Sample records for exchange factor vav2

  1. Association of VAV2 and VAV3 polymorphisms with cardiovascular risk factors

    PubMed Central

    Perretta-Tejedor, Nuria; Fernández-Mateos, Javier; García-Ortiz, Luis; Gómez-Marcos, Manuel A.; Recio-Rodríguez, José I.; Agudo-Conde, Cristina; Rodriguez-Sánchez, Emiliano; Morales, Ana I.; López-Hernández, Francisco J.; López-Novoa, José M.; González-Sarmiento, Rogelio; Martínez-Salgado, Carlos

    2017-01-01

    Hypertension, diabetes and obesity are cardiovascular risk factors closely associated to the development of renal and cardiovascular target organ damage. VAV2 and VAV3, members of the VAV family proto-oncogenes, are guanosine nucleotide exchange factors for the Rho and Rac GTPase family, which is related with cardiovascular homeostasis. We have analyzed the relationship between the presence of VAV2 rs602990 and VAV3 rs7528153 polymorphisms with cardiovascular risk factors and target organ damage (heart, vessels and kidney) in 411 subjects. Our results show that being carrier of the T allele in VAV2 rs602990 polymorphism is associated with an increased risk of obesity, reduced levels of ankle-brachial index and diastolic blood pressure and reduced retinal artery caliber. In addition, being carrier of T allele is associated with increased risk of target organ damage in males. On the other hand, being carrier of the T allele in VAV3 rs7528153 polymorphism is associated with a decreased susceptibility of developing a pathologic state composed by the presence of hypertension, diabetes, obesity or cardiovascular damage, and with an increased risk of developing altered basal glycaemia. This is the first report showing an association between VAV2 and VAV3 polymorphisms with cardiovascular risk factors and target organ damage. PMID:28157227

  2. Function of the nucleotide exchange activity of vav1 in T cell development and activation.

    PubMed

    Saveliev, Alexander; Vanes, Lesley; Ksionda, Olga; Rapley, Jonathan; Smerdon, Stephen J; Rittinger, Katrin; Tybulewicz, Victor L J

    2009-12-15

    The guanine nucleotide exchange factor (GEF) Vav1 is essential for transducing T cell antigen receptor (TCR) signals and therefore plays a critical role in the development and activation of T cells. It has been presumed that the GEF activity of Vav1 is important for its function; however, there has been no direct demonstration of this. Here, we generated mice expressing enzymatically inactive, but normally folded, Vav1 protein. Analysis of these mice showed that the GEF activity of Vav1 was necessary for the selection of thymocytes and for the optimal activation of T cells, including signal transduction to Rac1, Akt, and integrins. In contrast, the GEF activity of Vav1 was not required for TCR-induced calcium flux, activation of extracellular signal-regulated kinase and protein kinase D1, and cell polarization. Thus, in T cells, the GEF activity of Vav1 is essential for some, but not all, of its functions.

  3. Function of the Nucleotide Exchange Activity of Vav1 in T cell Development and Activation*

    PubMed Central

    Saveliev, Alexander; Vanes, Lesley; Ksionda, Olga; Rapley, Jonathan; Smerdon, Stephen J.; Rittinger, Katrin; Tybulewicz, Victor L. J.

    2012-01-01

    The guanine nucleotide exchange factor (GEF) Vav1 is essential for transducing T cell antigen receptor (TCR) signals and therefore plays a critical role in the development and activation of T cells. It has been presumed that the GEF activity of Vav1 is important for its function; however, there has been no direct demonstration of this. Here, we generated mice expressing enzymatically inactive, but normally folded, Vav1 protein. Analysis of these mice showed that the GEF activity of Vav1 was necessary for the selection of thymocytes and for the optimal activation of T cells, including signal transduction to Rac1, Akt, and integrins. In contrast, the GEF activity of Vav1 was not required for TCR-induced calcium flux, activation of extracellular signal–regulated kinase (ERK) and protein kinase D1 (PKD1), and cell polarization. Thus, in T cells, the GEF activity of Vav1 is essential for some, but not all, of its functions. PMID:20009105

  4. Clinical significance of increased guanine nucleotide exchange factor Vav3 expression in human gastric cancer.

    PubMed

    Lin, Kai-Yuan; Wang, Lu-Hai; Hseu, You-Cheng; Fang, Chia-Lang; Yang, Hsin-Ling; Kumar, K J Senthil; Tai, Chein; Uen, Yih-Huei

    2012-06-01

    Although gastric cancer is one of the most common malignancies worldwide, little is known on the molecular process of its development and progression. This study investigates the involvement of guanine nucleotide exchange factor Vav3 in tumor progression and in the prognosis of human gastric cancer. The two patient cohorts in this study consisted of 167 gastric cancer cases from 1997 through 2001, documenting pathologic and clinical factors, as well as the clinical outcomes. Immunohistochemistry, reverse transcription PCR, immunoblotting, and immunofluorescence were used to examine Vav3 expression in tumor and nontumor pairs of gastric tissues and gastric cell lines. Small hairpin RNA (shRNA) technology was used to study the effects of Vav3 knockdown on the growth and spread of gastric cancer cells. Finally, xenograph proliferation was used to study the tumor growth. Overexpression of Vav3 was associated with the depth of invasion (P = 0.0004), nodal status (P = 0.0260), distant metastasis (P = 0.0003), stage (P = 0.0002), and vascular invasion (P = 0.0286); and correlated with poor disease-free survival (P < 0.0001). Multivariate Cox regression analysis shows that overexpression of Vav3 is an independent prognostic marker for gastric cancer (P = 0.033). Disrupting the expression of Vav3 using shRNA technology inhibited gastric cancer cell growth, spread, and xenograph proliferation. This study suggests that overexpression of Vav3 can be a useful marker for predicting the outcome of patients with gastric cancer and that Vav3 targeting can represent a potential modality for treating gastric cancer. 2012 AACR

  5. Vav1 GEF activity is required for T cell mediated allograft rejection

    PubMed Central

    Haubert, Dirk; Li, Jianping; Saveliev, Alexander; Calzascia, Thomas; Sutter, Esther; Metzler, Barbara; Kaiser, Daniel; Tybulewicz, Victor L.J.; Weckbecker, Gisbert

    2012-01-01

    The GDP exchange factor (GEF) Vav1 is a central signal transducer downstream of the T cell receptor and has been identified as a key factor for T cell activation in the context of allograft rejection. Vav1 has been shown to transduce signals both dependent and independent of its GEF function. The most promising approach to disrupt Vav1 activity by pharmacological inhibition would be to target its GEF function. However, the contribution of Vav1 GEF activity for allogeneic T cell activation has not been clarified yet. To address this question, we used knock-in mice bearing a mutated Vav1 with disrupted GEF activity but intact GEF-independent functions. T cells from these mice showed strongly reduced proliferation and activation in response to allogeneic stimulation. Furthermore, lack of Vav1 GEF activity strongly abrogated the in vivo expansion of T cells in a systemic graft-versus-host model. In a cardiac transplantation model, mice with disrupted Vav1 GEF activity show prolonged allograft survival. These findings demonstrate a strong requirement for Vav1 GEF activity for allogeneic T cell activation and graft rejection suggesting that disruption of Vav1 GEF activity alone is sufficient to induce significant immunosuppression. PMID:22456277

  6. Mechanism and function of Vav1 localisation in TCR signalling

    PubMed Central

    Ksionda, Olga; Saveliev, Alexander; Köchl, Robert; Rapley, Jonathan; Faroudi, Mustapha; Smith-Garvin, Jennifer E.; Wülfing, Christoph; Rittinger, Katrin; Carter, Tom; Tybulewicz, Victor L. J.

    2012-01-01

    Summary The antigen-specific binding of T cells to antigen presenting cells results in recruitment of signalling proteins to microclusters at the cell-cell interface known as the immunological synapse (IS). The Vav1 guanine nucleotide exchange factor plays a critical role in T cell antigen receptor (TCR) signalling, leading to the activation of multiple pathways. We now show that it is recruited to microclusters and to the IS in primary CD4+ and CD8+ T cells. Furthermore, we show that this recruitment depends on the SH2 and C-terminal SH3 (SH3B) domains of Vav1, and on phosphotyrosines 112 and 128 of the SLP76 adaptor protein. Biophysical measurements show that Vav1 binds directly to these residues on SLP76 and that efficient binding depends on the SH2 and SH3B domains of Vav1. Finally, we show that the same two domains are critical for the phosphorylation of Vav1 and its signalling function in TCR-induced calcium flux. We propose that Vav1 is recruited to the IS by binding to SLP76 and that this interaction is critical for the transduction of signals leading to calcium flux. PMID:22956543

  7. Mechanism and function of Vav1 localisation in TCR signalling.

    PubMed

    Ksionda, Olga; Saveliev, Alexander; Köchl, Robert; Rapley, Jonathan; Faroudi, Mustapha; Smith-Garvin, Jennifer E; Wülfing, Christoph; Rittinger, Katrin; Carter, Tom; Tybulewicz, Victor L J

    2012-11-15

    The antigen-specific binding of T cells to antigen presenting cells results in recruitment of signalling proteins to microclusters at the cell-cell interface known as the immunological synapse (IS). The Vav1 guanine nucleotide exchange factor plays a critical role in T cell antigen receptor (TCR) signalling, leading to the activation of multiple pathways. We now show that it is recruited to microclusters and to the IS in primary CD4(+) and CD8(+) T cells. Furthermore, we show that this recruitment depends on the SH2 and C-terminal SH3 (SH3(B)) domains of Vav1, and on phosphotyrosines 112 and 128 of the SLP76 adaptor protein. Biophysical measurements show that Vav1 binds directly to these residues on SLP76 and that efficient binding depends on the SH2 and SH3(B) domains of Vav1. Finally, we show that the same two domains are critical for the phosphorylation of Vav1 and its signalling function in TCR-induced calcium flux. We propose that Vav1 is recruited to the IS by binding to SLP76 and that this interaction is critical for the transduction of signals leading to calcium flux.

  8. Vav1: Friend and Foe of Cancer.

    PubMed

    Guo, Fukun; Zheng, Yi

    2017-12-01

    A recent study shows that the protumorigenic guanine nucleotide exchange factor (GEF) Vav1 functions as a tumor suppressor in T cell acute lymphoblastic leukemia (T-ALL) through its ability to complex with the Cbl-b ubiquitin ligase and the intracellular domain of Notch1 (ICN1) and to promote ICN1 degradation. Vav1can act as a double-edged sword in tumorigenesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Vav1 GEF activity is required for T cell mediated allograft rejection.

    PubMed

    Haubert, Dirk; Li, Jianping; Saveliev, Alexander; Calzascia, Thomas; Sutter, Esther; Metzler, Barbara; Kaiser, Daniel; Tybulewicz, Victor L J; Weckbecker, Gisbert

    2012-06-01

    The GDP exchange factor (GEF) Vav1 is a central signal transducer downstream of the T cell receptor and has been identified as a key factor for T cell activation in the context of allograft rejection. Vav1 has been shown to transduce signals both dependent and independent of its GEF function. The most promising approach to disrupt Vav1 activity by pharmacological inhibition would be to target its GEF function. However, the contribution of Vav1 GEF activity for allogeneic T cell activation has not been clarified yet. To address this question, we used knock-in mice bearing a mutated Vav1 with disrupted GEF activity but intact GEF-independent functions. T cells from these mice showed strongly reduced proliferation and activation in response to allogeneic stimulation. Furthermore, lack of Vav1 GEF activity strongly abrogated the in vivo expansion of T cells in a systemic graft-versus-host model. In a cardiac transplantation model, mice with disrupted Vav1 GEF activity show prolonged allograft survival. These findings demonstrate a strong requirement for Vav1 GEF activity for allogeneic T cell activation and graft rejection suggesting that disruption of Vav1 GEF activity alone is sufficient to induce significant immunosuppression. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. PTP-PEST targets a novel tyrosine site in p120 catenin to control epithelial cell motility and Rho GTPase activity.

    PubMed

    Espejo, Rosario; Jeng, Yowjiun; Paulucci-Holthauzen, Adriana; Rengifo-Cam, William; Honkus, Krysta; Anastasiadis, Panos Z; Sastry, Sarita K

    2014-02-01

    Tyrosine phosphorylation is implicated in regulating the adherens junction protein, p120 catenin (p120), however, the mechanisms are not well defined. Here, we show, using substrate trapping, that p120 is a direct target of the protein tyrosine phosphatase, PTP-PEST, in epithelial cells. Stable shRNA knockdown of PTP-PEST in colon carcinoma cells results in an increased cytosolic pool of p120 concomitant with its enhanced tyrosine phosphorylation and decreased association with E-cadherin. Consistent with this, PTP-PEST knockdown cells exhibit increased motility, enhanced Rac1 and decreased RhoA activity on a collagen substrate. Furthermore, p120 localization is enhanced at actin-rich protrusions and lamellipodia and has an increased association with the guanine nucleotide exchange factor, VAV2, and cortactin. Exchange factor activity of VAV2 is enhanced by PTP-PEST knockdown whereas overexpression of a VAV2 C-terminal domain or DH domain mutant blocks cell motility. Analysis of point mutations identified tyrosine 335 in the N-terminal domain of p120 as the site of PTP-PEST dephosphorylation. A Y335F mutant of p120 failed to induce the 'p120 phenotype', interact with VAV2, stimulate cell motility or activate Rac1. Together, these data suggest that PTP-PEST affects epithelial cell motility by controlling the distribution and phosphorylation of p120 and its availability to control Rho GTPase activity.

  11. PTP-PEST targets a novel tyrosine site in p120 catenin to control epithelial cell motility and Rho GTPase activity

    PubMed Central

    Espejo, Rosario; Jeng, Yowjiun; Paulucci-Holthauzen, Adriana; Rengifo-Cam, William; Honkus, Krysta; Anastasiadis, Panos Z.; Sastry, Sarita K.

    2014-01-01

    ABSTRACT Tyrosine phosphorylation is implicated in regulating the adherens junction protein, p120 catenin (p120), however, the mechanisms are not well defined. Here, we show, using substrate trapping, that p120 is a direct target of the protein tyrosine phosphatase, PTP-PEST, in epithelial cells. Stable shRNA knockdown of PTP-PEST in colon carcinoma cells results in an increased cytosolic pool of p120 concomitant with its enhanced tyrosine phosphorylation and decreased association with E-cadherin. Consistent with this, PTP-PEST knockdown cells exhibit increased motility, enhanced Rac1 and decreased RhoA activity on a collagen substrate. Furthermore, p120 localization is enhanced at actin-rich protrusions and lamellipodia and has an increased association with the guanine nucleotide exchange factor, VAV2, and cortactin. Exchange factor activity of VAV2 is enhanced by PTP-PEST knockdown whereas overexpression of a VAV2 C-terminal domain or DH domain mutant blocks cell motility. Analysis of point mutations identified tyrosine 335 in the N-terminal domain of p120 as the site of PTP-PEST dephosphorylation. A Y335F mutant of p120 failed to induce the ‘p120 phenotype’, interact with VAV2, stimulate cell motility or activate Rac1. Together, these data suggest that PTP-PEST affects epithelial cell motility by controlling the distribution and phosphorylation of p120 and its availability to control Rho GTPase activity. PMID:24284071

  12. Molecular Basis for Failure of “Atypical” C1 Domain of Vav1 to Bind Diacylglycerol/Phorbol Ester*

    PubMed Central

    Geczy, Tamas; Peach, Megan L.; El Kazzouli, Saïd; Sigano, Dina M.; Kang, Ji-Hye; Valle, Christopher J.; Selezneva, Julia; Woo, Wonhee; Kedei, Noemi; Lewin, Nancy E.; Garfield, Susan H.; Lim, Langston; Mannan, Poonam; Marquez, Victor E.; Blumberg, Peter M.

    2012-01-01

    C1 domains, the recognition motif of the second messenger diacylglycerol and of the phorbol esters, are classified as typical (ligand-responsive) or atypical (not ligand-responsive). The C1 domain of Vav1, a guanine nucleotide exchange factor, plays a critical role in regulation of Vav activity through stabilization of the Dbl homology domain, which is responsible for exchange activity of Vav. Although the C1 domain of Vav1 is classified as atypical, it retains a binding pocket geometry homologous to that of the typical C1 domains of PKCs. This study clarifies the basis for its failure to bind ligands. Substituting Vav1-specific residues into the C1b domain of PKCδ, we identified five crucial residues (Glu9, Glu10, Thr11, Thr24, and Tyr26) along the rim of the binding cleft that weaken binding potency in a cumulative fashion. Reciprocally, replacing these incompatible residues in the Vav1 C1 domain with the corresponding residues from PKCδ C1b (δC1b) conferred high potency for phorbol ester binding. Computer modeling predicts that these unique residues in Vav1 increase the hydrophilicity of the rim of the binding pocket, impairing membrane association and thereby preventing formation of the ternary C1-ligand-membrane binding complex. The initial design of diacylglycerol-lactones to exploit these Vav1 unique residues showed enhanced selectivity for C1 domains incorporating these residues, suggesting a strategy for the development of ligands targeting Vav1. PMID:22351766

  13. Vav family exchange factors: an integrated regulatory and functional view

    PubMed Central

    Bustelo, Xosé R

    2014-01-01

    The Vav family is a group of tyrosine phosphorylation-regulated signal transduction molecules hierarchically located downstream of protein tyrosine kinases. The main function of these proteins is to work as guanosine nucleotide exchange factors (GEFs) for members of the Rho GTPase family. In addition, they can exhibit a variety of catalysis-independent roles in specific signaling contexts. Vav proteins play essential signaling roles for both the development and/or effector functions of a large variety of cell lineages, including those belonging to the immune, nervous, and cardiovascular systems. They also contribute to pathological states such as cancer, immune-related dysfunctions, and atherosclerosis. Here, I will provide an integrated view about the evolution, regulation, and effector properties of these signaling molecules. In addition, I will discuss the pros and cons for their potential consideration as therapeutic targets. PMID:25483299

  14. Vav1-mediated scaffolding interactions stabilize SLP-76 microclusters and contribute to antigen-dependent T cell responses.

    PubMed

    Sylvain, Nicholas R; Nguyen, Ken; Bunnell, Stephen C

    2011-03-08

    The guanine nucleotide exchange factor (GEF) Vav1 synergizes with the adaptor protein SLP-76 (Src homology 2 domain--containing leukocyte phosphoprotein of 76 kD) to support T cell development and activation. In response to ligation of the T cell receptor (TCR), SLP-76 is assembled into microclusters that provide an essential platform for the signaling events that drive T cell activation. We found that Vav1 selectively entered SLP-76 microclusters, rather than TCR microclusters, influencing their stability and function. The carboxyl terminus of Vav1, which consists of Src homology domains, was both necessary and sufficient for the entry of Vav1 into SLP-76 microclusters; however, this fragment of Vav1 was insufficient to stabilize the microclusters, and it potently suppressed T cell activation. This indicated that the amino terminus of Vav1, which has the GEF domain, also contributed to the integrity of SLP-76 microclusters and thereby to T cell activation. These microcluster-stabilizing functions were independent of the GEF activity in the amino terminus of Vav1 and were unaffected if the GEF function of Vav1 was either inactivated or constitutively activated by mutation. In contrast, Vav1 deletion mutants lacking either the calponin homology domain or the catalytic core of the GEF exhibited mild scaffolding defects, but they differentially affected TCR-dependent calcium ion (Ca²+) responses. We conclude that multiple GEF-independent scaffolding functions distributed throughout the amino terminus of Vav1 contribute to the activation of T cells by acting synergistically to increase the stability and function of SLP-76 microclusters.

  15. New insights into the Vav1 activation cycle in lymphocytes.

    PubMed

    Barreira, María; Rodríguez-Fdez, Sonia; Bustelo, Xosé R

    2018-05-01

    Vav1 is a hematopoietic-specific Rho GDP/GTP exchange factor and signaling adaptor. Although these activities are known to be stimulated by direct Vav1 phosphorylation, little information still exists regarding the regulatory layers that influence the overall Vav1 activation cycle. Using a collection of cell models and activation-mimetic Vav1 mutants, we show here that the dephosphorylated state of Vav1 in nonstimulated T cells requires the presence of a noncatalytic, phospholipase Cγ1-Slp76-mediated inhibitory pathway. Upon T cell stimulation, Vav1 becomes rapidly phosphorylated via the engagement of Lck and, to a much lesser extent, other Src family kinases and Zap70. In this process, Lck, Zap70 and the adaptor protein Lat contribute differently to the dynamics and amplitude of the Vav1 phosphorylated pool. Consistent with a multiphosphosite activation mechanism, the optimal stimulation of Vav1 can only be recapitulated by the combination of several activation-mimetic phosphosite mutants. The analysis of these mutants has also unveiled the presence of different Vav1 signaling competent states that are influenced by phosphosites present in the N- and C-terminal domains of the protein. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. The Amino-Terminus of Vav1 Regulates TCR-Induced SLP-76 Microclusters via the Calponin Homology Domain and Non-Catalytic Surfaces within the GEF Module

    PubMed Central

    Sylvain, Nicholas R.; Nguyen, Ken; Bunnell, Stephen C.

    2013-01-01

    The guanine nucleotide exchange factor (GEF) Vav1 synergizes with the adapter SLP-76 to support T cell development and activation. Here, we demonstrate that Vav1 controls the stability and movement T cell receptor-induced SLP-76 microclusters. The SH2 domain enables the recruitment of Vav1 into SLP-76 microclusters, whereas the SH3 domains of Vav1 cooperate to enhance microcluster stability and function. Although the amino-terminus of Vav1 is essential for downstream signaling, it possesses novel scaffolding functions that are unaffected by the inactivation of the Vav1 GEF or by the constitutive GEF activation that accompanies the mutation of the regulatory tyrosine residues 142, 160, and 174. In contrast, GEF-inactivating point mutations predicted to perturb the structural integrity of the Vav1 GEF abolish these scaffolding functions. Paradoxically, the excision of catalytic Dbl-homology (DH) / pleckstrin homology (PH) cassette produces a relatively mild scaffolding defect, indicating that the L213A and L278Q point mutations antagonize scaffolding functions mediated by adjacent domains. A deletion mutant lacking the CH domain potently inhibits calcium responses, but also exhibits mild scaffolding defects. We conclude multiple GEF-independent scaffolding functions contained within the amino-terminus of Vav1 contribute to T cell activation by acting synergistically to increase the stability and functionality of SLP-76 microclusters. PMID:21386095

  17. VAV-1 acts in a single interneuron to inhibit motor circuit activity in Caenorhabditis elegans.

    PubMed

    Fry, Amanda L; Laboy, Jocelyn T; Norman, Kenneth R

    2014-11-21

    The complex molecular and cellular mechanisms underlying neuronal control of animal movement are not well understood. Locomotion of Caenorhabditis elegans is mediated by a neuronal circuit that produces coordinated sinusoidal movement. Here we utilize this simple, yet elegant, behaviour to show that VAV-1, a conserved guanine nucleotide exchange factor for Rho-family GTPases, negatively regulates motor circuit activity and the rate of locomotion. While vav-1 is expressed in a small subset of neurons, we find that VAV-1 function is required in a single interneuron, ALA, to regulate motor neuron circuit activity. Furthermore, we show by genetic and optogenetic manipulation of ALA that VAV-1 is required for the excitation and activation of this neuron. We find that ALA signalling inhibits command interneuron activity by abrogating excitatory signalling in the command interneurons, which is responsible for promoting motor neuron circuit activity. Together, our data describe a novel neuromodulatory role for VAV-1-dependent signalling in the regulation of motor circuit activity and locomotion.

  18. Neutrophil-mediated oxidative burst and host defense are controlled by a Vav-PLCγ2 signaling axis in mice

    PubMed Central

    Graham, Daniel B.; Robertson, Charles M.; Bautista, Jhoanne; Mascarenhas, Francesca; Diacovo, M. Julia; Montgrain, Vivianne; Lam, Siu Kit; Cremasco, Viviana; Dunne, W. Michael; Faccio, Roberta; Coopersmith, Craig M.; Swat, Wojciech

    2007-01-01

    Oxidative burst, a critical antimicrobial mechanism of neutrophils, involves the rapid generation and release of reactive oxygen intermediates (ROIs) by the NADPH oxidase complex. Genetic mutations in an NADPH oxidase subunit, gp91 (also referred to as NOX2), are associated with chronic granulomatous disease (CGD), which is characterized by recurrent and life-threatening microbial infections. To combat such infections, ROIs are produced by neutrophils after stimulation by integrin-dependent adhesion to the ECM in conjunction with stimulation from inflammatory mediators, or microbial components containing pathogen-associated molecular patterns. In this report, we provide genetic evidence that both the Vav family of Rho GTPase guanine nucleotide exchange factors (GEFs) and phospholipase C–γ2 (PLC-γ2) are critical mediators of adhesion-dependent ROI production by neutrophils in mice. We also demonstrated that Vav was critically required for neutrophil-dependent host defense against systemic infection by Staphylococcus aureus and Pseudomonas aeruginosa, 2 common pathogens associated with fatal cases of hospital-acquired pneumonia. We identified a molecular pathway in which Vav GEFs linked integrin-mediated signaling with PLC-γ2 activation, release of intracellular Ca2+ cations, and generation of diacylglycerol to control assembly of the NADPH oxidase complex and ROI production by neutrophils. Taken together, our data indicate that integrin-dependent signals generated during neutrophil adhesion contribute to the activation of NADPH oxidase by a variety of distinct effector pathways, all of which require Vav. PMID:17932569

  19. The signaling pathway of Campylobacter jejuni-induced Cdc42 activation: Role of fibronectin, integrin beta1, tyrosine kinases and guanine exchange factor Vav2

    PubMed Central

    2011-01-01

    Background Host cell invasion by the foodborne pathogen Campylobacter jejuni is considered as one of the primary reasons of gut tissue damage, however, mechanisms and key factors involved in this process are widely unclear. It was reported that small Rho GTPases, including Cdc42, are activated and play a role during invasion, but the involved signaling cascades remained unknown. Here we utilised knockout cell lines derived from fibronectin-/-, integrin-beta1-/-, focal adhesion kinase (FAK)-/- and Src/Yes/Fyn-/- deficient mice, and wild-type control cells, to investigate C. jejuni-induced mechanisms leading to Cdc42 activation and bacterial uptake. Results Using high-resolution scanning electron microscopy, GTPase pulldowns, G-Lisa and gentamicin protection assays we found that each studied host factor is necessary for induction of Cdc42-GTP and efficient invasion. Interestingly, filopodia formation and associated membrane dynamics linked to invasion were only seen during infection of wild-type but not in knockout cells. Infection of cells stably expressing integrin-beta1 variants with well-known defects in fibronectin fibril formation or FAK signaling also exhibited severe deficiencies in Cdc42 activation and bacterial invasion. We further demonstrated that infection of wild-type cells induces increasing amounts of phosphorylated FAK and growth factor receptors (EGFR and PDGFR) during the course of infection, correlating with accumulating Cdc42-GTP levels and C. jejuni invasion over time. In studies using pharmacological inhibitors, silencing RNA (siRNA) and dominant-negative expression constructs, EGFR, PDGFR and PI3-kinase appeared to represent other crucial components upstream of Cdc42 and invasion. siRNA and the use of Vav1/2-/- knockout cells further showed that the guanine exchange factor Vav2 is required for Cdc42 activation and maximal bacterial invasion. Overexpression of certain mutant constructs indicated that Vav2 is a linker molecule between Cdc42 and activated EGFR/PDGFR/PI3-kinase. Using C. jejuni mutant strains we further demonstrated that the fibronectin-binding protein CadF and intact flagella are involved in Cdc42-GTP induction, indicating that the bacteria may directly target the fibronectin/integrin complex for inducing signaling leading to its host cell entry. Conclusion Collectively, our findings led us propose that C. jejuni infection triggers a novel fibronectin→integrin-beta1→FAK/Src→EGFR/PDGFR→PI3-kinase→Vav2 signaling cascade, which plays a crucial role for Cdc42 GTPase activity associated with filopodia formation and enhances bacterial invasion. PMID:22204307

  20. A Natural Variant of the T Cell Receptor-Signaling Molecule Vav1 Reduces Both Effector T Cell Functions and Susceptibility to Neuroinflammation.

    PubMed

    Kassem, Sahar; Gaud, Guillaume; Bernard, Isabelle; Benamar, Mehdi; Dejean, Anne S; Liblau, Roland; Fournié, Gilbert J; Colacios, Céline; Malissen, Bernard; Saoudi, Abdelhadi

    2016-07-01

    The guanine nucleotide exchange factor Vav1 is essential for transducing T cell antigen receptor signals and therefore plays an important role in T cell development and activation. Our previous genetic studies identified a locus on rat chromosome 9 that controls the susceptibility to neuroinflammation and contains a non-synonymous polymorphism in the major candidate gene Vav1. To formally demonstrate the causal implication of this polymorphism, we generated a knock-in mouse bearing this polymorphism (Vav1R63W). Using this model, we show that Vav1R63W mice display reduced susceptibility to experimental autoimmune encephalomyelitis (EAE) induced by MOG35-55 peptide immunization. This is associated with a lower production of effector cytokines (IFN-γ, IL-17 and GM-CSF) by autoreactive CD4 T cells. Despite increased proportion of Foxp3+ regulatory T cells in Vav1R63W mice, we show that this lowered cytokine production is intrinsic to effector CD4 T cells and that Treg depletion has no impact on EAE development. Finally, we provide a mechanism for the above phenotype by showing that the Vav1R63W variant has normal enzymatic activity but reduced adaptor functions. Together, these data highlight the importance of Vav1 adaptor functions in the production of inflammatory cytokines by effector T cells and in the susceptibility to neuroinflammation.

  1. A Natural Variant of the T Cell Receptor-Signaling Molecule Vav1 Reduces Both Effector T Cell Functions and Susceptibility to Neuroinflammation

    PubMed Central

    Kassem, Sahar; Bernard, Isabelle; Dejean, Anne S.; Liblau, Roland; Fournié, Gilbert J.; Colacios, Céline

    2016-01-01

    The guanine nucleotide exchange factor Vav1 is essential for transducing T cell antigen receptor signals and therefore plays an important role in T cell development and activation. Our previous genetic studies identified a locus on rat chromosome 9 that controls the susceptibility to neuroinflammation and contains a non-synonymous polymorphism in the major candidate gene Vav1. To formally demonstrate the causal implication of this polymorphism, we generated a knock-in mouse bearing this polymorphism (Vav1R63W). Using this model, we show that Vav1R63W mice display reduced susceptibility to experimental autoimmune encephalomyelitis (EAE) induced by MOG35-55 peptide immunization. This is associated with a lower production of effector cytokines (IFN-γ, IL-17 and GM-CSF) by autoreactive CD4 T cells. Despite increased proportion of Foxp3+ regulatory T cells in Vav1R63W mice, we show that this lowered cytokine production is intrinsic to effector CD4 T cells and that Treg depletion has no impact on EAE development. Finally, we provide a mechanism for the above phenotype by showing that the Vav1R63W variant has normal enzymatic activity but reduced adaptor functions. Together, these data highlight the importance of Vav1 adaptor functions in the production of inflammatory cytokines by effector T cells and in the susceptibility to neuroinflammation. PMID:27438086

  2. Pak and Rac GTPases promote oncogenic KIT–induced neoplasms

    PubMed Central

    Martin, Holly; Mali, Raghuveer Singh; Ma, Peilin; Chatterjee, Anindya; Ramdas, Baskar; Sims, Emily; Munugalavadla, Veerendra; Ghosh, Joydeep; Mattingly, Ray R.; Visconte, Valeria; Tiu, Ramon V.; Vlaar, Cornelis P.; Dharmawardhane, Suranganie; Kapur, Reuben

    2013-01-01

    An acquired somatic mutation at codon 816 in the KIT receptor tyrosine kinase is associated with poor prognosis in patients with systemic mastocytosis and acute myeloid leukemia (AML). Treatment of leukemic cells bearing this mutation with an allosteric inhibitor of p21–activated kinase (Pak) or its genetic inactivation results in growth repression due to enhanced apoptosis. Inhibition of the upstream effector Rac abrogates the oncogene-induced growth and activity of Pak. Although both Rac1 and Rac2 are constitutively activated via the guanine nucleotide exchange factor (GEF) Vav1, loss of Rac1 or Rac2 alone moderately corrected the growth of KIT-bearing leukemic cells, whereas the combined loss resulted in 75% growth repression. In vivo, the inhibition of Vav or Rac or Pak delayed the onset of myeloproliferative neoplasms (MPNs) and corrected the associated pathology in mice. To assess the role of Rac GEFs in oncogene-induced transformation, we used an inhibitor of Rac, EHop-016, which specifically targets Vav1 and found that EHop-016 was a potent inhibitor of human and murine leukemic cell growth. These studies identify Pak and Rac GTPases, including Vav1, as potential therapeutic targets in MPN and AML involving an oncogenic form of KIT. PMID:24091327

  3. Studying the dynamics of SLP-76, Nck, and Vav1 multimolecular complex formation in live human cells with triple-color FRET.

    PubMed

    Pauker, Maor H; Hassan, Nirit; Noy, Elad; Reicher, Barak; Barda-Saad, Mira

    2012-04-24

    Protein-protein interactions regulate and control many cellular functions. A multimolecular complex consisting of the adaptor proteins SLP-76 (Src homology 2 domain-containing leukocyte protein of 76 kD), Nck, and the guanine nucleotide exchange factor Vav1 is recruited to the T cell side of the interface with an antigen-presenting cell during initial T cell activation. This complex is crucial for regulation of the actin machinery, antigen recognition, and signaling in T cells. We studied the interactions between these proteins as well as the dynamics of their recruitment into a complex that governs cytoskeletal reorganization. We developed a triple-color Förster resonance energy transfer (3FRET) system to observe the dynamics of the formation of this trimolecular signaling complex in live human T cells and to follow the three molecular interactions in parallel. Using the 3FRET system, we demonstrated that dimers of Nck and Vav1 were constitutively formed independently of both T cell activation and the association between SLP-76 and Nck. After T cell receptor stimulation, SLP-76 was phosphorylated, which enabled the binding of Nck. A point mutation in the proline-rich site of Vav1, which abolishes its binding to Nck, impaired actin rearrangement, suggesting that Nck-Vav1 dimers play a critical role in regulation of the actin machinery. We suggest that these findings revise the accepted model of the formation of a complex of SLP-76, Nck, and Vav1 and demonstrate the use of 3FRET as a tool to study signal transduction in live cells.

  4. T-Cell Receptor- and CD28-induced Vav1 activity is required for the accumulation of primed T cells into antigenic tissue

    PubMed Central

    David, Rachel; Ma, Liang; Ivetic, Aleksandar; Takesono, Aya; Ridley, Anne J.; Chai, Jian-Guo; Tybulewicz, Victor; Marelli-Berg, Federica M.

    2016-01-01

    Localization of primed T cells to antigenic tissue is essential for the development of effective immunity. Together with tissue-selective homing molecules, T-cell receptor (TCR)- and CD28-mediated signals have been shown to promote transendothelial migration of specific T cells into non-lymphoid antigen-rich tissue tissue. However, the cellular and molecular requirements for T-cell accumulation to target tissue following their recruitment are largely undefined. The guanine nucleotide exchange factor (GEF) Vav1 has an integral role in coupling TCR and CD28 to signalling pathways that regulate T cell activation and migration. Here, we have investigated the contribution of TCR- and CD28-induced Vav1 activity to the trafficking and localization of primed HY-specific CD4+ T cells to antigenic sites. Severe migratory defects displayed by Vav1-/- T cells in vitro were fully compensated by a combination of shear flow and chemokines, leading to normal recruitment of Vav1-/- T cells in vivo. In contrast, Vav1-/- T-cell retention into antigen-rich tissue was severely impaired, reflecting their inability to engage in sustained TCR- and CD28-mediated interactions with tissue-resident antigen-presenting cells (APCs). This novel function of APC-induced, TCR- and CD28-mediated Vav1 activity in the regulation of effector T-cell immunity highlights its potential as a therapeutic target in T-cell-mediated tissue damage. PMID:19060239

  5. A Protein Scaffold Coordinates SRC-Mediated JNK Activation in Response to Metabolic Stress.

    PubMed

    Kant, Shashi; Standen, Claire L; Morel, Caroline; Jung, Dae Young; Kim, Jason K; Swat, Wojciech; Flavell, Richard A; Davis, Roger J

    2017-09-19

    Obesity is a major risk factor for the development of metabolic syndrome and type 2 diabetes. How obesity contributes to metabolic syndrome is unclear. Free fatty acid (FFA) activation of a non-receptor tyrosine kinase (SRC)-dependent cJun NH 2 -terminal kinase (JNK) signaling pathway is implicated in this process. However, the mechanism that mediates SRC-dependent JNK activation is unclear. Here, we identify a role for the scaffold protein JIP1 in SRC-dependent JNK activation. SRC phosphorylation of JIP1 creates phosphotyrosine interaction motifs that bind the SH2 domains of SRC and the guanine nucleotide exchange factor VAV. These interactions are required for SRC-induced activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module. The JIP1 scaffold protein, therefore, plays a dual role in FFA signaling by coordinating upstream SRC functions together with downstream effector signaling by the JNK pathway. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. Phage display discovery of novel molecular targets in glioblastoma-initiating cells.

    PubMed

    Liu, J K; Lubelski, D; Schonberg, D L; Wu, Q; Hale, J S; Flavahan, W A; Mulkearns-Hubert, E E; Man, J; Hjelmeland, A B; Yu, J; Lathia, J D; Rich, J N

    2014-08-01

    Glioblastoma is the most common primary intrinsic brain tumor and remains incurable despite maximal therapy. Glioblastomas display cellular hierarchies with self-renewing glioma-initiating cells (GICs) at the apex. To discover new GIC targets, we used in vivo delivery of phage display technology to screen for molecules selectively binding GICs that may be amenable for targeting. Phage display leverages large, diverse peptide libraries to identify interactions with molecules in their native conformation. We delivered a bacteriophage peptide library intravenously to a glioblastoma xenograft in vivo then derived GICs. Phage peptides bound to GICs were analyzed for their corresponding proteins and ranked based on prognostic value, identifying VAV3, a Rho guanine exchange factor involved tumor invasion, and CD97 (cluster of differentiation marker 97), an adhesion G-protein-coupled-receptor upstream of Rho, as potentially enriched in GICs. We confirmed that both VAV3 and CD97 were preferentially expressed by tumor cells expressing GIC markers. VAV3 expression correlated with increased activity of its downstream mediator, Rac1 (ras-related C3 botulinum toxin substrate 1), in GICs. Furthermore, targeting VAV3 by ribonucleic acid interference decreased GIC growth, migration, invasion and in vivo tumorigenesis. As CD97 is a cell surface protein, CD97 selection enriched for sphere formation, a surrogate of self-renewal. In silico analysis demonstrated VAV3 and CD97 are highly expressed in tumors and inform poor survival and tumor grade, and more common with epidermal growth factor receptor mutations. Finally, a VAV3 peptide sequence identified on phage display specifically internalized into GICs. These results show a novel screening method for identifying oncogenic pathways preferentially activated within the tumor hierarchy, offering a new strategy for developing glioblastoma therapies.

  7. Phage display discovery of novel molecular targets in glioblastoma-initiating cells

    PubMed Central

    Liu, J K; Lubelski, D; Schonberg, D L; Wu, Q; Hale, J S; Flavahan, W A; Mulkearns-Hubert, E E; Man, J; Hjelmeland, A B; Yu, J; Lathia, J D; Rich, J N

    2014-01-01

    Glioblastoma is the most common primary intrinsic brain tumor and remains incurable despite maximal therapy. Glioblastomas display cellular hierarchies with self-renewing glioma-initiating cells (GICs) at the apex. To discover new GIC targets, we used in vivo delivery of phage display technology to screen for molecules selectively binding GICs that may be amenable for targeting. Phage display leverages large, diverse peptide libraries to identify interactions with molecules in their native conformation. We delivered a bacteriophage peptide library intravenously to a glioblastoma xenograft in vivo then derived GICs. Phage peptides bound to GICs were analyzed for their corresponding proteins and ranked based on prognostic value, identifying VAV3, a Rho guanine exchange factor involved tumor invasion, and CD97 (cluster of differentiation marker 97), an adhesion G-protein-coupled-receptor upstream of Rho, as potentially enriched in GICs. We confirmed that both VAV3 and CD97 were preferentially expressed by tumor cells expressing GIC markers. VAV3 expression correlated with increased activity of its downstream mediator, Rac1 (ras-related C3 botulinum toxin substrate 1), in GICs. Furthermore, targeting VAV3 by ribonucleic acid interference decreased GIC growth, migration, invasion and in vivo tumorigenesis. As CD97 is a cell surface protein, CD97 selection enriched for sphere formation, a surrogate of self-renewal. In silico analysis demonstrated VAV3 and CD97 are highly expressed in tumors and inform poor survival and tumor grade, and more common with epidermal growth factor receptor mutations. Finally, a VAV3 peptide sequence identified on phage display specifically internalized into GICs. These results show a novel screening method for identifying oncogenic pathways preferentially activated within the tumor hierarchy, offering a new strategy for developing glioblastoma therapies. PMID:24832468

  8. T cell receptor-driven transendothelial migration of human effector memory CD4 T cells involves Vav, Rac and Myosin IIA

    PubMed Central

    Manes, Thomas D.; Pober, Jordan S.

    2013-01-01

    Human effector memory (EM) CD4 T cells may be recruited from the blood into a site of inflammation in response either to inflammatory chemokines displayed on or specific antigen presented by venular endothelial cells (ECs), designated as chemokine-driven or TCR-driven transendothelial migration (TEM), respectively. We have previously described differences in the morphological appearance of transmigrating T cells as well as in the molecules that mediate T cell-EC interactions distinguishing these two pathways. Here we report that TCR-driven TEM requires ZAP-70-dependent activation of a pathway involving Vav, Rac and myosin IIA. Chemokine-driven TEM also utilizes ZAP-70, albeit in a quantitatively and spatially different manner of activation, and is independent of Vav, Rac and mysosin IIA, depending instead on an as yet unidentified GTP exchange factor that activates Cdc42. The differential use of small Rho family GTPases to activate the cytoskeleton is consistent with the morphological differences observed in T cells that undergo TEM in response to these distinct recruitment signals. PMID:23420881

  9. Probing the Tyrosine Phosphorylation State in Breast Cancer by Src Homology 2 Domain Binding

    DTIC Science & Technology

    2006-08-01

    pervanadate, a potent tyrosine phosphatase inhibitor . In the absence of pervanadate, endogenous phosphatases very rapidly dephosphorylate tyrosine...Shd Loc90525 Crk CrkL Plcg1NCPlcg2NC P85aNC p55gNC Vav1 Vav2 Vav3 Tec Btk Emt Txk Bmx Slp76 Mist MistRK GapNC Chimerin Chimerin 2 Tensin Tem6 Tenc1...Plcg1NCPlcg2NC P85aNC Vav1 Vav2 Vav3 Tec Btk Emt Txk Bmx Slp76 Mist MistRK GapNC Chimerin Chimerin 2 Tensin Tem6 Tenc1 Cis1 Cten Nap4 Rin1 RIn2 Rin3

  10. SLP-76 couples Syk to the osteoclast cytoskeleton.

    PubMed

    Reeve, Jennifer L; Zou, Wei; Liu, Yuli; Maltzman, Jonathan S; Ross, F Patrick; Teitelbaum, Steven L

    2009-08-01

    The capacity of the osteoclast (OC) to resorb bone is dictated by cytoskeletal organization, which in turn emanates from signals derived from the alpha(v)beta(3) integrin and c-Fms. Syk is key to these signals and, in other cells, this tyrosine kinase exerts its effects via intermediaries including the SLP adaptors, SLP-76 and BLNK (B cell linker). Thus, we asked whether these two SLP proteins regulate OC function. We find BLNK-deficient OCs are normal, whereas cytoskeletal organization of those lacking SLP-76 is delayed, thus modestly reducing bone resorption in vitro. Cytoskeletal organization and bone resorption are more profoundly arrested in cultured OCs deficient in BLNK and SLP-76 double knockout (DKO) phenotypes. In contrast, stimulated bone resorption in vivo is inhibited approximately 40% in either SLP-76(-/-) or DKO mice. This observation, taken with the fact that DKO OCs are rescued by retroviral transduction of only SLP-76, indicates that SLP-76 is the dominant SLP family member in the resorptive process. We also find SLP-76 is phosphorylated in a Syk-dependent manner. Furthermore, in the absence of the adaptor protein, integrin-mediated phosphorylation of Vav3, the OC cytoskeleton-organizing guanine nucleotide exchange factor, is abrogated. In keeping with a central role of SLP-76/Vav3 association in osteoclastic resorption, retroviral transduction of SLP-76, in which the Vav binding site is disrupted (3YF), fails to normalize the cytoskeleton of DKO OCs and the resorptive capacity of the cells. Finally, c-Fms-activated Syk also exerts its OC cytoskeleton-organizing effect in a SLP-76/Vav3-dependent manner.

  11. Expression and activity of Rac1 is negatively affected in the dehydroepiandrosterone induced polycystic ovary of mouse

    PubMed Central

    2014-01-01

    Background Polycystic ovarian syndrome (PCOS) is characterized by the presence of multiple follicular cysts, giving rise to infertility due to anovulation. This syndrome affects about 10% of women, worldwide. The exact molecular mechanism leading to PCOS remains obscure. RhoGTPase has been associated with oogenesis, but its role in PCOS remains unexplored. Therefore, we attempted to elucidate the Vav-Rac1 signaling in PCOS mice model. Methods We generated a PCOS mice model by injecting dehydroepiandrosterone (DHEA) for a period of 20 days. The expression levels of Rac1, pRac1, Vav, pVav and Caveolin1 were analyzed by employing immuno-blotting and densitometry. The association between Vav and Rac1 proteins were studied by immuno-precipitation. Furthermore, we analyzed the activity of Rac1 and levels of inhibin B and 17β-estradiol in ovary using biochemical assays. Results The presence of multiple follicular cysts in ovary were confirmed by histology. The activity of Rac1 (GTP bound state) was significantly reduced in the PCOS ovary. Similarly, the expression levels of Rac1 and its phosphorylated form (pRac1) were decreased in PCOS in comparison to the sham ovary. The expression level and activity (phosphorylated form) of guanine nucleotide exchanger of Rac1, Vav, was moderately down-regulated. We observed comparatively increased expressions of Caveolin1, 17β-estradiol, and inhibin B in the polycystic ovary. Conclusion We conclude that hyperandrogenization (PCOS) by DHEA diminishes ovarian Rac1 and Vav expression and activity along with an increase in expression of Caveolin1. This is accompanied by an increase in the intra-ovarian level of '17 β-estradiol and inhibin B. PMID:24628852

  12. Complementary Phosphorylation Sites in the Adaptor Protein SLP-76 Promote Synergistic Activation of Natural Killer Cells

    PubMed Central

    Kim, Hun Sik; Long, Eric O.

    2013-01-01

    The cytotoxic effects of natural killer (NK) cells and their ability to secrete cytokines require the induction of synergistic signals from co-activation receptors, such as CD314 (NKG2D) and CD244 (2B4), which bind to ligands expressed on target cells. Synergy is required to overcome inhibition of the guanine nucleotide exchange factor (GEF) Vav1, a central regulator of NK cell activation, by the E3 ubiquitin ligase c-Cbl. However, the molecular basis for this synergy is unknown. Here, we showed that the adaptor protein Src homology 2 (SH2) domain–containing leukocyte phosphoprotein of 76 kD (SLP-76) was required for this synergy, and that distinct tyrosine residues in SLP-76 were phosphorylated by each receptor of a synergistic pair. Selective phosphorylation of tyrosine 113 or tyrosine 128 in SLP-76, each of which enables binding of SLP-76 to Vav1, was unique to receptors that stimulate ligand-dependent target cell killing, because antibody-dependent stimulation by Fc receptor CD16 promoted phosphorylation at both sites. Knockdown and reconstitution experiments with SLP-76 showed the distinct role of each tyrosine in the synergistic mobilization of Ca2+, revealing an unexpected degree of selectivity in the phosphorylation of SLP-76 by NK cell co-activation receptors. Together, these data suggest that complementation of separate phospho-tyrosine targets in SLP-76 forms the basis of synergistic NK cell activation. PMID:22786724

  13. Complementary phosphorylation sites in the adaptor protein SLP-76 promote synergistic activation of natural killer cells.

    PubMed

    Kim, Hun Sik; Long, Eric O

    2012-07-10

    The cytotoxic effects of natural killer (NK) cells and their ability to secrete cytokines require synergistic signals from specific pairs of co-activation receptors, such as CD314 (also known as NKG2D) and CD244 (2B4), which bind to distinct ligands present on target cells. These signals are required to overcome inhibition mediated by the E3 ubiquitin ligase c-Cbl of the guanine nucleotide exchange factor Vav1, which promotes activation of NK cells. Here, we showed that the adaptor protein SLP-76 (Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons) was required for this synergy and that distinct tyrosine residues in SLP-76 were phosphorylated by each member of a pair of synergistic receptors. Selective phosphorylation of tyrosine 113 or tyrosine 128 in SLP-76 enabled binding of SLP-76 to Vav1. Selective phosphorylation of SLP-76 at these residues was restricted to receptors that stimulated ligand-dependent target cell killing; antibody-dependent stimulation of the Fc receptor CD16 promoted phosphorylation at both sites. Knockdown and reconstitution experiments with SLP-76 mutant proteins showed the distinct role of each tyrosine in the synergistic mobilization of Ca2+, revealing an unexpected degree of selectivity in the phosphorylation of SLP-76 by NK cell co-activation receptors. Together, these data suggest that combined phosphorylation of separate tyrosine residues in SLP-76 forms the basis of synergistic NK cell activation.

  14. An Epistatic Interaction between Themis1 and Vav1 Modulates Regulatory T Cell Function and Inflammatory Bowel Disease Development.

    PubMed

    Pedros, Christophe; Gaud, Guillaume; Bernard, Isabelle; Kassem, Sahar; Chabod, Marianne; Lagrange, Dominique; Andréoletti, Olivier; Dejean, Anne S; Lesourne, Renaud; Fournié, Gilbert J; Saoudi, Abdelhadi

    2015-08-15

    The development of inflammatory diseases depends on complex interactions between several genes and various environmental factors. Discovering new genetic risk factors and understanding the mechanisms whereby they influence disease development is of paramount importance. We previously reported that deficiency in Themis1, a new actor of TCR signaling, impairs regulatory T cell (Treg) function and predisposes Brown-Norway (BN) rats to spontaneous inflammatory bowel disease (IBD). In this study, we reveal that the epistasis between Themis1 and Vav1 controls the occurrence of these phenotypes. Indeed, by contrast with BN rats, Themis1 deficiency in Lewis rats neither impairs Treg suppressive functions nor induces pathological manifestations. By using congenic lines on the BN genomic background, we show that the impact of Themis1 deficiency on Treg suppressive functions depends on a 117-kb interval coding for a R63W polymorphism that impacts Vav1 expression and functions. Indeed, the introduction of a 117-kb interval containing the Lewis Vav1-R63 variant restores Treg function and protects Themis1-deficient BN rats from spontaneous IBD development. We further show that Themis1 binds more efficiently to the BN Vav1-W63 variant and is required to stabilize its recruitment to the transmembrane adaptor LAT and to fully promote the activation of Erk kinases. Together, these results highlight the importance of the signaling pathway involving epistasis between Themis1 and Vav1 in the control of Treg suppressive function and susceptibility to IBD development. Copyright © 2015 by The American Association of Immunologists, Inc.

  15. Relationship between target organ damage and blood pressure, retinal vessel calibre, oxidative stress and polymorphisms in VAV-2 and VAV-3 genes in patients with hypertension: a case-control study protocol (LOD-Hipertension).

    PubMed

    Gomez-Marcos, Manuel A; Gonzalez-Sarmiento, Rogelio; Recio-Rodríguez, José I; Agudo-Conde, Cristina; Gamella-Pozuelo, Luis; Perretta-Tejedor, Nuria; Martínez-Salgado, Carlos; García-Ortiz, Luis

    2014-04-03

    Target organ damage (TOD) is associated with increased cardiovascular risk. The study objectives were to analyse the relationship of TOD to blood pressure, size of retinal arteries and veins, oxidative stress and different polymorphisms in the VAV-2 and VAV-3 genes in participants with hypertension. A case-control study to analyse the relationship between clinical, biochemical and genetic parameters and presence of cardiac, vascular and renal TOD in 486 patients with hypertension. Participants with TOD will be considered as cases, and those without TOD will be enrolled as controls. This will be a collaborative study conducted by the groups of Primary Care, Cardiovascular and Metabolic and Degenerative Diseases of the Instituto de Investigación Biomédica of Salamanca (IBSAL). Assessment of cardiac, renal and vascular TOD. Measurement of peripheral and central blood pressure, size of eye fundus arteries and veins, and oxidative stress, and polymorphisms in the VAV-2 and VAV-3 genes. The study will be conducted after approval is obtained from the Ethics Committee of Hospital Clínico Universitario of Salamanca. All study participants will sign an informed consent to agree to participate in the study, and another consent to agree on the genetic study, in compliance with the Declaration of Helsinki and the WHO standards for observational studies. The results of this study will allow for an understanding of the relationship of the different TODs with blood pressure, retinal artery and vein diameters, oxidative stress and polymorphisms in VAV-2 and VAV-3 genes. Clinical Trials. gov Identifier: NCT02022618.

  16. Relationship between target organ damage and blood pressure, retinal vessel calibre, oxidative stress and polymorphisms in VAV-2 and VAV-3 genes in patients with hypertension: a case–control study protocol (LOD-Hipertensión)

    PubMed Central

    Gomez-Marcos, Manuel A; Gonzalez-Sarmiento, Rogelio; Recio-Rodríguez, José I; Agudo-Conde, Cristina; Gamella-Pozuelo, Luis; Perretta-Tejedor, Nuria; Martínez-Salgado, Carlos; García-Ortiz, Luis

    2014-01-01

    Introduction Target organ damage (TOD) is associated with increased cardiovascular risk. The study objectives were to analyse the relationship of TOD to blood pressure, size of retinal arteries and veins, oxidative stress and different polymorphisms in the VAV-2 and VAV-3 genes in participants with hypertension. Methods and analysis A case–control study to analyse the relationship between clinical, biochemical and genetic parameters and presence of cardiac, vascular and renal TOD in 486 patients with hypertension. Participants with TOD will be considered as cases, and those without TOD will be enrolled as controls. This will be a collaborative study conducted by the groups of Primary Care, Cardiovascular and Metabolic and Degenerative Diseases of the Instituto de Investigación Biomédica of Salamanca (IBSAL). Assessment of cardiac, renal and vascular TOD. Measurement of peripheral and central blood pressure, size of eye fundus arteries and veins, and oxidative stress, and polymorphisms in the VAV-2 and VAV-3 genes. Ethics and dissemination The study will be conducted after approval is obtained from the Ethics Committee of Hospital Clínico Universitario of Salamanca. All study participants will sign an informed consent to agree to participate in the study, and another consent to agree on the genetic study, in compliance with the Declaration of Helsinki and the WHO standards for observational studies. The results of this study will allow for an understanding of the relationship of the different TODs with blood pressure, retinal artery and vein diameters, oxidative stress and polymorphisms in VAV-2 and VAV-3 genes. Trial registration number Clinical Trials. gov Identifier: NCT02022618. PMID:24699462

  17. CO2 concentration and occupancy density in the critical zones served by the VAV system

    NASA Astrophysics Data System (ADS)

    Etoua Evina, Ghislaine; Kajl, Stanislaw; Lamarche, Louis; Beltran-Galindo, Javier

    2017-11-01

    This article presents the results obtained from monitoring a VAV system with highly diversified zone occupancy density are presented in the article. The investigated VAV system meets the load for 72 zones (68 perimeters and 4 interiors) consisting of classrooms, offices, conference rooms, etc. with highly diversified occupancy densities from 1.875 to 2.5 m2/person for the classrooms and from 10 to 15 m2/person for the offices. The monitoring shows that the CO2 concentration can exceed the set point in the critical rooms. Simulation results are also presented in the article to show that it is often impossible to adjust the operation of such VAV systems because the adjusted System Outdoor Air Fractions, % OA, can reach 100% even where the zone CO2 concentration is not respected. The presented monitoring and simulation results were obtained in the winter, with the VAV system operating at partial load and with the minimum outdoor air flowrate required by the economizer system. As shown in the article, to respect the zone set point CO2 concentration in such period, the VAV system must operate mostly at a %OA equal to 100% instead of its minimum value. To circumvent this, the supply zone air flow rate may have to be designed taking into account the CO2 concentration resulting from the critical zones occupancy density.

  18. [Elucidating the molecular mechanism of prostate cancer progression under chronic hypoxia and development of the novel therapeutic approach].

    PubMed

    Nomura, Takeo; Yamasaki, Mutsushi; Mimata, Hiromitsu

    2014-12-01

    Cancer cells encounter a hypoxic microenvironment during tumor growth and progression. In addition, androgen-deprivation therapy against prostate cancer can develop secondary to a hypoxic condition caused by drastic blood supply reduction because androgen drives angiogenic inducers including vascular endothelial growth factor (VEGF) and inhibits angiogenesis inhibitor prostatic pigment epithelium-derived factor (PEDF). Extreme hypoxic conditions are not suitable for cancer survival, however, cancer cells soon adapt to a hypoxic environment and survive. We established a prostate cancer cell line cultured under chronic hypoxia and analyzed a castration-resistant phenotype. Here, the Vav3 was identified as a key oncogenic molecule associated with castration-resistance under chronic hypoxia. We analyzed the functions of Vav3 and Vav3-mediated signaling to establish a novel therapeutic target for castration-resistant prostate cancer.

  19. CD94/NKG2A inhibits NK cell activation by disrupting the actin network at the immunological synapse.

    PubMed

    Masilamani, Madhan; Nguyen, Connie; Kabat, Juraj; Borrego, Francisco; Coligan, John E

    2006-09-15

    An adequate immune response is the result of the fine balance between activation and inhibitory signals. The exact means by which inhibitory signals obviate activation signals in immune cells are not totally elucidated. Human CD94/NKG2A is an ITIM-containing inhibitory receptor expressed by NK cells and some CD8+ T cells that recognize HLA-E. We show that the engagement of this receptor prevents NK cell activation by disruption of the actin network and exclusion of lipid rafts at the point of contact with its ligand (inhibitory NK cell immunological synapse, iNKIS). CD94/NKG2A engagement leads to recruitment and activation of src homology 2 domain-bearing tyrosine phosphatase 1. This likely explains the observed dephosphorylation of guanine nucleotide exchange factor and regulator of actin, Vav1, as well as ezrin-radixin-moesin proteins that connect actin filaments to membrane structures. In contrast, NK cell activation by NKG2D induced Vav1 and ezrin-radixin-moesin phosphorylation. Thus, CD94/NKG2A prevents actin-dependent recruitment of raft-associated activation receptors complexes to the activating synapse. This was further substantiated by showing that inhibition of actin polymerization abolished lipid rafts exclusion at the iNKIS, whereas cholesterol depletion had no effect on actin disruption at the iNKIS. These data indicate that the lipid rafts exclusion at the iNKIS is an active process which requires an intact cytoskeleton to maintain lipid rafts outside the inhibitory synapse. The net effect is to maintain an inhibitory state in the proximity of the iNKIS, while allowing the formation of activation synapse at distal points within the same NK cell.

  20. A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus

    PubMed Central

    Alejo, Alí; Ruiz-Argüello, M. Begoña; Ho, Yin; Smith, Vincent P.; Saraiva, Margarida; Alcami, Antonio

    2006-01-01

    Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis. PMID:16581912

  1. A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus.

    PubMed

    Alejo, Alí; Ruiz-Argüello, M Begoña; Ho, Yin; Smith, Vincent P; Saraiva, Margarida; Alcami, Antonio

    2006-04-11

    Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis.

  2. Differential recognition of syk-binding sites by each of the two phosphotyrosine-binding pockets of the Vav SH2 domain.

    PubMed

    Chen, Chih-Hong; Piraner, Dan; Gorenstein, Nina M; Geahlen, Robert L; Beth Post, Carol

    2013-11-01

    The association of spleen tyrosine kinase (Syk), a central tyrosine kinase in B cell signaling, with Vav SH2 domain is controlled by phosphorylation of two closely spaced tyrosines in Syk linker B: Y342 and Y346. Previous studies established both singly phosphorylated and doubly phosphorylated forms play a role in signaling. The structure of the doubly phosphorylated form identified a new recognition of phosphotyrosine whereby two phosphotyrosines bind simultaneously to the Vav SH2 domain, one in the canonical pTyr pocket and one in the specificity pocket on the opposite side of the central β-sheet. It is unknown if the specificity pocket can bind phosphotyrosine independent of phosphotyrosine binding the pTyr pocket. To address this gap in knowledge, we determined the structure of the complex between Vav1 SH2 and a peptide (SykLB-YpY) modeling the singly phosphorylated-Y346 form of Syk with unphosphorylated Y342. The nuclear magnetic resonance (NMR) data conclusively establish that recognition of phosphotyrosine is swapped between the two pockets; phosphorylated pY346 binds the specificity pocket of Vav1 SH2, and unphosphorylated Y342 occupies what is normally the pTyr binding pocket. Nearly identical changes in chemical shifts occurred upon binding all three forms of singly and doubly phosphorylated peptides; however, somewhat smaller shift perturbations for SykLB-YpY from residues in regions of high internal mobility suggest that internal motions are coupled to binding affinity. The differential recognition that includes this swapped binding of phosphotyrosine to the specificity pocket of Vav SH2 increases the repertoire of possible phosphotyrosine binding by SH2 domains in regulating protein-protein interactions in cellular signaling. Copyright © 2013 Wiley Periodicals, Inc.

  3. VAV1 and BAFF, via NFκB pathway, are genetic risk factors for myasthenia gravis

    PubMed Central

    Avidan, Nili; Le Panse, Rozen; Harbo, Hanne F; Bernasconi, Pia; Poulas, Konstantinos; Ginzburg, Elizabeta; Cavalcante, Paola; Colleoni, Lara; Baggi, Fulvio; Antozzi, Carlo; Truffault, Frédérique; Horn-Saban, Shirley; Pöschel, Simone; Zagoriti, Zoi; Maniaol, Angelina; Lie, Benedicte A; Bernard, Isabelle; Saoudi, Abdelhadi; Illes, Zsolt; Casasnovas Pons, Carlos; Melms, Arthur; Tzartos, Socrates; Willcox, Nicholas; Kostera-Pruszczyk, Anna; Tallaksen, Chantal; Mantegazza, Renato; Berrih-Aknin, Sonia; Miller, Ariel

    2014-01-01

    Objective To identify novel genetic loci that predispose to early-onset myasthenia gravis (EOMG) applying a two-stage association study, exploration, and replication strategy. Methods Thirty-four loci and one confirmation loci, human leukocyte antigen (HLA)-DRA, were selected as candidate genes by team members of groups involved in different research aspects of MG. In the exploration step, these candidate genes were genotyped in 384 EOMG and 384 matched controls and significant difference in allele frequency were found in eight genes. In the replication step, eight candidate genes and one confirmation loci were genotyped in 1177 EOMG patients and 814 controls, from nine European centres. Results Allele frequency differences were found in four novel loci: CD86, AKAP12, VAV1, B-cell activating factor (BAFF), and tumor necrosis factor-alpha (TNF-α), and these differences were consistent in all nine cohorts. Haplotype trend test supported the differences in allele frequencies between cases and controls. In addition, allele frequency difference in female versus male patients at HLA-DRA and TNF-α loci were observed. Interpretation The genetic associations to EOMG outside the HLA complex are novel and of interest as VAV1 is a key signal transducer essential for T- and B-cell activation, and BAFF is a cytokine that plays important roles in the proliferation and differentiation of B-cells. Moreover, we noted striking epistasis between the predisposing VAV1 and BAFF haplotypes; they conferred a greater risk in combination than alone. These, and CD86, share the same signaling pathway, namely nuclear factor-kappaB (NFκB), thus implicating dysregulation of proinflammatory signaling in predisposition to EOMG. PMID:25356403

  4. Reducing airflow energy use in multiple zone vav systems

    NASA Astrophysics Data System (ADS)

    Tukur, Ahmed Gidado

    Variable Air Volume (VAV) systems are the most popular HVAC systems in commercial buildings. VAV systems are designed to deliver airflows at design conditions which only occur for a few hours in a year. Minimizing energy use in VAV systems requires reducing the amount of airflow delivered through the system at part load conditions. Air Handling Unit (AHU) fans are the major drivers of airflow in VAV systems and installing a Variable Frequency Drive (VFD) is the most common method of regulating airflow in VAV systems. A VFD drive does not necessarily save energy without use of an appropriate control strategy. Static pressure reset (SPR) is considered to be the most energy efficient control strategy for AHU fans with VFDs installed. The implementation of SPR however has many challenges; for example, rogue zones--zones which have faulty sensors or failed controls and actuators, system dynamics like hunting and system diversity. By investigating the parameters associated with the implementation of SPR in VAV systems, a new, improved, more stable SPR algorithm was developed and validated. This approach was further improved using Fault Detection and Diagnostics (FDD) to eliminate rogue zones. Additionally, a CO2-Demand Control Ventilation (DCV) based minimum airflow control was used to further reduce ventilation airflow and save more energy from SPR. Energy savings ranging from 25% to 51% were recorded in actual buildings with the new SPR algorithm. Finally, a methodology that utilizes historical VAV data was developed to estimate the potential savings that could be realized using SPR. The approach employed first determines an effective system loss coefficient as a function of mean damper position using the historical duct static pressure, VAV damper positions and airflows. Additionally, the historical data is used to identify the maximum mean duct damper position realizable as a result of insuring a sufficient number of VAVs are fully open at any time. Savings are estimated by shifting the damper distribution mean at each time to this maximum value and reducing the static pressure to achieve the same overall system airflow rate. The methodology was tested on three different buildings with varying system characteristics. Savings estimates correlated well to the savings actually realized from SPR. This result has significant implications for energy service providers, who could use the predictions to guarantee savings from SPR.

  5. Bruton's Tyrosine Kinase (BTK) and Vav1 Contribute to Dectin1-Dependent Phagocytosis of Candida albicans in Macrophages

    PubMed Central

    Strijbis, Karin; Tafesse, Fikadu G.; Fairn, Gregory D.; Witte, Martin D.; Dougan, Stephanie K.; Watson, Nicki; Spooner, Eric; Esteban, Alexandre; Vyas, Valmik K.; Fink, Gerald R.; Grinstein, Sergio; Ploegh, Hidde L.

    2013-01-01

    Phagocytosis of the opportunistic fungal pathogen Candida albicans by cells of the innate immune system is vital to prevent infection. Dectin-1 is the major phagocytic receptor involved in anti-fungal immunity. We identify two new interacting proteins of Dectin-1 in macrophages, Bruton's Tyrosine Kinase (BTK) and Vav1. BTK and Vav1 are recruited to phagocytic cups containing C. albicans yeasts or hyphae but are absent from mature phagosomes. BTK and Vav1 localize to cuff regions surrounding the hyphae, while Dectin-1 lines the full length of the phagosome. BTK and Vav1 colocalize with the lipid PI(3,4,5)P3 and F-actin at the phagocytic cup, but not with diacylglycerol (DAG) which marks more mature phagosomal membranes. Using a selective BTK inhibitor, we show that BTK contributes to DAG synthesis at the phagocytic cup and the subsequent recruitment of PKCε. BTK- or Vav1-deficient peritoneal macrophages display a defect in both zymosan and C. albicans phagocytosis. Bone marrow-derived macrophages that lack BTK or Vav1 show reduced uptake of C. albicans, comparable to Dectin1-deficient cells. BTK- or Vav1-deficient mice are more susceptible to systemic C. albicans infection than wild type mice. This work identifies an important role for BTK and Vav1 in immune responses against C. albicans. PMID:23825946

  6. Bruton's Tyrosine Kinase (BTK) and Vav1 contribute to Dectin1-dependent phagocytosis of Candida albicans in macrophages.

    PubMed

    Strijbis, Karin; Tafesse, Fikadu G; Fairn, Gregory D; Witte, Martin D; Dougan, Stephanie K; Watson, Nicki; Spooner, Eric; Esteban, Alexandre; Vyas, Valmik K; Fink, Gerald R; Grinstein, Sergio; Ploegh, Hidde L

    2013-01-01

    Phagocytosis of the opportunistic fungal pathogen Candida albicans by cells of the innate immune system is vital to prevent infection. Dectin-1 is the major phagocytic receptor involved in anti-fungal immunity. We identify two new interacting proteins of Dectin-1 in macrophages, Bruton's Tyrosine Kinase (BTK) and Vav1. BTK and Vav1 are recruited to phagocytic cups containing C. albicans yeasts or hyphae but are absent from mature phagosomes. BTK and Vav1 localize to cuff regions surrounding the hyphae, while Dectin-1 lines the full length of the phagosome. BTK and Vav1 colocalize with the lipid PI(3,4,5)P3 and F-actin at the phagocytic cup, but not with diacylglycerol (DAG) which marks more mature phagosomal membranes. Using a selective BTK inhibitor, we show that BTK contributes to DAG synthesis at the phagocytic cup and the subsequent recruitment of PKCε. BTK- or Vav1-deficient peritoneal macrophages display a defect in both zymosan and C. albicans phagocytosis. Bone marrow-derived macrophages that lack BTK or Vav1 show reduced uptake of C. albicans, comparable to Dectin1-deficient cells. BTK- or Vav1-deficient mice are more susceptible to systemic C. albicans infection than wild type mice. This work identifies an important role for BTK and Vav1 in immune responses against C. albicans.

  7. Tyrosine phosphorylation of 3BP2 is indispensable for the interaction with VAV3 in chicken DT40 cells

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

    Chihara, Kazuyasu; Organization for Life Science Advancement Programs, University of Fukui, Fukui 910-1193; Kimura, Yukihiro

    Adaptor protein c-Abl SH3 domain-binding protein-2 (3BP2) is known to play regulatory roles in immunoreceptor-mediated signal transduction. We have previously demonstrated that Tyr{sup 174}, Tyr{sup 183} and Tyr{sup 446} in mouse 3BP2 are predominantly phosphorylated by Syk, and the phosphorylation of Tyr{sup 183} and the Src homology 2 (SH2) domain of mouse 3BP2 are critical for B cell receptor (BCR)-induced activation of nuclear factor of activated T cells (NFAT) in human B cells. In this report, we have shown that Syk, but not Abl family protein-tyrosine kinases, is critical for BCR-mediated tyrosine phosphorylation of 3BP2 in chicken DT40 cells. Mutationalmore » analysis showed that Tyr{sup 174}, Tyr{sup 183} and Tyr{sup 426} of chicken 3BP2 are the major phosphorylation sites by Syk and the SH2 domain of 3BP2 is critical for tyrosine phosphorylation. In addition, phosphorylation of Tyr{sup 426} is required for the inducible interaction with the SH2 domain of Vav3. Moreover, the expression of the mutant form of 3BP2 in which Tyr{sup 426} was substituted to Phe resulted in the reduction in BCR-mediated Rac1 activation, when compared with the case of wild-type. Altogether, these data suggest that 3BP2 is involved in the activation of Rac1 through the regulation of Vav3 by Syk-dependent phosphorylation of Tyr{sup 426} following BCR stimulation. - Highlights: • 3BP2 is phosphorylated by Syk, but not Abl family kinases in BCR signaling. • Tyr183 and Tyr426 in chicken 3BP2 are the major phosphorylation sites by Syk. • The SH2 domain of 3BP2 is critical for tyrosine phosphorylation of 3BP2. • Phosphorylation of Tyr426 in 3BP2 is required for the inducible binding with Vav3. • 3BP2 is involved in the regulation of BCR-mediated Rac1 activation.« less

  8. Cooperative interactions at the SLP-76 complex are critical for actin polymerization.

    PubMed

    Barda-Saad, Mira; Shirasu, Naoto; Pauker, Maor H; Hassan, Nirit; Perl, Orly; Balbo, Andrea; Yamaguchi, Hiroshi; Houtman, Jon C D; Appella, Ettore; Schuck, Peter; Samelson, Lawrence E

    2010-07-21

    T-cell antigen receptor (TCR) engagement induces formation of multi-protein signalling complexes essential for regulating T-cell functions. Generation of a complex of SLP-76, Nck and VAV1 is crucial for regulation of the actin machinery. We define the composition, stoichiometry and specificity of interactions in the SLP-76, Nck and VAV1 complex. Our data reveal that this complex can contain one SLP-76 molecule, two Nck and two VAV1 molecules. A direct interaction between Nck and VAV1 is mediated by binding between the C-terminal SH3 domain of Nck and the VAV1 N-terminal SH3 domain. Disruption of the VAV1:Nck interaction deleteriously affected actin polymerization. These novel findings shed new light on the mechanism of actin polymerization after T-cell activation.

  9. Tyrosine phosphorylation of 3BP2 is indispensable for the interaction with VAV3 in chicken DT40 cells.

    PubMed

    Chihara, Kazuyasu; Kimura, Yukihiro; Honjoh, Chisato; Yamauchi, Shota; Takeuchi, Kenji; Sada, Kiyonao

    2014-03-10

    Adaptor protein c-Abl SH3 domain-binding protein-2 (3BP2) is known to play regulatory roles in immunoreceptor-mediated signal transduction. We have previously demonstrated that Tyr(174), Tyr(183) and Tyr(446) in mouse 3BP2 are predominantly phosphorylated by Syk, and the phosphorylation of Tyr(183) and the Src homology 2 (SH2) domain of mouse 3BP2 are critical for B cell receptor (BCR)-induced activation of nuclear factor of activated T cells (NFAT) in human B cells. In this report, we have shown that Syk, but not Abl family protein-tyrosine kinases, is critical for BCR-mediated tyrosine phosphorylation of 3BP2 in chicken DT40 cells. Mutational analysis showed that Tyr(174), Tyr(183) and Tyr(426) of chicken 3BP2 are the major phosphorylation sites by Syk and the SH2 domain of 3BP2 is critical for tyrosine phosphorylation. In addition, phosphorylation of Tyr(426) is required for the inducible interaction with the SH2 domain of Vav3. Moreover, the expression of the mutant form of 3BP2 in which Tyr(426) was substituted to Phe resulted in the reduction in BCR-mediated Rac1 activation, when compared with the case of wild-type. Altogether, these data suggest that 3BP2 is involved in the activation of Rac1 through the regulation of Vav3 by Syk-dependent phosphorylation of Tyr(426) following BCR stimulation. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Vav1-phospholipase C-γ1 (Vav1-PLC-γ1) pathway initiated by T cell antigen receptor (TCRγδ) activation is required to overcome inhibition by ubiquitin ligase Cbl-b during γδT cell cytotoxicity.

    PubMed

    Yin, Shanshan; Zhang, Jianmin; Mao, Yujia; Hu, Yu; Cui, Lianxian; Kang, Ning; He, Wei

    2013-09-13

    T cell antigen receptor γδ (TCRγδ) and natural killer group 2, member D (NKG2D) are two crucial receptors for γδT cell cytotoxicity. Compelling evidences suggest that γδT cell cytotoxicity is TCRγδ-dependent and can be co-stimulated by NKG2D. However, the molecular mechanism of underlying TCRγδ-dependent activation of γδT cells remains unclear. In this study we demonstrated that TCRγδ but not NKG2D engagement induced lytic granule polarization and promoted γδT cell cytotoxicity. TCRγδ activation alone was sufficient to trigger Vav1-dependent phospholipase C-γ1 signaling, resulting in lytic granule polarization and effective killing, whereas NKG2D engagement alone failed to trigger cytotoxicity-related signaling to overcome the inhibitory effect of Cbl-b; therefore, NKG2D engagement alone could not induce effective killing. However, NKG2D ligation augmented the activation of γδT cell cytotoxicity through the Vav1-phospholipase C-γ1 pathway. Vav1 overexpression or Cbl-b knockdown not only enhanced TCRγδ activation-initiated killing but also enabled NKG2D activation alone to induce γδT cell cytotoxicity. Taken together, our results suggest that the activation of γδT cell cytotoxicity requires a strong activation signal to overcome the inhibitory effect of Cbl-b. Our finding provides new insights into the molecular mechanisms underlying the initiation of γδT cell cytotoxicity and likely implications for optimizing γδT cell-based cancer immunotherapy.

  11. Assessment of the Activation of Rho Family GTP-Binding Proteins in Breast Cancer Cells and Specimens

    DTIC Science & Technology

    2001-08-01

    lymphopenia Vav2 GEF for Rho, Rac, and Cdc42 proto-oncogene product; NM009500 Vav3 GEF for Rho and Rac proto-oncogene product; NM020505 hPEM -2 GEF for...junctions, and desmosomes play a fundamental role in maintaining the polarized phenotype and vectorial transport functions of epithelial cells. The tight

  12. GrpL, a Grb2-related Adaptor Protein, Interacts with SLP-76 to Regulate Nuclear Factor of Activated T Cell Activation

    PubMed Central

    Law, Che-Leung; Ewings, Maria K.; Chaudhary, Preet M.; Solow, Sasha A.; Yun, Theodore J.; Marshall, Aaron J.; Hood, Leroy; Clark, Edward A.

    1999-01-01

    Propagation of signals from the T cell antigen receptor (TCR) involves a number of adaptor molecules. SH2 domain–containing protein 76 (SLP-76) interacts with the guanine nucleotide exchange factor Vav to activate the nuclear factor of activated cells (NF-AT), and its expression is required for normal T cell development. We report the cloning and characterization of a novel Grb2-like adaptor molecule designated as Grb2-related protein of the lymphoid system (GrpL). Expression of GrpL is restricted to hematopoietic tissues, and it is distinguished from Grb2 by having a proline-rich region. GrpL can be coimmunoprecipitated with SLP-76 but not with Sos1 or Sos2 from Jurkat cell lysates. In contrast, Grb2 can be coimmunoprecipitated with Sos1 and Sos2 but not with SLP-76. Moreover, tyrosine-phosphorylated LAT/pp36/38 in detergent lysates prepared from anti-CD3 stimulated T cells associated with Grb2 but not GrpL. These data reveal the presence of distinct complexes involving GrpL and Grb2 in T cells. A functional role of the GrpL–SLP-76 complex is suggested by the ability of GrpL to act alone or in concert with SLP-76 to augment NF-AT activation in Jurkat T cells. PMID:10209041

  13. Targeting AR Variant-Coactivator Interactions to Exploit Prostate Cancer Vulnerabilities.

    PubMed

    Magani, Fiorella; Peacock, Stephanie O; Rice, Meghan A; Martinez, Maria J; Greene, Ann M; Magani, Pablo S; Lyles, Rolando; Weitz, Jonathan R; Burnstein, Kerry L

    2017-11-01

    Castration-resistant prostate cancer (CRPC) progresses rapidly and is incurable. Constitutively active androgen receptor splice variants (AR-Vs) represent a well-established mechanism of therapeutic resistance and disease progression. These variants lack the AR ligand-binding domain and, as such, are not inhibited by androgen deprivation therapy (ADT), which is the standard systemic approach for advanced prostate cancer. Signaling by AR-Vs, including the clinically relevant AR-V7, is augmented by Vav3, an established AR coactivator in CRPC. Using mutational and biochemical studies, we demonstrated that the Vav3 Diffuse B-cell lymphoma homology (DH) domain interacted with the N-terminal region of AR-V7 (and full length AR). Expression of the Vav3 DH domain disrupted Vav3 interaction with and enhancement of AR-V7 activity. The Vav3 DH domain also disrupted AR-V7 interaction with other AR coactivators: Src1 and Vav2, which are overexpressed in PC. This Vav3 domain was used in proof-of-concept studies to evaluate the effects of disrupting the interaction between AR-V7 and its coactivators on CRPC cells. This disruption decreased CRPC cell proliferation and anchorage-independent growth, caused increased apoptosis, decreased migration, and resulted in the acquisition of morphological changes associated with a less aggressive phenotype. While disrupting the interaction between FL-AR and its coactivators decreased N-C terminal interaction, disrupting the interaction of AR-V7 with its coactivators decreased AR-V7 nuclear levels. Implications: This study demonstrates the potential therapeutic utility of inhibiting constitutively active AR-V signaling by disrupting coactivator binding. Such an approach is significant, as AR-Vs are emerging as important drivers of CRPC that are particularly recalcitrant to current therapies. Mol Cancer Res; 15(11); 1469-80. ©2017 AACR . ©2017 American Association for Cancer Research.

  14. Distinct mechanisms of a phosphotyrosyl peptide binding to two SH2 domains.

    PubMed

    Pang, Xiaodong; Zhou, Huan-Xiang

    2014-05-01

    Protein phosphorylation is very common post-translational modification, catalyzed by kinases, for signaling and regulation. Phosphotyrosines frequently target SH2 domains. The spleen tyrosine kinase (Syk) is critical for tyrosine phosphorylation of multiple proteins and for regulation of important pathways. Phosphorylation of both Y342 and Y346 in Syk linker B is required for optimal signaling. The SH2 domains of Vav1 and PLC-γ both bind this doubly phosphorylated motif. Here we used a recently developed method to calculate the effects of Y342 and Y346 phosphorylation on the rate constants of a peptide from Syk linker B binding to the SH2 domains of Vav1 and PLC-γ. The predicted effects agree well with experimental observations. Moreover, we found that the same doubly phosphorylated peptide binds the two SH2 domains via distinct mechanisms, with apparent rigid docking for Vav1 SH2 and dock-and-coalesce for PLC-γ SH2.

  15. Efficacy and Immunogenicity of Single-Dose AdVAV Intranasal Anthrax Vaccine Compared to Anthrax Vaccine Absorbed in an Aerosolized Spore Rabbit Challenge Model

    PubMed Central

    Krishnan, Vyjayanthi; Andersen, Bo H.; Shoemaker, Christine; Sivko, Gloria S.; Tordoff, Kevin P.; Stark, Gregory V.; Zhang, Jianfeng; Feng, Tsungwei; Duchars, Matthew

    2015-01-01

    AdVAV is a replication-deficient adenovirus type 5-vectored vaccine expressing the 83-kDa protective antigen (PA83) from Bacillus anthracis that is being developed for the prevention of disease caused by inhalation of aerosolized B. anthracis spores. A noninferiority study comparing the efficacy of AdVAV to the currently licensed Anthrax Vaccine Absorbed (AVA; BioThrax) was performed in New Zealand White rabbits using postchallenge survival as the study endpoint (20% noninferiority margin for survival). Three groups of 32 rabbits were vaccinated with a single intranasal dose of AdVAV (7.5 × 107, 1.5 × 109, or 3.5 × 1010 viral particles). Three additional groups of 32 animals received two doses of either intranasal AdVAV (3.5 × 1010 viral particles) or intramuscular AVA (diluted 1:16 or 1:64) 28 days apart. The placebo group of 16 rabbits received a single intranasal dose of AdVAV formulation buffer. All animals were challenged via the inhalation route with a targeted dose of 200 times the 50% lethal dose (LD50) of aerosolized B. anthracis Ames spores 70 days after the initial vaccination and were followed for 3 weeks. PA83 immunogenicity was evaluated by validated toxin neutralizing antibody and serum anti-PA83 IgG enzyme-linked immunosorbent assays (ELISAs). All animals in the placebo cohort died from the challenge. Three of the four AdVAV dose cohorts tested, including two single-dose cohorts, achieved statistical noninferiority relative to the AVA comparator group, with survival rates between 97% and 100%. Vaccination with AdVAV also produced antibody titers with earlier onset and greater persistence than vaccination with AVA. PMID:25673303

  16. Association Between Visceral Adiposity and Colorectal Polyps on CT Colonography

    PubMed Central

    Summers, Ronald M.; Liu, Jiamin; Sussman, Daniel L.; Dwyer, Andrew J.; Rehani, Bhavya; Pickhardt, Perry J.; Choi, J. Richard; Yao, Jianhua

    2012-01-01

    OBJECTIVE To determine if there is an association between visceral adiposity measured on CT colonography (CTC) and colorectal polyps. MATERIALS AND METHODS The study was HIPAA-compliant and approved by our Institutional Review Board and Office of Human Subjects Research. 1186 patients who underwent CTC and same day optical colonoscopy were analyzed. Visceral adipose tissue volumes (VAV) and volume percents relative to total internal body volume (VAV%) were measured on slices in the L2–L3 regions on supine CTC scan with validated fully-automated software. Student t-test, odds ratio (OR), logistic regression and receiver operating characteristic analyses were performed. RESULTS For subjects with and without adenomatous polyps, means and s. d. of VAV% were 31.2 ± 10.8% (n=345) and 28.2% ± 11.3% (n=841) (p<0.0001), respectively. For subjects with and without hyperplastic polyps they were 31.8% ± 10.7% (n=244) and 28.3% ± 11.2% (n=942) (p<0.0001), respectively. Comparing the lowest and highest quintiles of VAV%, the ORs for having at least one adenomatous polyp or hyperplastic polyp versus no polyp were 2.06 (95% CI: 1.36–3.13) and 1.71 [1.08, 2.71] and the prevalence of having adenomatous polyps or hyperplastic polyps increased 14% and 8%, respectively. CONCLUSION Subjects with higher visceral adiposity measurements on CTC have a greater risk for the presence of colonic polyps. PMID:22733893

  17. Efficacy and immunogenicity of single-dose AdVAV intranasal anthrax vaccine compared to anthrax vaccine absorbed in an aerosolized spore rabbit challenge model.

    PubMed

    Krishnan, Vyjayanthi; Andersen, Bo H; Shoemaker, Christine; Sivko, Gloria S; Tordoff, Kevin P; Stark, Gregory V; Zhang, Jianfeng; Feng, Tsungwei; Duchars, Matthew; Roberts, M Scot

    2015-04-01

    AdVAV is a replication-deficient adenovirus type 5-vectored vaccine expressing the 83-kDa protective antigen (PA83) from Bacillus anthracis that is being developed for the prevention of disease caused by inhalation of aerosolized B. anthracis spores. A noninferiority study comparing the efficacy of AdVAV to the currently licensed Anthrax Vaccine Absorbed (AVA; BioThrax) was performed in New Zealand White rabbits using postchallenge survival as the study endpoint (20% noninferiority margin for survival). Three groups of 32 rabbits were vaccinated with a single intranasal dose of AdVAV (7.5 × 10(7), 1.5 × 10(9), or 3.5 × 10(10) viral particles). Three additional groups of 32 animals received two doses of either intranasal AdVAV (3.5 × 10(10) viral particles) or intramuscular AVA (diluted 1:16 or 1:64) 28 days apart. The placebo group of 16 rabbits received a single intranasal dose of AdVAV formulation buffer. All animals were challenged via the inhalation route with a targeted dose of 200 times the 50% lethal dose (LD50) of aerosolized B. anthracis Ames spores 70 days after the initial vaccination and were followed for 3 weeks. PA83 immunogenicity was evaluated by validated toxin neutralizing antibody and serum anti-PA83 IgG enzyme-linked immunosorbent assays (ELISAs). All animals in the placebo cohort died from the challenge. Three of the four AdVAV dose cohorts tested, including two single-dose cohorts, achieved statistical noninferiority relative to the AVA comparator group, with survival rates between 97% and 100%. Vaccination with AdVAV also produced antibody titers with earlier onset and greater persistence than vaccination with AVA. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  18. Positive and negative regulation by SLP-76/ADAP and Pyk2 of chemokine-stimulated T-lymphocyte adhesion mediated by integrin α4β1

    PubMed Central

    Dios-Esponera, Ana; Isern de Val, Soledad; Sevilla-Movilla, Silvia; García-Verdugo, Rosa; García-Bernal, David; Arellano-Sánchez, Nohemí; Cabañas, Carlos; Teixidó, Joaquin

    2015-01-01

    Stimulation by chemokines of integrin α4β1–dependent T-lymphocyte adhesion is a crucial step for lymphocyte trafficking. The adaptor Vav1 is required for chemokine-activated T-cell adhesion mediated by α4β1. Conceivably, proteins associating with Vav1 could potentially modulate this adhesion. Correlating with activation by the chemokine CXCL12 of T-lymphocyte attachment to α4β1 ligands, a transient stimulation in the association of Vav1 with SLP-76, Pyk2, and ADAP was observed. Using T-cells depleted for SLP-76, ADAP, or Pyk2, or expressing Pyk2 kinase–inactive forms, we show that SLP-76 and ADAP stimulate chemokine-activated, α4β1-mediated adhesion, whereas Pyk2 opposes T-cell attachment. While CXCL12-promoted generation of high-affinity α4β1 is independent of SLP-76, ADAP, and Pyk2, the strength of α4β1-VCAM-1 interaction and cell spreading on VCAM-1 are targets of regulation by these three proteins. GTPase assays, expression of activated or dominant-negative Rac1, or combined ADAP and Pyk2 silencing indicated that Rac1 activation by CXCL12 is a common mediator response in SLP-76–, ADAP-, and Pyk2-regulated cell adhesion involving α4β1. Our data strongly suggest that chemokine-stimulated associations between Vav1, SLP-76, and ADAP facilitate Rac1 activation and α4β1-mediated adhesion, whereas Pyk2 opposes this adhesion by limiting Rac1 activation. PMID:26202465

  19. Characteristics of lentiviral vectors harboring the proximal promoter of the vav proto-oncogene: a weak and efficient promoter for gene therapy.

    PubMed

    Almarza, Elena; Río, Paula; Meza, Nestor W; Aldea, Montserrat; Agirre, Xabier; Guenechea, Guillermo; Segovia, José C; Bueren, Juan A

    2007-08-01

    Recent published data have shown the efficacy of gene therapy treatments of certain monogenic diseases. Risks of insertional oncogenesis, however, indicate the necessity of developing new vectors with weaker or cell-restricted promoters to minimize the trans-activation activity of integrated proviruses. We have inserted the proximal promoter of the vav proto-oncogene into self-inactivating lentiviral vectors (vav-LVs) and investigated the expression pattern and therapeutic efficacy of these vectors. Compared with other LVs frequently used in gene therapy, vav-LVs mediated a weak, though homogeneous and stable, expression in in vitro-cultured cells. Transplantation experiments using transduced mouse bone marrow and human CD34(+) cells confirmed the stable activity of the promoter in vivo. To investigate whether the weak activity of this promoter was compatible with a therapeutic effect, a LV expressing the Fanconi anemia A (FANCA) gene was constructed (vav-FANCA LV). Although this vector induced a low expression of FANCA, compared to the expression induced by a LV harboring the spleen focus-forming virus (SFFV) promoter, the two vectors corrected the phenotype of cells from a patient with FA-A with the same efficacy. We propose that self-inactivating vectors harboring weak promoters, such as the vav promoter, will improve the safety of gene therapy and will be of particular interest for the treatment of diseases where a high expression of the transgene is not required.

  20. Positive and negative regulation by SLP-76/ADAP and Pyk2 of chemokine-stimulated T-lymphocyte adhesion mediated by integrin α4β1.

    PubMed

    Dios-Esponera, Ana; Isern de Val, Soledad; Sevilla-Movilla, Silvia; García-Verdugo, Rosa; García-Bernal, David; Arellano-Sánchez, Nohemí; Cabañas, Carlos; Teixidó, Joaquin

    2015-09-15

    Stimulation by chemokines of integrin α4β1-dependent T-lymphocyte adhesion is a crucial step for lymphocyte trafficking. The adaptor Vav1 is required for chemokine-activated T-cell adhesion mediated by α4β1. Conceivably, proteins associating with Vav1 could potentially modulate this adhesion. Correlating with activation by the chemokine CXCL12 of T-lymphocyte attachment to α4β1 ligands, a transient stimulation in the association of Vav1 with SLP-76, Pyk2, and ADAP was observed. Using T-cells depleted for SLP-76, ADAP, or Pyk2, or expressing Pyk2 kinase-inactive forms, we show that SLP-76 and ADAP stimulate chemokine-activated, α4β1-mediated adhesion, whereas Pyk2 opposes T-cell attachment. While CXCL12-promoted generation of high-affinity α4β1 is independent of SLP-76, ADAP, and Pyk2, the strength of α4β1-VCAM-1 interaction and cell spreading on VCAM-1 are targets of regulation by these three proteins. GTPase assays, expression of activated or dominant-negative Rac1, or combined ADAP and Pyk2 silencing indicated that Rac1 activation by CXCL12 is a common mediator response in SLP-76-, ADAP-, and Pyk2-regulated cell adhesion involving α4β1. Our data strongly suggest that chemokine-stimulated associations between Vav1, SLP-76, and ADAP facilitate Rac1 activation and α4β1-mediated adhesion, whereas Pyk2 opposes this adhesion by limiting Rac1 activation. © 2015 Dios-Esponera, Isern de Val, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  1. The Analysis for Energy Consumption of Marine Air Conditioning System Based on VAV and VWV

    NASA Astrophysics Data System (ADS)

    Xu, Sai Feng; Yang, Xing Lin; Le, Zou Ying

    2018-06-01

    For ocean-going vessels sailing in different areas on the sea, the change of external environment factors will cause frequent changes in load, traditional ship air-conditioning system is usually designed with a fixed cooling capacity, this design method causes serious waste of resources. A new type of sea-based air conditioning system is proposed in this paper, which uses the sea-based source heat pump system, combined with variable air volume, variable water technology. The multifunctional cabins' dynamic loads for a ship navigating in a typical Eurasian route were calculated based on Simulink. The model can predict changes in full voyage load. Based on the simulation model, the effects of variable air volume and variable water volume on the energy consumption of the air-conditioning system are analyzed. The results show that: When the VAV is coupled with the VWV, the energy saving rate is 23.2%. Therefore, the application of variable air volume and variable water technology to marine air conditioning systems can achieve economical and energy saving advantages.

  2. Ofloxacin induces apoptosis via β1 integrin-EGFR-Rac1-Nox2 pathway in microencapsulated chondrocytes

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

    Sheng, Zhi-Guo; Huang, Wei; Liu, Yu-Xiang

    2013-02-15

    Quinolones (QNs)-induced arthropathy is an important toxic side-effect in immature animals leading to the restriction of their therapeutic use in pediatrics. Ofloxacin, a typical QN, was found to induce the chondrocytes apoptosis in the early phase (12–48 h) of arthropathy in our previous study. However, the exact mechanism(s) is unclear. Microencapsulated juvenile rabbit joint chondrocytes, a three-dimensional culture system, is utilized to perform the present study. Ofloxacin, at a therapeutically relevant concentration (10 μg/ml), disturbs the interaction between β1 integrin and activated intracellular signaling proteins at 12 h, which is inhibited when supplementing Mg{sup 2+}. Intracellular reactive oxygen species (ROS)more » significantly increases in a time-dependent manner after exposure to ofloxacin for 12–48 h. Furthermore, ofloxacin markedly enhances the level of activated Rac1 and epidermal growth factor receptor (EGFR) phosphorylation, and its inhibition in turn reduces the ROS production, apoptosis and Rac1 activation. Silencing Nox2, Rac1 or supplementing Mg{sup 2+} inhibits ROS accumulation, apoptosis occurrence and EGFR phosphorylation induced by ofloxacin. However, depletion of Nox2, Rac1 and inhibition of EGFR do not affect ofloxacin-mediated loss of interaction between β1 integrin and activated intracellular signaling proteins. In addition, ofloxacin also induces Vav2 phosphorylation, which is markedly suppressed after inactivating EGFR or supplementing Mg{sup 2+}. These results suggest that ofloxacin causes Nox2-mediated intracellular ROS production by disrupting the β1 integrin function and then activating the EGFR-Vav2-Rac1 pathway, finally resulting in apoptosis within 12–48 h exposure. The present study provides a novel insight regarding the potential role of Nox-driven ROS in QNs-induced arthropathy. - Highlights: ► Ofloxacin induces Nox2-driven ROS in encapsulated chondrocyte at 12–48 h. ► Ofloxacin stimulates ROS production via the β1 integrin-EGFR-Vav2-Rac1 pathway. ► Ofloxacin induces ROS-dependent apoptosis in encapsulated chondrocyte at 12–48 h.« less

  3. Evaluation of energy savings potential of variable refrigerant flow (VRF) from variable air volume (VAV) in the U.S. climate locations

    DOE PAGES

    Kim, Dongsu; Cox, Sam J.; Cho, Heejin; ...

    2017-05-22

    Variable refrigerant flow (VRF) systems are known for their high energy performance and thus can improve energy efficiency both in residential and commercial buildings. The energy savings potential of this system has been demonstrated in several studies by comparing the system performance with conventional HVAC systems such as rooftop variable air volume systems (RTU-VAV) and central chiller and boiler systems. This paper evaluates the performance of VRF and RTU-VAV systems in a simulation environment using widely-accepted whole building energy modeling software, EnergyPlus. A medium office prototype building model, developed by the U.S. Department of Energy (DOE), is used to assessmore » the performance of VRF and RTU-VAV systems. Each system is placed in 16 different locations, representing all U.S. climate zones, to evaluate the performance variations. Both models are compliant with the minimum energy code requirements prescribed in ASHRAE standard 90.1-2010 — energy standard for buildings except low-rise residential buildings. Finally, a comparison study between the simulation results of VRF and RTU-VAV models is made to demonstrate energy savings potential of VRF systems. The simulation results show that the VRF systems would save around 15–42% and 18–33% for HVAC site and source energy uses compared to the RTU-VAV systems. In addition, calculated results for annual HVAC cost savings point out that hot and mild climates show higher percentage cost savings for the VRF systems than cold climates mainly due to the differences in electricity and gas use for heating sources.« less

  4. Evaluation of energy savings potential of variable refrigerant flow (VRF) from variable air volume (VAV) in the U.S. climate locations

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

    Kim, Dongsu; Cox, Sam J.; Cho, Heejin

    Variable refrigerant flow (VRF) systems are known for their high energy performance and thus can improve energy efficiency both in residential and commercial buildings. The energy savings potential of this system has been demonstrated in several studies by comparing the system performance with conventional HVAC systems such as rooftop variable air volume systems (RTU-VAV) and central chiller and boiler systems. This paper evaluates the performance of VRF and RTU-VAV systems in a simulation environment using widely-accepted whole building energy modeling software, EnergyPlus. A medium office prototype building model, developed by the U.S. Department of Energy (DOE), is used to assessmore » the performance of VRF and RTU-VAV systems. Each system is placed in 16 different locations, representing all U.S. climate zones, to evaluate the performance variations. Both models are compliant with the minimum energy code requirements prescribed in ASHRAE standard 90.1-2010 — energy standard for buildings except low-rise residential buildings. Finally, a comparison study between the simulation results of VRF and RTU-VAV models is made to demonstrate energy savings potential of VRF systems. The simulation results show that the VRF systems would save around 15–42% and 18–33% for HVAC site and source energy uses compared to the RTU-VAV systems. In addition, calculated results for annual HVAC cost savings point out that hot and mild climates show higher percentage cost savings for the VRF systems than cold climates mainly due to the differences in electricity and gas use for heating sources.« less

  5. An Effective Model of the Retinoic Acid Induced HL-60 Differentiation Program.

    PubMed

    Tasseff, Ryan; Jensen, Holly A; Congleton, Johanna; Dai, David; Rogers, Katharine V; Sagar, Adithya; Bunaciu, Rodica P; Yen, Andrew; Varner, Jeffrey D

    2017-10-30

    In this study, we present an effective model All-Trans Retinoic Acid (ATRA)-induced differentiation of HL-60 cells. The model describes reinforcing feedback between an ATRA-inducible signalsome complex involving many proteins including Vav1, a guanine nucleotide exchange factor, and the activation of the mitogen activated protein kinase (MAPK) cascade. We decomposed the effective model into three modules; a signal initiation module that sensed and transformed an ATRA signal into program activation signals; a signal integration module that controlled the expression of upstream transcription factors; and a phenotype module which encoded the expression of functional differentiation markers from the ATRA-inducible transcription factors. We identified an ensemble of effective model parameters using measurements taken from ATRA-induced HL-60 cells. Using these parameters, model analysis predicted that MAPK activation was bistable as a function of ATRA exposure. Conformational experiments supported ATRA-induced bistability. Additionally, the model captured intermediate and phenotypic gene expression data. Knockout analysis suggested Gfi-1 and PPARg were critical to the ATRAinduced differentiation program. These findings, combined with other literature evidence, suggested that reinforcing feedback is central to hyperactive signaling in a diversity of cell fate programs.

  6. PTP1B inhibitor promotes endothelial cell motility by activating the DOCK180/Rac1 pathway.

    PubMed

    Wang, Yuan; Yan, Feng; Ye, Qing; Wu, Xiao; Jiang, Fan

    2016-04-07

    Promoting endothelial cell (EC) migration is important not only for therapeutic angiogenesis, but also for accelerating re-endothelialization after vessel injury. Several recent studies have shown that inhibition of protein tyrosine phosphatase 1B (PTP1B) may promote EC migration and angiogenesis by enhancing the vascular endothelial growth factor receptor-2 (VEGFR2) signalling. In the present study, we demonstrated that PTP1B inhibitor could promote EC adhesion, spreading and migration, which were abolished by the inhibitor of Rac1 but not RhoA GTPase. PTP1B inhibitor significantly increased phosphorylation of p130Cas, and the interactions among p130Cas, Crk and DOCK180; whereas the phosphorylation levels of focal adhesion kinase, Src, paxillin, or Vav2 were unchanged. Gene silencing of DOCK180, but not Vav2, abrogated the effects of PTP1B inhibitor on EC motility. The effects of PTP1B inhibitor on EC motility and p130Cas/DOCK180 activation persisted in the presence of the VEGFR2 antagonist. In conclusion, we suggest that stimulation of the DOCK180 pathway represents an alternative mechanism of PTP1B inhibitor-stimulated EC motility, which does not require concomitant VEGFR2 activation as a prerequisite. Therefore, PTP1B inhibitor may be a useful therapeutic strategy for promoting EC migration in cardiovascular patients in which the VEGF/VEGFR functions are compromised.

  7. Candidate Socioemotional Remediation Program for Individuals with Intellectual Disability

    ERIC Educational Resources Information Center

    Glaser, Bronwyn; Lothe, Amelie; Chabloz, Melanie; Dukes, Daniel; Pasca, Catherine; Redoute, Jerome; Eliez, Stephan

    2012-01-01

    The authors developed a computerized program, Vis-a-Vis (VAV), to improve socioemotional functioning and working memory in children with developmental disabilities. The authors subsequently tested whether participants showed signs of improving the targeted skills. VAV is composed of three modules: Focus on the Eyes, Emotion Recognition and…

  8. The Adaptor Molecule Nck Localizes the WAVE Complex to Promote Actin Polymerization during CEACAM3-Mediated Phagocytosis of Bacteria

    PubMed Central

    Delgado Tascón, Julia; Nyffenegger-Jann, Naja J.; Hauck, Christof R.

    2012-01-01

    Background CEACAM3 is a granulocyte receptor mediating the opsonin-independent recognition and phagocytosis of human-restricted CEACAM-binding bacteria. CEACAM3 function depends on an intracellular immunoreceptor tyrosine-based activation motif (ITAM)-like sequence that is tyrosine phosphorylated by Src family kinases upon receptor engagement. The phosphorylated ITAM-like sequence triggers GTP-loading of Rac by directly associating with the guanine nucleotide exchange factor (GEF) Vav. Rac stimulation in turn is critical for actin cytoskeleton rearrangements that generate lamellipodial protrusions and lead to bacterial uptake. Principal Findings In our present study we provide biochemical and microscopic evidence that the adaptor proteins Nck1 and Nck2, but not CrkL, Grb2 or SLP-76, bind to tyrosine phosphorylated CEACAM3. The association is phosphorylation-dependent and requires the Nck SH2 domain. Overexpression of the isolated Nck1 SH2 domain, RNAi-mediated knock-down of Nck1, or genetic deletion of Nck1 and Nck2 interfere with CEACAM3-mediated bacterial internalization and with the formation of lamellipodial protrusions. Nck is constitutively associated with WAVE2 and directs the actin nucleation promoting WAVE complex to tyrosine phosphorylated CEACAM3. In turn, dominant-negative WAVE2 as well as shRNA-mediated knock-down of WAVE2 or the WAVE-complex component Nap1 reduce internalization of bacteria. Conclusions Our results provide novel mechanistic insight into CEACAM3-initiated phagocytosis. We suggest that the CEACAM3 ITAM-like sequence is optimized to co-ordinate a minimal set of cellular factors needed to efficiently trigger actin-based lamellipodial protrusions and rapid pathogen engulfment. PMID:22448228

  9. The adaptor molecule Nck localizes the WAVE complex to promote actin polymerization during CEACAM3-mediated phagocytosis of bacteria.

    PubMed

    Pils, Stefan; Kopp, Kathrin; Peterson, Lisa; Delgado Tascón, Julia; Nyffenegger-Jann, Naja J; Hauck, Christof R

    2012-01-01

    CEACAM3 is a granulocyte receptor mediating the opsonin-independent recognition and phagocytosis of human-restricted CEACAM-binding bacteria. CEACAM3 function depends on an intracellular immunoreceptor tyrosine-based activation motif (ITAM)-like sequence that is tyrosine phosphorylated by Src family kinases upon receptor engagement. The phosphorylated ITAM-like sequence triggers GTP-loading of Rac by directly associating with the guanine nucleotide exchange factor (GEF) Vav. Rac stimulation in turn is critical for actin cytoskeleton rearrangements that generate lamellipodial protrusions and lead to bacterial uptake. In our present study we provide biochemical and microscopic evidence that the adaptor proteins Nck1 and Nck2, but not CrkL, Grb2 or SLP-76, bind to tyrosine phosphorylated CEACAM3. The association is phosphorylation-dependent and requires the Nck SH2 domain. Overexpression of the isolated Nck1 SH2 domain, RNAi-mediated knock-down of Nck1, or genetic deletion of Nck1 and Nck2 interfere with CEACAM3-mediated bacterial internalization and with the formation of lamellipodial protrusions. Nck is constitutively associated with WAVE2 and directs the actin nucleation promoting WAVE complex to tyrosine phosphorylated CEACAM3. In turn, dominant-negative WAVE2 as well as shRNA-mediated knock-down of WAVE2 or the WAVE-complex component Nap1 reduce internalization of bacteria. Our results provide novel mechanistic insight into CEACAM3-initiated phagocytosis. We suggest that the CEACAM3 ITAM-like sequence is optimized to co-ordinate a minimal set of cellular factors needed to efficiently trigger actin-based lamellipodial protrusions and rapid pathogen engulfment.

  10. Detection of protein-protein interactions by ribosome display and protein in situ immobilisation.

    PubMed

    He, Mingyue; Liu, Hong; Turner, Martin; Taussig, Michael J

    2009-12-31

    We describe a method for identification of protein-protein interactions by combining two cell-free protein technologies, namely ribosome display and protein in situ immobilisation. The method requires only PCR fragments as the starting material, the target proteins being made through cell-free protein synthesis, either associated with their encoding mRNA as ribosome complexes or immobilised on a solid surface. The use of ribosome complexes allows identification of interacting protein partners from their attached coding mRNA. To demonstrate the procedures, we have employed the lymphocyte signalling proteins Vav1 and Grb2 and confirmed the interaction between Grb2 and the N-terminal SH3 domain of Vav1. The method has promise for library screening of pairwise protein interactions, down to the analytical level of individual domain or motif mapping.

  11. Demonstration of Energy Savings in Commercial Buildings for Tiered Trim and Respond Method in Resetting Static Pressure for VAV Systems

    DTIC Science & Technology

    2017-03-01

    FINAL REPORT Demonstration of Energy Savings in Commercial Buildings for Tiered Trim and Respond Method in Resetting Static Pressure for VAV...release Page Intentionally Left Blank This report was prepared under contract to the Department of Defense Environmental Security Technology...Certification Program (ESTCP). The publication of this report does not indicate endorsement by the Department of Defense, nor should the contents be

  12. Characterisation of Triticum vavilovii-derived stripe rust resistance using genetic, cytogenetic and molecular analyses and its marker-assisted selection.

    PubMed

    Bariana, H. S.; Brown, G. N.; Ahmed, N. U.; Khatkar, S.; Conner, R. L.; Wellings, C. R.; Haley, S.; Sharp, P. J.; Laroche, A.

    2002-02-01

    Stripe rust resistance was identified in Triticum vavilovii( T. vaviloviiAus22498)-derived Russian wheat aphid (RWA)-resistant germplasm. Inheritance studies indicated monogenic control of resistance. The resistance gene was tentatively designated as Yrvav and was located on chromosome 1B by monosomic analysis. A close association (1.5+/-0.9% recombination) of Yrvav with a T. vavilovii-derived gliadin allele ( Gli-B1vav) placed it in chromosome arm 1BS. Yrvavwas allelic with Yr10. Tests with Yr10 avirulent and virulent pathotypes showed that Yrvav and Yr10 possess identical pathogenic specificity. Yrvav and Yr10 showed close genetic associations with alternate alleles at the Xpsp3000(microsatellite marker), Gli-B1 and Rg1 loci. Based on these observations Yrvav was named as Yr10vav. The close association between Xpsp3000 and Gli-B1 was also confirmed. The Yr10vav-linked Xpsp3000 allele (285 bp) was not present in 65 Australian cultivars, whereas seven Australian wheats lacking Yr10 carried the same Xpsp3000 allele (260 bp) as Yr10carrying wheat cultivar Moro. Xpsp3000 and/or Gli-B1 could be used in marker-assisted selection for pyramiding Yr10vavor Yr10 with other stripe rust resistance genes. Yr10vav was inherited independently of the T. vavilovii-derived RWA resistance.

  13. Using coordinate-based meta-analyses to explore structural imaging genetics.

    PubMed

    Janouschek, Hildegard; Eickhoff, Claudia R; Mühleisen, Thomas W; Eickhoff, Simon B; Nickl-Jockschat, Thomas

    2018-05-05

    Imaging genetics has become a highly popular approach in the field of schizophrenia research. A frequently reported finding is that effects from common genetic variation are associated with a schizophrenia-related structural endophenotype. Genetic contributions to a structural endophenotype may be easier to delineate, when referring to biological rather than diagnostic criteria. We used coordinate-based meta-analyses, namely the anatomical likelihood estimation (ALE) algorithm on 30 schizophrenia-related imaging genetics studies, representing 44 single-nucleotide polymorphisms at 26 gene loci investigated in 4682 subjects. To test whether analyses based on biological information would improve the convergence of results, gene ontology (GO) terms were used to group the findings from the published studies. We did not find any significant results for the main contrast. However, our analysis enrolling studies on genotype × diagnosis interaction yielded two clusters in the left temporal lobe and the medial orbitofrontal cortex. All other subanalyses did not yield any significant results. To gain insight into possible biological relationships between the genes implicated by these clusters, we mapped five of them to GO terms of the category "biological process" (AKT1, CNNM2, DISC1, DTNBP1, VAV3), then five to "cellular component" terms (AKT1, CNNM2, DISC1, DTNBP1, VAV3), and three to "molecular function" terms (AKT1, VAV3, ZNF804A). A subsequent cluster analysis identified representative, non-redundant subsets of semantically similar terms that aided a further interpretation. We regard this approach as a new option to systematically explore the richness of the literature in imaging genetics.

  14. Syk Mediates BCR- and CD40-Signaling Intergration during B Cell Activation

    PubMed Central

    Ying, Haiyan; Li, Zhenping; Yang, Lifen; Zhang, Jian

    2010-01-01

    CD40 is essential for optimal B cell activation. It has been shown that CD40 stimulation can augment BCR-induced B cell responses, but the molecular mechanism(s) by which CD40 regulates BCR signaling is poorly understood. In this report, we attempted to characterize the signaling synergy between BCR- and CD40-mediated pathways during B cell activation. We found that spleen tyrosine kinase (Syk) is involved in CD40 signaling, and is synergistically activated in B cells in response to BCR/CD40 costimulation. CD40 stimulation alone also activates B cell linker (BLNK), Bruton tyrosine kinase (Btk), and Vav-2 downstream of Syk, and significantly enhances BCR-induced formation of complex consisting of, Vav-2, Btk, BLNK, and phospholipase C-gamma2 (PLC-γ2) leading to activation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase, Akt, and NF-κB required for optimal B cell activation. Therefore, our data suggest that CD40 can strengthen BCR-signaling pathway and quantitatively modify BCR signaling during B cell activation. PMID:21074890

  15. Dissecting GRB7-mediated signals for proliferation and migration in HER2 overexpressing breast tumor cells: GTP-ase rules.

    PubMed

    Pradip, De; Bouzyk, Mark; Dey, Nandini; Leyland-Jones, Brian

    2013-01-01

    Amplification of human Her2 and its aberrant signaling in 20-30% of early breast cancer patients is responsible for highly aggressive tumors with poor outcome. Grb7 is reported to be co-amplified with Her2. We report a concurrent high expression of mRNA (from FFPE tumor samples; mRNA correlation, Pearson r(2)= 0.806), and high levels of GRB7 protein (immunoblot) in HER2+ breast cancer cell lines. We demonstrated the signaling mechanism of HER2 and downstream effectors that contributes to proliferation and migration. Using HER2+ and trastuzumab-resistant breast cancer cell lines, we identified the interaction between GRB7 and HER2 in the control of HER2+ cell proliferation. Our co-IP data show that GRB7 recruits SHC into the HER2-GRB7 signaling complex. This complex formation leads to activation of RAS-GTP. We also observed that following integrin engagement, GRB7 is phosphorylated at tyrosine in a p-FAK (Y397) dependent manner. This FAK-GRB7 complex leads to downstream activation of RAC1-GTP (responsible for migration) probably through the recruitment of VAV2. Our CO-IP data demonstrate that GRB7 directly binds with VAV2 following fibronectin engagement in HER2+ cells. To address whether GRB7 could serve as a pathway specific therapeutic target, we used siRNA to suppress GRB7 expression. Knockdown of GRB7 expression in the HER2+ breast cancer cell lines decreases RAS activation, cell proliferation, 2D and 3D colony formation and also blocked integrin-mediated RAC1 activation along with integrin-directed cell migration. These findings dissected the HER2-mediated signaling cascade into (1) HER2+ cell proliferation (HER2-GRB7-SHC-RAS) and (2) HER2+ cell migration (alpha5 beta1/alpha4 beta1-FAK-GRB7-VAV2-RAC1). Our data clearly demonstrate that a coupling of GRB7 with HER2 is required for the proliferative and migratory signals in HER2+ breast tumor cells.

  16. 2-(trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate suppresses osteoclast maturation and bone resorption by targeting macrophage-colony stimulating factor signaling.

    PubMed

    Park, So Jeong; Park, Doo Ri; Bhattarai, Deepak; Lee, Kyeong; Kim, Jaesang; Bae, Yun Soo; Lee, Soo Young

    2014-08-01

    2-(Trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient megakaryopoiesis. Here, we show that (R)-TEMOSPho blocks osteoclast maturation from progenitor cells of hematopoietic origin, as well as blocking the resorptive function of mature osteoclasts. The inhibitory effect of (R)-TEMOSPho on osteoclasts was due to a disruption of the actin cytoskeleton, resulting from impaired downstream signaling of c-Fms, a receptor for macrophage-colony stimulating factor linked to c-Cbl, phosphoinositol-3-kinase (PI3K), Vav3, and Rac1. In addition, (R)-TEMOSPho blocked inflammation-induced bone destruction by reducing the numbers of osteoclasts produced in mice. Thus, (R)-TEMOSPho may represent a promising new class of antiresorptive drugs for the treatment of bone loss associated with increased osteoclast maturation and activity.

  17. Kinematic Modeling of Normal Voluntary Mandibular Opening and Closing Velocity-Initial Study.

    PubMed

    Gawriołek, Krzysztof; Gawriołek, Maria; Komosa, Marek; Piotrowski, Paweł R; Azer, Shereen S

    2015-06-01

    Determination and quantification of voluntary mandibular velocity movement has not been a thoroughly studied parameter of masticatory movement. This study attempted to objectively define kinematics of mandibular movement based on numerical (digital) analysis of the relations and interactions of velocity diagram records in healthy female individuals. Using a computerized mandibular scanner (K7 Evaluation Software), 72 diagrams of voluntary mandibular velocity movements (36 for opening, 36 for closing) for women with clinically normal motor and functional activities of the masticatory system were recorded. Multiple measurements were analyzed focusing on the curve for maximum velocity records. For each movement, the loop of temporary velocities was determined. The diagram was then entered into AutoCad calculation software where movement analysis was performed. The real maximum velocity values on opening (Vmax ), closing (V0 ), and average velocity values (Vav ) as well as movement accelerations (a) were recorded. Additionally, functional (A1-A2) and geometric (P1-P4) analysis of loop constituent phases were performed, and the relations between the obtained areas were defined. Velocity means and correlation coefficient values for various velocity phases were calculated. The Wilcoxon test produced the following maximum and average velocity results: Vmax = 394 ± 102, Vav = 222 ± 61 for opening, and Vmax = 409 ± 94, Vav = 225 ± 55 mm/s for closing. Both mandibular movement range and velocity change showed significant variability achieving the highest velocity in P2 phase. Voluntary mandibular velocity presents significant variations between healthy individuals. Maximum velocity is obtained when incisal separation is between 12.8 and 13.5 mm. An improved understanding of the patterns of normal mandibular movements may provide an invaluable diagnostic aid to pathological changes within the masticatory system. © 2014 by the American College of Prosthodontists.

  18. Developmentally induced Mll1 loss reveals defects in postnatal haematopoiesis.

    PubMed

    Gan, T; Jude, C D; Zaffuto, K; Ernst, P

    2010-10-01

    The mixed lineage leukemia (MLL) gene is disrupted by chromosomal translocations in acute leukemia, producing a fusion oncogene with altered properties relative to the wild-type gene. Murine loss-of-function studies have shown an essential role for Mll in developing the haematopoietic system, yet studies using different conditional knockout models have yielded conflicting results regarding the requirement for Mll during adult steady-state haematopoiesis. In this study, we used a loxP-flanked Mll allele (Mll(F)) and a developmentally regulated, haematopoietic-specific VavCre transgene to reassess the consequences of Mll loss in the haematopoietic lineage, without the need for inducers of Cre recombinase. We show that VavCre;Mll mutants exhibit phenotypically normal fetal haematopoiesis, but rarely survive past 3 weeks of age. Surviving animals are anemic, thrombocytopenic and exhibit a significant reduction in bone marrow haematopoietic stem/progenitor populations, consistent with our previous findings using the inducible Mx1Cre transgene. Furthermore, the analysis of VavCre mutants revealed additional defects in B-lymphopoiesis that could not be assessed using Mx1Cre-mediated Mll deletion. Collectively, these data support the conclusion that Mll has an essential role in sustaining postnatal haematopoiesis.

  19. Avoiding low frequency noise in packaged HVAC equipment

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

    Ebbing, C.E.; Blazier, W.E.Jr.

    1993-06-01

    The purpose of this article is to help those involved in the design and commissioning of packaged HVAC systems to understand the root causes of low frequency noise problems and how to avoid many of them at the design stage. In the 1980's, two things happened to dramatically change the types of noise problems encountered in typical new construction. The first was the introduction of new energy regulations that favored variable air volume (VAV) distribution systems over constant volume air distribution systems. A by-product of VAV design is that mid- and high frequency sound pressure levels produced by current airmore » terminal devices and diffusers in many applications are significantly lower than in the past. The second factor was a trend away from the use of built-up central station fan equipment in favor of packaged, floor-by-floor air handlers or rooftop units. As a result, today's HVAC system noise problems are not confined to just the roar and hiss of the past, but now include intense low frequency rumble and time modulation. Indeed, most current noise problems in modern buildings occur in the frequency range well below 250 Hz. A large fraction of these are a result of the dominant sound pressure levels in the 12 to 40 Hz region. These factors, combined with a substantial increase in the level of low frequency sound from the rest of the system, can produce a non-neutral, time modulated, rumbly sounding background noise that many people find objectionable.« less

  20. Modulation of the Fcepsilon receptor I signaling by tyrosine kinase inhibitors: search for therapeutic targets of inflammatory and allergy diseases.

    PubMed

    Lusková, Petra; Dráber, Petr

    2004-01-01

    Mast cells and basophils are major effector cells in the immunoglobulin E (IgE)-dependent allergic reactions as well as in the innate immunity. They are distributed throughout the body and, upon allergen exposure, are stimulated via the high affinity IgE receptor (FcepsilonRI) to release several pro-inflammatory mediators such as leukotrienes, immunoregulatory cytokines and histamine. FcepsilonRI-mediated signaling is initiated by tyrosine phosphorylation of FcepsilonRI subunits by Src family kinase Lyn, which is followed by an activation of Syk/Zap family kinase Syk. The activated kinases then in turn phosphorylate and activate other enzymes [phospholipase Cgamma (PLCgamma) isoforms, phosphatidylinositol-3 kinase (PI3K) isoforms, protein kinase C (PKC) isoforms, Bruton's tyrosine kinase (Btk) and others], adaptors [linker for activation of T cells (LAT), Cbl, Grb2 and others] and GTP exchange factors/GTPases (Vav, Ras, Rho, and others), and subsequently induce the mobilization of stored and extracellular Ca(2+). These and other biochemical events lead within seconds and minutes to the secretory response and later to the production of chemokines. This review is focused on the use of tyrosine kinase inhibitors specific for Src family kinases (PP1/PP2, SU6656 and CT5269), Syk kinase (piceatannol, ER-27319 and BAY 61-3606) and Btk (terreic acid and LFM-A13) for a modulation of FcepsilonRI-mediated signaling in mast cells. Potential use of the inhibitors in the treatment of inflammatory and allergy diseases as well as future directions in the development of highly specific tyrosine kinases inhibitors of new generations and their use in an intended modulation of mast cell signaling are discussed.

  1. Role of IKK-alpha in the EGFR Signaling Regulation

    DTIC Science & Technology

    2014-09-01

    Rho family GTPase (VAV2), and Phospholipase C (PLC) (4). These signaling activities regulate cell proliferation, mobility , and differentiation in...correlation coefficient r=0.63, pɘ.05) was found, suggesting that high IKK promotes EGFR phosphorylation in breast cancer cells (Fig. 3G ...phosphorylation (Figure 2E). Since protein phosphorylation sometimes results in a mobility shift in SDS-PAGE, we used a phospho-tag to capture phospho

  2. IbeA and OmpA of Escherichia coli K1 Exploit Rac1 Activation for Invasion of Human Brain Microvascular Endothelial Cells

    PubMed Central

    Maruvada, Ravi

    2012-01-01

    Meningitis-causing Escherichia coli K1 internalization of the blood-brain barrier is required for penetration into the brain, but the host-microbial interactions involved in E. coli entry of the blood-brain barrier remain incompletely understood. We show here that a meningitis-causing E. coli K1 strain RS218 activates Rac1 (GTP-Rac1) of human brain microvascular endothelial cells (HBMEC) in a time-dependent manner. Both activation and bacterial invasion were significantly inhibited in the presence of a Rac1 inhibitor. We further showed that the guanine nucleotide exchange factor Vav2, not β-Pix, was involved in E. coli K1-mediated Rac1 activation. Since activated STAT3 is known to bind GTP-Rac1, the relationship between STAT3 and Rac1 was examined in E. coli K1 invasion of HBMEC. Downregulation of STAT3 resulted in significantly decreased E. coli invasion compared to control HBMEC, as well as a corresponding decrease in GTP-Rac1, suggesting that Rac1 activation in response to E. coli is under the control of STAT3. More importantly, two E. coli determinants contributing to HBMEC invasion, IbeA and OmpA, were shown to affect both Rac1 activation and their association with STAT3. These findings demonstrate for the first time that specific E. coli determinants regulate a novel mechanism of STAT3 cross talk with Rac1 in E. coli K1 invasion of HBMEC. PMID:22451524

  3. IbeA and OmpA of Escherichia coli K1 exploit Rac1 activation for invasion of human brain microvascular endothelial cells.

    PubMed

    Maruvada, Ravi; Kim, Kwang Sik

    2012-06-01

    Meningitis-causing Escherichia coli K1 internalization of the blood-brain barrier is required for penetration into the brain, but the host-microbial interactions involved in E. coli entry of the blood-brain barrier remain incompletely understood. We show here that a meningitis-causing E. coli K1 strain RS218 activates Rac1 (GTP-Rac1) of human brain microvascular endothelial cells (HBMEC) in a time-dependent manner. Both activation and bacterial invasion were significantly inhibited in the presence of a Rac1 inhibitor. We further showed that the guanine nucleotide exchange factor Vav2, not β-Pix, was involved in E. coli K1-mediated Rac1 activation. Since activated STAT3 is known to bind GTP-Rac1, the relationship between STAT3 and Rac1 was examined in E. coli K1 invasion of HBMEC. Downregulation of STAT3 resulted in significantly decreased E. coli invasion compared to control HBMEC, as well as a corresponding decrease in GTP-Rac1, suggesting that Rac1 activation in response to E. coli is under the control of STAT3. More importantly, two E. coli determinants contributing to HBMEC invasion, IbeA and OmpA, were shown to affect both Rac1 activation and their association with STAT3. These findings demonstrate for the first time that specific E. coli determinants regulate a novel mechanism of STAT3 cross talk with Rac1 in E. coli K1 invasion of HBMEC.

  4. Assessment of the Activation State of Rho Family GTP-Binding Proteins in Breast Cancer Cells and Specimens

    DTIC Science & Technology

    2004-08-01

    AF038388 Vav3 GEF for Rho and Rac Proto-oncogene product NM020505 hPEM -2 GEF for Cdc42 Predominantly expressed in brain AB007884 GEF-H1 GEF for Rac and Rho...fence tions, and desmosomes play a fundamental role in maintain- function). A functional tight junction is crucial to maintain ing the polarized phenotype

  5. Heating, ventilation and air conditioning system optimization: a study of the effect of climate, building design, system selection and control strategy on the energy consumption of a typical office building in London and Athens

    NASA Astrophysics Data System (ADS)

    Spasis, Georgios

    The increasing demand for air conditioning in commercial buildings imposes a serious threat to Europe's CO2 reduction targets. Architects and engineers are therefore in a key position to help reduce the impact of buildings on the environment by taking appropriate decisions concerning the design of the building and the associated heating, ventilation and air conditioning (HVAC) system. The thesis studies the effect of a number of building and HVAC system related design factors on the energy performance of a notional air-conditioned office building employing either a variable air volume (VAV) system with terminal re-heaters, or a four-pipe fan coil unit (FCU) system with fresh air supply from a central plant, using mainly a dynamic simulation tool and the response surface methodology. The evaluation of the energy performance of the HVAC systems is for two types of climate, using typical weather data for London (UK) and Athens (Greece). It has been found that the design variables associated with the solar radiation through the transparent building elements and the internal heat gains should be the main concern of the building designer. On the other hand, the HVAC system engineer should give emphasis to the parameters associated with the plant performance and operation, as well as the temperature control set-points. It has been shown that it is possible to reduce the carbon emissions of the base case scenario by up to 88% depending on the HVAC system and the climate for which it is simulated. The carbon savings, however, are reduced by up to 22% where humidification is provided. This reduction differs depending on the HVAC system and the climatic conditions. The VAV system is more energy efficient than the FCU system, mainly due to the exploitation of the free cooling capacity of the outdoor air. The difference in carbon emissions between the two systems drops when both of them are simulated for the Athens as opposed to the London typical weather conditions. It has been found that it is possible to turn the carbon scales in favour of the FCU system when humidification to a high RH set-point is provided throughout the year, since the adjustment of the RH of the air is particularly energy wasteful for the VAV system.

  6. Minimum airflow reset of single-duct VAV terminal boxes

    NASA Astrophysics Data System (ADS)

    Cho, Young-Hum

    Single duct Variable Air Volume (VAV) systems are currently the most widely used type of HVAC system in the United States. When installing such a system, it is critical to determine the minimum airflow set point of the terminal box, as an optimally selected set point will improve the level of thermal comfort and indoor air quality (IAQ) while at the same time lower overall energy costs. In principle, this minimum rate should be calculated according to the minimum ventilation requirement based on ASHRAE standard 62.1 and maximum heating load of the zone. Several factors must be carefully considered when calculating this minimum rate. Terminal boxes with conventional control sequences may result in occupant discomfort and energy waste. If the minimum rate of airflow is set too high, the AHUs will consume excess fan power, and the terminal boxes may cause significant simultaneous room heating and cooling. At the same time, a rate that is too low will result in poor air circulation and indoor air quality in the air-conditioned space. Currently, many scholars are investigating how to change the algorithm of the advanced VAV terminal box controller without retrofitting. Some of these controllers have been found to effectively improve thermal comfort, indoor air quality, and energy efficiency. However, minimum airflow set points have not yet been identified, nor has controller performance been verified in confirmed studies. In this study, control algorithms were developed that automatically identify and reset terminal box minimum airflow set points, thereby improving indoor air quality and thermal comfort levels, and reducing the overall rate of energy consumption. A theoretical analysis of the optimal minimum airflow and discharge air temperature was performed to identify the potential energy benefits of resetting the terminal box minimum airflow set points. Applicable control algorithms for calculating the ideal values for the minimum airflow reset were developed and applied to actual systems for performance validation. The results of the theoretical analysis, numeric simulations, and experiments show that the optimal control algorithms can automatically identify the minimum rate of heating airflow under actual working conditions. Improved control helps to stabilize room air temperatures. The vertical difference in the room air temperature was lower than the comfort value. Measurements of room CO2 levels indicate that when the minimum airflow set point was reduced it did not adversely affect the indoor air quality. According to the measured energy results, optimal control algorithms give a lower rate of reheating energy consumption than conventional controls.

  7. Impact of conditional deletion of the pro-apoptotic BCL-2 family member BIM in mice.

    PubMed

    Herold, M J; Stuchbery, R; Mérino, D; Willson, T; Strasser, A; Hildeman, D; Bouillet, P

    2014-10-09

    The pro-apoptotic BH3-only BCL-2 family member BIM is a critical determinant of hematopoietic cell development and homeostasis. It has been argued that the striking hematopoietic abnormalities of BIM-deficient mice (accumulation of lymphocytes and granulocytes) may be the result of the loss of the protein throughout the whole animal rather than a consequence intrinsic to the loss of BIM in hematopoietic cells. To address this issue and allow the deletion of BIM in specific cell types in future studies, we have developed a mouse strain with a conditional Bim allele as well as a new Cre transgenic strain, Vav-CreER, in which the tamoxifen-inducible CreER recombinase (fusion protein) is predominantly expressed in the hematopoietic system. We show that acute loss of BIM in the adult mouse rapidly results in the hematopoietic phenotypes previously observed in mice lacking BIM in all tissues. This includes changes in thymocyte subpopulations, increased white blood cell counts and resistance of lymphocytes to BIM-dependent apoptotic stimuli, such as cytokine deprivation. We have validated this novel conditional Bim knockout mouse model using established and newly developed CreER strains (Rosa26-CreER and Vav-CreER) and will make these exciting new tools for studies on cell death and cancer available.

  8. Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans

    PubMed Central

    Daghighi, Mojtaba; Özcan, Behiye; Akbarkhanzadeh, Vishtaseb; Sheedfar, Fareeba; Amini, Marzyeh; Mazza, Tommaso; Pazienza, Valerio; Motazacker, Mahdi M.; Mahmoudi, Morteza; De Rooij, Felix W. M.; Sijbrands, Eric; Peppelenbosch, Maikel P.; Rezaee, Farhad

    2015-01-01

    Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and pancreas with T2D for targeting to develop new drugs for DNs therapy. AT-T2D displayed 15 (e.g. SYT4 up-regulated and VGF down-regulated) and pancreas-T2D showed 10 (e.g. BAG3 up-regulated, VAV3 and APOA1 down-regulated) highly differentially expressed genes with neuronal functions as compared to control tissues. ELISA was blindly performed to measure proteins of 5 most differentially expressed genes in 41 human subjects. SYT4 protein was upregulated, VAV3 and APOA1 were down-regulated, and BAG3 remained unchanged in 1- Obese and 2- Obese-T2D without insulin, VGF protein was higher in these two groups as well as in group 3- Obese-T2D receiving insulin than 4-lean subjects. Interaction networks analysis of these 5 genes showed several metabolic pathways (e.g. lipid metabolism and insulin signaling). Pancreas is a novel site for APOA1 synthesis. VGF is synthesized in AT and could be considered as good diagnostic, and even prognostic, marker for age-induced diseases obesity and T2D. This study provides new targets for rational drugs development for the therapy of age-related DNs. PMID:26337083

  9. Class IA phosphoinositide 3-kinase β and δ regulate neutrophil oxidase activation in response to Aspergillus fumigatus hyphae.

    PubMed

    Boyle, Keith B; Gyori, David; Sindrilaru, Anca; Scharffetter-Kochanek, Karin; Taylor, Philip R; Mócsai, Attila; Stephens, Len R; Hawkins, Phillip T

    2011-03-01

    An effective immune response to the ubiquitous fungus Aspergillus fumigatus is dependent upon production of reactive oxygen species (ROS) by the NADPH oxidase. This is evidenced by the acute sensitivity of oxidase-deficient humans and mice to invasive aspergillosis. Neutrophils are recruited to the lungs shortly postinfection and respond by phagocytosing conidia and mediating extracellular killing of germinated hyphae in a ROS-dependent manner. However, the signaling mechanisms regulating the generation of ROS in response to hyphae are poorly understood. PI3Ks are important regulators of numerous cellular processes, with much recent work describing unique roles for the different class I PI3K isoforms. We showed by live-cell imaging that the lipid products of class I PI3Ks accumulated at the hyphal-bound neutrophil plasma membrane. Further, we used pharmacological and genetic approaches to demonstrate essential, but overlapping, roles for PI3Kβ and PI3Kδ in the ROS and spreading responses of murine neutrophils to Aspergillus hyphae. Hyphal-induced ROS responses were substantially inhibited by deletion of the common β2-integrin subunit CD18, with only a minor, redundant role for Dectin-1. However, addition of soluble algal glucans plus the genetic deletion of CD18 were required to significantly inhibit activation of the PI3K-effector protein kinase B. Hyphal ROS responses were also totally dependent on the presence of Syk, but not its ITAM-containing adaptor proteins FcRγ or DAP12, and the Vav family of Rac-guanine nucleotide exchange factors. These results start to define the signaling network controlling neutrophil ROS responses to A. fumigatus hyphae.

  10. Retinoic Acid Therapy Resistance Progresses from Unilineage to Bilineage in HL-60 Leukemic Blasts

    PubMed Central

    Jensen, Holly A.; Bunaciu, Rodica P.; Ibabao, Christopher N.; Myers, Rebecca; Varner, Jeffrey D.; Yen, Andrew

    2014-01-01

    Emergent resistance can be progressive and driven by global signaling aberrations. All-trans retinoic acid (RA) is the standard therapeutic agent for acute promyelocytic leukemia, but 10–20% of patients are not responsive, and initially responsive patients relapse and develop retinoic acid resistance. The patient-derived, lineage-bipotent acute myeloblastic leukemia (FAB M2) HL-60 cell line is a potent tool for characterizing differentiation-induction therapy responsiveness and resistance in t(15;17)-negative cells. Wild-type (WT) HL-60 cells undergo RA-induced granulocytic differentiation, or monocytic differentiation in response to 1,25-dihydroxyvitamin D3 (D3). Two sequentially emergent RA-resistant HL-60 cell lines, R38+ and R38-, distinguishable by RA-inducible CD38 expression, do not arrest in G1/G0 and fail to upregulate CD11b and the myeloid-associated signaling factors Vav1, c-Cbl, Lyn, Fgr, and c-Raf after RA treatment. Here, we show that the R38+ and R38- HL-60 cell lines display a progressive reduced response to D3-induced differentiation therapy. Exploiting the biphasic dynamic of induced HL-60 differentiation, we examined if resistance-related defects occurred during the first 24 h (the early or “precommitment” phase) or subsequently (the late or “lineage-commitment” phase). HL-60 were treated with RA or D3 for 24 h, washed and retreated with either the same, different, or no differentiation agent. Using flow cytometry, D3 was able to induce CD38, CD11b and CD14 expression, and G1/G0 arrest when present during the lineage-commitment stage in R38+ cells, and to a lesser degree in R38- cells. Clustering analysis of cytometry and quantified Western blot data indicated that WT, R38+ and R38- HL-60 cells exhibited decreasing correlation between phenotypic markers and signaling factor expression. Thus differentiation induction therapy resistance can develop in stages, with initial partial RA resistance and moderate vitamin D3 responsiveness (unilineage maturation block), followed by bilineage maturation block and progressive signaling defects, notably the reduced expression of Vav1, Fgr, and c-Raf. PMID:24922062

  11. Role of phosphoinositide 3-kinase regulatory isoforms in development and actin rearrangement.

    PubMed

    Brachmann, Saskia M; Yballe, Claudine M; Innocenti, Metello; Deane, Jonathan A; Fruman, David A; Thomas, Sheila M; Cantley, Lewis C

    2005-04-01

    Class Ia phosphoinositide 3-kinases (PI3Ks) are heterodimers of p110 catalytic and p85 regulatory subunits that mediate a variety of cellular responses to growth and differentiation factors. Although embryonic development is not impaired in mice lacking all isoforms of the p85alpha gene (p85alpha-/- p55alpha-/- p50alpha-/-) or in mice lacking the p85beta gene (p85beta-/-) (D. A. Fruman, F. Mauvais-Jarvis, D. A. Pollard, C. M. Yballe, D. Brazil, R. T. Bronson, C. R. Kahn, and L. C. Cantley, Nat Genet. 26:379-382, 2000; K. Ueki, C. M. Yballe, S. M. Brachmann, D. Vicent, J. M. Watt, C. R. Kahn, and L. C. Cantley, Proc. Natl. Acad. Sci. USA 99:419-424, 2002), we show here that loss of both genes results in lethality at embryonic day 12.5 (E12.5). The phenotypes of these embryos, including subepidermal blebs flanking the neural tube at E8 and bleeding into the blebs during the turning process, are similar to defects observed in platelet-derived growth factor receptor alpha null (PDGFRalpha-/-) mice (P. Soriano, Development 124:2691-2700, 1997), suggesting that PI3K is an essential mediator of PDGFRalpha signaling at this developmental stage. p85alpha-/- p55alpha+/+ p50alpha+/+ p85beta-/- mice had similar but less severe defects, indicating that p85alpha and p85beta have a critical and redundant function in development. Mouse embryo fibroblasts deficient in all p85alpha and p85beta gene products (p85alpha-/- p55alpha-/- p50alpha-/- p85beta-/-) are defective in PDGF-induced membrane ruffling. Overexpression of the Rac-specific GDP-GTP exchange factor Vav2 or reintroduction of p85alpha or p85beta rescues the membrane ruffling defect. Surprisingly, reintroduction of p50alpha also restored PDGF-dependent membrane ruffling. These results indicate that class Ia PI3K is critical for PDGF-dependent actin rearrangement but that the SH3 domain and the Rho/Rac/Cdc42-interacting domain of p85, which lacks p50alpha, are not required for this response.

  12. The AhR agonist VAF347 augments retinoic acid-induced differentiation in leukemia cells

    PubMed Central

    Ibabao, Christopher N.; Bunaciu, Rodica P.; Schaefer, Deanna M.W.; Yen, Andrew

    2015-01-01

    In binary cell-fate decisions, driving one lineage and suppressing the other are conjoined. We have previously reported that aryl hydrocarbon receptor (AhR) promotes retinoic acid (RA)-induced granulocytic differentiation of lineage bipotent HL-60 myeloblastic leukemia cells. VAF347, an AhR agonist, impairs the development of CD14+CD11b+ monocytes from granulo-monocytic (GM) stage precursors. We thus hypothesized that VAF347 propels RA-induced granulocytic differentiation and impairs D3-induced monocytic differentiation of HL-60 cells. Our results show that VAF347 enhanced RA-induced cell cycle arrest, CD11b integrin expression and neutrophil respiratory burst. Granulocytic differentiation is known to be driven by MAPK signaling events regulated by Fgr and Lyn Src-family kinases, the CD38 cell membrane receptor, the Vav1 GEF, the c-Cbl adaptor, as well as AhR, all of which are embodied in a putative signalsome. We found that the VAF347 AhR ligand regulates the signalsome. VAF347 augments RA-induced expression of AhR, Lyn, Vav1, and c-Cbl as well as p47phox. Several interactions of partners in the signalsome appear to be enhanced: Fgr interaction with c-Cbl, CD38, and with pS259c-Raf and AhR interaction with c-Cbl and Lyn. Thus, we report that, while VAF347 impedes monocytic differentiation induced by 1,25-dihydroxyvitamin D3, VAF347 promotes RA-induced differentiation. This effect seems to involve but not to be limited to Lyn, Vav1, c-Cbl, AhR, and Fgr. PMID:25941627

  13. The AhR agonist VAF347 augments retinoic acid-induced differentiation in leukemia cells.

    PubMed

    Ibabao, Christopher N; Bunaciu, Rodica P; Schaefer, Deanna M W; Yen, Andrew

    2015-01-01

    In binary cell-fate decisions, driving one lineage and suppressing the other are conjoined. We have previously reported that aryl hydrocarbon receptor (AhR) promotes retinoic acid (RA)-induced granulocytic differentiation of lineage bipotent HL-60 myeloblastic leukemia cells. VAF347, an AhR agonist, impairs the development of CD14(+)CD11b(+) monocytes from granulo-monocytic (GM) stage precursors. We thus hypothesized that VAF347 propels RA-induced granulocytic differentiation and impairs D3-induced monocytic differentiation of HL-60 cells. Our results show that VAF347 enhanced RA-induced cell cycle arrest, CD11b integrin expression and neutrophil respiratory burst. Granulocytic differentiation is known to be driven by MAPK signaling events regulated by Fgr and Lyn Src-family kinases, the CD38 cell membrane receptor, the Vav1 GEF, the c-Cbl adaptor, as well as AhR, all of which are embodied in a putative signalsome. We found that the VAF347 AhR ligand regulates the signalsome. VAF347 augments RA-induced expression of AhR, Lyn, Vav1, and c-Cbl as well as p47(phox). Several interactions of partners in the signalsome appear to be enhanced: Fgr interaction with c-Cbl, CD38, and with pS259c-Raf and AhR interaction with c-Cbl and Lyn. Thus, we report that, while VAF347 impedes monocytic differentiation induced by 1,25-dihydroxyvitamin D3, VAF347 promotes RA-induced differentiation. This effect seems to involve but not to be limited to Lyn, Vav1, c-Cbl, AhR, and Fgr.

  14. Verifying the body tide at the Canary Islands using tidal gravimetry observations

    NASA Astrophysics Data System (ADS)

    Arnoso, J.; Benavent, M.; Bos, M. S.; Montesinos, F. G.; Vieira, R.

    2011-05-01

    Gravity tide records from El Hierro, Tenerife and Lanzarote Islands (Canarian Archipelago) have been analyzed and compared to the theoretical body tide model (DDW) of Dehant el al. (1999). The use of more stringent criterion of tidal analysis using VAV program allowed us to reduce the error bars by a factor of two of the gravimetric factors at Tenerife and Lanzarote compared with previous published values. Also, the calibration values have been revisited at those sites. Precise ocean tide loading (OTL) corrections based on up-to-date global ocean models and improved regional ocean model have been obtained for the main tidal harmonics O 1, K 1, M 2, S 2. We also point out the importance of using the most accurate coastline definition for OTL calculations in the Canaries. The remaining observational errors depend on the accuracy of the calibration of the gravimeters and/or on the length of the observed data series. Finally, the comparison of the tidal observations with the theoretical body tide models has been done with an accuracy level of 0.1% at El Hierro, 0.4% at Tenerife and 0.5% at Lanzarote.

  15. Hematopoietic stem cell-specific GFP-expressing transgenic mice generated by genetic excision of a pan-hematopoietic reporter gene.

    PubMed

    Perez-Cunningham, Jessica; Boyer, Scott W; Landon, Mark; Forsberg, E Camilla

    2016-08-01

    Selective labeling of specific cell types by expression of green fluorescent protein (GFP) within the hematopoietic system would have great utility in identifying, localizing, and tracking different cell populations in flow cytometry, microscopy, lineage tracing, and transplantation assays. In this report, we describe the generation and characterization of a new transgenic mouse line with specific GFP labeling of all nucleated hematopoietic cells and platelets. This new "Vav-GFP" mouse line labels the vast majority of hematopoietic cells with GFP during both embryonic development and adulthood, with particularly high expression in hematopoietic stem and progenitor cells (HSPCs). With the exception of transient labeling of fetal endothelial cells, GFP expression is highly selective for hematopoietic cells and persists in donor-derived progeny after transplantation of HSPCs. Finally, we also demonstrate that the loxP-flanked reporter allows for specific GFP labeling of different hematopoietic cell subsets when crossed to various Cre reporter lines. By crossing Vav-GFP mice to Flk2-Cre mice, we obtained robust and highly selective GFP expression in hematopoietic stem cells (HSCs). These data describe a new mouse model capable of directing GFP labeling exclusively of hematopoietic cells or exclusively of HSCs. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  16. Validation Data for Mechanical System Algorithms Used in Building Energy Analysis Programs.

    DTIC Science & Technology

    1982-02-01

    15 Zone Design 15 Built-Up Air Handler 15 Ventilation Requirements 16 The DES 16 Duct Design 17 Air -Delivery System 17 VAV Operation 17 Constant Volume...observed to operate well at reduced air flows, even at low flow in the so- called surge region. Recommendations 1. The HVAC system and component...With Inlet Guide Vanes Operating Within a Built-Up Air Handler 31 Test 2 -- Boiler Operation, Capacity, Efficiency, and Stand-By Losses 32 Test 3

  17. Analysis of DNA Methylation at Specific Loci in Stool Samples Detects Colorectal Cancer and High-grade Dysplasia in Patients with Inflammatory Bowel Disease.

    PubMed

    Kisiel, John B; Klepp, Pasquale; Allawi, Hatim T; Taylor, William R; Giakoumopoulos, Maria; Sander, Tamara; Yab, Tracy C; Moum, Bjorn A; Lidgard, Graham P; Brackmann, Stephan; Mahoney, Douglas W; Roseth, Arne; Ahlquist, David A

    2018-05-15

    Patients with inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are at increased risk for colorectal cancer (CRC). Analyses of DNA methylation patterns in stool samples have been reported to detect CRC in patients with IBD. We sought to validate these findings in larger cohorts and assess the accuracy of analysis of DNA methylation patterns in stool for detection of CRC and high-grade dysplasia (HGD) normalized to methylation level at ZDHHC1. We obtained buffered, frozen stool samples from a United States case-control study and from 2 European surveillance cohorts (referral or population based) of patients with chronic UC (n=248), CD (n=82), indeterminate colitis (n=2), or IBD with primary sclerosing cholangitis (n=38). Stool samples were collected before bowel preparation for colonoscopy or at least 1 week after colonoscopy. Among the study samples, stools from individuals with IBD but without neoplasia were used as controls (n=291). DNA was isolated from stool, exposed to bisulfite, and then assayed by multiplex quantitative allele-specific real-time target and signal amplification. We analyzed methylation levels of BMP3, NDRG4, VAV3, and SFMBT2 relative to the methylation level of ZDHHC1, and compared these between patients with CRC or HGD and controls. Levels of methylation at BMP3 and VAV3, relative to ZDHHC1 methylation, identified patients with CRC and HGD with an area under curve value of 0.91 (95% CI, 0.77-1.00). Methylation levels at specific promotor regions of these genes identified 11 of the 12 patients with CRC and HGD, with 92% sensitivity (95% CI, 60%-100%) and 90% specificity (95% CI, 86%-93%). The proportion of false-positive results did not differ significantly among the case-control, referral cohort, and population cohort studies (P=.60) when the 90% specificity cut-off from the whole sample set was applied. In an analysis of stool samples from 3 independent studies, of 332 patients with IBD, we associated levels of methylation at 2 genes (BMP3 and VAV3), relative to level of methylation at ZDHHC1, with detection of CRC and HGD. These methylation patterns identified patients with CRC and HGD with more than 90% specificity, and might be used in CRC surveillance. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

  18. 75 FR 54446 - Voluntary Service National Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-07

    ...-four national voluntary organizations, advises the Secretary, through the Under Secretary for Health... DEPARTMENT OF VETERANS AFFAIRS Voluntary Service National Advisory Committee; Notice of Meeting... Committee Act) that the Executive Committee of the Department of Veterans Affairs Voluntary Service (VAVS...

  19. ANSI Standard: Complying with Background Noise Limits.

    ERIC Educational Resources Information Center

    Schaffer, Mark E.

    2003-01-01

    Discusses the new classroom acoustics standard, ANSI Standard S12.60, which specifies maximum sound level limits that are significantly lower than currently typical for classrooms. Addresses guidelines for unducted HVAC systems, ducted single-zone systems, and central VAV or multizone systems. (EV)

  20. Dual role of SLP-76 in mediating T cell receptor-induced activation of phospholipase C-gamma1.

    PubMed

    Beach, Dvora; Gonen, Ronnie; Bogin, Yaron; Reischl, Ilona G; Yablonski, Deborah

    2007-02-02

    Phospholipase C-gamma1 (PLC-gamma1) activation depends on a heterotrimeric complex of adaptor proteins composed of LAT, Gads, and SLP-76. Upon T cell receptor stimulation, a portion of PLC-gamma1 is recruited to a detergent-resistant membrane fraction known as the glycosphingolipid-enriched membrane microdomains (GEMs), or lipid rafts, to which LAT is constitutively localized. In addition to LAT, PLC-gamma1 GEM recruitment depended on SLP-76, and, in particular, required the Gads-binding domain of SLP-76. The N-terminal tyrosine phosphorylation sites and P-I region of SLP-76 were not required for PLC-gamma1 GEM recruitment, but were required for PLC-gamma1 phosphorylation at Tyr(783). Thus, GEM recruitment can be insufficient for full activation of PLC-gamma1 in the absence of a second SLP-76-mediated event. Indeed, a GEM-targeted derivative of PLC-gamma1 depended on SLP-76 for T cell receptor-induced phosphorylation at Tyr783 and subsequent NFAT activation. On a biochemical level, SLP-76 inducibly associated with both Vav and catalytically active ITK, which efficiently phosphorylated a PLC-gamma1 fragment at Tyr783 in vitro. Both associations were disrupted upon mutation of the N-terminal tyrosine phosphorylation sites of SLP-76. The P-I region deletion disrupted Vav association and reduced SLP-76-associated kinase activity. A smaller deletion within the P-I region, which does not impair PLC-gamma1 activation, did not impair the association with Vav, but reduced SLP-76-associated kinase activity. These results provide new insight into the multiple roles of SLP-76 and the functional importance of its interactions with other signaling proteins.

  1. VAV1-Cre mediated hematopoietic deletion of CBL and CBL-B leads to JMML-like aggressive early-neonatal myeloproliferative disease

    PubMed Central

    An, Wei; Mohapatra, Bhopal C.; Zutshi, Neha; Bielecki, Timothy A.; Goez, Benjamin T.; Luan, Haitao; Iseka, Fany; Mushtaq, Insha; Storck, Matthew D.; Band, Vimla; Band, Hamid

    2016-01-01

    CBL and CBL-B ubiquitin ligases play key roles in hematopoietic stem cell homeostasis and their aberrations are linked to leukemogenesis. Mutations of CBL, often genetically-inherited, are particularly common in Juvenile Myelomonocytic Leukemia (JMML), a disease that manifests early in children. JMML is fatal unless corrected by bone marrow transplant, which is effective in only half of the recipients, stressing the need for animal models that recapitulate the key clinical features of this disease. However, mouse models established so far only develop hematological malignancy in adult animals. Here, using VAV1-Cre-induced conditional CBL/CBL-B double knockout (DKO) in mice, we established an animal model that exhibits a neonatal myeloproliferative disease (MPD). VAV1-Cre induced DKO mice developed a strong hematological phenotype at postnatal day 10, including severe leukocytosis and hepatomegaly, bone marrow cell hypersensitivity to cytokines including GM-CSF, and rapidly-progressive disease and invariable lethality. Interestingly, leukemic stem cells were most highly enriched in neonatal liver rather than bone marrow, which, along with the spleen and thymus, were hypo-cellular. Nonetheless, transplantation assays showed that both DKO bone marrow and liver cells can initiate leukemic disease in the recipient mice with seeding of both spleen and bone marrow. Together, our results support the usefulness of the new hematopoietic-specific CBL/CBL-B double KO animal model to study JMML-related pathogenesis and to further understand the function of CBL family proteins in regulating fetal and neonatal hematopoiesis. To our knowledge, this is the first mouse model that exhibits neonatal MPD in infancy, by day 10 of postnatal life. PMID:27449297

  2. 77 FR 60507 - Voluntary Service National Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-03

    ... meeting is open to the public. The Committee, comprised of 57 national voluntary organizations, advises... DEPARTMENT OF VETERANS AFFAIRS Voluntary Service National Advisory Committee; Notice of Meeting... Committee Act) that the Executive Committee of the Department of Veterans Affairs Voluntary Service (VAVS...

  3. DNMT3B modulates the expression of cancer-related genes and downregulates the expression of the gene VAV3 via methylation

    PubMed Central

    Peralta-Arrieta, Irlanda; Hernández-Sotelo, Daniel; Castro-Coronel, Yaneth; Leyva-Vázquez, Marco Antonio; Illades-Aguiar, Berenice

    2017-01-01

    Altered promoter DNA methylation is one of the most important epigenetic abnormalities in human cancer. DNMT3B, de novo methyltransferase, is clearly related to abnormal methylation of tumour suppressor genes, DNA repair genes and its overexpression contributes to oncogenic processes and tumorigenesis in vivo. The purpose of this study was to assess the effect of the overexpression of DNMT3B in HaCaT cells on global gene expression and on the methylation of selected genes to the identification of genes that can be target of DNMT3B. We found that the overexpression of DNMT3B in HaCaT cells, modulate the expression of genes related to cancer, downregulated the expression of 151 genes with CpG islands and downregulated the expression of the VAV3 gene via methylation of its promoter. These results highlight the importance of DNMT3B in gene expression and human cancer. PMID:28123849

  4. DNMT3B modulates the expression of cancer-related genes and downregulates the expression of the gene VAV3 via methylation.

    PubMed

    Peralta-Arrieta, Irlanda; Hernández-Sotelo, Daniel; Castro-Coronel, Yaneth; Leyva-Vázquez, Marco Antonio; Illades-Aguiar, Berenice

    2017-01-01

    Altered promoter DNA methylation is one of the most important epigenetic abnormalities in human cancer. DNMT3B, de novo methyltransferase, is clearly related to abnormal methylation of tumour suppressor genes, DNA repair genes and its overexpression contributes to oncogenic processes and tumorigenesis in vivo . The purpose of this study was to assess the effect of the overexpression of DNMT3B in HaCaT cells on global gene expression and on the methylation of selected genes to the identification of genes that can be target of DNMT3B. We found that the overexpression of DNMT3B in HaCaT cells, modulate the expression of genes related to cancer, downregulated the expression of 151 genes with CpG islands and downregulated the expression of the VAV3 gene via methylation of its promoter. These results highlight the importance of DNMT3B in gene expression and human cancer.

  5. Evaluation of Variable Refrigerant Flow Systems Performance on Oak Ridge National Laboratory s Flexible Research Platform: Part 2 Heating Season Analysis

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

    Im, Piljae; Malhotra, Mini; Munk, Jeffrey D.

    The performance of two HVAC systems was evaluated using ORNL’s FRP, which is a two-story, 3,200 ft2 (297.3 m2) multi-zone unoccupied building that represents a typical low-rise, small office building common in the US existing building stock. The FRP is equipped with a conventional 12.5 ton (44 kW) RTU-VAV reheat system as the baseline system. For this study, a 12 ton (42 kW) VRF with a dedicated outdoor air system (DOAS) was installed to be compared with the baseline RTU system.

  6. A role for multiple chimeric antigen receptor-expressing leukocytes in antigen-specific responses to cancer

    PubMed Central

    Yong, Carmen S.M.; John, Liza B.; Devaud, Christel; Prince, Miles H.; Johnstone, Ricky W.; Trapani, Joseph A.

    2016-01-01

    While adoptive immunotherapy using chimeric antigen receptor (CAR)-modified T cells can induce remission of some tumors, the role of other CAR-modified leukocytes is not well characterized. In this study, we characterize the function of leukocytes including natural killer (NK) cells, macrophages and CAR T cells from transgenic mice expressing a CAR under the control of the pan-hematopoietic promoter, vav, and determine the ability of these mice to respond to ERB expressing tumors. We demonstrate the anti-tumor functions of leukocytes, including antigen specific cytotoxicity and cytokine secretion. The adoptive transfer of CAR T cells provided a greater survival advantage in the E0771ERB tumor model than their wildtype (WT) counterparts. In addition, CAR NK cells and CAR T cells also mediated increased survival in the RMAERB tumor model. When challenged with Her2 expressing tumors, F38 mice were shown to mount an effective immune response, resulting in tumor rejection and long-term survival. This was shown to be predominantly dependent on both CD8+ T cells and NK cells. However, macrophages and CD4+ T cells were also shown to contribute to this response. Overall, this study highlights the use of the vav-CAR mouse model as a unique tool to determine the anti-tumor function of various immune subsets, either alone or when acting alongside CAR T cells in adoptive immunotherapy. PMID:27153556

  7. Demonstration of Energy Savings in Commercial Buildings for Tiered Trim and Respond Method in Resetting Static Pressure for VAV Systems

    DTIC Science & Technology

    2017-03-01

    Systems March 2017 This document has been cleared for public release; Distribution Statement A REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704... FORM TO THE ABOVE ADDRESS. 1. REPORT DATE (DD-MM-YYYY) 28-02-2017 2. REPORT TYPE Cost and Performance Report 3. DATES COVERED (From - To) September...ABSTRACT c. THIS PAGE 71 19b. TELEPHONE NUMBER (include area code) (515)965-7342 Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 Page

  8. Dynamic evaluation of airflow rates for a variable air volume system serving an open-plan office.

    PubMed

    Mai, Horace K W; Chan, Daniel W T; Burnett, John

    2003-09-01

    In a typical air-conditioned office, the thermal comfort and indoor air quality are sustained by delivering the amount of supply air with the correct proportion of outdoor air to the breathing zone. However, in a real office, it is not easy to measure these airflow rates supplied to space, especially when the space is served by a variable air volume (VAV) system. The most accurate method depends on what is being measured, the details of the building and types of ventilation system. The constant concentration tracer gas method as a means to determine ventilation system performance, however, this method becomes more complicated when the air, including the tracer gas is allowed to recirculate. An accurate measurement requires significant resource support in terms of instrumentation set up and also professional interpretation. This method deters regular monitoring of the performance of an airside systems by building managers, and hence the indoor environmental quality, in terms of thermal comfort and indoor air quality, may never be satisfactory. This paper proposes a space zone model for the calculation of all the airflow parameters based on tracer gas measurements, including flow rates of outdoor air, VAV supply, return space, return and exfiltration. Sulphur hexafluoride (SF6) and carbon dioxide (CO2) are used as tracer gases. After using both SF6 and CO2, the corresponding results provide a reference to justify the acceptability of using CO2 as the tracer gas. The validity of using CO2 has the significance that metabolic carbon dioxide can be used as a means to evaluate real time airflow rates. This approach provides a practical protocol for building managers to evaluate the performance of airside systems.

  9. Liquid transmission characteristics of padding bandages under pressure.

    PubMed

    Kumar, Bipin; Das, Apurba; Pan, Ning; Alagirusamy, R; Gupta, Rupali; Singh, Jitender

    2015-11-01

    Padding is an essential component in a multilayer compression bandaging system, used inside the compression bandage through which substantial amount of pressure is exerted on the limb of patient for treatment of venous leg ulcers. As a result, the liquid transmission behavior of padding is also critical in managing body fluids or sweat exuded from the affected limb, reducing the excessive moisture build-up around the wound and thereby ensuring comfort to and hence a better compliance from the patients. This study investigates the in-plane fluid transport characteristics of needle-punched nonwoven padding bandages. It first reviewed the existing studies related to the problems, and discussed their limits and possible improvements in dealing with complex fluid transport issues in textile porous media. The measurement of fluid transport under different pressure levels was then done using a newly designed apparatus capable of simultaneously tracing the liquid in-plane spreading along different directions, and obtaining several transport characteristics of a testing sample, e.g. the liquid flow anisotropy, the rate of movement, the area of wet surface with time, etc. Also the effects of several important factors, such as the levels of pressure applied, the specimen bulk density, and needling density of the padding products, have been experimentally investigated. In addition, based on an extended Lucas-Washburn theory, we calculated the liquid flow distance, both instantaneous speed and a more useful time-averaged speed v(av) at any given direction, and also defined a flow anisotropy index I(A) as a convenient parameter to represent the material flow anisotropy. The applications of v(av) and I(A) to actual samples have demonstrated the usefulness of these parameters in characterizing the flow nature and behavior of the materials. © The Author(s) 2015.

  10. Prioritising and planning of urban stormwater treatment in the Alna watercourse in Oslo.

    PubMed

    Nordeidet, B; Nordeide, T; Astebøl, S O; Hvitved-Jacobsen, T

    2004-12-01

    The Oslo municipal Water and Sewage Works (VAV) intends to improve the water quality in the Alna watercourse, in particular, with regards to the biological diversity. In order to reduce existing discharges of polluted urban stormwater, a study has been carried out to rank subcatchment areas in descending order of magnitude and to assess possible measures. An overall ranking methodology was developed in order to identify and select the most suitable subcatchment areas for further assessment studies (74 subcatchment/drainage areas). The municipality's comprehensive geographical information system (GIS) was applied as a base for the ranking. A weighted ranking based on three selected parameters was chosen from several major influencing factors, namely total yearly discharge (kg pollution/year), specific pollution discharge (kg/area/year) and existing stormwater system (pipe lengths/area). Results show that the highest 15 ranked catchment areas accounted for 70% of the total calculated pollution load of heavy metals. The highest ranked areas are strongly influenced by three major highways. Based on the results from similar field studies, it would be possible to remove 75-85% of total solids and about 50-80% of heavy metals using wet detention ponds as Best Available Technology (BAT). Based on the final ranking, two subcatchment areas were selected for further practical assessment of possible measures. VAV plans to use wet detention ponds, in combination with other measures when relevant, to treat the urban runoff. Using calculated loading and aerial photographs (all done in the same GIS environment), a preliminary sketch design and location of ponds were performed. The resulting GIS methodology for urban stormwater management will be used as input to a holistic and long-term planning process for the management of the watercourse, taking into account future urban development and other pollution sources.

  11. Energy Performance Assessment of Radiant Cooling System through Modeling and Calibration at Component Level

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

    Khan, Yasin; Mathur, Jyotirmay; Bhandari, Mahabir S

    2016-01-01

    The paper describes a case study of an information technology office building with a radiant cooling system and a conventional variable air volume (VAV) system installed side by side so that performancecan be compared. First, a 3D model of the building involving architecture, occupancy, and HVAC operation was developed in EnergyPlus, a simulation tool. Second, a different calibration methodology was applied to develop the base case for assessing the energy saving potential. This paper details the calibration of the whole building energy model to the component level, including lighting, equipment, and HVAC components such as chillers, pumps, cooling towers, fans,more » etc. Also a new methodology for the systematic selection of influence parameter has been developed for the calibration of a simulated model which requires large time for the execution. The error at the whole building level [measured in mean bias error (MBE)] is 0.2%, and the coefficient of variation of root mean square error (CvRMSE) is 3.2%. The total errors in HVAC at the hourly are MBE = 8.7% and CvRMSE = 23.9%, which meet the criteria of ASHRAE 14 (2002) for hourly calibration. Different suggestions have been pointed out to generalize the energy saving of radiant cooling system through the existing building system. So a base case model was developed by using the calibrated model for quantifying the energy saving potential of the radiant cooling system. It was found that a base case radiant cooling system integrated with DOAS can save 28% energy compared with the conventional VAV system.« less

  12. 75 FR 4632 - Voluntary Service National Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-28

    ... Awards, VAVS Award for Excellence, and the NAC Volunteer of the Year Awards. The April 8 business session... volunteers, cultural transformation, and assisting homeless veterans. On April 9, the educational workshops will be repeated in the morning and the business session will be held in the afternoon and will include...

  13. CD25 and CD69 induction by α4β1 outside-in signalling requires TCR early signalling complex proteins

    PubMed Central

    Cimo, Ann-Marie; Ahmed, Zamal; McIntyre, Bradley W.; Lewis, Dorothy E.; Ladbury, John E.

    2013-01-01

    Distinct signalling pathways producing diverse cellular outcomes can utilize similar subsets of proteins. For example, proteins from the TCR (T-cell receptor) ESC (early signalling complex) are also involved in interferon-α receptor signalling. Defining the mechanism for how these proteins function within a given pathway is important in understanding the integration and communication of signalling networks with one another. We investigated the contributions of the TCR ESC proteins Lck (lymphocyte-specific kinase), ZAP-70 (ζ-chain-associated protein of 70 kDa), Vav1, SLP-76 [SH2 (Src homology 2)-domain-containing leukocyte protein of 76 kDa] and LAT (linker for activation of T-cells) to integrin outside-in signalling in human T-cells. Lck, ZAP-70, SLP-76, Vav1 and LAT were activated by α4β1 outside-in signalling, but in a manner different from TCR signalling. TCR stimulation recruits ESC proteins to activate the mitogen-activated protein kinase ERK (extracellular-signal-regulated kinase). α4β1 outside-in-mediated ERK activation did not require TCR ESC proteins. However, α4β1 outside-in signalling induced CD25 and co-stimulated CD69 and this was dependent on TCR ESC proteins. TCR and α4β1 outside-in signalling are integrated through the common use of TCR ESC proteins; however, these proteins display functionally distinct roles in these pathways. These novel insights into the cross-talk between integrin outside-in and TCR signalling pathways are highly relevant to the development of therapeutic strategies to overcome disease associated with T-cell deregulation. PMID:23758320

  14. Performance assessment of a photonic radiative cooling system for office buildings

    DOE PAGES

    Wang, Weimin; Fernandez, Nick; Katipamula, Srinivas; ...

    2017-11-08

    Recent advances in materials have demonstrated the ability to maintain radiator surfaces at below-ambient temperatures in the presence of intense, direct sunlight. Daytime radiative cooling is promising for building applications. Here, this paper estimates the energy savings from daytime radiative cooling, specifically based on photonic materials. A photonic radiative cooling system was proposed and modeled using the whole energy simulation program EnergyPlus. A typical medium-sized office building was used for the simulation analysis. Several reference systems were established to quantify the potential of energy savings from the photonic radiative cooling system. The reference systems include a variable-air-volume (VAV) system, amore » hydronic radiant system, and a nighttime radiative cooling system. The savings analysis was made for a number of locations with different climates. Simulation results showed that the photonic radiative cooling system saved between 45% and 68% cooling electricity relative to the VAV system and between 9% and 23% relative to the nighttime radiative cooling system featured with the best coating commercially available on market. Finally, a simple economic analysis was also made to estimate the maximum acceptable incremental cost for upgrading from nighttime cooling to photonic radiative cooling.« less

  15. Performance assessment of a photonic radiative cooling system for office buildings

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

    Wang, Weimin; Fernandez, Nick; Katipamula, Srinivas

    Recent advances in materials have demonstrated the ability to maintain radiator surfaces at below-ambient temperatures in the presence of intense, direct sunlight. Daytime radiative cooling is promising for building applications. Here, this paper estimates the energy savings from daytime radiative cooling, specifically based on photonic materials. A photonic radiative cooling system was proposed and modeled using the whole energy simulation program EnergyPlus. A typical medium-sized office building was used for the simulation analysis. Several reference systems were established to quantify the potential of energy savings from the photonic radiative cooling system. The reference systems include a variable-air-volume (VAV) system, amore » hydronic radiant system, and a nighttime radiative cooling system. The savings analysis was made for a number of locations with different climates. Simulation results showed that the photonic radiative cooling system saved between 45% and 68% cooling electricity relative to the VAV system and between 9% and 23% relative to the nighttime radiative cooling system featured with the best coating commercially available on market. Finally, a simple economic analysis was also made to estimate the maximum acceptable incremental cost for upgrading from nighttime cooling to photonic radiative cooling.« less

  16. FADD and the NF-κB family member Bcl-3 regulate complementary pathways to control T-cell survival and proliferation

    PubMed Central

    Rangelova, Svetla; Kirschnek, Susanne; Strasser, Andreas; Häcker, Georg

    2008-01-01

    Fas-associated protein with death domain/mediator of receptor induced toxicity (FADD/MORT1) was first described as a transducer of death receptor signalling but was later recognized also to be important for proliferation of T cells. B-cell lymphoma 3 (Bcl-3) is a relatively little understood member of the nuclear factor (NF)-κB family of transcription factors. We recently found that Bcl-3 is up-regulated in T cells from mice where FADD function is blocked by a dominant negative transgene (FADD-DN). To understand the importance of this, we generated FADD-DN/bcl-3−/− mice. Here, we report that T cells from these mice show massive cell death and severely reduced proliferation in response to T-cell receptor (TCR) stimulation in vitro. Transgenic co-expression of Bcl-2 (FADD-DN/bcl-3−/−/vav-bcl-2 mice) rescued the survival but not the proliferation of T cells. FADD-DN/bcl-3−/− mice had normal thymocyte numbers but reduced numbers of peripheral T cells despite an increase in cycling T cells in vivo. However, activation of the classical NF-κB and extracellular regulated kinase (ERK) pathways and expression of interleukin (IL)-2 mRNA upon stimulation were normal in T cells from FADD-DN/bcl-3−/− mice. These data suggest that FADD and Bcl-3 regulate separate pathways that both contribute to survival and proliferation in mouse T cells. PMID:18557791

  17. A critical role for the regulation of Syk from agglutination to aggregation in human platelets.

    PubMed

    Shih, Chun-Ho; Chiang, Tin-Bin; Wang, Wen-Jeng

    2014-01-10

    Agglucetin, a tetrameric glycoprotein (GP) Ibα agonist from Formosan Agkistrodon acutus venom, has been characterized as an agglutination inducer in human washed platelets (WPs). In platelet-rich plasma (PRP), agglucetin dramatically elicits a biphasic response of agglutination and subsequent aggregation. For clarifying the intracellular signaling events from agglutination to aggregation in human platelets, we examined the essential signaling molecules involved through the detection of protein tyrosine phosphorylation (PTP). In WPs, an anti-GPIbα monoclonal antibody (mAb) AP1, but not a Src kinase inhibitor PP1, completely inhibited agglucetin-induced agglutination. However, PP1 but not AP1 had a potent suppression on platelet aggregation by a GPVI activator convulxin. The PTP analyses showed agglucetin alone can cause a weak pattern involving sequential phosphorylation of Lyn/Fyn, Syk, SLP-76 and phospholipase Cγ2 (PLCγ2). Furthermore, a Syk-selective kinase inhibitor, piceatannol, significantly suppressed the aggregating response in agglucetin-activated PRP. Analyzed by flow cytometry, the binding capacity of fluorophore-conjugated PAC-1, a mAb recognizing activated integrin αIIbβ3, was shown to increase in agglucetin-stimulated platelets. Again, piceatannol but not PP1 had a concentration-dependent suppression on agglucetin-induced αIIbβ3 exposure. Moreover, the formation of signalosome, including Syk, SLP-76, VAV, adhesion and degranulation promoting adapter protein (ADAP) and PLCγ2, are required for platelet aggregation in agglucetin/fibrinogen-activated platelets. In addition, GPIbα-ligation via agglucetin can substantially promote the interactions between αIIbβ3 and fibrinogen. Therefore, the signal pathway of Lyn/Fyn/Syk/SLP-76/ADAP/VAV/PLCγ2/PKC is sufficient to trigger platelet aggregation in agglucetin/fibrinogen-pretreated platelets. Importantly, Syk may function as a major regulator for the response from GPIbα-initiated agglutination to integrin αIIbβ3-dependent aggregation in human platelets. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. History of Sex Exchange in Women with a History of Incarceration

    PubMed Central

    Noska, Amanda J.; Roberts, Mary B.; Sufrin, Carolyn; Stein, L.A.R.; Beckwith, Curt G.; Rich, Josiah D.; Dauria, Emily F.; Clarke, Jennifer G.

    2016-01-01

    Sex exchange among incarcerated women is not well-described in the literature. Sex exchange can lead to numerous adverse health outcomes, especially when combined with individual factors (e.g., depression and homelessness) and larger systemic inequalities. The purpose of this study was to explore factors associated with having a history of sex exchange among a sample of incarcerated women. Of 257 women surveyed in this study, 68 women (26.5%) reported a history of sex exchange. In multivariate logistic regression analysis, physical abuse history (p=.05, OR 2.20), history of two or more sexually transmitted infections (p=.01, OR 2.90), injection drug use (p=.04, OR 2.46) and crack-cocaine use (p<.01, OR 3.42) were associated with prior sex exchange. This is one of only two studies to examine factors associated with prior sex exchange among incarcerated women. Our study has important implications for corrections providers to provide more comprehensive care, directly addressing the unique needs of this population. PMID:27133516

  19. Polarity-Dependent Vortex Pinning and Spontaneous Vortex-Antivortex Structures in Superconductor/Ferromagnet Hybrids

    NASA Astrophysics Data System (ADS)

    Bending, Simon J.; Milošević, Milorad V.; Moshchalkov, Victor V.

    Hybrid structures composed of superconducting films that are magnetically coupled to arrays of nanoscale ferromagnetic dots have attracted enormous interest in recent years. Broadly speaking, such systems fall into one of two distinct regimes. Ferromagnetic dots with weak moments pin free vortices, leading to enhanced superconducting critical currents, particularly when the conditions for commensurability are satisfied. Dots with strong moments spontaneously generate one or more vortex-antivortex (V-AV) pairs which lead to a rich variety of pinning, anti-pinning and annihilation phenomena. We describe high resolution Hall probe microscopy of flux structures in various hybrid samples composed of superconducting Pb films deposited on arrays of ferromagnetic Co or Co/Pt dots with both weak and strong moments. We show directly that dots with very weak perpendicular magnetic moments do not induce vortex-antivortex pairs, but still act as strong polarity-dependent vortex pinning centres for free vortices. In contrast, we have directly observed spontaneous V-AV pairs induced by large moment dots with both in-plane and perpendicular magnetic anisotropy, and studied the rich physical phenomena that arise when they interact with added "free" (anti)fluxons in an applied magnetic field. The interpretation of our imaging results is supported by bulk magnetometry measurements and state-of-the-art Ginzburg-Landau and London theory calculations.

  20. Reliability Estimating Procedures for Electric and Thermochemical Propulsion Systems. Volume 1

    DTIC Science & Technology

    1977-02-01

    Laboratories, The Marquardt Company, NASA Goddard Space Flight Center, RCA Astro Elec- tronics, Rockwell International, Applied Physics Laboratory...E fX ) 2.3 Failure Rate Means and Bounds 5% Lower Bound Median Mean 95% Upper Bound A.05 X.05 . AIA. 9 5 0.00025 0.0024 0.06 0.022 x10- 6 per cycle, 1...Iq IIt. Xg4 4l Wl ~ 4𔃺 L Q ൘ I1-269 I- I J N1- 74-i Liu I- (~J~~~jto 1-27 r4J > U 0 1-271 T 27 fX ~𔃽 0L 1-273 -- va VAv( 13 1-272 %J% ~ii 000 41

  1. Structural outline of the detailed mechanism for elongation factor Ts-mediated guanine nucleotide exchange on elongation factor Tu.

    PubMed

    Thirup, Søren S; Van, Lan Bich; Nielsen, Tine K; Knudsen, Charlotte R

    2015-07-01

    Translation elongation factor EF-Tu belongs to the superfamily of guanine-nucleotide binding proteins, which play key cellular roles as regulatory switches. All G-proteins require activation via exchange of GDP for GTP to carry out their respective tasks. Often, guanine-nucleotide exchange factors are essential to this process. During translation, EF-Tu:GTP transports aminoacylated tRNA to the ribosome. GTP is hydrolyzed during this process, and subsequent reactivation of EF-Tu is catalyzed by EF-Ts. The reaction path of guanine-nucleotide exchange is structurally poorly defined for EF-Tu and EF-Ts. We have determined the crystal structures of the following reaction intermediates: two structures of EF-Tu:GDP:EF-Ts (2.2 and 1.8Å resolution), EF-Tu:PO4:EF-Ts (1.9Å resolution), EF-Tu:GDPNP:EF-Ts (2.2Å resolution) and EF-Tu:GDPNP:pulvomycin:Mg(2+):EF-Ts (3.5Å resolution). These structures provide snapshots throughout the entire exchange reaction and suggest a mechanism for the release of EF-Tu in its GTP conformation. An inferred sequence of events during the exchange reaction is presented. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Direct Digital Control of HVAC (Heating, Ventilating, and Air Conditioning).

    DTIC Science & Technology

    1985-01-01

    controller func- tions such as time-of-day, economizer cycles, reset, load shedding, chiller optimization , VAV fan synchronization, and optimum start/stop...control system such as that illustrated in Fig- urc 4. Data on setpoints , reset schedules, and event timing, such as that presented in Figure 6, are...program code (Figure 7). In addition to the control logic, setpoint and other data are readily available. Program logi:, setpoint and schedule data, and

  3. The ISWI ATPase Smarca5 (Snf2h) Is Required for Proliferation and Differentiation of Hematopoietic Stem and Progenitor Cells.

    PubMed

    Kokavec, Juraj; Zikmund, Tomas; Savvulidi, Filipp; Kulvait, Vojtech; Edelmann, Winfried; Skoultchi, Arthur I; Stopka, Tomas

    2017-06-01

    The imitation switch nuclear ATPase Smarca5 (Snf2h) is one of the most conserved chromatin remodeling factors. It exists in a variety of oligosubunit complexes that move DNA with respect to the histone octamer to generate regularly spaced nucleosomal arrays. Smarca5 interacts with different accessory proteins and represents a molecular motor for DNA replication, repair, and transcription. We deleted Smarca5 at the onset of definitive hematopoiesis (Vav1-iCre) and observed that animals die during late fetal development due to anemia. Hematopoietic stem and progenitor cells accumulated but their maturation toward erythroid and myeloid lineages was inhibited. Proerythroblasts were dysplastic while basophilic erythroblasts were blocked in G2/M and depleted. Smarca5 deficiency led to increased p53 levels, its activation at two residues, one associated with DNA damage (S15 Ph ° s ) second with CBP/p300 (K376 Ac ), and finally activation of the p53 targets. We also deleted Smarca5 in committed erythroid cells (Epor-iCre) and observed that animals were anemic postnatally. Furthermore, 4-hydroxytamoxifen-mediated deletion of Smarca5 in the ex vivo cultures confirmed its requirement for erythroid cell proliferation. Thus, Smarca5 plays indispensable roles during early hematopoiesis and erythropoiesis. Stem Cells 2017;35:1614-1623. © 2017 AlphaMed Press.

  4. Modulation of the reaction cycle of the Na+:Ca2+, K+ exchanger.

    PubMed

    Vedovato, Natascia; Rispoli, Giorgio

    2007-09-01

    Ca(2+) concentration in retinal photoreceptor rod outer segment (OS) strongly affects the generator potential kinetics and the receptor light adaptation. The response to intense light stimuli delivered in the dark produce potential changes exceeding 40 mV: since the Ca(2+) extrusion in the OS is entirely controlled by the Na(+):Ca(2+), K(+) exchanger, it is important to assess how the exchanger ion transport rate is affected by the voltage and, in general, by intracellular factors. It is indeed known that the cardiac Na(+):Ca(2+) exchanger is regulated by Mg-ATP via a still unknown metabolic pathway. In the present work, the Na(+):Ca(2+), K(+) exchanger regulation was investigated in isolated OS, recorded in whole-cell configuration, using ionic conditions that activated maximally the exchanger in both forward and reverse mode. In all species examined (amphibia: Rana esculenta and Ambystoma mexicanum; reptilia: Gecko gecko), the forward (reverse) exchange current increased about linearly for negative (positive) voltages and exhibited outward (inward) rectification for positive (negative) voltages. Since hyperpolarisation increases Ca(2+) extrusion rate, the recovery of the dark level of Ca(2+) (and, in turn, of the generator potential) after intense light stimuli results accelerated. Mg-ATP increased the size of forward and reverse exchange current by a factor of approximately 2.3 and approximately 2.6, respectively, without modifying their voltage dependence. This indicates that Mg-ATP regulates the number of active exchanger sites and/or the exchanger turnover number, although via an unknown mechanism.

  5. Quantitative Analysis of Guanine Nucleotide Exchange Factors (GEFs) as Enzymes

    PubMed Central

    Randazzo, Paul A; Jian, Xiaoying; Chen, Pei-Wen; Zhai, Peng; Soubias, Olivier; Northup, John K

    2014-01-01

    The proteins that possess guanine nucleotide exchange factor (GEF) activity, which include about ~800 G protein coupled receptors (GPCRs),1 15 Arf GEFs,2 81 Rho GEFs,3 8 Ras GEFs,4 and others for other families of GTPases,5 catalyze the exchange of GTP for GDP on all regulatory guanine nucleotide binding proteins. Despite their importance as catalysts, relatively few exchange factors (we are aware of only eight for ras superfamily members) have been rigorously characterized kinetically.5–13 In some cases, kinetic analysis has been simplistic leading to erroneous conclusions about mechanism (as discussed in a recent review14). In this paper, we compare two approaches for determining the kinetic properties of exchange factors: (i) examining individual equilibria, and; (ii) analyzing the exchange factors as enzymes. Each approach, when thoughtfully used,14,15 provides important mechanistic information about the exchange factors. The analysis as enzymes is described in further detail. With the focus on the production of the biologically relevant guanine nucleotide binding protein complexed with GTP (G•GTP), we believe it is conceptually simpler to connect the kinetic properties to cellular effects. Further, the experiments are often more tractable than those used to analyze the equilibrium system and, therefore, more widely accessible to scientists interested in the function of exchange factors. PMID:25332840

  6. A Knock-in Mouse Model of Human PHD2 Gene-associated Erythrocytosis Establishes a Haploinsufficiency Mechanism*

    PubMed Central

    Arsenault, Patrick R.; Pei, Fei; Lee, Rebecca; Kerestes, Heddy; Percy, Melanie J.; Keith, Brian; Simon, M. Celeste; Lappin, Terence R. J.; Khurana, Tejvir S.; Lee, Frank S.

    2013-01-01

    The central pathway for controlling red cell mass is the PHD (prolyl hydroxylase domain protein):hypoxia-inducible factor (HIF) pathway. HIF, which is negatively regulated by PHD, activates numerous genes, including ones involved in erythropoiesis, such as the ERYTHROPOIETIN (EPO) gene. Recent studies have implicated PHD2 as the key PHD isoform regulating red cell mass. Studies of humans have identified erythrocytosis-associated, heterozygous point mutations in the PHD2 gene. A key question concerns the mechanism by which human mutations lead to phenotypes. In the present report, we generated and characterized a mouse line in which a P294R knock-in mutation has been introduced into the mouse Phd2 locus to model the first reported human PHD2 mutation (P317R). Phd2P294R/+ mice display a degree of erythrocytosis equivalent to that seen in Phd2+/− mice. The Phd2P294R/+-associated erythrocytosis is reversed in a Hif2a+/−, but not a Hif1a+/− background. Additional studies using various conditional knock-outs of Phd2 reveal that erythrocytosis can be induced by homozygous and heterozygous knock-out of Phd2 in renal cortical interstitial cells using a Pax3-Cre transgene or by homozygous knock-out of Phd2 in hematopoietic progenitors driven by a Vav1-Cre transgene. These studies formally prove that a missense mutation in PHD2 is the cause of the erythrocytosis, show that this occurs through haploinsufficiency, and point to multifactorial control of red cell mass by PHD2. PMID:24121508

  7. USSR Report, Chemistry

    DTIC Science & Technology

    1985-08-19

    No 2, Mar-Apr 85) 15 Factors Which Determine Activity of Catalysts of Various Chemical Types in Hydrogen Oxidation Reactions . Part 1: Oxidation ...Factors Which Determine Activity of Catalysts of Various Chemical Types in Hydrogen Oxidation Reactions . Part 2: Oxidation and Isotope Exchange of...FACTORS WHICH DETERMINE ACTIVITY OF CATALYSTS OF VARIOUS CHEMICAL TYPES IN HYDROGEN OXIDATION REACTIONS . PART 1: OXIDATION AND ISOTOPE EXCHANGE OF

  8. Enhancement of B-cell receptor signaling by a point mutation of adaptor protein 3BP2 identified in human inherited disease cherubism.

    PubMed

    Ogi, Kazuhiro; Nakashima, Kenji; Chihara, Kazuyasu; Takeuchi, Kenji; Horiguchi, Tomoko; Fujieda, Shigeharu; Sada, Kiyonao

    2011-09-01

    Tyrosine phosphorylation of adaptor protein c-Abl-Src homology 3 (SH3) domain-binding protein-2 (3BP2, also referred to SH3BP2) positively regulates the B-cell antigen receptor (BCR)-mediated signal transduction, leading to the activation of nuclear factor of activated T cells (NFAT). Here we showed the effect of the proline to arginine substitution of 3BP2 in which is the most common mutation in patients with cherubism (P418R) on B-cell receptor signaling. Comparing to the wild type, overexpression of the mutant form of 3BP2 (3BP2-P416R, corresponding to P418R in human protein) enhanced BCR-mediated activation of NFAT. 3BP2-P416R increased the signaling complex formation with Syk, phospholipase C-γ2 (PLC-γ2), and Vav1. In contrast, 3BP2-P416R could not change the association with the negative regulator 14-3-3. Loss of the association mutant that was incapable to associate with 14-3-3 could not mimic BCR-mediated NFAT activation in Syk-deficient cells. Moreover, BCR-mediated phosphorylation of extracellular signal regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) was not affected by P416R mutation. These results showed that P416R mutation of 3BP2 causes the gain of function in B cells by increasing the interaction with specific signaling molecules. © 2011 The Authors. Journal compilation © 2011 by the Molecular Biology Society of Japan/Blackwell Publishing Ltd.

  9. Users Guide to Direct Digital Control of Heating, Ventilating, and Air Conditioning Equipment,

    DTIC Science & Technology

    1985-01-01

    cycles, reset, load shedding, chiller optimization , VAV fan synchronization, and optimum start/stop. The prospective buyer of a DDC system should...in Fig- ure 4. Data on setpoints , reset schedules, and event timing, such as that presented in Figure 6, are often even more difficult to find. In con...control logic, setpoint and other data are readily available. Program logic, setpoint and schedule data, and other information stored in a DDC unit

  10. Direct Digital Control of HVAC (Heating, Ventilating, and Air Conditioning Equipment (User’s Guide)

    DTIC Science & Technology

    1985-01-01

    reset, load shedding, chiller optimization , VAV fan synchronization, and optimum start/stop. The prospective buyer of a DDC system should investigate...current and accurate drawings for a conventional, built-up control system such as that illustrated in Fig- ure 4. Data on setpoints , reset schedules, and...are always available in the form of the computer program code (Figure 7). In addition to the control logic, setpoint and other data are readily

  11. An NMR-based quenched hydrogen exchange investigation of model amyloid fibrils formed by cold shock protein A.

    PubMed

    Alexandrescu, A T

    2001-01-01

    Acid-denatured cold shock protein A (CspA) self-assembles into polymers with properties typical of amyloid fibrils. In the present work, a quenched hydrogen exchange experiment was used to probe the interactions of CspA fibrils with solvent. Exchange was initiated by incubating suspensions of fibrils in D2O, and quenched by flash freezing. Following lyophilization, exchange-quenched samples were dissolved in 90% DMSO/10% D2O, giving DMSO-denatured monomers. Intrinsic exchange rates for denatured CspA in 90% DMSO/10% D2O (pH* 4.5) were sufficiently slow (approximately 1 x 10(-3) min-1) to enable quantification of NMR signal intensity decays due to H/D exchange in the fibrils. Hydrogen exchange rate constants for CspA fibrils were found to vary less than 3-fold from a mean value of 5 x 10(-5) min-1. The uniformity of rate constants suggests that exchange is in the EX1 limit, and that the mechanism of exchange involves a cooperative dissociation of CspA monomers from fibrils, concomitant with unfolding. Previous studies indicated that the highest protection factors in native CspA are approximately 10(3), and that protection factors for the acid-denatured monomer precursors of CspA fibrils are close to unity. Because exchange in is in the EX1 regime, it is only possible to place a lower limit of at least 10(5) on protection factors in CspA fibrils. The observation that all amide protons are protected from exchange indicates that the entire CspA polypeptide chain is structured in the fibrils.

  12. Evaluation of Variable Refrigerant Flow Systems Performance on Oak Ridge National Laboratory s Flexible Research Platform: Part 1 Cooling Season Analysis

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

    Im, Piljae; Malhotra, Mini; Munk, Jeffrey D.

    This report provides second-year cooling season test results for the multi-year project titled “Evaluation of Variable Refrigeration Flow (VRF) System on Oak Ridge National Laboratory (ORNL)’s Flexible Research Platform (FRP).” The purpose of the second-year project was to (1) evaluate the full- and partload performance of VRF systems compared with an existing baseline heating, ventilation, and airconditioning (HVAC) system, which is a conventional rooftop unit (RTU) variable-air-volume (VAV) system with electric resistance heating and (2) use hourly building energy simulation to evaluate the energy savings potential of using VRF systems in major US cities. The second-year project performance period wasmore » from July 2015 through June 2016.« less

  13. Coupling fast fluid dynamics and multizone airflow models in Modelica Buildings library to simulate the dynamics of HVAC systems

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

    Tian, Wei; Sevilla, Thomas Alonso; Zuo, Wangda

    Historically, multizone models are widely used in building airflow and energy performance simulations due to their fast computing speed. However, multizone models assume that the air in a room is well mixed, consequently limiting their application. In specific rooms where this assumption fails, the use of computational fluid dynamics (CFD) models may be an alternative option. Previous research has mainly focused on coupling CFD models and multizone models to study airflow in large spaces. While significant, most of these analyses did not consider the coupled simulation of the building airflow with the building's Heating, Ventilation, and Air-Conditioning (HVAC) systems. Thismore » paper tries to fill the gap by integrating the models for HVAC systems with coupled multizone and CFD simulations for airflows, using the Modelica simul ation platform. To improve the computational efficiency, we incorporated a simplified CFD model named fast fluid dynamics (FFD). We first introduce the data synchronization strategy and implementation in Modelica. Then, we verify the implementation using two case studies involving an isothermal and a non-isothermal flow by comparing model simulations to experiment data. Afterward, we study another three cases that are deemed more realistic. This is done by attaching a variable air volume (VAV) terminal box and a VAV system to previous flows to assess the capability of the models in studying the dynamic control of HVAC systems. Finally, we discuss further research needs on the coupled simulation using the models.« less

  14. Bypass Mechanisms of the Androgen Receptor Pathway in Therapy-Resistant Prostate Cancer Cell Models

    PubMed Central

    Marques, Rute B.; Dits, Natasja F.; Erkens-Schulze, Sigrun; van Weerden, Wytske M.; Jenster, Guido

    2010-01-01

    Background Prostate cancer is initially dependent on androgens for survival and growth, making hormonal therapy the cornerstone treatment for late-stage tumors. However, despite initial remission, the cancer will inevitably recur. The present study was designed to investigate how androgen-dependent prostate cancer cells eventually survive and resume growth under androgen-deprived and antiandrogen supplemented conditions. As model system, we used the androgen-responsive PC346C cell line and its therapy-resistant sublines: PC346DCC, PC346Flu1 and PC346Flu2. Methodology/Principal Findings Microarray technology was used to analyze differences in gene expression between the androgen-responsive and therapy-resistant PC346 cell lines. Microarray analysis revealed 487 transcripts differentially-expressed between the androgen-responsive and the therapy-resistant cell lines. Most of these genes were common to all three therapy-resistant sublines and only a minority (∼5%) was androgen-regulated. Pathway analysis revealed enrichment in functions involving cellular movement, cell growth and cell death, as well as association with cancer and reproductive system disease. PC346DCC expressed residual levels of androgen receptor (AR) and showed significant down-regulation of androgen-regulated genes (p-value = 10−7). Up-regulation of VAV3 and TWIST1 oncogenes and repression of the DKK3 tumor-suppressor was observed in PC346DCC, suggesting a potential AR bypass mechanism. Subsequent validation of these three genes in patient samples confirmed that expression was deregulated during prostate cancer progression. Conclusions/Significance Therapy-resistant growth may result from adaptations in the AR pathway, but androgen-independence may also be achieved by alternative survival mechanisms. Here we identified TWIST1, VAV3 and DKK3 as potential players in the bypassing of the AR pathway, making them good candidates as biomarkers and novel therapeutical targets. PMID:20976069

  15. Design of exchange-correlation functionals through the correlation factor approach

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

    Pavlíková Přecechtělová, Jana, E-mail: j.precechtelova@gmail.com, E-mail: Matthias.Ernzerhof@UMontreal.ca; Institut für Chemie, Theoretische Chemie / Quantenchemie, Sekr. C7, Technische Universität Berlin, Straße des 17. Juni 135, 10623 Berlin; Bahmann, Hilke

    The correlation factor model is developed in which the spherically averaged exchange-correlation hole of Kohn-Sham theory is factorized into an exchange hole model and a correlation factor. The exchange hole model reproduces the exact exchange energy per particle. The correlation factor is constructed in such a manner that the exchange-correlation energy correctly reduces to exact exchange in the high density and rapidly varying limits. Four different correlation factor models are presented which satisfy varying sets of physical constraints. Three models are free from empirical adjustments to experimental data, while one correlation factor model draws on one empirical parameter. The correlationmore » factor models are derived in detail and the resulting exchange-correlation holes are analyzed. Furthermore, the exchange-correlation energies obtained from the correlation factor models are employed to calculate total energies, atomization energies, and barrier heights. It is shown that accurate, non-empirical functionals can be constructed building on exact exchange. Avenues for further improvements are outlined as well.« less

  16. Age-related guanine nucleotide exchange factor, mouse Zizimin2, induces filopodia in bone marrow-derived dendritic cells

    PubMed Central

    2012-01-01

    Background We recently isolated and identified Zizimin2 as a functional factor that is highly expressed in murine splenic germinal center B cells after immunization with T-cell-dependent antigen. Zizimin2 was revealed to be a new family member of Dock (dedicator of cytokinesis), Dock11, which is the guanine nucleotide exchange factor for Cdc42, a low-molecular-weight GTPase. However, the molecular function of Zizimin2 in acquired immunity has not been elucidated. Results In this study, we show that the protein expression of Zizimin2, which is also restricted to lymphoid tissues and lymphocytes, is reduced in aged mice. Over-expression of full-length Zizimin2 induced filopodial formation in 293T cells, whereas expression of CZH2 domain inhibited it. Stimulation of Fcγ receptor and Toll-like receptor 4 triggered Zizimin2 up-regulation and Cdc42 activation in bone marrow-derived dendritic cells. Conclusions These data suggest that Zizimin2 is an immune-related and age-regulated guanine nucleotide exchange factor, which facilitates filopodial formation through activation of Cdc42, which results in activation of cell migration. PMID:22494997

  17. Interactions between Kar2p and Its Nucleotide Exchange Factors Sil1p and Lhs1p Are Mechanistically Distinct*

    PubMed Central

    Hale, Sarah J.; Lovell, Simon C.; de Keyzer, Jeanine; Stirling, Colin J.

    2010-01-01

    Kar2p, an essential Hsp70 chaperone in the endoplasmic reticulum of Saccharomyces cerevisiae, facilitates the transport and folding of nascent polypeptides within the endoplasmic reticulum lumen. The chaperone activity of Kar2p is regulated by its intrinsic ATPase activity that can be stimulated by two different nucleotide exchange factors, namely Sil1p and Lhs1p. Here, we demonstrate that the binding requirements for Lhs1p are complex, requiring both the nucleotide binding domain plus the linker domain of Kar2p. In contrast, the IIB domain of Kar2p is sufficient for binding of Sil1p, and point mutations within IIB specifically blocked Sil1p-dependent activation while remaining competent for activation by Lhs1p. Taken together, these results demonstrate that the interactions between Kar2p and its two nucleotide exchange factors can be functionally resolved and are thus mechanistically distinct. PMID:20430899

  18. ψ (2 S ) versus J /ψ suppression in proton-nucleus collisions from factorization violating soft color exchanges

    NASA Astrophysics Data System (ADS)

    Ma, Yan-Qing; Venugopalan, Raju; Watanabe, Kazuhiro; Zhang, Hong-Fei

    2018-01-01

    We argue that the large suppression of the ψ (2 S ) inclusive cross section relative to the J /ψ inclusive cross section in proton-nucleus (p+A) collisions can be attributed to factorization breaking effects in the formation of quarkonium. These factorization breaking effects arise from soft color exchanges between charm-anticharm pairs undergoing hadronization and comoving partons that are long lived on time scales of quarkonium formation. We compute the short distance pair production of heavy quarks in the color glass condensate (CGC) effective field theory and employ an improved color evaporation model (ICEM) to describe their hadronization into quarkonium at large distances. The combined CGC+ICEM model provides a quantitative description of J /ψ and ψ (2 S ) data in proton-proton (p+p) collisions from both RHIC and the LHC. Factorization breaking effects in hadronization, due to additional parton comovers in the nucleus, are introduced heuristically by imposing a cutoff Λ , representing the average momentum kick from soft color exchanges, in the ICEM. Such soft exchanges have no perceptible effect on J /ψ suppression in p+A collisions. In contrast, the interplay of the physics of these soft exchanges at large distances, with the physics of semihard rescattering at short distances, causes a significant additional suppression of ψ (2 S ) yields relative to that of the J /ψ . A good fit of all RHIC and LHC J /ψ and ψ (2 S ) data, for transverse momenta P⊥≤5 GeV in p+p and p+A collisions, is obtained for Λ ˜10 MeV.

  19. Success of Two-Stage Reimplantation in Patients Requiring an Interim Spacer Exchange.

    PubMed

    George, Jaiben; Miller, Evan M; Curtis, Gannon L; Klika, Alison K; Barsoum, Wael K; Mont, Michael A; Higuera, Carlos A

    2018-03-23

    Some patients undergoing a 2-stage revision for a periprosthetic joint infection require a repeat spacer in the interim (removal of existing spacer with insertion of a new spacer or spacer exchange) due to persistent infection. The objectives of this study are to (1) determine the factors associated with patients who receive a repeat spacer and (2) compare the infection-free survival (overall and stratified by joint type) of reimplantation in patients who did or did not receive a repeat spacer. From 2001 to 2014, 347 hip or knee 2-stage revisions that finally underwent reimplantation and had a minimum 2-year follow-up were identified. An interim spacer exchange was performed in 59 (17%) patients (exchange cohort). Patient-related and organism-related factors were compared between the exchange and non-exchange cohorts. Kaplan-Meier survival curves were performed to assess the success (absence of signs of infection, reoperation for infection, periprosthetic joint infection-related mortality) of both cohorts. Patients in the exchange group had higher comorbidity score (P = .020), prolonged time to reimplantation (P < .001), and higher prevalence of resistant organisms, though not statistically significant (P = .091). The 5-year infection-free survival rates were 64% (knee 62%, hip 64%) in the exchange cohort, and 78% (knee 77%, hip 78%) in the non-exchange cohort (P = .020). Patients requiring an interim spacer exchange were found to have more comorbidities, prolonged treatment period, and were more likely to be infected with a resistant organism. About one-third of such patients became reinfected within 5 years compared to only one-fifth of the patients without an interim spacer exchange. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. A prognostic mutation panel for predicting cancer recurrence in stages II and III colorectal cancer.

    PubMed

    Sho, Shonan; Court, Colin M; Winograd, Paul; Russell, Marcia M; Tomlinson, James S

    2017-12-01

    Approximately 20-40% of stage II/III colorectal cancer (CRC) patients develop relapse. Clinicopathological factors alone are limited in detecting these patients, resulting in potential under/over-treatment. We sought to identify a prognostic tumor mutational profile that could predict CRC recurrence. Whole-exome sequencing data were obtained for 207 patients with stage II/III CRC from The Cancer Genome Atlas. Mutational landscape in relapse-free versus relapsed cohort was compared using Fisher's exact test, followed by multivariate Cox regression to identify genes associated with cancer recurrence. Bootstrap-validation was used to examine internal/external validity. We identified five prognostic genes (APAF1, DIAPH2, NTNG1, USP7, and VAV2), which were combined to form a prognostic mutation panel. Patients with ≥1 mutation(s) within this five-gene panel had worse prognosis (3-yr relapse-free survival [RFS]: 53.0%), compared to patients with no mutation (3-yr RFS: 84.3%). In multivariate analysis, the five-gene panel remained prognostic for cancer recurrence independent of stage and high-risk features (hazard ratio 3.63, 95%CI [1.93-6.83], P < 0.0001). Furthermore, its prognostic accuracy was superior to the American Joint Commission on Cancer classification (concordance-index: 0.70 vs 0.54). Our proposed mutation panel identifies CRC patients at high-risk for recurrence, which may help guide adjuvant therapy and post-operative surveillance protocols. © 2017 Wiley Periodicals, Inc.

  1. Low-temperature, non-stoichiometric oxygen isotope exchange coupled to Fe(II)-goethite interactions

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

    Frierdich, Andrew J.; Beard, Brian L.; Rosso, Kevin M.

    2015-07-01

    The oxygen isotope composition of natural iron oxide minerals has been widely used as a paleoclimate proxy. Interpretation of their stable isotope compositions, however, requires accurate knowledge of isotopic fractionation factors and an understanding of their isotopic exchange kinetics, the latter of which informs us how diagenetic processes may alter their isotopic compositions. Prior work has demonstrated that crystalline iron oxides do not significantly exchange oxygen isotopes with pure water at low temperature, which has restricted studies of isotopic fractionation factors to precipitation experiments or theoretical calculations. Using a double three-isotope method (¹⁸O-¹⁷O-¹⁶O and ⁵⁷Fe-⁵⁶Fe-⁵⁴Fe) we compare O and Femore » isotope exchange kinetics, and demonstrate, for the first time, that O isotope exchange between structural O in crystalline goethite and water occurs in the presence of aqueous Fe(II) (Fe(II) aq) at ambient temperature (i.e., 22–50 °C). The three-isotope method was used to extrapolate partial exchange results to infer the equilibrium, mass-dependent isotope fractionations between goethite and water. In addition, this was combined with a reversal approach to equilibrium by reacting goethite in two unique waters that vary in composition by about 16‰ in ¹⁸O/¹⁶O ratios. Our results show that interactions between Fe(II) aq and goethite catalyzes O isotope exchange between the mineral and bulk fluid; no exchange (within error) is observed when goethite is suspended in ¹⁷O-enriched water in the absence of Fe(II) aq. In contrast, Fe(II)-catalyzed O isotope exchange is accompanied by significant changes in ¹⁸O/¹⁶O ratios. Despite significant O exchange, however, we observed disproportionate amounts of Fe versus O exchange, where Fe isotope exchange in goethite was roughly three times that of O. This disparity provides novel insight into the reactivity of oxide minerals in aqueous solutions, but presents a challenge for utilizing such an approach to determine equilibrium isotope fractionation factors. Despite the uncertainty from extrapolation, there is consistency in goethite-water fractionation factors for our reversal approach to equilibrium, with final weighted average fractionation factor values of Δ¹⁸O Gth-wate r = 0.2 (±0.9‰) and 3.0 (±2.5‰) at 22 °C and -1.6 (±0.8‰) and 1.9 (±1.5‰) at 50 °C for micron-sized and nano-particulate goethite, respectively (errors at 2σ level). Reaction of ferrihydrite with Fe(II) aq in two distinct waters resulted in a quantitative conversion to goethite and complete O isotope exchange in each case, and similar fractionation factors were observed for experiments using the two waters. Comparison of our results with previous studies of O isotope fractionation between goethite and water suggests that particle size may be a contributing factor to the disparity among experimental studies.« less

  2. Pressure-assisted cold denaturation of hen egg white lysozyme: the influence of co-solvents probed by hydrogen exchange nuclear magnetic resonance.

    PubMed

    Vogtt, K; Winter, R

    2005-08-01

    COSY proton nuclear magnetic resonance was used to measure the exchange rates of amide protons of hen egg white lysozyme (HEWL) in the pressure-assisted cold-denatured state and in the heat-denatured state. After dissolving lysozyme in deuterium oxide buffer, labile protons exchange for deuterons in such a way that exposed protons are substituted rapidly, whereas "protected" protons within structured parts of the protein are substituted slowly. The exchange rates k obs were determined for HEWL under heat treatment (80 degrees C) and under high pressure conditions at low temperature (3.75 kbar, -13 degrees C). Moreover, the influence of co-solvents (sorbitol, urea) on the exchange rate was examined under pressure-assisted cold denaturation conditions, and the corresponding protection factors, P, were determined. The exchange kinetics upon heat treatment was found to be a two-step process with initial slow exchange followed by a fast one, showing residual protection in the slow-exchange state and P-factors in the random-coil-like range for the final temperature-denatured state. Addition of sorbitol (500 mM) led to an increase of P-factors for the pressure-assisted cold denatured state, but not for the heat-denatured state. The presence of 2 M urea resulted in a drastic decrease of the P-factors of the pressure-assisted cold denatured state. For both types of co-solvents, the effect they exert appears to be cooperative, i.e., no particular regions within the protein can be identified with significantly diverse changes of P-factors.

  3. Kinetics of Interaction between ADP-ribosylation Factor-1 (Arf1) and the Sec7 Domain of Arno Guanine Nucleotide Exchange Factor, Modulation by Allosteric Factors, and the Uncompetitive Inhibitor Brefeldin A

    PubMed Central

    Rouhana, Jad; Padilla, André; Estaran, Sébastien; Bakari, Sana; Delbecq, Stephan; Boublik, Yvan; Chopineau, Joel; Pugnière, Martine; Chavanieu, Alain

    2013-01-01

    The GDP/GTP nucleotide exchange of Arf1 is catalyzed by nucleotide exchange factors (GEF), such as Arno, which act through their catalytic Sec7 domain. This exchange is a complex mechanism that undergoes conformational changes and intermediate complex species involving several allosteric partners such as nucleotides, Mg2+, and Sec7 domains. Using a surface plasmon resonance approach, we characterized the kinetic binding parameters for various intermediate complexes. We first confirmed that both GDP and GTP counteract equivalently to the free-nucleotide binary Arf1-Arno complex stability and revealed that Mg2+ potentiates by a factor of 2 the allosteric effect of GDP. Then we explored the uncompetitive inhibitory mechanism of brefeldin A (BFA) that conducts to an abortive pentameric Arf1-Mg2+-GDP-BFA-Sec7 complex. With BFA, the association rate of the abortive complex is drastically reduced by a factor of 42, and by contrast, the 15-fold decrease of the dissociation rate concurs to stabilize the pentameric complex. These specific kinetic signatures have allowed distinguishing the level and nature as well as the fate in real time of formed complexes according to experimental conditions. Thus, we showed that in the presence of GDP, the BFA-resistant Sec7 domain of Arno can also associate to form a pentameric complex, which suggests that the uncompetitive inhibition by BFA and the nucleotide allosteric effect combine to stabilize such abortive complex. PMID:23255605

  4. ψ ( 2 S ) versus J / ψ suppression in proton-nucleus collisions from factorization violating soft color exchanges

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

    Ma, Yan -Qing; Venugopalan, Raju; Watanabe, Kazuhiro

    Here, we argue that the large suppression of themore » $$\\psi(2S)$$ inclusive cross-section relative to the $$J/\\psi$$ inclusive cross-section in proton-nucleus (p+A) collisions can be attributed to factorization breaking effects in the formation of quarkonium. These factorization breaking effects arise from soft color exchanges between charm-anticharm pairs undergoing hadronization and comoving partons that are long-lived on time scales of quarkonium formation. We compute the short distance pair production of heavy quarks in the Color Glass Condensate (CGC) effective field theory and employ an improved Color Evaporation model (ICEM) to describe their hadronization into quarkonium at large distances. The combined CGC+ICEM model provides a quantitative description of $$J/\\psi$$ and $$\\psi(2S)$$ data in proton-proton (p+p) collisions from both RHIC and the LHC. Factorization breaking effects in hadronization, due to additional parton comovers in the nucleus, are introduced heuristically by imposing a cutoff $$\\Lambda$$, representing the momentum kick from soft color exchanges, in the ICEM model. Such soft exchanges have no perceptible effect on $$J/\\psi$$ suppression in p+A collisions. In contrast, the interplay of the physics of these soft exchanges at large distances, with the physics of semi-hard rescattering at short distances, causes a significant additional suppression of $$\\psi(2S)$$ yields relative to that of the $$J/\\psi$$. A good fit of all RHIC and LHC $$J/\\psi$$ and $$\\psi(2S)$$ data, for transverse momenta $$P_\\perp\\leq 5$$ GeV in p+p and p+A collisions, is obtained for $$\\Lambda\\sim 10$$ MeV.« less

  5. ψ ( 2 S ) versus J / ψ suppression in proton-nucleus collisions from factorization violating soft color exchanges

    DOE PAGES

    Ma, Yan -Qing; Venugopalan, Raju; Watanabe, Kazuhiro; ...

    2018-01-31

    Here, we argue that the large suppression of themore » $$\\psi(2S)$$ inclusive cross-section relative to the $$J/\\psi$$ inclusive cross-section in proton-nucleus (p+A) collisions can be attributed to factorization breaking effects in the formation of quarkonium. These factorization breaking effects arise from soft color exchanges between charm-anticharm pairs undergoing hadronization and comoving partons that are long-lived on time scales of quarkonium formation. We compute the short distance pair production of heavy quarks in the Color Glass Condensate (CGC) effective field theory and employ an improved Color Evaporation model (ICEM) to describe their hadronization into quarkonium at large distances. The combined CGC+ICEM model provides a quantitative description of $$J/\\psi$$ and $$\\psi(2S)$$ data in proton-proton (p+p) collisions from both RHIC and the LHC. Factorization breaking effects in hadronization, due to additional parton comovers in the nucleus, are introduced heuristically by imposing a cutoff $$\\Lambda$$, representing the momentum kick from soft color exchanges, in the ICEM model. Such soft exchanges have no perceptible effect on $$J/\\psi$$ suppression in p+A collisions. In contrast, the interplay of the physics of these soft exchanges at large distances, with the physics of semi-hard rescattering at short distances, causes a significant additional suppression of $$\\psi(2S)$$ yields relative to that of the $$J/\\psi$$. A good fit of all RHIC and LHC $$J/\\psi$$ and $$\\psi(2S)$$ data, for transverse momenta $$P_\\perp\\leq 5$$ GeV in p+p and p+A collisions, is obtained for $$\\Lambda\\sim 10$$ MeV.« less

  6. The role of meson exchanges in light-by-light scattering

    NASA Astrophysics Data System (ADS)

    Lebiedowicz, Piotr; Szczurek, Antoni

    2017-09-01

    We discuss the role of meson exchange mechanisms in γγ → γγ scattering. Several pseudoscalar (π0, η, η‧ (958), ηc (1 S), ηc (2 S)), scalar (f0 (500), f0 (980), a0 (980), f0 (1370), χc0 (1 P)) and tensor (f2 (1270), a2 (1320), f2‧ (1525), f2 (1565), a2 (1700)) mesons are taken into account. We consider not only s-channel but also for the first time t- and u-channel meson exchange amplitudes corrected for off-shell effects including vertex form factors. We find that, depending on not well known vertex form factors, the meson exchange amplitudes interfere among themselves and could interfere with fermion-box amplitudes and modify the resulting cross sections. The meson contributions are shown as a function of collision energy as well as angular distributions are presented. Interesting interference effects separately for light pseudoscalar, scalar and tensor meson groups are discussed. The meson exchange contributions may be potentially important in the context of a measurement performed recently in ultraperipheral collisions of heavy ions by the ATLAS collaboration. The light-by-light interactions could be studied in future in electron-positron collisions by the Belle II at SuperKEKB accelerator.

  7. Revision of Fontes & Garnier's model for the initial 14C content of dissolved inorganic carbon used in groundwater dating

    USGS Publications Warehouse

    Han, Liang-Feng; Plummer, Niel

    2013-01-01

    The widely applied model for groundwater dating using 14C proposed by Fontes and Garnier (F&G) (Fontes and Garnier, 1979) estimates the initial 14C content in waters from carbonate-rock aquifers affected by isotopic exchange. Usually, the model of F&G is applied in one of two ways: (1) using a single 13C fractionation factor of gaseous CO2 with respect to a solid carbonate mineral, εg/s, regardless of whether the carbon isotopic exchange is controlled by soil CO2 in the unsaturated zone, or by solid carbonate mineral in the saturated zone; or (2) using different fractionation factors if the exchange process is dominated by soil CO2 gas as opposed to solid carbonate mineral (typically calcite). An analysis of the F&G model shows an inadequate conceptualization, resulting in underestimation of the initial 14C values (14C0) for groundwater systems that have undergone isotopic exchange. The degree to which the 14C0 is underestimated increases with the extent of isotopic exchange. Examples show that in extreme cases, the error in calculated adjusted initial 14C values can be more than 20% modern carbon (pmc). A model is derived that revises the mass balance method of F&G by using a modified model conceptualization. The derivation yields a “global” model both for carbon isotopic exchange dominated by gaseous CO2 in the unsaturated zone, and for carbon isotopic exchange dominated by solid carbonate mineral in the saturated zone. However, the revised model requires different parameters for exchange dominated by gaseous CO2 as opposed to exchange dominated by solid carbonate minerals. The revised model for exchange dominated by gaseous CO2 is shown to be identical to the model of Mook (Mook, 1976). For groundwater systems where exchange occurs both in the unsaturated zone and saturated zone, the revised model can still be used; however, 14C0 will be slightly underestimated. Finally, in carbonate systems undergoing complex geochemical reactions, such as oxidation of organic carbon, radiocarbon ages are best estimated by inverse geochemical modeling techniques.

  8. Carbon dioxide exchange between an undisturbed old-growth temperate forest and the atmosphere

    Treesearch

    D.Y. Hollinger; F.M. Kelliher; J.N. Byers; J.E. Hunt; T.M. McSeveny; P.L. Weir

    1994-01-01

    We used the eddy-correlation technique to investigate the exchange of C02 between an undisturbed old-growth forest and the atmosphere at a remote Southern Hemisphere site on 15 d between 1989 and 1990. Our goal was to determine how environmental factors regulate ecosystem CO2 exchange, and to test whether present knowledge...

  9. Heat and fluid flow characteristics of an oval fin-and-tube heat exchanger with large diameters for textile machine dryer

    NASA Astrophysics Data System (ADS)

    Bae, Kyung Jin; Cha, Dong An; Kwon, Oh Kyung

    2016-11-01

    The objectives of this paper are to develop correlations between heat transfer and pressure drop for oval finned-tube heat exchanger with large diameters (larger than 20 mm) used in a textile machine dryer. Numerical tests using ANSYS CFX are performed for four different parameters; tube size, fin pitch, transverse tube pitch and longitudinal tube pitch. The numerical results showed that the Nusselt number and the friction factor are in a range of -16.2 ~ +3.1 to -7.7 ~ +3.9 %, respectively, compared with experimental results. It was found that the Nusselt number linearly increased with increasing Reynolds number, but the friction factor slightly decreased with increasing Reynolds number. It was also found that the variation of longitudinal tube pitch has little effect on the Nusselt number and friction factor than other parameters (below 2.0 and 2.5 %, respectively). This study proposed a new Nusselt number and friction factor correlation of the oval finned-tube heat exchanger with large diameters for textile machine dryer.

  10. Theory of g-factor enhancement in narrow-gap quantum well heterostructures.

    PubMed

    Krishtopenko, S S; Gavrilenko, V I; Goiran, M

    2011-09-28

    We report on the study of the exchange enhancement of the g-factor in the two-dimensional (2D) electron gas in n-type narrow-gap semiconductor heterostructures. Our approach is based on the eight-band k⋅p Hamiltonian and takes into account the band nonparabolicity, the lattice deformation, the spin-orbit coupling and the Landau level broadening in the δ-correlated random potential model. Using the 'screened' Hartree-Fock approximation we demonstrate that the exchange g-factor enhancement not only shows maxima at odd values of Landau level filling factors but, due to the conduction band nonparabolicity, persists at even filling factor values as well. The magnitude of the exchange enhancement, the amplitude and the shape of the g-factor oscillations are determined by both the screening of the electron-electron interaction and the Landau level width. The 'enhanced' g-factor values calculated for the 2D electron gas in InAs/AlSb quantum well heterostructures are compared with our earlier experimental data and with those obtained by Mendez et al (1993 Phys. Rev. B 47 13937) in magnetic fields up to 30 T.

  11. PH motifs in PAR1&2 endow breast cancer growth.

    PubMed

    Kancharla, A; Maoz, M; Jaber, M; Agranovich, D; Peretz, T; Grisaru-Granovsky, S; Uziely, B; Bar-Shavit, R

    2015-11-24

    Although emerging roles of protease-activated receptor1&2 (PAR1&2) in cancer are recognized, their underlying signalling events are poorly understood. Here we show signal-binding motifs in PAR1&2 that are critical for breast cancer growth. This occurs via the association of the pleckstrin homology (PH) domain with Akt/PKB as a key signalling event of PARs. Other PH-domain signal-proteins such as Etk/Bmx and Vav3 also associate with PAR1 and PAR2 through their PH domains. PAR1 and PAR2 bind with priority to Etk/Bmx. A point mutation in PAR2, H349A, but not in R352A, abrogates PH-protein association and is sufficient to markedly reduce PAR2-instigated breast tumour growth in vivo and placental extravillous trophoblast (EVT) invasion in vitro. Similarly, the PAR1 mutant hPar1-7A, which is unable to bind the PH domain, reduces mammary tumours and EVT invasion, endowing these motifs with physiological significance and underscoring the importance of these previously unknown PAR1 and PAR2 PH-domain-binding motifs in both pathological and physiological invasion processes.

  12. Spontaneous nucleotide exchange in low molecular weight GTPases by fluorescently labeled γ-phosphate-linked GTP analogs

    PubMed Central

    Korlach, Jonas; Baird, Daniel W.; Heikal, Ahmed A.; Gee, Kyle R.; Hoffman, Gregory R.; Webb, Watt W.

    2004-01-01

    Regulated guanosine nucleotide exchange and hydrolysis constitute the fundamental activities of low molecular weight GTPases. We show that three guanosine 5′-triphosphate analogs with BODIPY fluorophores coupled via the gamma phosphate bind to the GTPases Cdc42, Rac1, RhoA, and Ras and displace guanosine 5′-diphosphate with high intrinsic exchange rates in the presence of Mg2+ ions, thereby acting as synthetic, low molecular weight guanine nucleotide exchange factors. The accompanying large fluorescence enhancements (as high as 12-fold), caused by a reduction in guanine quenching of the environmentally sensitive BODIPY dye fluorescence on protein binding, allow for real-time monitoring of this spontaneous nucleotide exchange in the visible spectrum with high signal-to-noise ratios. Binding affinities increased with longer aliphatic linkers connecting the nucleotide and BODIPY fluorophore and were in the 10–100 nM range. Steady-state and time-resolved fluorescence spectroscopy showed an inverse relationship between linker length and fluorescence enhancement factors and differences in protein-bound fluorophore mobilities, providing optimization criteria for future applications of such compounds as efficient elicitors and reporters of nucleotide exchange. EDTA markedly enhanced nucleotide exchange, enabling rapid loading of GTPases with these probes. Differences in active site geometries, in the absence of Mg2+, caused qualitatively different reporting of the bound state by the different analogs. The BODIPY analogs also prevented the interaction of Cdc42 with p21 activated kinase. Together, these results validate the use of these analogs as valuable tools for studying GTPase functions and for developing potent synthetic nucleotide exchange factors for this important class of signaling molecules. PMID:14973186

  13. Seasonal and Inter-Annual Variations in Carbon Dioxide Exchange over an Alpine Grassland in the Eastern Qinghai-Tibetan Plateau.

    PubMed

    Shang, Lunyu; Zhang, Yu; Lyu, Shihua; Wang, Shaoying

    2016-01-01

    This work analyzed carbon dioxide exchange and its controlling factors over an alpine grassland on the eastern Qinghai-Tibetan Plateau. The main results show that air temperature and photosynthetically active radiation are two dominant factors controlling daily gross primary production. Soil temperature and soil water content are the main factors controlling ecosystem respiration. Canopy photosynthetic activity is also responsible for the variation of daily ecosystem respiration other than environmental factors. No clear correlation between net ecosystem exchange and environmental factors was observed at daily scale. Temperature sensitive coefficient was observed to increase with larger soil water content. High values of temperature sensitive coefficient occurred during the periods when soil water content was high and grass was active. Annual integrated net ecosystem exchange, gross primary production and ecosystem respiration were -191, 1145 and 954 g C m-2 for 2010, and -250, 975 and 725 g C m-2 for 2011, respectively. Thus, this alpine grassland was a moderate carbon sink in both of the two years. Compared to alpine grasslands on the Qinghai-Tibetan Plateau, this alpine grassland demonstrated a much greater potential for carbon sequestration than others. Annual precipitation is a dominant factor controlling the variation of annual net ecosystem exchange over this grassland. The difference in gross primary production between the two years was not caused by the variation in annual precipitation. Instead, air temperature and the length of growing season had an important impact on annual gross primary production. Variation of annual ecosystem respiration was closely related to annual gross primary production and soil water content during the growing season.

  14. Seasonal and Inter-Annual Variations in Carbon Dioxide Exchange over an Alpine Grassland in the Eastern Qinghai-Tibetan Plateau

    PubMed Central

    Shang, Lunyu; Zhang, Yu; Lyu, Shihua; Wang, Shaoying

    2016-01-01

    This work analyzed carbon dioxide exchange and its controlling factors over an alpine grassland on the eastern Qinghai-Tibetan Plateau. The main results show that air temperature and photosynthetically active radiation are two dominant factors controlling daily gross primary production. Soil temperature and soil water content are the main factors controlling ecosystem respiration. Canopy photosynthetic activity is also responsible for the variation of daily ecosystem respiration other than environmental factors. No clear correlation between net ecosystem exchange and environmental factors was observed at daily scale. Temperature sensitive coefficient was observed to increase with larger soil water content. High values of temperature sensitive coefficient occurred during the periods when soil water content was high and grass was active. Annual integrated net ecosystem exchange, gross primary production and ecosystem respiration were -191, 1145 and 954 g C m-2 for 2010, and -250, 975 and 725 g C m-2 for 2011, respectively. Thus, this alpine grassland was a moderate carbon sink in both of the two years. Compared to alpine grasslands on the Qinghai-Tibetan Plateau, this alpine grassland demonstrated a much greater potential for carbon sequestration than others. Annual precipitation is a dominant factor controlling the variation of annual net ecosystem exchange over this grassland. The difference in gross primary production between the two years was not caused by the variation in annual precipitation. Instead, air temperature and the length of growing season had an important impact on annual gross primary production. Variation of annual ecosystem respiration was closely related to annual gross primary production and soil water content during the growing season. PMID:27861616

  15. 75 FR 45584 - Planning and Establishment of State-Level Exchanges; Request for Comments Regarding Exchange...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-03

    ... Act): (1) Facilitate the purchase of qualified health plans (QHPs); (2) provide for the establishment... Federal government for their State? When will this decision be made? Can planning grants assist in identifying and assessing relevant factors and making this decision? 2. To what extent have States already...

  16. The effect of Sinabung volcanic ash and rock phosphate nanoparticle on CEC (cation exchange capacity) base saturation exchange (K, Na, Ca, Mg) and base saturation at Andisol soils Ciater, West Java

    NASA Astrophysics Data System (ADS)

    Yuniarti, Anni; Arifin, Mahfud; Sofyan, Emma Trinurasi; Natalie, Betty; Sudirja, Rija; Dahliani, Dewi

    2018-02-01

    Andisol, soil orders which covers an upland area dominantly. The aim of this research is to know the effect between the ameliorant of Sinabung volcanic ashes with the ameliorant of rock phosphatenanoparticle towards CEC and base saturation exchange (K, Na, Ca, Mg) and the base saturation on Ciater's Andisols, West Java. A randomized complete block design (RCBD) factorial with two factors was used in this research. The first factor is the volcanic ash and the second factor is rock phosphate which consists of four levels each amount of 0%, 2.5%, 5%, 7.5% with three replications. The result showed that there was no interaction between volcanic ash and rock phosphate nanoparticle formed in first month and fourth month towards the improvement of CEC and saturation base exchange rate unless magnesium cation exchange increased in fourth month. There was independent effect of volcanic ash formed nanoparticles towards base saturation exchange increased for 5% dose. There was independent effect of rock phosphate formed nanoparticles towards base saturation exchange and increased for 5% dose. The dose combination of volcanic ashes 7.5% with phosphate rock, 5% increased the base saturation in the first month incubation.

  17. On factors influencing air-water gas exchange in emergent wetlands

    USGS Publications Warehouse

    Ho, David T.; Engel, Victor C.; Ferron, Sara; Hickman, Benjamin; Choi, Jay; Harvey, Judson W.

    2018-01-01

    Knowledge of gas exchange in wetlands is important in order to determine fluxes of climatically and biogeochemically important trace gases and to conduct mass balances for metabolism studies. Very few studies have been conducted to quantify gas transfer velocities in wetlands, and many wind speed/gas exchange parameterizations used in oceanographic or limnological settings are inappropriate under conditions found in wetlands. Here six measurements of gas transfer velocities are made with SF6 tracer release experiments in three different years in the Everglades, a subtropical peatland with surface water flowing through emergent vegetation. The experiments were conducted under different flow conditions and with different amounts of emergent vegetation to determine the influence of wind, rain, water flow, waterside thermal convection, and vegetation on air-water gas exchange in wetlands. Measured gas transfer velocities under the different conditions ranged from 1.1 cm h−1 during baseline conditions to 3.2 cm h−1 when rain and water flow rates were high. Commonly used wind speed/gas exchange relationships would overestimate the gas transfer velocity by a factor of 1.2 to 6.8. Gas exchange due to thermal convection was relatively constant and accounted for 14 to 51% of the total measured gas exchange. Differences in rain and water flow among the different years were responsible for the variability in gas exchange, with flow accounting for 37 to 77% of the gas exchange, and rain responsible for up to 40%.

  18. 26 CFR 1.1031-0 - Table of contents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...(b)-1 Receipt of other property or money in tax-free exchange. § 1.1031(b)-2 Safe harbor for...-free exchange. § 1.1031(d)-1T Coordination of section 1060 with section 1031 (temporary). § 1.1031(d)-2...) Receipt of money or other property. (g) Safe harbors. (h) Interest and growth factors. (i) [Reserved] (j...

  19. Substrate water exchange in photosystem II depends on the peripheral proteins.

    PubMed

    Hillier, W; Hendry, G; Burnap, R L; Wydrzynski, T

    2001-12-14

    The (18)O exchange rates for the substrate water bound in the S(3) state were determined in different photosystem II sample types using time-resolved mass spectrometry. The samples included thylakoid membranes, salt-washed Triton X-100-prepared membrane fragments, and purified core complexes from spinach and cyanobacteria. For each sample type, two kinetically distinct isotopic exchange rates could be resolved, indicating that the biphasic exchange behavior for the substrate water is inherent to the O(2)-evolving catalytic site in the S(3) state. However, the fast phase of exchange became somewhat slower (by a factor of approximately 2) in NaCl-washed membrane fragments and core complexes from spinach in which the 16- and 23-kDa extrinsic proteins have been removed, compared with the corresponding rate for the intact samples. For CaCl(2)-washed membrane fragments in which the 33-kDa manganese stabilizing protein (MSP) has also been removed, the fast phase of exchange slowed down even further (by a factor of approximately 3). Interestingly, the slow phase of exchange was little affected in the samples from spinach. For core complexes prepared from Synechocystis PCC 6803 and Synechococcus elongatus, the fast and slow exchange rates were variously affected. Nevertheless, within the experimental error, nearly the same exchange rates were measured for thylakoid samples made from wild type and an MSP-lacking mutant of Synechocystis PCC 6803. This result could indicate that the MSP has a slightly different function in eukaryotic organisms compared with prokaryotic organisms. In all samples, however, the differences in the exchange rates are relatively small. Such small differences are unlikely to arise from major changes in the metal-ligand structure at the catalytic site. Rather, the observed differences may reflect subtle long range effects in which the exchange reaction coordinates become slightly altered. We discuss the results in terms of solvent penetration into photosystem II and the regional dielectric around the catalytic site.

  20. A multiple chamber, semicontinuous, crop carbon dioxide exchange system: design, calibration, and data interpretation

    NASA Technical Reports Server (NTRS)

    van Iersel, M. W.; Bugbee, B.

    2000-01-01

    Long-term, whole crop CO2 exchange measurements can be used to study factors affecting crop growth. These factors include daily carbon gain, cumulative carbon gain, and carbon use efficiency, which cannot be determined from short-term measurements. We describe a system that measures semicontinuously crop CO2 exchange in 10 chambers over a period of weeks or months. Exchange of CO2 in every chamber can be measured at 5 min intervals. The system was designed to be placed inside a growth chamber, with additional environmental control provided by the individual gas exchange chambers. The system was calibrated by generating CO2 from NaHCO3 inside the chambers, which indicated that accuracy of the measurements was good (102% and 98% recovery for two separate photosynthesis systems). Since the systems measure net photosynthesis (P-net, positive) and dark respiration(R-dark, negative), the data can be used to estimate gross photosynthesis, daily carbon gain, cumulative carbon gain, and carbon use efficiency. Continuous whole-crop measurements are a valuable tool that complements leaf photosynthesis measurements. Multiple chambers allow for replication and comparison among several environmental or cultural treatments that may affect crop growth. Example data from a 2 week study with petunia (Petunia x hybrida Hort. Vilm.-Andr.) are presented to illustrate some of the capabilities of this system.

  1. Physiological Srsf2 P95H expression causes impaired hematopoietic stem cell functions and aberrant RNA splicing in mice.

    PubMed

    Kon, Ayana; Yamazaki, Satoshi; Nannya, Yasuhito; Kataoka, Keisuke; Ota, Yasunori; Nakagawa, Masahiro Marshall; Yoshida, Kenichi; Shiozawa, Yusuke; Morita, Maiko; Yoshizato, Tetsuichi; Sanada, Masashi; Nakayama, Manabu; Koseki, Haruhiko; Nakauchi, Hiromitsu; Ogawa, Seishi

    2018-02-08

    Splicing factor mutations are characteristic of myelodysplastic syndromes (MDS) and related myeloid neoplasms and implicated in their pathogenesis, but their roles in the development of MDS have not been fully elucidated. In the present study, we investigated the consequence of mutant Srsf2 expression using newly generated Vav1-Cre -mediated conditional knockin mice. Mice carrying a heterozygous Srsf2 P95H mutation showed significantly reduced numbers of hematopoietic stem and progenitor cells (HSPCs) and differentiation defects both in the steady-state condition and transplantation settings. Srsf2 -mutated hematopoietic stem cells (HSCs) showed impaired long-term reconstitution compared with control mice in competitive repopulation assays. Although the Srsf2 mutant mice did not develop MDS under the steady-state condition, when their stem cells were transplanted into lethally irradiated mice, the recipients developed anemia, leukopenia, and erythroid dysplasia, which suggests the role of replicative stress in the development of an MDS-like phenotype in Srsf2 -mutated mice. RNA sequencing of the Srsf2 -mutated HSPCs revealed a number of abnormal splicing events and differentially expressed genes, including several potential targets implicated in the pathogenesis of hematopoietic malignancies, such as Csf3r , Fyn , Gnas , Nsd1 , Hnrnpa2b1 , and Trp53bp1 Among the mutant Srsf2 -associated splicing events, most commonly observed were the enhanced inclusion and/or exclusion of cassette exons, which were caused by the altered consensus motifs for the recognition of exonic splicing enhancers. Our findings suggest that the mutant Srsf2 leads to a compromised HSC function by causing abnormal RNA splicing and expression, contributing to the deregulated hematopoiesis that recapitulates the MDS phenotypes, possibly as a result of additional genetic and/or environmental insults. © 2018 by The American Society of Hematology.

  2. Design of distributed JT (Joule-Thomson) effect heat exchanger for superfluid 2 K cooling device

    NASA Astrophysics Data System (ADS)

    Jeong, S.; Park, C.; Kim, K.

    2018-03-01

    Superfluid at 2 K or below is readily obtained from liquid helium at 4.2 K by reducing its vapour pressure. For better cooling performance, however, the cold energy of vaporized helium at 2 K chamber can be effectively utilized in a recuperator which is specially designed in this paper for accomplishing so-called the distributed Joule-Thomson (JT) expansion effect. This paper describes the design methodology of distributed JT effect heat exchanger for 2 K JT cooling device. The newly developed heat exchanger allows continuous significant pressure drop at high-pressure part of the recuperative heat exchanger by using a capillary tube. Being different from conventional recuperative heat exchangers, the efficient JT effect HX must consider the pressure drop effect as well as the heat transfer characteristic. The heat exchanger for the distributed JT effect actively utilizes continuous pressure loss at the hot stream of the heat exchanger by using an OD of 0.64 mm and an ID of 0.4 mm capillary tube. The analysis is performed by dividing the heat exchanger into the multiple sub-units of the heat exchange part and JT valve. For more accurate estimation of the pressure drop of spirally wound capillary tube, preliminary experiments are carried out to investigate the friction factor at high Reynolds number. By using the developed pressure drop correlation and the heat transfer correlation, the specification of the heat exchanger with distributed JT effect for 2 K JT refrigerator is determined.

  3. The Adenylate Cyclase Toxins of Bacillus anthracis and Bordetella pertussis Promote Th2 Cell Development by Shaping T Cell Antigen Receptor Signaling

    PubMed Central

    Rossi Paccani, Silvia; Benagiano, Marisa; Capitani, Nagaja; Zornetta, Irene; Ladant, Daniel; Montecucco, Cesare; D'Elios, Mario M.; Baldari, Cosima T.

    2009-01-01

    The adjuvanticity of bacterial adenylate cyclase toxins has been ascribed to their capacity, largely mediated by cAMP, to modulate APC activation, resulting in the expression of Th2–driving cytokines. On the other hand, cAMP has been demonstrated to induce a Th2 bias when present during T cell priming, suggesting that bacterial cAMP elevating toxins may directly affect the Th1/Th2 balance. Here we have investigated the effects on human CD4+ T cell differentiation of two adenylate cyclase toxins, Bacillus anthracis edema toxin (ET) and Bordetella pertussis CyaA, which differ in structure, mode of cell entry, and subcellular localization. We show that low concentrations of ET and CyaA, but not of their genetically detoxified adenylate cyclase defective counterparts, potently promote Th2 cell differentiation by inducing expression of the master Th2 transcription factors, c-maf and GATA-3. We also present evidence that the Th2–polarizing concentrations of ET and CyaA selectively inhibit TCR–dependent activation of Akt1, which is required for Th1 cell differentiation, while enhancing the activation of two TCR–signaling mediators, Vav1 and p38, implicated in Th2 cell differentiation. This is at variance from the immunosuppressive toxin concentrations, which interfere with the earliest step in TCR signaling, activation of the tyrosine kinase Lck, resulting in impaired CD3ζ phosphorylation and inhibition of TCR coupling to ZAP-70 and Erk activation. These results demonstrate that, notwithstanding their differences in their intracellular localization, which result in focalized cAMP production, both toxins directly affect the Th1/Th2 balance by interfering with the same steps in TCR signaling, and suggest that their adjuvanticity is likely to result from their combined effects on APC and CD4+ T cells. Furthermore, our results strongly support the key role of cAMP in the adjuvanticity of these toxins. PMID:19266022

  4. Towards an Optimal Gradient-dependent Energy Functional of the PZ-SIC Form

    DOE PAGES

    Jónsson, Elvar Örn; Lehtola, Susi; Jónsson, Hannes

    2015-06-01

    Results of Perdew–Zunger self-interaction corrected (PZ-SIC) density functional theory calculations of the atomization energy of 35 molecules are compared to those of high-level quantum chemistry calculations. While the PBE functional, which is commonly used in calculations of condensed matter, is known to predict on average too high atomization energy (overbinding of the molecules), the application of PZ-SIC gives a large overcorrection and leads to significant underestimation of the atomization energy. The exchange enhancement factor that is optimal for the generalized gradient approximation within the Kohn-Sham (KS) approach may not be optimal for the self-interaction corrected functional. The PBEsol functional, wheremore » the exchange enhancement factor was optimized for solids, gives poor results for molecules in KS but turns out to work better than PBE in PZ-SIC calculations. The exchange enhancement is weaker in PBEsol and the functional is closer to the local density approximation. Furthermore, the drop in the exchange enhancement factor for increasing reduced gradient in the PW91 functional gives more accurate results than the plateaued enhancement in the PBE functional. A step towards an optimal exchange enhancement factor for a gradient dependent functional of the PZ-SIC form is taken by constructing an exchange enhancement factor that mimics PBEsol for small values of the reduced gradient, and PW91 for large values. The average atomization energy is then in closer agreement with the high-level quantum chemistry calculations, but the variance is still large, the F 2 molecule being a notable outlier.« less

  5. Factors influencing rural and urban emergency clinicians' participation in an online knowledge exchange intervention.

    PubMed

    Curran, Janet A; Murphy, Andrea L; Sinclair, Douglas; McGrath, Patrick

    2013-01-01

    Rural emergency departments (EDs) generally have limited access to continuing education and are typically staffed by clinicians without pediatric emergency specialty training. Emergency care of children is complex and the majority of children receive emergency care in non-pediatric tertiary care centers. In recent decades, there has been a call to action to improve quality and safety in the emergency care of children. Of the one million ED visits by children in Ontario in 2005-2006, one in three visited more than once in a year and one in 15 returned to the ED within 72 hours of the index visit. This study explored factors influencing rural and urban ED clinicians' participation in a Web-based knowledge exchange intervention that focused on best practice knowledge about pediatric emergency care. The following questions guided the study: (i) What are the individual, context of practice or knowledge factors which impact a clinician's decision to participate in a Web-based knowledge exchange intervention?; (ii) What are clinicians' perceptions of organizational expectations regarding knowledge and information sources to be used in practice?; and (iii) What are the preferred knowledge sources of rural and urban emergency clinicians? A Web-based knowledge exchange intervention, the Pediatric Emergency Care Web Based Knowledge Exchange Project, for rural and urban ED clinicians was developed. The website contained 12 pediatric emergency practice learning modules with linked asynchronous discussion forums. The topics for the modules were determined through a needs assessment and the module content was developed by known experts in the field. A follow-up survey was sent to a convenience sample of 187 clinicians from nine rural and two urban Canadian EDs participating in the pediatric emergency Web-based knowledge exchange intervention study. The survey response rate was 56% (105/187). Participation in the knowledge exchange intervention was related to individual involvement in research activities (χ(2)=5.23, p=0.019), consultation with colleagues from other EDs (χ(2)=6.37, p=0.01) and perception of organizational expectations to use research evidence to guide practice (χ(2)=5.52, p=0.015). Most clinicians (95/105 or 92%) reported relying on colleagues from their own ED as a primary knowledge source. Urban clinicians were more likely than their rural counterparts to perceive that use of research evidence to guide practice was an expectation. Rural clinicians were more likely to rely on physicians from their own ED as a preferred knowledge source. The decision made by emergency clinicians to participate in a Web-based knowledge exchange intervention was influenced by a number of individual and contextual factors. Differences in these factors and preferences for knowledge sources require further characterization to enhance engagement of rural ED clinicians in online knowledge exchange interventions.

  6. 26 CFR 1.1031-0 - Table of contents.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    .... § 1.1031(b)-1 Receipt of other property or money in tax-free exchange. § 1.1031(b)-2 Safe harbor for...-free exchange. § 1.1031(d)-1T Coordination of section 1060 with section 1031 (temporary). § 1.1031(d)-2...) Receipt of money or other property. (g) Safe harbors. (h) Interest and growth factors. (i) [Reserved] (j...

  7. 26 CFR 1.1031-0 - Table of contents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    .... § 1.1031(b)-1 Receipt of other property or money in tax-free exchange. § 1.1031(b)-2 Safe harbor for...-free exchange. § 1.1031(d)-1T Coordination of section 1060 with section 1031 (temporary). § 1.1031(d)-2...) Receipt of money or other property. (g) Safe harbors. (h) Interest and growth factors. (i) [Reserved] (j...

  8. 26 CFR 1.1031-0 - Table of contents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    .... § 1.1031(b)-1 Receipt of other property or money in tax-free exchange. § 1.1031(b)-2 Safe harbor for...-free exchange. § 1.1031(d)-1T Coordination of section 1060 with section 1031 (temporary). § 1.1031(d)-2...) Receipt of money or other property. (g) Safe harbors. (h) Interest and growth factors. (i) [Reserved] (j...

  9. 26 CFR 1.1031-0 - Table of contents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    .... § 1.1031(b)-1 Receipt of other property or money in tax-free exchange. § 1.1031(b)-2 Safe harbor for...-free exchange. § 1.1031(d)-1T Coordination of section 1060 with section 1031 (temporary). § 1.1031(d)-2...) Receipt of money or other property. (g) Safe harbors. (h) Interest and growth factors. (i) [Reserved] (j...

  10. Using Wavelets and Information Theory to Characterize the Direction, Strength, and Time Scale of Interaction between Environmental Drivers and Greenhouse Gas Exchange in Managed Wetlands of Northern California

    NASA Astrophysics Data System (ADS)

    Sturtevant, C. S.; Ruddell, B. L.; Knox, S. H.; Verfaillie, J. G.; Matthes, J. H.; Oikawa, P. Y.; Baldocchi, D. D.

    2014-12-01

    Restoring agricultural areas to wetlands in the Sacramento-San Joaquin River Delta of California can help reverse subsidence and reduce greenhouse gas (GHG) emissions. Predicting outcomes and developing best practices of wetland management therefore requires a robust understanding of the sensitivity of GHG exchange in these ecosystems to factors such as management and meteorology. However, wetlands can exhibit complex, overlapping, and asynchronous couplings between site characteristics, environmental drivers and GHG exchange. In this research we demonstrate the use of wavelets and information theory (process networks) as sophisticated tools to disentangle and characterize ecosystem couplings to CO2 and CH4 exchange (measured by eddy covariance) in two restored Delta wetlands. Using wavelets we isolated processes acting at different time scales, then used process networks to determine the direction, strength, and lag properties of ecosystem couplings. We found that despite differences in age, architecture and management, CO2 exchange at both wetlands was most sensitive to similar meteorological factors such as radiation and temperature up to a time scale of several days. At the monthly timescale, however, the effect of a more variable water table management in one wetland became dominant, revealing a reduction in net CO2 uptake during long term water table drawdowns. The analysis of CH4 exchange in this wetland revealed a more sensitive and complex coupling with water table. CH4 exchange was sensitive to relatively small, multi-day shifts in water table and displayed a lagged response to larger, longer shifts. With these methods we were able to disentangle the effects of management from meteorology and better understand the sensitivities of GHG exchange. Our results provide important insights for modeling efforts and management practices.

  11. Gas exchange rates across the sediment-water and air-water interfaces in south San Francisco Bay

    USGS Publications Warehouse

    Hartman, Blayne; Hammond, Douglas E.

    1984-01-01

    Radon 222 concentrations in the water and sedimentary columns and radon exchange rates across the sediment-water and air-water interfaces have been measured in a section of south San Francisco Bay. Two independent methods have been used to determine sediment-water exchange rates, and the annual averages of these methods agree within the uncertainty of the determinations, about 20%. The annual average of benthic fluxes from shoal areas is nearly a factor of 2 greater than fluxes from the channel areas. Fluxes from the shoal and channel areas exceed those expected from simple molecular diffusion by factors of 4 and 2, respectively, apparently due to macrofaunal irrigation. Values of the gas transfer coefficient for radon exchange across the air-water interface were determined by constructing a radon mass balance for the water column and by direct measurement using floating chambers. The chamber method appears to yield results which are too high. Transfer coefficients computed using the mass balance method range from 0.4 m/day to 1.8 m/day, with a 6-year average of 1.0 m/day. Gas exchange is linearly dependent upon wind speed over a wind speed range of 3.2–6.4 m/s, but shows no dependence upon current velocity. Gas transfer coefficients predicted from an empirical relationship between gas exchange rates and wind speed observed in lakes and the oceans are within 30% of the coefficients determined from the radon mass balance and are considerably more accurate than coefficients predicted from theoretical gas exchange models.

  12. Clinical outcomes and predictive factors related to good outcomes in plasma exchange in severe attack of NMOSD and long extensive transverse myelitis: Case series and review of the literature.

    PubMed

    Aungsumart, Saharat; Apiwattanakul, Metha

    2017-04-01

    To investigate the predictive factors associated with good outcomes of plasma exchange in severe attacks through neuromyelitis optica spectrum disorder (NMOSD) and long extensive transverse myelitis (LETM). In addition, to review the literature of predictive factors associated with the good outcomes of plasma exchange in central nervous system inflammatory demyelinating diseases (CNS IDDs). Retrospective study in 27 episodes of severe acute attacks myelitis and optic neuritis in 24 patients, including 20 patients with NMOSD seropositive, 1 patient with NMOSD seronegative and 3 patients with LETM. Plasma exchange was performed, reflecting poor responses to high-dose intravenous methylprednisolone (IVMP) therapy. The outcomes of the present study were the functional outcome improvements at 6 months after plasma exchange. The predictive factors of good outcomes after plasma exchange were determined in this cohort, and additional factors reported in the literature were reviewed. Plasma exchange was performed in 16 spinal cord attacks and 11 attacks of optic neuritis. Twenty patients were female (83%). The median age of the patients at the time of plasma exchange was 41 years old. The median disease duration was 0.6 years. The AQP4-IgG status was positive in 20 patients (83%). Plasma exchange following IVMP therapy led to a significant improvement in 81% of the cases after 6 months of follow up. A baseline Expanded Disability Status Scale (EDSS) score ≤6 before the attack was associated with significant improvement at 6 months (p=0.02, OR 58.33, 95%CI 1.92-1770). In addition, we reviewed the evidence for factors associated with good outcomes of plasma exchange in CNS IDDs, classified according to pre-plasma exchange, post-plasma exchange, and radiological features. Plasma exchange following IVMP therapy is effective as a treatment for patients experiencing a severe attack of NMOSD or LETM. The factors associated with good outcomes after plasma exchange in CNS IDDs are reviewed in the literature. We classified 3 different aspects, including pre-plasma exchange factors, based on minimal disability at baseline, preserved reflexes, early initiation, and short disease duration; post plasma exchange factors, including early improvement or lower disability at last follow up; and radiographic factors, for which the presence of active gadolinium lesions and the absence of spinal cord atrophy seem to be good outcomes for plasmapheresis. Copyright © 2017. Published by Elsevier B.V.

  13. RAC1 GTP-ase signals Wnt-beta-catenin pathway mediated integrin-directed metastasis-associated tumor cell phenotypes in triple negative breast cancers.

    PubMed

    De, Pradip; Carlson, Jennifer H; Jepperson, Tyler; Willis, Scooter; Leyland-Jones, Brian; Dey, Nandini

    2017-01-10

    The acquisition of integrin-directed metastasis-associated (ID-MA) phenotypes by Triple-Negative Breast Cancer (TNBC) cells is caused by an upregulation of the Wnt-beta-catenin pathway (WP). We reported that WP is one of the salient genetic features of TNBC. RAC-GTPases, small G-proteins which transduce signals from cell surface proteins including integrins, have been implicated in tumorigenesis and metastasis by their role in essential cellular functions like motility. The collective percentage of alteration(s) in RAC1 in ER+ve BC was lower as compared to ER-ve BC (35% vs 57%) (brca/tcga/pub2015). High expression of RAC1 was associated with poor outcome for RFS with HR=1.48 [CI: 1.15-1.9] p=0.0019 in the Hungarian ER-veBC cohort. Here we examined how WP signals are transduced via RAC1 in the context of ID-MA phenotypes in TNBC. Using pharmacological agents (sulindac sulfide), genetic tools (beta-catenin siRNA), WP modulators (Wnt-C59, XAV939), RAC1 inhibitors (NSC23766, W56) and WP stimulations (LWnt3ACM, Wnt3A recombinant) in a panel of 6-7 TNBC cell lines, we studied fibronectin-directed (1) migration, (2) matrigel invasion, (3) RAC1 and Cdc42 activation, (4) actin dynamics (confocal microscopy) and (5) podia-parameters. An attenuation of WP, which (a) decreased cellular levels of beta-catenin, as well as its nuclear active-form, (b) decreased fibronectin-induced migration, (c) decreased invasion, (d) altered actin dynamics and (e) decreased podia-parameters was successful in blocking fibronectin-mediated RAC1/Cdc42 activity. Both Wnt-antagonists and RAC1 inhibitors blocked fibronectin-induced RAC1 activation and inhibited the fibronectin-induced ID-MA phenotypes following specific WP stimulation by LWnt3ACM as well as Wnt3A recombinant protein. To test a direct involvement of RAC1-activation in WP-mediated ID-MA phenotypes, we stimulated brain-metastasis specific MDA-MB231BR cells with LWnt3ACM. LWnt3ACM-stimulated fibronectin-directed migration was blocked by RAC1 inhibition in MDA-MB231BR cells. In the light of our previous report that WP upregulation causes ID-MA phenotypes in TNBC tumor cells, here we provide the first mechanism based evidence to demonstrate that WP upregulation signals ID-MA tumor cell phenotypes in a RAC1-GTPase dependent manner involving exchange-factors like TIAM1 and VAV2. Our study demonstrates for the first time that beta-catenin-RAC1 cascade signals integrin-directed metastasis-associated tumor cell phenotypes in TNBC.

  14. Multiphase complete exchange on Paragon, SP2 and CS-2

    NASA Technical Reports Server (NTRS)

    Bokhari, Shahid H.

    1995-01-01

    The overhead of interprocessor communication is a major factor in limiting the performance of parallel computer systems. The complete exchange is the severest communication pattern in that it requires each processor to send a distinct message to every other processor. This pattern is at the heart of many important parallel applications. On hypercubes, multiphase complete exchange has been developed and shown to provide optimal performance over varying message sizes. Most commercial multicomputer systems do not have a hypercube interconnect. However, they use special purpose hardware and dedicated communication processors to achieve very high performance communication and can be made to emulate the hypercube quite well. Multiphase complete exchange has been implemented on three contemporary parallel architectures: the Intel Paragon, IBM SP2 and Meiko CS-2. The essential features of these machines are described and their basic interprocessor communication overheads are discussed. The performance of multiphase complete exchange is evaluated on each machine. It is shown that the theoretical ideas developed for hypercubes are also applicable in practice to these machines and that multiphase complete exchange can lead to major savings in execution time over traditional solutions.

  15. Destabilizing Mutations Alter the Hydrogen Exchange Mechanism in Ribonuclease A

    PubMed Central

    Bruix, Marta; Ribó, Marc; Benito, Antoni; Laurents, Douglas V.; Rico, Manuel; Vilanova, Maria

    2008-01-01

    The effect of strongly destabilizing mutations, I106A and V108G of Ribonuclease A (RNase A), on its structure and stability has been determined by NMR. The solution structures of these variants are essentially equivalent to RNase A. The exchange rates of the most protected amide protons in RNase A (35°C), the I106A variant (35°C), and the V108G variant (10°C) yield stability values of 9.9, 6.0, and 6.8 kcal/mol, respectively, when analyzed assuming an EX2 exchange mechanism. Thus, the destabilization induced by these mutations is propagated throughout the protein. Simulation of RNase A hydrogen exchange indicates that the most protected protons in RNase A and the V108G variant exchange via the EX2 regime, whereas those of I106A exchange through a mixed EX1 + EX2 process. It is striking that a single point mutation can alter the overall exchange mechanism. Thus, destabilizing mutations joins high temperatures, high pH and the presence of denaturating agents as a factor that induces EX1 exchange in proteins. The calculations also indicate a shift from the EX2 to the EX1 mechanism for less protected groups within the same protein. This should be borne in mind when interpreting exchange data as a measure of local stability in less protected regions. PMID:18192347

  16. The effect of post-synthesis aging on the ligand exchange activity of iron oxide nanoparticles.

    PubMed

    Davis, Kathleen; Vidmar, Michael; Khasanov, Airat; Cole, Brian; Ghelardini, Melanie; Mayer, Justin; Kitchens, Christopher; Nath, Amar; Powell, Brian A; Mefford, O Thompson

    2018-02-01

    Ligand exchange is a widely-used method of controlling the surface chemistry of nanomaterials. Exchange is dependent on many factors including the age of the core particle being modified. Aging of the particles can impact surface structure and composition, which in turn can affect ligand binding. To quantify the effects of aging on ligand exchange, we employed a technique to track the exchange of radiolabeled 14 C-oleic acid with unlabeled, oleic acid bound to iron oxide nanoparticles. Liquid scintillation counting (LSC) was used to determine the amount of 14 C-oleic acid adsorbing to the particles throughout the duration of the exchange for particles aged for 2days, 7days, and 30days. Results revealed an increase in the total amount of ligands exchanged with aging up to 30days. Kinetic analysis of these results revealed a significant decrease in the overall rate of ligand exchange between 2 and 30days. The change in extent of adsorption with age could suggest increased availability of free binding sites. A follow-up study comparing exchange with oxidized and unoxidized particles suggested this increase in ligand adsorption may be due to changes in the Fe 2+ /Fe 3+ ratio on the surface as the particles aged. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. A counter-intuitive approach to calculating non-exchangeable 2H isotopic composition of hair: treating the molar exchange fraction fE as a process-related rather than compound-specific variable

    USGS Publications Warehouse

    Landwehr, J.M.; Meier-Augenstein, W.; Kemp, H.F.

    2011-01-01

    Hair is a keratinous tissue that incorporates hydrogen from material that an animal consumes but it is metabolically inert following synthesis. The stable hydrogen isotope composition of hair has been used in ecological studies to track migrations of mammals as well as for forensic and archaeological purposes to determine the provenance of human remains or the recent geographic life trajectory of living people. Measurement of the total hydrogen isotopic composition of a hair sample yields a composite value comprised of both metabolically informative, non-exchangeable hydrogen and exchangeable hydrogen, with the latter reflecting ambient or sample preparation conditions. Neither of these attributes is directly measurable, and the non-exchangeable hydrogen composition is obtained by estimation using a commonly applied mathematical expression incorporating sample measurements obtained from two distinct equilibration procedures. This commonly used approach treats the fraction of exchangeable hydrogen as a mixing ratio, with a minimal procedural fractionation factor assumed to be close or equal to 1. Instead, we propose to use full molar ratios to derive an expression for the non-exchangeable hydrogen composition explicitly as a function of both the procedural fractionation factor α and the molar hydrogen exchange fraction fE. We apply these derivations in a longitudinal study of a hair sample and demonstrate that the molar hydrogen exchange fraction fE should, like the procedural fractionation factor α, be treated as a process-dependent parameter, i.e. a reaction-specific constant. This is a counter-intuitive notion given that maximum theoretical values for the molar hydrogen exchange fraction fE can be calculated that are arguably protein-type specific and, as such, fE could be regarded as a compound-specific constant. We also make some additional suggestions for future approaches to determine the non-exchangeable hydrogen composition of hair and the use of standards.

  18. 75 FR 25899 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-10

    ... Factor of 1 May 3, 2010. Pursuant to Section 19(b)(1) of the Securities Exchange Act of 1934 (``Act''),\\1... factor of 1. The Exchange is not proposing any rule text changes. The rule proposal is available on the... would apply a scaling factor of 10 to the underlying index. The Exchange proposed the use of the scaling...

  19. Grain Yield Observations Constrain Cropland CO2 Fluxes Over Europe

    NASA Astrophysics Data System (ADS)

    Combe, M.; de Wit, A. J. W.; Vilà-Guerau de Arellano, J.; van der Molen, M. K.; Magliulo, V.; Peters, W.

    2017-12-01

    Carbon exchange over croplands plays an important role in the European carbon cycle over daily to seasonal time scales. A better description of this exchange in terrestrial biosphere models—most of which currently treat crops as unmanaged grasslands—is needed to improve atmospheric CO2 simulations. In the framework we present here, we model gross European cropland CO2 fluxes with a crop growth model constrained by grain yield observations. Our approach follows a two-step procedure. In the first step, we calculate day-to-day crop carbon fluxes and pools with the WOrld FOod STudies (WOFOST) model. A scaling factor of crop growth is optimized regionally by minimizing the final grain carbon pool difference to crop yield observations from the Statistical Office of the European Union. In a second step, we re-run our WOFOST model for the full European 25 × 25 km gridded domain using the optimized scaling factors. We combine our optimized crop CO2 fluxes with a simple soil respiration model to obtain the net cropland CO2 exchange. We assess our model's ability to represent cropland CO2 exchange using 40 years of observations at seven European FluxNet sites and compare it with carbon fluxes produced by a typical terrestrial biosphere model. We conclude that our new model framework provides a more realistic and strongly observation-driven estimate of carbon exchange over European croplands. Its products will be made available to the scientific community through the ICOS Carbon Portal and serve as a new cropland component in the CarbonTracker Europe inverse model.

  20. Complications of Impulse Generator Exchange Surgery for Deep Brain Stimulation: A Single-Center, Retrospective Study.

    PubMed

    Helmers, Ann-Kristin; Lübbing, Isabel; Birkenfeld, Falk; Witt, Karsten; Synowitz, Michael; Mehdorn, Hubertus Maximilian; Falk, Daniela

    2018-05-01

    Nonrechargeable deep brain stimulation impulse generators (IGs) with low or empty battery status require surgical IG exchange several years after initial implantation. The aim of this study was to investigate complication rates after IG exchange surgery and identify risk factors. We retrospectively analyzed complications following IG exchange surgery from 2008 to 2015 in our department. Medical records of all patients who underwent IG exchange surgery were systematically reviewed. The shortest follow-up time was 19 months. From 2008 to 2015, 438 IGs were exchanged in 319 patients. Overall complication rate was 8.90%. Infection developed in 12 patients (2.74%). Six patients (1.37%) experienced local wound erosions. Hardware malfunctions were present in 11 patients (2.51%), and local hemorrhage was observed in 3 cases (0.68%). Repeated fixation of the IG was required in 2 patients (0.46%). Traction of the connecting cables necessitated surgical revision in 2 patients (0.46%). In 2 cases (0.46%), the IG was placed abdominally or exchanged for a smaller device owing to patient discomfort resulting from the initial positioning. One 80-year-old patient (0.23%) had severely worsening heart failure and died 4 days after IG exchange surgery. IG exchange surgery, although often considered a minor surgery, was associated with a complication rate of approximately 9% in our center. Patients and physicians should understand the complication rates associated with IG exchange surgery because this information might facilitate selection of a rechargeable IG. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. In vitro guanine nucleotide exchange activity of DHR-2/DOCKER/CZH2 domains.

    PubMed

    Côté, Jean-François; Vuori, Kristiina

    2006-01-01

    Rho family GTPases regulate a large variety of biological processes, including the reorganization of the actin cytoskeleton. Like other members of the Ras superfamily of small GTP-binding proteins, Rho GTPases cycle between a GDP-bound (inactive) and a GTP-bound (active) state, and, when active, the GTPases relay extracellular signals to a large number of downstream effectors. Guanine nucleotide exchange factors (GEFs) promote the exchange of GDP for GTP on Rho GTPases, thereby activating them. Most Rho-GEFs mediate their effects through their signature domain known as the Dbl Homology-Pleckstrin Homology (DH-PH) module. Recently, we and others identified a family of evolutionarily conserved, DOCK180-related proteins that also display GEF activity toward Rho GTPases. The DOCK180-family of proteins lacks the canonical DH-PH module. Instead, they rely on a novel domain, termed DHR-2, DOCKER, or CZH2, to exchange GDP for GTP on Rho targets. In this chapter, the experimental approach that we used to uncover the exchange activity of the DHR-2 domain of DOCK180-related proteins will be described.

  2. Thermal-hydraulic behavior of a mixed chevron single-pass plate-and-frame heat exchanger

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

    Manglik, R.M.; Muley, A.

    1995-12-31

    Effective heat exchange is very critical for improving the process efficiency and operating economy of chemical and process plants. Here, experimental friction factor and heat transfer data for single-phase water flows in a plate-and-frame heat exchanger are presented. A mixed chevron plate arrangement with {beta} = 30{degree}/60{degree} in a single-pass U-type, counterflow configuration is employed. The friction factor and heat transfer data are for isothermal flow and cooling conditions, respectively, and the flow rates correspond to transition and turbulent flow regimes (300 < Re < 6,000 and 2.4 < Pr < 4.5). Based on these data, Nusselt number and frictionmore » factor correlations for fully developed turbulent flows (Re {ge} 1,000) are presented. The results highlight the effects of {beta} on the thermal-hydraulic performance, transition to turbulent flows, and the relative impact of using symmetric or mixed chevron plate arrangements.« less

  3. LAT region factors mediating differential neuronal tropism of HSV-1 and HSV-2 do not act in trans.

    PubMed

    Bertke, Andrea S; Apakupakul, Kathleen; Ma, AyeAye; Imai, Yumi; Gussow, Anne M; Wang, Kening; Cohen, Jeffrey I; Bloom, David C; Margolis, Todd P

    2012-01-01

    After HSV infection, some trigeminal ganglion neurons support productive cycle gene expression, while in other neurons the virus establishes a latent infection. We previously demonstrated that HSV-1 and HSV-2 preferentially establish latent infection in A5+ and KH10+ sensory neurons, respectively, and that exchanging the latency-associated transcript (LAT) between HSV-1 and HSV-2 also exchanges the neuronal preference. Since many viral genes besides the LAT are functionally interchangeable between HSV-1 and HSV-2, we co-infected HSV-1 and HSV-2, both in vivo and in vitro, to determine if trans-acting viral factors regulate whether HSV infection follows a productive or latent pattern of gene expression in sensory neurons. The pattern of HSV-1 and HSV-2 latent infection in trigeminal neurons was no different following co-infection than with either virus alone, consistent with the hypothesis that a trans-acting viral factor is not responsible for the different patterns of latent infection of HSV-1 and HSV-2 in A5+ and KH10+ neurons. Since exchanging the LAT regions between the viruses also exchanges neuronal preferences, we infected transgenic mice that constitutively express 2.8 kb of the LAT region with the heterologous viral serotype. Endogenous expression of LAT did not alter the pattern of latent infection after inoculation with the heterologous serotype virus, demonstrating that the LAT region does not act in trans to direct preferential establishment of latency of HSV-1 and HSV-2. Using HSV1-RFP and HSV2-GFP in adult trigeminal ganglion neurons in vitro, we determined that HSV-1 and HSV-2 do not exert trans-acting effects during acute infection to regulate neuron specificity. Although some neurons were productively infected with both HSV-1 and HSV-2, no A5+ or KH10+ neurons were productively infected with both viruses. Thus, trans-acting viral factors do not regulate preferential permissiveness of A5+ and KH10+ neurons for productive HSV infection and preferential establishment of latent infection.

  4. LAT Region Factors Mediating Differential Neuronal Tropism of HSV-1 and HSV-2 Do Not Act in Trans

    PubMed Central

    Bertke, Andrea S.; Apakupakul, Kathleen; Ma, AyeAye; Imai, Yumi; Gussow, Anne M.; Wang, Kening; Cohen, Jeffrey I.; Bloom, David C.; Margolis, Todd P.

    2012-01-01

    After HSV infection, some trigeminal ganglion neurons support productive cycle gene expression, while in other neurons the virus establishes a latent infection. We previously demonstrated that HSV-1 and HSV-2 preferentially establish latent infection in A5+ and KH10+ sensory neurons, respectively, and that exchanging the latency-associated transcript (LAT) between HSV-1 and HSV-2 also exchanges the neuronal preference. Since many viral genes besides the LAT are functionally interchangeable between HSV-1 and HSV-2, we co-infected HSV-1 and HSV-2, both in vivo and in vitro, to determine if trans-acting viral factors regulate whether HSV infection follows a productive or latent pattern of gene expression in sensory neurons. The pattern of HSV-1 and HSV-2 latent infection in trigeminal neurons was no different following co-infection than with either virus alone, consistent with the hypothesis that a trans-acting viral factor is not responsible for the different patterns of latent infection of HSV-1 and HSV-2 in A5+ and KH10+ neurons. Since exchanging the LAT regions between the viruses also exchanges neuronal preferences, we infected transgenic mice that constitutively express 2.8 kb of the LAT region with the heterologous viral serotype. Endogenous expression of LAT did not alter the pattern of latent infection after inoculation with the heterologous serotype virus, demonstrating that the LAT region does not act in trans to direct preferential establishment of latency of HSV-1 and HSV-2. Using HSV1-RFP and HSV2-GFP in adult trigeminal ganglion neurons in vitro, we determined that HSV-1 and HSV-2 do not exert trans-acting effects during acute infection to regulate neuron specificity. Although some neurons were productively infected with both HSV-1 and HSV-2, no A5+ or KH10+ neurons were productively infected with both viruses. Thus, trans-acting viral factors do not regulate preferential permissiveness of A5+ and KH10+ neurons for productive HSV infection and preferential establishment of latent infection. PMID:23300908

  5. Functional hierarchy of the N-terminal tyrosines of SLP-76.

    PubMed

    Jordan, Martha S; Sadler, Jeffrey; Austin, Jessica E; Finkelstein, Lisa D; Singer, Andrew L; Schwartzberg, Pamela L; Koretzky, Gary A

    2006-02-15

    The adaptor protein Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) plays a central role in T cell activation and T cell development. SLP-76 has three functional modules: an acidic domain with three key tyrosines, a central proline-rich domain, and a C-terminal Src homology 2 domain. Of these, mutation of the three N-terminal tyrosines (Y112, Y128, and Y145) results in the most profound effects on T cell development and function. Y112 and Y128 associate with Vav and Nck, two proteins shown to be important for TCR-induced phosphorylation of proximal signaling substrates, Ca(2+) flux, and actin reorganization. Y145 has been shown to be important for optimal association of SLP-76 with inducible tyrosine kinase, a key regulator of T cell function. To investigate further the role of the phosphorylatable tyrosines of SLP-76 in TCR signaling, cell lines and primary T cells expressing SLP-76 with mutations in individual or paired tyrosine residues were analyzed. These studies show that Tyr(145) of SLP-76 is the most critical tyrosine for both T cell function in vitro and T cell development in vivo.

  6. The delta-subunit of murine guanine nucleotide exchange factor eIF-2B. Characterization of cDNAs predicts isoforms differing at the amino-terminal end.

    PubMed

    Henderson, R A; Krissansen, G W; Yong, R Y; Leung, E; Watson, J D; Dholakia, J N

    1994-12-02

    Protein synthesis in mammalian cells is regulated at the level of the guanine nucleotide exchange factor, eIF-2B, which catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP. We have isolated and sequenced cDNA clones encoding the delta-subunit of murine eIF-2B. The cDNA sequence encodes a polypeptide of 544 amino acids with molecular mass of 60 kDa. Antibodies against a synthetic polypeptide of 30 amino acids deduced from the cDNA sequence specifically react with the delta-subunit of mammalian eIF-2B. The cDNA-derived amino acid sequence shows significant homology with the yeast translational regulator Gcd2, supporting the hypothesis that Gcd2 may be the yeast homolog of the delta-subunit of mammalian eIF-2B. Primer extension studies and anchor polymerase chain reaction analysis were performed to determine the 5'-end of the transcript for the delta-subunit of eIF-2B. Results of these experiments demonstrate two different mRNAs for the delta-subunit of eIF-2B in murine cells. The isolation and characterization of two different full-length cDNAs also predicts the presence of two alternate forms of the delta-subunit of eIF-2B in murine cells. These differ at their amino-terminal end but have identical nucleotide sequences coding for amino acids 31-544.

  7. ERYTHROPOIETIC FACTOR PURIFICATION

    DOEpatents

    White, W.F.; Schlueter, R.J.

    1962-05-01

    A method is given for purifying and concentrating the blood plasma erythropoietic factor. Anemic sheep plasma is contacted three times successively with ion exchange resins: an anion exchange resin, a cation exchange resin at a pH of about 5, and a cation exchange resin at a pH of about 6. (AEC)

  8. [Ecosystem carbon exchange in Artemisia ordosica shrubland of Ordos Plateau in two different precipitation years].

    PubMed

    Gao, Li; Dong, Ting-Ting; Wang, Yu-Qing; Yan, Zhi-Jian; Baoyin, Tao-ge-tao; Wang, Hui; Dai, Ya-Ting

    2014-08-01

    Characteristics of ecosystem carbon exchange and its impact factors in Artemisia ordosica shrubland in 2011 (low precipitation) and 2012 (high precipitation), Ordos Plateau, were studied using eddy covariance methods. The results showed that the diurnal dynamics of ecosystem carbon exchange could be expressed as single-peak and double-peak curves in the two different precipitation years. In 2011, three carbon absorption peaks and three carbon release peaks of ecosystem carbon exchange presented in the growing season. In 2012, four carbon absorption peaks and one carbon release peak appeared in the growing season. The A. ordosica shrubland was a net carbon sink from June to September and a carbon source in October in 2011. In 2012, A. ordosica shrubland was a net carbon sink in the whole growing season. The amount of carbon fixed by A. ordosica shrubland in the growing season in 2012 was 268.90 mg CO2 x m(-2) x s(-1) higher than that in 2011. The ecosystem carbon exchange of A. ordosica shrubland was controlled by PAR (photosynthetically active radiation) on the day scale, and affected by both abiotic (precipitation and soil water content) and biotic (aboveground net primary, productivity) factors on the growing season scale.

  9. Binding of the Ras activator son of sevenless to insulin receptor substrate-1 signaling complexes.

    PubMed

    Baltensperger, K; Kozma, L M; Cherniack, A D; Klarlund, J K; Chawla, A; Banerjee, U; Czech, M P

    1993-06-25

    Signal transmission by insulin involves tyrosine phosphorylation of a major insulin receptor substrate (IRS-1) and exchange of Ras-bound guanosine diphosphate for guanosine triphosphate. Proteins containing Src homology 2 and 3 (SH2 and SH3) domains, such as the p85 regulatory subunit of phosphatidylinositol-3 kinase and growth factor receptor-bound protein 2 (GRB2), bind tyrosine phosphate sites on IRS-1 through their SH2 regions. Such complexes in COS cells were found to contain the heterologously expressed putative guanine nucleotide exchange factor encoded by the Drosophila son of sevenless gene (dSos). Thus, GRB2, p85, or other proteins with SH2-SH3 adapter sequences may link Sos proteins to IRS-1 signaling complexes as part of the mechanism by which insulin activates Ras.

  10. Highly tritiated water processing by isotopic exchange

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

    Shu, W.M.; Willms, R.S.; Glugla, M.

    2015-03-15

    Highly tritiated water (HTW) is produced in fusion machines and one of the promising technologies to process it is isotopic exchange. 3 kinds of Pt-catalyzed zeolite (13X-APG, CBV-100-CY and HiSiv-1000) were tested as candidates for isotopic exchange of highly tritiated water (HTW), and CBV-100-CY (Na-Y type with a SiO{sub 2}/Al{sub 2}O{sub 3} ratio of ∼ 5.0) shows the best performance. Small-scale tritium testing indicates that this method is efficient for reaching an exchange factor (EF) of 100. Full-scale non-tritium testing implies that an EF of 300 can be achieved in 24 hours of operation if a temperature gradient is appliedmore » along the column. For the isotopic exchange, deuterium recycled from the Isotope Separation System (deuterium with 1% T and/or 200 ppm T) should be employed, and the tritiated water regenerated from the Pt-catalyzed zeolite bed after isotopic exchange should be transferred to Water Detritiation System (WDS) for further processing.« less

  11. Short-duration respirometry underestimates metabolic rate for discontinuous breathers.

    PubMed

    Winwood-Smith, Hugh S; White, Craig R

    2018-06-07

    Metabolic rate is commonly estimated from rates of gas exchange. An underappreciated factor that can influence estimates is patterns of pulmonary respiration. Amphibians display discontinuous respiratory patterns, often including long apnoeas, in addition to cutaneous gas exchange. The contribution of cutaneous exchange increases at low temperatures when metabolic rate is low. Due to the relatively low permeability of skin, measurements that disproportionately capture cutaneous exchange can produce underestimates of metabolic rate. The permeability of amphibian skin to CO 2 is greater than O 2 , therefore calculating the ratio of whole-animal CO 2 emission to O 2 uptake (the respiratory exchange ratio, RER) can be used to avoid underestimates of metabolic rate by ensuring that observed values of RER fall within the normal physiological range (∼0.7 to 1). Using data for cane toads Rhinella marina we show that short-duration measurements lead to underestimates of metabolic rate and overestimates of RER. At low temperatures this problem is exacerbated, requiring over 12 hours for RER to fall within the normal physiological range. Many published values of metabolic rate in animals that utilise cutaneous exchange may be underestimates. © 2018. Published by The Company of Biologists Ltd.

  12. On Neglecting Chemical Exchange Effects When Correcting in Vivo 31P MRS Data for Partial Saturation

    NASA Astrophysics Data System (ADS)

    Ouwerkerk, Ronald; Bottomley, Paul A.

    2001-02-01

    Signal acquisition in most MRS experiments requires a correction for partial saturation that is commonly based on a single exponential model for T1 that ignores effects of chemical exchange. We evaluated the errors in 31P MRS measurements introduced by this approximation in two-, three-, and four-site chemical exchange models under a range of flip-angles and pulse sequence repetition times (TR) that provide near-optimum signal-to-noise ratio (SNR). In two-site exchange, such as the creatine-kinase reaction involving phosphocreatine (PCr) and γ-ATP in human skeletal and cardiac muscle, errors in saturation factors were determined for the progressive saturation method and the dual-angle method of measuring T1. The analysis shows that these errors are negligible for the progressive saturation method if the observed T1 is derived from a three-parameter fit of the data. When T1 is measured with the dual-angle method, errors in saturation factors are less than 5% for all conceivable values of the chemical exchange rate and flip-angles that deliver useful SNR per unit time over the range T1/5 ≤ TR ≤ 2T1. Errors are also less than 5% for three- and four-site exchange when TR ≥ T1*/2, the so-called "intrinsic" T1's of the metabolites. The effect of changing metabolite concentrations and chemical exchange rates on observed T1's and saturation corrections was also examined with a three-site chemical exchange model involving ATP, PCr, and inorganic phosphate in skeletal muscle undergoing up to 95% PCr depletion. Although the observed T1's were dependent on metabolite concentrations, errors in saturation corrections for TR = 2 s could be kept within 5% for all exchanging metabolites using a simple interpolation of two dual-angle T1 measurements performed at the start and end of the experiment. Thus, the single-exponential model appears to be reasonably accurate for correcting 31P MRS data for partial saturation in the presence of chemical exchange. Even in systems where metabolite concentrations change, accurate saturation corrections are possible without much loss in SNR.

  13. Proton and neutron electromagnetic form factors and uncertainties

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

    Ye, Zhihong; Arrington, John; Hill, Richard J.

    We determine the nucleon electromagnetic form factors and their uncertainties from world electron scattering data. The analysis incorporates two-photon exchange corrections, constraints on the low-Q 2 and high-Q 2 behavior, and additional uncertainties to account for tensions between different data sets and uncertainties in radiative corrections.

  14. Proton and neutron electromagnetic form factors and uncertainties

    DOE PAGES

    Ye, Zhihong; Arrington, John; Hill, Richard J.; ...

    2017-12-06

    We determine the nucleon electromagnetic form factors and their uncertainties from world electron scattering data. The analysis incorporates two-photon exchange corrections, constraints on the low-Q 2 and high-Q 2 behavior, and additional uncertainties to account for tensions between different data sets and uncertainties in radiative corrections.

  15. A highly stable gadolinium complex with a fast, associative mechanism of water exchange.

    PubMed

    Thompson, Marlon K; Botta, Mauro; Nicolle, Gaëlle; Helm, Lothar; Aime, Silvio; Merbach, André E; Raymond, Kenneth N

    2003-11-26

    The stability and water exchange dynamics of gadolinium (GdIII) complexes are critical characteristics that determine their effectiveness as contrast agents for magnetic resonance imaging (MRI). A new heteropodal GdIII chelate, [Gd-TREN-bis(6-Me-HOPO)-(TAM-TRI)(H2O)2] (Gd-2), is presented which is based on a hydroxypyridinate (HOPO)-terephthalamide (TAM) ligand design. Thermodynamic equilibrium constants for the acid-base properties and the GdIII complexation strength of TREN-bis(6-Me-HOPO)-(TAM-TRI) (2) were measured by potentiometric and spectrophotometric titration techniques, respectively. The pGd of 2 is 20.6 (pH 7.4, 25 degrees C, I = 0.1 M), indicating that Gd-2 is of more than sufficient thermodynamic stability for in vivo MRI applications. The water exchange rate of Gd-2 (kex = 5.3(+/-0.6) x 107 s-1) was determined by variable temperature 17O NMR and is in the fast exchange regime - ideal for MRI. Variable pressure 17O NMR was used to determine the volume of activation (DeltaV) of Gd-2. DeltaV for Gd-2 is -5 cm3 mol-1, indicative of an interchange associative (Ia) water exchange mechanism. The results reported herein are important as they provide insight into the factors influencing high stability and fast water exchange in the HOPO series of complexes, potentially future clinical contrast agents.

  16. Exchange-mediated contrast in CEST and spin-lock imaging.

    PubMed

    Cobb, Jared Guthrie; Li, Ke; Xie, Jingping; Gochberg, Daniel F; Gore, John C

    2014-01-01

    Magnetic resonance images of biological media based on chemical exchange saturation transfer (CEST) show contrast that depends on chemical exchange between water and other protons. In addition, spin-lattice relaxation rates in the rotating frame (R1ρ) are also affected by exchange, especially at high fields, and can be exploited to provide novel, exchange-dependent contrast. Here, we evaluate and compare the factors that modulate the exchange contrast for these methods using simulations and experiments on simple, biologically relevant samples. Simulations and experimental measurements at 9.4 T of rotating frame relaxation rate dispersion and CEST contrast were performed on solutions of macromolecules containing amide and hydroxyl exchanging protons. The simulations and experimental measurements confirm that both CEST and R1ρ measurements depend on similar exchange parameters, but they manifest themselves differently in their effects on contrast. CEST contrast may be larger in the slow and intermediate exchange regimes for protons with large resonant frequency offsets (e.g. >2 ppm). Spin-locking techniques can produce larger contrast enhancement when resonant frequency offsets are small (<2 ppm) and exchange is in the intermediate-to-fast regime. The image contrasts scale differently with field strength, exchange rate and concentration. CEST and R1ρ measurements provide different and somewhat complementary information about exchange in tissues. Whereas CEST can depict exchange of protons with specific chemical shifts, appropriate R1ρ-dependent acquisitions can be employed to selectively portray protons of specific exchange rates. © 2013.

  17. Exchange-Mediated Contrast in CEST and Spin-Lock Imaging

    PubMed Central

    Cobb, Jared Guthrie; Li, Ke; Xie, Jingping; Gochberg, Daniel F.; Gore, John C.

    2014-01-01

    PURPOSE Magnetic resonance images of biological media based on chemical exchange saturation transfer (CEST) show contrast that depends on chemical exchange between water and other protons. In addition, spin-lattice relaxation rates in the rotating frame (R1ρ) are also affected by exchange, especially at high fields, and can be exploited to provide novel, exchange-dependent contrast. Here, we evaluate and compare the factors that modulate the exchange contrast for these methods using simulations and experiments on simple, biologically relevant samples. METHODS Simulations and experimental measurements at 9.4T of rotating frame relaxation rate dispersion and CEST contrast were performed on solutions of macromolecules containing amide and hydroxyl exchanging protons. RESULTS The simulations and experimental measurements confirm that both CEST and R1ρ measurements depend on similar exchange parameters, but they manifest themselves differently in their effects on contrast. CEST contrast may be larger in the slow and intermediate exchange regimes for protons with large resonant frequency offsets (e.g. > 2ppm). Spin-locking techniques can produce larger contrast enhancement when resonant frequency offsets are small (< 2 ppm) and exchange is in the intermediate to fast regime. The image contrasts scale differently with field strength, exchange rate and concentration. CONCLUSION CEST and R1ρ measurements provide different and somewhat complementary information about exchange in tissues. Whereas CEST can depict exchange of protons with specific chemical shifts, appropriate R1ρ dependent acquisitions can be employed to selectively portray protons of specific exchange rates. PMID:24239335

  18. Deriving detector-specific correction factors for rectangular small fields using a scintillator detector.

    PubMed

    Qin, Yujiao; Zhong, Hualiang; Wen, Ning; Snyder, Karen; Huang, Yimei; Chetty, Indrin J

    2016-11-08

    The goal of this study was to investigate small field output factors (OFs) for flat-tening filter-free (FFF) beams on a dedicated stereotactic linear accelerator-based system. From this data, the collimator exchange effect was quantified, and detector-specific correction factors were generated. Output factors for 16 jaw-collimated small fields (from 0.5 to 2 cm) were measured using five different detectors including an ion chamber (CC01), a stereotactic field diode (SFD), a diode detector (Edge), Gafchromic film (EBT3), and a plastic scintillator detector (PSD, W1). Chamber, diodes, and PSD measurements were performed in a Wellhofer water tank, while films were irradiated in solid water at 100 cm source-to-surface distance and 10 cm depth. The collimator exchange effect was quantified for rectangular fields. Monte Carlo (MC) simulations of the measured configurations were also performed using the EGSnrc/DOSXYZnrc code. Output factors measured by the PSD and verified against film and MC calculations were chosen as the benchmark measurements. Compared with plastic scintillator detector (PSD), the small volume ion chamber (CC01) underestimated output factors by an average of -1.0% ± 4.9% (max. = -11.7% for 0.5 × 0.5 cm2 square field). The stereotactic diode (SFD) overestimated output factors by 2.5% ± 0.4% (max. = 3.3% for 0.5 × 1 cm2 rectangular field). The other diode detector (Edge) also overestimated the OFs by an average of 4.2% ± 0.9% (max. = 6.0% for 1 × 1 cm2 square field). Gafchromic film (EBT3) measure-ments and MC calculations agreed with the scintillator detector measurements within 0.6% ± 1.8% and 1.2% ± 1.5%, respectively. Across all the X and Y jaw combinations, the average collimator exchange effect was computed: 1.4% ± 1.1% (CC01), 5.8% ± 5.4% (SFD), 5.1% ± 4.8% (Edge diode), 3.5% ± 5.0% (Monte Carlo), 3.8% ± 4.7% (film), and 5.5% ± 5.1% (PSD). Small field detectors should be used with caution with a clear understanding of their behaviors, especially for FFF beams and small, elongated fields. The scintillator detector exhibited good agreement against Gafchromic film measurements and MC simulations over the range of field sizes studied. The collimator exchange effect was found to be impor-tant at these small field sizes. Detector-specific correction factors were computed using the scintillator measurements as the benchmark. © 2016 The Authors.

  19. Chinese Ph.D. Students on Exchange in European Union Countries: Experiences and Benefits

    ERIC Educational Resources Information Center

    Shen, Wen-Qin; Liu, Dong; Chen, Hongjie

    2017-01-01

    In the past decade, thousands of Chinese doctoral students received funding from the China Scholarship Council (CSC) to start a 1--2-year exchange study in European universities. Do these Chinese doctoral students significantly improve their academic skills and publications through such an overseas experience? What are the influencing factors for…

  20. Arf6 Guanine Nucleotide Exchange Factor Cytohesin-2 Binds to CCDC120 and Is Transported Along Neurites to Mediate Neurite Growth*

    PubMed Central

    Torii, Tomohiro; Miyamoto, Yuki; Tago, Kenji; Sango, Kazunori; Nakamura, Kazuaki; Sanbe, Atsushi; Tanoue, Akito; Yamauchi, Junji

    2014-01-01

    The mechanism of neurite growth is complicated, involving continuous cytoskeletal rearrangement and vesicular trafficking. Cytohesin-2 is a guanine nucleotide exchange factor for Arf6, an Arf family molecular switch protein, controlling cell morphological changes such as neuritogenesis. Here, we show that cytohesin-2 binds to a protein with a previously unknown function, CCDC120, which contains three coiled-coil domains, and is transported along neurites in differentiating N1E-115 cells. Transfection of the small interfering RNA (siRNA) specific for CCDC120 into cells inhibits neurite growth and Arf6 activation. When neurites start to extend, vesicles containing CCDC120 and cytohesin-2 are transported in an anterograde manner rather than a retrograde one. As neurites continue extension, anterograde vesicle transport decreases. CCDC120 knockdown inhibits cytohesin-2 localization into vesicles containing CCDC120 and diffuses cytohesin-2 in cytoplasmic regions, illustrating that CCDC120 determines cytohesin-2 localization in growing neurites. Reintroduction of the wild type CCDC120 construct into cells transfected with CCDC120 siRNA reverses blunted neurite growth and Arf6 activity, whereas the cytohesin-2-binding CC1 region-deficient CCDC120 construct does not. Thus, cytohesin-2 is transported along neurites by vesicles containing CCDC120, and it mediates neurite growth. These results suggest a mechanism by which guanine nucleotide exchange factor for Arf6 is transported to mediate neurite growth. PMID:25326380

  1. An Early Model for Value and Sustainability in Health Information Exchanges: Qualitative Study.

    PubMed

    Feldman, Sue S

    2018-04-30

    The primary value relative to health information exchange has been seen in terms of cost savings relative to laboratory and radiology testing, emergency department expenditures, and admissions. However, models are needed to statistically quantify value and sustainability and better understand the dependent and mediating factors that contribute to value and sustainability. The purpose of this study was to provide a basis for early model development for health information exchange value and sustainability. A qualitative study was conducted with 21 interviews of eHealth Exchange participants across 10 organizations. Using a grounded theory approach and 3.0 as a relative frequency threshold, 5 main categories and 16 subcategories emerged. This study identifies 3 core current perceived value factors and 5 potential perceived value factors-how interviewees predict health information exchanges may evolve as there are more participants. These value factors were used as the foundation for early model development for sustainability of health information exchange. Using the value factors from the interviews, the study provides the basis for early model development for health information exchange value and sustainability. This basis includes factors from the research: fostering consumer engagement; establishing a provider directory; quantifying use, cost, and clinical outcomes; ensuring data integrity through patient matching; and increasing awareness, usefulness, interoperability, and sustainability of eHealth Exchange. ©Sue S Feldman. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 30.04.2018.

  2. Pulmonary gas exchange in acute respiratory failure.

    PubMed

    Rodriguez-Roisin, R

    1994-01-01

    The principal function of the lung is to facilitate the exchange of the respiratory gases, oxygen (O2) and carbon dioxide (CO2). When the lung fails as a gas exchanger respiratory failure ensues. Clinically, it is generally accepted that an arterial oxygen tension (PaO2) of less than 60 mmHg or a PaCO2 of greater than 50 mmHg, or both, whilst breathing room air are values consistent with the concept of respiratory failure. This article will deal, firstly, with some basic aspects of the physiology of pulmonary gas exchange and more specifically on the measurement of ventilation-perfusion (VA/Q) relationships, the most influential factor determining hypoxaemia. The second part highlights the most important findings on pulmonary gas exchange in the adult respiratory distress syndrome (ARDS) and other common acute respiratory failure conditions, such as pneumonia, acute exacerbation of chronic obstructive pulmonary disease (COPD) and status asthmaticus, based on the data obtained by means of the multiple inert gas elimination approach, a technique which gives a detailed picture of VA/Q ratio distributions.

  3. Reconciling top-down and bottom-up estimates of CO2 fluxes to understand increased seasonal exchange in Northern ecosystems

    NASA Astrophysics Data System (ADS)

    Bastos, A.; Ciais, P.; Zhu, D.; Maignan, F.; Wang, X.; Chevallier, F.; Ballantyne, A.

    2017-12-01

    Continuous atmospheric CO2 monitoring data indicate enhanced seasonal exchange in the high-latitudes in the Northern Hemisphere (above 40oN), mainly attributed to terrestrial ecosystems. Whether this enhancement is mostly explained by increased vegetation growth due to CO2 fertilization and warming, or by changes in land-use and land-management practices is still an unsettled question (e.g. Forkel et al. (2016) and Zeng et al. (2013)). Previous studies have shown that models present variable performance in capturing trends in CO2 amplitude at CO2 monitoring sites, and that Earth System Models present large spread in their estimates of such trends. Here we integrate data of atmospheric CO2 exchange in terrestrial ecosystems by a set of atmospheric CO2 inversions and a range of land-surface models to evaluate the ability of models to reproduce changes in CO2 seasonal exchange within the observation uncertainty. We then analyze the factors that explain the model spread to understand if the trend in seasonal CO2 amplitude may indeed be a useful metric to constrain future changes in terrestrial photosynthesis (Wenzel et al., 2016). We then compare model simulations with satellite and other observation-based datasets of vegetation productivity, biomass stocks and land-cover change to test the contribution of natural (CO2 fertilization, climate) and human (land-use change) factors to the increasing trend in seasonal CO2 amplitude. Forkel, Matthias, et al. "Enhanced seasonal CO2 exchange caused by amplified plant productivity in northern ecosystems." Science 351.6274 (2016): 696-699. Wenzel, Sabrina, et al. "Projected land photosynthesis constrained by changes in the seasonal cycle of atmospheric CO2." Nature 538, no. 7626 (2016): 499-501.Zeng, Ning, et al. "Agricultural Green Revolution as a driver of increasing atmospheric CO2 seasonal amplitude." Nature 515.7527 (2014): 394.

  4. Minimizing back exchange in the hydrogen exchange-mass spectrometry experiment.

    PubMed

    Walters, Benjamin T; Ricciuti, Alec; Mayne, Leland; Englander, S Walter

    2012-12-01

    The addition of mass spectrometry (MS) analysis to the hydrogen exchange (HX) proteolytic fragmentation experiment extends powerful HX methodology to the study of large biologically important proteins. A persistent problem is the degradation of HX information due to back exchange of deuterium label during the fragmentation-separation process needed to prepare samples for MS measurement. This paper reports a systematic analysis of the factors that influence back exchange (solution pH, ionic strength, desolvation temperature, LC column interaction, flow rates, system volume). The many peptides exhibit a range of back exchange due to intrinsic amino acid HX rate differences. Accordingly, large back exchange leads to large variability in D-recovery from one residue to another as well as one peptide to another that cannot be corrected for by reference to any single peptide-level measurement. The usual effort to limit back exchange by limiting LC time provides little gain. Shortening the LC elution gradient by 3-fold only reduced back exchange by ~2%, while sacrificing S/N and peptide count. An unexpected dependence of back exchange on ionic strength as well as pH suggests a strategy in which solution conditions are changed during sample preparation. Higher salt should be used in the first stage of sample preparation (proteolysis and trapping) and lower salt (<20 mM) and pH in the second stage before electrospray injection. Adjustment of these and other factors together with recent advances in peptide fragment detection yields hundreds of peptide fragments with D-label recovery of 90% ± 5%.

  5. Minimizing Back Exchange in the Hydrogen Exchange-Mass Spectrometry Experiment

    NASA Astrophysics Data System (ADS)

    Walters, Benjamin T.; Ricciuti, Alec; Mayne, Leland; Englander, S. Walter

    2012-12-01

    The addition of mass spectrometry (MS) analysis to the hydrogen exchange (HX) proteolytic fragmentation experiment extends powerful HX methodology to the study of large biologically important proteins. A persistent problem is the degradation of HX information due to back exchange of deuterium label during the fragmentation-separation process needed to prepare samples for MS measurement. This paper reports a systematic analysis of the factors that influence back exchange (solution pH, ionic strength, desolvation temperature, LC column interaction, flow rates, system volume). The many peptides exhibit a range of back exchange due to intrinsic amino acid HX rate differences. Accordingly, large back exchange leads to large variability in D-recovery from one residue to another as well as one peptide to another that cannot be corrected for by reference to any single peptide-level measurement. The usual effort to limit back exchange by limiting LC time provides little gain. Shortening the LC elution gradient by 3-fold only reduced back exchange by ~2 %, while sacrificing S/N and peptide count. An unexpected dependence of back exchange on ionic strength as well as pH suggests a strategy in which solution conditions are changed during sample preparation. Higher salt should be used in the first stage of sample preparation (proteolysis and trapping) and lower salt (<20 mM) and pH in the second stage before electrospray injection. Adjustment of these and other factors together with recent advances in peptide fragment detection yields hundreds of peptide fragments with D-label recovery of 90 % ± 5 %.

  6. Characterisation of Translation Elongation Factor eEF1B Subunit Expression in Mammalian Cells and Tissues and Co-Localisation with eEF1A2

    PubMed Central

    Janikiewicz, Justyna; Doig, Jennifer; Abbott, Catherine M.

    2014-01-01

    Translation elongation is the stage of protein synthesis in which the translation factor eEF1A plays a pivotal role that is dependent on GTP exchange. In vertebrates, eEF1A can exist as two separately encoded tissue-specific isoforms, eEF1A1, which is almost ubiquitously expressed, and eEF1A2, which is confined to neurons and muscle. The GTP exchange factor for eEF1A1 is a complex called eEF1B made up of subunits eEF1Bα, eEF1Bδ and eEF1Bγ. Previous studies have cast doubt on the ability of eEF1B to interact with eEF1A2, suggesting that this isoform might use a different GTP exchange factor. We show that eEF1B subunits are all widely expressed to varying degrees in different cell lines and tissues, and at different stages of development. We show that ablation of any of the subunits in human cell lines has a small but significant impact on cell viability and cycling. Finally, we show that both eEF1A1 and eEF1A2 colocalise with all eEF1B subunits, in such close proximity that they are highly likely to be in a complex. PMID:25436608

  7. Analysis of Critical Success Factors of Online International Learning Exchange of Korean School Pupils with English-Speaking Counterparts

    ERIC Educational Resources Information Center

    Lee, Jong-Yeon; Park, Sanghoon

    2017-01-01

    This study identifies the factors influencing the success of online international learning exchange (ILE) among Korean school pupils who partnered with American and Australian pupils. In particular, it examined the effects of self-efficacy (SE), exchange infrastructure (EI) and quality of exchange activities (QEA) on the students' learning…

  8. Anion- or Cation-Exchange Membranes for NaBH4/H2O2 Fuel Cells?

    PubMed Central

    Šljukić, Biljana; Morais, Ana L.; Santos, Diogo M. F.; Sequeira, César A. C.

    2012-01-01

    Direct borohydride fuel cells (DBFC), which operate on sodium borohydride (NaBH4) as the fuel, and hydrogen peroxide (H2O2) as the oxidant, are receiving increasing attention. This is due to their promising use as power sources for space and underwater applications, where air is not available and gas storage poses obvious problems. One key factor to improve the performance of DBFCs concerns the type of separator used. Both anion- and cation-exchange membranes may be considered as potential separators for DBFC. In the present paper, the effect of the membrane type on the performance of laboratory NaBH4/H2O2 fuel cells using Pt electrodes is studied at room temperature. Two commercial ion-exchange membranes from Membranes International Inc., an anion-exchange membrane (AMI-7001S) and a cation-exchange membrane (CMI-7000S), are tested as ionic separators for the DBFC. The membranes are compared directly by the observation and analysis of the corresponding DBFC’s performance. Cell polarization, power density, stability, and durability tests are used in the membranes’ evaluation. Energy densities and specific capacities are estimated. Most tests conducted, clearly indicate a superior performance of the cation-exchange membranes over the anion-exchange membrane. The two membranes are also compared with several other previously tested commercial membranes. For long term cell operation, these membranes seem to outperform the stability of the benchmark Nafion membranes but further studies are still required to improve their instantaneous power load. PMID:24958292

  9. Anion- or Cation-Exchange Membranes for NaBH4/H2O2 Fuel Cells?

    PubMed

    Sljukić, Biljana; Morais, Ana L; Santos, Diogo M F; Sequeira, César A C

    2012-07-19

    Direct borohydride fuel cells (DBFC), which operate on sodium borohydride (NaBH4) as the fuel, and hydrogen peroxide (H2O2) as the oxidant, are receiving increasing attention. This is due to their promising use as power sources for space and underwater applications, where air is not available and gas storage poses obvious problems. One key factor to improve the performance of DBFCs concerns the type of separator used. Both anion- and cation-exchange membranes may be considered as potential separators for DBFC. In the present paper, the effect of the membrane type on the performance of laboratory NaBH4/H2O2 fuel cells using Pt electrodes is studied at room temperature. Two commercial ion-exchange membranes from Membranes International Inc., an anion-exchange membrane (AMI-7001S) and a cation-exchange membrane (CMI-7000S), are tested as ionic separators for the DBFC. The membranes are compared directly by the observation and analysis of the corresponding DBFC's performance. Cell polarization, power density, stability, and durability tests are used in the membranes' evaluation. Energy densities and specific capacities are estimated. Most tests conducted, clearly indicate a superior performance of the cation-exchange membranes over the anion-exchange membrane. The two membranes are also compared with several other previously tested commercial membranes. For long term cell operation, these membranes seem to outperform the stability of the benchmark Nafion membranes but further studies are still required to improve their instantaneous power load.

  10. Performance evaluation on an air-cooled heat exchanger for alumina nanofluid under laminar flow.

    PubMed

    Teng, Tun-Ping; Hung, Yi-Hsuan; Teng, Tun-Chien; Chen, Jyun-Hong

    2011-08-09

    This study analyzes the characteristics of alumina (Al2O3)/water nanofluid to determine the feasibility of its application in an air-cooled heat exchanger for heat dissipation for PEMFC or electronic chip cooling. The experimental sample was Al2O3/water nanofluid produced by the direct synthesis method at three different concentrations (0.5, 1.0, and 1.5 wt.%). The experiments in this study measured the thermal conductivity and viscosity of nanofluid with weight fractions and sample temperatures (20-60°C), and then used the nanofluid in an actual air-cooled heat exchanger to assess its heat exchange capacity and pressure drop under laminar flow. Experimental results show that the nanofluid has a higher heat exchange capacity than water, and a higher concentration of nanoparticles provides an even better ratio of the heat exchange. The maximum enhanced ratio of heat exchange and pressure drop for all the experimental parameters in this study was about 39% and 5.6%, respectively. In addition to nanoparticle concentration, the temperature and mass flow rates of the working fluid can affect the enhanced ratio of heat exchange and pressure drop of nanofluid. The cross-section aspect ratio of tube in the heat exchanger is another important factor to be taken into consideration.

  11. Performance evaluation on an air-cooled heat exchanger for alumina nanofluid under laminar flow

    PubMed Central

    2011-01-01

    This study analyzes the characteristics of alumina (Al2O3)/water nanofluid to determine the feasibility of its application in an air-cooled heat exchanger for heat dissipation for PEMFC or electronic chip cooling. The experimental sample was Al2O3/water nanofluid produced by the direct synthesis method at three different concentrations (0.5, 1.0, and 1.5 wt.%). The experiments in this study measured the thermal conductivity and viscosity of nanofluid with weight fractions and sample temperatures (20-60°C), and then used the nanofluid in an actual air-cooled heat exchanger to assess its heat exchange capacity and pressure drop under laminar flow. Experimental results show that the nanofluid has a higher heat exchange capacity than water, and a higher concentration of nanoparticles provides an even better ratio of the heat exchange. The maximum enhanced ratio of heat exchange and pressure drop for all the experimental parameters in this study was about 39% and 5.6%, respectively. In addition to nanoparticle concentration, the temperature and mass flow rates of the working fluid can affect the enhanced ratio of heat exchange and pressure drop of nanofluid. The cross-section aspect ratio of tube in the heat exchanger is another important factor to be taken into consideration. PMID:21827644

  12. Increase in the CO2 exchange rate of leaves of Ilex rotunda with elevated atmospheric CO2 concentration in an urban canyon

    NASA Astrophysics Data System (ADS)

    Takagi, M.; Gyokusen, Koichiro; Saito, Akira

    It was found that the atmospheric carbon dioxide (CO2) concentration in an urban canyon in Fukuoka city, Japan during August 1997 was about 30 µmol mol-1 higher than that in the suburbs. When fully exposed to sunlight, in situ the rate of photosynthesis in single leaves of Ilex rotunda planted in the urban canyon was higher when the atmospheric CO2 concentration was elevated. A biochemically based model was able to predict the in situ rate of photosynthesis well. The model also predicted an increase in the daily CO2 exchange rate for leaves in the urban canyon with an increase in atmospheric CO2 concentration. However, in situ such an increase in the daily CO2 exchange rate may be offset by diminished sunlight, a higher air temperature and a lower relative humidity. Thus, the daily CO2 exchange rate predicted using the model based soleley on the environmental conditions prevailing in the urban canyon was lower than that predicted based only on environmental factors found in the suburbs.

  13. Isotopic exchange during derivatization of platelet activating factor for gas chromatography-mass spectrometry

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

    Haroldsen, P.E.; Gaskell, S.J.; Weintraub, S.T.

    1991-04-01

    One approach to the quantitative analysis of platelet activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycerol-3-phosphocholine; also referred to as AGEPC, alkyl glyceryl ether phosphocholine) is hydrolytic removal of the phosphocholine group and conversion to an electron-capturing derivative for gas chromatography-negative ion mass spectrometry. (2H3)Acetyl-AGEPC has been commonly employed as an internal standard. When 1-hexadecyl-2-(2H3)acetyl glycerol (obtained by enzymatic hydrolysis of (2H3)-C16:0 AGEPC) is treated with pentafluorobenzoyl chloride at 120 degrees C, the resulting 3-pentafluorobenzoate derivative shows extensive loss of the deuterium label. This exchange is evidently acid-catalyzed since derivatization of 1-hexadecyl-2-acetyl glycerol under the same conditions in the presence of a trace ofmore » 2HCl results in the incorporation of up to three deuterium atoms. Isotope exchange can be avoided if the reaction is carried out at low temperature in the presence of base. Direct derivatization of (2H3)-C16:0 AGEPC by treatment with pentafluorobenzoyl chloride or heptafluorobutyric anhydride also results in loss of the deuterium label. The use of (13C2)-C16:0 AGEPC as an internal standard is recommended for rigorous quantitative analysis.« less

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

    Kim, Woohyun; Katipamula, Srinivas; Lutes, Robert G.

    This report describes how the intelligent load control (ILC) algorithm can be implemented to achieve peak demand reduction while minimizing impacts on occupant comfort. The algorithm was designed to minimize the additional sensors and minimum configuration requirements to enable a scalable and cost-effective implementation for both large and small-/medium-sized commercial buildings. The ILC algorithm uses an analytic hierarchy process (AHP) to dynamically prioritize the available curtailable loads based on both quantitative (deviation of zone conditions from set point) and qualitative rules (types of zone). Although the ILC algorithm described in this report was highly tailored to work with rooftop units,more » it can be generalized for application to other building loads such as variable-air-volume (VAV) boxes and lighting systems.« less

  15. Influence of a finite number of baffles on shell-and-tube heat exchanger performance

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

    Shah, R.K.; Pignotti, A.

    1997-01-01

    In single-phase shell-and-tube heat exchangers, thermal performance prediction is customarily accomplished with an idealization that the number of baffles used is very large and can be assumed to approach infinity. Under this idealization, the temperature change within each baffle compartment is very small in comparison with the total temperature change of the shell fluid through the heat exchanger. Thus the shell fluid can be considered as uniform (perfectly mixed) at every cross section (in a direction normal to the shell axis). It is with this model that the mean temperature difference correction factor is normally derived for single-phase exchangers. Inmore » reality, a finite number of baffles are used, and the condition stated above can be achieved only partially. In this article, a comprehensive review is made and new results are derived where needed to assess the influence of a finite number of baffles on heat transfer performance for 1-1, 1-2, and 1-N TEMA E, 1-2 TEMA J, and 1-2 TEMA G and H single-phase shell-and-tube exchangers. It is shown that the number of baffles required to achieve the performance within about 2% of an exchanger with an infinite number of baffles varies with the type of exchanger and the performance parameters. The new results are presented in tabular form.« less

  16. Willingness to Exchange Health Information via Mobile Devices: Findings From a Population-Based Survey.

    PubMed

    Serrano, Katrina J; Yu, Mandi; Riley, William T; Patel, Vaishali; Hughes, Penelope; Marchesini, Kathryn; Atienza, Audie A

    2016-01-01

    The rapid proliferation of mobile devices offers unprecedented opportunities for patients and health care professionals to exchange health information electronically, but little is known about patients' willingness to exchange various types of health information using these devices. We examined willingness to exchange different types of health information via mobile devices, and assessed whether sociodemographic characteristics and trust in clinicians were associated with willingness in a nationally representative sample. We analyzed data for 3,165 patients captured in the 2013 Health Information National Trends Survey. Multinomial logistic regression analysis was conducted to test differences in willingness. Ordinal logistic regression analysis assessed correlates of willingness to exchange 9 types of information separately. Participants were very willing to exchange appointment reminders (odds ratio [OR] = 6.66; 95% CI, 5.68-7.81), general health tips (OR = 2.03; 95% CI, 1.74-2.38), medication reminders (OR = 2.73; 95% CI, 2.35-3.19), laboratory/test results (OR = 1.76; 95% CI, 1.62-1.92), vital signs (OR = 1.63; 95% CI, 1.48-1.80), lifestyle behaviors (OR = 1.40; 95% CI, 1.24-1.58), and symptoms (OR = 1.62; 95% CI, 1.46-1.79) as compared with diagnostic information. Older adults had lower odds of being more willing to exchange any type of information. Education, income, and trust in health care professional information correlated with willingness to exchange certain types of information. Respondents were less willing to exchange via mobile devices information that may be considered sensitive or complex. Age, socioeconomic factors, and trust in professional information were associated with willingness to engage in mobile health information exchange. Both information type and demographic group should be considered when developing and tailoring mobile technologies for patient-clinician communication. © 2016 Annals of Family Medicine, Inc.

  17. Kinetics of hydrogen/deuterium exchanges in cometary ices

    NASA Astrophysics Data System (ADS)

    Faure, Mathilde; Quirico, Eric; Faure, Alexandre; Schmitt, Bernard; Theulé, Patrice; Marboeuf, Ulysse

    2015-11-01

    The D/H composition of volatile molecules composing cometary ices brings key constraints on the origin of comets, on the extent of their presolar heritage, as well as on the origin of atmospheres and hydrospheres of terrestrial planets. Nevertheless, the D/H composition may have been modified to various extents in the nucleus when a comet approaches the Sun and experiences deep physical and chemical modifications in its subsurface. We question here the evolution of the D/H ratio of organic species by proton exchanges with water ice. We experimentally studied the kinetics of D/H exchanges on the ice mixtures H2O:CD3OD, H2O:CD3ND2 and D2O:HCN. Our results show that fast exchanges occur on the -OH and -NH2 chemical groups, which are processed through hydrogen bonds exchanges with water and by the molecular mobility triggered by structural changes, such as glass transition or crystallization. D/H exchanges kinetic is best described by a second-order kinetic law with activation energies of 4300 ± 900 K and 3300 ± 100 K for H2O:CD3OD and H2O:CD3ND2 ice mixtures, respectively. The corresponding pre-exponential factors ln(A(s-1)) are 25 ± 7 and 20 ± 1, respectively. No exchange was observed in the case of HCN trapped in D2O ice. These results strongly suggest that upon thermal heating (1) -OH and -NH2 chemical groups of any organic molecules loose their primordial D/H composition and equilibrate with water ice, (2) HCN does not experience proton transfer and keeps a primordial D/H composition and (3) C-H chemical groups are not isotopically modified.

  18. A cross-country Exchange Market Pressure (EMP) dataset.

    PubMed

    Desai, Mohit; Patnaik, Ila; Felman, Joshua; Shah, Ajay

    2017-06-01

    The data presented in this article are related to the research article titled - "An exchange market pressure measure for cross country analysis" (Patnaik et al. [1]). In this article, we present the dataset for Exchange Market Pressure values (EMP) for 139 countries along with their conversion factors, ρ (rho). Exchange Market Pressure, expressed in percentage change in exchange rate, measures the change in exchange rate that would have taken place had the central bank not intervened. The conversion factor ρ can interpreted as the change in exchange rate associated with $1 billion of intervention. Estimates of conversion factor ρ allow us to calculate a monthly time series of EMP for 139 countries. Additionally, the dataset contains the 68% confidence interval (high and low values) for the point estimates of ρ 's. Using the standard errors of estimates of ρ 's, we obtain one sigma intervals around mean estimates of EMP values. These values are also reported in the dataset.

  19. Optimal design of the first stage of the plate-fin heat exchanger for the EAST cryogenic system

    NASA Astrophysics Data System (ADS)

    Qingfeng, JIANG; Zhigang, ZHU; Qiyong, ZHANG; Ming, ZHUANG; Xiaofei, LU

    2018-03-01

    The size of the heat exchanger is an important factor determining the dimensions of the cold box in helium cryogenic systems. In this paper, a counter-flow multi-stream plate-fin heat exchanger is optimized by means of a spatial interpolation method coupled with a hybrid genetic algorithm. Compared with empirical correlations, this spatial interpolation algorithm based on a kriging model can be adopted to more precisely predict the Colburn heat transfer factors and Fanning friction factors of offset-strip fins. Moreover, strict computational fluid dynamics simulations can be carried out to predict the heat transfer and friction performance in the absence of reliable experimental data. Within the constraints of heat exchange requirements, maximum allowable pressure drop, existing manufacturing techniques and structural strength, a mathematical model of an optimized design with discrete and continuous variables based on a hybrid genetic algorithm is established in order to minimize the volume. The results show that for the first-stage heat exchanger in the EAST refrigerator, the structural size could be decreased from the original 2.200 × 0.600 × 0.627 (m3) to the optimized 1.854 × 0.420 × 0.340 (m3), with a large reduction in volume. The current work demonstrates that the proposed method could be a useful tool to achieve optimization in an actual engineering project during the practical design process.

  20. Carbonyl sulfide (OCS) as a proxy for GPP: Complications derived from studies on the impact of CO2, soil humidity and sterilization on the OCS exchange between soils and atmosphere

    NASA Astrophysics Data System (ADS)

    Bunk, Rüdiger; Behrendt, Thomas; Yi, Zhigang; Kesselmeier, Jürgen

    2016-04-01

    Carbonyl sulfide is discussed to be used as a proxy for gross primary productivity (GPP) of forest ecosystems. However, soils may interfere. Soils play an important role in budgeting global and local carbonyl sulfide (OCS) fluxes, yet the available data on the uptake and emission behavior of soils in conjunction with environmental factors is limited. The work of many authors has shown that the OCS exchange of soils depends on various factors, such as soil type, atmospheric OCS concentrations, temperature or soil water content (Kesselmeier et al., J. Geophys. Res., 104, No. D9, 11577-11584, 1999; Van Diest & Kesselmeier, Biogeosciences, 5, 475-483, 2008; Masyek et al., PNAS, 111, No 25, 9064-9069, doi: 10.1073/pnas.1319132111, 2014; Whelan and Rhew, J. Geophys. Res. Biogeosciences., 120, 54-62, doi: 10.1002/2014JG002661, 2015) and the light dependent and obviously abiotic OCS production as reported by Whelan and Rhew (2015). To get a better constraint on the impact of some environmental factors on the OCS exchange of soils we used a new laser based integrated cavity output spectroscopy instrument (LGR COS/CO Analyzer Model 907-0028, Los Gatos, Mountain View, California, USA) in conjunction with an automated soil chamber system (as described in Behrendt et al, Biogeosciences, 11, 5463-5492, doi: 10.5194/bg-11-5463-2014, 2014). The OCS exchange of various soils under the full range of possible soil humidity and various CO2 mixing ratios was examined. Additionally OCS exchange of chloroform sterilized subsamples was compared to their live counterparts to illuminate the influence of microorganisms. Results were quite heterogeneous between different soils. With few exceptions, all examined soils show dependence between OCS exchange and soil humidity, usually with strongest uptake at a certain humidity range and less uptake or even emission at higher and lower humidity. Differences in CO2 mixing ratio also clearly impacts on OCS exchange, but trends for different soils vary strongly. One arable soil from organic farming even showed a trend directly opposed to the other arable soils examined. We interpret the heterogeneity in reaction of soils to different soil humidity and CO2 mixing ratios as related to activity of different microbiological communities within the soils. Preliminary experiments with sterilization agents that preferably act again bacteria (streptomycin) or fungi (nystatin) indicate that fungi might have played the dominant biotic role in the soils examined. These complex interactions will affect the exchange of OCS between forest ecosystems and the atmosphere and may hinder the use of this compound to catch GPP in a more CO2 independent way.

  1. Exchange of carbonyl sulfide (OCS) between soils and atmosphere under various CO2 concentrations

    NASA Astrophysics Data System (ADS)

    Bunk, Rüdiger; Behrendt, Thomas; Yi, Zhigang; Andreae, Meinrat O.; Kesselmeier, Jürgen

    2017-06-01

    A new continuous integrated cavity output spectroscopy analyzer and an automated soil chamber system were used to investigate the exchange processes of carbonyl sulfide (OCS) between soils and the atmosphere under laboratory conditions. The exchange patterns of OCS between soils and the atmosphere were found to be highly dependent on soil moisture and ambient CO2 concentration. With increasing soil moisture, OCS exchange ranged from emission under dry conditions to an uptake within an optimum moisture range, followed again by emission at high soil moisture. Elevated CO2 was found to have a significant impact on the exchange rate and direction as tested with several soils. There is a clear tendency toward a release of OCS at higher CO2 levels (up to 7600 ppm), which are typical for the upper few centimeters within soils. At high soil moisture, the release of OCS increased sharply. Measurements after chloroform vapor application show that there is a biotic component to the observed OCS exchange. Furthermore, soil treatment with the fungi inhibitor nystatin showed that fungi might be the dominant OCS consumers in the soils we examined. We discuss the influence of soil moisture and elevated CO2 on the OCS exchange as a change in the activity of microbial communities. Physical factors such as diffusivity that are governed by soil moisture also play a role. Comparing KM values of the enzymes to projected soil water CO2 concentrations showed that competitive inhibition is unlikely for carbonic anhydrase and PEPCO but might occur for RubisCO at higher CO2 concentrations.

  2. An Early Model for Value and Sustainability in Health Information Exchanges: Qualitative Study

    PubMed Central

    2018-01-01

    Background The primary value relative to health information exchange has been seen in terms of cost savings relative to laboratory and radiology testing, emergency department expenditures, and admissions. However, models are needed to statistically quantify value and sustainability and better understand the dependent and mediating factors that contribute to value and sustainability. Objective The purpose of this study was to provide a basis for early model development for health information exchange value and sustainability. Methods A qualitative study was conducted with 21 interviews of eHealth Exchange participants across 10 organizations. Using a grounded theory approach and 3.0 as a relative frequency threshold, 5 main categories and 16 subcategories emerged. Results This study identifies 3 core current perceived value factors and 5 potential perceived value factors—how interviewees predict health information exchanges may evolve as there are more participants. These value factors were used as the foundation for early model development for sustainability of health information exchange. Conclusions Using the value factors from the interviews, the study provides the basis for early model development for health information exchange value and sustainability. This basis includes factors from the research: fostering consumer engagement; establishing a provider directory; quantifying use, cost, and clinical outcomes; ensuring data integrity through patient matching; and increasing awareness, usefulness, interoperability, and sustainability of eHealth Exchange. PMID:29712623

  3. Prototype Vent Gas Heat Exchanger for Exploration EVA - Performance and Manufacturing Characteristics

    NASA Technical Reports Server (NTRS)

    Jennings, Mallory; Quinn, Gregory; Strange, Jeremy

    2012-01-01

    NASA is developing new portable life support system (PLSS) technologies, which it is demonstrating in an unmanned ground based prototype unit called PLSS 2.0. One set of technologies within the PLSS provides suitable ventilation to an astronaut while on an EVA. A new component within the ventilation gas loop is a liquid-to-gas heat exchanger to transfer excess heat from the gas to the thermal control system's liquid coolant loop. A unique bench top prototype heat exchanger was built and tested for use in PLSS 2.0. The heat exchanger was designed as a counter-flow, compact plate fin type using stainless steel. Its design was based on previous compact heat exchangers manufactured by United Technologies Aerospace Systems, but was half the size of any previous heat exchanger model and one third the size of previous liquid-to-gas heat exchangers. The prototype heat exchanger was less than 40 cubic inches and weighed 2.6 lb. The water side and gas side pressure drops were 0.8 psid and 0.5 inches of water, respectively. Performance of the heat exchanger at the nominal pressure of 4.1 psia was measured at 94%, while a gas inlet pressure of 25 psia resulted in an effectiveness of 84%. These results compared well with the model, which was scaled for the small size. Modeling of certain phenomena that affect performance, such as flow distribution in the headers was particularly difficult due to the small size of the heat exchanger. Data from the tests has confirmed the correction factors that were used in these parts of the model.

  4. 17 CFR 229.904 - (Item 904) Risk factors and other considerations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 2 2011-04-01 2011-04-01 false (Item 904) Risk factors and... 904) Risk factors and other considerations. (a) Immediately following the summary required by Item 903 of this subpart (§ 229.903), describe in reasonable detail each material risk and effect of the roll...

  5. A Critical Evaluation of the Influence of the Dark Exchange Current on the Performance of Dye-Sensitized Solar Cells

    PubMed Central

    García-Rodríguez, Rodrigo; Villanueva-Cab, Julio; Anta, Juan A.; Oskam, Gerko

    2016-01-01

    The influence of the thickness of the nanostructured, mesoporous TiO2 film on several parameters determining the performance of a dye-sensitized solar cell is investigated both experimentally and theoretically. We pay special attention to the effect of the exchange current density in the dark, and we compare the values obtained by steady state measurements with values extracted from small perturbation techniques. We also evaluate the influence of exchange current density, the solar cell ideality factor, and the effective absorption coefficient of the cell on the optimal film thickness. The results show that the exchange current density in the dark is proportional to the TiO2 film thickness, however, the effective absorption coefficient is the parameter that ultimately defines the ideal thickness. We illustrate the importance of the exchange current density in the dark on the determination of the current–voltage characteristics and we show how an important improvement of the cell performance can be achieved by decreasing values of the total series resistance and the exchange current density in the dark. PMID:28787833

  6. Human factors issues in aircraft maintenance and inspection : "information exchange and communications".

    DOT National Transportation Integrated Search

    1990-11-01

    The Federal Aviation Administration sponsored a 2-day meeting in December 1989 as part of a continuing program to address issues of human factors and personnel performance in aviation maintenance and inspection. This meeting focused on issues of "inf...

  7. Influence of disturbance on carbon exchange in a permafrost collapse and adjacent burned forest

    USGS Publications Warehouse

    Myers-Smith, I. H.; McGuire, A.D.; Harden, J.W.; Chapin, F. S.

    2007-01-01

    We measured CO2 and CH4 exchange from the center of a Sphagnum-dominated permafrost collapse, through an aquatic most, and into a recently burned black spruce forest on the Tanana River floodplain in interior Alaska. In the anomalously dry growing season of 2004, both the collapse and the surrounding burned area were net sink, s for CO2, with a mean daytime net ecosystem exchange of -1.4 ??mol CO2 m-2 s-1, while the moat was a CH4 source with a mean flux of 0.013 ??mol CH4 m-2 s-1. Regression analyses identified temperature as the dominant factor affecting intragrowing season variation in CO2 exchange and soil moisture as the primary control influencing CH4 emissions. CH4 emissions during the wettest portion of the growing season were four times higher than during the driest periods. If temperatures continue to warm, peatlahd vegetation will likely expand with permafrost degradation, resulting in greater carbon accumulation and methane emissions for the landscape as a whole. Copyright 2007 by the American Geophysical Union.

  8. Stable Fe isotope fractionation during anaerobic microbial dissimilatory iron reduction at low pH

    NASA Astrophysics Data System (ADS)

    Chanda, P.; Amenabar, M. J.; Boyd, E. S.; Beard, B. L.; Johnson, C.

    2017-12-01

    In low-temperature anaerobic environments microbial dissimilatory iron reduction (DIR) plays an important role in Fe cycling. At neutral pH, sorption of aqueous Fe(II) (Fe(II)aq, produced by DIR) catalyzes isotopic exchange between Fe(II) and solid Fe(III), producing 56Fe/54Fe fractionations on the order of 3‰ during DIR[1,2,3]. At low pH, however, the absence of sorbed Fe(II) produces only limited abiologic isotopic exchange[4]. Here we investigated the scope of isotopic exchange between Fe(II)aq and ferric (hydr)oxides (ferrihydrite and goethite) and the associated stable Fe isotope fractionation during DIR by Acidianus strain DS80 at pH 3.0 and 80°C[5]. Over 19 days, 13% reduction of both minerals via microbial DIR was observed. The δ56Fe values of the fluid varied from -2.31 to -1.63‰ (ferrihydrite) and -0.45 to 0.02‰ (goethite). Partial leaching of bulk solid from each reactor with dilute HCl showed no sorption of Fe(II), and the surface layers of the solids were composed of Fe(III) with high δ56Fe values (ferrihydrite: 0.20 to 0.48‰ and goethite: 1.20 to 1.30‰). These results contrast with the lack of Fe isotope exchange in abiologic low-pH systems and indicate a key role for biology in catalyzing Fe isotope exchange between Fe(II)aq and Fe(III) solids, despite the absence of sorbed Fe(II). The estimated fractionation factor (ΔFeFe(III) -Fe(II)aq 2.6‰) from leaching of ferrihydrite is similar to the abiologic equilibrium fractionation factor ( 3.0‰)[3]. The fractionation factor (ΔFeFe(III) -Fe(II)aq 2.0‰) for goethite is higher than the abiologic fractionation factor ( 1.05‰)[2], but is consistent with the previously proposed "distorted surface layer" of goethite produced during the exchange with Fe(II)aq at neutral pH[1]. This study indicates that significant variations in Fe isotope compositions may be produced in low-pH environments where biological cycling of Fe occurs, in contrast to the expected lack of isotopic fractionation in low-pH abiologic systems, and such results bear on the search for biosignatures in Mars and Mars-analog settings. [1] Crosby et al., 2007 Geobiol. 5, 169-189 [2] Beard et al., 2010 Earth Planet. Sci. Lett. 295, 241-250 [3] Wu et al., 2011 Environ. Sci. Technol. 45, 1847-1852 [4] Reddy et al., 2015 Chem. Geol. 397, 118-127 [5] Amenabar et al., 2017 Nat. Geosci. In press

  9. Influence of market factors on the pricing of exchange traded metals in the medium term

    NASA Astrophysics Data System (ADS)

    Bogdanov, S. V.; Shevelev, I. M.; Chernyi, S. A.

    2017-06-01

    On the basis of comparison of the influence of the stock exchange factors on the pricing of nonferrous metals for medium term with similar results for short term, it has been established that the main attention should be paid to the changes in the pricing environment on the metal market as a function of the prices of exchange traded metals. The situation on the market of energy carriers (hydrocarbons) and the European, American, and Asian stock exchanges can be based on parity and even significantly influence the variation of the metal prices. In the medium term, constructive development of metal trade should be reasonably promoted by changing the elasticity of supply with regard to prices for exchange traded metals and by applying the stock exchange factors that positively influence the pricing on commodity and stock markets.

  10. Moderating Effect of Intimate Exchange on Delinquent Socialization Processes

    ERIC Educational Resources Information Center

    Gaertner, Alden E.; Fite, Paula J.; Colder, Craig R.

    2011-01-01

    Research indicates peer socialization processes affect the development of problem behavior in childhood and adolescence; however moderating peer factors have not been readily examined. Friendship intimate exchange may be an important factor to consider, as literature suggests that intimate exchange becomes an increasingly important aspect of…

  11. Structure of the nucleotide exchange factor eIF2B reveals mechanism of memory-enhancing molecule.

    PubMed

    Tsai, Jordan C; Miller-Vedam, Lakshmi E; Anand, Aditya A; Jaishankar, Priyadarshini; Nguyen, Henry C; Renslo, Adam R; Frost, Adam; Walter, Peter

    2018-03-30

    Regulation by the integrated stress response (ISR) converges on the phosphorylation of translation initiation factor eIF2 in response to a variety of stresses. Phosphorylation converts eIF2 from a substrate to a competitive inhibitor of its dedicated guanine nucleotide exchange factor, eIF2B, thereby inhibiting translation. ISRIB, a drug-like eIF2B activator, reverses the effects of eIF2 phosphorylation, and in rodents it enhances cognition and corrects cognitive deficits after brain injury. To determine its mechanism of action, we solved an atomic-resolution structure of ISRIB bound in a deep cleft within decameric human eIF2B by cryo-electron microscopy. Formation of fully active, decameric eIF2B holoenzyme depended on the assembly of two identical tetrameric subcomplexes, and ISRIB promoted this step by cross-bridging a central symmetry interface. Thus, regulation of eIF2B assembly emerges as a rheostat for eIF2B activity that tunes translation during the ISR and that can be further modulated by ISRIB. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  12. Social network-related risk factors for bloodborne virus infections among injection drug users receiving syringes through secondary exchange.

    PubMed

    De, Prithwish; Cox, Joseph; Boivin, Jean-François; Platt, Robert W; Jolly, Ann M

    2008-01-01

    Secondary syringe exchange (SSE) refers to the exchange of sterile syringes between injection drug users (IDUs). To date there has been limited examination of SSE in relation to the social networks of IDUs. This study aimed to identify characteristics of drug injecting networks associated with the receipt of syringes through SSE. Active IDUs were recruited from syringe exchange and methadone treatment programs in Montreal, Canada, between April 2004 and January 2005. Information on each participant and on their drug-injecting networks was elicited using a structured, interviewer-administered questionnaire. Subjects' network characteristics were examined in relation to SSE using regression models with generalized estimating equations. Of 218 participants, 126 were SSE recipients with 186 IDUs in their injecting networks. The 92 non-recipients reported 188 network IDUs. Networks of SSE recipients and non-recipients were similar with regard to network size and demographics of network members. In multivariate analyses adjusted for age and gender, SSE recipients were more likely than non-recipients to self-report being HIV-positive (OR=3.56 [1.54-8.23]); require or provide help with injecting (OR=3.74 [2.01-6.95]); have a social network member who is a sexual partner (OR=1.90 [1.11-3.24]), who currently attends a syringe exchange or methadone program (OR=2.33 [1.16-4.70]), injects daily (OR=1.77 [1.11-2.84]), and shares syringes with the subject (OR=2.24 [1.13-4.46]). SSE is associated with several injection-related risk factors that could be used to help focus public health interventions for risk reduction. Since SSE offers an opportunity for the dissemination of important prevention messages, SSE-based networks should be used to improve public health interventions. This approach can optimize the benefits of SSE while minimizing the potential risks associated with the practice of secondary exchange.

  13. Analysis of factors affecting gas exchange in intravascular blood gas exchanger.

    PubMed

    Niranjan, S C; Clark, J W; San, K Y; Zwischenberger, J B; Bidani, A

    1994-10-01

    A mathematical model of an intravascular hollow-fiber gas-exchange device, called IVOX, has been developed using a Krogh cylinder-like approach with a repeating unit structure comprised of a single fiber with gas flowing through its lumen surrounded by a coaxial cylinder of blood flowing in the opposite direction. Species mass balances on O2 and CO2 result in a nonlinear coupled set of convective-diffusion parabolic partial differential equations that are solved numerically using an alternating-direction implicit finite-difference method. Computed results indicated the presence of a large resistance to gas transport on the external (blood) side of the hollow-fiber exchanger. Increasing gas flow through the device favored CO2 removal from but not O2 addition to blood. Increasing blood flow over the device favored both CO2 removal as well as O2 addition. The rate of CO2 removal increased linearly with the transmural PCO2 gradient imposed across the device. The effect of fiber crimping on blood phase mass transfer resistance was evaluated indirectly by varying species blood diffusivity. Computed results indicated that CO2 excretion by IVOX can be significantly enhanced with improved bulk mixing of vena caval blood around the IVOX fibers.

  14. Synaptopodin Is a Coincidence Detector of Tyrosine versus Serine/Threonine Phosphorylation for the Modulation of Rho Protein Crosstalk in Podocytes

    PubMed Central

    Buvall, Lisa; Wallentin, Hanna; Sieber, Jonas; Andreeva, Svetlana; Choi, Hoon Young; Mundel, Peter

    2017-01-01

    Tyrosine and serine/threonine signal-transduction pathways influence many aspects of cell behavior, including the spatial and temporal regulation of the actin cytoskeleton. However, little is known about how input from diverse tyrosine and serine/threonine kinases is integrated to control Rho protein crosstalk and actin remodeling, which are critically important in podocyte health and disease. Here we unveil the proteolytically-regulated, actin organizing protein synaptopodin as a coincidence detector of tyrosine versus serine/threonine phosphorylation. We show that serine/threonine and tyrosine kinases duel for synaptopodin stability versus degradation. EGFR/Src-mediated tyrosine phosphorylation of synaptopodin in podocytes promotes binding to the serine/threonine phosphatase calcineurin. This leads to the loss of 14–3-3 binding, resulting in synaptopodin degradation, Vav2 activation, enhanced Rac1 signaling, and ultimate loss of stress fibers. Our studies reveal how synaptopodin, a single proteolytically-controlled protein, integrates antagonistic tyrosine versus serine/threonine phosphorylation events for the dynamic control of the actin cytoskeleton in podocytes. PMID:27628902

  15. Synaptopodin Is a Coincidence Detector of Tyrosine versus Serine/Threonine Phosphorylation for the Modulation of Rho Protein Crosstalk in Podocytes.

    PubMed

    Buvall, Lisa; Wallentin, Hanna; Sieber, Jonas; Andreeva, Svetlana; Choi, Hoon Young; Mundel, Peter; Greka, Anna

    2017-03-01

    Tyrosine and serine/threonine signal-transduction pathways influence many aspects of cell behavior, including the spatial and temporal regulation of the actin cytoskeleton. However, little is known about how input from diverse tyrosine and serine/threonine kinases is integrated to control Rho protein crosstalk and actin remodeling, which are critically important in podocyte health and disease. Here we unveil the proteolytically-regulated, actin organizing protein synaptopodin as a coincidence detector of tyrosine versus serine/threonine phosphorylation. We show that serine/threonine and tyrosine kinases duel for synaptopodin stability versus degradation. EGFR/Src-mediated tyrosine phosphorylation of synaptopodin in podocytes promotes binding to the serine/threonine phosphatase calcineurin. This leads to the loss of 14-3-3 binding, resulting in synaptopodin degradation, Vav2 activation, enhanced Rac1 signaling, and ultimate loss of stress fibers. Our studies reveal how synaptopodin, a single proteolytically-controlled protein, integrates antagonistic tyrosine versus serine/threonine phosphorylation events for the dynamic control of the actin cytoskeleton in podocytes. Copyright © 2017 by the American Society of Nephrology.

  16. Fluorescein angiography and retinal vascular development in premature infants.

    PubMed

    Purcaro, Velia; Velia, Purcaro; Baldascino, Antonio; Antonio, Baldascino; Papacci, Patrizia; Patrizia, Papacci; Giannantonio, Carmen; Carmen, Giannantonio; Molisso, Anna; Anna, Molisso; Molle, Fernando; Fernando, Molle; Lepore, Domenico; Domenico, Lepore; Romagnoli, Costantino; Costantino, Romagnoli

    2012-10-01

    To investigate the role of fluorescein angiography (FA) in the management of retinopathy of prematurity (ROP) in preterm newborns. An observational case series of 13 extremely low birth weight infants. From September 2009 to March 2010, 13 newborn infants with a gestational age <29 weeks end/or birth weight <1000 g underwent serial fluorescein angiography with RetCam (Clarity, Pleasanton, CA) every 2 weeks. The fluorescein angiograms were examined to optimize the timing of diagnosis of ROP and to investigate development of retinal and choroidal vascularization. There were no side effects related to FA. Variable features of retinal and choroidal circulation in preterm infants with a high risk of developing ROP were noted. FA allows vessels branching at the junction between vascular and avascular retina (V-Av junction) to be viewed easily and shows the ROP findings that sometimes cannot be seen by indirect ophthalmoscopy. Dye leakage is the most significant sign of progression to severe ROP or the need for surgery in newborn babies with ROP. RetCam-assisted intravenous FA is safe and allows a more objective assessment of the ROP stage and zone.

  17. Development of a High-Throughput Ion-Exchange Resin Characterization Workflow.

    PubMed

    Liu, Chun; Dermody, Daniel; Harris, Keith; Boomgaard, Thomas; Sweeney, Jeff; Gisch, Daryl; Goltz, Bob

    2017-06-12

    A novel high-throughout (HTR) ion-exchange (IEX) resin workflow has been developed for characterizing ion exchange equilibrium of commercial and experimental IEX resins against a range of different applications where water environment differs from site to site. Because of its much higher throughput, design of experiment (DOE) methodology can be easily applied for studying the effects of multiple factors on resin performance. Two case studies will be presented to illustrate the efficacy of the combined HTR workflow and DOE method. In case study one, a series of anion exchange resins have been screened for selective removal of NO 3 - and NO 2 - in water environments consisting of multiple other anions, varied pH, and ionic strength. The response surface model (RSM) is developed to statistically correlate the resin performance with the water composition and predict the best resin candidate. In case study two, the same HTR workflow and DOE method have been applied for screening different cation exchange resins in terms of the selective removal of Mg 2+ , Ca 2+ , and Ba 2+ from high total dissolved salt (TDS) water. A master DOE model including all of the cation exchange resins is created to predict divalent cation removal by different IEX resins under specific conditions, from which the best resin candidates can be identified. The successful adoption of HTR workflow and DOE method for studying the ion exchange of IEX resins can significantly reduce the resources and time to address industry and application needs.

  18. 78 FR 36625 - Self-Regulatory Organizations; Chicago Mercantile Exchange Inc.; Notice of Designation of a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-18

    ...\\ and Rule 19b-4 thereunder,\\2\\ a proposed rule change to make adjustments to the liquidity risk factor... liquidity risk factor component. The proposed rule change was published for comment in the Federal Register... on Proposed Rule Change Related to the Liquidity Factor of CME's CDS Margin Methodology June 12, 2013...

  19. Backbone dynamics of a model membrane protein: measurement of individual amide hydrogen-exchange rates in detergent-solubilized M13 coat protein using /sup 13/C NMR hydrogen/deuterium isotope shifts

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

    Henry, G.D.; Weiner, J.H.; Sykes, B.D.

    Hydrogen-exchange rates have been measured for individual assigned amide protons in M13 coat protein, a 50-residue integral membrane protein, using a /sup 13/C nuclear magnetic resonance (NMR) equilibrium isotope shift technique. The locations of the more rapidly exchanging amides have been determined. In D/sub 2/O solutions, a peptide carbonyl resonance undergoes a small upfield isotope shift (0.08-0.09 ppm) from its position in H/sub 2/O solutions; in 1:1 H/sub 2/O/D/sub 2/O mixtures, the carbonyl line shape is determined by the exchange rate at the adjacent nitrogen atom. M13 coat protein was labeled biosynthetically with /sup 13/C at the peptide carbonyls ofmore » alanine, glycine, phenylalanine, proline, and lysine, and the exchange rates of 12 assigned amide protons in the hydrophilic regions were measured as a function of pH by using the isotope shift method. This equilibrium technique is sensitive to the more rapidly exchanging protons which are difficult to measure by classical exchange-out experiments. In proteins, structural factors, notably H bonding, can decrease the exchange rate of an amide proton by many orders of magnitude from that observed in the freely exposed amides of model peptides such as poly(DL-alanine). With corrections for sequence-related inductive effects, the retardation of amide exchange in sodium dodecyl sulfate solubilized coat protein has been calculated with respect to poly(DL-alanine). The most rapidly exchanging protons, which are retarded very little or not at all, are shown to occur at the N- and C-termini of the molecule. A model of the detergent-solubilized coat protein is constructed from these H-exchange data which is consistent with circular dichroism and other NMR results.« less

  20. The structure of social exchange in self-help support groups: development of a measure.

    PubMed

    Brown, Louis D; Tang, Xiaohui; Hollman, Ruth L

    2014-03-01

    Self-help support groups are indigenous community resources designed to help people manage a variety of personal challenges, from alcohol abuse to xeroderma pigmentosum. The social exchanges that occur during group meetings are central to understanding how people benefit from participation. This paper examines the different types of social exchange behaviors that occur during meetings, using two studies to develop empirically distinct scales that reliably measure theoretically important types of exchange. Resource theory informed the initial measurement development efforts. Exploratory factor analyses from the first study led to revisions in the factor structure of the social exchange scales. The revised measure captured the exchange of emotional support, experiential information, humor, unwanted behaviors, and exchanges outside meetings. Confirmatory factor analyses from a follow-up study with a different sample of self-help support groups provided good model fit, suggesting the revised structure accurately represented the data. Further, the scales demonstrated good convergent and discriminant validity with related constructs. Future research can use the scales to identify aspects of social exchange that are most important in improving health outcomes among self-help support group participants. Groups can use the scales in practice to celebrate strengths and address weaknesses in their social exchange dynamics.

  1. Oxygen and hydrogen isotope fractionation in serpentine-water and talc-water systems from 250 to 450 °C, 50 MPa

    USGS Publications Warehouse

    Saccocia, Peter J.; Seewald, Jeffrey S.; Shanks, Wayne C.

    2009-01-01

    Oxygen and hydrogen isotope fractionation factors in the talc–water and serpentine–water systems have been determined by laboratory experiment from 250 to 450 °C at 50 MPa using the partial exchange technique. Talc was synthesized from brucite + quartz, resulting in nearly 100% exchange during reaction at 350 and 450 °C. For serpentine, D–H exchange was much more rapid than 18O–16O exchange when natural chrysotile fibers were employed in the initial charge. In experiments with lizardite as the starting charge, recrystallization to chrysotile enhanced the rate of 18O–16O exchange with the coexisting aqueous phase. Oxygen isotope fractionation factors in both the talc–water and serpentine–water systems decrease with increasing temperature and can be described from 250 to 450 °C by the relationships: 1000 ln  = 11.70 × 106/T2 − 25.49 × 103/T + 12.48 and 1000 ln  = 3.49 × 106/T2 − 9.48 where T is temperature in Kelvin. Over the same temperature interval at 50 MPa, talc–water D–H fractionation is only weakly dependent on temperature, similar to brucite and chlorite, and can be described by the equation: 1000 ln  = 10.88 × 106/T2 − 41.52 × 103/T + 5.61 where T is temperature in Kelvin. Our D–H serpentine–water fractionation factors calibrated by experiment decrease with temperature and form a consistent trend with fractionation factors derived from lower temperature field calibrations. By regression of these data, we have refined and extended the D–H fractionation curve from 25 to 450 °C, 50 MPa as follows: 1000 ln  = 3.436 × 106/T2 − 34.736 × 103/T + 21.67 where T is temperature in Kelvin. These new data should improve the application of D–H and 18O–16O isotopes to constrain the temperature and origin of hydrothermal fluids responsible for serpentine formation in a variety of geologic settings.

  2. Investigation of Chemical Exchange at Intermediate Exchange Rates using a Combination of Chemical Exchange Saturation Transfer (CEST) and Spin-Locking methods (CESTrho)

    PubMed Central

    Kogan, Feliks; Singh, Anup; Cai, Keija; Haris, Mohammad; Hariharan, Hari; Reddy, Ravinder

    2011-01-01

    Proton exchange imaging is important as it allows for visualization and quantification of the distribution of specific metabolites with conventional MRI. Current exchange mediated MRI methods suffer from poor contrast as well as confounding factors that influence exchange rates. In this study we developed a new method to measure proton exchange which combines chemical exchange saturation transfer (CEST) and T1ρ magnetization preparation methods (CESTrho). We demonstrated that this new CESTrho sequence can detect proton exchange in the slow to intermediate exchange regimes. It has a linear dependence on proton concentration which allows it to be used to quantitatively measure changes in metabolite concentration. Additionally, the magnetization scheme of this new method can be customized to make it insensitive to changes in exchange rate while retaining its dependency on solute concentration. Finally, we showed the feasibility of using CESTrho in vivo. This sequence is able to detect proton exchange at intermediate exchange rates and is unaffected by the confounding factors that influence proton exchange rates thus making it ideal for the measurement of metabolites with exchangeable protons in this exchange regime. PMID:22009759

  3. Investigation of chemical exchange at intermediate exchange rates using a combination of chemical exchange saturation transfer (CEST) and spin-locking methods (CESTrho).

    PubMed

    Kogan, Feliks; Singh, Anup; Cai, Keija; Haris, Mohammad; Hariharan, Hari; Reddy, Ravinder

    2012-07-01

    Proton exchange imaging is important as it allows for visualization and quantification of the distribution of specific metabolites with conventional MRI. Current exchange mediated MRI methods suffer from poor contrast as well as confounding factors that influence exchange rates. In this study we developed a new method to measure proton exchange which combines chemical exchange saturation transfer and T(1)(ρ) magnetization preparation methods (CESTrho). We demonstrated that this new CESTrho sequence can detect proton exchange in the slow to intermediate exchange regimes. It has a linear dependence on proton concentration which allows it to be used to quantitatively measure changes in metabolite concentration. Additionally, the magnetization scheme of this new method can be customized to make it insensitive to changes in exchange rate while retaining its dependency on solute concentration. Finally, we showed the feasibility of using CESTrho in vivo. This sequence is able to detect proton exchange at intermediate exchange rates and is unaffected by the confounding factors that influence proton exchange rates thus making it ideal for the measurement of metabolites with exchangeable protons in this exchange regime. Copyright © 2011 Wiley Periodicals, Inc.

  4. Metal chalcogenide nanoparticle gel networks: Their formation mechanism and application for novel material generation and heavy metal water remediation via cation exchange reactions

    NASA Astrophysics Data System (ADS)

    Palhares, Leticia F.

    The dissertation research is focused on (1) uncovering the mechanism of metal chalcogenide nanoparticle gel formation; (2) extending the cation exchange reaction protocol to zinc sulfide gel networks, with the goal of accessing new aerogel chemistries and understanding the factors that drive the process; and (3) conducting a quantitative analysis of the ability of ZnS aerogels to remove heavy metal ions from aqueous solutions. The mechanism of metal chalcogenide nanoparticle gel formation was investigated using Raman spectroscopy and X-ray Photoelectron Spectroscopy to probe the chemical changes that occur during the gelation process. These techniques suggest that the bonding between the particles in the CdSe nanoparticle gels is due to the oxidation of surface selenide species, forming covalent Se--Se bonds. Treating the gel networks with a suitable reducing agent, such as a thiol, breaks the covalent bond and disperses the gel network. The addition of sodium borohydride, a "pure" reducing agent, also breaks down the gel network, strengthening the hypothesis that the reducing character of the thiols, not their ligation ability, is responsible for the gel network breakdown. UV-Vis spectroscopy, Transmission Electron Microscopy and Powder X-ray Diffraction were used to analyze the particles after successive gelation-dispersion cycles. The primary particle size decreases after repeated oxidation-reduction cycles, due to nanoparticle surface etching. This trend is observed for CdSe and CdS gel networks, allowing for the proposition that the oxidative-reductive mechanism responsible for the formation-dispersion of the gels is general, applying to other metal chalcogenide nanocrystals as well. The cation exchange reaction previously demonstrated for CdSe gels was extended to ZnS gel networks. The exchange occurs under mild reaction conditions (room temperature, methanol solvent) with exchanging ions of different size, charge and mobility (Ag+, Pb2+, Cd2+ , Cu2+). The overall reaction is kinetically controlled, since systems with similar solubility, and thus similar thermodynamic driving force (e.g. PbS and CdS) exchange at very different rates. A correlation exists between the speed of the reaction and the difference between the reduction potential of the incoming cation and that of Zn2+; the larger the difference, the faster the exchange. At the same time, the porosity of the aerogels and the surfactant-free surfaces hold great importance for the exchange reactions, allowing for exchange between cations of similar size and charge (i.e. Pb2+ for Zn2+), a phenomenon that was previously reported as impossible in ligand-capped metal chalcogenide nanoparticles. These observations allowed for a better understanding of the factors governing the cation exchange reaction in nanoscale metal chalcogenides. Quaternary ZnS-CuInS2 gels were obtained by cation exchange with Cu+ and In3+, but the pure CuInS2 phase was not obtained under the mild reaction conditions used, probably due to the very different mobility of the two exchanging cations. The kinetically fast cation exchange process and the propensity of the soft chalcogenide gel networks to bind heavy metal ions selectively, suggest that these materials could also be suitable for the removal of heavy metal ions from the environment. The dissertation research studied the capacity of ZnS aerogels to sequester heavy metal ions such as Pb2+ and Hg2+ from water. The materials are efficient in removing the heavy metal ions from aqueous solutions with a wide range of initial concentrations. For initial concentrations that mimic an environmental spill (i.e. 100 ppb Pb2+), the treatment with the aerogel affords a final concentration lower than the 15 ppm action level recommended by the EPA. Under thermodynamically forcing conditions, the water remediation capacity of the ZnS nanoparticle aerogels was determined to be 14.2 mmol Pb2+ / g ZnS aerogel, which is the highest value reported to date.

  5. Na+/Ca2+ exchange and regulation of cytoplasmic concentration of calcium in rat cerebellar neurons treated with glutamate.

    PubMed

    Storozhevykh, T P; Sorokina, E G; Vabnitz, A V; Senilova, Ya E; Tukhbatova, G R; Pinelis, V G

    2007-07-01

    In the present work, the forward and/or reversed Na+/Ca2+ exchange in cerebellar granular cells was suppressed by substitution of Na+o by Li+ before, during, and after exposure to glutamate for varied time and also using the inhibitor KB-R7943 of the reversed exchange. After glutamate challenge for 1 min, Na+o/Li+ substitution did not influence the recovery of low [Ca2+]i in a calcium-free medium. A 1-h incubation with 100 microM glutamate induced in the neurons a biphasic and irreversible [Ca2+]i rise (delayed calcium deregulation (DCD)), enhancement of [Na+]i, and decrease in the mitochondrial potential. If Na+o had been substituted by Li+ before the application of glutamate, i.e. the exchange reversal was suppressed during the exposure to glutamate, the number of cells with DCD was nearly fourfold lowered. However, addition of the Na+/K+-ATPase inhibitor ouabain (0.5 mM) not preventing the exchange reversal also decreased DCD in the presence of glutamate. Both exposures decreased the glutamate-caused loss of intracellular ATP. Glucose deprivation partially abolished protective effects of the Na+o/Li+ substitution and ouabain. KB-R7943 (10 microM) increased 7.4-fold the number of cells with the [Ca2+]i decreased to the basal level after the exposure to glutamate. Thus, reversal of the Na+/Ca2+ exchange reinforced the glutamate-caused perturbations of calcium homeostasis in the neurons and slowed the recovery of the decreased [Ca2+]i in the post-glutamate period. However, for development of DCD, in addition to the exchange reversal, other factors are required, in particular a decrease in the intracellular concentration of ATP.

  6. The relationship between social network characteristics and exchanging sex for drugs or money among drug users in Baltimore, MD, USA.

    PubMed

    Latkin, C A; Hua, W; Forman, V L

    2003-11-01

    The current study examined social network and drug use factors associated with buying and selling sex among a sample of opiate and cocaine users in Baltimore, Maryland. A sample of 702 drug users who were sexually active were administered a social network and risk behaviour inventory. Compared to 25% of men, only 1.7% of women reported a history of giving money or drugs to get sex during the past 90 days. Conversely, more women (21.2%) than men (4.7%) sold sex for money or drugs. Those who sold sex were more likely to be low frequency crack smokers, were more likely to drink alcohol at least once a day, had a higher average number of crack-only smokers in their network, and had a smaller number of kin in their network. Men who exchanged money or drugs for sex tended to be low frequency crack smokers and reported having more crack-only smokers and injectors and fewer kin in their networks. The results suggest that network composition may be a risk factor for exchanging sex, particularly with respect to crack users, while kin may be a protective factor. These associations may be either a cause or consequence of exchanging sex.

  7. Abiologic silicon isotope fractionation between aqueous Si and Fe(III)-Si gel in simulated Archean seawater: Implications for Si isotope records in Precambrian sedimentary rocks

    NASA Astrophysics Data System (ADS)

    Zheng, Xin-Yuan; Beard, Brian L.; Reddy, Thiruchelvi R.; Roden, Eric E.; Johnson, Clark M.

    2016-08-01

    Precambrian Si-rich sedimentary rocks, including cherts and banded iron formations (BIFs), record a >7‰ spread in 30Si/28Si ratios (δ30Si values), yet interpretation of this large variability has been hindered by the paucity of data on Si isotope exchange kinetics and equilibrium fractionation factors in systems that are pertinent to Precambrian marine conditions. Using the three-isotope method and an enriched 29Si tracer, a series of experiments were conducted to constrain Si isotope exchange kinetics and fractionation factors between amorphous Fe(III)-Si gel, a likely precursor to Precambrian jaspers and BIFs, and aqueous Si in artificial Archean seawater under anoxic conditions. Experiments were conducted at room temperature, and in the presence and absence of aqueous Fe(II) (Fe(II)aq). Results of this study demonstrate that Si solubility is significantly lower for Fe-Si gel than that of amorphous Si, indicating that seawater Si concentrations in the Precambrian may have been lower than previous estimates. The experiments reached ∼70-90% Si isotope exchange after a period of 53-126 days, and the highest extents of exchange were obtained where Fe(II)aq was present, suggesting that Fe(II)-Fe(III) electron-transfer and atom-exchange reactions catalyze Si isotope exchange through breakage of Fe-Si bonds. All experiments except one showed little change in the instantaneous solid-aqueous Si isotope fractionation factor with time, allowing extraction of equilibrium Si isotope fractionation factors through extrapolation to 100% isotope exchange. The equilibrium 30Si/28Si fractionation between Fe(III)-Si gel and aqueous Si (Δ30Sigel-aqueous) is -2.30 ± 0.25‰ (2σ) in the absence of Fe(II)aq. In the case where Fe(II)aq was present, which resulted in addition of ∼10% Fe(II) in the final solid, creating a mixed Fe(II)-Fe(III) Si gel, the equilibrium fractionation between Fe(II)-Fe(III)-Si gel and aqueous Si (Δ30Sigel-aqueous) is -3.23 ± 0.37‰ (2σ). Equilibrium Si isotope fractionation for Fe-Si gel systems is significantly larger in magnitude than estimates of a near-zero solid-aqueous fractionation factor between pure Si gel and aqueous Si, indicating a major influence of Fe atoms on Si-O bonds, and hence the isotopic properties, of Fe-Si gel. Larger Si isotope fractionation in the Fe(II)-bearing systems may be caused by incorporation of Fe(II) into the solid structure, which may further weaken Fe-Si bonds and thus change the Si isotope fractionation factor. The relatively large Si isotope fractionation for Fe-Si gel, relative to pure Si gel, provides a new explanation for the observed contrast in δ30Si values in the Precambrian BIFs and cherts, as well as an explanation for the relatively negative δ30Si values in BIFs, in contrast to previous proposals that the more negative δ30Si values in BIFs reflect hydrothermal sources of Si or sorption to Fe oxides/hydroxides.

  8. Inter-annual variability of carbon fluxes in temperate forest ecosystems: effects of biotic and abiotic factors

    NASA Astrophysics Data System (ADS)

    Chen, M.; Keenan, T. F.; Hufkens, K.; Munger, J. W.; Bohrer, G.; Brzostek, E. R.; Richardson, A. D.

    2014-12-01

    Carbon dynamics in terrestrial ecosystems are influenced by both abiotic and biotic factors. Abiotic factors, such as variation in meteorological conditions, directly drive biophysical and biogeochemical processes; biotic factors, referring to the inherent properties of the ecosystem components, reflect the internal regulating effects including temporal dynamics and memory. The magnitude of the effect of abiotic and biotic factors on forest ecosystem carbon exchange has been suggested to vary at different time scales. In this study, we design and conduct a model-data fusion experiment to investigate the role and relative importance of the biotic and abiotic factors for inter-annual variability of the net ecosystem CO2 exchange (NEE) of temperate deciduous forest ecosystems in the Northeastern US. A process-based model (FöBAAR) is parameterized at four eddy-covariance sites using all available flux and biometric measurements. We conducted a "transplant" modeling experiment, that is, cross- site and parameter simulations with different combinations of site meteorology and parameters. Using wavelet analysis and variance partitioning techniques, analysis of model predictions identifies both spatial variant and spatially invariant parameters. Variability of NEE was primarily modulated by gross primary productivity (GPP), with relative contributions varying from hourly to yearly time scales. The inter-annual variability of GPP and NEE is more regulated by meteorological forcing, but spatial variability in certain model parameters (biotic response) has more substantial effects on the inter-annual variability of ecosystem respiration (Reco) through the effects on carbon pools. Both the biotic and abiotic factors play significant roles in modulating the spatial and temporal variability in terrestrial carbon cycling in the region. Together, our study quantifies the relative importance of both, and calls for better understanding of them to better predict regional CO2 exchanges.

  9. A hierarchy of factors influence discontinuous gas exchange in the grasshopper Paracinema tricolor (Orthoptera: Acrididae).

    PubMed

    Groenewald, Berlizé; Chown, Steven L; Terblanche, John S

    2014-10-01

    The evolutionary origin and maintenance of discontinuous gas exchange (DGE) in tracheate arthropods are poorly understood and highly controversial. We investigated prioritization of abiotic factors in the gas exchange control cascade by examining oxygen, water and haemolymph pH regulation in the grasshopper Paracinema tricolor. Using a full-factorial design, grasshoppers were acclimated to hypoxic or hyperoxic (5% O2, 40% O2) gas conditions, or dehydrated or hydrated, whereafter their CO2 release was measured under a range of O2 and relative humidity (RH) conditions (5%, 21%, 40% O2 and 5%, 60%, 90% RH). DGE was significantly less common in grasshoppers acclimated to dehydrating conditions compared with the other acclimations (hypoxia, 98%; hyperoxia, 100%; hydrated, 100%; dehydrated, 67%). Acclimation to dehydrating conditions resulted in a significant decrease in haemolymph pH from 7.0±0.3 to 6.6±0.1 (mean ± s.d., P=0.018) and also significantly increased the open (O)-phase duration under 5% O2 treatment conditions (5% O2, 44.1±29.3 min; 40% O2, 15.8±8.0 min; 5% RH, 17.8±1.3 min; 60% RH, 24.0±9.7 min; 90% RH, 20.6±8.9 min). The observed acidosis could potentially explain the extension of the O-phase under low RH conditions, when it would perhaps seem more useful to reduce the O-phase to lower respiratory water loss. The results confirm that DGE occurrence and modulation are affected by multiple abiotic factors. A hierarchical framework for abiotic factors influencing DGE is proposed in which the following stressors are prioritized in decreasing order of importance: oxygen supply, CO2 excretion and pH modulation, oxidative damage protection and water savings. © 2014. Published by The Company of Biologists Ltd.

  10. Comparison of human radiation exchange models in outdoor areas

    NASA Astrophysics Data System (ADS)

    Park, Sookuk; Tuller, Stanton E.

    2011-10-01

    Results from the radiation components of seven different human thermal exchange models/methods are compared. These include the Burt, COMFA, MENEX, OUT_SET* and RayMan models, the six-directional method and the new Park and Tuller model employing projected area factors ( f p) and effective radiation area factors ( f eff) determined from a sample of normal- and over-weight Canadian Caucasian adults. Input data include solar and longwave radiation measured during a clear summer day in southern Ontario. Variations between models came from differences in f p and f eff and different estimates of longwave radiation from the open sky. The ranges between models for absorbed solar, net longwave and net all-wave radiation were 164, 31 and 187 W m-2, respectively. These differentials between models can be significant in total human thermal exchange. Therefore, proper f p and f eff values should be used to make accurate estimation of radiation on the human body surface.

  11. The Cdc42 guanine nucleotide exchange factor FGD6 coordinates cell polarity and endosomal membrane recycling in osteoclasts.

    PubMed

    Steenblock, Charlotte; Heckel, Tobias; Czupalla, Cornelia; Espírito Santo, Ana Isabel; Niehage, Christian; Sztacho, Martin; Hoflack, Bernard

    2014-06-27

    The initial step of bone digestion is the adhesion of osteoclasts onto bone surfaces and the assembly of podosomal belts that segregate the bone-facing ruffled membrane from other membrane domains. During bone digestion, membrane components of the ruffled border also need to be recycled after macropinocytosis of digested bone materials. How osteoclast polarity and membrane recycling are coordinated remains unknown. Here, we show that the Cdc42-guanine nucleotide exchange factor FGD6 coordinates these events through its Src-dependent interaction with different actin-based protein networks. At the plasma membrane, FGD6 couples cell adhesion and actin dynamics by regulating podosome formation through the assembly of complexes comprising the Cdc42-interactor IQGAP1, the Rho GTPase-activating protein ARHGAP10, and the integrin interactors Talin-1/2 or Filamin A. On endosomes and transcytotic vesicles, FGD6 regulates retromer-dependent membrane recycling through its interaction with the actin nucleation-promoting factor WASH. These results provide a mechanism by which a single Cdc42-exchange factor controlling different actin-based processes coordinates cell adhesion, cell polarity, and membrane recycling during bone degradation. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. MicroRNA-31 is a positive modulator of endothelial-mesenchymal transition and associated secretory phenotype induced by TGF-β.

    PubMed

    Katsura, Akihiro; Suzuki, Hiroshi I; Ueno, Toshihide; Mihira, Hajime; Yamazaki, Tomoko; Yasuda, Takahiko; Watabe, Tetsuro; Mano, Hiroyuki; Yamada, Yoshitsugu; Miyazono, Kohei

    2016-01-01

    Transforming growth factor-β (TGF-β) plays central roles in endothelial-mesenchymal transition (EndMT) involved in development and pathogenesis. Although EndMT and epithelial-mesenchymal transition are similar processes, roles of microRNAs in EndMT are largely unknown. Here, we report that constitutively active microRNA-31 (miR-31) is a positive regulator of TGF-β-induced EndMT. Although the expression is not induced by TGF-β, miR-31 is required for induction of mesenchymal genes including α-SMA, actin reorganization and MRTF-A activation during EndMT. We identified VAV3, a regulator of actin remodeling and MRTF-A activity, as a miR-31 target. Global transcriptome analysis further showed that miR-31 positively regulates EndMT-associated unique secretory phenotype (EndMT-SP) characterized by induction of multiple inflammatory chemokines and cytokines including CCL17, CX3CL1, CXCL16, IL-6 and Angptl2. As a mechanism for this phenomenon, TGF-β and miR-31 suppress Stk40, a negative regulator of NF-κB pathway. Interestingly, TGF-β induces alternative polyadenylation (APA)-coupled miR-31-dependent Stk40 suppression without concomitant miR-31 induction, and APA-mediated exclusion of internal poly(A) sequence in Stk40 3'UTR enhances target efficiency of Stk40. Finally, miR-31 functions as a molecular hub to integrate TGF-β and TNF-α signaling to enhance EndMT. These data confirm that constitutively active microRNAs, as well as inducible microRNAs, serve as phenotypic modifiers interconnected with transcriptome dynamics during EndMT. © 2015 The Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

  13. Proton Form Factor Puzzle and the CEBAF Large Acceptance Spectrometer (CLAS) Two-Photon Exchange Experiment

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

    Rimal, Dipak

    2014-05-01

    The electromagnetic form factors are the most fundamental observables that encode information about the internal structure of the nucleon. This dissertation explored dependence of R on kinematic variables such as squared four-momentum transfer (Q 2) and the virtual photon polarization parameter (ε).

  14. An exact solution for R2,eff in CPMG experiments in the case of two site chemical exchange

    PubMed Central

    Baldwin, Andrew J.

    2014-01-01

    The Carr–Purcell–Meiboom–Gill (CPMG) experiment is widely used to quantitatively analyse the effects of chemical exchange on NMR spectra. In a CPMG experiment, the effective transverse relaxation rate, R2,eff, is typically measured as a function of the pulse frequency, νCPMG. Here, an exact expression for how R2,eff varies with νCPMG is derived for the commonly encountered scenario of two-site chemical exchange of in-phase magnetisation. This result, summarised in Appendix A, generalises a frequently used equation derived by Carver and Richards, published in 1972. The expression enables more rapid analysis of CPMG data by both speeding up calculation of R2,eff over numerical methods by a factor of ca. 130, and yields exact derivatives for use in data analysis. Moreover, the derivation provides insight into the physical principles behind the experiment. PMID:24852115

  15. IDH1(R132H) mutation increases murine haematopoietic progenitors and alters epigenetics.

    PubMed

    Sasaki, Masato; Knobbe, Christiane B; Munger, Joshua C; Lind, Evan F; Brenner, Dirk; Brüstle, Anne; Harris, Isaac S; Holmes, Roxanne; Wakeham, Andrew; Haight, Jillian; You-Ten, Annick; Li, Wanda Y; Schalm, Stefanie; Su, Shinsan M; Virtanen, Carl; Reifenberger, Guido; Ohashi, Pamela S; Barber, Dwayne L; Figueroa, Maria E; Melnick, Ari; Zúñiga-Pflücker, Juan-Carlos; Mak, Tak W

    2012-08-30

    Mutations in the IDH1 and IDH2 genes encoding isocitrate dehydrogenases are frequently found in human glioblastomas and cytogenetically normal acute myeloid leukaemias (AML). These alterations are gain-of-function mutations in that they drive the synthesis of the ‘oncometabolite’ R-2-hydroxyglutarate (2HG). It remains unclear how IDH1 and IDH2 mutations modify myeloid cell development and promote leukaemogenesis. Here we report the characterization of conditional knock-in (KI) mice in which the most common IDH1 mutation, IDH1(R132H), is inserted into the endogenous murine Idh1 locus and is expressed in all haematopoietic cells (Vav-KI mice) or specifically in cells of the myeloid lineage (LysM-KI mice). These mutants show increased numbers of early haematopoietic progenitors and develop splenomegaly and anaemia with extramedullary haematopoiesis, suggesting a dysfunctional bone marrow niche. Furthermore, LysM-KI cells have hypermethylated histones and changes to DNA methylation similar to those observed in human IDH1- or IDH2-mutant AML. To our knowledge, our study is the first to describe the generation and characterization of conditional IDH1(R132H)-KI mice, and also the first report to demonstrate the induction of a leukaemic DNA methylation signature in a mouse model. Our report thus sheds light on the mechanistic links between IDH1 mutation and human AML.

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

    Ren, Jinqi; Cook, Aaron A.; Bergmeier, Wolfgang

    The dynamic regulation of ERK1 and -2 (ERK1/2) is required for precise signal transduction controlling cell proliferation, differentiation, and survival. However, the underlying mechanisms regulating the activation of ERK1/2 are not completely understood. In this study, we show that phosphorylation of RasGRP2, a guanine nucleotide exchange factor (GEF), inhibits its ability to activate the small GTPase Rap1 that ultimately leads to decreased activation of ERK1/2 in cells. ERK2 phosphorylates RasGRP2 at Ser394 located in the linker region implicated in its autoinhibition. These studies identify RasGRP2 as a novel substrate of ERK1/2 and define a negative-feedback loop that regulates the BRaf–MEK–ERKmore » signaling cascade. This negative-feedback loop determines the amplitude and duration of active ERK1/2. -- Highlights: •ERK2 phosphorylates the guanine nucleotide exchange factor RasGRP2 at Ser394. •Phosphorylated RasGRP2 has decreased capacity to active Rap1b in vitro and in cells. •Phosphorylation of RasGRP2 by ERK1/2 introduces a negative-feedback loop into the BRaf-MEK-ERK pathway.« less

  17. Willingness to Exchange Health Information via Mobile Devices: Findings From a Population-Based Survey

    PubMed Central

    Serrano, Katrina J.; Yu, Mandi; Riley, William T.; Patel, Vaishali; Hughes, Penelope; Marchesini, Kathryn; Atienza, Audie A.

    2016-01-01

    PURPOSE The rapid proliferation of mobile devices offers unprecedented opportunities for patients and health care professionals to exchange health information electronically, but little is known about patients’ willingness to exchange various types of health information using these devices. We examined willingness to exchange different types of health information via mobile devices, and assessed whether sociodemographic characteristics and trust in clinicians were associated with willingness in a nationally representative sample. METHODS We analyzed data for 3,165 patients captured in the 2013 Health Information National Trends Survey. Multinomial logistic regression analysis was conducted to test differences in willingness. Ordinal logistic regression analysis assessed correlates of willingness to exchange 9 types of information separately. RESULTS Participants were very willing to exchange appointment reminders (odds ratio [OR] = 6.66; 95% CI, 5.68–7.81), general health tips (OR = 2.03; 95% CI, 1.74–2.38), medication reminders (OR = 2.73; 95% CI, 2.35–3.19), laboratory/test results (OR = 1.76; 95% CI, 1.62–1.92), vital signs (OR = 1.63; 95% CI, 1.48–1.80), lifestyle behaviors (OR = 1.40; 95% CI, 1.24–1.58), and symptoms (OR = 1.62; 95% CI, 1.46–1.79) as compared with diagnostic information. Older adults had lower odds of being more willing to exchange any type of information. Education, income, and trust in health care professional information correlated with willingness to exchange certain types of information. CONCLUSIONS Respondents were less willing to exchange via mobile devices information that may be considered sensitive or complex. Age, socioeconomic factors, and trust in professional information were associated with willingness to engage in mobile health information exchange. Both information type and demographic group should be considered when developing and tailoring mobile technologies for patient-clinician communication. PMID:26755781

  18. Retroviral insertional mutagenesis identifies Zeb2 activation as a novel leukemogenic collaborating event in CALM-AF10 transgenic mice.

    PubMed

    Caudell, David; Harper, David P; Novak, Rachel L; Pierce, Rachel M; Slape, Christopher; Wolff, Linda; Aplan, Peter D

    2010-02-11

    The t(10;11) translocation results in a CALM-AF10 fusion gene in a subset of leukemia patients. Expression of a CALM-AF10 transgene results in leukemia, with prolonged latency and incomplete penetrance, suggesting that additional events are necessary for leukemic transformation. CALM-AF10 mice infected with the MOL4070LTR retrovirus developed acute leukemia, and ligation-mediated polymerase chain reaction was used to identify retroviral insertions at 19 common insertion sites, including Zeb2, Nf1, Mn1, Evi1, Ift57, Mpl, Plag1, Kras, Erg, Vav1, and Gata1. A total of 26% (11 of 42) of the mice had retroviral integrations near Zeb2, a transcriptional corepressor leading to overexpression of the Zeb2-transcript. A total of 91% (10 of 11) of mice with Zeb2 insertions developed B-lineage acute lymphoblastic leukemia, suggesting that Zeb2 activation promotes the transformation of CALM-AF10 hematopoietic precursors toward B-lineage leukemias. More than half of the mice with Zeb2 integrations also had Nf1 integrations, suggesting cooperativity among CALM-AF10, Zeb2, and Ras pathway mutations. We searched for Nras, Kras, and Ptpn11 point mutations in the CALM-AF10 leukemic mice. Three mutations were identified, all of which occurred in mice with Zeb2 integrations, consistent with the hypothesis that Zeb2 and Ras pathway activation promotes B-lineage leukemic transformation in concert with CALM-AF10.

  19. Retroviral insertional mutagenesis identifies Zeb2 activation as a novel leukemogenic collaborating event in CALM-AF10 transgenic mice

    PubMed Central

    Caudell, David; Harper, David P.; Novak, Rachel L.; Pierce, Rachel M.; Slape, Christopher; Wolff, Linda

    2010-01-01

    The t(10;11) translocation results in a CALM-AF10 fusion gene in a subset of leukemia patients. Expression of a CALM-AF10 transgene results in leukemia, with prolonged latency and incomplete penetrance, suggesting that additional events are necessary for leukemic transformation. CALM-AF10 mice infected with the MOL4070LTR retrovirus developed acute leukemia, and ligation-mediated polymerase chain reaction was used to identify retroviral insertions at 19 common insertion sites, including Zeb2, Nf1, Mn1, Evi1, Ift57, Mpl, Plag1, Kras, Erg, Vav1, and Gata1. A total of 26% (11 of 42) of the mice had retroviral integrations near Zeb2, a transcriptional corepressor leading to overexpression of the Zeb2-transcript. A total of 91% (10 of 11) of mice with Zeb2 insertions developed B-lineage acute lymphoblastic leukemia, suggesting that Zeb2 activation promotes the transformation of CALM-AF10 hematopoietic precursors toward B-lineage leukemias. More than half of the mice with Zeb2 integrations also had Nf1 integrations, suggesting cooperativity among CALM-AF10, Zeb2, and Ras pathway mutations. We searched for Nras, Kras, and Ptpn11 point mutations in the CALM-AF10 leukemic mice. Three mutations were identified, all of which occurred in mice with Zeb2 integrations, consistent with the hypothesis that Zeb2 and Ras pathway activation promotes B-lineage leukemic transformation in concert with CALM-AF10. PMID:20007546

  20. The Structure of Social Exchange in Self-Help Support Groups: Development of a Measure

    PubMed Central

    Brown, Louis D.; Tang, Xiaohui; Hollman, Ruth L.

    2014-01-01

    Self-help support groups are indigenous community resources designed to help people manage a variety of personal challenges, from alcohol abuse to xeroderma pigmentosum. The social exchanges that occur during group meetings are central to understanding how people benefit from participation. This paper examines the different types of social exchange behaviors that occur during meetings, using two studies to develop empirically distinct scales that reliably measure theoretically important types of exchange. Resource theory informed the initial measurement development efforts. Exploratory factor analyses from the first study led to revisions in the factor structure of the social exchange scales. The revised measure captured the exchange of emotional support, experiential information, humor, unwanted behaviors, and exchanges outside meetings. Confirmatory factor analyses from a follow-up study with a different sample of self-help support groups provided good model fit, suggesting the revised structure accurately represented the data. Further, the scales demonstrated good convergent and discriminant validity with related constructs. Future research can use the scales to identify aspects of social exchange that are most important in improving health outcomes among self-help support group participants. Groups can use the scales in practice to celebrate strengths and address weaknesses in their social exchange dynamics. PMID:24398622

  1. Kinetic theory of oxygen isotopic exchange between minerals and water

    USGS Publications Warehouse

    Criss, R.E.; Gregory, R.T.; Taylor, H.P.

    1987-01-01

    Kinetic and mass conservation equations are used to describe oxygen isotopic exchange between minerals and water in "closed" and open hydrothermal systems. In cases where n coexisting mineral phases having different reaction rates are present, the exchange process is described by a system of n + 1 simultaneous differential equations consisting of n pseudo first-order rate equations and a conservation of mass equation. The simultaneous solutions to these equations generate curved exchange trajectories on ??-?? plots. Families of such trajectories generated under conditions allowing for different fluid mole fractions, different fluid isotopic compositions, or different fluid flow rates are connected by positive-sloped isochronous lines. These isochrons reproduce the effects observed in hydrothermally exchanged mineral pairs including 1) steep positive slopes, 2) common reversals in the measured fractionation factors (??), and 3) measured fractionations that are highly variable over short distances where no thermal gradient can be geologically demonstrated. ?? 1987.

  2. Fifty Years of Research in ARDS. Gas Exchange in Acute Respiratory Distress Syndrome.

    PubMed

    Radermacher, Peter; Maggiore, Salvatore Maurizio; Mercat, Alain

    2017-10-15

    Acute respiratory distress syndrome (ARDS) is characterized by severe impairment of gas exchange. Hypoxemia is mainly due to intrapulmonary shunt, whereas increased alveolar dead space explains the alteration of CO 2 clearance. Assessment of the severity of gas exchange impairment is a requisite for the characterization of the syndrome and the evaluation of its severity. Confounding factors linked to hemodynamic status can greatly influence the relationship between the severity of lung injury and the degree of hypoxemia and/or the effects of ventilator settings on gas exchange. Apart from situations of rescue treatment, targeting optimal gas exchange in ARDS has become less of a priority compared with prevention of injury. A complex question for clinicians is to understand when improvement in oxygenation and alveolar ventilation is related to a lower degree or risk of injury for the lungs. In this regard, a full understanding of gas exchange mechanism in ARDS is imperative for individualized symptomatic support of patients with ARDS.

  3. Isotopic fractionation associated with [NiFe]- and [FeFe]-hydrogenases

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

    Yang, Hui; Gandhi, Hasand; Cornish, Adam J.

    2016-01-30

    Hydrogenases catalyze the reversible formation of H2 from electrons and protons with high efficiency. Understanding the relationships between H2 production, H2 uptake, and H2-H2O exchange can provide insight into the metabolism of microbial communities in which H2 is an essential component in energy cycling. In this manuscript, we used stable H isotopes (1H and 2H) to probe the isotope effects associated with three [FeFe]-hydrogenases and three [NiFe]-hydrogenases. All six hydrogenases displayed fractionation factors for H2 formation that were significantly less than 1, producing H2 that was severely depleted in 2H relative to the substrate, water. Consistent with differences in theirmore » active site structure, the fractionation factors for each class appear to cluster, with the three [NiFe]-hydrogenases (α = 0.27-0.40) generally having smaller values than the three [FeFe]-hydrogenases (α = 0.41-0.55). We also obtained isotopic fractionation factors associated with H2 uptake and H2-H2O exchange under conditions similar to those utilized for H2 production, providing us with a more complete picture of the three reactions catalyzed by hydrogenases. The fractionation factors determined in our studies can be used as signatures for different hydrogenases to probe their activity under different growth conditions and to ascertain which hydrogenases are most responsible for H2 production and/or uptake in complex microbial communities.« less

  4. Street Life and Drug Risk Behaviors Associated with Exchanging Sex Among Male Street Children in Lahore, Pakistan

    PubMed Central

    Towe, Vivian L.; Hasan, Salman ul; Zafar, S. Tariq; Sherman, Susan G.

    2009-01-01

    Background Throughout the developing world, children living on urban streets is a byproduct of economic deprivation. In Lahore, Pakistan, there are an estimated 5,000–7,000 street children. Purpose The study examined HIV risk behaviors and factors associated with exchanging sex among male street children in Lahore, Pakistan. Methods The survey was conducted from August 2003 to March 2004 among 565 registrants, ages 5–19, of Project Smile, a program that aimed to enhance the lives of street children in Lahore. We analyzed the frequency of and correlates of recent (past three months) sex exchange for money, drugs, or goods. Multivariate log-binomial regression was used to evaluate the independent effect of covariates on exchange sex. Results Approximately 40% of participants reported having exchanged sex during the past three months. In multivariate analysis, the factors associated with exchanging sex were living on the street for longer than 48 months (Prevalence Ratio [PR]=1.36, 95% Confidence Interval [CI]: 0.99–1.85), reporting ever having used drugs (PR=1.87, 1.10–3.16), cutting one’s self (PR=1.66, 95% CI: 1.26–2.19), and having heard of HIV/AIDS (PR=1.36, 95% CI: 1.03–1.80) after adjusting for demographic and street life variables. Conclusions We found high rates of sex exchange among a sample of street children in Lahore, Pakistan. The finding that children who have heard about HIV/AIDS are more likely to exchange sex suggests that children at HIV risk talk about HIV, but accuracy of their conversations is unclear. Street children in Pakistan are in great need of HIV education and safe alternatives for generating income. PMID:19237107

  5. Geographical distribution of genetic diversity in Secale landrace and wild accessions.

    PubMed

    Hagenblad, Jenny; Oliveira, Hugo R; Forsberg, Nils E G; Leino, Matti W

    2016-01-19

    Rye, Secale cereale L., has historically been a crop of major importance and is still a key cereal in many parts of Europe. Single populations of cultivated rye have been shown to capture a large proportion of the genetic diversity present in the species, but the distribution of genetic diversity in subspecies and across geographical areas is largely unknown. Here we explore the structure of genetic diversity in landrace rye and relate it to that of wild and feral relatives. A total of 567 SNPs were analysed in 434 individuals from 76 accessions of wild, feral and cultivated rye. Genetic diversity was highest in cultivated rye, slightly lower in feral rye taxa and significantly lower in the wild S. strictum Presl. and S. africanum Stapf. Evaluation of effects from ascertainment bias suggests underestimation of diversity primarily in S. strictum and S. africanum. Levels of ascertainment bias, STRUCTURE and principal component analyses all supported the proposed classification of S. africanum and S. strictum as a separate species from S. cereale. S. afghanicum (Vav.) Roshev, S. ancestrale Zhuk., S. dighoricum (Vav.) Roshev, S. segetale (Zhuk.) Roshev and S. vavilovii Grossh. seemed, in contrast, to share the same gene pool as S. cereale and their genetic clustering was more dependent on geographical origin than taxonomic classification. S. vavilovii was found to be the most likely wild ancestor of cultivated rye. Among cultivated rye landraces from Europe, Asia and North Africa five geographically discrete genetic clusters were identified. These had only limited overlap with major agro-climatic zones. Slash-and-burn rye from the Finnmark area in Scandinavia formed a distinct cluster with little similarity to other landrace ryes. Regional studies of Northern and South-West Europe demonstrate different genetic distribution patterns as a result of varying cultivation intensity. With the exception of S. strictum and S. africanum different rye taxa share the majority of the genetic variation. Due to the vast sharing of genetic diversity within the S. cereale clade, ascertainment bias seems to be a lesser problem in rye than in predominantly selfing species. By exploiting within accession diversity geographic structure can be shown on a much finer scale than previously reported.

  6. In-pore exchange and diffusion of carbonate solvent mixtures in nanoporous carbon

    DOE PAGES

    Alam, Todd M.; Osborn Popp, Thomas M.

    2016-06-04

    High resolution magic angle spinning (HRMAS) 1H NMR spectroscopy has been used to resolve different surface and in-pore solvent environments of ethylene carbonate (EC) and dimethyl carbonate (DMC) mixtures absorbed within nanoporous carbon (NPC). Two dimensional (2D) 1H HRMAS NMR exchange measurements revealed that the inhomogeneous broadened in-pore resonances have pore-to-pore exchange rates on the millisecond timescale. Pulsed-field gradient (PFG) NMR diffusometry revealed the in-pore self-diffusion constants for both EC and DMC were reduced by up to a factor of five with respect to the diffusion in the non-absorbed solvent mixtures.

  7. Temperature dependence of chloride, bromide, iodide, thiocyanate and salicylate transport in human red cells

    PubMed Central

    Dalmark, Mads; Wieth, Jens Otto

    1972-01-01

    1. The temperature dependence of the steady-state self-exchange of chloride between human red cells and a plasma-like electrolyte medium has been studied by measuring the rate of 36Cl- efflux from radioactively labelled cells. Between 0 and 10° C the rate increased by a factor of eight corresponding to an Arrhenius activation energy of 33 kcal/mole. 2. The rate of chloride exchange decreased significantly in experiments where 95% of the chloride ions in cells and medium were replaced by other monovalent anions of a lyotropic series. The rate of chloride self-exchange was increasingly reduced by bromide, bicarbonate, nitrate, iodide, thiocyanate, and salicylate. The latter aromatic anion was by far the most potent inhibitor, reducing the rate of chloride self-exchange to 0·2% of the value found in a chloride medium. 3. The temperature sensitivity of the chloride self-exchange was not affected significantly by the anionic inhibitors. The Arrhenius activation energies of chloride exchange were between 30 and 40 kcal/mole in the presence of the six inhibitory anions mentioned above. 4. The rate of self-exchange of bromide, thiocyanate, and iodide between human red cells and media was determined after washing and labelling cells in media containing 120 mM bromide, thiocyanate, or iodide respectively. The rate of self-exchange of the three anions were 12, 3, and 0·4% of the rate of chloride self-exchange found in the chloride medium. 5. The Arrhenius activation energies of the self-exchange of bromide, iodide, and thiocyanate were all between 29 and 37 kcal/mole, the same magnitude as found for the self-exchange of chloride. 6. Although approximately 40% of the intracellular iodide and salicylate ions appeared to be adsorbed to intracellular proteins, the rate of tracer anion efflux followed first order kinetics until at least 98% of the intracellular anions had been exchanged. 7. The self-exchange of salicylate across the human red cell membrane occurred by a different mechanism than the one utilized by the inorganic monovalent anions. The activation energy of salicylate exchange (13·2 kcal/mole) was significantly lower than that of inorganic anion exchange. Salicylate exchange increased with decreasing pH in contrast to the exchange of chloride, which decreases when pH is lowered. PMID:5071931

  8. High Efficiency Heat Exchanger for High Temperature and High Pressure Applications

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

    Sienicki, James J.; Lv, Qiuping; Moisseytsev, Anton

    CompRex, LLC (CompRex) specializes in the design and manufacture of compact heat exchangers and heat exchange reactors for high temperature and high pressure applications. CompRex’s proprietary compact technology not only increases heat exchange efficiency by at least 25 % but also reduces footprint by at least a factor of ten compared to traditional shell-and-tube solutions of the same capacity and by 15 to 20 % compared to other currently available Printed Circuit Heat Exchanger (PCHE) solutions. As a result, CompRex’s solution is especially suitable for Brayton cycle supercritical carbon dioxide (sCO2) systems given its high efficiency and significantly lower capitalmore » and operating expenses. CompRex has already successfully demonstrated its technology and ability to deliver with a pilot-scale compact heat exchanger that was under contract by the Naval Nuclear Laboratory for sCO2 power cycle development. The performance tested unit met or exceeded the thermal and hydraulic specifications with measured heat transfer between 95 to 98 % of maximum heat transfer and temperature and pressure drop values all consistent with the modeled values. CompRex’s vision is to commercialize its compact technology and become the leading provider for compact heat exchangers and heat exchange reactors for various applications including Brayton cycle sCO2 systems. One of the limitations of the sCO2 Brayton power cycle is the design and manufacturing of efficient heat exchangers at extreme operating conditions. Current diffusion-bonded heat exchangers have limitations on the channel size through which the fluid travels, resulting in excessive solid material per heat exchanger volume. CompRex’s design allows for more open area and shorter fluid proximity for increased heat transfer efficiency while sustaining the structural integrity needed for the application. CompRex is developing a novel improvement to its current heat exchanger design where fluids are directed to alternating channels so that each fluid is fully surrounded by the opposing fluid. As compared to similar existing compact heat exchangers, the new design converts most secondary surface area to primary surface area, eliminating fin inefficiencies. CompRex requests that all technical information about the heat exchanger designs be protected as proprietary information. To honor that request, only non-proprietay summaries are included in this report.« less

  9. Light water detritiation

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

    Fedorchenko, O.A.; Aleksee, I.A.; Bondarenko, S.D.

    2015-03-15

    Hundreds of thousands of tons of tritiated light water have been accumulating from the enterprises of nuclear fuel cycles around the world. The Dual-Temperature Water-Hydrogen (DTWH) process looks like the only practical alternative to Combined Electrolysis and Catalytic Exchange (CECE). In DTWH power-consuming lower reflux device (electrolytic cell) is replaced by a so-called 'hot tower' (LPCE column operating at conditions which ensure relatively small value of elementary separation factor α(hot)). In the upper, cold tower, the tritium transfers from hydrogen to water while in the lower, hot tower - in the opposite direction - from water to hydrogen. The DTWHmore » process is much more complicated compared to CECE; it must be thoroughly computed and strictly controlled by an automatic control system. The use of a simulation code for DTWH is absolutely important. The simulation code EVIO-5 deals with 3 flows inside a column (hydrogen gas, water vapour and liquid water) and 2 simultaneous isotope exchange sub-processes (counter-current phase exchange and co-current catalytic exchange). EVIO-5 takes into account the strong dependence of process performance on given conditions (temperature and pressure). It calculates steady-state isotope concentration profiles considering a full set of reversible exchange reactions between different isotope modifications of water and hydrogen (12 molecular species). So the code can be used for simulation of LPCE column operation for detritiation of hydrogen and water feed, which contains H and D not only at low concentrations but above 10 at.% also. EVIO-5 code is used to model a Tritium Removal Facility with a throughput capacity of about 400 m{sup 3}/day. Simulation results show that a huge amount of wet-proofed catalyst is required (about 6000 m{sup 3}), mainly (90%) in the first stage. One reason for these large expenses (apart from a big scale of the problem itself) is the relatively high tritium separation factor in the hot tower. The introduction of some quantity of deuterium into the gaseous flow before the hot tower lowers the tritium separation factor in that column. One possible variant of deuterium introduction to the hot tower of the first stage was modelled. The decontamination capacity increases by a 2.5 factor.« less

  10. Epigenetic Networks Regulate the Transcriptional Program in Memory and Terminally Differentiated CD8+ T Cells.

    PubMed

    Rodriguez, Ramon M; Suarez-Alvarez, Beatriz; Lavín, José L; Mosén-Ansorena, David; Baragaño Raneros, Aroa; Márquez-Kisinousky, Leonardo; Aransay, Ana M; Lopez-Larrea, Carlos

    2017-01-15

    Epigenetic mechanisms play a critical role during differentiation of T cells by contributing to the formation of stable and heritable transcriptional patterns. To better understand the mechanisms of memory maintenance in CD8 + T cells, we performed genome-wide analysis of DNA methylation, histone marking (acetylated lysine 9 in histone H3 and trimethylated lysine 9 in histone), and gene-expression profiles in naive, effector memory (EM), and terminally differentiated EM (TEMRA) cells. Our results indicate that DNA demethylation and histone acetylation are coordinated to generate the transcriptional program associated with memory cells. Conversely, EM and TEMRA cells share a very similar epigenetic landscape. Nonetheless, the TEMRA transcriptional program predicts an innate immunity phenotype associated with genes never reported in these cells, including several mediators of NK cell activation (VAV3 and LYN) and a large array of NK receptors (e.g., KIR2DL3, KIR2DL4, KIR2DL1, KIR3DL1, KIR2DS5). In addition, we identified up to 161 genes that encode transcriptional regulators, some of unknown function in CD8 + T cells, and that were differentially expressed in the course of differentiation. Overall, these results provide new insights into the regulatory networks involved in memory CD8 + T cell maintenance and T cell terminal differentiation. Copyright © 2017 by The American Association of Immunologists, Inc.

  11. Enhanced heat transfer and frictional losses in heat exchanger tube with modified helical coiled inserts

    NASA Astrophysics Data System (ADS)

    Verma, Aditya; Kumar, Manoj; Patil, Anil Kumar

    2018-04-01

    The application of compact heat exchangers in any thermal system improves overall performance with a considerable reduction in size and weight. Inserts of different geometrical features have been used as turbulence promoting devices to increase the heat transfer rates. The present study deals with the experimental investigation of heat transfer and fluid flow characteristics of a tubular heat exchanger fitted with modified helical coiled inserts. Experiments have been carried out for a smooth tube without insert, tube fitted with helical coiled inserts, and modified helical coiled inserts. The helical coiled inserts are tested by varying the pitch ratio and wire diameter ratio from 0.5-1.5, and 0.063-0.125, respectively for the Reynolds number range of 1400 to 11,000. Experimental data have also been collected for the modified helical coiled inserts with gradually increasing pitch (GIP) and gradually decreasing pitch (GDP) configurations. The Nusselt number and friction factor values for helical coiled inserts are enhanced in the range of 1.42-2.62, 3.4-27.4, relative to smooth tube, respectively. The modified helical coiled insert showed enhancements in Nusselt number and friction factor values in the range of 1.49-3.14, 11.2-19.9, relative to smooth tube, respectively. The helical coiled and modified helical coiled inserts have thermo-hydraulic performance factor in the range of 0.59-1.29, 0.6-1.39, respectively. The empirical correlations of Nusselt number and friction factor for helical coiled inserts are proposed.

  12. Aldosterone interaction with epidermal growth factor receptor signaling in MDCK cells.

    PubMed

    Gekle, Michael; Freudinger, Ruth; Mildenberger, Sigrid; Silbernagl, Stefan

    2002-04-01

    Epidermal growth factor (EGF) regulates cell proliferation, differentiation, and ion transport by using extracellular signal-regulated kinase (ERK)1/2 as a downstream signal. Furthermore, the EGF-receptor (EGF-R) is involved in signaling by G protein-coupled receptors, growth hormone, and cytokines by means of transactivation. It has been suggested that steroids interact with peptide hormones, in part, by rapid, potentially nongenomic, mechanisms. Previously, we have shown that aldosterone modulates Na(+)/H(+) exchange in Madin-Darby canine kidney (MDCK) cells by means of ERK1/2 in a way similar to growth factors. Here, we tested the hypothesis that aldosterone uses the EGF-R as a heterologous signal transducer in MDCK cells. Nanomolar concentrations of aldosterone induce a rapid increase in ERK1/2 phosphorylation, cellular Ca(2+) concentration, and Na(+)/H(+) exchange activity similar to increases induced by EGF. Furthermore, aldosterone induced a rapid increase in EGF-R-Tyr phosphorylation, and inhibition of EGF-R kinase abolished aldosterone-induced signaling. Inhibition of ERK1/2 phosphorylation reduced the Ca(2+) response, whereas prevention of Ca(2+) influx did not abolish ERK1/2 phosphorylation. Our data show that aldosterone uses the EGF-R-ERK1/2 signaling cascade to elicit its rapid effects in MDCK cells.

  13. Exchange-mediated spin-lattice relaxation of Fe3+ ions in borate glasses.

    PubMed

    Misra, Sushil K; Pilbrow, John R

    2007-03-01

    Spin-lattice relaxation times (T1) of two borate glasses doped with different concentrations of Fe2O3 were measured using the Electron Spin-Echo (ESE) technique at X-band (9.630 GHz) in the temperature range 2-6K. In comparison with a previous investigation of Fe3+-doped silicate glasses, the relaxation rates were comparable and differed by no more than a factor of two. The data presented here extend those previously reported for borate glasses in the 10-250K range but measured using the amplitude-modulation technique. The T1 values were found to depend on temperature (T) as T(n) with n approximately 1 for the 1% and 0.1% Fe2O3-doped glass samples. These results are consistent with spin-lattice relaxation as effected by exchange interaction of a Fe3+ spin exchange-coupled to another Fe3+ spin in an amorphous material.

  14. The impact of lower sea-ice extent on Arctic greenhouse-gas exchange

    USGS Publications Warehouse

    Parmentier, Frans-Jan W.; Christensen, Torben R.; Sørensen, Lise Lotte; Rysgaard, Søren; McGuire, A. David; Miller, Paul A.; Walker, Donald A.

    2013-01-01

    In September 2012, Arctic sea-ice extent plummeted to a new record low: two times lower than the 1979–2000 average. Often, record lows in sea-ice cover are hailed as an example of climate change impacts in the Arctic. Less apparent, however, are the implications of reduced sea-ice cover in the Arctic Ocean for marine–atmosphere CO2 exchange. Sea-ice decline has been connected to increasing air temperatures at high latitudes. Temperature is a key controlling factor in the terrestrial exchange of CO2 and methane, and therefore the greenhouse-gas balance of the Arctic. Despite the large potential for feedbacks, many studies do not connect the diminishing sea-ice extent with changes in the interaction of the marine and terrestrial Arctic with the atmosphere. In this Review, we assess how current understanding of the Arctic Ocean and high-latitude ecosystems can be used to predict the impact of a lower sea-ice cover on Arctic greenhouse-gas exchange.

  15. Australian Universities' Strategic Goals of Student Exchange and Participation Rates in Outbound Exchange Programmes

    ERIC Educational Resources Information Center

    Daly, Amanda; Barker, Michelle

    2010-01-01

    International student exchange programmes are acknowledged as one aspect of a broader suite of internationalisation strategies aimed at enhancing students' intercultural understanding and competence. The decision to participate in an exchange programme is dependent on both individual and contextual factors such as student exchange policies and…

  16. 6-Formylindolo(3,2-b)Carbazole (FICZ) Modulates the Signalsome Responsible for RA-Induced Differentiation of HL-60 Myeloblastic Leukemia Cells

    PubMed Central

    Bunaciu, Rodica P.; LaTocha, Dorian H.; Varner, Jeffrey D.; Yen, Andrew

    2015-01-01

    6-Formylindolo(3,2-b)carbazole (FICZ) is a photoproduct of tryptophan and an endogenous high affinity ligand for aryl hydrocarbon receptor (AhR). It was previously reported that, in patient-derived HL-60 myeloblastic leukemia cells, retinoic acid (RA)-induced differentiation is driven by a signalsome containing c-Cbl and AhR. FICZ enhances RA-induced differentiation, assessed by expression of the membrane differentiation markers CD38 and CD11b, cell cycle arrest and the functional differentiation marker, inducible oxidative metabolism. Moreover, FICZ augments the expression of a number of the members of the RA-induced signalsome, such as c-Cbl, Vav1, Slp76, PI3K, and the Src family kinases Fgr and Lyn. Pursuing the molecular signaling responsible for RA-induced differentiation, we characterized, using FRET and clustering analysis, associations of key molecules thought to drive differentiation. Here we report that, assayed by FRET, AhR interacts with c-Cbl upon FICZ plus RA-induced differentiation, whereas AhR constitutively interacts with Cbl-b. Moreover, correlation analysis based on the flow cytometric assessment of differentiation markers and western blot detection of signaling factors reveal that Cbl-b, p-p38α and pT390-GSK3β, are not correlated with other known RA-induced signaling components or with a phenotypic outcome. We note that FICZ plus RA elicited signaling responses that were not typical of RA alone, but may represent alternative differentiation-driving pathways. In clusters of signaling molecules seminal to cell differentiation, FICZ co-administered with RA augments type and intensity of the dynamic changes induced by RA. Our data suggest relevance for FICZ in differentiation-induction therapy. The mechanism of action includes modulation of a SFK and MAPK centered signalsome and c-Cbl-AhR association. PMID:26287494

  17. Positron beams and two-photon exchange: The key to precision form factors

    NASA Astrophysics Data System (ADS)

    Bernauer, Jan C.

    2018-05-01

    The proton elastic form factor ratio can be measured either via Rosenbluth separation in an unpolarized beam and target experiment, or via the use of polarization degrees of freedom. However, data produced by these two approaches show a discrepancy, increasing with Q2. The proposed explanation of this discrepancy—two-photon exchange—has been tested recently by three experiments. The results support the existence of a small two-photon exchange effect but cannot establish that theoretical treatment at the measured momentum transfers are valid. At larger momentum transfers, theory remains untested. This paper investigates the possibilities of measurements at DESY and Jefferson Lab to measure the effect at larger momentum transfers.

  18. Motivational Factors in Telecollaborative Exchanges among Teenagers

    ERIC Educational Resources Information Center

    Jauregi, Kristi; Melchor-Couto, Sabela

    2017-01-01

    Motivational factors play an important role in (language) learning processes and research indicates that this is also true for telecollaboration exchanges (Jauregi, de Graaff, van den Bergh, & Kriz, 2012; Melchor-Couto, 2017; in press). This short paper will introduce a study into how motivational factors play a role in telecollaboration…

  19. Gedanken densities and exact constraints in density functional theory.

    PubMed

    Perdew, John P; Ruzsinszky, Adrienn; Sun, Jianwei; Burke, Kieron

    2014-05-14

    Approximations to the exact density functional for the exchange-correlation energy of a many-electron ground state can be constructed by satisfying constraints that are universal, i.e., valid for all electron densities. Gedanken densities are designed for the purpose of this construction, but need not be realistic. The uniform electron gas is an old gedanken density. Here, we propose a spherical two-electron gedanken density in which the dimensionless density gradient can be an arbitrary positive constant wherever the density is non-zero. The Lieb-Oxford lower bound on the exchange energy can be satisfied within a generalized gradient approximation (GGA) by bounding its enhancement factor or simplest GGA exchange-energy density. This enhancement-factor bound is well known to be sufficient, but our gedanken density shows that it is also necessary. The conventional exact exchange-energy density satisfies no such local bound, but energy densities are not unique, and the simplest GGA exchange-energy density is not an approximation to it. We further derive a strongly and optimally tightened bound on the exchange enhancement factor of a two-electron density, which is satisfied by the local density approximation but is violated by all published GGA's or meta-GGA's. Finally, some consequences of the non-uniform density-scaling behavior for the asymptotics of the exchange enhancement factor of a GGA or meta-GGA are given.

  20. Observed Limits on Charge Exchange Contributions to the Diffuse X-Ray Background

    NASA Astrophysics Data System (ADS)

    Crowder, S. G.; Barger, K. A.; Brandl, D. E.; Eckart, M. E.; Galeazzi, M.; Kelley, R. L.; Kilbourne, C. A.; McCammon, D.; Pfendner, C. G.; Porter, F. S.; Rocks, L.; Szymkowiak, A. E.; Teplin, I. M.

    2012-10-01

    We present a high-resolution spectrum of the diffuse X-ray background from 0.1 to 1 keV for a ~1 sr region of the sky centered at l = 90°, b = +60° using a 36 pixel array of microcalorimeters flown on a sounding rocket. With an energy resolution of 11 eV FWHM below 1 keV, the spectrum's observed line ratios help separate charge exchange contributions originating within the heliosphere from thermal emission of hot gas in the interstellar medium. The X-ray sensitivity below 1 keV was reduced by about a factor of four from contamination that occurred early in the flight, limiting the significance of the results. The observed centroid of helium-like O VII is 568+2 - 3 eV at 90% confidence. Since the centroid expected for thermal emission is 568.4 eV and for charge exchange is 564.2 eV, thermal emission appears to dominate for this line complex. The dominance of thermal emission is consistent with much of the high-latitude O VII emission originating in 2-3 × 106 K gas in the Galactic halo. On the other hand, the observed ratio of C VI Lyγ to Lyα is 0.3 ± 0.2. The expected ratios are 0.04 for thermal emission and 0.24 for charge exchange, indicating that charge exchange must contribute strongly to this line and therefore potentially to the rest of the ROSAT R12 band usually associated with 106 K emission from the Local Hot Bubble. The limited statistics of this experiment and systematic uncertainties due to the contamination require only >32% thermal emission for O VII and >20% from charge exchange for C VI at the 90% confidence level. An experimental gold coating on the silicon substrate of the array greatly reduced extraneous signals induced on nearby pixels from cosmic rays passing through the substrate, reducing the triggered event rate by a factor of 15 from a previous flight of the instrument.

  1. Observed Limits on Charge Exchange Contributions to the Diffuse X-Ray Background

    NASA Technical Reports Server (NTRS)

    Crowder, S. G.; Barger, K. A.; Brandl, D. E.; Eckart, M. E.; Galeazzi, M.; Kelley, R. L.; Kilbourne, C. A.; McCammon, D.; Pfendner, C. G.; Porter, F. S.; hide

    2012-01-01

    We present a high-resolution spectrum of the diffuse X-ray background from 0.1 to 1 keV for an approximately 1 sr region of the sky centered at l = 90 degrees b = +60 degrees using a 36 pixel array of microcalorimeters flown on a sounding rocket. With an energy resolution of 11 eV FWHM below 1 keV, the spectrum s observed line ratios help separate charge exchange contributions originating within the heliosphere from thermal emission of hot gas in the interstellar medium. The X-ray sensitivity below 1 keV was reduced by about a factor of four from contamination that occurred early in the flight, limiting the significance of the results. The observed centroid of helium-like O VII is 568 (sup +2 (sub -3) eV at 90% confidence. Since the centroid expected for thermal emission is 568.4 eV and for charge exchange is 564.2 eV, thermal emission appears to dominate for this line complex. The dominance of thermal emission is consistent with much of the high-latitude O VII emission originating in 2-3 x 10(exp 6) K gas in the Galactic halo. On the other hand, the observed ratio of C VI Lygamma to Lyalpha is 0.3 plus or minus 0.2. The expected ratios are 0.04 for thermal emission and 0.24 for charge exchange, indicating that charge exchange must contribute strongly to this line and therefore potentially to the rest of the ROSAT R12 band usually associated with 10(sup 6) K emission from the Local Hot Bubble. The limited statistics of this experiment and systematic uncertainties due to the contamination require only greater than 32% thermal emission for O VII and greater than 20% from charge exchange for C VI at the 90% confidence level. An experimental gold coating on the silicon substrate of the array greatly reduced extraneous signals induced on nearby pixels from cosmic rays passing through the substrate, reducing the triggered event rate by a factor of 15 from a previous flight of the instrument.

  2. Therapeutic Plasma Exchange in Critically Ill Children Requiring Intensive Care.

    PubMed

    Cortina, Gerard; McRae, Rosemary; Chiletti, Roberto; Butt, Warwick

    2018-02-01

    To characterize the clinical indications, procedural safety, and outcome of critically ill children requiring therapeutic plasma exchange. Retrospective observational study based on a prospective registry. Tertiary and quaternary referral 30-bed PICU. Forty-eight critically ill children who received therapeutic plasma exchange during an 8-year period (2007-2014) were included in the study. Therapeutic plasma exchange. A total of 48 patients underwent 244 therapeutic plasma exchange sessions. Of those, therapeutic plasma exchange was performed as sole procedure in 193 (79%), in combination with continuous renal replacement therapy in 40 (16.4%) and additional extracorporeal membrane oxygenation in 11 (4.6%) sessions. The most common admission diagnoses were hematologic disorders (30%), solid organ transplantation (20%), neurologic disorders (20%), and rheumatologic disorders (15%). Complications associated with the procedure occurred in 50 (21.2%) therapeutic plasma exchange sessions. Overall, patient survival from ICU was 82%. Although patients requiring therapeutic plasma exchange alone (n = 31; 64%) had a survival rate of 97%, those with additional continuous renal replacement therapy (n = 13; 27%) and extracorporeal membrane oxygenation (n = 4; 8%) had survival rates of 69% and 50%, respectively. Factors associated with increased mortality were lower Pediatric Index of Mortality 2 score, need for mechanical ventilation, higher number of failed organs, and longer ICU stay. Our results indicate that, in specialized centers, therapeutic plasma exchange can be performed relatively safely in critically ill children, alone or in combination with continuous renal replacement therapy and extracorporeal membrane oxygenation. Outcome in children requiring therapeutic plasma exchange alone is excellent. However, survival decreases with the number of failed organs and the need for continuous renal replacement therapy and extracorporeal membrane oxygenation.

  3. Characterisation of landfill leachate by EEM-PARAFAC-SOM during physical-chemical treatment by coagulation-flocculation, activated carbon adsorption and ion exchange.

    PubMed

    Oloibiri, Violet; De Coninck, Sam; Chys, Michael; Demeestere, Kristof; Van Hulle, Stijn W H

    2017-11-01

    The combination of fluorescence excitation-emission matrices (EEM), parallel factor analysis (PARAFAC) and self-organizing maps (SOM) is shown to be a powerful tool in the follow up of dissolved organic matter (DOM) removal from landfill leachate by physical-chemical treatment consisting of coagulation, granular activated carbon (GAC) and ion exchange. Using PARAFAC, three DOM components were identified: C1 representing humic/fulvic-like compounds; C2 representing tryptophan-like compounds; and C3 representing humic-like compounds. Coagulation with ferric chloride (FeCl 3 ) at a dose of 7 g/L reduced the maximum fluorescence of C1, C2 and C3 by 52%, 17% and 15% respectively, while polyaluminium chloride (PACl) reduced C1 only by 7% at the same dose. DOM removal during GAC and ion exchange treatment of raw and coagulated leachate exhibited different profiles. At less than 2 bed volumes (BV) of treatment, the humic components C1 and C3 were rapidly removed, whereas at BV ≥ 2 the tryptophan-like component C2 was preferentially removed. Overall, leachate treated with coagulation +10.6 BV GAC +10.6 BV ion exchange showed the highest removal of C1 (39% - FeCl 3 , 8% - PACl), C2 (74% - FeCl 3 , 68% - PACl) and no C3 removal; whereas only 52% C2 and no C1 and C3 removal was observed in raw leachate treated with 10.6 BV GAC + 10.6 BV ion exchange only. Analysis of PARAFAC-derived components with SOM revealed that coagulation, GAC and ion exchange can treat leachate at least 50% longer than only GAC and ion exchange before the fluorescence composition of leachate remains unchanged. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. [Primary study on photosynthetic characteristics of Dendrobium nobile].

    PubMed

    Su, Wenhua; Zhang, Guangfei

    2003-03-01

    With LiCor-6400 Portable Photosynthesis System, carbon dioxide exchange pattern for leaves of Dendrobium nobile during 24 hours were studied in sunny day and rainy day, and the variation of CO2 exchange rate to light intensity was analysed. The results showed that in sunny day D. nobile absorbed CO2 in all day except at midday, at noon photorespiration took place. The CO2 exchange pattern was similar to Crassulacean Acid Metabolism(CAM). In rainy day CO2 uptake was in all day, at night CO2 uptake was monitored at 21:00, then CO2 released from 23:00 to dawn. Light saturation point was 1000 mumol/m2s. Over light saturation point photosynthesis, photoinhibition of photosynthesis will be induced by high-light. Exposed to high-light, the light saturation point and the CO2 uptake velocity would be decreased. With variation of environmental factors, photosynthetic pathway in D. nobile could change from CAM to C3 photosynthetic metabolism. It may be one of main reasons for D. nobile to adapt to the shade-requiring environment, the slow growth and rareness in nature.

  5. ATP Dependence of Na+/H+ Exchange

    PubMed Central

    Demaurex, Nicolas; Romanek, Robert R.; Orlowski, John; Grinstein, Sergio

    1997-01-01

    We studied the ATP dependence of NHE-1, the ubiquitous isoform of the Na+/H+ antiporter, using the whole-cell configuration of the patch-clamp technique to apply nucleotides intracellularly while measuring cytosolic pH (pHi) by microfluorimetry. Na+/H+ exchange activity was measured as the Na+-driven pHi recovery from an acid load, which was imposed via the patch pipette. In Chinese hamster ovary (CHO) fibroblasts stably transfected with NHE-1, omission of ATP from the pipette solution inhibited Na+/H+ exchange. Conversely, ATP perfusion restored exchange activity in cells that had been metabolically depleted by 2-deoxy-d-glucose and oligomycin. In cells dialyzed in the presence of ATP, no “run-down” was observed even after extended periods, suggesting that the nucleotide is the only diffusible factor required for optimal NHE-1 activity. Half-maximal activation of the antiporter was obtained at ∼5 mM Mg-ATP. Submillimolar concentrations failed to sustain Na+/H+ exchange even when an ATP regenerating system was included in the pipette solution. High ATP concentrations are also known to be required for the optimal function of other cation exchangers. In the case of the Na/Ca2+ exchanger, this requirement has been attributed to an aminophospholipid translocase, or “flippase.” The involvement of this enzyme in Na+/H+ exchange was examined using fluorescent phosphatidylserine, which is actively translocated by the flippase. ATP depletion decreased the transmembrane uptake of NBD-labeled phosphatidylserine (NBD-PS), indicating that the flippase was inhibited. Diamide, an agent reported to block the flippase, was as potent as ATP depletion in reducing NBD-PS uptake. However, diamide had no effect on Na+/H+ exchange, implying that the effect of ATP is not mediated by changes in lipid distribution across the plasma membrane. K-ATP and ATPγS were as efficient as Mg-ATP in sustaining NHE-1 activity, while AMP-PNP and AMP-PCP only partially substituted for ATP. In contrast, GTPγS was ineffective. We conclude that ATP is the only soluble factor necessary for optimal activity of the NHE-1 isoform of the antiporter. Mg2+ does not appear to be essential for the stimulatory effect of ATP. We propose that two mechanisms mediate the activation of the antiporter by ATP: one requires hydrolysis and is likely an energy-dependent event. The second process does not involve hydrolysis of the γ-phosphate, excluding mediation by protein or lipid kinases. We suggest that this effect is due to binding of ATP to an as yet unidentified, nondiffusible effector that activates the antiporter. PMID:9041442

  6. The effect of exchange interaction on quasiparticle Landau levels in narrow-gap quantum well heterostructures.

    PubMed

    Krishtopenko, S S; Gavrilenko, V I; Goiran, M

    2012-04-04

    Using the 'screened' Hartree-Fock approximation based on the eight-band k·p Hamiltonian, we have extended our previous work (Krishtopenko et al 2011 J. Phys.: Condens. Matter 23 385601) on exchange enhancement of the g-factor in narrow-gap quantum well heterostructures by calculating the exchange renormalization of quasiparticle energies, the density of states at the Fermi level and the quasiparticle g-factor for different Landau levels overlapping. We demonstrate that exchange interaction yields more pronounced Zeeman splitting of the density of states at the Fermi level and leads to the appearance of peak-shaped features in the dependence of the Landau level energies on the magnetic field at integer filling factors. We also find that the quasiparticle g-factor does not reach the maximum value at odd filling factors in the presence of large overlapping of spin-split Landau levels. We advance an argument that the behavior of the quasiparticle g-factor in weak magnetic fields is defined by a random potential of impurities in narrow-gap heterostructures. © 2012 IOP Publishing Ltd

  7. Inhibition of endogenous heat shock protein 70 attenuates inducible nitric oxide synthase induction via disruption of heat shock protein 70/Na(+) /H(+) exchanger 1-Ca(2+) -calcium-calmodulin-dependent protein kinase II/transforming growth factor β-activated kinase 1-nuclear factor-κB signals in BV-2 microglia.

    PubMed

    Huang, Chao; Lu, Xu; Wang, Jia; Tong, Lijuan; Jiang, Bo; Zhang, Wei

    2015-08-01

    Inducible nitric oxide synthase (iNOS) critically contributes to inflammation and host defense. The inhibition of heat shock protein 70 (Hsp70) prevents iNOS induction in lipopolysaccharide (LPS)-stimulated macrophages. However, the role and mechanism of endogenous Hsp70 in iNOS induction in microglia remains unclear. This study addresses this issue in BV-2 microglia, showing that Hsp70 inhibition or knockdown prevents LPS-induced iNOS protein expression and nitric oxide production. Real-time PCR experiments showed that LPS-induced iNOS mRNA transcription was blocked by Hsp70 inhibition. Further studies revealed that the inhibition of Hsp70 attenuated LPS-stimulated nuclear translocation and phosphorylation of nuclear factor (NF)-κB as well as the degradation of inhibitor of κB (IκB)-α and phosphorylation of IκB kinase β (IKKβ). This prevention effect of Hsp70 inhibition on IKKβ-NF-κB activation was found to be dependent on the Ca(2+) /calcium-calmodulin-dependent protein kinase II (CaMKII)/transforming growth factor β-activated kinase 1 (TAK1) signals based on the following observations: 1) chelation of intracellular Ca(2+) or inhibition of CaMKII reduced LPS-induced increases in TAK1 phosphorylation and 2) Hsp70 inhibition reduced LPS-induced increases in CaMKII/TAK1 phosphorylation, intracellular pH value, [Ca(2+) ]i , and CaMKII/TAK1 association. Mechanistic studies showed that Hsp70 inhibition disrupted the association between Hsp70 and Na(+) /H(+) exchanger 1 (NHE1), which is an important exchanger responsible for Ca(2+) influx in LPS-stimulated cells. These studies demonstrate that the inhibition of endogenous Hsp70 attenuates the induction of iNOS, which likely occurs through the disruption of NHE1/Hsp70-Ca(2+) -CaMKII/TAK1-NF-κB signals in BV-2 microglia, providing further insight into the functions of Hsp70 in the CNS. © 2015 Wiley Periodicals, Inc.

  8. CFD analysis of the plate heat exchanger - Mathematical modelling of mass and heat transfer in serial connection with tubular heat exchanger

    NASA Astrophysics Data System (ADS)

    Bojko, Marian; Kocich, Radim

    2016-06-01

    Application of numerical simulations based on the CFD calculation when the mass and heat transfer between the fluid flows is essential component of thermal calculation. In this article the mathematical model of the heat exchanger is defined, which is subsequently applied to the plate heat exchanger, which is connected in series with the other heat exchanger (tubular heat exchanger). The present contribution deals with the possibility to use the waste heat of the flue gas produced by small micro turbine. Inlet boundary conditions to the mathematical model of the plate heat exchanger are obtained from the results of numerical simulation of the tubular heat exchanger. Required parameters such for example inlet temperature was evaluated from temperature field, which was subsequently imported to the inlet boundary condition to the simulation of plate heat exchanger. From the results of 3D numerical simulations are evaluated basic flow variables including the evaluation of dimensionless parameters such as Colburn j-factor and friction ft factor. Numerical simulation is realized by software ANSYS Fluent15.0.

  9. Highly durable direct hydrazine hydrate anion exchange membrane fuel cell

    NASA Astrophysics Data System (ADS)

    Sakamoto, Tomokazu; Serov, Alexey; Masuda, Teruyuki; Kamakura, Masaki; Yoshimoto, Koji; Omata, Takuya; Kishi, Hirofumi; Yamaguchi, Susumu; Hori, Akihiro; Horiuchi, Yousuke; Terada, Tomoaki; Artyushkova, Kateryna; Atanassov, Plamen; Tanaka, Hirohisa

    2018-01-01

    The factors influenced on degradation of direct hydrazine hydrate fuel cells (DHFCs) under operation conditions are analyzed by in situ soft X-ray radiography. A durability of DHFCs is significantly improved by multi-step reaction DHFCs (MSR-DHFCs) approach designed to decrease the crossover of liquid fuel. An open circuit voltage (OCV) as well as cell voltage at 5 mA cm-2 of MSR-DHFC construct with commercial anion exchange membrane (AEM) maintained for over of 3500 h at 60 °C. Furthermore, the commercial proton exchange membrane (PEM) is integrated into AEM of MSR-DHFCs resulting in stable power output of MSR-DHFCs for over than 2800 h at 80 °C.

  10. Theory and applications of a novel ion exchange chromatographic technology using controlled pH gradients for separating proteins on anionic and cationic stationary phases.

    PubMed

    Tsonev, Latchezar I; Hirsh, Allen G

    2008-07-25

    pISep is a major new advance in low ionic strength ion exchange chromatography. It enables the formation of externally controlled pH gradients over the very broad pH range from 2 to 12. The gradients can be generated on either cationic or anionic exchangers over arbitrary pH ranges wherein the stationary phases remain totally charged. Associated pISep software makes possible the calculation of either linear, nonlinear or combined, multi-step, multi-slope pH gradients. These highly reproducible pH gradients, while separating proteins and glycoproteins in the order of their electrophoretic pIs, provide superior chromatographic resolution compared to salt. This paper also presents a statistical mechanical model for protein binding to ion exchange stationary phases enhancing the electrostatic interaction theory for the general dependence of retention factor k, on both salt and pH simultaneously. It is shown that the retention factors computed from short time isocratic salt elution data of a model protein can be used to accurately predict its salt elution concentration in varying slope salt elution gradients formed at varying isocratic pH as well as the pH at which it will be eluted from an anionic exchange column by a pISep pH gradient in the absence of salt.

  11. [Analysis of the incidence and causes of repeated surgical interventions in patients with early complications electrotherapy - 1 center experience from the period 2012-2015].

    PubMed

    Piątek, Łukasz; Polewczyk, Anna; Kurzawski, Jacek; Zachura, Małgorzata; Kaczmarczyk, Małgorzata; Janion, Marianna

    Due to increasing number of patients treated by cardiac implantable electronic devices we observe increasing number of complications after these procedures We analysed causes of early surgical revision of implantable devices connected with 1673 procedures of implantation (871 procedures) or exchange (802 procedures) of pacing systems (PM), cardioverter-difibrillators (ICD) and resynchronisation systems (CRT) in one local centre of electrotherapy in years 2012 to 2015. We characterised risk factors and its influence on encountered complications. In analysed period 72 reinterventions after implantations or exchanges of PM/ICD/CRT were performed. Main causes of early complications were: lead malfunction (2.5%), including the dislodgement of the leads in 1.9%, pocket hematoma (1.4%) and other abnormalities of the pocket (0.4 %), including pocket infections in 0.2%. The most important risk factors of early complications were often implantations of the leads with passive fixation and anticoagulation therapy in perioperative period. The knowledge of the early complications after implantations and exchanges of PM/ICD/CRT should improve the safety of procedures through more often used of the leads with active fixation and properly preparation of the patients requering the antithrombic therapy.

  12. Using MODFLOW with CFP to understand conduit-matrix exchange in a karst aquifer during flooding

    NASA Astrophysics Data System (ADS)

    Spellman, P.; Screaton, E.; Martin, J. B.; Gulley, J.; Brown, A.

    2011-12-01

    Karst springs may reverse flow when allogenic runoff increases river stage faster than groundwater heads and may exchange of surface water with groundwater in the surrounding aquifer matrix. Recharged flood water is rich in nutrients, metals, and organic matter and is undersaturated with respect to calcite. Understanding the physical processes controlling this exchange of water is critical to understanding metal cycling, redox chemistry and dissolution in the subsurface. Ultimately the magnitude of conduit-matrix exchange should be governed by head gradients between the conduit and the aquifer which are affected by the hydraulic conductivity of the matrix, conduit properties and antecedent groundwater heads. These parameters are interrelated and it is unknown which ones exert the greatest control over the magnitude of exchange. This study uses MODFLOW-2005 coupled with the Conduit Flow Processes (CFP) package to determine how physical properties of conduits and aquifers influence the magnitude of surface water-groundwater exchange. We use hydraulic data collected during spring reversals in a mapped underwater cave that sources Madison Blue Spring in north-central Florida to explore which factors are most important in governing exchange. The simulation focused on a major flood in 2009, when river stage increased by about 10 meters over 9 days. In a series of simulations, we varied hydraulic conductivity, conduit diameter, roughness height and tortuosity in addition to antecedent groundwater heads to estimate the relative effects of each parameter on the magnitude of conduit-matrix exchange. Each parameter was varied across plausible ranges for karst aquifers. Antecedent groundwater heads were varied using well data recorded through wet and dry seasons throughout the spring shed. We found hydraulic conductivity was the most important factor governing exchange. The volume of exchange increased by about 61% from the lowest value (1.8x10-6 m/d) to the highest value (6 m/d) of matrix hydraulic conductivity. Other factors increased the amount of exchange by 1% or less, with tortuosity (which varied from 1 to 2) being most significant with a 1% increase, followed by conduit diameter (1 to 5 m) and roughness height (0.1 to 5m) with increases in exchange of 0.4% and 0.3% respectively. Antecedent aquifer conditions were also seen to exert important controls on influencing exchange with greater exchange occurring in floods following dry periods than during wet periods. These preliminary results indicate that heterogeneity of the hydraulic conductivity across karst aquifers will control the distribution of flood waters that enter into the aquifer matrix. Because flood waters are typically undersaturated with respect to the carbonate minerals, the location of this infiltrated water into the highest hydraulic conductivity zones should enhance dissolution, thereby increasing hydraulic conductivity in a feedback loop that will enhance future infiltration of floodwater. Portions of the aquifer prone to infiltrating flood water and dissolution will also be most sensitive to contamination from surface water infiltration.

  13. Sensitivity of Temperate Desert Steppe Carbon Exchange to Seasonal Droughts and Precipitation Variations in Inner Mongolia, China

    PubMed Central

    Yang, Fulin; Zhou, Guangsheng

    2013-01-01

    Arid grassland ecosystems have significant interannual variation in carbon exchange; however, it is unclear how environmental factors influence carbon exchange in different hydrological years. In this study, the eddy covariance technique was used to investigate the seasonal and interannual variability of CO2 flux over a temperate desert steppe in Inner Mongolia, China from 2008 to 2010. The amounts and times of precipitation varied significantly throughout the study period. The precipitation in 2009 (186.4 mm) was close to the long-term average (183.9±47.6 mm), while the precipitation in 2008 (136.3 mm) and 2010 (141.3 mm) was approximately a quarter below the long-term average. The temperate desert steppe showed carbon neutrality for atmospheric CO2 throughout the study period, with a net ecosystem carbon dioxide exchange (NEE) of −7.2, −22.9, and 26.0 g C m−2 yr−1 in 2008, 2009, and 2010, not significantly different from zero. The ecosystem gained more carbon in 2009 compared to other two relatively dry years, while there was significant difference in carbon uptake between 2008 and 2010, although both years recorded similar annual precipitation. The results suggest that summer precipitation is a key factor determining annual NEE. The apparent quantum yield and saturation value of NEE (NEEsat) and the temperature sensitivity coefficient of ecosystem respiration (Reco) exhibited significant variations. The values of NEEsat were −2.6, −2.9, and −1.4 µmol CO2 m−2 s−1 in 2008, 2009, and 2010, respectively. Drought suppressed both the gross primary production (GPP) and Reco, and the drought sensitivity of GPP was greater than that of Reco. The soil water content sensitivity of GPP was high during the dry year of 2008 with limited soil moisture availability. Our results suggest the carbon balance of this temperate desert steppe was not only sensitive to total annual precipitation, but also to its seasonal distribution. PMID:23393576

  14. Role of the Guanine Nucleotide Exchange Factor Rom2 in Cell Wall Integrity Maintenance of Aspergillus fumigatus

    PubMed Central

    Samantaray, Sweta; Neubauer, Michael; Helmschrott, Christoph

    2013-01-01

    Aspergillus fumigatus is a mold and the causal agent of invasive aspergillosis, a systemic disease with high lethality. Recently, we identified and functionally characterized three stress sensors implicated in the cell wall integrity (CWI) signaling of this pathogen, namely, Wsc1, Wsc3, and MidA. Here, we functionally characterize Rom2, a guanine nucleotide exchange factor with essential function for the cell wall integrity of A. fumigatus. A conditional rom2 mutant has severe growth defects under repressive conditions and incorporates all phenotypes of the three cell wall integrity sensor mutants, e.g., the echinocandin sensitivity of the Δwsc1 mutant and the Congo red, calcofluor white, and heat sensitivity of the ΔmidA mutant. Rom2 interacts with Rho1 and shows a similar intracellular distribution focused at the hyphal tips. Our results place Rom2 between the cell surface stress sensors Wsc1, Wsc3, MidA, and Rho1 and their downstream effector mitogen-activated protein (MAP) kinase module Bck1-Mkk2-MpkA. PMID:23264643

  15. Multi-cell storage battery

    DOEpatents

    Brohm, Thomas; Bottcher, Friedhelm

    2000-01-01

    A multi-cell storage battery, in particular to a lithium storage battery, which contains a temperature control device and in which groups of one or more individual cells arranged alongside one another are separated from one another by a thermally insulating solid layer whose coefficient of thermal conductivity lies between 0.01 and 0.2 W/(m*K), the thermal resistance of the solid layer being greater by at least a factor .lambda. than the thermal resistance of the individual cell. The individual cell is connected, at least in a region free of insulating material, to a heat exchanger, the thermal resistance of the heat exchanger in the direction toward the neighboring cell being selected to be greater by at least a factor .lambda. than the thermal resistance of the individual cell and, in addition, the thermal resistance of the heat exchanger toward the temperature control medium being selected to be smaller by at least a factor of about 10 than the thermal resistance of the individual cell, and .lambda. being the ratio of the energy content of the individual cell to the amount of energy that is needed to trigger a thermally induced cell failure at a defined upper operating temperature limit.

  16. Estimating gas exchange of CO2 and CH4 between headwater systems and the atmosphere in Southwest Sweden

    NASA Astrophysics Data System (ADS)

    Somlai, Celia; Natchimuthu, Sivakiruthika; Bastviken, David; Lorke, Andreas

    2015-04-01

    Quantifying the role of inland water systems in terms of carbon sinks and sources and their connection to the terrestrial ecosystems and landscapes is fundamental for improving the balance approach of regional and global carbon budgets. Recent research showed that freshwater bodies emit significant amounts of CO2 and CH4 into the atmosphere. The extent of the emissions from small streams and headwaters, however, remains uncertain due to a limited availability of data. Studies have shown that headwater systems receive most of the terrestrial organic carbon, have the highest dissolved CO2 concentration and the highest gas exchange velocities and cover the largest fractional surface area within fluvial networks. The gas exchange between inland waters and the atmosphere is controlled by two factors: the difference between the dissolved gas concentration and its atmospheric equilibrium concentration, and the gas exchange velocity. The direct measurement of the dissolved gas concentration of greenhouse gases can be measured straightforwardly, for example, by gas chromatography from headspace extraction of water sample. In contrast, direct measurement of gas exchange velocity is more complex and time consuming, as simultaneous measurements with a volatile and nonvolatile inert tracer gas are needed. Here we analyze measurements of gas exchange velocities, concentrations and fluxes of dissolved CO2 and CH4, as well as loads of total organic and inorganic carbon in 10 reaches in headwater streams in Southwest Sweden. We compare the gas exchange velocities measured directly through tracer injections with those estimated through various empirical approaches, which are based on modelled and measured current velocity, stream depth and slope. Furthermore, we estimate the resulting uncertainties of the flux estimates. We also present different time series of dissolved CO2, CH4 and O2 concentration, water temperature, barometric pressure, electro conductivity, and pH values measured during the period of tracer injection.

  17. Spin Exchange Interaction in Substituted Copper Phthalocyanine Crystalline Thin Films

    NASA Astrophysics Data System (ADS)

    Rawat, Naveen; Pan, Zhenwen; Lamarche, Cody J.; Wetherby, Anthony; Waterman, Rory; Tokumoto, Takahisa; Cherian, Judy G.; Headrick, Randall L.; McGill, Stephen A.; Furis, Madalina I.

    2015-11-01

    The origins of spin exchange in crystalline thin films of Copper Octabutoxy Phthalocyanine (Cu-OBPc) are investigated using Magnetic Circular Dichroism (MCD) spectroscopy. These studies are made possible by a solution deposition technique which produces highly ordered films with macroscopic grain sizes suitable for optical studies. For temperatures lower than 2 K, the contribution of a specific state in the valence band manifold originating from the hybridized lone pair in nitrogen orbitals of the Phthalocyanine ring, bears the Brillouin-like signature of an exchange interaction with the localized d-shell Cu spins. A comprehensive MCD spectral analysis coupled with a molecular field model of a σπ - d exchange analogous to sp-d interactions in Diluted Magnetic Semiconductors (DMS) renders an enhanced Zeeman splitting and a modified g-factor of -4 for the electrons that mediate the interaction. These studies define an experimental tool for identifying electronic states involved in spin-dependent exchange interactions in organic materials.

  18. Spin Exchange Interaction in Substituted Copper Phthalocyanine Crystalline Thin Films

    PubMed Central

    Rawat, Naveen; Pan, Zhenwen; Lamarche, Cody J.; Wetherby, Anthony; Waterman, Rory; Tokumoto, Takahisa; Cherian, Judy G.; Headrick, Randall L.; McGill, Stephen A.; Furis, Madalina I.

    2015-01-01

    The origins of spin exchange in crystalline thin films of Copper Octabutoxy Phthalocyanine (Cu-OBPc) are investigated using Magnetic Circular Dichroism (MCD) spectroscopy. These studies are made possible by a solution deposition technique which produces highly ordered films with macroscopic grain sizes suitable for optical studies. For temperatures lower than 2 K, the contribution of a specific state in the valence band manifold originating from the hybridized lone pair in nitrogen orbitals of the Phthalocyanine ring, bears the Brillouin-like signature of an exchange interaction with the localized d-shell Cu spins. A comprehensive MCD spectral analysis coupled with a molecular field model of a σπ − d exchange analogous to sp-d interactions in Diluted Magnetic Semiconductors (DMS) renders an enhanced Zeeman splitting and a modified g-factor of −4 for the electrons that mediate the interaction. These studies define an experimental tool for identifying electronic states involved in spin-dependent exchange interactions in organic materials. PMID:26559337

  19. Spin Exchange Interaction in Substituted Copper Phthalocyanine Crystalline Thin Films.

    PubMed

    Rawat, Naveen; Pan, Zhenwen; Lamarche, Cody J; Wetherby, Anthony; Waterman, Rory; Tokumoto, Takahisa; Cherian, Judy G; Headrick, Randall L; McGill, Stephen A; Furis, Madalina I

    2015-11-12

    The origins of spin exchange in crystalline thin films of Copper Octabutoxy Phthalocyanine (Cu-OBPc) are investigated using Magnetic Circular Dichroism (MCD) spectroscopy. These studies are made possible by a solution deposition technique which produces highly ordered films with macroscopic grain sizes suitable for optical studies. For temperatures lower than 2 K, the contribution of a specific state in the valence band manifold originating from the hybridized lone pair in nitrogen orbitals of the Phthalocyanine ring, bears the Brillouin-like signature of an exchange interaction with the localized d-shell Cu spins. A comprehensive MCD spectral analysis coupled with a molecular field model of a σπ - d exchange analogous to sp-d interactions in Diluted Magnetic Semiconductors (DMS) renders an enhanced Zeeman splitting and a modified g-factor of -4 for the electrons that mediate the interaction. These studies define an experimental tool for identifying electronic states involved in spin-dependent exchange interactions in organic materials.

  20. Sediment exchange to mitigate pollutant exposure in urban soil.

    PubMed

    Walsh, Daniel; Glass, Katherine; Morris, Samantha; Zhang, Horace; McRae, Isabel; Anderson, Noel; Alfieri, Alysha; Egendorf, Sara Perl; Holberton, Shana; Owrang, Shahandeh; Cheng, Zhongqi

    2018-05-15

    Urban soil is an ongoing source for lead (Pb) and other pollutant exposure. Sources of clean soil that are locally-available, abundant and inexpensive are needed to place a protective cover layer over degraded urban soil to eliminate direct and indirect pollutant exposures. This study evaluates a novel sediment exchange program recently established in New York City (NYC Clean Soil Bank, CSB) and found that direct exchange of surplus sediment extracted from urban construction projects satisfies these criteria. The CSB has high total yield with 4.2 × 10 5  t of sediment exchanged in five years. Average annual yield (8.5 × 10 4  t yr -1 ) would be sufficient to place a 15-cm (6-in.) sediment cover layer over 3.2 × 10 5  m 2 (80 acres) of impacted urban soil or 1380 community gardens. In a case study of sediment exchange to mitigate community garden soil contamination, Pb content in sediment ranged from 2 to 5 mg kg -1 . This sediment would reduce surface Pb concentrations more than 98% if it was used to encapsulate soil with Pb content exceeding USEPA residential soil standards (400 mg kg -1 ). The maximum observed sediment Pb content is a factor of 42 and 71 lower than median surface soil and garden soil in NYC, respectively. All costs (transportation, chemical testing, etc.) in the CSB are paid by the donor indicating that urban sediment exchange could be an ultra-low-cost source for urban soil mitigation. Urban-scale sediment exchange has advantages over existing national- or provincial-scale sediment exchanges because it can retain and upcycle local sediment resources to attain their highest and best use (e.g. lowering pollutant exposure), achieve circular urban materials metabolism, improve livability and maximize urban sustainability. Published by Elsevier Ltd.

  1. Cell wall integrity modulates RHO1 activity via the exchange factor ROM2.

    PubMed Central

    Bickle, M; Delley, P A; Schmidt, A; Hall, M N

    1998-01-01

    The essential phosphatidylinositol kinase homologue TOR2 of Saccharomyces cerevisiae controls the actin cytoskeleton by activating a GTPase switch consisting of RHO1 (GTPase), ROM2 (GEF) and SAC7 (GAP). We have identified two mutations, rot1-1 and rot2-1, that suppress the loss of TOR2 and are synthetic-lethal. The wild-type ROT1 and ROT2 genes and a multicopy suppressor, BIG1, were isolated by their ability to rescue the rot1-1 rot2-1 double mutant. ROT2 encodes glucosidase II, and ROT1 and BIG1 encode novel proteins. We present evidence that cell wall defects activate RHO1. First, rot1, rot2, big1, cwh41, gas1 and fks1 mutations all confer cell wall defects and suppress tor2(ts). Second, destabilizing the cell wall by supplementing the growth medium with 0.005% SDS also suppresses a tor2(ts) mutation. Third, disturbing the cell wall with SDS or a rot1, rot2, big1, cwh41, gas1 or fks1 mutation increases GDP/GTP exchange activity toward RHO1. These results suggest that cell wall defects suppress a tor2 mutation by activating RHO1 independently of TOR2, thereby inducing TOR2-independent polarization of the actin cytoskeleton and cell wall synthesis. Activation of RHO1, a subunit of the cell wall synthesis enzyme glucan synthase, by a cell wall alteration would ensure that cell wall synthesis occurs only when and where needed. The mechanism of RHO1 activation by a cell wall alteration is via the exchange factor ROM2 and could be analogous to signalling by integrin receptors in mammalian cells. PMID:9545237

  2. Exchange of Sex for Drugs or Money in Adolescents and Young Adults: An Examination of Sociodemographic Factors, HIV-Related Risk, and Community Context.

    PubMed

    Boyer, Cherrie B; Greenberg, Lauren; Chutuape, Kate; Walker, Bendu; Monte, Dina; Kirk, Jennifer; Ellen, Jonathan M

    2017-02-01

    The goal of this research was to examine associations among sociodemographic factors, HIV risk, and community context (e.g., economic insecurity, job training, housing instability, crime victimization, and perceived community norms) in adolescents and young adults who ever exchanged sex for drugs or money. Anonymous survey data were collected using ACASIs at community venues where adolescents and young adults congregate in resource-challenged, STI prevalent, urban, US neighborhoods. Conventional descriptive statistics, Fisher's exact tests, and generalized estimating equations approaches were used to examine associations. Participants (1818, 95.5 % of those screened eligible) were, on average, aged 21.0 years; 42.2 % were males, and 4.6 % were transgender. Almost one-third (32.1 %) identified as gay or lesbian, 18.1 % identified as bisexual; 66.2 % were Black and 21.0 % were Hispanic; 1.3 % was 'living on the street'. A sizeable proportion reported HIV-related risk: 16.3 % exchanged sex, 12.6 % had sex with someone they knew to be HIV-infected, 7.8 % had sex with someone who injected drugs, and 1.3 % injected drugs. Multivariate comparisons identified a number of variables (e.g., being male or transgender, homelessness, sex with a partner who has HIV, STI history, unemployment, job training access, housing instability, crime victimization, perceived community norms) that were significantly associated with exchange of sex (p < 0.05). This research contributes to the knowledge-base regarding exchange of sex among adolescents and young adults, particularly as it relates to community context. Longitudinal studies to describe the trajectory of social, health, and physical risks and consequences are needed for development of effective evidence-based prevention strategies.

  3. Breaking the Blue Wall of Silence: Risk Factors for Experiencing Police Sexual Misconduct Among Female Offenders

    PubMed Central

    O’Leary, Catina C.; Nickel, Katelin B.; Reingle, Jennifer M.; Isom, Daniel

    2014-01-01

    Objectives. We assessed the prevalence of and risk factors for trading sex with a police officer among women recruited from drug courts in St Louis, Missouri. Methods. In 2005 to 2008, we recruited women into an HIV intervention study, which surveyed participants about multiple sociodemographic, lifestyle, and risk factors. Regression analyses assessed risk factors for trading sex, a form of police sexual misconduct (PSM). Results. Of the 318 participants, 78 (25%) reported a lifetime history of PSM. Among women who experienced PSM, 96% had sex with an officer on duty, 77% had repeated exchanges, 31% reported rape by an officer, and 54% were offered favors by officers in exchange for sex; 87% said officers kept their promise. Only 51% of these respondents always used a condom with an officer. Multivariable models identified 4 or more arrests (adjusted odds ratio [AOR] = 2.8; 95% confidence interval [CI] = 1.29, 5.97), adult antisocial personality (AOR = 9.0; 95% CI = 2.08, 38.79), and lifetime comorbid cocaine and opiate use (AOR = 2.9 [1.62, 5.20]) as risk factors; employment (AOR = 0.4; 95% CI = 0.22, 0.77) lowered the risk of PSM. Conclusions. Community-based interventions are critical to reduce risk of abuse of vulnerable women by police officers charged with protecting communities. PMID:24328629

  4. Breaking the blue wall of silence: risk factors for experiencing police sexual misconduct among female offenders.

    PubMed

    Cottler, Linda B; O'Leary, Catina C; Nickel, Katelin B; Reingle, Jennifer M; Isom, Daniel

    2014-02-01

    We assessed the prevalence of and risk factors for trading sex with a police officer among women recruited from drug courts in St Louis, Missouri. In 2005 to 2008, we recruited women into an HIV intervention study, which surveyed participants about multiple sociodemographic, lifestyle, and risk factors. Regression analyses assessed risk factors for trading sex, a form of police sexual misconduct (PSM). Of the 318 participants, 78 (25%) reported a lifetime history of PSM. Among women who experienced PSM, 96% had sex with an officer on duty, 77% had repeated exchanges, 31% reported rape by an officer, and 54% were offered favors by officers in exchange for sex; 87% said officers kept their promise. Only 51% of these respondents always used a condom with an officer. Multivariable models identified 4 or more arrests (adjusted odds ratio [AOR] = 2.8; 95% confidence interval [CI] = 1.29, 5.97), adult antisocial personality (AOR = 9.0; 95% CI = 2.08, 38.79), and lifetime comorbid cocaine and opiate use (AOR = 2.9 [1.62, 5.20]) as risk factors; employment (AOR = 0.4; 95% CI = 0.22, 0.77) lowered the risk of PSM. Community-based interventions are critical to reduce risk of abuse of vulnerable women by police officers charged with protecting communities.

  5. Reciprocal Exchange Patterned by Market Forces Helps Explain Cooperation in a Small-Scale Society.

    PubMed

    Jaeggi, Adrian V; Hooper, Paul L; Beheim, Bret A; Kaplan, Hillard; Gurven, Michael

    2016-08-22

    Social organisms sometimes depend on help from reciprocating partners to solve adaptive problems [1], and individual cooperation strategies should aim to offer high supply commodities at low cost to the donor in exchange for high-demand commodities with large return benefits [2, 3]. Although such market dynamics have been documented in some animals [4-7], naturalistic studies of human cooperation are often limited by focusing on single commodities [8]. We analyzed cooperation in five domains (meat sharing, produce sharing, field labor, childcare, and sick care) among 2,161 household dyads of Tsimane' horticulturalists, using Bayesian multilevel models and information-theoretic model comparison. Across domains, the best-fit models included kinship and residential proximity, exchanges in kind and across domains, measures of supply and demand and their interactions with exchange, and household-specific exchange slopes. In these best models, giving, receiving, and reciprocating were to some extent shaped by market forces, and reciprocal exchange across domains had a strong partial effect on cooperation independent of more exogenous factors like kinship and proximity. Our results support the view that reciprocal exchange can provide a reliable solution to adaptive problems [8-11]. Although individual strategies patterned by market forces may generate gains from trade in any species [3], humans' slow life history and skill-intensive foraging niche favor specialization and create interdependence [12, 13], thus stabilizing cooperation and fostering divisions of labor even in informal economies [14, 15]. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Building Energy Management Open Source Software

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

    This is the repository for Building Energy Management Open Source Software (BEMOSS), which is an open source operating system that is engineered to improve sensing and control of equipment in small- and medium-sized commercial buildings. BEMOSS offers the following key features: (1) Open source, open architecture – BEMOSS is an open source operating system that is built upon VOLTTRON – a distributed agent platform developed by Pacific Northwest National Laboratory (PNNL). BEMOSS was designed to make it easy for hardware manufacturers to seamlessly interface their devices with BEMOSS. Software developers can also contribute to adding additional BEMOSS functionalities and applications.more » (2) Plug & play – BEMOSS was designed to automatically discover supported load controllers (including smart thermostats, VAV/RTUs, lighting load controllers and plug load controllers) in commercial buildings. (3) Interoperability – BEMOSS was designed to work with load control devices form different manufacturers that operate on different communication technologies and data exchange protocols. (4) Cost effectiveness – Implementation of BEMOSS deemed to be cost-effective as it was built upon a robust open source platform that can operate on a low-cost single-board computer, such as Odroid. This feature could contribute to its rapid deployment in small- or medium-sized commercial buildings. (5) Scalability and ease of deployment – With its multi-node architecture, BEMOSS provides a distributed architecture where load controllers in a multi-floor and high occupancy building could be monitored and controlled by multiple single-board computers hosting BEMOSS. This makes it possible for a building engineer to deploy BEMOSS in one zone of a building, be comfortable with its operation, and later on expand the deployment to the entire building to make it more energy efficient. (6) Ability to provide local and remote monitoring – BEMOSS provides both local and remote monitoring ability with role-based access control. (7) Security – In addition to built-in security features provided by VOLTTRON, BEMOSS provides enhanced security features, including BEMOSS discovery approval process, encrypted core-to-node communication, thermostat anti-tampering feature and many more. (8) Support from the Advisory Committee – BEMOSS was developed in consultation with an advisory committee from the beginning of the project. BEMOSS advisory committee comprises representatives from 22 organizations from government and industry.« less

  7. Magnetic structure and excitation spectrum of the hyperhoneycomb Kitaev magnet β -Li2IrO3

    NASA Astrophysics Data System (ADS)

    Ducatman, Samuel; Rousochatzakis, Ioannis; Perkins, Natalia B.

    2018-03-01

    We present a theoretical study of the static and dynamical properties of the three-dimensional, hyperhoneycomb Kitaev magnet β -Li2IrO3 . We argue that the observed incommensurate order can be understood in terms of a long-wavelength twisting of a nearby commensurate period-3 state, with the same key qualitatively features. The period-3 state shows very different structure when either the Kitaev interaction K or the off-diagonal exchange anisotropy Γ is dominant. A comparison of the associated static spin structure factors with reported scattering experiments in zero and finite fields gives strong evidence that β -Li2IrO3 lies in the regime of dominant Kitaev coupling, and that the Heisenberg exchange J is much weaker than both K and Γ . Our predictions for the magnon excitation spectra, the dynamical spin structure factors, and their polarization dependence provide additional distinctive fingerprints that can be checked experimentally.

  8. Air-gas exchange reevaluated: clinically important results of a computer simulation.

    PubMed

    Shunmugam, Manoharan; Shunmugam, Sudhakaran; Williamson, Tom H; Laidlaw, D Alistair

    2011-10-21

    The primary aim of this study was to evaluate the efficiency of air-gas exchange techniques and the factors that influence the final concentration of an intraocular gas tamponade. Parameters were varied to find the optimum method of performing an air-gas exchange in ideal circumstances. A computer model of the eye was designed using 3D software with fluid flow analysis capabilities. Factors such as angular distance between ports, gas infusion gauge, exhaust vent gauge and depth were varied in the model. Flow rate and axial length were also modulated to simulate faster injections and more myopic eyes, respectively. The flush volume of gas required to achieve a 97% intraocular gas fraction concentration were compared. Modulating individual factors did not reveal any clinically significant difference in the angular distance between ports, exhaust vent size, and depth or rate of gas injection. In combination, however, there was a 28% increase in air-gas exchange efficiency comparing the most efficient with the least efficient studied parameters in this model. The gas flush volume required to achieve a 97% gas fill also increased proportionately at a ratio of 5.5 to 6.2 times the volume of the eye. A 35-mL flush is adequate for eyes up to 25 mm in axial length; however, eyes longer than this would require a much greater flush volume, and surgeons should consider using two separate 50-mL gas syringes to ensure optimal gas concentration for eyes greater than 25 mm in axial length.

  9. An Enhanced Engineering Perspective of Global Climate Systems and Statistical Formulation of Terrestrial CO2 Exchanges

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

    Dai, Yuanshun; Baek, Seung H.; Garcia-Diza, Alberto

    2012-01-01

    This paper designs a comprehensive approach based on the engineering machine/system concept, to model, analyze, and assess the level of CO2 exchange between the atmosphere and terrestrial ecosystems, which is an important factor in understanding changes in global climate. The focus of this article is on spatial patterns and on the correlation between levels of CO2 fluxes and a variety of influencing factors in eco-environments. The engineering/machine concept used is a system protocol that includes the sequential activities of design, test, observe, and model. This concept is applied to explicitly include various influencing factors and interactions associated with CO2 fluxes.more » To formulate effective models of a large and complex climate system, this article introduces a modeling technique that will be referred to as Stochastic Filtering Analysis of Variance (SFANOVA). The CO2 flux data observed from some sites of AmeriFlux are used to illustrate and validate the analysis, prediction and globalization capabilities of the proposed engineering approach and the SF-ANOVA technology. The SF-ANOVA modeling approach was compared to stepwise regression, ridge regression, and neural networks. The comparison indicated that the proposed approach is a valid and effective tool with similar accuracy and less complexity than the other procedures.« less

  10. International community health networking project: two year follow-up of graduates.

    PubMed

    Duffy, M E; Farmer, S; Ravert, P; Huittinen, L

    2005-03-01

    This paper presents the perceptions of graduates 2 years post-exchange in a USA-European Union funded programme. The primary goal of this 8-week exchange programme was to increase cultural knowledge and sensitivity by teaching a common module of community health assessment and planning to multi-national groups of undergraduate students in four countries. Cultural diversity and globalization are among the factors that encourage faculty in nursing to develop programmes of international exchange for students. The challenge is to combine the exchange with the teaching of other courses required by the home institution during the same semester. Twenty-one graduates of participating USA schools responded to an open-ended interview by telephone or email 2 years after graduation. Bennett's continuum (1993) of intercultural sensitivity was used to assess cultural development. Graduates overwhelmingly supported international education and described its continued impact personally and professionally. Gains in cultural sensitivity were perceived as the greatest benefit and influence on their practice. The majority of graduates were believed to be in Bennett's ethnorelative categories of acceptance and adaptation. The depth and breadth of previous cultural experiences, specific host and home schools, and previous travel were found to be related to development on the intercultural sensitivity continuum. Most important are the findings from this evaluation that provide insight into the factors enhancing growth of intercultural sensitivity. Previous travel, characteristics of the home and host institutions, and the opportunity and willingness to be a cultural outsider were important influences.

  11. The load and release characteristics on a strong cationic ion-exchange fiber: kinetics, thermodynamics, and influences.

    PubMed

    Yuan, Jing; Gao, Yanan; Wang, Xinyu; Liu, Hongzhuo; Che, Xin; Xu, Lu; Yang, Yang; Wang, Qifang; Wang, Yan; Li, Sanming

    2014-01-01

    Ion-exchange fibers were different from conventional ion-exchange resins in their non-cross-linked structure. The exchange was located on the surface of the framework, and the transport resistance reduced significantly, which might mean that the exchange is controlled by an ionic reaction instead of diffusion. Therefore, this work aimed to investigate the load and release characteristics of five model drugs with the strong cationic ion-exchange fiber ZB-1. Drugs were loaded using a batch process and released in United States Pharmacopoeia (USP) dissolution apparatus 2. Opposing exchange kinetics, suitable for the special structure of the fiber, were developed for describing the exchange process with the help of thermodynamics, which illustrated that the load was controlled by an ionic reaction. The molecular weight was the most important factor to influence the drug load and release rate. Strong alkalinity and rings in the molecular structures made the affinity between the drug and fiber strong, while logP did not cause any profound differences. The drug-fiber complexes exhibited sustained release. Different kinds and concentrations of counter ions or different amounts of drug-fiber complexes in the release medium affected the release behavior, while the pH value was independent of it. The groundwork for in-depth exploration and further application of ion-exchange fibers has been laid.

  12. The load and release characteristics on a strong cationic ion-exchange fiber: kinetics, thermodynamics, and influences

    PubMed Central

    Yuan, Jing; Gao, Yanan; Wang, Xinyu; Liu, Hongzhuo; Che, Xin; Xu, Lu; Yang, Yang; Wang, Qifang; Wang, Yan; Li, Sanming

    2014-01-01

    Ion-exchange fibers were different from conventional ion-exchange resins in their non-cross-linked structure. The exchange was located on the surface of the framework, and the transport resistance reduced significantly, which might mean that the exchange is controlled by an ionic reaction instead of diffusion. Therefore, this work aimed to investigate the load and release characteristics of five model drugs with the strong cationic ion-exchange fiber ZB-1. Drugs were loaded using a batch process and released in United States Pharmacopoeia (USP) dissolution apparatus 2. Opposing exchange kinetics, suitable for the special structure of the fiber, were developed for describing the exchange process with the help of thermodynamics, which illustrated that the load was controlled by an ionic reaction. The molecular weight was the most important factor to influence the drug load and release rate. Strong alkalinity and rings in the molecular structures made the affinity between the drug and fiber strong, while logP did not cause any profound differences. The drug–fiber complexes exhibited sustained release. Different kinds and concentrations of counter ions or different amounts of drug–fiber complexes in the release medium affected the release behavior, while the pH value was independent of it. The groundwork for in-depth exploration and further application of ion-exchange fibers has been laid. PMID:25114504

  13. Wsc1 and Mid2 Are Cell Surface Sensors for Cell Wall Integrity Signaling That Act through Rom2, a Guanine Nucleotide Exchange Factor for Rho1

    PubMed Central

    Philip, Bevin; Levin, David E.

    2001-01-01

    Wsc1 and Mid2 are highly O-glycosylated cell surface proteins that reside in the plasma membrane of Saccharomyces cerevisiae. They have been proposed to function as mechanosensors of cell wall stress induced by wall remodeling during vegetative growth and pheromone-induced morphogenesis. These proteins are required for activation of the cell wall integrity signaling pathway that consists of the small G-protein Rho1, protein kinase C (Pkc1), and a mitogen-activated protein kinase cascade. We show here by two-hybrid experiments that the C-terminal cytoplasmic domains of Wsc1 and Mid2 interact with Rom2, a guanine nucleotide exchange factor (GEF) for Rho1. At least with regard to Wsc1, this interaction is mediated by the Rom2 N-terminal domain. This domain is distinct from the Rho1-interacting domain, suggesting that the GEF can interact simultaneously with a sensor and with Rho1. We also demonstrate that extracts from wsc1 and mid2 mutants are deficient in the ability to catalyze GTP loading of Rho1 in vitro, providing evidence that the function of the sensor-Rom2 interaction is to stimulate nucleotide exchange toward this G-protein. In a related line of investigation, we identified the PMT2 gene in a genetic screen for mutations that confer an additive cell lysis defect with a wsc1 null allele. Pmt2 is a member of a six-protein family in yeast that catalyzes the first step in O mannosylation of target proteins. We demonstrate that Mid2 is not mannosylated in a pmt2 mutant and that this modification is important for signaling by Mid2. PMID:11113201

  14. Studies on Some Factors Affecting the Quantitative Estimation of the Exchange Capacity of Organic Matter

    Treesearch

    Walter M. Broadfoot; Edward H. Tyner

    1939-01-01

    Methods which are satisfactory for determining the base-exchange capacity of mineral soils can not be applied indiscriminately for determining the exchange capacity of fresh or decomposed plant residues.

  15. Positive and negative peptide signals control stomatal density.

    PubMed

    Shimada, Tomoo; Sugano, Shigeo S; Hara-Nishimura, Ikuko

    2011-06-01

    The stoma is a micro valve found on aerial plant organs that promotes gas exchange between the atmosphere and the plant body. Each stoma is formed by a strict cell lineage during the early stages of leaf development. Molecular genetics research using the model plant Arabidopsis has revealed the genes involved in stomatal differentiation. Cysteine-rich secretory peptides of the EPIDERMAL PATTERNING FACTOR-LIKE (EPFL) family play crucial roles as extracellular signaling factors. Stomatal development is orchestrated by the positive factor STOMAGEN/EPFL9 and the negative factors EPF1, EPF2, and CHALLAH/EPFL6 in combination with multiple receptors. EPF1 and EPF2 are produced in the stomatal lineage cells of the epidermis, whereas STOMAGEN and CHALLAH are derived from the inner tissues. These findings highlight the complex cell-to-cell and intertissue communications that regulate stomatal development. To optimize gas exchange, particularly the balance between the uptake of carbon dioxide (CO(2)) and loss of water, plants control stomatal activity in response to environmental conditions. The CO(2) level and light intensity influence stomatal density. Plants sense environmental cues in mature leaves and adjust the stomatal density of newly forming leaves, indicating the involvement of long-distance systemic signaling. This review summarizes recent research progress in the peptide signaling of stomatal development and discusses the evolutionary model of the signaling machinery.

  16. Separation of Anisotropy and Exchange Broadening Using 15N CSA- 15N- 1H Dipole-Dipole Relaxation Cross-Correlation Experiments

    NASA Astrophysics Data System (ADS)

    Renner, Christian; Holak, Tad A.

    2000-08-01

    Based on the measurement of cross-correlation rates between 15N CSA and 15N-1H dipole-dipole relaxation we propose a procedure for separating exchange contributions to transverse relaxation rates (R2 = 1/T2) from effects caused by anisotropic rotational diffusion of the protein molecule. This approach determines the influence of anisotropy and chemical exchange processes independently and therefore circumvents difficulties associated with the currently standard use of T1/T2 ratios to determine the rotational diffusion tensor. We find from computer simulations that, in the presence of even small amounts of internal flexibility, fitting T1/T2 ratios tends to underestimate the anisotropy of overall tumbling. An additional problem exists when the N-H bond vector directions are not distributed homogeneously over the surface of a unit sphere, such as in helix bundles or β-sheets. Such a case was found in segment 4 of the gelation factor (ABP 120), an F-actin cross-linking protein, in which the diffusion tensor cannot be calculated from T1/T2 ratios. The 15N CSA tensor of the residues for this β-sheet protein was found to vary even within secondary structure elements. The use of a common value for the whole protein molecule therefore might be an oversimplification. Using our approach it is immediately apparent that no exchange broadening exists for segment 4 although strongly reduced T2 relaxation times for several residues could be mistaken as indications for exchange processes.

  17. Gas exchange on Mono Lake and Crowley Lake, California

    NASA Technical Reports Server (NTRS)

    Wanninkhof, Rik; Ledwell, James R.; Broecker, Wallace S.

    1987-01-01

    Gas exchange coefficients (k) have been determined for freshwater Crowley Lake and saline Mono Lake through the use of a man-made purposefully injected gas, SF6. The concentration decreased from an initial value of 40 to 4 pmol/L for Mono Lake and from 20 to 1 pmol/L for Crowley lake over a period of 6 wks. Wind-speed (u) records from anemometers on the shore of each lake made it possible to determine the relationship between k and u. The average u and k values for the experiment were identical for the two lakes, despite the large chemical differences. It is estimated that, for the u values observed over Mono Lake from July to December 1984, the exchange of CO2 occurred 2.5 times faster than without chemical enhancement. This is a factor of 4 lower than needed to explain the high invasion rate of C-14 produced by nuclear bomb tests.

  18. Solvent effects on polysulfide redox kinetics and ionic conductivity in lithium-sulfur batteries

    DOE PAGES

    Fan, Frank Y.; Pan, Menghsuan Sam; Lau, Kah Chun; ...

    2016-11-25

    Lithium-sulfur (Li-S) batteries have high theoretical energy density and low raw materials cost compared to present lithium-ion batteries and are thus promising for use in electric transportation and other applications. A major obstacle for Li-S batteries is low rate capability, especially at the low electrolyte/sulfur (E/S) ratios required for high energy density. Herein, we investigate several potentially rate-limiting factors for Li-S batteries. We study the ionic conductivity of lithium polysulfide solutions of varying concentration and in different ether-based solvents and their exchange current density on glassy carbon working electrodes. We believe this is the first such investigation of exchange currentmore » density for lithium polysulfide in solution. Exchange current densities are measured using both electrochemical impedance spectroscopy and steady-state galvanostatic polarization. In the range of interest (1-8 M [S]), the ionic conductivity monotonically decreases with increasing sulfur concentration while exchange current density shows a more complicated relationship to sulfur concentration. The electrolyte solvent dramatically affects ionic conductivity and exchange current density. Finally, the measured ionic conductivities and exchange current densities are also used to interpret the overpotential and rate capability of polysulfide-nanocarbon suspensions; this analysis demonstrates that ionic conductivity is the rate-limiting property in the solution regime (i.e. between Li 2S 8 and Li 2S 4).« less

  19. Helium escape from the Earth's atmosphere - The charge exchange mechanism revisited

    NASA Technical Reports Server (NTRS)

    Lie-Svendsen, O.; Rees, M. H.; Stamnes, K.

    1992-01-01

    We have studied the escape of neutral helium from the terrestrial atmosphere through exothermic charge exchange reactions between He(+) ions and the major atmospheric constituents N2, O2 and O. Elastic collisions with the neutral background particles were treated quantitatively using a recently developed kinetic theory approach. An interhemispheric plasma transport model was employed to provide a global distribution of He(+) ions as a function of altitude, latitude and local solar time and for different levels of solar ionization. Combining these ion densities with neutral densities from an MSIS model and best estimates for the reaction rate coefficients of the charge exchange reactions, we computed the global distribution of the neutral He escape flux. The escape rates show large diurnal and latitudinal variations, while the global average does not vary by more than a factor of three over a solar cycle. We find that this escape mechanism is potentially important for the overall balance of helium in the Earth's atmosphere. However, more accurate values for the reaction rate coefficients of the charge exchange reactions are required to make a definitive assessment of its importance.

  20. Charge exchange collisions of slow C6 + with atomic and molecular H

    NASA Astrophysics Data System (ADS)

    Saha, Bidhan C.; Guevara, Nicolais L.; Sabin, John R.; Deumens, Erik; Öhrn, Yngve

    2016-04-01

    Charge exchange in collisions of C6+ ions with H and H2 is investigated theoretically at projectile energies 0.1 < E < 10 keV/amu, using electron nuclear dynamics (END) - a semi-classical approximation which not only includes electron translation factors for avoiding spurious couplings but also employs full dynamical trajectories to treat nuclear motions. Both the total and partial cross sections are reported for the collision of C6+ ions with atomic and molecular hydrogen. A comparison with other theoretical and experimental results shows, in general good agreement except at very low energy, considered here. For H2, the one- and two-electron charge exchange cross sections are calculated and compared with other theoretical and experimental results. Small but non-negligible isotope effects are found at the lowest energy studied in the charge transfer of C6+ with H. In low energy region, it is observed that H2 has larger isotope effects than H atom due to the polarizability effect which is larger than the mass effect.

  1. Performance evaluation of radiant cooling system application on a university building in Indonesia

    NASA Astrophysics Data System (ADS)

    Satrio, Pujo; Sholahudin, S.; Nasruddin

    2017-03-01

    The paper describes a study developed to estimate the energy savings potential of a radiant cooling system installed in an institutional building in Indonesia. The simulations were carried out using IESVE to evaluate thermal performance and energy consumption The building model was calibrated using the measured data for the installed radiant system. Then this calibrated model was used to simulate the energy consumption and temperature distribution to determine the proportional energy savings and occupant comfort under different systems. The result was radiant cooling which integrated with a Dedicated Outside Air System (DOAS) could make 41,84% energy savings compared to the installed cooling system. The Computational Fluid Dynamics (CFD) simulation showed that a radiant system integrated with DOAS provides superior human comfort than a radiant system integrated with Variable Air Volume (VAV). Percentage People Dissatisfied was kept below 10% using the proposed system.

  2. Physicians' acceptance of electronic medical records exchange: an extension of the decomposed TPB model with institutional trust and perceived risk.

    PubMed

    Hsieh, Pi-Jung

    2015-01-01

    Electronic medical records (EMRs) exchange improves clinical quality and reduces medical costs. However, few studies address the antecedent factors of physicians' intentions to use EMR exchange. Based on institutional trust and perceived risk integrated with the decomposed theory of planned behavior (TPB) model, we propose a theoretical model to explain the intention of physicians to use an EMR exchange system. We conducted a field survey in Taiwan to collect data from physicians who had experience using the EMR exchange systems. A valid sample of 191 responses was collected for data analysis. To test the proposed research model, we employed structural equation modeling using the partial least squares method. The study findings show that the following five factors have a significant influence on the physicians' intentions to use EMR exchange systems: (a) attitude; (b) subjective norm; (c) perceived behavior control; (d) institutional trust; and (e) perceived risk. These five factors are predictable by perceived usefulness, perceived ease of use, and compatibility, interpersonal and governmental influence, facilitating conditions and self-efficacy, situational normality and structural assurance, and institutional trust, respectively. The results also indicate that institutional trust and perceived risk integrated with the decomposed TPB model improve the prediction of physician's intentions to use EMR exchange. The results of this study indicate that our research model effectively predicts the intention of physicians to use EMR exchange, and provides valuable implications for academics and practitioners. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Exchange enhancement of the electron g-factor in a two-dimensional semimetal in HgTe quantum wells

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

    Bovkun, L. S., E-mail: bovkun@ipmras.ru; Krishtopenko, S. S.; Zholudev, M. S.

    The exchange enhancement of the electron g-factor in perpendicular magnetic fields to 12 T in HgTe/CdHgTe quantum wells 20 nm wide with a semimetal band structure is studied. The electron effective mass and g-factor at the Fermi level are determined by analyzing the temperature dependence of the amplitude of Shubnikov–de Haas oscillation in weak fields and near odd Landau-level filling factors ν ≤ 9. The experimental values are compared with theoretical calculations performed in the one-electron approximation using the eight-band kp Hamiltonian. The found dependence of g-factor enhancement on the electron concentration is explained by changes in the contributions ofmore » hole- and electron-like states to exchange corrections to the Landau-level energies in the conduction band.« less

  4. Prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae, and HIV infection among drug users attending an STD/HIV prevention and needle-exchange program in Quebec City, Canada.

    PubMed

    Poulin, C; Alary, M; Bernier, F; Ringuet, J; Joly, J R

    1999-08-01

    To determine the prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae, and human immunodeficiency virus (HIV) infection among injection and noninjection drug users in Quebec City and to identify associated risk factors. Cross-sectional study of 738 drug users attending a sexually transmitted disease/HIV prevention and needle-exchange program in Quebec City, Canada. The prevalences of N. gonorrhoeae and C. trachomatis were, respectively, 0.4% (95% CI: 0.08%-1.2%) and 3.4% (95% Cl: 2.2%-5.0%). Through multivariate analysis, risk factors associated with sexually transmitted diseases were: among women, being aged between 20 and 24 years and having unprotected sex with commercial partners; in noninjection drug users; cocaine use and first intercourse before 13 years of age; in male noninjection drug users, having regular sexual partners in the previous 6 months. No case of HIV was found in participants who have never injected drugs, but the prevalence was 5.5% (6/110) among the exinjectors and 10.1% (35/347) in current injectors. Moderate sexually transmitted disease and HIV prevalences were found, although a high proportion of drug users reported risky behaviors. Needle-exchange program sites may offer a good opportunity to provide sexually transmitted disease/HIV prevention and medical services to drug users.

  5. Intrinsic and extrinsic drivers of source-sink dynamics

    EPA Science Inventory

    1. Many factors affect the presence and exchange of individuals among subpopulations and influence not only the emergence, but the strength of ensuing source-sink dynamics within metapopulations, yet their relative contributions remain largely unexplored. 2. To help identify the...

  6. SPQR II: A beam-plasma interaction experiment

    NASA Astrophysics Data System (ADS)

    Bimbot, R.; Della-Negra, S.; Gardès, D.; Rivet, M. F.; Fleurier, C.; Dumax, B.; Hoffman, D. H. H.; Weyrich, K.; Deutsch, C.; Maynard, G.

    1986-01-01

    SPQR II is an interaction experiment designed to probe energy -and charge-exchange of Cn+ ions at 2 MeV/a.m.u., flowing through a fully ionized plasma column of hydrogen with nℓ=1019 e-cm-2 at T=5 eV. One expects a factor of two enhanced stopping over the cold gas case.

  7. Subterranean ventilation of allochthonous CO2 governs net CO2 exchange in a semiarid Mediterranean grassland

    USDA-ARS?s Scientific Manuscript database

    Recent research highlights the important role of (semi-) arid ecosystems in the global carbon (C) cycle. However, detailed process based investigations are still necessary in order to fully understand how drylands behave and to determine the main factors currently affecting their C balance with the ...

  8. Quasi-two-dimensional Bose-Einstein condensation of spin triplets in the dimerized quantum magnet Ba 2 CuSi 2 O 6 Cl 2

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

    Okada, Makiko; Tanaka, Hidekazu; Kurita, Nobuyuki

    We synthesized single crystals of composition Ba 2CuSi 2O 6Cl 2 and investigated their quantum magnetic properties. The crystal structure is closely related to that of the quasi-two-dimensional (2D) dimerized magnet BaCuSi 2O 6 also known as Han purple. Ba 2CuSi 2O 6Cl 2 has a singlet ground state with an excitation gap of Δ/k B = 20.8 K. The magnetization curves for two different field directions almost perfectly coincide when normalized by the g factor except for a small jump anomaly for a magnetic field perpendicular to the c axis. The magnetization curve with a nonlinear slope above themore » critical field is in excellent agreement with exact-diagonalization calculations based on a 2D coupled spin-dimer model. Individual exchange constants are also evaluated using density functional theory (DFT). The DFT results demonstrate a 2D exchange network and weak frustration between interdimer exchange interactions, supported by weak spin-lattice coupling implied from our magnetostriction data. Lastly, the magnetic-field-induced spin ordering in Ba 2CuSi 2O 6Cl 2 is described as the quasi-2D Bose-Einstein condensation of triplets.« less

  9. Quasi-two-dimensional Bose-Einstein condensation of spin triplets in the dimerized quantum magnet Ba 2 CuSi 2 O 6 Cl 2

    DOE PAGES

    Okada, Makiko; Tanaka, Hidekazu; Kurita, Nobuyuki; ...

    2016-09-20

    We synthesized single crystals of composition Ba 2CuSi 2O 6Cl 2 and investigated their quantum magnetic properties. The crystal structure is closely related to that of the quasi-two-dimensional (2D) dimerized magnet BaCuSi 2O 6 also known as Han purple. Ba 2CuSi 2O 6Cl 2 has a singlet ground state with an excitation gap of Δ/k B = 20.8 K. The magnetization curves for two different field directions almost perfectly coincide when normalized by the g factor except for a small jump anomaly for a magnetic field perpendicular to the c axis. The magnetization curve with a nonlinear slope above themore » critical field is in excellent agreement with exact-diagonalization calculations based on a 2D coupled spin-dimer model. Individual exchange constants are also evaluated using density functional theory (DFT). The DFT results demonstrate a 2D exchange network and weak frustration between interdimer exchange interactions, supported by weak spin-lattice coupling implied from our magnetostriction data. Lastly, the magnetic-field-induced spin ordering in Ba 2CuSi 2O 6Cl 2 is described as the quasi-2D Bose-Einstein condensation of triplets.« less

  10. FACTORS AFFECTING AIR EXCHANGE IN TWO HOUSES

    EPA Science Inventory

    Air exchange rate is critical to determining the relationship between indoor and outdoor concentrations of hazardous pollutants. Approximately 150 air exchange experiments were completed in two residences: a two-story detached house located in Redwood City, CA and a three-story...

  11. Transfer factors of natural radionuclides and (137)Cs from soil to plants used in traditional medicine in central Serbia.

    PubMed

    Djelic, Gorica; Krstic, Dragana; Stajic, Jelena M; Milenkovic, Biljana; Topuzovic, Marina; Nikezic, Dragoslav; Vucic, Dusica; Zeremski, Tijana; Stankovic, Milan; Kostic, Dragana

    2016-07-01

    Transfer factors of natural radionuclides and (137)Cs from soil to plants used in traditional medicine were determined. The transfer factors (TF) were calculated as Bq kg(-1) of dry plant per Bq kg(-1) of dry soil. Mass activity concentrations of (226)Ra, (232)Th, (40)K and (137)Cs in soil and plant samples were measured with high purity germanium detector (HPGe). The concentrations of As, Co, Cr, Cu, Mn, Ni, Pb and Zn were determined, as well as the cation exchange capacity (CEC) and the content of exchangeable cations (Ca, Mg, K, Na). Wide ranges of values were obtained for all the metals, especially for Cr and Ni. The Absalom model was used for determination of the amount of (137)Cs transferred from soil to plant based on soil characteristics such as pH, exchangeable potassium, humus and clay contents. The estimated transfer factors were in the range from 0.011 to 0.307 with an arithmetic mean of 0.071, median of 0.050, geometric mean of 0.053 and geometric standard deviation (GSD) of 2.08. This value agreed well with that calculated from the measurements of 0.069, geometric mean 0.040 and GSD 3.19. Correlations between radionuclides, metals, physicochemical properties and transfer factors were determined by Spearman correlation coefficient. There was a strong positive correlation between (137)Cs transfer factor and the ratio of transfer factor for K and (137)Cs. Principal Component Analysis (PCA) was performed in order to identify some pattern of data. Copyright © 2016. Published by Elsevier Ltd.

  12. Net ecosystem exchange in a sedge-sphagnum fen at the South of West Siberia, Russia

    NASA Astrophysics Data System (ADS)

    Dyukarev, Egor

    2017-04-01

    The model of net ecosystem exchange was used to study the influence of different environmental factors and to calculate daily and growing season carbon budget for minerotrophic fen at South of West Siberia, Russia. Minerotrophic sedge-sphagnum fen occupies the central part of the Bakcharskoe bog. The model uses air and soil temperature, incoming photosynthetically active radiation, and leaf area index as the explanatory factors for gross primary production, heterotrophic and autotrophic respiration. The model coefficients were calibrated using data collected by automated soil CO2 flux system with clear long-term chamber. The studied ecosystem is a sink of carbon according to modelling and observation results. This study was supported by Russian Foundation for Basic Researches (grant numbers 16-07-01205 and 16-45-700562.

  13. 75 FR 66829 - Determination of Foreign Exchange Swaps and Forwards

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-29

    ... Commodity Exchange Act (``CEA''), as amended by Title VII of the Dodd-Frank Wall Street Reform and Consumer... the application of the factors that the Secretary must consider in making a determination regarding... Treasury must consider the following factors: \\7\\ Notwithstanding any such determination by the Secretary...

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

    Wally Melnitchouk; John Tjon

    We compute the corrections from two-photon and \\gamma-Z exchange in parity-violating elastic electron--proton scattering, used to extract the strange form factors of the proton. We use a hadronic formalism that successfully reconciled the earlier discrepancy in the proton's electron to magnetic form factor ratio, suitably extended to the weak sector. Implementing realistic electroweak form factors, we find effects of the order 2-3% at Q^2 <~ 0.1 GeV^2, which are largest at backward angles, and have a strong Q^2 dependence at low Q^2. Two-boson contributions to the weak axial current are found to be enhanced at low Q^2 and for forwardmore » angles. We provide corrections at kinematics relevant for recent and upcoming parity-violating experiments.« less

  15. Hydrophobic Peptides Affect Binding of Calmodulin and Ca2+ as Explored by H/D Amide Exchange and Mass Spectrometry

    PubMed Central

    Sperry, Justin B.; Huang, Richard Y-C.; Zhu, Mei M.; Rempel, Don L.; Gross, Michael L.

    2010-01-01

    Calmodulin (CaM), a ubiquitous intracellular sensor protein, binds Ca2+ and interacts with various targets as part of signal transduction. Using hydrogen/deuterium exchange (H/DX) and a high resolution PLIMSTEX (Protein-Ligand Interactions by Mass Spectrometry, Titration, and H/D Exchange) protocol, we examined five different states of calmodulin: calcium-free, calcium-loaded, and three states of calcium-loaded in the presence of either melittin, mastoparan, or skeletal myosin light-chain kinase (MLCK). When CaM binds Ca2+, the extent of HDX decreased, consistent with the protein becoming stabilized upon binding. Furthermore, Ca2+-saturated calmodulin exhibits increased protection when bound to the peptides, forming high affinity complexes. The protocol reveals significant changes in EF hands 1, 3, and 4 with saturating levels of Ca2+. Titration of the protein using PLIMSTEX provides the binding affinity of Ca2+ to calmodulin within previously reported values. The affinities of calmodulin to Ca2+ increase by factors of 300 and 1000 in the presence of melittin and mastoparan, respectively. A modified PLIMSTEX protocol whereby the protein is digested to component peptides gives a region-specific titration. The titration data taken in this way show a decrease in the root mean square fit of the residuals, indicating a better fit of the data. The global H/D exchange results and those obtained in a region-specific way provide new insight into the Ca2+-binding properties of this well-studied protein. PMID:21765646

  16. Knowledge exchange and integrated services: experiences from an integrated community intellectual (learning) disability service for adults.

    PubMed

    Farrington, C; Clare, I C H; Holland, A J; Barrett, M; Oborn, E

    2015-03-01

    This paper examines knowledge exchange dynamics in a specialist integrated intellectual (learning) disability service, comprising specialist healthcare provision with social care commissioning and management, and considers their significance in terms of integrated service delivery. A qualitative study focusing on knowledge exchange and integrated services. Semi-structured interviews (n = 25) were conducted with members of an integrated intellectual disability service in England regarding their perceptions of knowledge exchange within the service and the way in which knowledge exchange impinges on the operation of the integrated service. Exchange of 'explicit' (codifiable) knowledge between health and care management components of the service is problematic because of a lack of integrated clinical governance and related factors such as IT and care record systems and office arrangements. Team meetings and workplace interactions allowed for informal exchange of explicit and 'tacit' (non-codifiable) knowledge, but presented challenges in terms of knowledge exchange completeness and sustainability. Knowledge exchange processes play an important role in the functioning of integrated services incorporating health and care management components. Managers need to ensure that knowledge exchange processes facilitate both explicit and tacit knowledge exchange and do not rely excessively on informal, 'ad hoc' interactions. Research on integrated services should take account of micro-scale knowledge exchange dynamics and relationships between social dynamics and physical factors. © 2014 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

  17. Asparagine promotes cancer cell proliferation through use as an amino acid exchange factor

    PubMed Central

    Krall, Abigail S.; Xu, Shili; Graeber, Thomas G.; Braas, Daniel; Christofk, Heather R.

    2016-01-01

    Cellular amino acid uptake is critical for mTOR complex 1 (mTORC1) activation and cell proliferation. However, the regulation of amino acid uptake is not well-understood. Here we describe a role for asparagine as an amino acid exchange factor: intracellular asparagine exchanges with extracellular amino acids. Through asparagine synthetase knockdown and altering of media asparagine concentrations, we show that intracellular asparagine levels regulate uptake of amino acids, especially serine, arginine and histidine. Through its exchange factor role, asparagine regulates mTORC1 activity and protein synthesis. In addition, we show that asparagine regulation of serine uptake influences serine metabolism and nucleotide synthesis, suggesting that asparagine is involved in coordinating protein and nucleotide synthesis. Finally, we show that maintenance of intracellular asparagine levels is critical for cancer cell growth. Collectively, our results indicate that asparagine is an important regulator of cancer cell amino acid homeostasis, anabolic metabolism and proliferation. PMID:27126896

  18. One-step refolding and purification of recombinant human tumor necrosis factor-α (rhTNF-α) using ion-exchange chromatography.

    PubMed

    Wang, Yan; Ren, Wenxuan; Gao, Dong; Wang, Lili; Yang, Ying; Bai, Quan

    2015-02-01

    Protein refolding is a key step for the production of recombinant proteins, especially at large scales, and usually their yields are very low. Chromatographic-based protein refolding techniques have proven to be superior to conventional dilution refolding methods. High refolding yield can be achieved using these methods compared with dilution refolding of proteins. In this work, recombinant human tumor necrosis factor-α (rhTNF-α) from inclusion bodies expressed in Escherichia coli was renatured with simultaneous purification by ion exchange chromatography with a DEAE Sepharose FF column. Several chromatographic parameters influencing the refolding yield of the denatured/reduced rhTNF-α, such as the urea concentration, pH value and concentration ratio of glutathione/oxidized glutathione in the mobile phase, were investigated in detail. Under optimal conditions, rhTNF-α can be renatured and purified simultaneously within 30 min by one step. Specific bioactivity of 2.18 × 10(8) IU/mg, purity of 95.2% and mass recovery of 76.8% of refolded rhTNF-α were achieved. Compared with the usual dilution method, the ion exchange chromatography method developed here is simple and more effective for rhTNF-α refolding in terms of specific bioactivity and mass recovery. Copyright © 2014 John Wiley & Sons, Ltd.

  19. Are BVOC exchanges in agricultural ecosystems overestimated? Insights from fluxes measured in a maize field over a whole growing season

    NASA Astrophysics Data System (ADS)

    Bachy, Aurélie; Aubinet, Marc; Schoon, Niels; Amelynck, Crist; Bodson, Bernard; Moureaux, Christine; Heinesch, Bernard

    2016-04-01

    Although maize is the second most important crop worldwide, and the most important C4 crop, no study on biogenic volatile organic compounds (BVOCs) has yet been conducted on this crop at ecosystem scale and over a whole growing season. This has led to large uncertainties in cropland BVOC emission estimations. This paper seeks to fill this gap by presenting, for the first time, BVOC fluxes measured in a maize field at ecosystem scale (using the disjunct eddy covariance by mass scanning technique) over a whole growing season in Belgium. The maize field emitted mainly methanol, although exchanges were bi-directional. The second most exchanged compound was acetic acid, which was taken up mainly in the growing season. Bi-directional exchanges of acetaldehyde, acetone and other oxygenated VOCs also occurred, whereas the terpenes, benzene and toluene exchanges were small, albeit significant. Surprisingly, BVOC exchanges were of the same order of magnitude on bare soil and on well developed vegetation, suggesting that soil is a major BVOC reservoir in agricultural ecosystems. Quantitatively, the maize BVOC emissions observed were lower than those reported in other maize, crops and grasses studies. The standard emission factors (SEFs) estimated in this study (231 ± 19 µg m-2 h-1 for methanol, 8 ± 5 µg m-2 h-1 for isoprene and 4 ± 6 µg m-2 h-1 for monoterpenes) were also much lower than those currently used by models for C4 crops, particularly for terpenes. These results suggest that maize fields are small BVOC exchangers in north-western Europe, with a lower BVOC emission impact than that modelled for growing C4 crops in this part of the world. They also reveal the high variability in BVOC exchanges across world regions for maize and suggest that SEFs should be estimated for each region separately.

  20. Emission of neutron–proton and proton–proton pairs in neutrino scattering

    DOE PAGES

    Ruiz Simo, I.; Amaro, J. E.; Barbaro, M. B.; ...

    2016-11-10

    For this paper, we use a recently developed model of relativistic meson-exchange currents to compute the neutron–proton and proton–proton yields in (νμ, μ -)scattering from 12C in the 2p–2h channel. We compute the response functions and cross sections with the relativistic Fermi gas model for different kinematics from intermediate to high momentum transfers. We find a large contribution of neutron–proton configurations in the initial state, as compared to proton–proton pairs. In the case of charge-changing neutrino scattering the 2p–2h cross section of proton–proton emission (i.e.,np in the initial state) is much larger than for neutron–proton emission (i.e.,two neutrons in themore » initial state) by a (ω, q)-dependent factor. The different emission probabilities of distinct species of nucleon pairs are produced in our model only by meson-exchange currents, mainly by the Δ isobar current. We also analyze other effects including exchange contributions and the effect of the axial and vector currents.« less

  1. Hadronic light-by-light contribution to the muon g — 2

    NASA Astrophysics Data System (ADS)

    Guevara, Adolfo

    2016-10-01

    We have computed the hadronic light-by-light (LbL) contribution to the muon anomalous magnetic moment aμ in the frame of Chiral Perturbation Theory with the inclusion of the lightest resonance multiplets as dynamical fields (RχT). It is essential to give a more accurate prediction of this hadronic contribution due to the future projects of J-Parc and FNAL on reducing the uncertainty in this observable. We, therefore, computed the pseudoscalar transition form factor and proposed the measurement of the e+ e - →μ+ μ- π0 cross section and dimuon invariant mass spectrum to determine more accurately its parameters. Then, we evaluated the pion exchange contribution to αμ, obtaining (6.66 ± 0.21) • 10-10. By comparing the pion exchange contribution and the pion-pole approximation to the corresponding transition form factor (πTFF) we recalled that the latter underestimates the complete πTFF by (15-20)%. Then, we obtained the η(') TFF, obtaining a total contribution of the lightest pseudoscalar exchanges of (10.47 ± 0.54) • 10-10, in agreement with previous results and with smaller error.

  2. Precipitation-mediated responses of soil acid buffering capacity to long-term nitrogen addition in a semi-arid grassland

    NASA Astrophysics Data System (ADS)

    Cai, Jiangping; Luo, Wentao; Liu, Heyong; Feng, Xue; Zhang, Yongyong; Wang, Ruzhen; Xu, Zhuwen; Zhang, Yuge; Jiang, Yong

    2017-12-01

    Atmospheric nitrogen (N) deposition can result in soil acidification and reduce soil acid buffering capacity. However, it remains poorly understood how changes in precipitation regimes with elevated atmospheric N deposition affect soil acidification processes in a water-limited grassland. Here, we conducted a 9-year split-plot experiment with water addition as the main factor and N addition as the second factor. Results showed that soil acid buffering capacity significantly decreased with increased N inputs, mainly due to the decline of soil effective cation exchange capacity (ECEC) and exchangeable basic cations (especially Ca2+), indicating an acceleration of soil acidification status in this steppes. Significant interactive N and water effects were detected on the soil acid buffering capacity. Water addition enhanced the soil ECEC and exchangeable base cations and thus alleviated the decrease of soil acid buffering capacity under N addition. Our findings suggested that precipitation can mitigate the impact of increased N deposition on soil acidification in semi-arid grasslands. This knowledge should be used to improve models predicting soil acidification processes in terrestrial ecosystems under changing environmental conditions.

  3. Discovery of Aminopiperidine Indoles That Activate the Guanine Nucleotide Exchange Factor SOS1 and Modulate RAS Signaling.

    PubMed

    Abbott, Jason R; Hodges, Timothy R; Daniels, R Nathan; Patel, Pratiq A; Kennedy, Jack Phillip; Howes, Jennifer E; Akan, Denis T; Burns, Michael C; Sai, Jiqing; Sobolik, Tammy; Beesetty, Yugandhar; Lee, Taekyu; Rossanese, Olivia W; Phan, Jason; Waterson, Alex G; Fesik, Stephen W

    2018-06-01

    Deregulated RAS activity, often the result of mutation, is implicated in approximately 30% of all human cancers. Despite this statistic, no clinically successful treatment for RAS-driven tumors has yet been developed. One approach for modulating RAS activity is to target and affect the activity of proteins that interact with RAS, such as the guanine nucleotide exchange factor (GEF) son of sevenless homologue 1 (SOS1). Here, we report on structure-activity relationships (SAR) in an indole series of compounds. Using structure-based design, we systematically explored substitution patterns on the indole nucleus, the pendant amino acid moiety, and the linker unit that connects these two fragments. Best-in-class compounds activate the nucleotide exchange process at sub-micromolar concentrations in vitro, increase levels of active RAS-GTP in HeLa cells, and elicit signaling changes in the mitogen-activated protein kinase/extracellular regulated kinase (MAPK/ERK) pathway, resulting in a decrease in pERK1/2 T202/Y204 protein levels at higher compound concentrations.

  4. Regulation of leaf-gas exchange strategies of woody plants under elevated CO2

    NASA Astrophysics Data System (ADS)

    Belmecheri, S.; Guerrieri, R.; Voelker, S.

    2016-12-01

    Estimates of vegetation water use efficiency (WUE) have increasingly been assessed using both eddy covariance and plant stable isotope techniques but these data have often lead to differing conclusions. Eddy covariance can provide forest ecosystem-level responses of coupled carbon and water exchanges to recent global change phenomena. These direct observations, however, are generally less than one or two decades, thus documenting ecosystem-level responses at elevated [CO2] concentrations (350-400 ppm). Therefore, eddy covariance data cannot directly address plant physiological mechanisms and adaptation to climate variability and anthropogenic factors, e.g., increasing atmospheric [CO2]. By contrast, tree based carbon isotope approaches can retrospectively assess intrinsic WUE over long periods and have documented physiological responses to ambient atmospheric [CO2] (ca), which have often been contextualized within generalized strategies for stomatal regulation of leaf gas-exchange. These include maintenance of a constant leaf internal [CO2] (ci), a constant drawdown in [CO2] (ca - ci), and a constant ci/ca . Tree carbon isotope studies, however, cannot account for changes in leaf area of individual trees or canopies, which makes scaling up a difficult task. The limitations of these different approaches to understanding how forest water use efficiency has been impacted by rising [CO2] has contributed to the uncertainty in global terrestrial carbon cycling and the "missing" terrestrial carbon sink. We examined stable C isotope ratios (d13C) from woody plants over a wide range of [CO2] (200-400 ppm) to test for patterns of ci-regulation in response to rising ca. The analyses are not consistent with any of the leaf gas-exchange regulation strategies noted above. The data suggest that ca - ci is still recently increasing in most species but that the rate of increase is less than expected from paleo trees which grew at much lower [CO2]. This evidence demonstrates that a broadly conserved suite of functional traits allow woody plants to adapt their leaf gas exchange to elevated [CO2]. To improve projections of how rising [CO2] will affect terrestrial carbon uptake, dynamic global vegetation models should incorporate leaf gas exchange responses that mimic these adaptive responses to [CO2].

  5. Microtube strip heat exchanger

    NASA Astrophysics Data System (ADS)

    Doty, F. D.

    1992-07-01

    The purpose of this contract has been to explore the limits of miniaturization of heat exchangers with the goals of (1) improving the theoretical understanding of laminar heat exchangers, (2) evaluating various manufacturing difficulties, and (3) identifying major applications for the technology. A low-cost, ultra-compact heat exchanger could have an enormous impact on industry in the areas of cryocoolers and energy conversion. Compact cryocoolers based on the reverse Brayton cycle (RBC) would become practical with the availability of compact heat exchangers. Many experts believe that hardware advances in personal computer technology will rapidly slow down in four to six years unless lowcost, portable cryocoolers suitable for the desktop supercomputer can be developed. Compact refrigeration systems would permit dramatic advances in high-performance computer work stations with 'conventional' microprocessors operating at 150 K, and especially with low-cost cryocoolers below 77 K. NASA has also expressed strong interest in our MTS exchanger for space-based RBC cryocoolers for sensor cooling. We have demonstrated feasibility of higher specific conductance by a factor of five than any other work in high-temperature gas-to-gas exchangers. These laminar-flow, microtube exchangers exhibit extremely low pressure drop compared to alternative compact designs under similar conditions because of their much shorter flow length and larger total flow area for lower flow velocities. The design appears to be amenable to mass production techniques, but considerable process development remains. The reduction in materials usage and the improved heat exchanger performance promise to be of enormous significance in advanced engine designs and in cryogenics.

  6. Alcohols inhibit translation to regulate morphogenesis in C. albicans

    PubMed Central

    Egbe, Nkechi E.; Paget, Caroline M.; Wang, Hui; Ashe, Mark P.

    2015-01-01

    Many molecules are secreted into the growth media by microorganisms to modulate the metabolic and physiological processes of the organism. For instance, alcohols like butanol, ethanol and isoamyl alcohol are produced by the human pathogenic fungus, Candida albicans and induce morphological differentiation. Here we show that these same alcohols cause a rapid inhibition of protein synthesis. More specifically, the alcohols target translation initiation, a complex stage of the gene expression process. Using molecular techniques, we have identified the likely translational target of these alcohols in C. albicans as the eukaryotic translation initiation factor 2B (eIF2B). eIF2B is the guanine nucleotide exchange factor for eIF2, which supports the exchange reaction where eIF2.GDP is converted to eIF2.GTP. Even minimal regulation at this step will lead to alterations in the levels of specific proteins that may allow the exigencies of the fungus to be realised. Indeed, similar to the effects of alcohols, a minimal inhibition of protein synthesis with cycloheximide also causes an induction of filamentous growth. These results suggest a molecular basis for the effect of various alcohols on morphological differentiation in C. albicans. PMID:25843913

  7. Experimental study on heat transfer performance of fin-tube exchanger and PSHE for waste heat recovery

    NASA Astrophysics Data System (ADS)

    Chen, Ting; Bae, Kyung Jin; Kwon, Oh Kyung

    2018-02-01

    In this paper, heat transfer characteristics of fin-tube heat exchanger and primary surface heat exchanger (PSHE) used in waste heat recovery were investigated experimentally. The flow in the fin-tube heat exchanger is cross flow and in PSHE counter flow. The variations of friction factor and Colburn j factor with air mass flow rate, and Nu number with Re number are presented. Various comparison methods are used to evaluate heat transfer performance, and the results show that the heat transfer rate of the PSHE is on average 17.3% larger than that of fin-tube heat exchanger when air mass flow rate is ranging from 1.24 to 3.45 kg/min. However, the PSHE causes higher pressure drop, and the fin-tube heat exchanger has a wider application range which leads to a 31.7% higher value of maximum heat transfer rate compared to that of the PSHE. Besides, under the same fan power per unit frontal surface, a higher heat transfer rate value is given in the fin-tube heat exchanger.

  8. Statistical analysis and definition of blockages-prediction formulae for the wastewater network of Oslo by evolutionary computing.

    PubMed

    Ugarelli, Rita; Kristensen, Stig Morten; Røstum, Jon; Saegrov, Sveinung; Di Federico, Vittorio

    2009-01-01

    Oslo Vann og Avløpsetaten (Oslo VAV)-the water/wastewater utility in the Norwegian capital city of Oslo-is assessing future strategies for selection of most reliable materials for wastewater networks, taking into account not only material technical performance but also material performance, regarding operational condition of the system.The research project undertaken by SINTEF Group, the largest research organisation in Scandinavia, NTNU (Norges Teknisk-Naturvitenskapelige Universitet) and Oslo VAV adopts several approaches to understand reasons for failures that may impact flow capacity, by analysing historical data for blockages in Oslo.The aim of the study was to understand whether there is a relationship between the performance of the pipeline and a number of specific attributes such as age, material, diameter, to name a few. This paper presents the characteristics of the data set available and discusses the results obtained by performing two different approaches: a traditional statistical analysis by segregating the pipes into classes, each of which with the same explanatory variables, and a Evolutionary Polynomial Regression model (EPR), developed by Technical University of Bari and University of Exeter, to identify possible influence of pipe's attributes on the total amount of predicted blockages in a period of time.Starting from a detailed analysis of the available data for the blockage events, the most important variables are identified and a classification scheme is adopted.From the statistical analysis, it can be stated that age, size and function do seem to have a marked influence on the proneness of a pipeline to blockages, but, for the reduced sample available, it is difficult to say which variable it is more influencing. If we look at total number of blockages the oldest class seems to be the most prone to blockages, but looking at blockage rates (number of blockages per km per year), then it is the youngest class showing the highest blockage rate. EPR allowed identifying the relation between attitude to block and pipe's attributes in order to understand what affects the possibility to have a blockage in the pipe. EPR provides formulae to compute the accumulated number of blockages for a pipe class at the end of a given period of time. Those formulae do not represent simply regression models but highlight those variables which affect the physical phenomenon in question.

  9. [Summer Greenhouse Gases Exchange Flux Across Water-air Interface in Three Water Reservoirs Located in Different Geologic Setting in Guangxi, China].

    PubMed

    Li, Jian-hong; Pu, Jun-bing; Sun, Ping-an; Yuan, Dao-xian; Liu, Wen; Zhang, Tao; Mo, Xue

    2015-11-01

    Due to special hydrogeochemical characteristics of calcium-rich, alkaline and DIC-rich ( dissolved inorganic carbon) environment controlled by the weathering products from carbonate rock, the exchange characteristics, processes and controlling factors of greenhouse gas (CO2 and CH4) across water-air interface in karst water reservoir show obvious differences from those of non-karst water reservoir. Three water reservoirs (Dalongdong reservoir-karst reservoir, Wulixia reservoir--semi karst reservoir, Si'anjiang reservoir-non-karst reservoir) located in different geologic setting in Guangxi Zhuang Autonomous Region, China were chosen to reveal characteristics and controlling factors of greenhouse gas exchange flux across water-air interface. Two common approaches, floating chamber (FC) and thin boundary layer models (TBL), were employed to research and contrast greenhouse gas exchange flux across water-air interface from three reservoirs. The results showed that: (1) surface-layer water in reservoir area and discharging water under dam in Dalongdong water reservoir were the source of atmospheric CO2 and CH4. Surface-layer water in reservoir area in Wulixia water reservoir was the sink of atmospheric CO2 and the source of atmospheric CH4, while discharging water under dam was the source of atmospheric CO2 and CH4. Surface-layer water in Si'anjiang water reservoir was the sink of atmospheric CO2 and source of atmospheric CH4. (2) CO2 and CH4 effluxes in discharging water under dam were much more than those in surface-layer water in reservoir area regardless of karst reservoir or non karst reservoir. Accordingly, more attention should be paid to the CO2 and CH4 emission from discharging water under dam. (3) In the absence of submerged soil organic matters and plants, the difference of CH4 effluxes between karst groundwater-fed reservoir ( Dalongdong water reservoir) and non-karst area ( Wulixia water reservoir and Si'anjiang water reservoir) was less. However, CO2 efflux in karst groundwater-fed reservoir was much higher than that of reservoir in non-karst area due to groundwater of DIC-rich input from karst aquifer and thermal stratification.

  10. Multi-Inhibitory Effects of A2A Adenosine Receptor Signaling on Neutrophil Adhesion Under Flow.

    PubMed

    Yago, Tadayuki; Tsukamoto, Hiroki; Liu, Zhenghui; Wang, Ying; Thompson, Linda F; McEver, Rodger P

    2015-10-15

    A2A adenosine receptor (A2AAR) signaling negatively regulates inflammatory responses in many disease models, but the detailed mechanisms remain unclear. We used the selective A2AAR agonist, ATL313, to examine how A2AAR signaling affects human and murine neutrophil adhesion under flow. Treating neutrophils with ATL313 inhibited selectin-induced, β2 integrin-dependent slow rolling and chemokine-induced, β2 integrin-dependent arrest on ICAM-1. ATL313 inhibited selectin-induced β2 integrin extension, which supports slow rolling, and chemokine-induced hybrid domain "swing-out," which supports arrest. Furthermore, ATL313 inhibited integrin outside-in signaling as revealed by reduced neutrophil superoxide production and spreading on immobilized anti-β2 integrin Ab. ATL313 suppressed selectin-triggered activation of Src family kinases (SFKs) and p38 MAPK, chemokine-triggered activation of Ras-related protein 1, and β2 integrin-triggered activation of SFKs and Vav cytoskeletal regulatory proteins. ATL313 activated protein kinase A and its substrate C-terminal Src kinase, an inhibitor of SFKs. Treating neutrophils with a protein kinase A inhibitor blocked the actions of ATL313. In vivo, ATL313-treated neutrophils rolled faster and arrested much less frequently in postcapillary venules of the murine cremaster muscle after TNF-α challenge. Furthermore, ATL313 markedly suppressed neutrophil migration into the peritoneum challenged with thioglycollate. ATL313 did not affect A2AAR-deficient neutrophils, confirming its specificity. Our findings provide new insights into the anti-inflammatory mechanisms of A2AAR signaling and the potential utility of A2AAR agonists in inflammatory diseases. Copyright © 2015 by The American Association of Immunologists, Inc.

  11. Multi-inhibitory effects of A2A adenosine receptor signaling on neutrophil adhesion under flow**

    PubMed Central

    Yago, Tadayuki; Tsukamoto, Hiroki; Liu, Zhenghui; Wang, Ying; Thompson, Linda F.; McEver, Rodger P.

    2015-01-01

    A2A adenosine receptor (A2AAR) signaling negatively regulates inflammatory responses in many disease models, but the detailed mechanisms remain unclear. We used the selective A2AAR agonist, ATL313, to examine how A2AAR signaling affects human and murine neutrophil adhesion under flow. Treating neutrophils with ATL313 inhibited selectin-induced, β2 integrin-dependent slow rolling and chemokine-induced, β2 integrin-dependent arrest on ICAM-1. ATL313 inhibited selectin-induced β2 integrin extension, which supports slow rolling, and chemokine-induced hybrid domain “swing-out”, which supports arrest. Furthermore, ATL313 inhibited integrin outside-in signaling as revealed by reduced neutrophil superoxide production and spreading on immobilized anti-β2 integrin antibody. ATL313 suppressed selectin-triggered activation of Src family kinases (SFKs) and p38 MAPK, chemokine-triggered activation of Ras-related protein 1 (Rap1), and β2 integrin-triggered activation of SFKs and Vav cytoskeletal regulatory proteins. ATL313 activated protein kinase A (PKA) and its substrate C-terminal Src kinase (Csk), an inhibitor of SFKs. Treating neutrophils with a PKA inhibitor blocked the actions of ATL313. In vivo, ATL313-treated neutrophils rolled faster and arrested much less frequently in postcapillary venules of the murine cremaster muscle after TNF-α challenge. Furthermore, ATL313 markedly suppressed neutrophil migration into the peritoneum challenged with thioglycollate. ATL313 did not affect A2AAR-deficient neutrophils, confirming its specificity. Our findings provide new insights into the anti-inflammatory mechanisms of A2AAR signaling and the potential utility of A2AAR agonists in inflammatory diseases. PMID:26355151

  12. Net ecosystem CO2 exchange of a primary tropical peat swamp forest in Sarawak, Malaysia

    NASA Astrophysics Data System (ADS)

    Tang Che Ing, A.; Stoy, P. C.; Melling, L.

    2014-12-01

    Tropical peat swamp forests are widely recognized as one of the world's most efficient ecosystems for the sequestration and storage of carbon through both their aboveground biomass and underlying thick deposits of peat. As the peat characteristics exhibit high spatial and temporal variability as well as the structural and functional complexity of forests, tropical peat ecosystems can act naturally as both carbon sinks and sources over their life cycles. Nonetheless, few reports of studies on the ecosystem-scale CO2 exchange of tropical peat swamp forests are available to-date and their present roles in the global carbon cycle remain uncertain. To quantify CO2 exchange and unravel the prevailing factors and potential underlying mechanism regulating net CO2 fluxes, an eddy covariance tower was erected in a tropical peat swamp forest in Sarawak, Malaysia. We observed that the diurnal and seasonal patterns of net ecosystem CO2 exchange (NEE) and its components (gross primary productivity (GPP) and ecosystem respiration (RE)) varied between seasons and years. Rates of NEE declined in the wet season relative to the dry season. Conversely, both the gross primary productivity (GPP) and ecosystem respiration (RE) were found to be higher during the wet season than the dry season, in which GPP was strongly negatively correlated with NEE. The average annual NEE was 385 ± 74 g C m-2 yr-1, indicating the primary peat swamp forest functioned as net source of CO2 to the atmosphere over the observation period.

  13. Applying Outdoor Environment to Develop Health, Comfort, and Energy Saving in the Office in Hot-Humid Climate

    PubMed Central

    Chen, Rong; Sung, Wen-Pei; Chang, Hung-Chang; Chi, Yi-Rou

    2013-01-01

    A human life demand set to emerge in the future is the achievement of sustainability by maintaining a comfortable indoor environment without excessive reliance on energy-consuming air conditioners. The major research processes in this study are: (1) measuring indoor air quality and thermal comfort to evaluate the comfort of an indoor environment; (2) implementing questionnaire survey analysis to explore people's environmental self-perceptions and conducting a meta-analysis of the measurement results for air quality and physical aspects; and (3) constructing an indoor monitoring and management system. The experimental and analysis results of this research reveal that most of the office occupants preferred a cooler environment with a lower temperature. Additionally, because the summers in Taiwan are humid and hot, the occupants of an indoor space tend to feel uncomfortable because of the high humidity and poor indoor air quality. Therefore, Variable Air Volume (VAV), two air intakes, and exhaust plant are installed to improve indoor environment. After improvement, a lower temperature (approximately 21.2–23.9°C) indirectly reduces humidity, thereby making the occupants comfortable. Increasing air velocity to 0.1 ~ 0.15 m/s, the carbon dioxide concentrations decrease below the requirement of the WHO. Ninety-five percent of the workers corresponded to the standard comfort zone after this improvement. PMID:24311976

  14. Fluoride occurrence in the groundwater in a coastal region of Andhra Pradesh, India

    NASA Astrophysics Data System (ADS)

    Rao, N. Subba; Rao, P. Surya; Dinakar, A.; Rao, P. V. Nageswara; Marghade, Deepali

    2017-06-01

    Fluoride (F-) content varies from 0.60 to 1.80 mg/L in the coastal region between Chirala and Ongole of Andhra Pradesh, India. It exceeds the threshold limit of 1.20 mg/L in 20 % of the total groundwater samples. The aim of the present study is to assess the controlling factors of F- content. The study area experiences a dry climate and is underlain by Charnockite Group of rocks over which the river and coastal alluvium occur. The results of the study identify the four factors that control the high F- content. First one is related to alkalinity, leading to active dissolution and leaching of F--bearing minerals, which supports the positive correlation of F- with pH and HCO3 -. A longer water residence time in the clays is the second factor, which activates not only solubility and dissolution of F--bearing minerals, but also anion exchange between F- and OH-. Third factor is a result of higher Na+ due to impact of saline water, ion exchange between Na+ and Ca2+, and precipitation of CaCO3. This reduces the Ca2+ content, causing dissolution of CaF2 to maintain the chemical equilibria, which is supported by positive correlation between Na2+ and F-. The influence of anthropogenic activities is the last factor, which acts as an additional source of F-. Thus, the shallow groundwater shows higher content of F- and the hydrogeochemical facies also support this hypothesis. The study suggests the remedial measures to reduce the F- content.

  15. A profile of high school students in rural Canada who exchange sex for substances.

    PubMed

    Homma, Yuko; Nicholson, Dean; Saewyc, Elizabeth M

    2012-01-01

    The exchange of sexual activities for money, drugs, or other compensation is considered a form of sexual exploitation when it occurs among underage youth. Such practices have been associated with sexual behaviours that increase the risk of sexually transmitted infections. Much of the research on this issue has been conducted on homeless or street-involved youth while adolescents in regular schools have received less attention in this area. The present study examined the prevalence of and factors associated with the exchange of sex for drugs among substance-using students in rural western Canada. Our data source was the 2009 East Kootenay Adolescent Drug Use Survey, a census of students in grades 7-12, who had ever used alcohol, marijuana, or other illicit drugs. In the sample of 2,360 youth, 2% of boys and 3% of girls reported that they had ever exchanged sex for alcohol or drugs, i.e., "exploited" youth, the majority of whom (83% - 98%) were living with family members. The most frequent patterns of past-year substance use were "using alcohol only" for "non-exploited" youth, and using alcohol, marijuana, and other drugs for exploited youth. The exchange of sex was associated with the use of drugs other than alcohol in the past year and with a higher level of impulsivity. The odds of exchanging sex were lower among youth who reported positive family relationships. The findings suggest a need for in-school education about healthy relationships, sexual exploitation, substance use, and impulse control.

  16. Factors Influencing Electronic Clinical Information Exchange in Small Medical Group Practices

    ERIC Educational Resources Information Center

    Kralewski, John E.; Zink, Therese; Boyle, Raymond

    2012-01-01

    Purpose: The purpose of this study was to identify the organizational factors that influence electronic health information exchange (HIE) by medical group practices in rural areas. Methods: A purposive sample of 8 small medical group practices in 3 experimental HIE regions were interviewed to determine the extent of clinical information exchange…

  17. Coming to Canada to Study: Factors that Influence Student's Decisions to Participate in International Exchange

    ERIC Educational Resources Information Center

    Massey, Jennifer; Burrow, Jeff

    2012-01-01

    Increasing numbers of students are participating in study abroad programs. Outcomes associated with these programs have been studied extensively, but relatively little is known about what motivates and influences students to participate. This study investigated factors that motivate and influence students to study on exchange and explored how…

  18. Sum rules for quasifree scattering of hadrons

    NASA Astrophysics Data System (ADS)

    Peterson, R. J.

    2018-02-01

    The areas d σ /d Ω of fitted quasifree scattering peaks from bound nucleons for continuum hadron-nucleus spectra measuring d2σ /d Ω d ω are converted to sum rules akin to the Coulomb sums familiar from continuum electron scattering spectra from nuclear charge. Hadronic spectra with or without charge exchange of the beam are considered. These sums are compared to the simple expectations of a nonrelativistic Fermi gas, including a Pauli blocking factor. For scattering without charge exchange, the hadronic sums are below this expectation, as also observed with Coulomb sums. For charge exchange spectra, the sums are near or above the simple expectation, with larger uncertainties. The strong role of hadron-nucleon in-medium total cross sections is noted from use of the Glauber model.

  19. Pharmacological dimerization and activation of the exchange factor eIF2B antagonizes the integrated stress response

    PubMed Central

    Sidrauski, Carmela; Tsai, Jordan C; Kampmann, Martin; Hearn, Brian R; Vedantham, Punitha; Jaishankar, Priyadarshini; Sokabe, Masaaki; Mendez, Aaron S; Newton, Billy W; Tang, Edward L; Verschueren, Erik; Johnson, Jeffrey R; Krogan, Nevan J; Fraser, Christopher S; Weissman, Jonathan S; Renslo, Adam R; Walter, Peter

    2015-01-01

    The general translation initiation factor eIF2 is a major translational control point. Multiple signaling pathways in the integrated stress response phosphorylate eIF2 serine-51, inhibiting nucleotide exchange by eIF2B. ISRIB, a potent drug-like small molecule, renders cells insensitive to eIF2α phosphorylation and enhances cognitive function in rodents by blocking long-term depression. ISRIB was identified in a phenotypic cell-based screen, and its mechanism of action remained unknown. We now report that ISRIB is an activator of eIF2B. Our reporter-based shRNA screen revealed an eIF2B requirement for ISRIB activity. Our results define ISRIB as a symmetric molecule, show ISRIB-mediated stabilization of activated eIF2B dimers, and suggest that eIF2B4 (δ-subunit) contributes to the ISRIB binding site. We also developed new ISRIB analogs, improving its EC50 to 600 pM in cell culture. By modulating eIF2B function, ISRIB promises to be an invaluable tool in proof-of-principle studies aiming to ameliorate cognitive defects resulting from neurodegenerative diseases. DOI: http://dx.doi.org/10.7554/eLife.07314.001 PMID:25875391

  20. Multidimensional generalized-ensemble algorithms for complex systems.

    PubMed

    Mitsutake, Ayori; Okamoto, Yuko

    2009-06-07

    We give general formulations of the multidimensional multicanonical algorithm, simulated tempering, and replica-exchange method. We generalize the original potential energy function E(0) by adding any physical quantity V of interest as a new energy term. These multidimensional generalized-ensemble algorithms then perform a random walk not only in E(0) space but also in V space. Among the three algorithms, the replica-exchange method is the easiest to perform because the weight factor is just a product of regular Boltzmann-like factors, while the weight factors for the multicanonical algorithm and simulated tempering are not a priori known. We give a simple procedure for obtaining the weight factors for these two latter algorithms, which uses a short replica-exchange simulation and the multiple-histogram reweighting techniques. As an example of applications of these algorithms, we have performed a two-dimensional replica-exchange simulation and a two-dimensional simulated-tempering simulation using an alpha-helical peptide system. From these simulations, we study the helix-coil transitions of the peptide in gas phase and in aqueous solution.

  1. Application of Monte Carlo techniques to transient thermal modeling of cavity radiometers having diffuse-specular surfaces

    NASA Technical Reports Server (NTRS)

    Mahan, J. R.; Eskin, L. D.

    1981-01-01

    A viable alternative to the net exchange method of radiative analysis which is equally applicable to diffuse and diffuse-specular enclosures is presented. It is particularly more advantageous to use than the net exchange method in the case of a transient thermal analysis involving conduction and storage of energy as well as radiative exchange. A new quantity, called the distribution factor is defined which replaces the angle factor and the configuration factor. Once obtained, the array of distribution factors for an ensemble of surface elements which define an enclosure permits the instantaneous net radiative heat fluxes to all of the surfaces to be computed directly in terms of the known surface temperatures at that instant. The formulation of the thermal model is described, as is the determination of distribution factors by application of a Monte Carlo analysis. The results show that when fewer than 10,000 packets are emitted, an unsatisfactory approximation for the distribution factors is obtained, but that 10,000 packets is sufficient.

  2. Chapter 5: Thermal Indices and Their Applications for Livestock Environments

    USDA-ARS?s Scientific Manuscript database

    Heat exchanges with the environment are a crucial process for maintaining homeothermy by humans and other animals. These exchanges involve heat production, conservation and dissipation, and are dependent on both biological and physical factors. The complexity of these exchanges has led to many attem...

  3. Effect of mobile phone reminder messages on adherence of stent removal or exchange in patients with benign pancreaticobiliary diseases: a prospectively randomized, controlled study.

    PubMed

    Gu, Yong; Wang, Limei; Zhao, Lina; Liu, Zhiguo; Luo, Hui; Tao, Qin; Zhang, Rongchun; He, Shuixiang; Wang, Xiangping; Huang, Rui; Zhang, Linhui; Pan, Yanglin; Guo, Xuegang

    2016-08-26

    Plastic and covered metal stents need to be removed or exchanged within appropriate time in case of undesirable complications. However, it is not uncommon that patients do not follow the recommendation for further stent management after Endoscopic Retrograde Cholangiopancreatography (ERCP). The effect of short message service (SMS) intervention monthly on the stent removal/exchange adherence in patients after ERCP is unknown at this time. A prospective, randomized controlled study was conducted. After receiving regular instructions, patients were randomly assigned to receive SMS reminding monthly (SMS group) for stent removal/exchange or not (control group). The primary outcome was stent removal/exchange adherence within appropriate time (4 months for plastic stent or 7 months for covered stent). Multivariate analysis was performed to assess factors associated with stent removal/exchange adherence within appropriate time. Intention-to-treat analysis was used. A total of 48 patients were randomized, 23 to the SMS group and 25 to the control. Adherence to stent removal/exchange was reported in 78.2 % (18/23) of patients receiving the SMS intervention compared with 40 % (10/25) in the control group (RR 1.98, 95 % CI 1.16-3.31; p = 0 · 010). Among patients with plastic stent insertion, the median interval time from stent implantation to stent removal/exchange were 90 days in the SMS group and 136 days in the control respectively (HR 0.36, 95 % CI 0.16-0.84, p = 0.018). No difference was found between the two groups regarding late-stage stent-related complications. The rate of recurrent abdominal pain tended to be lower in SMS group without significant difference (8.7 vs 28 %, p = 0.144). Multivariate logistic regression analyses revealed that SMS reminding was the only factor associated with adherence of stent removal/exchange (OR 6.73, 95 % CI 1.64-27.54, p = 0.008). This first effectiveness trial demonstrated that SMS reminding monthly could significantly increase the patient adherence to stent removal/exchange after ERCP. The study was respectively registered on July 10 in 2016 at ClinicalTrials.gov ( NCT02831127 ).

  4. Structure of Shigella IpgB2 in Complex with Human RhoA

    PubMed Central

    Klink, Björn U.; Barden, Stephan; Heidler, Thomas V.; Borchers, Christina; Ladwein, Markus; Stradal, Theresia E. B.; Rottner, Klemens; Heinz, Dirk W.

    2010-01-01

    A common theme in bacterial pathogenesis is the manipulation of eukaryotic cells by targeting the cytoskeleton. This is in most cases achieved either by modifying actin, or indirectly via activation of key regulators controlling actin dynamics such as Rho-GTPases. A novel group of bacterial virulence factors termed the WXXXE family has emerged as guanine nucleotide exchange factors (GEFs) for these GTPases. The precise mechanism of nucleotide exchange, however, has remained unclear. Here we report the structure of the WXXXE-protein IpgB2 from Shigella flexneri and its complex with human RhoA. We unambiguously identify IpgB2 as a bacterial RhoA-GEF and dissect the molecular mechanism of GDP release, an essential prerequisite for GTP binding. Our observations uncover that IpgB2 induces conformational changes on RhoA mimicking DbI- but not DOCK family GEFs. We also show that dissociation of the GDP·Mg2+ complex is preceded by the displacement of the metal ion to the α-phosphate of the nucleotide, diminishing its affinity to the GTPase. These data refine our understanding of the mode of action not only of WXXXE GEFs but also of mammalian GEFs of the DH/PH family. PMID:20363740

  5. Andrographolide derivatives inhibit guanine nucleotide exchange and abrogate oncogenic Ras function

    PubMed Central

    Hocker, Harrison J.; Cho, Kwang-Jin; Chen, Chung-Ying K.; Rambahal, Nandini; Sagineedu, Sreenivasa Rao; Shaari, Khozirah; Stanslas, Johnson; Hancock, John F.; Gorfe, Alemayehu A.

    2013-01-01

    Aberrant signaling by oncogenic mutant rat sarcoma (Ras) proteins occurs in ∼15% of all human tumors, yet direct inhibition of Ras by small molecules has remained elusive. Recently, several small-molecule ligands have been discovered that directly bind Ras and inhibit its function by interfering with exchange factor binding. However, it is unclear whether, or how, these ligands could lead to drugs that act against constitutively active oncogenic mutant Ras. Using a dynamics-based pocket identification scheme, ensemble docking, and innovative cell-based assays, here we show that andrographolide (AGP)—a bicyclic diterpenoid lactone isolated from Andrographis paniculata—and its benzylidene derivatives bind to transient pockets on Kirsten-Ras (K-Ras) and inhibit GDP–GTP exchange. As expected for inhibitors of exchange factor binding, AGP derivatives reduced GTP loading of wild-type K-Ras in response to acute EGF stimulation with a concomitant reduction in MAPK activation. Remarkably, however, prolonged treatment with AGP derivatives also reduced GTP loading of, and signal transmission by, oncogenic mutant K-RasG12V. In sum, the combined analysis of our computational and cell biology results show that AGP derivatives directly bind Ras, block GDP–GTP exchange, and inhibit both wild-type and oncogenic K-Ras signaling. Importantly, our findings not only show that nucleotide exchange factors are required for oncogenic Ras signaling but also demonstrate that inhibiting nucleotide exchange is a valid approach to abrogating the function of oncogenic mutant Ras. PMID:23737504

  6. Factors motivating and affecting health information exchange usage

    PubMed Central

    Zhao, Hongwei; Jaspserson, 'Jon; Gamm, Larry D; Ohsfeldt, Robert L

    2011-01-01

    Objective Health information exchange (HIE) is the process of electronically sharing patient-level information between providers. However, where implemented, reports indicate HIE system usage is low. The aim of this study was to determine the factors associated with different types of HIE usage. Design Cross-sectional analysis of clinical data from emergency room encounters included in an operational HIE effort linked to system user logs using crossed random-intercept logistic regression. Measurements Independent variables included factors indicative of information needs. System usage was measured as none, basic usage, or a novel pattern of usage. Results The system was accessed for 2.3% of all encounters (6142 out of 271 305). Novel usage patterns were more likely for more complex patients. The odds of HIE usage were lower in the face of time constraints. In contrast to expectations, system usage was lower when the patient was unfamiliar to the facility. Limitations Because of differences between HIE efforts and the fact that not all types of HIE usage (ie, public health) could be included in the analysis, results are limited in terms of generalizablity. Conclusions This study of actual HIE system usage identifies patients and circumstances in which HIE is more likely to be used and factors that are likely to discourage usage. The paper explores the implications of the findings for system redesign, information integration across exchange partners, and for meaningful usage criteria emerging from provisions of the Health Information Technology for Economic & Clinical Health Act. PMID:21262919

  7. Carbonyl sulfide (COS) as a tracer for canopy photosynthesis, transpiration and stomatal conductance: potential and limitations

    PubMed Central

    Wohlfahrt, Georg; Brilli, Federico; Hörtnagl, Lukas; Xu, Xiaobin; Bingemer, Heinz; Hansel, Armin; Loreto, Francesco

    2012-01-01

    The theoretical basis for the link between the leaf exchange of carbonyl sulfide (COS), carbon dioxide (CO2) and water vapour (H2O) and the assumptions that need to be made in order to use COS as a tracer for canopy net photosynthesis, transpiration and stomatal conductance, are reviewed. The ratios of COS to CO2 and H2O deposition velocities used to this end are shown to vary with the ratio of the internal to ambient CO2 and H2O mole fractions and the relative limitations by boundary layer, stomatal and internal conductance for COS. It is suggested that these deposition velocity ratios exhibit considerable variability, a finding that challenges current parameterizations, which treat these as vegetation-specific constants. COS is shown to represent a better tracer for CO2 than H2O. Using COS as a tracer for stomatal conductance is hampered by our present poor understanding of the leaf internal conductance to COS. Estimating canopy level CO2 and H2O fluxes requires disentangling leaf COS exchange from other ecosystem sources/sinks of COS. We conclude that future priorities for COS research should be to improve the quantitative understanding of the variability in the ratios of COS to CO2 and H2O deposition velocities and the controlling factors, and to develop operational methods for disentangling ecosystem COS exchange into contributions by leaves and other sources/sinks. To this end, integrated studies, which concurrently quantify the ecosystem-scale CO2, H2O and COS exchange and the corresponding component fluxes, are urgently needed. We investigate the potential of carbonyl sulfide (COS) for being used as a tracer for canopy net photosynthesis, transpiration and stomatal conductance by examining the theoretical basis of the link between leaf COS, carbon dioxide (CO2) and water vapour (H2O) exchange. Our analysis identifies several limitations that need to be overcome to this end, however at present we lack appropriate ecosystem-scale field measurements for assessing their practical significance. It however appears that COS represents a better tracer for CO2 than H2O. Concurrent measurements of ecosystem scale COS, CO2 and H2O exchange are advocated. PMID:22017586

  8. Retardation of ammonium and potassium transport through a contaminated sand and gravel aquifer: The Role of cation exchange

    USGS Publications Warehouse

    Ceazan, M.L.; Thurman, E.M.; Smith, R.L.

    1989-01-01

    The role of cation exchange in the retardation of ammonium (NH4+) and potassium (K+) transport in a shallow sand and gravel aquifer was evaluated by use of observed distributions of NH4+ and K+ within a plume of sewage-contaminated groundwater, small-scale tracer injection tests, and batch sorption experiments on aquifer material. Both NH4+ and K+ were transported ???2 km in the 4-km-long contaminant plume (retardation factor, Rf = 2.0). Sediments from the NH4+-containing zone of the plume contained significant quantities of KCl-extractable NH4+ (extraction distribution coefficient, Kd,extr = 0.59-0.87 mL/g of dry sediment), and when added to uncontaminated sediments, NH4+ sorption followed a linear isotherm. Small-scale tracer tests demonstrated that NH4+ and K+ were retarded (Rf =3.5) relative to a nonreactive tracer (Br-). Sorption of dissolved NH4+ was accompanied by concomitant release of calcium (Ca2+), magnesium (Mg2+), and sodium (Na+) from aquifer sediments, suggesting involvement of cation exchange. In contrast, nitrate (NO3-) was not retarded and cleanly separated from NH4+ and K+ in the small-scale tracer tests. This study demonstrates that transport of NH4+ and K+ through a sand and gravel aquifer can be markedly affected by cation-exchange processes even at a clay content less than 0.1%.

  9. An Excel tool for deriving key photosynthetic parameters from combined gas exchange and chlorophyll fluorescence: theory and practice.

    PubMed

    Bellasio, Chandra; Beerling, David J; Griffiths, Howard

    2016-06-01

    Combined photosynthetic gas exchange and modulated fluorometres are widely used to evaluate physiological characteristics associated with phenotypic and genotypic variation, whether in response to genetic manipulation or resource limitation in natural vegetation or crops. After describing relatively simple experimental procedures, we present the theoretical background to the derivation of photosynthetic parameters, and provide a freely available Excel-based fitting tool (EFT) that will be of use to specialists and non-specialists alike. We use data acquired in concurrent variable fluorescence-gas exchange experiments, where A/Ci and light-response curves have been measured under ambient and low oxygen. From these data, the EFT derives light respiration, initial PSII (photosystem II) photochemical yield, initial quantum yield for CO2 fixation, fraction of incident light harvested by PSII, initial quantum yield for electron transport, electron transport rate, rate of photorespiration, stomatal limitation, Rubisco (ribulose 1·5-bisphosphate carboxylase/oxygenase) rate of carboxylation and oxygenation, Rubisco specificity factor, mesophyll conductance to CO2 diffusion, light and CO2 compensation point, Rubisco apparent Michaelis-Menten constant, and Rubisco CO2 -saturated carboxylation rate. As an example, a complete analysis of gas exchange data on tobacco plants is provided. We also discuss potential measurement problems and pitfalls, and suggest how such empirical data could subsequently be used to parameterize predictive photosynthetic models. © 2015 John Wiley & Sons Ltd.

  10. The Small Molecule Inhibitor G6 Significantly Reduces Bone Marrow Fibrosis and the Mutant Burden in a Mouse Model of Jak2-Mediated Myelofibrosis

    PubMed Central

    Kirabo, Annet; Park, Sung O.; Wamsley, Heather L.; Gali, Meghanath; Baskin, Rebekah; Reinhard, Mary K.; Zhao, Zhizhuang J.; Bisht, Kirpal S.; Keserű, György M.; Cogle, Christopher R.; Sayeski, Peter P.

    2013-01-01

    Philadelphia chromosome–negative myeloproliferative neoplasms, including polycythemia vera, essential thrombocytosis, and myelofibrosis, are disorders characterized by abnormal hematopoiesis. Among these myeloproliferative neoplasms, myelofibrosis has the most unfavorable prognosis. Furthermore, currently available therapies for myelofibrosis have little to no efficacy in the bone marrow and hence, are palliative. We recently developed a Janus kinase 2 (Jak2) small molecule inhibitor called G6 and found that it exhibits marked efficacy in a xenograft model of Jak2-V617F–mediated hyperplasia and a transgenic mouse model of Jak2-V617F–mediated polycythemia vera/essential thrombocytosis. However, its efficacy in Jak2-mediated myelofibrosis has not previously been examined. Here, we hypothesized that G6 would be efficacious in Jak2-V617F–mediated myelofibrosis. To test this, mice expressing the human Jak2-V617F cDNA under the control of the vav promoter were administered G6 or vehicle control solution, and efficacy was determined by measuring parameters within the peripheral blood, liver, spleen, and bone marrow. We found that G6 significantly reduced extramedullary hematopoiesis in the liver and splenomegaly. In the bone marrow, G6 significantly reduced pathogenic Jak/STAT signaling by 53%, megakaryocytic hyperplasia by 70%, and the Jak2 mutant burden by 68%. Furthermore, G6 significantly improved the myeloid to erythroid ratio and significantly reversed the myelofibrosis. Collectively, these results indicate that G6 is efficacious in Jak2-V617F–mediated myelofibrosis, and given its bone marrow efficacy, it may alter the natural history of this disease. PMID:22796437

  11. Reconsideration of data and correlations for plate finned-tube heat exchangers

    NASA Astrophysics Data System (ADS)

    Otović, Milena; Mihailović, Miloš; Genić, Srbislav; Jaćimović, Branislav; Milovančević, Uroš; Marković, Saša

    2018-04-01

    This paper deals with heat exchangers having plain finned tubes in staggered (triangular) pattern. The objective of this paper is to provide the heat transfer and friction factor correlation which can be used in engineering practice. For this purpose, the experimental data of several (most cited) authors who deal with this type of heat exchangers are used. The new correlations are established to predict the air-side heat transfer coefficient and friction factor as a function of the Reynolds number and geometric variables of the heat exchanger - tube diameter, tube pitch, fin spacing, tube rows, etc. In those correlations the characteristic dimension in Reynolds number is calculated by using the new parameter - volumetric porosity. Also, there are given the errors of those correlations.

  12. Carbon dioxide fluxes from a degraded woodland in West Africa and their responses to main environmental factors.

    PubMed

    Ago, Expedit Evariste; Serça, Dominique; Agbossou, Euloge Kossi; Galle, Sylvie; Aubinet, Marc

    2015-12-01

    In West Africa, natural ecosystems such as woodlands are the main source for energy, building poles and livestock fodder. They probably behave like net carbon sinks, but there are only few studies focusing on their carbon exchange with the atmosphere. Here, we have analyzed CO 2 fluxes measured for 17 months by an eddy-covariance system over a degraded woodland in northern Benin. Specially, temporal evolution of the fluxes and their relationships with the main environmental factors were investigated between the seasons. This study shows a clear response of CO 2 absorption to photosynthetic photon flux density (Q p ), but it varies according to the seasons. After a significant and long dry period, the ecosystem respiration (R) has increased immediately to the first significant rains. No clear dependency of ecosystem respiration on temperature has been observed. The degraded woodlands are probably the "carbon neutral" at the annual scale. The net ecosystem exchange (NEE) was negative during wet season and positive during dry season, and its annual accumulation was equal to +29 ± 16 g C m -2 . The ecosystem appears to be more efficient in the morning and during the wet season than in the afternoon and during the dry season. This study shows diurnal and seasonal contrasted variations in the CO 2 fluxes in relation to the alternation between dry and wet seasons. The Nangatchori site is close to the equilibrium state according to its carbon exchanges with the atmosphere. The length of the observation period was too short to justify the hypothesis about the "carbon neutrality" of the degraded woodlands at the annual scale in West Africa. Besides, the annual net ecosystem exchange depends on the intensity of disturbances due to the site management system. Further research works are needed to define a woodland management policy that might keep these ecosystems as carbon sinks.

  13. Effects of land use on surface–atmosphere exchanges of trace gases and energy in Borneo: comparing fluxes over oil palm plantations and a rainforest

    PubMed Central

    Fowler, David; Nemitz, Eiko; Misztal, Pawel; Di Marco, Chiara; Skiba, Ute; Ryder, James; Helfter, Carole; Cape, J. Neil; Owen, Sue; Dorsey, James; Gallagher, Martin W.; Coyle, Mhairi; Phillips, Gavin; Davison, Brian; Langford, Ben; MacKenzie, Rob; Muller, Jennifer; Siong, Jambery; Dari-Salisburgo, Cesare; Di Carlo, Piero; Aruffo, Eleonora; Giammaria, Franco; Pyle, John A.; Hewitt, C. Nicholas

    2011-01-01

    This paper reports measurements of land–atmosphere fluxes of sensible and latent heat, momentum, CO2, volatile organic compounds (VOCs), NO, NO2, N2O and O3 over a 30 m high rainforest canopy and a 12 m high oil palm plantation in the same region of Sabah in Borneo between April and July 2008. The daytime maximum CO2 flux to the two canopies differs by approximately a factor of 2, 1200 mg C m−2 h−1 for the oil palm and 700 mg C m−2 h−1 for the rainforest, with the oil palm plantation showing a substantially greater quantum efficiency. Total VOC emissions are also larger over the oil palm than over the rainforest by a factor of 3. Emissions of isoprene from the oil palm canopy represented 80 per cent of the VOC emissions and exceeded those over the rainforest in similar light and temperature conditions by on average a factor of 5. Substantial emissions of estragole (1-allyl-4-methoxybenzene) from the oil palm plantation were detected and no trace of this VOC was detected in or above the rainforest. Deposition velocities for O3 to the rainforest were a factor of 2 larger than over oil palm. Emissions of nitrous oxide were larger from the soils of the oil palm plantation than from the soils of the rainforest by approximately 25 per cent. It is clear from the measurements that the large change in the species composition generated by replacing rainforest with oil palm leads to profound changes in the net exchange of most of the trace gases measured, and thus on the chemical composition of the boundary layer over these surfaces. PMID:22006962

  14. Effects of land use on surface-atmosphere exchanges of trace gases and energy in Borneo: comparing fluxes over oil palm plantations and a rainforest.

    PubMed

    Fowler, David; Nemitz, Eiko; Misztal, Pawel; Di Marco, Chiara; Skiba, Ute; Ryder, James; Helfter, Carole; Cape, J Neil; Owen, Sue; Dorsey, James; Gallagher, Martin W; Coyle, Mhairi; Phillips, Gavin; Davison, Brian; Langford, Ben; MacKenzie, Rob; Muller, Jennifer; Siong, Jambery; Dari-Salisburgo, Cesare; Di Carlo, Piero; Aruffo, Eleonora; Giammaria, Franco; Pyle, John A; Hewitt, C Nicholas

    2011-11-27

    This paper reports measurements of land-atmosphere fluxes of sensible and latent heat, momentum, CO(2), volatile organic compounds (VOCs), NO, NO(2), N(2)O and O(3) over a 30 m high rainforest canopy and a 12 m high oil palm plantation in the same region of Sabah in Borneo between April and July 2008. The daytime maximum CO(2) flux to the two canopies differs by approximately a factor of 2, 1200 mg C m(-2) h(-1) for the oil palm and 700 mg C m(-2) h(-1) for the rainforest, with the oil palm plantation showing a substantially greater quantum efficiency. Total VOC emissions are also larger over the oil palm than over the rainforest by a factor of 3. Emissions of isoprene from the oil palm canopy represented 80 per cent of the VOC emissions and exceeded those over the rainforest in similar light and temperature conditions by on average a factor of 5. Substantial emissions of estragole (1-allyl-4-methoxybenzene) from the oil palm plantation were detected and no trace of this VOC was detected in or above the rainforest. Deposition velocities for O(3) to the rainforest were a factor of 2 larger than over oil palm. Emissions of nitrous oxide were larger from the soils of the oil palm plantation than from the soils of the rainforest by approximately 25 per cent. It is clear from the measurements that the large change in the species composition generated by replacing rainforest with oil palm leads to profound changes in the net exchange of most of the trace gases measured, and thus on the chemical composition of the boundary layer over these surfaces.

  15. The Yeast Nuclear Pore Complex and Transport Through It

    PubMed Central

    Aitchison, John D.; Rout, Michael P.

    2012-01-01

    Exchange of macromolecules between the nucleus and cytoplasm is a key regulatory event in the expression of a cell’s genome. This exchange requires a dedicated transport system: (1) nuclear pore complexes (NPCs), embedded in the nuclear envelope and composed of proteins termed nucleoporins (or “Nups”), and (2) nuclear transport factors that recognize the cargoes to be transported and ferry them across the NPCs. This transport is regulated at multiple levels, and the NPC itself also plays a key regulatory role in gene expression by influencing nuclear architecture and acting as a point of control for various nuclear processes. Here we summarize how the yeast Saccharomyces has been used extensively as a model system to understand the fundamental and highly conserved features of this transport system, revealing the structure and function of the NPC; the NPC’s role in the regulation of gene expression; and the interactions of transport factors with their cargoes, regulatory factors, and specific nucleoporins. PMID:22419078

  16. The Inter-Annual Variability Analysis of Carbon Exchange in Low Artic Fen Uncovers The Climate Sensitivity And The Uncertainties Around Net Ecosystem Exchange Partitioning

    NASA Astrophysics Data System (ADS)

    Blanco, E. L.; Lund, M.; Williams, M. D.; Christensen, T. R.; Tamstorf, M. P.

    2015-12-01

    An improvement in our process-based understanding of CO2 exchanges in the Arctic, and their climate sensitivity, is critical for examining the role of tundra ecosystems in changing climates. Arctic organic carbon storage has seen increased attention in recent years due to large potential for carbon releases following thaw. Our knowledge about the exact scale and sensitivity for a phase-change of these C stocks are, however, limited. Minor variations in Gross Primary Production (GPP) and Ecosystem Respiration (Reco) driven by changes in the climate can lead to either C sink or C source states, which likely will impact the overall C cycle of the ecosystem. Eddy covariance data is usually used to partition Net Ecosystem Exchange (NEE) into GPP and Reco achieved by flux separation algorithms. However, different partitioning approaches lead to different estimates. as well as undefined uncertainties. The main objectives of this study are to use model-data fusion approaches to (1) determine the inter-annual variability in C source/sink strength for an Arctic fen, and attribute such variations to GPP vs Reco, (2) investigate the climate sensitivity of these processes and (3) explore the uncertainties in NEE partitioning. The intention is to elaborate on the information gathered in an existing catchment area under an extensive cross-disciplinary ecological monitoring program in low Arctic West Greenland, established under the auspices of the Greenland Ecosystem Monitoring (GEM) program. The use of such a thorough long-term (7 years) dataset applied to the exploration in inter-annual variability of carbon exchange, related driving factors and NEE partition uncertainties provides a novel input into our understanding about land-atmosphere CO2 exchange.

  17. Overall heat transfer coefficient and pressure drop in a typical tubular exchanger employing alumina nano-fluid as the tube side hot fluid

    NASA Astrophysics Data System (ADS)

    Kabeel, A. E.; Abdelgaied, Mohamed

    2016-08-01

    Nano-fluids are used to improve the heat transfer rates in heat exchangers, especially; the shell-and-tube heat exchanger that is considered one of the most important types of heat exchangers. In the present study, an experimental loop is constructed to study the thermal characteristics of the shell-and-tube heat exchanger; at different concentrations of Al2O3 nonmetallic particles (0.0, 2, 4, and 6 %). This material concentrations is by volume concentrations in pure water as a base fluid. The effects of nano-fluid concentrations on the performance of shell and tube heat exchanger have been conducted based on the overall heat transfer coefficient, the friction factor, the pressure drop in tube side, and the entropy generation rate. The experimental results show that; the highest heat transfer coefficient is obtained at a nano-fluid concentration of 4 % of the shell side. In shell side the maximum percentage increase in the overall heat transfer coefficient has reached 29.8 % for a nano-fluid concentration of 4 %, relative to the case of the base fluid (water) at the same tube side Reynolds number. However; in the tube side the maximum relative increase in pressure drop has recorded the values of 12, 28 and 48 % for a nano-material concentration of 2, 4 and 6 %, respectively, relative to the case without nano-fluid, at an approximate value of 56,000 for Reynolds number. The entropy generation reduces with increasing the nonmetallic particle volume fraction of the same flow rates. For increase the nonmetallic particle volume fraction from 0.0 to 6 % the rate of entropy generation decrease by 10 %.

  18. Severe Hypoglycemia and Diabetic Ketoacidosis among Youth with Type 1 Diabetes in the T1D Exchange Clinic Registry

    PubMed Central

    Cengiz, Eda; Xing, Dongyuan; Wong, Jenise C.; Wolfsdorf, Joseph I.; Haymond, Morey W.; Rewers, Arleta; Shanmugham, Satya; Tamborlane, William V.; Willi, Steven M.; Seiple, Diane L.; Miller, Kellee M.; DuBose, Stephanie N.; Beck, Roy W.

    2014-01-01

    Objective Severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) are common serious acute complications of type 1 diabetes (T1D). The aim of this study was to determine the frequency of SH and DKA and identify factors related to their occurrence in the T1D Exchange pediatric and young adult cohort. Research Design and Methods The analysis included 13,487 participants in the T1D Exchange clinic registry aged 2-<26 years with T1D ≥2 years. Separate logistic regression models were used to evaluate the association of baseline demographic and clinical factors with the occurrence of SH or DKA in the prior 12 months. Results Non-White race, no private health insurance and lower household income were associated with higher frequencies of both SH and DKA (p<0.001). SH frequency was highest in children <6 years old (p=0.005), but across the age range, SH was not associated with HbA1c levels after controlling for other factors (p=0.72). DKA frequency was highest in adolescents (p<0.001) and associated with higher HbA1c (p<0.001). Conclusions Our data show that poor glycemic control increases the risk of DKA but does not protect against severe hypoglycemia in youth and young adults with type 1 diabetes. The high frequencies of SH and DKA observed in disadvantaged minorities with T1D highlight the need for targeted interventions and new treatment paradigms for patients in these high risk groups. PMID:23469984

  19. Control of the Ability of Profilin to Bind and Facilitate Nucleotide Exchange from G-actin*

    PubMed Central

    Wen, Kuo-Kuang; McKane, Melissa; Houtman, Jon C. D.; Rubenstein, Peter A.

    2008-01-01

    A major factor in profilin regulation of actin cytoskeletal dynamics is its facilitation of G-actin nucleotide exchange. However, the mechanism of this facilitation is unknown. We studied the interaction of yeast (YPF) and human profilin 1 (HPF1) with yeast and mammalian skeletal muscle actins. Homologous pairs (YPF and yeast actin, HPF1 and muscle actin) bound more tightly to one another than heterologous pairs. However, with saturating profilin, HPF1 caused a faster etheno-ATP exchange with both yeast and muscle actins than did YPF. Based on the -fold change in ATP exchange rate/Kd, however, the homologous pairs are more efficient than the heterologous pairs. Thus, strength of binding of profilin to actin and nucleotide exchange rate are not tightly coupled. Actin/HPF interactions were entropically driven, whereas YPF interactions were enthalpically driven. Hybrid yeast actins containing subdomain 1 (sub1) or subdomain 1 and 2 (sub12) muscle actin residues bound more weakly to YPF than did yeast actin (Kd = 2 μm versus 0.6 μm). These hybrids bound even more weakly to HPF than did yeast actin (Kd = 5 μm versus 3.2 μm). sub1/YPF interactions were entropically driven, whereas the sub12/YPF binding was enthalpically driven. Compared with WT yeast actin, YPF binding to sub1 occurred with a 5 times faster koff and a 2 times faster kon. sub12 bound with a 3 times faster koff and a 1.5 times slower kon. Profilin controls the energetics of its interaction with nonhybrid actin, but interactions between actin subdomains 1 and 2 affect the topography of the profilin binding site. PMID:18223293

  20. Influence of Human Activity Patterns, particle composition, and residential air exchange rates on modeled distributions of PM 2.5 exposure compared with central-site monitoring data

    EPA Science Inventory

    Central-site monitors do not account for factors such as outdoor-to-indoor transport and human activity patterns that influence personal exposures to ambient fine-particulate matter (PM2.5). We describe and compare different ambient PM2.5 exposure estimation...

  1. Spatially variable stage-driven groundwater-surface water interaction inferred from time-frequency analysis of distributed temperature sensing data

    USGS Publications Warehouse

    Mwakanyamale, Kisa; Slater, Lee; Day-Lewis, Frederick D.; Elwaseif, Mehrez; Johnson, Carole D.

    2012-01-01

    Characterization of groundwater-surface water exchange is essential for improving understanding of contaminant transport between aquifers and rivers. Fiber-optic distributed temperature sensing (FODTS) provides rich spatiotemporal datasets for quantitative and qualitative analysis of groundwater-surface water exchange. We demonstrate how time-frequency analysis of FODTS and synchronous river stage time series from the Columbia River adjacent to the Hanford 300-Area, Richland, Washington, provides spatial information on the strength of stage-driven exchange of uranium contaminated groundwater in response to subsurface heterogeneity. Although used in previous studies, the stage-temperature correlation coefficient proved an unreliable indicator of the stage-driven forcing on groundwater discharge in the presence of other factors influencing river water temperature. In contrast, S-transform analysis of the stage and FODTS data definitively identifies the spatial distribution of discharge zones and provided information on the dominant forcing periods (≥2 d) of the complex dam operations driving stage fluctuations and hence groundwater-surface water exchange at the 300-Area.

  2. Manganese availability is negatively associated with carbon storage in northern coniferous forest humus layers.

    PubMed

    Stendahl, Johan; Berg, Björn; Lindahl, Björn D

    2017-11-14

    Carbon sequestration below ground depends on organic matter input and decomposition, but regulatory bottlenecks remain unclear. The relative importance of plant production, climate and edaphic factors has to be elucidated to better predict carbon storage in forests. In Swedish forest soil inventory data from across the entire boreal latitudinal range (n = 2378), the concentration of exchangeable manganese was singled out as the strongest predictor (R 2  = 0.26) of carbon storage in the extensive organic horizon (mor layer), which accounts for one third of the total below ground carbon. In comparison, established ecosystem models applied on the same data have failed to predict carbon stocks (R 2  < 0.05), and in our study manganese availability overshadowed both litter production and climatic factors. We also identified exchangeable potassium as an additional strong predictor, however strongly correlated with manganese. The negative correlation between manganese and carbon highlights the importance of Mn-peroxidases in oxidative decomposition of recalcitrant organic matter. The results support the idea that the fungus-driven decomposition could be a critical factor regulating humus carbon accumulation in boreal forests, as Mn-peroxidases are specifically produced by basidiomycetes.

  3. Meaningful use: a roadmap for the advancement of health information exchange

    PubMed Central

    2013-01-01

    Frankel and colleagues have compared Israel and the U.S.’s experiences with health information exchange (HIE). They highlight the importance of institutional factors in fostering HIE development, notably the influence of local structures, experience and incentives. Historically, information infrastructure in the U.S. has been limited due to lack of standards, fragmented institutions and competition. The Health Information Technology for Economic and Clinical Health (HITECH) Act of 2009 authorized billions of dollars for the adoption and “Meaningful Use” of electronic health records. HITECH programs and Meaningful Use incentives target the advancement of HIE through 1) building blocks, 2) local support and 3) payment incentives. Meaningful Use requirements create a roadmap to broader electronic exchange of health information among providers and with patients. Ultimately, successful HIE in the U.S. will depend on whether Meaningful Use can address institutional needs within local markets. This is a commentary on http://www.ijhpr.org/content/2/1/722 PMID:23880399

  4. Process gas hear recovery

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

    Anderson, W.M.; Thurner, R.P.

    1977-01-01

    In considering the use of regenerative and recuperative heat exchangers for process-gas heat recovery general information regarding heat-exchanger effectiveness versus initial capital investment and operating costs is discussed. Specific examples for preheating combustion air for process furnaces and for using primary and secondary heat exchangers in conjunction with an air-pollution-control system for drying and curing ovens cover basic heat-exchanger design and application considerations as well as investment-payback factors.

  5. Raising the Curtain. A Report with Recommendations on Academic Exchanges with East Central Europe and the USSR. East Central Europe Information Exchange Report 1.

    ERIC Educational Resources Information Center

    Burn, Barbara B.

    This report provides an overview of the changes in the development of academic exchange activity between the United States, the Soviet Union, and East Central Europe in the context of far-reaching reforms throughout the region. It also explores the factors which may facilitate or inhibit further growth in academic exchanges. The report begins with…

  6. Influence of genome and bio-ecology on the prevalence of genome exchange in unisexuals of the Ambystoma complex.

    PubMed

    Beauregard, France; Angers, Bernard

    2018-05-31

    Unisexuals of the blue-spotted salamander complex are thought to reproduce by kleptogenesis. Genome exchanges associated with this sperm-dependent mode of reproduction are expected to result in a higher genetic variation and multiple ploidy levels compared to clonality. However, the existence of some populations exclusively formed of genetically identical individuals suggests that factors could prevent genome exchanges. This study aimed at assessing the prevalence of genome exchange among unisexuals of the Ambystoma laterale-jeffersonianum complex from 10 sites in the northern part of their distribution. A total of 235 individuals, including 207 unisexuals, were genotyped using microsatellite loci and AFLP. Unisexual individuals could be sorted in five genetically distinct groups, likely derived from the same paternal A. jeffersonianum haplome. One of these groups exclusively reproduced clonally, even when found in sympatry with lineages presenting signature of genome exchange. Genome exchange was site-dependent for another group. Genome exchange was detected at all sites for the three remaining groups. Prevalence of genome exchange appears to be associated with ecological conditions such as availability of effective sperm donors. Intrinsic genomic factors may also affect this process, since different lineages in sympatry present highly variable rate of genome exchange. The coexistence of clonal and genetically diversified lineages opens the door to further research on alternatives to genetic variation.

  7. [Characteristics of mercury pollution in soil and atmosphere in Songhua River upstream Jia-pi-gou gold mining area].

    PubMed

    Zhang, Gang; Wang, Ning; Wang, Yuan; Liu, Te; Ai, Jian-Chao

    2012-09-01

    In the studied area of Jia-pi-gou at the upstream area of Songhua River, algamation process has been applied as a dominant method to extract gold for more than one hundred and eighty years, resulting in severe mercury environmental pollution. The total mercury contents in the atmosphere and soil have been determined by mercury analyzer (Zeeman RA915+) and cold atomic absorption spectrophotometry (GB/T 17136-1997), respectively. To study the pollution characteristics of mercury in the soil and atmosphere, the mercury flux at the interface between the soil and the atmosphere of 4 sampling sites Lao-jin-chang, Er-dao-gou, Er-dao-cha and community of Jia-pi-gou have been determined with the method of dynamic flux chamber. Furthermore, linear regression analyses on the total mercury contents between soil and atmosphere have been carried out and the correlation coefficient of mercury exchange flux between soil and atmosphere and meteorological factors has been studied. The results are as follows: (1) The mean value of mercury content in the atmosphere is (71.08 +/- 38.22) ng x m(-3). (2) The mean value of mercury content in the soil is (0.913 1 +/- 0.040 8) mg x kg(-1); it shows remarkably positive correlation between the mercury contents in soil and in the atmosphere. (3) The mercury exchange flux between soil and atmosphere in different locations are Lao-jin-chang [(129.13 +/- 496.07) ng (m2 x h)(-1)], Er-dao-gou [(98.64 +/- 43.96) ng x (m2 x h)(-1)], Er-dao-cha [(23.17 +/- 171.23) ng x (m2 x h)(-1)], and community of Jia-pi-gou [(7.12 +/- 46.33) ng x (m2 x h)(-1)]. (4) Solar radiation is the major influential factor in the mercury exchange flux between the soil and atmosphere in Lao-jin-chang, Er-dao-cha and community of Jia-pi-gou. Solar radiation, air temperature and soil temperature jointly influence the process of the mercury exchange flux between the soil and atmosphere in Er-dao-gou. Under the disturbance of terrain, three noticeably distinctive trend features of daily change of mercury exchange flux between the soil and atmosphere have been formed.

  8. The C-terminal Helix of Pseudomonas aeruginosa Elongation Factor Ts Tunes EF-Tu Dynamics to Modulate Nucleotide Exchange.

    PubMed

    De Laurentiis, Evelina Ines; Mercier, Evan; Wieden, Hans-Joachim

    2016-10-28

    Little is known about the conservation of critical kinetic parameters and the mechanistic strategies of elongation factor (EF) Ts-catalyzed nucleotide exchange in EF-Tu in bacteria and particularly in clinically relevant pathogens. EF-Tu from the clinically relevant pathogen Pseudomonas aeruginosa shares over 84% sequence identity with the corresponding elongation factor from Escherichia coli Interestingly, the functionally closely linked EF-Ts only shares 55% sequence identity. To identify any differences in the nucleotide binding properties, as well as in the EF-Ts-mediated nucleotide exchange reaction, we performed a comparative rapid kinetics and mutagenesis analysis of the nucleotide exchange mechanism for both the E. coli and P. aeruginosa systems, identifying helix 13 of EF-Ts as a previously unnoticed regulatory element in the nucleotide exchange mechanism with species-specific elements. Our findings support the base side-first entry of the nucleotide into the binding pocket of the EF-Tu·EF-Ts binary complex, followed by displacement of helix 13 and rapid binding of the phosphate side of the nucleotide, ultimately leading to the release of EF-Ts. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Plasma exchange in the treatment of thyroid storm secondary to type II amiodarone-induced thyrotoxicosis.

    PubMed

    Zhu, Ling; Zainudin, Sueziani Binte; Kaushik, Manish; Khor, Li Yan; Chng, Chiaw Ling

    2016-01-01

    Type II amiodarone-induced thyrotoxicosis (AIT) is an uncommon cause of thyroid storm. Due to the rarity of the condition, little is known about the role of plasma exchange in the treatment of severe AIT. A 56-year-old male presented with thyroid storm 2months following cessation of amiodarone. Despite conventional treatment, his condition deteriorated. He underwent two cycles of plasma exchange, which successfully controlled the severe hyperthyroidism. The thyroid hormone levels continued to fall up to 10h following plasma exchange. He subsequently underwent emergency total thyroidectomy and the histology of thyroid gland confirmed type II AIT. Management of thyroid storm secondary to type II AIT can be challenging as patients may not respond to conventional treatments, and thyroid storm may be more harmful in AIT patients owing to the underlying cardiac disease. If used appropriately, plasma exchange can effectively reduce circulating hormones, to allow stabilisation of patients in preparation for emergency thyroidectomy. Type II AIT is an uncommon cause of thyroid storm and may not respond well to conventional thyroid storm treatment.Prompt diagnosis and therapy are important, as patients may deteriorate rapidly.Plasma exchange can be used as an effective bridging therapy to emergency thyroidectomy.This case shows that in type II AIT, each cycle of plasma exchange can potentially lower free triiodothyronine levels for 10h.Important factors to consider when planning plasma exchange as a treatment for thyroid storm include timing of each session, type of exchange fluid to be used and timing of surgery.

  10. Distinct Brca1 Mutations Differentially Reduce Hematopoietic Stem Cell Function.

    PubMed

    Mgbemena, Victoria E; Signer, Robert A J; Wijayatunge, Ranjula; Laxson, Travis; Morrison, Sean J; Ross, Theodora S

    2017-01-24

    BRCA1 is a well-known DNA repair pathway component and a tissue-specific tumor suppressor. However, its role in hematopoiesis is uncertain. Here, we report that a cohort of patients heterozygous for BRCA1 mutations experienced more hematopoietic toxicity from chemotherapy than those with BRCA2 mutations. To test whether this reflects a requirement for BRCA1 in hematopoiesis, we generated mice with Brca1 mutations in hematopoietic cells. Mice homozygous for a null Brca1 mutation in the embryonic hematopoietic system (Vav1-iCre;Brca1 F22-24/F22-24 ) developed hematopoietic defects in early adulthood that included reduced hematopoietic stem cells (HSCs). Although mice homozygous for a huBRCA1 knockin allele (Brca1 BRCA1/BRCA1 ) were normal, mice with a mutant huBRCA1/5382insC allele and a null allele (Mx1-Cre;Brca1 F22-24/5382insC ) had severe hematopoietic defects marked by a complete loss of hematopoietic stem and progenitor cells. Our data show that Brca1 is necessary for HSC maintenance and normal hematopoiesis and that distinct mutations lead to different degrees of hematopoietic dysfunction. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  11. Influence of wind and river discharge on the vertical exchange process in the Pearl River Estuary

    NASA Astrophysics Data System (ADS)

    Hong, B.; Peng, S.

    2016-02-01

    Vertical exchange process is controlled by the buoyancy input from river discharge and the momentum input by wind forcing. This study investigates the vertical exchange process in the Pearl River Estuary by using a 3-D numerical model. The vertical exchange time (VET) is used to quantify the magnitude of vertical exchange process in response to changing local wind and river discharge. During the dry season, it only takes about 2 days for the surface layer water mass being transported to the bottom layer. During the wet season, such transport will take more than 20 days in a large portion of the main channel. The water in the slope area can be well ventilated. Linear regression of VET indicates that water column stratification can be used to estimate the VET and up to 71% of the variance can be accounted. The estimation by using river runoff can only account for about 49% of the variance. The effects of wind speed and direction are investigated separately. Neither river runoff nor the stratification can properly predict the VET during the typical wet season. Further investigations are needed to reveal the dynamics of vertical exchange process and find out other factors that influence the VET during the wet season.

  12. Nucleotide Binding by Lhs1p Is Essential for Its Nucleotide Exchange Activity and for Function in Vivo*

    PubMed Central

    de Keyzer, Jeanine; Steel, Gregor J.; Hale, Sarah J.; Humphries, Daniel; Stirling, Colin J.

    2009-01-01

    Protein translocation and folding in the endoplasmic reticulum of Saccharomyces cerevisiae involves two distinct Hsp70 chaperones, Lhs1p and Kar2p. Both proteins have the characteristic domain structure of the Hsp70 family consisting of a conserved N-terminal nucleotide binding domain and a C-terminal substrate binding domain. Kar2p is a canonical Hsp70 whose substrate binding activity is regulated by cochaperones that promote either ATP hydrolysis or nucleotide exchange. Lhs1p is a member of the Grp170/Lhs1p subfamily of Hsp70s and was previously shown to function as a nucleotide exchange factor (NEF) for Kar2p. Here we show that in addition to this NEF activity, Lhs1p can function as a holdase that prevents protein aggregation in vitro. Analysis of the nucleotide requirement of these functions demonstrates that nucleotide binding to Lhs1p stimulates the interaction with Kar2p and is essential for NEF activity. In contrast, Lhs1p holdase activity is nucleotide-independent and unaffected by mutations that interfere with ATP binding and NEF activity. In vivo, these mutants show severe protein translocation defects and are unable to support growth despite the presence of a second Kar2p-specific NEF, Sil1p. Thus, Lhs1p-dependent nucleotide exchange activity is vital for ER protein biogenesis in vivo. PMID:19759005

  13. Exchange nailing for nonunion of diaphyseal fractures of the tibia: our results and an analysis of the risk factors for failure.

    PubMed

    Tsang, S T J; Mills, L A; Frantzias, J; Baren, J P; Keating, J F; Simpson, A H R W

    2016-04-01

    The aim of this study was to identify risk factors for the failure of exchange nailing in nonunion of tibial diaphyseal fractures. A cohort of 102 tibial diaphyseal nonunions in 101 patients with a mean age of 36.9 years (15 to 74) were treated between January 1992 and December 2012 by exchange nailing. Of which 33 (32%) were initially open injuries. The median time from primary fixation to exchange nailing was 6.5 months (interquartile range (IQR) 4.3 to 9.8 months). The main outcome measures were union, number of secondary fixation procedures required to achieve union and time to union. Univariate analysis and multiple regression were used to identify risk factors for failure to achieve union. Multiple causes for the primary nonunion were found for 28 (27%) tibiae, with infection present in 32 (31%). Six patients were lost to follow-up. Further surgical procedures were required in 35 (36%) nonunions. Other fixation modalities were required in five fractures. A single nail exchange procedure achieved union in 60/96 (63%) of all nonunions. Only 11 out of 31 infected nonunions (35.4%) healed after one exchange nail procedure. Up to five repeated exchange nailings, with or without bone grafting, ultimately achieved union in 89 (93%) fractures. The median time to union after exchange nailing was 8.7 months (IQR 5.7 to 14.0 months). Univariate analysis confirmed that an oligotrophic/atrophic pattern of nonunion (p = 0.002), a bone gap of 5 mm or more (p = 0.04) and infection (p < 0.001), were predictive for failure of exchange nailing Multiple regression analysis found that infection was the strongest predictor of failure (p < 0.001). Exchange nailing is an effective treatment for aseptic tibial diaphyseal nonunion. However, in the presence of severe infection with a highly resistant organism, or extensive sclerosis of the bone, other fixation modalities, such as Ilizarov treatment, should be considered. Exchange nailing is an effective treatment for aseptic tibial diaphyseal nonunion. ©2016 The British Editorial Society of Bone & Joint Surgery.

  14. Health information exchange policies of 11 diverse health systems and the associated impact on volume of exchange.

    PubMed

    Downing, N Lance; Adler-Milstein, Julia; Palma, Jonathan P; Lane, Steven; Eisenberg, Matthew; Sharp, Christopher; Longhurst, Christopher A

    2017-01-01

    Provider organizations increasingly have the ability to exchange patient health information electronically. Organizational health information exchange (HIE) policy decisions can impact the extent to which external information is readily available to providers, but this relationship has not been well studied. Our objective was to examine the relationship between electronic exchange of patient health information across organizations and organizational HIE policy decisions. We focused on 2 key decisions: whether to automatically search for information from other organizations and whether to require HIE-specific patient consent. We conducted a retrospective time series analysis of the effect of automatic querying and the patient consent requirement on the monthly volume of clinical summaries exchanged. We could not assess degree of use or usefulness of summaries, organizational decision-making processes, or generalizability to other vendors. Between 2013 and 2015, clinical summary exchange volume increased by 1349% across 11 organizations. Nine of the 11 systems were set up to enable auto-querying, and auto-querying was associated with a significant increase in the monthly rate of exchange (P = .006 for change in trend). Seven of the 11 organizations did not require patient consent specifically for HIE, and these organizations experienced a greater increase in volume of exchange over time compared to organizations that required consent. Automatic querying and limited consent requirements are organizational HIE policy decisions that impact the volume of exchange, and ultimately the information available to providers to support optimal care. Future efforts to ensure effective HIE may need to explicitly address these factors. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association.

  15. Coupling between p210bcr-abl and Shc and Grb2 adaptor proteins in hematopoietic cells permits growth factor receptor-independent link to ras activation pathway.

    PubMed

    Tauchi, T; Boswell, H S; Leibowitz, D; Broxmeyer, H E

    1994-01-01

    Enforced expression of p210bcr-abl transforms interleukin 3 (IL-3)-dependent hematopoietic cell lines to growth factor-independent proliferation. It has been demonstrated that nonreceptor tyrosine kinase oncogenes may couple to the p21ras pathway to exert their transforming effect. In particular, p210bcr-abl was recently found to effect p21ras activation in hematopoietic cells. In this context, experiments were performed to evaluate a protein signaling pathway by which p210bcr-abl might regulate p21ras. It was asked whether Shc p46/p52, a protein containing a src-homology region 2 (SH2) domain, and known to function upstream from p21ras, might form specific complexes with p210bcr-abl and thus, possibly alter p21ras activity by coupling to the guanine nucleotide exchange factor (Sos/CDC25) through the Grb2 protein-Sos complex. This latter complex has been previously demonstrated to occur ubiquitously. We found that p210bcr-abl formed a specific complex with Shc and with Grb2 in three different murine cell lines transfected with a p210bcr-abl expression vector. There appeared to be a higher order complex containing Shc, Grb2, and bcr-abl proteins. In contrast to p210bcr-abl transformed cells, in which there was constitutive tight association between Grb2 and Shc, binding between Grb2 and Shc was Steel factor (SLF)-dependent in a SLF-responsive, nontransformed parental cell line. The SLF-dependent association between Grb2 and Shc in nontransformed cells involved formation of a complex of Grb2 with c-kit receptor after SLF treatment. Thus, p210bcr-abl appears to function in a hematopoietic p21ras activation pathway to allow growth factor-independent coupling between Grb2, which exists in a complex with the guanine nucleotide exchange factor (Sos), and p21ras. Shc may not be required for Grb2-c-kit interaction, because it fails to bind strongly to c-kit.

  16. Environment-Dependent Guest Exchange in Supramolecular Hosts

    PubMed Central

    2015-01-01

    Dynamic exchange of guest molecules, encapsulated in host assemblies, is a phenomenon in supramolecular chemistry that has important implications in several applications. While the mechanism of exchange in micellar assemblies has been previously investigated, the effect of host and guest environment upon the guest-exchange dynamics has received little attention, if any. In this paper, we study the guest-exchange mechanism in pH-sensitive nanogels along with pH-insensitive nanogels as a control. By systematically comparing the behavior of these nanogels, we show that size, concentration, and hydrophobicity can all play a critical role in guest-exchange dynamics. More importantly, these studies reveal that the dominant mechanism of guest exchange can intimately depend on environmental factors. PMID:25244305

  17. Production of heavy water in India

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

    Fareeduddin, S.

    From symposium on nuclear science and engineering; Bombay, India (13 Mar 1973). To meet the requirements of heavy water for the power reactors now under construction and those being planned, a program for providing adequate production capacity has been started. Various processes have been surveyed and the factors which have been considered in the choice of the processes adopted in India are presented. The H/sub 2/S--H/sub 2/0 exchange process adopted for the plant being set up at Kota and the ammoria--hydrogen exchange process adopted for the Baroda plant are briefly described. The status of the various plants under construction hasmore » been presented. The operating experience of the Nangal plant during the last ten years is included. (auth)« less

  18. Influence of pine bark particle size and pH on cation exchange capacity

    USDA-ARS?s Scientific Manuscript database

    Cation exchange capacity (CEC) describes the maximum quantity of cations a soil or substrate can hold while being exchangeable with the soil solution. While CEC has been studied for peat-based substrates, relatively little work has documented factors that affect CEC of pine bark substrates. The ob...

  19. Social Exchange and Sexual Behavior in Young Women's Premarital Relationships in Kenya

    ERIC Educational Resources Information Center

    Luke, Nancy; Goldberg, Rachel E.; Mberu, Blessing U.; Zulu, Eliya M.

    2011-01-01

    Transactional sex, or the exchange of money and gifts for sexual activities within nonmarital relationships, has been widely considered a contributing factor to the disproportionate prevalence of HIV/AIDS among young women in sub-Saharan Africa. This study applied social exchange theory to premarital relationships in order to investigate the…

  20. International Sexual Partnerships May Be Shaped by Sexual Histories and Socioeconomic Status.

    PubMed

    Truong, Hong-Ha M; Mehrotra, Megha; Montoya, Orlando; Lama, Javier R; Guanira, Juan V; Casapía, Martín; Veloso, Valdiléa G; Buchbinder, Susan P; Mayer, Kenneth H; Chariyalertsak, Suwat; Schechter, Mauro; Bekker, Linda-Gail; Kallás, Esper G; Grant, Robert M

    2017-05-01

    Exchange sex and higher education were associated with an increased likelihood of international sexual partnerships (ISPs). Exchange sex and older age were associated with an increased likelihood of condomless sex in ISPs. Educational and socioeconomic factors may create unbalanced power dynamics that influence exchange sex and condomless sex in ISPs.

  1. Landscape determinants of exchangeable calcium and magnesium in Ozark Highland forest soils

    Treesearch

    John M. Kabrick; Keith W. Goyne; Zhaofei Fan; Dennis Meinert

    2011-01-01

    Exchangeable base cations, particularly Ca and Mg, largely govern soil acidity and, consequently, plant species composition in temperate forests. Although studies have identified soil and terrain characteristics affecting exchangeable Ca and Mg, few studies have identified the relative importance of factors affecting Ca and Mg distribution across landscapes. Objectives...

  2. Oxo-exchange of gas-phase uranyl, neptunyl, and plutonyl with water and methanol.

    PubMed

    Lucena, Ana F; Odoh, Samuel O; Zhao, Jing; Marçalo, Joaquim; Schreckenbach, Georg; Gibson, John K

    2014-02-17

    A challenge in actinide chemistry is activation of the strong bonds in the actinyl ions, AnO2(+) and AnO2(2+), where An = U, Np, or Pu. Actinyl activation in oxo-exchange with water in solution is well established, but the exchange mechanisms are unknown. Gas-phase actinyl oxo-exchange is a means to probe these processes in detail for simple systems, which are amenable to computational modeling. Gas-phase exchange reactions of UO2(+), NpO2(+), PuO2(+), and UO2(2+) with water and methanol were studied by experiment and density functional theory (DFT); reported for the first time are experimental results for UO2(2+) and for methanol exchange, as well as exchange rate constants. Key findings are faster exchange of UO2(2+) versus UO2(+) and faster exchange with methanol versus water; faster exchange of UO2(+) versus PuO2(+) was quantified. Computed potential energy profiles (PEPs) are in accord with the observed kinetics, validating the utility of DFT to model these exchange processes. The seemingly enigmatic result of faster exchange for uranyl, which has the strongest oxo-bonds, may reflect reduced covalency in uranyl as compared with plutonyl.

  3. Large-scale synthesis of lead telluride (PbTe) nanotube-based nanocomposites with tunable morphology, crystallinity and thermoelectric properties

    NASA Astrophysics Data System (ADS)

    Park, Kee-Ryung; Cho, Hong-Baek; Song, Yoseb; Kim, Seil; Kwon, Young-Tae; Ryu, Seung Han; Lim, Jae-Hong; Lee, Woo-Jin; Choa, Yong-Ho

    2018-04-01

    A few millimeter-long lead telluride (PbTe) hollow nanofibers with thermoelectric properties was synthesized for the first time with high through manner via three-step sequential process of electrospinning, electrodeposition and cationic exchange reaction. As-synthesized electrospun Ag nanofibers with ultra-long aspect ratio of 10,000 were Te electrodeposited to obtain silver telluride nanotubes and underwent cationic exchange reaction in Pb(NO3)2 solution to obtain polycrystalline PbTe nanotubes with average diameter of 100 nm with 20 nm of wall thickness. Variation of the Ag-to-Pb ratio in the AgxTey-PbTe nanocomposites during the cationic exchange reaction enabled to control the thermoelectric properties of resulting 1D hollow nanofibers. The diameter of Ag nanofiber is the key factor to determine the final dimension of the PbTe nanotubes in the topotactic transformation and the content of Ag ion leads to the enhancement of thermoelectric properties in the AgxTey-PbTe nanocomposites. The synthesized 1D nanocomposite mats showed the highest value of Seebeck coefficient of 433 μV/K (at 300 K) when the remained Ag content was 30%, while the power factor reached highest to 0.567 μW/mK2 for the pure PbTe nanotubes. The enhancement of thermoelectric properties and the composite crystallinity are elucidated with relation to Ag contents in the resulting 1D nanocomposites.

  4. Roles of Bacillus subtilis DprA and SsbA in RecA-mediated genetic recombination.

    PubMed

    Yadav, Tribhuwan; Carrasco, Begoña; Serrano, Ester; Alonso, Juan C

    2014-10-03

    Bacillus subtilis competence-induced RecA, SsbA, SsbB, and DprA are required to internalize and to recombine single-stranded (ss) DNA with homologous resident duplex. RecA, in the ATP · Mg(2+)-bound form (RecA · ATP), can nucleate and form filament onto ssDNA but is inactive to catalyze DNA recombination. We report that SsbA or SsbB bound to ssDNA blocks the RecA filament formation and fails to activate recombination. DprA facilitates RecA filamentation; however, the filaments cannot engage in DNA recombination. When ssDNA was preincubated with SsbA, but not SsbB, DprA was able to activate DNA strand exchange dependent on RecA · ATP. This work demonstrates that RecA · ATP, in concert with SsbA and DprA, catalyzes DNA strand exchange, and SsbB is an accessory factor in the reaction. In contrast, RecA · dATP efficiently catalyzes strand exchange even in the absence of single-stranded binding proteins or DprA, and addition of the accessory factors marginally improved it. We proposed that the RecA-bound nucleotide (ATP and to a lesser extent dATP) might dictate the requirement for accessory factors. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. MODELLING THE UPTAKE AND DISPOSITION OF HYDROPHOBIC ORGANIC CHEMICALS IN FISH USING A PHYSIOLOGICALLY BASED APPROACH

    EPA Science Inventory

    The development of physiologically based toxicokinetic (PBTK) models for hydrophobic chemicals in fish requires: 1) an understanding of chemical efflux at fish gills; 2) knowledge of the factors that limit chemical exchange between blood and tissues; and, 3) a mechanistic descrip...

  6. An investigation of accelerator head scatter and output factor in air.

    PubMed

    Ding, George X

    2004-09-01

    Our purpose in this study was to investigate whether the Monte Carlo simulation can accurately predict output factors in air. Secondary goals were to study the head scatter components and investigate the collimator exchange effect. The Monte Carlo code, BEAMnrc, was used in the study. Photon beams of 6 and 18 MV were from a Varian Clinac 2100EX accelerator and the measurements were performed using an ionization chamber in a mini-phantom. The Monte Carlo calculated in air output factors was within 1% of measured values. The simulation provided information of the origin and the magnitude of the collimator exchange effect. It was shown that the collimator backscatter to the beam monitor chamber played a significant role in the beam output factors. However the magnitude of the scattered dose contributions from the collimator at the isocenter is negligible. The maximum scattered dose contribution from the collimators was about 0.15% and 0.4% of the total dose at the isocenter for a 6 and 18 MV beam, respectively. The scattered dose contributions from the flattening filter at the isocenter were about 0.9-3% and 0.2-6% of the total dose for field sizes of 4x4 cm2-40x40 cm2 for the 6 and 18 MV beam, respectively. The study suggests that measurements of head scatter factors be done at large depth well beyond the depth of electron contamination. The insight information may have some implications for developing generalized empirical models to calculate the head scatter.

  7. Predicting adolescents' disclosure of personal information in exchange for commercial incentives: an application of an extended theory of planned behavior.

    PubMed

    Heirman, Wannes; Walrave, Michel; Ponnet, Koen

    2013-02-01

    This study adopts a global theoretical framework to predict adolescents' disclosure of personal information in exchange for incentives offered by commercial Websites. The study postulates and tests the validity of a model based on the theory of planned behavior (TPB), including antecedent factors of attitude and perceived behavioral control (PBC). A survey was conducted among 1,042 respondents. Results from SEM analyses show that the hypothesized model fits the empirical data well. The model accounts for 61.9 percent of the variance in adolescents' intention to disclose and 43.7 percent of the variance in self-reported disclosure. Perceived social pressure exerted by significant others (subjective norm) is the most important TPB factor in predicting intention to disclose personal information in exchange for incentives. This finding suggests that in discussions of adolescents' information privacy, the importance of social factors outweighs the individually oriented TPB factors of attitude and PBC. Moreover, privacy concern and trust propensity are significant predictors of respondents' attitudes toward online disclosure in exchange for commercial incentives, whereas the frequency of Internet use significantly affects their level of PBC.

  8. The transmission characteristics of indoor particles under different ventilation conditions

    NASA Astrophysics Data System (ADS)

    Lv, Yang; Wang, Haifeng; Wei, Shanshan

    2017-11-01

    In modern society, ventilation is an important method for removing indoor particles. This study applies the parameter of attenuation index to analyze the effect of the removal of indoor particles in the two typical ventilation strategies called ceiling exhaust and slit exhaust strategy. Experiment was conducted in a chamber and riboflavin particles were used as the indoor particles source, instantaneous microbial detection (IMD) used to measure the particulate concentration. Conclusions can be found that air exchange rate is an important factor affecting the indoor particle concentration distribution. In the process of indoor free settling(air exchange rate is 0 h-1), the deposition rate were 0.086 h-1, 0.122 h-1, 0.173 h-1 for the particles of 0.5-1.0 μm, 1.0-3.0μm and 3.0-5.0 μm. When the air exchange rate increased to 2.5 h-1, the differences in the attenuation index is significant. There was also a significant linear relationship between air exchange rate and attenuation index. Furthermore, the effect of the slit exhaust strategy on the removal of coarse particles is more remarkable as the increasing air exchange rate.

  9. Spin-1/2 Heisenberg antiferromagnet on an anisotropic triangular lattice

    NASA Astrophysics Data System (ADS)

    Starykh, Oleg

    2007-03-01

    The Triangular lattice spin-1/2 Heisenberg AntiFerromagnet (TAF) is a prototypical model of frustrated quantum magnetism. While it is believed to exhibit long-range order in the isotropic limit, changes such as spatial anisotropy can alter the delicate balance amongst competing ground states. I will describe the static and dynamic properties of the spatially anisotropic TAF, with inter-chain diagonal exchange J' much weaker than the intrachain exchange J. Treating J' as a perturbation of decoupled Heisenberg spin-1/2 chains, I find that the ground state is spontaneously dimerized in a four-fold degenerate zig-zag pattern. This dimerization instability is driven by quantum fluctuations, which are dramatically enhanced here by the frustrated nature of inter-chain exchange. A magnetic field partially relieves frustration, by canting the spins along the field direction, and causes a quantum phase transition into a magnetically-ordered spin-density-wave phase. This is followed by cone and, finally, fully polarized (saturated) phases, as a function of increasing magnetic field. I show that many of these features are in fact observed in experiments on the celebrated material Cs2CuCl4 (J'/J =1/3). I will also discuss the significant modification of the phase diagram by symmetry-breaking anisotropic Dzyaloshinskii-Moriya (DM) interactions, present in this interesting magnet. In addition to static and thermodynamic properties, the proposed ``one-dimensional'' approach offers a compelling explanation of the unusual experimentally measured dynamical structure factor of Cs2CuCl4 in terms of descendants of one-dimensional spinons. Quite generally, I find characteristic features of a momentum-dependent spinon bound state and a dispersing incoherent excitation in the structure factor, in agreement with experiments.

  10. Factors influencing intentions to use social recommender systems: a social exchange perspective.

    PubMed

    Chang, Tsung-Sheng; Hsiao, Wei-Hung

    2013-05-01

    This study employs the perspective of social exchange theory and seeks to understand users' intentions to use social recommender systems (SRS) through three psychological factors: trust, shared values, and reputation. We use structural equation modeling to analyze 221 valid questionnaires. The results show that trust has a direct positive influence on the intention to use SRS, followed by shared values, whereas reputation has an indirect influence on SRS use. We further discuss specific recommendations concerning these factors for developing SRS.

  11. Genetic Biomarker Prevalence Is Similar in Fecal Immunochemical Test Positive and Negative Colorectal Cancer Tissue.

    PubMed

    Levin, Theodore R; Corley, Douglas A; Jensen, Christopher D; Marks, Amy R; Zhao, Wei K; Zebrowski, Alexis M; Quinn, Virginia P; Browne, Lawrence W; Taylor, William R; Ahlquist, David A; Lidgard, Graham P; Berger, Barry M

    2017-03-01

    Fecal immunochemical test (FIT) screening detects most asymptomatic colorectal cancers. Combining FIT screening with stool-based genetic biomarkers increases sensitivity for cancer, but whether DNA biomarkers (biomarkers) differ for cancers detected versus missed by FIT screening has not been evaluated in a community-based population. To evaluate tissue biomarkers among Kaiser Permanente Northern California patients diagnosed with colorectal cancer within 2 years after FIT screening. FIT-negative and FIT-positive colorectal cancer patients 50-77 years of age were matched on age, sex, and cancer stage. Adequate DNA was isolated from paraffin-embedded specimens in 210 FIT-negative and 211 FIT-positive patients. Quantitative allele-specific real-time target and signal amplification assays were performed for 7 K-ras mutations and 10 aberrantly methylated DNA biomarkers (NDRG4, BMP3, SFMBT2_895, SFMBT2_896, SFMBT2_897, CHST2_7890, PDGFD, VAV3, DTX1, CHST2_7889). One or more biomarkers were found in 414 of 421 CRCs (98.3%). Biomarker expression was not associated with FIT status, with the exception of higher SFMBT2_897 expression in FIT-negative (194 of 210; 92.4%) than in FIT-positive cancers (180 of 211; 85.3%; p = 0.02). There were no consistent differences in biomarker expression by FIT status within age, sex, stage, and cancer location subgroups. The biomarkers of a currently in-use multi-target stool DNA test (K-ras, NDRG4, and BMP3) and eight newly characterized methylated biomarkers were commonly expressed in tumor tissue specimens, independent of FIT result. Additional study using stool-based testing with these new biomarkers will allow assessment of sensitivity, specificity, and clinical utility.

  12. Influence of ligand-bridged substitution on the exchange coupling constant of chromium-wheels host complexes: a density functional theory study

    NASA Astrophysics Data System (ADS)

    Sadeghi Googheri, Motahare; Abolhassani, Mohammad Reza; Mirzaei, Mahmoud

    2018-05-01

    Designing and introducing novel wheel-shaped supramolecular as host complexes with new magnetic properties is the theme of the day. So in this study, new eight binuclear chromium (III) complexes, as models of real chromium-wheel host complexes, were designed based on changing of bridged-ligands and exchange coupling constants (J) of them were calculated using the broken symmetry density functional theory approach. Substitution of fluorine ligand in fluoro-bridged model [Cr2F(tBuCO2)2(H2O)2(OH)4]-1 by halogen anions (Cl-, Br- and I- ) decreased the antiferromagnetic exchange coupling between Cr(III) centres such that by going from F- to I- the J values became more positive. In the case of hydroxo-bridged model [Cr2OH(tBuCO2)2(H2O)2(OH)4]-1, replacement of hydroxyl by methoxy anion (OMe-) strengthened the antiferromagnetic property of the complex but substitution by sulfanide (SH-) and amide (NH2-) anions weakened it and changed the nature of complexes to ferromagnetic. Because of their different magnetic properties, these new investigated complexes can be suggested as interesting synthetic targets. Also, the J value changes due to ligand substitution were evaluated and it was found that the Cr-X bond strength and partial charges of involved atoms were the most effective factors on it.

  13. Understanding the Digital Gap Among US Adults With Disability: Cross-Sectional Analysis of the Health Information National Trends Survey 2013.

    PubMed

    Kim, Eun Ji; Yuan, Yiyang; Liebschutz, Jane; Cabral, Howard; Kazis, Lewis

    2018-03-16

    Disabilities affect more than 1 in 5 US adults, and those with disabilities face multiple barriers in accessing health care. A digital gap, defined as the disparity caused by differences in the ability to use advanced technologies, is assumed to be prevalent among individuals with disabilities. This study examined the associations between disability and use of information technology (IT) in obtaining health information and between trust factors and IT use. We hypothesized that compared to US adults without disabilities, those with disabilities are less likely to refer to the internet for health information, more likely to refer to a health care provider to obtain health information, and less likely to use IT to exchange medical information with a provider. Additionally, we hypothesized that trust factors, such as trust toward health information source and willingness to exchange health information, are associated with IT use. The primary database was the 2013 Health Information National Trends Survey 4 Cycle 3 (N=3185). Disability status, the primary study covariate, was based on 6 questions that encompassed a wide spectrum of conditions, including impairments in mobility, cognition, independent living, vision, hearing, and self-care. Study covariates included sociodemographic factors, respondents' trust toward the internet and provider as information sources, and willingness to exchange medical information via IT with providers. Study outcomes were the use of the internet as the primary health information source, use of health care providers as the primary health information source, and use of IT to exchange medical information with providers. We conducted multivariate logistic regressions to examine the association between disability and study outcomes controlling for study covariates. Multiple imputations with fully conditional specification were used to impute missing values. We found presence of any disability was associated with decreased odds (adjusted odds ratio [AOR] 0.65, 95% CI 0.43-0.98) of obtaining health information from the internet, in particular for those with vision disability (AOR 0.27, 95% CI 0.11-0.65) and those with mobility disability (AOR 0.51, 95% CI 0.30-0.88). Compared to those without disabilities, those with disabilities were significantly more likely to consult a health care provider for health information in both actual (OR 2.21, 95% CI 1.54-3.18) and hypothetical situations (OR 1.80, 95% CI 1.24-2.60). Trust toward health information from the internet (AOR 3.62, 95% CI 2.07-6.33), and willingness to exchange via IT medical information with a provider (AOR 1.88, 95% CI 1.57-2.24) were significant predictors for seeking and exchanging such information, respectively. A potential digital gap may exist among US adults with disabilities in terms of their recent use of the internet for health information. Trust toward health information sources and willingness play an important role in people's engagement in use of the internet for health information. Future studies should focus on addressing trust factors associated with IT use and developing tools to improve access to care for those with disabilities. ©Eun Ji Kim, Yiyang Yuan, Jane Liebschutz, Howard Cabral, Lewis Kazis. Originally published in JMIR Rehabilitation and Assistive Technology (http://rehab.jmir.org), 16.03.2018.

  14. Isotopic exchange of carbon-bound hydrogen over geologic timescales

    NASA Astrophysics Data System (ADS)

    Sessions, Alex L.; Sylva, Sean P.; Summons, Roger E.; Hayes, John M.

    2004-04-01

    The increasing popularity of compound-specific hydrogen isotope (D/H) analyses for investigating sedimentary organic matter raises numerous questions about the exchange of carbon-bound hydrogen over geologic timescales. Important questions include the rates of isotopic exchange, methods for diagnosing exchange in ancient samples, and the isotopic consequences of that exchange. This article provides a review of relevant literature data along with new data from several pilot studies to investigate such issues. Published experimental estimates of exchange rates between organic hydrogen and water indicate that at warm temperatures (50-100°C) exchange likely occurs on timescales of 104 to 108 yr. Incubation experiments using organic compounds and D-enriched water, combined with compound-specific D/H analyses, provide a new and highly sensitive method for measuring exchange at low temperatures. Comparison of δD values for isoprenoid and n-alkyl carbon skeletons in sedimentary organic matter provides no evidence for exchange in young (<1 Ma), cool sediments, but strong evidence for exchange in ancient (>350 Ma) rocks. Specific rates of exchange are probably influenced by the nature and abundance of organic matter, pore-water chemistry, the presence of catalytic mineral surfaces, and perhaps even enzymatic activity. Estimates of equilibrium fractionation factors between organic H and water indicate that typical lipids will be depleted in D relative to water by ∼75 to 140‰ at equilibrium (30°C). Thus large differences in δD between organic molecules and water cannot be unambiguously interpreted as evidence against hydrogen exchange. A better approach may be to use changes in stereochemistry as a proxy for hydrogen exchange. For example, estimated rates of H exchange in pristane are similar to predicted rates for stereochemical inversion in steranes and hopanes. The isotopic consequences of this exchange remain in question. Incubations of cholestene with D2O indicate that the number of D atoms incorporated during structural rearrangements can be far less than the number of C-H bonds that are broken. Sample calculations indicate that, for steranes in immature sediments, the D/H ratio imparted by biosynthesis may be largely preserved in spite of significant structural changes.

  15. 43 CFR 2201.7-2 - Exchange agreement.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Exchange agreement. 2201.7-2 Section 2201... Exchanges-Specific Requirements § 2201.7-2 Exchange agreement. (a) The parties to a proposed exchange may enter into an exchange agreement subsequent to a decision by the authorized officer to approve the...

  16. 43 CFR 2201.7-2 - Exchange agreement.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Exchange agreement. 2201.7-2 Section 2201... Exchanges-Specific Requirements § 2201.7-2 Exchange agreement. (a) The parties to a proposed exchange may enter into an exchange agreement subsequent to a decision by the authorized officer to approve the...

  17. 43 CFR 2201.7-2 - Exchange agreement.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Exchange agreement. 2201.7-2 Section 2201... Exchanges-Specific Requirements § 2201.7-2 Exchange agreement. (a) The parties to a proposed exchange may enter into an exchange agreement subsequent to a decision by the authorized officer to approve the...

  18. Patient safety culture and associated factors: A quantitative and qualitative study of healthcare workers' view in Jimma zone Hospitals, Southwest Ethiopia.

    PubMed

    Wami, Sintayehu Daba; Demssie, Amsalu Feleke; Wassie, Molla Mesele; Ahmed, Ansha Nega

    2016-09-20

    Patient safety culture is an important aspect for quality healthcare delivery and is an issue of high concern globally. In Ethiopia health system little is known and information is limited in scope about patient safety culture. Therefore, the aim of this study was to assess the level of patient safety culture and associated factors in Jimma zone Hospitals, southwest Ethiopia. Facility based cross sectional quantitative study triangulated with qualitative approaches was employed from March to April 30/2015. Stratified sampling technique was used to select 637 study participants among 4 hospitals. The standardized tool which measures 12 patient safety culture composites was used for data collection. Bivariate and multivariate linear regression analyses were performed using SPSS version 20. Significance level was obtained at 95 % CI and p-value < 0.05. Semi structured guide in depth interview was used to collect the qualitative data. Content analysis of the interview was performed. The overall level of patient safety culture was 46.7 % (95 % CI: 43.0, 51.2). Hours worked per week (β =-0.06, 95 % CI:-0.12,-0.001), reporting adverse event (β = 3.34, 95 % CI: 2.12, 4.57), good communication (β = 2.78, 95 % CI: 2.29, 3.28), teamwork within hospital (β = 1.91, 95 % CI: 1.37, 2.46), level of staffing (β = 1.32, 95 % CI: 0.89, 1.75), exchange of feedback about error (β = 1.37, 95 % CI: 0.91, 1.83) and participation in patient safety program (β = 1.3, 95 % CI: 0.57, 2.03) were factors significantly associated with the patient safety culture. The in depth interview indicated incident reporting, resources, healthcare worker attitude and patient involvement as important factors that influence patient safety culture. The overall level of patient safety culture was low. Working hours, level of staffing, teamwork, communications openness, reporting an event and exchange of feedback about error were associated with patient safety culture. Therefore, interventions of systemic approach through facilitating opportunities for communication openness, cooperation and exchange of ideas between healthcare workers are needed to improve the level of patient safety culture.

  19. Analysis of Heat Transfers inside Counterflow Plate Heat Exchanger Augmented by an Auxiliary Fluid Flow

    PubMed Central

    Khaled, A.-R. A.

    2014-01-01

    Enhancement of heat transfers in counterflow plate heat exchanger due to presence of an intermediate auxiliary fluid flow is investigated. The intermediate auxiliary channel is supported by transverse conducting pins. The momentum and energy equations for the primary fluids are solved numerically and validated against a derived approximate analytical solution. A parametric study including the effect of the various plate heat exchanger, and auxiliary channel dimensionless parameters is conducted. Different enhancement performance indicators are computed. The various trends of parameters that can better enhance heat transfer rates above those for the conventional plate heat exchanger are identified. Large enhancement factors are obtained under fully developed flow conditions. The maximum enhancement factors can be increased by above 8.0- and 5.0-fold for the step and exponential distributions of the pins, respectively. Finally, counterflow plate heat exchangers with auxiliary fluid flows are recommended over the typical ones if these flows can be provided with the least cost. PMID:24719572

  20. Analysis of heat transfers inside counterflow plate heat exchanger augmented by an auxiliary fluid flow.

    PubMed

    Khaled, A-R A

    2014-01-01

    Enhancement of heat transfers in counterflow plate heat exchanger due to presence of an intermediate auxiliary fluid flow is investigated. The intermediate auxiliary channel is supported by transverse conducting pins. The momentum and energy equations for the primary fluids are solved numerically and validated against a derived approximate analytical solution. A parametric study including the effect of the various plate heat exchanger, and auxiliary channel dimensionless parameters is conducted. Different enhancement performance indicators are computed. The various trends of parameters that can better enhance heat transfer rates above those for the conventional plate heat exchanger are identified. Large enhancement factors are obtained under fully developed flow conditions. The maximum enhancement factors can be increased by above 8.0- and 5.0-fold for the step and exponential distributions of the pins, respectively. Finally, counterflow plate heat exchangers with auxiliary fluid flows are recommended over the typical ones if these flows can be provided with the least cost.

  1. Measuring Collaboration and Communication to Increase Implementation of Evidence-Based Practices: The Cultural Exchange Inventory

    ERIC Educational Resources Information Center

    Palinkas, Lawrence A.; Garcia, Antonio; Aarons, Gregory; Finno-Velasquez, Megan; Fuentes, Dahlia; Holloway, Ian; Chamberlain, Patricia

    2018-01-01

    The Cultural Exchange Inventory (CEI) is a 15-item instrument designed to measure the process (7 items) and outcomes (8 items) of exchanges of knowledge, attitudes and practices between members of different organisations collaborating in implementing evidence-based practice. We conducted principal axis factor analyses and parallel analyses of data…

  2. International Sexual Partnerships May Be Shaped by Sexual Histories and Socioeconomic Status

    PubMed Central

    Truong, Hong-Ha M.; Mehrotra, Megha; Montoya, Orlando; Lama, Javier R.; Guanira, Juan V.; Casapía, Martín; Veloso, Valdiléa G.; Buchbinder, Susan P.; Mayer, Kenneth H.; Chariyalertsak, Suwat; Schechter, Mauro; Bekker, Linda-Gail; Kallás, Esper G.; Grant, Robert M.

    2017-01-01

    Exchange sex and higher education were associated with an increased likelihood of international sexual partnerships (ISPs). Exchange sex and older age were associated with an increased likelihood of condomless sex in ISPs. Educational and socioeconomic factors may create unbalanced power dynamics that influence exchange sex and condomless sex in ISPs. PMID:28407648

  3. 75 FR 62137 - Notice of Public Meeting; Proposed Alluvial Valley Floor Coal Exchange Public Interest Factors...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-07

    ...; MTM-99236] Notice of Public Meeting; Proposed Alluvial Valley Floor Coal Exchange Public Interest... (SMCRA) of 1977. This exchange (serial number MTM-99236) has been proposed by Jay Nance, Brett A... Director. [FR Doc. 2010-25060 Filed 10-6-10; 8:45 am] BILLING CODE 4310-DN-P ...

  4. Research on Heat Exchange Process in Aircraft Air Conditioning System

    NASA Astrophysics Data System (ADS)

    Chichindaev, A. V.

    2017-11-01

    Using of heat-exchanger-condenser in the air conditioning system of the airplane Tu-204 (Boeing, Airbus, Superjet 100, MS-21, etc.) for cooling the compressed air by the cold air with negative temperature exiting the turbine results in a number of operational problems. Mainly it’s frosting of the heat exchange surface, which is the cause of live-section channels frosting, resistance increasing and airflow in the system decreasing. The purpose of this work is to analyse the known freeze-up-fighting methods for heat-exchanger-condenser, description of the features of anti-icing protection and offering solutions to this problem. For the problem of optimizing the design of heat exchangers in this work used generalized criterion that describes the ratio of thermal resistances of cold and hot sections, which include: the ratio of the initial values of heat transfer agents flow state; heat exchange surface finning coefficients; factors which describes the ratio of operating parameters and finning area. By controlling the ratio of the thermal resistances can be obtained the desired temperature of the heat exchange surface, which would prevent freezing. The work presents the results of a numerical study of the effect of different combinations of regime and geometrical factors changes on reduction of the heat-exchanger-condenser freezing surface area, including using of variable ratio of thermal resistances.

  5. Extraction of the neutron magnetic form factor from quasielastic 3He→(e→,e') at Q2=0.1-0.6(GeV/c)2

    NASA Astrophysics Data System (ADS)

    Anderson, B.; Auberbach, L.; Averett, T.; Bertozzi, W.; Black, T.; Calarco, J.; Cardman, L.; Cates, G. D.; Chai, Z. W.; Chen, J. P.; Choi, Seonho; Chudakov, E.; Churchwell, S.; Corrado, G. S.; Crawford, C.; Dale, D.; Deur, A.; Djawotho, P.; Dutta, D.; Finn, J. M.; Gao, H.; Gilman, R.; Glamazdin, A. V.; Glashausser, C.; Glöckle, W.; Golak, J.; Gomez, J.; Gorbenko, V. G.; Hansen, J.-O.; Hersman, F. W.; Higinbotham, D. W.; Holmes, R.; Howell, C. R.; Hughes, E.; Humensky, B.; Incerti, S.; Jager, C. W. De; Jensen, J. S.; Jiang, X.; Jones, C. E.; Jones, M.; Kahl, R.; Kamada, H.; Kievsky, A.; Kominis, I.; Korsch, W.; Kramer, K.; Kumbartzki, G.; Kuss, M.; Lakuriqi, E.; Liang, M.; Liyanage, N.; Lerose, J.; Malov, S.; Margaziotis, D. J.; Martin, J. W.; McCormick, K.; McKeown, R. D.; McIlhany, K.; Meziani, Z.-E.; Michaels, R.; Miller, G. W.; Mitchell, J.; Nanda, S.; Pace, E.; Pavlin, T.; Petratos, G. G.; Pomatsalyuk, R. I.; Pripstein, D.; Prout, D.; Ransome, R. D.; Roblin, Y.; Rvachev, M.; Saha, A.; Salmè, G.; Schnee, M.; Seely, J.; Shin, T.; Slifer, K.; Souder, P. A.; Strauch, S.; Suleiman, R.; Sutter, M.; Tipton, B.; Todor, L.; Viviani, M.; Vlahovic, B.; Watson, J.; Williamson, C. F.; Witała, H.; Wojtsekhowski, B.; Xiong, F.; Xu, W.; Yeh, J.; Żołnierczuk, P.

    2007-03-01

    We have measured the transverse asymmetry AT' in the quasielastic 3He→(e→,e') process with high precision at Q2 values from 0.1 to 0.6(GeV/c)2. The neutron magnetic form factor GMn was extracted at Q2 values of 0.1 and 0.2(GeV/c)2 using a nonrelativistic Faddeev calculation which includes both final-state interactions (FSI) and meson-exchange currents (MEC). Theoretical uncertainties due to the FSI and MEC effects were constrained with a precision measurement of the spin-dependent asymmetry in the threshold region of 3He→(e→,e'). We also extracted the neutron magnetic form factor GMn at Q2 values of 0.3 to 0.6(GeV/c)2 based on plane wave impulse approximation calculations.

  6. An effective field theory for forward scattering and factorization violation

    DOE PAGES

    Rothstein, Ira Z.; Stewart, Iain W.

    2016-08-03

    Starting with QCD, we derive an effective field theory description for forward scattering and factorization violation as part of the soft-collinear effective field theory (SCET) for high energy scattering. These phenomena are mediated by long distance Glauber gluon exchanges, which are static in time, localized in the longitudinal distance, and act as a kernel for forward scattering where |t| << s. In hard scattering, Glauber gluons can induce corrections which invalidate factorization. With SCET, Glauber exchange graphs can be calculated explicitly, and are distinct from graphs involving soft, collinear, or ultrasoft gluons. We derive a complete basis of operators whichmore » describe the leading power effects of Glauber exchange. Key ingredients include regulating light-cone rapidity singularities and subtractions which prevent double counting. Our results include a novel all orders gauge invariant pure glue soft operator which appears between two collinear rapidity sectors. The 1-gluon Feynman rule for the soft operator coincides with the Lipatov vertex, but it also contributes to emissions with ≥ 2 soft gluons. Our Glauber operator basis is derived using tree level and one-loop matching calculations from full QCD to both SCET II and SCET I. The one-loop amplitude’s rapidity renormalization involves mixing of color octet operators and yields gluon Reggeization at the amplitude level. The rapidity renormalization group equation for the leading soft and collinear functions in the forward scattering cross section are each given by the BFKL equation. Various properties of Glauber gluon exchange in the context of both forward scattering and hard scattering factorization are described. For example, we derive an explicit rule for when eikonalization is valid, and provide a direct connection to the picture of multiple Wilson lines crossing a shockwave. In hard scattering operators Glauber subtractions for soft and collinear loop diagrams ensure that we are not sensitive to the directions for soft and collinear Wilson lines. Conversely, certain Glauber interactions can be absorbed into these soft and collinear Wilson lines by taking them to be in specific directions. Finally, we also discuss criteria for factorization violation.« less

  7. Prediction of e± elastic scattering cross-section ratio based on phenomenological two-photon exchange corrections

    NASA Astrophysics Data System (ADS)

    Qattan, I. A.

    2017-06-01

    I present a prediction of the e± elastic scattering cross-section ratio, Re+e-, as determined using a new parametrization of the two-photon exchange (TPE) corrections to electron-proton elastic scattering cross section σR. The extracted ratio is compared to several previous phenomenological extractions, TPE hadronic calculations, and direct measurements from the comparison of electron and positron scattering. The TPE corrections and the ratio Re+e- show a clear change of sign at low Q2, which is necessary to explain the high-Q2 form factors discrepancy while being consistent with the known Q2→0 limit. While my predictions are in generally good agreement with previous extractions, TPE hadronic calculations, and existing world data including the recent two measurements from the CLAS and VEPP-3 Novosibirsk experiments, they are larger than the new OLYMPUS measurements at larger Q2 values.

  8. Maternal obesity and overnutrition alter fetal growth rate and cotyledonary vascularity and angiogenic factor expression in the ewe.

    PubMed

    Ma, Yan; Zhu, Mei J; Zhang, Liren; Hein, Sarah M; Nathanielsz, Peter W; Ford, Stephen P

    2010-07-01

    In pregnant sheep, maternal:fetal exchange occurs across placentomes composed of placental cotyledonary and uterine caruncular tissues. Recently, we reported that fetal weights of obese (OB) ewes [fed a diet of 150% of National Research Council (NRC) recommendations] were approximately 30% greater than those of control (C) ewes (fed a diet 100% of NRC recommendations) at midgestation (MG), but fetal weights were similar in late gestation (LG). Transplacental nutrient exchange is dependent on placental blood flow, which itself is dependent on placental vascularity. The current study investigated whether the observed initial faster and subsequent slower fetal growth rate of OB compared with C was associated with changes in cotyledonary vascularity and expression of angiogenic factors (vascular endothelial growth factor, fibroblast growth factor-2, placental growth factor, angiopoietin-1 and -2). Cotyledonary arteriole diameters were markedly greater (P < 0.05) in OB than C ewes at MG, but while arteriole diameter of C ewes increased (P < 0.05) from MG to LG, they remained unchanged in OB ewes. Cotyledonary arterial angiogenic factors mRNA and protein expression were lower (P < 0.05) in OB than C ewes at MG and remained low from MG to LG. In contrast, mRNA levels of angiogenic factors in C ewes declined from high levels at MG to reach those of OB ewes by LG. The increase in cotyledonary arteriole diameter in early to MG may function to accelerate fetal growth rate in OB ewes, while the decreased cotyledonary arterial angiogenic factors from MG-LG may function to protect the fetus from excessive placental vascular development, increased maternal nutrient delivery, and excessive weight gain.

  9. Maternal obesity and overnutrition alter fetal growth rate and cotyledonary vascularity and angiogenic factor expression in the ewe

    PubMed Central

    Ma, Yan; Zhu, Mei J.; Zhang, Liren; Hein, Sarah M.; Nathanielsz, Peter W.

    2010-01-01

    In pregnant sheep, maternal:fetal exchange occurs across placentomes composed of placental cotyledonary and uterine caruncular tissues. Recently, we reported that fetal weights of obese (OB) ewes [fed a diet of 150% of National Research Council (NRC) recommendations] were ∼30% greater than those of control (C) ewes (fed a diet 100% of NRC recommendations) at midgestation (MG), but fetal weights were similar in late gestation (LG). Transplacental nutrient exchange is dependent on placental blood flow, which itself is dependent on placental vascularity. The current study investigated whether the observed initial faster and subsequent slower fetal growth rate of OB compared with C was associated with changes in cotyledonary vascularity and expression of angiogenic factors (vascular endothelial growth factor, fibroblast growth factor-2, placental growth factor, angiopoietin-1 and -2). Cotyledonary arteriole diameters were markedly greater (P < 0.05) in OB than C ewes at MG, but while arteriole diameter of C ewes increased (P < 0.05) from MG to LG, they remained unchanged in OB ewes. Cotyledonary arterial angiogenic factors mRNA and protein expression were lower (P < 0.05) in OB than C ewes at MG and remained low from MG to LG. In contrast, mRNA levels of angiogenic factors in C ewes declined from high levels at MG to reach those of OB ewes by LG. The increase in cotyledonary arteriole diameter in early to MG may function to accelerate fetal growth rate in OB ewes, while the decreased cotyledonary arterial angiogenic factors from MG-LG may function to protect the fetus from excessive placental vascular development, increased maternal nutrient delivery, and excessive weight gain. PMID:20427725

  10. Prevalence and predictors of transitions to and away from syringe exchange use over time in 3 US cities with varied syringe dispensing policies

    PubMed Central

    Green, Traci C.; Bluthenthal, Ricky N.; Singer, Merrill; Beletsky, Leo; Grau, Lauretta E.; Marshall, Patricia; Heimer, Robert

    2010-01-01

    Syringe exchange programs (SEPs) can reduce HIV risk among injecting drug users (IDUs) but their use may depend heavily on contextual factors such as local syringe policies. The frequency and predictors of transitioning over time to and from direct, indirect, and non-use of SEPs are unknown. We sought, over one year, to: (1) quantify and characterize transition probabilities of SEP attendance typologies; (2) identify factors associated with (a) change in typology, and (b) becoming and maintaining direct SEP use; and (3) quantify and characterize transition probabilities of SEP attendance before and after changes in policy designed to increase access. Using data collected from 583 IDUs participating in a three-city cohort study of SEPs, we conducted a latent transition analysis and multinomial regressions. Three typologies were detected: Direct SEP users, Indirect SEP users and Isolated IDUs. Transitions to direct SEP use were most prevalent. Factors associated with becoming or maintaining direct SEP use were female sex, Latino ethnicity, fewer injections per syringe, homelessness, recruitment city, injecting speedballs (cocaine and heroin), and police contact involving drug paraphernalia possession. Similar factors influenced transitions in the syringe policy change analysis. Policy change cities experienced an increase in Indirect SEP users (43% to 51%) with little increased direct use (29% to 31%). We found that, over time, IDUs tended to become Direct SEP users. Policies improving syringe availability influenced SEP use by increasing secondary syringe exchange. Interactions with police around drug paraphernalia may encourage SEP use for some IDUs and may provide opportunities for other health interventions. PMID:20537814

  11. Scaling Hydrologic Exchange Flows and Biogeochemical Reactions from Bedforms to Basins

    NASA Astrophysics Data System (ADS)

    Harvey, J. W.; Gomez-Velez, J. D.

    2015-12-01

    River water moves in and out of the main channel along pathways that are perpendicular to the channel's main axis that flow across or beneath the ground surface. These hydrologic exchange flows (HEFs) are difficult to measure, yet no less important than a river's downstream flow, or exchanges with the atmosphere and deeper groundwater (Harvey and Gooseff, 2015, WRR). There are very few comprehensive investigations of exchange fluxes to understand patterns with river size and relative importance of specific types of exchanges. We used the physically based model NEXSS to simulate multiple scales of hyporheic flow and their cumulative effects on solute reaction in large basins (on the order of Chesapeake Bay basin or larger). Our goal was to explain where and when particular types of hyporheic flow are important in enhancing key biogeochemical reactions, such as organic carbon respiration and denitrification. Results demonstrate that hyporheic flux (expressed per unit area of streambed) varies surprisingly little across the continuum of first-order streams to eighth-order rivers, and vertical exchange beneath small bedforms dominates in comparison with lateral flow beneath gravel bars and meanders. Also, the river's entire volume is exchanged many times with hyporheic flow within a basin, and the turnover length (after one entire river volume is exchanged) is strongly influenced by hydrogeomorphic differences between physiographic regions as well as by river size. The cumulative effects on biogeochemical reactions were assessed using a the reaction significance factor, RSF, which computes the cumulative potential for hyporheic reactions using a dimensionless index that balances reaction progress in a single hyporheic flow path against overall processing efficiency of river turnover through hyporheic flow paths of that type. Reaction significance appears to be strongly dominated by hydrologic factors rather than biogeochemical factors, and seems to be dominated by vertical exchange beneath small bedforms throughout river networks. Future implementations of NEXSS will expand the model to consider flow variation and to consider HEFs beyond hyporheic flow to include exchange with marginal surface waters such as riparian wetlands, floodplains, and ponded water.

  12. Sequence variations and protein expression levels of the two immune evasion proteins Gpm1 and Pra1 influence virulence of clinical Candida albicans isolates.

    PubMed

    Luo, Shanshan; Hipler, Uta-Christina; Münzberg, Christin; Skerka, Christine; Zipfel, Peter F

    2015-01-01

    Candida albicans, the important human fungal pathogen uses multiple evasion strategies to control, modulate and inhibit host complement and innate immune attack. Clinical C. albicans strains vary in pathogenicity and in serum resistance, in this work we analyzed sequence polymorphisms and variations in the expression levels of two central fungal complement evasion proteins, Gpm1 (phosphoglycerate mutase 1) and Pra1 (pH-regulated antigen 1) in thirteen clinical C. albicans isolates. Four nucleotide (nt) exchanges, all representing synonymous exchanges, were identified within the 747-nt long GPM1 gene. For the 900-nt long PRA1 gene, sixteen nucleotide exchanges were identified, which represented synonymous, as well as non-synonymous exchanges. All thirteen clinical isolates had a homozygous exchange (A to G) at position 73 of the PRA1 gene. Surface levels of Gpm1 varied by 8.2, and Pra1 levels by 3.3 fold in thirteen tested isolates and these differences influenced fungal immune fitness. The high Gpm1/Pra1 expressing candida strains bound the three human immune regulators more efficiently, than the low expression strains. The difference was 44% for Factor H binding, 51% for C4BP binding and 23% for plasminogen binding. This higher Gpm1/Pra1 expressing strains result in enhanced survival upon challenge with complement active, Factor H depleted human serum (difference 40%). In addition adhesion to and infection of human endothelial cells was increased (difference 60%), and C3b surface deposition was less effective (difference 27%). Thus, variable expression levels of central immune evasion protein influences immune fitness of the human fungal pathogen C. albicans and thus contribute to fungal virulence.

  13. Sensitivity of temperate desert steppe carbon exchange to seasonal droughts and precipitation variations in Inner Mongolia, China.

    PubMed

    Yang, Fulin; Zhou, Guangsheng

    2013-01-01

    Arid grassland ecosystems have significant interannual variation in carbon exchange; however, it is unclear how environmental factors influence carbon exchange in different hydrological years. In this study, the eddy covariance technique was used to investigate the seasonal and interannual variability of CO₂ flux over a temperate desert steppe in Inner Mongolia, China from 2008 to 2010. The amounts and times of precipitation varied significantly throughout the study period. The precipitation in 2009 (186.4 mm) was close to the long-term average (183.9±47.6 mm), while the precipitation in 2008 (136.3 mm) and 2010 (141.3 mm) was approximately a quarter below the long-term average. The temperate desert steppe showed carbon neutrality for atmospheric CO₂ throughout the study period, with a net ecosystem carbon dioxide exchange (NEE) of -7.2, -22.9, and 26.0 g C m⁻² yr⁻¹ in 2008, 2009, and 2010, not significantly different from zero. The ecosystem gained more carbon in 2009 compared to other two relatively dry years, while there was significant difference in carbon uptake between 2008 and 2010, although both years recorded similar annual precipitation. The results suggest that summer precipitation is a key factor determining annual NEE. The apparent quantum yield and saturation value of NEE (NEE(sat)) and the temperature sensitivity coefficient of ecosystem respiration (R(eco)) exhibited significant variations. The values of NEE(sat) were -2.6, -2.9, and -1.4 µmol CO₂ m⁻² s⁻¹ in 2008, 2009, and 2010, respectively. Drought suppressed both the gross primary production (GPP) and R(eco), and the drought sensitivity of GPP was greater than that of R(eco). The soil water content sensitivity of GPP was high during the dry year of 2008 with limited soil moisture availability. Our results suggest the carbon balance of this temperate desert steppe was not only sensitive to total annual precipitation, but also to its seasonal distribution.

  14. Dynamics of CO2 fluxes and environmental responses in the rain-fed winter wheat ecosystem of the Loess Plateau, China.

    PubMed

    Wang, Wen; Liao, Yuncheng; Wen, Xiaoxia; Guo, Qiang

    2013-09-01

    Chinese Loess Plateau plays an important role in carbon balance of terrestrial ecosystems. Continuous measurement of CO2 fluxes in cropland ecosystem is of great significance to accurately evaluate the carbon sequestration potential and to better explain the carbon cycle process in this region. By using the eddy covariance system we conducted a long-term (from Sep 2009 to Jun 2010) CO2 fluxes measurement in the rain-fed winter wheat field of the Chinese Loess Plateau and elaborated the responses of CO2 fluxes to environmental factors. The results show that the winter wheat ecosystem has distinct seasonal dynamics of CO2 fluxes. The total net ecosystem CO2 exchange (NEE) of -218.9±11.5 gC m(-2) in the growing season, however, after considering the harvested grain, the agro-ecosystem turned into a weak carbon sink (-36.2 gC m(-2)). On the other hand, the responses of CO2 fluxes to environmental factors depended on different growth stages of winter wheat and different ranges of environmental variables, suggesting that the variations in CO2 exchange were sensitive to the changes in controlling factors. Particularly, we found the pulse response of ecosystem respiration (Reco) to a large rainfall event, and the strong fluctuations of CO2 fluxes usually appeared after effective rainfall events (daily precipitation > 5 mm) during middle growing season. Such phenomenon also occurred in the case of the drastic changes in air temperature and within 5 days after field management (e.g. tillage and plough). Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  15. A General Econometric Model of the Determinants of Library Subscription Prices of Scholarly Journals: The Role of Exchange Rate Risk and Other Factors.

    ERIC Educational Resources Information Center

    Chressanthis, George A.; Chressanthis, June D.

    1994-01-01

    Provides regression-based empirical evidence of the effects of variations in exchange rate risk on 1985 library prices of the top-ranked 99 journals in economics. The relationship between individual journal prices and library prices is shown, and other factors associated with increases and decreases in library journal prices are given. (Contains…

  16. The leukemia-associated Rho guanine nucleotide exchange factor LARG is required for efficient replication stress signaling

    PubMed Central

    Beveridge, Ryan D; Staples, Christopher J; Patil, Abhijit A; Myers, Katie N; Maslen, Sarah; Skehel, J Mark; Boulton, Simon J; Collis, Spencer J

    2014-01-01

    We previously identified and characterized TELO2 as a human protein that facilitates efficient DNA damage response (DDR) signaling. A subsequent yeast 2-hybrid screen identified LARG; Leukemia-Associated Rho Guanine Nucleotide Exchange Factor (also known as Arhgef12), as a potential novel TELO2 interactor. LARG was previously shown to interact with Pericentrin (PCNT), which, like TELO2, is required for efficient replication stress signaling. Here we confirm interactions between LARG, TELO2 and PCNT and show that a sub-set of LARG co-localizes with PCNT at the centrosome. LARG-deficient cells exhibit replication stress signaling defects as evidenced by; supernumerary centrosomes, reduced replication stress-induced γH2AX and RPA nuclear foci formation, and reduced activation of the replication stress signaling effector kinase Chk1 in response to hydroxyurea. As such, LARG-deficient cells are sensitive to replication stress-inducing agents such as hydroxyurea and mitomycin C. Conversely we also show that depletion of TELO2 and the replication stress signaling kinase ATR leads to RhoA signaling defects. These data therefore reveal a level of crosstalk between the RhoA and DDR signaling pathways. Given that mutations in both ATR and PCNT can give rise to the related primordial dwarfism disorders of Seckel Syndrome and Microcephalic osteodysplastic primordial dwarfism type II (MOPDII) respectively, which both exhibit defects in ATR-dependent checkpoint signaling, these data also raise the possibility that mutations in LARG or disruption to RhoA signaling may be contributory factors to the etiology of a sub-set of primordial dwarfism disorders. PMID:25485589

  17. Influence of smoking and obesity on alveolar-arterial gas pressure differences and dead space ventilation at rest and peak exercise in healthy men and women.

    PubMed

    Gläser, Sven; Ittermann, Till; Koch, Beate; Schäper, Christoph; Felix, Stephan B; Völzke, Henry; Könemann, Raik; Ewert, Ralf; Hansen, James E

    2013-06-01

    Besides exercise intolerance, the assessment of ventilatory and perfusion adequacy allows additional insights in the disease pathophysiology in many cardiovascular or pulmonary diseases. Valid measurements of dead space/tidal volume ratios (VD/VT), arterial (a') - end-tidal (et) carbon dioxide (CO2) and oxygen (O2) pressure differences (p(a'-et)CO2) and (p(et-a')O2), and alveolar (A)-a' O2 pressure differences (p(A-a')O2) require using blood samples in addition to gas exchange analyses on a breath-by-breath-basis. Smoking and nutritional status are also important factors in defining disorders. Using a large healthy population we considered the impact of these factors to develop useful prediction equations. Incremental cycle exercise protocols were applied to apparently healthy volunteer adults who did not have structural heart disease or echocardiographic or lung function pathologies. Age, height, weight, and smoking were analysed for their influence on the target parameters in each gender. Reference values were determined by regression analyses. The final study sample consisted of 476 volunteers (190 female), aged 25-85 years. Smoking significantly influences p(A-a')O2 and p(a'-et)CO2 at rest and peak exercise, and VD/VT during exercise. Obesity influences upper limits of VD/VT, p(a'-et)CO2 and p(et-a')O2 at rest as well as p(A-a')O2 and p(et-a')O2 at exercise. Reference equations for never-smokers as well as for apparently healthy smokers considering influencing factors are given. Gender, age, height, weight, and smoking significantly influence gas exchange. Considering all of these factors this study provides a comprehensive set of reference equations derived from a large number of participants of a population-based study. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Energy and Cost Savings of Retro-Commissioning and Retrofit Measures for Large Office Buildings

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

    Wang, Weimin; Zhang, Jian; Moser, Dave

    2012-08-03

    This paper evaluates the energy and cost savings of seven retro-commissioning measures and 29 retrofit measures applicable to most large office buildings. The baseline model is for a hypothetical building with characteristics of large office buildings constructed before 1980. Each retro-commissioning measure is evaluated against the original baseline in terms of its potential of energy and cost savings while each retrofit measure is evaluated against the commissioned building. All measures are evaluated in five locations (Miami, Las Vegas, Seattle, Chicago and Duluth) to understand the impact of weather conditions on energy and cost savings. The results show that implementation ofmore » the seven operation and maintenance measures as part of a retro-commissioning process can yield an average of about 22% of energy use reduction and 14% of energy cost reduction. Widening zone temperature deadband, lowering VAV terminal minimum air flow set points and lighting upgrades are effective retrofit measures to be considered.« less

  19. Slow-electron collisions with CO molecules in an exact-exchange plus parameter-free polarization model

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

    Jain, A.; Norcross, D.W.

    1992-02-01

    We report low-energy (0.001--10-eV) electron-CO scattering cross sections obtained using an exact-exchange (via a separable-exchange formulation) plus a parameter-free correlation-polarization model in the fixed-nuclei approximation (FNA). The differential, total, and momentum-transfer cross sections are reported for rotationally elastic, inelastic, and summed processes. To remove the limitations of the FNA with respect to the convergence of total and differential cross sections, the multipole-extracted-adiabatic-nuclei approximation is used. The position and width of the well-known {sup 2}{Pi} shape-resonance structure in the cross section around 2 eV are reproduced quite well; however, some discrepancy between theory and experiment in the magnitude of the totalmore » cross section in the resonance region exists. We also present results for {sup 2}{Pi} shape-resonance parameters as a function of internuclear separation. Differential-cross-section results agree well with the measurements of Tanaka, Srivastava, and Chutjian (J. Chem. Phys. 69, 5329 (1978)) but are about a factor of 2 larger than the results obtained by Jung {ital et} {ital al}. (J. Phys. B 15, 3535 (1982)) in the vicinity of the {sup 2}{Pi} resonance.« less

  20. Experimental and numerical investigation on heat transfer augmentation in a circular tube under forced convection with annular differential blockages/inserts

    NASA Astrophysics Data System (ADS)

    Waghole, D. R.

    2018-06-01

    Investigation on heat transfer by generating turbulence in the fluid stream inside the circular tube is an innovative area of research for researchers. Hence, many techniques are been investigated and adopted for enhancement of heat transfer rate to reduce the size and the cost of the heat exchanger/circular tube. In the present study the effect of differential solid ring inserts /turbulators on heat transfer, friction factor of heat exchanger/circular tube was evaluated through experimentally and numerically. The experiments were conducted in range of 3000 ≤Re≤ 6500 and annular blockages 0 ≤ɸ≤50 %. The heat transfer rate was higher for differential combination of inserts as compared to tube fitted with uniform inserts. The maximum heat transfer was obtained by the use of differential metal circular ring inserts/blockages. From this study, Nusselt number, friction factor and enhancement factor are found as 2.5-3.5 times, 12% - 50.5% and 155% - 195%, respectively with water. Finally new possible correlations for predicting heat transfer and friction factor in the flow of water through the circular tube with differential blockages/inserts are proposed.

  1. NCX-DB: a unified resource for integrative analysis of the sodium calcium exchanger super-family.

    PubMed

    Bode, Katrin; O'Halloran, Damien M

    2018-04-13

    Na + /Ca 2+ exchangers are low-affinity high-capacity transporters that mediate Ca 2+ extrusion by coupling Ca 2+ efflux to the influx of Na + ions. The Na + /Ca 2+ exchangers form a super-family comprised of three branches each differing in ion-substrate selectivity: Na + /Ca 2+ exchangers (NCX), Na + /Ca 2+ /K + exchangers, and Ca 2+ /cation exchangers. Their primary function is to maintain Ca 2+ homeostasis and play a particularly important role in excitable cells that experience transient Ca 2+ fluxes. Research into the role and activity of Na + /Ca 2+ exchangers has focused extensively on the cardio-vascular system, however, growing evidence suggests that Na + /Ca 2+ exchangers play a key role in neuronal processes such as memory formation, learning, oligodendrocyte differentiation, neuroprotection during brain ischemia and axon guidance. They have also been implicated in pathologies such as Alzheimer's disease, Parkinson's disease, Multiple Sclerosis and Epilepsy, however, a clear understanding of their mechanism during disease is lacking. To date, there has never been a central resource or database for Na + /Ca 2+ exchangers. With clear disease relevance and ever-increasing research on Na + /Ca 2+ exchangers from both model and non-model species, a database that unifies the data on Na + /Ca 2+ exchangers is needed for future research. NCX-DB is a publicly available database with a web interface that enables users to explore various Na + /Ca 2+ exchangers, perform cross-species sequence comparison, identify new exchangers, and stay-up to date with recent literature. NCX-DB is available on the web via an interactive user interface with an intuitive design, which is applicable for the identification and comparison of Na + /Ca 2+ exchanger proteins across diverse species.

  2. Turn on, fade out - methane exchange in a coastal fen over a period of six years after rewetting

    NASA Astrophysics Data System (ADS)

    Jurasinski, Gerald; Glatzel, Stephan; Hahn, Juliane; Koch, Stefan; Koch, Marian; Koebsch, Franziska

    2016-04-01

    The rewetting of drained peatlands is widely regarded as an adequate measure for the mitigation of greenhouse gas emissions. Therefore, especially in NE Germany, many peatlands are being rewetted. Our knowledge about greenhouse gas exchange associated with rewetting is mainly based on short-term experiments or space-for-time substitutions. These approaches do not consider the transient character of ecosystem acclimatization to flooding by rewetting. Moreover data in this regard on coastal peatland ecosystems are sparse. Here, we present 7 years of data on CH4-exchange in a coastal fen after rewetting by flooding. On the site „Rodewiese", which is located within the NSG "Hütelmoor und Heiligensee" in the Northeast of Rostock, NE Germany, we have established a long term research observatory addressing atmospheric C-exchange. The site is part of the TERENO network. Since summer 2009 we determine CH4 fluxes with closed chambers distributed widely across the study site and CO2-exchange with eddy covariance as well as ancillary data on vegetation, hydrology, and biogeochemistry. This talk addresses the CH4-exchange over time whereas CO2-exchange data are presented by Koebsch et al. in the same session. Rewetting turned the site from a summer dry fen with mean annual water levels of around -0.08m into a shallow lake with water levels up to 0.60m. In the first year after flooding, we observed a substantial die-back of vegetation, especially in stands of Carex acutiformis. Flooding increased methane release rates to extremely high levels of up to 4.3 t ha-1 a-1 for sedge stands and 2.7 t ha-1 a-1 on average, which amounts to 75.6 t ha-1 a-1 in CO2-equivalents. Thereafter, the averaged annual CH4 emissions decreased asymptotically and where at an average of 0.5 t ha-1 a-1 (14 t ha-1 a-1 in CO2-equivalents) in 2015. Factoring in the NEE of the growing season (from Eddy measurements) suggests that the system may be slightly above neutral with respect to the greenhouse warming potential of its atmospheric C-exchange 7 years after flooding. Analyses of peat and water biochemistry showed that the system had been destabilized in the first year following flooding and repeated vegetation analysis combined with remote sensing reveal strong and directed change in vegetation patterns. The successional development in atmospheric C-exchange in the 6 years after flooding hint at an adaptation of ecosystem functioning to the flooded conditions associated with reaching desirable annual rates of C-exchange and vegetation development during an acceptable time frame. However, high CH4 emissions and a slow recovery to lower CH4 emissions that likely occur directly after rewetting by flooding should be considered when forecasting the overall effect of rewetting on GHG exchange of a particular site.

  3. Diurnal and Seasonal Variations in the Net Ecosystem CO2 Exchange of a Pasture in the Three-River Source Region of the Qinghai−Tibetan Plateau

    PubMed Central

    Wang, Bin; Jin, Haiyan; Li, Qi; Chen, Dongdong; Zhao, Liang; Tang, Yanhong; Kato, Tomomichi; Gu, Song

    2017-01-01

    Carbon dioxide (CO2) exchange between the atmosphere and grassland ecosystems is very important for the global carbon balance. To assess the CO2 flux and its relationship to environmental factors, the eddy covariance method was used to evaluate the diurnal cycle and seasonal pattern of the net ecosystem CO2 exchange (NEE) of a cultivated pasture in the Three-River Source Region (TRSR) on the Qinghai−Tibetan Plateau from January 1 to December 31, 2008. The diurnal variations in the NEE and ecosystem respiration (Re) during the growing season exhibited single-peak patterns, the maximum and minimum CO2 uptake observed during the noon hours and night; and the maximum and minimum Re took place in the afternoon and early morning, respectively. The minimum hourly NEE rate and the maximum hourly Re rate were −7.89 and 5.03 μmol CO2 m−2 s−1, respectively. The NEE and Re showed clear seasonal variations, with lower values in winter and higher values in the peak growth period. The highest daily values for C uptake and Re were observed on August 12 (−2.91 g C m−2 d−1) and July 28 (5.04 g C m−2 day−1), respectively. The annual total NEE and Re were −140.01 and 403.57 g C m−2 year−1, respectively. The apparent quantum yield (α) was −0.0275 μmol μmol−1 for the entire growing period, and the α values for the pasture’s light response curve varied with the leaf area index (LAI), air temperature (Ta), soil water content (SWC) and vapor pressure deficit (VPD). Piecewise regression results indicated that the optimum Ta and VPD for the daytime NEE were 14.1°C and 0.65 kPa, respectively. The daytime NEE decreased with increasing SWC, and the temperature sensitivity of respiration (Q10) was 3.0 during the growing season, which was controlled by the SWC conditions. Path analysis suggested that the soil temperature at a depth of 5 cm (Tsoil) was the most important environmental factor affecting daily variations in NEE during the growing season, and the photosynthetic photon flux density (PPFD) was the major limiting factor for this cultivated pasture. PMID:28129406

  4. Simultaneous determination of cations, zwitterions and neutral compounds using mixed-mode reversed-phase and cation-exchange high-performance liquid chromatography.

    PubMed

    Li, Jingyi; Shao, Shan; Jaworsky, Markian S; Kurtulik, Paul T

    2008-03-28

    A novel mixed-mode reversed-phase and cation-exchange high-performance liquid chromatography (HPLC) method is described to simultaneously determine four related impurities of cations, zwitterions and neutral compounds in developmental Drug A. The commercial column is Primesep 200 containing hydrophobic alkyl chains with embedded acidic groups in H(+) form on a silica support. The mobile phase variables of acid additives, contents of acetonitrile and concentrations of potassium chloride have been thoroughly investigated to optimize the separation. The retention factors as a function of the concentrations of potassium chloride and the percentages of acetonitrile in the mobile phases are investigated to get an insight into the retention and separation mechanisms of each related impurity and Drug A. Furthermore, the elution orders of the related impurities and Drug A in an ion-pair chromatography (IPC) are compared to those in the mixed-mode HPLC to further understand the chromatographic retention behaviors of each related impurity and Drug A. The study found that the positively charged Degradant 1, Degradant 2 and Drug A were retained by both ion-exchange and reversed-phase partitioning mechanisms. RI2, a small ionic compound, was primarily retained by ion-exchange. RI4, a neutral compound, was retained through reversed-phase partitioning without ion-exchange. Moreover, the method performance characteristics of selectivity, sensitivity and accuracy have been demonstrated to be suitable to determine the related impurities in the capsules of Drug A.

  5. Factors controlling CO2 exchange on timescales from hourly to decadal at Harvard Forest

    Treesearch

    Shawn Urbanski; C. Barford; S. Wofsy; C. Kucharik; E. Pyle; J. Budney; K. McKain; D. Fitzjarrald; M. Czikowsky; J. W. Munger

    2007-01-01

    We analyzed 13 years (1992-2004) of CO2 flux data, biometry, and meteorology from a mixed deciduous forest in central Massachusetts. Annual net uptake of CO2 ranged from 1.0 to 4.7 Mg-C ha-1yr-1, with an average of 2.5 Mg-C ha-1yr-1. Uptake rates increased systematically, nearly doubling over the period despite forest age of 75–110 years; there were...

  6. Factors influencing consumer adoption of USB-based Personal Health Records in Taiwan

    PubMed Central

    2012-01-01

    Background Usually patients receive healthcare services from multiple hospitals, and consequently their healthcare data are dispersed over many facilities’ paper and electronic-based record systems. Therefore, many countries have encouraged the research on data interoperability, access, and patient authorization. This study is an important part of a national project to build an information exchange environment for cross-hospital digital medical records carried out by the Department of Health (DOH) of Taiwan in May 2008. The key objective of the core project is to set up a portable data exchange environment in order to enable people to maintain and own their essential health information. This study is aimed at exploring the factors influencing behavior and adoption of USB-based Personal Health Records (PHR) in Taiwan. Methods Quota sampling was used, and structured questionnaires were distributed to the outpatient department at ten medical centers which participated in the DOH project to establish the information exchange environment across hospitals. A total of 3000 questionnaires were distributed and 1549 responses were collected, out of those 1465 were valid, accumulating the response rate to 48.83%. Results 1025 out of 1465 respondents had expressed their willingness to apply for the USB-PHR. Detailed analysis of the data reflected that there was a remarkable difference in the “usage intention” between the PHR adopters and non-adopters (χ2 =182.4, p < 0.001). From the result of multivariate logistic regression analyses, we found the key factors affecting patients’ adoption pattern were Usage Intention (OR, 9.43, 95%C.I., 5.87-15.16), Perceived Usefulness (OR, 1.60; 95%C.I., 1.11-2.29) and Subjective Norm (OR, 1.47; 95%C.I., 1.21-1.78). Conclusions Higher Usage Intentions, Perceived Usefulness and Subjective Norm of patients were found to be the key factors influencing PHR adoption. Thus, we suggest that government and hospitals should promote the potential usefulness of PHR, and physicians should encourage patients' to adopt the PHR. PMID:22925029

  7. Investigation and optimization of the depth of flue gas heat recovery in surface heat exchangers

    NASA Astrophysics Data System (ADS)

    Bespalov, V. V.; Bespalov, V. I.; Melnikov, D. V.

    2017-09-01

    Economic issues associated with designing deep flue gas heat recovery units for natural gas-fired boilers are examined. The governing parameter affecting the performance and cost of surface-type condensing heat recovery heat exchangers is the heat transfer surface area. When firing natural gas, the heat recovery depth depends on the flue gas temperature at the condenser outlet and determines the amount of condensed water vapor. The effect of the outlet flue gas temperature in a heat recovery heat exchanger on the additionally recovered heat power is studied. A correlation has been derived enabling one to determine the best heat recovery depth (or the final cooling temperature) maximizing the anticipated reduced annual profit of a power enterprise from implementation of energy-saving measures. Results of optimization are presented for a surface-type condensing gas-air plate heat recovery heat exchanger for the climatic conditions and the economic situation in Tomsk. The predictions demonstrate that it is economically feasible to design similar heat recovery heat exchangers for a flue gas outlet temperature of 10°C. In this case, the payback period for the investment in the heat recovery heat exchanger will be 1.5 years. The effect of various factors on the optimal outlet flue gas temperature was analyzed. Most climatic, economical, or technological factors have a minor effect on the best outlet temperature, which remains between 5 and 20°C when varying the affecting factors. The derived correlation enables us to preliminary estimate the outlet (final) flue gas temperature that should be used in designing the heat transfer surface of a heat recovery heat exchanger for a gas-fired boiler as applied to the specific climatic conditions.

  8. Methods for Estimating Adsorbed Uranium(VI) and Distribution Coefficients of Contaminated Sediments

    USGS Publications Warehouse

    Kohler, M.; Curtis, G.P.; Meece, D.E.; Davis, J.A.

    2004-01-01

    Assessing the quantity of U(VI) that participates in sorption/desorption processes in a contaminated aquifer is an important task when investigating U migration behavior. U-contaminated aquifer sediments were obtained from 16 different locations at a former U mill tailings site at Naturita, CO (U.S.A.) and were extracted with an artificial groundwater, a high pH sodium bicarbonate solution, hydroxylamine hydrochloride solution, and concentrated nitric acid. With an isotopic exchange method, both a KD value for the specific experimental conditions as well as the total exchangeable mass of U(VI) was determined. Except for one sample, KD values determined by isotopic exchange with U-contaminated sediments that were in equilibrium with atmospheric CO2 agreed within a factor of 2 with KD values predicted from a nonelectrostatic surface complexation model (NEM) developed from U(VI) adsorption experiments with uncontaminated sediments. The labile fraction of U(VI) and U extracted by the bicarbonate solution were highly correlated (r2 = 0.997), with a slope of 0.96 ?? 0.01. The proximity of the slope to one suggests that both methods likely access the same reservoir of U(VI) associated with the sediments. The results indicate that the bicarbonate extraction method is useful for estimating the mass of labile U(VI) in sediments that do not contain U(IV). In-situ KD values calculated from the measured labile U(VI) and the dissolved U(VI) in the Naturita alluvial aquifer agreed within a factor of 3 with in-situ K D values predicted with the NEM and groundwater chemistry at each well.

  9. Performance Optimization of Irreversible Air Heat Pumps Considering Size Effect

    NASA Astrophysics Data System (ADS)

    Bi, Yuehong; Chen, Lingen; Ding, Zemin; Sun, Fengrui

    2018-06-01

    Considering the size of an irreversible air heat pump (AHP), heating load density (HLD) is taken as thermodynamic optimization objective by using finite-time thermodynamics. Based on an irreversible AHP with infinite reservoir thermal-capacitance rate model, the expression of HLD of AHP is put forward. The HLD optimization processes are studied analytically and numerically, which consist of two aspects: (1) to choose pressure ratio; (2) to distribute heat-exchanger inventory. Heat reservoir temperatures, heat transfer performance of heat exchangers as well as irreversibility during compression and expansion processes are important factors influencing on the performance of an irreversible AHP, which are characterized with temperature ratio, heat exchanger inventory as well as isentropic efficiencies, respectively. Those impacts of parameters on the maximum HLD are thoroughly studied. The research results show that HLD optimization can make the size of the AHP system smaller and improve the compactness of system.

  10. Controlling electron beam-induced structure modifications and cation exchange in cadmium sulfide-copper sulfide heterostructured nanorods.

    PubMed

    Zheng, Haimei; Sadtler, Bryce; Habenicht, Carsten; Freitag, Bert; Alivisatos, A Paul; Kisielowski, Christian

    2013-11-01

    The atomic structure and interfaces of CdS/Cu2S heterostructured nanorods are investigated with the aberration-corrected TEAM 0.5 electron microscope operated at 80 kV and 300 kV applying in-line holography and complementary techniques. Cu2S exhibits a low-chalcocite structure in pristine CdS/Cu2S nanorods. Under electron beam irradiation the Cu2S phase transforms into a high-chalcocite phase while the CdS phase maintains its wurtzite structure. Time-resolved experiments reveal that Cu(+)-Cd(2+) cation exchange at the CdS/Cu2S interfaces is stimulated by the electron beam and proceeds within an undisturbed and coherent sulfur sub-lattice. A variation of the electron beam current provides an efficient way to control and exploit such irreversible solid-state chemical processes that provide unique information about system dynamics at the atomic scale. Specifically, we show that the electron beam-induced copper-cadmium exchange is site specific and anisotropic. A resulting displacement of the CdS/Cu2S interfaces caused by beam-induced cation interdiffusion equals within a factor of 3-10 previously reported Cu diffusion length measurements in heterostructured CdS/Cu2S thin film solar cells with an activation energy of 0.96 eV. © 2013 Elsevier B.V. All rights reserved.

  11. Effect of γ-Al2O3/water nanofluid on the thermal performance of shell and coil heat exchanger with different coil torsions

    NASA Astrophysics Data System (ADS)

    Elshazly, K. M.; Sakr, R. Y.; Ali, R. K.; Salem, M. R.

    2017-06-01

    This work investigated experimentally the thermal performance of shell and coil heat exchanger with different coil torsions (λ) for γ-Al2O3/water nanofluid flow. Five helically coiled tube (HCT) with 0.0442 ≤ λ ≤ 0.1348 were tested within turbulent flow regime. The average size of γ-Al2O3 particles is 40 nm and volume concentration (φ) is varied from 0 to 2%. Results showed that reducing coil torsion enhances the heat transfer rate and increases HCT-friction factor (fc). Also, it is noticed that HCT average Nusselt number (Nut) and fc of nanofluids increase with increasing γ-Al2O3 volume concentration. The thermal performance index, TPI = (ht,nf/ht,bf)/(ΔPc,nf/ΔPc,bf). increases with increasing nanoparticles concentration, coil torsion, HCT-side inlet temperature and nanofluid flow rate. Over the studied range of HCT-Reynolds number, the average value of TPI is of 1.34 and 2.24 at φ = 0.5% and φ = 2%, respectively. The average value of TPI is of 1.64 at λ = 0.0442 while its average value at λ = 0.1348 is of 2.01. One of the main contributions is to provide heat equipments designers with Nut and fc correlations for practical configurations shell and coil heat exchangers with a wide range of nanofluid concentration.

  12. The Juxtamembrane and carboxy-terminal domains of Arabidopsis PRK2 are critical for ROP-induced growth in pollen tubes

    USDA-ARS?s Scientific Manuscript database

    Polarized growth of pollen tubes is a critical step for successful reproduction in angiosperms and is controlled by ROP GTPases. Spatiotemporal activation of ROP (Rho GTPases of plants) necessitates a complex and sophisticated regulatory system, in which guanine nucleotide exchange factors (RopGEFs)...

  13. Hard two-photon contribution to elastic lepton-proton scattering determined by the OLYMPUS experiment

    NASA Astrophysics Data System (ADS)

    Hasell, D. K.; OLYMPUS Collaboration

    2018-02-01

    The OLYMPUS collaboration has recently made a precise measurement of the positron-proton to electron-proton elastic scattering cross section ratio, R 2γ, over a wide range of the virtual photon polarization, 0.456 < ɛ < 0.978. This provides a direct measure of hard two-photon exchange in elastic lepton-proton scattering widely thought to explain the discrepancy observed between unpolarized and polarized measurements of the proton form factor ratio, {μ }p{G}Ep/{G}Mp. The OLYMPUS results are small, within 1% on unity, over the range of momentum transfers measured and significantly lower than theoretical calculations that can explain part of the observed discrepancy in terms of two-photon exchange at higher momentum transfers. However, the results are in reasonable agreement with predictions based on phenomenological fits to the available form factor data. The motivation for measuring R 2γ will be presented followed by a description of the OLYMPUS experiment. The importance of radiative corrections in the analysis will be shown also. Then we will present the OLYMPUS results and compare with results from two similar experiments and theoretical calculations.

  14. Simplified in vitro refolding and purification of recombinant human granulocyte colony stimulating factor using protein folding cation exchange chromatography.

    PubMed

    Vemula, Sandeep; Dedaniya, Akshay; Thunuguntla, Rahul; Mallu, Maheswara Reddy; Parupudi, Pavani; Ronda, Srinivasa Reddy

    2015-01-30

    Protein folding-strong cation exchange chromatography (PF-SCX) has been employed for efficient refolding with simultaneous purification of recombinant human granulocyte colony stimulating factor (rhG-CSF). To acquire a soluble form of renatured and purified rhG-CSF, various chromatographic conditions, including the mobile phase composition and pH was evaluated. Additionally, the effects of additives such as urea, amino acids, polyols, sugars, oxidizing agents and their amalgamations were also investigated. Under the optimal conditions, rhG-CSF was efficaciously solubilized, refolded and simultaneously purified by SCX in a single step. The experimental results using ribose (2.0M) and arginine (0.6M) combination were found to be satisfactory with mass yield, purity and specific activity of 71%, ≥99% and 2.6×10(8)IU/mg respectively. Through this investigation, we concluded that the SCX refolding method was more efficient than conventional methods which has immense potential for the large-scale production of purified rhG-CSF. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Predictors of Adolescent Successful Development after an Exchange: The Importance of Activity Qualities and Youth Input

    ERIC Educational Resources Information Center

    Lawford, Heather L.; Ramey, Heather L.; Rose-Krasnor, Linda; Proctor, Andrea S.

    2012-01-01

    The purpose of this study is to examine the factors involved in predicting successful development after an intensive exchange experience in adolescence. Specifically, we considered the eight positive features, as conceptualized by Eccles and Gootman (2002), as well as the amount of input youth had into their exchange experience as predictors of…

  16. 26 CFR 1.631-1 - Election to consider cutting as sale or exchange.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... necessary factor. See paragraph (e) of this section. (4) For any taxable year for which the cutting of... 26 Internal Revenue 7 2011-04-01 2009-04-01 true Election to consider cutting as sale or exchange... consider cutting as sale or exchange. (a) Effect of election. (1) Section 631 (a) provides an election to...

  17. Photon and vector meson exchanges in the production of light meson pairs and elementary atoms

    NASA Astrophysics Data System (ADS)

    Gevorkyan, S. R.; Kuraev, E. A.; Volkov, M. K.

    2013-01-01

    The production of pseudoscalar and scalar meson pairs ππ, ηη, η‧η‧, σσ as well as bound states in high energy γγ collisions are considered. The exchange by a vector particle in the binary process γ + γ → ha + hb with hadronic states ha, hb in fragmentation regions of the initial particle leads to nondecreasing cross sections with increasing energy, that is a priority of peripheral kinematics. Unlike the photon exchange the vector meson exchange needs a reggeization leading to fall with energy growth. Nevertheless, due to the peripheral kinematics beyond very forward production angles the vector meson exchanges dominate over all possible exchanges. The proposed approach allows one to express the matrix elements of the considered processes through impacting factors, which can be calculated in perturbation models like chiral perturbation theory (ChPT) or the Nambu-Jona-Lasinio (NJL) model. In particular cases the impact factors can be determined from relevant γγ sub-processes or the vector meson radiative decay width. The pionium atom production in the collisions of high energy electrons and pions with protons is considered and the relevant cross sections have been estimated.

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

    Stuart Adler; L. Dunyushkina; S. Huff

    The goal of this project was to develop an improved understanding of factors governing performance and degradation of mixed-conducting SOFC cathodes. Two new diagnostic tools were developed to help achieve this goal: (1) microelectrode half-cells for improved isolation of cathode impedance on thin electrolytes, and (2) nonlinear electrochemical impedance spectroscopy (NLEIS), a variant of traditional impedance that allows workers to probe nonlinear rates as a function of frequency. After reporting on the development and efficacy of these tools, this document reports on the use of these and other tools to better understand performance and degradation of cathodes based on themore » mixed conductor La{sub 1-x}Sr{sub x}CoO{sub 3-{delta}} (LSC) on gadolinia or samaria-doped ceria (GDC or SDC). We describe the use of NLEIS to measure O{sub 2} exchange on thin-film LSC electrodes, and show that O{sub 2} exchange is most likely governed by dissociative adsorption. We also describe parametric studies of porous LSC electrodes using impedance and NLEIS. Our results suggest that O{sub 2} exchange and ion transport co-limit performance under most relevant conditions, but it is O{sub 2} exchange that is most sensitive to processing, and subject to the greatest degradation and sample-to-sample variation. We recommend further work that focuses on electrodes of well-defined or characterized geometry, and probes the details of surface structure, composition, and impurities. Parallel work on primarily electronic conductors (LSM) would also be of benefit to developers, and to improved understanding of surface vs. bulk diffusion.« less

  19. A New, Noninvasive Method of Measuring Impaired Pulmonary Gas Exchange in Lung Disease: An Outpatient Study.

    PubMed

    West, John B; Crouch, Daniel R; Fine, Janelle M; Makadia, Dipen; Wang, Daniel L; Prisk, G Kim

    2018-02-13

    It would be valuable to have a noninvasive method of measuring impaired pulmonary gas exchange in patients with lung disease and thus reduce the need for repeated arterial punctures. This study reports the results of using a new test in a group of outpatients attending a pulmonary clinic. Inspired and expired partial pressure of oxygen (PO 2 ) and Pco 2 are continually measured by small, rapidly responding analyzers. The arterial PO 2 is calculated from the oximeter blood oxygen saturation level and the oxygen dissociation curve. The PO 2 difference between the end-tidal gas and the calculated arterial value is called the oxygen deficit. Studies on 17 patients with a variety of pulmonary diseases are reported. The mean ± SE oxygen deficit was 48.7 ± 3.1 mm Hg. This finding can be contrasted with a mean oxygen deficit of 4.0 ± 0.88 mm Hg in a group of 31 normal subjects who were previously studied (P < .0001). The analysis emphasizes the value of measuring the composition of alveolar gas in determining ventilation-perfusion ratio inequality. This factor is largely ignored in the classic index of impaired pulmonary gas exchange using the ideal alveolar PO 2 to calculate the alveolar-arterial oxygen gradient. The results previously reported in normal subjects and the present studies suggest that this new noninvasive test will be valuable in assessing abnormal gas exchange in the clinical setting. Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  20. GDP-bound and nucleotide-free intermediates of the guanine nucleotide exchange in the Rab5·Vps9 system.

    PubMed

    Uejima, Tamami; Ihara, Kentaro; Goh, Tatsuaki; Ito, Emi; Sunada, Mariko; Ueda, Takashi; Nakano, Akihiko; Wakatsuki, Soichi

    2010-11-19

    Many GTPases regulate intracellular transport and signaling in eukaryotes. Guanine nucleotide exchange factors (GEFs) activate GTPases by catalyzing the exchange of their GDP for GTP. Here we present crystallographic and biochemical studies of a GEF reaction with four crystal structures of Arabidopsis thaliana ARA7, a plant homolog of Rab5 GTPase, in complex with its GEF, VPS9a, in the nucleotide-free and GDP-bound forms, as well as a complex with aminophosphonic acid-guanylate ester and ARA7·VPS9a(D185N) with GDP. Upon complex formation with ARA7, VPS9 wedges into the interswitch region of ARA7, inhibiting the coordination of Mg(2+) and decreasing the stability of GDP binding. The aspartate finger of VPS9a recognizes GDP β-phosphate directly and pulls the P-loop lysine of ARA7 away from GDP β-phosphate toward switch II to further destabilize GDP for its release during the transition from the GDP-bound to nucleotide-free intermediates in the nucleotide exchange reaction.

  1. Evaluation of Variable Refrigerant Flow Systems Performance and the Enhanced Control Algorithm on Oak Ridge National Laboratory s Flexible Research Platform

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

    Im, Piljae; Munk, Jeffrey D; Gehl, Anthony C

    2015-06-01

    A research project “Evaluation of Variable Refrigerant Flow (VRF) Systems Performance and the Enhanced Control Algorithm on Oak Ridge National Laboratory’s (ORNL’s) Flexible Research Platform” was performed to (1) install and validate the performance of Samsung VRF systems compared with the baseline rooftop unit (RTU) variable-air-volume (VAV) system and (2) evaluate the enhanced control algorithm for the VRF system on the two-story flexible research platform (FRP) in Oak Ridge, Tennessee. Based on the VRF system designed by Samsung and ORNL, the system was installed from February 18 through April 15, 2014. The final commissioning and system optimization were completed onmore » June 2, 2014, and the initial test for system operation was started the following day, June 3, 2014. In addition, the enhanced control algorithm was implemented and updated on June 18. After a series of additional commissioning actions, the energy performance data from the RTU and the VRF system were monitored from July 7, 2014, through February 28, 2015. Data monitoring and analysis were performed for the cooling season and heating season separately, and the calibrated simulation model was developed and used to estimate the energy performance of the RTU and VRF systems. This final report includes discussion of the design and installation of the VRF system, the data monitoring and analysis plan, the cooling season and heating season data analysis, and the building energy modeling study« less

  2. Investigating Liquid CO2 as a Coolant for a MTSA Heat Exchanger Design

    NASA Technical Reports Server (NTRS)

    Paul, Heather L.; Padilla, Sebastian; Powers, Aaron; Iacomini, Christie

    2009-01-01

    Metabolic heat regenerated Temperature Swing Adsorption (MTSA) technology is being developed for thermal and carbon dioxide (CO 2) control for a future Portable Life Support System (PLSS), as well as water recycling. CO 2 removal and rejection is accomplished by driving a sorbent through a temperature swing of approximately 210 K to 280 K . The sorbent is cooled to these sub-freezing temperatures by a Sublimating Heat Exchanger (SHX) with liquid coolant expanded to sublimation temperatures. Water is the baseline coolant available on the moon, and if used, provides a competitive solution to the current baseline PLSS schematic. Liquid CO2 (LCO2) is another non-cryogenic coolant readily available from Martian resources which can be produced and stored using relatively low power and minimal infrastructure. LCO 2 expands from high pressure liquid (5800 kPa) to Mars ambient (0.8 kPa) to produce a gas / solid mixture at temperatures as low as 156 K. Analysis and experimental work are presented to investigate factors that drive the design of a heat exchanger to effectively use this sink. Emphasis is given to enabling efficient use of the CO 2 cooling potential and mitigation of heat exchanger clogging due to solid formation. Minimizing mass and size as well as coolant delivery are also considered. The analysis and experimental work is specifically performed in an MTSA-like application to enable higher fidelity modeling for future optimization of a SHX design. In doing so, the work also demonstrates principles and concepts so that the design can be further optimized later in integrated applications (including Lunar application where water might be a choice of coolant).

  3. Migration of the population.

    PubMed

    Krasinets, E

    1998-03-01

    Two factors influence foreign migration balance of the Russian Federation. The first factor involves the migration process between Russia and former union republics. The influx of population to the Russian Federation from other republics of the former Soviet Union is considered as one of the largest in the world. The average annual migratory growth of Russia during the years 1991-94 as a result of this migration exchange has tripled as compared with 1986-90, with a total of 2.7 million Russians who migrated into Russia. However, from 1996 up to the present time, the number of persons arriving in Russia declined dramatically. Meanwhile, the second factor that determines the country's migration balance is emigration to the far abroad. The most significant trend in determining the development of internal migration in Russia is the outflow of population from northern and eastern regions. The directions of internal and external migratory flows have a large influence on the migration balance in Russia's rural areas. The reduction of migratory flows in rural areas is the direct result of processes in the economic sphere. It confirms the reconstruction of rural-urban migratory exchange.

  4. Regional variability of grassland CO2 fluxes in Tyrol/Austria

    NASA Astrophysics Data System (ADS)

    Irschick, Christoph; Hammerle, Albin; Haslwanter, Alois; Wohlfahrt, Georg

    2010-05-01

    The FLUXNET project [1] aims at quantifying the magnitude and controls on the CO2, H2O and energy exchange of terrestrial ecosystems. Ideally, the various biomes of the Earth would be sampled in proportion to their spatial extent - in reality, however, study site selection is usually based on other (more practical) criteria so that a bias exists towards certain biomes and ecosystem types. This may be problematic because FLUXNET data are used to calibrate/parameterize models at various scales - if certain ecosystems are poorly replicated this may bias model predictions. Here we present data from a project in Tyrol/Austria where we have been investigating the CO2, H2O and energy exchange of five grassland sites during 2005-2007. The five permanent grassland sites were exposed to similar climate, but differed slightly in management. In a FLUXNET style approach, any of these sites might have been selected for making long-term flux measurements - the aim of this project was to examine the representativeness of these sites and, if evident, elucidate the causes for and controls on differences between sites. To this end we conducted continuous eddy covariance flux measurements at one (anchor) site [2, 3], and episodic, month long flux measurements at the four additional sites using a roving eddy covariance tower. These data were complemented by measurements of environmental drivers, the amount of above ground phytomass and basic data on vegetation and soil type, as well as management. Data are subject to a rigorous statistical analysis in order to quantify significant differences in the CO2, H2O and energy exchange between the sites and to identify the factors which are responsible for these differences. In the present contribution we report results on CO2 fluxes. Our major findings are that (i) site-identity of the surveyed grassland ecosystems was a significant factor for the net ecosystem CO2 exchange (NEE), somewhat less for gross primary production (GPP) and not for ecosystem respiration (RECO), (ii) GPP depended mainly on the amount of incident photosynthetically active radiation and the amount of green plant matter, the scale of influence of these two factors varying fourfold between the sites, and not so much on the available water, (iii) RECO was mainly affected by the soil temperature, but some evidence for priming effects was also found, (iv) the NEE was mainly influenced by GPP and to a lower extent by RECO. Taken together our results indicate that even within the same ecosystem type exposed to similar climate and land use, site selection may strongly affect the resulting NEE estimates. References: [1] D.D. Baldocchi, "Breathing of the terrestrial biosphere: lessons learned from a global network of carbon dioxide flux measurement systems", Australian Journal of Botany vol.56 (2008) pp. 1-26. [2] A. Hammerle, A. Haslwanter, U. Tappeiner, A. Cernusca, G. Wohlfahrt, "Leaf area controls on energy partitioning of a temperate mountain grassland", Biogeosciences vol.5 (2008) pp. 421 431. [3] G. Wohlfahrt, A. Hammerle, A. Haslwanter, M. Bahn, U. Tappeiner, A. Cernusca, "Seasonal and inter-annual variability of the net ecosystem CO2 exchange of a temperate mountain grassland: effects of weather and management", Journal of Geophysical Research 113 (2008) D08110, doi:10.1029/2007JD009286.

  5. Accessing the Elastic Form-Factors of the $Delta(1232)$ Using the Beam-Normal Asymmetry

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

    Dalton, Mark M.

    2016-08-01

    The beam-normal single-spin asymmetry,more » $$B_n$$, exists in the scattering of high energy electrons, polarized transverse to their direction of motion, from nuclear targets. To first order, this asymmetry is caused by the interference of the one-photon exchange amplitude with the imaginary part of the two-photon exchange amplitude. Measurements of $$B_n$$, for the production of a $$\\Delta(1232)$$ resonance from a proton target, will soon become available from the Qweak experiment at Jefferson Lab and the A4 experiment at Mainz. The imaginary part of two-photon exchange allows only intermediate states that are on-shell, including the $$\\Delta$$ itself. Therefore such data is sensitive to $$\\gamma\\Delta\\Delta$$, the elastic form-factors of the $$\\Delta$$. This article will introduce the form-factors of the $$\\Delta$$, discuss what might be learned about the elastic form-factors from these new data, describe ongoing efforts in calculation and measurement, and outline the possibility of future measurements.« less

  6. 43 CFR 2203.2 - Submission of information concerning proposed exchange.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...: GENERAL PROCEDURES Exchanges Involving Fee Federal Coal Deposits § 2203.2 Submission of information concerning proposed exchange. (a) Any person submitting a proposal for a fee exchange of Federal coal... proposed exchange. 2203.2 Section 2203.2 Public Lands: Interior Regulations Relating to Public Lands...

  7. 43 CFR 2203.2 - Submission of information concerning proposed exchange.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...: GENERAL PROCEDURES Exchanges Involving Fee Federal Coal Deposits § 2203.2 Submission of information concerning proposed exchange. (a) Any person submitting a proposal for a fee exchange of Federal coal... proposed exchange. 2203.2 Section 2203.2 Public Lands: Interior Regulations Relating to Public Lands...

  8. 43 CFR 2203.2 - Submission of information concerning proposed exchange.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...: GENERAL PROCEDURES Exchanges Involving Fee Federal Coal Deposits § 2203.2 Submission of information concerning proposed exchange. (a) Any person submitting a proposal for a fee exchange of Federal coal... proposed exchange. 2203.2 Section 2203.2 Public Lands: Interior Regulations Relating to Public Lands...

  9. 43 CFR 2203.2 - Submission of information concerning proposed exchange.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...: GENERAL PROCEDURES Exchanges Involving Fee Federal Coal Deposits § 2203.2 Submission of information concerning proposed exchange. (a) Any person submitting a proposal for a fee exchange of Federal coal... proposed exchange. 2203.2 Section 2203.2 Public Lands: Interior Regulations Relating to Public Lands...

  10. [Determination of net exchange of CO2 between paddy fields and atmosphere with static poaque-chamber-based measurements].

    PubMed

    Zheng, Xunhua; Xu, Zhongjun; Wang, Yuesi; Han, Shenghui; Huang, Yao; Cai, Zucong; Zhu, Jianguo

    2002-10-01

    We firstly introduced the method for determining the net ecosystem exchange fluxes of CO2 (NEE) between croplands and atmosphere, based on field measurements using static opaquechamber/gas chromatography methods was introduced, and the application of this method in the FACE (free-air CO2 enrichment) study to examine the effects of elevated CO2 on the NEE over a typical paddy ecosystem was carried out, because of lacking in observation data for some necessary parameters, e.g., dark maintenance respiration coefficient, only the minimum value of NEE (NEEmin) was calculated based on opaque-chamber measurements. The NEEmin data indicate that CO2 elevated by 200 +/- 40 mumol.mol-1 significantly increased the ecosystem uptake of atmospheric CO2 by a factor ca. 3. To accurately determine the NEE based on opaquechamber measurements, dark maintenance respiration coefficient, above-ground biomass and root: shoot, i.e. R:S, ratio of root to shoot should be observed over the whole growing season.

  11. Anxiety and depression with neurogenesis defects in exchange protein directly activated by cAMP 2-deficient mice are ameliorated by a selective serotonin reuptake inhibitor, Prozac

    PubMed Central

    Zhou, L; Ma, S L; Yeung, P K K; Wong, Y H; Tsim, K W K; So, K F; Lam, L C W; Chung, S K

    2016-01-01

    Intracellular cAMP and serotonin are important modulators of anxiety and depression. Fluoxetine, a selective serotonin reuptake inhibitor (SSRI) also known as Prozac, is widely used against depression, potentially by activating cAMP response element-binding protein (CREB) and increasing brain-derived neurotrophic factor (BDNF) through protein kinase A (PKA). However, the role of Epac1 and Epac2 (Rap guanine nucleotide exchange factors, RAPGEF3 and RAPGEF4, respectively) as potential downstream targets of SSRI/cAMP in mood regulations is not yet clear. Here, we investigated the phenotypes of Epac1 (Epac1−/−) or Epac2 (Epac2−/−) knockout mice by comparing them with their wild-type counterparts. Surprisingly, Epac2−/− mice exhibited a wide range of mood disorders, including anxiety and depression with learning and memory deficits in contextual and cued fear-conditioning tests without affecting Epac1 expression or PKA activity. Interestingly, rs17746510, one of the three single-nucleotide polymorphisms (SNPs) in RAPGEF4 associated with cognitive decline in Chinese Alzheimer's disease (AD) patients, was significantly correlated with apathy and mood disturbance, whereas no significant association was observed between RAPGEF3 SNPs and the risk of AD or neuropsychiatric inventory scores. To further determine the detailed role of Epac2 in SSRI/serotonin/cAMP-involved mood disorders, we treated Epac2−/− mice with a SSRI, Prozac. The alteration in open field behavior and impaired hippocampal cell proliferation in Epac2−/− mice were alleviated by Prozac. Taken together, Epac2 gene polymorphism is a putative risk factor for mood disorders in AD patients in part by affecting the hippocampal neurogenesis. PMID:27598965

  12. Increased incidence of chromosomal aberrations in peripheral lymphocytes of retired nickel workers.

    PubMed

    Waksvik, H; Boysen, M; Høgetveit, A C

    1984-11-01

    Chromosomal aberrations and sister chromatid exchanges were analysed in the peripheral lymphocytes of nine retired nickel refinery workers 4-15 years after the retirement and compared with 11 matched non-nickel exposed controls. None of the controls had previous occupations with known relation to induction of chromosomal aberrations nor sister chromatid exchanges. The groups were equal as to socioeconomic status and environmental factors other than the occupational ones, which could influence the chromosome parameters, were to the largest possible extent excluded. The nickel workers' previous occupational employment involved exposure to inhalation of furnace dust of Ni3S2 and NiO or aerosols of NiCl2 and NiSO4. The concentration of nickel in the working atmospheres has been higher than 1.0 mg/m3 air and the exposure time more than 25 years. The retired nickel workers showed an increased incidence of breaks (p less than 0.001) and gaps (p less than 0.05) but no difference in the incidence of sister chromatid exchanges when compared with the controls.

  13. Expression of a Rho guanine nucleotide exchange factor, Ect2, in the developing mouse pituitary.

    PubMed

    Islam, M S; Tsuji, T; Higashida, C; Takahashi, M; Higashida, H; Koizumi, K

    2010-05-01

    The pituitary gland is a highly mitotically active tissue after birth. Various cell types are known to undergo proliferation in the anterior pituitary. However, little is known about the mechanisms regulating mitotic activity in this tissue. When searching for genes specifically expressed in the pituitary gland among those that we previously screened in Drosophila, we found epithelial cell-transforming gene 2 (Ect2). Ect2 is a guanine nucleotide exchange factor for Rho GTPases, which is known to play an essential role in cytokinesis. Although there have been many cellular studies regarding the function of Ect2, the temporal and spatial expression patterns of Ect2 in vivo have not been determined. In the present study, we examined the postnatal developmental expression of Ect2 in the mouse pituitary. Enhanced Ect2 expression was detected in the mouse pituitary gland during the first 3 weeks after birth, which coincided well with the period of rapid pituitary expansion associated with increased growth rate. Immunostaining analysis showed that Ect2-expressing cells were distributed in the anterior and intermediate lobes, but not the posterior lobe, of the pituitary. These Ect2-expressing cells frequently incorporated the thymidine analogue, EdU (5-ethynyl-2'-deoxyuridine), indicating that these cells were mitotically active. Taken together, the results demonstrate the functional role of Ect2 in postnatal proliferating cells in the two lobes of the pituitary, thereby suggesting roles in developmental growth of the mammalian pituitary.

  14. An Analysis of International Air Freight Forwarding Support for the United States Navy.

    DTIC Science & Technology

    1985-06-01

    2. The Role of IATA in Ratemaking ... ...... 23 3. Current Environment ..... ........... 24 III. BURLINGTON-NORTHERN AIR FREIGHT, INCORPORATED . . 28...Postgraduate School Library, Defense Logistics Studies Information Exchange, service guides provided by air freight forwarders, and MAC airlift data. Additional...carrier is permitted access [Ref. 16]. 2. The Role of IATA in Ratemaking Factors other than shipper demand and carrier costs affect international freight

  15. Daily Social Exchanges and Affect in Middle and Later Adulthood: The Impact of Loneliness and Age

    ERIC Educational Resources Information Center

    Russell, Alissa; Bergeman, C. S.; Scott, Stacey B.

    2012-01-01

    Although daily social exchanges are important for well-being, it is unclear how different types of exchanges affect daily well-being, as well as which factors influence the way in which individuals react to their daily social encounters. The present study included a sample of 705 adults aged 31 to 91, and using Multilevel Modeling analyses…

  16. Effect of soil organic matter on antimony bioavailability after the remediation process.

    PubMed

    Nakamaru, Yasuo Mitsui; Martín Peinado, Francisco José

    2017-09-01

    We evaluated the long-term (18 year) and short-term (4 weeks) changes of Sb in contaminated soil with SOM increase under remediation process. In the Aznalcóllar mine accident (1998) contaminated area, the remediation measurement implemented the Guadiamar Green Corridor, where residual pollution is still detected. Soils of the re-vegetated area (O2) with high pH and high SOM content, moderately re-vegetated area (O1) and unvegetated area (C) were sampled. Soil pH, CEC, SOM amount and soil Sb forms were evaluated. Soil Sb was measured as total, soluble, exchangeable, EDTA extractable, acid oxalate extractable, and pyro-phosphate extractable fractions. Further, the short-term effect of artificial organic matter addition was also evaluated with incubation study by adding compost to the sampled soil from C, O1 and O2 areas. After 4 weeks of incubation, soil chemical properties and Sb forms were evaluated. In re-vegetated area (O2), soil total Sb was two times lower than in unvegetated area (C); however, soluble, exchangeable, and EDTA extractable Sb were 2-8 times higher. The mobile/bioavailable Sb increase was also observed after 4 weeks of incubation with the addition of compost. Soluble, exchangeable, and EDTA extractable Sb was increased 2-4 times by compost addition. By the linear regression analysis, the significantly related factors for soluble, exchangeable, and EDTA extractable Sb values were pH, CEC, and SOM, respectively. Soluble Sb increase was mainly related to pH rise. Exchangeable Sb should be bound by SOM-metal complex and increased with CEC. EDTA extractable fraction should be increased with increase of SOM as SOM-Fe associated Sb complex. From these results, it was shown that increase of SOM under natural conditions or application of organic amendment under remediation process should increase availability of Sb to plants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Selection during crop diversification involves correlated evolution of the circadian clock and ecophysiological traits in Brassica rapa.

    PubMed

    Yarkhunova, Yulia; Edwards, Christine E; Ewers, Brent E; Baker, Robert L; Aston, Timothy Llewellyn; McClung, C Robertson; Lou, Ping; Weinig, Cynthia

    2016-04-01

    Crop selection often leads to dramatic morphological diversification, in which allocation to the harvestable component increases. Shifts in allocation are predicted to impact (as well as rely on) physiological traits; yet, little is known about the evolution of gas exchange and related anatomical features during crop diversification. In Brassica rapa, we tested for physiological differentiation among three crop morphotypes (leaf, turnip, and oilseed) and for correlated evolution of circadian, gas exchange, and phenological traits. We also examined internal and surficial leaf anatomical features and biochemical limits to photosynthesis. Crop types differed in gas exchange; oilseed varieties had higher net carbon assimilation and stomatal conductance relative to vegetable types. Phylogenetically independent contrasts indicated correlated evolution between circadian traits and both gas exchange and biomass accumulation; shifts to shorter circadian period (closer to 24 h) between phylogenetic nodes are associated with higher stomatal conductance, lower photosynthetic rate (when CO2 supply is factored out), and lower biomass accumulation. Crop type differences in gas exchange are also associated with stomatal density, epidermal thickness, numbers of palisade layers, and biochemical limits to photosynthesis. Brassica crop diversification involves correlated evolution of circadian and physiological traits, which is potentially relevant to understanding mechanistic targets for crop improvement. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  18. Orthogonal test design for optimization of synthesis of MTX/LDHs hybrids by ion-exchange method

    NASA Astrophysics Data System (ADS)

    Liu, Su-Qing; Dai, Chao-Fan; Wang, Lin; Li, Shu-Ping; Li, Xiao-Dong

    2015-04-01

    Based on orthogonal test design, the factors influencing the synthesis of methotrexate intercalated magnesium-aluminum layered double hydroxides (MTX/LDHs for short) by ion-exchange method, such as weight ratio of pristine LDHs to MTX (R for short), exchange temperature, time and pH value were investigated. Of the four controllable independent variables, R had the strongest effect on the crystallinity and the drug-loading capacity and the optimum synthesis conditions considered from the crystallinity and the drug-loading capacity both pointed to the same values, i.e., R=2:1, pH=9.5, temperature of 80 °C and exchange time of 3 day. The XRD diffractions indicated that high MTX content was in favor of the formation of intercalated hybrids, while low content lead to the failure of it. TEM photos indicated that the intercalated hybrids all exhibited aggregated hexagonal plates. In order to improve the morphology, two different states of pristine LDHs, i.e., powder and colloid, were chosen to prepare MTX/LDHs hybrids and the results indicated that colloid state of pristine was advantageous to obtain regular particles. The study also revealed that the properties of hybrids obtained at optimum conditions by ion-exchange were superior to that obtained from standard methods, such as co-precipitation method.

  19. Characteristics associated with regional health information organization viability.

    PubMed

    Adler-Milstein, Julia; Landefeld, John; Jha, Ashish K

    2010-01-01

    Regional Health Information Organizations (RHIOs) will likely play a key role in our nation's effort to catalyze health information exchange. Yet we know little about why some efforts succeed while others fail. We sought to identify factors associated with RHIO viability. Using data from a national survey of RHIOs that we conducted in mid-2008, we examined factors associated with becoming operational and factors associated with financial viability. We used multivariate logistic regression models to identify unique predictors. We classified RHIOs actively facilitating data exchange as operational and measured financial viability as the percent of operating costs covered by revenue from participants in data exchange (0-24%, 25-74%, 75-100%). Predictors included breadth of participants, breadth of data exchanged, whether the RHIO focused on a specific population, whether RHIO participants had a history of collaborating, and sources of revenue during the planning phase. Exchanging a narrow set of data and involving a broad group of stakeholders were independently associated with a higher likelihood of being operational. Involving hospitals and ambulatory physicians, and securing early funding from participants were associated with a higher likelihood of financial viability, while early grant funding seemed to diminish the likelihood. Finding ways to help RHIOs become operational and self-sustaining will bolster the current approach to nationwide health information exchange. Our work suggests that convening a broad coalition of stakeholders to focus on a narrow set of data is an important step in helping RHIOs become operational. Convincing stakeholders to financially commit early in the process may help RHIOs become self-sustaining.

  20. Patient Protection and Affordable Care Act; establishment of exchanges and qualified health plans; exchange standards for employers. Final rule, Interim final rule.

    PubMed

    2012-03-27

    This final rule will implement the new Affordable Insurance Exchanges ("Exchanges"), consistent with title I of the Patient Protection and Affordable Care Act of 2010 as amended by the Health Care and Education Reconciliation Act of 2010, referred to collectively as the Affordable Care Act. The Exchanges will provide competitive marketplaces for individuals and small employers to directly compare available private health insurance options on the basis of price, quality, and other factors. The Exchanges, which will become operational by January 1, 2014, will help enhance competition in the health insurance market, improve choice of affordable health insurance, and give small businesses the same purchasing clout as large businesses.

  1. Factors Associated With Revision Surgery After Internal Fixation of Hip Fractures.

    PubMed

    Sprague, Sheila; Schemitsch, Emil H; Swiontkowski, Marc; Della Rocca, Gregory J; Jeray, Kyle J; Liew, Susan; Slobogean, Gerard P; Bzovsky, Sofia; Heels-Ansdell, Diane; Zhou, Qi; Bhandari, Mohit

    2018-05-01

    Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (for every 5-point increase) (HR 1.19, 95% CI 1.02-1.39; P = 0.027), displaced fracture (HR 2.16, 95% CI 1.44-3.23; P < 0.001), unacceptable quality of implant placement (HR 2.70, 95% CI 1.59-4.55; P < 0.001), and smokers treated with cancellous screws versus smokers treated with a sliding hip screw (HR 2.94, 95% CI 1.35-6.25; P = 0.006). Additionally, for every 10-year decrease in age, participants experienced an average increased risk of 39% for hardware removal. Results of this study may inform future research by identifying high-risk patients who may be better treated with arthroplasty and may benefit from adjuncts to care (HR 1.39, 95% CI 1.05-1.85; P = 0.020). Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

  2. Proton Form Factor Puzzle and the CEBAF Large Acceptance Spectrometer (CLAS) two-photon exchange experiment

    NASA Astrophysics Data System (ADS)

    Rimal, Dipak

    The electromagnetic form factors are the most fundamental observables that encode information about the internal structure of the nucleon. The electric (GE) and the magnetic ( GM) form factors contain information about the spatial distribution of the charge and magnetization inside the nucleon. A significant discrepancy exists between the Rosenbluth and the polarization transfer measurements of the electromagnetic form factors of the proton. One possible explanation for the discrepancy is the contributions of two-photon exchange (TPE) effects. Theoretical calculations estimating the magnitude of the TPE effect are highly model dependent, and limited experimental evidence for such effects exists. Experimentally, the TPE effect can be measured by comparing the ratio of positron-proton elastic scattering cross section to that of the electron-proton [R = sigma(e +p)/sigma(e+p)]. The ratio R was measured over a wide range of kinematics, utilizing a 5.6 GeV primary electron beam produced by the Continuous Electron Beam Accelerator Facility (CEBAF) at Jefferson Lab. This dissertation explored dependence of R on kinematic variables such as squared four-momentum transfer (Q2) and the virtual photon polarization parameter (epsilon). A mixed electron-positron beam was produced from the primary electron beam in experimental Hall B. The mixed beam was scattered from a liquid hydrogen (LH2) target. Both the scattered lepton and the recoil proton were detected by the CEBAF Large Acceptance Spectrometer (CLAS). The elastic events were then identified by using elastic scattering kinematics. This work extracted the Q2 dependence of R at high epsilon(epsilon > 0.8) and the $epsilon dependence of R at approx 0.85 GeV2. In these kinematics, our data confirm the validity of the hadronic calculations of the TPE effect by Blunden, Melnitchouk, and Tjon. This hadronic TPE effect, with additional corrections contributed by higher excitations of the intermediate state nucleon, largely reconciles the Rosenbluth and the polarization transfer measurements of the electromagnetic form factors.

  3. Sex-for-Crack exchanges: associations with risky sexual and drug use niches in an urban Canadian city

    PubMed Central

    2013-01-01

    Background While crack cocaine has been associated with elevated sexual risks and transmission of HIV/STIs, particularly in the context of street-based sex work, few empirical studies have examined correlates of direct sex-for-crack exchanges. This study longitudinally examined the correlates of sex-for-crack exchanges and associated effects on sexual risk outcomes among street-based female sex workers (SW) who use drugs in Vancouver, Canada. Methods Data were drawn from a prospective cohort of street-based SWs (2006–2008), restricted to those who smoke crack cocaine. Multivariable generalized estimating equations (GEE) were employed to examine the correlates of exchanging sex for crack. A confounding model using GEE quasi-Poisson regression modeled the independent effect of exchanging sex for crack on number of clients/week. Results Of 206 SWs, 101 (49%) reported sex-for-crack exchanges over 18 months of follow-up. In multivariable GEE analyses, sharing a crack pipe with a client (aOR = 1.98; 95%CI: 1.27-3.08) and smoking crack in a group of strangers (e.g., in an alley or crackhouse) (aOR = 1.70; 95% CI: 1.13-2.58) were independently correlated with sex-for-crack exchanges. In our confounding model, exchanging sex for crack (aIRR = 1.34; 95% CI: 1.07-1.69) remained significantly associated with servicing a greater number (>10) of clients/week. Conclusions These findings reveal elevated sexual- and drug- risk patterns among those who exchange sex for crack. The physical and social environment featured prominently in our results as a driver of sex-for-crack exchanges, highlighting the need for gender-sensitive multilevel approaches to harm reduction, STI and HIV prevention that address SWs’ environment, individual level factors, and the interplay between them. PMID:24238367

  4. Using Riverboat-Mounted Eddy Covariance for Direct Measurements of Air-water Gas Exchange in Amazonia

    NASA Astrophysics Data System (ADS)

    Miller, S. D.; Freitas, H.; Read, E.; Goulden, M. L.; Rocha, H.

    2007-12-01

    Gas evasion from Amazonian rivers and lakes to the atmosphere has been estimated to play an important role in the regional budget of carbon dioxide (Richey et al., 2002) and the global budget of methane (Melack et al., 2004). These flux estimates were calculated by combining remote sensing estimates of inundation area with water-side concentration gradients and gas transfer rates (piston velocities) estimated primarily from floating chamber measurements (footprint ~1 m2). The uncertainty in these fluxes was large, attributed primarily to uncertainty in the gas exchange parameterization. Direct measurements of the gas exchange coefficient are needed to improve the parameterizations in these environments, and therefore reduce the uncertainty in fluxes. The micrometeorological technique of eddy covariance is attractive since it is a direct measurement of gas exchange that samples over a much larger area than floating chambers, and is amenable to use from a moving platform. We present eddy covariance carbon dioxide exchange measurements made using a small riverboat in rivers and lakes in the central Amazon near Santarem, Para, Brazil. Water-side carbon dioxide concentration was measured in situ, and the gas exchange coefficient was calculated. We found the piston velocity at a site on the Amazon River to be similar to existing ocean-based parameterizations, whereas the piston velocity at a site on the Tapajos River was roughly a factor 5 higher. We hypothesize that the enhanced gas exchange at the Tapajos site was due to a shallow upwind fetch. Our results demonstrate the feasibility of boat-based eddy covariance on these rivers, and also the utility of a mobile platform to investigate spatial variability of gas exchange.

  5. Circadian rhythms have significant effects on leaf-to-canopy scale gas exchange under field conditions.

    PubMed

    Resco de Dios, Víctor; Gessler, Arthur; Ferrio, Juan Pedro; Alday, Josu G; Bahn, Michael; Del Castillo, Jorge; Devidal, Sébastien; García-Muñoz, Sonia; Kayler, Zachary; Landais, Damien; Martín-Gómez, Paula; Milcu, Alexandru; Piel, Clément; Pirhofer-Walzl, Karin; Ravel, Olivier; Salekin, Serajis; Tissue, David T; Tjoelker, Mark G; Voltas, Jordi; Roy, Jacques

    2016-10-20

    Molecular clocks drive oscillations in leaf photosynthesis, stomatal conductance, and other cell and leaf-level processes over ~24 h under controlled laboratory conditions. The influence of such circadian regulation over whole-canopy fluxes remains uncertain; diurnal CO 2 and H 2 O vapor flux dynamics in the field are currently interpreted as resulting almost exclusively from direct physiological responses to variations in light, temperature and other environmental factors. We tested whether circadian regulation would affect plant and canopy gas exchange at the Montpellier European Ecotron. Canopy and leaf-level fluxes were constantly monitored under field-like environmental conditions, and under constant environmental conditions (no variation in temperature, radiation, or other environmental cues). We show direct experimental evidence at canopy scales of the circadian regulation of daytime gas exchange: 20-79 % of the daily variation range in CO 2 and H 2 O fluxes occurred under circadian entrainment in canopies of an annual herb (bean) and of a perennial shrub (cotton). We also observed that considering circadian regulation improved performance by 8-17 % in commonly used stomatal conductance models. Our results show that circadian controls affect diurnal CO 2 and H 2 O flux patterns in entire canopies in field-like conditions, and its consideration significantly improves model performance. Circadian controls act as a 'memory' of the past conditions experienced by the plant, which synchronizes metabolism across entire plant canopies.

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

    Radchenko, Valery; Engle, Jonathan Ward; Medvedev, Dmitri G.

    Scandium-44 g (half-life 3.97 h) shows promise for application in positron emission tomography (PET), due to favorable decay parameters. One of the sources of 44gSc is the 44Ti/ 44gSc generator, which can conveniently provide this radioisotope on a daily basis at a diagnostic facility. Titanium-44 (half-life 60.0 a), in turn, can be obtained via proton irradiation of scandium metal targets. A substantial 44Ti product batch, however, requires high beam currents, long irradiation times and an elaborate chemical procedure for 44Ti isolation and purification. This study describes the production of a combined 175 MBq (4.7 mCi) batch yield of 44Ti inmore » week long proton irradiations at the Los Alamos Isotope Production Facility (LANL-IPF) and the Brookhaven Linac Isotope Producer (BNL-BLIP). A two-step ion exchange chromatography based chemical separation method is introduced: first, a coarse separation of 44Ti via anion exchange sorption in concentrated HCl results in a 44Tc/Sc separation factor of 10 2–10 3. A second, cation exchange based step in HCl media is then applied for 44Ti fine purification from residual Sc mass. In conclusion, this method yields a 90–97% 44Ti recovery with an overall Ti/Sc separation factor of ≥10 6.« less

  7. Arf6 guanine-nucleotide exchange factor, cytohesin-2, interacts with actinin-1 to regulate neurite extension.

    PubMed

    Torii, Tomohiro; Miyamoto, Yuki; Nakamura, Kazuaki; Maeda, Masahiro; Yamauchi, Junji; Tanoue, Akito

    2012-09-01

    Proper regulation of morphological changes in neuronal cells is essential for their differentiation. Complex signaling mechanisms mediate a variety of morphological changes such as formation of neurites. It is well established that a number of small GTPases control neurite behavior before the connection with the target tissue. However, their regulatory mechanisms remain to be fully understood. Here, we show that the Arf6 guanine-nucleotide exchange factor (GEF), cytohesin-2 (CYTH2), interacts with the cytoskeletal protein actinin-1 (ACTN1) and regulates neurite extension in N1E-115 cells used as the model. Knockdown of ACTN1, as well as that of CYTH2, in cells inhibits cellular Arf6 activity and neurite extension. The C-terminal polybasic region of CYTH2 participates in interacting directly with the EFh2 domain of ACTN1. Expression of CYTH2 mutant deficient of the EFh2 domain in cells also inhibits Arf6 activation and neurite extension. Furthermore, FRET analysis detects that the respective interactive region peptides, tagged with cell-permeable short peptides, greatly decrease Arf6 activation at growth cones in a time-dependent manner. Collectively, the signaling through CYTH2 and ACTN1 properly regulates neurite extension in N1E-115 cells, demonstrating the unexpected interaction of CYTH2 and ACTN1 in the regulation of cellular Arf6 activity involved in neurite extension. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Juvenile Hormone Regulation of Drosophila Epac - A Guanine Nucleotide Exchange Factor for Rap1 Small GTPase

    USDA-ARS?s Scientific Manuscript database

    Previously, we utilized a microchip array encompassing probes for 14,010 genes of Drosophila melanogaster to analyze the effect of (10R) juvenile hormone III (JH) on genome-wide gene expression in Drosophila S2 cells. Treatment with JH yielded a collection of 32 gene transcripts that demonstrated a ...

  9. 77 FR 20471 - Self-Regulatory Organizations; C2 Options Exchange, Incorporated; Order Approving Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-04

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66677; File No. SR-C2-2012-006] Self-Regulatory... Improvement Mechanism March 29, 2012. On January 31, 2012, the C2 Options Exchange, Incorporated (``Exchange... C2 Rule 6.51, which relates to the Exchange's Automated Improvement Mechanism (``AIM''). The proposal...

  10. Redefining the utility of the three-isotope method

    NASA Astrophysics Data System (ADS)

    Cao, Xiaobin; Bao, Huiming

    2017-09-01

    The equilibrium isotope fractionation factor αeq is a fundamental parameter in the study of stable isotope effects. Experimentally, it has been difficult to establish that a system has attained equilibrium. The three-isotope method, using the initial trajectory of changing isotope ratios (e.g. 16O, 17O, and 18O) to deduce the final equilibrium point of isotope exchange, has long been hailed as the most rigorous experimental approach. However, over the years some researchers have cautioned on the limitations of this method, but the foundation of three-isotope method has not been properly examined and the method is still widely used in calibrating αeq for both traditional and increasingly non-traditional isotope systems today. Here, using water-water and dissolved CO2-water oxygen exchange as model systems, we conduct an isotopologues-specific kinetic analysis of the exchange processes and explore the underlying assumptions and validity of the three-isotope method. We demonstrate that without knowing the detailed exchange kinetics a priori the three-isotope method cannot lead to a reliable αeq. For a two-reservoir exchanging system, α determined by this method may be αeq, kinetic isotope effect, or apparent kinetic isotope effect, which can all bear different values. When multiple reservoirs exist during exchange, the evolving trajectory can be complex and hard to predict. Instead of being a tool for αeq determination, three-isotope method should be used as a tool for studying kinetic isotope effect, apparent kinetic isotope effect, and detailed exchange kinetics in diverse systems.

  11. 43 CFR 3436.2 - Fee coal exchanges.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Fee coal exchanges. 3436.2 Section 3436.2..., DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) NONCOMPETITIVE LEASES Coal Lease and Coal Land Exchanges: Alluvial Valley Floors § 3436.2 Fee coal exchanges. ...

  12. 43 CFR 3436.2 - Fee coal exchanges.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Fee coal exchanges. 3436.2 Section 3436.2..., DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) NONCOMPETITIVE LEASES Coal Lease and Coal Land Exchanges: Alluvial Valley Floors § 3436.2 Fee coal exchanges. ...

  13. 43 CFR 3436.2 - Fee coal exchanges.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Fee coal exchanges. 3436.2 Section 3436.2..., DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) NONCOMPETITIVE LEASES Coal Lease and Coal Land Exchanges: Alluvial Valley Floors § 3436.2 Fee coal exchanges. ...

  14. 43 CFR 3436.2 - Fee coal exchanges.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Fee coal exchanges. 3436.2 Section 3436.2..., DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) NONCOMPETITIVE LEASES Coal Lease and Coal Land Exchanges: Alluvial Valley Floors § 3436.2 Fee coal exchanges. ...

  15. Positive Culture During Reimplantation Increases the Risk of Subsequent Failure in Two-Stage Exchange Arthroplasty.

    PubMed

    Tan, Timothy L; Gomez, Miguel M; Manrique, Jorge; Parvizi, Javad; Chen, Antonia F

    2016-08-03

    It is strongly recommended that tissue and synovial fluid culture samples be obtained during reimplantation performed as part of a 2-stage exchange arthroplasty. The rate of positive cultures during reimplantation and the influence of positive cultures on subsequent outcomes, to our knowledge, are unknown. This study was designed to determine the rate of positive cultures during reimplantation and to investigate the association between positive cultures at reimplantation and subsequent outcomes. We retrospectively reviewed the data of 259 patients who met the Musculoskeletal Infection Society criteria for periprosthetic joint infection (PJI) and who underwent both stages of 2-stage exchange arthroplasty at our institution from 1999 to 2013. Among these patients were 267 PJIs (186 knees and 81 hips); 33 (12.4%) had ≥1 positive culture result at reimplantation. Treatment failure was assessed according to the Delphi-based consensus definition. Logistic regression analysis was performed to assess the predictors of positive culture and risk factors for failure of 2-stage exchange arthroplasty. Of the 33 cases with PJI, 15 (45.5%) had a subsequent failure of the 2-stage exchange arthroplasty compared with 49 (20.9%) of the cases that were culture-negative at reimplantation. When controlling for other variables using multivariate analyses, the risk of treatment failure was higher (odds ratio = 2.53; 95% confidence interval [CI] = 1.13 to 5.64) and reinfection occurred earlier (hazard ratio = 2.00; 95% CI = 1.05 to 3.82) for the cases with a positive culture during reimplantation. The treatment failure rate did not differ (p = 0.73) between cases with ≥2 positive cultures (36.4%) and 1 positive culture (50%). Positive intraoperative culture at the time of reimplantation, regardless of the number of positive samples, was independently associated with >2 times the risk of subsequent treatment failure and earlier reinfection. Surgeons should be aware that a positive culture at the time of reimplantation independently increases the risk of subsequent failure. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.

  16. Preoperative Anemia Is Associated With Failure of Open Debridement Polyethylene Exchange in Acute and Acute Hematogenous Prosthetic Joint Infection.

    PubMed

    Swenson, Richard D; Butterfield, James A; Irwin, Timothy J; Zurlo, John J; Davis, Charles M

    2018-06-01

    Acute and acute hematogenous prosthetic joint infections (PJIs) are often treated with open debridement and polyethylene exchange (ODPE) in an effort to save the prosthesis, decrease morbidity, and reduce costs. However, failure of ODPE may compromise a subsequent 2-stage treatment. The purpose of this study is to identify patient factors that impact the success of ODPE for acute and acute hematogenous PJIs. A retrospective review examined comorbidities, preoperative laboratory values, and patient history for patients with successful and failed ODPE treatment for acute perioperative or acute hematogenous periprosthetic hip or knee joint infections. Successful treatment was defined as retaining a well-fixed implant without the need for additional surgery for a minimum of 6-month follow-up with or without lifelong oral maintenance antibiotics. Fifty-three of 72 patients (73.6%) underwent successful ODPE. Of the 19 failures, 14 completed 2-stage revision with one subsequent known failure for recurrent infection. Patients with a Staphylococcus aureus infection were more likely to fail ODPE (48.3% vs 11.6%, P = .0012, odds ratio 7.1, 95% confidence interval 2.3-25.3). Patients with a preoperative hematocrit ≤32.1 were also more likely to fail ODPE (55% vs 16%, P = .0013, odds ratio 6.7, 95% confidence interval 2.2-22.4). When neither risk factor was present, 97.1% of PJIs were successfully treated with ODPE. S aureus infection and preoperative hematocrit ≤32.1 are independent risk factors for ODPE failure. ODPE is a safe alternative to 2-stage revision in patients without preoperative anemia and without S aureus infection. Two-thirds of patients with a failed ODPE were successfully treated with a 2-stage reimplantation. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Ionic Control of the Reversal Response of Cilia in Paramecium caudatum

    PubMed Central

    Naitoh, Yutaka

    1968-01-01

    The duration of ciliary reversal of Paramecium caudatum in response to changes in external ionic factors was determined with various ionic compositions of both equilibration and stimulation media. The reversal response was found to occur when calcium ions bound by an inferred cellular cation exchange system were liberated in exchange for externally applied cations other than calcium. Factors which affect the duration of the response were (a) initial amount of calcium bound by the cation exchange system, (b) final amount of calcium bound by the system after equilibration with the stimulation medium, and (c) concentration of calcium ions in the stimulation medium. An empirical equation is presented which relates the duration of the response to these three factors. On the basis of these and previously published data, the following hypothesis is proposed for the mechanism underlying ciliary reversal in response to cationic stimulation: Ca++ liberated from the cellular cation exchange system activates a contractile system which is energized by ATP. Contraction of this component results in the reversal of effective beat direction of cilia by a mechanism not yet understood. The duration of reversal in live paramecia is related to the time course of bound calcium release. PMID:4966766

  18. Contrasting dynamics of leaf potential and gas exchange during progressive drought cycles and recovery in Amorpha fruticosa and Robinia pseudoacacia.

    PubMed

    Yan, Weiming; Zheng, Shuxia; Zhong, Yangquanwei; Shangguan, Zhouping

    2017-06-30

    Leaf gas exchange is closely associated with water relations; however, less attention has been given to this relationship over successive drought events. Dynamic changes in gas exchange and water potential in the seedlings of two woody species, Amorpha fruticosa and Robinia pseudoacacia, were monitored during recurrent drought. The pre-dawn leaf water potential declined in parallel with gas exchange in both species, and sharp declines in gas exchange occurred with decreasing water potential. A significant correlation between pre-dawn water potential and gas exchange was observed in both species and showed a right shift in R. pseudoacacia in the second drought. The results suggested that stomatal closure in early drought was mediated mainly by elevated foliar abscisic acid (ABA) in R. pseudoacacia, while a shift from ABA-regulated to leaf-water-potential-driven stomatal closure was observed in A. fruticosa. After re-watering, the pre-dawn water potential recovered quickly, whereas stomatal conductance did not fully recover from drought in R. pseudoacacia, which affected the ability to tightly control transpiration post-drought. The dynamics of recovery from drought suggest that stomatal behavior post-drought may be restricted mainly by hydraulic factors, but non-hydraulic factors may also be involved in R. pseudoacacia.

  19. Preparation and characterization of cobalt-substituted anthrax lethal factor

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

    Saebel, Crystal E.; Carbone, Ryan; Dabous, John R.

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer Cobalt-substituted anthrax lethal factor (CoLF) is highly active. Black-Right-Pointing-Pointer CoLF can be prepared by bio-assimilation and direct exchange. Black-Right-Pointing-Pointer Lethal factor binds cobalt tightly. Black-Right-Pointing-Pointer The electronic spectrum of CoLF reveals penta-coordination. Black-Right-Pointing-Pointer Interaction of CoLF with thioglycolic acid follows a 2-step mechanism. -- Abstract: Anthrax lethal factor (LF) is a zinc-dependent endopeptidase involved in the cleavage of mitogen-activated protein kinase kinases near their N-termini. The current report concerns the preparation of cobalt-substituted LF (CoLF) and its characterization by electronic spectroscopy. Two strategies to produce CoLF were explored, including (i) a bio-assimilation approach involving the cultivation of LF-expressingmore » Bacillus megaterium cells in the presence of CoCl{sub 2}, and (ii) direct exchange by treatment of zinc-LF with CoCl{sub 2}. Independent of the method employed, the protein was found to contain one Co{sup 2+} per LF molecule, and was shown to be twice as active as its native zinc counterpart. The electronic spectrum of CoLF suggests the Co{sup 2+} ion to be five-coordinate, an observation similar to that reported for other Co{sup 2+}-substituted gluzincins, but distinct from that documented for the crystal structure of native LF. Furthermore, spectroscopic studies following the exposure of CoLF to thioglycolic acid (TGA) revealed a sequential mechanism of metal removal from LF, which likely involves the formation of an enzyme: Co{sup 2+}:TGA ternary complex prior to demetallation of the active site. CoLF reported herein constitutes the first spectroscopic probe of LF's active site, which may be utilized in future studies to gain further insight into the enzyme's mechanism and inhibitor interactions.« less

  20. Biosphere/atmosphere CO2 exchange in tundra ecosystems - Community characteristics and relationships with multispectral surface reflectance

    NASA Technical Reports Server (NTRS)

    Whiting, Gary J.; Bartlett, David S.; Fan, Song-Miao; Bakwin, Peter S.; Wofsy, Steven C.

    1992-01-01

    CO2 exchange rates were measured at selected tundra sites near Bethel, Alaska using portable, climate-controlled, instrumented enclosures. The empirically modeled exchange rate for a representative area of vegetated tundra was 1.2 +/- 1.2 g/sq m/d, compared to a tower-measured exchange over the same time period of 1.1 +.0- 1.2 g/sq m/d. Net exchange in response to varying light levels was compared to wet meadow and dry upland tundra, and to the net exchange measured by the micrometeoroidal tower technique. The multispectral reflectance properties of the sites were measured and related to exchange rates in order to provide a quantitative foundation for the use of satellite remote sensing to monitor biosphere/atmosphere CO2 exchange in the tundra biome.

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