Sample records for facilitates cross-class ephrin

  1. Ligand Recognition by A-Class Eph Receptors: Crystal Structures of the EphA2 Ligand-Binding Domain and the EphA2/ephrin-A1 Complex

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Himanen, J.; Goldgur, Y; Miao, H

    2009-01-01

    Ephrin (Eph) receptor tyrosine kinases fall into two subclasses (A and B) according to preferences for their ephrin ligands. All published structural studies of Eph receptor/ephrin complexes involve B-class receptors. Here, we present the crystal structures of an A-class complex between EphA2 and ephrin-A1 and of unbound EphA2. Although these structures are similar overall to their B-class counterparts, they reveal important differences that define subclass specificity. The structures suggest that the A-class Eph receptor/ephrin interactions involve smaller rearrangements in the interacting partners, better described by a 'lock-and-key'-type binding mechanism, in contrast to the 'induced fit' mechanism defining the B-class molecules.more » This model is supported by structure-based mutagenesis and by differential requirements for ligand oligomerization by the two subclasses in cell-based Eph receptor activation assays. Finally, the structure of the unligated receptor reveals a homodimer assembly that might represent EphA2-specific homotypic cell adhesion interactions.« less

  2. Ephs and Ephrins in Cancer: Ephrin-A1 Signaling

    PubMed Central

    Beauchamp, Amanda; Debinski, Waldemar

    2011-01-01

    Ephrin-A1 and its primary receptor, EphA2, are involved in numerous physiological processes and have been intensely studied for their roles in malignancy. Ephrin-Eph signalling is complex on its own and is also cell-type dependent, making elucidation of the exact role of ephrin-A1 in neoplasia challenging. Multiple oncogenic signalling pathways, such as MAP/ERK and PI3K are affected by ephrin-A1, and in some cases evidence suggests the promotion of a specific pathway in one cell or cancer type and inhibition of the same pathway in another type of cell or cancer. EphrinA1 also plays an integral role in angiogenesis and tumor neovascularization. Until recently, studies investigating ephrins focused on the ligands as GPI-anchored proteins that required membrane anchoring or artificial clustering for Eph receptor activation. However, recent studies have demonstrated a functional role for soluble, monomeric ephrin-A1. This review will focus on various forms of ephrin-A1-specific signalling in human malignancy. PMID:22040911

  3. Ephrin-B3 regulates glutamate receptor signaling at hippocampal synapses

    PubMed Central

    Antion, Marcia D.; Christie, Louisa A.; Bond, Allison M.; Dalva, Matthew B.; Contractor, Anis

    2010-01-01

    B-ephrin - EphB receptor signaling modulates NMDA receptors by inducing tyrosine phosphorylation of NR2 subunits. Ephrins and EphB RTKs are localized to postsynaptic compartments in the CA1, and therefore potentially interact in a non-canonical cis-configuration. However, it is not known whether cis- configured receptor-ligand signaling is utilized by this class of RTKs, and whether this might influence excitatory synapses. We found that ablation of ephrin-B3 results in an enhancement of the NMDA receptor component of synaptic transmission relative to the AMPA receptor component in CA1 synapses. Synaptic AMPA receptor expression is reduced in ephrin-B3 knockout mice, and there is a marked enhancement of tyrosine phosphorylation of the NR2B receptor subunit. In a reduced system co-expression of ephrin-B3 attenuated EphB2-mediated NR2B tyrosine phosphorylation. Moreover, phosphorylation of EphB2 was elevated in the hippocampus of ephrin-B3 knockout mice, suggesting that regulation of EphB2 activity is lost in these mice. Direct activation of EphB RTKs resulted in phosphorylation of NR2B and a potential signaling partner, the non-receptor tyrosine kinase Pyk2. Our data suggests that ephrin-B3 limits EphB RTK-mediated phosphorylation of the NR2B subunit through an inhibitory cis- interaction which is required for the correct function of glutamatergic CA1 synapses. PMID:20678574

  4. Ephrin-B3 is the midline barrier that prevents corticospinal tract axons from recrossing, allowing for unilateral motor control.

    PubMed

    Kullander, K; Croll, S D; Zimmer, M; Pan, L; McClain, J; Hughes, V; Zabski, S; DeChiara, T M; Klein, R; Yancopoulos, G D; Gale, N W

    2001-04-01

    Growing axons follow highly stereotypical pathways, guided by a variety of attractive and repulsive cues, before establishing specific connections with distant targets. A particularly well-known example that illustrates the complexity of axonal migration pathways involves the axonal projections of motor neurons located in the motor cortex. These projections take a complex route during which they first cross the midline, then form the corticospinal tract, and ultimately connect with motor neurons in the contralateral side of the spinal cord. These obligatory contralateral connections account for why one side of the brain controls movement on the opposing side of the body. The netrins and slits provide well-known midline signals that regulate axonal crossings at the midline. Herein we report that a member of the ephrin family, ephrin-B3, also plays a key role at the midline to regulate axonal crossing. In particular, we show that ephrin-B3 acts as the midline barrier that prevents corticospinal tract projections from recrossing when they enter the spinal gray matter. We report that in ephrin-B3(-/-) mice, corticospinal tract projections freely recross in the spinal gray matter, such that the motor cortex on one side of the brain now provides bilateral input to the spinal cord. This neuroanatomical abnormality in ephrin-B3(-/-) mice correlates with loss of unilateral motor control, yielding mice that simultaneously move their right and left limbs and thus have a peculiar hopping gait quite unlike the alternate step gait displayed by normal mice. The corticospinal and walking defects in ephrin-B3(-/-) mice resemble those recently reported for mice lacking the EphA4 receptor, which binds ephrin-B3 as well as other ephrins, suggesting that the binding of EphA4-bearing axonal processes to ephrin-B3 at the midline provides the repulsive signal that prevents corticospinal tract projections from recrossing the midline in the developing spinal cord.

  5. ADAM13 Induces Cranial Neural Crest by Cleaving Class B Ephrins and Regulating Wnt Signaling

    PubMed Central

    Wei, Shuo; Xu, Guofeng; Bridges, Lance C.; Williams, Phoebe; White, Judith M.; DeSimone, Douglas W.

    2010-01-01

    SUMMARY The cranial neural crest (CNC) are multipotent embryonic cells that contribute to craniofacial structures and other cells and tissues of the vertebrate head. During embryogenesis, CNC is induced at the neural plate boundary through the interplay of several major signaling pathways. Here we report that the metalloproteinase activity of ADAM13 is required for early induction of CNC in Xenopus. In both cultured cells and X. tropicalis embryos, membrane-bound Ephrins (Efns) B1 and B2 were identified as substrates for ADAM13. ADAM13 upregulates canonical Wnt signaling and early expression of the transcription factor snail2, whereas EfnB1 inhibits the canonical Wnt pathway and snail2 expression. We propose that by cleaving class B Efns, ADAM13 promotes canonical Wnt signaling and early CNC induction. PMID:20708595

  6. REGULATION OF EPHRIN-A EXPRESSION IN COMPRESSED RETINOCOLLICULAR MAPS

    PubMed Central

    Tadesse, T.; Cheng, Q.; Xu, M.; Baro, D.J.; Young, L.J.; Pallas, S.L.

    2012-01-01

    Retinotopic maps can undergo compression and expansion in response to changes in target size, but the mechanism underlying this compensatory process has remained a mystery. The discovery of ephrins as molecular mediators of Sperry’s chemoaffinity process allows a mechanistic approach to this important issue. In Syrian hamsters, neonatal, partial (PT) ablation of posterior superior colliculus (SC) leads to compression of the retinotopic map, independent of neural activity. Graded, repulsive EphA receptor/ephrin-A ligand interactions direct the formation of the retinocollicular map, but whether ephrins might also be involved in map compression is unknown. To examine whether map compression might be directed by changes in the ephrin expression pattern, we compared ephrin-A2 and ephrin-A5 mRNA expression between normal SC and PT SC using in situ hybridization and quantitative real-time PCR. We found that ephrin-A ligand expression in the compressed maps was low anteriorly and high posteriorly, as in normal animals. Consistent with our hypothesis, the steepness of the ephrin gradient increased in the lesioned colliculi. Interestingly, overall levels of ephrin-A2 and -A5 expression declined immediately after neonatal target damage, perhaps promoting axon outgrowth. These data establish a correlation between changes in ephrin-A gradients and map compression, and suggest that ephrin-A expression gradients may be regulated by target size. This in turn could lead to compression of the retinocollicular map onto the reduced target. These findings have important implications for mechanisms of recovery from traumatic brain injury. PMID:23008269

  7. REVERSE SIGNALING BY GPI-LINKED MANDUCA EPHRIN REQUIRES A SRC FAMILY KINASE TO RESTRICT NEURONAL MIGRATION IN VIVO

    PubMed Central

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

    2011-01-01

    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

  8. EPHRIN-A5 REGULATES INTER-MALE AGGRESSION IN MICE

    PubMed Central

    Sheleg, Michal; Yochum, Carrie L.; Richardson, Jason R.; Wagner, George C.; Zhou, Renping

    2015-01-01

    The Eph family of receptor tyrosine kinases play key roles in both the patterning of the developing nervous system and neural plasticity in the mature brain. To determine functions of ephrin-A5, a GPI-linked ligand to the Eph receptors, in animal behavior regulations, we examined effects of its inactivation on male mouse aggression. When tested in the resident-intruder paradigm for offensive aggression, ephrin-A5-mutant animals (ephrin-A5−/−) exhibited severe reduction in conspecific aggression compared to wild-type controls. On the contrary, defensive aggression in the form of target biting was higher in ephrin-A5−/− mice, indicating that the mutant mice are capable of attacking behavior. In addition, given the critical role of olfaction in aggressive behavior, we examined the ability of the ephrin-A5−/− mice to smell and found no differences between the mutant and control animals. Testosterone levels in the mutant mice were also found to be within the normal range. Taken together, our data reveal a new role of ephrin-A5 in the regulation of aggressive behavior in mice. PMID:25746458

  9. Bidirectional juxtacrine ephrinB2/Ephs signaling promotes angiogenesis of ECs and maintains self-renewal of MSCs.

    PubMed

    Cao, Cen; Huang, Ying; Tang, Qingming; Zhang, Chenguang; Shi, Lei; Zhao, Jiajia; Hu, Li; Hu, Zhewen; Liu, Yun; Chen, Lili

    2018-07-01

    Co-transplantation of endothelial cells (ECs) and mesenchymal stem cells (MSCs) is an important strategy for repairing complex and large bone defects. However, the ways in which ECs and MSCs interact remain to be fully clarified. We found that forward ephrinB2/Ephs signaling from hBMSCs to hUVECs promoted the tube formation of hUVECs by activating the PI3K/AKT/mTOR pathway. Reverse ephrinB2/Ephs signaling from hUVECs to hBMSCs promoted the proliferation and maintenance of hBMSCs self-renewal via upregulation of OCT4, SOX2, and YAP1. Subcutaneous co-transplantation of ECs and MSCs in nude mice confirmed that forward ephrinB2/Ephs signaling could increase the cross-sectional area of blood vessels in the transplanted area, and reverse ephrinB2/Ephs signaling could maintain the self-renewal of transplanted hBMSCs in vivo. Based on these results, ephrinB2/Ephs bidirectional juxtacrine regulation between ECs and MSCs plays a pivotal role in improving the healing of bone defects by promoting angiogenesis and achieving a sufficient number of MSCs. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. EphrinA5 protein distribution in the developing mouse brain

    PubMed Central

    2010-01-01

    Background EphrinA5 is one of the best-studied members of the Eph-ephrin family of guidance molecules, known to be involved in brain developmental processes. Using in situ hybridization, ephrinA5 mRNA expression has been detected in the retinotectal, the thalamocortical, and the olfactory systems; however, no study focused on the distribution of the protein. Considering that this membrane-anchored molecule may act far from the neuron soma expressing the transcript, it is of a crucial interest to localize ephrinA5 protein to better understand its function. Results Using immunohistochemistry, we found that ephrinA5 protein is highly expressed in the developing mouse brain from E12.5 to E16.5. The olfactory bulb, the cortex, the striatum, the thalamus, and the colliculi showed high intensity of labelling, suggesting its implication in topographic mapping of olfactory, retinocollicular, thalamocortical, corticothalamic and mesostriatal systems. In the olfactory nerve, we found an early ephrinA5 protein expression at E12.5 suggesting its implication in the guidance of primary olfactory neurons into the olfactory bulb. In the thalamus, we detected a dynamic graduated protein expression, suggesting its role in the corticothalamic patterning, whereas ephrinA5 protein expression in the target region of mesencephalic dopaminergic neurones indicated its involvement in the mesostriatal topographic mapping. Following E16.5, the signal faded gradually and was barely detectable at P0, suggesting a main role for ephrinA5 in primary molecular events in topographic map formation. Conclusion Our work shows that ephrinA5 protein is expressed in restrictive regions of the developing mouse brain. This expression pattern points out the potential sites of action of this molecule in the olfactory, retinotectal, thalamocortical, corticothalamic and mesostriatal systems, during development. This study is essential to better understand the role of ephrinA5 during developmental topographic

  11. Suppression of gastric cancer dissemination by ephrin-B1-derived peptide.

    PubMed

    Tanaka, Masamitsu; Kamata, Reiko; Yanagihara, Kazuyoshi; Sakai, Ryuichi

    2010-01-01

    Interaction of the Eph family of receptor protein tyrosine kinases and their ligands, ephrin family members, induces bidirectional signaling through cell-cell contacts. High expression of B-type ephrin is associated with high invasion potential of tumors, and we previously observed that signaling through the C-terminus of ephrin-B1 mediates the migration and invasion of cells, and is involved in the promotion of carcinomatous peritonitis in vivo. Here we show that the intracellular introduction of a synthetic peptide derived from ephrin-B1 C-terminus blocks ephrin-B1 mediated signaling in scirrhous gastric cancer cells. Treatment of cancer cells with a fusion peptide consisting of HIV-TAT and amino acids 331-346 of ephrin-B1 (PTD-EFNB1-C) suppressed the activation of RhoA, mediated by the association of ephrin-B1 with an adaptor protein Dishevelled, and also inhibited extracellular secretion of metalloproteinase. Moreover, injection of PTD-EFNB1-C peptide into the peritoneal cavity of nude mice suppressed carcinomatous peritonitis of intraperitoneally transplanted scirrhous gastric cancer cells. These results indicate the possible application of ephrin-B1 C-terminal peptide to develop novel protein therapy for scirrhous gastric carcinoma, especially in the stage of tumor progression, including peritoneal dissemination.

  12. Host cell recognition by the henipaviruses: Crystal structures of the Nipah G attachment glycoprotein and its complex with ephrin-B3

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xu, Kai; Rajashankar, Kanagalaghatta R.; Chan, Yee-Peng

    2008-07-28

    Nipah virus (NiV) and Hendra virus are the type species of the highly pathogenic paramyxovirus genus Henipavirus, which can cause severe respiratory disease and fatal encephalitis infections in humans, with case fatality rates approaching 75%. NiV contains two envelope glycoproteins, the receptor-binding G glycoprotein (NiV-G) that facilitates attachment to host cells and the fusion (F) glycoprotein that mediates membrane merger. The henipavirus G glycoproteins lack both hemagglutinating and neuraminidase activities and, instead, engage the highly conserved ephrin-B2 and ephrin-B3 cell surface proteins as their entry receptors. Here, we report the crystal structures of the NiV-G both in its receptor-unbound statemore » and in complex with ephrin-B3, providing, to our knowledge, the first view of a paramyxovirus attachment complex in which a cellular protein is used as the virus receptor. Complex formation generates an extensive protein-protein interface around a protruding ephrin loop, which is inserted in the central cavity of the NiV-G {beta}-propeller. Analysis of the structural data reveals the molecular basis for the highly specific interactions of the henipavirus G glycoproteins with only two members (ephrin-B2 and ephrin-B3) of the very large ephrin family and suggests how they mediate in a unique fashion both cell attachment and the initiation of membrane fusion during the virus infection processes. The structures further suggest that the NiV-G/ephrin interactions can be effectively targeted to disrupt viral entry and provide the foundation for structure-based antiviral drug design.« less

  13. The Role of Ephs and Ephrins in Memory Formation.

    PubMed

    Dines, Monica; Lamprecht, Raphael

    2016-04-01

    The ability to efficiently store memories in the brain is a fundamental process and its impairment is associated with multiple human mental disorders. Evidence indicates that long-term memory formation involves alterations of synaptic efficacy produced by modifications in neural transmission and morphology. The Eph receptors and their cognate ephrin ligands have been shown to be involved in these key neuronal processes by regulating events such as presynaptic transmitter release, postsynaptic glutamate receptor conductance and trafficking, synaptic glutamate reuptake, and dendritic spine morphogenesis. Recent findings show that Ephs and ephrins are needed for memory formation in different organisms. These proteins participate in the formation of various types of memories that are subserved by different neurons and brain regions. Ephs and ephrins are involved in brain disorders and diseases with memory impairment symptoms, including Alzheimer's disease and anxiety. Drugs that agonize or antagonize Ephs/ephrins signaling have been developed and could serve as therapeutic agents to treat such diseases. Ephs and ephrins may therefore induce cellular alterations mandatory for memory formation and serve as a target for pharmacological intervention for treatment of memory-related brain diseases. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  14. The Role of Ephs and Ephrins in Memory Formation

    PubMed Central

    Dines, Monica

    2016-01-01

    The ability to efficiently store memories in the brain is a fundamental process and its impairment is associated with multiple human mental disorders. Evidence indicates that long-term memory formation involves alterations of synaptic efficacy produced by modifications in neural transmission and morphology. The Eph receptors and their cognate ephrin ligands have been shown to be involved in these key neuronal processes by regulating events such as presynaptic transmitter release, postsynaptic glutamate receptor conductance and trafficking, synaptic glutamate reuptake, and dendritic spine morphogenesis. Recent findings show that Ephs and ephrins are needed for memory formation in different organisms. These proteins participate in the formation of various types of memories that are subserved by different neurons and brain regions. Ephs and ephrins are involved in brain disorders and diseases with memory impairment symptoms, including Alzheimer’s disease and anxiety. Drugs that agonize or antagonize Ephs/ephrins signaling have been developed and could serve as therapeutic agents to treat such diseases. Ephs and ephrins may therefore induce cellular alterations mandatory for memory formation and serve as a target for pharmacological intervention for treatment of memory-related brain diseases. PMID:26371183

  15. ADAM10-mediated ephrin-B2 shedding promotes myofibroblast activation and organ fibrosis

    PubMed Central

    Lagares, David; Ghassemi-Kakroodi, Parisa; Tremblay, Caroline; Santos, Alba; Probst, Clemens K.; Franklin, Alicia; Santos, Daniela M.; Grasberger, Paula; Ahluwalia, Neil; Montesi, Sydney B.; Shea, Barry S.; Black, Katharine E.; Knipe, Rachel; Blati, Meryem; Baron, Murray; Wu, Brian; Fahmi, Hassan; Gandhi, Rajiv; Pardo, Annie; Selman, Moisés; Wu, Jiangping; Pelletier, Jean-Pierre; Martel-Pelletier, Johanne; Tager, Andrew M.; Kapoor, Mohit

    2017-01-01

    Maladaptive wound healing responses to chronic tissue injury result in organ fibrosis. Fibrosis, which entails excessive extracellular matrix (ECM) deposition and tissue remodelling by activated myofibroblasts, leads to loss of proper tissue architecture and organ function; however the molecular mediators of myofibroblast activation remain to be fully identified. Here we identify soluble ephrin-B2 as a novel pro-fibrotic mediator in lung and skin fibrosis. We provide molecular, functional and translational evidence that the ectodomain of membrane-bound ephrin-B2 is shed from fibroblasts into the alveolar airspace after lung injury. Shedding of soluble ephrin-B2 (sEphrin-B2) promotes fibroblast chemotaxis and activation via EphB3/EphB4 receptor signaling. We found that mice lacking ephrin-B2 in fibroblasts are protected from skin and lung fibrosis and that a distintegrin and metalloproteinase 10 (ADAM10) is the major ephrin-B2 sheddase in fibroblasts. ADAM10 is induced by transforming growth factor-β1 (TGF-β1), and ADAM10-mediated sEphrin-B2 generation is required for TGF-β1–induced myofibroblast activation. Pharmacological inhibition of ADAM10 reduces sEphrin-B2 levels in bronchoalveolar lavage and prevents lung fibrosis in mice. Consistent with the mouse data, ADAM10/sEphrin-B2 signaling is upregulated in fibroblasts from human subjects with idiopathic pulmonary fibrosis. These results uncover a new molecular mechanism of tissue fibrogenesis and identify sEphrin-B2, its receptors Eph3/Eph4, and ADAM10 as potential therapeutic targets in the treatment of fibrotic diseases. PMID:29058717

  16. Ephrin-A1/EphA4-mediated adhesion of monocytes to endothelial cells.

    PubMed

    Jellinghaus, Stefanie; Poitz, David M; Ende, Georg; Augstein, Antje; Weinert, Sönke; Stütz, Beryl; Braun-Dullaeus, Rüdiger C; Pasquale, Elena B; Strasser, Ruth H

    2013-10-01

    The Eph receptors represent the largest family of receptor tyrosine kinases. Both Eph receptors and their ephrin ligands are cell-surface proteins, and they typically mediate cell-to-cell communication by interacting at sites of intercellular contact. The major aim of the present study was to investigate the involvement of EphA4-ephrin-A1 interaction in monocyte adhesion to endothelial cells, as this process is a crucial step during the initiation and progression of the atherosclerotic plaque. Immunohistochemical analysis of human atherosclerotic plaques revealed expression of EphA4 receptor and ephrin-A1 ligand in major cell types within the plaque. Short-time stimulation of endothelial cells with the soluble ligand ephrin-A1 leads to a fourfold increase in adhesion of human monocytes to endothelial cells. In addition, ephrin-A1 further increases monocyte adhesion to already inflamed endothelial cells. EphrinA1 mediates its effect on monocyte adhesion via the activated receptor EphA4. This ephrinA1/EphA4 induced process involves the activation of the Rho signaling pathway and does not require active transcription. Rho activation downstream of EphA4 leads to increased polymerization of actin filaments in endothelial cells. This process was shown to be crucial for the proadhesive effect of ephrin-A1. The results of the present study show that ephrin-A1-induced EphA4 forward signaling promotes monocyte adhesion to endothelial cells via activation of RhoA and subsequent stress-fiber formation by a non-transcriptional mechanism. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Meigo governs dendrite targeting specificity by modulating Ephrin level and N-glycosylation

    PubMed Central

    Sekine, Sayaka U; Haraguchi, Shuka; Chao, Kinhong; Kato, Tomoko; Luo, Liqun; Miura, Masayuki; Chihara, Takahiro

    2016-01-01

    Neural circuit assembly requires precise dendrite and axon targeting. We identified an evolutionarily conserved endoplasmic reticulum (ER) protein, Meigo, from a mosaic genetic screen in Drosophila melanogaster. Meigo was cell-autonomously required in olfactory receptor neurons and projection neurons to target their axons and dendrites to the lateral antennal lobe and to refine projection neuron dendrites into individual glomeruli. Loss of Meigo induced an unfolded protein response and reduced the amount of neuronal cell surface proteins, including Ephrin. Ephrin overexpression specifically suppressed the projection neuron dendrite refinement defect present in meigo mutant flies, and ephrin knockdown caused a similar projection neuron dendrite refinement defect. Meigo positively regulated the level of Ephrin N-glycosylation, which was required for its optimal function in vivo. Thus, Meigo, an ER-resident protein, governs neuronal targeting specificity by regulating ER folding capacity and protein N-glycosylation. Furthermore, Ephrin appears to be an important substrate that mediates Meigo’s function in refinement of glomerular targeting. PMID:23624514

  18. Axonal/Glial Upregulation of EphB/ephrin-B Signaling in Mouse Experimental Ocular Hypertension

    PubMed Central

    Tran, Tony; Sretavan, David

    2010-01-01

    Purpose. To use a laser-induced ocular hypertension (LIOH) mouse model to examine the optic nerve head (ONH) expression of EphB/ephrin-B, previously shown to be upregulated in glaucomatous DBA/2J mice. To relate ephrin-B reverse signaling with states of axonal response to disease. Methods. LIOH was induced unilaterally in CD-1 mice by laser photocoagulation of limbal and episcleral veins. Intraocular pressure (IOP) was measured with a tonometer. EphB/ephrin-B mRNA expression was assessed by in situ hybridization on eyecup cryosections and real-time PCR. Cell specific markers were used to identify the cellular origin of EphB/ephrin-B expression. Activation of ephrin-B signaling was investigated with a phosphospecific antibody on cryosections and retinal whole-mounts. Results. Upregulation of EphB/ephrin-B expression occurred early within a day of IOP elevation. A transient increase of phosphorylation-dependent ephrin-B (pEB) reverse signaling was observed in ONH axons, microglia, and some astrocytes. Morphologically unaffected retinal ganglion cell (RGC) axons differed from axons with reactive aberrant trajectories by exhibiting increased pEB activation, whereas pEB levels in morphologically affected axons were comparable to those of controls. Conclusions. An Eph-ephrin signaling network is activated at the ONH after LIOH in CD-1 mice, either before or coincident with the initial morphologic signs of RGC axon damage reported previously. Of note, ephrin-B reverse signaling was transiently upregulated in RGC axons at the ONH early in their response to IOP elevation but was downregulated in axons that had been damaged by glaucomatous injury and exhibited aberrant trajectories. Ephrin-B reverse signaling may mark RGC axons for damage or confer a protective advantage against injury. PMID:19815726

  19. The Caenorhabditis elegans Ephrin EFN-4 Functions Non-cell Autonomously with Heparan Sulfate Proteoglycans to Promote Axon Outgrowth and Branching

    PubMed Central

    Schwieterman, Alicia A.; Steves, Alyse N.; Yee, Vivian; Donelson, Cory J.; Bentley, Melissa R.; Santorella, Elise M.; Mehlenbacher, Taylor V.; Pital, Aaron; Howard, Austin M.; Wilson, Melissa R.; Ereddia, Danielle E.; Effrein, Kelsie S.; McMurry, Jonathan L.; Ackley, Brian D.; Chisholm, Andrew D.; Hudson, Martin L.

    2016-01-01

    The Eph receptors and their cognate ephrin ligands play key roles in many aspects of nervous system development. These interactions typically occur within an individual tissue type, serving either to guide axons to their terminal targets or to define boundaries between the rhombomeres of the hindbrain. We have identified a novel role for the Caenorhabditis elegans ephrin EFN-4 in promoting primary neurite outgrowth in AIY interneurons and D-class motor neurons. Rescue experiments reveal that EFN-4 functions non-cell autonomously in the epidermis to promote primary neurite outgrowth. We also find that EFN-4 plays a role in promoting ectopic axon branching in a C. elegans model of X-linked Kallmann syndrome. In this context, EFN-4 functions non-cell autonomously in the body-wall muscle and in parallel with HS modification genes and HSPG core proteins. This is the first report of an epidermal ephrin providing a developmental cue to the nervous system. PMID:26645816

  20. Abnormal expression of ephrin-A5 affects brain development of congenital hypothyroidism rats.

    PubMed

    Suo, Guihai; Shen, Feifei; Sun, Baolan; Song, Honghua; Xu, Meiyu; Wu, Youjia

    2018-05-14

    EphA5 and its ligand ephrin-A5 interaction can trigger synaptogenesis during early hippocampus development. We have previously reported that abnormal EphA5 expression can result in synaptogenesis disorder in congenital hypothyroidism (CH) rats. To better understand its precise molecular mechanism, we further analyzed the characteristics of ephrin-A5 expression in the hippocampus of CH rats. Our study revealed that ephrin-A5 expression was downregulated by thyroid hormone deficiency in the developing hippocampus and hippocampal neurons in rats. Thyroxine treatment for hypothyroid hippocampus and triiodothyronine treatment for hypothyroid hippocampal neurons significantly improved ephrin-A5 expression but could not restore its expression to control levels. Hypothyroid hippocampal neurons in-vitro showed synaptogenesis disorder characterized by a reduction in the number and length of neurites. Furthermore, the synaptogenesis-associated molecular expressions of NMDAR-1 (NR1), PSD95 and CaMKII were all downregulated correspondingly. These results suggest that ephrin-A5 expression may be decreased in CH, and abnormal activation of ephrin-A5/EphA5 signaling affects synaptogenesis during brain development. Such findings provide an important basis for exploring the pathogenesis of CH genetically.

  1. Anatomical-Molecular Distribution of EphrinA1 in Infarcted Mouse Heart Using MALDI Mass Spectrometry Imaging

    NASA Astrophysics Data System (ADS)

    Lefcoski, Stephan; Kew, Kimberly; Reece, Shaun; Torres, Maria J.; Parks, Justin; Reece, Sky; de Castro Brás, Lisandra E.; Virag, Jitka A. I.

    2018-03-01

    EphrinA1 is a tyrosine kinase receptor localized in the cellular membrane of healthy cardiomyocytes, the expression of which is lost upon myocardial infarction (MI). Intra-cardiac injection of the recombinant form of ephrinA1 (ephrinA1-Fc) at the time of ligation in mice has shown beneficial effects by reducing infarct size and myocardial necrosis post-MI. To date, immunohistochemistry and Western blotting comprise the only experimental approaches utilized to localize and quantify relative changes of ephrinA1 in sections and homogenates of whole left ventricle, respectively. Herein, we used matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) coupled with a time-of-flight mass spectrometer (MALDI/TOF MS) to identify intact as well as tryptic fragments of ephrinA1 in healthy controls and acutely infarcted murine hearts. The purpose of the present study was 3-fold: (1) to spatially resolve the molecular distribution of endogenous ephrinA1, (2) to determine the anatomical expression profile of endogenous ephrinA1 after acute MI, and (3) to identify molecular targets of ephrinA1-Fc action post-MI. The tryptic fragments detected were identified as the ephrinA1-isoform with 38% and 34% sequence coverage and Mascot scores of 25 for the control and MI hearts, respectively. By using MALDI-MSI, we have been able to simultaneously measure the distribution and spatial localization of ephrinA1, as well as additional cardiac proteins, thus offering valuable information for the elucidation of molecular partners, mediators, and targets of ephrinA1 action in cardiac muscle. [Figure not available: see fulltext.

  2. EphrinB3 restricts endogenous neural stem cell migration after traumatic brain injury.

    PubMed

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

    2016-11-01

    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. Copyright © 2016 Michael Boutros, German Cancer Research Center, Heidelberg, Germany. Published by Elsevier B.V. All rights reserved.

  3. EphrinB2 Stabilizes Vascularlike Structures Generated by Endothelial Cells and Stem Cells from Apical Papilla.

    PubMed

    Yuan, Changyong; Wang, Penglai; Zhu, Shaoyue; Zou, Ting; Wang, Shuai; Xu, Jianguang; Heng, Boon Chin; Diogenes, Anibal; Zhang, Chengfei

    2016-09-01

    This study aimed to investigate the roles of ephrinB2 in stabilizing vascularlike structures generated by stem cells from apical papilla (SCAPs) and human umbilical vein endothelial cells (HUVECs). HUVECs were seeded alone or with SCAPs concurrently or 12 hours later. Angiogenesis and ephrinB2 phosphorylation were assayed at different time points. Additionally, ephrinB2 expression in SCAPs and HUVECs was silenced with small interfering RNA, and vascularlike structure formation within coculture was assessed; 1 × 10(5) HUVECs were seeded in transwell inserts, and 6 × 10(5) SCAPs were plated in lower wells with or without ephrinB2-Fc. Migratory cells were stained and counted. Delayed addition of ephrinB2-Fc to the coculture of HUVECs and SCAPs was performed to evaluate the role of ephrinB2 on the stabilization of vascularlike structures. Concurrent coculture of SCAPs and HUVECs yielded significantly longer tubule lengths at 4, 8, and 12 hours (P < .05). Delayed addition of SCAPs to coculture with HUVECs resulted in vascularlike structures persisting longer than the HUVEC monoculture. Western blot confirmed that ephrinB2 phosphorylation was initiated at 0.5 hours of coculture and peaked at 1 hour. Silencing ephrinB2 expression in SCAPs and HUVECs resulted in the absence of vascularlike structures. Enhanced migration of HUVECs by SCAPs could be inhibited by ephrinB2-Fc. When ephrinB2-Fc was added at 3 hours of coculture, the vascularlike structures were stabilized for more than 12 hours as compared with 9 hours in the control group. EphrinB2 plays an important role in the stabilization of vascularlike structures generated by HUVECs and SCAPs. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  4. EphrinA1-Fc attenuates myocardial ischemia/reperfusion injury in mice

    PubMed Central

    DuSablon, Augustin; Parks, Justin; Whitehurst, K’Shylah; Estes, Heather; Chase, Robert; Vlahos, Eleftherios; Sharma, Uma; Wert, David

    2017-01-01

    EphrinA1, a membrane-bound receptor tyrosine kinase ligand expressed in healthy cardiomyocytes, is lost in injured cells following myocardial infarction. Previously, we have reported that a single intramyocardial injection of chimeric ephrinA1-Fc at the time of ischemia reduced injury in the nonreperfused myocardium by 50% at 4 days post-MI by reducing apoptosis and inflammatory cell infiltration. In a clinically relevant model of acute ischemia (30min)/reperfusion (24hr or 4 days) injury, we now demonstrate that ephrinA1-Fc reduces infarct size by 46% and completely preserves cardiac function (ejection fraction, fractional shortening, and chamber dimensions) in the short-term (24hrs post-MI) as well as long-term (4 days). At 24 hours post-MI, diminished serum inflammatory cell chemoattractants in ephrinA1-Fc-treated mice reduces recruitment of neutrophils and leukocytes into the myocardium. Differences in relative expression levels of EphA-Rs are described in the context of their putative role in mediating cardioprotection. Validation by Western blotting of selected targets from mass spectrometry analyses of pooled samples of left ventricular tissue homogenates from mice that underwent 30min ischemia and 24hr of reperfusion (I/R) indicates that ephrinA1-Fc administration alters several regulators of signaling pathways that attenuate apoptosis, promote autophagy, and shift from FA metabolism in favor of increased glycolysis to optimize anaerobic ATP production. Taken together, reduced injury is due a combination of adaptive metabolic reprogramming, improved cell survival, and decreased inflammatory cell recruitment, suggesting that ephrinA1-Fc enhances the capacity of the heart to withstand an ischemic insult. PMID:29236774

  5. EphrinA1-Fc attenuates myocardial ischemia/reperfusion injury in mice.

    PubMed

    DuSablon, Augustin; Parks, Justin; Whitehurst, K'Shylah; Estes, Heather; Chase, Robert; Vlahos, Eleftherios; Sharma, Uma; Wert, David; Virag, Jitka

    2017-01-01

    EphrinA1, a membrane-bound receptor tyrosine kinase ligand expressed in healthy cardiomyocytes, is lost in injured cells following myocardial infarction. Previously, we have reported that a single intramyocardial injection of chimeric ephrinA1-Fc at the time of ischemia reduced injury in the nonreperfused myocardium by 50% at 4 days post-MI by reducing apoptosis and inflammatory cell infiltration. In a clinically relevant model of acute ischemia (30min)/reperfusion (24hr or 4 days) injury, we now demonstrate that ephrinA1-Fc reduces infarct size by 46% and completely preserves cardiac function (ejection fraction, fractional shortening, and chamber dimensions) in the short-term (24hrs post-MI) as well as long-term (4 days). At 24 hours post-MI, diminished serum inflammatory cell chemoattractants in ephrinA1-Fc-treated mice reduces recruitment of neutrophils and leukocytes into the myocardium. Differences in relative expression levels of EphA-Rs are described in the context of their putative role in mediating cardioprotection. Validation by Western blotting of selected targets from mass spectrometry analyses of pooled samples of left ventricular tissue homogenates from mice that underwent 30min ischemia and 24hr of reperfusion (I/R) indicates that ephrinA1-Fc administration alters several regulators of signaling pathways that attenuate apoptosis, promote autophagy, and shift from FA metabolism in favor of increased glycolysis to optimize anaerobic ATP production. Taken together, reduced injury is due a combination of adaptive metabolic reprogramming, improved cell survival, and decreased inflammatory cell recruitment, suggesting that ephrinA1-Fc enhances the capacity of the heart to withstand an ischemic insult.

  6. Anchoring and Synaptic stability of PSD-95 is driven by ephrin-B3

    PubMed Central

    Hruska, Martin; Henderson, Nathan T.; Xia, Nan L.; Le Marchand, Sylvain J.; Dalva, Matthew B.

    2015-01-01

    Summary Organization of signaling complexes at excitatory synapses by Membrane Associated Guanylate Kinase (MAGUK) proteins regulates synapse development, plasticity, senescence, and disease. Post-translational modification of MAGUK family proteins can drive their membrane localization, yet it is unclear how these intracellular proteins are targeted to sites of synaptic contact. Here we show using super-resolution imaging, biochemical approaches, and in vivo models that the trans-synaptic organizing protein, ephrin-B3, controls the synaptic localization and stability of PSD-95 and links these events to changes in neuronal activity via negative regulation of a novel MAPK-dependent phosphorylation site on ephrin-B3 (S332). Unphosphorylated ephrin-B3 is enriched at synapses, interacts directly with and stabilizes PSD-95 at synapses. Activity induced phosphorylation of S332 disperses ephrin-B3 from synapses, prevents the interaction with, and enhances the turnover of PSD-95. Thus, ephrin-B3 specifies the synaptic localization of PSD-95 and likely links the synaptic stability of PSD-95 to changes in neuronal activity. PMID:26479588

  7. Anchoring and synaptic stability of PSD-95 is driven by ephrin-B3.

    PubMed

    Hruska, Martin; Henderson, Nathan T; Xia, Nan L; Le Marchand, Sylvain J; Dalva, Matthew B

    2015-11-01

    Organization of signaling complexes at excitatory synapses by membrane-associated guanylate kinase (MAGUK) proteins regulates synapse development, plasticity, senescence and disease. Post-translational modification of MAGUK family proteins can drive their membrane localization, yet it is unclear how these intracellular proteins are targeted to sites of synaptic contact. Here we show using super-resolution imaging, biochemical approaches and in vivo models that the trans-synaptic organizing protein ephrin-B3 controls the synaptic localization and stability of PSD-95 and links these events to changes in neuronal activity via negative regulation of a newly identified mitogen-associated protein kinase (MAPK)-dependent phosphorylation site on ephrin-B3, Ser332. Unphosphorylated ephrin-B3 was enriched at synapses, and interacted directly with and stabilized PSD-95 at synapses. Activity-induced phosphorylation of Ser332 dispersed ephrin-B3 from synapses, prevented the interaction with PSD-95 and enhanced the turnover of PSD-95. Thus, ephrin-B3 specifies the synaptic localization of PSD-95 and likely links the synaptic stability of PSD-95 to changes in neuronal activity.

  8. Graded and discontinuous EphA-ephrinB expression patterns in the developing auditory brainstem

    PubMed Central

    Wallace, Matthew M.; Harris, J. Aaron; Brubaker, Donald Q.; Klotz, Caitlyn A.; Gabriele, Mark L.

    2016-01-01

    Eph-ephrin interactions guide topographic mapping and pattern formation in a variety of systems. In contrast to other sensory pathways, their precise role in the assembly of central auditory circuits remains poorly understood. The auditory midbrain, or inferior colliculus (IC) is an intriguing structure for exploring guidance of patterned projections as adjacent subdivisions exhibit distinct organizational features. The central nucleus of the IC (CNIC) and deep aspects of its neighboring lateral cortex (LCIC, Layer 3) are tonotopically-organized and receive layered inputs from primarily downstream auditory sources. While less is known about more superficial aspects of the LCIC, its inputs are multimodal, lack a clear tonotopic order, and appear discontinuous, terminating in modular, patch/matrix-like distributions. Here we utilize X-Gal staining approaches in lacZ mutant mice (ephrin-B2, -B3, and EphA4) to reveal EphA-ephrinB expression patterns in the nascent IC during the period of projection shaping that precedes hearing onset. We also report early postnatal protein expression in the cochlear nuclei, the superior olivary complex, the nuclei of the lateral lemniscus, and relevant midline structures. Continuous ephrin-B2 and EphA4 expression gradients exist along frequency axes of the CNIC and LCIC Layer 3. In contrast, more superficial LCIC localization is not graded, but confined to a series of discrete ephrin-B2 and EphA4-positive Layer 2 modules. While heavily expressed in the midline, much of the auditory brainstem is devoid of ephrin-B3, including the CNIC, LCIC Layer 2 modular fields, the dorsal nucleus of the lateral lemniscus (DNLL), as well as much of the superior olivary complex and cochlear nuclei. Ephrin-B3 LCIC expression appears complementary to that of ephrin-B2 and EphA4, with protein most concentrated in presumptive extramodular zones. Described tonotopic gradients and seemingly complementary modular/extramodular patterns suggest Eph-ephrin

  9. Graded and discontinuous EphA-ephrinB expression patterns in the developing auditory brainstem.

    PubMed

    Wallace, Matthew M; Harris, J Aaron; Brubaker, Donald Q; Klotz, Caitlyn A; Gabriele, Mark L

    2016-05-01

    Eph-ephrin interactions guide topographic mapping and pattern formation in a variety of systems. In contrast to other sensory pathways, their precise role in the assembly of central auditory circuits remains poorly understood. The auditory midbrain, or inferior colliculus (IC) is an intriguing structure for exploring guidance of patterned projections as adjacent subdivisions exhibit distinct organizational features. The central nucleus of the IC (CNIC) and deep aspects of its neighboring lateral cortex (LCIC, Layer 3) are tonotopically-organized and receive layered inputs from primarily downstream auditory sources. While less is known about more superficial aspects of the LCIC, its inputs are multimodal, lack a clear tonotopic order, and appear discontinuous, terminating in modular, patch/matrix-like distributions. Here we utilize X-Gal staining approaches in lacZ mutant mice (ephrin-B2, -B3, and EphA4) to reveal EphA-ephrinB expression patterns in the nascent IC during the period of projection shaping that precedes hearing onset. We also report early postnatal protein expression in the cochlear nuclei, the superior olivary complex, the nuclei of the lateral lemniscus, and relevant midline structures. Continuous ephrin-B2 and EphA4 expression gradients exist along frequency axes of the CNIC and LCIC Layer 3. In contrast, more superficial LCIC localization is not graded, but confined to a series of discrete ephrin-B2 and EphA4-positive Layer 2 modules. While heavily expressed in the midline, much of the auditory brainstem is devoid of ephrin-B3, including the CNIC, LCIC Layer 2 modular fields, the dorsal nucleus of the lateral lemniscus (DNLL), as well as much of the superior olivary complex and cochlear nuclei. Ephrin-B3 LCIC expression appears complementary to that of ephrin-B2 and EphA4, with protein most concentrated in presumptive extramodular zones. Described tonotopic gradients and seemingly complementary modular/extramodular patterns suggest Eph-ephrin

  10. Critical role of the axonal guidance cue EphrinB2 in lung growth, angiogenesis, and repair.

    PubMed

    Vadivel, Arul; van Haaften, Tim; Alphonse, Rajesh S; Rey-Parra, Gloria-Juliana; Ionescu, Lavinia; Haromy, Al; Eaton, Farah; Michelakis, Evangelos; Thébaud, Bernard

    2012-03-01

    Lung diseases characterized by alveolar damage currently lack efficient treatments. The mechanisms contributing to normal and impaired alveolar growth and repair are incompletely understood. Axonal guidance cues (AGC) are molecules that guide the outgrowth of axons to their targets. Among these AGCs, members of the Ephrin family also promote angiogenesis, cell migration, and organogenesis outside the nervous system. The role of Ephrins during alveolar growth and repair is unknown. We hypothesized that EphrinB2 promotes alveolar development and repair. We used in vitro and in vivo manipulation of EphrinB2 signaling to assess the role of this AGC during normal and impaired lung development. In vivo EphrinB2 knockdown using intranasal siRNA during the postnatal stage of alveolar development in rats arrested alveolar and vascular growth. In a model of O(2)-induced arrested alveolar growth in newborn rats, air space enlargement, loss of lung capillaries, and pulmonary hypertension were associated with decreased lung EphrinB2 and receptor EphB4 expression. In vitro, EphrinB2 preserved alveolar epithelial cell viability in O(2), decreased O(2)-induced alveolar epithelial cell apoptosis, and accelerated alveolar epithelial cell wound healing, maintained lung microvascular endothelial cell viability, and proliferation and vascular network formation. In vivo, treatment with intranasal EphrinB2 decreased alveolar epithelial and endothelial cell apoptosis, preserved alveolar and vascular growth in hyperoxic rats, and attenuated pulmonary hypertension. The AGC EphrinB2 may be a new therapeutic target for lung repair and pulmonary hypertension.

  11. EphA2 and ephrin-A5 are not a receptor-ligand pair in the ocular lens.

    PubMed

    Cheng, Catherine; Fowler, Velia M; Gong, Xiaohua

    2017-09-01

    Eph-ephrin bidirectional signaling is essential for eye lens transparency in humans and mice. Our previous studies in mouse lenses demonstrate that ephrin-A5 is mainly expressed in the anterior epithelium, where it is required for maintaining the anterior epithelial monolayer. In contrast, EphA2 is localized in equatorial epithelial and fiber cells where it is essential for equatorial epithelial and fiber cell organization and hexagonal cell shape. Immunostaining of lens epithelial and fiber cells reveals that EphA2 and ephrin-A5 are also co-expressed in anterior fiber cell tips, equatorial epithelial cells and newly formed lens fibers, although they are not precisely colocalized. Due to this complex expression pattern and the promiscuous interactions between Eph receptors and ephrin ligands, as well as their complex bidirectional signaling pathways, cataracts in ephrin-A5(-/-) or EphA2(-/-) lenses may arise from loss of function or abnormal signaling mechanisms. To test whether abnormal signaling mechanisms may play a role in cataractogenesis in ephrin-A5(-/-) or EphA2(-/-) lenses, we generated EphA2 and ephrin-A5 double knockout (DKO) mice. We compared the phenotypes of EphA2(-/-) and ephrin-A5(-/-) lenses to that of DKO lenses. DKO lenses displayed an additive lens phenotype that was not significantly different from the two single KO lens phenotypes. Similar to ephrin-A5(-/-) lenses, DKO lenses had abnormal anterior epithelial cells leading to a large mass of epithelial cells that invade into the underlying fiber cell layer, directly resulting in anterior cataracts in ephrin-A5(-/-) and DKO lenses. Yet, similar to EphA2(-/-) lenses, DKO lenses also had abnormal packing of equatorial epithelial cells with disorganized meridional rows, lack of a lens fulcrum and disrupted fiber cells. The DKO lens phenotype rules out abnormal signaling by EphA2 in ephrin-A5(-/-) lenses or by ephrin-A5 in EphA2(-/-) lenses as possible cataract mechanisms. Thus, these results

  12. Cell type-specific localization of Ephs pairing with ephrin-B2 in the rat postnatal pituitary gland.

    PubMed

    Yoshida, Saishu; Kato, Takako; Kanno, Naoko; Nishimura, Naoto; Nishihara, Hiroto; Horiguchi, Kotaro; Kato, Yukio

    2017-10-01

    Sox2-expressing stem/progenitor cells in the anterior lobe of the pituitary gland form two types of micro-environments (niches): the marginal cell layer and dense cell clusters in the parenchyma. In relation to the mechanism of regulation of niches, juxtacrine signaling via ephrin and its receptor Eph is known to play important roles in various niches. The ephrin and Eph families are divided into two subclasses to create ephrin/Eph signaling in co-operation with confined partners. Recently, we reported that ephrin-B2 localizes specifically to both pituitary niches. However, the Ephs interacting with ephrin-B2 in these pituitary niches have not yet been identified. Therefore, the present study aims to identify the Ephs interacting with ephrin-B2 and the cells that produce them in the rat pituitary gland. In situ hybridization and immunohistochemistry demonstrated cell type-specific localization of candidate interacting partners for ephrin-B2, including EphA4 in cells located in the posterior lobe, EphB1 in gonadotropes, EphB2 in corticotropes, EphB3 in stem/progenitor cells and EphB4 in endothelial cells in the adult pituitary gland. In particular, double-immunohistochemistry showed cis-interactions between EphB3 and ephrin-B2 in the apical cell membranes of stem/progenitor cell niches throughout life and trans-interactions between EphB2 produced by corticotropes and ephrin-B2 located in the basolateral cell membranes of stem/progenitor cells in the early postnatal pituitary gland. These data indicate that ephrin-B2 plays a role in pituitary stem/progenitor cell niches by selective interaction with EphB3 in cis and EphB2 in trans.

  13. Molecular recognition of human ephrinB2 cell surface receptor by an emergent African henipavirus

    PubMed Central

    Lee, Benhur; Pernet, Olivier; Ahmed, Asim A.; Zeltina, Antra; Beaty, Shannon M.; Bowden, Thomas A.

    2015-01-01

    The discovery of African henipaviruses (HNVs) related to pathogenic Hendra virus (HeV) and Nipah virus (NiV) from Southeast Asia and Australia presents an open-ended health risk. Cell receptor use by emerging African HNVs at the stage of host-cell entry is a key parameter when considering the potential for spillover and infection of human populations. The attachment glycoprotein from a Ghanaian bat isolate (GhV-G) exhibits <30% sequence identity with Asiatic NiV-G/HeV-G. Here, through functional and structural analysis of GhV-G, we show how this African HNV targets the same human cell-surface receptor (ephrinB2) as the Asiatic HNVs. We first characterized this virus−receptor interaction crystallographically. Compared with extant HNV-G–ephrinB2 structures, there was significant structural variation in the six-bladed β-propeller scaffold of the GhV-G receptor-binding domain, but not the Greek key fold of the bound ephrinB2. Analysis revealed a surprisingly conserved mode of ephrinB2 interaction that reflects an ongoing evolutionary constraint among geographically distal and phylogenetically divergent HNVs to maintain the functionality of ephrinB2 recognition during virus–host entry. Interestingly, unlike NiV-G/HeV-G, we could not detect binding of GhV-G to ephrinB3. Comparative structure–function analysis further revealed several distinguishing features of HNV-G function: a secondary ephrinB2 interaction site that contributes to more efficient ephrinB2-mediated entry in NiV-G relative to GhV-G and cognate residues at the very C terminus of GhV-G (absent in Asiatic HNV-Gs) that are vital for efficient receptor-induced fusion, but not receptor binding per se. These data provide molecular-level details for evaluating the likelihood of African HNVs to spill over into human populations. PMID:25825759

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

    PubMed

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

    2014-09-01

    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.

  15. Berberine inhibits the proliferation and migration of breast cancer ZR-75-30 cells by targeting Ephrin-B2.

    PubMed

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

    2017-02-15

    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.

  16. Ephrin-B reverse signaling controls septation events at the embryonic midline through separate tyrosine phosphorylation-independent signaling avenues.

    PubMed

    Dravis, Christopher; Henkemeyer, Mark

    2011-07-01

    We report that the disruption of bidirectional signaling between ephrin-B2 and EphB receptors impairs morphogenetic cell-cell septation and closure events during development of the embryonic midline. A novel role for reverse signaling is identified in tracheoesophageal foregut septation, as animals lacking the cytoplasmic domain of ephrin-B2 present with laryngotracheoesophageal cleft (LTEC), while both EphB2/EphB3 forward signaling and ephrin-B2 reverse signaling are shown to be required for midline fusion of the palate. In a third midline event, EphB2/EphB3 are shown to mediate ventral abdominal wall closure by acting principally as ligands to stimulate ephrin-B reverse signaling. Analysis of new ephrin-B2(6YFΔV) and ephrin-B2(ΔV) mutants that specifically ablate ephrin-B2 tyrosine phosphorylation- and/or PDZ domain-mediated signaling indicates there are at least two distinct phosphorylation-independent components of reverse signaling. These involve both PDZ domain interactions and a non-canonical SH2/PDZ-independent form of reverse signaling that may utilize associations with claudin family tetraspan molecules, as EphB2 and activated ephrin-B2 molecules are specifically co-localized with claudins in epithelia at the point of septation. Finally, the developmental phenotypes described here mirror common human midline birth defects found with the VACTERL association, suggesting a molecular link to bidirectional signaling through B-subclass Ephs and ephrins. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. The effects of Eph-ephrin mutations on pre-pulse inhibition in mice.

    PubMed

    Liuzzo, Andrea; Gray, Lincoln; Wallace, Matthew; Gabriele, Mark

    2014-08-01

    Eph-ephrin signaling is known to be important in directing topographic projections in the afferent auditory pathway, including connections to various subdivisions of the inferior colliculus (IC). The acoustic startle-response (ASR) is a reliable reflexive behavioral response in mammals elicited by an unexpected intense acoustic startle-eliciting stimulus (ES). It is mediated by a sub-cortical pathway that includes the IC. The ASR amplitude can be measured with an accelerometer under the subject and can be decreased in amplitude by presenting a less intense, non-startling stimulus 5-300ms before the ES. This reflexive decrement in ASR is called pre-pulse inhibition (PPI) and indicates that the relatively soft pre-pulse was heard. PPI is a general trait among mammals. Mice have been used recently to study this response and to reveal how genetic mutations affect neural circuits and hence the ASR and PPI. In this experiment, we measured the effect of Eph-ephrin mutations using control mice (C57BL/6J), mice with compromised EphA4 signaling (EphA4(lacZ/+), EphA4(lacZ/lacZ)), and knockout ephrin-B3 mice (ephrin-B3 (+/-, -/-)). Control and EphA4(lacZ/+s)trains showed robust PPI (up to 75% decrement in ASR) to an offset of a 70dB SPL background noise at 50ms before the ES. Ephrin-B3 knockout mice and EphA4 homozygous mutants were only marginally significant in PPI (<25% decrement and <33% decrement, respectively) to the same conditions. This decrement in PPI highlights the importance of ephrin-B3 and EphA4 interactions in ordering auditory behavioral circuits. Thus, different mutations in certain members of the signaling family produce a full range of changes in PPI, from minimal to nearly maximal. This technique can be easily adapted to study other aspects of hearing in a wider range of mutations. Along with ongoing neuroanatomical studies, this allows careful quantification of how the auditory anatomical, physiological and now behavioral phenotype is affected by changes

  18. The EphA2 Receptor and EphrinA1 Ligand in Solid Tumors: Function and Therapeutic Targeting

    PubMed Central

    Wykosky, Jill; Debinski, Waldemar

    2013-01-01

    The Eph receptor tyrosine kinases and ephrin ligands have been studied extensively for their roles in developmental processes. In recent years, Eph receptors and ephrins have been found to be integral players in cancer formation and progression. Among these are EphA2 and ephrinA1, which are involved in the development and maintenance of many different types of solid tumors. The function of EphA2 and ephrinA1 in tumorigenesis and tumor progression is complex and seems to be dependent on cell type and microenvironment. These variables affect the expression of the EphA2 and ephrinA1 proteins, the pathways through which they induce signaling, and the functional consequences of that signaling on the behavior of tumor cells and tumor-associated cells. This review will specifically focus on the roles that EphA2 and ephrinA1 play in the different cell types that contribute to the malignancy of solid tumors, with emphasis on the opportunities for therapeutic targeting. PMID:19074825

  19. Functional Consequences of Synapse Remodeling Following Astrocyte-Specific Regulation of Ephrin-B1 in the Adult Hippocampus.

    PubMed

    Koeppen, Jordan; Nguyen, Amanda Q; Nikolakopoulou, Angeliki M; Garcia, Michael; Hanna, Sandy; Woodruff, Simone; Figueroa, Zoe; Obenaus, Andre; Ethell, Iryna M

    2018-06-20

    Astrocyte-derived factors can control synapse formation and functions, making astrocytes an attractive target for regulating neuronal circuits and associated behaviors. Abnormal astrocyte-neuronal interactions are also implicated in neurodevelopmental disorders and neurodegenerative diseases associated with impaired learning and memory. However, little is known about astrocyte-mediated mechanisms that regulate learning and memory. Here, we propose astrocytic ephrin-B1 as a regulator of synaptogenesis in adult hippocampus and mouse learning behaviors. We found that astrocyte-specific ablation of ephrin-B1 in male mice triggers an increase in the density of immature dendritic spines and excitatory synaptic sites in the adult CA1 hippocampus. However, the prevalence of immature dendritic spines is associated with decreased evoked postsynaptic firing responses in CA1 pyramidal neurons, suggesting impaired maturation of these newly formed and potentially silent synapses or increased excitatory drive on the inhibitory neurons resulting in the overall decreased postsynaptic firing. Nevertheless, astrocyte-specific ephrin-B1 knock-out male mice exhibit normal acquisition of fear memory but enhanced contextual fear memory recall. In contrast, overexpression of astrocytic ephrin-B1 in the adult CA1 hippocampus leads to the loss of dendritic spines, reduced excitatory input, and impaired contextual memory retention. Our results suggest that astrocytic ephrin-B1 may compete with neuronal ephrin-B1 and mediate excitatory synapse elimination through its interactions with neuronal EphB receptors. Indeed, a deletion of neuronal EphB receptors impairs the ability of astrocytes expressing functional ephrin-B1 to engulf synaptosomes in vitro Our findings demonstrate that astrocytic ephrin-B1 regulates long-term contextual memory by restricting new synapse formation in the adult hippocampus. SIGNIFICANCE STATEMENT These studies address a gap in our knowledge of astrocyte

  20. Synergistic integration of Netrin and ephrin axon guidance signals by spinal motor neurons

    PubMed Central

    Poliak, Sebastian; Morales, Daniel; Croteau, Louis-Philippe; Krawchuk, Dayana; Palmesino, Elena; Morton, Susan; Cloutier, Jean-François; Charron, Frederic; Dalva, Matthew B; Ackerman, Susan L; Kao, Tzu-Jen; Kania, Artur

    2015-01-01

    During neural circuit assembly, axonal growth cones are exposed to multiple guidance signals at trajectory choice points. While axonal responses to individual guidance cues have been extensively studied, less is known about responses to combination of signals and underlying molecular mechanisms. Here, we studied the convergence of signals directing trajectory selection of spinal motor axons entering the limb. We first demonstrate that Netrin-1 attracts and repels distinct motor axon populations, according to their expression of Netrin receptors. Quantitative in vitro assays demonstrate that motor axons synergistically integrate both attractive or repulsive Netrin-1 signals together with repulsive ephrin signals. Our investigations of the mechanism of ephrin-B2 and Netrin-1 integration demonstrate that the Netrin receptor Unc5c and the ephrin receptor EphB2 can form a complex in a ligand-dependent manner and that Netrin–ephrin synergistic growth cones responses involve the potentiation of Src family kinase signaling, a common effector of both pathways. DOI: http://dx.doi.org/10.7554/eLife.10841.001 PMID:26633881

  1. Ephrin-B3 coordinates timed axon targeting and amygdala spinogenesis for innate fear behaviour

    PubMed Central

    Zhu, Xiao-Na; Liu, Xian-Dong; Sun, Suya; Zhuang, Hanyi; Yang, Jing-Yu; Henkemeyer, Mark; Xu, Nan-Jie

    2016-01-01

    Innate emotion response to environmental stimuli is a fundamental brain function that is controlled by specific neural circuits. Dysfunction of early emotional circuits may lead to neurodevelopmental disorders such as autism and schizophrenia. However, how the functional circuits are formed to prime initial emotional behaviours remain elusive. We reveal here using gene-targeted mutations an essential role for ephrin-B3 ligand-like activity in the development of innate fear in the neonatal brain. We further demonstrate that ephrin-B3 controls axon targeting and coordinates spinogenesis and neuronal activity within the amygdala. The morphological and behavioural abnormalities in ephrin-B3 mutant mice are rescued by conditional knock-in of wild-type ephrin-B3 during the critical period when axon targeting and fear responses are initiated. Our results thus define a key axonal molecule that participates in the wiring of amygdala circuits and helps bring about fear emotion during the important adolescence period. PMID:27008987

  2. Ephrin-B3 coordinates timed axon targeting and amygdala spinogenesis for innate fear behaviour.

    PubMed

    Zhu, Xiao-Na; Liu, Xian-Dong; Sun, Suya; Zhuang, Hanyi; Yang, Jing-Yu; Henkemeyer, Mark; Xu, Nan-Jie

    2016-03-24

    Innate emotion response to environmental stimuli is a fundamental brain function that is controlled by specific neural circuits. Dysfunction of early emotional circuits may lead to neurodevelopmental disorders such as autism and schizophrenia. However, how the functional circuits are formed to prime initial emotional behaviours remain elusive. We reveal here using gene-targeted mutations an essential role for ephrin-B3 ligand-like activity in the development of innate fear in the neonatal brain. We further demonstrate that ephrin-B3 controls axon targeting and coordinates spinogenesis and neuronal activity within the amygdala. The morphological and behavioural abnormalities in ephrin-B3 mutant mice are rescued by conditional knock-in of wild-type ephrin-B3 during the critical period when axon targeting and fear responses are initiated. Our results thus define a key axonal molecule that participates in the wiring of amygdala circuits and helps bring about fear emotion during the important adolescence period.

  3. Effect of hydrogel elasticity and ephrinB2-immobilized manner on Runx2 expression of human mesenchymal stem cells.

    PubMed

    Toda, Hiroyuki; Yamamoto, Masaya; Uyama, Hiroshi; Tabata, Yasuhiko

    2017-08-01

    The objective of this study is to design the manner of ephrinB2 immobilized onto polyacrylamide (PAAm) hydrogels with varied elasticity and evaluate the effect of hydrogels elasticity and the immobilized manner of ephrinB2 on the Runx2 expression of human mesenchymal stem cells (hMSC). The PAAm hydrogels were prepared by the radical polymerization of acrylamide (AAm), and N,N'-methylenebisacrylamide (BIS). By changing the BIS concentration, the elasticity of PAAm hydrogels changed from 1 to 70kPa. For the bio-specific immobilization of ephrinB2, a chimeric protein of ephrinB2 and Fc domain was immobilized onto protein A-conjugated PAAm hydrogels by making use of the bio-specific interaction between the Fc domain and protein A. When hMSC were cultured on the ephrinB2-immobilized PAAm hydrogels with varied elasticity, the morphology of hMSC was of cuboidal shape on the PAAm hydrogels immobilized with ephrinB2 compared with non-conjugated ones, irrespective of the hydrogels elasticity. The bio-specific immobilization of ephrinB2 enhanced the level of Runx2 expression. The expression level was significantly high for the hydrogels of 3.6 and 5.9kPa elasticity with bio-specific immobilization of ephrinB2 compared with other hydrogels with the same elasticity. The hydrogels showed a significantly down-regulated RhoA activity. It is concluded that the Runx2 expression of hMSC is synergistically influenced by the hydrogels elasticity and their immobilized manner of ephrinB2 immobilized. Differentiation fate of mesenchymal stem cells (MSC) is modified by biochemical and biophysical factors, such as elasticity and signal proteins. However, there are few experiments about combinations of them. In this study, to evaluate the synergistic effect of them on cell properties of MSC, we established to design the manner of Eph signal ligand, ephrinB2, immobilized onto polyacrylamide hydrogels with varied elasticity. The gene expression level of an osteogenic maker, Runx2, was enhanced

  4. The Ephrin-A1/EPHA2 Signaling Axis Regulates Glutamine Metabolism in HER2-Positive Breast Cancer.

    PubMed

    Youngblood, Victoria M; Kim, Laura C; Edwards, Deanna N; Hwang, Yoonha; Santapuram, Pranav R; Stirdivant, Steven M; Lu, Pengcheng; Ye, Fei; Brantley-Sieders, Dana M; Chen, Jin

    2016-04-01

    Dysregulation of receptor tyrosine kinases (RTK) contributes to cellular transformation and cancer progression by disrupting key metabolic signaling pathways. The EPHA2 RTK is overexpressed in aggressive forms of breast cancer, including the HER2(+) subtype, and correlates with poor prognosis. However, the role of EPHA2 in tumor metabolism remains unexplored. In this study, we used in vivo and in vitro models of HER2-overexpressing breast cancer to investigate the mechanisms by which EPHA2 ligand-independent signaling promotes tumorigenesis in the absence of its prototypic ligand, ephrin-A1. We demonstrate that ephrin-A1 loss leads to upregulated glutamine metabolism and lipid accumulation that enhanced tumor growth. Global metabolic profiling of ephrin-A1-null, HER2-overexpressing mammary tumors revealed a significant increase in glutaminolysis, a critical metabolic pathway that generates intermediates for lipogenesis. Pharmacologic inhibition of glutaminase activity reduced tumor growth in both ephrin-A1-depleted and EPHA2-overexpressing tumor allografts in vivo Mechanistically, we show that the enhanced proliferation and glutaminolysis in the absence of ephrin-A1 were attributed to increased RhoA-dependent glutaminase activity. EPHA2 depletion or pharmacologic inhibition of Rho, glutaminase, or fatty acid synthase abrogated the increased lipid content and proliferative effects of ephrin-A1 knockdown. Together, these findings highlight a novel, unsuspected connection between the EPHA2/ephrin-A1 signaling axis and tumor metabolism, and suggest potential new therapeutic targets in cancer subtypes exhibiting glutamine dependency. Cancer Res; 76(7); 1825-36. ©2016 AACR. ©2016 American Association for Cancer Research.

  5. Tiam–Rac signaling mediates trans-endocytosis of ephrin receptor EphB2 and is important for cell repulsion

    PubMed Central

    2016-01-01

    Ephrin receptors interact with membrane-bound ephrin ligands to regulate contact-mediated attraction or repulsion between opposing cells, thereby influencing tissue morphogenesis. Cell repulsion requires bidirectional trans-endocytosis of clustered Eph–ephrin complexes at cell interfaces, but the mechanisms underlying this process are poorly understood. Here, we identified an actin-regulating pathway allowing ephrinB+ cells to trans-endocytose EphB receptors from opposing cells. Live imaging revealed Rac-dependent F-actin enrichment at sites of EphB2 internalization, but not during vesicle trafficking. Systematic depletion of Rho family GTPases and their regulatory proteins identified the Rac subfamily and the Rac-specific guanine nucleotide exchange factor Tiam2 as key components of EphB2 trans-endocytosis, a pathway previously implicated in Eph forward signaling, in which ephrins act as in trans ligands of Eph receptors. However, unlike in Eph signaling, this pathway is not required for uptake of soluble ligands in ephrinB+ cells. We also show that this pathway is required for EphB2-stimulated contact repulsion. These results support the existence of a conserved pathway for EphB trans-endocytosis that removes the physical tether between cells, thereby enabling cell repulsion. PMID:27597758

  6. A Model for Teaching Large Classes: Facilitating a "Small Class Feel"

    ERIC Educational Resources Information Center

    Lynch, Rosealie P.; Pappas, Eric

    2017-01-01

    This paper presents a model for teaching large classes that facilitates a "small class feel" to counteract the distance, anonymity, and formality that often characterize large lecture-style courses in higher education. One author (E. P.) has been teaching a 300-student general education critical thinking course for ten years, and the…

  7. Lubrol-RAFTs in melanoma cells: a molecular platform for tumor-promoting ephrin-B2-integrin-beta1 interaction.

    PubMed

    Meyer, Stefanie; Orsó, Evelyn; Schmitz, Gerd; Landthaler, Michael; Vogt, Thomas

    2007-07-01

    Ephrins control cell motility and matrix adhesion. These functions play a pivotal role in cancer progression, for example, in malignant melanomas. We have previously shown that the ephrin-B2-tumor-promoting action is partly mediated by integrin-beta1 interaction. However, the subcellular prerequisites for molecular interaction like molecular proximity and co-compartmentalization have not been elucidated yet. Specific cholesterol-rich microdomains, termed lipid rafts (RAFTs), are known to be essential for functional ephrin-B2 signalling and integrin-mediated effects. Therefore, we addressed the question whether RAFT co-compartmentalization of both molecules could provide the molecular platform for their tumor-promoting interaction. In this study, we show that overexpressed ephrin-B2 is not only compartmentalized to classical Triton X-100 RAFTs in B16 melanoma cells, but also to the recently defined Lubrol-RAFTs. Interestingly, in the melanoma cells investigated, integrin-beta1 is also preferentially detected in such Lubrol-RAFTs. Accordingly, the presence of ephrin-B2 and integrin-beta1 in RAFTs and their function in cell migration and matrix attachment are highly sensitive to RAFT disruption by cholesterol depletion. Confocal fluorescence microscopy analyses also support the concept of a close molecular proximity and functional interplay of ephrin-B2 and integrin-beta1 in the plasma membrane. We conclude that Lubrol-RAFTs probably represent the platform for tumor-promoting ephrin-B2-integrin-beta1 interaction, which could become an interesting target for future antitumoral therapies.

  8. Inhibition of angiogenesis by leflunomide via targeting the soluble ephrin-A1/EphA2 system in bladder cancer.

    PubMed

    Chu, Maolin; Zhang, Chunying

    2018-01-24

    Angiogenesis plays an important role in bladder cancer (BCa). The immunosuppressive drug leflunomide has attracted worldwide attention. However, the effects of leflunomide on angiogenesis in cancer remain unclear. Here, we report the increased expression of soluble ephrin-A1 (sEphrin-A1) in supernatants of BCa cell lines (RT4, T24, and TCCSUP) co-cultured with human umbilical vein endothelial cells (HUVECs) compared with that in immortalized uroepithelial cells (SV-HUC-1) co-cultured with HUVECs. sEphrin-A1 is released from BCa cells as a monomeric protein that is a functional form of the ligand. The co-culture supernatants containing sEphrin-A1 caused the internalization and down-regulation of EphA2 on endothelial cells and dramatic functional activation of HUVECs. This sEphrin-A1/EphA2 system is mainly functional in regulating angiogenesis in BCa tissue. We showed that leflunomide (LEF) inhibited angiogenesis in a N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced bladder carcinogenesis model and a tumor xenograft model, as well as in BCa cell and HUVEC co-culture systems, via significant inhibition of the sEphrin-A1/EphA2 system. Ephrin-A1 overexpression could partially reverse LEF-induced suppression of angiogenesis and subsequent tumor growth inhibition. Thus, LEF has a significant anti-angiogenesis effect on BCa cells and BCa tissue via its inhibition of the functional angiogenic sEphrin-A1/EphA2 system and may have potential for treating BCa beyond immunosuppressive therapy.

  9. EphA2 transmembrane domain is uniquely required for keratinocyte migration by regulating ephrin-A1 levels.

    PubMed

    Ventrella, Rosa; Kaplan, Nihal; Hoover, Paul; Perez White, Bethany E; Lavker, Robert M; Getsios, Spiro

    2018-04-26

    EphA2 receptor tyrosine kinase (RTK) is activated by ephrin-A1 ligand, which harbors a GPI-anchor that enhances lipid raft localization. While EphA2 and ephrin-A1 modulate keratinocyte migration and differentiation, the ability of this cell-cell communication complex to localize to different membrane regions in keratinocytes remains unknown. Using a combination of biochemical and imaging approaches, we provide evidence that ephrin-A1 and a ligand-activated form of EphA2 partition outside of lipid raft domains in response to calcium-mediated cell-cell contact stabilization in normal human epidermal keratinocytes (NHEKs). EphA2 transmembrane domain (TMD) swapping with a shorter and molecularly distinct TMD of EphA1 resulted in decreased localization of this RTK at cell-cell junctions and increased expression of ephrin-A1, which is a negative regulator of keratinocyte migration. Accordingly, altered EphA2 membrane distribution at cell-cell contacts limited the ability of keratinocytes to seal linear scratch wounds in vitro in an ephrin-A1-dependent manner. Collectively, these studies highlight a key role for the EphA2 TMD in receptor-ligand membrane distribution at cell-cell contacts that modulates ephrin-A1 levels to allow for efficient keratinocyte migration with relevance for cutaneous wound healing. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  10. EphA2/Ephrin-A1 Mediate Corneal Epithelial Cell Compartmentalization via ADAM10 Regulation of EGFR Signaling

    PubMed Central

    Kaplan, Nihal; Ventrella, Rosa; Peng, Han; Pal-Ghosh, Sonali; Arvanitis, Constadina; Rappoport, Joshua Z.; Mitchell, Brian J.; Stepp, Mary Ann; Lavker, Robert M.

    2018-01-01

    Purpose Progenitor cells of the limbal epithelium reside in a discrete area peripheral to the more differentiated corneal epithelium and maintain tissue homeostasis. What regulates the limbal–corneal epithelial boundary is a major unanswered question. Ephrin-A1 ligand is enriched in the limbal epithelium, whereas EphA2 receptor is concentrated in the corneal epithelium. This reciprocal pattern led us to assess the role of ephrin-A1 and EphA2 in limbal–corneal epithelial boundary organization. Methods EphA2-expressing corneal epithelial cells engineered to express ephrin-A1 were used to study boundary formation in vitro in a manner that mimicked the relative abundance of these juxtamembrane signaling proteins in the limbal and corneal epithelium in vivo. Interaction of these two distinct cell populations following initial seeding into discrete culture compartments was assessed by live cell imaging. Immunofluoresence and immunoblotting was used to evaluate the contribution of downstream growth factor signaling and cell–cell adhesion systems to boundary formation at sites of heterotypic contact between ephrin-A1 and EphA2 expressing cells. Results Ephrin-A1–expressing cells impeded and reversed the migration of EphA2-expressing corneal epithelial cells upon heterotypic contact formation leading to coordinated migration of the two cell populations in the direction of an ephrin-A1–expressing leading front. Genetic silencing and pharmacologic inhibitor studies demonstrated that the ability of ephrin-A1 to direct migration of EphA2-expressing cells depended on an a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) and epidermal growth factor receptor (EGFR) signaling pathway that limited E-cadherin–mediated adhesion at heterotypic boundaries. Conclusions Ephrin-A1/EphA2 signaling complexes play a key role in limbal–corneal epithelial compartmentalization and the response of these tissues to injury. PMID:29351356

  11. EphA2/Ephrin-A1 Mediate Corneal Epithelial Cell Compartmentalization via ADAM10 Regulation of EGFR Signaling.

    PubMed

    Kaplan, Nihal; Ventrella, Rosa; Peng, Han; Pal-Ghosh, Sonali; Arvanitis, Constadina; Rappoport, Joshua Z; Mitchell, Brian J; Stepp, Mary Ann; Lavker, Robert M; Getsios, Spiro

    2018-01-01

    Progenitor cells of the limbal epithelium reside in a discrete area peripheral to the more differentiated corneal epithelium and maintain tissue homeostasis. What regulates the limbal-corneal epithelial boundary is a major unanswered question. Ephrin-A1 ligand is enriched in the limbal epithelium, whereas EphA2 receptor is concentrated in the corneal epithelium. This reciprocal pattern led us to assess the role of ephrin-A1 and EphA2 in limbal-corneal epithelial boundary organization. EphA2-expressing corneal epithelial cells engineered to express ephrin-A1 were used to study boundary formation in vitro in a manner that mimicked the relative abundance of these juxtamembrane signaling proteins in the limbal and corneal epithelium in vivo. Interaction of these two distinct cell populations following initial seeding into discrete culture compartments was assessed by live cell imaging. Immunofluoresence and immunoblotting was used to evaluate the contribution of downstream growth factor signaling and cell-cell adhesion systems to boundary formation at sites of heterotypic contact between ephrin-A1 and EphA2 expressing cells. Ephrin-A1-expressing cells impeded and reversed the migration of EphA2-expressing corneal epithelial cells upon heterotypic contact formation leading to coordinated migration of the two cell populations in the direction of an ephrin-A1-expressing leading front. Genetic silencing and pharmacologic inhibitor studies demonstrated that the ability of ephrin-A1 to direct migration of EphA2-expressing cells depended on an a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) and epidermal growth factor receptor (EGFR) signaling pathway that limited E-cadherin-mediated adhesion at heterotypic boundaries. Ephrin-A1/EphA2 signaling complexes play a key role in limbal-corneal epithelial compartmentalization and the response of these tissues to injury.

  12. Variable Combinations of Specific Ephrin Ligand/Eph Receptor Pairs Control Embryonic Tissue Separation

    PubMed Central

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

    2014-01-01

    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. PMID:25247423

  13. Expressions of EphA2 and EphrinA-1 in early squamous cell cervical carcinomas and their relation to prognosis

    PubMed Central

    Holm, Ruth; de Putte, Gregg Van; Suo, Zhenhe; Lie, A Kathrine; Kristensen, Gunnar B

    2008-01-01

    By using immunohistochemistry we investigated the expression of EphA2 and EphrinA-1 in 217 early squamous cell cervical carcinomas and examine their prognostic relevance. For EphA2 expression, 21 tumors (10%) showed negative, 108 (50%) weak positive, 69 (32%) moderate positive and 19 (9%) strong positive, whereas for EphrinA-1 expression, 33 tumors (15%) showed negative, 91 (42%) weak positive, 67 (31%) moderate positive and 26 (12%) strong positive. In univariate analysis high expression (strong staining) of EphrinA-1 was associated with poor disease-free (P = 0.033) and disease-specific (P = 0.039) survival. However, in the multivariate analyses neither EphrinA-1 nor EphA2 was significantly associated to survival. The increased levels of EphA2 and EphrinA-1 in a relative high number of early stage squamous cell carcinomas suggested that these two proteins may play an important role in the development of a subset of early cervical cancers. However, EphA2 and EphrinA-1 were not independently associated with clinical outcome. PMID:18566674

  14. Expression of EphA2 and Ephrin A-1 in carcinoma of the urinary bladder.

    PubMed

    Abraham, Shaji; Knapp, Deborah W; Cheng, Liang; Snyder, Paul W; Mittal, Suresh K; Bangari, Dinesh S; Kinch, Michael; Wu, Lan; Dhariwal, Jay; Mohammed, Sulma I

    2006-01-15

    The EphA2 receptor tyrosine kinase is believed to play a role in tumor growth and metastasis. The clinical significance of the expression of EphA2 was observed in breast, prostate, colon, skin, cervical, ovarian, and lung cancers. The purpose of this work was to determine the expression of EphA2 and its ligand, Ephrin A-1, and E-cadherin in carcinoma of the urinary bladder, and determine EphA2 as a new target for therapy in bladder cancer. EphA2 mRNA and protein expression was investigated by reverse transcription-PCR and Western blot, respectively, in bladder cancer cell lines. In addition, the expression of EphA2, Ephrin A-1, and E-cadherin in tissues from patients with different stages of urinary bladder cancer was determined by immunohistochemistry. Furthermore, the ability of Ephrin A-1 to inhibit growth of bladder cancer cells was also investigated using an adenoviral delivery system. Western blot analysis showed high EphA2 expression in TCCSUP, T24, and UMUC-3 cell lines. In tissues, the staining intensity of EphA2 was less in normal urothelium but increased greatly in advancing stages of urothelial carcinoma (P < 0.05). Similarly, the staining intensity of Ephrin A-1 was low in normal tissues and high in cancerous tissues, but it was similar across the various stages of urothelial carcinoma (T(a)-T(4)). E-cadherin immunoreactivity decreased in urothelial cancer. Association of EphA2 and Ephrin A-1 expression was found to be significant between T(a) stage and T(1)-T(2) (P < 0.04) and T(a) and T(3)-T(4) stages (P < 0.0001). Adenovirus delivery of Ephrin A-1 inhibited proliferation of TCCSUP cells. EphA2 may serve as a novel target for bladder cancer therapy.

  15. EPHRIN-B1 Mosaicism Drives Cell Segregation in Craniofrontonasal Syndrome hiPSC-Derived Neuroepithelial Cells.

    PubMed

    Niethamer, Terren K; Larson, Andrew R; O'Neill, Audrey K; Bershteyn, Marina; Hsiao, Edward C; Klein, Ophir D; Pomerantz, Jason H; Bush, Jeffrey O

    2017-03-14

    Although human induced pluripotent stem cells (hiPSCs) hold great potential for the study of human diseases affecting disparate cell types, they have been underutilized in seeking mechanistic insights into the pathogenesis of congenital craniofacial disorders. Craniofrontonasal syndrome (CFNS) is a rare X-linked disorder caused by mutations in EFNB1 and characterized by craniofacial, skeletal, and neurological anomalies. Heterozygous females are more severely affected than hemizygous males, a phenomenon termed cellular interference that involves mosaicism for EPHRIN-B1 function. Although the mechanistic basis for cellular interference in CFNS has been hypothesized to involve Eph/ephrin-mediated cell segregation, no direct evidence for this has been demonstrated. Here, by generating hiPSCs from CFNS patients, we demonstrate that mosaicism for EPHRIN-B1 expression induced by random X inactivation in heterozygous females results in robust cell segregation in human neuroepithelial cells, thus supplying experimental evidence that Eph/ephrin-mediated cell segregation is relevant to pathogenesis in human CFNS patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2005-01-01

    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 ephrin-B1/2 expressing rat IEC-6-cells with recombinant EphB1-Fc 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. PMID:15996027

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

    PubMed Central

    Lee, Hung-Yen; Mohammed, Kamal A; Kaye, Fredric; Sharma, Parvesh; Moudgil, Brij M; Clapp, William L; Nasreen, Najmunnisa

    2013-01-01

    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-dioleoyloxy)propyl]-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 (miR–LNP) showed improved transfection efficiency against MPM and NSCLC. The effectiveness of targeted delivery of let-7a miR encapsulated ephrin-A1 conjugated LNP (miR–ephrin-A1–LNP) was determined on MPM and NSCLC tumor growth in vitro. miR–ephrin-A1–LNP significantly increased the delivery of let-7a miR in lung cancer cells when compared with free let-7a miR. In addition, the expression of target gene Ras was significantly repressed following miR–ephrin-A1–LNP treatment. Furthermore, the miR–ephrin-A1–LNP complex significantly inhibited MPM and NSCLC proliferation, migration, and tumor growth. Our results demonstrate that the engineered miR–ephrin

  18. A taspine derivative supresses Caco-2 cell growth by competitively targeting EphrinB2 and regulating its pathway.

    PubMed

    Dai, Bingling; Wang, Wenjie; Ma, Yujiao; Liu, Rui; Zhang, Yanmin

    2016-09-01

    Colorectal cancer is a common gastrointestinal malignancy worldwide and it is a lethal and aggressive malignancy with a dismal prognosis. In the present study, we investigated the effect of taspine derivative 12k on human colorectal cancer targeted at EphrinB2 and its PDZ. The results indicated that 12k could bind to EphrinB2 and showed a higher suppressive effect on EphrinB2/HEK293 than on HEK293 cells. Caco‑2 cells were screened for high expression of EphrinB2. We found that 12k not only significantly decreased Caco‑2 cell viability and colony formation but impaired migration. Meanwhile, 12k effectively inhibited blood vessel formation in a tissue model of angiogenesis. Mechanistic studies revealed that 12k significantly reduced the phosphorylation of EphrinB2 and PDZ protein PICK1. Accordingly, it was associated with the downregulation by 12k of the PI3K/AKT/mTOR and MAPK signaling pathways which were downstream of VEGFR2, yet it had no effect on VEGFR3. Moreover, the expression of CD34, CD45 and HIF‑1α were downregulated in the Caco‑2 cells. In conclusion, our findings showed that 12k had an inhibitory effect on the growth of Caco-2 cells, and it functioned by interrupting the phosphorylation of EphrinB2 and its related signaling pathway.

  19. Asymmetric dimethylarginine contributes to retinal neovascularization of diabetic retinopathy through EphrinB2 pathway.

    PubMed

    Du, Mei-Rong; Yan, Li; Li, Nian-Sheng; Wang, Yu-Jie; Zhou, Ting; Jiang, Jun-Lin

    2018-05-16

    Diabetic retinopathy (DR) is a leading cause of vision loss with retinal neovascularization. This study aims to investigate whether Asymmetric dimethylarginine (ADMA) impacts the pathogenesis of DR via focusing on promoting retinal neovascularization and its underlying molecular mechanisms. Diabetic rats were induced by a single intraperitoneal injection of streptozotocin (STZ) for 20 weeks. ADMA levels in aqueous and the influence of hypoxia on ADMA and angiogenesis in RF/6A cells were examined. The effects and underlying molecular mechanisms of ADMA on neovascularization of RF/6A cells were further evaluated by administration of ADMA, DDAH siRNA or ephrinB2 siRNA. Results showed that ADMA levels were elevated in both aqueous from diabetic rats and culture medium in RF/6A cells pretreated with hypoxia. Administration of ADMA directly promoted proliferation, migration, adhesion and tube formation of RF/6A cells, which was further confirmed by DDAH1 siRNA or DDAH2 siRNA. In addition, ephrinB2 expression was increased under diabetic conditions, and the angiogenic effects of ADMA were blocked by ephrinB2 siRNA. In conclusion, ADMA contributes to the neovascularization of retina in diabetic mellitus, which is regulated by ephrinB2. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. EphrinA1-EphA2 interaction-mediated apoptosis and Flt3L-induced immunotherapy inhibits tumor growth in a breast cancer mouse model

    PubMed Central

    Tandon, Manish; Vemula, Sai V.; Sharma, Anurag; Ahi, Yadvinder S.; Mittal, Shalini; Bangari, Dinesh S.; Mittal, Suresh K.

    2014-01-01

    Background The receptor tyrosine kinase EphA2 is overexpressed in several types of cancers and is currently being pursued as a target for breast cancer therapeutics. The EphA2 ligand EphrinA1 induces EphA2 phosphorylation and intracellular internalization and degradation, thus inhibiting tumor progression. The hematopoietic growth factor, FMS-like tyrosine kinase receptor ligand (Flt3L), promotes expansion and mobilization of functional dendritic cells. Methods We tested the EphrinA1-EphA2 interaction in MDA-MB-231 breast cancer cells focusing on the receptor-ligand-mediated apoptosis of breast cancer cells. In order to determine whether the EphrinA1-EphA2 interaction-associated apoptosis and Flt3L-mediated immunotherapy would have an additive effect in inhibiting tumor growth, we used an immunocompetent mouse model of breast cancer to evaluate intratumoral (i.t.) inoculation strategies with human adenovirus (HAd) vectors expressing either EphrinA1 (HAd-EphrinA1-Fc), Flt3L (HAd-Flt3L) or a combination of EphrinA1-Fc + Flt3L (HAd-EphrinA1-Fc + HAd-Flt3L). Results In vitro analysis demonstrated that an EphrinA1-EphA2 interaction led to apoptosis-related changes in breast cancer cells. In vivo, three i.t. inoculations of HAd-EphrinA1-Fc showed potent inhibition of tumor growth. Furthermore, increased inhibition in tumor growth was observed with the combination of HAd-EphrinA1-Fc and HAd-Flt3L accompanied by the generation of an anti-tumor adaptive immune response. Conclusions The results indicating induction of apoptosis and inhibition of mammary tumor growth show the potential therapeutic benefits of HAd-EphrinA1-Fc. In combination with HAd-Flt3L, this represents a promising strategy to effectively induce mammary tumor regression by HAd vector-based therapy. PMID:22228563

  1. Up-regulated ephrinB3/EphB3 expression in intractable temporal lobe epilepsy patients and pilocarpine induced experimental epilepsy rat model.

    PubMed

    Huang, Hao; Li, Ruohan; Yuan, Jinxian; Zhou, Xin; Liu, Xi; Ou, Shu; Xu, Tao; Chen, Yangmei

    2016-05-15

    EphB family receptor tyrosine kinases, in cooperation with cell surface-bound ephrinB ligands, play a critical role in maintenance of dendritic spine morphogenesis, axons guidance, synaptogenesis, synaptic reorganization and plasticity in the central nervous system (CNS). However, the expression pattern of ephrinB/EphB in intractable temporal lobe epilepsy (TLE) and the underlying molecular mechanisms during epileptogenesis remain poorly understood. Here we investigated the expression pattern and cellular distribution of ephrinB/EphB in intractable TLE patients and lithium chloride-pilocarpine induced TLE rats using real-time quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry, double-labeled immunofluorescence and Western blot analysis. Compared to control groups, ephrinB3 and EphB3 mRNA expression were significantly up-regulated in intractable TLE patients and TLE rats, while the mRNA expression trend of ephrinB1/2 and EphB1/2/4/6 in intractable TLE patients and TLE rats were inconsistent. Western blot analysis and semi-quantitative immunohistochemistry confirmed that ephrinB3 and EphB3 protein level were up-regulated in intractable TLE patients and TLE rats. At the same time, double-labeled immunofluorescence indicate that ephrinB3 was expressed mainly in the cytoplasm and protrusions of glia and neurons, while EphB3 was expressed mainly in the cytoplasm of neurons. Taken together, up-regulated expression of ephrinB3/EphB3 in intractable TLE patients and experimental TLE rats suggested that ephrinB3/EphB3 might be involved in the pathogenesis of TLE. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Eph/Ephrin signalling maintains eye field segregation from adjacent neural plate territories during forebrain morphogenesis

    PubMed Central

    Cavodeassi, Florencia; Ivanovitch, Kenzo; Wilson, Stephen W.

    2013-01-01

    During forebrain morphogenesis, there is extensive reorganisation of the cells destined to form the eyes, telencephalon and diencephalon. Little is known about the molecular mechanisms that regulate region-specific behaviours and that maintain the coherence of cell populations undergoing specific morphogenetic processes. In this study, we show that the activity of the Eph/Ephrin signalling pathway maintains segregation between the prospective eyes and adjacent regions of the anterior neural plate during the early stages of forebrain morphogenesis in zebrafish. Several Ephrins and Ephs are expressed in complementary domains in the prospective forebrain and combinatorial abrogation of their activity results in incomplete segregation of the eyes and telencephalon and in defective evagination of the optic vesicles. Conversely, expression of exogenous Ephs or Ephrins in regions of the prospective forebrain where they are not usually expressed changes the adhesion properties of the cells, resulting in segregation to the wrong domain without changing their regional fate. The failure of eye morphogenesis in rx3 mutants is accompanied by a loss of complementary expression of Ephs and Ephrins, suggesting that this pathway is activated downstream of the regional fate specification machinery to establish boundaries between domains undergoing different programmes of morphogenesis. PMID:24026122

  3. Ephrin reverse signaling mediates palatal fusion and epithelial-to-mesenchymal transition independently of Tgfß3.

    PubMed

    Serrano, Maria J; Liu, Jingpeng; Svoboda, Kathy K H; Nawshad, Ali; Benson, M Douglas

    2015-12-01

    The mammalian secondary palate forms from shelves of epithelia-covered mesenchyme that meet at midline and fuse. The midline epithelial seam (MES) is thought to degrade by apoptosis, epithelial-to-mesenchymal transition (EMT), or both. Failure to degrade the MES blocks fusion and causes cleft palate. It was previously thought that transforming growth factor ß3 (Tgfß3) is required to initiate fusion. Members of the Eph tyrosine kinase receptor family and their membrane-bound ephrin ligands are expressed on the MES. We demonstrated that treatment of mouse palates with recombinant EphB2/Fc to activate ephrin reverse signaling (where the ephrin acts as a receptor and transduces signals from its cytodomain) was sufficient to cause mouse palatal fusion when Tgfß3 signaling was blocked by an antibody against Tgfß3 or by an inhibitor of the TgfßrI serine/threonine receptor kinase. Cultured palatal epithelial cells traded their expression of epithelial cell markers for that of mesenchymal cells and became motile after treatment with EphB2/Fc. They concurrently increased their expression of the EMT-associated transcription factors Snail, Sip1, and Twist1. EphB2/Fc did not cause apoptosis in these cells. These data reveal that ephrin reverse signaling directs palatal fusion in mammals through a mechanism that involves EMT but not apoptosis and activates a gene expression program not previously associated with ephrin reverse signaling. © 2015 Wiley Periodicals, Inc.

  4. Ephrin-B2 Reverse Signaling Is Required for Topography but Not Pattern Formation of Lateral Superior Olivary Inputs to the Inferior Colliculus

    PubMed Central

    Wallace, Matthew M.; Kavianpour, Sarah M.; Gabriele, Mark L.

    2014-01-01

    Graded and modular expressions of Eph-ephrins are known to provide positional information for the formation of topographic maps and patterning in the developing nervous system. Previously we have shown that ephrin-B2 is expressed in a continuous gradient across the tonotopic axis of the central nucleus of the inferior colliculus (CNIC), whereas patterns are discontinuous and modular in the lateral cortex of the IC (LCIC). The present study explores the involvement of ephrin-B2 signaling in the development of projections to the CNIC and LCIC arising from the lateral superior olivary nuclei (LSO) prior to hearing onset. Anterograde and retrograde fluorescent tracing methods in neonatal fixed tissue preparations were used to compare topographic mapping and the establishment of LSO layers/modules in wild-type and ephrin-B2lacZ/+ mice (severely compromised reverse signaling). At birth, pioneer LSO axons occupy the ipsilateral IC in both groups but are delayed contralaterally in ephrin-B2lacZ/+ mutants. By the onset of hearing, both wild-type and mutant projections form discernible layers bilaterally in the CNIC and modular arrangements within the ipsilateral LCIC. In contrast, ephrin-B2lacZ/+ mice lack a reliable topography in LSO-IC projections, suggesting that fully functional ephrin-B2 reverse signaling is required for normal projection mapping. Taken together, these ephrin-B2 findings paired with known coexpression of EphA4 suggest the importance of these signaling proteins in establishing functional auditory circuits prior to experience. PMID:23042409

  5. Ephrin-B2 reverse signaling is required for topography but not pattern formation of lateral superior olivary inputs to the inferior colliculus.

    PubMed

    Wallace, Matthew M; Kavianpour, Sarah M; Gabriele, Mark L

    2013-05-01

    Graded and modular expressions of Eph-ephrins are known to provide positional information for the formation of topographic maps and patterning in the developing nervous system. Previously we have shown that ephrin-B2 is expressed in a continuous gradient across the tonotopic axis of the central nucleus of the inferior colliculus (CNIC), whereas patterns are discontinuous and modular in the lateral cortex of the IC (LCIC). The present study explores the involvement of ephrin-B2 signaling in the development of projections to the CNIC and LCIC arising from the lateral superior olivary nuclei (LSO) prior to hearing onset. Anterograde and retrograde fluorescent tracing methods in neonatal fixed tissue preparations were used to compare topographic mapping and the establishment of LSO layers/modules in wild-type and ephrin-B2(lacZ/+) mice (severely compromised reverse signaling). At birth, pioneer LSO axons occupy the ipsilateral IC in both groups but are delayed contralaterally in ephrin-B2(lacZ/+) mutants. By the onset of hearing, both wild-type and mutant projections form discernible layers bilaterally in the CNIC and modular arrangements within the ipsilateral LCIC. In contrast, ephrin-B2(lacZ/+) mice lack a reliable topography in LSO-IC projections, suggesting that fully functional ephrin-B2 reverse signaling is required for normal projection mapping. Taken together, these ephrin-B2 findings paired with known coexpression of EphA4 suggest the importance of these signaling proteins in establishing functional auditory circuits prior to experience. Copyright © 2012 Wiley Periodicals, Inc.

  6. Regulation of hippocampal synaptic plasticity by the tyrosine kinase receptor, REK7/EphA5, and its ligand, AL-1/Ephrin-A5.

    PubMed

    Gao, W Q; Shinsky, N; Armanini, M P; Moran, P; Zheng, J L; Mendoza-Ramirez, J L; Phillips, H S; Winslow, J W; Caras, I W

    1998-08-01

    The Eph-related tyrosine kinase receptor, REK7/EphA5, mediates the effects of AL-1/Ephrin-A5 and related ligands and is involved in the guidance of retinal, cortical, and hippocampal axons during development. The continued expression of REK7/EphA5 in the adult brain, in particular in areas associated with a high degree of synaptic plasticity such as the hippocampus, raises the question of its function in the mature nervous system. In this report we examined the role of REK7/EphA5 in synaptic remodeling by asking if agents that either block or activate REK7/EphA5 affect synaptic strength in hippocampal slices from adult mouse brain. We show that a REK7/EphA5 antagonist, soluble REK7/EphA5-IgG, impairs the induction of long-term potentiation (LTP) without affecting other synaptic parameters such as normal synaptic transmission or paired-pulse facilitation. In contrast, perfusion with AL-1/Ephrin-A5-IgG, an activator of REK7/EphA5, induces a sustained increase in normal synaptic transmission that partially mimics LTP. The sustained elevation of normal synaptic transmission could be attributable to a long-lasting binding of the AL-1/Ephrin-A5-IgG to the endogenous REK7/EphA5 receptor, as revealed by immunohistochemistry. Furthermore, maximal electrical induction of LTP occludes the potentiating effects of subsequent treatment with AL-1/Ephrin-A5-IgG. Taken together these results implicate REK7/EphA5 in the regulation of synaptic plasticity in the mature hippocampus and suggest that REK7/EphA5 activation is recruited in the LTP induced by tetanization. Copyright 1998 Academic Press.

  7. Interaction between EphrinB1 and CNK1 Found to Play Role in Tumor Progression | Poster

    Cancer.gov

    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

  8. EphrinA4 plays a critical role in α4 and αL mediated survival of human CLL cells during extravasation

    PubMed Central

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

    2016-01-01

    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

  9. Interaction between EphrinB1 and CNK1 Found to Play Role in Tumor Progression | Poster

    Cancer.gov

    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.”

  10. Stimulation of EphB2/ephrin-B1 signalling by tumour necrosis factor alpha in human dental pulp stem cells.

    PubMed

    Zhu, Lifang; Dissanayaka, Waruna Lakmal; Green, David William; Zhang, Chengfei

    2015-04-01

    The aim of this study was to investigate whether in vitro stimulation of dental pulp stem cells (DPSCs) by tumour necrosis factor alpha (TNF-α) would induce secretion of EphB2/ephrin-B1 signalling. Dental pulp stem cells isolated from human dental pulp were treated with TNF-α (5-100 ng/ml) over 2-48 h. EphB2/ephrin-B1 mRNA and protein levels were measured by real-time polymerase chain reaction (RT-PCR) and western blot analysis respectively. Additionally, DPSCs were pre-incubated with TNF-α receptor neutralizing antibodies or infected with nuclear factor-kappa B (NF-ĸB) inhibitor, p38 MAPK inhibitor, Jun N-terminal kinase (JNK) inhibitor and MEK inhibitor before TNF-α treatment. Results were analysed by one-way ANOVA. Tumour necrosis factor alpha increased EphB2 mRNA expression in DPSCs at concentrations up to 20 ng/ml and ephrin-B1 at concentrations up to 40 ng/ml (P < 0.05). Its mRNA expression reached maximum at 24 h when treated with TNF-α at 20 ng/ml (P < 0.05). EphB2/ephrin-B1 protein expression levels were high at 16 and 24 h as shown by western blotting. Neutralizing antibodies for TNFR1/2 receptors down-regulated EphB2/ephrin-B1 mRNA expression (P < 0.05) and ephrin-B1 protein expression, but not EphB2 protein expression. JNK-inhibitor inhibited EphB2 mRNA expression only (P < 0.05). EphB2/ephrin-B1 were invoked in DPSCs with TNF-α treatment via the JNK-dependent pathway, but not NF-ĸB, p38 MAPK or MEK signalling. © 2015 John Wiley & Sons Ltd.

  11. PTP-PEST controls EphA3 activation and ephrin-induced cytoskeletal remodelling.

    PubMed

    Mansour, Mariam; Nievergall, Eva; Gegenbauer, Kristina; Llerena, Carmen; Atapattu, Lakmali; Hallé, Maxime; Tremblay, Michel L; Janes, Peter W; Lackmann, Martin

    2016-01-15

    Eph receptors and their corresponding membrane-bound ephrin ligands regulate cell positioning and establish tissue patterns during embryonic and oncogenic development. Emerging evidence suggests that assembly of polymeric Eph signalling clusters relies on cytoskeletal reorganisation and underlies regulation by protein tyrosine phosphatases (PTPs). PTP-PEST (also known as PTPN12) is a central regulator of actin cytoskeletal dynamics. Here, we demonstrate that an N-terminal fragment of PTP-PEST, generated through an ephrinA5-triggered and spatially confined cleavage mediated by caspase-3, attenuates EphA3 receptor activation and its internalisation. Isolation of EphA3 receptor signalling clusters within intact plasma membrane fragments obtained by detergent-free cell fractionation reveals that stimulation of cells with ephrin triggers effective recruitment of this catalytically active truncated form of PTP-PEST together with key cytoskeletal and focal adhesion proteins. Importantly, modulation of actin polymerisation using pharmacological and dominant-negative approaches affects EphA3 phosphorylation in a similar manner to overexpression of PTP-PEST. We conclude that PTP-PEST regulates EphA3 activation both by affecting cytoskeletal remodelling and through its direct action as a PTP controlling EphA3 phosphorylation, indicating its multifaceted regulation of Eph signalling. © 2016. Published by The Company of Biologists Ltd.

  12. Loss of ephrinB1 in osteogenic progenitor cells impedes endochondral ossification and compromises bone strength integrity during skeletal development.

    PubMed

    Nguyen, Thao M; Arthur, Agnieszka; Paton, Sharon; Hemming, Sarah; Panagopoulos, Romana; Codrington, John; Walkley, Carl R; Zannettino, Andrew C W; Gronthos, Stan

    2016-12-01

    The EphB receptor tyrosine kinase family and their ephrinB ligands have been implicated as mediators of skeletal development and bone homeostasis in humans, where mutations in ephrinB1 contribute to frontonasal dysplasia and coronal craniosynostosis. In mouse models, ephrinB1 has been shown to be a critical factor mediating osteoblast function. The present study examined the functional importance of ephrinB1 during endochondral ossification using the Cre recombination system with targeted deletion of ephrinB1 (EfnB1 fl/fl ) in osteogenic progenitor cells, under the control of the osterix (Osx:Cre) promoter. The Osx:EfnB1 -/- mice displayed aberrant bone growth during embryonic and postnatal skeletal development up to 4weeks of age, when compared to the Osx:Cre controls. Furthermore, compared to the Osx:Cre control mice, the Osx:EfnB1 -/- mice exhibited significantly weaker and less rigid bones, with a reduction in trabecular/ cortical bone formation, reduced trabecular architecture and a reduction in the size of the growth plates at the distal end of the femora from newborn through to 4weeks of age. The aberrant bone formation correlated with increased numbers of tartrate resistant acid phosphatase positive osteoclasts and decreased numbers of bone lining osteoblasts in 4week old Osx:EfnB1 -/- mice, compared to Osx:Cre control mice. Taken together, these observations demonstrate the importance of ephrinB1 signalling between cells of the skeleton required for endochondral ossification. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Assessing EphA2 and Ephrin-A as Novel Diagnostic and Prognostic Biomarkers of Prostate Cancer

    DTIC Science & Technology

    2017-10-01

    prostatectomy at our institution. We will correlate their levels of EphA2 and ephrin-A1 mRNA as well as staining of phosphorylated pS897-EphA2 to the...protein. These values will then be correlated to the presence or absence of PCa, the aggressiveness of PCa as determined by traditional clinical...from malignant prostate tissue and/or correlate with cancer aggressiveness. ▪ Major Task 1: Characterize EphA2 and ephrin-A expression levels in

  14. All-trans retinoic acid attenuates bleomycin-induced pulmonary fibrosis via downregulating EphA2-EphrinA1 signaling.

    PubMed

    Leem, Ah Young; Shin, Mi Hwa; Douglas, Ivor S; Song, Joo Han; Chung, Kyung Soo; Kim, Eun Young; Jung, Ji Ye; Kang, Young Ae; Chang, Joon; Kim, Young Sam; Park, Moo Suk

    2017-09-23

    The role of all-trans retinoic acid (ATRA) in pulmonary fibrosis is relatively unknown, although this metabolite modulates cell differentiation, proliferation, and development. We aimed to evaluate the role of ATRA in bleomycin-induced pulmonary fibrosis, and whether the mechanism involves EphA2-EphrinA1 and PI3K-Akt signaling. We evaluated three groups of mice: a control group (intraperitoneal DMSO injection 3 times weekly after PBS instillation), bleomycin group (intraperitoneal DMSO injection 3 times weekly after bleomycin instillation), and bleomycin + ATRA group (intraperitoneal ATRA injection 3 times weekly after bleomycin instillation). The cell counts and protein concentration in the bronchoalveolar lavage fluid (BALF), changes in histopathology, Ashcroft score, hydroxyproline assay, expression of several signal pathway proteins including EphA2-EphrinA1, and PI3K-Akt, and cytokine levels were compared among the groups. We found that bleomycin significantly increased the protein concentration in the BALF, Ashcroft score in lung tissue, and hydroxyproline contents in lung lysates. Furthermore, bleomycin upregulated EphA2, EphrinA1, PI3K 110γ, Akt, IL-6 and TNF-α. However, administration of ATRA attenuated the upregulation of EphA2-EphrinA1 and PI3K-Akt after bleomycin instillation, and decreased pulmonary fibrosis. In addition, ATRA suppressed IL-6 and TNF-α production induced by bleomycin-induced injury. Collectively, these data suggest that ATRA attenuates bleomycin-induced pulmonary fibrosis by regulating EphA2-EphrinA1 and PI3K-Akt signaling. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. EphrinA1 Inhibits Vascular Endothelial Growth Factor-Induced Intracellular Signaling and Suppresses Retinal Neovascularization and Blood-Retinal Barrier Breakdown

    PubMed Central

    Ojima, Tomonari; Takagi, Hitoshi; Suzuma, Kiyoshi; Oh, Hideyasu; Suzuma, Izumi; Ohashi, Hirokazu; Watanabe, Daisuke; Suganami, Eri; Murakami, Tomoaki; Kurimoto, Masafumi; Honda, Yoshihito; Yoshimura, Nagahisa

    2006-01-01

    The Eph receptor/ephrin system is a recently discovered regulator of vascular development during embryogenesis. Activation of EphA2, one of the Eph receptors, reportedly suppresses cell proliferation and adhesion in a wide range of cell types, including vascular endothelial cells. Vascular endothelial growth factor (VEGF) plays a primary role in both pathological angiogenesis and abnormal vascular leakage in diabetic retinopathy. In the study described herein, we demonstrated that EphA2 stimulation by ephrinA1 in cultured bovine retinal endothelial cells inhibits VEGF-induced VEGFR2 receptor phosphorylation and its downstream signaling cascades, including PKC (protein kinase C)-ERK (extracellular signal-regulated kinase) 1/2 and Akt. This inhibition resulted in the reduction of VEGF-induced angiogenic cell activity, including migration, tube formation, and cellular proliferation. These inhibitory effects were further confirmed in animal models. Intraocular injection of ephrinA1 suppressed ischemic retinal neovascularization in a dose-dependent manner in a mouse model. At a dose of 125 ng/eye, the inhibition was 36.0 ± 14.9% (P < 0.001). EphrinA1 also inhibited VEGF-induced retinal vascular permeability in a rat model by 46.0 ± 10.0% (P < 0.05). These findings suggest a novel therapeutic potential for EphA2/ephrinA1 in the treatment of neovascularization and vasopermeability abnormalities in diabetic retinopathy. PMID:16400034

  16. Inhibition of EphB4-ephrin-B2 signaling enhances response to Cetuximab-radiation therapy in head and neck cancers.

    PubMed

    Bhatia, Shilpa; Sharma, Jaspreet; Bukkapatnam, Sanjana; Oweida, Ayman; Lennon, Shelby; Phan, Andy V; Milner, Dallin; Uyanga, Nomin; Jimeno, Antonio; Raben, David; Somerset, Hilary; Heasley, Lynn; Karam, Sana D

    2018-05-30

    The clinical success of targeted therapies such as cetuximab and radiation (RT) is hampered by the low response rates and development of therapeutic resistance. In the current study, we investigated the involvement of EphB4-ephrin-B2 pro-tumorigenic signaling in mediating resistance to EGFR inhibition and radiation therapy in head and neck cancers. We used patient-derived xenograft (PDX) models of head and neck squamous cell carcinoma (HNSCC) and HNSCC cell lines to test our hypothesis. Tumor tissues were subjected to PhosphoRTK array, and western blotting to detect changes in EphB4-ephrin-B2 targets. mRNA sequencing and microarray data analysis was performed on PDX tumors and HNSCC cell lines respectively to determine differences in gene expression of molecules involved in tumor cell growth, proliferation, and survival pathways. Effects on cell growth were determined by MTT assay on HNSCC cells downregulated for EphB4/ephrin-B2 expression, with and without EGFR inhibitor and radiation. Our data from locally-advanced HNSCC patients treated with standard of care definitive chemo-RT show elevated EphB4 and ephrin-B2 levels after failure of treatment. We observed significant response towards cetuximab and radiation therapy following EphB4-ephrin-B2 inhibition resulting in improved survival in tumor-bearing mice. Tumor growth inhibition was accompanied by decrease in the levels of proliferation and pro-survival molecules and increased apoptosis. Our findings underscore the importance of adopting rational drug combinations to enhance therapeutic effect. Our study documenting enhanced response of HNSCC to cetuximab-RT therapy with EphB4-ephrin-B2 blockade has the potential to translate into clinic to benefit this patient population. Copyright ©2018, American Association for Cancer Research.

  17. Structure-activity relationships and mechanism of action of Eph-ephrin antagonists: interaction of cholanic acid with the EphA2 receptor

    PubMed Central

    Tognolini, Massimiliano; Incerti, Matteo; Mohamed, Iftiin Hassan; Giorgio, Carmine; Russo, Simonetta; Bruni, Renato; Lelli, Barbara; Bracci, Luisa; Noberini, Roberta; Pasquale, Elena B.; Barocelli, Elisabetta; Vicini, Paola; Mor, Marco

    2012-01-01

    The Eph–ephrin system, including the EphA2 receptor and the ephrin-A1 ligand, plays a critical role in tumor and vascular functions during carcinogenesis. We previously identified (3α,5β)-3-hydroxycholan-24-oic acid (lithocholic acid) as an Eph-ephrin antagonist able to inhibit EphA2 receptor activation and therefore potentially useful as a novel EphA2 receptor targeting agent. Here, we explore the structure-activity relationships of a focused set of lithocholic acid derivatives, based on molecular modelling investigation and displacement binding assays. Our exploration shows that while the 3-α-hydroxyl group of lithocholic acid has a negligible role in the recognition of the EphA2 receptor, its carboxylate group is critical for disrupting the binding of ephrin-A1 to the EphA2. As a result of our investigation, we identified (5β)-cholan-24-oic acid (cholanic acid) as a novel compound that competitively inhibits EphA2-ephrin-A1 interaction with higher potency than lithocholic acid. Surface plasmon resonance analysis indicates that cholanic acid binds specifically and reversibly to the ligand-binding domain of EphA2, with a steady-state dissociation constant (KD) in the low micromolar range. Furthermore, cholanic acid blocks the phosphorylation of EphA2 and cell retraction and rounding in PC3 prostate cancer cells, two effects that depend on EphA2 activation by the ephrin-A1 ligand. These findings suggest that cholanic acid can be used as a template structure to design effective EphA2 antagonists, with potential impact in the elucidation of the role played by this receptor in pathological conditions. PMID:22529030

  18. Generic Language Facilitates Children's Cross-Classification

    ERIC Educational Resources Information Center

    Nguyen, Simone P.; Gelman, A.

    2012-01-01

    Four studies examined the role of generic language in facilitating 4- and 5-year-old children's ability to cross-classify. Participants were asked to classify an item into a familiar (taxonomic or script) category, then cross-classify it into a novel (script or taxonomic) category with the help of a clue expressed in either generic or specific…

  19. RBPJ and EphrinB2 as Molecular Targets to Treat Brain Arteriovenous Malformation in Notch4 Induced Mouse Model

    DTIC Science & Technology

    2017-10-01

    mouse genetic breeding, provided genotyping, immunostaining, histological analysis, and molecular expertise. Funding Support NIH/NHLBI Name: Bert...AWARD NUMBER: W81XWH-16-1-0665 TITLE: RBPJ and EphrinB2 as Molecular Targets to Treat Brain Arteriovenous Malformation in Notch4-Induced Mouse...2016 - 29 Sep 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER RBPJ and EphrinB2 as Molecular Targets to Treat Brain Arteriovenous Malformation in

  20. Spatially modulated ephrinA1:EphA2 signaling increases local contractility and global focal adhesion dynamics to promote cell motility.

    PubMed

    Chen, Zhongwen; Oh, Dongmyung; Biswas, Kabir H; Yu, Cheng-Han; Zaidel-Bar, Ronen; Groves, Jay T

    2018-06-19

    Recent studies have revealed pronounced effects of the spatial distribution of EphA2 receptors on cellular response to receptor activation. However, little is known about molecular mechanisms underlying this spatial sensitivity, in part due to lack of experimental systems. Here, we introduce a hybrid live-cell patterned supported lipid bilayer experimental platform in which the sites of EphA2 activation and integrin adhesion are spatially controlled. Using a series of live-cell imaging and single-molecule tracking experiments, we map the transmission of signals from ephrinA1:EphA2 complexes. Results show that ligand-dependent EphA2 activation induces localized myosin-dependent contractions while simultaneously increasing focal adhesion dynamics throughout the cell. Mechanistically, Src kinase is activated at sites of ephrinA1:EphA2 clustering and subsequently diffuses on the membrane to focal adhesions, where it up-regulates FAK and paxillin tyrosine phosphorylation. EphrinA1:EphA2 signaling triggers multiple cellular responses with differing spatial dependencies to enable a directed migratory response to spatially resolved contact with ephrinA1 ligands.

  1. Ephrin-B2 prevents N-methyl-D-aspartate receptor antibody effects on memory and neuroplasticity.

    PubMed

    Planagumà, Jesús; Haselmann, Holger; Mannara, Francesco; Petit-Pedrol, Mar; Grünewald, Benedikt; Aguilar, Esther; Röpke, Luise; Martín-García, Elena; Titulaer, Maarten J; Jercog, Pablo; Graus, Francesc; Maldonado, Rafael; Geis, Christian; Dalmau, Josep

    2016-09-01

    To demonstrate that ephrin-B2 (the ligand of EphB2 receptor) antagonizes the pathogenic effects of patients' N-methyl-D-aspartate receptor (NMDAR) antibodies on memory and synaptic plasticity. One hundred twenty-two C57BL/6J mice infused with cerebrospinal fluid (CSF) from patients with anti-NMDAR encephalitis or controls, with or without ephrin-B2, were investigated. CSF was infused through ventricular catheters connected to subcutaneous osmotic pumps over 14 days. Memory, behavioral tasks, locomotor activity, presence of human antibodies specifically bound to hippocampal NMDAR, and antibody effects on the density of cell-surface and synaptic NMDAR and EphB2 were examined at different time points using reported techniques. Short- and long-term synaptic plasticity were determined in acute brain sections; the Schaffer collateral pathway was stimulated and the field excitatory postsynaptic potentials were recorded in the CA1 region of the hippocampus. Mice infused with patients' CSF, but not control CSF, developed progressive memory deficit and depressive-like behavior along with deposits of NMDAR antibodies in the hippocampus. These findings were associated with a decrease of the density of cell-surface and synaptic NMDAR and EphB2, and marked impairment of long-term synaptic plasticity without altering short-term plasticity. Administration of ephrin-B2 prevented the pathogenic effects of the antibodies in all the investigated paradigms assessing memory, depressive-like behavior, density of cell-surface and synaptic NMDAR and EphB2, and long-term synaptic plasticity. Administration of ephrin-B2 prevents the pathogenic effects of anti-NMDAR encephalitis antibodies on memory and behavior, levels of cell-surface NMDAR, and synaptic plasticity. These findings reveal a strategy beyond immunotherapy to antagonize patients' antibody effects. Ann Neurol 2016;80:388-400. © 2016 American Neurological Association.

  2. Social affiliation in same-class and cross-class interactions.

    PubMed

    Côté, Stéphane; Kraus, Michael W; Carpenter, Nichelle C; Piff, Paul K; Beermann, Ursula; Keltner, Dacher

    2017-02-01

    Historically high levels of economic inequality likely have important consequences for relationships between people of the same and different social class backgrounds. Here, we test the prediction that social affiliation among same-class partners is stronger at the extremes of the class spectrum, given that these groups are highly distinctive and most separated from others by institutional and economic forces. An internal meta-analysis of 4 studies (N = 723) provided support for this hypothesis. Participant and partner social class were interactively, rather than additively, associated with social affiliation, indexed by affiliative behaviors and emotions during structured laboratory interactions and in daily life. Further, response surface analyses revealed that paired upper or lower class partners generally affiliated more than average-class pairs. Analyses with separate class indices suggested that these patterns are driven more by parental income and subjective social class than by parental education. The findings illuminate the dynamics of same- and cross-class interactions, revealing that not all same-class interactions feature the same degree of affiliation. They also reveal the importance of studying social class from an intergroup perspective. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  3. Bifunctional role of ephrin A1-Eph system in stimulating cell proliferation and protecting cells from cell death through the attenuation of ER stress and inflammatory responses in bovine mammary epithelial cells.

    PubMed

    Kang, Minkyung; Jeong, Wooyoung; Bae, Hyocheol; Lim, Whasun; Bazer, Fuller W; Song, Gwonhwa

    2018-03-01

    Structural and functional development of the mammary gland is constant in the mammary gland life cycle. Eph receptors and their ligands, ephrins, control events through cell-to-cell interactions during embryonic development, and adult tissue homeostasis; however, little information on participation of ephrin A1, a representative ligand of the Eph receptor, in the development and function of normal mammary glands is known. In this study, we demonstrated functional effects of the ephrin A1-Eph system and mechanisms of its action on bovine mammary epithelial (MAC-T) cells. The in vitro cultured MAC-T cells expressed the ephrin A1 ligand and EphA1, A2, A4, A7, and A8 among the eight members of the Eph A family. Our results revealed that ephrin A1 induced MAC-T cell cycle progression and stimulated cell proliferation with abundant expression of nucleic PCNA and cyclin D1 proteins. Additionally, ephrin A1 induced activation of intracellular signaling molecules involved in PI3 K/AKT and MAPK signaling, and the proliferation-stimulating effect of ephrin A1 was mediated by activation of these pathways. Furthermore, ephrin A1 influenced expression and activation of various ER stress-related proteins and protected MAC-T cells from stress-induced cell death. Finally, ephrin A1 alleviated LPS-induced cell death through down-regulation of inflammatory cytokines. In conclusion, the results of this study suggest that the Eph A-ephrin A1 system is a positive factor in the increase and maintenance of epithelial cells in mammary glands of cows; the signaling system contributes to development, remodeling, and functionality of normal mammary glands and could overcome mastitis in cows and other mammals. © 2017 Wiley Periodicals, Inc.

  4. Binding of the Kaposi's Sarcoma-Associated Herpesvirus to the Ephrin Binding Surface of the EphA2 Receptor and Its Inhibition by a Small Molecule

    PubMed Central

    Hahn, Alexander S.

    2014-01-01

    ABSTRACT The ephrin receptor tyrosine kinase A2 (EphA2) is an entry receptor for Kaposi's sarcoma-associated herpesvirus (KSHV) that is engaged by the virus through its gH/gL glycoprotein complex. We describe here that natural ephrin ligands inhibit the gH/gL-EphA2 interaction. The effects of point mutations within EphA2 demonstrated that KSHV gH/gL interacts with EphA2 through a restricted set of the same residues that mediate binding of A-type ephrins. Two previously described inhibitors of the EphA2 interaction with ephrin A5 also inhibited binding of KSHV gH/gL to EphA2. The more potent of the two compounds inhibited KSHV infection of blood vessel and lymphatic endothelial cells in the micromolar concentration range. Our results demonstrate that interaction of KSHV with EphA2 occurs in a fashion similar to that of the natural ephrin ligands. Our data further indicate a new avenue for drug development against KSHV. IMPORTANCE Our study reports two important findings. First, we show that KSHV engages its receptor, the receptor tyrosine kinase EphA2, at a site that overlaps the binding site of the natural ephrin ligands. Second, we demonstrate that KSHV infection of target cells can be blocked by a small-molecule inhibitor of the viral glycoprotein-EphA2 interaction. These findings represent a novel avenue for the development of strategies to treat KSHV-associated diseases. PMID:24899181

  5. Monomeric ephrinB2 binding induces allosteric changes in Nipah virus G that precede its full activation.

    PubMed

    Wong, Joyce J W; Young, Tracy A; Zhang, Jiayan; Liu, Shiheng; Leser, George P; Komives, Elizabeth A; Lamb, Robert A; Zhou, Z Hong; Salafsky, Joshua; Jardetzky, Theodore S

    2017-10-03

    Nipah virus is an emergent paramyxovirus that causes deadly encephalitis and respiratory infections in humans. Two glycoproteins coordinate the infection of host cells, an attachment protein (G), which binds to cell surface receptors, and a fusion (F) protein, which carries out the process of virus-cell membrane fusion. The G protein binds to ephrin B2/3 receptors, inducing G conformational changes that trigger F protein refolding. Using an optical approach based on second harmonic generation, we show that monomeric and dimeric receptors activate distinct conformational changes in G. The monomeric receptor-induced changes are not detected by conformation-sensitive monoclonal antibodies or through electron microscopy analysis of G:ephrinB2 complexes. However, hydrogen/deuterium exchange experiments confirm the second harmonic generation observations and reveal allosteric changes in the G receptor binding and F-activating stalk domains, providing insights into the pathway of receptor-activated virus entry.Nipah virus causes encephalitis in humans. Here the authors use a multidisciplinary approach to study the binding of the viral attachment protein G to its host receptor ephrinB2 and show that monomeric and dimeric receptors activate distinct conformational changes in G and discuss implications for receptor-activated virus entry.

  6. Eph receptor interclass cooperation is required for the regulation of cell proliferation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jurek, Aleksandra; Genander, Maria; Kundu, Parag

    2016-10-15

    Cancer often arises by the constitutive activation of mitogenic pathways by mutations in stem cells. Eph receptors are unusual in that although they regulate the proliferation of stem/progenitor cells in many adult organs, they typically fail to transform cells. Multiple ephrins and Eph receptors are often co-expressed and are thought to be redundant, but we here describe an unexpected dichotomy with two homologous ligands, ephrin-B1 and ephrin-B2, regulating specifically migration or proliferation in the intestinal stem cell niche. We demonstrate that the combined activity of two different coexpressed Eph receptors of the A and B class assembled into common signalingmore » clusters in response to ephrin-B2 is required for mitogenic signaling. The requirement of two different Eph receptors to convey mitogenic signals identifies a new type of cooperation within this receptor family and helps explain why constitutive activation of a single receptor fails to transform cells. - Highlights: • We demonstrate that ephrin-B1 and ephrin-B2 have largely non-overlapping functions in the intestinal stem cell niche. • Ephrin-B1 regulates cell positioning and ephrin-B2 regulates cell proliferation in the intestinal stem cell niche. • EphA4/B2 receptor cooperation in response to ephrin-B2 binding is obligatory to convey mitogenic signals in the intestine. • EphA4 facilitates EphB2 phosphorylation in response to ephrin-B2 in SW480 adenocarcinoma cells. • Ephrin-B1 and ephrin-B2 induce phosphorylation and degradation of the EphB2 receptor with different kinetics.« less

  7. [Expressions of angiogenesis-related factors: CD105, EphA2 and EphrinA1 in laryngeal squamous cell carcinoma and clinical implication].

    PubMed

    Su, J; Ji, X B; Xie, J H; Li, W

    2016-12-07

    Objective: To investigate the expressions of endoglin (CD105), erythropoietin-producing hepatocyte receptor A2 (EphA2) and its ligand ephrinA1 proteins in laryngeal squamous cell carcinoma (LSCC) and the relationship between their expressions and the clinicopathological factors of LSCC. Methods: The expressions of CD105, EphA2 and EphrinA1 proteins were detected with immunohistochemical staining in LSCC in 76 cases and adjacent normal laryngeal tissues (ANLT) (S-P) in 25 cases.SPSS 17.0 software was used to analyze the data. Results: The mean microvessel density (MVD) value marked by CD105 staining in LSCC was 10.33±2.29, which was significantly higher than that in ANLT(1.20±1.04, t =18.732, P <0.05). The CD105-MVD was correlated with T stage, histological grading, clinical stage, lymph node metastasis, recurrence and prognosis in LSCC (F value was 5.34, 4.79, 5.36, t value was -2.70, 2.56, all P <0.05). The positive expression rates of EphA2 and EphrinA1 in LSCC were 78.95% (60/76), and 81.85% (62/76), which were respectively significantly higher than 40% (10/25) for EphA2 expression and 44% (11/25) for EphrinA1, expression in ANLT (χ 2 value was 13.41, 13.26, both P <0.05). EphA2 expression was correlated with histological grading, T stage, clinical stage, lymph node metastasis, recurrence and prognosis in LSCC (χ 2 value was 6.25, 14.60, 15.11, 8.52, 5.54, all P <0.05). EphrinA1 expression was correlated with T stage, clinical stage, lymph node metastasis, recurrence and prognosis in LSCC (χ 2 value was 6.44, 12.28, 16.78, 6.44, all P <0.05). The expressions of CD105, EphA2 and EphrinA1 were positively correlated with each other r value was 0.72, 0.74, 0.64, all P <0.05. Survival analysis indicated that the expressions of CD105 and EphA2, histological grading, lymph node metastasis, clinical stage and recurrence were independent factors for tumor prognosis in LSCC ( P <0.05). Conclusions: The expressions of CD105, EphA2 and EphrinA1 protein were positively

  8. Bidirectional signalling between EphA2 and ephrinA1 increases tubular cell attachment, laminin secretion and modulates erythropoietin expression after renal hypoxic injury.

    PubMed

    Rodriguez, Stéphane; Rudloff, Stefan; Koenig, Katrin Franziska; Karthik, Swapna; Hoogewijs, David; Huynh-Do, Uyen

    2016-08-01

    Acute kidney injury (AKI) is common in hospitalized patients and has a poor prognosis, the severity of AKI being linked to progression to chronic kidney disease. This stresses the need to search for protective mechanisms during the acute phase. We investigated kidney repair after hypoxic injury using a rat model of renal artery branch ligation, which led to an oxygen gradient vertical to the corticomedullary axis. Three distinct zones were observed: tubular necrosis, infarction border zone and preserved normal tissue. EphA2 is a receptor tyrosine kinase with pivotal roles in cell architecture, migration and survival, upon juxtacrine contact with its membrane-bound ligand EphrinA1. Following hypoxia, EphA2 was up-regulated in cortical and medullary tubular cells, while EphrinA1 was up-regulated in interstitial cells adjacent to peritubular capillaries. Moreover, erythropoietin (EPO) messenger RNA (mRNA) was strongly expressed in the border zone of infarcted kidney within the first 6 h. To gain more insight into the biological impact of EphA2 and EphrinA1 up-regulation, we activated the signalling pathways in vitro using recombinant EphrinA1/Fc or EphA2/Fc proteins. Stimulation of EphA2 forward signalling in the proximal tubular cell line HK2 increased cell attachment and laminin secretion at the baso-lateral side. Conversely, activation of reverse signalling through EphrinA1 expressed by Hep3B cells promoted EPO production at both the transcriptional and protein level. Strikingly, in co-culture experiments, juxtacrine contact between EphA2 expressing MDCK and EphrinA1 expressing Hep3B was sufficient to induce a significant up-regulation of EPO mRNA production in the latter cells, even in the absence of hypoxic conditions. The synergistic effects of EphA2 and hypoxia led to a 15-20-fold increase of EPO expression. Collectively, our results suggest an important role of EphA2/EphrinA1 signalling in kidney repair after hypoxic injury through stimulation of (i) tubular

  9. BMP9 induces EphrinB2 expression in endothelial cells through an Alk1-BMPRII/ActRII-ID1/ID3-dependent pathway: Implications for Hereditary Hemorrhagic Telangiectasia Type II

    PubMed Central

    Kim, Jai-Hyun; Peacock, Matthew R.; George, Steven C.; Hughes, Christopher C.W.

    2012-01-01

    ALK1 (ACVRL1) is a member of the TGFβ receptor family and is expressed predominantly by arterial endothelial cells (EC). Mutations in ACVRL1 are responsible for Hereditary Hemorrhagic Telangiectasia Type 2 (HHT2), a disease manifesting as fragile vessels, capillary overgrowth, and numerous arterio-venous malformations (AVMs). Arterial EC also express EphrinB2, which has multiple roles in vascular development and angiogenesis and is known to be reduced in ACVRL1 knockout mice. Using an in vitro angiogenesis model we find that the Alk1 ligand BMP9 induces EphrinB2 in EC, and this is entirely dependent on expression of Alk1 and at least one of the co-receptors BMPRII or ActRII. BMP9 induces both ID1 and ID3, and both are necessary for full induction of EphrinB2. Loss of Alk1 or EphrinB2 results in increased arterial-venous anastomosis, while loss of Alk1 but not EphrinB2 results in increased VEGFR2 expression and enhanced capillary sprouting. Conversely, BMP9 blocks EC sprouting and this is dependent on Alk1, BMPRII/ActRII and ID1/ID3. Finally, notch signaling overcomes the loss of Alk1 – restoring EphrinB2 expression in EC, and curbing excess sprouting. Thus, in an in vitro model of HHT2, loss of Alk1 blocks BMP9 signaling, resulting in reduced EphrinB2 expression, enhanced VEGFR2 expression, and misregulated EC sprouting and anastomosis. PMID:22622516

  10. MicroRNA-210 Modulates Endothelial Cell Response to Hypoxia and Inhibits the Receptor Tyrosine Kinase Ligand Ephrin-A3*S⃞

    PubMed Central

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

    2008-01-01

    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

  11. EphA2 receptor activation with ephrin-A1 ligand restores cetuximab efficacy in NRAS-mutant colorectal cancer cells.

    PubMed

    Cuyàs, Elisabet; Queralt, Bernardo; Martin-Castillo, Begoña; Bosch-Barrera, Joaquim; Menendez, Javier A

    2017-07-01

    Patients with wild-type KRAS metastatic colorectal cancer (mCRC) that harbors NRAS activating mutations do not benefit from anti-EGFR therapies. Very little is known about oncogenic NRAS signaling driving mCRC unresponsiveness to the EGFR-directed antibody cetuximab. Using a system of paired NRAS-mutant and wild-type isogenic mCRC cell lines to explore signaling pathways engaged by the common oncogenic NRAS Q61K variant upon challenge with cetuximab, we uncovered an unexpected mechanism of resistance to cetuximab involving dysregulation of the ephrin-A1/EphA2 signaling axis. Parental NRAS+/+ cells, but not NRASQ61K/+ cells, activated the ephrin receptor ephA1 in response to cetuximab treatment. Moreover, whereas cetuximab treatment significantly downregulated EPHA2 gene expression in NRAS+/+ cells, EPHA2 expression in NRASQ61K/+ cells was refractory to cetuximab. Remarkably, pharmacologically mimicked ephrin-A1 engagement to ephA2 converted NRAS-mutant into RAS wild-type mCRC cells in terms of cetuximab efficacy. Accordingly, activation of the ephA2 receptor by bioactive recombinant human ephrin-A1/Fc-fusion protein suppressed the cetuximab-unresponsive hyperactivation of MAPK and AKT and fully restored cetuximab activity in NRAS-mutant colorectal cells. Collectively, these findings reveal that the clinical benefit of cetuximab in mCRC might necessarily involve the suppression of the ligandless oncogenic signaling of the ephA2 receptor. Hence, ligand-dependent tumor suppressor signaling using therapeutic ephA2 agonists might offer new therapeutic opportunities to clinically widen the use of cetuximab in NRAS-mutated and/or ephA2-dependent mCRC tumors.

  12. Expression of the ephrin receptor B2 in the embryonic chicken bursa of Fabricius

    USDA-ARS?s Scientific Manuscript database

    Chicken B-cells develop in a specific organ, the bursa of Fabricius. To understand the bursal microenvironment guiding B-cell development, previous studies identified ephrin (Eph) receptor B2 (EphB2) gene transcripts in the embryonic bursa. We hypothesize that the EphB2 receptors and their ligands r...

  13. Cultural hegemony? Educators' perspectives on facilitating cross-cultural dialogue.

    PubMed

    Zaidi, Zareen; Verstegen, Daniëlle; Vyas, Rashmi; Hamed, Omayma; Dornan, Tim; Morahan, Page

    2016-01-01

    We live in an age when education is being internationalized. This can confront students with 'cultural hegemony' that can result from the unequal distribution of power and privilege in global society. The name that is given to awareness of social inequality is 'critical consciousness'. Cross-cultural dialogue provides an opportunity for learners to develop critical consciousness to counter cultural hegemony. The purpose of this research was to understand how learners engage with cross-cultural dialogue, so we can help them do so more effectively in the future. The setting for this research was an online discussion in an international health professions educator fellowship program. We introduced scenarios with cultural references to study the reaction of participants to cultural conversation cues. We used an inductive thematic analysis to explore power and hegemony issues. Participants reflected that personally they were more likely to take part in cross-cultural discussions if they recognized the context discussed or had prior exposure to educational settings with cultural diversity. They identified barriers as lack of skills in facilitating cross-cultural discussions and fear of offending others. They suggested deliberately introducing cultural issues throughout the curriculum. Our results indicate that developing critical consciousness and cross-cultural competency will require instructional design to identify longitudinal opportunities to bring up cross-cultural issues, and training facilitators to foster cross-cultural discussions by asking clarifying questions and navigating crucial/sensitive conversations.

  14. Fully-human Monoclonal Antibodies Against Human EphrinB2 and EphB4 | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute's Cancer and Inflammation Program is seeking statements of capability or interest from parties interested in licensing fully-human monoclonal antibodies against human EphrinB2 and EphB4.

  15. Oxycodone Self-Administration Induces Alterations in Expression of Integrin, Semaphorin and Ephrin Genes in the Mouse Striatum.

    PubMed

    Yuferov, Vadim; Zhang, Yong; Liang, Yupu; Zhao, Connie; Randesi, Matthew; Kreek, Mary J

    2018-01-01

    Oxycodone is one a commonly used medication for pain, and is also a widely abused prescription opioid, like other short-acting MOPr agonists. Neurochemical and structural adaptations in brain following chronic MOPr-agonist administration are thought to underlie pathogenesis and persistence of opiate addiction. Many axon guidance molecules, such as integrins, semaphorins, and ephrins may contribute to oxycodone-induced neuroadaptations through alterations in axon-target connections and synaptogenesis, that may be implicated in the behaviors associated with opiate addiction. However, little is known about this important area. The aim of this study is to investigate alterations in expression of selected integrin, semaphorin, ephrins, netrin, and slit genes in the nucleus accumbens (NAc) and caudate putamen (CPu) of mice following extended 14-day oxycodone self-administration (SA), using RNAseq. Methods: Total RNA from the NAc and CPu were isolated from adult male C57BL/6J mice within 1 h after the last session of oxycodone in a 14-day self-administration paradigm (4h/day, 0.25 mg/kg/infusion, FR1) or from yoked saline controls. Gene expressions were examined using RNA sequencing (RNA-Seq) technology. RNA-Seq libraries were prepared using Illumina's TruSeq® Stranded Total RNA LT kit. The reads were aligned to the mouse reference genome (version mm10) using STAR. DESeq2 was applied to the counts of protein coding genes to estimate the fold change between the treatment groups. False Discovery Rate (FDR) q < 0.1 were used to select genes that have a significant expression change. For selection of a subset of genes related to axon guidance pathway, REACTOME was used. Results: Among 38 known genes of the integrin, semaphorin, and ephrin gene families, RNA-seq data revealed up-regulation of six genes in the NAc: heterodimer receptor, integrins Itgal, Itgb2 , and Itgam , and its ligand semaphorin Sema7a , two semaphorin receptors, plexins Plxnd1 and Plxdc1 . There was down

  16. Cultural hegemony? Educators’ perspectives on facilitating cross-cultural dialogue

    PubMed Central

    Zaidi, Zareen; Verstegen, Daniëlle; Vyas, Rashmi; Hamed, Omayma; Dornan, Tim; Morahan, Page

    2016-01-01

    Background We live in an age when education is being internationalized. This can confront students with ‘cultural hegemony’ that can result from the unequal distribution of power and privilege in global society. The name that is given to awareness of social inequality is ‘critical consciousness’. Cross-cultural dialogue provides an opportunity for learners to develop critical consciousness to counter cultural hegemony. The purpose of this research was to understand how learners engage with cross-cultural dialogue, so we can help them do so more effectively in the future. Method The setting for this research was an online discussion in an international health professions educator fellowship program. We introduced scenarios with cultural references to study the reaction of participants to cultural conversation cues. We used an inductive thematic analysis to explore power and hegemony issues. Results Participants reflected that personally they were more likely to take part in cross-cultural discussions if they recognized the context discussed or had prior exposure to educational settings with cultural diversity. They identified barriers as lack of skills in facilitating cross-cultural discussions and fear of offending others. They suggested deliberately introducing cultural issues throughout the curriculum. Conclusion Our results indicate that developing critical consciousness and cross-cultural competency will require instructional design to identify longitudinal opportunities to bring up cross-cultural issues, and training facilitators to foster cross-cultural discussions by asking clarifying questions and navigating crucial/sensitive conversations. PMID:27890048

  17. Facilitating Learning in Large Lecture Classes: Testing the "Teaching Team" Approach to Peer Learning

    ERIC Educational Resources Information Center

    Stanger-Hall, Kathrin F.; Lang, Sarah; Maas, Martha

    2010-01-01

    We tested the effect of voluntary peer-facilitated study groups on student learning in large introductory biology lecture classes. The peer facilitators (preceptors) were trained as part of a Teaching Team (faculty, graduate assistants, and preceptors) by faculty and Learning Center staff. Each preceptor offered one weekly study group to all…

  18. Ephrin-A/EphA specific co-adaptation as a novel mechanism in topographic axon guidance

    PubMed Central

    Fiederling, Felix; Weschenfelder, Markus; Fritz, Martin; von Philipsborn, Anne; Bastmeyer, Martin; Weth, Franco

    2017-01-01

    Genetic hardwiring during brain development provides computational architectures for innate neuronal processing. Thus, the paradigmatic chick retinotectal projection, due to its neighborhood preserving, topographic organization, establishes millions of parallel channels for incremental visual field analysis. Retinal axons receive targeting information from quantitative guidance cue gradients. Surprisingly, novel adaptation assays demonstrate that retinal growth cones robustly adapt towards ephrin-A/EphA forward and reverse signals, which provide the major mapping cues. Computational modeling suggests that topographic accuracy and adaptability, though seemingly incompatible, could be reconciled by a novel mechanism of coupled adaptation of signaling channels. Experimentally, we find such ‘co-adaptation’ in retinal growth cones specifically for ephrin-A/EphA signaling. Co-adaptation involves trafficking of unliganded sensors between the surface membrane and recycling endosomes, and is presumably triggered by changes in the lipid composition of membrane microdomains. We propose that co-adaptative desensitization eventually relies on guidance sensor translocation into cis-signaling endosomes to outbalance repulsive trans-signaling. DOI: http://dx.doi.org/10.7554/eLife.25533.001 PMID:28722651

  19. Association Analysis of the Ephrin-B2 Gene in African-Americans with End-Stage Renal Disease

    PubMed Central

    Hicks, Pamela J.; Staten, Jennifer L.; Palmer, Nicholette D.; Langefeld, Carl D.; Ziegler, Julie T.; Keene, Keith L.; Sale, Michele M.; Bowden, Donald W.; Freedman, Barry I.

    2008-01-01

    Background Genome scans in African-Americans with end-stage renal disease (ESRD) identified linkage on chromosome 13q33 in the region containing the ephrin-B2 ligand (EFNB2) genes. Interactions between the ephrin-B2 receptor and ephrin-B2 ligand play essential roles in renal angiogenesis, blood vessel maturation, and kidney disease. Methods The EFNB2 gene was evaluated as a positional candidate for non-diabetic and diabetic ESRD susceptibility in 1,071 unrelated African-American subjects; 316 with non-diabetic etiologies of ESRD, 394 with type 2 diabetes-associated ESRD and 361 healthy controls. Single nucleotide polymorphism (SNP) genotyping was performed on the Sequenom Mass Array System. Statistical analyses were computed using Dandelion version 1.26, Snpaddmix version 1.4 and Haploview version 3.32. Results Twenty-eight HapMap tag SNPs were genotyped spanning the 39 kilobases (kb) of the EFNB2 coding region, with average spacing of 1.43 kb. Analysis of 710 ESRD patient samples and 361 controls provided no evidence of single SNP associations in either diabetic or non-diabetic ESRD; although nominal evidence of association with all-cause ESRD was observed with a two SNP (p = 0.022) and three SNP (p = 0.023) haplotype, both containing SNPs rs7490924 and rs2391335 in intron 1. Conclusions Although an attractive positional candidate gene, polymorphisms in the EFNB2 gene do not appear to contribute in a substantial way to non-diabetic, diabetic or all-cause ESRD susceptibility in African-Americans. Additional genes within the chromosome 13q33 linkage interval are likely contributors to African-American non-diabetic ESRD. PMID:18580054

  20. Eph and Ephrin function in dispersal and epithelial insertion of pigmented immunocytes in sea urchin embryos

    PubMed Central

    Krupke, Oliver A; Zysk, Ivona; Mellott, Dan O; Burke, Robert D

    2016-01-01

    The mechanisms that underlie directional cell migration are incompletely understood. Eph receptors usually guide migrations of cells by exclusion from regions expressing Ephrin. In sea urchin embryos, pigmented immunocytes are specified in vegetal epithelium, transition to mesenchyme, migrate, and re-enter ectoderm, distributing in dorsal ectoderm and ciliary band, but not ventral ectoderm. Immunocytes express Sp-Eph and Sp-Efn is expressed throughout dorsal and ciliary band ectoderm. Interfering with expression or function of Sp-Eph results in rounded immunocytes entering ectoderm but not adopting a dendritic form. Expressing Sp-Efn throughout embryos permits immunocyte insertion in ventral ectoderm. In mosaic embryos, immunocytes insert preferentially in ectoderm expressing Sp-Efn. We conclude that Sp-Eph signaling is necessary and sufficient for epithelial insertion. As well, we propose that immunocytes disperse when Sp-Eph enhances adhesion, causing haptotactic movement to regions of higher ligand abundance. This is a distinctive example of Eph/Ephrin signaling acting positively to pattern migrating cells. DOI: http://dx.doi.org/10.7554/eLife.16000.001 PMID:27474796

  1. Developing and Evaluating Medical Humanities Problem-Based Learning Classes Facilitated by the Teaching Assistants Majored in the Liberal Arts

    PubMed Central

    Tseng, Fen-Yu; Shieh, Jeng-Yi; Kao, Tze-Wah; Wu, Chau-Chung; Chu, Tzong-Shinn; Chen, Yen-Yuan

    2016-01-01

    Abstract Although medical humanities courses taught by teachers from nonmedical backgrounds are not unusual now, few studies have compared the outcome of medical humanities courses facilitated by physicians to that by teaching assistants majored in the liberal arts. The objectives of this study were to (1) analyze the satisfaction of medical students with medical humanities problem-based learning (PBL) classes facilitated by nonmedical teaching assistants (TAF) majored in the liberal arts, and those facilitated by the attending physicians (APF) and (2) examine the satisfaction of medical students with clinical medicine-related and clinical medicine-unrelated medical humanities PBL classes. A total of 123 medical students, randomly assigned to 16 groups, participated in this study. There were 16 classes in the course: 8 of them were TAF classes; and the others were APF classes. Each week, each group rotated from 1 subject of the 16 subjects of PBL to another subject. All of the 16 groups went through all the 16 subjects in the 2013 spring semester. We examined the medical students’ satisfaction with each class, based on a rating score collected after each class was completed, using a scale from 0 (the lowest satisfaction) to 100 (the highest satisfaction). We also conducted multivariate linear regression analysis to examine the association between the independent variables and the students’ satisfaction. Medical students were more satisfied with the TAF (91.35 ± 7.75) medical humanities PBL classes than APF (90.40 ± 8.42) medical humanities PBL classes (P = 0.01). Moreover, medical students were more satisfied with the clinical medicine-unrelated topics (92.00 ± 7.10) than the clinical medicine-related topics (90.36 ± 7.99) in the medical humanities PBL course (P = 0.01). This medical humanities PBL course, including nonmedical subjects and topics, and nonmedical teaching assistants from the liberal arts as class facilitators, was

  2. GluA2 trafficking is involved in apoptosis of retinal ganglion cells induced by activation of EphB/EphrinB reverse signaling in a rat chronic ocular hypertension model.

    PubMed

    Dong, Ling-Dan; Gao, Feng; Wang, Xiao-Han; Miao, Yanying; Wang, Shu-Yue; Wu, Yi; Li, Fang; Wu, Jihong; Cheng, Xiang-Lin; Sun, Xing-Huai; Yang, Xiong-Li; Wang, Zhongfeng

    2015-04-01

    EphB1, expressed in Müller cells, and ephrinB2, expressed in both Müller cells and retinal ganglion cells (RGCs), constitute an EphB/ephrinB reverse signaling in RGCs. Whether and how this reverse signaling is involved in RGC apoptosis in a rat chronic ocular hypertension (COH) model was investigated. In the COH model, both EphB1 and ephrinB2 were significantly increased and the reverse signaling was activated, which was accompanied by increased protein levels of phosphorylated (p) src, GluA2, and p-GluA2. Intravitreal injection of EphB2-Fc, an activator of ephrinB2, induced an increase in TUNEL-positive signals in normal retinae. A coimmunoprecipitation assay demonstrated direct interactions among ephrinB2, p-src, and GluA2. Moreover, in COH rats the expression of GluA2 proteins on the surface of retinal cells was decreased. Such GluA2 endocytosis could be prevented by preoperational intravitreal injection of 4-amino-3-(4-chlorophenyl)-1-(t-butyl)-1H-pyrazolo [3,4-d] pyrimidine (PP2), an inhibitor of src family tyrosine kinases, and possibly involved the protein interacting with C kinase 1 and phosphorylation of GluA2. In normal rats, intravitreal injection of EphB2-Fc caused changes in these protein levels similar to those observed in COH rats, which all could be avoided by preinjection of PP2. Patch-clamp experiments further showed that the current-voltage relationship of AMPA receptor-mediated EPSCs of RGCs exhibited stronger inward rectification in EphB2-Fc-injected rats. Furthermore, preinjection of PP2 or N-[3-[[4-[(3-aminopropyl)amino]butyl]amino]propyl]-1-naphthaleneacetamide trihydrochloride) (Naspm), a Ca(2+)-permeable GluA2-lacking AMPA receptor inhibitor, remarkably inhibited RGC apoptosis in either EphB2-Fc-injected or COH rats. Together, elevated GluA2 trafficking induced by activated EphB2/ephrinB2 reverse signaling likely contributes to RGC apoptosis in COH rats. Copyright © 2015 the authors 0270-6474/15/355409-13$15.00/0.

  3. Negotiating Cross-Class Identities While Living a Curriculum of Moral Education

    ERIC Educational Resources Information Center

    Cutri, Ramona Maile; Manning, Jill; Weight, Cecilia Santiago

    2012-01-01

    Background/Context: A person's socioeconomic class is not a stagnant category based on her income level, but is rather an ongoing lived identity that includes a dynamic process of political struggle. In our self-study, we unpack both our poverty and upper-middle-class experiences and in so doing examine our intergenerational cross-class identity…

  4. Cross-Linguistic Activation in Bilingual Sentence Processing: The Role of Word Class Meaning

    ERIC Educational Resources Information Center

    Baten, Kristof; Hofman, Fabrice; Loeys, Tom

    2011-01-01

    This study investigates how categorial (word class) semantics influences cross-linguistic interactions when reading in L2. Previous homograph studies paid little attention to the possible influence of different word classes in the stimulus material on cross-linguistic activation. The present study examines the word recognition performance of…

  5. Generalization of cross-modal stimulus equivalence classes: operant processes as components in human category formation.

    PubMed Central

    Lane, S D; Clow, J K; Innis, A; Critchfield, T S

    1998-01-01

    This study employed a stimulus-class rating procedure to explore whether stimulus equivalence and stimulus generalization can combine to promote the formation of open-ended categories incorporating cross-modal stimuli. A pretest of simple auditory discrimination indicated that subjects (college students) could discriminate among a range of tones used in the main study. Before beginning the main study, 10 subjects learned to use a rating procedure for categorizing sets of stimuli as class consistent or class inconsistent. After completing conditional discrimination training with new stimuli (shapes and tones), the subjects demonstrated the formation of cross-modal equivalence classes. Subsequently, the class-inclusion rating procedure was reinstituted, this time with cross-modal sets of stimuli drawn from the equivalence classes. On some occasions, the tones of the equivalence classes were replaced by novel tones. The probability that these novel sets would be rated as class consistent was generally a function of the auditory distance between the novel tone and the tone that was explicitly included in the equivalence class. These data extend prior work on generalization of equivalence classes, and support the role of operant processes in human category formation. PMID:9821680

  6. Facilitating Learning in Large Lecture Classes: Testing the “Teaching Team” Approach to Peer Learning

    PubMed Central

    Lang, Sarah; Maas, Martha

    2010-01-01

    We tested the effect of voluntary peer-facilitated study groups on student learning in large introductory biology lecture classes. The peer facilitators (preceptors) were trained as part of a Teaching Team (faculty, graduate assistants, and preceptors) by faculty and Learning Center staff. Each preceptor offered one weekly study group to all students in the class. All individual study groups were similar in that they applied active-learning strategies to the class material, but they differed in the actual topics or questions discussed, which were chosen by the individual study groups. Study group participation was correlated with reduced failing grades and course dropout rates in both semesters, and participants scored better on the final exam and earned higher course grades than nonparticipants. In the spring semester the higher scores were clearly due to a significant study group effect beyond ability (grade point average). In contrast, the fall study groups had a small but nonsignificant effect after accounting for student ability. We discuss the differences between the two semesters and offer suggestions on how to implement teaching teams to optimize learning outcomes, including student feedback on study groups. PMID:21123696

  7. Truncated EphA2 likely potentiates cell adhesion via integrins as well as infiltration and/or lodgment of a monocyte/macrophage cell line in the red pulp and marginal zone of the mouse spleen, where ephrin-A1 is prominently expressed in the vasculature.

    PubMed

    Konda, Naoko; Saeki, Noritaka; Nishino, Shingo; Ogawa, Kazushige

    2017-03-01

    We previously established a J774.1 monocyte/macrophage subline expressing a truncated EphA2 construct lacking the kinase domain. We demonstrated that following ephrin-A1 stimulation, endogenous EphA2 promotes cell adhesion through interaction with integrins and integrin ligands such as ICAM1 and that truncated EphA2 potentiates the adhesion and becomes associated with the integrin/integrin ligand complex. Based on these findings, we hypothesized that the EphA/ephrin-A system, particularly EphA2/ephrin-A1, regulates transendothelial migration/tissue infiltration of monocytes/macrophages, because ephrin-A1 is widely recognized to be upregulated in inflammatory vasculatures. To evaluate whether this hypothesis is applicable in the spleen, we screened for EphA2/ephrin-A1 expression and reexamined the cellular properties of the J774.1 subline. We found that ephrin-A1 was expressed in the vasculature of the marginal zone and the red pulp and that its expression was upregulated in response to phagocyte depletion; further, CD115, F4/80, and CXCR4 were expressed in J774.1 cells, which serve as a usable substitute for monocytes/macrophages. Moreover, following ephrin-A1 stimulation, truncated EphA2 did not detectably interfere with the phosphorylation of endogenous EphA2, and it potentiated cell adhesion possibly through modulation of integrin avidity. Accordingly, by intravenously injecting mice with equal numbers of J774.1 and the subline cells labeled with distinct fluorochromes, we determined that truncated EphA2 markedly potentiated preferential cell infiltration into the red pulp and the marginal zone. Thus, modulation of EphA2 signaling might contribute to effective transplantation of tissue-specific resident macrophages and/or monocytes.

  8. Synergistic Effect of TPD7 and Berberine against Leukemia Jurkat Cell Growth through Regulating Ephrin-B2 Signaling.

    PubMed

    Ma, Weina; Zhu, Man; Yang, Liu; Yang, Tianfeng; Zhang, Yanmin

    2017-09-01

    TPD7, a novel biphenyl urea taspine derivative, and berberine have presented inhibition on VEGFR2 that can be regulated by ephrin-B2 reverse signaling through interactions with the PDZ domain. The purpose of this study is to investigate the inhibitory effect of the combination of TPD7 and berberine (TAB) on T-cell acute lymphoblastic leukemia cell growth. TPD7 and berberine together synergistically inhibited the proliferation of Jurkat cells. Also, the combination of TAB induced G 1 -phase cell-cycle arrest by downregulating the level of cyclin D1, cyclin E, and CDC2. Furthermore, the combination of TAB significantly enhanced apoptosis in Jurkat cells, and the apoptosis most likely resulted from the modulation of the level of Bcl-2 family members. Most importantly, the concomitant treatment simultaneously regulated the ephrin-B2 and VEGFR2 signaling, as well as modulated the MEK/ERK and PTEN/PI3K/AKT/mTOR signaling. Therefore, the combination treatment of TAB may be a promising therapeutic method in treating T-cell acute lymphoblastic leukemia. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  9. Dendritic spine density and EphrinB2 levels of hippocampal and anterior cingulate cortex neurons increase sequentially during formation of recent and remote fear memory in the mouse.

    PubMed

    Abate, Georgia; Colazingari, Sandra; Accoto, Alessandra; Conversi, David; Bevilacqua, Arturo

    2018-05-15

    Memory consolidation is a dynamic process that involves a sequential remodeling of hippocampal-cortical circuits. Although synaptic events underlying memory consolidation are well assessed, fine molecular events controlling this process deserve further characterization. To this aim, we challenged male C57BL/6N mice in a contextual fear conditioning (CFC) paradigm and tested their memory 24 h, 7 days or 36 days later. Mice displayed a strong fear response at all time points with an increase in dendritic spine density and protein levels of the cell adhesion factor EphrinB2 in CA1 hippocampal neurons 24 h and 7 days post conditioning (p.c.), and in anterior cingulate cortex (ACC) neurons 36 days p.c. We then investigated whether the formation of remote memory and neuronal modifications in the ACC would depend on p.c. protein synthesis in hippocampal neurons. Bilateral intrahippocampal infusions with the protein synthesis inhibitor anisomycin administered immediately p.c. decreased fear response, neuronal spine growth and EphrinB2 protein levels of hippocampal and ACC neurons 24 h and 36 days p.c., respectively. Anisomycin infusion 24 h p.c. had no effects on fear response, increase in spine density and in EphrinB2 protein levels in ACC neurons 36 days p.c. Our results thus confirm that early but not late p.c. hippocampal protein synthesis is necessary for the formation of remote memory and provide the first evidence of a possible involvement of EphrinB2 in neuronal plasticity in the ACC. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Diabetic Ephrin-B2-Stimulated Peripheral Blood Mononuclear Cells Enhance Poststroke Recovery in Mice.

    PubMed

    Hilal, Rose; Poittevin, Marine; Pasteur-Rousseau, Adrien; Cogo, Adrien; Mangin, Gabrielle; Chevauché, Marie; Ziat, Yasmine; Vilar, José; Launay, Jean-Marie; Gautier, Jean-François; Broquères-You, Dong; Levy, Bernard I; Merkulova-Rainon, Tatyana; Kubis, Nathalie

    2018-01-01

    Clinical trials of cell therapy in stroke favor autologous cell transplantation. To date, feasibility studies have used bone marrow-derived mononuclear cells, but harvesting bone marrow cells is invasive thus complicating bedside treatment. We investigated the therapeutic potential of peripheral blood-derived mononuclear cells (PB-MNC) harvested from diabetic patients and stimulated by ephrin-B2 (PB-MNC+) (500,000 cells), injected intravenously 18-24 hours after induced cerebral ischemia in mice. Infarct volume, neurological deficit, neurogenesis, angiogenesis, and inflammation were investigated as were the potential mechanisms of PB-MNC+ cells in poststroke neurorepair. At D3, infarct volume was reduced by 60% and 49% compared to unstimulated PB-MNC and PBS-treated mice, respectively. Compared to PBS, injection of PB-MNC+ increased cell proliferation in the peri-infarct area and the subventricular zone, decreased microglia/macrophage cell density, and upregulated TGF- β expression. At D14, microvessel density was decreased and functional recovery was enhanced compared to PBS-treated mice, whereas plasma levels of BDNF, a major regulator of neuroplasticity, were increased in mice treated with PB-MNC+ compared to the other two groups. Cell transcriptional analysis showed that ephrin-B2 induced phenotype switching of PB-MNC by upregulating genes controlling cell proliferation, inflammation, and angiogenesis, as confirmed by adhesion and Matrigel assays. Conclusions . This feasibility study suggests that PB-MNC+ transplantation poststroke could be a promising approach but warrants further investigation. If confirmed, this rapid, noninvasive bedside cell therapy strategy could be applied to stroke patients at the acute phase.

  11. Diabetic Ephrin-B2-Stimulated Peripheral Blood Mononuclear Cells Enhance Poststroke Recovery in Mice

    PubMed Central

    Hilal, Rose; Poittevin, Marine; Pasteur-Rousseau, Adrien; Cogo, Adrien; Mangin, Gabrielle; Chevauché, Marie; Ziat, Yasmine; Vilar, José; Launay, Jean-Marie; Gautier, Jean-François; Broquères-You, Dong; Levy, Bernard I.; Merkulova-Rainon, Tatyana

    2018-01-01

    Clinical trials of cell therapy in stroke favor autologous cell transplantation. To date, feasibility studies have used bone marrow-derived mononuclear cells, but harvesting bone marrow cells is invasive thus complicating bedside treatment. We investigated the therapeutic potential of peripheral blood-derived mononuclear cells (PB-MNC) harvested from diabetic patients and stimulated by ephrin-B2 (PB-MNC+) (500,000 cells), injected intravenously 18–24 hours after induced cerebral ischemia in mice. Infarct volume, neurological deficit, neurogenesis, angiogenesis, and inflammation were investigated as were the potential mechanisms of PB-MNC+ cells in poststroke neurorepair. At D3, infarct volume was reduced by 60% and 49% compared to unstimulated PB-MNC and PBS-treated mice, respectively. Compared to PBS, injection of PB-MNC+ increased cell proliferation in the peri-infarct area and the subventricular zone, decreased microglia/macrophage cell density, and upregulated TGF-β expression. At D14, microvessel density was decreased and functional recovery was enhanced compared to PBS-treated mice, whereas plasma levels of BDNF, a major regulator of neuroplasticity, were increased in mice treated with PB-MNC+ compared to the other two groups. Cell transcriptional analysis showed that ephrin-B2 induced phenotype switching of PB-MNC by upregulating genes controlling cell proliferation, inflammation, and angiogenesis, as confirmed by adhesion and Matrigel assays. Conclusions. This feasibility study suggests that PB-MNC+ transplantation poststroke could be a promising approach but warrants further investigation. If confirmed, this rapid, noninvasive bedside cell therapy strategy could be applied to stroke patients at the acute phase. PMID:29736174

  12. Inhibition of EphA2/EphrinA1 signal attenuates lipopolysaccharide-induced lung injury.

    PubMed

    Hong, Ji Young; Shin, Mi Hwa; Douglas, Ivor S; Chung, Kyung Soo; Kim, Eun Young; Jung, Ji Ye; Kang, Young Ae; Kim, Se Kyu; Chang, Joon; Kim, Young Sam; Park, Moo Suk

    2016-11-01

    Eph-Ephrin signalling mediates various cellular processes, including vasculogenesis, angiogenesis, cell migration, axon guidance, fluid homoeostasis and repair after injury. Although previous studies have demonstrated that stimulation of the EphA receptor induces increased vascular permeability and inflammatory response in lung injury, the detailed mechanisms of EphA2 signalling are unknown. In the present study, we evaluated the role of EphA2 signalling in mice with lipopolysaccharide (LPS)-induced lung injury. Acute LPS exposure significantly up-regulated EphA2 and EphrinA1 expression. Compared with LPS+IgG mice (IgG instillation after LPS exposure), LPS+EphA2 mAb mice [EphA2 monoclonal antibody (mAb) instillation posttreatment after LPS exposure] had attenuated lung injury and reduced cell counts and protein concentration of bronchoalveolar lavage fluid (BALF). EphA2 mAb posttreatment down-regulated the expression of phosphoinositide 3-kinases (PI3K) 110γ, phospho-Akt, phospho-NF-κB p65, phospho-Src and phospho-S6K in lung lysates. In addition, inhibiting the EphA2 receptor augmented the expression of E-cadherin, which is involved in cell-cell adhesion. Our study identified EphA2 receptor as an unrecognized modulator of several signalling pathways-including PI3K-Akt-NF-kB, Src-NF-κB, E-cadherin and mTOR-in LPS-induced lung injury. These results suggest that EphA2 receptor inhibitors may function as novel therapeutic agents for LPS-induced lung injury. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  13. Developing and Evaluating Medical Humanities Problem-Based Learning Classes Facilitated by the Teaching Assistants Majored in the Liberal Arts: A Longitudinal Crossover Study.

    PubMed

    Tseng, Fen-Yu; Shieh, Jeng-Yi; Kao, Tze-Wah; Wu, Chau-Chung; Chu, Tzong-Shinn; Chen, Yen-Yuan

    2016-02-01

    Although medical humanities courses taught by teachers from nonmedical backgrounds are not unusual now, few studies have compared the outcome of medical humanities courses facilitated by physicians to that by teaching assistants majored in the liberal arts. The objectives of this study were to (1) analyze the satisfaction of medical students with medical humanities problem-based learning (PBL) classes facilitated by nonmedical teaching assistants (TAF) majored in the liberal arts, and those facilitated by the attending physicians (APF) and (2) examine the satisfaction of medical students with clinical medicine-related and clinical medicine-unrelated medical humanities PBL classes.A total of 123 medical students, randomly assigned to 16 groups, participated in this study. There were 16 classes in the course: 8 of them were TAF classes; and the others were APF classes. Each week, each group rotated from 1 subject of the 16 subjects of PBL to another subject. All of the 16 groups went through all the 16 subjects in the 2013 spring semester. We examined the medical students' satisfaction with each class, based on a rating score collected after each class was completed, using a scale from 0 (the lowest satisfaction) to 100 (the highest satisfaction). We also conducted multivariate linear regression analysis to examine the association between the independent variables and the students' satisfaction.Medical students were more satisfied with the TAF (91.35 ± 7.75) medical humanities PBL classes than APF (90.40 ± 8.42) medical humanities PBL classes (P = 0.01). Moreover, medical students were more satisfied with the clinical medicine-unrelated topics (92.00 ± 7.10) than the clinical medicine-related topics (90.36 ± 7.99) in the medical humanities PBL course (P = 0.01).This medical humanities PBL course, including nonmedical subjects and topics, and nonmedical teaching assistants from the liberal arts as class facilitators, was satisfactory. This

  14. Taspine derivative 12k suppressed A549 cell migration through the Wnt/β-catenin and EphrinB2 signaling pathway.

    PubMed

    Dai, Bingling; Ma, Yujiao; Yang, Tianfeng; Wang, Wenjie; Zhang, Yanmin

    2017-03-01

    12k, a taspine derivative, has been demonstrated to have the potent anti-tumor activity in lung cancer and colorectal cancer. The study aims to further explore the underlying mechanisms of 12k on A549 cell migration in vitro. Our data demonstrated that 12k negatively regulated Wnt signaling pathway by suppressing the phosphorylation of LRP5/6, and inhibiting the expression and nuclear translocation of β-catenin. 12k was shown to downregulate MMP3 and MMP7 expression which regulated by β-catenin interacts with TCF/LEF in the nucleus, and effectively impaired the related migration protein expression of MMP2 and MMP9 in A549 cells. In addition, 12k repressed the EphrinB2 and its PDZ protein, impairing the VEGFR2 and VEGFR3 expression in A549 cells, as well as inhibited the downstream of VEGFR2 included PI3K/AKT/mTOR and ERK/MAPK signaling pathways. Taken together, our findings revealed that 12k suppressed migration of A549 cells through the Wnt/β-catenin signaling pathway and EphrinB2 related signaling pathway. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  15. High-definition transcranial direct-current stimulation of the right M1 further facilitates left M1 excitability during crossed facilitation.

    PubMed

    Cabibel, Vincent; Muthalib, Makii; Teo, Wei-Peng; Perrey, Stephane

    2018-04-01

    The crossed-facilitation (CF) effect refers to when motor-evoked potentials (MEPs) evoked in the relaxed muscles of one arm are facilitated by contraction of the opposite arm. The aim of this study was to determine whether high-definition transcranial direct-current stimulation (HD-tDCS) applied to the right primary motor cortex (M1) controlling the left contracting arm [50% maximum voluntary isometric contraction (MVIC)] would further facilitate CF toward the relaxed right arm. Seventeen healthy right-handed subjects participated in an anodal and cathodal or sham HD-tDCS session of the right M1 (2 mA for 20 min) separated by at least 48 h. Single-pulse transcranial magnetic stimulation (TMS) was used to elicit MEPs and cortical silent periods (CSPs) from the left M1 at baseline and 10 min into and after right M1 HD-tDCS. At baseline, compared with resting, CF (i.e., right arm resting, left arm 50% MVIC) increased left M1 MEP amplitudes (+97%) and decreased CSPs (-11%). The main novel finding was that right M1 HD-tDCS further increased left M1 excitability (+28.3%) and inhibition (+21%) from baseline levels during CF of the left M1, with no difference between anodal and cathodal HD-tDCS sessions. No modulation of CSP or MEP was observed during sham HD-tDCS sessions. Our findings suggest that CF of the left M1 combined with right M1 anodal or cathodal HD-tDCS further facilitated interhemispheric interactions during CF from the right M1 (contracting left arm) toward the left M1 (relaxed right arm), with effects on both excitatory and inhibitory processing. NEW & NOTEWORTHY This study shows modulation of the nonstimulated left M1 by right M1 HD-tDCS combined with crossed facilitation, which was probably achieved through modulation of interhemispheric interactions.

  16. [Class III surgical patients facilitated by accelerated osteogenic orthodontic treatment].

    PubMed

    Wu, Jia-qi; Xu, Li; Liang, Cheng; Zou, Wei; Bai, Yun-yang; Jiang, Jiu-hui

    2013-10-01

    To evaluate the treatment time and the anterior and posterior teeth movement pattern as closing extraction space for the Class III surgical patients facilitated by accelerated osteogenic orthodontic treatment. There were 10 skeletal Class III patients in accelerated osteogenic orthodontic group (AOO) and 10 patients in control group. Upper first premolars were extracted in all patients. After leveling and alignment (T2), corticotomy was performed in the area of maxillary anterior teeth to accelerate space closing.Study models of upper dentition were taken before orthodontic treatment (T1) and after space closing (T3). All the casts were laser scanned, and the distances of the movement of incisors and molars were digitally measured. The distances of tooth movement in two groups were recorded and analyzed. The alignment time between two groups was not statistically significant. The treatment time in AOO group from T2 to T3 was less than that in the control group (less than 9.1 ± 4.1 months). The treatment time in AOO group from T1 to T3 was less than that in the control group (less than 6.3 ± 4.8 months), and the differences were significant (P < 0.01). Average distances of upper incisor movement (D1) in AOO group and control group were (2.89 ± 1.48) and (3.10 ± 0.95) mm, respectively. Average distances of upper first molar movement (D2) in AOO group and control group were (2.17 ± 1.13) and (2.45 ± 1.04) mm, respectively.No statistically significant difference was found between the two groups (P > 0.05). Accelerated osteogenic orthodontic treatment could accelerate space closing in Class III surgical patients and shorten preoperative orthodontic time. There were no influence on the movement pattern of anterior and posterior teeth during pre-surgical orthodontic treatment.

  17. Cross-Cultural Socialization at Tibetan Classes (Schools) in the Interior: An Empirical Analysis

    ERIC Educational Resources Information Center

    Guo, Longyan

    2010-01-01

    Education by means of the Tibetan Classes (schools) in "neidi," or China's interior regions (or the Tibet Class), was a creative measure in the history of China's ethnic minority education, and the cross-cultural growth and experiences of the Tibetan students as they went to school in China's interior regions was of special significance…

  18. Facilitators and barriers experienced by federal cross-sector partners during the implementation of a healthy eating campaign.

    PubMed

    Fernandez, Melissa Anne; Desroches, Sophie; Marquis, Marie; Turcotte, Mylène; Provencher, Véronique

    2017-09-01

    To identify facilitators and barriers that Health Canada's (HC) cross-sector partners experienced while implementing the Eat Well Campaign: Food Skills (EWC; 2013-2014) and describe how these experiences might differ according to distinct partner types. A qualitative study using hour-long semi-structured telephone interviews conducted with HC partners that were transcribed verbatim. Facilitators and barriers were identified inductively and analysed according partner types. Implementation of a national mass-media health education campaign. Twenty-one of HC's cross-sector partners (food retailers, media and health organizations) engaged in the EWC. Facilitators and barriers were grouped into seven major themes: operational elements, intervention factors, resources, collaborator traits, developer traits, partnership factors and target population factors. Four of these themes had dual roles as both facilitators and barriers (intervention factors, resources, collaborator traits and developer traits). Sub-themes identified as both facilitators and barriers illustrate the extent to which a facilitator can easily become a barrier. Partnership factors were unique facilitators, while operational and target population factors were unique barriers. Time was a barrier that was common to almost all partners regardless of partnership type. There appeared to be a greater degree of uniformity among facilitators, whereas barriers were more diverse and unique to the realities of specific types of partner. Collaborative planning will help public health organizations anticipate barriers unique to the realities of specific types of organizations. It will also prevent facilitators from becoming barriers. Advanced planning will help organizations manage time constraints and integrate activities, facilitating implementation.

  19. Instructor Facilitation of Whole-Class Discussion in Two Mathematics Classes for Preservice Teachers

    ERIC Educational Resources Information Center

    Young, Sarah Helen

    2014-01-01

    This study investigated how instructors engage preservice teachers (PSTs) in whole-class discussion in mathematics classes for PSTs. Participating in discussions of mathematical ideas by explaining mathematical ideas to others and responding to others' ideas and arguments might be beneficial for PSTs both to help them develop deeper knowledge of…

  20. Poly-Cross-Linked PEI Through Aromatically Conjugated Imine Linkages as a New Class of pH-Responsive Nucleic Acids Packing Cationic Polymers

    PubMed Central

    Chen, Shun; Jin, Tuo

    2016-01-01

    Cationic polyimines polymerized through aromatically conjugated bis-imine linkages and intra-molecular cross-linking were found to be a new class of effective transfection materials for their flexibility in structural optimization, responsiveness to intracellular environment, the ability to facilitate endosome escape and cytosol release of the nucleic acids, as well as self-metabolism. When three phthalaldehydes of different substitution positions were used to polymerize highly branched low-molecular weight polyethylenimine (PEI 1.8K), the product through ortho-phthalimines (named PPOP) showed significantly higher transfection activity than its two tere- and iso-analogs (named PPTP and PPIP). Physicochemical characterization confirmed the similarity of three polyimines in pH-responded degradability, buffer capacity, as well as the size and Zeta potential of the polyplexes formed from the polymers. A mechanistic speculation may be that the ortho-positioned bis-imine linkage of PPOP may only lead to the straight trans-configuration due to steric hindrance, resulting in larger loops of intra-polymer cross-linking and more flexible backbone. PMID:26869931

  1. A Pilot Study: Facilitating Cross-Cultural Understanding with Project-Based Collaborative Learning in an Online Environment

    ERIC Educational Resources Information Center

    Shadiev, Rustam; Hwang, Wu-Yuin; Huang, Yueh-Min

    2015-01-01

    This study investigated three aspects: how project-based collaborative learning facilitates cross-cultural understanding; how students perceive project-based collaborative learning implementation in a collaborative cyber community (3C) online environment; and what types of communication among students are used. A qualitative case study approach…

  2. Soluble ephrin a1 is necessary for the growth of HeLa and SK-BR3 cells

    PubMed Central

    2010-01-01

    Background Ephrin A1 (EFNA1) is a member of the A-type ephrin family of cell surface proteins that function as ligands for the A-type Eph receptor tyrosine kinase family. In malignancy, the precise role of EFNA1 and its preferred receptor, EPHA2, is controversial. Several studies have found that EFNA1 may suppress EPHA2-mediated oncogenesis, or enhance it, depending on cell type and context. However, little is known about the conditions that influence whether EFNA1 promotes or suppresses tumorigenicity. EFNA1 exists in a soluble form as well as a glycophosphatidylinositol (GPI) membrane attached form. We investigated whether the contradictory roles of EFNA1 in malignancy might in part be related to the existence of both soluble and membrane attached forms of EFNA1 and potential differences in the manner in which they interact with EPHA2. Results Using a RNAi strategy to reduce the expression of endogenous EFNA1 and EPHA2, we found that both EFNA1 and EPHA2 are required for growth of HeLa and SK-BR3 cells. The growth defects could be rescued by conditioned media from cells overexpressing soluble EFNA1. Interestingly, we found that overexpression of the membrane attached form of EFNA1 suppresses growth of HeLa cells in 3D but not 2D. Knockdown of endogenous EFNA1, or overexpression of full-length EFNA1, resulted in relocalization of EPHA2 from the cell surface to sites of cell-cell contact. Overexpression of soluble EFNA1 however resulted in more EPHA2 distributed on the cell surface, away from cell-cell contacts, and promoted the growth of HeLa cells. Conclusions We conclude that soluble EFNA1 is necessary for the transformation of HeLa and SK-BR3 cells and participates in the relocalization of EPHA2 away from sites of cell-cell contact during transformation. PMID:20979646

  3. Assessing Facilitator Performance as an Influence on Student Satisfaction

    ERIC Educational Resources Information Center

    Dunlap, Scotty; May, David

    2011-01-01

    Growth in class size within the online environment has resulted in a facilitator model in which an instructor teaches the class with the assistance of facilitators who interact with students in smaller groups. This research sought to determine the effectiveness of a structured performance evaluation for facilitators and the correlation to student…

  4. Dynamics of two-strain influenza model with cross-immunity and no quarantine class.

    PubMed

    Chung, K W; Lui, Roger

    2016-12-01

    The question about whether a periodic solution can exists for a given epidemiological model is a complicated one and has a long history (Hethcote and Levin, Applied math. ecology, biomathematics, vol 18. Springer, Berlin, pp 193-211, 1989). For influenza models, it is well known that a periodic solution can exists for a single-strain model with periodic contact rate (Aron and Schwartz, J Math Biol 110:665-679, 1984; Kuznetsov and Piccardi, J Math Biol 32:109-121, 1994), or a multiple-strain model with cross-immunity and quarantine class or age-structure (Nuño et al., Mathematical epidemiology. Lecture notes in mathematics, vol 1945. Springer, Berlin, 2008, chapter 13). In this paper, we prove the local asymptotic stability of the interior steady-state of a two-strain influenza model with sufficiently close cross-immunity and no quarantine class or age-structure. We also show that if the cross-immunity between two strains are far apart; then it is possible for the interior steady-state to lose its stability and bifurcation of periodic solutions can occur. Our results extend those obtained by Nuño et.al. (SIAM J Appl Math 65:964-982, 2005). This problem is important because understanding the reasons behind periodic outbreaks of seasonal flu is an important issue in public health.

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

    PubMed Central

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

    2015-01-01

    Summary 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. PMID:26549443

  6. EphrinB3/EphA4-mediated guidance of ascending and descending spinal tracts.

    PubMed

    Paixão, Sónia; Balijepalli, Aarathi; Serradj, Najet; Niu, Jingwen; Luo, Wenqin; Martin, John H; Klein, Rüdiger

    2013-12-18

    The spinal cord contains many descending and ascending longitudinal tracts whose development appears to be controlled by distinct guidance systems. We identified a population of dorsal spinal neurons marked by coexpression of the transcription factor Zic2 and the guidance receptor EphA4. Zic2+;EphA4+ neurons are surrounded by mechanosensory terminals, suggesting innervation by mechanoreceptor afferents. Their axons form an ipsilateral ascending pathway that develops during embryogenesis and projects within the ventral aspect of the dorsal funiculus, the same location as the descending corticospinal tract (CST), which develops postnatally. Interestingly, the same guidance mechanism, namely, ephrinB3-induced EphA4 forward signaling, is required for the guidance of both ascending and descending axon tracts. Our analysis of conditional EphA4 mutant mice also revealed that the development of the dorsal funiculus occurs independently of EphA4 expression in descending CST axons and is linked to the distribution of Zic2+;EphA4+ spinal neurons and the formation of the ascending pathway. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Effects of Student-Facilitated Learning on Instructional Facilitators

    ERIC Educational Resources Information Center

    Bonner, Sarah M.; Somers, Jennifer A.; Rivera, Gwendelyn J.; Keiler, Leslie S.

    2017-01-01

    We investigated perceptions about learning strategy use and instructional roles among a sample of high needs adolescents (n = 230) who acted as near-peer instructional facilitators. The sample was drawn from science and mathematics classes in nonselective public secondary schools in New York City. Students participated in an inschool intervention…

  8. Unique Structure and Dynamics of the EphA5 Ligand Binding Domain Mediate Its Binding Specificity as Revealed by X-ray Crystallography, NMR and MD Simulations

    PubMed Central

    Mitra, Sayantan; Zhu, Wanlong; Qin, Haina; Pasquale, Elena B.; Song, Jianxing

    2013-01-01

    The 16 EphA and EphB receptors represent the largest family of receptor tyrosine kinases, and their interactions with 9 ephrin-A and ephrin-B ligands initiate bidirectional signals controlling many physiological and pathological processes. Most interactions occur between receptor and ephrins of the same class, and only EphA4 can bind all A and B ephrins. To understand the structural and dynamic principles that enable Eph receptors to utilize the same jellyroll β-sandwich fold to bind ephrins, the VAPB-MSP domain, peptides and small molecules, we have used crystallography, NMR and molecular dynamics (MD) simulations to determine the first structure and dynamics of the EphA5 ligand-binding domain (LBD), which only binds ephrin-A ligands. Unexpectedly, despite being unbound, the high affinity ephrin-binding pocket of EphA5 resembles that of other Eph receptors bound to ephrins, with a helical conformation over the J–K loop and an open pocket. The openness of the pocket is further supported by NMR hydrogen/deuterium exchange data and MD simulations. Additionally, the EphA5 LBD undergoes significant picosecond-nanosecond conformational exchanges over the loops, as revealed by NMR and MD simulations, but lacks global conformational exchanges on the microsecond-millisecond time scale. This is markedly different from the EphA4 LBD, which shares 74% sequence identity and 87% homology. Consequently, the unbound EphA5 LBD appears to comprise an ensemble of open conformations that have only small variations over the loops and appear ready to bind ephrin-A ligands. These findings show how two proteins with high sequence homology and structural similarity are still able to achieve distinctive binding specificities through different dynamics, which may represent a general mechanism whereby the same protein fold can serve for different functions. Our findings also suggest that a promising strategy to design agonists/antagonists with high affinity and selectivity might be to

  9. Cross-Linking and Mass Spectrometry Methodologies to Facilitate Structural Biology: Finding a Path through the Maze

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Merkley, Eric D.; Cort, John R.; Adkins, Joshua N.

    2013-09-01

    Multiprotein complexes, rather than individual proteins, make up a large part of the biological macromolecular machinery of a cell. Understanding the structure and organization of these complexes is critical to understanding cellular function. Chemical cross-linking coupled with mass spectrometry is emerging as a complementary technique to traditional structural biology methods and can provide low-resolution structural information for a multitude of purposes, such as distance constraints in computational modeling of protein complexes. In this review, we discuss the experimental considerations for successful application of chemical cross-linking-mass spectrometry in biological studies and highlight three examples of such studies from the recent literature.more » These examples (as well as many others) illustrate the utility of a chemical cross-linking-mass spectrometry approach in facilitating structural analysis of large and challenging complexes.« less

  10. Working-class Filipino women's perspectives on factors that facilitate or hinder prenatal micronutrients supplementation to prevent congenital anomalies.

    PubMed

    Daack-Hirsch, Sandra; Gamboa, Henrietta

    2012-11-01

    The study was conducted to plan for a community-health campaign to inform working-class Filipinos about the causes and prevention of orofacial clefting. Prenatal micronutrients may play a role in preventing orofacial clefting. Therefore, women's practices and perspectives on barriers to and facilitators of micronutrient supplementation were elicited. A total of 43 women and 22 health care workers were interviewed. Barriers to taking supplements included side effects, late prenatal care, the view that micronutrients are medications, inadequate supply, and health care workers who were unaware that prenatal vitamin supplements prevent congenital anomalies. The main facilitator was women's understanding that prenatal micronutrients improve the physical well-being of both mother and child. Given that women view having healthy babies as a reason to take micronutrients and that the health care workers lacked knowledge related to the use of micronutrients to prevent congenital anomalies, uptake of prenatal micronutrient supplementation programs may improve by specifically promoting the health benefit of preventing congenital anomalies.

  11. Iranian Nurses' Views on Barriers and Facilitators in Patient Education: A Cross-Sectional Study.

    PubMed

    Ramezanli, Somayeh; Badiyepeymaie Jahromi, Zohreh

    2015-03-18

    As a major factor in patient-centered care, patient education has a great impact on the quality of care provided by nurses; however, clinical nurses' performance with regard to patient education is not satisfactory. This study is an attempt to investigate barriers and facilitators in patient education from nurses' point of view. 122 nurses at Jahrom University of Medical Sciences participated in this descriptive-cross sectional study. Sampling was based on the census method. The questionnaire used to collect data included questions about nurses' demography, barriers (10 questions), and facilitators (10 questions) in patient education. The questionnaire was designed to be completed independently. To analyze the data, the researchers used descriptive statistics, including frequency, mean and standard deviation. The highest scores related to barriers to patient education were: nurses' insufficient knowledge, patients' physical and emotional unpreparedness, and lack of a proper environment for education. The most important facilitators, on the other hand, were: enhancement of instructing nurses' knowledge and skills, motivating nurses, and a step-by-step approach to patient education. It is important that nurses be prepared and motivated to train their patients. By satisfactory patient education on the part of nurses, patients will be more willing to cooperate in the treatment process.

  12. Iranian Nurses’ Views on Barriers and Facilitators in Patient Education: A Cross-Sectional Study

    PubMed Central

    Ramezanli, Somayeh; Jahromi, Zohreh Badiyepeymaie

    2015-01-01

    Background: As a major factor in patient-centered care, patient education has a great impact on the quality of care provided by nurses; however, clinical nurses’ performance with regard to patient education is not satisfactory. This study is an attempt to investigate barriers and facilitators in patient education from nurses’ point of view. Methods: 122 nurses at Jahrom University of Medical Sciences participated in this descriptive-cross sectional study. Sampling was based on the census method. The questionnaire used to collect data included questions about nurses’ demography, barriers (10 questions), and facilitators (10 questions) in patient education. The questionnaire was designed to be completed independently. To analyze the data, the researchers used descriptive statistics, including frequency, mean and standard deviation. Results: The highest scores related to barriers to patient education were: nurses’ insufficient knowledge, patients’ physical and emotional unpreparedness, and lack of a proper environment for education. The most important facilitators, on the other hand, were: enhancement of instructing nurses’ knowledge and skills, motivating nurses, and a step-by-step approach to patient education. Conclusion: It is important that nurses be prepared and motivated to train their patients. By satisfactory patient education on the part of nurses, patients will be more willing to cooperate in the treatment process. PMID:26156926

  13. EphrinA2 Receptor (EphA2) Is an Invasion and Intracellular Signaling Receptor for Chlamydia trachomatis

    PubMed Central

    Subbarayal, Prema; Karunakaran, Karthika; Winkler, Ann-Cathrin; Rother, Marion; Gonzalez, Erik; Meyer, Thomas F.; Rudel, Thomas

    2015-01-01

    The obligate intracellular bacterium Chlamydia trachomatis invades into host cells to replicate inside a membrane-bound vacuole called inclusion. Multiple different host proteins are recruited to the inclusion and are functionally modulated to support chlamydial development. Invaded and replicating Chlamydia induces a long-lasting activation of the PI3 kinase signaling pathway that is required for efficient replication. We identified the cell surface tyrosine kinase EphrinA2 receptor (EphA2) as a chlamydial adherence and invasion receptor that induces PI3 kinase (PI3K) activation, promoting chlamydial replication. Interfering with binding of C. trachomatis serovar L2 (Ctr) to EphA2, downregulation of EphA2 expression or inhibition of EphA2 activity significantly reduced Ctr infection. Ctr interacts with and activates EphA2 on the cell surface resulting in Ctr and receptor internalization. During chlamydial replication, EphA2 remains active accumulating around the inclusion and interacts with the p85 regulatory subunit of PI3K to support the activation of the PI3K/Akt signaling pathway that is required for normal chlamydial development. Overexpression of full length EphA2, but not the mutant form lacking the intracellular cytoplasmic domain, enhanced PI3K activation and Ctr infection. Despite the depletion of EphA2 from the cell surface, Ctr infection induces upregulation of EphA2 through the activation of the ERK pathway, which keeps the infected cell in an apoptosis-resistant state. The significance of EphA2 as an entry and intracellular signaling receptor was also observed with the urogenital C. trachomatis-serovar D. Our findings provide the first evidence for a host cell surface receptor that is exploited for invasion as well as for receptor-mediated intracellular signaling to facilitate chlamydial replication. In addition, the engagement of a cell surface receptor at the inclusion membrane is a new mechanism by which Chlamydia subverts the host cell and

  14. EphrinA2 receptor (EphA2) is an invasion and intracellular signaling receptor for Chlamydia trachomatis.

    PubMed

    Subbarayal, Prema; Karunakaran, Karthika; Winkler, Ann-Cathrin; Rother, Marion; Gonzalez, Erik; Meyer, Thomas F; Rudel, Thomas

    2015-04-01

    The obligate intracellular bacterium Chlamydia trachomatis invades into host cells to replicate inside a membrane-bound vacuole called inclusion. Multiple different host proteins are recruited to the inclusion and are functionally modulated to support chlamydial development. Invaded and replicating Chlamydia induces a long-lasting activation of the PI3 kinase signaling pathway that is required for efficient replication. We identified the cell surface tyrosine kinase EphrinA2 receptor (EphA2) as a chlamydial adherence and invasion receptor that induces PI3 kinase (PI3K) activation, promoting chlamydial replication. Interfering with binding of C. trachomatis serovar L2 (Ctr) to EphA2, downregulation of EphA2 expression or inhibition of EphA2 activity significantly reduced Ctr infection. Ctr interacts with and activates EphA2 on the cell surface resulting in Ctr and receptor internalization. During chlamydial replication, EphA2 remains active accumulating around the inclusion and interacts with the p85 regulatory subunit of PI3K to support the activation of the PI3K/Akt signaling pathway that is required for normal chlamydial development. Overexpression of full length EphA2, but not the mutant form lacking the intracellular cytoplasmic domain, enhanced PI3K activation and Ctr infection. Despite the depletion of EphA2 from the cell surface, Ctr infection induces upregulation of EphA2 through the activation of the ERK pathway, which keeps the infected cell in an apoptosis-resistant state. The significance of EphA2 as an entry and intracellular signaling receptor was also observed with the urogenital C. trachomatis-serovar D. Our findings provide the first evidence for a host cell surface receptor that is exploited for invasion as well as for receptor-mediated intracellular signaling to facilitate chlamydial replication. In addition, the engagement of a cell surface receptor at the inclusion membrane is a new mechanism by which Chlamydia subverts the host cell and

  15. Analytical design equations for self-tuned Class-E power amplifier.

    PubMed

    Hu, Zhe; Troyk, Philip

    2011-01-01

    For many emerging neural prosthesis designs that are powered by inductive coupling, their small physical size requires large current in the extracorporeal transmitter coil, and the Class-E power amplifier topology is often used for the transmitter design. Tuning of Class-E circuits for efficient operation is difficult and a self-tuned circuit can facilitate the tuning. The coil current is sensed and used to tune the switching of the transistor switch in the Class-E circuit in order to maintain its high-efficiency operation. Although mathematically complex, the analysis and design procedure for the self-tuned Class-E circuit can be simplified due to the current feedback control, which makes the phase angle between the switching pulse and the coil current predetermined. In this paper explicit analytical design equations are derived and a detailed design procedure is presented and compared with the conventional Class-E design approaches.

  16. 'Til Eph do us part': intercellular signaling via Eph receptors and ephrin ligands guides cerebral cortical development from birth through maturation.

    PubMed

    North, Hilary A; Clifford, Meredith A; Donoghue, Maria J

    2013-08-01

    Eph receptors, the largest family of surface-bound receptor tyrosine kinases and their ligands, the ephrins, mediate a wide variety of cellular interactions in most organ systems throughout both development and maturity. In the forming cerebral cortex, Eph family members are broadly and dynamically expressed in particular sets of cortical cells at discrete times. Here, we review the known functions of Eph-mediated intercellular signaling in the generation of progenitors, the migration of maturing cells, the differentiation of neurons, the formation of functional connections, and the choice between life and death during corticogenesis. In synthesizing these results, we posit a signaling paradigm in which cortical cells maintain a life history of Eph-mediated intercellular interactions that guides subsequent cellular decision-making.

  17. Diminutives facilitate word segmentation in natural speech: cross-linguistic evidence.

    PubMed

    Kempe, Vera; Brooks, Patricia J; Gillis, Steven; Samson, Graham

    2007-06-01

    Final-syllable invariance is characteristic of diminutives (e.g., doggie), which are a pervasive feature of the child-directed speech registers of many languages. Invariance in word endings has been shown to facilitate word segmentation (Kempe, Brooks, & Gillis, 2005) in an incidental-learning paradigm in which synthesized Dutch pseudonouns were used. To broaden the cross-linguistic evidence for this invariance effect and to increase its ecological validity, adult English speakers (n=276) were exposed to naturally spoken Dutch or Russian pseudonouns presented in sentence contexts. A forced choice test was given to assess target recognition, with foils comprising unfamiliar syllable combinations in Experiments 1 and 2 and syllable combinations straddling word boundaries in Experiment 3. A control group (n=210) received the recognition test with no prior exposure to targets. Recognition performance improved with increasing final-syllable rhyme invariance, with larger increases for the experimental group. This confirms that word ending invariance is a valid segmentation cue in artificial, as well as naturalistic, speech and that diminutives may aid segmentation in a number of languages.

  18. Nurses’ Perceived Barriers to and Facilitators of Research Utilization in Mainland China: A Cross-Sectional Survey

    PubMed Central

    Chien, Wai-Tong; Bai, Qin; Wong, Wai-Kit; Wang, Huizhen; Lu, Xueqin

    2013-01-01

    Despite the drive towards evidence-based practice, the extent to which research evidence is being implemented in nursing practice is unclear, particularly in developing countries. This study was to assess the levels of perceived barriers to and facilitators of research utilization in practice among Chinese nurses and inter-relationships between these barriers and facilitators and their socio-demographic characteristics. A cross-sectional, descriptive survey was conducted in 2011 with 743 registered nurses randomly selected from four general hospitals in China. They completed the Barriers to Research Utilization and Facilitators of Research Utilization scales. Correlation tests were used to test the relationships between the nurses’ perceived barriers and facilitators, their demographic characteristics and research training and involvement. The Chinese nurses’ level of perceived barriers was moderate on average and lower than that in previous research. Among the 10 top-ranked items, six were from the subscale ‘Organizational Characteristics’. Their perceived barriers were correlated positively with age and post-registration experience and negatively with research training undertaken. Junior diplomatic nurses reported a significantly higher degree of barriers than those senior ones with postgraduate education. Higher and more diverse barriers to research utilization in practice are perceived by Chinese nurses than those in Western countries and they are associated with a few socio-demographic factors. Future research on these barriers/facilitators and their relationships with occupational and socio-cultural factors in Chinese and other Asian nurses is recommended. PMID:23919099

  19. EphA2 signalling following endocytosis: role of Tiam1

    PubMed Central

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

    2013-01-01

    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 behaviours 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 signalling 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 signalling. PMID:24112471

  20. Contrast class cues and performance facilitation in a hypothesis-testing task: evidence for an iterative counterfactual model.

    PubMed

    Gale, Maggie; Ball, Linden J

    2012-04-01

    Hypothesis-testing performance on Wason's (Quarterly Journal of Experimental Psychology 12:129-140, 1960) 2-4-6 task is typically poor, with only around 20% of participants announcing the to-be-discovered "ascending numbers" rule on their first attempt. Enhanced solution rates can, however, readily be observed with dual-goal (DG) task variants requiring the discovery of two complementary rules, one labeled "DAX" (the standard "ascending numbers" rule) and the other labeled "MED" ("any other number triples"). Two DG experiments are reported in which we manipulated the usefulness of a presented MED exemplar, where usefulness denotes cues that can establish a helpful "contrast class" that can stand in opposition to the presented 2-4-6 DAX exemplar. The usefulness of MED exemplars had a striking facilitatory effect on DAX rule discovery, which supports the importance of contrast-class information in hypothesis testing. A third experiment ruled out the possibility that the useful MED triple seeded the correct rule from the outset and obviated any need for hypothesis testing. We propose that an extension of Oaksford and Chater's (European Journal of Cognitive Psychology 6:149-169, 1994) iterative counterfactual model can neatly capture the mechanisms by which DG facilitation arises.

  1. Modeling Development in Retinal Afferents: Retinotopy, Segregation, and EphrinA/EphA Mutants

    PubMed Central

    Godfrey, Keith B.; Swindale, Nicholas V.

    2014-01-01

    During neural development, neurons extend axons to target areas of the brain. Through processes of growth, branching and retraction these axons establish stereotypic patterns of connectivity. In the visual system, these patterns include retinotopic organization and the segregation of individual axons onto different subsets of target neurons based on the eye of origin (ocular dominance) or receptive field type (ON or OFF). Characteristic disruptions to these patterns occur when neural activity or guidance molecule expression is perturbed. In this paper we present a model that explains how these developmental patterns might emerge as a result of the coordinated growth and retraction of individual axons and synapses responding to position-specific markers, trophic factors and spontaneous neural activity. This model derives from one presented earlier (Godfrey et al., 2009) but which is here extended to account for a wider range of phenomena than previously described. These include ocular dominance and ON-OFF segregation and the results of altered ephrinA and EphA guidance molecule expression. The model takes into account molecular guidance factors, realistic patterns of spontaneous retinal wave activity, trophic molecules, homeostatic mechanisms, axon branching and retraction rules and intra-axonal signaling mechanisms that contribute to the survival of nearby synapses on an axon. We show that, collectively, these mechanisms can account for a wider range of phenomena than previous models of retino-tectal development. PMID:25122119

  2. A cross-sectional study of facilitators and barriers of Iranian nurses' participation in continuing education programs.

    PubMed

    Hamzehgardeshi, Zeinab; Shahhosseini, Zohreh

    2013-12-27

    Continuing education is one of the modern strategies to maintain and elevate knowledge and professional skills of nurses which in turn elevate the health status of society. Since several factors affect nurses' participation in continuing education, it's essential to know promoters and obstacles in this issue and plan accordingly. In this cross-sectional study, 361 Iranian nurses who were recruited by convenience sampling method completed an anonymous, self-administered questionnaire from October 2012 to April 2013. Topics covered the participants' attitudes towards facilitators and barriers of their participation in continuing education. Mean and standard deviation of participants ' age were 37.14±7.58 years and 93.94% were female. The maximum score of facilitators and barriers to nurses' participation in continuing education were related to "Update my knowledge" and "Work commitments" respectively. The results showed among Iranian nurses, the mean score of personal and structural barriers was significantly higher than the mean score of interpersonal ones (F=2122.66, p<0.001). Results highlight policy makers and nursing managers' role on improving the accessibility to provided continuing education programs by enforcement of facilitators and reducing barriers focusing on the personal and structural barriers.

  3. Social class, marginality and self-assessed health: a cross-sectional analysis of the health gradient in Mexico

    PubMed Central

    Valle, Adolfo Martinez

    2009-01-01

    Background Examining the association between social inequality and health is not new. However, there is little empirical evidence of this association in the Latin American literature, much less from the Mexican scholars. Its research, including the one conducted in Mexico, has mostly followed a theoretical approach and has not been able to provide strong empirical evidence of their important theoretical and conceptual contributions, mainly because reliable, complete and valid data are unavailable. Methods To empirically examine the gradient effect of social class on self-rated health in Mexico, a secondary cross-sectional mixed-level analysis was designed. Using individual level data from the Second National Health Survey (ENSA II), social class categories were specified following a stratification approach according to the occupation and education indicators available from ENSA II. Two types of categories were made, one for t urban and one for the rural labor force. Two indicators of perceived health status were used as health outcomes: self-assessed health and reported morbidity. Furthermore, the marginality index, an indicator of relative deprivation was used to examine its contextual effect at the state and regional level. The analysis was conducted using logistic multivariate models. Results The cross-sectional analysis showed a gradient effect of social class for good assessed-health. Relative to the low urban class, the odds ratio (OR) for a good perception of health for individuals belonging to the high urban class was 2.9 (95% confidence interval: 2.1–3.9). The OR for the middle high class was 2.8 (95% confidence interval: 2.4–3.4), while the OR for the middle low class was 1.8 (95% confidence interval: 1.6–2.1). However, for the rural labour force an OR of 1.5 was only significant between the high class who considered their health as good relative to the low class (95% confidence interval: 1.02–2.2). At the aggregate level, the results also showed

  4. Crossing Class Lines: A Diary.

    ERIC Educational Resources Information Center

    Cassebaum, Anne

    2001-01-01

    Presents a diary of one month spent by a professional-track professor as an adjunct. Discusses the large salary decrease, the turmoil of job insecurity, and the "invisibility" of adjunct faculty. Asserts that although faculty should feel bound together by the work they have chosen, the class rift between tenure-track and adjunct faculty has…

  5. Long-Peptide Cross-Presentation by Human Dendritic Cells Occurs in Vacuoles by Peptide Exchange on Nascent MHC Class I Molecules.

    PubMed

    Ma, Wenbin; Zhang, Yi; Vigneron, Nathalie; Stroobant, Vincent; Thielemans, Kris; van der Bruggen, Pierre; Van den Eynde, Benoît J

    2016-02-15

    Cross-presentation enables dendritic cells to present on their MHC class I molecules antigenic peptides derived from exogenous material, through a mechanism that remains partly unclear. It is particularly efficient with long peptides, which are used in cancer vaccines. We studied the mechanism of long-peptide cross-presentation using human dendritic cells and specific CTL clones against melanoma Ags gp100 and Melan-A/MART1. We found that cross-presentation of those long peptides does not depend on the proteasome or the transporter associated with Ag processing, and therefore follows a vacuolar pathway. We also observed that it makes use of newly synthesized MHC class I molecules, through peptide exchange in vesicles distinct from the endoplasmic reticulum and classical secretory pathway, in an SEC22b- and CD74-independent manner. Our results indicate a nonclassical secretion pathway followed by nascent HLA-I molecules that are used for cross-presentation of those long melanoma peptides in the vacuolar pathway. Our results may have implications for the development of vaccines based on long peptides. Copyright © 2016 by The American Association of Immunologists, Inc.

  6. Using Text Mining to Characterize Online Discussion Facilitation

    ERIC Educational Resources Information Center

    Ming, Norma; Baumer, Eric

    2011-01-01

    Facilitating class discussions effectively is a critical yet challenging component of instruction, particularly in online environments where student and faculty interaction is limited. Our goals in this research were to identify facilitation strategies that encourage productive discussion, and to explore text mining techniques that can help…

  7. Using Technology to Facilitate Grading Consistency in Large Classes

    ERIC Educational Resources Information Center

    Cathcart, Abby; Neale, Larry

    2012-01-01

    University classes in marketing are often large and therefore require teams of teachers to cover all of the necessary activities. A major problem with teaching teams is the inconsistency that results from myriad individuals offering subjective opinions (Preston 1997). This innovation uses the latest moderation techniques along with Audience…

  8. Characteristic sounds facilitate visual search.

    PubMed

    Iordanescu, Lucica; Guzman-Martinez, Emmanuel; Grabowecky, Marcia; Suzuki, Satoru

    2008-06-01

    In a natural environment, objects that we look for often make characteristic sounds. A hiding cat may meow, or the keys in the cluttered drawer may jingle when moved. Using a visual search paradigm, we demonstrated that characteristic sounds facilitated visual localization of objects, even when the sounds carried no location information. For example, finding a cat was faster when participants heard a meow sound. In contrast, sounds had no effect when participants searched for names rather than pictures of objects. For example, hearing "meow" did not facilitate localization of the word cat. These results suggest that characteristic sounds cross-modally enhance visual (rather than conceptual) processing of the corresponding objects. Our behavioral demonstration of object-based cross-modal enhancement complements the extensive literature on space-based cross-modal interactions. When looking for your keys next time, you might want to play jingling sounds.

  9. Characteristic sounds facilitate visual search

    PubMed Central

    Iordanescu, Lucica; Guzman-Martinez, Emmanuel; Grabowecky, Marcia; Suzuki, Satoru

    2009-01-01

    In a natural environment, objects that we look for often make characteristic sounds. A hiding cat may meow, or the keys in the cluttered drawer may jingle when moved. Using a visual search paradigm, we demonstrated that characteristic sounds facilitated visual localization of objects, even when the sounds carried no location information. For example, finding a cat was faster when participants heard a meow sound. In contrast, sounds had no effect when participants searched for names rather than pictures of objects. For example, hearing “meow” did not facilitate localization of the word cat. These results suggest that characteristic sounds cross-modally enhance visual (rather than conceptual) processing of the corresponding objects. Our behavioral demonstration of object-based cross-modal enhancement complements the extensive literature on space-based cross-modal interactions. When looking for your keys next time, you might want to play jingling sounds. PMID:18567253

  10. Cross-linking staphylococcal enterotoxin A bound to major histocompatibility complex class I is required for TNF-alpha secretion

    NASA Technical Reports Server (NTRS)

    Wright, A. D.; Chapes, S. K.

    1999-01-01

    The mechanism of how superantigens function to activate cells has been linked to their ability to bind and cross-link the major histocompatibility complex class II (MHCII) molecule. Cells that lack the MHCII molecule also respond to superantigens, however, with much less efficiency. Therefore, the purpose of this study was to confirm that staphylococcal enterotoxin A (SEA) could bind the MHCI molecule and to test the hypothesis that cross-linking SEA bound to MHCII-deficient macrophages would induce a more robust cytokine response than without cross-linking. We used a capture enzyme-linked immunosorbent assay and an immunprecipitation assay to directly demonstrate that MHCI molecules bind SEA. Directly cross-linking MHCI using monoclonal antibodies or cross-linking bound SEA with an anti-SEA antibody or biotinylated SEA with avidin increased TNF-alpha and IL-6 secretion by MHCII(-/-) macrophages. The induction of a vigorous macrophage cytokine response by SEA/anti-SEA cross-linking of MHCI offers a mechanism to explain how MHCI could play an important role in superantigen-mediated pathogenesis. Copyright 1999 Academic Press.

  11. Testing a Mobile Version of a Cross-Chain Loran Atmospheric (M-CLASS) Sounding System.

    NASA Astrophysics Data System (ADS)

    Rust, W. David; Burgess, Donald W.; Maddox, Robert A.; Showell, Lester C.; Marshall, Thomas C.; Lauritsen, Dean K.

    1990-02-01

    We have Rested the NCAR Cross-Chain LORAN Atmospheric Sounding System (CLASS) in a fully mobile configuration, which we call M-CLASS. The sondes use LORAN-C navigation signals to allow calculation of balloon position and horizontal winds. In nonstormy environments, thermodynamics and wind data were almost always of high quality. Besides providing special soundings for operational forecasts and research programs, a major feature of mobile ballooning with M-CLASS is the ability to obtain additional data by flying other instruments on the balloons. We flew an electric field meter, along with a sonde, into storms on 8 of the initial 47 test flights in the spring of 1987. In storms, pressure, temperature, humidity, and wind data were of good quality about 80%, 75%, 60%, and 40% of the time, respectively. In a flight into a mesocyclone, we measured electric fields as high as 135 kV/m (at 10 km MSL) in a region of negative charge. The electric field data from several storms allow a quantitative assessment of conditions that accompany loss of LORAN data. LORAN tracking was lost at a median field of about 16 kV/m, and it returned at a median field of about 7 kV/m. Corona discharge from the LORAN antenna on the sonde was a cause of the loss of LORAN. We provided our early-afternoon M-CLASS test soundings to the National Weather Service Forecast Office in Norman, Oklahoma, in near real-time via amateur packet radio and also to the National Severe Storms Forecast Center. These soundings illustrate the potential for improving operational forecasts. Other test flights showed that M-CLASS data can provide high-resolution information on evolution of the Great Plains low-level jet stream. Our intercept of Hurricane Gilbert provided M-CLASS soundings in the right quadrant of the storm. We observed substantial wind shear in the lowest levels of the soundings around the time tornadoes were reported in south Texas. This intercept demonstrated the feasibility of taking M-CLASS data

  12. Is the Affordable Care Act Cultivating a Cross-Class Constituency? Income, Partisanship, and a Proposal for Tracing the Contingent Nature of Positive Policy Feedback Effects.

    PubMed

    Chattopadhyay, Jacqueline

    2018-02-01

    Social Security and Medicare enjoy strong political coalitions within the mass public because middle-class Americans believe they derive benefits from these programs and stand alongside lower-income beneficiaries in defending them from erosion. By pooling data from nine nationally representative surveys, this article examines whether the Affordable Care Act (ACA) is cultivating a similar cross-class constituency. The results show that middle-income Americans are less likely than low-income Americans to say the ACA has helped them personally so far. On the other hand, partisanship conditions the relationship between income and beliefs about benefits likely to be derived from the ACA in the long run. In total, the results suggest that cross-class Democratic optimism about long-run benefits may enable the ACA to reap positive beneficiary feedbacks, but a large and bipartisan cross-class constituency appears unlikely. Drawing on these results, this article also makes theoretical contributions to the policy feedback literature by underscoring the need for research on prospections' power in policy feedbacks and proposing a strategy for researchers, policy makers, and public managers to identify where partisanship intervenes in the standard policy feedback logic model, and thereby to better assess how it fragments and conditions positive feedback effects in target populations. Copyright © 2018 by Duke University Press 2018.

  13. X-Windows Socket Widget Class

    NASA Technical Reports Server (NTRS)

    Barry, Matthew R.

    2006-01-01

    The X-Windows Socket Widget Class ("Class" is used here in the object-oriented-programming sense of the word) was devised to simplify the task of implementing network connections for graphical-user-interface (GUI) computer programs. UNIX Transmission Control Protocol/Internet Protocol (TCP/IP) socket programming libraries require many method calls to configure, operate, and destroy sockets. Most X Windows GUI programs use widget sets or toolkits to facilitate management of complex objects. The widget standards facilitate construction of toolkits and application programs. The X-Windows Socket Widget Class encapsulates UNIX TCP/IP socket-management tasks within the framework of an X Windows widget. Using the widget framework, X Windows GUI programs can treat one or more network socket instances in the same manner as that of other graphical widgets, making it easier to program sockets. Wrapping ISP socket programming libraries inside a widget framework enables a programmer to treat a network interface as though it were a GUI.

  14. Binding and Function of Phosphotyrosines of the Ephrin A2 (EphA2) Receptor Using Synthetic Sterile α Motif (SAM) Domains*

    PubMed Central

    Borthakur, Susmita; Lee, HyeongJu; Kim, SoonJeung; Wang, Bing-Cheng; Buck, Matthias

    2014-01-01

    The sterile α motif (SAM) domain of the ephrin receptor tyrosine kinase, EphA2, undergoes tyrosine phosphorylation, but the effect of phosphorylation on the structure and interactions of the receptor is unknown. Studies to address these questions have been hindered by the difficulty of obtaining site-specifically phosphorylated proteins in adequate amounts. Here, we describe the use of chemically synthesized and specifically modified domain-length peptides to study the behavior of phosphorylated EphA2 SAM domains. We show that tyrosine phosphorylation of any of the three tyrosines, Tyr921, Tyr930, and Tyr960, has a surprisingly small effect on the EphA2 SAM structure and stability. However, phosphorylation at Tyr921 and Tyr930 enables differential binding to the Src homology 2 domain of the adaptor protein Grb7, which we propose will lead to distinct functional outcomes. Setting up different signaling platforms defined by selective interactions with adaptor proteins thus adds another level of regulation to EphA2 signaling. PMID:24825902

  15. Learning Geomorphology Using Aerial Photography in a Web-Facilitated Class

    ERIC Educational Resources Information Center

    Palmer, R. Evan

    2013-01-01

    General education students taking freshman-level physical geography and geomorphology classes at Arizona State University completed an online laboratory whose main tool was Google Earth. Early in the semester, oblique and planimetric views introduced students to a few volcanic, tectonic, glacial, karst, and coastal landforms. Semi-quantitative…

  16. Teacher’s Mathematical Communication Profile in Facilitating and Guiding Discussion

    NASA Astrophysics Data System (ADS)

    Umami, R.; Budayasa, I. K.; Suwarsono, St.

    2018-01-01

    Teacher’s communication skill plays an important role, one of which is to guide a class discussion for teaching purposes. This study aimed to investigate a teacher’s mathematical communication profile in facilitating and guiding a class discussion. This study is qualitative. A junior teacher of high school (i.e., a teacher with 1 to 5 year teaching experience) teaching mathematics at X-Social Class was selected as the subject of this study. The data was collected by observing the teacher’s mathematical communication in facilitating and guiding a discussion with the rules of sinus as the teaching material, and it was followed by a deep interview. The result showed that the junior teacher facilitated and guided a class discussion include providing responses (answer) addressing students’ difficulties and providing chances for students to propose and explain their ideas and be active in discussion. The junior teacher provides responses at sharp, optimal, and specific manner. In addition, she provides chances for her students to explain their thinking and have a discussion in anticipative, observative, selective, and connective manner. However, the study found that some of high-school teachers develop mathematical communication skills and use them to develop students’ mathematical communication skills.

  17. Antigen processing and remodeling of the endosomal pathway: requirements for antigen cross-presentation.

    PubMed

    Compeer, Ewoud Bernardus; Flinsenberg, Thijs Willem Hendrik; van der Grein, Susanna Geertje; Boes, Marianne

    2012-01-01

    Cross-presentation of endocytosed antigen as peptide/class I major histocompatibility complex complexes plays a central role in the elicitation of CD8(+) T cell clones that mediate anti-viral and anti-tumor immune responses. While it has been clear that there are specific subsets of professional antigen presenting cells capable of antigen cross-presentation, identification of mechanisms involved is still ongoing. Especially amongst dendritic cells (DC), there are specialized subsets that are highly proficient at antigen cross-presentation. We here present a focused survey on the cell biological processes in the endosomal pathway that support antigen cross-presentation. This review highlights DC-intrinsic mechanisms that facilitate the cross-presentation of endocytosed antigen, including receptor-mediated uptake, maturation-induced endosomal sorting of membrane proteins, dynamic remodeling of endosomal structures and cell surface-directed endosomal trafficking. We will conclude with the description of pathogen-induced deviation of endosomal processing, and discuss how immune evasion strategies pertaining endosomal trafficking may preclude antigen cross-presentation.

  18. Violence against Congolese refugee women in Rwanda and mental health: a cross-sectional study using latent class analysis

    PubMed Central

    Sipsma, Heather L; Falb, Kathryn L; Willie, Tiara; Bradley, Elizabeth H; Bienkowski, Lauren; Meerdink, Ned; Gupta, Jhumka

    2015-01-01

    Objective To examine patterns of conflict-related violence and intimate partner violence (IPV) and their associations with emotional distress among Congolese refugee women living in Rwanda. Design Cross-sectional study. Setting Two Congolese refugee camps in Rwanda. Participants 548 ever-married Congolese refugee women of reproductive age (15–49 years) residing in Rwanda. Primary outcome measure Our primary outcome was emotional distress as measured using the Self-Report Questionnaire-20 (SRQ-20). For analysis, we considered participants with scores greater than 10 to be experiencing emotional distress and participants with scores of 10 or less not to be experiencing emotional distress. Results Almost half of women (49%) reported experiencing physical, emotional or sexual violence during the conflict, and less than 10% of women reported experiencing of any type of violence after fleeing the conflict. Lifetime IPV was reported by approximately 22% of women. Latent class analysis derived four distinct classes of violence experiences, including the Low All Violence class, the High Violence During Conflict class, the High IPV class and the High Violence During and After Conflict class. In multivariate regression models, latent class was strongly associated with emotional distress. Compared with women in the Low All Violence class, women in the High Violence During and After Conflict class and women in the High Violence During Conflict had 2.7 times (95% CI 1.11 to 6.74) and 2.3 times (95% CI 1.30 to 4.07) the odds of experiencing emotional distress in the past 4 weeks, respectively. Furthermore, women in the High IPV class had a 4.7 times (95% CI 2.53 to 8.59) greater odds of experiencing emotional distress compared with women in the Low All Violence class. Conclusions Experiences of IPV do not consistently correlate with experiences of conflict-related violence, and women who experience high levels of IPV may have the greatest likelihood for poor mental health

  19. Do Facilitated Online Dual Credit Classes Result in Deep Learning?

    ERIC Educational Resources Information Center

    Stark Education Partnership, 2015

    2015-01-01

    This study, with funding from the Jennings Foundation, sought to answer the following broad research question: Do facilitated online dual credit courses result in deep learning? The answer to this question is key to addressing barriers many students face in bridging from high school to college. This report includes a descriptive case study that…

  20. Inhibition of the archaeal beta-class (Cab) and gamma-class (Cam) carbonic anhydrases.

    PubMed

    Zimmerman, Sabrina A; Ferry, James G; Supuran, Claudiu T

    2007-01-01

    Five independently evolved classes (alpha-, beta-, gamma-, delta-, zeta-) of carbonic anhydrases facilitate the reversible hydration of carbon dioxide to bicarbonate of which the alpha-class is the most extensively studied. Detailed inhibition studies of the alpha-class with the two main classes of inhibitors, sulfonamides and metal-complexing anions, revealed many inhibitors that are used as therapeutic agents to prevent and treat many diseases. Recent inhibitor studies of the archaeal beta-class (Cab) and the gamma-class (Cam) carbonic anhydrases show differences in inhibition response to sulfonamides and metal-complexing anions, when compared to the alpha-class carbonic anhydrases. In addition, inhibition between Cab and Cam differ. These inhibition patterns are consistent with the idea that although, alpha-, beta-, and gamma-class carbonic anhydrases participate in the same two-step isomechanism, diverse active site architecture among these classes predicts variations on the catalytic mechanism. These inhibitor studies of the archaeal beta- and gamma-class carbonic anhydrases give insight to new applications of current day carbonic anhydrase inhibitors, as well as direct research to develop new compounds that may be specific inhibitors of prokaryotic carbonic anhydrases.

  1. RNA oxidation catalyzed by cytochrome c leads to its depurination and cross-linking, which may facilitate cytochrome c release from mitochondria

    PubMed Central

    Tanaka, Mikiei; Jaruga, Pawel; Küpfer, Pascal A.; Leumann, Christian J.; Dizdaroglu, Miral; Sonntag, William E.; Chock, P. Boon

    2015-01-01

    Growing evidence indicates that RNA oxidation is correlated with a number of age-related neurodegen-erative diseases, and RNA oxidation has also been shown to induce dysfunction in protein synthesis. Here we study in vitro RNA oxidation catalyzed by cytochrome c (cyt c)/H2O2 or by the Fe(II)/ascorbate/H2O2 system. Our results reveal that the products of RNA oxidation vary with the oxidant used. Guanosine residues are preferentially oxidized by cyt c/H2O2 relative to the Fe(II)/ascorbate/H2O2 system. GC/MS and LC/MS analyses demonstrated that the guanine base was not only oxidized but also depurinated to form an abasic sugar moiety. Results from gel electrophoresis and HPLC analyses show that RNA formed a cross-linked complex with cyt c in an H2O2 concentration-dependent manner. Furthermore, when cyt c was associated with liposomes composed of cardiolipin/phosphatidylcholine, and incubated with RNA and H2O2, it was found cross-linked with the oxidized RNA and dissociated from the liposome. Results of the quantitative analysis indicate that the release of the cyt c from the liposome is facilitated by the formation of an RNA–cyt c cross-linked complex. Thus, RNA oxidation may facilitate the release of cyt c from the mitochondrial membrane to induce apoptosis in response to oxidative stress. PMID:22683603

  2. Functional Disruption of the Netrin-1 Guidance Gue Leads to Disruption in Mammary Gland Development and Increased Tumor Incidence

    DTIC Science & Technology

    2005-07-01

    interactions will be complicated by the observation that cues, such as Netrin ( Yebra et al., 2003) and a class 7, GPI-linked Semaphorin (Pasterkamp et al...In vivo cell sorting in complementary segmental domains mediated by Eph receptors and ephrins. Nature 399, 267-271. Yebra , M., Montgomery, A. M

  3. Writing To Facilitate Learning in Microbiology.

    ERIC Educational Resources Information Center

    Fisher, Linda E.

    This paper describes a microbiology course that utilizes writing to facilitate learning of complex concepts, for communicating experimental results, and as a diagnostic tool for the instructor in monitoring the students' understanding of material on an on-going basis. In-class writing assignments that summarize subject units are accompanied by a…

  4. Teaching Very Large Classes

    ERIC Educational Resources Information Center

    DeRogatis, Amy; Honerkamp, Kenneth; McDaniel, Justin; Medine, Carolyn; Nyitray, Vivian-Lee; Pearson, Thomas

    2014-01-01

    The editor of "Teaching Theology and Religion" facilitated this reflective conversation with five teachers who have extensive experience and success teaching extremely large classes (150 students or more). In the course of the conversation these professors exchange and analyze the effectiveness of several active learning strategies they…

  5. Undergraduate Cross Registration.

    ERIC Educational Resources Information Center

    Grupe, Fritz H.

    This report discusses various aspects of undergraduate cross-registration procedures, including the dimensions, values, roles and functions, basic assumptions, and facilitating and encouragment of cross-registration. Dimensions of cross-registration encompass financial exchange, eligibility, program limitations, type of grade and credit; extent of…

  6. Facilitating and Bridging Out-of-Class and In-Class Learning: An Interactive E-Book-Based Flipped Learning Approach for Math Courses

    ERIC Educational Resources Information Center

    Hwang, Gwo-Jen; Lai, Chiu-Lin

    2017-01-01

    Flipped learning is a well-recognized learning mode that reverses the traditional in-class instruction arrangement by delivering learning content outside of the classroom and engaging students in more activities in class. However, it remains a challenge for students to comprehend the learning material by themselves, particularly when learning…

  7. Class, Identity, and Teacher Education

    ERIC Educational Resources Information Center

    Van Galen, Jane A.

    2010-01-01

    This paper explores the possibilities of working with White, working-class teacher education students to explore the "complex social trajectory" (Reay in Women's Stud Int Forum 20(2):225-233, 1997a, p. 19) of class border crossing as they progress through college. Through analysis of a course that I have developed, "Education and the American…

  8. Medical returns as class transformation: situating migrants' medical returns within a framework of transnationalism.

    PubMed

    Horton, Sarah B

    2013-01-01

    Because studies of migrants' 'medical returns' have been largely confined to the field of public health, such forms of return migration are rarely contextualized within the rich social scientific literature on transnational migration. Drawing on ethnographic interviews with Mexican migrants in an immigrant enclave in central California, I show that migrants' reasons for returning to their hometowns for care must be understood within the class disjunctures facilitated by migration. While migrants' Medicaid insurance confined them to public clinics and hospitals in the United States, their migrant dollars enabled them to visit private doctors and clinics in Mexico. Yet medical returns were not mere medical arbitrage, but also allowed migrants to access care that had previously been foreclosed to them as poor peasants in Mexico. Thus crossing the border enabled a dual class transformation, as Mexican migrants transitioned from Medicaid recipients to cash-paying patients, and from poor rural peasants to 'returning royalty.'

  9. In Search of Cross-Talk Facilitation in a Dual-Cued Recall Task

    ERIC Educational Resources Information Center

    Rickard, Timothy C.; Bajic, Daniel

    2005-01-01

    Despite earlier evidence that the presence of 2 redundant cues can facilitate activation of a common response, T. C. Rickard and D. Bajic (2004) found no dual-cue facilitation in the case of cued recall, provided that each cue-response association was learned independently. In this study the authors investigated the generality of their results…

  10. Phosphotyrosine profiling identifies ephrin receptor A2 as a potential therapeutic target in esophageal squamous‐cell carcinoma

    PubMed Central

    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

    2015-01-01

    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. PMID:25366905

  11. Ephrin-B2 governs morphogenesis of endolymphatic sac and duct epithelia in the mouse inner ear.

    PubMed

    Raft, Steven; Andrade, Leonardo R; Shao, Dongmei; Akiyama, Haruhiko; Henkemeyer, Mark; Wu, Doris K

    2014-06-01

    Control over ionic composition and volume of the inner ear luminal fluid endolymph is essential for normal hearing and balance. Mice deficient in either the EphB2 receptor tyrosine kinase or the cognate transmembrane ligand ephrin-B2 (Efnb2) exhibit background strain-specific vestibular-behavioral dysfunction and signs of abnormal endolymph homeostasis. Using various loss-of-function mouse models, we found that Efnb2 is required for growth and morphogenesis of the embryonic endolymphatic epithelium, a precursor of the endolymphatic sac (ES) and duct (ED), which mediate endolymph homeostasis. Conditional inactivation of Efnb2 in early-stage embryonic ear tissues disrupted cell proliferation, cell survival, and epithelial folding at the origin of the endolymphatic epithelium. This correlated with apparent absence of an ED, mis-localization of ES ion transport cells relative to inner ear sensory organs, dysplasia of the endolymph fluid space, and abnormally formed otoconia (extracellular calcite-protein composites) at later stages of embryonic development. A comparison of Efnb2 and Notch signaling-deficient mutant phenotypes indicated that these two signaling systems have distinct and non-overlapping roles in ES/ED development. Homozygous deletion of the Efnb2 C-terminus caused abnormalities similar to those found in the conditional Efnb2 null homozygote. Analyses of fetal Efnb2 C-terminus deletion heterozygotes found mis-localized ES ion transport cells only in the genetic background exhibiting vestibular dysfunction. We propose that developmental dysplasias described here are a gene dose-sensitive cause of the vestibular dysfunction observed in EphB-Efnb2 signaling-deficient mice. Published by Elsevier Inc.

  12. Ephrin-B2 governs morphogenesis of endolymphatic sac and duct epithelia in the mouse inner ear

    PubMed Central

    Raft, Steven; Andrade, Leonardo R.; Shao, Dongmei; Akiyama, Haruhiko; Henkemeyer, Mark; Wu, Doris K.

    2014-01-01

    Control over ionic composition and volume of the inner ear luminal fluid endolymph is essential for normal hearing and balance. Mice deficient in either the EphB2 receptor tyrosine kinase or the cognate transmembrane ligand ephrin-B2 (Efnb2) exhibit background strain-specific vestibular behavioral dysfunction and signs of abnormal endolymph homeostasis. Using various loss-of-function mouse models, we found that Efnb2 is required for growth and morphogenesis of the embryonic endolymphatic epithelium, a precursor of the endolymphatic sac (ES) and duct (ED), which mediate endolymph homeostasis. Conditional inactivation of Efnb2 in early-stage embryonic ear tissues disrupted cell proliferation, cell survival, and epithelial folding at the origin of the endolymphatic epithelium. This correlated with apparent absence of an ED, mis-localization of ES ion transport cells relative to inner ear sensory organs, dysplasia of the endolymph fluid space, and abnormally formed otoconia (extracellular calcite protein composites) at later stages of embryonic development. A comparison of Efnb2 and Notch signaling deficient mutant phenotypes indicated that these two signaling systems have distinct and non overlapping roles in ES/ED development. Homozygous deletion of the Efnb2 C terminus caused abnormalities similar to those found in the conditional Efnb2 null homozygote. Analyses of fetal Efnb2 C-terminus deletion heterozygotes found mis-localized ES ion transport cells only in the genetic background exhibiting vestibular dysfunction. We propose that developmental dysplasias described here are a gene dose sensitive cause of the vestibular dysfunction observed in EphB-Efnb2 signaling-deficient mice. PMID:24583262

  13. Four Distinct Subgroups of Self-Injurious Behavior among Chinese Adolescents: Findings from a Latent Class Analysis

    PubMed Central

    Xin, Xiuhong; Ming, Qingsen; Zhang, Jibiao; Wang, Yuping; Liu, Mingli; Yao, Shuqiao

    2016-01-01

    Self-injurious behavior (SIB) among adolescents is an important public health issue worldwide. It is still uncertain whether homogeneous subgroups of SIB can be identified and whether constellations of SIBs can co-occur due to the high heterogeneity of these behaviors. In this study, a cross-sectional study was conducted on a large school-based sample and latent class analysis was performed (n = 10,069, mean age = 15 years) to identify SIB classes based on 11 indicators falling under direct SIB (DSIB), indirect SIB (ISIB), and suicide attempts (SAs). Social and psychological characteristics of each subgroup were examined after controlling for age and gender. Results showed that a four-class model best fit the data and each class had a distinct pattern of co-occurrence of SIBs and external measures. Class 4 (the baseline/normative group, 65.3%) had a low probability of SIB. Class 3 (severe SIB group, 3.9%) had a high probability of SIB and the poorest social and psychological status. Class 1 (DSIB+SA group, 14.2%) had similar scores for external variables compared to class 3, and included a majority of girls [odds ratio (OR) = 1.94]. Class 2 (ISIB group, 16.6%) displayed moderate endorsement of ISIB items, and had a majority of boys and older adolescents (OR = 1.51). These findings suggest that SIB is a heterogeneous entity, but it may be best explained by four homogenous subgroups that display quantitative and qualitative differences. Findings in this study will improve our understanding on SIB and may facilitate the prevention and treatment of SIB. PMID:27392132

  14. Connections: Facilitating Social Supports for Students with Deaf-Blindness in General Education Classrooms.

    ERIC Educational Resources Information Center

    Goetz, Lori; O'Farrell, Nora

    1999-01-01

    This article describes a three-component package to facilitate social supports for students who are deaf-blind in general education classes. The components are: ongoing provision of information, provision of interactive, multiple communication media, and facilitation of social interactions. Case studies of four students with deaf-blindness…

  15. Social Networking Tools to Facilitate Cross-Program Collaboration

    ERIC Educational Resources Information Center

    Wallace, Paul; Howard, Barbara

    2010-01-01

    Students working on a highly collaborative project used social networking technology for community building activities as well as basic project-related communication. Requiring students to work on cross-program projects gives them real-world experience working in diverse, geographically dispersed groups. An application used at Appalachian State…

  16. CrossLink: a novel method for cross-condition classification of cancer subtypes.

    PubMed

    Ma, Chifeng; Sastry, Konduru S; Flore, Mario; Gehani, Salah; Al-Bozom, Issam; Feng, Yusheng; Serpedin, Erchin; Chouchane, Lotfi; Chen, Yidong; Huang, Yufei

    2016-08-22

    We considered the prediction of cancer classes (e.g. subtypes) using patient gene expression profiles that contain both systematic and condition-specific biases when compared with the training reference dataset. The conventional normalization-based approaches cannot guarantee that the gene signatures in the reference and prediction datasets always have the same distribution for all different conditions as the class-specific gene signatures change with the condition. Therefore, the trained classifier would work well under one condition but not under another. To address the problem of current normalization approaches, we propose a novel algorithm called CrossLink (CL). CL recognizes that there is no universal, condition-independent normalization mapping of signatures. In contrast, it exploits the fact that the signature is unique to its associated class under any condition and thus employs an unsupervised clustering algorithm to discover this unique signature. We assessed the performance of CL for cross-condition predictions of PAM50 subtypes of breast cancer by using a simulated dataset modeled after TCGA BRCA tumor samples with a cross-validation scheme, and datasets with known and unknown PAM50 classification. CL achieved prediction accuracy >73 %, highest among other methods we evaluated. We also applied the algorithm to a set of breast cancer tumors derived from Arabic population to assign a PAM50 classification to each tumor based on their gene expression profiles. A novel algorithm CrossLink for cross-condition prediction of cancer classes was proposed. In all test datasets, CL showed robust and consistent improvement in prediction performance over other state-of-the-art normalization and classification algorithms.

  17. EphA2 promotes infiltrative invasion of glioma stem cells in vivo through cross-talk with Akt and regulates stem cell properties.

    PubMed

    Miao, H; Gale, N W; Guo, H; Qian, J; Petty, A; Kaspar, J; Murphy, A J; Valenzuela, D M; Yancopoulos, G; Hambardzumyan, D; Lathia, J D; Rich, J N; Lee, J; Wang, B

    2015-01-29

    Diffuse infiltrative invasion is a major cause for the dismal prognosis of glioblastoma multiforme (GBM), but the underlying mechanisms remain incompletely understood. Using human glioma stem cells (GSCs) that recapitulate the invasive propensity of primary GBM, we find that EphA2 critically regulates GBM invasion in vivo. EphA2 was expressed in all seven GSC lines examined, and overexpression of EphA2 enhanced intracranial invasion. The effects required Akt-mediated phosphorylation of EphA2 on serine 897. In vitro the Akt-EphA2 signaling axis is maintained in the absence of ephrin-A ligands and is disrupted upon ligand stimulation. To test whether ephrin-As in tumor microenvironment can regulate GSC invasion, the newly established Efna1;Efna3;Efna4 triple knockout mice (TKO) were used in an ex vivo brain slice invasion assay. We observed significantly increased GSC invasion through the brain slices of TKO mice relative to wild-type (WT) littermates. Mechanistically EphA2 knockdown suppressed stem cell properties of GSCs, causing diminished self-renewal, reduced stem marker expression and decreased tumorigenicity. In a subset of GSCs, the reduced stem cell properties were associated with lower Sox2 expression. Overexpression of EphA2 promoted stem cell properties in a kinase-independent manner and increased Sox2 expression. Disruption of Akt-EphA2 cross-talk attenuated stem cell marker expression and neurosphere formation while having minimal effects on tumorigenesis. Taken together, the results show that EphA2 endows invasiveness of GSCs in vivo in cooperation with Akt and regulates glioma stem cell properties.

  18. Haem-assisted dityrosine-cross-linking of fibrinogen under non-thermal plasma exposure: one important mechanism of facilitated blood coagulation

    PubMed Central

    Ke, Zhigang; Huang, Qing

    2016-01-01

    Although blood coagulation facilitated by non-thermal plasma has been reported several years ago, the insight to the involved mechanisms is still rather limited. In this work, we report our discovery of a new mechanism for the haem-promoted blood-coagulation caused by non-thermal plasma treatment. The reason for the haem role is due to that its oxidized form, namely, hematin, can promote the dityrosine cross-linking of fibrinogen, the most important coagulation protein, to form a membrane-like layer on the surface of the treated blood with plasma exposure. Both haem and non-thermal-plasma generated hydrogen peroxide are requisite for the cross-linking process. We confirmed that fibrinogen can coordinate with the haem iron to form a protein-haem complex which shows pseudo-peroxidase activity, and in the presence of hydrogen peroxide, the complex can induce the dityrosine formation between fibrinogen molecules, leading to the fibrin network necessary for the blood coagulation. Understanding of such an underlying mechanism can be useful to guide more efficient application of non-thermal plasma in the management of hemostasis, thrombosis and etc. PMID:27229173

  19. Effects of neuromuscular joint facilitation on bridging exercises with respect to deep muscle changes.

    PubMed

    Zhou, Bin; Huang, QiuChen; Zheng, Tao; Huo, Ming; Maruyama, Hitoshi

    2015-05-01

    [Purpose] This study examined the effects of neuromuscular joint facilitation on bridging exercises by assessing the cross-sectional area of the multifidus muscle and thickness of the musculus transversus abdominis. [Subjects] Twelve healthy men. [Methods] Four exercises were evaluated: (a) supine resting, (b) bridging resistance exercise involving posterior pelvic tilting, (c) bridging resistance exercise involving anterior pelvic tilting, and (d) bridging resistance exercise involving neuromuscular joint facilitation. The cross-sectional area of the multifidus muscle and thickness of the musculus transversus abdominis were measured during each exercise. [Results] The cross-sectional area of the multifidus muscle and thickness of the musculus transversus abdominis were significantly greater in the neuromuscular joint facilitation group than the others. [Conclusion] Neuromuscular joint facilitation intervention improves the function of deep muscles such as the multifidus muscle and musculus transversus abdominis. Therefore, it can be recommended for application in clinical treatments such as that for back pain.

  20. How African American, Middle Class Parents Learn and Enact a Racism Resistant Critical Race Achievement Ideology in Their Adolescents in Gifted and AP Classes

    ERIC Educational Resources Information Center

    Fisher, Tracey Simmons

    2015-01-01

    The purpose of this qualitative study was to examine African American, middle class parents' facilitation of an academic achievement ideology that is racism-resistant in their adolescent offspring in AP and Gifted Education classrooms. Three research questions guided the study: (1) how do African American, middle class parents come to acquire or…

  1. 40 CFR 146.82 - Required Class VI permit information.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., Class II, or Class V experimental wells, certain maps, cross-sections, tabulations of wells within the.../facies changes based on field data which may include geologic cores, outcrop data, seismic surveys, well...

  2. 40 CFR 146.82 - Required Class VI permit information.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., Class II, or Class V experimental wells, certain maps, cross-sections, tabulations of wells within the.../facies changes based on field data which may include geologic cores, outcrop data, seismic surveys, well...

  3. 40 CFR 146.82 - Required Class VI permit information.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., Class II, or Class V experimental wells, certain maps, cross-sections, tabulations of wells within the.../facies changes based on field data which may include geologic cores, outcrop data, seismic surveys, well...

  4. 40 CFR 146.82 - Required Class VI permit information.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., Class II, or Class V experimental wells, certain maps, cross-sections, tabulations of wells within the.../facies changes based on field data which may include geologic cores, outcrop data, seismic surveys, well...

  5. Efficacy of Sibling Preparation Classes.

    PubMed

    Beyers-Carlson, Emma E A; Volling, Brenda L

    To examine the effectiveness of sibling preparation classes to facilitate the adjustment of a firstborn child to the birth of a sibling. Longitudinal study with five measurement occasions: third trimester of the mother's pregnancy and 1, 4, 8, and 12 months after the sibling's birth. Communities in southeastern Michigan. A total of 241 families, including mothers, fathers, and firstborn children. Mothers and fathers completed questionnaires to assess changes in children's adjustment. Parents were also asked about their children's attendance at a sibling preparation class focused specifically on preparation for the newborn. Effects of attendance were tested using linear mixed models. Other than avoidance of the infant, children who attended sibling preparation classes did not differ from children who did not attend. Sibling preparation classes for adjustment after the birth of an infant sibling had few effects on participants. Copyright © 2017 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.

  6. Supervisor Behaviours that Facilitate Training Transfer

    ERIC Educational Resources Information Center

    Lancaster, Sue; Di Milia, Lee; Cameron, Roslyn

    2013-01-01

    Purpose: The purpose of this paper is to describe the supervisor behaviours that employees found to be helpful and unhelpful in facilitating training transfer. The study aims to provide rich qualitative data from the employee's perspective. Design/methodology/approach: This study utilises a cross-sectional design. A case study and a qualitative…

  7. 78 FR 78298 - Proposed Establishment of Class E Airspace; Phoenix, AZ

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-26

    ...-0956; Airspace Docket No. 13-AWP-17] Proposed Establishment of Class E Airspace; Phoenix, AZ AGENCY... rulemaking (NPRM). SUMMARY: This action proposes to establish Class E airspace at the Phoenix VHF Omni-Directional Radio Range Tactical Air Navigation Aid (VORTAC), Phoenix, AZ, to facilitate vectoring of...

  8. 78 FR 45478 - Proposed Establishment of Class E Airspace; Salmon, ID

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-29

    ...-0531; Airspace Docket No. 13-ANM-20] Proposed Establishment of Class E Airspace; Salmon, ID AGENCY... action proposes to establish Class E airspace at the Salmon VHF Omni-Directional Radio Range/Distance Measuring Equipment (VOR/DME) navigation aid, Salmon, ID, to facilitate vectoring of Instrument Flight Rules...

  9. X-Windows Information Sharing Protocol Widget Class

    NASA Technical Reports Server (NTRS)

    Barry, Matthew R.

    2006-01-01

    The X-Windows Information Sharing Protocol (ISP) Widget Class ("Class") is used here in the object-oriented-programming sense of the word) was devised to simplify the task of implementing ISP graphical-user-interface (GUI) computer programs. ISP programming tasks require many method calls to identify, query, and interpret the connections and messages exchanged between a client and an ISP server. Most X-Windows GUI programs use widget sets or toolkits to facilitate management of complex objects. The widget standards facilitate construction of toolkits and application programs. The X-Windows Information Sharing Protocol (ISP) Widget Class encapsulates the client side of the ISP programming libraries within the framework of an X-Windows widget. Using the widget framework, X-Windows GUI programs can interact with ISP services in an abstract way and in the same manner as that of other graphical widgets, making it easier to write ISP GUI client programs. Wrapping ISP client services inside a widget framework enables a programmer to treat an ISP server interface as though it were a GUI. Moreover, an alternate subclass could implement another communication protocol in the same sort of widget.

  10. p130Cas scaffolds the signalosome to direct adaptor-effector cross talk during Kaposi's sarcoma-associated herpesvirus trafficking in human microvascular dermal endothelial cells.

    PubMed

    Bandyopadhyay, Chirosree; Veettil, Mohanan Valiya; Dutta, Sujoy; Chandran, Bala

    2014-12-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) interacts with cell surface receptors, such as heparan sulfate, integrins (α3β1, αVβ3, and αVβ5), and EphrinA2 (EphA2), and activates focal adhesion kinase (FAK), Src, phosphoinositol 3-kinase (PI3-K), c-Cbl, and RhoA GTPase signal molecules early during lipid raft (LR)-dependent productive macropinocytic entry into human dermal microvascular endothelial cells. Our recent studies have identified CIB1 as a signal amplifier facilitating EphA2 phosphorylation and subsequent cytoskeletal cross talk during KSHV macropinocytosis. Although CIB1 lacks an enzymatic activity and traditional adaptor domain or known interacting sequence, it associated with the KSHV entry signal complex and the CIB1-KSHV association was sustained over 30 min postinfection. To identify factors scaffolding the EphA2-CIB1 signal axis, the role of major cellular scaffold protein p130Cas (Crk-associated substrate of Src) was investigated. Inhibitor and small interfering RNA (siRNA) studies demonstrated that KSHV induced p130Cas in an EphA2-, CIB1-, and Src-dependent manner. p130Cas and Crk were associated with KSHV, LRs, EphA2, and CIB1 early during infection. Live-cell microscopy and biochemical studies demonstrated that p130Cas knockdown did not affect KSHV entry but significantly reduced productive nuclear trafficking of viral DNA and routed KSHV to lysosomal degradation. p130Cas aided in scaffolding adaptor Crk to downstream guanine nucleotide exchange factor phospho-C3G possibly to coordinate GTPase signaling during KSHV trafficking. Collectively, these studies demonstrate that p130Cas acts as a bridging molecule between the KSHV-induced entry signal complex and the downstream trafficking signalosome in endothelial cells and suggest that simultaneous targeting of KSHV entry receptors with p130Cas would be an attractive potential avenue for therapeutic intervention in KSHV infection. Eukaryotic cell adaptor molecules, without any intrinsic

  11. Extension Education: Training Coordinators to Facilitate Distance Education through the Assemblies of God Bible Institute in Belize

    ERIC Educational Resources Information Center

    Castleberry, Terry Lane

    2010-01-01

    The specific objective of this project was to train coordinators to open new extension classes and effectively facilitate existing extension classes offered by the Assemblies of God Bible Institute (AGBI) in Belize. Extensive biblical and literary research and a thorough evaluation of current extension classes led to the development of a…

  12. A cross-sectional investigation of parenting style and friendship as mediators of the relation between social class and mental health in a university community.

    PubMed

    Rubin, Mark; Kelly, Benjamin M

    2015-10-05

    This study tested a novel explanation for the positive relation between social class and mental health among university students. Students with a higher social class were expected to have experienced more authoritative and less authoritarian parenting styles; these parenting styles were expected to lead to greater friendship and social integration at university; and greater friendship and integration were expected to lead to better mental health. To test this model, the researchers asked 397 Australian undergraduate students to complete an online survey. The research used a cross-sectional correlational design, and the data was analysed using bootstrapped multiple serial mediation tests. Consistent with predictions, parenting style, general friendship and support, and social integration at university mediated the relation between social class and mental health. The present results suggest that working-class parenting styles may inhibit the development of socially-supportive friendships that protect against mental health problems. The potential effectiveness of interventions based on (a) social integration and (b) parenting style is discussed. Future research in this area should employ a longitudinal research design in order to arrive at clearer causal conclusions about the relations between social class, parenting styles, friendship, social integration, and mental health.

  13. Thin-plate spline analysis of craniofacial growth in Class I and Class II subjects.

    PubMed

    Franchi, Lorenzo; Baccetti, Tiziano; Stahl, Franka; McNamara, James A

    2007-07-01

    To compare the craniofacial growth characteristics of untreated subjects with Class II division 1 malocclusion with those of subjects with normal (Class I) occlusion from the prepubertal through the postpubertal stages of development. The Class II division 1 sample consisted of 17 subjects (11 boys and six girls). The Class I sample also consisted of 17 subjects (13 boys and four girls). Three craniofacial regions (cranial base, maxilla, and mandible) were analyzed on the lateral cephalograms of the subjects in both groups by means of thin-plate spline analysis at T1 (prepubertal) and T2 (postpubertal). Both cross-sectional and longitudinal comparisons were performed on both size and shape differences between the two groups. The results showed an increased cranial base angulation as a morphological feature of Class II malocclusion at the prepubertal developmental phase. Maxillary changes in either shape or size were not significant. Subjects with Class II malocclusion exhibited a significant deficiency in the size of the mandible at the completion of active craniofacial growth as compared with Class I subjects. A significant deficiency in the size of the mandible became apparent in Class II subjects during the circumpubertal period and it was still present at the completion of active craniofacial growth.

  14. Ephrin type-A receptor 2 regulates sensitivity to paclitaxel in nasopharyngeal carcinoma via the phosphoinositide 3-kinase/Akt signalling pathway

    PubMed Central

    WANG, YUNYUN; LIU, YONG; LI, GUO; SU, ZHONGWU; REN, SHULING; TAN, PINGQING; ZHANG, XIN; QIU, YUANZHENG; TIAN, YONGQUAN

    2015-01-01

    Ephrin type-A receptor 2 (EphA2) is a receptor tyrosine kinase that is associated with cancer cell metastasis. There has been little investigation into its impact on the regulation of sensitivity to paclitaxel in nasopharyngeal carcinoma (NPC). In the present study, upregulation of EphA2 expression enhanced the survival of NPC 5-8F cells, compared with control cells exposed to the same concentrations of paclitaxel. Flow cytometry and western blot analysis demonstrated that over-expression of EphA2 decreased NPC cancer cell sensitivity to paclitaxel by regulating paclitaxel-mediated cell cycle progression but not apoptosis in vitro. This was accompanied by alterations in the expression of cyclin-dependent kinase inhibitors, p21 and p27, and of inactive phosphorylated-retinoblastoma protein. Furthermore, paclitaxel stimulation and EphA2 over-expression resulted in activation of the phosphoinositide 3-kinase (PI3K)/Akt signalling pathway in NPC cells. Inhibition of the PI3K/Akt signalling pathway restored sensitivity to paclitaxel in 5-8F cells over-expressing EphA2, which indicated that the PI3K/Akt pathway is involved in EphA2-mediated paclitaxel sensitivity. The current study demonstrated that EphA2 mediates sensitivity to paclitaxel via the regulation of the PI3K/Akt signalling pathway in NPC. PMID:25351620

  15. Class Size and Language Learning in Hong Kong: The Students' Perspective

    ERIC Educational Resources Information Center

    Harfitt, Gary James

    2012-01-01

    Background: There is currently ongoing debate in Hong Kong between the teachers' union and the Government on the reduction of large class size (typically more than 40 students) in secondary schools and whether smaller class sizes might facilitate improvements in teaching and learning. In fact, many Hong Kong secondary schools have already started…

  16. Group Work vs. Whole Class Activity

    ERIC Educational Resources Information Center

    Tanveer, Asma

    2008-01-01

    Group work has only been recently introduced in the education system of Pakistan but many primary teachers, especially in the public schools, are still not aware of how different kinds of strategies that is group work and whole class teaching facilitate learning among students. This paper aims to provide an overview of teaching strategies to…

  17. Barriers and facilitators to participation in workplace health promotion (WHP) activities: results from a cross-sectional survey of public-sector employees in Tasmania, Australia.

    PubMed

    Kilpatrick, Michelle; Blizzard, Leigh; Sanderson, Kristy; Teale, Brook; Jose, Kim; Venn, Alison

    2017-12-01

    Issue addressed Workplaces are promising settings for health promotion, yet employee participation in workplace health promotion (WHP) activities is often low or variable. This study explored facilitating factors and barriers associated with participation in WHP activities that formed part of a comprehensive WHP initiative run within the Tasmanian State Service (TSS) between 2009 and 2013. Methods TSS employee (n=3228) completed surveys in 2013. Data included sociodemographic characteristics, employee-perceived availability of WHP activities, employee-reported participation in WHP activities, and facilitators and barriers to participation. Ordinal log-link regression was used in cross-sectional analyses. Results Significant associations were found for all facilitating factors and participation. Respondents who felt their organisation placed a high priority on WHP, who believed that management supported participation or that the activities could improve their health were more likely to participate. Time- and health-related barriers were associated with participation in fewer activities. All associations were independent of age, sex, work schedule and employee-perceived availability of programs. Part-time and shift-work patterns, and location of activities were additionally identified barriers. Conclusion Facilitating factors relating to implementation, peer and environmental support, were associated with participation in more types of activities, time- and health-related barriers were associated with less participation. So what? Large and diverse organisations should ensure WHP efforts have manager support and adopt flexible approaches to maximise employee engagement.

  18. 78 FR 18268 - Proposed Establishment of Class E Airspace; Blue Mesa, CO

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-26

    ...-0193; Airspace Docket No. 13-ANM-9] Proposed Establishment of Class E Airspace; Blue Mesa, CO AGENCY... action proposes to establish Class E airspace at the Blue Mesa VHF Omni-Directional Radio Range/Distance Measuring Equipment (VOR/DME), Blue Mesa, CO to facilitate vectoring of Instrument Flight Rules (IFR...

  19. 78 FR 45474 - Proposed Establishment of Class E Airspace; Cut Bank, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-29

    ...-0532; Airspace Docket No. 13-ANM-21] Proposed Establishment of Class E Airspace; Cut Bank, MT AGENCY... action proposes to establish Class E airspace at the Cut Bank VHF Omni-Directional Radio Range Tactical Air Navigational Aid (VORTAC) navigation aid, Cut Bank, MT, to facilitate vectoring of Instrument...

  20. Membrane-bound heat shock proteins facilitate the uptake of dying cells and cross-presentation of cellular antigen.

    PubMed

    Zhu, Haiyan; Fang, Xiaoyun; Zhang, Dongmei; Wu, Weicheng; Shao, Miaomiao; Wang, Lan; Gu, Jianxin

    2016-01-01

    Heat shock proteins (HSPs) were originally identified as stress-responsive proteins and serve as molecular chaperones in different intracellular compartments. Translocation of HSPs to the cell surface and release of HSPs into the extracellular space have been observed during the apoptotic process and in response to a variety of cellular stress. Here, we report that UV irradiation and cisplatin treatment rapidly induce the expression of membrane-bound Hsp60, Hsp70, and Hsp90 upstream the phosphatidylserine exposure. Membrane-bound Hsp60, Hsp70 and Hsp90 could promote the release of IL-6 and IL-1β as well as DC maturation by the evaluation of CD80 and CD86 expression. On the other hand, Hsp60, Hsp70 and Hsp90 on cells could facilitate the uptake of dying cells by bone marrow-derived dendritic cells. Lectin-like oxidized LDL receptor-1 (LOX-1), as a common receptor for Hsp60, Hsp70, and Hsp90, is response for their recognition and mediates the uptake of dying cells. Furthermore, membrane-bound Hsp60, Hsp70 and Hsp90 could promote the cross-presentation of OVA antigen from E.G7 cells and inhibition of the uptake of dying cells by LOX-1 decreases the cross-presentation of cellular antigen. Therefore, the rapid exposure of HSPs on dying cells at the early stage allows for the recognition by and confers an activation signal to the immune system.

  1. How social-class stereotypes maintain inequality.

    PubMed

    Durante, Federica; Fiske, Susan T

    2017-12-01

    Social class stereotypes support inequality through various routes: ambivalent content, early appearance in children, achievement consequences, institutionalization in education, appearance in cross-class social encounters, and prevalence in the most unequal societies. Class-stereotype content is ambivalent, describing lower-SES people both negatively (less competent, less human, more objectified), and sometimes positively, perhaps warmer than upper-SES people. Children acquire the wealth aspects of class stereotypes early, which become more nuanced with development. In school, class stereotypes advantage higher-SES students, and educational contexts institutionalize social-class distinctions. Beyond school, well-intentioned face-to-face encounters ironically draw on stereotypes to reinforce the alleged competence of higher-status people and sometimes the alleged warmth of lower-status people. Countries with more inequality show more of these ambivalent stereotypes of both lower-SES and higher-SES people. At a variety of levels and life stages, social-class stereotypes reinforce inequality, but constructive contact can undermine them; future efforts need to address high-status privilege and to query more heterogeneous samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Age-Associated Defects in EphA2 Signaling Impair the Migration of Human Cardiac Progenitor Cells

    PubMed Central

    Goichberg, Polina; Kannappan, Ramaswamy; Cimini, Maria; Bai, Yingnan; Sanada, Fumihiro; Sorrentino, Andrea; Signore, Sergio; Kajstura, Jan; Rota, Marcello; Anversa, Piero; Leri, Annarosa

    2014-01-01

    Background Aging negatively impacts on the function of resident human cardiac progenitor cells (hCPCs). Effective regeneration of the injured heart requires mobilization of hCPCs to the sites of damage. In the young heart, signaling by the guidance receptor EphA2 in response to the ephrin A1 ligand promotes hCPC motility and improves cardiac recovery after infarction. Methods and Results We report that old hCPCs are characterized by cell-autonomous inhibition of their migratory ability ex vivo and impaired translocation in vivo in the damaged heart. EphA2 expression was not decreased in old hCPCs; however, the elevated level of reactive oxygen species in aged cells induced post-translational modifications of the EphA2 protein. EphA2 oxidation interfered with ephrin A1-stimulated receptor auto-phosphorylation, activation of Src family kinases, and caveolin-1-mediated internalization of the receptor. Cellular aging altered the EphA2 endocytic route, affecting the maturation of EphA2-containing endosomes and causing premature signal termination. Over-expression of functionally intact EphA2 in old hCPCs corrected the defects in endocytosis and downstream signaling, enhancing cell motility. Based on the ability of phenotypically young hCPCs to respond efficiently to ephrin A1, we developed a novel methodology for the prospective isolation of live hCPCs with preserved migratory capacity and growth reserve. Conclusions Our data demonstrate that the ephrin A1/EphA2 pathway may serve as a target to facilitate trafficking of hCPCs in the senescent myocardium. Importantly, EphA2 receptor function can be implemented for the selection of hCPCs with high therapeutic potential, a clinically relevant strategy that does not require genetic manipulation of stem cells. PMID:24141256

  3. Emerging strategies for EphA2 receptor targeting for cancer therapeutics.

    PubMed

    Tandon, Manish; Vemula, Sai Vikram; Mittal, Suresh K

    2011-01-01

    High mortality rates with cancers warrant further development of earlier diagnostics and better treatment strategies. Membrane-bound erythropoietin-producing hepatocellular receptor tyrosine kinase class A2 (EphA2) is overexpressed in breast, prostate, urinary bladder, skin, lung, ovary and brain cancers. EphA2 overexpression in cancers, its signaling mechanisms and strategies to target its deregulation. High EphA2 expression in cancer cells is correlated with a poor prognosis associated with recurrence due to enhanced metastasis. Interaction of the EphA2 receptor with its ligand (e.g., ephrinA1) triggers events that are deregulated and implicated in carcinogenesis. EphrinA1-independent oncogenic activity and ephrinA1-dependent tumor suppressor roles for EphA2 are described. Molecular interactions of EphA2 with signaling proteins are associated with the modulation of cytoskeleton dynamics, cell adhesion, proliferation, differentiation and metastasis. The deregulated signaling by EphA2 and its involvement in oncogenesis provide multiple avenues for the rational design of intervention approaches. EphA2 has been tested as a drug target using multiple approaches such as agonist antibodies, RNA interference, immunotherapy, virus vector-mediated gene transfer, small-molecule inhibitors and nanoparticles. With over a decade of research, encouraging results with targeting of EphA2 expression in various pre-clinical cancer models necessitate further studies.

  4. Teaching strategies and student achievement in high school block scheduled biology classes

    NASA Astrophysics Data System (ADS)

    Louden, Cynthia Knapp

    The objectives of this study included determining whether teachers in block or traditionally scheduled biology classes (1) implement inquiry-based instruction more often or with different methods, (2) understand the concept of inquiry-based instruction as it is described in the National Science Standards, (3) have classes with significantly different student achievement, and (4) believe that their school schedule facilitates their use of inquiry-based instruction in the classroom. Biology teachers in block and non-block scheduled classes were interviewed, surveyed, and observed to determine the degree to which they implement inquiry-based instructional practices in their classrooms. State biology exams were used to indicate student achievement. Teachers in block scheduled and traditional classes used inquiry-based instruction with nearly the same frequency. Approximately 30% of all teachers do not understand the concept of inquiry-based instruction as described by the National Science Standards. No significant achievement differences between block and traditionally scheduled biology classes were found using ANCOVA analyses and a nonequivalent control-group quasi-experimental design. Using the same analysis techniques, significant achievement differences were found between biology classes with teachers who used inquiry-based instruction frequently and infrequently. Teachers in block schedules believed that their schedules facilitated inquiry-based instruction more than teachers in traditional schedules.

  5. How Academic Teachers Perceive and Facilitate Creativity

    ERIC Educational Resources Information Center

    Bjørner, Thomas; Kofoed, Lise Busk

    2013-01-01

    We will present a case study result from a cross-disciplinary education called Medialogy, which is taught in the Technical and Science Faculty at Aalborg University. The aim of Medialogy is to facilitate creativity within technical solutions. The intention of this paper is to answer the following: how do the Medialogy teachers perceive creativity…

  6. Facilitating Community-Based Exercise for People With Stroke: Cross-Sectional e-Survey of Physical Therapist Practice and Perceived Needs

    PubMed Central

    Lau, Carrie; Chitussi, Danielle; Elliot, Sarah; Giannone, Jennifer; McMahon, Mary-Katherine; Sibley, Kathryn M.; Tee, Alda; Matthews, Julie

    2016-01-01

    Background Educating people with stroke about community-based exercise programs (CBEPs) is a recommended practice that physical therapists are well positioned to implement. Objective The aim of this study was to evaluate the provision of education about CBEPs to people with stroke, barriers to providing education, and preferences for resources to facilitate education among physical therapists in neurological practice. Design A cross-sectional e-survey of physical therapists treating adults with stroke in Ontario, Canada, was conducted. Methods A link to the questionnaire was emailed to physical therapists in a provincial stroke network, a provincial physical therapy association, and on hospital and previous research lists. Results Responses from 186 physical therapists were analyzed. The percentage of respondents who reported providing CBEP education was 84.4%. Only 36.6% reported typically providing education to ≥7 out of 10 patients with stroke. Physical (90.5%) and preventative (84.6%) health benefits of exercise were most frequently discussed. Therapists reported most commonly delivering education at discharge (73.7%). Most frequently cited barriers to educating patients were a perceived lack of suitable programs (53.2%) and a lack of awareness of local CBEPs (23.8%). Lists of CBEPs (94.1%) or brochures (94.1%) were considered to be facilitators. The percentage of physical therapists providing CBEP education varied across acute, rehabilitation, and public outpatient settings. Limitations The percentage of physical therapists providing education may have been overestimated if respondents who deliver CBEP education were more likely to participate and if participants answered in a socially desirable way. Conclusions Even though a high proportion of physical therapists provide CBEP education, education is not consistently delivered to the majority of patients poststroke. Although a CBEP list or brochure would facilitate education regarding existing CBEPs, efforts

  7. Facilitating Community-Based Exercise for People With Stroke: Cross-Sectional e-Survey of Physical Therapist Practice and Perceived Needs.

    PubMed

    Lau, Carrie; Chitussi, Danielle; Elliot, Sarah; Giannone, Jennifer; McMahon, Mary-Katherine; Sibley, Kathryn M; Tee, Alda; Matthews, Julie; Salbach, Nancy M

    2016-04-01

    Educating people with stroke about community-based exercise programs (CBEPs) is a recommended practice that physical therapists are well positioned to implement. The aim of this study was to evaluate the provision of education about CBEPs to people with stroke, barriers to providing education, and preferences for resources to facilitate education among physical therapists in neurological practice. A cross-sectional e-survey of physical therapists treating adults with stroke in Ontario, Canada, was conducted. A link to the questionnaire was emailed to physical therapists in a provincial stroke network, a provincial physical therapy association, and on hospital and previous research lists. Responses from 186 physical therapists were analyzed. The percentage of respondents who reported providing CBEP education was 84.4%. Only 36.6% reported typically providing education to ≥7 out of 10 patients with stroke. Physical (90.5%) and preventative (84.6%) health benefits of exercise were most frequently discussed. Therapists reported most commonly delivering education at discharge (73.7%). Most frequently cited barriers to educating patients were a perceived lack of suitable programs (53.2%) and a lack of awareness of local CBEPs (23.8%). Lists of CBEPs (94.1%) or brochures (94.1%) were considered to be facilitators. The percentage of physical therapists providing CBEP education varied across acute, rehabilitation, and public outpatient settings. The percentage of physical therapists providing education may have been overestimated if respondents who deliver CBEP education were more likely to participate and if participants answered in a socially desirable way. Even though a high proportion of physical therapists provide CBEP education, education is not consistently delivered to the majority of patients poststroke. Although a CBEP list or brochure would facilitate education regarding existing CBEPs, efforts to implement CBEPs are needed to help overcome the lack of suitable

  8. Assessing climate change risks to the natural environment to facilitate cross-sectoral adaptation policy.

    PubMed

    Brown, Iain

    2018-06-13

    Climate change policy requires prioritization of adaptation actions across many diverse issues. The policy agenda for the natural environment includes not only biodiversity, soils and water, but also associated human benefits through agriculture, forestry, water resources, hazard alleviation, climate regulation and amenity value. To address this broad agenda, the use of comparative risk assessment is investigated with reference to statutory requirements of the UK Climate Change Risk Assessment. Risk prioritization was defined by current adaptation progress relative to risk magnitude and implementation lead times. Use of an ecosystem approach provided insights into risk interactions, but challenges remain in quantifying ecosystem services. For all risks, indirect effects and potential systemic risks were identified from land-use change, responding to both climate and socio-economic drivers, and causing increased competition for land and water resources. Adaptation strategies enhancing natural ecosystem resilience can buffer risks and sustain ecosystem services but require improved cross-sectoral coordination and recognition of dynamic change. To facilitate this, risk assessments need to be reflexive and explicitly assess decision outcomes contingent on their riskiness and adaptability, including required levels of human intervention, influence of uncertainty and ethical dimensions. More national-scale information is also required on adaptation occurring in practice and its efficacy in moderating risks.This article is part of the theme issue 'Advances in risk assessment for climate change adaptation policy'. © 2018 The Author(s).

  9. Assessing climate change risks to the natural environment to facilitate cross-sectoral adaptation policy

    NASA Astrophysics Data System (ADS)

    Brown, Iain

    2018-06-01

    Climate change policy requires prioritization of adaptation actions across many diverse issues. The policy agenda for the natural environment includes not only biodiversity, soils and water, but also associated human benefits through agriculture, forestry, water resources, hazard alleviation, climate regulation and amenity value. To address this broad agenda, the use of comparative risk assessment is investigated with reference to statutory requirements of the UK Climate Change Risk Assessment. Risk prioritization was defined by current adaptation progress relative to risk magnitude and implementation lead times. Use of an ecosystem approach provided insights into risk interactions, but challenges remain in quantifying ecosystem services. For all risks, indirect effects and potential systemic risks were identified from land-use change, responding to both climate and socio-economic drivers, and causing increased competition for land and water resources. Adaptation strategies enhancing natural ecosystem resilience can buffer risks and sustain ecosystem services but require improved cross-sectoral coordination and recognition of dynamic change. To facilitate this, risk assessments need to be reflexive and explicitly assess decision outcomes contingent on their riskiness and adaptability, including required levels of human intervention, influence of uncertainty and ethical dimensions. More national-scale information is also required on adaptation occurring in practice and its efficacy in moderating risks. This article is part of the theme issue `Advances in risk assessment for climate change adaptation policy'.

  10. Definition of spectrally separable classes for soil survey research

    NASA Technical Reports Server (NTRS)

    Cipra, J. E.; Swain, P. H.; Gill, J. H.; Baumgardner, M. F.; Kristof, S. J.

    1972-01-01

    A procedure is outlined for defining spectral classes such that the differences between classes can be quantified. It also facilitates determination of a number of classes such that the classes are spectrally discriminable. This is accomplished by partitioning the data into many classes and then combining similar spectral classes on the basis of appropriate criteria. Multispectral data were collected over a 12-mile flightline in White County, Indiana, in connection with the 1971 Corn Blight Watch Experiment. Data were collected in May by the University of Michigan airborne scanning spectrometer at an altitude of 5000 feet. Spectral maps resulting from the analysis were compared to existing soil surveys of the National Cooperative Soil Survey. The method should help determine the extent to which spectral properties of soil surfaces can be associated with morphologic and topographic differences of interest to soil surveyors engaged in operational soil mapping.

  11. Mediator facilitates transcriptional activation and dynamic long-range contacts at the IgH locus during class switch recombination.

    PubMed

    Thomas-Claudepierre, Anne-Sophie; Robert, Isabelle; Rocha, Pedro P; Raviram, Ramya; Schiavo, Ebe; Heyer, Vincent; Bonneau, Richard; Luo, Vincent M; Reddy, Janardan K; Borggrefe, Tilman; Skok, Jane A; Reina-San-Martin, Bernardo

    2016-03-07

    Immunoglobulin (Ig) class switch recombination (CSR) is initiated by the transcription-coupled recruitment of activation-induced cytidine deaminase (AID) to Ig switch regions (S regions). During CSR, the IgH locus undergoes dynamic three-dimensional structural changes in which promoters, enhancers, and S regions are brought to close proximity. Nevertheless, little is known about the underlying mechanisms. In this study, we show that Med1 and Med12, two subunits of the mediator complex implicated in transcription initiation and long-range enhancer/promoter loop formation, are dynamically recruited to the IgH locus enhancers and the acceptor regions during CSR and that their knockdown in CH12 cells results in impaired CSR. Furthermore, we show that conditional inactivation of Med1 in B cells results in defective CSR and reduced acceptor S region transcription. Finally, we show that in B cells undergoing CSR, the dynamic long-range contacts between the IgH enhancers and the acceptor regions correlate with Med1 and Med12 binding and that they happen at a reduced frequency in Med1-deficient B cells. Our results implicate the mediator complex in the mechanism of CSR and are consistent with a model in which mediator facilitates the long-range contacts between S regions and the IgH locus enhancers during CSR and their transcriptional activation. © 2016 Thomas-Claudepierre et al.

  12. Using Mobile Devices to Facilitate Student Questioning in a Large Undergraduate Science Class

    ERIC Educational Resources Information Center

    Crompton, Helen; Burgin, Stephen R.; De Paor, Declan G.; Gregory, Kristen

    2018-01-01

    Asking scientific questions is the first practice of science and engineering listed in the Next Generation Science Standards. However, getting students to ask unsolicited questions in a large class can be difficult. In this qualitative study, undergraduate students sent SMS text messages to the instructor who received them on his mobile phone and…

  13. The unity assumption facilitates cross-modal binding of musical, non-speech stimuli: The role of spectral and amplitude envelope cues.

    PubMed

    Chuen, Lorraine; Schutz, Michael

    2016-07-01

    An observer's inference that multimodal signals originate from a common underlying source facilitates cross-modal binding. This 'unity assumption' causes asynchronous auditory and visual speech streams to seem simultaneous (Vatakis & Spence, Perception & Psychophysics, 69(5), 744-756, 2007). Subsequent tests of non-speech stimuli such as musical and impact events found no evidence for the unity assumption, suggesting the effect is speech-specific (Vatakis & Spence, Acta Psychologica, 127(1), 12-23, 2008). However, the role of amplitude envelope (the changes in energy of a sound over time) was not previously appreciated within this paradigm. Here, we explore whether previous findings suggesting speech-specificity of the unity assumption were confounded by similarities in the amplitude envelopes of the contrasted auditory stimuli. Experiment 1 used natural events with clearly differentiated envelopes: single notes played on either a cello (bowing motion) or marimba (striking motion). Participants performed an un-speeded temporal order judgments task; viewing audio-visually matched (e.g., marimba auditory with marimba video) and mismatched (e.g., cello auditory with marimba video) versions of stimuli at various stimulus onset asynchronies, and were required to indicate which modality was presented first. As predicted, participants were less sensitive to temporal order in matched conditions, demonstrating that the unity assumption can facilitate the perception of synchrony outside of speech stimuli. Results from Experiments 2 and 3 revealed that when spectral information was removed from the original auditory stimuli, amplitude envelope alone could not facilitate the influence of audiovisual unity. We propose that both amplitude envelope and spectral acoustic cues affect the percept of audiovisual unity, working in concert to help an observer determine when to integrate across modalities.

  14. Identification and validation of a gene causing cross-resistance between insecticide classes in Anopheles gambiae from Ghana.

    PubMed

    Mitchell, Sara N; Stevenson, Bradley J; Müller, Pie; Wilding, Craig S; Egyir-Yawson, Alexander; Field, Stuart G; Hemingway, Janet; Paine, Mark J I; Ranson, Hilary; Donnelly, Martin James

    2012-04-17

    In the last decade there have been marked reductions in malaria incidence in sub-Saharan Africa. Sustaining these reductions will rely upon insecticides to control the mosquito malaria vectors. We report that in the primary African malaria vector, Anopheles gambiae sensu stricto, a single enzyme, CYP6M2, confers resistance to two classes of insecticide. This is unique evidence in a disease vector of cross-resistance associated with a single metabolic gene that simultaneously reduces the efficacy of two of the four classes of insecticide routinely used for malaria control. The gene-expression profile of a highly DDT-resistant population of A. gambiae s.s. from Ghana was characterized using a unique whole-genome microarray. A number of genes were significantly overexpressed compared with two susceptible West African colonies, including genes from metabolic families previously linked to insecticide resistance. One of the most significantly overexpressed probe groups (false-discovery rate-adjusted P < 0.0001) belonged to the cytochrome P450 gene CYP6M2. This gene is associated with pyrethroid resistance in wild A. gambiae s.s. populations) and can metabolize both type I and type II pyrethroids in recombinant protein assays. Using in vitro assays we show that recombinant CYP6M2 is also capable of metabolizing the organochlorine insecticide DDT in the presence of solubilizing factor sodium cholate.

  15. Identification and validation of a gene causing cross-resistance between insecticide classes in Anopheles gambiae from Ghana

    PubMed Central

    Mitchell, Sara N.; Stevenson, Bradley J.; Müller, Pie; Wilding, Craig S.; Egyir-Yawson, Alexander; Field, Stuart G.; Hemingway, Janet; Paine, Mark J. I.; Ranson, Hilary; Donnelly, Martin James

    2012-01-01

    In the last decade there have been marked reductions in malaria incidence in sub-Saharan Africa. Sustaining these reductions will rely upon insecticides to control the mosquito malaria vectors. We report that in the primary African malaria vector, Anopheles gambiae sensu stricto, a single enzyme, CYP6M2, confers resistance to two classes of insecticide. This is unique evidence in a disease vector of cross-resistance associated with a single metabolic gene that simultaneously reduces the efficacy of two of the four classes of insecticide routinely used for malaria control. The gene-expression profile of a highly DDT-resistant population of A. gambiae s.s. from Ghana was characterized using a unique whole-genome microarray. A number of genes were significantly overexpressed compared with two susceptible West African colonies, including genes from metabolic families previously linked to insecticide resistance. One of the most significantly overexpressed probe groups (false-discovery rate-adjusted P < 0.0001) belonged to the cytochrome P450 gene CYP6M2. This gene is associated with pyrethroid resistance in wild A. gambiae s.s. populations) and can metabolize both type I and type II pyrethroids in recombinant protein assays. Using in vitro assays we show that recombinant CYP6M2 is also capable of metabolizing the organochlorine insecticide DDT in the presence of solubilizing factor sodium cholate. PMID:22460795

  16. Working-Class Girls in a Foreign Land. Social Class and Settling into University in a Cross-Current between Two Cultures

    ERIC Educational Resources Information Center

    Käyhkö, Mari

    2015-01-01

    In Finland, the financial status of a family does not in general place any restrictions on a person's studies. However, in spite of equality of opportunity, class as a cultural and social issue is a significant factor guiding the education of young people. In the article, I analyse women with a working-class background studying at university,…

  17. Class Size and Student Performance at a Public Research University: A Cross-Classified Model

    ERIC Educational Resources Information Center

    Johnson, Iryna Y.

    2010-01-01

    This study addresses several methodological problems that have confronted prior research on the effect of class size on student achievement. Unlike previous studies, this analysis accounts for the hierarchical data structure of student achievement, where grades are nested within classes and students, and considers a wide range of class sizes…

  18. Facilitators of Survivorship Care Among Underserved Breast Cancer Survivors: a Qualitative Study.

    PubMed

    Ustjanauskas, Amy E; Quinn, Gwendolyn P; Pan, Tonya M; Rivera, Maria; Vázquez-Otero, Coralia; Ung, Danielle; Roetzheim, Richard G; Laronga, Christine; Johnson, Kenneth; Norton, Marilyn; Carrizosa, Claudia; Muñoz, Dariana; Goldenstein, Marissa; Nuhaily, Sumayah; Wells, Kristen J

    2017-12-01

    Research investigating facilitators of survivorship care among underserved breast cancer survivors (BCS) is sparse. This study aimed to explore facilitators of survivorship care among underserved BCS within the first 5 years following chemotherapy, radiation, or surgery for breast cancer. In-depth interviews were conducted, using a semi-structured interview guide, with underserved BCS exploring survivorship care experiences. Content analysis of the verbatim transcripts was applied, and results were summarized according to themes related to facilitators of breast cancer survivorship care. Interviews were conducted with 25 BCS. Eight main themes were identified: coordination of care; positive perceptions of health care providers; communication between patient and health care providers; financial and insurance facilitators; information, classes, and programs provided; assistance provided by organizations and health care professionals; transportation facilitators; and job flexibility. This study provides a comprehensive look at facilitators of survivorship care among underserved BCS. BCS endorsed several facilitators of their survivorship care, mainly at the interpersonal, organizational, and societal level. This study adds to the research literature on catalysts of care among underserved BCS. Results from this study are currently being used to inform a patient navigation intervention to facilitate care among this population.

  19. Social Class Differentiation in Cognitive Development: A Longitudinal Study.

    ERIC Educational Resources Information Center

    Golden, Mark; And Others

    In an effort to isolate the emergence and causes of social class differences in intellectual performance, this longitudinal study was undertaken as a follow-up on a cross-sectional study that yielded no social class differences on the Cattell Infant Intelligence Scale for 12-, 18-, and 24-month-old black children. In the present study, 89 children…

  20. Duplication of the EFNB1 Gene in Familial Hypertelorism: Imbalance in Ephrin-B1 Expression and Abnormal Phenotypes in Humans and Mice

    PubMed Central

    Babbs, Christian; Stewart, Helen S; Williams, Louise J; Connell, Lyndsey; Goriely, Anne; Twigg, Stephen RF; Smith, Kim; Lester, Tracy; Wilkie, Andrew OM

    2011-01-01

    Familial hypertelorism, characterized by widely spaced eyes, classically shows autosomal dominant inheritance (Teebi type), but some pedigrees are compatible with X-linkage. No mechanism has been described previously, but clinical similarity has been noted to craniofrontonasal syndrome (CFNS), which is caused by mutations in the X-linked EFNB1 gene. Here we report a family in which females in three generations presented with hypertelorism, but lacked either craniosynostosis or a grooved nasal tip, excluding CFNS. DNA sequencing of EFNB1 was normal, but further analysis revealed a duplication of 937 kb including EFNB1 and two flanking genes: PJA1 and STARD8. We found that the X chromosome bearing the duplication produces ∼1.6-fold more EFNB1 transcript than the normal X chromosome and propose that, in the context of X-inactivation, this difference in expression level of EFNB1 results in abnormal cell sorting leading to hypertelorism. To support this hypothesis, we provide evidence from a mouse model carrying a targeted human EFNB1 cDNA, that abnormal cell sorting occurs in the cranial region. Hence, we propose that X-linked cases resembling Teebi hypertelorism may have a similar mechanism to CFNS, and that cellular mosaicism for different levels of ephrin-B1 (as well as simple presence/absence) leads to craniofacial abnormalities. Hum Mutat 32:1–9, 2011. © 2011 Wiley-Liss, Inc. PMID:21542058

  1. Facilitating Peer Discourse to Support Third Graders' Comprehension of the News

    ERIC Educational Resources Information Center

    Jordan, Michelle; Massad, Michael, Sr.

    2014-01-01

    This study explored how one third-grade teacher facilitated daily peer-led discussions around articles from a local newspaper. Two students were assigned to select and summarize an article, then lead a whole-class discussion with the teacher's help. The teacher differentially scaffolded engagement with newspaper articles, adaptively responding to…

  2. Naming, the formation of stimulus classes, and applied behavior analysis.

    PubMed

    Stromer, R; Mackay, H A; Remington, B

    1996-01-01

    The methods used in Sidman's original studies on equivalence classes provide a framework for analyzing functional verbal behavior. Sidman and others have shown how teaching receptive, name-referent matching may produce rudimentary oral reading and word comprehension skills. Eikeseth and Smith (1992) have extended these findings by showing that children with autism may acquire equivalence classes after learning to supply a common oral name to each stimulus in a potential class. A stimulus class analysis suggests ways to examine (a) the problem of programming generalization from teaching situations to other environments, (b) the expansion of the repertoires that occur in those settings, and (c) the use of naming to facilitate these forms of generalization. Such research will help to clarify and extend Horne and Lowe's recent (1996) account of the role of verbal behavior in the formation of stimulus classes.

  3. Naming, the formation of stimulus classes, and applied behavior analysis.

    PubMed Central

    Stromer, R; Mackay, H A; Remington, B

    1996-01-01

    The methods used in Sidman's original studies on equivalence classes provide a framework for analyzing functional verbal behavior. Sidman and others have shown how teaching receptive, name-referent matching may produce rudimentary oral reading and word comprehension skills. Eikeseth and Smith (1992) have extended these findings by showing that children with autism may acquire equivalence classes after learning to supply a common oral name to each stimulus in a potential class. A stimulus class analysis suggests ways to examine (a) the problem of programming generalization from teaching situations to other environments, (b) the expansion of the repertoires that occur in those settings, and (c) the use of naming to facilitate these forms of generalization. Such research will help to clarify and extend Horne and Lowe's recent (1996) account of the role of verbal behavior in the formation of stimulus classes. PMID:8810064

  4. Gender inequalities in health: exploring the contribution of living conditions in the intersection of social class.

    PubMed

    Malmusi, Davide; Vives, Alejandra; Benach, Joan; Borrell, Carme

    2014-01-01

    Women experience poorer health than men despite their longer life expectancy, due to a higher prevalence of non-fatal chronic illnesses. This paper aims to explore whether the unequal gender distribution of roles and resources can account for inequalities in general self-rated health (SRH) by gender, across social classes, in a Southern European population. Cross-sectional study of residents in Catalonia aged 25-64, using data from the 2006 population living conditions survey (n=5,817). Poisson regression models were used to calculate the fair/poor SRH prevalence ratio (PR) by gender and to estimate the contribution of variables assessing several dimensions of living conditions as the reduction in the PR after their inclusion in the model. Analyses were stratified by social class (non-manual and manual). SRH was poorer for women among both non-manual (PR 1.39, 95% CI 1.09-1.76) and manual social classes (PR 1.36, 95% CI 1.20-1.56). Adjustment for individual income alone eliminated the association between sex and SRH, especially among manual classes (PR 1.01, 95% CI 0.85-1.19; among non-manual 1.19, 0.92-1.54). The association was also reduced when adjusting by employment conditions among manual classes, and household material and economic situation, time in household chores and residential environment among non-manual classes. Gender inequalities in individual income appear to contribute largely to women's poorer health. Individual income may indicate the availability of economic resources, but also the history of access to the labour market and potentially the degree of independence and power within the household. Policies to facilitate women's labour market participation, to close the gender pay gap, or to raise non-contributory pensions may be helpful to improve women's health.

  5. Gender inequalities in health: exploring the contribution of living conditions in the intersection of social class

    PubMed Central

    Malmusi, Davide; Vives, Alejandra; Benach, Joan; Borrell, Carme

    2014-01-01

    Background Women experience poorer health than men despite their longer life expectancy, due to a higher prevalence of non-fatal chronic illnesses. This paper aims to explore whether the unequal gender distribution of roles and resources can account for inequalities in general self-rated health (SRH) by gender, across social classes, in a Southern European population. Methods Cross-sectional study of residents in Catalonia aged 25–64, using data from the 2006 population living conditions survey (n=5,817). Poisson regression models were used to calculate the fair/poor SRH prevalence ratio (PR) by gender and to estimate the contribution of variables assessing several dimensions of living conditions as the reduction in the PR after their inclusion in the model. Analyses were stratified by social class (non-manual and manual). Results SRH was poorer for women among both non-manual (PR 1.39, 95% CI 1.09–1.76) and manual social classes (PR 1.36, 95% CI 1.20–1.56). Adjustment for individual income alone eliminated the association between sex and SRH, especially among manual classes (PR 1.01, 95% CI 0.85–1.19; among non-manual 1.19, 0.92–1.54). The association was also reduced when adjusting by employment conditions among manual classes, and household material and economic situation, time in household chores and residential environment among non-manual classes. Discussion Gender inequalities in individual income appear to contribute largely to women's poorer health. Individual income may indicate the availability of economic resources, but also the history of access to the labour market and potentially the degree of independence and power within the household. Policies to facilitate women's labour market participation, to close the gender pay gap, or to raise non-contributory pensions may be helpful to improve women's health. PMID:24560257

  6. Emerging strategies for EphA2 receptor targeting for cancer therapeutics

    PubMed Central

    Tandon, Manish; Vemula, Sai Vikram; Mittal, Suresh K.

    2010-01-01

    Importance of the field High mortality rates with cancers warrant further development of earlier diagnostics and better treatment strategies. Membrane-bound hepatocellular receptor tyrosine kinase class A2 (EphA2) is overexpressed in breast, prostate, urinary bladder, skin, lung, ovary and brain cancers. Areas covered in this review This review describes EphA2 overexpression in cancers, its signaling mechanisms and strategies to target its deregulation. What will the reader will gain High EphA2 expression in cancer cells is correlated to a poor prognosis associated with recurrence due to enhanced metastasis. Interaction of the EphA2 receptor with its ligand (e.g., EphrinA1) triggers events that are deregulated and implicated in carcinogenesis. Both EphrinA1-independent oncogenic activity and EphrinA1-dependent tumor suppressor roles for EphA2 are described. Molecular interactions of EphA2 with signaling proteins are associated with the modulation of cytoskeleton dynamics, cell adhesion, proliferation, differentiation and metastasis. The deregulated signaling by EphA2 and its involvement in oncogenesis provide multiple avenues for the rational design of intervention approaches. Take home message EphA2 has been tested as a drug target using multiple approaches such as agonist antibodies, RNA interference, immunotherapy, virus vectors-mediated gene transfer, small molecule inhibitors and nanoparticles. With over a decade of research, encouraging results with successful targeting of EphA2 expression in various pre-clinical cancer models necessitate further studies. PMID:21142802

  7. Peer Facilitators as Border Crossers in Community Service Learning

    ERIC Educational Resources Information Center

    Chesler, Mark A.; Ford, Kristie A.; Galura, Joseph A.; Charbeneau, Jessica M.

    2006-01-01

    Community service learning offers students the opportunity to cross socially constructed and epistemological borders of power and privilege, allowing them to come into contact with groups of people who are different from themselves and to learn in different ways. Peer facilitators, undergraduate student instructional leaders who guide others…

  8. Self-rated health in different social classes of Slovenian adult population: nationwide cross-sectional study.

    PubMed

    Farkas, Jerneja; Pahor, Majda; Zaletel-Kragelj, Lijana

    2011-02-01

    Self-rated health can be influenced by several characteristics of the social environment. The aim of this study was to evaluate the relationship between self-rated health and self-assessed social class in Slovenian adult population. The study was based on the Countrywide Integrated Non-communicable Diseases Intervention Health Monitor database. During 2004, 8,741/15,297 (57.1%) participants aged 25-64 years returned posted self-administered questionnaire. Logistic regression was used to determine unadjusted and adjusted estimates of association between poor self-rated health and self-assessed social class. Poor self-rated health was reported by 9.6% of participants with a decrease from lower to upper-middle/upper self-assessed social class (35.9 vs. 3.7%). Logistic regression showed significant association between self-rated health and all self-assessed social classes. In an adjusted model, poor self-rated health remained associated with self-assessed social class (odds ratio for lower vs. upper-middle/upper self-assessed social class 4.23, 95% confidence interval 2.46-7.25; P < 0.001). Our study confirmed differences in the prevalence of poor self-rated health across self-assessed social classes. Participants from lower self-assessed social class reported poor self-rated health most often and should comprise the focus of multisectoral interventions.

  9. Lives in Context: Facilitating Online, Cross-Course, Collaborative Service Projects

    ERIC Educational Resources Information Center

    Elwood, Susan A.

    2014-01-01

    An inquiry-based, cross-course, collaborative structure is being implemented toward a graduate program's goals of using project-based learning as a consistent, core learning experience in each course cycle. This paper focuses upon the course collaborative structure and the two key forms of assessment used in each collaborative cycle: a progressive…

  10. Cross-Reactivity among Beta-Lactams.

    PubMed

    Romano, Antonino; Gaeta, Francesco; Arribas Poves, Maria Francisca; Valluzzi, Rocco Luigi

    2016-03-01

    Penicillins and cephalosporins are the major classes of beta-lactam (BL) antibiotics in use today and one of the most frequent causes of hypersensitivity reactions to drugs. Monobactams, carbapenems, oxacephems, and beta-lactamase inhibitors constitute the four minor classes of BLs. This review takes into account mainly the prospective studies which evaluated cross-reactivity among BLs in subjects with a well-demonstrated hypersensitivity to a certain class of BLs by performing allergy tests with alternative BLs and, in case of negative results, administering them. In subjects with either IgE-mediated or T-cell-mediated hypersensitivity, cross-reactivity among BLs, particularly among penicillins and among cephalosporins, as well as between penicillins and cephalosporins, seems to be mainly related to structural similarities among their side-chain determinants. Specifically, in penicillin-allergic subjects, cross-reactivity between penicillins and cephalosporins may exceed 30% when they are administered cephalosporins with identical side chains to those of responsible penicillins. In these subjects, a few prospective studies have demonstrated a rate of cross-reactivity between penicillins and both carbapenems and aztreonam lower than 1%. With regard to subjects with an IgE-mediated hypersensitivity to cephalosporins, in a single study, about 25% of the 98 subjects with such hypersensitivity had positive results to penicillins, 3% to aztreonam, 2% to imipenem/cilastatin, and 1% to meropenem. The cross-reactivity related to the selective recognition of the BL ring by IgE or T lymphocytes, which entails positive responses to all BLs tested, appears to be exceptional. Some studies concerning cross-reactivity among BLs have found patterns of allergy-test positivity which cannot be explained by either the common BL ring or by similar or identical side chains, thus indicating the possibility of coexisting sensitivities to different BLs because of prior exposures to them.

  11. Whole-Class Scaffolding for Learning to Solve Mathematics Problems Together in a Computer-Supported Environment

    ERIC Educational Resources Information Center

    Abdu, Rotem; Schwarz, Baruch; Mavrikis, Manolis

    2015-01-01

    We investigate teachers' practices in a whole-class context when they scaffold students' learning in situations where students use technologies that facilitate group learning to solve mathematical problems in small groups. We describe teachers' practices in order to evaluate their contribution to "Whole-Class Scaffolding" in the context…

  12. Direct binding to antigen-coated beads refines the specificity and cross-reactivity of four monoclonal antibodies that recognize polymorphic epitopes of HLA class I molecules.

    PubMed

    Hilton, H G; Parham, P

    2013-04-01

    Monoclonal antibodies with specificity for human leukocyte antigen (HLA) class I determinants of HLA were originally characterized using serological assays in which the targets were cells expressing three to six HLA class I variants. Because of this complexity, the specificities of the antibodies were defined indirectly by correlation. Here we use a direct binding assay, in which the targets are synthetic beads coated with 1 of 111 HLA class I variants, representing the full range of HLA-A, -B and -C variation. We studied one monoclonal antibody with monomorphic specificity (W6/32) and four with polymorphic specificity (MA2.1, PA2.1, BB7.2 and BB7.1) and compared the results with those obtained previously. W6/32 reacted with all HLA class I variants. MA2.1 not only exhibits high specificity for HLA-A*02, -B*57 and -B*58, but also exhibited cross-reactivity with HLA-A*11 and -B*15:16. At low concentration (1 µg/ml), PA2.1 and BB7.2 were both specific for HLA-A*02 and -A*69, and at high concentration (50 µg/ml) exhibited significant cross-reactions with HLA-A*68, -A*23 and -A*24. BB7.1 exhibits specificity for HLA-B*07 and -B*42, as previously described, but reacts equally well with HLA-B*81, a rare allotype defined some 16 years after the description of BB7.1. The results obtained with cell-based and bead-based assays are consistent and, in combination with amino acid sequence comparison, increase understanding of the polymorphic epitopes recognized by the MA2.1, PA2.1, BB7.2 and BB7.1 antibodies. Comparison of two overlapping but distinctive bead sets from two sources gave similar results, but the overall levels of binding were significantly different. Several weaker reactions were observed with only one of the bead sets. © 2013 John Wiley & Sons A/S.

  13. Direct binding to antigen-coated beads refines the specificity and cross-reactivity of four monoclonal antibodies that recognize polymorphic epitopes of HLA class I molecules

    PubMed Central

    Hilton, Hugo G; Parham, Peter

    2013-01-01

    Monoclonal antibodies with specificity for HLA class I determinants of HLA were originally characterized using serological assays in which the targets were cells expressing 3-6 HLA class I variants. Because of this complexity, the specificities of the antibodies were defined indirectly by correlation. Here we use a direct binding assay, in which the targets are synthetic beads coated with one of 111 HLA class I variants, representing the full range of HLA-A, -B and -C variation. We studied one monoclonal antibody with monomorphic specificity (W6/32) and four with polymorphic specificity (MA2.1, PA2.1, BB7.2 and BB7.1) and compared the results with those obtained previously. W6/32 reacted with all HLA class I variants. MA2.1 exhibits high specificity for HLA-A*02, -B*57 and -B*58, but also exhibited cross-reactivity with HLA-A*11 and -B*15:16. At low concentration (1μg/ml) PA2.1 and BB7.2 were both specific for HLA-A*02 and -A*69, and at high concentration (50μg/ml) exhibited significant cross-reactions with HLA-A*68, -A*23, and -A*24. BB7.1 exhibits specificity for HLA-B*07 and -B*42, as previously described, but reacts equally well with HLA-B*81, a rare allotype defined some 16 years after the description of BB7.1. The results obtained with cell-based and bead-based assays are consistent and, in combination with amino acid sequence comparison, increase understanding of the polymorphic epitopes recognized by the MA2.1, PA2.1, BB7.2 and BB7.1 antibodies. Comparison of two overlapping but distinctive bead sets from two sources gave similar results, but the overall levels of binding were significantly different. Several weaker reactions were observed with only one of the bead sets. PMID:23510417

  14. Molecular mechanisms underlying the effects of acupuncture on neuropathic pain.

    PubMed

    Ju, Ziyong; Cui, Huashun; Guo, Xiaohui; Yang, Huayuan; He, Jinsen; Wang, Ke

    2013-09-05

    Acupuncture has been used to treat neuropathic pain for a long time, but its mechanisms of action remain unknown. In this study, we observed the effects of electroacupuncture and manual acu-puncture on neuropathic pain and on ephrin-B/EphB signaling in rats models of chronic constriction injury-induced neuropathic pain. The results showed that manual acupuncture and elec-puncture significantly reduced mechanical hypersensitivity following chronic constriction injury, es-pecially electroacupuncture treatment. Real-time PCR results revealed that ephrin-B1/B3 and EphB1/B2 mRNA expression levels were significantly increased in the spinal dorsal horns of chronic constriction injury rats. Electroacupuncture and manual acupuncture suppressed the high sion of ephrin-B1 mRNA, and elevated EphB3/B4 mRNA expression. Electroacupuncture signifi-cantly enhanced the mRNA expression of ephrin-B3 and EphB3/B6 in the dorsal horns of neuro-pathic pain rats. Western blot results revealed that electroacupuncture in particular, and manual acupuncture, significantly up-regulated ephrin-B3 protein levels in rat spinal dorsal horns. The re-sults of this study suggest that acupuncture could activate ephrin-B/EphB signaling in neuropathic pain rats and improve neurological function.

  15. Molecular mechanisms underlying the effects of acupuncture on neuropathic pain

    PubMed Central

    Ju, Ziyong; Cui, Huashun; Guo, Xiaohui; Yang, Huayuan; He, Jinsen; Wang, Ke

    2013-01-01

    Acupuncture has been used to treat neuropathic pain for a long time, but its mechanisms of action remain unknown. In this study, we observed the effects of electroacupuncture and manual acu-puncture on neuropathic pain and on ephrin-B/EphB signaling in rats models of chronic constriction injury-induced neuropathic pain. The results showed that manual acupuncture and elec-puncture significantly reduced mechanical hypersensitivity following chronic constriction injury, es-pecially electroacupuncture treatment. Real-time PCR results revealed that ephrin-B1/B3 and EphB1/B2 mRNA expression levels were significantly increased in the spinal dorsal horns of chronic constriction injury rats. Electroacupuncture and manual acupuncture suppressed the high sion of ephrin-B1 mRNA, and elevated EphB3/B4 mRNA expression. Electroacupuncture signifi-cantly enhanced the mRNA expression of ephrin-B3 and EphB3/B6 in the dorsal horns of neuro-pathic pain rats. Western blot results revealed that electroacupuncture in particular, and manual acupuncture, significantly up-regulated ephrin-B3 protein levels in rat spinal dorsal horns. The re-sults of this study suggest that acupuncture could activate ephrin-B/EphB signaling in neuropathic pain rats and improve neurological function. PMID:25206545

  16. Who Should Be Targeted for the Prevention of Birth Defects? A Latent Class Analysis Based on a Large, Population-Based, Cross-Sectional Study in Shaanxi Province, Western China.

    PubMed

    Zhu, Zhonghai; Cheng, Yue; Yang, Wenfang; Li, Danyang; Yang, Xue; Liu, Danli; Zhang, Min; Yan, Hong; Zeng, Lingxia

    2016-01-01

    The wide range and complex combinations of factors that cause birth defects impede the development of primary prevention strategies targeted at high-risk subpopulations. Latent class analysis (LCA) was conducted to identify mutually exclusive profiles of factors associated with birth defects among women between 15 and 49 years of age using data from a large, population-based, cross-sectional study conducted in Shaanxi Province, western China, between August and October, 2013. The odds ratios (ORs) and 95% confidence intervals (CIs) of associated factors and the latent profiles of indicators of birth defects and congenital heart defects were computed using a logistic regression model. Five discrete subpopulations of participants were identified as follows: No folic acid supplementation in the periconceptional period (reference class, 21.37%); low maternal education level + unhealthy lifestyle (class 2, 39.75%); low maternal education level + unhealthy lifestyle + disease (class 3, 23.71%); unhealthy maternal lifestyle + advanced age (class 4, 4.71%); and multi-risk factor exposure (class 5, 10.45%). Compared with the reference subgroup, the other subgroups consistently had a significantly increased risk of birth defects (ORs and 95% CIs: class 2, 1.75 and 1.21-2.54; class 3, 3.13 and 2.17-4.52; class 4, 5.02 and 3.20-7.88; and class 5, 12.25 and 8.61-17.42, respectively). For congenital heart defects, the ORs and 95% CIs were all higher, and the magnitude of OR differences ranged from 1.59 to 16.15. A comprehensive intervention strategy targeting maternal exposure to multiple risk factors is expected to show the strongest results in preventing birth defects.

  17. Beta-lactam hypersensitivity and cross-reactivity.

    PubMed

    Terico, Adrienne T; Gallagher, Jason C

    2014-12-01

    Penicillin is the most frequently reported cause of drug allergy, and cross-reactivity of penicillins with other beta-lactam antibiotics is an area of debate. This review evaluates the available data on immunoglobulin E-mediated penicillin hypersensitivity and cross-reactivity with cephalosporin, carbapenem, and monobactam antibiotics. A MEDLINE search was conducted from 1950 to October 2013, and selected references from review articles were also evaluated. There is a wide variety in reported incidences of cross-reactivity between penicillins and cephalosporins or carbapenems, with early retrospective studies suggesting up to 41.7% and 47.4% cross-reactivity, respectively. Conversely, the use of monobactam antibiotics is frequently employed in the case of a penicillin allergy, as prescribers believe that there is no cross-reactivity between the 2 drug classes. More recent prospective studies suggest that the rates of cross-reactivity with cephalosporins and carbapenems are <5% and <1%, respectively. Similarities in penicillin and cephalosporin side chains may play a role in cross-reactivity between these classes. Cross-reactivity with monobactams is essentially negligible; however, there are some clinical data to support an interaction between ceftazidime and aztreonam, due to the similarity of their side chains. The data reviewed suggest that avoidance of other beta-lactams in patients with type 1 hypersensitivity to penicillins should be reconsidered. © The Author(s) 2014.

  18. Evaluation of doctors’ performance as facilitators in basic medical science lecture classes in a new Malaysian medical school

    PubMed Central

    Ismail, Salwani; Salam, Abdus; Alattraqchi, Ahmed G; Annamalai, Lakshmi; Chockalingam, Annamalai; Elena, Wan Putri; Rahman, Nor Iza A; Abubakar, Abdullahi Rabiu; Haque, Mainul

    2015-01-01

    Background Didactic lecture is the oldest and most commonly used method of teaching. In addition, it is considered one of the most efficient ways to disseminate theories, ideas, and facts. Many critics feel that lectures are an obsolete method to use when students need to perform hands-on activities, which is an everyday need in the study of medicine. This study evaluates students’ perceptions regarding lecture quality in a new medical school. Methods This was a cross-sectional study conducted of the medical students of Universiti Sultan Zainal Abidin. The study population was 468 preclinical medical students from years 1 and 2 of academic year 2012–2013. Data were collected using a validated instrument. There were six different sections of questions using a 5-point Likert scale. The data were then compiled and analyzed, using SPSS version 20. Results The response rate was 73%. Among 341 respondents, 30% were male and 70% were female. Eighty-five percent of respondents agree or strongly agree that the lectures had met the criteria with regard to organization of lecture materials. Similarly, 97% of students agree or strongly agree that lecturers maintained adequate voices and gestures. Conclusion Medical students are quite satisfied with the lecture classes and the lectures. However, further research is required to identify student-centered teaching and learning methods to promote active learning. PMID:25878516

  19. Evaluation of doctors' performance as facilitators in basic medical science lecture classes in a new Malaysian medical school.

    PubMed

    Ismail, Salwani; Salam, Abdus; Alattraqchi, Ahmed G; Annamalai, Lakshmi; Chockalingam, Annamalai; Elena, Wan Putri; Rahman, Nor Iza A; Abubakar, Abdullahi Rabiu; Haque, Mainul

    2015-01-01

    Didactic lecture is the oldest and most commonly used method of teaching. In addition, it is considered one of the most efficient ways to disseminate theories, ideas, and facts. Many critics feel that lectures are an obsolete method to use when students need to perform hands-on activities, which is an everyday need in the study of medicine. This study evaluates students' perceptions regarding lecture quality in a new medical school. This was a cross-sectional study conducted of the medical students of Universiti Sultan Zainal Abidin. The study population was 468 preclinical medical students from years 1 and 2 of academic year 2012-2013. Data were collected using a validated instrument. There were six different sections of questions using a 5-point Likert scale. The data were then compiled and analyzed, using SPSS version 20. The response rate was 73%. Among 341 respondents, 30% were male and 70% were female. Eighty-five percent of respondents agree or strongly agree that the lectures had met the criteria with regard to organization of lecture materials. Similarly, 97% of students agree or strongly agree that lecturers maintained adequate voices and gestures. Medical students are quite satisfied with the lecture classes and the lectures. However, further research is required to identify student-centered teaching and learning methods to promote active learning.

  20. CLASS Reliability Training as Professional Development for Preschool Teachers

    ERIC Educational Resources Information Center

    Casbergue, Renée M.; Bedford, April Whatley; Burstein, Karen

    2014-01-01

    Use of the Classroom Assessment Scoring System (CLASS) is increasing across the United States as an important indicator of the quality of programs for young children. Professional development is required to facilitate teachers' understanding of the instructional behaviors upon which they will be judged. This study investigated the use of the…

  1. 78 FR 65555 - Establishment of Class E Airspace; Salmon, ID

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-01

    ...-0531; Airspace Docket No. 13-ANM-20] Establishment of Class E Airspace; Salmon, ID AGENCY: Federal... at the Salmon VHF Omni-Directional Radio Range/Distance Measuring Equipment (VOR/DME) navigation aid, Salmon, ID, to facilitate vectoring of Instrument Flight Rules (IFR) aircraft under control of Salt Lake...

  2. Effect of Class III bone anchor treatment on airway.

    PubMed

    Nguyen, Tung; De Clerck, Hugo; Wilson, Michael; Golden, Brent

    2015-07-01

    To compare airway volumes and minimum cross-section area changes of Class III patients treated with bone-anchored maxillary protraction (BAMP) versus untreated Class III controls. Twenty-eight consecutive skeletal Class III patients between the ages of 10 and 14 years (mean age, 11.9 years) were treated using Class III intermaxillary elastics and bilateral miniplates (two in the infra-zygomatic crests of the maxilla and two in the anterior mandible). The subjects had cone beam computed tomographs (CBCTs) taken before initial loading (T1) and 1 year out (T2). Twenty-eight untreated Class III patients (mean age, 12.4 years) had CBCTs taken and cephalograms generated. The airway volumes and minimum cross-sectional area measurements were performed using Dolphin Imaging 11.7 3D software. The superior border of the airway was defined by a plane that passes through the posterior nasal spine and basion, while the inferior border included the base of the epiglottis to the lower border of C3. From T1 to T2, airway volume from BAMP-treated subjects showed a statistically significant increase (1499.64 mm(3)). The area in the most constricted section of the airway (choke point) increased slightly (15.44 mm(2)). The airway volume of BAMP patients at T2 was 14136.61 mm(3), compared with 14432.98 mm(3) in untreated Class III subjects. Intraexaminer correlation coefficients values and 95% confidence interval values were all greater than .90, showing a high degree of reliability of the measurements. BAMP treatment did not hinder the development of the oropharynx.

  3. A class Hierarchical, object-oriented approach to virtual memory management

    NASA Technical Reports Server (NTRS)

    Russo, Vincent F.; Campbell, Roy H.; Johnston, Gary M.

    1989-01-01

    The Choices family of operating systems exploits class hierarchies and object-oriented programming to facilitate the construction of customized operating systems for shared memory and networked multiprocessors. The software is being used in the Tapestry laboratory to study the performance of algorithms, mechanisms, and policies for parallel systems. Described here are the architectural design and class hierarchy of the Choices virtual memory management system. The software and hardware mechanisms and policies of a virtual memory system implement a memory hierarchy that exploits the trade-off between response times and storage capacities. In Choices, the notion of a memory hierarchy is captured by abstract classes. Concrete subclasses of those abstractions implement a virtual address space, segmentation, paging, physical memory management, secondary storage, and remote (that is, networked) storage. Captured in the notion of a memory hierarchy are classes that represent memory objects. These classes provide a storage mechanism that contains encapsulated data and have methods to read or write the memory object. Each of these classes provides specializations to represent the memory hierarchy.

  4. A novel framework for molecular characterization of atmospherically relevant organic compounds based on collision cross section and mass-to-charge ratio

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Xuan; Krechmer, Jordan E.; Groessl, Michael

    Here, a new metric is introduced for representing the molecular signature of atmospherically relevant organic compounds, the collision cross section (Ω), a quantity that is related to the structure and geometry of molecules and is derived from ion mobility measurements. By combination with the mass-to-charge ratio ( m/z), a two-dimensional Ω – m/z space is developed to facilitate the comprehensive investigation of the complex organic mixtures. A unique distribution pattern of chemical classes, characterized by functional groups including amine, alcohol, carbonyl, carboxylic acid, ester, and organic sulfate, is developed on the 2-D Ω – m/z space. Species of the samemore » chemical class, despite variations in the molecular structures, tend to situate as a narrow band on the space and follow a trend line. Reactions involving changes in functionalization and fragmentation can be represented by the directionalities along or across these trend lines, thus allowing for the interpretation of atmospheric transformation mechanisms of organic species. The characteristics of trend lines for a variety of functionalities that are commonly present in the atmosphere can be predicted by the core model simulations, which provide a useful tool to identify the chemical class to which an unknown species belongs on the Ω – m/z space. Within the band produced by each chemical class on the space, molecular structural assignment can be achieved by utilizing collision-induced dissociation as well as by comparing the measured collision cross sections in the context of those obtained via molecular dynamics simulations.« less

  5. A novel framework for molecular characterization of atmospherically relevant organic compounds based on collision cross section and mass-to-charge ratio

    DOE PAGES

    Zhang, Xuan; Krechmer, Jordan E.; Groessl, Michael; ...

    2016-10-19

    Here, a new metric is introduced for representing the molecular signature of atmospherically relevant organic compounds, the collision cross section (Ω), a quantity that is related to the structure and geometry of molecules and is derived from ion mobility measurements. By combination with the mass-to-charge ratio ( m/z), a two-dimensional Ω – m/z space is developed to facilitate the comprehensive investigation of the complex organic mixtures. A unique distribution pattern of chemical classes, characterized by functional groups including amine, alcohol, carbonyl, carboxylic acid, ester, and organic sulfate, is developed on the 2-D Ω – m/z space. Species of the samemore » chemical class, despite variations in the molecular structures, tend to situate as a narrow band on the space and follow a trend line. Reactions involving changes in functionalization and fragmentation can be represented by the directionalities along or across these trend lines, thus allowing for the interpretation of atmospheric transformation mechanisms of organic species. The characteristics of trend lines for a variety of functionalities that are commonly present in the atmosphere can be predicted by the core model simulations, which provide a useful tool to identify the chemical class to which an unknown species belongs on the Ω – m/z space. Within the band produced by each chemical class on the space, molecular structural assignment can be achieved by utilizing collision-induced dissociation as well as by comparing the measured collision cross sections in the context of those obtained via molecular dynamics simulations.« less

  6. Learning Discriminative Binary Codes for Large-scale Cross-modal Retrieval.

    PubMed

    Xu, Xing; Shen, Fumin; Yang, Yang; Shen, Heng Tao; Li, Xuelong

    2017-05-01

    Hashing based methods have attracted considerable attention for efficient cross-modal retrieval on large-scale multimedia data. The core problem of cross-modal hashing is how to learn compact binary codes that construct the underlying correlations between heterogeneous features from different modalities. A majority of recent approaches aim at learning hash functions to preserve the pairwise similarities defined by given class labels. However, these methods fail to explicitly explore the discriminative property of class labels during hash function learning. In addition, they usually discard the discrete constraints imposed on the to-be-learned binary codes, and compromise to solve a relaxed problem with quantization to obtain the approximate binary solution. Therefore, the binary codes generated by these methods are suboptimal and less discriminative to different classes. To overcome these drawbacks, we propose a novel cross-modal hashing method, termed discrete cross-modal hashing (DCH), which directly learns discriminative binary codes while retaining the discrete constraints. Specifically, DCH learns modality-specific hash functions for generating unified binary codes, and these binary codes are viewed as representative features for discriminative classification with class labels. An effective discrete optimization algorithm is developed for DCH to jointly learn the modality-specific hash function and the unified binary codes. Extensive experiments on three benchmark data sets highlight the superiority of DCH under various cross-modal scenarios and show its state-of-the-art performance.

  7. Simulation Modeling of a Facility Layout in Operations Management Classes

    ERIC Educational Resources Information Center

    Yazici, Hulya Julie

    2006-01-01

    Teaching quantitative courses can be challenging. Similarly, layout modeling and lean production concepts can be difficult to grasp in an introductory OM (operations management) class. This article describes a simulation model developed in PROMODEL to facilitate the learning of layout modeling and lean manufacturing. Simulation allows for the…

  8. Bacteria facilitate prey retention by the pitcher plant Darlingtonia californica

    PubMed Central

    2016-01-01

    Bacteria are hypothesized to provide a variety of beneficial functions to plants. Many carnivorous pitcher plants, for example, rely on bacteria for digestion of captured prey. This bacterial community may also be responsible for the low surface tensions commonly observed in pitcher plant digestive fluids, which might facilitate prey capture. I tested this hypothesis by comparing the physical properties of natural pitcher fluid from the pitcher plant Darlingtonia californica and cultured ‘artificial’ pitcher fluids and tested these fluids' prey retention capabilities. I found that cultures of pitcher leaves' bacterial communities had similar physical properties to raw pitcher fluids. These properties facilitated the retention of insects by both fluids and hint at a previously undescribed class of plant–microbe interaction. PMID:27881762

  9. Bacteria facilitate prey retention by the pitcher plant Darlingtonia californica.

    PubMed

    Armitage, David W

    2016-11-01

    Bacteria are hypothesized to provide a variety of beneficial functions to plants. Many carnivorous pitcher plants, for example, rely on bacteria for digestion of captured prey. This bacterial community may also be responsible for the low surface tensions commonly observed in pitcher plant digestive fluids, which might facilitate prey capture. I tested this hypothesis by comparing the physical properties of natural pitcher fluid from the pitcher plant Darlingtonia californica and cultured 'artificial' pitcher fluids and tested these fluids' prey retention capabilities. I found that cultures of pitcher leaves' bacterial communities had similar physical properties to raw pitcher fluids. These properties facilitated the retention of insects by both fluids and hint at a previously undescribed class of plant-microbe interaction. © 2016 The Author(s).

  10. Cross-generational trans fat intake facilitates mania-like behavior: oxidative and molecular markers in brain cortex.

    PubMed

    Trevizol, F; Roversi, Kr; Dias, V T; Roversi, K; Barcelos, R C S; Kuhn, F T; Pase, C S; Golombieski, R; Veit, J C; Piccolo, J; Pochmann, D; Porciúncula, L O; Emanuelli, T; Rocha, J B T; Bürger, M E

    2015-02-12

    Since that fast food consumption have raised concerns about people's health, we evaluated the influence of trans fat consumption on behavioral, biochemical and molecular changes in the brain-cortex of second generation rats exposed to a model of mania. Two successive generations of female rats were supplemented with soybean oil (SO, rich in n-6 FA, control group), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in trans FA) from pregnancy, lactation to adulthood, when male rats from 2nd generation received amphetamine (AMPH-4 mg/kg-i.p., once a day, for 14 days) treatment. AMPH increased locomotor index in all animals, which was higher in the HVF group. While the FO group showed increased n-3 polyunsaturated fatty acid (PUFA) incorporation and reduced n-6/n-3 PUFA ratio, HVF allowed trans fatty acid (TFA) incorporation and increased n-6/n-3 PUFA ratio in the brain-cortex. In fact, the FO group showed minor AMPH-induced hyperactivity, decreased reactive species (RS) generation per se, causing no changes in protein carbonyl (PC) levels and dopamine transporter (DAT). FO supplementation showed molecular changes, since proBDNF was increased per se and reduced by AMPH, decreasing the brain-derived neurotrophic factor (BDNF) level following drug treatment. Conversely, HVF was related to increased hyperactivity, higher PC level per se and higher AMPH-induced PC level, reflecting on DAT, whose levels were decreased per se as well as in AMPH-treated groups. In addition, while HVF increased BDNF-mRNA per se, AMPH reduced this value, acting on BDNF, whose level was lower in the same AMPH-treated experimental group. ProBDNF level was influenced by HVF supplementation, but it was not sufficient to modify BDNF level. These findings reinforce that prolonged consumption of trans fat allows TFA incorporation in the cortex, facilitating hyperactive behavior, oxidative damages and molecular changes. Our study is a warning about cross-generational consumption

  11. Facilitating Facilitators: Enhancing PBL through a Structured Facilitator Development Program

    ERIC Educational Resources Information Center

    Salinitri, Francine D.; Wilhelm, Sheila M.; Crabtree, Brian L.

    2015-01-01

    With increasing adoption of the problem-based learning (PBL) model, creative approaches to enhancing facilitator training and optimizing resources to maintain effective learning in small groups is essential. We describe a theoretical framework for the development of a PBL facilitator training program that uses the constructivist approach as the…

  12. Expression of Eph receptor tyrosine kinases and their ligands in human Granulosa lutein cells and human umbilical vein endothelial cells.

    PubMed

    Xu, Y; Zagoura, D; Keck, C; Pietrowski, D

    2006-11-01

    Corpus luteum development is regulated by gonadotropins and accompanied by extremely rapid vascularization of the avascular granulosa cell compartiment by endothelial cells (EC). The proliferation of Granulosa cells (GC) and EC is a complex interplay and takes place in a spatially and temporarily coordinated manner. The erythropoietin-producing hepatoma amplified sequence (Eph) receptors and their ligands-the ephrins- are a recently detected family of membrane located protein tyrosine kinases which play a crucial role in the growth and development of nerve and blood vessel network. We report about the mRNA expression pattern of Ephs and their ligands in human GC, in human EC, and in carcinoma cell lines OvCar-3 and Hela. The mRNA of EphA4, EphA7, ephrinA4, ephrinB1 and ephrinB2 was detected in GC and EC, while EphA2 was expressed only in GC. The expression of various Ephs and ephrins did not change in GC after stimulation with human chorion gonadotropin. Our study analyzes for the first time the expression of the complete human Eph/ephriny-system in GC and in EC. The remarkable similarity between these two cell types supports the theory of a functional relationship of EC and GC. In addition, it was shown that hCG is not a major determinant of Eph/ephrin regulation in GC.

  13. Vertical Integration: Results from a Cross-Course Student Collaboration

    ERIC Educational Resources Information Center

    Sloan, Thomas; Lewis, David

    2011-01-01

    The authors report the results of a cross-class project involving sophomore-level students in an Operations Analysis (OA) class with junior-level students in an Operations Management (OM) class. The students formed virtual teams and developed a simulation model of a call center. The OM students provided the management expertise, while the OA…

  14. Analysis of MHC class I folding: novel insights into intermediate forms

    PubMed Central

    Simone, Laura C.; Tuli, Amit; Simone, Peter D.; Wang, Xiaojian; Solheim, Joyce C.

    2012-01-01

    Folding around a peptide ligand is integral to the antigen presentation function of major histocompatibility complex (MHC) class I molecules. Several lines of evidence indicate that the broadly cross-reactive 34-1-2 antibody is sensitive to folding of the MHC class I peptide-binding groove. Here, we show that peptide-loading complex proteins associated with the murine MHC class I molecule Kd are found primarily in association with the 34-1-2+ form. This led us to hypothesize that the 34-1-2 antibody may recognize intermediately, as well as fully, folded MHC class I molecules. In order to further characterize the form(s) of MHC class I molecules recognized by 34-1-2, we took advantage of its cross-reactivity with Ld. Recognition of the open and folded forms of Ld by the 64-3-7 and 30-5-7 antibodies, respectively, has been extensively characterized, providing us with parameters against which to compare 34-1-2 reactivity. We found that the 34-1-2+ Ld molecules displayed characteristics indicative of incomplete folding, including increased tapasin association, endoplasmic reticulum retention, and instability at the cell surface. Moreover, we demonstrate that an Ld-specific peptide induced folding of the 34-1-2+ Ld intermediate. Altogether, these results yield novel insights into the nature of MHC class I molecules recognized by the 34-1-2 antibody. PMID:22329842

  15. Social class, Mexican culture, and fatalism: their effects on psychological distress.

    PubMed

    Ross, C E; Mirowsky, J; Cockerham, W C

    1983-08-01

    We examine the causes and consequences of fatalism in a cross-cultural setting, focusing on the ways in which a fatalistic world view may mediate the effects of social class and Mexican ethnic identity on psychological distress. We find that persons in the lower social classes and Mexicans tend to be more fatalistic than persons in the upper classes and Anglos, and that fatalism, in turn, increases psychological distress. We attempt to integrate research on the social and cultural determinants of cognitive orientations with studies of the effects of social class and Mexican culture on distress.

  16. Cross-Cultural HRD.

    ERIC Educational Resources Information Center

    1995

    These five papers are from a symposium that was facilitated by David C. Bjorkquist on cross-cultural human resource development (HRD) at the 1995 Academy of Human Resource Development conference. "Developing Managers for Overseas Assignments in the Pacific Rim: A Study of International HRD Issues in Singapore" (A. Ahad M. Osman-Gani,…

  17. PBL Group Autonomy in a High School Environmental Science Class

    ERIC Educational Resources Information Center

    Weiss, D. Mark; Belland, Brian R.

    2018-01-01

    With increasing class sizes, teachers and facilitators alike hope for learning groups where students work together in self-contained and autonomous ways requiring reduced teacher support. Yet many instructors find the idea of developing independent learning in small groups to be elusive particularly in K-12 settings (Ertmer and Simons in…

  18. Living in the city: school friendships, diversity and the middle classes.

    PubMed

    Vincent, Carol; Neal, Sarah; Iqbal, Humera

    2018-06-01

    Much of the literature on the urban middle classes describes processes of both affiliation (often to the localities) and disaffiliation (often from some of the non-middle-class residents). In this paper, we consider this situation from a different position, drawing on research exploring whether and how children and adults living in diverse localities develop friendships with those different to themselves in terms of social class and ethnicity. This paper focuses on the interviews with the ethnically diverse, but predominantly white British, middle-class parent participants, considering their attitudes towards social and cultural difference. We emphasize the importance of highlighting inequalities that arise from social class and its intersection with ethnicity in analyses of complex urban populations. The paper's contribution is, first, to examine processes of clustering amongst the white British middle-class parents, particularly in relation to social class. Second, we contrast this process, and its moments of reflection and unease, with the more deliberate and purposeful efforts of one middle-class, Bangladeshi-origin mother who engages in active labour to facilitate relationships across social and ethnic difference. © London School of Economics and Political Science 2017.

  19. Service Learning with Children Affected by Poverty: Facilitating Multicultural Competence in Counseling Education Students

    ERIC Educational Resources Information Center

    Baggerly, Jennifer

    2006-01-01

    The author defines and presents a rationale for service learning, provides procedures for implementing service learning with children affected by poverty, and describes methods of facilitating multicultural counseling competence. Examples are provided from a graduate counseling class that conducted group play therapy with 11 African American…

  20. A three-dimensional soft tissue analysis of Class III malocclusion: a case-controlled cross-sectional study.

    PubMed

    Johal, Ama; Chaggar, Amrit; Zou, Li Fong

    2018-03-01

    The present study used the optical surface laser scanning technique to compare the facial features of patients aged 8-18 years presenting with Class I and Class III incisor relationship in a case-control design. Subjects with a Class III incisor relationship, aged 8-18 years, were age and gender matched with Class I control and underwent a 3-dimensional (3-D) optical surface scan of the facial soft tissues. Landmark analysis revealed Class III subjects displayed greater mean dimensions compared to the control group most notably between the ages of 8-10 and 17-18 years in both males and females, in respect of antero-posterior (P = 0.01) and vertical (P = 0.006) facial dimensions. Surface-based analysis, revealed the greatest difference in the lower facial region, followed by the mid-face, whilst the upper face remained fairly consistent. Significant detectable differences were found in the surface facial features of developing Class III subjects.

  1. Making cross-racial therapy work: A phenomenological study of clients’ experiences of cross-racial therapy

    PubMed Central

    Chang, Doris F.; Berk, Alexandra

    2010-01-01

    A phenomenological/consensual qualitative study of clients’ lived experiences of cross-racial therapy was conducted to enhance our understanding of whether, how, and under what conditions race matters in the therapy relationship. The sample consisted of 16 racial/ethnic minority clients who received treatment from 16 White, European American therapists across a range of treatment settings. Participants who reported a satisfying experience of cross-racial therapy (n=8) were examined in relation to gender- and in most cases, race/ethnicity-matched controls (n=8) who reported an overall unsatisfying experience. Therapy satisfaction was assessed during the screening process and confirmed during the research interview. Therapy narratives were analyzed using consensual qualitative research to identify the client, therapist, and relational factors that distinguished satisfied from unsatisfied cases. Findings reveal substantial differences at the level of individual characteristics and relational processes, providing evidence of both universal (etic) as well as culture/context-specific (emic) aspects of healing relationships. Recommendations for facilitating positive alliance formation in cross-racial therapy are provided based on clients’ descriptions of facilitative conditions in the therapy relationship. PMID:20414342

  2. Social closure, micro-class immobility and the intergenerational reproduction of the upper class: a comparative study.

    PubMed

    Ruggera, Lucia; Barone, Carlo

    2017-06-01

    This article assesses how processes of social closure enhance intergenerational immobility in the regulated professions and thus promote persistence at the top of the occupational hierarchy. We compare four European countries (GB, Germany, Denmark and Sweden) that differ considerably in their degree of professional regulation and in their broader institutional arrangements. We run log-linear and logistic regression models on a cumulative dataset based on three large-scale surveys with detailed and highly comparable information at the level of unit occupations. Our analyses indicate that children of licensed professionals are far more likely to inherit the occupation of their parents and that this stronger micro-class immobility translates into higher chances of persistence in the upper class. These results support social closure theory and confirm the relevance of a micro-class approach for the explanation of social fluidity and of its cross-national variations. Moreover, we find that, when children of professionals do not reproduce the micro-class of their parents, they still display disproportionate chances of persistence in professional employment. Hence, on the one hand, processes of social closure erect barriers between professions and fuel micro-class immobility at the top. On the other hand, the cultural proximity of different professional groups drives intense intergenerational exchanges between them. Our analyses indicate that these micro- and meso-class rigidities work as complementary routes to immobility at the top. © London School of Economics and Political Science 2017.

  3. Coding of Class I and II aminoacyl-tRNA synthetases

    PubMed Central

    Carter, Charles W.

    2018-01-01

    SUMMARY The aminoacyl-tRNA synthetases and their cognate transfer RNAs translate the universal genetic code. The twenty canonical amino acids are sufficiently diverse to create a selective advantage for dividing amino acid activation between two distinct, apparently unrelated superfamilies of synthetases, Class I amino acids being generally larger and less polar, Class II amino acids smaller and more polar. Biochemical, bioinformatic, and protein engineering experiments support the hypothesis that the two Classes descended from opposite strands of the same ancestral gene. Parallel experimental deconstructions of Class I and II synthetases reveal parallel losses in catalytic proficiency at two novel modular levels—protozymes and Urzymes—associated with the evolution of catalytic activity. Bi-directional coding supports an important unification of the proteome; affords a genetic relatedness metric—middle base-pairing frequencies in sense/antisense alignments—that probes more deeply into the evolutionary history of translation than do single multiple sequence alignments; and has facilitated the analysis of hitherto unknown coding relationships in tRNA sequences. Reconstruction of native synthetases by modular thermodynamic cycles facilitated by domain engineering emphasizes the subtlety associated with achieving high specificity, shedding new light on allosteric relationships in contemporary synthetases. Synthetase Urzyme structural biology suggests that they are catalytically active molten globules, broadening the potential manifold of polypeptide catalysts accessible to primitive genetic coding and motivating revisions of the origins of catalysis. Finally, bi-directional genetic coding of some of the oldest genes in the proteome places major limitations on the likelihood that any RNA World preceded the origins of coded proteins. PMID:28828732

  4. Pseudomonas Genome Database: facilitating user-friendly, comprehensive comparisons of microbial genomes.

    PubMed

    Winsor, Geoffrey L; Van Rossum, Thea; Lo, Raymond; Khaira, Bhavjinder; Whiteside, Matthew D; Hancock, Robert E W; Brinkman, Fiona S L

    2009-01-01

    Pseudomonas aeruginosa is a well-studied opportunistic pathogen that is particularly known for its intrinsic antimicrobial resistance, diverse metabolic capacity, and its ability to cause life threatening infections in cystic fibrosis patients. The Pseudomonas Genome Database (http://www.pseudomonas.com) was originally developed as a resource for peer-reviewed, continually updated annotation for the Pseudomonas aeruginosa PAO1 reference strain genome. In order to facilitate cross-strain and cross-species genome comparisons with other Pseudomonas species of importance, we have now expanded the database capabilities to include all Pseudomonas species, and have developed or incorporated methods to facilitate high quality comparative genomics. The database contains robust assessment of orthologs, a novel ortholog clustering method, and incorporates five views of the data at the sequence and annotation levels (Gbrowse, Mauve and custom views) to facilitate genome comparisons. A choice of simple and more flexible user-friendly Boolean search features allows researchers to search and compare annotations or sequences within or between genomes. Other features include more accurate protein subcellular localization predictions and a user-friendly, Boolean searchable log file of updates for the reference strain PAO1. This database aims to continue to provide a high quality, annotated genome resource for the research community and is available under an open source license.

  5. Facilitating cultural border crossing in urban secondary science classrooms: A study of inservice teachers

    NASA Astrophysics Data System (ADS)

    Monteiro, Anna Karina

    Research acknowledges that if students are to be successful science, they must learn to navigate and cross cultural borders that exist between their own cultures and the subculture of science. This dissertation utilized a mixed methods approach to explore how inservice science teachers working in urban schools construct their ideas of and apply the concepts about the culture of science and cultural border crossing as relevant to the teaching and learning of science. The study used the lenses of cultural capital, social constructivism, and cultural congruency in the design and analysis of each of the three phases of data collection. Phase I identified the perspectives of six inservice science teachers on science culture, cultural border crossing, and which border crossing methods, if any, they used during science teaching. Phase II took a dialectical approach as the teachers read about science culture and cultural border crossing during three informal professional learning community meetings. This phase explored how teachers constructed their understanding of cultural border crossing and how the concept applied to the teaching and learning of science. Phase III evaluated how teachers' perspectives changed from Phase I. In addition, classroom observations were used to determine whether teachers' practices in their science classrooms changed from Phase I to Phase III. All three phases collected data through qualitative (i.e., interviews, classroom observations, and surveys) and quantitative (Likert items) means. The findings indicated that teachers found great value in learning about the culture of science and cultural border crossing as it pertained to their teaching methods. This was not only evidenced by their interviews and surveys, but also in the methods they used in their classrooms. Final conclusions included how the use of student capital resources (prior experiences, understandings and knowledge, ideas an interests, and personal beliefs), if supported by

  6. Web-based medical facilitators in medical tourism: the third party in decision-making.

    PubMed

    Wagle, Suchitra

    2013-01-01

    The emergence of web-based medical tourism facilitators (MTFs) has added a new dimension to the phenomenon of cross-border travel. These facilitators are crucial connectors between foreign patients and host countries. They help patients navigate countries, doctors and specialties. However, little attention has been paid to the authenticity of information displayed on the facilitators' web portals, and whether they follow ethical guidelines and standards. This paper analyses the available information on MTF portals from an ethics perspective. It compares 208 facilitators across 47 countries for the services offered. Data were collected from the databases of the Medical Tourism Association and World Medical Resources. India was the most common destination country linked to 81 facilitators. The five countries with the maximum number of facilitators were the USA, the UK, India, Canada and Poland. This paper identifies concerns regarding the information displayed about patients' safety, and the maintenance of confidentiality. There is a need to develop ethical standards for this field.

  7. Facilitating the Critique of Racism and Classism: An Experimental Model for Euro-American Middle-Class Students.

    ERIC Educational Resources Information Center

    Cohen, Lorraine

    1995-01-01

    Maintains that, during the 1980s, it was difficult to find classroom approaches that effectively challenged racial and class stereotypes. Describes a college community service project designed to teach students about racial, social, and gender discrimination. (CFR)

  8. Paths to tobacco abstinence: A repeated-measures latent class analysis.

    PubMed

    McCarthy, Danielle E; Ebssa, Lemma; Witkiewitz, Katie; Shiffman, Saul

    2015-08-01

    Knowledge of smoking change processes may be enhanced by identifying pathways to stable abstinence. We sought to identify latent classes of smokers based on their day-to-day smoking status in the first weeks of a cessation attempt. We examined treatment effects on class membership and compared classes on baseline individual differences and 6-month abstinence rates. In this secondary analysis of a double-blind randomized placebo-controlled clinical trial (N = 1,433) of 5 smoking cessation pharmacotherapies (nicotine patch, nicotine lozenge, bupropion SR, patch and lozenge, or bupropion SR and lozenge), we conducted repeated-measures latent class analysis of daily smoking status (any smoking vs. none) for the first 27 days of a quit attempt. Treatment and covariate relations with latent class membership were examined. Distal outcome analysis compared confirmed 6-month abstinence rates among the latent classes. A 5-class solution was selected. Three-quarters of smokers were in stable smoking or abstinent classes, but 25% were in classes with unstable abstinence probabilities over time. Active treatment (compared to placebo), and particularly the patch and lozenge combination, promoted early quitting. Latent classes differed in 6-month abstinence rates and on several baseline variables, including nicotine dependence, quitting history, self-efficacy, sleep disturbance, and minority status. Repeated-measures latent class analysis identified latent classes of smoking change patterns affected by treatment, related to known risk factors, and predictive of distal outcomes. Tracking behavior early in a change attempt may identify prognostic patterns of change and facilitate adaptive treatment planning. (c) 2015 APA, all rights reserved).

  9. Navigating Cross-Boundary Connections in Educational Research

    ERIC Educational Resources Information Center

    Oikonomidoy, Eleni; Wiest, Lynda R.

    2017-01-01

    Drawing on insights from reflective research accounts in the social sciences, this paper attends to the complexities of conducting cross-boundary educational research. Cross-boundary research is defined as any type of inquiry that is conducted across cultural and/or structural boundaries, including but not limited to race, class, gender, language,…

  10. 78 FR 65556 - Establishment of Class E Airspace; Cut Bank, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-01

    ...-0532; Airspace Docket No. 13-ANM-21] Establishment of Class E Airspace; Cut Bank, MT AGENCY: Federal... at the Cut Bank VHF Omni-Directional Radio Range Tactical Air Navigational Aid (VORTAC) navigation aid, Cut Bank, MT, to facilitate vectoring of Instrument Flight Rules (IFR) aircraft under control of...

  11. Teaching Cross-Cultural Psychology: Providing the Missing Link.

    ERIC Educational Resources Information Center

    Cushner, Kenneth H.

    1987-01-01

    This article describes the development and evaluation of materials designed to facilitate the teaching of cross-cultural psychology to students who are internationally and interculturally naive. The materials consist of 100 cross-cultural incidents contained in 18 essays. Two incidents are described and evaluative evidence is presented.…

  12. Cross-Species Withdrawal of MCL1 Facilitates Postpartum Uterine Involution in Both the Mouse and Baboon

    PubMed Central

    Kyathanahalli, Chandrashekara; Marks, Jason; Nye, Kennedy; Lao, Belinda; Albrecht, Eugene D.; Aberdeen, Graham W.; Nathanielsz, Peter W.; Jeyasuria, Pancharatnam

    2013-01-01

    A successful postpartum involution permits the postnatal uterus to rapidly regain its prepregnancy function and size to ultimately facilitate an ensuing blastocyst implantation. This study investigates the molecular mechanisms that govern the initiation of the involution process by examining the signaling events that occur as the uterus transitions from the pregnant to postnatal state. Using mouse and baboon uteri, we found a remarkable cross-species conservation at the signal transduction level as the pregnant uterus initiates and progresses through the involution process. This study originated with the observation of elevated levels of caspase-3 activation in both the laboring mouse and baboon uterus, which we found to be apoptotic in nature as evidenced by the concurrent appearance of cleaved poly(ADP-ribose) polymerase. We previously defined a nonapoptotic and potential tocolytic role for uterine caspase-3 during pregnancy regulated by increased antiapoptotic signaling mediated by myeloid cell leukemia sequence 1 and X-linked inhibitor of apoptosis. In contrast, this study determined that diminished antiapoptotic signaling in the postpartum uterus allowed for both endometrial apoptotic and myometrial autophagic episodes, which we speculate are responsible for the rapid reduction in size of the postpartum uterus. Using our human telomerase immortalized myometrial cell line and the Simian virus-40 immortalized endometrial cell line (12Z), we demonstrated that the withdrawal of antiapoptotic signaling was also an upstream event for both the autophagic and apoptotic processes in the human uterine myocyte and endometrial epithelial cell. PMID:24140717

  13. T cell receptor cross-reactivity directed by antigen-dependent tuning of peptide-MHC molecular flexibility

    PubMed Central

    Borbulevych, Oleg Y.; Piepenbrink, Kurt H.; Gloor, Brian E.; Scott, Daniel R.; Sommese, Ruth F.; Cole, David K.; Sewell, Andrew K.; Baker, Brian M.

    2011-01-01

    Summary Tell mediated immunity requires T cell receptor (TCR) cross-reactivity, the mechanisms behind which remain incompletely elucidated. The αβ TCR A6 recognizes both the Tax (LLFGYPVYV) and Tel1p (MLWGYLQYV) peptides presented by the human class I MHC molecule HLA-A2. Here we found that although the two ligands are ideal structural mimics, they form substantially different interfaces with A6, with conformational differences in the peptide, the TCR, and unexpectedly, the MHC molecule. The differences between the Tax and Tel1p ternary complexes could not be predicted from the free peptide-MHC structures and are inconsistent with a traditional induced-fit mechanism. Instead, the differences were attributable to peptide and MHC molecular motion present in Tel1p-HLA-A2 but absent in Tax-HLA-A2. Differential “tuning” of the dynamic properties of HLA-A2 by the Tax and Tel1p peptides thus facilitates cross-recognition and impacts how structural diversity can be presented to and accommodated by receptors of the immune system. PMID:20064447

  14. Electronic Learning-Spaced Education to Facilitate Resident Knowledge and Guide Program Didactics.

    PubMed

    Gandhi, Manisha; Beasley, Anitra; Vinas, Emily; Sangi-Haghpeykar, Haleh; Ramin, Susan M; Kilpatrick, Charlie C

    2016-10-01

    To evaluate the use of mobile technology to facilitate resident learning, assess clinical knowledge, and guide curricular development in a busy clinical environment. This was a cross-sectional study conducted in a large (N=48) urban obstetrics and gynecology residency program. Question sets were created in the following areas: office gynecology, general obstetrics, gynecologic surgery and urogynecology, maternal-fetal medicine and ultrasonography, reproductive endocrinology and pediatric gynecology, and gynecologic oncology. Using an educational mobile application (app), questions were sent monthly to resident smartphones with immediate feedback on answer accuracy along with answer explanation and references. Outcomes included app use, which was determined by how quickly participants answered questions (very active-active indicates questions answered within 7 days) and proficiency (mean percentage correct) calculated for individuals, resident class level, and by content area. All 48 residents participated and 77.4% were very active or active app users. On average, participants answered correctly 61.0% on the first attempt and improved to 78.3% on repeat attempt (P<.001). Proficiency was lowest for gynecologic surgery and highest for general obstetrics. A mobile app to support e-learning was successfully implemented in our program; its use was associated with knowledge retention and identification of low-proficiency topics to guide curriculum development.

  15. Collaboration between Mathematics Facilitators and Preschool Teachers Using the Innovative "Senso-Math" Preschool Program

    ERIC Educational Resources Information Center

    Hassidov, Dina; Ilany, Bat-Sheva

    2018-01-01

    This article presents a mixed-method study of the innovative "Senso-Math" preschool program and the reactions of both the facilitators, who underwent a special training program, and the preschool teachers in whose classes the program was implemented. The goal of the program is to enhance mathematical development in preschool children…

  16. Technology Supported Facilitation and Assessment of Small Group Collaborative Inquiry Learning in Large First-Year Classes

    ERIC Educational Resources Information Center

    Lawrie, Gwendolyn A.; Gahan, Lawrence R.; Matthews, Kelly E.; Weaver, Gabriela C.; Bailey, Chantal; Adams, Peter; Kavanagh, Lydia J.; Long, Phillip D.; Taylor, Matthew

    2014-01-01

    Collaborative learning activities offer the potential to support mutual knowledge construction and shared understanding amongst students. Introducing collaborative tasks into large first-year undergraduate science classes to create learning environments that foster student engagement and enhance communication skills is appealing. However,…

  17. 78 FR 58158 - Establishment of Class E Airspace; Wasatch, UT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-23

    ...., long. 111[deg]07'28'' W.; to Lat. 39[deg]03'55'' N., long. 110[deg]37'49'' W.; to Lat. 38[deg]28'51'' N... Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action establishes Class E airspace..., Wasatch, UT, to facilitate vectoring of Instrument Flight Rules (IFR) aircraft under control of Salt Lake...

  18. Direct antigen presentation and gap junction mediated cross-presentation during apoptosis.

    PubMed

    Pang, Baoxu; Neijssen, Joost; Qiao, Xiaohang; Janssen, Lennert; Janssen, Hans; Lippuner, Christoph; Neefjes, Jacques

    2009-07-15

    MHC class I molecules present peptides from endogenous proteins. Ags can also be presented when derived from extracellular sources in the form of apoptotic bodies. Cross-presentation of such Ags by dendritic cells is required for proper CTL responses. The fate of Ags in cells initiated for apoptosis is unclear as is the mechanism of apoptosis-derived Ag transfer into dendritic cells. Here we show that novel Ags can be generated by caspases and be presented by MHC class I molecules of apoptotic cells. Since gap junctions function until apoptotic cells remodel to form apoptotic bodies, transfer and cross-presentation of apoptotic peptides by neighboring and dendritic cells occurs. We thus define a novel phase in classical Ag presentation and cross-presentation by MHC class I molecules: presentation of Ags created by caspase activities in cells in apoptosis.

  19. Web 2.0 in Education: A Study of the Explorative Use of Blogs with a Postgraduate Class

    ERIC Educational Resources Information Center

    Churchill, Daniel

    2011-01-01

    This paper outlines a study that explored educational applications of blogs with a class of postgraduate students in a Hong Kong university over a period of one semester in 2006, and considers its outcomes. Rather than using the usual learning management system to support learning in the class, the facilitator-researcher organised a blog-based…

  20. Using Group Drawings Activities to Facilitate the Understanding of the Systemic Aspects of Projects

    ERIC Educational Resources Information Center

    Arantes do Amaral, João Alberto; Hess, Aurélio; Gonçalves, Paulo; Rodrigues, Vinícius Picanço

    2017-01-01

    In this article, we present our findings regarding promoting group drawing activities in order to facilitate the learning of systemic aspects of projects. We discuss the approach we used to engage the students and foster learning in our classes. We used group drawing activities in two project management undergraduate courses. The courses, which…

  1. Integrating cross-cultural psychology research methods into ethnic minority psychology.

    PubMed

    Leong, Frederick T L; Leung, Kwok; Cheung, Fanny M

    2010-10-01

    Multicultural psychology has 2 related but often disconnected streams, namely cross-cultural psychology and racial and ethnic minority psychology (Hall & Maramba, 2001). We propose that advances in both fields will be facilitated if there is greater cross-fertilization, especially in methodological approaches given that proponents in both fields are interested in studying and understanding the role and impact of culture on human behavior. To facilitate this cross-fertilization, we present 3 methodological approaches that would be of value in racial and ethnic minority psychology. First, we present an overview of the importance of and the approaches to evaluating and establishing measurement equivalence. Second, we discuss recent advances in the understanding of conceptual equivalence in light of indigenous approaches, cultural manipulation, and multilevel analysis. Third, we present a combined etic-emic approach to cross-cultural personality research as illustrated by the Cross-Cultural Personality Assessment Inventory developed by Fanny Cheung and her colleagues. PsycINFO Database Record (c) 2010 APA, all rights reserved.

  2. Filipino Teachers Sense of Efficacy in Inclusion Classes

    ERIC Educational Resources Information Center

    Dalanon, Junhel; Matsuka, Yoshizo

    2017-01-01

    Self-efficacy beliefs produce their effects through cognitive, motivational, affective, and elective processes. These processes usually operate in concert rather than on their own. In 2016, cross-sectional survey method to determine the teachers' sense of efficacy (TSE) in inclusion classes was done in a rural, private, basic-education school in…

  3. Academic status of deaf and hard-of-hearing students in public schools: student, home, and service facilitators and detractors.

    PubMed

    Reed, Susanne; Antia, Shirin D; Kreimeyer, Kathryn H

    2008-01-01

    We examined facilitators and detractors of academic success of 25 deaf or hard-of-hearing (DHH) students selected from a pool of 187 students attending general education classes and enrolled in a study of academic progress. Interviews with their teachers of DHH, general education teachers, principals, parents, interpreters, and students themselves were analyzed for child, family, and school facilitators and detractors of academic status. Facilitators included student self-advocacy and motivation, high family and school expectations, families' ability to help with homework, and good communication between professionals. Detractors included additional disabilities and poor family-school communication. A comparison of above- and below-average students revealed no single distinguishing facilitator or detractor. Each above-average student had many facilitators, whereas each below-average student had several significant detractors.

  4. Race, Ethnicity, Language, Social Class, and Health Communication Inequalities: A Nationally-Representative Cross-Sectional Study

    PubMed Central

    Viswanath, Kasisomayajula; Ackerson, Leland K.

    2011-01-01

    Background While mass media communications can be an important source of health information, there are substantial social disparities in health knowledge that may be related to media use. The purpose of this study is to investigate how the use of cancer-related health communications is patterned by race, ethnicity, language, and social class. Methodology/Principal Findings In a nationally-representative cross-sectional telephone survey, 5,187 U.S. adults provided information about demographic characteristics, cancer information seeking, and attention to and trust in health information from television, radio, newspaper, magazines, and the Internet. Cancer information seeking was lowest among Spanish-speaking Hispanics (odds ratio: 0.42; 95% confidence interval: 0.28–0.63) compared to non-Hispanic whites. Spanish-speaking Hispanics were more likely than non-Hispanic whites to pay attention to (odds ratio: 3.10; 95% confidence interval: 2.07–4.66) and trust (odds ratio: 2.61; 95% confidence interval: 1.53–4.47) health messages from the radio. Non-Hispanic blacks were more likely than non-Hispanic whites to pay attention to (odds ratio: 2.39; 95% confidence interval: 1.88–3.04) and trust (odds ratio: 2.16; 95% confidence interval: 1.61–2.90) health messages on television. Those who were college graduates tended to pay more attention to health information from newspapers (odds ratio: 1.98; 95% confidence interval: 1.42–2.75), magazines (odds ratio: 1.86; 95% confidence interval: 1.32–2.60), and the Internet (odds ratio: 4.74; 95% confidence interval: 2.70–8.31) and had less trust in cancer-related health information from television (odds ratio: 0.44; 95% confidence interval: 0.32–0.62) and radio (odds ratio: 0.54; 95% confidence interval: 0.34–0.86) compared to those who were not high school graduates. Conclusions/Significance Health media use is patterned by race, ethnicity, language and social class. Providing greater access to and enhancing the

  5. Class-Size Effects on Adolescents' Mental Health and Well-Being in Swedish Schools

    ERIC Educational Resources Information Center

    Jakobsson, Niklas; Persson, Mattias; Svensson, Mikael

    2013-01-01

    This paper analyzes whether class size has an effect on the prevalence of mental health problems and well-being among adolescents in Swedish schools. We use cross-sectional data collected in year 2008 covering 2755 Swedish adolescents in ninth grade from 40 schools and 159 classes. We utilize different econometric approaches to address potential…

  6. Professor as Facilitator: Shaping an Emerging, Living System of Shared Leadership in the Classroom

    ERIC Educational Resources Information Center

    Bright, David S.; Turesky, Elizabeth Fisher; Putzel, Roger; Stang, Thomas

    2012-01-01

    From the perspective of emergence, professors can facilitate and shape a class as a complex, adaptive, and living system. A case study illustrates phases of emergence in the classroom by tracing how a professor may use this perspective to empower students to share in the leadership of the classroom. Instead of presenting lessons, the professor…

  7. An object-oriented class library for medical software development.

    PubMed

    O'Kane, K C; McColligan, E E

    1996-12-01

    The objective of this research is the development of a Medical Object Library (MOL) consisting of reusable, inheritable, portable, extendable C++ classes that facilitate rapid development of medical software at reduced cost and increased functionality. The result of this research is a library of class objects that range in function from string and hierarchical file handling entities to high level, procedural agents that perform increasingly complex, integrated tasks. A system built upon these classes is compatible with any other system similarly constructed with respect to data definitions, semantics, data organization and storage. As new objects are built, they can be added to the class library for subsequent use. The MOL is a toolkit of software objects intended to support a common file access methodology, a unified medical record structure, consistent message processing, standard graphical display facilities and uniform data collection procedures. This work emphasizes the relationship that potentially exists between the structure of a hierarchical medical record and procedural language components by means of a hierarchical class library and tree structured file access facility. In doing so, it attempts to establish interest in and demonstrate the practicality of the hierarchical medical record model in the modern context of object oriented programming.

  8. Transparent aligners: An invisible approach to correct mild skeletal class III malocclusion

    PubMed Central

    Yezdani, A. Arif

    2015-01-01

    This case report highlights the treatment of a mild skeletal class III malocclusion with an invisible thermoplastic retainer. A 15-year-old female patient presented with a mild skeletal class III malocclusion with a retrognathic maxilla, orthognathic mandible, a low mandibular plane angle with Angle's class III malocclusion with maxillary lateral incisors in anterior cross-bite with crowding of maxillary anteriors, imbricated and rotated mandibular incisors and deep bite. Accurate upper and lower impressions and a bite registration were taken with polyvinyl siloxane rubber base impression material. This was then sent to the lab for the processing of a series of ClearPath aligners. The ClearPath virtual set-up sent from the lab provided the treatment plan and interproximal reduction estimation complete with posttreatment results. This enabled the clinician to actively participate in the treatment plan and provide the necessary suggestions. The ClearPath three-dimensional aligner was found to have effectively corrected the anterior cross-bite and crowding of the maxillary anteriors. PMID:26015738

  9. Food allergens: molecular and immunological aspects, allergen databases and cross-reactivity.

    PubMed

    Lorenz, Anne-Regine; Scheurer, Stephan; Vieths, Stefan

    2015-01-01

    The currently known food allergens are assigned to a relatively small number of protein families. Food allergens grouped into protein families share common functional and structural features that can be attributed to the allergenic potency and potential cross-reactivity of certain proteins. Molecular data, in terms of structural information, biochemical characteristics and clinical relevance for each known allergen, including isoforms and variants, are mainly compiled into four open-access databases. Allergens are designated according to defined criteria by the World Health Organization and the International Union of Immunological Societies Allergen Nomenclature Sub-committee. Food allergies are caused by primary sensitisation to the disease-eliciting food allergens (class I food allergen), or they can be elicited as a consequence of a primary sensitisation to inhalant allergens and subsequent IgE cross-reaction to homologous proteins in food (class II food allergens). Class I and class II allergens display different clinical significance in children and adults and are characterised by different molecular features. In line with this, high stability when exposed to gastrointestinal digestion and heat treatment is attributed to many class I food allergens that frequently induce severe reactions. The stability of a food allergen is determined by its molecular characteristics and can be influenced by structural (chemical) modifications due to thermal processing. Moreover, the immunogenicity and allergenicity of food allergens further depends on specific T cell and B cell epitopes. Although the T cell epitope pattern can be highly diverse for individual patients, several immuno-prominent T cell epitopes have been identified. Such conserved T cell epitopes and IgE cross-reactive B cell epitopes contribute to cross-reactivity between food allergens of the same family and to clinical cross-reactivity, similar to the birch pollen-food syndrome. © 2015 S. Karger AG, Basel.

  10. Modes of Paramyxovirus Fusion: a Henipavirus perspective

    PubMed Central

    Lee, Benhur; Akyol-Ataman, Zeynep

    2011-01-01

    Henipavirus is a new genus of paramyxovirus that uses protein-based receptors (EphrinB2 and EphrinB3) for virus entry. Paramyxovirus entry requires the coordinated action of the fusion (F) and attachment viral envelope glycoproteins. Receptor binding to the attachment protein triggers F to undergo a conformational cascade that results in membrane fusion. The accumulation of structural and functional studies on many paramyxoviral fusion and attachment proteins, including recent structures of Nipah and Hendra virus G bound and unbound to cognate ephrinB receptors, indicate that henipavirus entry and fusion differs mechanistically from paramyxoviruses that use glycan-based receptors. PMID:21511478

  11. Coexistence of Eph receptor B1 and ephrin B2 in port-wine stain endothelial progenitor cells contributes to clinicopathological vasculature dilatation.

    PubMed

    Tan, W; Wang, J; Zhou, F; Gao, L; Yin, R; Liu, H; Sukanthanag, A; Wang, G; Mihm, M C; Chen, D-B; Nelson, J S

    2017-12-01

    Port-wine stain (PWS) is a vascular malformation characterized by progressive dilatation of postcapillary venules, but the molecular pathogenesis remains obscure. To illustrate that PWS endothelial cells (ECs) present a unique molecular phenotype that leads to pathoanatomical PWS vasculatures. Immunohistochemistry and transmission electron microscopy were used to characterize the ultrastructure and molecular phenotypes of PWS blood vessels. Primary culture of human dermal microvascular endothelial cells and in vitro tube formation assay were used for confirmative functional studies. Multiple clinicopathological features of PWS blood vessels during the development and progression of the disease were shown. There were no normal arterioles and venules observed phenotypically and morphologically in PWS skin; arterioles and venules both showed differentiation impairments, resulting in a reduction of arteriole-like vasculatures and defects in capillary loop formation in PWS lesions. PWS ECs showed stemness properties with expression of endothelial progenitor cell markers CD133 and CD166 in non-nodular lesions. They also expressed dual venous/arterial identities, Eph receptor B1 (EphB1) and ephrin B2 (EfnB2). Co-expression of EphB1 and EfnB2 in normal human dermal microvascular ECs led to the formation of PWS-like vasculatures in vitro, for example larger-diameter and thick-walled capillaries. PWS ECs are differentiation-impaired, late-stage endothelial progenitor cells with a specific phenotype of CD133 + /CD166 + /EphB1 + /EfnB2 + , which form immature venule-like pathoanatomical vasculatures. The disruption of normal EC-EC interactions by coexistence of EphB1 and EfnB2 contributes to progressive dilatation of PWS vasculatures. © 2017 British Association of Dermatologists.

  12. Transmission of Turnip yellows virus by Myzus persicae Is Reduced by Feeding Aphids on Double-Stranded RNA Targeting the Ephrin Receptor Protein

    PubMed Central

    Mulot, Michaël; Monsion, Baptiste; Boissinot, Sylvaine; Rastegar, Maryam; Meyer, Sophie; Bochet, Nicole; Brault, Véronique

    2018-01-01

    Aphid-transmitted plant viruses are a threat for major crops causing massive economic loss worldwide. Members in the Luteoviridae family are transmitted by aphids in a circulative and non-replicative mode. Virions are acquired by aphids when ingesting sap from infected plants and are transported through the gut and the accessory salivary gland (ASG) cells by a transcytosis mechanism relying on virus-specific receptors largely unknown. Once released into the salivary canal, virions are inoculated to plants, together with saliva, during a subsequent feeding. In this paper, we bring in vivo evidence that the membrane-bound Ephrin receptor (Eph) is a novel aphid protein involved in the transmission of the Turnip yellows virus (TuYV, Polerovirus genus, Luteoviridae family) by Myzus persicae. The minor capsid protein of TuYV, essential for aphid transmission, was able to bind the external domain of Eph in yeast. Feeding M. persicae on in planta- or in vitro-synthesized dsRNA targeting Eph-mRNA (dsRNAEph) did not affect aphid feeding behavior but reduced accumulation of TuYV genomes in the aphid's body. Consequently, TuYV transmission efficiency by the dsRNAEph-treated aphids was reproducibly inhibited and we brought evidence that Eph is likely involved in intestinal uptake of the virion. The inhibition of virus uptake after dsRNAEph acquisition was also observed for two other poleroviruses transmitted by M. persicae, suggesting a broader role of Eph in polerovirus transmission. Finally, dsRNAEph acquisition by aphids did not affect nymph production. These results pave the way toward an ecologically safe alternative of insecticide treatments that are used to lower aphid populations and reduce polerovirus damages. PMID:29593696

  13. Transmission of Turnip yellows virus by Myzus persicae Is Reduced by Feeding Aphids on Double-Stranded RNA Targeting the Ephrin Receptor Protein.

    PubMed

    Mulot, Michaël; Monsion, Baptiste; Boissinot, Sylvaine; Rastegar, Maryam; Meyer, Sophie; Bochet, Nicole; Brault, Véronique

    2018-01-01

    Aphid-transmitted plant viruses are a threat for major crops causing massive economic loss worldwide. Members in the Luteoviridae family are transmitted by aphids in a circulative and non-replicative mode. Virions are acquired by aphids when ingesting sap from infected plants and are transported through the gut and the accessory salivary gland (ASG) cells by a transcytosis mechanism relying on virus-specific receptors largely unknown. Once released into the salivary canal, virions are inoculated to plants, together with saliva, during a subsequent feeding. In this paper, we bring in vivo evidence that the membrane-bound Ephrin receptor (Eph) is a novel aphid protein involved in the transmission of the Turnip yellows virus (TuYV, Polerovirus genus, Luteoviridae family) by Myzus persicae . The minor capsid protein of TuYV, essential for aphid transmission, was able to bind the external domain of Eph in yeast. Feeding M. persicae on in planta - or in vitro -synthesized dsRNA targeting Eph -mRNA (dsRNA Eph ) did not affect aphid feeding behavior but reduced accumulation of TuYV genomes in the aphid's body. Consequently, TuYV transmission efficiency by the dsRNA Eph -treated aphids was reproducibly inhibited and we brought evidence that Eph is likely involved in intestinal uptake of the virion. The inhibition of virus uptake after dsRNA Eph acquisition was also observed for two other poleroviruses transmitted by M. persicae , suggesting a broader role of Eph in polerovirus transmission. Finally, dsRNA Eph acquisition by aphids did not affect nymph production. These results pave the way toward an ecologically safe alternative of insecticide treatments that are used to lower aphid populations and reduce polerovirus damages.

  14. A new class of organic nitrates: investigations on bioactivation, tolerance and cross-tolerance phenomena.

    PubMed

    Schuhmacher, S; Schulz, E; Oelze, M; König, A; Roegler, C; Lange, K; Sydow, L; Kawamoto, T; Wenzel, P; Münzel, T; Lehmann, J; Daiber, A

    2009-09-01

    The chronic use of organic nitrates is limited by serious side effects including oxidative stress, nitrate tolerance and/or endothelial dysfunction. The side effects and potency of nitroglycerine depend on mitochondrial aldehyde dehydrogenase (ALDH-2). We sought to determine whether this concept can be extended to a new class of organic nitrates with amino moieties (aminoalkyl nitrates). Vasodilator potency of the organic nitrates, in vitro tolerance and in vivo tolerance (after continuous infusion for 3 days) were assessed in wild-type and ALDH-2 knockout mice by isometric tension studies. Mitochondrial oxidative stress was analysed by L-012-dependent chemiluminescence and protein tyrosine nitration. Aminoethyl nitrate (AEN) showed an almost similar potency to glyceryl trinitrate (GTN), even though it is only a mononitrate. AEN-dependent vasodilatation was mediated by cGMP and nitric oxide. In contrast to triethanolamine trinitrate (TEAN) and GTN, AEN bioactivation did not depend on ALDH-2 and caused no in vitro tolerance. In vivo treatment with TEAN and GTN, but not with AEN, induced cross-tolerance to acetylcholine (ACh)-dependent and GTN-dependent relaxation. Although all nitrates tested induced tolerance to themselves, only TEAN and GTN significantly increased mitochondrial oxidative stress in vitro and in vivo. The present results demonstrate that not all high potency nitrates are bioactivated by ALDH-2 and that high potency of a given nitrate is not necessarily associated with induction of oxidative stress or nitrate tolerance. Obviously, there are distinct pathways for bioactivation of organic nitrates, which for AEN may involve xanthine oxidoreductase rather than P450 enzymes.

  15. 78 FR 78299 - Proposed Establishment of Class E Airspace; Truth or Consequences, NM

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-26

    ...-0995; Airspace Docket No. 13-ASW-30] Proposed Establishment of Class E Airspace; Truth or Consequences... Truth or Consequences VHF Omni-Directional Radio Range Tactical Air Navigation Aid (VORTAC), Truth or Consequences, NM, to facilitate vectoring of Instrument Flight Rules (IFR) aircraft under control of...

  16. Social class and policy preferences: implications for economic inequality and interclass relations.

    PubMed

    Bullock, Heather E

    2017-12-01

    Record-setting levels of income and wealth inequality are deepening social class divisions. The adoption of strong progressive redistributive policies is crucial to reducing class inequities, yet many barriers to doing so exist. This review examines class-based policy preferences, focusing on the effects of economic self-interest, system justification, and classist, racist, and sexist stereotypes on policy support. The impact of broader economic conditions is also considered. Collectively, this body of research makes clear that building stronger cross-class support for redistributive policies and programs will prove difficult without addressing both class-based power differences and beliefs that justify inequality. Reducing stereotypes and developing a shared sense of societal responsibility that cuts across class lines can help advance these goals. Social psychological research is vital to informing these efforts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. The Use of a Structured Literacy Program To Facilitate the Inclusion of Marginal and Special Education Students into Regular Classes.

    ERIC Educational Resources Information Center

    Center, Yola; Freeman, Louella

    This research review examined the use of a whole class early literacy program in classes which included disadvantaged and at-risk children in Australia. The program, Schoolwide Early Language and Literacy (SWELL), is based on an interactive compensatory theory of literacy acquisition adapted from Success for All, a U.S. early literacy program. The…

  18. Land before coal: class and regional development in southeast Kentucky

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pudup, M.B.

    1987-01-01

    At the turn of the century southeast Kentucky's economy was transformed from household subsistence farming and manufacturing to industrial coal production. During prior decades the economy had lapsed into subsistence, failing to generate demands for local industry, and blocking export-oriental development. Three county case studies reveal each possessed a resident middle class whose social bases were large property ownership, control over local commerce, and dominance of county politics. The emergence and constitution of the local middle class is explained in terms of longevity, kinship, and the political economic localisms endemic to the southern United States. Although it did not becomemore » a regional capitalist vanguard, the local middle class nonetheless became essential in the local edifice of capitalism by investing in county seat commercial and service industries and by continuing its control of local politics. The middle class also facilitated the capitalization of mountain resources. Case studies illuminate this role, distinguish among categories of resource investors, and describe geographical outcomes of capital investment.« less

  19. 78 FR 34554 - Establishment of Class E Airspace; Blue Mesa, CO

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-10

    ...This action establishes Class E airspace at Blue Mesa VHF Omni-Directional Radio Range/Distance Measuring Equipment (VOR/DME), Blue Mesa, CO, to facilitate vectoring of Instrument Flight Rules (IFR) aircraft under control of Denver and Albuquerque Air Route Traffic Control Centers (ARTCCs). This improves the safety and management of IFR operations within the National Airspace System.

  20. 22 CFR 501.4 - Junior Level Career Candidate Program (Class 6, 5, or 4).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Junior Level Career Candidate Program (Class 6, 5, or 4). 501.4 Section 501.4 Foreign Relations BROADCASTING BOARD OF GOVERNORS APPOINTMENT OF FOREIGN SERVICE OFFICERS § 501.4 Junior Level Career Candidate Program (Class 6, 5, or 4). Cross-reference...

  1. Cross-Matching of Very Large Catalogs

    NASA Astrophysics Data System (ADS)

    Martynov, M. V.; Bodryagin, D. V.

    Modern astronomical catalogs and sky surveys, that contain billions of objects, belong to the "big data" data class. Existing available services have limited functionality and do not include all required and available catalogs. The software package ACrId (Astronomical Cross Identification) for cross-matching large astronomical catalogs, which uses an sphere pixelation algorithm HEALPix, ReiserFS file system and JSON-type text files for storage, has been developed at the Research Institution "Mykolaiv Astronomical Observatory".

  2. How Do World-Class Nordic Combined Athletes Differ From Specialized Cross-Country Skiers and Ski Jumpers in Sport-Specific Capacity and Training Characteristics?

    PubMed

    Sandbakk, Øyvind; Rasdal, Vegard; Bråten, Steinar; Moen, Frode; Ettema, Gertjan

    2016-10-01

    To compare sport-specific laboratory capacities and the annual training of world-class Nordic combined (NC) athletes with specialized ski jumpers (SJ) and cross-country (XC) skiers. Five world-class athletes from each sports discipline were compared. Ski jump imitations were performed on a 3-dimensional force plate in NC athletes and SJ, whereas XC skiing characteristics were obtained from submaximal and maximal roller ski skating on a treadmill in NC athletes and XC skiers. In addition, anthropometrics and annual training characteristics were determined. NC athletes demonstrated 9% higher body mass and showed 17% lower vertical speed in the ski jump imitation than SJ (all P < .05). NC athletes had 12% lower body mass and showed 10% lower peak treadmill speed and 12% lower body-mass-normalized peak oxygen uptake than XC skiers (all P < .05). NC athletes performed half the number of ski-jumping-specific sessions and outdoor ski jumps compared with SJ. NC athletes performed 31% less endurance training, mainly caused by lower amounts of low- and moderate-intensity training in the classical technique, whereas high-intensity strength and speed training and endurance training in the skating technique did not differ substantially from XC skiers. To simultaneously optimize endurance, explosive, and technical capacities in 2 different disciplines, world-class NC athletes train approximately two-thirds of the XC skier's endurance training volume and perform one-half of the ski-jump-specific training compared with SJ. Still, the various laboratory capacities differed only 10-17% compared with SJ and XC skiers.

  3. Comparing Facilitator Priorities of Suicide Survivor Support Groups: A Cross-Cultural Comparison Between Japanese and American Groups.

    PubMed

    Feigelman, William; Feigelman, Beverly; Kawashima, Daisuke; Shiraga, Keisuke; Kawano, Kenji

    2017-08-01

    A total of 56 Japanese and 59 American survivor of suicide support group facilitators were asked to rank the mutual aid objectives of their groups following Shulman's scheme in terms of their frequency and importance. Both American and Japanese facilitators showed an emphasis on personal adaptation goals (such as helping bereaved feel less isolated in their grief or encouraging bereaved to share their coping with loss experiences) over collective goals (such as raising monies for more research on mental illness or trying to combat societal suicide stigma in their local communities). Differences were also noted with American facilitators evaluating helping with problem solving, sharing different ways of coping, viewing personal issues as societal problems, and advocating for promoting social change as significantly higher than the Japanese did. We believe some of these contrasts reflect differences in American and Japanese cultural values.

  4. Stimulation of Nipah Fusion: Small Intradomain Changes Trigger Extensive Interdomain Rearrangements.

    PubMed

    Dutta, Priyanka; Siddiqui, Ahnaf; Botlani, Mohsen; Varma, Sameer

    2016-10-18

    Nipah is an emerging paramyxovirus that is of serious concern to human health. It invades host cells using two of its membrane proteins-G and F. G binds to host ephrins and this stimulates G to activate F. Upon activation, F mediates virus-host membrane fusion. Here we focus on mechanisms that underlie the stimulation of G by ephrins. Experiments show that G interacts with ephrin and F through separate sites located on two different domains, the receptor binding domain (RBD) and the F activation domain (FAD). No models explain this allosteric coupling. In fact, the analogous mechanisms in other paramyxoviruses also remain undetermined. The structural organization of G is such that allosteric coupling must involve at least one of the two interfaces-the RBD-FAD interface and/or the RBD-RBD interface. Here we examine using molecular dynamics the effect of ephrin binding on the RBD-RBD interface. We find that despite inducing small changes in individual RBDs, ephrin reorients the RBD-RBD interface extensively, and in a manner that will enhance solvent exposure of the FAD. While this finding supports a proposed model of G stimulation, we also find from additional simulations that ephrin induces a similar RBD-RBD reorientation in a stimulation-deficient G mutant, V 209 VG → AAA. Together, our simulations suggest that while inter-RBD reorientation may be important, it is not, by itself, a sufficient condition for G stimulation. Additionally, we find that the mutation affects the conformational ensemble of RBD globally, including the RBD-FAD interface, suggesting the latter's role in G stimulation. Because ephrin induces small changes in individual RBDs, a proper analysis of conformational ensembles required that they are compared directly-we employ a method we developed recently, which we now release at SimTK, and show that it also performs excellently for non-Gaussian distributions. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  5. Spatial separation of the processing and MHC class I loading compartments for cross-presentation of the tumor-associated antigen HER2/neu by human dendritic cells

    PubMed Central

    Baleeiro, Renato B; Rietscher, René; Diedrich, Andrea; Czaplewska, Justyna A; Lehr, Claus-Michael; Scherließ, Regina; Hanefeld, Andrea; Gottschaldt, Michael; Walden, Peter

    2015-01-01

    Cross-presentation is the process by which professional antigen presenting cells (APCs) (B cells, dendritic cells (DCs) and macrophages) present endocytosed antigens (Ags) via MHC-I to CD8+ T cells. This process is crucial for induction of adaptive immune responses against tumors and infected cells. The pathways and cellular compartments involved in cross-presentation are unresolved and controversial. Among the cells with cross-presenting capacity, DCs are the most efficient, which was proposed to depend on prevention of endosomal acidification to block degradation of the epitopes. Contrary to this view, we show in this report that some cargoes induce strong endosomal acidification following uptake by human DCs, while others not. Moreover, processing of the tumor-associated antigen HER2/neu delivered in nanoparticles (NP) for cross-presentation of the epitope HER2/neu369–377 on HLA-A2 depended on endosomal acidification and cathepsin activity as well as proteasomes, and newly synthesized HLA class I. However, the HLA-A*0201/HER2/neu369–377 complexes were not found in the endoplasmic reticulum (ER) nor in endolysosomes but in hitherto not described vesicles. The data thus indicate spatial separation of antigen processing and loading of MHC-I for cross-presentation: antigen processing occurs in the uptake compartment and the cytosol whereas MHC-I loading with peptide takes place in a distinct subcellular compartment. The findings further elucidate the cellular pathways involved in the cross-presentation of a full-length, clinically relevant tumor-associated antigen by human DCs, and the impact of the vaccine formulation on antigen processing and CD8+ T cell induction. PMID:26985398

  6. Translation Ambiguity but Not Word Class Predicts Translation Performance

    ERIC Educational Resources Information Center

    Prior, Anat; Kroll, Judith F.; Macwhinney, Brian

    2013-01-01

    We investigated the influence of word class and translation ambiguity on cross-linguistic representation and processing. Bilingual speakers of English and Spanish performed translation production and translation recognition tasks on nouns and verbs in both languages. Words either had a single translation or more than one translation. Translation…

  7. Computer classes and games in virtual reality environment to reduce loneliness among students of an elderly reference center: Study protocol for a randomised cross-over design.

    PubMed

    Antunes, Thaiany Pedrozo Campos; Oliveira, Acary Souza Bulle de; Crocetta, Tania Brusque; Antão, Jennifer Yohanna Ferreira de Lima; Barbosa, Renata Thais de Almeida; Guarnieri, Regiani; Massetti, Thais; Monteiro, Carlos Bandeira de Mello; Abreu, Luiz Carlos de

    2017-03-01

    Physical and mental changes associated with aging commonly lead to a decrease in communication capacity, reducing social interactions and increasing loneliness. Computer classes for older adults make significant contributions to social and cognitive aspects of aging. Games in a virtual reality (VR) environment stimulate the practice of communicative and cognitive skills and might also bring benefits to older adults. Furthermore, it might help to initiate their contact to the modern technology. The purpose of this study protocol is to evaluate the effects of practicing VR games during computer classes on the level of loneliness of students of an elderly reference center. This study will be a prospective longitudinal study with a randomised cross-over design, with subjects aged 50 years and older, of both genders, spontaneously enrolled in computer classes for beginners. Data collection will be done in 3 moments: moment 0 (T0) - at baseline; moment 1 (T1) - after 8 typical computer classes; and moment 2 (T2) - after 8 computer classes which include 15 minutes for practicing games in VR environment. A characterization questionnaire, the short version of the Short Social and Emotional Loneliness Scale for Adults (SELSA-S) and 3 games with VR (Random, MoviLetrando, and Reaction Time) will be used. For the intervention phase 4 other games will be used: Coincident Timing, Motor Skill Analyser, Labyrinth, and Fitts. The statistical analysis will compare the evolution in loneliness perception, performance, and reaction time during the practice of the games between the 3 moments of data collection. Performance and reaction time during the practice of the games will also be correlated to the loneliness perception. The protocol is approved by the host institution's ethics committee under the number 52305215.3.0000.0082. Results will be disseminated via peer-reviewed journal articles and conferences. This clinical trial is registered at ClinicalTrials.gov identifier: NCT

  8. Nicotinamide N-methyltransferase expression in SH-SY5Y neuroblastoma and N27 mesencephalic neurones induces changes in cell morphology via ephrin-B2 and Akt signalling

    PubMed Central

    Thomas, M G; Saldanha, M; Mistry, R J; Dexter, D T; Ramsden, D B; Parsons, R B

    2013-01-01

    Nicotinamide N-methyltransferase (NNMT, E.C. 2.1.1.1) N-methylates nicotinamide to produce 1-methylnicotinamide (MeN). We have previously shown that NNMT expression protected against neurotoxin-mediated cell death by increasing Complex I (CxI) activity, resulting in increased ATP synthesis. This was mediated via protection of the NDUFS3 subunit of CxI from degradation by increased MeN production. In the present study, we have investigated the effects of NNMT expression on neurone morphology and differentiation. Expression of NNMT in SH-SY5Y human neuroblastoma and N27 rat mesencephalic dopaminergic neurones increased neurite branching, synaptophysin expression and dopamine accumulation and release. siRNA gene silencing of ephrin B2 (EFNB2), and inhibition of Akt phosphorylation using LY294002, demonstrated that their sequential activation was responsible for the increases observed. Incubation of SH-SY5Y with increasing concentrations of MeN also increased neurite branching, suggesting that the effects of NNMT may be mediated by MeN. NNMT had no significant effect on the expression of phenotypic and post-mitotic markers, suggesting that NNMT is not involved in determining phenotypic fate or differentiation status. These results demonstrate that NNMT expression regulates neurone morphology in vitro via the sequential activation of the EFNB2 and Akt cellular signalling pathways. PMID:23764850

  9. Nicotinamide N-methyltransferase expression in SH-SY5Y neuroblastoma and N27 mesencephalic neurones induces changes in cell morphology via ephrin-B2 and Akt signalling.

    PubMed

    Thomas, M G; Saldanha, M; Mistry, R J; Dexter, D T; Ramsden, D B; Parsons, R B

    2013-06-13

    Nicotinamide N-methyltransferase (NNMT, E.C. 2.1.1.1) N-methylates nicotinamide to produce 1-methylnicotinamide (MeN). We have previously shown that NNMT expression protected against neurotoxin-mediated cell death by increasing Complex I (CxI) activity, resulting in increased ATP synthesis. This was mediated via protection of the NDUFS3 subunit of CxI from degradation by increased MeN production. In the present study, we have investigated the effects of NNMT expression on neurone morphology and differentiation. Expression of NNMT in SH-SY5Y human neuroblastoma and N27 rat mesencephalic dopaminergic neurones increased neurite branching, synaptophysin expression and dopamine accumulation and release. siRNA gene silencing of ephrin B2 (EFNB2), and inhibition of Akt phosphorylation using LY294002, demonstrated that their sequential activation was responsible for the increases observed. Incubation of SH-SY5Y with increasing concentrations of MeN also increased neurite branching, suggesting that the effects of NNMT may be mediated by MeN. NNMT had no significant effect on the expression of phenotypic and post-mitotic markers, suggesting that NNMT is not involved in determining phenotypic fate or differentiation status. These results demonstrate that NNMT expression regulates neurone morphology in vitro via the sequential activation of the EFNB2 and Akt cellular signalling pathways.

  10. Cooperative Games as an Intervention to Promote Cross-racial Acceptance.

    ERIC Educational Resources Information Center

    Rogers, Marian; And Others

    1981-01-01

    More cross-racial interaction was found among boys because they participate in more team sports. Cooperative games have a strong potential for facilitating social acceptance among desegregated elementary school girls. Observations of cross-racial prosocial and antagonistic interactions revealed the practical value of games for increasing…

  11. Gender differences in the association of individual social class and neighbourhood unemployment rate with prevalent type 2 diabetes mellitus: a cross-sectional study from the DIAB-CORE consortium.

    PubMed

    Müller, Grit; Hartwig, Saskia; Greiser, Karin Halina; Moebus, Susanne; Pundt, Noreen; Schipf, Sabine; Völzke, Henry; Maier, Werner; Meisinger, Christa; Tamayo, Teresa; Rathmann, Wolfgang; Berger, Klaus

    2013-06-21

    To analyse gender differences in the relationship of individual social class, employment status and neighbourhood unemployment rate with present type 2 diabetes mellitus (T2DM). Five cross-sectional studies. Studies were conducted in five regions of Germany from 1997 to 2006. The sample consisted of 8871 individuals residing in 226 neighbourhoods from five urban regions. Prevalent T2DM. We found significant multiplicative interactions between gender and the individual variables--social class and employment status. Social class was statistically significantly associated with T2DM in men and women, whereby this association was stronger in women (lower vs higher social class: OR 2.68 (95% CIs 1.66 to 4.34)) than men (lower vs higher social class: OR 1.78 (95% CI 1.22 to 2.58)). Significant associations of employment status and T2DM were only found in women (unemployed vs employed: OR 1.73 (95% CI 1.02 to 2.92); retired vs employed: OR 1.77 (95% CI 1.10 to 2.84); others vs employed: OR 1.64 (95% CI 1.01 to 2.67)). Neighbourhood unemployment rate was associated with T2DM in men (high vs low tertile: OR 1.52 (95% CI 1.18 to 1.96)). Between-study and between-neighbourhood variations in T2DM prevalence were more pronounced in women. The considered covariates helped to explain statistically the variation in T2DM prevalence among men, but not among women. Social class was inversely associated with T2DM in both men and women, whereby the association was more pronounced in women. Employment status only affected T2DM in women. Neighbourhood unemployment rate is an important predictor of T2DM in men, but not in women.

  12. Comparing Two Forms of Concept Map Critique Activities to Facilitate Knowledge Integration Processes in Evolution Education

    ERIC Educational Resources Information Center

    Schwendimann, Beat A.; Linn, Marcia C.

    2016-01-01

    Concept map activities often lack a subsequent revision step that facilitates knowledge integration. This study compares two collaborative critique activities using a Knowledge Integration Map (KIM), a form of concept map. Four classes of high school biology students (n?=?81) using an online inquiry-based learning unit on evolution were assigned…

  13. Making friends at antenatal classes: a qualitative exploration of friendship across the transition to motherhood.

    PubMed

    Nolan, Mary L; Mason, Victoria; Snow, Sarah; Messenger, Wendy; Catling, Jonathon; Upton, Penney

    2012-01-01

    This study explored how friendships made at antenatal classes preserve new mothers' well-being, postnatally. Eight women from the United Kingdom who had attended antenatal classes in the third trimester were interviewed following the birth of their first baby. Transcripts were analyzed using a constant comparative method. Findings suggest that friendships made at antenatal classes are not only unique but also support women's mental health and enhance self-efficacy because the women give and gain reassurance that their babies are developing normally. Such friendships may reduce demands on overstretched social and health-care services. Childbirth educators, midwives, and nurses can be encouraged to capitalize on the opportunity provided by antenatal classes to facilitate the formation of friendships that can help mothers to find "a new equilibrium."

  14. Barriers and facilitators to exchanging health information: a systematic review.

    PubMed

    Eden, Karen B; Totten, Annette M; Kassakian, Steven Z; Gorman, Paul N; McDonagh, Marian S; Devine, Beth; Pappas, Miranda; Daeges, Monica; Woods, Susan; Hersh, William R

    2016-04-01

    We conducted a systematic review of studies assessing facilitators and barriers to use of health information exchange (HIE). We searched MEDLINE, PsycINFO, CINAHL, and the Cochrane Library databases between January 1990 and February 2015 using terms related to HIE. English-language studies that identified barriers and facilitators of actual HIE were included. Data on study design, risk of bias, setting, geographic location, characteristics of the HIE, perceived barriers and facilitators to use were extracted and confirmed. Ten cross-sectional, seven multiple-site case studies, and two before-after studies that included data from several sources (surveys, interviews, focus groups, and observations of users) evaluated perceived barriers and facilitators to HIE use. The most commonly cited barriers to HIE use were incomplete information, inefficient workflow, and reports that the exchanged information that did not meet the needs of users. The review identified several facilitators to use. Incomplete patient information was consistently mentioned in the studies conducted in the US but not mentioned in the few studies conducted outside of the US that take a collective approach toward healthcare. Individual patients and practices in the US may exercise the right to participate (or not) in HIE which effects the completeness of patient information available to be exchanged. Workflow structure and user roles are key but understudied. We identified several facilitators in the studies that showed promise in promoting electronic health data exchange: obtaining more complete patient information; thoughtful workflow that folds in HIE; and inclusion of users early in implementation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Practice Facilitators' and Leaders' Perspectives on a Facilitated Quality Improvement Program.

    PubMed

    McHugh, Megan; Brown, Tiffany; Liss, David T; Walunas, Theresa L; Persell, Stephen D

    2018-04-01

    Practice facilitation is a promising approach to helping practices implement quality improvements. Our purpose was to describe practice facilitators' and practice leaders' perspectives on implementation of a practice facilitator-supported quality improvement program and describe where their perspectives aligned and diverged. We conducted interviews with practice leaders and practice facilitators who participated in a program that included 35 improvement strategies aimed at the ABCS of heart health (aspirin use in high-risk individuals, blood pressure control, cholesterol management, and smoking cessation). Rapid qualitative analysis was used to collect, organize, and analyze the data. We interviewed 17 of the 33 eligible practice leaders, and the 10 practice facilitators assigned to those practices. Practice leaders and practice facilitators both reported value in the program's ability to bring needed, high-quality resources to practices. Practice leaders appreciated being able to set the schedule for facilitation and select among the 35 interventions. According to practice facilitators, however, relying on practice leaders to set the pace of the intervention resulted in a lower level of program intensity than intended. Practice leaders preferred targeted assistance, particularly electronic health record documentation guidance and linkages to state smoking cessation programs. Practice facilitators reported that the easiest interventions were those that did not alter care practices. The dual perspectives of practice leaders and practice facilitators provide a more holistic picture of enablers and barriers to program implementation. There may be greater opportunities to assist small practices through simple, targeted practice facilitator-supported efforts rather than larger, comprehensive quality improvement projects. © 2018 Annals of Family Medicine, Inc.

  16. Cross-sector surveys assessing perceptions of key stakeholders towards barriers, concerns and facilitators to the appropriate use of adaptive designs in confirmatory trials.

    PubMed

    Dimairo, Munyaradzi; Julious, Steven A; Todd, Susan; Nicholl, Jonathan P; Boote, Jonathan

    2015-12-23

    Appropriately conducted adaptive designs (ADs) offer many potential advantages over conventional trials. They make better use of accruing data, potentially saving time, trial participants, and limited resources compared to conventional, fixed sample size designs. However, one can argue that ADs are not implemented as often as they should be, particularly in publicly funded confirmatory trials. This study explored barriers, concerns, and potential facilitators to the appropriate use of ADs in confirmatory trials among key stakeholders. We conducted three cross-sectional, online parallel surveys between November 2014 and January 2015. The surveys were based upon findings drawn from in-depth interviews of key research stakeholders, predominantly in the UK, and targeted Clinical Trials Units (CTUs), public funders, and private sector organisations. Response rates were as follows: 30(55 %) UK CTUs, 17(68 %) private sector, and 86(41 %) public funders. A Rating Scale Model was used to rank barriers and concerns in order of perceived importance for prioritisation. Top-ranked barriers included the lack of bridge funding accessible to UK CTUs to support the design of ADs, limited practical implementation knowledge, preference for traditional mainstream designs, difficulties in marketing ADs to key stakeholders, time constraints to support ADs relative to competing priorities, lack of applied training, and insufficient access to case studies of undertaken ADs to facilitate practical learning and successful implementation. Associated practical complexities and inadequate data management infrastructure to support ADs were reported as more pronounced in the private sector. For funders of public research, the inadequate description of the rationale, scope, and decision-making criteria to guide the planned AD in grant proposals by researchers were all viewed as major obstacles. There are still persistent and important perceptions of individual and organisational obstacles

  17. Crossing the Class and Color Lines: From Public Housing to White Suburbia.

    ERIC Educational Resources Information Center

    Rubinowitz, Leonard S.; Rosenbaum, James E.

    In 1976, thousands of low-income African Americans, mostly women and children, began to move out of the public housing developments of Chicago, Illinois, to the mostly white middle class suburbs. These families were part of the Gautreaux program, one of the largest court-ordered desegregation efforts in the United States. This book tells the story…

  18. Crossed Module Bundle Gerbes; Classification, String Group and Differential Geometry

    NASA Astrophysics Data System (ADS)

    Jurčo, Branislav

    We discuss nonabelian bundle gerbes and their differential geometry using simplicial methods. Associated to any crossed module there is a simplicial group NC, the nerve of the 1-category defined by the crossed module and its geometric realization |NC|. Equivalence classes of principal bundles with structure group |NC| are shown to be one-to-one with stable equivalence classes of what we call crossed module gerbes bundle gerbes. We can also associate to a crossed module a 2-category C'. Then there are two equivalent ways how to view classifying spaces of NC-bundles and hence of |NC|-bundles and crossed module bundle gerbes. We can either apply the W-construction to NC or take the nerve of the 2-category C'. We discuss the string group and string structures from this point of view. Also a simplicial principal bundle can be equipped with a simplicial connection and a B-field. It is shown how in the case of a simplicial principal NC-bundle these simplicial objects give the bundle gerbe connection and the bundle gerbe B-field.

  19. A new class of organic nitrates: investigations on bioactivation, tolerance and cross-tolerance phenomena

    PubMed Central

    Schuhmacher, S; Schulz, E; Oelze, M; König, A; Roegler, C; Lange, K; Sydow, L; Kawamoto, T; Wenzel, P; Münzel, T; Lehmann, J; Daiber, A

    2009-01-01

    Background and purpose: The chronic use of organic nitrates is limited by serious side effects including oxidative stress, nitrate tolerance and/or endothelial dysfunction. The side effects and potency of nitroglycerine depend on mitochondrial aldehyde dehydrogenase (ALDH-2). We sought to determine whether this concept can be extended to a new class of organic nitrates with amino moieties (aminoalkyl nitrates). Experimental approach: Vasodilator potency of the organic nitrates, in vitro tolerance and in vivo tolerance (after continuous infusion for 3 days) were assessed in wild-type and ALDH-2 knockout mice by isometric tension studies. Mitochondrial oxidative stress was analysed by L-012-dependent chemiluminescence and protein tyrosine nitration. Key results: Aminoethyl nitrate (AEN) showed an almost similar potency to glyceryl trinitrate (GTN), even though it is only a mononitrate. AEN-dependent vasodilatation was mediated by cGMP and nitric oxide. In contrast to triethanolamine trinitrate (TEAN) and GTN, AEN bioactivation did not depend on ALDH-2 and caused no in vitro tolerance. In vivo treatment with TEAN and GTN, but not with AEN, induced cross-tolerance to acetylcholine (ACh)-dependent and GTN-dependent relaxation. Although all nitrates tested induced tolerance to themselves, only TEAN and GTN significantly increased mitochondrial oxidative stress in vitro and in vivo. Conclusions and implications: The present results demonstrate that not all high potency nitrates are bioactivated by ALDH-2 and that high potency of a given nitrate is not necessarily associated with induction of oxidative stress or nitrate tolerance. Obviously, there are distinct pathways for bioactivation of organic nitrates, which for AEN may involve xanthine oxidoreductase rather than P450 enzymes. PMID:19563531

  20. 78 FR 33091 - Limitations on the Filing and Processing of Full Power and Class A Television Station...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-03

    ... Mandate. See Middle Class Tax Relief and Job Creation Act of 2012, Public Law 112-96, Title VI, 125 Stat. 156 (2012) (``Spectrum Act''). This action will facilitate Commission analysis of repacking...

  1. School and class-level variations and patterns of physical activity: a multilevel analysis of Danish high school students.

    PubMed

    Steenholt, Carina Bjørnskov; Pisinger, Veronica Sofie Clara; Danquah, Ida Høgstedt; Tolstrup, Janne Schurmann

    2018-02-14

    There is limited knowledge of physical activity (PA) patterns among high school students. High schools plays an important role as context for the students, but it is uncertain to what extent schools influence student participation in PA during leisure time. The purpose of this study is to describe patterns of PA and assess variations between schools and classes in PA, in a large cohort of Danish high school students. Self-reported cross-sectional data came from The Danish National Youth Study, comprising a total of 70,674 students attending 119 different schools and 3213 classes. Multilevel logistic regressions were applied to evaluate the association between socio-demographic variables and patterns of PA, and to assess the impact of schools and classes on PA measures. Students whose parents have achieved a lower level of education, older students and girls of perceived ethnic minority generally participated less in several forms of PA during leisure time. Substantial variations between schools were observed in terms of participation in PA at school during leisure time and in terms of use of active transportation to and from school. The school-level accounted for 9% (intra-class correlation coefficient (ICC) = 0.09 (95% CI: 0.06-0.11)) and 8% (ICC = 0.08 (95% CI: 0.07-0.11)) of the variation for participation in PA during leisure time and active transportation. Overall, students whose parents achieved a lower level of education, older students and girls of perceived ethnic minority represent vulnerable groups in relation to participation in several forms of PA during leisure time. The ICCs indicate that schools, in particular, have the potential to influence participation in PA at school during leisure time and active transportation to and from school. Thus, high schools should encourage and facilitate activities aimed at engaging students in PA during leisure time as well as encourage active transportation.

  2. Introducing StatHand: A Cross-Platform Mobile Application to Support Students' Statistical Decision Making.

    PubMed

    Allen, Peter J; Roberts, Lynne D; Baughman, Frank D; Loxton, Natalie J; Van Rooy, Dirk; Rock, Adam J; Finlay, James

    2016-01-01

    Although essential to professional competence in psychology, quantitative research methods are a known area of weakness for many undergraduate psychology students. Students find selecting appropriate statistical tests and procedures for different types of research questions, hypotheses and data types particularly challenging, and these skills are not often practiced in class. Decision trees (a type of graphic organizer) are known to facilitate this decision making process, but extant trees have a number of limitations. Furthermore, emerging research suggests that mobile technologies offer many possibilities for facilitating learning. It is within this context that we have developed StatHand, a free cross-platform application designed to support students' statistical decision making. Developed with the support of the Australian Government Office for Learning and Teaching, StatHand guides users through a series of simple, annotated questions to help them identify a statistical test or procedure appropriate to their circumstances. It further offers the guidance necessary to run these tests and procedures, then interpret and report their results. In this Technology Report we will overview the rationale behind StatHand, before describing the feature set of the application. We will then provide guidelines for integrating StatHand into the research methods curriculum, before concluding by outlining our road map for the ongoing development and evaluation of StatHand.

  3. Comparative Analysis of Virtual Screening Approaches in the Search for Novel EphA2 Receptor Antagonists.

    PubMed

    Callegari, Donatella; Pala, Daniele; Scalvini, Laura; Tognolini, Massimiliano; Incerti, Matteo; Rivara, Silvia; Mor, Marco; Lodola, Alessio

    2015-09-17

    The EphA2 receptor and its ephrin-A1 ligand form a key cell communication system, which has been found overexpressed in many cancer types and involved in tumor growth. Recent medicinal chemistry efforts have identified bile acid derivatives as low micromolar binders of the EphA2 receptor. However, these compounds suffer from poor physicochemical properties, hampering their use in vivo. The identification of compounds able to disrupt the EphA2-ephrin-A1 complex lacking the bile acid scaffold may lead to new pharmacological tools suitable for in vivo studies. To identify the most promising virtual screening (VS) protocol aimed at finding novel EphA2 antagonists, we investigated the ability of both ligand-based and structure-based approaches to retrieve known EphA2 antagonists from libraries of decoys with similar molecular properties. While ligand-based VSs were conducted using UniPR129 and ephrin-A1 ligand as reference structures, structure-based VSs were performed with Glide, using the X-ray structure of the EphA2 receptor/ephrin-A1 complex. A comparison of enrichment factors showed that ligand-based approaches outperformed the structure-based ones, suggesting ligand-based methods using the G-H loop of ephrin-A1 ligand as template as the most promising protocols to search for novel EphA2 antagonists.

  4. CMPF: class-switching minimized pathfinding in metabolic networks.

    PubMed

    Lim, Kevin; Wong, Limsoon

    2012-01-01

    The metabolic network is an aggregation of enzyme catalyzed reactions that converts one compound to another. Paths in a metabolic network are a sequence of enzymes that describe how a chemical compound of interest can be produced in a biological system. As the number of such paths is quite large, many methods have been developed to score paths so that the k-shortest paths represent the set of paths that are biologically meaningful or efficient. However, these approaches do not consider whether the sequence of enzymes can be manufactured in the same pathway/species/localization. As a result, a predicted sequence might consist of groups of enzymes that operate in distinct pathway/species/localization and may not truly reflect the events occurring within cell. We propose a path weighting method CMPF (Class-switching Minimized Pathfinder) to search for routes in a metabolic network which minimizes pathway switching. In biological terms, a pathway is a series of chemical reactions which define a specific function (e.g. glycolysis). We conjecture that routes that cross many pathways are inefficient since different pathways define different metabolic functions. In addition, native routes are also well characterized within pathways, suggesting that reasonable paths should not involve too many pathway switches. Our method can be generalized when reactions participate in a class set (e.g., pathways, species or cellular localization) so that the paths predicted have minimal class crossings. We show that our method generates k-paths that involve the least number of class switching. In addition, we also show that native paths are recoverable and alternative paths deviates less from native paths compared to other methods. This suggests that paths ranked by our method could be a way to predict paths that are likely to occur in biological systems.

  5. Technological Innovation in Grade Crossing Protective Systems

    DOT National Transportation Integrated Search

    1971-06-01

    The constraints on innovative grade crossing protective systems are delineated and guidelines for development indicated. Inventory data has been arranged to permit an estimate of the classes of systems needed, the allowable costs, and contribution of...

  6. Chiropractors` experience and readiness to work in Indigenous Australian Communities: a preliminary cross-sectional survey to explore preparedness, perceived barriers and facilitators for chiropractors practising cross-culturally.

    PubMed

    Vindigni, Dein; Polus, Barbara I; Cleary, Sonja; Doyle, Aunty Kerrie

    2017-01-01

    Indigenous people make up approximately 3% of the total Australian population and score poorer on all health indices, including back pain. Chiropractors are well placed to alleviate back pain, yet there is no research that considers chiropractors' readiness to treat Indigenous patients. This study explores chiropractors` experience working with Indigenous Australians, describes perceived barriers and facilitators to chiropractors' participation in Indigenous Healthcare and their willingness to engage in cultural competency training. This study used a non-representative cross-sectional design and a convenience sample. Participants were recruited via email invitation to complete an online survey and encouraged to send the invitation on to colleagues. A 17-item online-survey measured demographic data, perceived barriers and facilitators related to caring for Indigenous Australians, participants` level of comfort when working in Indigenous health, and their willingness to participate in cultural competency programs to enhance their skills, knowledge and cultural capacity when engaging with Indigenous Australians. Analysis of the data included descriptive statistics as well as thematic analysis of qualitative free text. One hundred and twenty-five chiropractors participated in the survey. The majority of participants (86%, n  = 108) were employed in private practice. 62% of respondents were members of the Chiropractors' Association of Australia, 41% were Chiropractic and Osteopathic College of Australasia members. 60% of chiropractors considered that they had, or do treat Indigenous patients yet only 4% of respondents asked their patients if they identified as Indigenous. A majority of participants expressed a high level of 'comfort' or confidence in working with Indigenous people while only 17% of respondents had undertaken some form of cultural proficiency training. A majority of respondents (62.7%, n  = 74) expressed an interest in working with Indigenous

  7. Fitness-valley crossing with generalized parent-offspring transmission.

    PubMed

    Osmond, Matthew M; Otto, Sarah P

    2015-11-01

    Simple and ubiquitous gene interactions create rugged fitness landscapes composed of coadapted gene complexes separated by "valleys" of low fitness. Crossing such fitness valleys allows a population to escape suboptimal local fitness peaks to become better adapted. This is the premise of Sewall Wright's shifting balance process. Here we generalize the theory of fitness-valley crossing in the two-locus, bi-allelic case by allowing bias in parent-offspring transmission. This generalization extends the existing mathematical framework to genetic systems with segregation distortion and uniparental inheritance. Our results are also flexible enough to provide insight into shifts between alternate stable states in cultural systems with "transmission valleys". Using a semi-deterministic analysis and a stochastic diffusion approximation, we focus on the limiting step in valley crossing: the first appearance of the genotype on the new fitness peak whose lineage will eventually fix. We then apply our results to specific cases of segregation distortion, uniparental inheritance, and cultural transmission. Segregation distortion favouring mutant alleles facilitates crossing most when recombination and mutation are rare, i.e., scenarios where crossing is otherwise unlikely. Interactions with more mutable genes (e.g., uniparental inherited cytoplasmic elements) substantially reduce crossing times. Despite component traits being passed on poorly in the previous cultural background, small advantages in the transmission of a new combination of cultural traits can greatly facilitate a cultural transition. While peak shifts are unlikely under many of the common assumptions of population genetic theory, relaxing some of these assumptions can promote fitness-valley crossing. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. CROPPER: a metagene creator resource for cross-platform and cross-species compendium studies.

    PubMed

    Paananen, Jussi; Storvik, Markus; Wong, Garry

    2006-09-22

    Current genomic research methods provide researchers with enormous amounts of data. Combining data from different high-throughput research technologies commonly available in biological databases can lead to novel findings and increase research efficiency. However, combining data from different heterogeneous sources is often a very arduous task. These sources can be different microarray technology platforms, genomic databases, or experiments performed on various species. Our aim was to develop a software program that could facilitate the combining of data from heterogeneous sources, and thus allow researchers to perform genomic cross-platform/cross-species studies and to use existing experimental data for compendium studies. We have developed a web-based software resource, called CROPPER that uses the latest genomic information concerning different data identifiers and orthologous genes from the Ensembl database. CROPPER can be used to combine genomic data from different heterogeneous sources, allowing researchers to perform cross-platform/cross-species compendium studies without the need for complex computational tools or the requirement of setting up one's own in-house database. We also present an example of a simple cross-platform/cross-species compendium study based on publicly available Parkinson's disease data derived from different sources. CROPPER is a user-friendly and freely available web-based software resource that can be successfully used for cross-species/cross-platform compendium studies.

  9. Tooth size discrepancies in Class II division 1 and Class III malocclusion requiring surgical-orthodontic or orthodontic treatment.

    PubMed

    McSwiney, Timothy P; Millett, Declan T; McIntyre, Grant T; Barry, Mark K; Cronin, Michael S

    2014-06-01

    To compare mean anterior (AR) and mean overall (OR) tooth size ratios, prevalence of clinically significant tooth size discrepancies (TSDs) and correlation between AR and OR in subjects with Class II division 1 and Class III malocclusion treated by surgical-orthodontic or orthodontic means. Retrospective, cross-sectional. State-funded and private clinics. From pre-treatment cohorts of 770 surgical and 610 non-surgical subjects, Class II division 1 and Class III malocclusion groups were identified with 60 surgical and 60 non-surgical subjects, comprising 30 males and 30 females, in each. AR and OR were calculated by landmarking digital models. Differences in AR and OR and their relationship were analysed using two-way analysis of variance (ANOVA) and a correlation coefficient, respectively. The proportions of the surgical and non-surgical groups with a TSD were assessed using logistic regression. Intra-examiner reproducibility involved re-landmarking 30 randomly selected image sets and differences in ARs and ORs were compared using a paired t-test. Random error was assessed using the intraclass correlation coefficient (ICC). Analyses were performed using SAS (SAS Institute Inc., Cary, NC, USA) at the 5% level of significance. There were no statistically significant differences associated with the measurement of either the mean AR (P = 0·913) or the mean OR (P = 0·874). ICC values were very high (AR = 0·95; OR = 0·90). Differences existed between both Class II and Class III surgical (AR: P<0·001; OR: P<0·001) and non-surgical groups (AR: P = 0·012; OR: P = 0·003). The AR and OR relationship was strong (correlation coefficient = 0·72). The highest percentage of clinically significant TSDs was seen in the AR of both Class II and Class III surgical groups (23·3%). In the cohort examined: AR and OR differed significantly for malocclusion groups. The prevalence of clinically significant TSDs did not differ significantly between

  10. Cross-flow electrochemical reactor cells, cross-flow reactors, and use of cross-flow reactors for oxidation reactions

    DOEpatents

    Balachandran, Uthamalingam; Poeppel, Roger B.; Kleefisch, Mark S.; Kobylinski, Thaddeus P.; Udovich, Carl A.

    1994-01-01

    This invention discloses cross-flow electrochemical reactor cells containing oxygen permeable materials which have both electron conductivity and oxygen ion conductivity, cross-flow reactors, and electrochemical processes using cross-flow reactor cells having oxygen permeable monolithic cores to control and facilitate transport of oxygen from an oxygen-containing gas stream to oxidation reactions of organic compounds in another gas stream. These cross-flow electrochemical reactors comprise a hollow ceramic blade positioned across a gas stream flow or a stack of crossed hollow ceramic blades containing a channel or channels for flow of gas streams. Each channel has at least one channel wall disposed between a channel and a portion of an outer surface of the ceramic blade, or a common wall with adjacent blades in a stack comprising a gas-impervious mixed metal oxide material of a perovskite structure having electron conductivity and oxygen ion conductivity. The invention includes reactors comprising first and second zones seprated by gas-impervious mixed metal oxide material material having electron conductivity and oxygen ion conductivity. Prefered gas-impervious materials comprise at least one mixed metal oxide having a perovskite structure or perovskite-like structure. The invention includes, also, oxidation processes controlled by using these electrochemical reactors, and these reactions do not require an external source of electrical potential or any external electric circuit for oxidation to proceed.

  11. Barriers and facilitators to care for the terminally ill: a cross-country case comparison study of Canada, England, Germany, and the United States.

    PubMed

    Klinger, Christopher A; Howell, Doris; Zakus, David; Deber, Raisa B

    2014-02-01

    Why do many patients not die at their preferred location? Analyze system-level characteristics influencing the ability to implement best practices in delivering care for terminally ill adults (barriers and facilitators). Cross-country comparison study from a "most similar-most different" perspective, triangulating evidence from a scoping review of the literature, document analyses, and semi-structured key informant interviews. Case study of Canada, England, Germany, and the United States. While similar with regard to leading causes of death, patient needs, and potential avenues to care, different models of service provision were employed in the four countries studied. Although hospice and palliative care services were generally offered with standard care along the disease continuum and in various settings, and featured common elements such as physical, psycho-social, and spiritual care, outcomes (access, utilization, etc.) varied across jurisdictions. Barriers to best practice service provision included legislative (including jurisdictional), regulatory (e.g. education and training), and financial issues as well as public knowledge and perception ("giving up hope") challenges. Advance care planning, dedicated and stable funding toward hospice and palliative care, including caregiver benefits, population aging, and standards of practice and guidelines to hospice and palliative care, were identified as facilitators. Successful implementation of effective and efficient best practice approaches to care for the terminally ill, such as shared care, requires concerted action to align these system-level characteristics; many factors were identified as being essential but not sufficient. Policy implementation needs to be tailored to the respective health-care system(s), monitored, and fine-tuned.

  12. Kick, Glide, Pole! Cross-Country Skiing Fun (Part I)

    ERIC Educational Resources Information Center

    Duoos, Bridget A.

    2011-01-01

    Cross-country skiing is a great activity for taking a physical education class outside during the cold winter months. It is also a diverse activity that appeals to students of all ages, and is an excellent cardio-respiratory activity to keep students active. This article has provided the first steps in preparing a cross-country skiing lesson in…

  13. 78 FR 78794 - Proposed Establishment of Class E Airspace; Flagstaff, AZ

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-27

    ...This action proposes to establish Class E airspace at the Flagstaff VHF Omni-Directional Radio Range/Distance Measuring Equipment (VOR/DME) navigation aid, Flagstaff, AZ, to facilitate vectoring of Instrument Flight Rules (IFR) aircraft under control of Albuquerque Air Route Traffic Control Center (ARTCC). The FAA is proposing this action to enhance the safety and management of aircraft operations within the National Airspace System.

  14. The Influence of Facilitator and Facilitation Characteristics on Participants' Ratings of Stepfamily Education

    ERIC Educational Resources Information Center

    Higginbotham, Brian J.; Myler, Cory

    2010-01-01

    We examine the relative importance of facilitator and facilitation characteristics on participant ratings of a stepfamily education program. Data from 48 facilitators and 598 participants suggest that quality facilitation is more meaningful to participants than whether facilitators have comparable demographic characteristics or life experiences.…

  15. Applications of Palladium-Catalyzed C-N Cross-Coupling Reactions.

    PubMed

    Ruiz-Castillo, Paula; Buchwald, Stephen L

    2016-10-12

    Pd-catalyzed cross-coupling reactions that form C-N bonds have become useful methods to synthesize anilines and aniline derivatives, an important class of compounds throughout chemical research. A key factor in the widespread adoption of these methods has been the continued development of reliable and versatile catalysts that function under operationally simple, user-friendly conditions. This review provides an overview of Pd-catalyzed N-arylation reactions found in both basic and applied chemical research from 2008 to the present. Selected examples of C-N cross-coupling reactions between nine classes of nitrogen-based coupling partners and (pseudo)aryl halides are described for the synthesis of heterocycles, medicinally relevant compounds, natural products, organic materials, and catalysts.

  16. Applications of Palladium-Catalyzed C–N Cross-Coupling Reactions

    PubMed Central

    2016-01-01

    Pd-catalyzed cross-coupling reactions that form C–N bonds have become useful methods to synthesize anilines and aniline derivatives, an important class of compounds throughout chemical research. A key factor in the widespread adoption of these methods has been the continued development of reliable and versatile catalysts that function under operationally simple, user-friendly conditions. This review provides an overview of Pd-catalyzed N-arylation reactions found in both basic and applied chemical research from 2008 to the present. Selected examples of C–N cross-coupling reactions between nine classes of nitrogen-based coupling partners and (pseudo)aryl halides are described for the synthesis of heterocycles, medicinally relevant compounds, natural products, organic materials, and catalysts. PMID:27689804

  17. A Blended Approach to Active Learning in a Physiology Laboratory-Based Subject Facilitated by an e-Learning Component

    ERIC Educational Resources Information Center

    Dantas, Arianne M.; Kemm, Robert E.

    2008-01-01

    Learning via online activities (e-learning) was introduced to facilitate existing face-to-face teaching to encourage more effective student preparation and then informed participation in an undergraduate physiology laboratory-based course. Active learning was encouraged by hypothesis formation and predictions prior to classes, with opportunities…

  18. FLOWS WITH CROSS SECTIONS

    PubMed Central

    Verjovsky, Alberto

    1970-01-01

    Let M be a compact connected C∞-manifold, of dimension n, without boundary. Let ft: M → M be a Cr-flow with cross section. Let Dr(M) be the topological group of diffeomorphisms of M with Cr-topology (1 ≤ r ≤ ∞) and let Dor(M) be its connected component of the identity. Let [unk](M) be the group of I-cobordism classes in Dr(M) generated by orientation-preserving diffeomorphisms. For fεDr(M) denote by [f] its I-cobordism class. Theorem 1 deals with the dependence of M(f) on [f]. Theorem 2: S6 × S1 has at least 28 distinct differentiable structures. Let xoεS1 and let [unk]r be the set of Cr-flows (r ≥ 1) in M × S1 with cross section M × {xo} and inducing in it the identity. Theorem 3: Intuitively to a loop in Dor based at the identity there corresponds a flow in [unk]r, and to homotopic loops correspond isotopic flows. COROLLARY. complete analysis of [unk]r/ [unk] for dim M = 2. Theorems 4 and 5 refer to Anosov flows for dim M > 3. PMID:16591849

  19. Cross-Informant Agreement on Child and Adolescent Withdrawn Behavior: A Latent Class Approach

    ERIC Educational Resources Information Center

    Rubin, David H.; Althoff, Robert R.; Walkup, John T.; Hudziak, James J.

    2013-01-01

    Withdrawn behavior (WB) relates to many developmental outcomes, including pervasive developmental disorders, anxiety, depression, psychosis, personality disorders and suicide. No study has compared the latent profiles of different informants' reports on WB. This study uses multi-informant latent class analyses (LCA) of the child behavior checklist…

  20. Regulation of calreticulin–major histocompatibility complex (MHC) class I interactions by ATP

    PubMed Central

    Wijeyesakere, Sanjeeva Joseph; Gagnon, Jessica K.; Arora, Karunesh; Brooks, Charles L.; Raghavan, Malini

    2015-01-01

    The MHC class I peptide loading complex (PLC) facilitates the assembly of MHC class I molecules with peptides, but factors that regulate the stability and dynamics of the assembly complex are largely uncharacterized. Based on initial findings that ATP, in addition to MHC class I-specific peptide, is able to induce MHC class I dissociation from the PLC, we investigated the interaction of ATP with the chaperone calreticulin, an endoplasmic reticulum (ER) luminal, calcium-binding component of the PLC that is known to bind ATP. We combined computational and experimental measurements to identify residues within the globular domain of calreticulin, in proximity to the high-affinity calcium-binding site, that are important for high-affinity ATP binding and for ATPase activity. High-affinity calcium binding by calreticulin is required for optimal nucleotide binding, but both ATP and ADP destabilize enthalpy-driven high-affinity calcium binding to calreticulin. ATP also selectively destabilizes the interaction of calreticulin with cellular substrates, including MHC class I molecules. Calreticulin mutants that affect ATP or high-affinity calcium binding display prolonged associations with monoglucosylated forms of cellular MHC class I, delaying MHC class I dissociation from the PLC and their transit through the secretory pathway. These studies reveal central roles for ATP and calcium binding as regulators of calreticulin–substrate interactions and as key determinants of PLC dynamics. PMID:26420867

  1. Imbalance in chemical space: How to facilitate the identification of protein-protein interaction inhibitors.

    PubMed

    Kuenemann, Mélaine A; Labbé, Céline M; Cerdan, Adrien H; Sperandio, Olivier

    2016-04-01

    Protein-protein interactions (PPIs) play vital roles in life and provide new opportunities for therapeutic interventions. In this large data analysis, 3,300 inhibitors of PPIs (iPPIs) were compared to 17 reference datasets of collectively ~566,000 compounds (including natural compounds, existing drugs, active compounds on conventional targets, etc.) using a chemoinformatics approach. Using this procedure, we showed that comparable classes of PPI targets can be formed using either the similarity of their ligands or the shared properties of their binding cavities, constituting a proof-of-concept that not only can binding pockets be used to group PPI targets, but that these pockets certainly condition the properties of their corresponding ligands. These results demonstrate that matching regions in both chemical space and target space can be found. Such identified classes of targets could lead to the design of PPI-class-specific chemical libraries and therefore facilitate the development of iPPIs to the stage of drug candidates.

  2. Using learning theory, interprofessional facilitation competencies, and behavioral indicators to evaluate facilitator training.

    PubMed

    LeGros, Theresa A; Amerongen, Helen M; Cooley, Janet H; Schloss, Ernest P

    2015-01-01

    Despite the increasing need for faculty and preceptors skilled in interprofessional facilitation (IPF), the relative novelty of the field poses a challenge to the development and evaluation of IPF programs. We use learning theory and IPF competencies with associated behavioral indicators to develop and evaluate six key messages in IPF training and experience. Our mixed methods approach included two phases: quantitative data collection with embedded qualitative data, followed by qualitative data collection in explanatory sequential fashion. This enabled triangulated analyses of both data types and of facilitation behaviors from facilitator and student perspectives. Results indicate the competency-based training was effective. Facilitators felt comfortable performing behaviors associated with IPF competencies; student observations of those behaviors supported facilitator self-reported performance. Overall, students perceived more facilitation opportunities than facilitators. Findings corroborate the importance of recruiting seasoned facilitators and establishing IPF guidelines that acknowledge variable team dynamics and help facilitators recognize teachable moments.

  3. Drug-target interaction prediction via class imbalance-aware ensemble learning.

    PubMed

    Ezzat, Ali; Wu, Min; Li, Xiao-Li; Kwoh, Chee-Keong

    2016-12-22

    Multiple computational methods for predicting drug-target interactions have been developed to facilitate the drug discovery process. These methods use available data on known drug-target interactions to train classifiers with the purpose of predicting new undiscovered interactions. However, a key challenge regarding this data that has not yet been addressed by these methods, namely class imbalance, is potentially degrading the prediction performance. Class imbalance can be divided into two sub-problems. Firstly, the number of known interacting drug-target pairs is much smaller than that of non-interacting drug-target pairs. This imbalance ratio between interacting and non-interacting drug-target pairs is referred to as the between-class imbalance. Between-class imbalance degrades prediction performance due to the bias in prediction results towards the majority class (i.e. the non-interacting pairs), leading to more prediction errors in the minority class (i.e. the interacting pairs). Secondly, there are multiple types of drug-target interactions in the data with some types having relatively fewer members (or are less represented) than others. This variation in representation of the different interaction types leads to another kind of imbalance referred to as the within-class imbalance. In within-class imbalance, prediction results are biased towards the better represented interaction types, leading to more prediction errors in the less represented interaction types. We propose an ensemble learning method that incorporates techniques to address the issues of between-class imbalance and within-class imbalance. Experiments show that the proposed method improves results over 4 state-of-the-art methods. In addition, we simulated cases for new drugs and targets to see how our method would perform in predicting their interactions. New drugs and targets are those for which no prior interactions are known. Our method displayed satisfactory prediction performance and was

  4. Shot noise cross-correlation functions and cross spectra - Implications for models of QPO X-ray sources

    NASA Technical Reports Server (NTRS)

    Shibazaki, N.; Elsner, R. F.; Bussard, R. W.; Ebisuzaki, T.; Weisskopf, M. C.

    1988-01-01

    The cross-correlation functions (CCFs) and cross spectra expected for quasi-periodic oscillation (QPO) shot noise models are calculated under various assumptions, and the results are compared to observations. Effects due to possible coherence of the QPO oscillations are included. General formulas for the cross spectrum, the cross-phase spectrum, and the time-delay spectrum for QPO shot models are calculated and discussed. It is shown that the CCFs, cross spectra, and power spectra observed for Cyg X-e2 imply that the spectrum of the shots evolves with time, with important implications for the interpretation of these functions as well as of observed average energy spectra. The possible origins for the observed hard lags are discussed, and some physical difficulties for the Comptonization model are described. Classes of physical models for QPO sources are briefly addressed, and it is concluded that models involving shot formation at the surface of neutron stars are favored by observation.

  5. Management of a growing Skeletal Class II Patient: A Case Report.

    PubMed

    Sharma, Narendra Shriram

    2013-01-01

    Sagittal and transverse discrepancies often coexist in skeletal class II malocclusions. Orthopedic growth modification can work well in such cases, provided that the remaining pubertal growth is adequate and that the clinician can provide timely treatment to coincide with the peak growth period. The transverse discrepancy is generally corrected first, establishing a proper base for the sagittal correction to follow. For example, in a skeletal class II case with a narrow maxillary arch and retrusive mandible, maxillary expansion is performed initially to facilitate functional mandibular advancement. The present article illustrates an exception to this rule, in a case where sagittal correction was undertaken before transverse correction to make optimal use of the patient's pubertal growth spurt in first phase followed by a second phase of fixed appliance therapy during adolescence to achieve optimal results. How to cite this article: Sharma NS. Management of a growing Skeletal Class II Patient: A Case Report. Int J Clin Pediatr Dent 2013;6(1):48-54.

  6. Intensity and duration of physical efforts in Physical Education classes.

    PubMed

    Kremer, Marina Marques; Reichert, Felipe Fossati; Hallal, Pedro Curi

    2012-04-01

    To evaluate the intensity and duration of physical efforts in Physical Education classes in primary and secondary school. School-based cross-sectional study carried out by means of the observation of 218 Physical Education classes, including a total of 272 students (each one of the students was evaluated three times). The study was carried out in the city of Pelotas (Southern Brazil), between August and December 2009. In order to evaluate the intensity of the efforts, accelerometers were used and the following cut-off points were adopted (in counts per minute): sedentary activities (0-100), light activities (101-2,000), moderate (2,001-4,999), vigorous (5,000-7,999), and very vigorous activities (>8000). The mean duration of the classes was 35.6 minutes (SD 6.0). The mean proportion of time spent in moderate to vigorous physical activity was 32.7% (SD 25.2). Boys (44.1%) were involved significantly more in moderate to vigorous physical activity as compared to girls (21.0%; p<0.01). Students who practice physical activities outside the classes participated more in moderate to vigorous physical activity in the Physical Education classes. Besides the fact that Physical Education classes have a short duration, students practice moderate to vigorous physical activity during one third of the class, with a poor significant contribution to students' level of physical activity.

  7. Barriers and facilitators for the implementation of an online clinical health community in addition to usual fertility care: a cross-sectional study.

    PubMed

    Aarts, Johanna W M; Faber, Marjan J; den Boogert, Anne G; Cohlen, Ben J; van der Linden, Paul J Q; Kremer, Jan A M; Nelen, Willianne L D M

    2013-08-30

    Online health communities are becoming more popular in health care. Patients and professionals can communicate with one another online, patients can find peer support, and professionals can use it as an additional information channel to their patients. However, the implementation of online health communities into daily practice is challenging. These challenges relate to the fact that patients need to be activated to (1) become a member (ie, subscription) and (2) participate actively within the community before any effect can be expected. Therefore, we aimed at answering 2 research questions: (1) what factors are associated with subscription to an online health community, and (2) which are associated with becoming an active participant within an online health community. To identify barriers and facilitators as perceived by patients for the implementation of an online health community. We performed a cross-sectional study. Three Dutch fertility clinics (2 IVF-licensed) offered their patients a secure online clinical health community through which clinicians can provide online information and patients can ask questions to the medical team or share experiences and find support from peers. We randomly selected and invited 278 men and women suffering from infertility and attending 1 of the participating clinics. Participants filled out a questionnaire about their background characteristics and current use of the online community. Possible barriers and facilitators were divided into 2 parts: (1) those for subscription to the community, and (2) those for active participation in the community. We performed 2 multivariate logistic regression analyses to calculate determinants for both subscription and active participation. Subscription appeared to be associated with patients' background characteristics (eg, gender, treatment phase), intervention-related facilitators (odds ratio [OR] 2.45, 95% CI 1.14-5.27), and patient-related barriers (OR 0.20, 95% CI 0.08-0.54), such as

  8. Gender, social class and illness among young people.

    PubMed

    Rahkonen, O; Lahelma, E

    1992-03-01

    Gender and social class differences in illness among young people have been a neglected area in research on social inequities in health. It has been assumed that the illness differentials among adults persist throughout their lives. Only recently have social class health differentials among young people become a topic for research. The aim of this study is, first, to examine gender and social class differences in self-reported illness among young Finns; secondly, to determine whether the relationship between social class and limiting long-standing illness is similar among young men and women. In addition to the two main aims, we also examined whether several background variables have any impact on the relationship between class and illness or, directly, on illness. The data were derived from a nationwide Finnish 'Level of Living Survey', which was carried out by the Central Statistical Office of Finland in 1986. This interview material represents the noninstitutional Finnish population aged 15 years old or older. The number of respondents were 12,057, and the response rate was 87%. In the present study we only examined those who were 15-24-year-olds (N = 2238); i.e. 1101 men and 1137 women; the response rates were 91% and 92% respectively. Young women reported a limiting long-standing illness more often than young men. The prevalence of limiting long-standing illness increased with age. Cross-tabulation analyses showed virtually no relationship between social class and limiting long-standing illness. This held true irrespective of the various measures of social class that were used. Controlling the impact of several background variables in the logistic regression analyses did not alter this general result.

  9. Cross-sensor iris recognition through kernel learning.

    PubMed

    Pillai, Jaishanker K; Puertas, Maria; Chellappa, Rama

    2014-01-01

    Due to the increasing popularity of iris biometrics, new sensors are being developed for acquiring iris images and existing ones are being continuously upgraded. Re-enrolling users every time a new sensor is deployed is expensive and time-consuming, especially in applications with a large number of enrolled users. However, recent studies show that cross-sensor matching, where the test samples are verified using data enrolled with a different sensor, often lead to reduced performance. In this paper, we propose a machine learning technique to mitigate the cross-sensor performance degradation by adapting the iris samples from one sensor to another. We first present a novel optimization framework for learning transformations on iris biometrics. We then utilize this framework for sensor adaptation, by reducing the distance between samples of the same class, and increasing it between samples of different classes, irrespective of the sensors acquiring them. Extensive evaluations on iris data from multiple sensors demonstrate that the proposed method leads to improvement in cross-sensor recognition accuracy. Furthermore, since the proposed technique requires minimal changes to the iris recognition pipeline, it can easily be incorporated into existing iris recognition systems.

  10. The Interdisciplinary Mini-Course: Instructional Development for Language Classes.

    ERIC Educational Resources Information Center

    Wilkins, Wynona H.; Boswau, Herbert H.

    Curricula for interdisciplinary courses that enable second language classes to employ the arts are proposed. At the University of North Dakota, mini-courses provide one-semester credit and are given for 2 hours 1 day a week over a period of 8 weeks. Some of the courses are cross-listed with other departments. Two of these courses, Joan of Arc and…

  11. Using Culturally Relevant Teaching in a Co-Educational Mathematics Class of a Patriarchal Community

    ERIC Educational Resources Information Center

    Mogari, David

    2017-01-01

    The paper reports on the use of culturally relevant teaching in a class located in a patriarchal community. The paper is conceptualised around the notion that learners' familiar context provided by the socio-cultural activities can facilitate mathematics learning and make it fun to learn. Data were derived from a lesson activity using…

  12. Student Perceptions and Experiences Using Jing and Skype in an Accounting Information Systems Class

    ERIC Educational Resources Information Center

    Charron, Kimberly; Raschke, Robyn

    2014-01-01

    The authors examine the use of technology to support students in their learning of practical accounting software applications while taking a traditional on-campus class. Specifically, they look at how Jing and Skype are used to facilitate successful completion of a series of simulations using Netsuite (NetSuite, Inc., San Mateo, CA) accounting…

  13. EphrinA2 Regulates Clathrin Mediated KSHV Endocytosis in Fibroblast Cells by Coordinating Integrin-Associated Signaling and c-Cbl Directed Polyubiquitination

    PubMed Central

    Dutta, Dipanjan; Chakraborty, Sayan; Bandyopadhyay, Chirosree; Valiya Veettil, Mohanan; Ansari, Mairaj Ahmed; Singh, Vivek Vikram; Chandran, Bala

    2013-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) interacts with human dermal endothelial cell surface tyrosine kinase EphrinA2 (EphA2) and integrins (α3β1 and αVβ3) in the lipid raft (LR) region, and EphA2 regulates macropinocytic virus entry by coordinating integrin-c-Cbl associated signaling. In contrast, KSHV enters human foreskin fibroblast (HFF) cells by LR-independent clathrin mediated endocytosis. The present studies conducted to identify the key molecules regulating KSHV entry in HFF cells showed that KSHV induces association with integrins (αVβ5, αVβ3 and α3β1) and EphA2 in non-LR regions early during infection and activates EphA2, which in turn associates with phosphorylated c-Cbl, myosin IIA, FAK, Src, and PI3-K, as well as clathrin and its adaptor AP2 and effector Epsin-15 proteins. EphA2 knockdown significantly reduced these signal inductions, virus internalization and gene expression. c-Cbl knockdown ablated the c-Cbl mediated K63 type polyubiquitination of EphA2 and clathrin association with EphA2 and KSHV. Mutations in EphA2's tyrosine kinase domain (TKD) or sterile alpha motif (SAM) abolished its interaction with c-Cbl. Mutations in tyrosine kinase binding (TKB) or RING finger (RF) domains of c-Cbl resulted in very poor association of c-Cbl with EphA2 and decreased EphA2 polyubiquitination. These studies demonstrated the contributions of these domains in EphA2 and c-Cbl association, EphA2 polyubiquitination and virus-EphA2 internalization. Collectively, these results revealed for the first time that EphA2 influences the tyrosine phosphorylation of clathrin, the role of EphA2 in clathrin mediated endocytosis of a virus, and c-Cbl mediated EphA2 polyubiquitination directing KSHV entry in HFF cells via coordinated signal induction and progression of endocytic events, all of which suggest that targeting EphA2 and c-Cbl could block KSHV entry and infection. PMID:23874206

  14. [Inequalities in health according to social class in Catalonia, 1994].

    PubMed

    Fernández, E; Schiaffino, A; Rajmil, L; Borrell, C; García, M; Segura, A

    2000-05-15

    To study social inequalities in health in Catalonia. Cross-sectional survey of a representative sample of the population of Catalonia, Spain (Catalan Health Interview Survey, 1994). Responses from 5641 males and 6604 women aged 15 years or over were included for analysis. We analysed the information about self-perceived health, restriction of activity, and presence of chronic conditions according to social class by means of logistic regression models. The proportion of subjects that rated their health as fair or poor was higher in social classes IV-V than in classes I-II (men: 25.0% vs. 14.5%; OR, 1.8, 95% CI, 1.5-2.3; women: 34.4% vs. 21.5%; OR, 1.7, 95% CI, 1.4-2.1). There were differences by social class in respect to restriction of activity and presence of chronic conditions. Despite the decrease of social inequalities in accesibility and use of health services due to the universalisation of health coverage, differences by social class remain in the perception of health status. These inequalities should be addressed by the health system within the framework of broad public and social policies.

  15. Geographic epidemiology of cardiometabolic risk factors in middle class urban residents in India: cross-sectional study.

    PubMed

    Gupta, Rajeev; Sharma, Krishna Kumar; Gupta, Bal Kishan; Gupta, Arvind; Saboo, Banshi; Maheshwari, Anuj; Mahanta, Tulika; Deedwania, Prakash C

    2015-06-01

    To determine epidemiology of cardiovascular risk factors according to geographic distribution and macrolevel social development index among urban middle class subjects in India. We performed cross-sectional surveys in 11 cities in India during years 2005-2009. 6198 subjects aged 20-75 years (men 3426, women 2772, response 62%) were evaluated for cardiovascular risk factors. Cities were grouped according to geographic distribution into northern (3 cities, n = 1321), western (2 cities, n = 1814), southern (3 cities, n = 1237) and eastern (3 cities, n = 1826). They were also grouped according to human social development index into low (3 cities, n = 1794), middle (5 cities, n = 2634) and high (3 cities, n = 1825). Standard definitions were used to determine risk factors. Differences in risk factors were evaluated using χ(2) test. Trends were examined by least squares regression. Age-adjusted prevalence (95% confidence intervals) of various risk factors was: low physical activity 42.1% (40.9-43.3), high dietary fat 49.9% (47.8-52.0), low fruit/vegetables 26.9% (25.8-28.0), smoking 10.1% (9.1-11.1), smokeless tobacco use 9.8% (9.1-10.5), overweight 42.9% (41.7-44.1), obesity 11.6% (10.8-12.4), high waist circumference 45.5% (44.3-46.7), high waist-hip ratio 75.7% (74.7-76.8), hypertension 31.6% (30.4-32.8), hypercholesterolemia 25.0% (23.9-26.9), low HDL cholesterol 42.5% (41.3-43.7), hypertriglyceridemia 36.9% (35.7-38.1), diabetes 15.7% (14.8-16.6), and metabolic syndrome 35.7% (34.5-36.9). Compared with national average, prevalence of most risk factors was not significantly different in various geographic regions, however, cities in eastern region had significantly lower prevalence of overweight, hypertension, hypercholesterolemia, diabetes and metabolic syndrome compared with other regions (P < 0.05 for various comparisons). It was also observed that cities with low human social development index had lowest prevalence of these risk

  16. Perceived facilitators of and barriers to healthful eating among university students.

    PubMed

    Garcia, Alicia C; Sykes, Lesley; Matthews, June; Martin, Noelle; Leipert, Beverly

    2010-01-01

    Photovoice, an innovative qualitative research method in health care, has not been used to its full potential in nutrition/dietetics. We explored the use of Photovoice to determine perceived facilitators of and barriers to healthful eating among university students. The study included 28 students enrolled in a 2008 introductory nutrition class. The students participated in a camera orientation session to review ethics and privacy issues. They took photographs and selected two for discussion in a focus group moderated by a graduate student who used a semi-structured facilitation guide. Researchers coded the transcripts, analyzed the pictures and students' written comments about the project, and ensured data trustworthiness through credibility, dependability, confirmability, and transferability of data and methods. Six major themes emerged as facilitators and/or barriers: environment, nutrition knowledge, convenience foods, time, media influence, and food cost. More than one-third of the students thought the study "stimulated their critical thinking." They felt more empowered in sharing their perceptions and "getting their voices heard." Photovoice was a useful, "motivating," and "engaging" method for research on nutrition knowledge and dietary patterns of university students. Registered dietitians and other health professionals may benefit from the use of the Photovoice method when they are working with students.

  17. Predictors of breast feeding self-efficacy in the immediate postpartum period: A cross-sectional study.

    PubMed

    Yang, Xiao; Gao, Ling-Ling; Ip, Wan-Yim; Sally Chan, Wai Chi

    2016-10-01

    to examine breast feeding self-efficacy and identify its predictors among mainland Chinese mothers in the early postpartum period. a cross-sectional descriptive questionnaire survey was conducted in a regional teaching hospital with childbirth rate over 3000 per year at Guangzhou, China from April 1 to July 14, 2014. a total of 571 Chinese mothers who were within 72-96hours post partum were recruited consecutively to the study. data were collected by the Chinese version of the Breastfeeding Self-efficacy Scale-Short Form (BSES-SF), the Network Support for Breastfeeding Scale (NSBS) and a socio-demographic data sheet. a total of 640 eligible women was approached and 571 mothers completed the study with the response rate of 89%. Mothers reported moderate level of breast feeding self-efficacy in the immediate postpartum period. The best-fit regression analysis revealed six variables that explained 43.9% of the variance in breast feeding self-efficacy in the immediate postpartum period. They were intention of breast feeding, support from husband, support from nurses/midwives, attending antenatal breast feeding classes, time from childbirth to initiate breast feeding and previous breast feeding experience. this study found six predictors of breast feeding self-efficacy in the immediate postpartum period. In order to increase maternal breast feeding self-efficacy level, a more women-centred approach is recommended. Mothers and fathers should be facilitated to attend antenatal classes on breast feeding. New mother' husband could be encouraged in supporting breast feeding. Nurses and midwives could encourage new mothers to initiate breast feeding as soon as possible. Further work to promote early mother-infant contact post birth, such as via skin to skin contact should also be facilitated where possible. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Chinese nurses' perceived barriers and facilitators of ethical sensitivity.

    PubMed

    Huang, Fei Fei; Yang, Qing; Zhang, Jie; Khoshnood, Kaveh; Zhang, Jing Ping

    2016-08-01

    An overview of ethical sensitivity among Chinese registered nurses is needed to develop and optimize the education programs and interventions to cultivate and improve ethical sensitivity. The study was conducted to explore the barriers to and facilitators of ethical sensitivity among Chinese registered nurses working in hospital settings. A convergent parallel mixed-methods research design was adopted. In the cross-sectional quantitative study, the Chinese Moral Sensitivity Questionnaire-revised version was used to assess the levels of ethical sensitivity among registered nurses, and the scores were correlated with key demographics, training experiences in ethics, and workplace cultural environments (n = 306). In the qualitative study, semi-structured interviews were used to elicit the nurses' perceptions of the barriers and facilitators in nurturing ethical sensitivity (n = 15). The data were collected from February to June 2014. This study was approved by the Institutional Review Boards of Yale University and Central South University. Despite moderately high overall Chinese Moral Sensitivity Questionnaire-revised version scores, the ethical sensitivity among Chinese nurses lags in practice. Barriers to ethical sensitivity include the lack of knowledge related to ethics, lack of working experience as a nurse, the hierarchical organizational climate, and the conformist working attitude. The positive workplace cultural environments and application of ethical knowledge in practice were considered potential facilitators of ethical sensitivity. The findings of this study were compared with studies from other countries to examine the barriers and facilitators of ethical sensitivity in Chinese nurses. This mixed-methods study showed that even though the Chinese nurses have moderately high sensitivity to the ethical issues encountered in hospitals, there is still room for improvement. The barriers to and facilitators of ethical sensitivity identified here offer new and

  19. The Cradleboard Teaching Project: Using Curriculum and Cross-Cultural Partnering To Change Perceptions.

    ERIC Educational Resources Information Center

    Sainte-Marie, Buffy

    1999-01-01

    Native Americans developed core curriculum units at the elementary, intermediate, and secondary levels in geography, history, music, social studies, and science presented from a Native American cultural perspective. Mainstream classes are paired with Native American classes and learn authentic information through cross-cultural exchange via…

  20. A new modified tandem appliance for management of developing Class III malocclusion.

    PubMed

    Sukh, Ram; Singh, Gyan P; Tandon, Pradeep

    2013-10-01

    Most developing Class III patients display a retruded maxilla. Early intervention in mixed dentition is associated with better patient compliance and possibly a better orthopedic response, which can produce favorable results. The aim of this article is to present the fabrication of the new modified tandem appliance and its use in management of developing Class III malocclusion. The therapeutic results of a new modified tandem appliance are presented in an 8 year-old male patient with anterior cross bite and retrognathic maxilla at the mixed dentition stage. Anterior cross bite was corrected in 3 months and the positive overjet of 4 mm after continued use of the appliance for 1 year. There was a significant improvement in profile of the patient. The use of this appliance in this type of malocclusion enabled the correction of malocclusion in a few months and encouraging favorable skeletal growth in the future.

  1. Class III orthognathic surgical cases facilitated by accelerated osteogenic orthodontics: a preliminary report.

    PubMed

    Wu, JiaQi; Xu, Li; Liang, Cheng; Jiang, JiuHui

    2015-11-01

    To describe a multidisciplinary treatment approach that includes corticotomy, orthodontic force and orthognathic surgery for the management of skeletal Class III surgical cases. The main advantage of the combined techniques is a reduction in treatment time for young adult patients. Accelerated Osteogenic Orthodontics (AOO) was delivered to three young adult patients during their pre-surgical orthodontic treatment. After aligning and levelling the dental arches, a piezosurgical corticotomy was performed to the buccal aspect of the alveolar bone. Bone graft materials were used to cover the decorticated area and soft tissue flaps were replaced. The mean time for extraction space closure was 5.4 ± 1.3 months and the mean time for pre-surgical orthodontic treatment was 12.0 ± 0.9 months. The average total treatment time was 20.4 ± 2.4 months. A pre-existing bony fenestration in the buccal cortex adjacent to the right lateral incisor root apex of Case 1 was corrected. The facial aesthetics of three patients improved following multidisciplinary treatment. This approach may be an efficient method for the orthognathic patient who desires a reduced treatment time, but further clinical research is required.

  2. Intentions of Muslim Arab women in Israel to attend prenatal classes.

    PubMed

    Ben Natan, Merav; Ashkenazi, Maayan; Masarwe, Safaa

    2016-02-01

    Prenatal education has many benefits to both mother and child. In Israel, prenatal classes are offered to pregnant women in their third trimester from all cultures and sectors. However, Israeli Muslim Arab women often do not attend these classes. To explore factors influencing the intention of Muslim Arab women in Israel to attend prenatal classes, using the Theory of Planned Behavior. The study was a cross-sectional quantitative correlational design. A convenience sample consisting of 200 Arab Muslim women completed a questionnaire based on the literature review and the theoretical model. The research findings indicate that women's intention to attend prenatal classes increases with more positive beliefs and attitudes toward prenatal education, greater subjective social pressure to attend classes, and with higher perceived control of attending such classes. The higher a woman's age and level of education, the greater her intention to attend classes. This study shows that the spouse is the most significant factor influencing women's decisions on this matter. In order to raise the intentions of Muslim Arab women in Israel to attend prenatal classes, policy makers must design programs to increase the awareness of prenatal education among both women and men in the Muslim Arab sector, emphasizing its benefits for mothers, infants, and families as a whole. Classes should reflect the uniqueness of Israeli Muslim Arab culture and combine traditional and modern outlooks. Copyright © 2015 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  3. Designing and Delivering Cross-Cultural Instruction.

    ERIC Educational Resources Information Center

    Ben-Yoseph, Miriam

    A course on management in a cross-cultural environment was designed to address dilemmas and opportunities that individuals might encounter in work or study. The course attracted students with a broad variety of backgrounds. A main textbook was supplemented with readings, guest lectures, and a variety of class activities including case studies,…

  4. Opioid Facilitation of β-Adrenergic Blockade: A New Pharmacological Condition?

    PubMed Central

    Vamecq, Joseph; Mention-Mulliez, Karine; Leclerc, Francis; Dobbelaere, Dries

    2015-01-01

    Recently, propranolol was suggested to prevent hyperlactatemia in a child with hypovolemic shock through β-adrenergic blockade. Though it is a known inhibitor of glycolysis, propranolol, outside this observation, has never been reported to fully protect against lactate overproduction. On the other hand, literature evidence exists for a cross-talk between β-adrenergic receptors (protein targets of propranolol) and δ-opioid receptor. In this literature context, it is hypothesized here that anti-diarrheic racecadotril (a pro-drug of thiorphan, an inhibitor of enkephalinases), which, in the cited observation, was co-administered with propranolol, might have facilitated the β-blocker-driven inhibition of glycolysis and resulting lactate production. The opioid-facilitated β-adrenergic blockade would be essentially additivity or even synergism putatively existing between antagonism of β-adrenergic receptors and agonism of δ-opioid receptor in lowering cellular cAMP and dependent functions. PMID:26426025

  5. Social Class Dialogues and the Fostering of Class Consciousness

    ERIC Educational Resources Information Center

    Madden, Meredith

    2015-01-01

    How do critical pedagogies promote undergraduate students' awareness of social class, social class identity, and social class inequalities in education? How do undergraduate students experience class consciousness-raising in the intergroup dialogue classroom? This qualitative study explores undergraduate students' class consciousness-raising in an…

  6. Crossing Pedagogical Borders in the Yucatan Peninsula

    ERIC Educational Resources Information Center

    Willhauck, Susan

    2009-01-01

    A challenging intercultural teaching experience provided an opportunity for engaging embodied pedagogies that facilitated border crossings of language, age, gender, and experience. Influenced by the work of Augusto Boal, the author describes how improvisation, role-play, music, and drawing led seminary students in Mexico into sacred time and space…

  7. The Influence of Cross-Language Similarity on within- and between-Language Stroop Effects in Trilinguals

    PubMed Central

    van Heuven, Walter J. B.; Conklin, Kathy; Coderre, Emily L.; Guo, Taomei; Dijkstra, Ton

    2011-01-01

    This study investigated effects of cross-language similarity on within- and between-language Stroop interference and facilitation in three groups of trilinguals. Trilinguals were either proficient in three languages that use the same-script (alphabetic in German–English–Dutch trilinguals), two similar scripts and one different script (Chinese and alphabetic scripts in Chinese–English–Malay trilinguals), or three completely different scripts (Arabic, Chinese, and alphabetic in Uyghur–Chinese–English trilinguals). The results revealed a similar magnitude of within-language Stroop interference for the three groups, whereas between-language interference was modulated by cross-language similarity. For the same-script trilinguals, the within- and between-language interference was similar, whereas the between-language Stroop interference was reduced for trilinguals with languages written in different scripts. The magnitude of within-language Stroop facilitation was similar across the three groups of trilinguals, but smaller than within-language Stroop interference. Between-language Stroop facilitation was also modulated by cross-language similarity such that these effects became negative for trilinguals with languages written in different scripts. The overall pattern of Stroop interference and facilitation effects can be explained in terms of diverging and converging color and word information across languages. PMID:22180749

  8. Describing three-class task performance: three-class linear discriminant analysis and three-class ROC analysis

    NASA Astrophysics Data System (ADS)

    He, Xin; Frey, Eric C.

    2007-03-01

    Binary ROC analysis has solid decision-theoretic foundations and a close relationship to linear discriminant analysis (LDA). In particular, for the case of Gaussian equal covariance input data, the area under the ROC curve (AUC) value has a direct relationship to the Hotelling trace. Many attempts have been made to extend binary classification methods to multi-class. For example, Fukunaga extended binary LDA to obtain multi-class LDA, which uses the multi-class Hotelling trace as a figure-of-merit, and we have previously developed a three-class ROC analysis method. This work explores the relationship between conventional multi-class LDA and three-class ROC analysis. First, we developed a linear observer, the three-class Hotelling observer (3-HO). For Gaussian equal covariance data, the 3- HO provides equivalent performance to the three-class ideal observer and, under less strict conditions, maximizes the signal to noise ratio for classification of all pairs of the three classes simultaneously. The 3-HO templates are not the eigenvectors obtained from multi-class LDA. Second, we show that the three-class Hotelling trace, which is the figureof- merit in the conventional three-class extension of LDA, has significant limitations. Third, we demonstrate that, under certain conditions, there is a linear relationship between the eigenvectors obtained from multi-class LDA and 3-HO templates. We conclude that the 3-HO based on decision theory has advantages both in its decision theoretic background and in the usefulness of its figure-of-merit. Additionally, there exists the possibility of interpreting the two linear features extracted by the conventional extension of LDA from a decision theoretic point of view.

  9. A Cross-Cultural Examination of Semantic Relations.

    ERIC Educational Resources Information Center

    Raybeck, Douglas; Herrmann, Douglas

    1990-01-01

    Reports on a cross-cultural investigation of semantic relations, including antonyms, synonyms, and class inclusion, among bilingual adult subjects in the United States, England, Italy, Greece, Yugoslavia, Pakistan, and Hong Kong. Found significant agreement across cultures, especially for antinomy. Results in general support theories of linguistic…

  10. Transforming a large-class lecture course to a smaller-group interactive course.

    PubMed

    Persky, Adam M; Pollack, Gary M

    2010-11-10

    To transition a large pharmacokinetics course that was delivered using a traditional lecture format into a smaller-group course with a discussion format. An e-book and Web-based multimedia learning modules were utilized to facilitate students' independent learning which allowed the number of classes they were required to attend to be reduced from 3 to 1 per week. Students were assigned randomly to 1 of 3 weekly class sessions. The majority of lecture time was replaced with active-learning activities including discussion, problem solving, and case studies to encourage higher-order learning. Changes in course delivery were assessed over a 4-year period by comparing students' grades and satisfaction ratings on course evaluations. Although student satisfaction with the course did not improve significantly, students preferred the smaller-group setting to a large lecture-based class. The resources and activities designed to shift responsibility for learning to the students did not affect examination grades even though a larger portion of examination questions focused on higher orders of learning (eg, application) in the smaller-group format. Transitioning to a smaller-group discussion format is possible in a pharmacokinetics course by increasing student accountability for acquiring factual content outside of the classroom. Students favored the smaller-class format over a large lecture-based class.

  11. Irish set dancing classes for people with Parkinson's disease: The needs of participants and dance teachers.

    PubMed

    Shanahan, Joanne; Bhriain, Orfhlaith Ní; Morris, Meg E; Volpe, Daniele; Clifford, Amanda M

    2016-08-01

    As the number of people diagnosed with Parkinson's disease increases, there is a need to develop initiatives that promote health and wellbeing and support self-management. Additionally, as exercise may slow physical decline, there is a need to develop methods that facilitate greater engagement with community-based exercise. The aim of this study is to examine the needs of (1) people with Parkinson's disease and (2) set dancing teachers to enable the development of participant-centred community set dance classes. A mixed methods study design was used. Two consensus group discussions using nominal group technique were held to (1) identify factors pertaining to the needs of people with Parkinson's disease from a set dance class and (2) the educational needs of set dancing teachers to enable them to teach set dancing to people with Parkinson's disease. Group discussions began with silent generation of ideas. A round-robin discussion and grouping of ideas into broader topic areas followed. Finally, participants ranked, by order of priority (1-5), the topic areas developed. Final data analysis involved summation of participants' ranking scores for each topic area. Rich information on the needs of people with Parkinson's disease from a dance class and the educational guidance sought by set dancing teachers was gathered. Topic areas developed include "teaching method" for set dances and "class environment". Accessing community exercise programmes is important for this population. The results of this study will inform the development of an educational resource on Parkinson's disease for set dancing teachers. This resource may facilitate a larger number of teachers to establish sustainable community set dancing classes for people with Parkinson's disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. The Subjective Experience of Social Class and Upward Mobility Among African American Men in Graduate School

    PubMed Central

    Sánchez, Francisco J.; Liu, William Ming; Leathers, Leslie; Goins, Joyce; Vilain, Eric

    2011-01-01

    We used Consensual Qualitative Research Methodology to analyze responses from 14 African American men (MdnAge = 25 years-old) in graduate school at a predominantly-White university in the Midwestern region of the United Sates regarding how they acquired awareness of their social-class status; how social class was related to their sense of masculinity; how social class was related to race and skin tone; and the role that education and a romantic partner could play in upward mobility. School peers were the main source for their early awareness of social class. Many believed that discrimination maintains social class stratification that disadvantages racial minorities and that one's race will always trump any personal characteristics—including having light-complected skin and an advanced degree. Finally many overcame several obstacles during their educational career, and most believed that a romantic relationship with a woman from a privileged background could facilitate upward mobility. Psychological scientists and practitioners are encouraged to consider the role that social class plays when examining men's well-being. PMID:22058659

  13. Universality class of the two-dimensional polymer collapse transition

    NASA Astrophysics Data System (ADS)

    Nahum, Adam

    2016-05-01

    The nature of the θ point for a polymer in two dimensions has long been debated, with a variety of candidates put forward for the critical exponents. This includes those derived by Duplantier and Saleur for an exactly solvable model. We use a representation of the problem via the CPN -1σ model in the limit N →1 to determine the stability of this critical point. First we prove that the Duplantier-Saleur (DS) critical exponents are robust, so long as the polymer does not cross itself: They can arise in a generic lattice model and do not require fine-tuning. This resolves a longstanding theoretical question. We also address an apparent paradox: Two different lattice models, apparently both in the DS universality class, show different numbers of relevant perturbations, apparently leading to contradictory conclusions about the stability of the DS exponents. We explain this in terms of subtle differences between the two models, one of which is fine-tuned (and not strictly in the DS universality class). Next we allow the polymer to cross itself, as appropriate, e.g., to the quasi-two-dimensional case. This introduces an additional independent relevant perturbation, so we do not expect the DS exponents to apply. The exponents in the case with crossings will be those of the generic tricritical O (n ) model at n =0 and different from the case without crossings. We also discuss interesting features of the operator content of the CPN -1 model. Simple geometrical arguments show that two operators in this field theory, with very different symmetry properties, have the same scaling dimension for any value of N (or, equivalently, any value of the loop fugacity). Also we argue that for any value of N the CPN -1 model has a marginal odd-parity operator that is related to the winding angle.

  14. Facial soft tissue thickness differences among three skeletal classes in Japanese population.

    PubMed

    Utsuno, Hajime; Kageyama, Toru; Uchida, Keiichi; Kibayashi, Kazuhiko

    2014-03-01

    Facial reconstruction is used in forensic anthropology to recreate the face from unknown human skeletal remains, and to elucidate the antemortem facial appearance. This requires accurate assessment of the skull (age, sex, ancestry, etc.) and thickness data. However, additional information is required to reconstruct the face as the information obtained from the skull is limited. Here, we aimed to examine the information from the skull that is required for accurate facial reconstruction. The human facial profile is classified into 3 shapes: straight, convex, and concave. These facial profiles facilitate recognition of individuals. The skeletal classes used in orthodontics are classified according to these 3 facial types. We have previously reported the differences between Japanese females. In the present study, we applied this classification for facial tissue measurement, compared the differences in tissue depth of each skeletal class for both sexes in the Japanese population, and elucidated the differences between the skeletal classes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Lactation-Based Maternal Educational Immunity Crosses MHC Class I Barriers and Can Impart Th1 Immunity to Th2-Biased Recipients

    PubMed Central

    Ghosh, Mrinal K.; Muller, H. Konrad

    2017-01-01

    We have previously demonstrated lactational transfer of T cell–based immunity from dam to foster pup. In the short term, a significant part of transferred immunity is passive cellular immunity. However, as time progresses, this is replaced by what we have described as maternal educational immunity such that by young adulthood, all immune cells responding to a foster dam immunogen are the product of the foster pup’s thymus. To reduce confounding factors, this original demonstration used congenic/syngeneic dam and foster pup pairs. In this study, we investigated lactational transfer of immunity to Mycobacterium tuberculosis in MHC class I–mismatched animals, as well as from Th1-biased dams to Th2-biased foster pups. Using immunized C57BL/6J dams, lactational transfer to nonimmunized BALB/cJ foster pups resulted in much greater immunity than direct immunization in 5-wk-old pups (ex vivo assay of pup splenocytes). At this age, 82% of immunogen-responding cells in the pup spleen were produced through maternal educational immunity. FVB/NJ nonimmunized foster recipients had a greater number of maternal cells in the spleen and thymus but a much larger percentage was Foxp3+, resulting in equivalent immunity to direct immunization. Depletion of maternal Foxp3+ cells from pup splenocytes illustrated a substantial role for lactationally transferred dam regulatory T cells in suppression of the ex vivo response in FVB/NJ, but not BALB/cJ, recipients. We conclude that lactational transfer of immunity can cross MHC class I barriers and that Th1 immunity can be imparted to Th2-biased offspring; in some instances, it can be greater than that achieved by direct immunization. PMID:28747348

  16. ProXL (Protein Cross-Linking Database): A Platform for Analysis, Visualization, and Sharing of Protein Cross-Linking Mass Spectrometry Data

    PubMed Central

    2016-01-01

    ProXL is a Web application and accompanying database designed for sharing, visualizing, and analyzing bottom-up protein cross-linking mass spectrometry data with an emphasis on structural analysis and quality control. ProXL is designed to be independent of any particular software pipeline. The import process is simplified by the use of the ProXL XML data format, which shields developers of data importers from the relative complexity of the relational database schema. The database and Web interfaces function equally well for any software pipeline and allow data from disparate pipelines to be merged and contrasted. ProXL includes robust public and private data sharing capabilities, including a project-based interface designed to ensure security and facilitate collaboration among multiple researchers. ProXL provides multiple interactive and highly dynamic data visualizations that facilitate structural-based analysis of the observed cross-links as well as quality control. ProXL is open-source, well-documented, and freely available at https://github.com/yeastrc/proxl-web-app. PMID:27302480

  17. ProXL (Protein Cross-Linking Database): A Platform for Analysis, Visualization, and Sharing of Protein Cross-Linking Mass Spectrometry Data.

    PubMed

    Riffle, Michael; Jaschob, Daniel; Zelter, Alex; Davis, Trisha N

    2016-08-05

    ProXL is a Web application and accompanying database designed for sharing, visualizing, and analyzing bottom-up protein cross-linking mass spectrometry data with an emphasis on structural analysis and quality control. ProXL is designed to be independent of any particular software pipeline. The import process is simplified by the use of the ProXL XML data format, which shields developers of data importers from the relative complexity of the relational database schema. The database and Web interfaces function equally well for any software pipeline and allow data from disparate pipelines to be merged and contrasted. ProXL includes robust public and private data sharing capabilities, including a project-based interface designed to ensure security and facilitate collaboration among multiple researchers. ProXL provides multiple interactive and highly dynamic data visualizations that facilitate structural-based analysis of the observed cross-links as well as quality control. ProXL is open-source, well-documented, and freely available at https://github.com/yeastrc/proxl-web-app .

  18. Are white evangelical Protestants lower class? A partial test of church-sect theory.

    PubMed

    Schwadel, Philip

    2014-07-01

    Testing hypotheses derived from church-sect theory and contemporary research about changes in evangelical Protestants' social status, I use repeated cross-sectional survey data spanning almost four decades to examine changes in the social-class hierarchy of American religious traditions. While there is little change in the social-class position of white evangelical Protestants from the early 1970s to 2010, there is considerable change across birth cohorts. Results from hierarchical age-period-cohort models show: (1) robust, across-cohort declines in social-class differences between white evangelical Protestants and liberal Protestants, affiliates of "other" religions, and the unaffiliated, (2) stability in social-class differences between white evangelical Protestants and moderate, Pentecostal, and nondenominational Protestants, (3) moderate across-cohort growth in social-class differences between white evangelical Protestants and Catholics, and (4) these patterns vary across indicators of social class. The findings in this article provide partial support for church-sect theory as well as other theories of social change that emphasize the pivotal role of generations. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Spectroscopic Investigation of the Mechanisms Responsible for the Superior Stability of Hybrid Class 1/Class 2 CO 2 Sorbents: A New Class 4 Category

    DOE PAGES

    Wilfong, Walter Christopher; Kail, Brian W.; Jones, Christopher W.; ...

    2016-05-04

    Hybrid Class 1/Class 2 supported amine CO 2 sorbents demonstrate superior performance under practical steam conditions, yet their amine immobilization and stabilization mechanisms are unclear. Uncovering the interactions responsible for the sorbents’ robust features is critical for further improvements and can facilitate practical applications. We employ solid state 29Si CP-MAS and 2-D FSLG 1H– 13C CP HETCOR NMR spectroscopies to probe the overall molecular interactions of aminosilane/silica, polyamine [poly(ethylenimine), PEI]/silica, and hybrid aminosilane/PEI/silica sorbents. A unique, sequential impregnation sorbent preparation method is executed in a diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) setup to decouple amine binding mechanisms at themore » amine–silica interface from those within bulk amine layers. These mechanisms are correlated with each sorbents’ resistance to accelerated liquid H 2O and TGA steam treatments (H 2O stability) and to oxidative degradation (thermal stability). High percentages of CO 2 capture retained (PCR) and organic content retained (OCR) values after H 2O testing of N-(3-(trimethoxysilyl)propyl)ethylenediamine (TMPED)/PEI and (3-aminopropyl)trimethoxysilane (APTMS)/PEI hybrid sorbents are associated with a synergistic stabilizing effect of the amine species observed during oxidative degradation (thermal gravimetric analysis-differential scanning calorimetry, TGA-DSC). Solid state NMR spectroscopy reveals that the synergistic effect of the TMPED/PEI mixture is manifested by the formation of hydrogen-bonded PEI–NH 2···NH 2–TMPED and PEI–NH 2···HO–Si/O–Si–O (TMPED, T 2) linkages within the sorbent. DRIFTS further determines that PEI enhances the grafting of TMPED to silica and that PEI is dispersed among a stable network of polymerized TMPED in the bulk, utilizing H-bonded linkages. These findings provide the scientific basis for establishing a Class 4 category for aminosilane

  20. Barriers to oral health care amongst different social classes in India.

    PubMed

    Garcha, V; Shetiya, S H; Kakodkar, P

    2010-09-01

    To investigate and compare the influence of social and cultural factors as access barriers to oral health care amongst people from various social classes. A cross sectional survey in Pimpri, was conducted using a pilot tested 15 item-structured, close-ended and self-administered questionnaire. Two hundred and fifty people aged 35-45 years (50 participants each in five social classes as per British Registrar's General classification of occupation) were selected. The chi-square test was applied to check statistical differences between social classes at 5% level of significance. Overall, it was observed that irrespective of the social class difference 88% participants wished to seek only expert/professional advice for the dental treatment. Unavailability of services on Sunday (63%), going to dentist only when in pain (57%), trying self care or home remedy (54%), inadequate government policies (50%), budgetary constraints (40%) were among the major access barriers. Statistically significant difference in the access barriers among the social classes were found related to: Inadequate government policies, budgetary constraints, appointment schedules, far-off located clinics, myths and fear about dental treatment. Social and cultural factors act as access barriers to oral health care and social class differences have a significant influence on the access barriers.

  1. Understanding Facilitation: Theory and Principles.

    ERIC Educational Resources Information Center

    Hogan, Christine

    This book introduces newcomers to the concept of facilitation, and it presents a critical analysis of established and current theory on facilitation for existing practitioners. The following are among the topics discussed: (1) emergence of the field of facilitation; (2) development of facilitation in management; (3) development of facilitation in…

  2. Mediator links transcription and DNA repair by facilitating Rad2/XPG recruitment.

    PubMed

    Eyboulet, Fanny; Cibot, Camille; Eychenne, Thomas; Neil, Helen; Alibert, Olivier; Werner, Michel; Soutourina, Julie

    2013-12-01

    Mediator is a large multiprotein complex conserved in all eukaryotes. The crucial function of Mediator in transcription is now largely established. However, we found that this complex also plays an important role by connecting transcription with DNA repair. We identified a functional contact between the Med17 Mediator subunit and Rad2/XPG, the 3' endonuclease involved in nucleotide excision DNA repair. Genome-wide location analyses revealed that Rad2 is associated with RNA polymerase II (Pol II)- and Pol III-transcribed genes and telomeric regions in the absence of exogenous genotoxic stress. Rad2 occupancy of Pol II-transcribed genes is transcription-dependent. Genome-wide Rad2 occupancy of class II gene promoters is well correlated with that of Mediator. Furthermore, UV sensitivity of med17 mutants is correlated with reduced Rad2 occupancy of class II genes and concomitant decrease of Mediator interaction with Rad2 protein. Our results suggest that Mediator is involved in DNA repair by facilitating Rad2 recruitment to transcribed genes.

  3. Wall-crossing in coupled 2d-4d systems

    NASA Astrophysics Data System (ADS)

    Gaiotto, Davide; Moore, Gregory W.; Neitzke, Andrew

    2012-12-01

    We introduce a new wall-crossing formula which combines and generalizes the Cecotti-Vafa and Kontsevich-Soibelman formulas for supersymmetric 2d and 4d systems respectively. This 2d-4d wall-crossing formula governs the wall-crossing of BPS states in an {N}=2 supersymmetric 4d gauge theory coupled to a supersymmetric surface defect. When the theory and defect are compactified on a circle, we get a 3d theory with a supersymmetric line operator, corresponding to a hyperholomorphic connection on a vector bundle over a hyperkähler space. The 2d-4d wall-crossing formula can be interpreted as a smoothness condition for this hyperholomorphic connection. We explain how the 2d-4d BPS spectrum can be determined for 4d theories of class {S} , that is, for those theories obtained by compactifying the six-dimensional (0, 2) theory with a partial topological twist on a punctured Riemann surface C. For such theories there are canonical surface defects. We illustrate with several examples in the case of A 1 theories of class {S} . Finally, we indicate how our results can be used to produce solutions to the A 1 Hitchin equations on the Riemann surface C.

  4. Barriers and Facilitators of Utilizing Research Among Nurses in Nepal.

    PubMed

    Kc, Srijana; Subramaniam, Prithwi Raj; Paudel, Sarita

    2016-04-01

    This study determined the perceived barriers to and facilitators of Nepalese nurses in utilizing research in the workplace. Evidence-based nursing practice provides the synergy for high-quality patient care, but it does not seem to be the case in underdeveloped countries, such as Nepal. A descriptive, cross-sectional study involving 97 nurses from Nepal was conducted. Data were collected using the BARRIERS Scale and a facilitator questionnaire. The top three barriers to research utilization in Nepalese nurses are (a) research reports and articles are not readily available (80.5%), (b) inadequate facilities for implementation (75.3%), and (c) research reports and articles are not published fast enough (71.6%). The top three facilitators perceived to encourage Nepalese nurses to utilize or participate in research are (a) initiation of nursing research projects (27.4%), (b) educational update on research methods (16.7%), and (c) provision of funding for research (15.5%). Findings from this study mirror the barriers to research utilization experienced by nurses in other countries. Macro- and micro-level support are needed to foster a culture of evidence-based practice among Nepalese nurses to empower them in making informed decisions based on research in providing quality patient care. Copyright 2016, SLACK Incorporated.

  5. Non-surgical Management of Skeletal Class III Malocclusion with Bilateral Posterior Crossbite: A Case Report.

    PubMed

    Kumari, Lalima; Nayan, Kamal

    2016-12-01

    A 16-year-old female patient with skeletal Class III malocclusion and bilateral posterior cross bite complaining of difficulty in chewing was treated orthodontically without surgery (camouflage treatment). The treatment comprised of fixed orthodontic treatment with MBT prescription (0.022˝×0.028˝ slot) using quad helix appliance for bilateral expansion of maxillary arch and Class III elastics for occlusal correction. Post-treatment records showed normal overbite and overjet with acceptable occlusion. So with this treatment strategy of expanding the maxillary arch using a quad helix appliance and use of Class III elastics, we achieved a good result with optimal occlusion.

  6. Training at non-damaging intensities facilitates recovery from muscle atrophy.

    PubMed

    Itoh, Yuta; Murakami, Taro; Mori, Tomohiro; Agata, Nobuhide; Kimura, Nahoko; Inoue-Miyazu, Masumi; Hayakawa, Kimihide; Hirano, Takayuki; Sokabe, Masahiro; Kawakami, Keisuke

    2017-02-01

    Resistance training promotes recovery from muscle atrophy, but optimum training programs have not been established. We aimed to determine the optimum training intensity for muscle atrophy. Mice recovering from atrophied muscles after 2 weeks of tail suspension underwent repeated isometric training with varying joint torques 50 times per day. Muscle recovery assessed by maximal isometric contraction and myofiber cross-sectional areas (CSAs) were facilitated at 40% and 60% maximum contraction strength (MC), but at not at 10% and 90% MC. At 60% and 90% MC, damaged and contained smaller diameter fibers were observed. Activation of myogenic satellite cells and a marked increase in myonuclei were observed at 40%, 60%, and 90% MC. The increases in myofiber CSAs were likely caused by increased myonuclei formed through fusion of resistance-induced myofibers with myogenic satellite cells. These data indicate that resistance training without muscle damage facilitates efficient recovery from atrophy. Muscle Nerve 55: 243-253, 2017. © 2016 Wiley Periodicals, Inc.

  7. Exploring social class: voices of inter-class couples.

    PubMed

    McDowell, Teresa; Melendez-Rhodes, Tatiana; Althusius, Erin; Hergic, Sara; Sleeman, Gillian; Ton, Nicky Kieu My; Zimpfer-Bak, A J

    2013-01-01

    Social class is not often discussed or examined in-depth in couple and family therapy research and literature even though social class shapes familial relationships and is considered an important variable in marital satisfaction. In this qualitative study, we explored the perceptions of eight couples who made lasting commitments across class lines by asking them about the impact of their social class backgrounds on their relationships. Three categories of themes emerged including: (a) differences and similarities in values and attitudes toward education, work, money, and class awareness/classism, (b) relationship issues involving families of origin, friends, and class-based couple conflict, and (c) differences in economic resources, social capital and privileges/opportunities. Implications for assessment and treatment of couples are included. © 2012 American Association for Marriage and Family Therapy.

  8. The effects of stream crossings on total suspended sediment in North Carolina Piedmont forests

    Treesearch

    Johnny Boggs; Ge Sun; Steve McNulty

    2017-01-01

    This study determined total suspended sediment (TSS) at six stream crossings that represented a range of site conditions and forest operations in the Piedmont of North Carolina. Two wood and three steel bridgemats and one culvert were installed to cross the streams. The road classes for the crossings included four temporary skid trails and two permanent forest haul...

  9. Progressive Elaboration and Cross-Validation of a Latent Class Typology of Adolescent Alcohol Involvement in a National Sample

    PubMed Central

    Donovan, John E.; Chung, Tammy

    2015-01-01

    Objective: Most studies of adolescent drinking focus on single alcohol use behaviors (e.g., high-volume drinking, drunkenness) and ignore the patterning of adolescents’ involvement across multiple alcohol behaviors. The present latent class analyses (LCAs) examined a procedure for empirically determining multiple cut points on the alcohol use behaviors in order to establish a typology of adolescent alcohol involvement. Method: LCA was carried out on six alcohol use behavior indicators collected from 6,504 7th through 12th graders who participated in Wave I of the National Longitudinal Study of Adolescent Health (AddHealth). To move beyond dichotomous indicators, a “progressive elaboration” strategy was used, starting with six dichotomous indicators and then evaluating a series of models testing additional cut points on the ordinal indicators at progressively higher points for one indicator at a time. Analyses were performed on one random half-sample, and confirmatory LCAs were performed on the second random half-sample and in the Wave II data. Results: The final model consisted of four latent classes (never or non–current drinkers, low-intake drinkers, non–problem drinkers, and problem drinkers). Confirmatory LCAs in the second random half-sample from Wave I and in Wave II support this four-class solution. The means on the four latent classes were also generally ordered on an array of measures reflecting psychosocial risk for problem behavior. Conclusions: These analyses suggest that there may be four different classes or types of alcohol involvement among adolescents, and, more importantly, they illustrate the utility of the progressive elaboration strategy for moving beyond dichotomous indicators in latent class models. PMID:25978828

  10. Observing golden-mean universality class in the scaling of thermal transport.

    PubMed

    Xiong, Daxing

    2018-02-01

    We address the issue of whether the golden-mean [ψ=(sqrt[5]+1)/2≃1.618] universality class, as predicted by several theoretical models, can be observed in the dynamical scaling of thermal transport. Remarkably, we show strong evidence that ψ appears to be the scaling exponent of heat mode correlation in a purely quartic anharmonic chain. This observation seems to somewhat deviate from the previous expectation and we explain it by the unusual slow decay of the cross correlation between heat and sound modes. Whenever the cubic anharmonicity is included, this cross correlation gradually dies out and another universality class with scaling exponent γ=5/3, as commonly predicted by theories, seems recovered. However, this recovery is accompanied by two interesting phase transition processes characterized by a change of symmetry of the potential and a clear variation of the dynamic structure factor, respectively. Due to these transitions, an additional exponent close to γ≃1.580 emerges. All this evidence suggests that, to gain a full prediction of the scaling of thermal transport, more ingredients should be taken into account.

  11. Observing golden-mean universality class in the scaling of thermal transport

    NASA Astrophysics Data System (ADS)

    Xiong, Daxing

    2018-02-01

    We address the issue of whether the golden-mean [ψ =(√{5 }+1 ) /2 ≃1.618 ] universality class, as predicted by several theoretical models, can be observed in the dynamical scaling of thermal transport. Remarkably, we show strong evidence that ψ appears to be the scaling exponent of heat mode correlation in a purely quartic anharmonic chain. This observation seems to somewhat deviate from the previous expectation and we explain it by the unusual slow decay of the cross correlation between heat and sound modes. Whenever the cubic anharmonicity is included, this cross correlation gradually dies out and another universality class with scaling exponent γ =5 /3 , as commonly predicted by theories, seems recovered. However, this recovery is accompanied by two interesting phase transition processes characterized by a change of symmetry of the potential and a clear variation of the dynamic structure factor, respectively. Due to these transitions, an additional exponent close to γ ≃1.580 emerges. All this evidence suggests that, to gain a full prediction of the scaling of thermal transport, more ingredients should be taken into account.

  12. MFV-class: a multi-faceted visualization tool of object classes.

    PubMed

    Zhang, Zhi-meng; Pan, Yun-he; Zhuang, Yue-ting

    2004-11-01

    Classes are key software components in an object-oriented software system. In many industrial OO software systems, there are some classes that have complicated structure and relationships. So in the processes of software maintenance, testing, software reengineering, software reuse and software restructure, it is a challenge for software engineers to understand these classes thoroughly. This paper proposes a class comprehension model based on constructivist learning theory, and implements a software visualization tool (MFV-Class) to help in the comprehension of a class. The tool provides multiple views of class to uncover manifold facets of class contents. It enables visualizing three object-oriented metrics of classes to help users focus on the understanding process. A case study was conducted to evaluate our approach and the toolkit.

  13. Detection of Pesticides and Pesticide Metabolites Using the Cross Reactivity of Enzyme Immunoassays

    USGS Publications Warehouse

    Thurman, E.M.; Aga, D.S.

    2001-01-01

    Enzyme immunoassay is an important environmental analysis method that may be used to identify many pesticide analytes in water samples. Because of similarities in chemical structure between various members of a pesticide class, there often may be an unwanted response that is characterized by a percentage of cross reactivity. Also, there may be cross reactivity caused by degradation products of the target analyte that may be present in the sample. In this paper, the concept of cross reactivity caused by degradation products or by nontarget analytes is explored as a tool for identification of metabolites or structurally similar compounds not previously known to be present in water samples. Two examples are examined in this paper from various water quality studies. They are alachlor and its metabolite, alachlor ethane sulfonic acid, and atrazine and its class members, prometryn and propazine. A method for using cross reactivity for the detection of these compounds is explained in this paper.

  14. Dance is more than therapy: Qualitative analysis on therapeutic dancing classes for Parkinson's.

    PubMed

    Rocha, Priscila A; Slade, Susan C; McClelland, Jodie; Morris, Meg E

    2017-10-01

    To understand the benefits and limitations of therapeutic dancing classes for people with Parkinson's disease (PD) and how best to design and implement classes. A stakeholder forum explored the opinions of 18 allied health clinicians, dance instructors, people with PD and caregivers. Data were thematically analysed and interpreted within a grounded theory framework. Four main themes were identified: (1) the need to consider the stage of disease progression when designing classes; (2) recognition that dance is more than just therapy; (3) the benefits of carefully selecting music to move by; (4) ways to design classes that are both feasible and engaging. These themes give rise to the theory that dancing classes can provide more than just therapeutic benefits. Dance affords creative expression and enables people to immerse themselves in the art-form, rather than focussing on the disease. The results highlight the benefits of enabling individuals with PD to be able to express themselves in a supportive environment that does not see them solely through the lens of Parkinson's. The feasibility of dance programs can be increased by educating dancing teachers about PD and the unique needs of people living with this condition. Well-structured dance classes can promote social-connectedness and joy, in addition to facilitating movement to music and physical activity. Consumers advised that careful planning of the classes and tailoring them to participant needs optimizes outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. A benefit-risk assessment of class III antiarrhythmic agents.

    PubMed

    Brendorp, Bente; Pedersen, Oledyg; Torp-Pedersen, Christian; Sahebzadah, Naji; Køber, Lars

    2002-01-01

    With beta-blockers as the exception, increasing doubt is emerging on the value of antiarrhythmic drug therapy following a series of trials that have either shown no mortality benefit or even an excess mortality. Vaughan Williams class I drugs are generally avoided in patients with structural heart disease, and class IV drugs are avoided in heart failure. Unfortunately, arrhythmias are a growing problem due to an increase in the incidence of atrial fibrillation and sudden death. The population is becoming older and more patients survive for a longer time period with congestive heart failure, which again increases the frequency of both supraventricular as well as ventricular arrhythmias. Class III antiarrhythmic drugs act by blocking repolarising currents and thereby prolong the effective refractory period of the myocardium. This is believed to facilitate termination of re-entry tachyarrhythmias. This class of drugs is developed for treatment of both supraventricular and ventricular arrhythmias. Amiodarone, sotalol, dofetilide, and ibutilide are examples of class III drugs that are currently available. Amiodarone and sotalol have other antiarrhythmic properties in addition to pure class III action, which differentiates them from the others. However, all have potential serious adverse events. Proarrhythmia, especially torsade de pointes, is a common problem making the benefit-risk ratio of these drugs a key question. Class III drugs have been evaluated in different settings: primary and secondary prevention of ventricular arrhythmias and in treatment of atrial fibrillation or flutter. Based on existing evidence there is no routine indication for antiarrhythmic drug therapy other than beta-blockers in patients at high risk of sudden death. Subgroup analyses of trials with amiodarone and dofetilide suggest that patients with atrial fibrillation may have a mortality reduction with these drugs. However, this needs to be tested in a prospective trial. Similarly, subgroups

  16. Four classes of interactions for evolutionary games.

    PubMed

    Szabó, György; Bodó, Kinga S; Allen, Benjamin; Nowak, Martin A

    2015-08-01

    The symmetric four-strategy games are decomposed into a linear combination of 16 basis games represented by orthogonal matrices. Among these basis games four classes can be distinguished as it is already found for the three-strategy games. The games with self-dependent (cross-dependent) payoffs are characterized by matrices consisting of uniform rows (columns). Six of 16 basis games describe coordination-type interactions among the strategy pairs and three basis games span the parameter space of the cyclic components that are analogous to the rock-paper-scissors games. In the absence of cyclic components the game is a potential game and the potential matrix is evaluated. The main features of the four classes of games are discussed separately and we illustrate some characteristic strategy distributions on a square lattice in the low noise limit if logit rule controls the strategy evolution. Analysis of the general properties indicates similar types of interactions at larger number of strategies for the symmetric matrix games.

  17. Sounds can boost the awareness of visual events through attention without cross-modal integration.

    PubMed

    Pápai, Márta Szabina; Soto-Faraco, Salvador

    2017-01-31

    Cross-modal interactions can lead to enhancement of visual perception, even for visual events below awareness. However, the underlying mechanism is still unclear. Can purely bottom-up cross-modal integration break through the threshold of awareness? We used a binocular rivalry paradigm to measure perceptual switches after brief flashes or sounds which, sometimes, co-occurred. When flashes at the suppressed eye coincided with sounds, perceptual switches occurred the earliest. Yet, contrary to the hypothesis of cross-modal integration, this facilitation never surpassed the assumption of probability summation of independent sensory signals. A follow-up experiment replicated the same pattern of results using silent gaps embedded in continuous noise, instead of sounds. This manipulation should weaken putative sound-flash integration, although keep them salient as bottom-up attention cues. Additional results showed that spatial congruency between flashes and sounds did not determine the effectiveness of cross-modal facilitation, which was again not better than probability summation. Thus, the present findings fail to fully support the hypothesis of bottom-up cross-modal integration, above and beyond the independent contribution of two transient signals, as an account for cross-modal enhancement of visual events below level of awareness.

  18. A dual-mode highly efficient class-E stimulator controlled by a low-Q class-E power amplifier through duty cycle.

    PubMed

    Chiu, Hung-Wei; Lu, Chien-Chi; Chuang, Jia-min; Lin, Wei-Tso; Lin, Chii-Wann; Kao, Ming-Chien; Lin, Mu-Lien

    2013-06-01

    This paper presents the design flow of two high-efficiency class-E amplifiers for the implantable electrical stimulation system. The implantable stimulator is a high-Q class-E driver that delivers a sine-wave pulsed radiofrequency (PRF) stimulation, which was verified to have a superior efficacy in pain relief to a square wave. The proposed duty-cycle-controlled class-E PRF driver designed with a high-Q factor has two operational modes that are able to achieve 100% DC-AC conversion, and involves only one switched series inductor and an unchanged parallel capacitor. The measured output amplitude under low-voltage (LV) mode using a 22% duty cycle was 0.98 V with 91% efficiency, and under high-voltage (HV) mode using a 47% duty cycle was 2.95 V with 92% efficiency. These modes were inductively controlled by a duty-cycle detector, which can detect the duty-cycle modulated signal generated from the external complementary low-Q class-E power amplifier (PA). The design methodology of the low-Q inductive interface for a non-50% duty cycle is presented. The experimental results exhibits that the 1.5-V PA that consumes DC power of 14.21 mW was able to deliver a 2.9-V sine wave to a 500 Ω load. The optimal 60% drain efficiency of the system from the PA to the load was obtained at a 10-mm coupling distance.

  19. Facilitated versus Non-Facilitated Online Case Discussions: Comparing Differences in Problem Space Coverage

    ERIC Educational Resources Information Center

    Ertmer, Peggy A.; Koehler, Adrie A.

    2015-01-01

    The facilitator plays a key role in guiding students' efforts during case discussions. However, few studies have compared differences in learning outcomes for students participating in facilitated versus non-facilitated discussions. In this research, we used "problem space coverage" as a learning measure to compare outcomes between…

  20. Design for fish passage at roadway-stream crossings : synthesis report.

    DOT National Transportation Integrated Search

    2007-06-01

    Cataloging and synthesizing existing methods for the design of roadway-stream crossings for fish passage began in : January 2005 with an extensive literature review covering the topics of culvert design and assessment to facilitate : fish passage. A ...

  1. Barriers and facilitators to provide quality TIA care in the Veterans Healthcare Administration

    PubMed Central

    Miech, Edward J.; Sico, Jason J.; Phipps, Michael S.; Arling, Greg; Ferguson, Jared; Austin, Charles; Myers, Laura; Baye, Fitsum; Luckhurst, Cherie; Keating, Ava B.; Moran, Eileen; Bravata, Dawn M.

    2017-01-01

    Objective: To identify key barriers and facilitators to the delivery of guideline-based care of patients with TIA in the national Veterans Health Administration (VHA). Methods: We conducted a cross-sectional, observational study of 70 audiotaped interviews of multidisciplinary clinical staff involved in TIA care at 14 VHA hospitals. We de-identified and analyzed all transcribed interviews. We identified emergent themes and patterns of barriers to providing TIA care and of facilitators applied to overcome these barriers. Results: Identified barriers to providing timely acute and follow-up TIA care included difficulties accessing brain imaging, a constantly rotating pool of housestaff, lack of care coordination, resource constraints, and inadequate staff education. Key informants revealed that both stroke nurse coordinators and system-level factors facilitated the provision of TIA care. Few facilities had specific TIA protocols. However, stroke nurse coordinators often expanded upon their role to include TIA. They facilitated TIA care by (1) coordinating patient care across services, communicating across service lines, and educating clinical staff about facility policies and evidence-based practices; (2) tracking individual patients from emergency departments to inpatient settings and to discharge for timely follow-up care; (3) providing and referring TIA patients to risk factor management programs; and (4) performing regular audit and feedback of quality performance data. System-level facilitators included clinical service leadership engagement and use of electronic tools for continuous care across services. Conclusions: The local organization within a health care facility may be targeted to cultivate internal facilitators and a systemic infrastructure to provide evidence-based TIA care. PMID:29117959

  2. Implementation of integrated dual disorders treatment: a qualitative analysis of facilitators and barriers.

    PubMed

    Brunette, Mary F; Asher, Dianne; Whitley, Rob; Lutz, Wilma J; Wieder, Barbara L; Jones, Amanda M; McHugo, Gregory J

    2008-09-01

    Approximately half of the people who have serious mental illnesses experience a co-occurring substance use disorder at some point in their lifetime. Integrated dual disorders treatment, a program to treat persons with co-occurring disorders, improves outcomes but is not widely available in public mental health settings. This report describes the extent to which this intervention was implemented by 11 community mental health centers participating in a large study of practice implementation. Facilitators and barriers to implementation are described. Trained implementation monitors conducted regular site visits over two years. During visits, monitors interviewed key informants, conducted ethnographic observations of implementation efforts, and assessed fidelity to the practice model. These data were coded and used as a basis for detailed site reports summarizing implementation processes. The authors reviewed the reports and distilled the three top facilitators and barriers for each site. The most prominent cross-site facilitators and barriers were identified. Two sites reached high fidelity, six sites reached moderate fidelity, and three sites remained at low fidelity over the two years. Prominent facilitators and barriers to implementation with moderate to high fidelity were administrative leadership, consultation and training, supervisor mastery and supervision, chronic staff turnover, and finances. Common facilitators and barriers to implementation of integrated dual disorders treatment emerged across sites. The results confirmed the importance of the use of the consultant-trainer in the model of implementation, as well as the need for intensive activities at multiple levels to facilitate implementation. Further research on service implementation is needed, including but not limited to clarifying strategies to overcome barriers.

  3. Discourses of Volunteer/Service Work and Their Discontents: Border Crossing, Construction of Hierarchy, and Paying Dues

    ERIC Educational Resources Information Center

    Doerr, Neriko Musha

    2017-01-01

    This article examines four discourses of volunteer/service work--charity, leisure, citizenship, and border crossing--in terms of how they construct relationships between those who serve and those who are served. Specifically, it analyzes the discourse of border crossing, which assumes White middle-class students crossing a border to work in…

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

    PubMed Central

    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.

    2016-01-01

    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

  5. Cross-Link Guided Molecular Modeling with ROSETTA

    PubMed Central

    Leitner, Alexander; Rosenberger, George; Aebersold, Ruedi; Malmström, Lars

    2013-01-01

    Chemical cross-links identified by mass spectrometry generate distance restraints that reveal low-resolution structural information on proteins and protein complexes. The technology to reliably generate such data has become mature and robust enough to shift the focus to the question of how these distance restraints can be best integrated into molecular modeling calculations. Here, we introduce three workflows for incorporating distance restraints generated by chemical cross-linking and mass spectrometry into ROSETTA protocols for comparative and de novo modeling and protein-protein docking. We demonstrate that the cross-link validation and visualization software Xwalk facilitates successful cross-link data integration. Besides the protocols we introduce XLdb, a database of chemical cross-links from 14 different publications with 506 intra-protein and 62 inter-protein cross-links, where each cross-link can be mapped on an experimental structure from the Protein Data Bank. Finally, we demonstrate on a protein-protein docking reference data set the impact of virtual cross-links on protein docking calculations and show that an inter-protein cross-link can reduce on average the RMSD of a docking prediction by 5.0 Å. The methods and results presented here provide guidelines for the effective integration of chemical cross-link data in molecular modeling calculations and should advance the structural analysis of particularly large and transient protein complexes via hybrid structural biology methods. PMID:24069194

  6. A Cross-National Study of Secondary Science Classroom Environments in Australia and Indonesia

    ERIC Educational Resources Information Center

    Fraser, Barry J.; Aldridge, Jill M.; Adolphe, F. S. Gerard

    2010-01-01

    This article reports a cross-national study of classroom environments in Australia and Indonesia. A modified version of the What Is Happening In this Class? (WIHIC) questionnaire was used simultaneously in these two countries to: 1) cross validate the modified WIHIC; 2) investigate differences between countries and sexes in perceptions of…

  7. ISW-galaxy cross-correlation in K-mouflage

    NASA Astrophysics Data System (ADS)

    Benevento, G.; Bartolo, N.; Liguori, M.

    2018-01-01

    Cross-correlations between the cosmic microwave background and the galaxy distribution can probe the linear growth rate of cosmic structures, thus providing a powerful tool to investigate different Dark Energy and Modified Gravity models. We explore the possibility of using this observable to probe a particular class of Modified Gravity models, called K-mouflage.

  8. Joint use of over- and under-sampling techniques and cross-validation for the development and assessment of prediction models.

    PubMed

    Blagus, Rok; Lusa, Lara

    2015-11-04

    Prediction models are used in clinical research to develop rules that can be used to accurately predict the outcome of the patients based on some of their characteristics. They represent a valuable tool in the decision making process of clinicians and health policy makers, as they enable them to estimate the probability that patients have or will develop a disease, will respond to a treatment, or that their disease will recur. The interest devoted to prediction models in the biomedical community has been growing in the last few years. Often the data used to develop the prediction models are class-imbalanced as only few patients experience the event (and therefore belong to minority class). Prediction models developed using class-imbalanced data tend to achieve sub-optimal predictive accuracy in the minority class. This problem can be diminished by using sampling techniques aimed at balancing the class distribution. These techniques include under- and oversampling, where a fraction of the majority class samples are retained in the analysis or new samples from the minority class are generated. The correct assessment of how the prediction model is likely to perform on independent data is of crucial importance; in the absence of an independent data set, cross-validation is normally used. While the importance of correct cross-validation is well documented in the biomedical literature, the challenges posed by the joint use of sampling techniques and cross-validation have not been addressed. We show that care must be taken to ensure that cross-validation is performed correctly on sampled data, and that the risk of overestimating the predictive accuracy is greater when oversampling techniques are used. Examples based on the re-analysis of real datasets and simulation studies are provided. We identify some results from the biomedical literature where the incorrect cross-validation was performed, where we expect that the performance of oversampling techniques was heavily

  9. Architecture of Eph receptor clusters

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Himanen, Juha P.; Yermekbayeva, Laila; Janes, Peter W.

    2010-10-04

    Eph receptor tyrosine kinases and their ephrin ligands regulate cell navigation during normal and oncogenic development. Signaling of Ephs is initiated in a multistep process leading to the assembly of higher-order signaling clusters that set off bidirectional signaling in interacting cells. However, the structural and mechanistic details of this assembly remained undefined. Here we present high-resolution structures of the complete EphA2 ectodomain and complexes with ephrin-A1 and A5 as the base unit of an Eph cluster. The structures reveal an elongated architecture with novel Eph/Eph interactions, both within and outside of the Eph ligand-binding domain, that suggest the molecular mechanismmore » underlying Eph/ephrin clustering. Structure-function analysis, by using site-directed mutagenesis and cell-based signaling assays, confirms the importance of the identified oligomerization interfaces for Eph clustering.« less

  10. Common Mental Disorders among Occupational Groups: Contributions of the Latent Class Model

    PubMed Central

    Martins Carvalho, Fernando; de Araújo, Tânia Maria

    2016-01-01

    Background. The Self-Reporting Questionnaire (SRQ-20) is widely used for evaluating common mental disorders. However, few studies have evaluated the SRQ-20 measurements performance in occupational groups. This study aimed to describe manifestation patterns of common mental disorders symptoms among workers populations, by using latent class analysis. Methods. Data derived from 9,959 Brazilian workers, obtained from four cross-sectional studies that used similar methodology, among groups of informal workers, teachers, healthcare workers, and urban workers. Common mental disorders were measured by using SRQ-20. Latent class analysis was performed on each database separately. Results. Three classes of symptoms were confirmed in the occupational categories investigated. In all studies, class I met better criteria for suspicion of common mental disorders. Class II discriminated workers with intermediate probability of answers to the items belonging to anxiety, sadness, and energy decrease that configure common mental disorders. Class III was composed of subgroups of workers with low probability to respond positively to questions for screening common mental disorders. Conclusions. Three patterns of symptoms of common mental disorders were identified in the occupational groups investigated, ranging from distinctive features to low probabilities of occurrence. The SRQ-20 measurements showed stability in capturing nonpsychotic symptoms. PMID:27630999

  11. Listeria monocytogenes InlP interacts with afadin and facilitates basement membrane crossing.

    PubMed

    Faralla, Cristina; Bastounis, Effie E; Ortega, Fabian E; Light, Samuel H; Rizzuto, Gabrielle; Nocadello, Salvatorre; Anderson, Wayne F; Robbins, Jennifer R; Theriot, Julie A; Bakardjiev, Anna I

    2018-05-30

    During pregnancy, the placenta protects the fetus against the maternal immune response, as well as bacterial and viral pathogens. Bacterial pathogens that have evolved specific mechanisms of breaching this barrier, such as Listeria monocytogenes, present a unique opportunity for learning how the placenta carries out its protective function. We previously identified the L. monocytogenes protein Internalin P (InlP) as a secreted virulence factor critical for placental infection. Here, we show that InlP, but not the highly similar L. monocytogenes internalin Lmo2027, binds to human afadin (encoded by AF-6), a protein associated with cell-cell junctions. A crystal structure of InlP reveals several unique features, including an extended leucine-rich repeat (LRR) domain with a distinctive Ca2+-binding site. Despite afadin's involvement in the formation of cell-cell junctions, MDCK epithelial cells expressing InlP displayed a decrease in the magnitude of the traction stresses they could exert on deformable substrates, similar to the decrease in traction exhibited by AF-6 knock-out MDCK cells. L. monocytogenes ΔinlP mutants were deficient in their ability to form actin-rich protrusions from the basal face of polarized epithelial monolayers, a necessary step in the crossing of such monolayers (transcytosis). A similar phenotype was observed for bacteria expressing an internal in-frame deletion in inlP (inlP ΔLRR5) that specifically disrupts its interaction with afadin. However, afadin deletion in the host cells did not rescue the transcytosis defect. We conclude that secreted InlP targets cytosolic afadin to specifically promote L. monocytogenes transcytosis across the basal face of epithelial monolayers, which may contribute to the crossing of the basement membrane during placental infection.

  12. 47 CFR 73.25 - Clear channels; Class A, Class B and Class D stations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., 770, 780, 820, 830, 840, 870, 880, 890, 1020, 1030, 1040, 1100, 1120, 1160, 1180, 1200, and 1210 kHz..., 1530, 1540, 1550, and 1560 kHz. Note: Until superseded by a new agreement, protection of the Bahama Islands shall be in accordance with NARBA. Accordingly, a Class A, Class B or Class D station on 1540 kHz...

  13. 47 CFR 73.25 - Clear channels; Class A, Class B and Class D stations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., 770, 780, 820, 830, 840, 870, 880, 890, 1020, 1030, 1040, 1100, 1120, 1160, 1180, 1200, and 1210 kHz..., 1530, 1540, 1550, and 1560 kHz. Note: Until superseded by a new agreement, protection of the Bahama Islands shall be in accordance with NARBA. Accordingly, a Class A, Class B or Class D station on 1540 kHz...

  14. 47 CFR 73.25 - Clear channels; Class A, Class B and Class D stations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., 770, 780, 820, 830, 840, 870, 880, 890, 1020, 1030, 1040, 1100, 1120, 1160, 1180, 1200, and 1210 kHz..., 1530, 1540, 1550, and 1560 kHz. Note: Until superseded by a new agreement, protection of the Bahama Islands shall be in accordance with NARBA. Accordingly, a Class A, Class B or Class D station on 1540 kHz...

  15. 47 CFR 73.25 - Clear channels; Class A, Class B and Class D stations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., 770, 780, 820, 830, 840, 870, 880, 890, 1020, 1030, 1040, 1100, 1120, 1160, 1180, 1200, and 1210 kHz..., 1530, 1540, 1550, and 1560 kHz. Note: Until superseded by a new agreement, protection of the Bahama Islands shall be in accordance with NARBA. Accordingly, a Class A, Class B or Class D station on 1540 kHz...

  16. 47 CFR 73.25 - Clear channels; Class A, Class B and Class D stations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., 770, 780, 820, 830, 840, 870, 880, 890, 1020, 1030, 1040, 1100, 1120, 1160, 1180, 1200, and 1210 kHz..., 1530, 1540, 1550, and 1560 kHz. Note: Until superseded by a new agreement, protection of the Bahama Islands shall be in accordance with NARBA. Accordingly, a Class A, Class B or Class D station on 1540 kHz...

  17. Drug carrier systems for solubility enhancement of BCS class II drugs: a critical review.

    PubMed

    Kumar, Sumit; Bhargava, Deepak; Thakkar, Arti; Arora, Saahil

    2013-01-01

    Poor aqueous solubility impedes a drug's bioavailability and challenges its pharmaceutical development. Pharmaceutical development of drugs with poor water solubility requires the establishment of a suitable formulation layout among various techniques. Various approaches have been investigated extensively to improve the aqueous solubility and poor dissolution rate of BCS class II and IV drugs. In this literature review, novel formulation options, particularly for class II drugs designed for applications such as micronization, self-emulsification, cyclodextrin complexation, co-crystallisation, super critical fluid technology, solubilisation by change in pH, salt formation, co-solvents, melt granulation, and solid dispersion, liposomal/niosomal formulations, are discussed in detail to introduce biopharmaceutical challenges and recent approaches to facilitate more efficient drug formulation and development.

  18. Safety assessment of plant varieties using transcriptomics profiling and a one-class classifier.

    PubMed

    van Dijk, Jeroen P; de Mello, Carla Souza; Voorhuijzen, Marleen M; Hutten, Ronald C B; Arisi, Ana Carolina Maisonnave; Jansen, Jeroen J; Buydens, Lutgarde M C; van der Voet, Hilko; Kok, Esther J

    2014-10-01

    An important part of the current hazard identification of novel plant varieties is comparative targeted analysis of the novel and reference varieties. Comparative analysis will become much more informative with unbiased analytical approaches, e.g. omics profiling. Data analysis estimating the similarity of new varieties to a reference baseline class of known safe varieties would subsequently greatly facilitate hazard identification. Further biological and eventually toxicological analysis would then only be necessary for varieties that fall outside this reference class. For this purpose, a one-class classifier tool was explored to assess and classify transcriptome profiles of potato (Solanum tuberosum) varieties in a model study. Profiles of six different varieties, two locations of growth, two year of harvest and including biological and technical replication were used to build the model. Two scenarios were applied representing evaluation of a 'different' variety and a 'similar' variety. Within the model higher class distances resulted for the 'different' test set compared with the 'similar' test set. The present study may contribute to a more global hazard identification of novel plant varieties. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Cross-cultural communication and use of the family meeting in palliative care.

    PubMed

    Sharma, Rashmi K; Dy, Sydney M

    2011-09-01

    Terminally-ill patients and their families often report poor communication and limited understanding of the patient's diagnosis, prognosis, and treatment plan; these deficits can be exacerbated by cross-cultural issues. Although family meetings are frequently recommended to facilitate provider-family communication, a more structured, evidence-based approach to their use may improve outcomes. Drawing on research and guidelines from critical care, palliative care, and cross-cultural communication, we propose a framework for conducting family meetings with consideration for cross-cultural issues.

  20. Organizational and physician perspectives about facilitating handheld computer use in clinical practice: results of a cross-site qualitative study.

    PubMed

    McAlearney, Ann Scheck; Schweikhart, Sharon B; Medow, Mitchell A

    2005-01-01

    To describe strategies that organizations select to support physicians' use of handheld computers (HHCs) in clinical practice and to explore issues about facilitating HHC use. A multidisciplinary team used focus groups and interviews with clinical, administrative, and information technology (IT) staff to gather data from 161 informants at seven sites. Transcripts were coded using a combination of deductive and inductive approaches to both answer research questions and identify patterns and themes that emerged in the data. Answers to questions about strategies for HHC support and themes about (1) how to facilitate physician adoption and use and (2) organizational concerns. Three main organizational strategies for HHC support were characterized among sites: (1) active support for broad-based use, (2) active support for niche use, and (3) basic support for individual physician users. Three high-level themes emerged around how to best facilitate physician adoption and use of HHCs: (1) improving usability and usefulness, (2) promoting HHCs and device use, and (3) providing training and support. However, four major themes also emerged related to organizations' concerns about HHC use: (1) security-related concerns, (2) economic concerns, (3) technical concerns, and (4) strategic concerns. An organizational approach to HHC support that involves individualized attention to existing and potential physician users rather than one-size-fits-all, organization-wide implementation efforts was an important facilitator promoting physician use of HHCs. Health care organizations interested in supporting HHC use must consider issues related to security, economics, and IT strategy that may not be prominent concerns for physician users.

  1. The Impact of HLA Class I-Specific Killer Cell Immunoglobulin-Like Receptors on Antibody-Dependent Natural Killer Cell-Mediated Cytotoxicity and Organ Allograft Rejection.

    PubMed

    Rajalingam, Raja

    2016-01-01

    Natural killer (NK) cells of the innate immune system are cytotoxic lymphocytes that play an important roles following transplantation of solid organs and hematopoietic stem cells. Recognition of self-human leukocyte antigen (HLA) class I molecules by inhibitory killer cell immunoglobulin-like receptors (KIRs) is involved in the calibration of NK cell effector capacities during the developmental stage, allowing the subsequent recognition and elimination of target cells with decreased expression of self-HLA class I (due to virus infection or tumor transformation) or HLA class I disparities (in the setting of allogeneic transplantation). NK cells expressing an inhibitory KIR-binding self-HLA can be activated when confronted with allografts lacking a ligand for the inhibitory receptor. Following the response of the adaptive immune system, NK cells can further destroy allograft endothelium by antibody-dependent cell-mediated cytotoxicity (ADCC), triggered through cross-linking of the CD16 Fc receptor by donor-specific antibodies bound to allograft. Upon recognizing allogeneic target cells, NK cells also secrete cytokines and chemokines that drive maturation of dendritic cells to promote cellular and humoral adaptive immune responses against the allograft. The cumulative activating and inhibitory signals generated by ligation of the receptors regulates mature NK cell killing of target cells and their production of cytokines and chemokines. This review summarizes the role of NK cells in allograft rejection and proposes mechanistic concepts that indicate a prominent role for KIR-HLA interactions in facilitating NK cells for Fc receptor-mediated ADCC effector function involved in antibody-mediated rejection of solid organ transplants.

  2. The Impact of HLA Class I-Specific Killer Cell Immunoglobulin-Like Receptors on Antibody-Dependent Natural Killer Cell-Mediated Cytotoxicity and Organ Allograft Rejection

    PubMed Central

    Rajalingam, Raja

    2016-01-01

    Natural killer (NK) cells of the innate immune system are cytotoxic lymphocytes that play an important roles following transplantation of solid organs and hematopoietic stem cells. Recognition of self-human leukocyte antigen (HLA) class I molecules by inhibitory killer cell immunoglobulin-like receptors (KIRs) is involved in the calibration of NK cell effector capacities during the developmental stage, allowing the subsequent recognition and elimination of target cells with decreased expression of self-HLA class I (due to virus infection or tumor transformation) or HLA class I disparities (in the setting of allogeneic transplantation). NK cells expressing an inhibitory KIR-binding self-HLA can be activated when confronted with allografts lacking a ligand for the inhibitory receptor. Following the response of the adaptive immune system, NK cells can further destroy allograft endothelium by antibody-dependent cell-mediated cytotoxicity (ADCC), triggered through cross-linking of the CD16 Fc receptor by donor-specific antibodies bound to allograft. Upon recognizing allogeneic target cells, NK cells also secrete cytokines and chemokines that drive maturation of dendritic cells to promote cellular and humoral adaptive immune responses against the allograft. The cumulative activating and inhibitory signals generated by ligation of the receptors regulates mature NK cell killing of target cells and their production of cytokines and chemokines. This review summarizes the role of NK cells in allograft rejection and proposes mechanistic concepts that indicate a prominent role for KIR–HLA interactions in facilitating NK cells for Fc receptor-mediated ADCC effector function involved in antibody-mediated rejection of solid organ transplants. PMID:28066408

  3. Creating Cross-disciplinary Courses.

    PubMed

    Reynolds, Elaine R

    2012-01-01

    Because of its focus on the biological underpinnings of action and behavior, neuroscience intersects with many fields of human endeavor. Some of these cross-disciplinary intersections have been long standing, while others, such as neurotheology or neuroeconomics, are more recently formed fields. Many undergraduate institutions have sought to include cross-disciplinary courses in their curriculum because this style of pedagogy is often seen as applicable to real world problems. However, it can be difficult for faculty with specialized training within their discipline to expand beyond their own fields to offer cross-disciplinary courses. I have been creating a series of multi- or cross-disciplinary courses and have found some strategies that have helped me successfully teach these classes. I will discuss general strategies and tools in developing these types of courses including: 1) creating mixed experience classrooms of students and contributing faculty 2) finding the right tools that will allow you to teach to a mixed population without prerequisites 3) examining the topic using multiple disciplinary perspectives 4) feeding off student experience and interest 5) assessing the impact of these courses on student outcomes and your neuroscience program. This last tool in particular is important in establishing the validity of this type of teaching for neuroscience students and the general student population.

  4. Creating Cross-disciplinary Courses

    PubMed Central

    Reynolds, Elaine R.

    2012-01-01

    Because of its focus on the biological underpinnings of action and behavior, neuroscience intersects with many fields of human endeavor. Some of these cross-disciplinary intersections have been long standing, while others, such as neurotheology or neuroeconomics, are more recently formed fields. Many undergraduate institutions have sought to include cross-disciplinary courses in their curriculum because this style of pedagogy is often seen as applicable to real world problems. However, it can be difficult for faculty with specialized training within their discipline to expand beyond their own fields to offer cross-disciplinary courses. I have been creating a series of multi- or cross-disciplinary courses and have found some strategies that have helped me successfully teach these classes. I will discuss general strategies and tools in developing these types of courses including: 1) creating mixed experience classrooms of students and contributing faculty 2) finding the right tools that will allow you to teach to a mixed population without prerequisites 3) examining the topic using multiple disciplinary perspectives 4) feeding off student experience and interest 5) assessing the impact of these courses on student outcomes and your neuroscience program. This last tool in particular is important in establishing the validity of this type of teaching for neuroscience students and the general student population. PMID:23494491

  5. Preparing TESOL Students for the ESOL Classroom: A Cross-Cultural Project in Intercultural Communication

    ERIC Educational Resources Information Center

    Medina-López-Portillo, Adriana

    2014-01-01

    Intercultural communication classes for TESOL students give them a solid foundation for their work with their own ESOL students. This article presents the cross-cultural project that TESOL students have to complete in a required intercultural communication class at the University of Maryland, Baltimore County and the case study that was used to…

  6. An Operationally Simple Sonogashira Reaction for an Undergraduate Organic Chemistry Laboratory Class

    ERIC Educational Resources Information Center

    Cranwell, Philippa B.; Peterson, Alexander M.; Littlefield, Benjamin T. R.; Russell, Andrew T.

    2015-01-01

    An operationally simple, reliable, and cheap Sonogashira reaction suitable for an undergraduate laboratory class that can be completed within a day-long (8 h) laboratory session has been developed. Cross-coupling is carried out between 2-methyl-3-butyn-2-ol and various aryl iodides using catalytic amounts of bis(triphenylphosphine)palladium(II)…

  7. Cross-talk between the Tissue Factor/coagulation factor VIIa complex and the tyrosine kinase receptor EphA2 in cancer.

    PubMed

    Eriksson, Oskar; Thulin, Åsa; Asplund, Anna; Hegde, Geeta; Navani, Sanjay; Siegbahn, Agneta

    2016-05-31

    Tissue Factor (TF) forms a proteolytically active complex together with coagulation factor VIIa (FVIIa) and functions as the trigger of blood coagulation or alternatively activates cell signaling. We recently described that EphA2 of the Eph tyrosine kinase receptor family is cleaved directly by the TF/FVIIa complex. The aim of the present study was to further characterize the cross-talk between TF/FVIIa and EphA2 using in vitro model systems and human cancer specimens. Cleavage and phosphorylation of EphA2 was studied by Western blot. Subcellular localization of TF and EphA2 was investigated by a proximity ligation assay and confocal microscopy. Phalloidin staining of the actin cytoskeleton was used to study cell rounding and retraction fiber formation. Expression of TF and EphA2 in human colorectal cancer specimens was examined by immunohistochemistry. TF and EphA2 co-localized constitutively in MDA-MB-231 cells, and addition of FVIIa resulted in cleavage of EphA2 by a PAR2-independent mechanism. Overexpression of TF in U251 glioblastoma cells lead to co-localization with EphA2 at the leading edge and FVIIa-dependent cleavage of EphA2. FVIIa potentiated ephrin-A1-induced cell rounding and retraction fiber formation in MDA-MB-231 cells through a RhoA/ROCK-dependent pathway that did not require PAR2-activation. TF and EphA2 were expressed in colorectal cancer specimens, and were significantly correlated. These results suggest that TF/FVIIa-EphA2 cross-talk might potentiate ligand-dependent EphA2 signaling in human cancers, and provide initial evidence that it is possible for this interaction to occur in vivo.

  8. Cross-linking and the molecular packing of corneal collagen

    NASA Technical Reports Server (NTRS)

    Yamauchi, M.; Chandler, G. S.; Tanzawa, H.; Katz, E. P.

    1996-01-01

    We have quantitatively characterized, for the first time, the cross-linking in bovine cornea collagen as a function of age. The major iminium reducible cross-links were dehydro-hydroxylysinonorleucine (deH-HLNL) and dehydro-histidinohydroxymerodesmosine (deH-HHMD). The former rapidly diminished after birth; however, the latter persisted in mature animals at a level of 0.3 - 0.4 moles/mole of collagen. A nonreducible cross-link, histidinohydroxylysinonorleucine (HHL), previously found only in skin, was also found to be a major mature cross-link in cornea. The presence of HHL indicates that cornea fibrils have a molecular packing similar to skin collagen. However, like deH-HHMD, the HHL content in corneal fibrils only reaches a maximum value with time about half that of skin. These data suggest that the corneal fibrils are comprised of discrete filaments that are internally stabilized by HHL and deH-HHMD cross-links. This pattern of intermolecular cross-linking would facilitate the special collagen swelling property required for corneal transparency.

  9. Cross-Boundary Leadership: A Framework for Understanding Leadership Preparation

    ERIC Educational Resources Information Center

    Curry, Katherine; Krumm, Bernita

    2016-01-01

    Through the conceptual framework of Cross-boundary leadership, this case study examines the influence of EDLE 6633 School/Community Collaboration, a doctoral course at Oklahoma State University, on course completer's capacity to effectively facilitate and sustain collaborative partnerships between schools and communities. Findings suggest that the…

  10. A qualitative theory guided analysis of stroke survivors' perceived barriers and facilitators to physical activity.

    PubMed

    Nicholson, Sarah L; Donaghy, Marie; Johnston, Marie; Sniehotta, Falko F; van Wijck, Frederike; Johnston, Derek; Greig, Carolyn; McMurdo, Marion E T; Mead, Gillian

    2014-01-01

    After stroke, physical activity and physical fitness levels are low, impacting on health, activity and participation. It is unclear how best to support stroke survivors to increase physical activity. Little is known about the barriers and facilitators to physical activity after stroke. Thus, our aim was to explore stroke survivors' perceived barriers and facilitators to physical activity. Semi-structured interviews with 13 ambulatory stroke survivors exploring perceived barriers and facilitators to physical activity post stroke were conducted in participants' homes, audio-recorded and transcribed verbatim. The Theoretical Domains Framework (TDF) informed content analysis of the interview transcripts. Data saturation was reached after interviews with 13 participants (median age of 76 years (inter-quartile range (IQR) = 69-83 years). The median time since stroke was 345 d (IQR = 316-366 d). The most commonly reported TDF domains were "beliefs about capabilities", "environmental context and resources" and "social influence". The most commonly reported perceived motivators were: social interaction, beliefs of benefits of exercise, high self-efficacy and the necessity of routine behaviours. The most commonly reported perceived barriers were: lack of professional support on discharge from hospital and follow-up, transport issues to structured classes/interventions, lack of control and negative affect. Stroke survivors perceive several different barriers and facilitators to physical activity. Stroke services need to address barriers to physical activity and to build on facilitators to promote physical activity after stroke. Physical activity post stroke can improve physical fitness and function, yet physical activity remains low among stroke survivors. Understanding stroke survivors' perceived barriers and facilitators to physical activity is essential to develop targeted interventions to increase physical activity. Beliefs about capabilities, environmental

  11. A Dialogue with Carl Rogers: Cross-Cultural Challenges of Facilitating Person-Centered Groups in Africa.

    ERIC Educational Resources Information Center

    Hain-Hill, Alicia; Rogers, Carl R.

    1988-01-01

    Presents brainstorming dialogue with Carl Rogers which was held in January of 1987, shortly before Rogers's death. Explores basic challenges involved in a large-scale, cross-cultural application of person-centered group work in South Africa. (Author)

  12. Building Cross-Cultural Competence: A Handbook for Teachers.

    ERIC Educational Resources Information Center

    Mangan, Michael

    The handbook presents guidelines for cross-cultural understanding and communication to assist teachers in culturally and linguistically diverse classes. The guidelines are presented in the form of suggestions in ten areas: (1) become familiar with basic concepts in anthropology, sociology, and related disciplines, and use the knowledge to build an…

  13. Cross-Curricular Sequence: An Approach for Teaching Business Communication.

    ERIC Educational Resources Information Center

    Clarke, Lillian W.; Franklin, Carl M.

    1985-01-01

    The Cross-Curricular Sequencing (CCS) approach to teaching business communications is explored. Its uses in word processing, principles of management, and business policy courses are discussed. Techniques for integrating materials from these courses into business communication classes are described. The implications of CCS for business…

  14. The dhnA gene of Escherichia coli encodes a class I fructose bisphosphate aldolase.

    PubMed Central

    Thomson, G J; Howlett, G J; Ashcroft, A E; Berry, A

    1998-01-01

    The gene encoding the Escherichia coli Class I fructose-1, 6-bisphosphate aldolase (FBP aldolase) has been cloned and the protein overproduced in high amounts. This gene sequence has previously been identified as encoding an E. coli dehydrin in the GenBanktrade mark database [gene dhnA; entry code U73760; Close and Choi (1996) Submission to GenBanktrade mark]. However, the purified protein overproduced from the dhnA gene shares all its properties with those known for the E. coli Class I FBP aldolase. The protein is an 8-10-mer with a native molecular mass of approx. 340 kDa, each subunit consisting of 349 amino acids. The Class I enzyme shows low sequence identity with other known FBP aldolases, both Class I and Class II (in the order of 20%), which may be reflected by some novel properties of this FBP aldolase. The active-site peptide has been isolated and the Schiff-base-forming lysine residue (Lys236) has been identified by a combination of site-directed mutagenesis, kinetics and electrospray-ionization MS. A second lysine residue (Lys238) has been implicated in substrate binding. The cloning of this gene and the high levels of overexpression obtained will facilitate future structure-function studies. PMID:9531482

  15. From parent to 'peer facilitator': a qualitative study of a peer-led parenting programme.

    PubMed

    Thomson, S; Michelson, D; Day, C

    2015-01-01

    Peer-led interventions are increasingly common in community health settings. Although peer-led approaches have proven benefits for service users, relatively little is known about the process and outcomes of participation for peer leaders. This study investigated experiences of parents who had participated as 'peer facilitators' in Empowering Parents, Empowering Communities (EPEC), a peer-led programme designed to improve access to evidence-based parenting support in socially disadvantaged communities. A qualitative cross-sectional design was used. Semi-structured interviews were conducted with 14 peer facilitators and scrutinized using thematic analysis. Peer facilitators developed their knowledge and skills through personal experience of receiving parenting support, participation in formal training and supervised practice, access to an intervention manual, and peer modelling. Peer facilitators described positive changes in their own families, confidence and social status. Transformative personal gains reinforced peer facilitators' role commitment and contributed to a cohesive 'family' identity among EPEC staff and service users. Peer facilitators' enthusiasm, openness and mutual identification with families were seen as critical to EPEC's effectiveness and sustainability. Peer facilitators also found the training emotionally and intellectually demanding. There were particular difficulties around logistical issues (e.g. finding convenient supervision times), managing psychosocial complexity and child safeguarding. The successful delivery and sustained implementation of peer-led interventions requires careful attention to the personal qualities and support of peer leaders. Based on the findings of this study, support should include training, access to intervention manuals, regular and responsive supervision, and logistical/administrative assistance. Further research is required to elaborate and extend these findings to other peer-led programmes. © 2014 John Wiley

  16. Base-Free Photoredox/Nickel Dual-Catalytic Cross-Coupling of Ammonium Alkylsilicates.

    PubMed

    Jouffroy, Matthieu; Primer, David N; Molander, Gary A

    2016-01-20

    Single-electron transmetalation is recognized as an enabling technology for the mild transfer of alkyl groups to transition metal catalysts in cross-coupling reactions. Hypercoordinate silicates represent a new and improved class of radical precursors because of their low oxidation potentials and the innocuous byproducts generated upon oxidation. Herein, we report the cross-coupling of secondary and primary ammonium alkylsilicates with (hetero)aryl bromides in good to excellent yields. The base-free conditions have exceptional protic group tolerance on both partners, permitting the cross-coupling of unprotected primary and secondary amines.

  17. Teachers in Class

    ERIC Educational Resources Information Center

    Van Galen, Jane

    2008-01-01

    In this article, I argue for a closer read of the daily "class work" of teachers, as posited by Reay, 1998. In developing exploratory class portraits of four teachers who occupy distinctive social positions (two from working-class homes now teaching upper-middle-class children and two from upper-middle-class homes now teaching poor children), I…

  18. Mediator links transcription and DNA repair by facilitating Rad2/XPG recruitment

    PubMed Central

    Eyboulet, Fanny; Cibot, Camille; Eychenne, Thomas; Neil, Helen; Alibert, Olivier; Werner, Michel; Soutourina, Julie

    2013-01-01

    Mediator is a large multiprotein complex conserved in all eukaryotes. The crucial function of Mediator in transcription is now largely established. However, we found that this complex also plays an important role by connecting transcription with DNA repair. We identified a functional contact between the Med17 Mediator subunit and Rad2/XPG, the 3′ endonuclease involved in nucleotide excision DNA repair. Genome-wide location analyses revealed that Rad2 is associated with RNA polymerase II (Pol II)- and Pol III-transcribed genes and telomeric regions in the absence of exogenous genotoxic stress. Rad2 occupancy of Pol II-transcribed genes is transcription-dependent. Genome-wide Rad2 occupancy of class II gene promoters is well correlated with that of Mediator. Furthermore, UV sensitivity of med17 mutants is correlated with reduced Rad2 occupancy of class II genes and concomitant decrease of Mediator interaction with Rad2 protein. Our results suggest that Mediator is involved in DNA repair by facilitating Rad2 recruitment to transcribed genes. PMID:24298055

  19. CNN-BLPred: a Convolutional neural network based predictor for β-Lactamases (BL) and their classes.

    PubMed

    White, Clarence; Ismail, Hamid D; Saigo, Hiroto; Kc, Dukka B

    2017-12-28

    The β-Lactamase (BL) enzyme family is an important class of enzymes that plays a key role in bacterial resistance to antibiotics. As the newly identified number of BL enzymes is increasing daily, it is imperative to develop a computational tool to classify the newly identified BL enzymes into one of its classes. There are two types of classification of BL enzymes: Molecular Classification and Functional Classification. Existing computational methods only address Molecular Classification and the performance of these existing methods is unsatisfactory. We addressed the unsatisfactory performance of the existing methods by implementing a Deep Learning approach called Convolutional Neural Network (CNN). We developed CNN-BLPred, an approach for the classification of BL proteins. The CNN-BLPred uses Gradient Boosted Feature Selection (GBFS) in order to select the ideal feature set for each BL classification. Based on the rigorous benchmarking of CCN-BLPred using both leave-one-out cross-validation and independent test sets, CCN-BLPred performed better than the other existing algorithms. Compared with other architectures of CNN, Recurrent Neural Network, and Random Forest, the simple CNN architecture with only one convolutional layer performs the best. After feature extraction, we were able to remove ~95% of the 10,912 features using Gradient Boosted Trees. During 10-fold cross validation, we increased the accuracy of the classic BL predictions by 7%. We also increased the accuracy of Class A, Class B, Class C, and Class D performance by an average of 25.64%. The independent test results followed a similar trend. We implemented a deep learning algorithm known as Convolutional Neural Network (CNN) to develop a classifier for BL classification. Combined with feature selection on an exhaustive feature set and using balancing method such as Random Oversampling (ROS), Random Undersampling (RUS) and Synthetic Minority Oversampling Technique (SMOTE), CNN-BLPred performs

  20. Class Construction: White Working-Class Student Identity in the New Millennium

    ERIC Educational Resources Information Center

    Freie, Carrie

    2007-01-01

    "Class Construction" explores class, racial, and gender identity construction among white, working-class students. Delving into River City High School, Freie asks what happens to the adolescent children of working-class families when economic changes such as globalization and technological advancements have altered the face of working-class jobs.…

  1. Barriers and facilitators to provide quality TIA care in the Veterans Healthcare Administration.

    PubMed

    Damush, Teresa M; Miech, Edward J; Sico, Jason J; Phipps, Michael S; Arling, Greg; Ferguson, Jared; Austin, Charles; Myers, Laura; Baye, Fitsum; Luckhurst, Cherie; Keating, Ava B; Moran, Eileen; Bravata, Dawn M

    2017-12-12

    To identify key barriers and facilitators to the delivery of guideline-based care of patients with TIA in the national Veterans Health Administration (VHA). We conducted a cross-sectional, observational study of 70 audiotaped interviews of multidisciplinary clinical staff involved in TIA care at 14 VHA hospitals. We de-identified and analyzed all transcribed interviews. We identified emergent themes and patterns of barriers to providing TIA care and of facilitators applied to overcome these barriers. Identified barriers to providing timely acute and follow-up TIA care included difficulties accessing brain imaging, a constantly rotating pool of housestaff, lack of care coordination, resource constraints, and inadequate staff education. Key informants revealed that both stroke nurse coordinators and system-level factors facilitated the provision of TIA care. Few facilities had specific TIA protocols. However, stroke nurse coordinators often expanded upon their role to include TIA. They facilitated TIA care by (1) coordinating patient care across services, communicating across service lines, and educating clinical staff about facility policies and evidence-based practices; (2) tracking individual patients from emergency departments to inpatient settings and to discharge for timely follow-up care; (3) providing and referring TIA patients to risk factor management programs; and (4) performing regular audit and feedback of quality performance data. System-level facilitators included clinical service leadership engagement and use of electronic tools for continuous care across services. The local organization within a health care facility may be targeted to cultivate internal facilitators and a systemic infrastructure to provide evidence-based TIA care. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  2. Water Dynamics at Protein-Protein Interfaces: Molecular Dynamics Study of Virus-Host Receptor Complexes.

    PubMed

    Dutta, Priyanka; Botlani, Mohsen; Varma, Sameer

    2014-12-26

    The dynamical properties of water at protein-water interfaces are unlike those in the bulk. Here we utilize molecular dynamics simulations to study water dynamics in interstitial regions between two proteins. We consider two natural protein-protein complexes, one in which the Nipah virus G protein binds to cellular ephrin B2 and the other in which the same G protein binds to ephrin B3. While the two complexes are structurally similar, the two ephrins share only a modest sequence identity of ∼50%. X-ray crystallography also suggests that these interfaces are fairly extensive and contain exceptionally large amounts of waters. We find that while the interstitial waters tend to occupy crystallographic sites, almost all waters exhibit residence times of less than hundred picoseconds in the interstitial region. We also find that while the differences in the sequence of the two ephrins result in quantitative differences in the dynamics of interstitial waters, the trends in the shifts with respect to bulk values are similar. Despite the high wetness of the protein-protein interfaces, the dynamics of interstitial waters are considerably slower compared to the bulk-the interstitial waters diffuse an order of magnitude slower and have 2-3 fold longer hydrogen bond lifetimes and 2-1000 fold slower dipole relaxation rates. To understand the role of interstitial waters, we examine how implicit solvent models compare against explicit solvent models in producing ephrin-induced shifts in the G conformational density. Ephrin-induced shifts in the G conformational density are critical to the allosteric activation of another viral protein that mediates fusion. We find that in comparison with the explicit solvent model, the implicit solvent model predicts a more compact G-B2 interface, presumably because of the absence of discrete waters at the G-B2 interface. Simultaneously, we find that the two models yield strikingly different induced changes in the G conformational density, even

  3. Research on cross - Project software defect prediction based on transfer learning

    NASA Astrophysics Data System (ADS)

    Chen, Ya; Ding, Xiaoming

    2018-04-01

    According to the two challenges in the prediction of cross-project software defects, the distribution differences between the source project and the target project dataset and the class imbalance in the dataset, proposing a cross-project software defect prediction method based on transfer learning, named NTrA. Firstly, solving the source project data's class imbalance based on the Augmented Neighborhood Cleaning Algorithm. Secondly, the data gravity method is used to give different weights on the basis of the attribute similarity of source project and target project data. Finally, a defect prediction model is constructed by using Trad boost algorithm. Experiments were conducted using data, come from NASA and SOFTLAB respectively, from a published PROMISE dataset. The results show that the method has achieved good values of recall and F-measure, and achieved good prediction results.

  4. Cross-Cultural School-Based Encounters as Global Health Education

    ERIC Educational Resources Information Center

    Bruselius-Jensen, Maria; Renwick, Kerry; Aagaard-Hansen, Jens

    2017-01-01

    Objective: Drawing on the concepts of the cosmopolitan person and democratic health education, this article explores the merits of primary school-based, cross-cultural dialogues for global health education. Design: A qualitative study of the learning outcomes of the Move/Eat/Learn (MEL) project. MEL facilitates cultural meetings, primarily…

  5. Quantitating T cell cross-reactivity for unrelated peptide antigens.

    PubMed

    Ishizuka, Jeffrey; Grebe, Kristie; Shenderov, Eugene; Peters, Bjoern; Chen, Qiongyu; Peng, Yanchun; Wang, Lili; Dong, Tao; Pasquetto, Valerie; Oseroff, Carla; Sidney, John; Hickman, Heather; Cerundolo, Vincenzo; Sette, Alessandro; Bennink, Jack R; McMichael, Andrew; Yewdell, Jonathan W

    2009-10-01

    Quantitating the frequency of T cell cross-reactivity to unrelated peptides is essential to understanding T cell responses in infectious and autoimmune diseases. Here we used 15 mouse or human CD8+ T cell clones (11 antiviral, 4 anti-self) in conjunction with a large library of defined synthetic peptides to examine nearly 30,000 TCR-peptide MHC class I interactions for cross-reactions. We identified a single cross-reaction consisting of an anti-self TCR recognizing a poxvirus peptide at relatively low sensitivity. We failed to identify any cross-reactions between the synthetic peptides in the panel and polyclonal CD8+ T cells raised to viral or alloantigens. These findings provide the best estimate to date of the frequency of T cell cross-reactivity to unrelated peptides ( approximately 1/30,000), explaining why cross-reactions between unrelated pathogens are infrequently encountered and providing a critical parameter for understanding the scope of self-tolerance.

  6. Cross-Linked Nanohybrid Polymer Electrolytes With POSS Cross-Linker for Solid-State Lithium Ion Batteries.

    PubMed

    Zhang, Jinfang; Li, Xiaofeng; Li, Ying; Wang, Huiqi; Ma, Cheng; Wang, Yanzhong; Hu, Shengliang; Wei, Weifeng

    2018-01-01

    A new class of freestanding cross-linked hybrid polymer electrolytes (HPEs) with POSS as the cross-linker was prepared by a one-step free radical polymerization reaction. Octavinyl octasilsesquioxane (OV-POSS) with eight functional corner groups was used to provide cross-linking sites for the connection of polymer segments and the required mechanical strength to separate the cathode and anode. The unique cross-linked structure offers additional free volume for the motion of EO chains and provides fast and continuously interconnected ion-conducting channels along the nanoparticles/polymer matrix interface. The HPE exhibits the highest ionic conductivity of 1.39 × 10 -3 S cm -1 , as well as excellent interfacial compatibility with the Li electrode at 80°C. In particular, LiFePO 4 /Li cells based on the HPE deliver good rate capability and long-term cycling performance with an initial discharge capacity of 152.1 mAh g -1 and a capacity retention ratio of 88% after 150 cycles with a current density of 0.5 C at 80°C, demonstrating great potential application in high-performance LIBs at elevated temperatures.

  7. Cross-linked Nanohybrid Polymer Electrolytes with POSS Cross-linker for Solid-state Lithium Ion Batteries

    NASA Astrophysics Data System (ADS)

    Zhang, Jinfang; Li, Xiaofeng; Li, Ying; Wang, Huiqi; Ma, Cheng; Wang, Yanzhong; Hu, Shengliang; Wei, Weifeng

    2018-05-01

    A new class of freestanding cross-linked hybrid polymer electrolytes (HPEs) with POSS as the cross-linker was prepared by a one-step free radical polymerization reaction. Octavinyl octasilsesquioxane (OV-POSS) with eight functional corner groups was used to provide cross-linking sites for the connection of polymer segments and the required mechanical strength to separate the cathode and anode. The unique cross-linked structure offers additional free volume for the motion of EO chains and provides fast and continuously interconnected ion-conducting channels along the nanoparticles/polymer matrix interface. The HPE exhibits the highest ionic conductivity of 1.39×10-3 S cm-1, as well as excellent interfacial compatibility with the Li electrode at 80 oC. In particular, LiFePO4/Li cells based on the HPE deliver good rate capability and long-term cycling performance with an initial discharge capacity of 152.1 mAh g-1 and a capacity retention ratio of 88% after 150 cycles with a current density of 0.5 C at 80 oC, demonstrating great potential application in high-performance LIBs at elevated temperatures.

  8. 47 CFR 73.6017 - Digital Class A TV station protection of Class A TV and digital Class A TV stations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 4 2011-10-01 2011-10-01 false Digital Class A TV station protection of Class A TV and digital Class A TV stations. 73.6017 Section 73.6017 Telecommunication FEDERAL... Broadcast Stations § 73.6017 Digital Class A TV station protection of Class A TV and digital Class A TV...

  9. 47 CFR 73.6017 - Digital Class A TV station protection of Class A TV and digital Class A TV stations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Digital Class A TV station protection of Class A TV and digital Class A TV stations. 73.6017 Section 73.6017 Telecommunication FEDERAL... Broadcast Stations § 73.6017 Digital Class A TV station protection of Class A TV and digital Class A TV...

  10. A latent class distance association model for cross-classified data with a categorical response variable.

    PubMed

    Vera, José Fernando; de Rooij, Mark; Heiser, Willem J

    2014-11-01

    In this paper we propose a latent class distance association model for clustering in the predictor space of large contingency tables with a categorical response variable. The rows of such a table are characterized as profiles of a set of explanatory variables, while the columns represent a single outcome variable. In many cases such tables are sparse, with many zero entries, which makes traditional models problematic. By clustering the row profiles into a few specific classes and representing these together with the categories of the response variable in a low-dimensional Euclidean space using a distance association model, a parsimonious prediction model can be obtained. A generalized EM algorithm is proposed to estimate the model parameters and the adjusted Bayesian information criterion statistic is employed to test the number of mixture components and the dimensionality of the representation. An empirical example highlighting the advantages of the new approach and comparing it with traditional approaches is presented. © 2014 The British Psychological Society.

  11. Use of multi-frequency, multi-polarization, multi-angle airborne radars for class discrimination in a southern temperature forest

    NASA Technical Reports Server (NTRS)

    Mehta, N. C.

    1984-01-01

    The utility of radar scatterometers for discrimination and characterization of natural vegetation was investigated. Backscatter measurements were acquired with airborne multi-frequency, multi-polarization, multi-angle radar scatterometers over a test site in a southern temperate forest. Separability between ground cover classes was studied using a two-class separability measure. Very good separability is achieved between most classes. Longer wavelength is useful in separating trees from non-tree classes, while shorter wavelength and cross polarization are helpful for discrimination among tree classes. Using the maximum likelihood classifier, 50% overall classification accuracy is achieved using a single, short-wavelength scatterometer channel. Addition of multiple incidence angles and another radar band improves classification accuracy by 20% and 50%, respectively, over the single channel accuracy. Incorporation of a third radar band seems redundant for vegetation classification. Vertical transmit polarization is critically important for all classes.

  12. Quantitative Research on the Outcomes of China's Inland Tibetan Classes and Schools Policy: A Survey of Graduates

    ERIC Educational Resources Information Center

    Xiaorong, Wu

    2015-01-01

    Under the Inland Tibetan Classes and Schools Policy, China has trained a large number of personnel to facilitate the social, economic, and cultural development of Tibet. This study used a multistage, random sample survey to collect data on the comprehensive qualities of two sample groups of personnel in Tibet: graduates and nongraduates of inland…

  13. Cross-presentation of IgG-containing immune complexes

    PubMed Central

    Baker, Kristi; Rath, Timo; Lencer, Wayne I.; Fiebiger, Edda

    2012-01-01

    IgG is a molecule that functionally combines facets of both innate and adaptive immunity and therefore bridges both arms of the immune system. On the one hand, IgG is created by adaptive immune cells, but can be generated by B cells independently of T cell help. On the other hand, once secreted, IgG can rapidly deliver antigens into intracellular processing pathways, which enable efficient priming of T cell responses towards epitopes from the cognate antigen initially bound by the IgG. While this process has long been known to participate in CD4+ T cell activation, IgG-mediated delivery of exogenous antigens into a major histocompatibility complex (MHC) class I processing pathway has received less attention. The coordinated engagement of IgG with IgG receptors expressed on the cell-surface (FcγR) and within the endolysosomal system (FcRn) is a highly potent means to deliver antigen into processing pathways that promote cross-presentation of MHC class I and presentation of MHC class II-restricted epitopes within the same dendritic cell. This review focuses on the mechanisms by which IgG-containing immune complexes mediate such cross-presentation and the implications that this understanding has for manipulation of immune-mediated diseases that depend upon or are due to the activities of CD8+ T cells. PMID:22847331

  14. WeSaySo Case Study: Designing and Implementing a Case Study for Use in an Instructional Design Class.

    ERIC Educational Resources Information Center

    Graves, Rick; Barnett, Mardee; Gamble, Yolanda; Kolak, Mike

    A case study was used in an instructional design class to facilitate the transfer of conceptual knowledge to concrete concerns and to aid instructional technology graduate students' understanding of the steps involved in designing, analyzing, and implementing an effective needs analysis. The case study involved real events at fictitious company…

  15. Cross-orientation interactions in human vision.

    PubMed

    Roeber, Urte; Wong, Elaine M Y; Freeman, Alan W

    2008-03-18

    Humans can discriminate one visual contour from another on the basis of small differences in orientation. This capability depends on cortical detectors that are selective for a small range of orientations. We have measured this orientation bandwidth and the suppression that helps to shape it, with a reverse correlation technique. Human subjects were presented with a stream of randomly oriented gratings at a rate of 30 per second. Their task was to press a key whenever they saw an orientation nominated as the target. We analyzed the data by finding the probability density of two orientations: One preceded the key-press by the reaction time, and the second preceded the first by up to 100 ms. The results were as follows: (1) One grating facilitated the following one in producing a key-press when the gratings differed little in orientation. The estimate of orientation bandwidth resulting from this facilitation was 38 degrees . (2) A large angle between the two orientations reduced the probability of a key-press. This finding was best modelled as a suppression that did not vary with orientation, consistent with the idea that cross-orientation suppression is non-oriented. (3) Analysis of non-consecutive grating pairs showed that cross-orientation interactions lasted no longer than 67 ms.

  16. Variable NK cell receptors and their MHC class I ligands in immunity, reproduction and human evolution.

    PubMed

    Parham, Peter; Moffett, Ashley

    2013-02-01

    Natural killer (NK) cells have roles in immunity and reproduction that are controlled by variable receptors that recognize MHC class I molecules. The variable NK cell receptors found in humans are specific to simian primates, in which they have progressively co-evolved with MHC class I molecules. The emergence of the MHC-C gene in hominids drove the evolution of a system of NK cell receptors for MHC-C molecules that is most elaborate in chimpanzees. By contrast, the human system of MHC-C receptors seems to have been subject to different selection pressures that have acted in competition on the immunological and reproductive functions of MHC class I molecules. We suggest that this compromise facilitated the development of the bigger brains that enabled archaic and modern humans to migrate out of Africa and populate other continents.

  17. Class and ideological orientations revisited: an exploration of class-based mechanisms.

    PubMed

    Bengtsson, Mattias; Berglund, Tomas; Oskarson, Maria

    2013-12-01

    Studies of the relationship between class position and political outlooks still only have a limited understanding of the class-related mechanisms that matter for ideological orientations. This article presents a comprehensive analysis of the mechanisms that link class position and left/right and authoritarian/libertarian orientations. Besides main factors such as income, career prospects, job security, education, class origin and class identification, the significance of work-related factors such as work autonomy, working in a team, a physically demanding job and a mentally demanding job is studied. The findings are based on a survey specifically designed for this purpose and collected in Sweden in 2008/2009. A great deal of the association between class position and left/right orientations is explained by socio-economic conditions; different classes sympathize with policies that will benefit them economically. Another important factor is class identification. Work-related factors also have relevance, but the effect of class position on left/right orientations works mainly through the remuneration system. Class position is also related to authoritarian/libertarian orientations. However, this relationship is less explained by socio-economic position per se, but is rather an effect of the educational system and its allocation of the workforce into different class positions. It also turns out that work-related factors do not explain the class effects; however, a physically demanding job shows a unique effect. Overall, our findings suggest that besides factors such as class position, income, education and class identification, we need to consider work-related aspects to derive a more complete understanding of the distribution of ideological orientations in Western societies. © London School of Economics and Political Science 2013.

  18. Qualitative Differences Between Learning Environments Using Videos in Small Groups and Whole Class Discussions: A Preliminary Study in Physics

    NASA Astrophysics Data System (ADS)

    Mayo, Ashleigh; Sharma, Manjula D.; Muller, Derek A.

    2009-08-01

    Interactivity, group learning and student engagement are accepted as key features of social constructivist learning theories. The challenge is to understand the interplay between such features in different learning environments. This study focused on the qualitative differences between two interventions—small-groups and whole-class discussions. In both interventions, three short video slices on the abstract topic ‘the physics of superconductivity’ were interspersed with the different discussion styles. The video slices are based on the Bruner stages. Twenty-nine first year university physics students completed a pre-test, underwent the intervention and completed a post-test. The remainder of the data were collected from student drawings, video recordings, observer notes and facilitator feedback. Results indicate that the use of the video slices in both interventions were successful in changing students’ understandings of superconductivity. However, the small groups treatment tended to facilitate questioning, meaning-making and subsequent changes of ideas more so than the whole class discussions. Implications for research and practice are discussed.

  19. Molecular identification of venous progenitors in the dorsal aorta reveals an aortic origin for the cardinal vein in mammals

    PubMed Central

    Lindskog, Henrik; Kim, Yung Hae; Jelin, Eric B.; Kong, Yupeng; Guevara-Gallardo, Salvador; Kim, Tyson N.; Wang, Rong A.

    2014-01-01

    Coordinated arterial-venous differentiation is crucial for vascular development and function. The origin of the cardinal vein (CV) in mammals is unknown, while conflicting theories have been reported in chick and zebrafish. Here, we provide the first molecular characterization of endothelial cells (ECs) expressing venous molecular markers, or venous-fated ECs, within the emergent dorsal aorta (DA). These ECs, expressing the venous molecular markers Coup-TFII and EphB4, cohabited the early DA with ECs expressing the arterial molecular markers ephrin B2, Notch and connexin 40. These mixed ECs in the early DA expressed either the arterial or venous molecular marker, but rarely both. Subsequently, the DA exhibited uniform arterial markers. Real-time imaging of mouse embryos revealed EC movement from the DA to the CV during the stage when venous-fated ECs occupied the DA. We analyzed mutants for EphB4, which encodes a receptor tyrosine kinase for the ephrin B2 ligand, as we hypothesized that ephrin B2/EphB4 signaling may mediate the repulsion of venous-fated ECs from the DA to the CV. Using an EC quantification approach, we discovered that venous-fated ECs increased in the DA and decreased in the CV in the mutants, whereas the rest of the ECs in each vessel were unaffected. This result suggests that the venous-fated ECs were retained in the DA and missing in the CV in the EphB4 mutant, and thus that ephrin B2/EphB4 signaling normally functions to clear venous-fated ECs from the DA to the CV by cell repulsion. Therefore, our cellular and molecular evidence suggests that the DA harbors venous progenitors that move to participate in CV formation, and that ephrin B2/EphB4 signaling regulates this aortic contribution to the mammalian CV. PMID:24550118

  20. The Neural Cell Adhesion Molecule (NCAM) Promotes Clustering and Activation of EphA3 Receptors in GABAergic Interneurons to Induce Ras Homolog Gene Family, Member A (RhoA)/Rho-associated protein kinase (ROCK)-mediated Growth Cone Collapse*

    PubMed Central

    Sullivan, Chelsea S.; Kümper, Maike; Temple, Brenda S.; Maness, Patricia F.

    2016-01-01

    Establishment of a proper balance of excitatory and inhibitory connectivity is achieved during development of cortical networks and adjusted through synaptic plasticity. The neural cell adhesion molecule (NCAM) and the receptor tyrosine kinase EphA3 regulate the perisomatic synapse density of inhibitory GABAergic interneurons in the mouse frontal cortex through ephrin-A5-induced growth cone collapse. In this study, it was demonstrated that binding of NCAM and EphA3 occurred between the NCAM Ig2 domain and EphA3 cysteine-rich domain (CRD). The binding interface was further refined through molecular modeling and mutagenesis and shown to be comprised of complementary charged residues in the NCAM Ig2 domain (Arg-156 and Lys-162) and the EphA3 CRD (Glu-248 and Glu-264). Ephrin-A5 induced co-clustering of surface-bound NCAM and EphA3 in GABAergic cortical interneurons in culture. Receptor clustering was impaired by a charge reversal mutation that disrupted NCAM/EphA3 association, emphasizing the importance of the NCAM/EphA3 binding interface for cluster formation. NCAM enhanced ephrin-A5-induced EphA3 autophosphorylation and activation of RhoA GTPase, indicating a role for NCAM in activating EphA3 signaling through clustering. NCAM-mediated clustering of EphA3 was essential for ephrin-A5-induced growth cone collapse in cortical GABAergic interneurons, and RhoA and a principal effector, Rho-associated protein kinase, mediated the collapse response. This study delineates a mechanism in which NCAM promotes ephrin-A5-dependent clustering of EphA3 through interaction of the NCAM Ig2 domain and the EphA3 CRD, stimulating EphA3 autophosphorylation and RhoA signaling necessary for growth cone repulsion in GABAergic interneurons in vitro, which may extend to remodeling of axonal terminals of interneurons in vivo. PMID:27803162

  1. Class Matters

    ERIC Educational Resources Information Center

    Valdata, Patricia

    2005-01-01

    Ever since George Washington opted for the title of president rather than king, Americans have been uncomfortable with the idea of class distinctions. This article presents an interview with Dr. Janet Galligani Casey regarding the idea of class distinctions. Galligani Casey, who grew up in a working-class neighborhood in Somerville, Massachusetts,…

  2. Facilitating Facilitators to Facilitate, in Problem or Enquiry Based Learning Sessions

    ERIC Educational Resources Information Center

    Coelho, Catherine

    2014-01-01

    Problem based learning (PBL) has been used in dental education over the past 20 years and uses a patient case scenario to stimulate learning in a small group setting, where a trained facilitator does not teach but guides the group to bring about deep contextualized learning, to be empathetic to each other and to encourage fair and equitable…

  3. The building of the EUDAT Cross-Disciplinary Data Infrastructure

    NASA Astrophysics Data System (ADS)

    Lecarpentier, Damien; Michelini, Alberto; Wittenburg, Peter

    2013-04-01

    The EUDAT project is a European data initiative that brings together a unique consortium of 25 partners - including research communities, national data and high performance computing (HPC) centers, technology providers, and funding agencies - from 13 countries. EUDAT aims to build a sustainable cross-disciplinary and cross-national Commom Data Infrastructure (CDI) that provides a set of shared services for accessing and preserving research data. The design and deployment of these services is being coordinated by multi-disciplinary task forces comprising representatives from research communities and data centers. One of EUDAT's fundamental goals is the facilitation of cross-disciplinary data-intensive science. By providing opportunity for disciplines from across the spectrum to share data and cross-fertilize ideas, the CDI will encourage progress towards this vision of open and participatory data-intensive science. EUDAT will also facilitate this process through the creation of teams of experts from different disciplines, aiming to cooperatively develop services to meet the needs of several communities. Five research communities joined the EUDAT initiative at the start - CLARIN (Linguistics), ENES (Climate Modeling), EPOS (Earth Sciences), LifeWatch (Environmental Sciences - Biodiversity), VPH (Biological and Medical Sciences). They are acting as partners in the project, and have clear tasks and commitments. Since EUDAT started on the 1st of October 2011, we have been reviewing the approaches and requirements of these five communities regarding the deployment and use of a cross-disciplinary and persistent data e-Infrastructure. This analysis was conducted through interviews and frequent interactions with representatives of the communities. In this talk will be provided an updated status of the current CDI with specific refernce to the solid Earth science commnity of EPOS.

  4. The Potential of Dual-Language Cross-Cultural Peer Review

    ERIC Educational Resources Information Center

    Ruecker, Todd

    2011-01-01

    This article explores the potential of dual-language cross-cultural peer review and how it improves on traditional monolingual and monocultural peer review. Drawing on scholarship related to international exchange programmes, peer review, and two-way immersion programmes in the United States as well as data collected while facilitating the…

  5. Physical Education Classes, Physical Activity, and Sedentary Behavior in Children.

    PubMed

    Silva, Diego Augusto Santos; Chaput, Jean-Philippe; Katzmarzyk, Peter T; Fogelholm, Mikael; Hu, Gang; Maher, Carol; Olds, Timothy; Onywera, Vincent; Sarmiento, Olga L; Standage, Martyn; Tudor-Locke, Catrine; Tremblay, Mark S

    2018-05-01

    This study aimed to examine the associations between participation frequency in physical education (PE) classes and objective measures of physical activity (PA) and sedentary behavior (SB) in children from 12 countries at different levels of development. This multinational, cross-sectional study included 5874 children 9-11 yr old from sites in Australia, Brazil, Canada, China, Colombia, Finland, India, Kenya, Portugal, South Africa, the United Kingdom, and the United States. PA and SB were monitored for seven consecutive days using a waist-worn accelerometer. PA and SB data were presented for weekdays (times in and out of school) and weekend days. Participation frequency in PE classes was determined by questionnaire. Multilevel modeling analyses stratified by sex were used. Overall, 24.8% of children self-reported participation in PE classes ≥3 times per week (25.3% in high-income countries [HIC] and 24.3% in low- and middle-income countries [LMIC]). After adjusting for age, sex, parental education, and body mass index z-score, results showed that children from low- and middle-income countries who took PE classes one to two times per week were more likely to present better indicators of PA and shorter time in SB in and out of school. In HIC, boys that participated in PE classes were more likely to meet the moderate-to-vigorous PA recommendations and to present better indicators of PA (in school) and shorter time in SB in and out of school. For girls in HIC, attending PE classes increased the likelihood of spending more time in moderate-to-vigorous PA, especially if they attended ≥3 times per week. Attending PE classes is associated with a higher level of PA and a lower level of SB in and out of school during weekdays in children from countries at various levels of development.

  6. Explaining Electronic Learning Management Systems (ELMS) Continued Usage Intentions among Facilitators in Higher Education Institutions (HEIs) in Tanzania

    ERIC Educational Resources Information Center

    Muries, Bruckse; Masele, Juma James

    2017-01-01

    This study sought to explain ELMS continued usage intentions among HEIs in Tanzania. The study was guided by main research question, "What explains ELMS continued usage intentions among facilitators in HEIs in Tanzania?" The study used descriptive cross sectional design administered to 264 respondents drawn from five universities…

  7. Patterns and predictors of posttraumatic stress disorder in refugees: A latent class analysis.

    PubMed

    Minihan, Savannah; Liddell, Belinda J; Byrow, Yulisha; Bryant, Richard A; Nickerson, Angela

    2018-05-01

    Although elevated rates of posttraumatic stress disorder (PTSD) have been well-documented in refugees, no study has investigated the heterogeneity of DSM-5 PTSD symptomatology in such populations. This study aimed to determine whether there are unique patterns of DSM-5 defined PTSD symptomatology in refugees, and investigate whether factors characteristic of the refugee experience, including trauma exposure and post-migration stress, predict symptom profiles. Participants were 246 refugees and asylum-seekers from an Arabic-, English-, Farsi-, or Tamil-speaking background who had been resettled in Australia. Participants completed measures of post-migration living difficulties, trauma exposure, PTSD symptoms and functional disability. Latent class analysis was used to identify PTSD symptom profiles, and predictors of class membership were elucidated via multinomial logistic regression. Four classes were identified: a high-PTSD class (21.3%), a high-re-experiencing/avoidance class (15.3%), a moderate-PTSD class (23%), and a no PTSD class (40.3%). Trauma exposure and post-migration stress significantly predicted class membership and classes differed in degree of functional disability. The current study employed a cross-sectional design, which precluded inferences regarding the stability of classes of PTSD symptomatology. This study provides evidence for distinct patterns of PTSD symptomatology in refugees. We identified a novel class, characterized by high-re-experiencing and avoidance symptoms, as well as classes characterized by pervasive, moderate, and no symptomatology. Trauma exposure and post-migration stress differentially contributed to the emergence of these profiles. Individuals with high and moderate probability of PTSD symptoms evidenced substantial disability. These results support conceptualizations of PTSD as a heterogeneous construct, and highlight the importance of considering sub-clinical symptom presentations, as well as the post

  8. Effects of In-Class Hands-On Laboratories in a Large Enrollment, Multiple Section Blended Linear Circuits Course

    ERIC Educational Resources Information Center

    Ferri, Bonni H.; Ferri, Aldo A.; Majerich, David M.; Madden, Amanda G.

    2016-01-01

    This paper examines the effects of hands-on learning in an undergraduate circuits class that is taught to non-majors; i.e., students outside of electrical and computing engineering. The course, ECE3710, is taught in a blended format facilitated by the video lectures prepared for two Massive Open Online Courses developed for the Coursera Platform.…

  9. Photoinduced intramolecular charge transfer in a cross-conjugated push-pull enediyne: implications toward photoreaction.

    PubMed

    Singh, Anuja; Pati, Avik Kumar; Mishra, Ashok Kumar

    2018-05-30

    Push-pull organic fluorophores are important owing to their interesting optoelectronical properties. Here we report the photophysics of a new cross-conjugated push-pull enediynyl dye which belongs to an unexplored class of π-conjugated donor-acceptor systems. Two N,N-dimethylaniline moieties serve as donors and one pyrene ring functions as an acceptor via a common Y-shaped 'enediyne' bridge which facilitates the cross-electronic communication. The dye exhibits dual emission from locally excited (LE) and intramolecular charge transfer (ICT) states. While the LE emission is dominant in non-polar solvents, the ICT emission predominates in polar solvents. Time-resolved fluorescence decay experiments reveal a relatively shorter lifetime component (∼0.5-0.9 ns) belonging to an ICT state and a relatively longer lifetime species (∼1.6-2.8 ns) corresponding to the LE state. The strong ICT behavior of the dye is manifested through the huge red-shift (4166 cm-1) of the emission spectra from non-polar cyclohexane to polar N,N-dimethylformamide. In contrast to many small push-pull organic dyes, the LE and ICT states of the push-pull enediynyl dye follow the same excitation pathway. The dominant red-shifted ICT emission (∼550 nm) intensity of the dye in polar solvent decreases with a concomitant appearance of the blue-shifted LE emission (∼385 nm) upon prolonged exposure to photons. This opens up a new photophysical strategy of achieving high contrast two fluorescence color conversion from yellow to blue.

  10. Patterns of Alcohol Policy Enforcement Activities among Local Law Enforcement Agencies: A Latent Class Analysis

    PubMed Central

    Erickson, Darin J.; Rutledge, Patricia C.; Lenk, Kathleen M.; Nelson, Toben F.; Jones-Webb, Rhonda; Toomey, Traci L.

    2015-01-01

    Aims We assessed levels and patterns of alcohol policy enforcement activities among U.S. local law enforcement agencies. Design/Setting/Participants We conducted a cross-sectional survey of a representative sample of 1,631 local law enforcement agencies across the 50 states. Measures/Methods We assessed 29 alcohol policy enforcement activities within each of five enforcement domains—underage alcohol possession/consumption, underage alcohol provision, underage alcohol sales, impaired driving, and overservice of alcohol—and conducted a series of latent class analyses to identify unique classes or patterns of enforcement activity for each domain. Findings We identified three to four unique enforcement activity classes for each of the enforcement domains. In four of the domains, we identified a Uniformly Low class (i.e., little or no enforcement) and a Uniformly High enforcement activity class (i.e., relatively high levels of enforcement), with one or two middle classes where some but not all activities were conducted. The underage provision domain had a Uniformly Low class but not a Uniformly High class. The Uniformly Low class was the most prevalent class in three domains: underage provision (58%), underage sales (61%), and overservice (79%). In contrast, less than a quarter of agencies were in Uniformly High classes. Conclusions We identified qualitatively distinct patterns of enforcement activity, with a large proportion of agencies in classes characterized by little or no enforcement and fewer agencies in high enforcement classes. An important next step is to determine if these patterns are associated with rates of alcohol use and alcohol-related injury and mortality. PMID:26877822

  11. GPCRs and EGFR - Cross-talk of membrane receptors in cancer.

    PubMed

    Köse, Meryem

    2017-08-15

    G protein-coupled receptors (GPCRs) and receptor-tyrosine kinases (RTKs) are two important classes of cell surface receptors proven to be highly tractable as drug targets. Both receptor classes are involved in various complex (patho-) physiological processes in the human body including cellular growth and differentiation. More recently, accumulating data suggest that GPCR-induced activation of EGFR, the prototyp of RTKs represents a major mechanism in various cancers. The present review will focus on this cross-talk with particular emphasis on intracellular scaffold proteins regulating EGFR transactivation. It will give an overview about the current status of the research and future directions, highlight recent trends in the field, and discuss the potential of therapeutic strategies combining GPCR and EGFR targeting on the one hand and specific targeting of the cross-talk on the other hand in cancer therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Facilitating biomedical researchers' interrogation of electronic health record data: Ideas from outside of biomedical informatics.

    PubMed

    Hruby, Gregory W; Matsoukas, Konstantina; Cimino, James J; Weng, Chunhua

    2016-04-01

    Electronic health records (EHR) are a vital data resource for research uses, including cohort identification, phenotyping, pharmacovigilance, and public health surveillance. To realize the promise of EHR data for accelerating clinical research, it is imperative to enable efficient and autonomous EHR data interrogation by end users such as biomedical researchers. This paper surveys state-of-art approaches and key methodological considerations to this purpose. We adapted a previously published conceptual framework for interactive information retrieval, which defines three entities: user, channel, and source, by elaborating on channels for query formulation in the context of facilitating end users to interrogate EHR data. We show the current progress in biomedical informatics mainly lies in support for query execution and information modeling, primarily due to emphases on infrastructure development for data integration and data access via self-service query tools, but has neglected user support needed during iteratively query formulation processes, which can be costly and error-prone. In contrast, the information science literature has offered elaborate theories and methods for user modeling and query formulation support. The two bodies of literature are complementary, implying opportunities for cross-disciplinary idea exchange. On this basis, we outline the directions for future informatics research to improve our understanding of user needs and requirements for facilitating autonomous interrogation of EHR data by biomedical researchers. We suggest that cross-disciplinary translational research between biomedical informatics and information science can benefit our research in facilitating efficient data access in life sciences. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Deciphering complex patterns of class-I HLA-peptide cross-reactivity via hierarchical grouping.

    PubMed

    Mukherjee, Sumanta; Warwicker, Jim; Chandra, Nagasuma

    2015-07-01

    T-cell responses in humans are initiated by the binding of a peptide antigen to a human leukocyte antigen (HLA) molecule. The peptide-HLA complex then recruits an appropriate T cell, leading to cell-mediated immunity. More than 2000 HLA class-I alleles are known in humans, and they vary only in their peptide-binding grooves. The polymorphism they exhibit enables them to bind a wide range of peptide antigens from diverse sources. HLA molecules and peptides present a complex molecular recognition pattern, as many peptides bind to a given allele and a given peptide can be recognized by many alleles. A powerful grouping scheme that not only provides an insightful classification, but is also capable of dissecting the physicochemical basis of recognition specificity is necessary to address this complexity. We present a hierarchical classification of 2010 class-I alleles by using a systematic divisive clustering method. All-pair distances of alleles were obtained by comparing binding pockets in the structural models. By varying the similarity thresholds, a multilevel classification was obtained, with 7 supergroups, each further subclassifying to yield 72 groups. An independent clustering performed based only on similarities in their epitope pools correlated highly with pocket-based clustering. Physicochemical feature combinations that best explain the basis of clustering are identified. Mutual information calculated for the set of peptide ligands enables identification of binding site residues contributing to peptide specificity. The grouping of HLA molecules achieved here will be useful for rational vaccine design, understanding disease susceptibilities and predicting risk of organ transplants.

  14. Simplified Design Equations for Class-E Neural Prosthesis Transmitters

    PubMed Central

    Troyk, Philip; Hu, Zhe

    2013-01-01

    Extreme miniaturization of implantable electronic devices is recognized as essential for the next generation of neural prostheses, owing to the need for minimizing the damage and disruption of the surrounding neural tissue. Transcutaneous power and data transmission via a magnetic link remains the most effective means of powering and controlling implanted neural prostheses. Reduction in the size of the coil, within the neural prosthesis, demands the generation of a high-intensity radio frequency magnetic field from the extracoporeal transmitter. The Class-E power amplifier circuit topology has been recognized as a highly effective means of producing large radio frequency currents within the transmitter coil. Unfortunately, design of a Class-E circuit is most often fraught by the need to solve a complex set of equations so as to implement both the zero-voltage-switching and zero-voltage-derivative-switching conditions that are required for efficient operation. This paper presents simple explicit design equations for designing the Class-E circuit topology. Numerical design examples are presented to illustrate the design procedure. PMID:23292784

  15. Factors Related to In-Class Spiritual Experience: Relationship between Pre-Class Scripture Reading, In-Class Note-Taking, and Perceived In-Class Spiritual Experiences

    ERIC Educational Resources Information Center

    Hilton, John, III; Sweat, Anthony R.; Plummer, Kenneth

    2015-01-01

    The purpose of this study is to examine the relationship between student in-class note-taking and pre-class reading with perceived in-class spiritual and religious outcomes. This study surveyed 620 students enrolled in six different sections of an introductory religion course at a private religious university. Full-time religious faculty members…

  16. Mapping Coaches' Views of Participation in CrossFit to the Integrated Theory of Health Behavior Change and Sense of Community.

    PubMed

    Heinrich, Katie M; Carlisle, Taran; Kehler, Ainslie; Cosgrove, Sarah J

    Group-based training through CrossFit has recently exploded in popularity. Anecdotally, participants often make lifestyle changes and experience improved fitness. Participation factors were mapped to the Integrated Theory of Health Behavior Change and "sense of community" constructs. Key informant interviews were conducted with 6 CrossFit gym owners/coaches. Data were thematically coded with NVivo 10. Results revealed key factors that both facilitated and restricted participation in CrossFit. Findings provide implications for future theory application and highlight how to improve initiation and adherence by capitalizing on community building and taking steps to reduce intimidation and cost, facilitate realistic goals, and ensure social support.

  17. Mapping Coaches’ Views of Participation in CrossFit to the Integrated Theory of Health Behavior Change and Sense of Community

    PubMed Central

    Heinrich, Katie M.; Carlisle, Taran; Kehler, Ainslie; Cosgrove, Sarah J.

    2017-01-01

    Group-based training through CrossFit has recently exploded in popularity. Anecdotally, participants often make lifestyle changes and experience improved fitness. Participation factors were mapped to the Integrated Theory of Health Behavior Change and “sense of community” constructs. Key informant interviews were conducted with 6 CrossFit gym owners/coaches. Data were thematically coded with NVivo 10. Results revealed key factors that both facilitated and restricted participation in CrossFit. Findings provide implications for future theory application and highlight how to improve initiation and adherence by capitalizing on community building and taking steps to reduce intimidation and cost, facilitate realistic goals, and ensure social support. PMID:27870750

  18. The job content questionnaire in various occupational contexts: applying a latent class model

    PubMed Central

    Santos, Kionna Oliveira Bernardes; de Araújo, Tânia Maria; Karasek, Robert

    2017-01-01

    Objective To evaluate Job Content Questionnaire(JCQ) performance using the latent class model. Methods We analysed cross-sectional studies conducted in Brazil and examined three occupational categories: petroleum industry workers (n=489), teachers (n=4392) and primary healthcare workers (3078)and 1552 urban workers from a representative sample of the city of Feira de Santana in Bahia, Brazil. An appropriate number of latent classes was extracted and described each occupational category using latent class analysis, a multivariate method that evaluates constructs and takes into account the latent characteristics underlying the structure of measurement scales. The conditional probabilities of workers belonging to each class were then analysed graphically. Results Initially, the latent class analysis extracted four classes corresponding to the four job types (active, passive, low strain and high strain) proposed by the Job-Strain model (JSM) and operationalised by the JCQ. However, after taking into consideration the adequacy criteria to evaluate the number of extracted classes, three classes (active, low strain and high strain) were extracted from the studies of urban workers and teachers and four classes (active, passive, low strain and high strain) from the study of primary healthcare and petroleum industry workers. Conclusion The four job types proposed by the JSM were identified among primary healthcare and petroleum industry workers—groups with relatively high levels of skill discretion and decision authority. Three job types were identified for teachers and urban workers; however, passive job situations were not found within these groups. The latent class analysis enabled us to describe the conditional standard responses of the job types proposed by the model, particularly in relation to active jobs and high and low strain situations. PMID:28515185

  19. Psychosocial job characteristics and psychological distress / well-being: the mediating role of personal goal facilitation.

    PubMed

    Pisanti, Renato; van der Doef, Margot; Maes, Stan; Violani, Cristiano; Lazzari, David

    2016-01-01

    This study examined the mediating role of personal goal facilitation through work (PGFW), defined as perceptions of the extent to which one's job facilitates the attainment of one's personal goals, in the association between psychosocial job characteristics and psychological distress and job-related well-being. Questionnaire data from 217 nurses (84% female, with a mean age of 42.7 years, SD=7.2) were analyzed. Participants completed the following measures: the Leiden Quality of Work Questionnaire for Nurses, Workplace Goal Facilitation Inventory, Maslach Burnout Inventory-Human Services Survey, and Utrecht Work Engagement Scale (short version). A cross-sectional study design was applied. Hierarchical multiple regression analyses were conducted. The results indicated that unfavorable psychosocial job characteristics (high demands, low control, and low social support) were associated with lower PGFW. Furthermore, personal goal facilitation through work explained significant additional variance (from 2 to 11%) in psychological distress (somatic complaints and emotional exhaustion) and job-related well-being (personal accomplishment, job satisfaction, and work engagement), controlling for demographic indicators and psychosocial job characteristics. Finally, the results provided support for the mediating effects of PGFW between all psychosocial job characteristics and all outcomes, except in the case of depersonalization. This study suggests that hindered personal goal facilitation may be a mechanism through which psychosocial job characteristics have a negative impact on employees' well-being.

  20. Asymmetric viability of reciprocal-cross hybrids between crested and marbled newts (Triturus cristatus and T. Marmoratus).

    PubMed

    Arntzen, Jan W; Jehle, Robert; Bardakci, Fevzi; Burke, Terry; Wallis, Graham P

    2009-05-01

    Hybridization between divergent lineages often results in reduced hybrid viability. Here we report findings from a series of independent molecular analyses over several seasons on four life stages of F1 hybrids between the newts Triturus cristatus and T. marmoratus. These two species form a bimodal hybrid zone of broad overlap in France, with F1 hybrids making up about 4% of the adult population. We demonstrate strong asymmetry in the direction of the cross, with one class (cristatus-mothered) making up about 90% of F1 hybrids. By analyzing embryos and hatchlings, we show that this asymmetry is not due to prezygotic effects, as both classes of hybrid embryos are present at similar frequencies, implicating differential selection on the two hybrid classes after hatching. Adult F1 hybrids show a weak Haldane effect overall, with a 72% excess of females. The rarer marmoratus-mothered class, however, consists entirely of males. The absence of females from this class of adult F1 hybrids is best explained by an incompatibility between the cristatus X chromosome and marmoratus cytoplasm. It is thus important to distinguish the two classes of reciprocal-cross hybrids before making general statements about whether Haldane's rule is observed.

  1. Barriers to and Facilitators of Research Utilization: A Survey of Registered Nurses in China

    PubMed Central

    Wang, Li-Ping; Jiang, Xiao-Lian; Wang, Lei; Wang, Guo-Rong; Bai, Yang-Jing

    2013-01-01

    Aims This survey aims to describe the perception of barriers to and facilitators of research utilization by registered nurses in Sichuan province, China, and to explore the factors influencing the perceptions of the barriers to and facilitators of research utilization. Methods A cross sectional survey design and a double cluster sampling method were adopted. A total of 590 registered nurses from 3 tertiary level hospitals in Sichuan province, China, were recruited in a period from September 2006 to January 2007. A modified BARRUERS Scale and a Facilitators Scale were used. Data were analyzed with descriptive statistics, rank transformation test, and multiple linear regression. Results Barriers related to the setting subscale were more influential than barriers related to other subscales. The lack of authority was ranked as the top greatest barrier (15.7%), followed by the lack of time (13.4%) and language barrier (15.0%). Additional barriers identified were the reluctance of patients to research utilization, the lack of funding, and the lack of legal protection. The top three greatest facilitators were enhancing managerial support (36.9%), advancing education to increase knowledge base (21.1%), and increasing time for reviewing and implementing (17.5%), while cooperation of patients to research utilization, establishing a panel to evaluate researches, and funding were listed as additional facilitators. Hospital, educational background, research experience, and knowledge on evidence-based nursing were the factors influencing perceptions of the barriers and facilitators. Conclusions Nurses in China are facing a number of significant barriers in research utilization. Enhancing managerial support might be the most promising facilitator, given Chinese traditional culture and existing health care system. Hospital, educational background, research experience and knowledge on evidence-based nursing should be taken into account to promote research utilization. The BARRIERS

  2. NNLO jet cross sections by subtraction

    NASA Astrophysics Data System (ADS)

    Somogyi, G.; Bolzoni, P.; Trócsányi, Z.

    2010-08-01

    We report on the computation of a class of integrals that appear when integrating the so-called iterated singly-unresolved approximate cross section of the NNLO subtraction scheme of Refs. [G. Somogyi, Z. Trócsányi, and V. Del Duca, JHEP 06, 024 (2005), arXiv:hep-ph/0502226; G. Somogyi and Z. Trócsányi, (2006), arXiv:hep-ph/0609041; G. Somogyi, Z. Trócsányi, and V. Del Duca, JHEP 01, 070 (2007), arXiv:hep-ph/0609042; G. Somogyi and Z. Trócsányi, JHEP 01, 052 (2007), arXiv:hep-ph/0609043] over the factorised phase space of unresolved partons. The integrated approximate cross section itself can be written as the product of an insertion operator (in colour space) times the Born cross section. We give selected results for the insertion operator for processes with two and three hard partons in the final state.

  3. Facilitating hydrological data analysis workflows in R: the RHydro package

    NASA Astrophysics Data System (ADS)

    Buytaert, Wouter; Moulds, Simon; Skoien, Jon; Pebesma, Edzer; Reusser, Dominik

    2015-04-01

    The advent of new technologies such as web-services and big data analytics holds great promise for hydrological data analysis and simulation. Driven by the need for better water management tools, it allows for the construction of much more complex workflows, that integrate more and potentially more heterogeneous data sources with longer tool chains of algorithms and models. With the scientific challenge of designing the most adequate processing workflow comes the technical challenge of implementing the workflow with a minimal risk for errors. A wide variety of new workbench technologies and other data handling systems are being developed. At the same time, the functionality of available data processing languages such as R and Python is increasing at an accelerating pace. Because of the large diversity of scientific questions and simulation needs in hydrology, it is unlikely that one single optimal method for constructing hydrological data analysis workflows will emerge. Nevertheless, languages such as R and Python are quickly gaining popularity because they combine a wide array of functionality with high flexibility and versatility. The object-oriented nature of high-level data processing languages makes them particularly suited for the handling of complex and potentially large datasets. In this paper, we explore how handling and processing of hydrological data in R can be facilitated further by designing and implementing a set of relevant classes and methods in the experimental R package RHydro. We build upon existing efforts such as the sp and raster packages for spatial data and the spacetime package for spatiotemporal data to define classes for hydrological data (HydroST). In order to handle simulation data from hydrological models conveniently, a HM class is defined. Relevant methods are implemented to allow for an optimal integration of the HM class with existing model fitting and simulation functionality in R. Lastly, we discuss some of the design challenges

  4. 77 FR 40488 - Amendment of Class D and Class E Airspace; Lakehurst, NJ

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-10

    ...-0456; Airspace Docket No. 12-AEA-9] Amendment of Class D and Class E Airspace; Lakehurst, NJ AGENCY... changes the name of the airport associated with the Class D and Class E airspace at Lakehurst, NJ. The... associated with the Class D airspace and Class E airspace designated as an extension to a Class D airspace...

  5. A Fundamental Study for Efficient Implementaion of Online Collaborative Activities in Large-Scale Classes

    ERIC Educational Resources Information Center

    Matsuba, Ryuichi; Suzuki, Yusei; Kubota, Shin-Ichiro; Miyazaki, Makoto

    2015-01-01

    We study tactics for writing skills development through cross-disciplinary learning in online large-scale classes, and particularly are interested in implementation of online collaborative activities such as peer reviewing of writing. The goal of our study is to carry out collaborative works efficiently via online effectively in large-scale…

  6. Parameters for Successful Management of Cross Cultural Virtual Teams

    ERIC Educational Resources Information Center

    Gullett, Evelyn; Sixl-Daniell, Karin

    2008-01-01

    Virtual teams are a common phenomenon in organizations today. Universities are no exception to this trend and, in response, are offering class rooms without boundaries by introducing online programs which allow individuals from all walks of life and diverse geographical locations to come together. Cross-cultural virtual teams, collaborating with…

  7. Reflections on "YouTestTube.com": An Online Video-Sharing Platform to Engage Students with Chemistry Laboratory Classes

    ERIC Educational Resources Information Center

    McClean, Stephen; McCartan, Kenneth G.; Meskin, Sheryl; Gorges, Beronia; Hagan, W. Paul

    2016-01-01

    This paper describes the construction and development of YouTestTube.com, a YouTube clone website to facilitate video-sharing, social networking, and reflections of chemistry laboratory classes for year one students within the School of Biomedical Sciences at Ulster University. The practice was first introduced in the 2008/09 academic year and has…

  8. Peer Assessment Enhances Student Learning: The Results of a Matched Randomized Crossover Experiment in a College Statistics Class.

    PubMed

    Sun, Dennis L; Harris, Naftali; Walther, Guenther; Baiocchi, Michael

    2015-01-01

    Feedback has a powerful influence on learning, but it is also expensive to provide. In large classes it may even be impossible for instructors to provide individualized feedback. Peer assessment is one way to provide personalized feedback that scales to large classes. Besides these obvious logistical benefits, it has been conjectured that students also learn from the practice of peer assessment. However, this has never been conclusively demonstrated. Using an online educational platform that we developed, we conducted an in-class matched-set, randomized crossover experiment with high power to detect small effects. We establish that peer assessment causes a small but significant gain in student achievement. Our study also demonstrates the potential of web-based platforms to facilitate the design of high-quality experiments to identify small effects that were previously not detectable.

  9. Peptide-binding motifs of two common equine class I MHC molecules in Thoroughbred horses.

    PubMed

    Bergmann, Tobias; Lindvall, Mikaela; Moore, Erin; Moore, Eugene; Sidney, John; Miller, Donald; Tallmadge, Rebecca L; Myers, Paisley T; Malaker, Stacy A; Shabanowitz, Jeffrey; Osterrieder, Nikolaus; Peters, Bjoern; Hunt, Donald F; Antczak, Douglas F; Sette, Alessandro

    2017-05-01

    Quantitative peptide-binding motifs of MHC class I alleles provide a valuable tool to efficiently identify putative T cell epitopes. Detailed information on equine MHC class I alleles is still very limited, and to date, only a single equine MHC class I allele, Eqca-1*00101 (ELA-A3 haplotype), has been characterized. The present study extends the number of characterized ELA class I specificities in two additional haplotypes found commonly in the Thoroughbred breed. Accordingly, we here report quantitative binding motifs for the ELA-A2 allele Eqca-16*00101 and the ELA-A9 allele Eqca-1*00201. Utilizing analyses of endogenously bound and eluted ligands and the screening of positional scanning combinatorial libraries, detailed and quantitative peptide-binding motifs were derived for both alleles. Eqca-16*00101 preferentially binds peptides with aliphatic/hydrophobic residues in position 2 and at the C-terminus, and Eqca-1*00201 has a preference for peptides with arginine in position 2 and hydrophobic/aliphatic residues at the C-terminus. Interestingly, the Eqca-16*00101 motif resembles that of the human HLA A02-supertype, while the Eqca-1*00201 motif resembles that of the HLA B27-supertype and two macaque class I alleles. It is expected that the identified motifs will facilitate the selection of candidate epitopes for the study of immune responses in horses.

  10. The Latent Class Structure of Chinese Patients with Eating Disorders in Shanghai.

    PubMed

    Zheng, Yuchen; Kang, Qing; Huang, Jiabin; Jiang, Wenhui; Liu, Qiang; Chen, Han; Fan, Qing; Wang, Zhen; Chen, Jue; Xiao, Zeping

    2017-08-25

    Eating disorder is culture related, and the clinical symptoms are different between eastern and western patients. So the validity of feeding and eating disorders in the upcoming ICD-11 guide for Chinese patients is unclear. To explore the latent class structure of Chinese patients with eating disorder and the cross-cultural validity of the eating disorder section of the new ICD-11 guide in China. A total of 379 patients with eating disorders at Shanghai Mental Health Center were evaluated using the EDI questionnaire and a questionnaire developed by researchers from 2010 to 2016. SPSS 20.0 was used to enter data and analyze demographic data, and Latent GOLD was employed to conduct latent profile analysis. According to the results of latent profile analysis, patients with eating disorder were divided into five classes: low-weight fasting class (23.1%), non-fat-phobic binge/purge class (21.54%), low-fat-phobic binge class (19.27%), fat-phobic binge class (19.27%), and non-fat-phobic low-weight class (16.76%). Among the clinical symptoms extracted, there were significant differences in Body Mass Index (BMI), binge eating behavior, self-induced vomiting, laxative use and fat-phobic opinion; while there was no significant difference in restrictive food intake. Based on the clinical symptoms, there are five latent classes in Chinese patients with eating disorder, which is in accordance with the diagnostic categories of feeding and eating disorder in ICD-11. However, further work is needed in improving the fat-phobic opinion of patients with eating disorder and clarifying the BMI standard of thinness in the Chinese population.

  11. Role-playing in the problem-based learning class.

    PubMed

    Chan, Zenobia C Y

    2012-01-01

    Learning and teaching have been conceptualized and executed in many styles, such as self-learning, peer learning, and interaction between the learner and mentor. Today, openness to alternative ideas and embracing innovative approaches in nursing education are encouraged in order to meet students' learning interests and needs, and to address ever-changing healthcare requests. Problem-based learning has been widely adopted in nursing education, with various positive effects on students' learning, such as motivated learning, team work, problem-solving skills and critical thinking. Role-plays have been demonstrated as an effective learning strategy that includes an active and experiential feature that facilitates students' autonomy in their health-related learning. However, there is a lack of discussion of whether and how role-play can be used in problem-based learning (PBL). This paper shows the development of a classroom-based innovation using role-play in the PBL class for higher diploma year-one nurse students (a total of 20 students, five per group). This paper consists of five sections: a) the literature on PBL and nurse education, and role-plays as the innovation; b) the PBL case scenario with the illustration of the two role-play scripts, c) student evaluation on role-play in the PBL class; d) discussions on both achievements and limitations of this innovation, and e) the conclusion. It is hoped that this paper will be an example to other nurse educators who are keen on exploring interactive and student-driven learning and teaching strategies in the PBL class. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Cross-Linked Micellar Spherical Nucleic Acids from Thermoresponsive Templates

    PubMed Central

    2017-01-01

    A one-pot synthesis of micellar spherical nucleic acid (SNA) nanostructures using Pluronic F127 as a thermoresponsive template is reported. These novel constructs are synthesized in a chemically straightforward process that involves intercalation of the lipid tails of DNA amphiphiles (CpG motifs for TLR-9 stimulation) into the hydrophobic regions of Pluronic F127 micelles, followed by chemical cross-linking and subsequent removal of non-cross-linked structures. The dense nucleic acid shell of the resulting cross-linked micellar SNA enhances their stability in physiological media and facilitates their rapid cellular internalization, making them effective TLR-9 immunomodulatory agents. These constructs underscore the potential of SNAs in regulating immune response and address the relative lack of stability of noncovalent constructs. PMID:28207251

  13. The immunoglobulin class of anti-hapten antibody secreted during secondary responses in vitro and in vivo.

    PubMed Central

    North, J R; Dresser, D W

    1977-01-01

    A comparison has been made of the in vitro and in vivo response of primed mouse spleen cells to the hapten DNP. The responses were analysed in terms of six classes (sub-classes) of humoral antibody directed against the cross-reacting hapten TNP. By comparison with the response in intact mice the adoptive secondary response is delayed by 3 days in addition to being somewhat lesser in magnitude. The timing of the response in vitro is similar to that observed in intact mice. The preponderant class in all three responses was gammaG1 with gammaA and gammaG3 secreting cells consistently comprising the smallest proportion of the total of antibody-secreting cells. PMID:863475

  14. The immunoglobulin class of anti-hapten antibody secreted during secondary responses in vitro and in vivo.

    PubMed

    North, J R; Dresser, D W

    1977-05-01

    A comparison has been made of the in vitro and in vivo response of primed mouse spleen cells to the hapten DNP. The responses were analysed in terms of six classes (sub-classes) of humoral antibody directed against the cross-reacting hapten TNP. By comparison with the response in intact mice the adoptive secondary response is delayed by 3 days in addition to being somewhat lesser in magnitude. The timing of the response in vitro is similar to that observed in intact mice. The preponderant class in all three responses was gammaG1 with gammaA and gammaG3 secreting cells consistently comprising the smallest proportion of the total of antibody-secreting cells.

  15. Magnetic navigation facilitates percutaneous coronary intervention for complex lesions.

    PubMed

    Sandhu, Gurpreet S; Sanon, Saurabh; Holmes, David R; Gulati, Rajiv; Brilakis, Emmanouil S; Lennon, Ryan J; Rihal, Charanjit S

    2014-10-01

    We sought to determine the utility of a magnetic navigation system (MNS) in treating a variety of coronary artery lesions including those that could not be revascularized with standard percutaneous coronary intervention (PCI). MNS may add value in the treatment of tortuous arteries and bifurcation lesions; however its widespread adoption has lagged because of cost and a lack of clear advantage over conventional PCI. We performed a retrospective analysis to determine whether MNS improved procedural success for highly complex lesions. One hundred and forty-eight patients underwent treatment with MNS at Mayo Clinic, Rochester. Clinical data, angiographic and procedural characteristics, lesion crossing success and outcomes were reviewed. Overall 133 patients underwent successful revascularization with 87% (143) of 164 lesions crossed using MNS alone. Another six lesions required a combination of MNS and conventional devices resulting in overall success of 91% (149/164). Eighteen complex lesions had previously failed PCI and 12 (67%) were successfully treated with MNS. Success after failed PCI was higher (88%) when a frequent user operated MNS, but occasional users also noted incremental success (30%). Twenty-five chronic total occlusions were included amongst these 164 lesions, with observed antegrade MNS lesion crossing rates of 78% for regular and 14% for occasional users. MNS is a useful adjunct to performance of PCI. This specialized technology has a clear learning curve and can facilitate treatment of highly complex lesions. © 2013 Wiley Periodicals, Inc.

  16. Analysis and design of continuous class-E power amplifier at sub-nominal condition

    NASA Astrophysics Data System (ADS)

    Chen, Peng; Yang, Kai; Zhang, Tianliang

    2017-12-01

    The continuous class-E power amplifier at sub-nominal condition is proposed in this paper. The class-E power amplifier at continuous mode means it can be high efficient on a series matching networks while at sub-nominal condition means it only requires the zero-voltage-switching condition. Comparing with the classical class-E power amplifier, the proposed design method releases two additional design freedoms, which increase the class-E power amplifier's design flexibility. Also, the proposed continuous class-E power amplifier at sub-nominal condition can perform high efficiency over a broad bandwidth. The performance study of the continuous class-E power amplifier at sub-nominal condition is derived and the design procedure is summarised. The normalised switch voltage and current waveforms are investigated. Furthermore, the influences of different sub-nominal conditions on the power losses of the switch-on resistor and the output power capability are also discussed. A broadband continuous class-E power amplifier based on a Gallium Nitride (GaN) transistor is designed and testified to verify the proposed design methodology. The measurement results show, it can deliver 10-15 W output power with 64-73% power-added efficiency over 1.4-2.8 GHz.

  17. Airport take-off noise assessment aimed at identify responsible aircraft classes.

    PubMed

    Sanchez-Perez, Luis A; Sanchez-Fernandez, Luis P; Shaout, Adnan; Suarez-Guerra, Sergio

    2016-01-15

    Assessment of aircraft noise is an important task of nowadays airports in order to fight environmental noise pollution given the recent discoveries on the exposure negative effects on human health. Noise monitoring and estimation around airports mostly use aircraft noise signals only for computing statistical indicators and depends on additional data sources so as to determine required inputs such as the aircraft class responsible for noise pollution. In this sense, the noise monitoring and estimation systems have been tried to improve by creating methods for obtaining more information from aircraft noise signals, especially real-time aircraft class recognition. Consequently, this paper proposes a multilayer neural-fuzzy model for aircraft class recognition based on take-off noise signal segmentation. It uses a fuzzy inference system to build a final response for each class p based on the aggregation of K parallel neural networks outputs Op(k) with respect to Linear Predictive Coding (LPC) features extracted from K adjacent signal segments. Based on extensive experiments over two databases with real-time take-off noise measurements, the proposed model performs better than other methods in literature, particularly when aircraft classes are strongly correlated to each other. A new strictly cross-checked database is introduced including more complex classes and real-time take-off noise measurements from modern aircrafts. The new model is at least 5% more accurate with respect to previous database and successfully classifies 87% of measurements in the new database. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Class categories and the subjective dimension of class: the case of Denmark.

    PubMed

    Harrits, Gitte Sommer; Pedersen, Helene Helboe

    2018-03-01

    Class relations have been proven to affect various aspects of social life, even in modern individualized societies. However, following claims on individualization and the so-called 'death of class' thesis, studying the subjective dimension of class - that is, the way individuals perceive of class relations and their own position within them - has gone out of style. We argue that even in equalized societies, subjective class perceptions may still influence attitudes and behaviour as they evolve to fit modern class relations. To explore the existence as well as structure and content of perceived social classes, this article investigates how people describe society and social groups in focus group discussions. We find that groups in different positions in terms of education and economy all tend to apply hierarchical class categories to describe Danish society, which is normally seen as one of the most equal societies and political systems in the world. In addition, we find that economic resources serve as a baseline for the hierarchical ordering, often supplemented with notions of education, lifestyle and/or occupational profile. Even though people are somewhat uncomfortable with the notion of class, their descriptions of Danish society and classes are surprisingly similar within and across groups. We conclude that not only do class relations matter; people are also highly aware of the existing classes and able to position themselves and others according to their notion of classes. © London School of Economics and Political Science 2017.

  19. Restriction of Receptor Movement Alters Cellular Response: Physical Force Sensing by EphA2

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Salaita, Khalid; Nair, Pradeep M; Petit, Rebecca S

    2009-09-09

    Activation of the EphA2 receptor tyrosine kinase by ephrin-A1 ligands presented on apposed cell surfaces plays important roles in development and exhibits poorly understood functional alterations in cancer. We reconstituted this intermembrane signaling geometry between live EphA2-expressing human breast cancer cells and supported membranes displaying laterally mobile ephrin-A1. Receptor-ligand binding, clustering, and subsequent lateral transport within this junction were observed. EphA2 transport can be blocked by physical barriers nanofabricated onto the underlying substrate. This physical reorganization of EphA2 alters the cellular response to ephrin-A1, as observed by changes in cytoskeleton morphology and recruitment of a disintegrin and metalloprotease 10. Quantitativemore » analysis of receptor-ligand spatial organization across a library of 26 mammary epithelial cell lines reveals characteristic differences that strongly correlate with invasion potential. These observations reveal a mechanism for spatio-mechanical regulation of EphA2 signaling pathways.« less

  20. A neuroprotective astrocyte state is induced by neuronal signal EphB1 but fails in ALS models.

    PubMed

    Tyzack, Giulia E; Hall, Claire E; Sibley, Christopher R; Cymes, Tomasz; Forostyak, Serhiy; Carlino, Giulia; Meyer, Ione F; Schiavo, Giampietro; Zhang, Su-Chun; Gibbons, George M; Newcombe, Jia; Patani, Rickie; Lakatos, András

    2017-10-27

    Astrocyte responses to neuronal injury may be beneficial or detrimental to neuronal recovery, but the mechanisms that determine these different responses are poorly understood. Here we show that ephrin type-B receptor 1 (EphB1) is upregulated in injured motor neurons, which in turn can activate astrocytes through ephrin-B1-mediated stimulation of signal transducer and activator of transcription-3 (STAT3). Transcriptional analysis shows that EphB1 induces a protective and anti-inflammatory signature in astrocytes, partially linked to the STAT3 network. This is distinct from the response evoked by interleukin (IL)-6 that is known to induce both pro inflammatory and anti-inflammatory processes. Finally, we demonstrate that the EphB1-ephrin-B1 pathway is disrupted in human stem cell derived astrocyte and mouse models of amyotrophic lateral sclerosis (ALS). Our work identifies an early neuronal help-me signal that activates a neuroprotective astrocytic response, which fails in ALS, and therefore represents an attractive therapeutic target.