sPrP(c)) is increased in the cerebrospinal fluid of HIV-infected people with cognitive deficits as compared with infected people with no impairment. In this article, we demonstrate that CCL2 and TNF-α, inflammatory mediators that are elevated in the CNS of HIV-infected people, increase shedding of PrP(c) from human astrocytes by increasing the active form of the metalloprotease ADAM10. We show that the consequence of this shedding can be the production of inflammatory mediators, because treatment of astrocytes with rPrP(c) increased secretion of CCL2, CXCL-12, and IL-8. Supernatants from rPrP(c)-treated astrocytes containing factors produced in response to this treatment, but not rPrP(c) by itself, cause increased chemotaxis of both uninfected and HIV-infected human monocytes, suggesting a role for sPrP(c) in monocyte recruitment into the brain. Furthermore, we examined whether PrP(c) participates in glutamate uptake and found that rPrP(c) decreased uptake of this metabolite in astrocytes, which could lead to neurotoxicity and neuronal loss. Collectively, our data characterize mediators involved in PrP(c) shedding and the effect of this sPrP(c) on monocyte chemotaxis and glutamate uptake from astrocytes. We propose that shedding of PrP(c) could be a potential target for therapeutics to limit the cognitive impairment characteristic of neuroAIDS. Copyright © 2017 by The American Association of Immunologists, Inc.

  17. Avian influenza shedding patterns in waterfowl: implications for surveillance, environmental transmission, and disease spread (United States)

    Viviane Henaux,; Samuel, Michael D.


    Despite the recognized importance of fecal/oral transmission of low pathogenic avian influenza (LPAI) via contaminated wetlands, little is known about the length, quantity, or route of AI virus shed by wild waterfowl. We used published laboratory challenge studies to evaluate the length and quantity of low pathogenic (LP) and highly pathogenic (HP) virus shed via oral and cloacal routes by AI-infected ducks and geese, and how these factors might influence AI epidemiology and virus detection. We used survival analysis to estimate the duration of infection (from virus inoculation to the last day virus was shed) and nonlinear models to evaluate temporal patterns in virus shedding. We found higher mean virus titer and longer median infectious period for LPAI-infected ducks (10–11.5 days in oral and cloacal swabs) than HPAI-infected ducks (5 days) and geese (7.5 days). Based on the median bird infectious dose, we found that environmental contamination is two times higher for LPAI- than HPAI-infectious ducks, which implies that susceptible birds may have a higher probability of infection during LPAI than HPAI outbreaks. Less environmental contamination during the course of infection and previously documented shorter environmental persistence for HPAI than LPAI suggest that the environment is a less favorable reservoir for HPAI. The longer infectious period, higher virus titers, and subclinical infections with LPAI viruses favor the spread of these viruses by migratory birds in comparison to HPAI. Given the lack of detection of HPAI viruses through worldwide surveillance, we suggest monitoring for AI should aim at improving our understanding of AI dynamics (in particular, the role of the environment and immunity) using long-term comprehensive live bird, serologic, and environmental sampling at targeted areas. Our findings on LPAI and HPAI shedding patterns over time provide essential information to parameterize environmental transmission and virus spread in predictive

  18. Faecal shedding of canine parvovirus after modified-live vaccination in healthy adult dogs. (United States)

    Freisl, M; Speck, S; Truyen, U; Reese, S; Proksch, A-L; Hartmann, K


    Since little is known about the persistence and faecal shedding of canine parvovirus (CPV) in dogs after modified-live vaccination, diagnostic tests for CPV can be difficult to interpret in the post-vaccination period. The primary aim of this study was to determine the incidence, duration and extent of CPV vaccine virus shedding in adult dogs and to investigate related factors, including the presence of protective antibodies, increase in anti-CPV antibody titres and development of any gastrointestinal side-effects. A secondary objective was to assess prevalence of CPV field virus shedding in clinically healthy dogs due to subclinical infections. One hundred adult, healthy privately owned dogs were vaccinated with a commercial CPV-2 modified-live vaccine (MLV). Faeces were tested for the presence of CPV DNA on days 0 (prior to vaccination), 3, 7, 14, 21 and 28 by quantitative real-time PCR. Pre- and post-vaccination serum titres were determined by haemagglutination inhibition on days 0, 7 and 28. Transient excretion of CPV DNA was detected in 2.0% of dogs before vaccination. About one quarter of dogs (23.0%) shed CPV DNA during the post-vaccination period, but field and vaccine virus differentiation by VP2 gene sequencing was only successful in few samples. Faecal CPV excretion occurred despite protective serum antibody titres. Post-vaccination CPV shedding was not related to adequate antibody response after vaccination or to the occurrence of gastrointestinal side-effects. Despite individual differences, CPV DNA was detectable for up to 28 days after vaccination, although the faecal CPV DNA load in these clinically healthy dogs was very low. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Bovine tuberculosis in African buffaloes: observations regarding Mycobacterium bovis shedding into water and exposure to environmental mycobacteria

    Directory of Open Access Journals (Sweden)

    van Helden Paul D


    Full Text Available Abstract Background African buffaloes are the maintenance host for Mycobacterium bovis in the endemically infected Kruger National Park (KNP. The infection is primarily spread between buffaloes via the respiratory route, but it is not known whether shedding of M. bovis in nasal and oral excretions may lead to contamination of ground and surface water and facilitate the transmission to other animal species. A study to investigate the possibility of water contamination with M. bovis was conducted in association with a BCG vaccination trial in African buffalo. Groups of vaccinated and nonvaccinated buffaloes were kept together with known infected in-contact buffalo cows to allow natural M. bovis transmission under semi-free ranging conditions. In the absence of horizontal transmission vaccinated and control buffaloes were experimentally challenged with M. bovis. Hence, all study buffaloes in the vaccination trial could be considered potential shedders and provided a suitable setting for investigating questions relating to the tenacity of M. bovis shed in water. Results Serial water samples were collected from the drinking troughs of the buffaloes once per season over an eleven-month period and cultured for presence of mycobacteria. All water samples were found to be negative for M. bovis, but 16 non-tuberculous Mycobacterium spp. isolates were cultured. The non-tuberculous Mycobacterium species were further characterised using 5'-16S rDNA PCR-sequencing, resulting in the identification of M. terrae, M. vaccae (or vanbaalenii, M. engbaekii, M. thermoresistibile as well as at least two species which have not yet been classified. Conclusion The absence of detectable levels of Mycobacterium bovis in the trough water suggests that diseased buffalo do not commonly shed the organism in high quantities in nasal and oral discharges. Surface water may therefore not be likely to play an important role in the transmission of bovine tuberculosis from buffalo

  20. Sevoflurane mitigates shedding of hyaluronan from the coronary endothelium, also during ischemia/reperfusion: an ex vivo animal study

    Directory of Open Access Journals (Sweden)

    Chen C


    Full Text Available Congcong Chen,1,3 Daniel Chappell,2,3 Thorsten Annecke,2,3 Peter Conzen,2 Matthias Jacob,2,3 Ulrich Welsch,4 Bernhard Zwissler,2 Bernhard F Becker3 1Department of Anesthesiology, Second Affiliated Hospital of Zhejiang University, Hangzhou, People's Republic of China; 2Clinic of Anesthesiology, Ludwig-Maximilians-University, Munich, Germany; 3Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians-University, Munich, Germany; 4Institute of Anatomy, Ludwig-Maximilians-University, Munich, Germany Abstract: Glycosaminoglycan hyaluronan (HA, a major constituent of the endothelial glycocalyx, helps to maintain vascular integrity. Preconditioning the heart with volatile anesthetic agents protects against ischemia/reperfusion injury. We investigated a possible protective effect of sevoflurane on the glycocalyx, especially on HA. The effect of pre-ischemic treatment with sevoflurane (15 minutes at 2% vol/vol gas on shedding of HA was evaluated in 28 isolated, beating guinea pig hearts, subjected to warm ischemia (20 minutes at 37°C followed by reperfusion (40 minutes, half with and half without preconditioning by sevoflurane. HA concentration was measured in the coronary effluent. Over the last 20 minutes of reperfusion hydroxyethyl starch (1 g% was continuously infused and the epicardial transudate collected over the last 5 minutes for measuring the colloid extravasation. Additional hearts were fixed by perfusion after the end of reperfusion for immunohistology and electron microscopy. Sevoflurane did not significantly affect post-ischemic oxidative stress, but strongly inhibited shedding of HA during the whole period, surprisingly even prior to ischemia. Immunohistology demonstrated that heparan sulfates and SDC1 of the glycocalyx were also preserved by sevoflurane. Electron microscopy revealed shedding of glycocalyx caused by ischemia and a mostly intact glycocalyx in hearts exposed to sevoflurane. Coronary vascular permeability of the


    Directory of Open Access Journals (Sweden)



    Full Text Available During generation and overload contingencies in a power system, the system voltage and frequency will decline due to the deficiency of real and reactive powers. Consequently cascaded failures may occur which will lead to complete blackout of certain parts of the power system. Load shedding is considered as the ultimate step of emergency control action that is necessary to prevent a blackout in the power system. This paper proposes a memetic meta-heuristic algorithm known as shuffled frog leaping algorithm (SFLA to find a solution for the steady state load shedding problem presented here. The optimum steady state load shedding problem uses squares of the difference between the connected active and the reactive load and the supplied active and reactive power. The supplied active and reactive powers are treated as dependent variables modeled as functions of bus voltages only. The proposed algorithm is tested on IEEE 14 and 30 bus test systems. The viability of the proposed method is established by comparison with the other conventional methods presented earlier in terms of solution quality and convergence properties.

  2. Analytical simulation of the far-field jet noise and the unsteady jet flow-field by a model of periodic shedding of vortex ring from the jet exit (United States)

    Liu, C. H.


    The construction of a theoretical flow field due to shedding of vortex rings, the identification of the controlling parameters, and the determination of whether the theoretical model successfully simulated the unsteady pressure field near jet (and consequently the far field noise) was studied. The basic parameters contained in the analytic solutions were the epoch at which a vortex ring was shed near the jet exit and the eddy viscosity coefficient. These parameters were identified from the experimental data for the real-time pressure and from the spread of the mixing layer of the jet. Results of the theoretical analysis show good qualitative agreement with the experimental data.

  3. Effect of phylogenetic diversity of velogenic Newcastle disease virus challenge on virus shedding post homologous and heterologous DNA vaccination in chickens. (United States)

    Mohamed, Mahmoud H A; Abdelaziz, Adel M; Kumar, Sachin; Al-Habib, Malik A; Megahed, Mohamed M


    Newcastle disease (ND) is a highly devastating disease for the poultry industry as it causes high economic losses. In this present study, a DNA vaccine containing the F and HN surface antigens of a highly virulent Newcastle disease virus (NDV), NDV/1/Chicken/2005 (FJ939313), was successfully generated. Cell transfection test indicated that the vaccine expressed the F and HN genes in Hep-2 cells. The main objective of this study was to compare the extent of protection induced by DNA vaccination after homologous and heterologous NDV-challenge as determined by the amount of NDV shedding after challenge. NDV-antibody-negative chickens were vaccinated either once, twice or thrice intramuscularly at 7, 14 and 21 days old and were challenged 14 days post vaccination with either homologous virus (vaccine-matched velogenic viscerotropic Newcastle disease virus (vvNDV) strain, FJ939313), phylogenetically related to group VII, or a phylogenetically divergent heterologous virus (unmatched vvNDV strain, AY968809), which belongs to genogroup VI and shows 84.1% nucleotide similarity to the NDV-sequences of the DNA vaccine. Our data indicate that birds, which received a single dose of the DNA vaccine were poorly protected, and only 30-40% of these birds survived after challenge with high virus shedding titre. Multiple administration of the DNA vaccine induced high protection rates of 70-90% with reduced virus shedding compared to the non-vaccinated and challenged birds. Generally, homologous challenge led to reduced tracheal and cloacal shedding compared to the heterologous vvNDV strain. This study provides a promising approach for the control of ND in chickens using DNA vaccines, which are phylogenetically closely related to the circulating field strains.

  4. Blown Away: The Shedding and Oscillation of Sessile Drops by Cross Flowing Air (United States)

    Milne, Andrew James Barnabas

    For drops sessile on a solid surface, cross flowing air can drive drop oscillation or shedding, based on the balance and interaction of aerodynamic drag force (based on drop size/shape and air speed) and adhesion/capillary forces (based on surface tension and drop size/shape). Better understanding of the above has applications to, e.g., fuel cell flooding, airfoil icing, and visibility in rain. To understand the basic physics, experiments studying individual sessile drops in a low speed wind tunnel were performed in this thesis. Analysis of high speed video gave time resolved profiles and airspeed for shedding. Testing 0.5 mul to 100 mul drops of water and hexadecane on poly(methyl methacrylate) PMMA, Teflon, and a superhydrophobic surface (SHS) yielded a master curve describing critical airspeed for shedding for water drops on all surface tested. This curve predicts behavior for new surfaces, and explains experimental results published previously. It also indicates that the higher contact angle leads to easier shedding due to decreased adhesion and increased drag. Developing a novel floating element differential drag sensor gave the first measurements of the microNewton drag force experienced by drops. Forces magnitude is comparable to gravitational shedding from a tilted plate and to simplified models for drop adhesion, with deviations that suggest effects due to the air flow. Fluid properties are seen to have little effect on drag versus airspeed, and decreased adhesion is seen to be more important than increased drag for easing shedding. The relation between drag coefficient and Reynolds number increases slightly with liquid-solid contact angle, and with drop volume. Results suggest that the drop experiences increased drag compared to similarly shaped solid bodies due to drop oscillations aeroelasticly coupling into the otherwise laminar flow. The bulk and surface oscillations of sessile drops in cross flow was also studied, using a full profile analysis

  5. Porcine Epidemic Diarrhea Virus Shedding and Antibody Response in Swine Farms: a Longitudinal Study

    Directory of Open Access Journals (Sweden)

    Cristina Bertasio


    Full Text Available The porcine epidemic diarrhea virus (PEDV causes an acute and highly contagious enteric disease characterized by severe enteritis, vomiting, watery diarrhea and a high mortality rate in seronegative neonatal piglets. In the last few years, PED had a large economic impact on the swine industries in Asia and the United States, and in 2014, the PEDV also re-emerged in Europe. Two main PEDV variants circulate worldwide but only the S INDEL variant, considered a mild strain, is spreading in Europe. To gain insights into the pathogenicity of this variant, its viral load and temporal shedding pattern were evaluated in piglets from infected farms. Quantitative real-time PCR (qPCR targeting the spike gene, was validated according to the minimum information for quantitative real-time PCR experiments guidelines. The qPCR was applied to longitudinal studies conducted in four swine farms naturally infected with the PEDV S INDEL variant. Clinical data, fecal swabs and blood samples were collected from 103 piglets at 15–30-day intervals for 2–5 months. On all four farms, diarrhea was observed in sows during gestation and in farrowing units, and the mortality rates of piglets were 18, 25, 30 and 35%. Different clinical pictures (0-50% of diarrhea positivity, viral titer levels (mean 5.3-7.2 log10 genome copies/mL and antibody conditions (30-80% of positivity were registered among sows on the four farms. The percentage of qPCR positive piglets varied greatly from the beginning (63–100% to the end (0% of the infection course. Clinical signs were present in 96% of the qPCR positive animals. Viral loads ranged from 8.5 log10 to 4 log10 genome copies/mL in suckling pigs at 3–6 days of age and were not statistically different among farms, despite the different patterns observed in sows. After 2–3 weeks, only a few piglets still showed detectable viral levels and clinical signs, and they developed antibody responses. Moreover, co-infections with other

  6. A narrative review of Men's Sheds literature: reducing social isolation and promoting men's health and well-being. (United States)

    Wilson, Nathan J; Cordier, Reinie


    Men's Sheds are community-based organisations that typically provide a space for older men to participate in meaningful occupation such as woodwork. Men's Sheds are considered an exemplar for the promotion of men's health and well-being by health and social policy-makers. The objective of this literature review was to determine the state of the science about the potential for Men's Sheds to promote male health and well-being. Between October 2011 and February 2012, we conducted searches of databases, the grey literature and manual searches of websites and reference lists. In total, we found 5 reports and 19 articles about Men's Sheds. The majority of the literature has emanated from Australian academics and is about older men's learning in community contexts. There is a limited body of research literature about Men's Sheds; the literature consists of either descriptive surveys or small qualitative studies. The range of variables that might contribute towards best practice in Men's Sheds has not yet been adequately conceptualised, measured, tested or understood. Future research should be focussed on the health and well-being benefits of Men's Sheds; it needs to incorporate social determinants of health and well-being within the study designs to enable comparison against other health promotion research. Without this research focus, there is a danger that the potential health and well-being benefits of Men's Sheds as supportive and socially inclusive environments for health will not be incorporated into future male health policy and practice.

  7. PKCa and PKCd regulate ADAM17-mediated ectodomain shedding of heparin binding-EGF through separate pathways

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Instrell, Rachael; Rowlands, Christina;


    -EGF. We identified PKCa as the key participant in the activation of ADAM17 and suggest that it acts in parallel with a pathway linking PKCd and ERK activity. While PKCa specifically regulated PMA-induced shedding, PKCd and ERK influenced both constitutive and inducible shedding by apparently affecting...

  8. Transmission and shedding patterns of Salmonella in naturally infected captive wild roof rats (Rattus rattus) from a Salmonella-contaminated layer farm. (United States)

    Umali, Dennis V; Lapuz, Randy Rhon Simoun P; Suzuki, Terumasa; Shirota, Kazutoshi; Katoh, Hiromitsu


    Rodents play a major role in the transmission and maintenance of Salmonella contamination cycles in poultry facilities. However, very limited field data are available regarding the transmission routes, infection cycle, and shedding patterns of Salmonella by naturally infected wild rodents from commercial layer farms. In this study, a total of 128 resident wild roof rats (Rattus ratus) were captured from a Salmonella-contaminated layer facility. All roof rats were divided into 51 laboratory cages, and weekly monitoring of Salmonella fecal shedding patterns was conducted for 53 wk. Seven roof rats from cages that were observed to frequently shed Salmonella were isolated in individual cages, and daily Salmonella monitoring was performed for 35 days. At the end of monitoring, each roof rat was euthanatized, and isolation of Salmonella from different organs was performed. Results of weekly monitoring of Salmonella showed that 21 of 51 cages (41.2%) were positive for Salmonella Infantis, while two cages (3.92%) were positive for Salmonella Enteritidis. Moreover, 11 cages were positive for Salmonella for at least two sampling weeks. Isolation of Salmonella from fecal droppings was mainly observed during the first 12 wk of captivity. The longest interval between two Salmonella-positive fecal dropping was 24 wk. In the daily Salmonella monitoring, only Salmonella Infantis was isolated from fecal droppings, in which the highest number of Salmonella Infantis organisms per fecal dropping was at 1 x 10(8) colony-forming units (cfu), while the lowest measured quantity was 1 x 10(3) cfu. It was noted that the frequency of Salmonella shedding in fecal droppings appeared to have a linear correlation (r = 0.85) with the number of Salmonella organisms (cfu) per fecal pellet (P poultry facilities through intermittent fecal shedding. Moreover, Salmonella Enteritidis in wild roof rats appears to be more of a systemic infection, in which isolation is most likely to occur in internal

  9. GSO based optimization of steady state load shedding in power systems to mitigate blackout during generation contingencies

    Directory of Open Access Journals (Sweden)

    R. Mageshvaran


    Full Text Available Load shedding is considered as a last alternative to avoid the cascaded tripping and blackout in power systems during generation contingencies. It is essential to optimize the amount of load to be shed in order to prevent excessive load shedding. To minimize load shedding, this paper proposes the implementation of nature inspired optimization algorithm known as glowworm swarm optimization (GSO algorithm. The optimal solution of steady state load shedding is carried out by squaring the difference between the connected and supplied power (active and reactive. The proposed algorithm is tested on IEEE 14, 30, 57, 118 and Northern Regional Power Grid (NRPG-(India 246 bus test systems. The viability of the proposed method in terms of solution quality and convergence properties is compared with the conventional methods, namely, projected augmented Lagrangian method (PALM, gradient technique based on Kuhn–Tucker theorem (GTBKTT and second order gradient technique (SOGT.

  10. Numerical evaluation of cavitation shedding structure around 3D Hydrofoil: Comparison of PANS, LES and RANS results with experiments (United States)

    Ji, B.; Peng, X. X.; Long, X. P.; Luo, X. W.; Wu, Y. L.


    Results of cavitating turbulent flow simulation around a twisted hydrofoil were presented in the paper using the Partially-Averaged Navier-Stokes (PANS) method (Ji et al. 2013a), Large-Eddy Simulation (LES) (Ji et al. 2013b) and Reynolds-Averaged Navier-Stokes (RANS). The results are compared with available experimental data (Foeth 2008). The PANS and LES reasonably reproduce the cavitation shedding patterns around the twisted hydrofoil with primary and secondary shedding, while the RANS model fails to simulate the unsteady cavitation shedding phenomenon and yields an almost steady flow with a constant cavity shape and vapor volume. Besides, it is noted that the predicted shedding vapor cavity by PANS is more turbulent and the shedding vortex is stronger than that by LES, which is more consistent with experimental photos.

  11. Further validation of the hybrid particle-mesh method for vortex shedding flow simulations

    Directory of Open Access Journals (Sweden)

    Lee Seung-Jae


    Full Text Available This is the continuation of a numerical study on vortex shedding from a blunt trailing-edge of a hydrofoil. In our previous work (Lee et al., 2015, numerical schemes for efficient computations were successfully implemented; i.e. multiple domains, the approximation of domain boundary conditions using cubic spline functions, and particle-based domain decomposition for better load balancing. In this study, numerical results through a hybrid particle-mesh method which adopts the Vortex-In-Cell (VIC method and the Brinkman penalization model are further rigorously validated through comparison to experimental data at the Reynolds number of 2 × 106. The effects of changes in numerical parameters are also explored herein. We find that the present numerical method enables us to reasonably simulate vortex shedding phenomenon, as well as turbulent wakes of a hydrofoil.

  12. Cessation of feline calicivirus shedding coincident with resolution of chronic gingivostomatitis in a cat. (United States)

    Addie, D D; Radford, A; Yam, P S; Taylor, D J


    Feline calicivirus (FCV) shedding and oral bacterial flora were monitored over a period of 22 months in a case of feline gingivostomatitis (FGS). The cat was treated daily with 50 mg thalidomide capsules by mouth, and 200 mg lactoferrin powder was applied directly to the lesions. Clinical signs began to resolve after 11 months when, in addition to treatment, the diet had been changed to an additive-free cat food supplemented with antioxidant vitamins A, D3 and E. Resolution of clinical signs of FGS coincided with the cessation of FCV shedding, and this is the first report documenting such an association. Which part of the treatment, if any, contributed to the cure requires further investigation.

  13. A Policy Switching Approach to Consolidating Load Shedding and Islanding Protection Schemes

    CERN Document Server

    Meier, Rich; Fern, Alan


    In recent years there have been many improvements in the reliability of critical infrastructure systems. Despite these improvements, the power systems industry has seen relatively small advances in this regard. For instance, power quality deficiencies, a high number of localized contingencies, and large cascading outages are still too widespread. Though progress has been made in improving generation, transmission, and distribution infrastructure, remedial action schemes (RAS) remain non-standardized and are often not uniformly implemented across different utilities, ISOs, and RTOs. Traditionally, load shedding and islanding have been successful protection measures in restraining propagation of contingencies and large cascading outages. This paper proposes a novel, algorithmic approach to selecting RAS policies to optimize the operation of the power network during and after a contingency. Specifically, we use policy-switching to consolidate traditional load shedding and islanding schemes. In order to model and...

  14. Molting Materials: Restoring Superhydrophobicity after Severe Damage via Snakeskin-like Shedding. (United States)

    Hönes, Roland; Kondrashov, Vitaliy; Rühe, Jürgen


    The nanostructures that are required to generate superhydrophobic surfaces are always sensitive to shear and are easily damaged, especially by scratching with sharp objects. As a result of this destruction, the water repellency will be lost. We introduce a novel approach to restoring the original surface properties after mechanical damage. In this approach, the damaged layer is shed like the skin of a snake. This is demonstrated with a three-layer stack as a proof-of-principle system: when the original, superhydrophobic surface layer is damaged, this leads to the dissolution of a sacrificial layer below it. Thus, the damaged layer is shed, a new unscathed surface is uncovered, and superhydrophobicity can easily be restored after a short washing.

  15. Oral shedding of Marburg virus in experimentally infected Egyptian fruit bats (Rousettus aegyptiacus). (United States)

    Amman, Brian R; Jones, Megan E B; Sealy, Tara K; Uebelhoer, Luke S; Schuh, Amy J; Bird, Brian H; Coleman-McCray, JoAnn D; Martin, Brock E; Nichol, Stuart T; Towner, Jonathan S


    Marburg virus (Marburg marburgvirus; MARV) causes sporadic outbreaks of Marburg hemorrhagic fever (MHF) in Africa. The Egyptian fruit bat (Rousettus aegyptiacus) has been identified as a natural reservoir based most-recently on the repeated isolation of MARV directly from bats caught at two locations in southwestern Uganda where miners and tourists separately contracted MHF from 2007-08. Despite learning much about the ecology of MARV through extensive field investigations, there remained unanswered questions such as determining the primary routes of virus shedding and the severity of disease, if any, caused by MARV in infected bats. To answer these questions and others, we experimentally infected captive-bred R. aegyptiacus with MARV under high (biosafety level 4) containment. These experiments have shown infection profiles consistent with R. aegyptiacus being a bona fide natural reservoir host for MARV and demonstrated routes of viral shedding capable of infecting humans and other animals.

  16. On the origins of vortex shedding in two-dimensional incompressible flows (United States)

    Boghosian, M. E.; Cassel, K. W.


    An exegesis of a novel mechanism leading to vortex splitting and subsequent shedding that is valid for two-dimensional incompressible, inviscid or viscous, and external or internal or wall-bounded flows, is detailed in this research. The mechanism, termed the vortex shedding mechanism (VSM) is simple and intuitive, requiring only two coincident conditions in the flow: (1) the existence of a location with zero momentum and (2) the presence of a net force having a positive divergence. Numerical solutions of several model problems illustrate causality of the VSM. Moreover, the VSM criteria is proved to be a necessary and sufficient condition for a vortex splitting event in any two-dimensional, incompressible flow. The VSM is shown to exist in several canonical problems including the external flow past a circular cylinder. Suppression of the von Kármán vortex street is demonstrated for Reynolds numbers of 100 and 400 by mitigating the VSM.

  17. Frequent Zika Virus Sexual Transmission and Prolonged Viral RNA Shedding in an Immunodeficient Mouse Model

    Directory of Open Access Journals (Sweden)

    Nisha K. Duggal


    Full Text Available Circulation of Zika virus (ZIKV was first identified in the Western hemisphere in late 2014. Primarily transmitted through mosquito bite, ZIKV can also be transmitted through sex and from mother to fetus, and maternal ZIKV infection has been associated with fetal malformations. We assessed immunodeficient AG129 mice for their capacity to shed ZIKV in semen and to infect female mice via sexual transmission. Infectious virus was detected in semen between 7 and 21 days post-inoculation, and ZIKV RNA was detected in semen through 58 days post-inoculation. During mating, 73% of infected males transmitted ZIKV to uninfected females, and 50% of females became infected, with evidence of fetal infection in resulting pregnancies. Semen from vasectomized mice contained significantly lower levels of infectious virus, though sexual transmission still occurred. This model provides a platform for studying the kinetics of ZIKV sexual transmission and prolonged RNA shedding also observed in human semen.

  18. Shedding Rates and SeroPrevalence of Brucella melitensis in Lactating Goats of Shahrekord, Iran


    Ebrahimi, Azizollah; Milan, Jalal Sheykh kanluye; Mahzoonieh, Mohamad Reza; Khaksar, Khadijeh


    Background: Brucellosis remains a major worldwide zoonosis. Caprine brucellosis is a significant problem for both public health and animal production. Brucella melitensis causes disease in goats, sheep, humans, and occasionally cattle. Transmission is by ingestion or contact with infected materials, vaginal discharge, or milk. Objectives: The current study aimed to determine the rate of B. melitensis seropositives and its probable shedding in lactating goats from flocks in Shahrekord district...

  19. Selenium supplementation induces metalloproteinase-dependent L-selectin shedding from monocytes. (United States)

    Ahrens, Ingo; Ellwanger, Christoph; Smith, Belinda K; Bassler, Nicole; Chen, Yung Chih; Neudorfer, Irene; Ludwig, Andreas; Bode, Christoph; Peter, Karlheinz


    Selenium therapy in patients with severe sepsis improves clinical outcome and has been associated with increased activity of the selenoprotein glutathione peroxidase. However, the mechanism of the observed beneficial effects remains unclear. We determined the effect of selenium treatment on the monocyte adhesion molecule L-selectin and L-selectin-related monocyte functions in vitro and transferred our findings to an in vivo mouse model. Monocytes were purified, cultured, and incubated in the presence or absence of supplemented selenium and metalloproteinase (MP) inhibitors for up to 16 h. Expression of L-selectin was unaffected after 2 and 6 h but decreased after 16 h of incubation in the presence of selenium. Soluble L-selectin (sL-selectin) in the supernatant was determined by ELISA. A 2.3-fold increase as a result of shedding of L-selectin was observed after 16 h of selenium treatment. Addition of the MP inhibitors GM6001, TNF-alpha-converting enzyme inhibitor 2, or GW280264X strongly reduced selenium-induced L-selectin shedding, indicating a MP-dependent mechanism. The functional consequences of L-selectin shedding were examined in a flow chamber model. Selenium-treated monocytes showed significantly decreased rolling and adhesion to the L-selectin ligand Sialyl-Lewis(a) under conditions of venous shear stress (0.5 dyne/cm(2)). Selenium treatment of C57BL6 mice led to increased serum levels of sL-selectin, underscoring the in vivo relevance of our findings. We describe a selenium-induced down-regulation of L-selectin on monocytes as a consequence of MP-dependent shedding of this membrane-anchored adhesion molecule. The impairment of monocyte adhesion by selenium supplementation may represent an important, underlying mechanism for the modulation of inflammatory reactions in patients with severe sepsis.

  20. Individual Subject Meta-Analysis of Parameters for Giardia duodenalis Shedding in Animal Experimental Models

    Directory of Open Access Journals (Sweden)

    A. D. Adell


    Full Text Available Giardia duodenalis is a zoonotic protozoan parasite with public health importance worldwide. While articles about animal model infectivity have been published for G. duodenalis, the studies have used diverse protocols and parameters to evaluate the infectivity of this protozoan parasite. Hence, the objectives of this study were to (1 conduct a meta-analysis of published literature for cyst shedding and diarrhea outcomes in animal models and (2 develop recommendations to help standardize experimental dose response studies. Results showed that, for the outcome of cyst shedding in faeces, the covariates of infective stage (cyst versus trophozoite, Giardia dose, and the interactions between doses and infective stage, as well as dose and species of experimental host, were all significant (P value ≤ 0.05. This study suggests inoculation of the experimental host with cysts rather than trophozoites and administration of higher doses of Giardia will most likely result in cyst shedding. Based on the results of this meta-analysis, the infective stage (cyst versus trophozoite, parasite dose, and the interactions between dose and infective stage, as well as dose and species of experimental host, should be considered when designing experimental dose response studies that will assist in the study of zoonotic neglected tropical diseases globally.

  1. Periodical shedding of cloud cavitation from a single hydrofoil in high-speed cryogenic channel flow

    Institute of Scientific and Technical Information of China (English)

    Yutaka ITO; Koichi SETO; Takao NAGASAKI


    In order to explain criteria for periodical shedding of the cloud cavitation, flow patterns of cavitation around a piano-convex hydrofoil were observed using a cryogenic cavitation tunnel of a blowdown type. Two hydrofoils of similarity of 20 and 60 mm in chord length with two test sections of 20 and 60 mm in width were prepared. Working fluids were water at ambient temperature, hot water and liquid nitrogen. The parameter range was varied between 0.3 and 1.4 for cavitation number, 9 and 17 m/sec for inlet flow velocity, and -8° and 8° for the flow in-cidence angle, respectively. At incidence angle 8°, that is, the convex surface being suction surface, periodical shedding of the whole cloud cavitation was observed on the convex surface under the specific condition with cavitation number and inlet flow velocity, respectively, 0.5, 9 m/sec for liquid nitrogen at 192℃ and 1.4, 11 m/sec for water at 88℃, whereas under the supercavitation condition, it was not observable. Periodical shedding of cloud cavitation occurs only in the case that there are both the adverse pressure gradient and the slow flow region on the hydrofoil.

  2. Study of Cavitation Shedding Dynamics on a NACA0015 Hydrofoil Using X-Ray Densitometry (United States)

    Ganesh, Harish; Wu, Juliana; Ceccio, Steven


    Cavitation dynamics on the NACA0015 hydrofoil at several attack angles are found to be spectrally rich, being multi-modal with abrupt changes in Strouhal number with change in cavitation number. Present study focusses on identifying the physical mechanisms responsible for the change in cavitation dynamics on a NACA0015 hydrofoil in a re-circulating water tunnel using time resolved X-ray densitometry. Time-resolved void fraction flow fields obtained using X-ray densitometry, synchronized with acoustic noise measurements using a hydrophone, are used to identify different flow features and mechanisms that are responsible for the change in the observed spectral behavior. It is shown that under higher cavitation numbers, the shedding mechanism is predominantly re-entrant liquid flow based, but as the cavitation number drops many different processes are at play. At lower cavitation numbers, the shed cavity cloud collapse arrests cavity growth and this results in altered cycle dynamics and hence the Strouhal number. In addition, propagation bubbly shock waves are also found to be a dominant mechanism of shedding for certain conditions. The multi-modal nature of the acoustic pressure signature is explained by presence of different flow features, which could be concurrent or alternating. Office of Naval Research.

  3. Parametric CFD study of micro-energy harvesting in a flow channel exploiting vortex shedding (United States)

    Koubogiannis, Dimitrios G.


    Miniature energy harvesting devices are increasingly used in various fields. For example, Wireless Sensor Networks have recently made great progress in many applications. However, their main drawback, i.e. the limited duration of operation, poses the requirement for an effective way to recharge their batteries. In this context, the presentwork focuses on the study of micro-energy harvesting from flow by exploiting vortex shedding behind bluff bodies, in order to cause oscillations to a piezoelectric film and generate the required electrical power. To this end, a Computational Fluid Dynamics (CFD) tool is validated on a particular miniature device configuration proposed in the literature and implemented for the numerical simulations of flow around bluff micro-bodies in a very small channel. Aiming to enhance vortex shedding, parametric studies corresponding to different bluff body shapes and arrangements for a fixed Reynolds number are performed, the main parameters involved in the phenomenon are highlighted and the potential for vortex shedding exploitation is qualitatively assessed.

  4. IL-8-induced L-selectin shedding regulates its binding kinetics to PSGL-1

    Institute of Scientific and Technical Information of China (English)

    JIA XiaoLing; CHEN Juan; LONG Mian


    L-selectin plays a crucial role in inflammation cascade by initiating the tethering and rolling of leukocytes on endothelium wall.While many L-selectin molecules are rapidly shed from the cell surface upon activation,the remaining membrane-anchored L-selectin may still play an important role in regulating leukocyte rolling and adhesion with different binding kinetics.Here we developed an in vitro model to activate Jurkat cells via interlukin-8 (IL-8) and quantified the two-dimensional (2D) binding kinetics,using a micropipette aspiration assay,of membrane-anchored L-selectin to P-selectin glycoprotein ligand 1 (PSGL-1) ligand coupled onto human red blood cells (RBCs).The data indicated that L-selectin shedding reduced the amount of membrane-anchored L-selecUn and lowered both its reverse and forward rates.These results suggested that the rolling dynamics of activated leukocytes was determined by two opposite impacts:reducing the surface presentation would enhance the rolling but lowering the kinetic rates would decrease the rolling.This finding provides a new insight into understanding how L-selectin shedding regulates leukocyte rolling and adhesion.

  5. Numerical Study of Eddy Shedding By The Loop Current With Ogcm (United States)

    Tanahara, S.; Crèpon, M.

    The high resolution CLIPPER model for the Atlantic Ocean running at 1/6o was used to study the dynamic of the Gulf of Mexico. The model was daily forced with the ECMWF re-analysis air-sea fluxes during 20 years. A spin-up phase of 10 years is done in the experience. The results show the formation of the Loop Current in the interior of the Gulf of Mexico. This loop detach an anticyclonic eddy northward to Yucatan shelf Peninsula. The size of the eddy is close to 290 Km and 1000 m depth. The eddy shedding periodicity is between 7 to 9 months for the 5 first years of numer- ical forcing simulation. After that, the eddy shedding is blocked and an intensification and deepening of the loop happens. It is found that barotropic transport through Yu- catan channel and vertical structure of cross velocity's Yucatan current are important for eddy shedding process. A hypothesis for the generation and blocking of westward propagation of eddies in the Gulf of Mexico is proposed according to the numerical results.

  6. Long-term viremia and fecal shedding in pups after modified-live canine parvovirus vaccination. (United States)

    Decaro, Nicola; Crescenzo, Giuseppe; Desario, Costantina; Cavalli, Alessandra; Losurdo, Michele; Colaianni, Maria Loredana; Ventrella, Gianpiero; Rizzi, Stefania; Aulicino, Stefano; Lucente, Maria Stella; Buonavoglia, Canio


    Canine parvovirus (CPV) modified live virus vaccines are able to infect vaccinated dogs replicating in the bloodstream and enteric mucosa. However, the exact duration and extent of CPV vaccine-induced viremia and fecal shedding are not known. With the aim to fill this gap, 26 dogs were administered two commercial vaccines containing a CPV-2 or CPV-2b strain and monitored for 28 days after vaccination. By using real-time PCR, vaccine-induced viremia and shedding were found to be long lasting for both vaccinal strains. Vaccinal CPV-2b shedding was detected for a shorter period than CPV-2 (12 against 19 mean days) but with greater viral loads, whereas viremia occurred for a longer period (22 against 19 mean days) and with higher titers for CPV-2b. Seroconversion appeared as early as 7 and 14 days post-vaccination for CPV-2b and CPV-2 vaccines, respectively. With no vaccine there was any diagnostic interference using in-clinic or hemagglutination test, since positive results were obtained only by fecal real-time PCR testing. The present study adds new insights into the CPV vaccine persistence in the organism and possible interference with diagnostic tests.

  7. Preventing noise caused by vortex shedding in gate valves and orifices

    Energy Technology Data Exchange (ETDEWEB)

    Smith, B.A.W.; Luloff, B.V.; Tromp, J.H. [Atomic Energy of Canada Ltd., Chalk River, Ontario (Canada)


    Gate valves and high-energy orifices can both act as sources of noise. This noise can represent a simple environmental problem or, in severe cases, can cause piping failures within hours. This paper presents the results of two studies, one to eliminate noise in the main steam lines of a new reactor, and, the other, to develop design guidelines for preventing noise in multi-stage, high-energy orifices. Both the valves and orifices were found to have a common noise generation mechanism, namely, an unstable fluid shear layer (e.g., vortex shedding) coupled with a fluid-resonant condition (i.e., an acoustic resonance). The main steam line noise was round to be caused by periodic vortex shedding across the seat cavities of the main steam isolation valves. The orifice noise is thought to be due to vortex shedding within the orifice holes themselves. This paper reviews the findings of both studies and presents measures that can be taken to eliminate noise problems. (author)

  8. Prioritization of pesticides based on daily dietary exposure potential as determined from the SHEDS model. (United States)

    Melnyk, Lisa Jo; Wang, Zhaohui; Li, Zhilin; Xue, Jianping


    A major pathway for exposure to many pesticides is through diet. The objectives were to rank pesticides by comparing their calculated daily dietary exposure as determined by EPA's Stochastic Human Exposure and Dose Simulation (SHEDS) to single pesticides for different age groups to acceptable daily intakes (ADI), characterize pesticide trends in exposures over different time periods, and determine commodities contributing to pesticide exposures. SHEDS was applied, using Pesticide Data Program (PDP) (1991-2011) and pesticide usage data on crops from USDA combined with NHANES dietary consumption data, to generate exposure estimates by age group. ADI data collected from EPA, WHO, and other sources were used to rank pesticides based on relativeness of the dietary exposure potential to ADI by age groups. Sensitivity analysis provided trends in pesticide exposures. Within SHEDS, commodities contributing the majority of pesticides with greatest exposure potential were determined. The results indicated that the highest ranking pesticides were methamidophos and diazinon which exceeded 100% of the ADI. Sensitivity analysis indicated that exposure to methamidophos, diazinon, malathion, ethion and formetanate hydrochloride had a marked decrease from 1991-1999 to 2000-2011. Contributions analysis indicated that apples, mushroom, carrots, and lettuce contributed to diazinon exposure. Beans and pepper contributed to methamidophos exposure. Published by Elsevier Ltd.

  9. Internal Structure of Asteroids Having Surface Shedding due to Rotational Instability

    CERN Document Server

    Hirabayashi, Masatoshi; Scheeres, Daniel J


    Surface shedding of an asteroid is a failure mode where surface materials fly off due to strong centrifugal forces beyond the critical spin period, while the internal structure does not deform significantly. This paper proposes a possible structure of an asteroid interior that leads to such surface shedding due to rapid rotation rates. A rubble pile asteroid is modeled as a spheroid composed of a surface shell and a concentric internal core, the entire assembly called the test body. The test body is assumed to be uniformly rotating around a constant rotation axis. We also assume that while the bulk density and the friction angle are constant, the cohesion of the surface shell is different from that of the internal core. First, developing an analytical model based on limit analysis, we provide the upper and lower bounds for the actual surface shedding condition. Second, we use a Soft-Sphere Discrete Element Method (SSDEM) to study dynamical deformation of the test body due to a quasi-static spin-up. In this pa...

  10. A new-type flexible rock-shed under the impact of rock block: experimental investigation

    Directory of Open Access Journals (Sweden)

    S. Shi


    Full Text Available The main disadvantage of conventional concrete rock-shed is the need for a massive foundation due to the deadweight of the structure. In order to overcome such construction difficulty and to reduce costs, a new concept of flexible rock-shed is proposed in this paper. The flexible rock-shed is made of flexible nets held up by specially designed steel vaulted structure. An 1:1 prototype is manufactured and tested for functional evaluation with impact experiment. It is shown that the structure can stand for an impact energy of about 250 kJ without observable rupture of the flexible nets or cables and can be put into service again with some maintenances on the steel vaulted structure. Expermental data such as local strains, peak loads and impact times are recorded by dynamic strain gauges, load cells and high speed camera for structural analysis and some complementary suggestions of improving and designing are offered with respect to the joints and components.

  11. Hammondia heydorni: Oocyst shedding by dogs fed in vitro generated tissue cysts, and evaluation of cross-immunity between H. heydorni and Neospora caninum in mice. (United States)

    Meneses, I D S; Schares, G; Rezende-Gondim, M M; Galvão, G S; Gondim, L F P


    Hammondia heydorni is a coccidian parasite believed to be nonpathogenic for naturally-infected animals, but it is biologically and genetically related to Neospora caninum, a worldwide cause of abortion in cattle. The major aim of the present work was to determine whether dogs shed H. heydorni oocysts after consuming in vitro generated tissue cysts of the parasite. In addition, we investigated cross-immunity between H. heydorni and N. caninum in mice. Two dogs were fed cultured cells containing tissue cysts of H. heydorni mixed with canned dog food, and a third dog (negative control) received only non-infected cells mixed with canned food. The two dogs that consumed in vitro produced tissue cysts shed high numbers of oocysts, which were induced to sporulate and tested positive for H. heydorni by a species-specific PCR. The third uninfected dog did not shed H. heydorni oocysts in the feces. Oocysts shed by the dogs induced the formation of encysted bradyzoites of H. heydorni on KH-R cells. Nineteen BALB/c mice were employed in the cross-immunity study. Nine mice were orally inoculated with 1×10(5) sporulated oocysts of H. heydorni and challenged with N. caninum tachyzoites 30days after infection with H. heydorni. Other ten mice, which did not receive H. heydorni oocysts, were infected with 2×10(5)N. caninum tachyzoites. Thirty days after challenging with N. caninum, all mice were euthanized and N. caninum DNA in their tissues was quantified by real time PCR. No statistically significant difference in N. caninum DNA concentrations were observed between the two groups. We concluded that in vitro generated cysts of H. heydorni are biologically active, because they induced oocyst shedding in dogs. As no cross-protection occurred in mice inoculated with H. heydorni and challenged with N. caninum, it is suspected that these parasites do not express significant numbers of homologous proteins during infection, or the immune response of BALB/c mice after H. heydorni

  12. Viral shedding in Chinese young adults with mild 2009 H1N1 influenza

    Institute of Scientific and Technical Information of China (English)

    JIA Ning; GAO Yan; SUO Ji-jiang; XIE Li-jun; YAN Zhong-qiang; XING Yu-bin; HE Lei; LIU Yun-xi


    Background The duration of viral shedding and the transmission of 2009 H1N1 influenza among individuals, especially among the younger population with mild illness, are not well understood now. The aim of this study was to determine the viral shedding of the young adult patients with mild 2009 H1N1 influenza in China.Methods From September 2009 to January 2010, the clinical data and serial nasopharyngeal swabs of 67 patients with 2009 H1N1 influenza and 37 patients with seasonal influenza aged from 18 years to 35 years were collected. The nasopharyngeal swab samples were detected by real time RT-PCR to determine the viral shedding. All the patients did not receive the antiviral therapy but Chinese medicine for detoxicating.Results Among the patients with H1N1 virus infection, 82.1% (55/67) patients presented with fever symptom, while more patients with high fever (≥39℃) were found in seasonal influenza patients (P<0.05). For the H1N1 patients, the median interval between the symptom onset and the undetectable RNA was six days (4-10 days). But viral shedding was still found in 31.3% patients after 7 days following illness onset. The median interval between disappearance of fever and an undetectable viral RNA level was three days (2-8 days), and 17.9% patients were found to be viral shedding 6 days later after normalization of body temperature. For the seasonal influenza patients, 94.6% patients were detected out viral RNA within 7 days. The median interval of seasonal influenza between the symptom onset and the undetectable RNA was four days (3-8 days). The median interval between disappearance of fever and an undetectable viral RNA level was three days (2-6 days).Conclusion It suggests that 7 days isolation period from the illness onset or 24 hours after the resolution of fever and respiratory symptoms are not long enough to cut off the transmission among Chinese young adults with mild illness.

  13. Developmental mechanisms patterning thalamocortical projections: intrinsic, extrinsic and in between. (United States)

    Vanderhaeghen, Pierre; Polleux, Franck


    Roger Sperry proposed 40 years ago that topographic neural connections are established through complementary expression of chemoaffinity labels in projecting neurons and their final targets. This led to the identification of ephrins as key molecular cues controlling the topography of retinotectal projections. Recent studies have revealed a surprising twist to this model, shedding light on the developmental mechanisms patterning the projections between the thalamus and the cortex: ephrins, unexpectedly expressed in an intermediate target, control the establishment of topography of axonal projections between these two structures. The same cues are re-used later to control the mapping of thalamocortical projections within a given cortical area, which strikingly illustrates how a limited set of genes can contribute to generate several levels of complexity of a neuronal network.

  14. Mesenchymal stem cells derived from human exfoliated deciduous teeth (SHEDs induce immune modulatory profile in monocyte-derived dendritic cells.

    Directory of Open Access Journals (Sweden)

    Fernando de Sá Silva

    Full Text Available BACKGROUND: Mesenchymal stem cells have prominent immune modulatory properties, which may have clinical applications; however their major source, bone marrow, is of limited availability. On the other hand, mesenchymal stem cells derived from human exfoliated deciduous teeth (SHEDs are readily accessible, but their immune regulatory properties have not been completely investigated. This study was designed, therefore, to evaluate the SHEDs influence on DCs differentiation, maturation, ability to activate T cells and to expand CD4(+Foxp3(+ T cells. METHODOLOGY/PRINCIPAL FINDINGS: The experiments were based in cellular co-culture during differentiation and maturation of monocyte derived-DCs (moDCs, with, or not, presence of SHEDs. After co-culture with SHEDs, (moDCs presented lower expression of BDCA-1 and CD11c, in comparison to DC cultivated without SHEDs. CD40, CD80, CD83 and CD86 levels were also decreased in mature DCs (mDCs after co-cultivation with SHEDs. To assess the ability of SHEDs-exposed moDCs to modulate T cell responses, the former were separated from SHEDs, and co-cultured with peripheral blood lymphocytes. After 5 days, the proliferation of CD4(+ and CD8(+ T cells was evaluated and found to be lower than that induced by moDCs cultivated without SHEDs. In addition, an increase in the proportion of CD4(+Foxp3(+IL-10(+ T cells was observed among cells stimulated by mature moDCs that were previously cultivated with SHEDs. Soluble factors released during co-cultures also showed a reduction in the pro-inflammatory cytokines (IL-2, TNF-α and IFN-γ, and an increase in the anti-inflammatory molecule IL-10. CONCLUSION/SIGNIFICANCE: This study shows that SHEDs induce an immune regulatory phenotype in moDCs cells, evidenced by changes in maturation and differentiation rates, inhibition of lymphocyte stimulation and ability to expand CD4(+Foxp3(+ T cells. Further characterization and validation of this phenomenon could support the use of SHEDs

  15. Effect of a probiotic on prevention of diarrhea and Clostridium difficile and Clostridium perfringens shedding in foals

    DEFF Research Database (Denmark)

    Schoster, Angelika; Staempfli, H R; Abrahams, M;


    of incidence and duration of diarrhea and fecal shedding of Clostridium perfringens and Clostridium difficile between treatment and age groups. RESULTS: The overall incidence of diarrhea was 41 of 72 (59%) and did not differ (P = 0.37) between treatment groups. Foals treated with probiotics were more likely...... of C. perfringens shedding was 55% with no difference between treatment groups (P = 0.23). The prevalence of C. difficile shedding was 11%. CONCLUSION AND CLINICAL IMPORTANCE: There was no benefit of administering a 3-week course of probiotics, but potential adverse effects were noted. Whether...

  16. 湛江地区肉牛棚舍环境评价%Environmental evaluation of the beef cattle shed in Zhanjiang region of Guangdong province

    Institute of Scientific and Technical Information of China (English)

    洪小华; 魏天盛; 蔡思佳; 万江虹; 马驰骋; 颜培实


    In order to investigate the environmental characteristics of the open ridge shed with coconut trees overshadowing in tropical sum-mer, the determination of temperature, relative humidity, wind velocity, and PM10 index in the beef cattle shed were carried out in Zhanjiang region of Guangdong province. The result indicated that the temperature and relative humidity were almost the same inside and outside the shed. The ventilation rate of the shed met and exceeded the requirement of the maximal ventilation rate. The concentration of PM10 in the shed was better than the standard of environmental sanitation. The THI ranged from 78 to 85 , and the beef cattle were in the heat stress. The THVI which considered the influence of wind ranged from 25°C to 30. 5°C. At 14 ;00 and 19 :00 of sunny days, the wind velocity was be-tween 0. 95m/s and 1. 30m/s. The wind reduced the impact of high temperature evidently. The temperatures between the inside and outside roof surface during the testing period were all smaller than 1 °C , therefore, the ability of heat insulation was not strong. The highest tempera-ture of the inside roof was 60. 8°C , and the temperature in the shed at the same time was only 33. 4°C The main part of the environmental control was the natural ventilation of the shed.%为了解热带地区双坡式棚舍散栏饲养模式下的环境特征,在湛江测定了肉牛舍的温度、湿度、气流、PM10等指标.结果表明:棚舍内温湿度几乎相同,换气量超过了最大换气量,PM10优于卫生标准,温湿指数范围为78~ 85,处于热应激状态.考虑了气流影响的体感温度范围25~ 30.5℃,晴天的14:00和19:00,风速为0.95~ 1.30 m/s,气流显著地减少了高温的影响.棚顶隔热能力差,晴天棚顶内外表面温差不1℃,棚顶内表面最高可达60.8℃,此时的舍内气温仅为33.4℃,棚舍自然换气调节是环境控制的主体.

  17. Evaluation of the shedding routes and serological patterns in experimentally-induced Brucella melitensis infection in dexamethasonetreated and transport-stressed goats

    Directory of Open Access Journals (Sweden)

    Polycarp Nwunuji Tanko


    Full Text Available Aim: To identify and evaluate the shedding routes and patterns following experimentally-induced Brucella melitensis infection in dexamethasone-treated and transport-stressed goats. Materials and Methods: Twenty four healthy, adult goats were divided into 4 groups: A, B, C and D respectively. Group A was treated with dexamethasone for 8 days prior to inoculation with 10 (7 Colony Forming Units of B. melitensis via the intraocular route. Group B was transported for 3 hours prior to inoculation with a similar dose. Group C was inoculated with a similar dose without subjecting the animals to any prior treatment, and this group served as our positive control. Group D was not inoculated with the infective dose and served as our negative control. Blood samples along with nasal, ocular, and vaginal swabs were collected on days 0, 3, 7, 10, 14, and weekly thereafter until day 63 post inoculation (pi and were analyzed by PCR, Rose Bengal Plate Test (RBPT, and indirect ELISAtechniques. Results: The nasal, ocular and vaginal swabs tested positive for Brucellosis with PCR from day 7, with nasal route being the first and most consistent route to reveal the positive results. Group B showed the earliest onset of shedding the bacterium (day 7 followed by group Awhich started from day 10 and shed relatively more positive of the bacterium via the routes examined. Blood samples tested positive with PCR from day 7 through 14 and the results were inconsistent subsequently. Sera samples tested positive with RBPT on day 14 in all the 3 infected groups but more consistent in group C. On the other hand, tests using ELISAshowed positive results from day 7 pi, with group C having a 100% seroconvertion –while groups Aand B showed only 50% seroconvertion. Conclusion: The consistent shedding via the nasal, ocular, and vaginal routes in groups A and B implied possible immunosuppression in the infected animals. We recommend that programs designed to control Brucellosis should

  18. Vaccination with attenuated Salmonella enterica Dublin expressing E coli O157:H7 outer membrane protein Intimin induces transient reduction of fecal shedding of E coli O157:H7 in cattle

    Directory of Open Access Journals (Sweden)

    Fang Ferric C


    Full Text Available Abstract Background Escherichia coli serogroup O157:H7 has emerged as an important zoonotic bacterial pathogen, causing a range of symptoms from self-limiting bloody diarrhea to severe hemorrhagic colitis and hemolytic-uremic syndrome in humans. Beef and dairy cattle are considered the most important animal reservoirs for this pathogen. One of the important virulence characteristics of E. coli O157:H7 is the eaeA gene encoding the 97 kDa surface protein intimin. Intimin is required for attachment and effacement during the interaction of enterohemorrhagic E. coli with human and bovine neonatal enterocytes. The present study was undertaken to test the hypothesis that an adaptive mucosal immune response directed against intimin will reduce or prevent enteric colonization and fecal shedding of E. coli O157:H7 in cattle. Results Cattle were orally inoculated with either milk (control, milk with live attenuated Salmonella enterica serovar Dublin (vector, or milk with live attenuated recombinant S. Dublin expressing intimin (vaccinated on days 0, 14 and 28. On day 98, all calves were challenged orally with E. coli O157:H7 to evaluate whether vaccination with the recombinant S. Dublin expressing intimin would reduce the level of E. coli O157:H7 fecal shedding. During the first 28 days, vaccinated calves shed both the vector strain and the intimin-expressing S. Dublin strain at a similar level. The vector strain was shed for a significantly longer period as compared to the level of recombinant vaccine strain. Calves that received the intimin-expressed vaccine ceased shedding S. Dublin from day 28 to day 63. All calves were challenged with E. coli O157:H7 on day 98 to determine the effect on fecal shedding of E. coli O157:H7. The amount of E. coli O157:H7 in feces was measured for 30 days post-challenge. We observed a transient clearance of E. coli O157:H7 from the feces in the vaccinated calves. The magnitude of fecal E. coli O157:H7 shedding did not

  19. Optimal control of circular cylinder wakes using long control horizons

    CERN Document Server

    Flinois, Thibault L B


    The classical problem of minimizing the drag of a circular cylinder by using body rotation is revisited in an adjoint-based optimal control framework. The cylinder's unsteady and fully unconstrained rotation rate is optimized at Reynolds numbers of 100 and 200 and over horizons that are longer than in previous studies, where they are typically of the order of a vortex shedding period or shorter. In the best configuration, the drag is reduced by $19\\%$, the vortex shedding is effectively suppressed, and this low drag state is maintained with minimal cylinder rotation after transients. Without closed-loop control, which maintains a specific phase relationship between the actuation and the shedding, the wake is not stabilized. A comparison is also given between the performance of optimizations for different horizon lengths and cost functions. It is shown that the long horizons used are necessary in order to stabilize the vortex shedding efficiently.

  20. Detection and characterization of diverse coccidian protozoa shed by California sea lions

    Directory of Open Access Journals (Sweden)

    Yvette A. Girard


    Full Text Available Tissue-cyst forming coccidia in the family Sarcocystidae are etiologic agents of protozoal encephalitis in marine mammals including the federally listed Southern sea otter (Enhydra lutris. California sea lions (Zalophus californianus, whose coastal habitat overlaps with sea otters, are definitive hosts for coccidian protozoa provisionally named Coccidia A, B and C. While Coccidia A and B have unknown clinical effects on aquatic wildlife hosts, Coccidia C is associated with severe protozoal disease in harbor seals (Phoca vitulina. In this study, we conducted surveillance for protozoal infection and fecal shedding in hospitalized and free-ranging California sea lions on the Pacific Coast and examined oocyst morphology and phenotypic characteristics of isolates via mouse bioassay and cell culture. Coccidia A and B were shed in similar frequency, particularly by yearlings. Oocysts shed by one free-ranging sea lion sampled at Año Nuevo State Park in California were previously unidentified in sea lions and were most similar to coccidia infecting Guadalupe fur seals (Arctocephalus townsendi diagnosed with protozoal disease in Oregon (USA. Sporulated Coccidia A and B oocysts did not replicate in three strains of mice or in African green monkey kidney cells. However, cultivation experiments revealed that the inoculum of fecally-derived Coccidia A and B oocysts additionally contained organisms with genetic and antigenic similarity to Sarcocystis neurona; despite the absence of detectable free sporocysts in fecal samples by microscopic examination. In addition to the further characterization of Coccidia A and B in free-ranging and hospitalized sea lions, these results provide evidence of a new role for sea lions as putative mechanical vectors of S. neurona, or S. neurona-like species. Future work is needed to clarify the distribution, taxonomical status, and pathogenesis of these parasites in sea lions and other marine mammals that share their the near

  1. Detection and characterization of diverse coccidian protozoa shed by California sea lions (United States)

    Girard, Yvette A.; Johnson, Christine K.; Fritz, Heather M.; Shapiro, Karen; Packham, Andrea E.; Melli, Ann C.; Carlson-Bremer, Daphne; Gulland, Frances M.; Rejmanek, Daniel; Conrad, Patricia A.


    Tissue-cyst forming coccidia in the family Sarcocystidae are etiologic agents of protozoal encephalitis in marine mammals including the federally listed Southern sea otter (Enhydra lutris). California sea lions (Zalophus californianus), whose coastal habitat overlaps with sea otters, are definitive hosts for coccidian protozoa provisionally named Coccidia A, B and C. While Coccidia A and B have unknown clinical effects on aquatic wildlife hosts, Coccidia C is associated with severe protozoal disease in harbor seals (Phoca vitulina). In this study, we conducted surveillance for protozoal infection and fecal shedding in hospitalized and free-ranging California sea lions on the Pacific Coast and examined oocyst morphology and phenotypic characteristics of isolates via mouse bioassay and cell culture. Coccidia A and B were shed in similar frequency, particularly by yearlings. Oocysts shed by one free-ranging sea lion sampled at Año Nuevo State Park in California were previously unidentified in sea lions and were most similar to coccidia infecting Guadalupe fur seals (Arctocephalus townsendi) diagnosed with protozoal disease in Oregon (USA). Sporulated Coccidia A and B oocysts did not replicate in three strains of mice or in African green monkey kidney cells. However, cultivation experiments revealed that the inoculum of fecally-derived Coccidia A and B oocysts additionally contained organisms with genetic and antigenic similarity to Sarcocystis neurona; despite the absence of detectable free sporocysts in fecal samples by microscopic examination. In addition to the further characterization of Coccidia A and B in free-ranging and hospitalized sea lions, these results provide evidence of a new role for sea lions as putative mechanical vectors of S. neurona, or S. neurona-like species. Future work is needed to clarify the distribution, taxonomical status, and pathogenesis of these parasites in sea lions and other marine mammals that share their the near-shore marine

  2. Semen Bacterial Concentrations and HIV-1 RNA Shedding Among HIV-1–Seropositive Kenyan Men (United States)

    Srinivasan, Sujatha; Huang, Dandi; Ko, Daisy L.; Sanders, Eduard J.; Peshu, Norbert M.; Krieger, John N.; Muller, Charles H.; Coombs, Robert W.; Fredricks, David N.; Graham, Susan M.


    Introduction: HIV-1 is transmitted through semen from men to their sexual partners. Genital infections can increase HIV-1 RNA shedding in semen, but shedding also occurs in the absence of typical pathogens. We hypothesized that higher bacterial concentrations in semen would be associated with higher HIV-1 RNA levels. Methods: We analyzed semen samples from 42 HIV-1–seropositive Kenyan men using quantitative polymerase chain reaction (PCR) to assess bacterial concentrations and real-time PCR to measure HIV-1 RNA levels. Generalized estimation equations were used to evaluate associations between these 2 measures. Broad-range 16S rRNA gene PCR with pyrosequencing was performed on a subset of 13 samples to assess bacterial community composition. Results: Bacteria were detected in 96.6% of 88 samples by quantitative PCR. Semen bacterial concentration and HIV-1 RNA levels were correlated 0.30 (P = 0.01). The association between bacterial concentration and HIV-1 RNA detection was not significant after adjustment for antiretroviral therapy (ART) (adjusted odds ratio: 1.27, 95% CI: 0.84 to 1.91). Factors associated with semen bacterial concentration included insertive anal sex (adjusted beta 0.92, 95% CI: 0.12 to 1.73) and ART use (adjusted beta: −0.77, 95% CI: −1.50 to 0.04). Among 13 samples with pyrosequencing data, Corynebacterium spp., Staphylococcus spp., and Streptococcus spp. were most frequently detected. Conclusion: Most of these HIV-1–infected men had bacteria in their semen. ART use was associated with undetectable semen HIV-1 RNA and lower semen bacterial concentrations, whereas insertive anal sex was associated with higher bacterial concentrations. Additional studies evaluating the relationship between semen bacteria, inflammation, mucosal immunity, and HIV-1 shedding are needed to understand implications for HIV-1 transmission. PMID:27861240

  3. Housing a Raspberry Pi Connected AS-1 Seismometer in a Solar-Paneled Shed (United States)

    Marton, F.; Tokman, T. L.; Echreshzadeh, M.; Palaric, K. D.; Filippone, N. V.; Sivo, J.


    Last year, students working on the SeismoSTEM project at Bergen Community College successfully manufactured and assembled an AS-1 seismometer1. However, issues students encountered were not knowing where to place the TC-1 and AS-1 seismometers, nor how to configure the instruments with a computer for monitoring and measuring earthquakes. Our solution was to purchase a Raspberry Pi 3 model B, which has four USB ports and a Wi-Fi adapter. We then installed the Raspbian operating system that can run jAmaSeis, which allows for the collection and analysis of seismic data. In terms of the shed that was constructed last summer2, we installed roof shingles, as well as a ventilation system to prevent overheating. The seismometers will then be placed on a concrete slab. In the future, we plan on applying a wood varnish around the exterior of the shed, as well as gravel around the shed for water drainage as well as to make it more visually appealing. Moreover, we plan on mounting a 170-W solar panel on the roof to charge a 12-V deep cycle marine battery, which will provide electricity to the system. References: 1Tokman, T.L. et al., What's shaking? Manufacturing & assembling an AS-1 educational seismometer for undergraduate stem research, Geological Society of America Abstracts with Programs. Vol. 47, No. 7, p.524, 2015. 2Palaric, K.D., et al., Constructing a solar-powered seismic station for educational seismometers, Geological Society of America Abstracts with Programs. Vol. 47, No. 7, p.524, 2015.

  4. Detection and characterization of diverse coccidian protozoa shed by California sea lions. (United States)

    Girard, Yvette A; Johnson, Christine K; Fritz, Heather M; Shapiro, Karen; Packham, Andrea E; Melli, Ann C; Carlson-Bremer, Daphne; Gulland, Frances M; Rejmanek, Daniel; Conrad, Patricia A


    Tissue-cyst forming coccidia in the family Sarcocystidae are etiologic agents of protozoal encephalitis in marine mammals including the federally listed Southern sea otter (Enhydra lutris). California sea lions (Zalophus californianus), whose coastal habitat overlaps with sea otters, are definitive hosts for coccidian protozoa provisionally named Coccidia A, B and C. While Coccidia A and B have unknown clinical effects on aquatic wildlife hosts, Coccidia C is associated with severe protozoal disease in harbor seals (Phoca vitulina). In this study, we conducted surveillance for protozoal infection and fecal shedding in hospitalized and free-ranging California sea lions on the Pacific Coast and examined oocyst morphology and phenotypic characteristics of isolates via mouse bioassay and cell culture. Coccidia A and B were shed in similar frequency, particularly by yearlings. Oocysts shed by one free-ranging sea lion sampled at Año Nuevo State Park in California were previously unidentified in sea lions and were most similar to coccidia infecting Guadalupe fur seals (Arctocephalus townsendi) diagnosed with protozoal disease in Oregon (USA). Sporulated Coccidia A and B oocysts did not replicate in three strains of mice or in African green monkey kidney cells. However, cultivation experiments revealed that the inoculum of fecally-derived Coccidia A and B oocysts additionally contained organisms with genetic and antigenic similarity to Sarcocystis neurona; despite the absence of detectable free sporocysts in fecal samples by microscopic examination. In addition to the further characterization of Coccidia A and B in free-ranging and hospitalized sea lions, these results provide evidence of a new role for sea lions as putative mechanical vectors of S. neurona, or S. neurona-like species. Future work is needed to clarify the distribution, taxonomical status, and pathogenesis of these parasites in sea lions and other marine mammals that share their the near-shore marine

  5. Effects of Newcastle disease virus vaccine antibodies on the shedding and transmission of challenge viruses. (United States)

    Miller, Patti J; Afonso, Claudio L; El Attrache, John; Dorsey, Kristi M; Courtney, Sean C; Guo, Zijing; Kapczynski, Darrell R


    Different genotypes of avian paramyxovirus serotype-1 virus (APMV-1) circulate in many parts of the world. Traditionally, Newcastle disease virus (NDV) is recognized as having two major divisions represented by classes I and II, with class II being further divided into sixteen genotypes. Although all NDV are members of APMV-1 and are of one serotype, antigenic and genetic diversity is observed between the different genotypes. Reports of vaccine failure from many countries and reports by our lab on the reduced ability of classical vaccines to significantly decrease viral replication and shedding have created renewed interest in developing vaccines formulated with genotypes homologous to the virulent NDV (vNDV) circulating in the field. We assessed how the amount and specificity of humoral antibodies induced by inactivated vaccines affected viral replication, clinical protection and evaluated how non-homologous (heterologous) antibody levels induced by live NDV vaccines relate to transmission of vNDV. In an experimental setting, all inactivated NDV vaccines protected birds from morbidity and mortality, but higher and more specific levels of antibodies were required to significantly decrease viral replication. It was possible to significantly decrease viral replication and shedding with high levels of antibodies and those levels could be more easily reached with vaccines formulated with NDV of the same genotype as the challenge viruses. However, when the levels of heterologous antibodies were sufficiently high, it was possible to prevent transmission. As the level of humoral antibodies increase in vaccinated birds, the number of infected birds and the amount of vNDV shed decreased. Thus, in an experimental setting the effective levels of humoral antibodies could be increased by (1) increasing the homology of the vaccine to the challenge virus, or (2) allowing optimal time for the development of the immune response.

  6. On vortex shedding and prediction of vortex-induced vibrations of circular cylinders

    Energy Technology Data Exchange (ETDEWEB)

    Halse, Karl Henning


    In offshore installations, many crucial components can be classified as slender marine structures: risers, mooring lines, umbilicals and cables, pipelines. This thesis studies the vortex shedding phenomenon and the problem of predicting vortex-induced vibrations of such structures. As the development of hydrocarbons move to deeper waters, the importance of accurately predicting the vortex-induced response has increased and so the need for proper response prediction methods is large. This work presents an extensive review of existing research publications about vortex shedding from circular cylinders and the vortex-induced vibrations of cylinders and the different numerical approaches to modelling the fluid flow. The response predictions from different methods are found to disagree, both in response shapes and in vibration amplitudes. This work presents a prediction method that uses a fully three-dimensional structural finite element model integrated with a laminar two-dimensional Navier-Stokes solution modelling the fluid flow. This solution is used to study the flow both around a fixed cylinder and in a flexibly mounted one-degree-of-freedom system. It is found that the vortex-shedding process (in the low Reynolds number regime) is well described by the computer program, and that the vortex-induced vibration of the flexibly mounted section do reflect the typical dynamic characteristics of lock-in oscillations. However, the exact behaviour of the experimental results found in the literature was not reproduced. The response of the three-dimensional structural model is larger than the expected difference between a mode shape and a flexibly mounted section. This is due to the use of independent hydrodynamic sections along the cylinder. The predicted response is not unrealistic, and the method is considered a powerful tool. 221 refs., 138 figs., 36 tabs.

  7. Awareness of Stem cells & Health Implications of SHED found in Pediatric Dentition among Indian Population. (United States)

    Goomer, Pallvi; Sidhu, Arshpreet Kaur; Tuli, Preety; Kansal, Shinam; Bansal, Kanishka; Thakre, Gauri R


    Primary teeth may be an ideal source of postnatal stem cells to regenerate tooth structures and bone, and possibly to treat neural tissue injury or degenerative diseases. SHED (stem cells from human exfoliated deciduous teeth) were identified to be a population of highly proliferative, clonogenic cells capable of differentiating into a variety of cell types including neural cells, adipocytes, and odontoblasts. The present study was carried out to assess the knowledge, awareness & attitude of parents visiting various dental clinics in tricity area of india regarding stem cells from primary teeth and their potential health benefits. A total of 250 parents of pediatric patients seeking dental treatment at various dental clinics in tricity area were included in the study. Parents were personally interviewed with a questionnaire and their responses were immediately computed. Among 250 parents only 95(62%) had knowledge regarding stem cells. While only 47(18.8) were informed regarding stem cells from baby teeth & their benefits. Maximum subjects were informed through internet 21(44.6%) followed by information through friends(23.4%) and dentist(21.2%). Very few were informed through magazines, newspaper and only one (2.1%) person was informed by television. It is important to create more awareness among the populace of our country about the potential health benefits of stem cells from primary teeth. Dentist should educate parents, caregivers and teachers regarding SHED & its benefits, ensuring good health for every Indian child and hence health of future citizens. How to cite the article: Goomer P, Sidhu AK, Tuli P, Kansal S, Bansal K, Thakre GR. Awareness of Stem cells & Health Implications of SHED found in Pediatric Dentition among Indian Population. J Int Oral Health 2014;6(1):44-7.

  8. Endometrial Shedding Effect on Conception and Live Birth in Women With Polycystic Ovary Syndrome (United States)

    Diamond, Michael P.; Kruger, Michael; Santoro, Nanette; Zhang, Heping; Casson, Peter; Schlaff, William; Coutifaris, Christos; Brzyski, Robert; Christman, Gregory; Carr, Bruce R.; McGovern, Peter G.; Cataldo, Nicholas A.; Steinkampf, Michael P.; Gosman, Gabriella G.; Nestler, John E.; Carson, Sandra; Myers, Evan E.; Eisenberg, Esther; Legro, Richard S.


    Objective To estimate whether progestin-induced endometrial shedding, prior to ovulation induction with clomiphene citrate, metformin, or a combination of both, affects ovulation, conception, and live birth rates in women with polycystic ovary syndrome (PCOS). Methods A secondary analysis of the data from 626 women with PCOS from the National Institutes of Child Health and Human Development Cooperative Reproductive Medicine Network trial was performed. Women had been randomized to up to six cycles of clomiphene citrate alone, metformin alone, or clomiphene citrate plus metformin. Women were assessed for occurrence of ovulation, conception, and live birth in relation to prior bleeding episodes (after either ovulation or exogenous progestin-induced withdrawal bleed). Results While ovulation rates were higher in cycles preceded by spontaneous endometrial shedding than after anovulatory cycles (with or without prior progestin withdrawal), both conception and live birth rates were significantly higher after anovulatory cycles without progestin-induced withdrawal bleeding (live birth per cycle: spontaneous menses 2.2%; anovulatory with progestin withdrawal 1.6%; anovulatory without progestin withdrawal 5.3%; p<0.001). The difference was more marked when rate was calculated per ovulation (live birth per ovulation: spontaneous menses 3.0%; anovulatory with progestin withdrawal 5.4%; anovulatory without progestin withdrawal 19.7%; p < .001). Conclusion Conception and live birth rates are lower in women with PCOS after a spontaneous menses or progestin-induced withdrawal bleeding as compared to anovulatory cycles without progestin withdrawal. The common clinical practice of inducing endometrial shedding with progestin prior to ovarian stimulation may have an adverse effect on rates of conception and live birth in anovulatory women with PCOS. PMID:22525900

  9. Reduced human herpesvirus-8 oropharyngeal shedding associated with protease inhibitor-based antiretroviral therapy. (United States)

    Gantt, Soren; Cattamanchi, Ashok; Krantz, Elizabeth; Magaret, Amalia; Selke, Stacy; Kuntz, Steven R; Huang, Meei-Li; Corey, Lawrence; Wald, Anna; Casper, Corey


    Human herpesvirus 8 (HHV-8) replication increases the risk of Kaposi sarcoma (KS). Highly-active antiretroviral therapy (HAART) reduces the incidence of KS, and regimens that contain protease inhibitors (PIs) may be particularly effective. To determine whether PI-based HAART regimens may more effectively inhibit HHV-8 shedding compared to regimens without PIs. Prospective, observational study of 142 HIV-1 and HHV-8 co-infected men conducted in Seattle, Washington. Quantitative HHV-8 PCR testing was performed on daily swabs of the oropharynx, the primary site of HHV-8 replication. Associations between antiretroviral regimen and detection of HHV-8 DNA in swabs were evaluated using generalized estimating equations. HHV-8 DNA was detected in 3016 (26%) of 11,608 specimens collected. PI-based HAART was associated with a statistically significantly lower frequency of detection (RR 0.2; 95% CI 0.1-0.5) compared to ART-naïve persons, whereas HAART without a PI was not (RR 0.7; 95% CI 0.4-1.3). Compared to ART-naïve persons, there was also a trend toward lower quantities of HHV-8 detected during treatment with HAART regimens that contained a PI. These associations between PIs and measures of HHV-8 shedding could not be attributed to use of nelfinavir, which inhibits HHV-8 replication in vitro, and were independent of CD4 count and HIV plasma viral load (VL). HAART regimens that contain PIs appear to decrease HHV-8 shedding compared to NNRTIs. Further study of PI-based HAART is warranted to determine the optimal regimens for prevention and treatment of KS. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Multivalent ligands control stem cell behaviour in vitro and in vivo (United States)

    Conway, Anthony; Vazin, Tandis; Spelke, Dawn P.; Rode, Nikhil A.; Healy, Kevin E.; Kane, Ravi S.; Schaffer, David V.


    There is broad interest in designing nanostructured materials that can interact with cells and regulate key downstream functions. In particular, materials with nanoscale features may enable control over multivalent interactions, which involve the simultaneous binding of multiple ligands on one entity to multiple receptors on another and are ubiquitous throughout biology. Cellular signal transduction of growth factor and morphogen cues (which have critical roles in regulating cell function and fate) often begins with such multivalent binding of ligands, either secreted or cell-surface-tethered to target cell receptors, leading to receptor clustering. Cellular mechanisms that orchestrate ligand-receptor oligomerization are complex, however, so the capacity to control multivalent interactions and thereby modulate key signalling events within living systems is currently very limited. Here, we demonstrate the design of potent multivalent conjugates that can organize stem cell receptors into nanoscale clusters and control stem cell behaviour in vitro and in vivo. The ectodomain of ephrin-B2, normally an integral membrane protein ligand, was conjugated to a soluble biopolymer to yield multivalent nanoscale conjugates that potently induce signalling in neural stem cells and promote their neuronal differentiation both in culture and within the brain. Super-resolution microscopy analysis yielded insights into the organization of the receptor-ligand clusters at the nanoscale. We also found that synthetic multivalent conjugates of ephrin-B1 strongly enhance human embryonic and induced pluripotent stem cell differentiation into functional dopaminergic neurons. Multivalent bioconjugates are therefore powerful tools and potential nanoscale therapeutics for controlling the behaviour of target stem cells in vitro and in vivo.

  11. A review of Sarcocystis spp. shed by opossums (Didelphis spp. in Brazil

    Directory of Open Access Journals (Sweden)

    Samantha Yuri Oshiro Branco Valadas


    Full Text Available South American opossums are the definitive hosts of Sarcocystis neurona, Sarcocystis falcatula, Sarcocystis speeri and Sarcocystis lindsayi. The sporocysts of these species of Sarcocystis are morphologically similar and methods like infectivity and pathogenicity for intermediate hosts (immunodeficient mice and psittacine birds and molecular tools are used for identification. Opossums are synanthropic wild animals, and widely distributed in Brazilian territory. Previous studies have shown high environmental contamination with S. neurona sporocysts in several Brazilian regions. This paper reviews information on Sarcocystis spp. shed by various opossum species and its occurrence in Brazil.

  12. EPA's SHEDS-multimedia model: children's cumulative pyrethroid exposure estimates and evaluation against NHANES biomarker data. (United States)

    Xue, Jianping; Zartarian, Valerie; Tornero-Velez, Rogelio; Tulve, Nicolle S


    The U.S. EPA's SHEDS-Multimedia model was applied to enhance the understanding of children's exposures and doses to multiple pyrethroid pesticides, including major contributing chemicals and pathways. This paper presents combined dietary and residential exposure estimates and cumulative doses for seven commonly used pyrethroids, and comparisons of model evaluation results with NHANES biomarker data for 3-PBA and DCCA metabolites. Model input distributions were fit to publicly available pesticide usage survey data, NHANES, and other studies, then SHEDS-Multimedia was applied to estimate total pyrethroid exposures and doses for 3-5 year olds for one year variability simulations. For dose estimations we used a pharmacokinetic model and two approaches for simulating dermal absorption. SHEDS-Multimedia predictions compared well to NHANES biomarker data: ratios of 3-PBA observed data to SHEDS-Multimedia modeled results were 0.88, 0.51, 0.54 and 1.02 for mean, median, 95th, and 99th percentiles, respectively; for DCCA, the ratios were 0.82, 0.53, 0.56, and 0.94. Modeled time-averaged cumulative absorbed dose of the seven pyrethroids was 3.1 nmol/day (versus 8.4 nmol/day for adults) in the general population (residential pyrethroid use and non-use homes) and 6.7 nmol/day (versus 10.5 nmol/day for adults) in the simulated residential pyrethroid use population. For the general population, contributions to modeled cumulative dose by chemical were permethrin (60%), cypermethrin (22%), and cyfluthrin (16%); for residential use homes, contributions were cypermethrin (49%), permethrin (29%), and cyfluthrin (17%). The primary exposure route for 3-5 year olds in the simulated residential use population was non-dietary ingestion exposure; whereas for the simulated general population, dietary exposure was the primary exposure route. Below the 95th percentile, the major exposure pathway was dietary for the general population; non-dietary ingestion was the major pathway starting below

  13. Force balance and membrane shedding at the Red Blood Cell surface


    Sens, Pierre; Gov, Nir


    During the aging of the red-blood cell, or under conditions of extreme echinocytosis, membrane is shed from the cell plasma membrane in the form of nano-vesicles. We propose that this process is the result of the self-adaptation of the membrane surface area to the elastic stress imposed by the spectrin cytoskeleton, via the local buckling of membrane under increasing cytoskeleton stiffness. This model introduces the concept of force balance as a regulatory process at the cell membrane, and qu...

  14. Application of cable-supported spatial grid in dry coal shed

    Institute of Scientific and Technical Information of China (English)

    Haidong XING; Jiping HAO; Guobin XU


    This paper presented a new structural style cable-supported spatial grid, which was applied in large span dry coal sheds. The influence of configuration of cable on the force of cable and beam, the ratio of beam force to cable force and the deflection of span was investigated, and a rational configuration of cable was obtained. The results show that the cable-supported spatial grid can maximize the use of material strength, and have the advantages of low usage of steel, large span and sufficient headroom.

  15. Relative roles of doxycycline and cation chelation in endothelial glycan shedding and adhesion of leukocytes. (United States)

    Lipowsky, Herbert H; Sah, Rachna; Lescanic, Anne


    Leukocyte [white blood cell (WBC)] adhesion and shedding of glycans from the endothelium [endothelial cells (ECs)] in response to the chemoattractant f-Met-Leu-Phe (fMLP) has been shown to be attenuated by topical inhibition of matrix metalloproteases (MMPs) with doxycycline (Doxy). Since Doxy also chelates divalent cations, these responses were studied to elucidate the relative roles of cation chelation and MMP inhibition. WBC-EC adhesion, WBC rolling flux, and WBC rolling velocity were studied in postcapillary venules in the rat mesentery during superfusion with the cation chelator EDTA or Doxy. Shedding and accumulation of glycans on ECs, with and without fMLP, were quantified by the surface concentration of lectin (BS-1)-coated fluorescently labeled microspheres (FLMs) during constant circulating concentration. Without fMLP, low concentrations of EDTA (1-3 mM) increased FLM-EC sequestration due to disruption of the permeability barrier with prolonged exposure. In contrast, with 0.5 μM Doxy alone, FLM adhesion remained constant (i.e., no change in glycan content) on ECs, and WBC adhesion increased with prolonged superfusion. Without fMLP, EDTA did not affect firm WBC-EC adhesion but reduced WBC rolling flux in a dose-dependent manner. With fMLP, EDTA did not inhibit WBC adhesion, whereas Doxy did during the first 20 min of superfusion. Thus, the inhibition by Doxy of glycan (FLM) shedding and WBC adhesion in response to fMLP results from MMP inhibition, in contrast to cation chelation. With either Doxy or the MMP inhibitor GM-6001, WBC rolling velocity decreased by 50%, as in the case with fMLP, suggesting that MMP inhibition reduces sheddase activity, which increases the adhesiveness of rolling WBCs. These events increase the effective leukocrit on the venular wall and increase firm WBC-EC adhesion. Thus, MMP inhibitors have both a proadhesion effect by reducing sheddase activity while exerting an antiadhesion effect by inhibiting glycocalyx shedding and

  16. Shedding and seroprevalence of pathogenic Leptospira spp. in sheep and cattle at a New Zealand Abattoir. (United States)

    Fang, F; Collins-Emerson, J M; Cullum, A; Heuer, C; Wilson, P R; Benschop, J


    A cross-sectional study was carried out on sheep and cattle slaughtered at a New Zealand abattoir from September to November 2010 to investigate the supplier-specific shedding rate, renal carriage rate and seroprevalence of leptospires. In the 2008/2009 season, this abattoir experienced three human leptospirosis cases from 20 staff, of which two were hospitalized. Urine, kidney and blood samples were collected from carcasses of 399 sheep (six suppliers, 17 slaughter lines) and 146 cattle (three suppliers, 22 slaughter lines). The urine and kidney samples were tested by quantitative real-time PCR (qPCR), while serum samples (from coagulated blood samples) were tested by microscopic agglutination test (MAT). In total, 27% (73/274; 95% CI: 18-37) of urine samples tested positive by qPCR. Species-specific shedding rates (prevalence of positive urine qPCR) were 31% (95% CI: 17-48) for sheep and 21% (95% CI: 14-30) for cattle. For 545 kidney samples tested, 145 were qPCR positive (27%; 95% CI: 17-39). The average prevalence of kidney qPCR positivity was 29% (95% CI: 17-45) for sheep and 21% (95% CI: 15-28) for cattle. Three hundred and thirty of 542 sampled sheep and cattle had antibodies against Leptospira borgpetersenii serovar Hardjobovis (Hardjobovis) and/or Leptospira interrogans serovar Pomona (Pomona), based on reciprocal MAT titre ≥1 : 48 (overall seroprevalence of 61%; 95% CI: 48-73). Seroprevalence was 57% (95% CI: 40-72) for sheep and 73% (95% CI: 59-83) for cattle. Among the seropositive animals, 41% (70/170; 95% CI: 30-54) were shedding (tested positive by urine qPCR) and 42% (137/330; 95% CI: 30-54) had renal carriage (tested positive by kidney qPCR). Some risk management options for abattoirs or farms to prevent human leptospirosis infections include vaccination of maintenance hosts, the use of personal protective equipment, and the application of urine qPCR to detect shedding status of stock as surveillance and as an alert.

  17. Haplometra cylindracea (Zeder, 1800 (Trematoda: Plagiorchiidae: variation in the dates of cercarial shedding for overwintering Galba truncatula

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    Vignoles P.


    Full Text Available Natural infections of Galba truncatula with Haplometra cylindracea were followed from 2001 to 2009 to determine if their characteristics were similar when snails came from water collections frequented by Bufo bufo or by frogs and newts for their egg-laying. Snail samples were collected from both types of sites to count shed cercariae for three days and also free cercariae when snails were dissected. In sites only frequented by B. bufo, cercarial shedding occurred earlier than in those colonized by frogs and newts (March instead of April-May. In contrast, the number of cercariae shed during three successive days was significantly higher in May. This variation in the dates of cercarial shedding might be due, either to a synchronism between cercaria-releasing snails and the presence of the definitive host (tadpoles in water collections, or to an earlier infection of overwintering snails in autumn by H. cylindracea miracidia in the case of toad-frequented sites.

  18. A prediction model for the vortex shedding noise from the wake of an airfoil or axial flow fan blades (United States)

    Lee, C.; Chung, M. K.; Kim, Y.-H.


    An analytical model is presented for predicting the vortex shedding noise generated from the wake of axial flow fan blades. The downstream wake of a fan blade is assumed to be dominated by the von Karman vortex street, and the strength and the shedding frequency of the wake vortex are determined from the wake structure model. The fluctuating pressure and lift on the blade surface, which are induced from the vortices in the wake, are analyzed by incorporating the wake model for the von Karman vortex street with thin airfoil theory. The predicted vortex shedding frequency and the overall sound pressure level compare favorably with the measured results for the vortex shedding noise from axial flow fans.

  19. Shedding of live Eimeria vaccine progeny is delayed in chicks with delayed access to feed after vaccination. (United States)

    Price, Kayla R; Freeman, Megan; Van-Heerden, Kobus; Barta, John R


    Hatching, processing and transportation result in inevitable delays before chicks are placed into brooding and receive their first feed and drinking water after hatching. To determine if delayed access to feed for different durations following live Eimeria vaccination affected initial shedding of vaccine progeny, replacement layer chicks (480, Lohmann-LSL Lite) aged approximately 6h after hatch were administered a commercial live Eimeria vaccine. Vaccinated chicks were divided randomly into groups and were provided access to feed immediately (0 h) or after a delay of 6, 12, or 24 h (4 treatments × 6 replicates per treatment × 20 pullets per replicate). All pullets were provided drinking water immediately following vaccination. Fecal oocysts shed per gram of feces for each cage replicate was determined daily from 4 to 9 days post inoculation. Chicks provided feed immediately had peak oocyst shedding at 5 days post-inoculation but delayed access to feed for 24h was associated with a 2 days delay in peak oocyst shedding to 7 days post-inoculation. Chicks with delays in access to feed of intermediate duration (i.e. 6 or 12h) had peak oocyst shedding at 6 days post-inoculation. Overall oocyst shedding was not affected. Live Eimeria vaccination success may be measured by evaluating initial shedding of oocysts at some pre-established time after vaccine application, usually by a single fecal collection conducted at 5, 6 or 7 days post-inoculation. Recognizing that withholding feed following live Eimeria vaccination shifts the time of the resultant peak oocyst shedding complicates the assessment of vaccine application; if delayed access to feed is not taken into account, it is possible that false conclusions could be drawn regarding the relative success of vaccine administration.

  20. Fluvial transport potential of shed and root-bearing dinosaur teeth from the late Jurassic Morrison Formation

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    Joseph E. Peterson


    Full Text Available Shed dinosaur teeth are commonly collected microvertebrate remains that have been used for interpretations of dinosaur feeding behaviors, paleoecology, and population studies. However, such interpretations may be biased by taphonomic processes such as fluvial sorting influenced by tooth shape: shed teeth, removed from the skull during life, and teeth possessing roots, removed from the skull after death. As such, teeth may behave differently in fluvial systems due to their differences in shape. In order to determine the influence of fluvial processes on the preservation and distribution of shed and root-bearing dinosaur teeth, the hydrodynamic behaviors of high-density urethane resin casts of shed and root-bearing Allosaurus and Camarasaurus teeth were experimentally tested for relative transport distances at increasing flow velocities in an artificial fluviatile environment. Results show that tooth cast specimens exhibited comparable patterns of transport at lower velocities, though the shed Camarasaurus teeth transported considerably farther in medium to higher flow velocities. Two-Way ANOVA tests indicate significant differences in the mean transport distances of tooth casts oriented perpendicular to flow (p < 0.05 with varying tooth morphologies and flow velocities. The differences exhibited in the transportability of shed and root-bearing teeth has important implications for taphonomic reconstructions, as well as future studies on dinosaur population dynamics, paleoecology, and feeding behaviors.

  1. Evaluation of the Modeling of Exposure to Environmental Tobacco Smoke (ETS) in the SHEDS-PM Model. (United States)

    Cao, Ye; Frey, H Christopher; Liu, Xiaozhen; Deshpande, Bela K


    Environmental tobacco smoke (ETS) is estimated to be a major contributor to indoor PM concentration and human exposures to fine particulate matter of 2.5 microns or smaller (PM2.5). The Stochastic Human Exposure and Dose Simulation for Particulate Matter (SHEDS-PM) model developed by the US Environmental Protection Agency estimates distributions of outdoor and indoor PM2.5 exposure for a specified population based on ambient concentrations and indoor emissions sources. Because indoor exposures to ETS can be high, especially in indoor residential microenvironments, a critical assessment was conducted of the methodology and data used in SHEDS-PM for estimation of indoor exposure to ETS. For the residential microenvironment, SHEDS uses a mass-balance approach which is comparable to best practices. The default inputs in SHEDS-PM were reviewed and more recent and extensive data sources were identified. Sensitivity analysis was used to determine which inputs should be prioritized for updating. Data regarding the cigarette emission rate was found to be the most important. SHEDS-PM does not currently account for in-vehicle ETS exposure; however, in-vehicle ETS-related PM2.5 levels can exceed those in residential microenvironments by a factor of 10 or more. Therefore, a mass-balance based methodology for estimating in-vehicle ETS PM2.5 concentration is evaluated. Recommendations are made regarding updating of input data and algorithms related to ETS exposure in the SHEDS-PM model.

  2. Use of probiotics to reduce faecal shedding of Shiga toxin-producing Escherichia coli in sheep. (United States)

    Rigobelo, E E C; Karapetkov, N; Maestá, S A; Avila, F A; McIntosh, D


    Shiga toxin-producing Escherichia coli (STEC) are zoonotic, foodborne pathogens of humans. Ruminants, including sheep, are the primary reservoirs of STEC and there is a need to develop intervention strategies to reduce the entry of STEC into the food chain. The initiation of the majority of bacterial, enteric infections involves colonisation of the gut mucosal surface by the pathogen. However, probiotic bacteria can serve to decrease the severity of infection via a number of mechanisms including competition for receptors and nutrients, and/or the synthesis of organic acids and bacteriocins that create an environment unfavourable for pathogen development. The aim of the current study was to determine whether the administration of a probiotic mixture to sheep experimentally infected with a non-O157 STEC strain, carrying stx1, stx2 and eae genes, was able to decrease faecal shedding of the pathogen. The probiotic mixture contained Lactobacillus acidophilus, Lactobacillus helveticus, Lactobacillus bulgaricus, Lactobacillus lactis, Streptococcus thermophilus and Enterococcus faecium. The numbers of non-O157 STEC in faecal samples collected from sheep receiving daily doses of the probiotic mixture were significantly lower at the 3rd, 5th and 6th week post-inoculation when compared to the levels recorded in untreated animals. It was concluded that administration of the probiotic mixture reduced faecal shedding of non-O157 STEC in sheep, and holds potential as a pre-harvest intervention method to reduce transmission to humans.

  3. Passive secondary biological treatment systems reduce estrogens in dairy shed effluent. (United States)

    Gadd, Jennifer B; Northcott, Grant L; Tremblay, Louis A


    Steroid estrogens are found at high concentrations in untreated dairy shed effluents. Reduction of estrogenic activity and steroid estrogen concentrations was assessed in two systems used to treat dairy shed effluents: the two-pond system and the advanced pond system. Both include anaerobic and aerobic treatment stages. Samples of effluent were collected from the systems and analyzed for free estrogens, conjugated estrogens and total estrogenic activity using E-Screen assay. Both systems showed increases of up to 8000% in aqueous free estrogens and estrogenic activity after anaerobic treatment, followed by decreases after aerobic treatment (36-83%). The complete systems decreased total steroid estrogen concentrations by 50-100% and estrogen activity by 62-100%, with little difference between systems. Removal rates were lower in winter for both systems. Final effluents from the advanced pond system contained total estrogens at <15-1400 ng/L and estrogenic activity at 3.2-43 ng/L. Final effluent from the two-pond system contained total estrogens at <15-300 ng/L and estrogenic activity at 3.3-25 ng/L. At times the final effluent EEQs exceeded guideline values for protection of freshwater fish and suggest further treatment may be required.

  4. Enterocyte shedding and epithelial lining repair following ischemia of the human small intestine attenuate inflammation. (United States)

    Matthijsen, Robert A; Derikx, Joep P M; Kuipers, Dian; van Dam, Ronald M; Dejong, Cornelis H C; Buurman, Wim A


    Recently, we observed that small-intestinal ischemia and reperfusion was found to entail a rapid loss of apoptotic and necrotic cells. This study was conducted to investigate whether the observed shedding of ischemically damaged epithelial cells affects IR induced inflammation in the human small gut. Using a newly developed IR model of the human small intestine, the inflammatory response was studied on cellular, protein and mRNA level. Thirty patients were consecutively included. Part of the jejunum was subjected to 30 minutes of ischemia and variable reperfusion periods (mean reperfusion time 120 (+/-11) minutes). Ethical approval and informed consent were obtained. Increased plasma intestinal fatty acid binding protein (I-FABP) levels indicated loss in epithelial cell integrity in response to ischemia and reperfusion (pintestine, thirty minutes of ischemia followed by up to 4 hours of reperfusion, does not seem to lead to an explicit inflammatory response. This may be explained by a unique mechanism of shedding of damaged enterocytes, reported for the first time by our group.

  5. Comparison of Murine Cervicovaginal Infection by Chlamydial Strains: Identification of Extrusions Shed In vivo (United States)

    Shaw, Jennifer H.; Behar, Amanda R.; Snider, Timothy A.; Allen, Noah A.; Lutter, Erika I.


    Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infections (STIs) and preventable blindness. Untreated, asymptomatic infection as well as frequent re-infection are common and may drive pelvic inflammatory disease, ectopic pregnancy, and infertility. In vivo models of chlamydial infection continue to be instrumental in progress toward a vaccine and further elucidating the pathogenesis of this intracellular bacterium, however significant gaps in our understanding remain. Chlamydial host cell exit occurs via two mechanisms, lysis and extrusion, although the latter has yet to be reported in vivo and its biological role is unclear. The objective of this study was to investigate whether chlamydial extrusions are shed in vivo following infection with multiple strains of Chlamydia. We utilized an established C3H/HeJ murine cervicovaginal infection model with C. trachomatis serovars D and L2 and the Chlamydia muridarum strain MoPn to monitor the (i) time course of infection and mode of host cell exit, (ii) mucosal and systemic immune response to infection, and (iii) gross and histopathology following clearance of active infection. The key finding herein is the first identification of chlamydial extrusions shed from host cells in an in vivo model. Extrusions, a recently appreciated mode of host cell exit and potential means of dissemination, had been previously observed solely in vitro. The results of this study demonstrate that chlamydial extrusions exist in vivo and thus warrant further investigation to determine their role in chlamydial pathogenesis. PMID:28217555

  6. Platelet receptor expression and shedding: glycoprotein Ib-IX-V and glycoprotein VI. (United States)

    Gardiner, Elizabeth E; Andrews, Robert K


    Quantity, quality, and lifespan are 3 important factors in the physiology, pathology, and transfusion of human blood platelets. The aim of this review is to discuss the proteolytic regulation of key platelet-specific receptors, glycoprotein(GP)Ib and GPVI, involved in the function of platelets in hemostasis and thrombosis, and nonimmune or immune thrombocytopenia. The scope of the review encompasses the basic science of platelet receptor shedding, practical aspects related to laboratory analysis of platelet receptor expression/shedding, and clinical implications of using the proteolytic fragments as platelet-specific biomarkers in vivo in terms of platelet function and clearance. These topics can be relevant to platelet transfusion regarding both changes in platelet receptor expression occurring ex vivo during platelet storage and/or clinical use of platelets for transfusion. In this regard, quantitative analysis of platelet receptor profiles on blood samples from individuals could ultimately enable stratification of bleeding risk, discrimination between causes of thrombocytopenia due to impaired production vs enhanced clearance, and monitoring of response to treatment prior to change in platelet count.

  7. Changes in the Loop Current's Eddy Shedding in the Period 2001–2010

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    Fred M. Vukovich


    Full Text Available A major change in the Loop Current's eddy shedding was found in the decade 2001–2010. Sixteen (16 rings separated from the Loop Current in that decade, whereas in two previous decades, 11 rings separated in each decade. More than half the rings (i.e., 56% that separated from the Loop Current in the decade 2001–2010 had separation periods ≤8 months. In the period prior to 2001, only 26% of the rings had separation periods ≤8 months. Furthermore, the dataset average period for ring separation for the period prior to 2001, an average over a 29-year period, was about 11 months, and the dataset average Loop Current's westward tilt angle—a factor that indicates whether the Loop Current will soon shed an eddy or not—was about 16°. After the year 2000, the dataset average period for ring separation, an average over a 39-year period, decreased by about 1 month and was about 10 months. The average ring-separation period in the decade 2001–2010 was about 9 months. The dataset average of the Loop Current's westward tilt angle increased by about 5° in the period 1998–2008 and was about 20° in 2010. Potential causes for these changes are discussed.

  8. A comparative analysis on the shed vortices from the wake of finned, foam-wrapped cylinders (United States)

    Khashehchi, Morteza; Ashtiani Abdi, Iman; Hooman, Kamel


    The wake characteristics behind a finned and a foam-wrapped circular cylinder has been compared in a study (Khashehchi et al 2014 Exp. Therm. Fluid Sci. 52 328-38) done by the Authors. In this paper, the shed vortices from the wake of the same cylinders have been studied. Shedding in a bluff body has an important effect on increasing the pressure drop downstream of the object. Here, we have used particle image velocimetry to investigate the detached vortices from the wake behind a foam-wrapped and a finned cylinder. The standard case of cross-flow over a bare cylinder, i.e. no surface extension, has also been tested as a benchmark. The experiments have been performed for Reynolds numbers 2000 based on the mean air velocity and the cylinder’s outer diameter. To identify the features of each aforementioned case, linear stochastic estimation has been applied to the velocity fields. Results show that unlike the fin, adding foam to the cylinder surface increases the size of detached vortices and amplifies the core strength. Moreover, foam-wrapped cylinder in contrast to the finned one produces strong three-dimensionality. Interestingly, finned cylinder’s results show less three-dimensionality compared to the bare cylinder.

  9. Dominance induction of fruitlet shedding in Malus × domestica (L. Borkh: molecular changes associated with polar auxin transport

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    Velasco Riccardo


    Full Text Available Abstract Background Apple fruitlet abscission is induced by dominance, a process in which hormones such as auxin, cytokinins and strigolactone play a pivotal role. The response to these hormones is controlled by transcription regulators such as Aux/IAA and ARR, whereas auxin transport is controlled by influx and efflux carriers. Results Seven partial clones encoding auxin efflux carriers (MdPIN1_A, MdPIN1_B, MdPIN10_A, MdPIN10_B, MdPIN4, MdPIN7_A and MdPIN7_B, three encoding auxin influx carriers (MdLAX1, MdLAX2 and MdLAX3 and three encoding type A ARR cytokinin response regulators (MdARR3, MdARR4 and MdARR6 were isolated by the use of degenerate primers. The organization of the PIN multigene family in apple is closer to Medicago truncatula than to Arabidopsis thaliana. The genes are differentially expressed in diverse plant organs and at different developmental stages. MdPIN1 and MdPIN7 are largely more expressed than MdPIN10 and MdPIN4. During abscission, the transcription of these genes increased in the cortex whereas in the seed a sharp fall was observed. The expression of these genes was found to be at least partially controlled by ethylene and auxin. Conclusion The ethylene burst preceding abscission of fruitlets may be responsible for the decrease in transcript level of MDPIN1, MDARR5 and MDIAA3 in seed. This situation modulates the status of the fruitlet and its fate by hampering the PAT from the seeds down through the abscission zone (AZ and this brings about the shedding of the fruitlet.

  10. 基于双共振的涡街信号检测方法%A method based on dual-resonance to detect vortex shedding signals

    Institute of Scientific and Technical Information of China (English)

    郑俊; 林敏


    A coupled bistable system was composed of a controlled system and a control system by means of nonlinear coupling.The dual-resonance characteristics of the coupled bistable system under a controlling signal action were analyzed.A method based on dual-resonance to enhance stochastic resonance was proposed,and the method was applied to detect vortex shedding signals.Numerical simulations and experimental results showed that with a controlling signal added to the control system,adjusting signal frequency can excite resonances of the system to enhance stochastic resonance of the controlled system substantially;the output power spectral values of the system at the eigen-frequencies increase obviously,and weak signals of vortex shedding submerged in noise can be detected effectively.%耦合双稳系统由控制系统和被控系统经非线性方式耦合而成。分析了控制信号作用下耦合双稳系统的双共振特性,提出了基于双共振的随机共振增强方法,并将该方法应用于涡街流量信号的检测。数值仿真和实验结果表明,改变控制信号的频率可在控制系统中产生共振,进而增强被控系统中的随机共振,系统输出功率谱在特征频率处的谱值显著提高,从而准确检测出噪声背景中的微弱涡街信号。

  11. Shedding of soluble glycoprotein 1 detected during acute Lassa virus infection in human subjects

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    Momoh Mambu


    Full Text Available Abstract Background Lassa hemorrhagic fever (LHF is a neglected tropical disease with significant impact on the health care system, society, and economy of Western and Central African nations where it is endemic. With a high rate of infection that may lead to morbidity and mortality, understanding how the virus interacts with the host's immune system is of great importance for generating vaccines and therapeutics. Previous work by our group identified a soluble isoform of the Lassa virus (LASV GP1 (sGP1 in vitro resulting from the expression of the glycoprotein complex (GPC gene 12. Though no work has directly been done to demonstrate the function of this soluble isoform in arenaviral infections, evidence points to immunomodulatory effects against the host's immune system mediated by a secreted glycoprotein component in filoviruses, another class of hemorrhagic fever-causing viruses. A significant fraction of shed glycoprotein isoforms during viral infection and biogenesis may attenuate the host's inflammatory response, thereby enhancing viral replication and tissue damage. Such shed glycoprotein mediated effects were previously reported for Ebola virus (EBOV, a filovirus that also causes hemorrhagic fever with nearly 90% fatality rates 345. The identification of an analogous phenomenon in vivo could establish a new correlate of LHF infection leading to the development of sensitive diagnostics targeting the earliest molecular events of the disease. Additionally, the reversal of potentially untoward immunomodulatory functions mediated by sGP1 could potentiate the development of novel therapeutic intervention. To this end, we investigated the presence of sGP1 in the serum of suspected LASV patients admitted to the Kenema Government Hospital (KGH Lassa Fever Ward (LFW, in Kenema, Sierra Leone that tested positive for viral antigen or displayed classical signs of Lassa fever. Results It is reasonable to expect that a narrow window exists for

  12. A mouse model of pathological small intestinal epithelial cell apoptosis and shedding induced by systemic administration of lipopolysaccharide

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    Jonathan M. Williams


    The gut barrier, composed of a single layer of intestinal epithelial cells (IECs held together by tight junctions, prevents the entrance of harmful microorganisms, antigens and toxins from the gut lumen into the blood. Small intestinal homeostasis is normally maintained by the rate of shedding of senescent enterocytes from the villus tip exactly matching the rate of generation of new cells in the crypt. However, in various localized and systemic inflammatory conditions, intestinal homeostasis can be disturbed as a result of increased IEC shedding. Such pathological IEC shedding can cause transient gaps to develop in the epithelial barrier and result in increased intestinal permeability. Although pathological IEC shedding has been implicated in the pathogenesis of conditions such as inflammatory bowel disease, our understanding of the underlying mechanisms remains limited. We have therefore developed a murine model to study this phenomenon, because IEC shedding in this species is morphologically analogous to humans. IEC shedding was induced by systemic lipopolysaccharide (LPS administration in wild-type C57BL/6 mice, and in mice deficient in TNF-receptor 1 (Tnfr1−/−, Tnfr2 (Tnfr2−/−, nuclear factor kappa B1 (Nfκb1−/− or Nfĸb2 (Nfĸb2−/−. Apoptosis and cell shedding was quantified using immunohistochemistry for active caspase-3, and gut-to-circulation permeability was assessed by measuring plasma fluorescence following fluorescein-isothiocyanate–dextran gavage. LPS, at doses ≥0.125 mg/kg body weight, induced rapid villus IEC apoptosis, with peak cell shedding occurring at 1.5 hours after treatment. This coincided with significant villus shortening, fluid exudation into the gut lumen and diarrhea. A significant increase in gut-to-circulation permeability was observed at 5 hours. TNFR1 was essential for LPS-induced IEC apoptosis and shedding, and the fate of the IECs was also dependent on NFκB, with signaling via NFκB1 favoring cell survival and

  13. Juxtamembrane shedding of Plasmodium falciparum AMA1 is sequence independent and essential, and helps evade invasion-inhibitory antibodies.

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    Anna Olivieri


    Full Text Available The malarial life cycle involves repeated rounds of intraerythrocytic replication interspersed by host cell rupture which releases merozoites that rapidly invade fresh erythrocytes. Apical membrane antigen-1 (AMA1 is a merozoite protein that plays a critical role in invasion. Antibodies against AMA1 prevent invasion and can protect against malaria in vivo, so AMA1 is of interest as a malaria vaccine candidate. AMA1 is efficiently shed from the invading parasite surface, predominantly through juxtamembrane cleavage by a membrane-bound protease called SUB2, but also by limited intramembrane cleavage. We have investigated the structural requirements for shedding of Plasmodium falciparum AMA1 (PfAMA1, and the consequences of its inhibition. Mutagenesis of the intramembrane cleavage site by targeted homologous recombination abolished intramembrane cleavage with no effect on parasite viability in vitro. Examination of PfSUB2-mediated shedding of episomally-expressed PfAMA1 revealed that the position of cleavage is determined primarily by its distance from the parasite membrane. Certain mutations at the PfSUB2 cleavage site block shedding, and parasites expressing these non-cleavable forms of PfAMA1 on a background of expression of the wild type gene invade and replicate normally in vitro. The non-cleavable PfAMA1 is also functional in invasion. However - in contrast to the intramembrane cleavage site - mutations that block PfSUB2-mediated shedding could not be stably introduced into the genomic pfama1 locus, indicating that some shedding of PfAMA1 by PfSUB2 is essential. Remarkably, parasites expressing shedding-resistant forms of PfAMA1 exhibit enhanced sensitivity to antibody-mediated inhibition of invasion. Drugs that inhibit PfSUB2 activity should block parasite replication and may also enhance the efficacy of vaccines based on AMA1 and other merozoite surface proteins.

  14. Juxtamembrane shedding of Plasmodium falciparum AMA1 is sequence independent and essential, and helps evade invasion-inhibitory antibodies. (United States)

    Olivieri, Anna; Collins, Christine R; Hackett, Fiona; Withers-Martinez, Chrislaine; Marshall, Joshua; Flynn, Helen R; Skehel, J Mark; Blackman, Michael J


    The malarial life cycle involves repeated rounds of intraerythrocytic replication interspersed by host cell rupture which releases merozoites that rapidly invade fresh erythrocytes. Apical membrane antigen-1 (AMA1) is a merozoite protein that plays a critical role in invasion. Antibodies against AMA1 prevent invasion and can protect against malaria in vivo, so AMA1 is of interest as a malaria vaccine candidate. AMA1 is efficiently shed from the invading parasite surface, predominantly through juxtamembrane cleavage by a membrane-bound protease called SUB2, but also by limited intramembrane cleavage. We have investigated the structural requirements for shedding of Plasmodium falciparum AMA1 (PfAMA1), and the consequences of its inhibition. Mutagenesis of the intramembrane cleavage site by targeted homologous recombination abolished intramembrane cleavage with no effect on parasite viability in vitro. Examination of PfSUB2-mediated shedding of episomally-expressed PfAMA1 revealed that the position of cleavage is determined primarily by its distance from the parasite membrane. Certain mutations at the PfSUB2 cleavage site block shedding, and parasites expressing these non-cleavable forms of PfAMA1 on a background of expression of the wild type gene invade and replicate normally in vitro. The non-cleavable PfAMA1 is also functional in invasion. However - in contrast to the intramembrane cleavage site - mutations that block PfSUB2-mediated shedding could not be stably introduced into the genomic pfama1 locus, indicating that some shedding of PfAMA1 by PfSUB2 is essential. Remarkably, parasites expressing shedding-resistant forms of PfAMA1 exhibit enhanced sensitivity to antibody-mediated inhibition of invasion. Drugs that inhibit PfSUB2 activity should block parasite replication and may also enhance the efficacy of vaccines based on AMA1 and other merozoite surface proteins.

  15. Zinc Up-Regulates Insulin Secretion from β Cell-Like Cells Derived from Stem Cells from Human Exfoliated Deciduous Tooth (SHED) (United States)

    Kim, Gyuyoup; Shin, Ki-Hyuk; Pae, Eung-Kwon


    Stem cells from human exfoliated deciduous tooth (SHED) offer several advantages over other stem cell sources. Using SHED, we examined the roles of zinc and the zinc uptake transporter ZIP8 (Zrt- and irt-like protein 8) while inducing SHED into insulin secreting β cell-like stem cells (i.e., SHED-β cells). We observed that ZIP8 expression increased as SHED differentiated into SHED-β cells, and that zinc supplementation at day 10 increased the levels of most pancreatic β cell markers—particularly Insulin and glucose transporter 2 (GLUT2). We confirmed that SHED-β cells produce insulin successfully. In addition, we note that zinc supplementation significantly increases insulin secretion with a significant elevation of ZIP8 transporters in SHED-β cells. We conclude that SHED can be converted into insulin-secreting β cell-like cells as zinc concentration in the cytosol is elevated. Insulin production by SHED-β cells can be regulated via modulation of zinc concentration in the media as ZIP8 expression in the SHED-β cells increases. PMID:27983594

  16. Zinc Up-Regulates Insulin Secretion from β Cell-Like Cells Derived from Stem Cells from Human Exfoliated Deciduous Tooth (SHED

    Directory of Open Access Journals (Sweden)

    Gyuyoup Kim


    Full Text Available Stem cells from human exfoliated deciduous tooth (SHED offer several advantages over other stem cell sources. Using SHED, we examined the roles of zinc and the zinc uptake transporter ZIP8 (Zrt- and irt-like protein 8 while inducing SHED into insulin secreting β cell-like stem cells (i.e., SHED-β cells. We observed that ZIP8 expression increased as SHED differentiated into SHED-β cells, and that zinc supplementation at day 10 increased the levels of most pancreatic β cell markers—particularly Insulin and glucose transporter 2 (GLUT2. We confirmed that SHED-β cells produce insulin successfully. In addition, we note that zinc supplementation significantly increases insulin secretion with a significant elevation of ZIP8 transporters in SHED-β cells. We conclude that SHED can be converted into insulin-secreting β cell-like cells as zinc concentration in the cytosol is elevated. Insulin production by SHED-β cells can be regulated via modulation of zinc concentration in the media as ZIP8 expression in the SHED-β cells increases.

  17. Use of Booster Sheds to Improve Performance of 800 kV Multicone Type Insulators Under Heavy Rain%Use of Booster Sheds to Improve Performance of 800 kV Multicone Type Insulators Under Heavy Rain

    Institute of Scientific and Technical Information of China (English)

    Orsino Oliveira Filho; Jose Antonio Cardoso; Darcy Ramalho de Mello; Rogerio Magalhges de Azevedo; Sylvia G Carvalho


    Studies based on AC high voltage tests have been done at Cepel to investigate the performance of 800 kV bushar insulators under heavy wetting conditions. Insulators were tested which are now used on site and also with dif- ferent configurations of booster sheds. Images recorded by ultra-violet (UV) camera were used to help the investiga- tions on the effectiveness of booster sheds. By comparing UV images of the insulator being stressed with high voltage under heavy artificial rain, with and without booster sheds, it was possible to observe how significant the reduction on the flashover formation process was when booster sheds were used. The effectiveness of booster sheds was also quan- tified by determining the disruptive discharge of the insulator with and without them. The results of these studies can also be considered as contribution to national and international standard technical committees to improving the standardized procedure for tests on ultra high voltage (UHV) insulators under heavy rain. Subjects such as the clear definition of relevant UHV test procedure and test arrangements, including the use of UV camera, have to be taken into account.

  18. Effect of Organic Acids on Salmonella Shedding and Colonization in Pigs on a Farm with High Salmonella Prevalence. (United States)

    Rasschaert, G; Michiels, J; Tagliabue, M; Missotten, J; De Smet, S; Heyndrickx, M


    This study builds on the results of a previous study in which six commercial feed products based on organic acids were evaluated with respect to Salmonella contamination of piglets in an artificially challenged seeder model. In the present study, the efficacy of three of these commercial products was assessed for Salmonella reduction in fattening pigs on one closed farm with a natural high Salmonella prevalence. In each of four fattening compartments, one of the following feed treatments was evaluated during two consecutive fattening rounds: (i) butyric acid (active ingredients at 1.3 kg/ton of feed; supplement A1), (ii) a combination of short-chain organic acids (mixture of free acids and salts) and natural extracts (2.92 kg/ton; supplement A4), (iii) a 1:1 blend of two commercial products consisting of medium-chain fatty acids, lactic acid, and oregano oil (3.71 kg/ton; supplement A5+A6), and (iv) a control feed. On the farm, the Salmonella status of the fattening pigs was evaluated by taking fecal samples twice during the fattening period. At the slaughterhouse, samples were collected from the cecal contents and the ileocecal lymph nodes. Salmonella isolates were serotyped and characterized by pulsed-field gel electrophoresis. This farm had a particularly high number of pigs shedding Salmonella with a wide variety of sero- and pulsotypes. Only the feed blend based on the medium-chain fatty acids was able to significantly reduce Salmonella prevalence both on the farm and at the slaughterhouse. With this combined supplement, the Salmonella reduction in the feces at slaughter age, in cecal contents at slaughter, and the lymph nodes was 50, 36, and 67%, respectively, compared with the control animals. This promising finding calls for further investigation including cost-efficiency of this combined feed product and its effect on the animals.

  19. Zika virus shedding in human milk during lactation: an unlikely source of infection?

    Directory of Open Access Journals (Sweden)

    Marta G. Cavalcanti


    Full Text Available Zika virus (ZIKV transmission through non-mosquito-dependent routes has become increasingly important since reports of sexual transmission. Breastfeeding is a potential means of ZIKV transmission, but data on this remain limited. The cases of four mothers with laboratory-proven infections are reported. No disease evolved in three of the breastfed babies despite detectable maternal viremia and viruria, the presence of viral RNA shedding, and the isolation of infective particles in one milk sample. Fever and rash in one infant of a ZIKV-infected mother proved to be related to chikungunya virus infection. The results suggest that the presence of infective particles in breast milk may not be sufficient for the efficient perinatal transmission of ZIKV.

  20. Vibration frequency and lock-in bandwidth of tensioned, flexible cylinders experiencing vortex shedding (United States)

    Lee, L.; Allen, D.


    In-water vortex-induced vibration (VIV) tests of top-tensioned, flexible cylindrical structures were conducted at Shell Westhollow Technology Center current tank. These tests revealed that the top tension and structural stiffness (both lateral and axial) can have a significant impact on vibration frequencies. During lock-in between the vortex-shedding frequency and the structure's natural frequency, the increase of the vibration frequency with flow speeds is strongly related to the rise of the axial tension. After an initial abrupt rise, the vibration frequency of a bending-stiffness-dominated structure only increased slightly during lock-in. Alternative explanations are provided on why the vibration frequency does not rise significantly but there can still exist a broad lock-in band, and why a more massive structure has a narrower lock-in bandwidth.

  1. Shedding Light on Eco-Innovation in Tourism: A Critical Analysis

    Directory of Open Access Journals (Sweden)

    Maria-del-Mar Alonso-Almeida


    Full Text Available The recent global increase in the competitiveness of tourism has made the implementation of eco-innovations a differentiating element among both the destinations and companies in the sector, with quality management and contribution to sustainable development being increasingly valued. However, the eco-innovations that have been developed and implemented in tourist industries have rarely been studied. In this study, the eco-innovations that have been developed and implemented by 57 tourism businesses worldwide are analysed. The identified eco-innovations are classified by using different qualitative methodologies. The obtained results shed light on the limited development of eco-innovations in the tourism industry and the industry focuses mainly on product eco-innovations. Several examples by the tourist sub-industry and types of eco-innovation are analysed. Furthermore, this study provides practical information about measures that both businesses and governmental organisations can adopt to promote eco-innovation in the sector.

  2. Quantitative assessment of faecal shedding of β-lactam-resistant Escherichia coli and enterococci in dogs

    DEFF Research Database (Denmark)

    Gongora, Carmen Espinosa; Shah, Syed Qaswar Ali; Jessen, Lisbeth Rem


    Quantitative data on faecal shedding of antimicrobial resistant bacteria are crucial to assess the risk of transmission from dogs to other animals as well as humans. In this study we investigated prevalence and concentrations of β-lactam-resistant Escherichia coli and enterococci in the faeces...... of 108 dogs presenting at a veterinary hospital in Denmark. The dogs had not been treated with antimicrobials for 4 weeks prior to the study. Total E. coli and enterococci were quantified by counts on MacConkey and Slanetz-Bartley, respectively. Resistant E. coli and enterococci were counted on the same...... media containing relevant antibiotic concentrations, followed by species identification using MALDI-TOF. Ampicillin- and cefotaxime-resistant E. coli were detected in 40% and 8% of the dogs, respectively, whereas approximately 15% carried ampicillin-resistant enterococci, mainly Enterococcus faecium...

  3. Prediction models for 90Sr in shed deciduous teeth and infant bone

    DEFF Research Database (Denmark)

    Aarkrog, Asker


    Shed deciduous teeth were collected in 1966-69 in Denmark, the Faroes and Greenland from children born in the period 1953-63. 235 samples of crowns were analysed for 90Sr. The 90Sr levels in deciduous tooth crowns were related to the fall-out rate and the accumulated fall-out. The tooth levels...... in children born in 1950-62 could be described with the same equation as the 90Sr bone levels in 1-yr-old infants born in 1962-68. The prediction models for 90Sr in teeth and bones showed that for given amount of fall-out the Faroese levels became nearly twice as high as the Danish. The maximum teeth and bone...... levels were found in children born in 1963, where the Faroese level was estimated from the prediction model to be 24 pCi 90Sr/g Ca....

  4. HIV-1 DNA shedding in genital ulcers and its associated risk factors in Pune, India. (United States)

    Gadkari, D A; Quinn, T C; Gangakhedkar, R R; Mehendale, S M; Divekar, A D; Risbud, A R; Chan-Tack, K; Shepherd, M; Gaydos, C; Bollinger, R C


    HIV infection status was determined in 302 consecutive patients with genital ulcer disease (GUD) presenting to two sexually transmitted disease (STD) clinics in Pune, India. Of the 71 (24%) individuals with HIV infection, 67 (94%) were HIV antibody-positive, and 4 (6%) were HIV antibody-negative but p24 antigen-positive at the time of presentation. HIV-1 DNA was detected in 24 (34%) specimens. The genital ulcers of all four acutely infected p24-antigenemic subjects were HIV-1 DNA-positive by polymerase chain reaction (PCR) assay, compared with 20 of 67 (30%) seropositive patients (p = .01). Presence of chancroid, GUD symptoms for > 10 days, and concurrent diagnosis of cervicitis or urethritis were significantly associated risk factors for HIV-1 DNA shedding in ulcers. Early GUD diagnosis and aggressive treatment of HIV-infected patients may significantly reduce secondary transmission of HIV to other sex partners.

  5. Clausius’ Disgregation: A Conceptual Relic that Sheds Light on the Second Law

    Directory of Open Access Journals (Sweden)

    Emilio Marco Pellegrino


    Full Text Available The present work analyzes the cognitive process that led Clausius towards the translation of the Second Law of Thermodynamics into mathematical expressions. We show that Clausius’ original formal expression of the Second Law was achieved by making extensive use of the concept of disgregation, a quantity which has subsequently disappeared from the thermodynamic language. Our analysis demonstrates that disgregation stands as a crucial logical step of such process and sheds light on the comprehension of such fundamental relation. The introduction of entropy—which occurred three years after the first formalization of the Second Law—was aimed at making the Second Law exploitable in practical contexts. The reasons for the disappearance of disgregation, as well as of other “pre-modern” quantities, from the thermodynamics language are discussed.

  6. Risk factors for fecal shedding of Salmonella from horses in a veterinary teaching hospital. (United States)

    Alinovi, Catherine A; Ward, Michael P; Couëtil, Laurent L; Wu, Ching Ching


    Identification of risk factors for horses shedding Salmonella in their feces helps identify patients at-risk of infection and protect the overall population through heightened biosecurity. Fecal samples from 230 hospitalized horses were cultured for Salmonella spp. Historical data were collected on 21 putative risk factors and assessed for association with the risk of a horse being culture positive using forwards stepwise logistic regression. Salmonella was isolated from 13 horses--most commonly from either the first (n=5) or second (n=4) sample collected. Only presenting complaint (confounded by age, breed and gender) was significantly (P < or = 0.05) associated with positive Salmonella-culture results. Analysis of residuals showed that the model was robust, but individual risk-factor estimates were changed by removal of outliers. Overall, presenting complaint (for example, lower-respiratory-tract disease) was the most important indicator of culture status.

  7. Shedding light on the dark side of identity: Introduction to the special issue. (United States)

    Crocetti, Elisabetta; Beyers, Wim; Çok, Figen


    The aim of this special issue is to shed light in the dark side of identity formation in adolescence and emerging adulthood, that is, to provide some understanding in what exactly can go wrong in identity development. After summarizing the recent developments in identity development literature, in this introduction the main findings of all thirteen empirical papers are summarized into three overarching themes: (1) lack of identity integration as a risk factor, (2) reconsideration of commitment as a sign of identity uncertainty, and (3) ruminative exploration as another risk factor undermining healthy identity development. Finally, given that all papers in this special issue are based on conference presentations at the 14th Biennial Conference of the European Association for Research on Adolescence (EARA), some more information on that conference is included in this introduction.

  8. Unusual modes of reproduction in social insects: shedding light on the evolutionary paradox of sex. (United States)

    Wenseleers, Tom; Van Oystaeyen, Annette


    The study of alternative genetic systems and mixed modes of reproduction, whereby sexual and asexual reproduction is combined within the same lifecycle, is of fundamental importance as they may shed light on classical evolutionary issues, such as the paradox of sex. Recently, several such cases were discovered in social insects. A closer examination of these systems has revealed many amazing facts, including the mixed use of asexual and sexual reproduction for the production of new queens and workers, males that can clone themselves and the routine use of incest without deleterious genetic consequences. In addition, in several species, remarkable cases of asexually reproducing socially parasitic worker lineages have been discovered. The study of these unusual systems promises to provide insight into many basic evolutionary questions, including the maintenance of sex, the expression of sexual conflict and kin conflict and the evolution of cheating in asexual lineages.

  9. Determining Influenza Virus Shedding at Different Time Points in Madin-Darby Canine Kidney Cell Line

    Directory of Open Access Journals (Sweden)

    Asghar Abdoli


    Full Text Available Objective: Monitoring of influenza virus shedding and optimization of multiplicities of infection (MOI is important in the investigation of a virus one step growth cycle and for obtaining a high yield of virus in vaccine development and conventional basic diagnostic methods. However, eluted infectious viruses may still be present immediately after virus inoculation and when cells are washed following virus cultivation which may lead to a false positive virus infectivity assay.Materials and Methods: In this experimental study, we investigated influenza virus progeny production in Madin-Darby canine kidney (MDCK cells with five different MOI at determined time points. The results were analyzed by end point titration tests and immunofluorescence assay.Results: Higher titers of eluted virus were observed following a high MOI inoculation of virus in cell culture. Most probably, this was the result of sialic acid residues from viral hemagglutin in proteins that were cleaved by neuraminidase glycoproteins on the surface of the influenza virus, which promoted viral spread from the host cell to the culture supernatant or during endocytosis, where viruses recycle to the cell surface by recycling endosomes which culminated in virus shedding without replication.Conclusion: We demonstrated that the pattern of influenza virus progeny production was dose-dependent and not uniform. This production was influenced by several factors, particularly MOI. Understanding the exact features of viral particle propagation has a major impact in producing high virus yields in the development of vaccines. Use of lower MOI (0.01 could result in accurate, precise quantitative assays in virus diagnosis and titration methods.

  10. Enterocyte shedding and epithelial lining repair following ischemia of the human small intestine attenuate inflammation.

    Directory of Open Access Journals (Sweden)

    Robert A Matthijsen

    Full Text Available BACKGROUND: Recently, we observed that small-intestinal ischemia and reperfusion was found to entail a rapid loss of apoptotic and necrotic cells. This study was conducted to investigate whether the observed shedding of ischemically damaged epithelial cells affects IR induced inflammation in the human small gut. METHODS AND FINDINGS: Using a newly developed IR model of the human small intestine, the inflammatory response was studied on cellular, protein and mRNA level. Thirty patients were consecutively included. Part of the jejunum was subjected to 30 minutes of ischemia and variable reperfusion periods (mean reperfusion time 120 (+/-11 minutes. Ethical approval and informed consent were obtained. Increased plasma intestinal fatty acid binding protein (I-FABP levels indicated loss in epithelial cell integrity in response to ischemia and reperfusion (p<0.001 vs healthy. HIF-1alpha gene expression doubled (p = 0.02 and C3 gene expression increased 4-fold (p = 0.01 over the course of IR. Gut barrier failure, assessed as LPS concentration in small bowel venous effluent blood, was not observed (p = 0.18. Additionally, mRNA expression of HO-1, IL-6, IL-8 did not alter. No increased expression of endothelial adhesion molecules, TNFalpha release, increased numbers of inflammatory cells (p = 0.71 or complement activation, assessed as activated C3 (p = 0.14, were detected in the reperfused tissue. CONCLUSIONS: In the human small intestine, thirty minutes of ischemia followed by up to 4 hours of reperfusion, does not seem to lead to an explicit inflammatory response. This may be explained by a unique mechanism of shedding of damaged enterocytes, reported for the first time by our group.

  11. Effect of acute Plasmodium falciparum malaria on reactivation and shedding of the eight human herpes viruses.

    Directory of Open Access Journals (Sweden)

    Arnaud Chêne

    Full Text Available Human herpes viruses (HHVs are widely distributed pathogens. In immuno-competent individuals their clinical outcomes are generally benign but in immuno-compromised hosts, primary infection or extensive viral reactivation can lead to critical diseases. Plasmodium falciparum malaria profoundly affects the host immune system. In this retrospective study, we evaluated the direct effect of acute P. falciparum infection on reactivation and shedding of all known human herpes viruses (HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8. We monitored their presence by real time PCR in plasma and saliva of Ugandan children with malaria at the day of admission to the hospital (day-0 and 14 days later (after treatment, or in children with mild infections unrelated to malaria. For each child screened in this study, at least one type of HHV was detected in the saliva. HHV-7 and HHV-6 were detected in more than 70% of the samples and CMV in approximately half. HSV-1, HSV-2, VZV and HHV-8 were detected at lower frequency. During salivary shedding the highest mean viral load was observed for HSV-1 followed by EBV, HHV-7, HHV-6, CMV and HHV-8. After anti-malarial treatment the salivary HSV-1 levels were profoundly diminished or totally cleared. Similarly, four children with malaria had high levels of circulating EBV at day-0, levels that were cleared after anti-malarial treatment confirming the association between P. falciparum infection and EBV reactivation. This study shows that acute P. falciparum infection can contribute to EBV reactivation in the blood and HSV-1 reactivation in the oral cavity. Taken together our results call for further studies investigating the potential clinical implications of HHVs reactivation in children suffering from malaria.

  12. Fecal shedding of thermophilic Campylobacter in a dairy herd producing raw milk for direct human consumption. (United States)

    Merialdi, Giuseppe; Giacometti, Federica; Bardasi, Lia; Stancampiano, Laura; Taddei, Roberta; Serratore, Patrizia; Serraino, Andrea


    Factors affecting the fecal shedding of thermophilic Campylobacter in Italian dairy farms were investigated in a 12-month longitudinal study performed on a dairy farm authorized to sell raw milk in Italy. Fifty animals were randomly selected from 140 adult and young animals, and fecal samples were collected six times at 2-month intervals. At each sampling time, three trough water samples and two trough feed samples also were collected for both adult and young animals. Samples were analyzed with real-time PCR assay and culture examination. Overall, 33 samples (9.7%) were positive for thermophilic Campylobacter by real-time PCR: 26 (9.2%) of 280 fecal samples, 6 (16.6%) of 36 water samples, and 1 (4.2%) of 24 feed samples. Campylobacter jejuni was isolated from 6 of 280 samples; no other Campylobacter species was isolated. A higher (but not significantly) number of positive fecal samples were found in younger animals (11.33 versus 6.92% of adult animals), and a significantly higher number of positive water samples were collected from the water troughs of young animals. A distinct temporal trend was observed during the study period for both cows and calves, with two prevalence peaks between November and December and between May and July. Several factors such as calving, housing practices, herd size, management practices forcing together a higher number of animals, and variations in feed or water sources (previously reported as a cause of temporal variation in different farming conditions) were excluded as the cause of the two seasonal peaks in this study. The factors affecting the seasonality of Campylobacter shedding in the dairy herds remain unclear and warrant further investigation. The results of the present study indicate that special attention should be paid to farm hygiene management on farms authorized to produce and sell raw milk, with increased surveillance by the authorities at certain times of the year.

  13. 高岭棚洞结构设计%Structure design of Gaoling shed-tunnel

    Institute of Scientific and Technical Information of China (English)

    王文华; 赵文丁; 刘义河


    In order to protect the slope and natural environment along mountain side at the Gaoling section of Tumen-Huichun highway, a combination of anchor bar support and shed-tunnel is designed.Thus it can protect the ecological environment and maintain the stability of the mountain slope.Numerical simulations on plane strain at the most disadvantageous position show that the structural system is rational, the deformation and stress of the structure satisfies the requirements of safety standard.The design uses the structural style of shed-tunnel and takes the measures for waterproof and drainage, which are suitable for the seasonal freezing region.The design for this project provides a useful experience for the same structure at a seasonal freezing region.%为保护图们至珲春高速公路高岭傍山段的边坡和自然环境,将傍山边坡的锚喷支护与棚洞结构有机结合起来,从而最大限度地保护生态环境并保持山体稳定,避免由于大开挖引起的边坡或山体不稳定而产生的落石、滑坡滑塌等灾害发生.最不利位置处的平面应变弹性数值模拟分析表明:该种结构体系是合理的,其变形与受力满足相关规范要求.该结构设计采用了适合季冻区的傍山棚洞结构型式和防、排水措施,对季冻区此类结构的建设具有一定的参考价值和指导意义.

  14. Fluvial transport potential of shed and root-bearing dinosaur teeth from the late Jurassic Morrison Formation. (United States)

    Peterson, Joseph E; Coenen, Jason J; Noto, Christopher R


    Shed dinosaur teeth are commonly collected microvertebrate remains that have been used for interpretations of dinosaur feeding behaviors, paleoecology, and population studies. However, such interpretations may be biased by taphonomic processes such as fluvial sorting influenced by tooth shape: shed teeth, removed from the skull during life, and teeth possessing roots, removed from the skull after death. As such, teeth may behave differently in fluvial systems due to their differences in shape. In order to determine the influence of fluvial processes on the preservation and distribution of shed and root-bearing dinosaur teeth, the hydrodynamic behaviors of high-density urethane resin casts of shed and root-bearing Allosaurus and Camarasaurus teeth were experimentally tested for relative transport distances at increasing flow velocities in an artificial fluviatile environment. Results show that tooth cast specimens exhibited comparable patterns of transport at lower velocities, though the shed Camarasaurus teeth transported considerably farther in medium to higher flow velocities. Two-Way ANOVA tests indicate significant differences in the mean transport distances of tooth casts oriented perpendicular to flow (p dinosaur population dynamics, paleoecology, and feeding behaviors.

  15. A kinetic study of egg production, fecal egg output, and the rate of proglottid shedding in Hymenolepis nana. (United States)

    Kumazawa, H


    To estimate the rate of shedding of the proglottids during normal development of Hymenolepis nana in mice, 2 parameters, i.e., egg production and fecal egg output, have been determined. Changes in the number of eggs/proglottid along the length of the worm showed that, not only in vitro but also in vivo, a considerable number of eggs is discharged in situ while the proglottids are still attached to the worm. The in situ egg discharge, however, accounts only for a small fraction of the eggs appearing in the feces, and it can be neglected in the estimation of the shedding of proglottids. In H. nana the larva rotates 90 degrees in the egg during its development. This seems to occur in a short period, quite in concert within each proglottid. The transition point (the proglottid where 50% of the eggs have begun rotating) can be a useful landmark to estimate the rate of proglottid shedding. Egg numbers at the transition points approximate the genuine egg production, because in situ egg discharge mostly occurs only after the proglottids have passed the transition point. The 3 processes, i.e., the rotation of the larva in the egg, the in situ egg discharge, and the shedding of proglottids, usually occur in an orderly way. However, on day 20 of infection, just before the worms are lost (or destrobilated), shedding of proglottids seems to be inhibited, whereas the other processes are apparently normal.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Herpes simplex virus-2 genital tract shedding is not predictable over months or years in infected persons.

    Directory of Open Access Journals (Sweden)

    Varsha Dhankani


    Full Text Available Herpes simplex virus-2 (HSV-2 is a chronic reactivating infection that leads to recurrent shedding episodes in the genital tract. A minority of episodes are prolonged, and associated with development of painful ulcers. However, currently, available tools poorly predict viral trajectories and timing of reactivations in infected individuals. We employed principal components analysis (PCA and singular value decomposition (SVD to interpret HSV-2 genital tract shedding time series data, as well as simulation output from a stochastic spatial mathematical model. Empirical and model-derived, time-series data gathered over >30 days consists of multiple complex episodes that could not be reduced to a manageable number of descriptive features with PCA and SVD. However, single HSV-2 shedding episodes, even those with prolonged duration and complex morphologies consisting of multiple erratic peaks, were consistently described using a maximum of four dominant features. Modeled and clinical episodes had equivalent distributions of dominant features, implying similar dynamics in real and simulated episodes. We applied linear discriminant analysis (LDA to simulation output and identified that local immune cell density at the viral reactivation site had a predictive effect on episode duration, though longer term shedding suggested chaotic dynamics and could not be predicted based on spatial patterns of immune cell density. These findings suggest that HSV-2 shedding patterns within an individual are impossible to predict over weeks or months, and that even highly complex single HSV-2 episodes can only be partially predicted based on spatial distribution of immune cell density.

  17. Experimental feline enteric coronavirus infection reveals an aberrant infection pattern and shedding of mutants with impaired infectivity in enterocyte cultures (United States)

    Desmarets, Lowiese M. B.; Vermeulen, Ben L.; Theuns, Sebastiaan; Conceição-Neto, Nádia; Zeller, Mark; Roukaerts, Inge D. M.; Acar, Delphine D.; Olyslaegers, Dominique A. J.; Van Ranst, Marc; Matthijnssens, Jelle; Nauwynck, Hans J.


    Feline infectious peritonitis (FIP) results from mutations in the viral genome during a common feline enteric coronavirus (FECV) infection. Since many virological and immunological data on FECV infections are lacking, the present study investigated these missing links during experimental infection of three SPF cats with FECV strain UCD. Two cats showed mild clinical signs, faecal shedding of infectious virus from 4 dpi, a cell-associated viraemia at inconsistent time points from 5 dpi, a highly neutralising antibody response from 9 dpi, and no major abnormalities in leukocyte numbers. Faecal shedding lasted for 28–56 days, but virus shed during this stage was less infectious in enterocyte cultures and affected by mutations. Remarkably, in the other cat neither clinical signs nor acute shedding were seen, but virus was detected in blood cells from 3 dpi, and shedding of non-enterotropic, mutated viruses suddenly occurred from 14 dpi onwards. Neutralising antibodies arose from 21 dpi. Leukocyte numbers were not different compared to the other cats, except for the CD8+ regulatory T cells. These data indicate that FECV can infect immune cells even in the absence of intestinal replication and raise the hypothesis that the gradual adaptation to these cells can allow non-enterotropic mutants to arise. PMID:26822958

  18. An implementation of particle swarm optimization to evaluate optimal under-voltage load shedding in competitive electricity markets (United States)

    Hosseini-Bioki, M. M.; Rashidinejad, M.; Abdollahi, A.


    Load shedding is a crucial issue in power systems especially under restructured electricity environment. Market-driven load shedding in reregulated power systems associated with security as well as reliability is investigated in this paper. A technoeconomic multi-objective function is introduced to reveal an optimal load shedding scheme considering maximum social welfare. The proposed optimization problem includes maximum GENCOs and loads' profits as well as maximum loadability limit under normal and contingency conditions. Particle swarm optimization (PSO) as a heuristic optimization technique, is utilized to find an optimal load shedding scheme. In a market-driven structure, generators offer their bidding blocks while the dispatchable loads will bid their price-responsive demands. An independent system operator (ISO) derives a market clearing price (MCP) while rescheduling the amount of generating power in both pre-contingency and post-contingency conditions. The proposed methodology is developed on a 3-bus system and then is applied to a modified IEEE 30-bus test system. The obtained results show the effectiveness of the proposed methodology in implementing the optimal load shedding satisfying social welfare by maintaining voltage stability margin (VSM) through technoeconomic analyses.

  19. Bifidobacterium breve reduces apoptotic epithelial cell shedding in an exopolysaccharide and MyD88-dependent manner (United States)

    Hughes, K. R.; Harnisch, L. C.; Alcon-Giner, C.; Mitra, S.; Wright, C. J.; Ketskemety, J.


    Certain members of the microbiota genus Bifidobacterium are known to positively influence host well-being. Importantly, reduced bifidobacterial levels are associated with inflammatory bowel disease (IBD) patients, who also have impaired epithelial barrier function, including elevated rates of apoptotic extrusion of small intestinal epithelial cells (IECs) from villi—a process termed ‘cell shedding’. Using a mouse model of pathological cell shedding, we show that mice receiving Bifidobacterium breve UCC2003 exhibit significantly reduced rates of small IEC shedding. Bifidobacterial-induced protection appears to be mediated by a specific bifidobacterial surface exopolysaccharide and interactions with host MyD88 resulting in downregulation of intrinsic and extrinsic apoptotic responses to protect epithelial cells under highly inflammatory conditions. Our results reveal an important and previously undescribed role for B. breve, in positively modulating epithelial cell shedding outcomes via bacterial- and host-dependent factors, supporting the notion that manipulation of the microbiota affects intestinal disease outcomes. PMID:28123052

  20. Changes in surface glycosylation and glycocalyx shedding in Trichobilharzia regenti (Schistosomatidae) during the transformation of cercaria to schistosomulum (United States)

    Řimnáčová, Jana; Turjanicová, Libuše; Bulantová, Jana; Horák, Petr


    The invasive larvae (cercariae) of schistosomes penetrate the skin of their definitive hosts. During the invasion, they undergo dramatic ultrastructural and physiological transitions. These changes result in the development of the subsequent stage, schistosomulum, which migrates through host tissues in close contact with host’s immune system. One of the striking changes in the transforming cercariae is the shedding of their thick tegumental glycocalyx, which represents an immunoattractive structure; therefore its removal helps cercariae to avoid immune attack. A set of commercial fluorescently labeled lectin probes, their saccharide inhibitors and monoclonal antibodies against the trisaccharide Lewis-X antigen (LeX, CD15) were used to characterize changes in the surface saccharide composition of the neuropathogenic avian schistosome Trichobilharzia regenti during the transformation of cercariae to schistosomula, both in vitro and in vivo. The effect of various lectins on glycocalyx shedding was evaluated microscopically. The involvement of peptidases and their inhibitors on the shedding of glycocalyx was investigated using T. regenti recombinant cathepsin B2 and a set of peptidase inhibitors. The surface glycocalyx of T. regenti cercariae was rich in fucose and mannose/glucose residues. After the transformation of cercariae in vitro or in vivo within their specific duck host, reduction and vanishing of these epitopes was observed, and galactose/N-acetylgalactosamine emerged. The presence of LeX was not observed on the cercariae, but the antigen was gradually expressed from the anterior part of the body in the developing schistosomula. Some lectins which bind to the cercarial surface also induced secretion from the acetabular penetration glands. Seven lectins induced the shedding of glycocalyx by cercariae, among which five bound strongly to cercarial surface; the effect could be blocked by saccharide inhibitors. Mannose-binding protein, part of the lectin pathway

  1. Prevalence and risk factors for shedding of thermophilic Campylobacter in calves with and without diarrhea in Austrian dairy herds. (United States)

    Klein, D; Alispahic, M; Sofka, D; Iwersen, M; Drillich, M; Hilbert, F


    The objectives of this study were to evaluate the presence of thermophilic Campylobacter in feces of calves with and without diarrhea on dairy farms and to survey farm characteristics and management practices to define risk factors for the presence of Campylobacter. Fifty dairy farms were chosen based on the presence of calf diarrhea, and 50 farms in which calves were free from diarrhea served as a standard of comparison. In total, fecal samples were taken from 382 calves. Farm data and management practices were surveyed using a questionnaire on farm. Campylobacter were isolated from fecal samples and colonies were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis. Campylobacter spp., mainly Campylobacter jejuni (93% of isolated species), were detected on 33% of the farms and in 14.9% of the calves. Detection of Campylobacter did not differ between farms or between calves with and without diarrhea, although we found a tendency for calves suffering from diarrhea to shed Campylobacter more often. Calves may act as a reservoir of Campylobacter and may therefore lead to infections of other animals and humans. To define control strategies to reduce Campylobacter in calves, we identified on-farm risk factors. The presence of poultry on the farm, the time of cow-calf separation following birth, the use of an individual bucket for each calf, the feeding of waste milk, and the duration of individual housing were variables significantly associated with the appearance or absence of Campylobacter. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.


    Institute of Scientific and Technical Information of China (English)

    Zhang Ning; Li Guang-zheng; Huang Jian-chun


    The influence of buoyancy on vortex shedding from a heated square cylinder and its effects on the heat transfer of mixed convection were simulated.The flow equations, based on the velocity and the pressure, were solved along with the energy equation by a modified SIMPLER algorithm-the Quick Scheme and small Control Volume (QSCV) algorithm developed by the authors of the present paper.A set of optimized computational domain and artificial lateral boundary conditions were used along with the QSCV algorithm.Several cases were simulated for the Grashof numbers up to 1.8×105, the Reynolds numbers up to 500, and a range of angles between free stream velocity and gravity from 0 to 1.5π.In opposing flow, the results distinguish two different flow patterns: periodic flow for Gr<Grc and steady flow with attached twin vortices for Gr>Grc, and a precise correlation between Grc and Re expressed as Grc=0.00166(Re)2.97795 for Re up to 500 was firstly obtained.In cross flow, it could be seen that the Ri=Gr/Re2 plays a great role in the wake vortex patterns and the temperature fields.In aiding flow, it is found that the main flow currents cause a large expansion of the streamlines and isotherms in the direction normal to the free stream velocity.These changes in the wake vortex patterns and the temperature fields greatly modify the heat flux along the surface of the square cylinder and consequently, the heat transfer rate is strongly dependent upon the Reynolds numbers, the Grashof numbers, and the gravity direction.

  3. Distribution of Salmonella serovars in breeding, nursery, and grow-to-finish pigs, and risk factors for shedding in ten farrow-to-finish swine farms in Alberta and Saskatchewan. (United States)

    Wilkins, Wendy; Rajić, Andrijana; Waldner, Cheryl; McFall, Margaret; Chow, Eva; Muckle, Anne; Rosengren, Leigh


    The study objectives were to investigate Salmonella prevalence, serovar distribution, and risk factors for shedding in 10 purposively selected farrow-to-finish farms in Saskatchewan and Alberta. Pooled fecal samples from the breeding and grow-finish phases and individual fecal samples from breeding, nursery, and grow-finish pigs were cultured for Salmonella; serotyping of isolates was performed. Pig and pen characteristics were recorded for each pig and pen sampled.Overall, 407/1143 (36%) of samples were Salmonella positive; within-farm prevalence ranged from 1% to 79%. Sows, nursery, and grow-finish pigs accounted for 43%, 29%, and 28% of positive samples, respectively. More Salmonella were detected in pooled pen than individual pig samples (P finisher (OR 2.9, P finish farms and should be targeted in control efforts. The latter might also apply to the use of pelleted feed, which remains the most consistently reported significant risk factor for Salmonella shedding in pigs.

  4. Subclinical Reactivation and Shed of Infectious Varicella Zoster Virus in Saliva of Astronauts (United States)

    Cohrs, Randall J.; Mehta, Satish K.; Schmid, D. Scott; Gilden, Donald H.; Pierson, Duane L.


    We have previously detected VZV in healthy astronauts both during spaceflight and shortly after landing. Herein, we show that VZV shed in seropositive astronauts is infectious. A total of 40 saliva samples were obtained from each of the 3 astronauts. From each astronaut, 14 samples were taken 109 to 133 days before liftoff, 1 sample was taken every day during 12 days in space, and one sample was taken for 14 consecutive days beginning the second day after landing. Quantitative PCR was used to detect VZV DNA in saliva. None of 42 preflight saliva samples contained VZV DNA. VZV DNA was detected in saliva from 2 of 3 astronauts. In 1 astronaut, 6 of 12 samples obtained during space flight contained 120 to 2,500 copies of VZV DNA per ml; after landing, 1250 copies of VZV DNA were present on day 2, 45 copies on day 3, and 110 copies on day 5. All samples taken 6 to 15 days after touchdown were negative for VZV DNA. In the second astronaut, 5 of 12 samples obtained during space flight contained 18 to 650 copies of VZV DNA per ml; after landing, 560 copies of VZV DNA were present in saliva on day 2, 340 copies on day 4, 45 copies on day 5, and 23 copes on day 6. All samples taken 7 to 15 days after touchdown were negative for VZV DNA. Saliva taken 2 to 6 days after landing from all 3 astronauts was cultured on human fetal lung cells. After one subcultivation, a cytopathic effect developed in cultures inoculated with saliva from the two astronauts whose saliva contained VZV DNA. Both PCR and immunostaining identified the isolates to be VZV and not HSV-1. Importantly, the astronaut in whom no VZV was detected had a history of zoster 9 years earlier. It is possible that a boost in cell-mediated immunity to VZV which is known to develop after zoster protected him from subclinical reactivation. The genotype of the two VZV isolates was determined by VZV ORF22-based PCR/sequencing along with FRET-based PCR assays that target specific nucleotide polymorphisms. Both VZV isolates

  5. Vaccination of pigs with attenuated Lawsonia intracellularis induced acute phase protein responses and primed cell-mediated immunity without reduction in bacterial shedding after challenge

    DEFF Research Database (Denmark)

    Riber, Ulla; Heegaard, Peter M. H.; Hvass, Henriette Cordes;


    nomically important diseases in modern pig production worldwide. The Enterisol®Ileitis vaccine havebeen shown to reduce clinical disease and to increase weight gain, however, while the natural infectionwith L. intracellularis can provide complete protection against re-infection, this has not been...... achievedby this vaccine. We therefore undertook a detailed characterization of immune responses to L. intracel-lularis infection in vaccinated pigs (VAC) compared to previously infected pigs (RE) in order to pinpointimmunological determinants of protection.Results: The VAC pigs shed L. intracellularis...... response was diminished and L. intracellularis specific IgG responseswere delayed and reduced compared to non-vaccinated pigs. On the other hand L. intracellularis specificIFN- responses tended to develop faster in the VAC group compared to controls.Conclusion: Although vaccinated and non-vaccinated pigs...

  6. Mitochondrial genomes of the jungle crow Corvus macrorhynchos (Passeriformes: Corvidae) from shed feathers and a phylogenetic analysis of genus Corvus using mitochondrial protein-coding genes. (United States)

    Krzeminska, Urszula; Wilson, Robyn; Rahman, Sadequr; Song, Beng Kah; Seneviratne, Sampath; Gan, Han Ming; Austin, Christopher M


    The complete mitochondrial genomes of two jungle crows (Corvus macrorhynchos) were sequenced. DNA was extracted from tissue samples obtained from shed feathers collected in the field in Sri Lanka and sequenced using the Illumina MiSeq Personal Sequencer. Jungle crow mitogenomes have a structural organization typical of the genus Corvus and are 16,927 bp and 17,066 bp in length, both comprising 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal subunit genes, and a non-coding control region. In addition, we complement already available house crow (Corvus spelendens) mitogenome resources by sequencing an individual from Singapore. A phylogenetic tree constructed from Corvidae family mitogenome sequences available on GenBank is presented. We confirm the monophyly of the genus Corvus and propose to use complete mitogenome resources for further intra- and interspecies genetic studies.

  7. Fecal shedding of Brachyspira spp. on a farrow-to-finish swine farm with a clinical history of “Brachyspira hampsonii”-associated colitis (United States)


    Background Brachyspira associated diarrhea is a re-emerging concern for Canadian swine producers. To identify critical control points for reducing the impact of Brachyspira on production, improved diagnostic tools and a better understanding of the on-farm epidemiology of these pathogens are required. A cross-sectional study was conducted for the detection of Brachyspira on a commercial, two-site, farrow-to-finish pork production unit in Saskatchewan, Canada with a clinical history of mucohaemorrhagic colitis associated with “B. hampsonii”. Results Rectal swabs from pigs at all production stages were collected over 13 weeks (n = 866). Two swabs were collected per pig for culture and Gram stain, and for PCR. Ninety-one culture positive samples were detected, with the highest prevalence of Brachyspira shedding in grower pigs (21%). No Brachyspira were detected in pre-weaned piglets. PCR and Gram stain of rectal swabs detected fewer positive samples than culture. The most prevalent species detected was B. murdochii; other species detected included B. pilosicoli, B. innocens, and “Brachyspira hampsonii”. Phylogenetic analysis revealed that several of the isolates, including some strongly beta-haemolytic isolates, might represent novel taxa. Conclusions Our results indicate that apparently healthy pigs can be colonized with diverse Brachyspira species, including some potential pathogens, and that frequency of shedding peaks in the grower stage. Difference in the detection rates of Brachyspira amongst culture, Gram stain or PCR on rectal swabs have implications for choice of detection methods and surveillance approaches that may be most effective in Brachyspira control strategies. PMID:23844564

  8. The protease inhibitor HAI-2, but not HAI-1, regulates matriptase activation and shedding through prostasin. (United States)

    Friis, Stine; Sales, Katiuchia Uzzun; Schafer, Jeffrey Martin; Vogel, Lotte K; Kataoka, Hiroaki; Bugge, Thomas H


    The membrane-anchored serine proteases, matriptase and prostasin, and the membrane-anchored serine protease inhibitors, hepatocyte growth factor activator inhibitor (HAI)-1 and HAI-2, are critical effectors of epithelial development and postnatal epithelial homeostasis. Matriptase and prostasin form a reciprocal zymogen activation complex that results in the formation of active matriptase and prostasin that are targets for inhibition by HAI-1 and HAI-2. Conflicting data, however, have accumulated as to the existence of auxiliary functions for both HAI-1 and HAI-2 in regulating the intracellular trafficking and activation of matriptase. In this study, we, therefore, used genetically engineered mice to determine the effect of ablation of endogenous HAI-1 and endogenous HAI-2 on endogenous matriptase expression, subcellular localization, and activation in polarized intestinal epithelial cells. Whereas ablation of HAI-1 did not affect matriptase in epithelial cells of the small or large intestine, ablation of HAI-2 resulted in the loss of matriptase from both tissues. Gene silencing studies in intestinal Caco-2 cell monolayers revealed that this loss of cell-associated matriptase was mechanistically linked to accelerated activation and shedding of the protease caused by loss of prostasin regulation by HAI-2. Taken together, these data indicate that HAI-1 regulates the activity of activated matriptase, whereas HAI-2 has an essential role in regulating prostasin-dependent matriptase zymogen activation.

  9. Zebrafish models flex their muscles to shed light on muscular dystrophies

    Directory of Open Access Journals (Sweden)

    Joachim Berger


    Full Text Available Muscular dystrophies are a group of genetic disorders that specifically affect skeletal muscle and are characterized by progressive muscle degeneration and weakening. To develop therapies and treatments for these diseases, a better understanding of the molecular basis of muscular dystrophies is required. Thus, identification of causative genes mutated in specific disorders and the study of relevant animal models are imperative. Zebrafish genetic models of human muscle disorders often closely resemble disease pathogenesis, and the optical clarity of zebrafish embryos and larvae enables visualization of dynamic molecular processes in vivo. As an adjunct tool, morpholino studies provide insight into the molecular function of genes and allow rapid assessment of candidate genes for human muscular dystrophies. This unique set of attributes makes the zebrafish model system particularly valuable for the study of muscle diseases. This review discusses how recent research using zebrafish has shed light on the pathological basis of muscular dystrophies, with particular focus on the muscle cell membrane and the linkage between the myofibre cytoskeleton and the extracellular matrix.

  10. A novel mouse Dscam mutation inhibits localization and shedding of DSCAM.

    Directory of Open Access Journals (Sweden)

    R Dee Schramm

    Full Text Available The differential adhesion hypothesis of development states that patterning of organisms, organs and tissues is mediated in large part by expression of cell adhesion molecules. The cues provided by cell adhesion molecules are also hypothesized to facilitate specific connectivity within the nervous system. In this study we characterize a novel mouse mutation in the gene Dscam (Down Syndrome Cell Adhesion Molecule. Vertebrate DSCAM is required for normal development of the central nervous system and has been best characterized in the visual system. In the visual system DSCAM is required for regulation of cell number, mosaic formation, laminar specificity, and refinement of retinal-tectal projections. We have identified a novel mutation in Dscam that results in a single amino acid substitution, R1018P, in the extracellular domain of the DSCAM protein. Mice homozygous for the R1018P mutation develop a subset of defects observed in Dscam null mice. In vitro analysis identified defects in DSCAM(R1018P localization to filopodia. We also find that wild type DSCAM protein is constitutively cleaved and shed from transfected cells. This secretion is inhibited by the R1018P mutation. We also characterized a novel splice isoform of Dscam and identified defects in lamination of type 2 and type 6 cone bipolar cells in Dscam mutant mice. The identification and characterization of partial loss of function mutations in genes such as Dscam will be helpful in predicting signs and symptoms that may be observed in human patients with partial loss of DSCAM function.

  11. Hellbender genome sequences shed light on genomic expansion at the base of crown salamanders. (United States)

    Sun, Cheng; Mueller, Rachel Lockridge


    Among animals, genome sizes range from 20 Mb to 130 Gb, with 380-fold variation across vertebrates. Most of the largest vertebrate genomes are found in salamanders, an amphibian clade of 660 species. Thus, salamanders are an important system for studying causes and consequences of genomic gigantism. Previously, we showed that plethodontid salamander genomes accumulate higher levels of long terminal repeat (LTR) retrotransposons than do other vertebrates, although the evolutionary origins of such sequences remained unexplored. We also showed that some salamanders in the family Plethodontidae have relatively slow rates of DNA loss through small insertions and deletions. Here, we present new data from Cryptobranchus alleganiensis, the hellbender. Cryptobranchus and Plethodontidae span the basal phylogenetic split within salamanders; thus, analyses incorporating these taxa can shed light on the genome of the ancestral crown salamander lineage, which underwent expansion. We show that high levels of LTR retrotransposons likely characterize all crown salamanders, suggesting that disproportionate expansion of this transposable element (TE) class contributed to genomic expansion. Phylogenetic and age distribution analyses of salamander LTR retrotransposons indicate that salamanders' high TE levels reflect persistence and diversification of ancestral TEs rather than horizontal transfer events. Finally, we show that relatively slow DNA loss rates through small indels likely characterize all crown salamanders, suggesting that a decreased DNA loss rate contributed to genomic expansion at the clade's base. Our identification of shared genomic features across phylogenetically distant salamanders is a first step toward identifying the evolutionary processes underlying accumulation and persistence of high levels of repetitive sequence in salamander genomes.

  12. Transient Stability Improvement for Combined Heat and Power System Using Load Shedding

    Directory of Open Access Journals (Sweden)

    Hung-Cheng Chen


    Full Text Available The purpose of the paper is to analyze and improve the transient stability of an industrial combined heat and power (CHP system in a high-tech science park in Taiwan. The CHP system installed two 161 kV/161 kV high-impendence transformers to connect with Taipower System (TPS for both decreasing the short-circuit fault current and increasing the fault critical clearing time. The transient stabilities of three types of operation modes in CHP units, 3G1S, 2G1S, and 1G1S, are analyzed. Under the 3G1S operation mode, the system frequency is immediately restored to 60 Hz after tie line tripping with the TPS. Under the 1G1S and 2G1S operation modes, the system frequencies will continuously decrease and eventually become unstable. A novel transient stability improvement approach using load shedding technique based on the change in frequency is proposed to improve the transient stability.

  13. Genetic and Epigenetic Diversities Shed Light on Domestication of Cultivated Ginseng (Panax ginseng). (United States)

    Li, Ming-Rui; Shi, Feng-Xue; Zhou, Yu-Xin; Li, Ya-Ling; Wang, Xin-Feng; Zhang, Cui; Wang, Xu-Tong; Liu, Bao; Xiao, Hong-Xing; Li, Lin-Feng


    Chinese ginseng (Panax ginseng) is a medically important herb within Panax and has crucial cultural values in East Asia. As the symbol of traditional Chinese medicine, Chinese ginseng has been used as a herbal remedy to restore stamina and capacity in East Asia for thousands of years. To address the evolutionary origin and domestication history of cultivated ginseng, we employed multiple molecular approaches to investigate the genetic structures of cultivated and wild ginseng across their distribution ranges in northeastern Asia. Phylogenetic and population genetic analyses revealed that the four cultivated ginseng landraces, COMMON, BIANTIAO, SHIZHU, and GAOLI (also known as Korean ginseng), were not domesticated independently and Fusong Town is likely one of the primary domestication centers. In addition, our results from population genetic and epigenetic analyses demonstrated that cultivated ginseng maintained high levels of genetic and epigenetic diversity, but showed distinct cytosine methylation patterns compared with wild ginseng. The patterns of genetic and epigenetic variation revealed by this study have shed light on the domestication history of cultivated ginseng, which may serve as a framework for future genetic improvements.

  14. Integrative analyses shed new light on human ribosomal protein gene regulation (United States)

    Li, Xin; Zheng, Yiyu; Hu, Haiyan; Li, Xiaoman


    Ribosomal protein genes (RPGs) are important house-keeping genes that are well-known for their coordinated expression. Previous studies on RPGs are largely limited to their promoter regions. Recent high-throughput studies provide an unprecedented opportunity to study how human RPGs are transcriptionally modulated and how such transcriptional regulation may contribute to the coordinate gene expression in various tissues and cell types. By analyzing the DNase I hypersensitive sites under 349 experimental conditions, we predicted 217 RPG regulatory regions in the human genome. More than 86.6% of these computationally predicted regulatory regions were partially corroborated by independent experimental measurements. Motif analyses on these predicted regulatory regions identified 31 DNA motifs, including 57.1% of experimentally validated motifs in literature that regulate RPGs. Interestingly, we observed that the majority of the predicted motifs were shared by the predicted distal and proximal regulatory regions of the same RPGs, a likely general mechanism for enhancer-promoter interactions. We also found that RPGs may be differently regulated in different cells, indicating that condition-specific RPG regulatory regions still need to be discovered and investigated. Our study advances the understanding of how RPGs are coordinately modulated, which sheds light to the general principles of gene transcriptional regulation in mammals. PMID:27346035

  15. Full-scale field measurements of wave kinematics and vortex shedding induced vibrations in slender structures

    Energy Technology Data Exchange (ETDEWEB)

    Thomsen, J.R.; Pedersen, B. [LIC Engineering (Denmark); Nielsen, K.G.; Bryndum, M.B. [Dansk Hydraulisk Inst., (Denmark)


    Vortex induced vibrations of pipes generated by high and steep waves in the crest zone have been investigated by full-scale field testing, An instrumented cylinder has been suspended from a platform bridge in the North Sea. Adjacent to it a newly developed acoustic system capable of measuring the three dimensional wave kinematics was placed. The kinematics were measured all the way up to the instantaneous water surface elevation, i.e. it included the wave crest. The paper presents time series of measured water surface elevations and orbital velocities at the instantaneous water surface together with the response of the instrumented pipe in a storm. The sea state was measured to H{sub s} {approx_equal} 6.4 m and T{sub z} = 8.4 sec. It was clearly seen that vortex shedding locking-on takes place in some of the rather high modes at the passage of large waves. Intermittent cross flow vortex induced vibrations of between 0.3 diameters up to 0.8 diameters were found in the 8th and the 4th mode respectively. The Reynolds numbers and KC numbers were up to 5 . 10{sup 5} and KC {approx} 250 respectively. (au)


    Institute of Scientific and Technical Information of China (English)


    Vortex street flowmeter has been used in steady flo w measurement for about three decades. The benefits of this type of flowmeter i nclude high accuracy,good linearty,wide measuring range,and excellent reliabilit y. However,in unsteady flow measurement,the pressure disturbance as well as the noise from the system or surrounding can reduce the signal-to-noise ra tio of the flowmeter seriously. Aimed to use vortex street flowmeters in unstea dy flow measurement,the characteristics of the vortex shedding induced hydrodyna mic vibration around the prism bluff body in a vortex street flowmeter are inves tigated numerically and by expriments. The results show that the hydrodynamic vibrations with 180° phase shift occur at the axisymmetric points of the channe l around the bluff body. The most intense vibration occurs at the points on the lateral faces close to the base of the prism. The results provide therefore a useful reference for developing an anti-interference vortex flowmeter using the differential sensing technique.

  17. Varicella-Zoster Virus Keratitis with Asymptomatic Conjunctival Viral Shedding in the Contralateral Eye

    Directory of Open Access Journals (Sweden)

    Akio Miyakoshi


    Full Text Available Purpose: To report a case of varicella-zoster virus (VZV keratitis with detection of VZV DNA in the tear fluid of not only the symptomatic eye but also the contralateral asymptomatic eye by polymerase chain reaction (PCR. Methods: This is a case report. A 63-year-old otherwise healthy woman presented with circu