Association of VAV2 and VAV3 polymorphisms with cardiovascular risk factors
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
Function of the nucleotide exchange activity of vav1 in T cell development and activation.
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.
Function of the Nucleotide Exchange Activity of Vav1 in T cell Development and Activation*
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
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
Vav1 GEF activity is required for T cell mediated allograft rejection
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
Vav1: Friend and Foe of Cancer.
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.
Vav1 GEF activity is required for T cell mediated allograft rejection.
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.
Molecular Basis for Failure of “Atypical” C1 Domain of Vav1 to Bind Diacylglycerol/Phorbol Ester*
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
Vav family exchange factors: an integrated regulatory and functional view
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
New insights into the Vav1 activation cycle in lymphocytes.
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.
VAV-1 acts in a single interneuron to inhibit motor circuit activity in Caenorhabditis elegans.
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.
Mechanism and function of Vav1 localisation in TCR signalling
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
Mechanism and function of Vav1 localisation in TCR signalling.
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.
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.
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
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.
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
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.
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
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
Phage display discovery of novel molecular targets in glioblastoma-initiating cells.
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.
Phage display discovery of novel molecular targets in glioblastoma-initiating cells
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
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.
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
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
Pak and Rac GTPases promote oncogenic KIT–induced neoplasms
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
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
A Protein Scaffold Coordinates SRC-Mediated JNK Activation in Response to Metabolic Stress.
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.
SLP-76 couples Syk to the osteoclast cytoskeleton.
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.
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
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.
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.
A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus
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
A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus.
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.
Probing the Tyrosine Phosphorylation State in Breast Cancer by Src Homology 2 Domain Binding
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
VAV1 and BAFF, via NFκB pathway, are genetic risk factors for myasthenia gravis
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
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
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.
Cooperative interactions at the SLP-76 complex are critical for actin polymerization.
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.
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
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.
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
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.
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
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.
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.
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.
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.
Targeting AR Variant-Coactivator Interactions to Exploit Prostate Cancer Vulnerabilities.
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.
CD94/NKG2A inhibits NK cell activation by disrupting the actin network at the immunological synapse.
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.
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
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
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.
An Effective Model of the Retinoic Acid Induced HL-60 Differentiation Program.
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.
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…
Assessment of the Activation of Rho Family GTP-Binding Proteins in Breast Cancer Cells and Specimens
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
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.
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
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.
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
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
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.
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.
Distinct mechanisms of a phosphotyrosyl peptide binding to two SH2 domains.
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.
Association Between Visceral Adiposity and Colorectal Polyps on CT Colonography
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
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
Developmentally induced Mll1 loss reveals defects in postnatal haematopoiesis.
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.
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
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).
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
PTP1B inhibitor promotes endothelial cell motility by activating the DOCK180/Rac1 pathway.
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.
Detection of protein-protein interactions by ribosome display and protein in situ immobilisation.
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.
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
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.
The AhR agonist VAF347 augments retinoic acid-induced differentiation in leukemia cells
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
The AhR agonist VAF347 augments retinoic acid-induced differentiation in leukemia cells.
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.
Using coordinate-based meta-analyses to explore structural imaging genetics.
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.
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...
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)
Dual role of SLP-76 in mediating T cell receptor-induced activation of phospholipase C-gamma1.
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.
Kinematic Modeling of Normal Voluntary Mandibular Opening and Closing Velocity-Initial Study.
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.
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
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...
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
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.
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.
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.
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
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.
Liquid transmission characteristics of padding bandages under pressure.
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.
Prioritising and planning of urban stormwater treatment in the Alna watercourse in Oslo.
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.
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...
Syk Mediates BCR- and CD40-Signaling Intergration during B Cell Activation
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
Retinoic Acid Therapy Resistance Progresses from Unilineage to Bilineage in HL-60 Leukemic Blasts
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
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.
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.
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.
Role of phosphoinositide 3-kinase regulatory isoforms in development and actin rearrangement.
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.
Performance assessment of a photonic radiative cooling system for office buildings
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
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
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
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.
Role of IKK-alpha in the EGFR Signaling Regulation
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
Impact of conditional deletion of the pro-apoptotic BCL-2 family member BIM in mice.
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.
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.
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.
Direct Digital Control of HVAC (Heating, Ventilating, and Air Conditioning).
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
Users Guide to Direct Digital Control of Heating, Ventilating, and Air Conditioning Equipment,
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
Direct Digital Control of HVAC (Heating, Ventilating, and Air Conditioning Equipment (User’s Guide)
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
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
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.
Validation Data for Mechanical System Algorithms Used in Building Energy Analysis Programs.
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
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
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.
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
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
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
Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans
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
Dynamic evaluation of airflow rates for a variable air volume system serving an open-plan office.
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.
CD25 and CD69 induction by α4β1 outside-in signalling requires TCR early signalling complex proteins
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
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.
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.
Quantitative Analysis of Guanine Nucleotide Exchange Factors (GEFs) as Enzymes
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
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...
Reliability Estimating Procedures for Electric and Thermochemical Propulsion Systems. Volume 1
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 ~ 4 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 ~ 0L 1-273 -- va VAv( 13 1-272 %J% ~ii 000 41
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
ERYTHROPOIETIC FACTOR PURIFICATION
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)
A critical role for the regulation of Syk from agglutination to aggregation in human platelets.
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.
Bypass Mechanisms of the Androgen Receptor Pathway in Therapy-Resistant Prostate Cancer Cell Models
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
An Early Model for Value and Sustainability in Health Information Exchanges: Qualitative Study.
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.
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…
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
A cross-country Exchange Market Pressure (EMP) dataset.
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.
An Early Model for Value and Sustainability in Health Information Exchanges: Qualitative Study
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
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.
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…
History of Sex Exchange in Women with a History of Incarceration
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
The structure of social exchange in self-help support groups: development of a measure.
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.
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
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.
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
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.
The Structure of Social Exchange in Self-Help Support Groups: Development of a Measure
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
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.
Geographical distribution of genetic diversity in Secale landrace and wild accessions.
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.
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…
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…
Gedanken densities and exact constraints in density functional theory.
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.
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
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.
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.
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.
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
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.
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.
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
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.
A prognostic mutation panel for predicting cancer recurrence in stages II and III colorectal cancer.
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.
Towards an Optimal Gradient-dependent Energy Functional of the PZ-SIC Form
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
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.
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
FACTORS AFFECTING AIR EXCHANGE IN TWO HOUSES
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...
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...
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.
Asparagine promotes cancer cell proliferation through use as an amino acid exchange factor
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
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.
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.
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.
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…
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…
Multidimensional generalized-ensemble algorithms for complex systems.
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.
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.
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...
Andrographolide derivatives inhibit guanine nucleotide exchange and abrogate oncogenic Ras function
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
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.
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.
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…
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.
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.
Modulation of the reaction cycle of the Na+:Ca2+, K+ exchanger.
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.
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
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.
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
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.
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.
Environment-Dependent Guest Exchange in Supramolecular Hosts
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
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...
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…
International Sexual Partnerships May Be Shaped by Sexual Histories and Socioeconomic Status.
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.
Landscape determinants of exchangeable calcium and magnesium in Ozark Highland forest soils
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...
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.
Factors influencing intentions to use social recommender systems: a social exchange perspective.
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.
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.
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
On factors influencing air-water gas exchange in emergent wetlands
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%.
Minimizing back exchange in the hydrogen exchange-mass spectrometry experiment.
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%.
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 %.
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
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.
Carbon dioxide exchange between an undisturbed old-growth temperate forest and the atmosphere
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...
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…
International Sexual Partnerships May Be Shaped by Sexual Histories and Socioeconomic Status
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
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 ...
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.
Success of Two-Stage Reimplantation in Patients Requiring an Interim Spacer Exchange.
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.
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.
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…
Theory of g-factor enhancement in narrow-gap quantum well heterostructures.
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.
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
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.
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…
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...
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.
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
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.
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.
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…
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
Characteristics associated with regional health information organization viability.
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.
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.
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.
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
Substrate water exchange in photosystem II depends on the peripheral proteins.
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.
Ionic Control of the Reversal Response of Cilia in Paramecium caudatum
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
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.
Federal Register 2010, 2011, 2012, 2013, 2014
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.
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
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
10 CFR 626.7 - Royalty transfer and exchange.
Code of Federal Regulations, 2011 CFR
2011-01-01
... DEPARTMENT OF ENERGY (CONTINUED) SALES REGULATION PROCEDURES FOR ACQUISITION OF PETROLEUM FOR THE STRATEGIC PETROLEUM RESERVE § 626.7 Royalty transfer and exchange. (a) General. DOE shall conduct royalty transfers... supply or refining capability, logistical problems for moving petroleum products, macroeconomic factors...
Financial Performance of Health Insurers: State-Run Versus Federal-Run Exchanges.
Hall, Mark A; McCue, Michael J; Palazzolo, Jennifer R
2018-06-01
Many insurers incurred financial losses in individual markets for health insurance during 2014, the first year of Affordable Care Act mandated changes. This analysis looks at key financial ratios of insurers to compare profitability in 2014 and 2013, identify factors driving financial performance, and contrast the financial performance of health insurers operating in state-run exchanges versus the federal exchange. Overall, the median loss of sampled insurers was -3.9%, no greater than their loss in 2013. Reduced administrative costs offset increases in medical losses. Insurers performed better in states with state-run exchanges than insurers in states using the federal exchange in 2014. Medical loss ratios are the underlying driver more than administrative costs in the difference in performance between states with federal versus state-run exchanges. Policy makers looking to improve the financial performance of the individual market should focus on features that differentiate the markets associated with state-run versus federal exchanges.
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.
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.
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.
Mavronicolas, Heather A; Laraque, Fabienne; Shankar, Arti; Campbell, Claudia
2017-05-01
Care coordination programmes are an important aspect of HIV management whose success depends largely on HIV primary care provider (PCP) and case manager collaboration. Factors influencing collaboration among HIV PCPs and case managers remain to be studied. The study objective was to test an existing theoretical model of interprofessional collaborative practice and determine which factors play the most important role in facilitating collaboration. A self-administered, anonymous mail survey was sent to HIV PCPs and case managers in New York City. An adapted survey instrument elicited information on demographic, contextual, and perceived social exchange (trustworthiness, role specification, and relationship initiation) characteristics. The dependent variable, perceived interprofessional practice, was constructed from a validated scale. A sequential block wise regression model specifying variable entry order examined the relative importance of each group of factors and of individual variables. The analysis showed that social exchange factors were the dominant drivers of collaboration. Relationship initiation was the most important predictor of interprofessional collaboration. Additional influential factors included organisational leadership support of collaboration, practice settings, and frequency of interprofessional meetings. Addressing factors influencing collaboration among providers will help public health programmes optimally design their structural, hiring, and training strategies to foster effective social exchanges and promote collaborative working relationships.
Gene-specific cell labeling using MiMIC transposons
Gnerer, Joshua P.; Venken, Koen J. T.; Dierick, Herman A.
2015-01-01
Binary expression systems such as GAL4/UAS, LexA/LexAop and QF/QUAS have greatly enhanced the power of Drosophila as a model organism by allowing spatio-temporal manipulation of gene function as well as cell and neural circuit function. Tissue-specific expression of these heterologous transcription factors relies on random transposon integration near enhancers or promoters that drive the binary transcription factor embedded in the transposon. Alternatively, gene-specific promoter elements are directly fused to the binary factor within the transposon followed by random or site-specific integration. However, such insertions do not consistently recapitulate endogenous expression. We used Minos-Mediated Integration Cassette (MiMIC) transposons to convert host loci into reliable gene-specific binary effectors. MiMIC transposons allow recombinase-mediated cassette exchange to modify the transposon content. We developed novel exchange cassettes to convert coding intronic MiMIC insertions into gene-specific binary factor protein-traps. In addition, we expanded the set of binary factor exchange cassettes available for non-coding intronic MiMIC insertions. We show that binary factor conversions of different insertions in the same locus have indistinguishable expression patterns, suggesting that they reliably reflect endogenous gene expression. We show the efficacy and broad applicability of these new tools by dissecting the cellular expression patterns of the Drosophila serotonin receptor gene family. PMID:25712101
Wu, Hsiang-Ling; Tai, Ying-Hsuan; Wei, Ling-Fang; Cheng, Hung-Wei; Ho, Chiu-Ming
2017-10-01
There is no current consensus on which lumen an airway exchange catheter (AEC) should be passed through in double-lumen endotracheal tube (DLT) to exchange for a single-lumen endotracheal tube (SLT) after thoracic surgery. We report an unusual case to provide possible solution on this issue. A 71-year-old man with lung adenocarcinoma had an event of a broken exchange catheter used during a DLT replacement with a SLT, after a video-assisted thoracic surgery. The exchange catheter was impinged at the distal tracheal lumen and snapped during manipulation. All three segments of the catheter were retrieved without further airway compromises. Placement of airway tube exchanger into the tracheal lumen of double-lumen tube is a potential contributing factor of the unusual complication. We suggest an exchange catheter be inserted into the bronchial lumen in optimal depth with the adjunct of video laryngoscope, as the safe method for double-lumen tube exchange.
Chen, Shyi-Ming; Manalu, Gandhi Maruli Tua; Pan, Jeng-Shyang; Liu, Hsiang-Chuan
2013-06-01
In this paper, we present a new method for fuzzy forecasting based on two-factors second-order fuzzy-trend logical relationship groups and particle swarm optimization (PSO) techniques. First, we fuzzify the historical training data of the main factor and the secondary factor, respectively, to form two-factors second-order fuzzy logical relationships. Then, we group the two-factors second-order fuzzy logical relationships into two-factors second-order fuzzy-trend logical relationship groups. Then, we obtain the optimal weighting vector for each fuzzy-trend logical relationship group by using PSO techniques to perform the forecasting. We also apply the proposed method to forecast the Taiwan Stock Exchange Capitalization Weighted Stock Index and the NTD/USD exchange rates. The experimental results show that the proposed method gets better forecasting performance than the existing methods.
Microtube strip heat exchanger
NASA Astrophysics Data System (ADS)
Doty, F. D.
1991-10-01
This progress report is for the September-October 1991 quarter. 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.
Koya, Kushwanth; Anderson, Jane; Sice, Petia
2017-12-01
To report a potential knowledge exchange between nursing studies and the results obtained from a study conducted into the attributes of embodied leadership. Leadership theories have been applied to evaluate, improve, and train nursing practitioners in several previous studies. However, leadership research has entered a new phase where the focus is to produce sustainable leaders through authenticity and compassion, the same two characteristics identified as being of most success in emergent nursing practice. There are few studies that have indicated a knowledge exchange between the latest developments in leadership studies and nursing. An exploratory and qualitative study. Between February 2012 - July 2012, a focused sample of 14 medical care professionals was interviewed across a chain of hospitals. The aim was to evaluate embodied leadership characteristics and understand the factors that contribute to the manifestation of these characteristics. The transcribed interviews were analysed using thematic analysis. Several factors that contribute to the characteristics of embodied leadership have been identified in the interviews and in subsequent literature searches on the characteristics and contributing factors found to be associated with nursing research. These could prompt a knowledge exchange. The results suggest common ground between nursing and contemporary leadership research in the exposition of behaviours; namely, being non-judgmental, listening actively, reflective practice and embracing uncertainty. Several implications can therefore be expected through the exchange of knowledge resulting from collaboration between researchers in the two disciplines. © 2017 John Wiley & Sons Ltd.
1976-11-11
exchange. The basis for this choice was derived from several factors . One was a timing analysis that was made for certain basic time-critical software...randidate 6jrstem designs were developed and _*xamined with respect to L their capability to demonstrate the workability of the basic concept and for factors ...algorithm recuires a bit time completion, while SOF production allows byte timing and the involved = SOF correlation procedure may be perfor-med during
NASA Technical Reports Server (NTRS)
Kassemi, M.; Naraghi, M. H. N.
1993-01-01
A new numerical method is presented for the analysis of combined natural convection and radiation heat transfer with applications in many engineering situations such as materials processing, combustion and fire research. Because of the recent interest in the low gravity environment of space, attention is devoted to both 1-g and low-g applications. The two-dimensional mathematical model is represented by a set of coupled nonlinear integro-partial differential equations. Radiative exchange is formulated using the Discrete Exchange Factor method (DEF). This method considers point to point exchange and provides accurate results over a wide range of radiation parameters. Numerical results show that radiation significantly influences the flow and heat transfer in both low-g and 1-g applications. In the low-g environment, convection is weak, and radiation can easily become the dominant heat transfer mode. It is also shown that volumetric heating by radiation gives rise to an intricate cell pattern in the top heated enclosure.
Rudolph, Abby E; Linton, Sabriya; Dyer, Typhanye Penniman; Latkin, Carl
2012-01-01
The “HIV risk environment” has been characterized as a dynamic interplay between structural and network factors. However, most HIV prevention research has not examined the independent and combined impact of network and structural factors. We aimed to identify individual, network, and neighborhood correlates of exchange sex (≥1 exchange sex partner, past 90 days) among female non-injection drug users (NIDUs). We used baseline data from 417 NIDUs enrolled in a randomized HIV prevention trial in Baltimore (2005–2007). Surveys ascertained demographic variables, drug/sex risk behaviors, neighborhood perceptions, and social/sexual network characteristics. Correlates of exchange sex were identified with descriptive statistics and log-binomial regression. Our findings suggest that sex and drug relationships among female NIDUs are interlinked and may be difficult to modify without altering social norms. Strengthening ties that provide social support but not drug support and reducing ties that provide both drug and social support may facilitate reductions in individual-level HIV-risk behaviors. PMID:22983502
Using register data to deduce patterns of social exchange.
Jansson, Fredrik
2017-07-01
This paper presents a novel method for deducting propensities for social exchange between individuals based on the choices they make, and based on factors such as country of origin, sex, school grades and socioeconomic background. The objective here is to disentangle the effect of social ties from the other factors, in order to find patterns of social exchange. This is done through a control-treatment design on analysing available data, where the 'treatment' is similarity of choices between socially connected individuals, and the control is similarity of choices between non-connected individuals. Structural dependencies are controlled for and effects from different classes are pooled through a mix of methods from network and meta-analysis. The method is demonstrated and tested on Swedish register data on students at upper secondary school. The results show that having similar grades is a predictor of social exchange. Also, previous results from Norwegian data are replicated, showing that students cluster based on country of origin.
Solar photoionization as a loss mechanism of neutral interstellar hydrogen in interplanetary space
NASA Technical Reports Server (NTRS)
Ogawa, H. S.; Wu, C. Y. Robert; Gangopadhyay, P.; Judge, D. L.
1995-01-01
Two primary loss mechanisms of interstellar neutral hydrogen in interplanetary space are resonance charge exchange ionization with solar wind protons and photoionization by solar EUV radiation. The later process has often been neglected since the average photoionization rate has been estimated to be as much as 5 to 10 times smaller than the charge exchange rate. These factors are based on ionization rates from early measurements of solar EUV and solar wind fluxes. Using revised solar EUV and solar wind fluxes measured near the ecliptic plane we have reinvestigated the ionization rates of interplanetary hydrogen. The result of our analysis indicates that indeed the photoionization rate during solar minimum can be smaller than charge exchange by a factor of 5; however, during solar maximum conditions when solar EUV fluxes are high, and solar wind fluxes are low, photoionization can be over 60% of the charge exchange rate at Earth orbit. To obtain an accurate estimate of the importance of photoionization relative to charge exchange, we have included photoionization from both the ground and metastable states of hydrogen. We find, however, that the photoionization from the metastable state does not contribute significantly to the overall photoionization rate.
A conceptual model of Verbal Exchange Health Literacy
Harrington, Kathleen F.; Valerio, Melissa A.
2014-01-01
Objective To address a gap in understanding of verbal exchange (oral and aural) health literacy by describing the systematic development of a verbal exchange health literacy (VEHL) definition and model which hypothesizes the role of VEHL in health outcomes. Methods Current health literacy and communication literature was systematically reviewed and combined with qualitative patient and provider data that were analyzed using a grounded theory approach. Results Analyses of current literature and formative data indicated the importance of verbal exchange in the clinical setting and revealed various factors associated with the patient-provider relationship and their characteristics that influence decision making and health behaviors. VEHL is defined as the ability to speak and listen that facilitates exchanging, understanding, and interpreting of health information for health-decision making, disease management and navigation of the healthcare system. A model depiction of mediating and influenced factors is presented. Conclusion A definition and model of VEHL is a step towards addressing a gap in health literacy knowledge and provides a foundation for examining the influence of VEHL on health outcomes. Practice Implications VEHL is an extension of current descriptions of health literacy and has implications for patient-provider communication and health decision making. PMID:24291145
Walters, Suzan M; Rivera, Alexis V; Reilly, Kathleen H; Anderson, Bridget J; Bolden, Barbara; Wogayehu, Afework; Neaigus, Alan; Braunstein, Sarah
2018-02-21
Exchanging sex for money or drugs is known to increase risk for HIV among persons who inject drugs (PWID). To better understand determinants of exchange sex among PWID we examined factors associated with exchange sex in the New York metropolitan area-defined as New York City (NYC), NY; Newark, NJ; and Long Island, NY-using data from the 2012 National HIV Behavioral Surveillance system cycle on injection drug use. Of the 1160 PWID in this analysis, 24% reported exchange sex, with differences in gender and sexual identity by location. In multivariable analysis gay/bisexual men, heterosexual women, and lesbian, gay, or bisexual (LGB) women were more likely to exchange sex compared to heterosexual men. Exchange sex was also associated with race/ethnicity, homelessness, incarceration, location, and non-injection crack and cocaine use. We find that heterosexual women and LGB women who injected drugs residing in Newark were more likely to report exchange sex compared to NYC. This study highlights how local conditions impact exchange sex.
Barber, Jonathan L; Thomas, Gareth O; Kerstiens, Gerhard; Jones, Kevin C
2004-01-01
Air-vegetation exchange of POPs is an important process controlling the entry of POPs into terrestrial food chains, and may also have a significant effect on the global movement of these compounds. Many factors affect the air-vegetation transfer including: the physicochemical properties of the compounds of interest; environmental factors such as temperature, wind speed, humidity and light conditions; and plant characteristics such as functional type, leaf surface area, cuticular structure, and leaf longevity. The purpose of this review is to quantify the effects these differences might have on air/plant exchange of POPs, and to point out the major gaps in the knowledge of this subject that require further research. Uptake mechanisms are complicated, with the role of each factor in controlling partitioning, fate and behaviour process still not fully understood. Consequently, current models of air-vegetation exchange do not incorporate variability in these factors, with the exception of temperature. These models instead rely on using average values for a number of environmental factors (e.g. plant lipid content, surface area), ignoring the large variations in these values. The available models suggest that boundary layer conductance is of key importance in the uptake of POPs, although large uncertainties in the cuticular pathway prevents confirmation of this with any degree of certainty, and experimental data seems to show plant-side resistance to be important. Models are usually based on the assumption that POP uptake occurs through the lipophilic cuticle which covers aerial surfaces of plants. However, some authors have recently attached greater importance to the stomatal route of entry into the leaf for gas phase compounds. There is a need for greater mechanistic understanding of air-plant exchange and the 'scaling' of factors affecting it. The review also suggests a number of key variables that researchers should measure in their experiments to allow comparisons to be made between studies in order to improve our understanding of what causes any differences in measured data between sites.
Critical Success Factors in a TRIDEM Exchange
ERIC Educational Resources Information Center
Hauck, Mirjam
2007-01-01
Computer-mediated-communication (CMC) tools allowing learners to be in contact with native speakers of their target language in other locations are becoming increasingly flexible, often combining different modes of communication in a single web- and internet-based environment. The literature on telecollaborative exchanges reveals, however, that…
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
DNA Strand Exchange and RecA Homologs in Meiosis
Brown, M. Scott; Bishop, Douglas K.
2015-01-01
Homology search and DNA strand–exchange reactions are central to homologous recombination in meiosis. During meiosis, these processes are regulated such that the probability of choosing a homolog chromatid as recombination partner is enhanced relative to that of choosing a sister chromatid. This regulatory process occurs as homologous chromosomes pair in preparation for assembly of the synaptonemal complex. Two strand–exchange proteins, Rad51 and Dmc1, cooperate in regulated homology search and strand exchange in most organisms. Here, we summarize studies on the properties of these two proteins and their accessory factors. In addition, we review current models for the assembly of meiotic strand–exchange complexes and the possible mechanisms through which the interhomolog bias of recombination partner choice is achieved. PMID:25475089
Lee, Eun Kyung; Ji, Eun Joo
2018-03-01
This study aimed to identify the moderating effect of leader-member exchange in the relationship between emotional labor and burnout among clinical nurses. A cross-sectional study design was used. Participants were 170 registered nurses working in the general wards of two tertiary hospitals in Seoul, South Korea. The data were collected through convenience sampling using self-report measures of emotional labor, leader-member exchange, and burnout. The data were analyzed using hierarchical multiple regression. Data from 165 nurses (response rate 97.1%) were utilized. The mean age of the participants was 28.42 years (SD = 5.43), and their mean years of experience as a nurse was 5.80 years (SD = 5.51). First, emotional modulation efforts in their profession and patient-focused emotional suppression (both factors of emotional labor) showed significant negative and positive effects, respectively, on burnout. Second, leader-member exchange showed a significant negative effect on burnout. Finally, when controlling for marital status and work unit, leader-member exchange had a moderating effect on the relationship between burnout and the two aforementioned factors of emotional labor. The results of this study suggest that as a way to reduce burnout, institutional support to enhance leader-member exchange should be established for nurses who are experiencing emotional labor. Copyright © 2018. Published by Elsevier B.V.
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
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.
Lippé, Roger; Miaczynska, Marta; Rybin, Vladimir; Runge, Anja; Zerial, Marino
2001-01-01
Rab GTPases are central elements of the vesicular transport machinery. An emerging view is that downstream effectors of these GTPases are multiprotein complexes that include nucleotide exchange factors to ensure coupling between GTPase activation and effector function. We have previously shown that Rab5, which regulates various steps of transport along the early endocytic pathway, is activated by a complex consisting of Rabex-5, a Rab5 nucleotide exchange factor, and the effector Rabaptin-5. We postulated that the physical association of these two proteins is necessary for their activity in Rab5-dependent endocytic membrane transport. To evaluate the functional implications of such complex formation, we have reconstituted it with the use of recombinant proteins and characterized its properties. First, we show that Rabaptin-5 increases the exchange activity of Rabex-5 on Rab5. Second, Rab5-dependent recruitment of Rabaptin-5 to early endosomes is completely dependent on its physical association with Rabex-5. Third, complex formation between Rabaptin-5 and Rabex-5 is essential for early endosome homotypic fusion. These results reveal a functional synergy between Rabaptin-5 and Rabex-5 in the complex and have implications for the function of analogous complexes for Rab and Rho GTPases. PMID:11452015
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.
σ and κ mesons as broad dynamical resonances in one-meson-exchange model
NASA Astrophysics Data System (ADS)
Hong Xiem, Ngo Thi; Shinmura, Shoji
2014-09-01
The existences of broad scalar σ (600) and κ (700) mesons have been discussed intensively in the experimental and theoretical studies on ππ and πK scatterings. By using chiral perturbation model, J. Oller, A. Gómez and J. R. Peláez confirmed the existence of these mesons as dynamical resonances. In meson-exchange models, their existence has not been established yet. In this talk, using the quasi-potential of meson-exchange model and Lippmann-Schwinger equation, we determine the T and S-matrices, from which we could find the positions of poles in physical amplitudes in the complex E-plane. With the full treatment of meson-meson interactions (ππ - πK - πη - ηη and πK - ηK) , for the first time, the existence of the scalar σ (600) and κ (700) mesons are confirmed in one-meson-exchange model. There are two kinds of form factors in our model: the monopole and the Gaussian. Our recent results show that the poles σ and κ appear at around 410 - i 540 MeV and 650 - i 20 MeV for monopole form factors, respectively. For Gaussian form factors, the poles σ and κ, respectively, are at 360 - i 510 MeV and 649 - i 190 MeV.
Dechawatanapaisal, Decha
2018-06-01
The aim of this study was to examine the influence of three factors on turnover intention: leader-member exchange quality, organizational identification and job embeddedness. This area of inquiry has not been fully investigated in the literature. Employee turnover, particularly of professionals, becomes a very challenging issue. It continually affects organizations in terms of resourcing and developmental costs, manpower instability, day-to-day operations, perception of quality care and efficiency. Therefore, employees' working attitude and behaviour have drawn increasing attention for further research to determine which factors keep them with their employer. A cross-sectional survey was conducted with self-report questionnaires. Data were collected from 1,966 nurses from sixteen private general hospitals in Thailand during February-June 2016. Hypotheses were tested and analysed by means of a confirmatory factor analysis, structural equation modelling and a bootstrapping procedure. The results revealed the direct relationship between leader-member exchange quality and job embeddedness. Organizational identification played an intermediary role that partially mediated the relationship between leader-member exchange quality on job embeddedness. Analysis also provided support for the mediating effect of organizational identification and turnover intention through job embeddedness. This study extends the job embeddedness theory and gains understanding of the antecedent factors that directly and indirectly cause employees to become embedded and lead to predict turnover intention. The findings are pertinent, as few studies have investigated such relationships. The implications provide insights into how organizations can better retain their workforce. © 2018 John Wiley & Sons Ltd.
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.
Leader Influences on Training Effectiveness: Motivation and Outcome Expectation Processes
ERIC Educational Resources Information Center
Scaduto, Anne; Lindsay, Douglas; Chiaburu, Dan S.
2008-01-01
Training effectiveness is a function of trainee characteristics, training design and contextual factors. Social exchanges in the work environment have received less attention compared with other training effectiveness predictors. We focus on the extent to which leaders (through their relationships and exchanges with followers) influence skill…
Epidemiological studies frequently use central site concentrations as surrogates of exposure to air pollutants. Variability in air pollutant infiltration due to differential air exchange rates (AERs) is potentially a major factor affecting the relationship between central site c...
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
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.
Lifelong haematopoiesis is established by hundreds of precursors throughout mammalian ontogeny.
Ganuza, Miguel; Hall, Trent; Finkelstein, David; Chabot, Ashley; Kang, Guolian; McKinney-Freeman, Shannon
2017-10-01
Current dogma asserts that mammalian lifelong blood production is established by a small number of blood progenitors. However, this model is based on assays that require the disruption, transplantation and/or culture of embryonic tissues. Here, we used the sample-to-sample variance of a multicoloured lineage trace reporter to assess the frequency of emerging lifelong blood progenitors while avoiding the disruption, culture or transplantation of embryos. We find that approximately 719 Flk1 + mesodermal precursors, 633 VE-cadherin + endothelial precursors and 545 Vav1 + nascent blood stem and progenitor cells emerge to establish the haematopoietic system at embryonic days (E)7-E8.5, E8.5-E11.5 and E11.5-E14.5, respectively. We also determined that the spatio-temporal recruitment of endothelial blood precursors begins at E8.5 and ends by E10.5, and that many c-Kit + clusters of newly specified blood progenitors in the aorta are polyclonal in origin. Our work illuminates the dynamics of the developing mammalian blood system during homeostasis.
Kiryluk, Krzysztof; Li, Yifu; Scolari, Francesco; Sanna-Cherchi, Simone; Choi, Murim; Verbitsky, Miguel; Fasel, David; Lata, Sneh; Prakash, Sindhuri; Shapiro, Samantha; Fischman, Clara; Snyder, Holly J.; Appel, Gerald; Izzi, Claudia; Viola, Battista Fabio; Dallera, Nadia; Vecchio, Lucia Del; Barlassina, Cristina; Salvi, Erika; Bertinetto, Francesca Eleonora; Amoroso, Antonio; Savoldi, Silvana; Rocchietti, Marcella; Amore, Alessandro; Peruzzi, Licia; Coppo, Rosanna; Salvadori, Maurizio; Ravani, Pietro; Magistroni, Riccardo; Ghiggeri, Gian Marco; Caridi, Gianluca; Bodria, Monica; Lugani, Francesca; Allegri, Landino; Delsante, Marco; Maiorana, Mariarosa; Magnano, Andrea; Frasca, Giovanni; Boer, Emanuela; Boscutti, Giuliano; Ponticelli, Claudio; Mignani, Renzo; Marcantoni, Carmelita; Di Landro, Domenico; Santoro, Domenico; Pani, Antonello; Polci, Rosaria; Feriozzi, Sandro; Chicca, Silvana; Galliani, Marco; Gigante, Maddalena; Gesualdo, Loreto; Zamboli, Pasquale; Maixnerová, Dita; Tesar, Vladimir; Eitner, Frank; Rauen, Thomas; Floege, Jürgen; Kovacs, Tibor; Nagy, Judit; Mucha, Krzysztof; Pączek, Leszek; Zaniew, Marcin; Mizerska-Wasiak, Małgorzata; Roszkowska-Blaim, Maria; Pawlaczyk, Krzysztof; Gale, Daniel; Barratt, Jonathan; Thibaudin, Lise; Berthoux, Francois; Canaud, Guillaume; Boland, Anne; Metzger, Marie; Panzer, Ulf; Suzuki, Hitoshi; Goto, Shin; Narita, Ichiei; Caliskan, Yasar; Xie, Jingyuan; Hou, Ping; Chen, Nan; Zhang, Hong; Wyatt, Robert J.; Novak, Jan; Julian, Bruce A.; Feehally, John; Stengel, Benedicte; Cusi, Daniele; Lifton, Richard P.; Gharavi, Ali G.
2014-01-01
We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six novel genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geo-spatial distribution of risk alleles is highly suggestive of multi-locus adaptation and the genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN. PMID:25305756
Fluorescein angiography and retinal vascular development in premature infants.
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.
Gas exchange rates across the sediment-water and air-water interfaces in south San Francisco Bay
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.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Amor,J.; Swails, J.; Zhu, X.
2005-01-01
The Legionella pneumophila protein RalF is secreted into host cytosol via the Dot/Icm type IV transporter where it acts to recruit ADP-ribosylation factor (Arf) to pathogen-containing phagosomes in the establishment of a replicative organelle. The presence in RalF of the Sec7 domain, present in all Arf guanine nucleotide exchange factors, has suggested that recruitment of Arf is an early step in pathogenesis. We have determined the crystal structure of RalF and of the isolated Sec7 domain and found that RalF is made up of two domains. The Sec7 domain is homologous to mammalian Sec7 domains. The C-terminal domain forms amore » cap over the active site in the Sec7 domain and contains a conserved folding motif, previously observed in adaptor subunits of vesicle coat complexes. The importance of the capping domain and of the glutamate in the 'glutamic finger,' conserved in all Sec7 domains, to RalF functions was examined using three different assays. These data highlight the functional importance of domains other than Sec7 in Arf guanine nucleotide exchange factors to biological activities and suggest novel mechanisms of regulation of those activities.« less
Energy saving technologies of the decentralized ventilation of buildings
NASA Astrophysics Data System (ADS)
Mansurov, R. Sh; Rafalskaya, T. A.
2017-11-01
The growing aspiration to energy saving and efficiency of energy leads to necessity to build tight enough buildings. As a result of this the quantity of infiltration air appears insufficient for realization of necessary air exchange in. One of decisions of the given problem is development and application for ventilation of premises of the decentralized forced-air and exhaust systems (DFAES) with recuperative or regenerative heat-exchangers. For an estimation of efficiency of DFAES following basic parameters have been certain: factor of energy saving; factor of efficiency of energy; factor of a heat transfer; factor of an effective utilization of a surface of heat exchange. Were estimated temperature of forced air; actual speed of an air jet on an entrance in a served zone; actual noise level; the charge of external air. Tests of DFAES were spent in natural conditions at which DFAES influenced all set of factors both an external climate, and an internal microclimate of a premise, and also the arrangement on a wind side or behind wind side of a building, influence of surrounding building, fluctuation of temperature of external air is considered. Proceeding from results and the analysis of the lead researches recommendations have been developed for development and manufacture of new sample of DFAES.
Contribution made by parabiosis to the understanding of energy balance regulation
Harris, Ruth
2013-01-01
Parabiosis is a chronic preparation that allows exchange of whole blood between two animals. It has been used extensively to test for involvement of circulating factors in feedback regulation of physiological systems. The total blood volume of each animal exchanges approximately ten times each day, therefore, factors that are rapidly cleared from the circulation do not reach equilibrium across the parabiotic union whereas those with a long half-life achieve a uniform concentration and bioactivity in both members of a pair. Involvement of a circulating factor in the regulation of energy balance was first demonstrated when one member of a pair of parabiosed rats became hyperphagic and obese following bilateral lesioning of the ventromedial hypothalamus. The non-lesioned partner stopped eating, lost a large amount of weight and appeared to be responding to a circulating “satiety” factor released by the obese rat. These results were confirmed using different techniques to induce obesity in one member of a pair. Studies with phenotypically similar ob/ob obese and db/db diabetic mice indicated that the obese mouse lacked a circulating signal that regulated energy balance, whereas the diabetic mouse appeared insensitive to such a signal. Positional cloning studies identified leptin as the circulating factor and subsequent parabiosis studies confirmed leptin’s ability to exchange effectively between parabionts. These studies also suggest the presence of additional unidentified factors that influence body composition. PMID:23470554
Gene-specific cell labeling using MiMIC transposons.
Gnerer, Joshua P; Venken, Koen J T; Dierick, Herman A
2015-04-30
Binary expression systems such as GAL4/UAS, LexA/LexAop and QF/QUAS have greatly enhanced the power of Drosophila as a model organism by allowing spatio-temporal manipulation of gene function as well as cell and neural circuit function. Tissue-specific expression of these heterologous transcription factors relies on random transposon integration near enhancers or promoters that drive the binary transcription factor embedded in the transposon. Alternatively, gene-specific promoter elements are directly fused to the binary factor within the transposon followed by random or site-specific integration. However, such insertions do not consistently recapitulate endogenous expression. We used Minos-Mediated Integration Cassette (MiMIC) transposons to convert host loci into reliable gene-specific binary effectors. MiMIC transposons allow recombinase-mediated cassette exchange to modify the transposon content. We developed novel exchange cassettes to convert coding intronic MiMIC insertions into gene-specific binary factor protein-traps. In addition, we expanded the set of binary factor exchange cassettes available for non-coding intronic MiMIC insertions. We show that binary factor conversions of different insertions in the same locus have indistinguishable expression patterns, suggesting that they reliably reflect endogenous gene expression. We show the efficacy and broad applicability of these new tools by dissecting the cellular expression patterns of the Drosophila serotonin receptor gene family. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.
Exchange-mediated contrast in CEST and spin-lock imaging.
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.
Exchange-Mediated Contrast in CEST and Spin-Lock Imaging
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
Performance optimization of a miniature Joule-Thomson cryocooler using numerical model
NASA Astrophysics Data System (ADS)
Ardhapurkar, P. M.; Atrey, M. D.
2014-09-01
The performance of a miniature Joule-Thomson cryocooler depends on the effectiveness of the heat exchanger. The heat exchanger used in such cryocooler is Hampson-type recuperative heat exchanger. The design of the efficient heat exchanger is crucial for the optimum performance of the cryocooler. In the present work, the heat exchanger is numerically simulated for the steady state conditions and the results are validated against the experimental data available from the literature. The area correction factor is identified for the calculation of effective heat transfer area which takes into account the effect of helical geometry. In order to get an optimum performance of the cryocoolers, operating parameters like mass flow rate, pressure and design parameters like heat exchanger length, helical diameter of coil, fin dimensions, fin density have to be identified. The present work systematically addresses this aspect of design for miniature J-T cryocooler.
Modeling Philippine Stock Exchange Composite Index Using Time Series Analysis
NASA Astrophysics Data System (ADS)
Gayo, W. S.; Urrutia, J. D.; Temple, J. M. F.; Sandoval, J. R. D.; Sanglay, J. E. A.
2015-06-01
This study was conducted to develop a time series model of the Philippine Stock Exchange Composite Index and its volatility using the finite mixture of ARIMA model with conditional variance equations such as ARCH, GARCH, EG ARCH, TARCH and PARCH models. Also, the study aimed to find out the reason behind the behaviorof PSEi, that is, which of the economic variables - Consumer Price Index, crude oil price, foreign exchange rate, gold price, interest rate, money supply, price-earnings ratio, Producers’ Price Index and terms of trade - can be used in projecting future values of PSEi and this was examined using Granger Causality Test. The findings showed that the best time series model for Philippine Stock Exchange Composite index is ARIMA(1,1,5) - ARCH(1). Also, Consumer Price Index, crude oil price and foreign exchange rate are factors concluded to Granger cause Philippine Stock Exchange Composite Index.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hammond, Glenn Edward; Bao, J; Huang, M
Hyporheic exchange is a critical mechanism shaping hydrological and biogeochemical processes along a river corridor. Recent studies on quantifying the hyporheic exchange were mostly limited to local scales due to field inaccessibility, computational demand, and complexity of geomorphology and subsurface geology. Surface flow conditions and subsurface physical properties are well known factors on modulating the hyporheic exchange, but quantitative understanding of their impacts on the strength and direction of hyporheic exchanges at reach scales is absent. In this study, a high resolution computational fluid dynamics (CFD) model that couples surface and subsurface flow and transport is employed to simulate hyporheicmore » exchanges in a 7-km long reach along the main-stem of the Columbia River. Assuming that the hyporheic exchange does not affect surface water flow conditions due to its negligible magnitude compared to the volume and velocity of river water, we developed a one-way coupled surface and subsurface water flow model using the commercial CFD software STAR-CCM+. The model integrates the Reynolds-averaged Navier-Stokes (RANS) equation solver with a realizable κ-ε two-layer turbulence model, a two-layer all y + wall treatment, and the volume of fluid (VOF) method, and is used to simulate hyporheic exchanges by tracking the free water-air interface as well as flow in the river and the subsurface porous media. The model is validated against measurements from acoustic Doppler current profiler (ADCP) in the stream water and hyporheic fluxes derived from a set of temperature profilers installed across the riverbed. The validated model is then employed to systematically investigate how hyporheic exchanges are influenced by surface water fluid dynamics strongly regulated by upstream dam operations, as well as subsurface structures (e.g. thickness of riverbed and subsurface formation layers) and hydrogeological properties (e.g. permeability). The results suggest that the thickness of riverbed alluvium layer is the dominant factor for reach-scale hyporheic exchanges, followed by the alluvium permeability, the depth of the underlying impermeable layer, and the assumption of hydrostatic pressure.« less
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
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.
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
Universal model for water costs of gas exchange by animals and plants
Woods, H. Arthur; Smith, Jennifer N.
2010-01-01
For terrestrial animals and plants, a fundamental cost of living is water vapor lost to the atmosphere during exchange of metabolic gases. Here, by bringing together previously developed models for specific taxa, we integrate properties common to all terrestrial gas exchangers into a universal model of water loss. The model predicts that water loss scales to gas exchange with an exponent of 1 and that the amount of water lost per unit of gas exchanged depends on several factors: the surface temperature of the respiratory system near the outside of the organism, the gas consumed (oxygen or carbon dioxide), the steepness of the gradients for gas and vapor, and the transport mode (convective or diffusive). Model predictions were largely confirmed by data on 202 species in five taxa—insects, birds, bird eggs, mammals, and plants—spanning nine orders of magnitude in rate of gas exchange. Discrepancies between model predictions and data seemed to arise from biologically interesting violations of model assumptions, which emphasizes how poorly we understand gas exchange in some taxa. The universal model provides a unified conceptual framework for analyzing exchange-associated water losses across taxa with radically different metabolic and exchange systems. PMID:20404161
Universal model for water costs of gas exchange by animals and plants.
Woods, H Arthur; Smith, Jennifer N
2010-05-04
For terrestrial animals and plants, a fundamental cost of living is water vapor lost to the atmosphere during exchange of metabolic gases. Here, by bringing together previously developed models for specific taxa, we integrate properties common to all terrestrial gas exchangers into a universal model of water loss. The model predicts that water loss scales to gas exchange with an exponent of 1 and that the amount of water lost per unit of gas exchanged depends on several factors: the surface temperature of the respiratory system near the outside of the organism, the gas consumed (oxygen or carbon dioxide), the steepness of the gradients for gas and vapor, and the transport mode (convective or diffusive). Model predictions were largely confirmed by data on 202 species in five taxa--insects, birds, bird eggs, mammals, and plants--spanning nine orders of magnitude in rate of gas exchange. Discrepancies between model predictions and data seemed to arise from biologically interesting violations of model assumptions, which emphasizes how poorly we understand gas exchange in some taxa. The universal model provides a unified conceptual framework for analyzing exchange-associated water losses across taxa with radically different metabolic and exchange systems.
Impact of exchanges and client-therapist alliance in online-text psychotherapy.
Reynolds, D'Arcy J; Stiles, William B; Bailer, A John; Hughes, Michael R
2013-05-01
The impact of exchanges and client-therapist alliance of online therapy text exchanges were compared to previously published results in face-to-face therapy, and the moderating effects of four participant factors found significant in previously published face-to-face studies were investigated using statistical mixed-effect modeling analytic techniques. Therapists (N=30) and clients (N=30) engaged in online therapy were recruited from private practitioner sites, e-clinics, online counseling centers, and mental-health-related discussion boards. In a naturalistic design, they each visited an online site weekly and completed the standard impact and alliance questionnaires for at least 6 weeks. Results indicated that the impact of exchanges and client-therapist alliance in text therapy was similar to, but in some respects more positive than, previous evaluations of face-to-face therapy. The significance of participant factors previously found to influence impact and alliance in face-to-face therapy (client symptom severity, social support, therapist theoretical orientation, and therapist experience) was not replicated, except that therapists with the more symptomatic clients rated their text exchanges as less smooth and comfortable. Although its small size and naturalistic design impose limitations on sensitivity and generalizability, this study provides some insights into treatment impact and the alliance in online therapy.
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.
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.
USDA-ARS?s Scientific Manuscript database
It is well known that cotton fibers readily exchange moisture content with their surrounding atmosphere. As moisture exchange progresses, several physical properties of the fiber are significantly affected. In this study, the effects of relative humidity (RH), a factor that affects the atmospheric m...
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...
A Fruitful Exchange/Conflict: Engineers and Mathematicians in Early Modern Italy
ERIC Educational Resources Information Center
Maffioli, Cesare S.
2013-01-01
Exchanges of learning and controversies between engineers and mathematicians were important factors in the development of early modern science. This theme is discussed by focusing, first, on architectural and mathematical dynamism in mid 16th-century Milan. While some engineers-architects referred to Euclid and Vitruvius for improving their…
Structural Dynamics Control Allosteric Activation of Cytohesin Family Arf GTPase Exchange Factors
DOE Office of Scientific and Technical Information (OSTI.GOV)
Malaby, Andrew W.; Das, Sanchaita; Chakravarthy, Srinivas
Membrane dynamic processes including vesicle biogenesis depend on Arf guanosine triphosphatase (GTPase) activation by guanine nucleotide exchange factors (GEFs) containing a catalytic Sec7 domain and a membrane-targeting module such as a pleckstrin homology (PH) domain. The catalytic output of cytohesin family Arf GEFs is controlled by autoinhibitory interactions that impede accessibility of the exchange site in the Sec7 domain. These restraints can be relieved through activator Arf-GTP binding to an allosteric site comprising the PH domain and proximal autoinhibitory elements (Sec7-PH linker and C-terminal helix). Small-angle X-ray scattering and negative-stain electron microscopy were used to investigate the structural organization andmore » conformational dynamics of cytohesin-3 (Grp1) in autoinhibited and active states. The results support a model in which hinge dynamics in the autoinhibited state expose the activator site for Arf-GTP binding, while subsequent C-terminal helix unlatching and repositioning unleash conformational entropy in the Sec7-PH linker to drive exposure of the exchange site.« less
CONTRIBUTIONS OF CHEMICAL EXCHANGE TO T1ρ DISPERSION IN A TISSUE MODEL
Cobb, Jared G.; Xie, Jingping; Gore, John C.
2015-01-01
Variations in T1ρ with locking-field strength (T1ρ dispersion) may be used to estimate proton exchange rates. We developed a novel approach utilizing the second derivative of the dispersion curve to measure exchange in a model system of cross-linked polyacrylamide gels. These gels were varied in relative composition of co-monomers, increasing stiffness, and in pH, modifying exchange rates. MR images were recorded with a spin-locking sequence as described by Sepponen et al. These measurements were fit to a mono-exponential decay function yielding values for T1ρ at each locking-field measured. These values were then fit to a model by Chopra et al. for estimating exchange rates. For low stiffness gels, the calculated exchange values increased by a factor of 4 as pH increased, consistent with chemical exchange being the dominant contributor to T1ρ dispersion. Interestingly, calculated chemical exchange rates also increased with stiffness, likely due to modified side-chain exchange kinetics as the composition varied. This paper demonstrates a new method to assess the structural and chemical effects on T1ρ relaxation dispersion with a suitable model. These phenomena may be exploited in an imaging context to emphasize the presence of nuclei of specific exchange rates, rather than chemical shifts. PMID:21590720
2016-03-01
Medicinal plants provide indigenous and peasant communities worldwide with means to meet their healthcare needs. Homegardens often act as medicine cabinets, providing easily accessible medicinal plants for household needs. Social structure and social exchanges have been proposed as factors influencing the species diversity that people maintain in their homegardens. Here, we assess the association between the exchange of medicinal knowledge and plant material and medicinal plant richness in homegardens. Using Tsimane' Amazonian homegardens as a case study, we explore whether social organization shapes exchanges of medicinal plant knowledge and medicinal plant material. We also use network centrality measures to evaluate people's location and performance in medicinal plant knowledge and plant material exchange networks. Our results suggest that social organization, specifically kinship and gender relations, influences medicinal plant exchange patterns significantly. Homegardens total and medicinal plant species richness are related to gardeners' centrality in the networks, whereby people with greater centrality maintain greater plant richness. Thus, together with agroecological conditions, social relations among gardeners and the culturally specific social structure seem to be important determinants of plant richness in homegardens. Understanding which factors pattern general species diversity in tropical homegardens, and medicinal plant diversity in particular, can help policy makers, health providers, and local communities to understand better how to promote and preserve medicinal plants in situ. Biocultural approaches that are also gender sensitive offer a culturally appropriate means to reduce the global and local loss of both biological and cultural diversity.
Marital quality and diabetes: results from the Health and Retirement Study.
Whisman, Mark A; Li, Angela; Sbarra, David A; Raison, Charles L
2014-08-01
Poor marital quality is associated with many different indicators of poor health, including immunologic and metabolic responses that have relevance for distal disease outcomes such as diabetes. We conducted this study to evaluate whether poor marital quality was associated with the prevalence of diabetes in a population-based sample of Americans over the age of 50. Participants were married adults from the 2006 (N = 3,898) and 2008 (N = 3,452) waves of the Health and Retirement Study. Participants completed an interview and a self-report questionnaire, and current use of diabetes medication and glycosylated hemoglobin obtained from blood spot samples were used to index diabetes status. Marital quality was assessed with items regarding perceived frequency of positive and negative exchanges with partner. Decreasing frequency of positive exchanges and increasing frequency of negative exchanges with one's spouse were associated with higher prevalence of diabetes among men, but not women at both waves; gender significantly moderated the associations between partner exchanges and diabetes status for the 2006 data. The association between frequency of partner exchanges and diabetes status generally remained significant in men after accounting for demographic characteristics and other risk factors (obesity, hypertension, low physical activity). Poor marital quality as operationalized by rates of positive and negative partner exchanges was associated with increased prevalence of diabetes in men. These results are consistent with prior work on marriage and health, and suggest that poor marital quality may be a unique risk factor for diabetes.
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.
Chiva-Blanch, Gemma; Crespo, Javier; Suades, Rosa; Arderiu, Gemma; Padro, Teresa; Vilahur, Gemma; Cubedo, Judith; Corella, Dolores; Salas-Salvadó, Jordi; Arós, Fernando; Martínez-González, Miguel-Angel; Ros, Emilio; Fitó, Montse; Estruch, Ramon; Badimon, Lina
2016-07-04
Circulating microparticles (cMPs) are small phospholipid-rich microvesicles shed by activated cells that play a pivotal role in cell signalling related to the pathogenesis of atherothrombosis. We aimed to investigate the prognostic value of cMPs released from different vascular cells for cardiovascular event (CVE) presentation in asymptomatic patients at high cardiovascular risk factors under nutritional and pharmacologic treatment. This is a nested case-control study of 50 patients from the five-year follow-up prospective PREDIMED trial enrolled in the nuts arm of the Mediterranean diet (MedDiet-nuts). We randomly selected 25 patients who had suffered a CVE during follow-up and pair-matched them for sex, age, and classical CV risk factors to 25 patients who remained asymptomatic (no-CVE). Total Annexin V-(AV)+ cMPs and cMPs from cells of the vascular compartment were quantified by flow cytometry at baseline and after one year follow-up. MedDiet-nuts and pharmacological treatment neither modified levels nor source of MP shedding in CVE patients. However, no-CVE patients showed 40-86 % decreased total AV+, PAC-1+/AV+, CD61+/AV+, CD142+/CD61+/AV+, CD62P+/AV+, CD146+/AV+, CD63+/AV+ and CD11a+/AV+ cMPs at one year follow-up (p≤0.046, all). CD142+/CD61+/AV+, CD146+/AV+ and CD45+/AV+ cMPs were decreased in no-CVE patients compared to CVE patients. A ROC-curve clustered model for CD142+/CD61+/AV+, CD45+/AV+ and CD146+/AV+ cMPs predicted a future CVE [p<0.0001, AUC=0.805 (0.672 to 0.938)]. In patients at high CV risk profile treated with a controlled MedDiet supplemented with nuts and receiving up-to-date CV drug treatment, reduced cMPs derived from activated platelets, leukocytes and endothelial cells are predictive of protection against CVE within the next four years.
NASA Astrophysics Data System (ADS)
Falter, Christoph; Sizmann, Andreas; Pitz-Paal, Robert
2017-06-01
A modular reactor model is presented for the description of solar thermochemical syngas production involving counter-flow heat exchangers that recuperate heat from the solid phase. The development of the model is described including heat diffusion within the reactive material as it travels through the heat exchanger, which was previously identified to be a possibly limiting factor in heat exchanger design. Heat transfer within the reactive medium is described by conduction and radiation, where the former is modeled with the three-resistor model and the latter with the Rosseland diffusion approximation. The applicability of the model is shown by the analysis of heat exchanger efficiency for different material thicknesses and porosities in a system with 8 chambers and oxidation and reduction temperatures of 1000 K and 1800 K, respectively. Heat exchanger efficiency is found to rise strongly for a reduction of material thickness, as the element mass is reduced and a larger part of the elements takes part in the heat exchange process. An increase of porosity enhances radiation heat exchange but deteriorates conduction. The overall heat exchange in the material is improved for high temperatures in the heat exchanger, as radiation dominates the energy transfer. The model is shown to be a valuable tool for the development and analysis of solar thermochemical reactor concepts involving heat exchange from the solid phase.
The importance of social exchange to nurses and nurse assistants: impact on retention factors.
Trybou, Jeroen; De Pourcq, Kaat; Paeshuyse, Michel; Gemmel, Paul
2014-07-01
The purpose of this study was to test the norm of reciprocity by examining relationships between perceived organisational support (POS), the quality of leader-member exchange (LMX) and psychological contract breach (PCB) and important nurse retention factors identified in the literature. A major cause of turnover among nurses is related to unsatisfying workplaces. Previous research, mainly outside the nursing setting, found that social exchange affects employees' work-related attitudes. A cross-sectional survey was conducted on 217 nurses and nursing assistants to test and refine a model linking POS, LMX, PCB with job satisfaction, trust and turnover intentions. Hierarchical multiple linear regression revealed that POS, PCB and LMX explained significant variance in all three retention factors: job satisfaction (adjusted R² = 0.502), trust (adjusted R² = 0.462) and turnover intentions (adjusted R² = 0.196). POS and PCB predicted most strongly job satisfaction (P < 0.001) and trust (P < 0.001 and P < 0.01, respectively). LMX predicted most strongly intention to leave (P < 0.01). In our study, POS, the quality of LMX and PCB were strongly related to job satisfaction, trust and turnover intentions. Nursing managers and leaders should recognize the importance of social exchange within their organisation to build trust, satisfy and retain scarce nurses and nursing assistants. © 2013 John Wiley & Sons Ltd.
Freidman, Benjamin L; Gras, Sally L; Snape, Ian; Stevens, Geoff W; Mumford, Kathryn A
2016-08-05
Nitrogen deficiency has been identified as the main inhibiting factor for biodegradation of petroleum hydrocarbons in low nutrient environments. This study examines the performance of ammonium exchanged zeolite to enhance biodegradation of petroleum hydrocarbons migrating in soil water within laboratory scale flow cells. Biofilm formation and biodegradation were accelerated by the exchange of cations in soil water with ammonium in the pores of the exchanged zeolite when compared with natural zeolite flow cells. These results have implications for sequenced permeable reactive barrier design and the longevity of media performance within such barriers at petroleum hydrocarbon contaminated sites deficient in essential soil nutrients. Copyright © 2016 Elsevier B.V. All rights reserved.
Separation of thorium and uranium in nitric acid solution using silica based anion exchange resin.
Chen, Yanliang; Wei, Yuezhou; He, Linfeng; Tang, Fangdong
2016-09-30
To separate thorium and uranium in nitric acid solution using anion exchange process, a strong base silica-based anion exchange resin (SiPyR-N4) was synthesized. Batch experiments were conducted and the separation factor of thorium and uranium in 9M nitric acid was about 10. Ion exchange chromatography was applied to separate thorium and uranium in different ratios. Uranium could be eluted by 9M nitric acid and thorium was eluted by 0.1M nitric acid. It was proved that thorium and uranium can be separated and recovered successfully by this method. Copyright © 2016 Elsevier B.V. All rights reserved.
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...
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…
Federal Register 2010, 2011, 2012, 2013, 2014
2012-12-26
... well as other factors that influence exchange rates such as flows, market technical trends, and... Foreign Currency Strategy Exchange-Traded Fund Under NYSE Arca Equities Rule 8.600 December 19, 2012... following under NYSE Arca Equities Rule 8.600 (``Managed Fund Shares''): PIMCO Foreign Currency Strategy...
De l'enseignement de la grammaire par l'Internet (Grammar Instruction using the Internet).
ERIC Educational Resources Information Center
Beaudoin, Martin
1998-01-01
Examines pedagogical advantages and limitations of the Internet for teaching French grammar, and shows how these factors were taken into consideration in creating a Web site at the University of Alberta (Canada), with special emphasis on the integration of exchanges between learners, and exchanges between learners and the virtual francophone…
Knowledge Exchange: Capacity Building in a Small University
ERIC Educational Resources Information Center
Davis, Sally Fowler
2009-01-01
Purpose: The aim of this paper is to examine an early articulation of some of the key factors in building capacity and the potential for knowledge exchange (KE) within a small, learning and teaching-oriented organization. Design/methodology/approach: An action research study is planned as a practical enquiry. In common with other action research,…
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.
17 CFR 229.1103 - (Item 1103) Transaction summary and risk factors.
Code of Federal Regulations, 2010 CFR
2010-04-01
... summary and risk factors. 229.1103 Section 229.1103 Commodity and Securities Exchanges SECURITIES AND... (Regulation AB) § 229.1103 (Item 1103) Transaction summary and risk factors. (a) Prospectus summary. In... be assigned. (b) Risk factors. In providing the information required by Item 503(c) of Regulation S-K...
17 CFR 229.1103 - (Item 1103) Transaction summary and risk factors.
Code of Federal Regulations, 2011 CFR
2011-04-01
... summary and risk factors. 229.1103 Section 229.1103 Commodity and Securities Exchanges SECURITIES AND... (Regulation AB) § 229.1103 (Item 1103) Transaction summary and risk factors. (a) Prospectus summary. In... be assigned. (b) Risk factors. In providing the information required by Item 503(c) of Regulation S-K...
Federal Register 2010, 2011, 2012, 2013, 2014
2012-12-31
... Liquidity Factor of CME's CDS Margin Methodology December 21, 2012. Pursuant to Section 19(b)(1) of the.... * * * * * CME CDS Liquidity Margin Factor Calculation Methodology The Liquidity Factor will be calculated as the... Liquidity Factor using the current Gross Notional Function with the following modifications: (1) the...
The effect of post-synthesis aging on the ligand exchange activity of iron oxide nanoparticles.
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.
Performance evaluation on an air-cooled heat exchanger for alumina nanofluid under laminar flow.
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.
Performance evaluation on an air-cooled heat exchanger for alumina nanofluid under laminar flow
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
A piloted simulation study of data link ATC message exchange
NASA Technical Reports Server (NTRS)
Waller, Marvin C.; Lohr, Gary W.
1989-01-01
Data link Air Traffic Control (ATC) and Air Traffic Service (ATS) message and data exchange offers the potential benefits of increased flight safety and efficiency by reducing communication errors and allowing more information to be transferred between aircraft and ground facilities. Digital communication also presents an opportunity to relieve the overloading of ATC radio frequencies which hampers message exchange during peak traffic hours in many busy terminal areas. A piloted simulation study to develop pilot factor guidelines and assess potential flight crew benefits and liabilities from using data link ATC message exchange was completed. The data link ATC message exchange concept, implemented on an existing navigation computer Control Display Unit (CDU) required maintaining a voice radio telephone link with an appropriate ATC facility. Flight crew comments, scanning behavior, and measurements of time spent in ATC communication activities for data link ATC message exchange were compared to similar measures for simulated conventional voice radio operations. The results show crew preference for the quieter flight deck environment and a perception of lower communication workload.
Individual Basepair Stability of DNA and RNA Studied by NMR-Detected Solvent Exchange
Steinert, Hannah S.; Rinnenthal, Jörg; Schwalbe, Harald
2012-01-01
In this study, we have optimized NMR methodology to determine the thermodynamic parameters of basepair opening in DNA and RNA duplexes by characterizing the temperature dependence of imino proton exchange rates of individual basepairs. Contributions of the nuclear Overhauser effect to exchange rates measured with inversion recovery experiments are quantified, and the influence of intrinsic and external catalysis exchange mechanisms on the imino proton exchange rates is analyzed. Basepairs in DNA and RNA have an approximately equal stability, and the enthalpy and entropy values of their basepair dissociation are correlated linearly. Furthermore, the compensation temperature, Tc, which is derived from the slope of the correlation, coincides with the melting temperature, and duplex unfolding occurs at that temperature where all basepairs are equally thermodynamically stable. The impact of protium-deuterium exchange of the imino hydrogen on the free energy of RNA basepair opening is investigated, and it is found that two A·U basepairs show distinct fractionation factors. PMID:22713572
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
Perceived Appearance Judgments Moderate the Biological Stress Effects of Social Exchanges
Geiger, Ashley M.; Sabik, Natalie J.; Lupis, Sarah B.; Rene, Kirsten M.; Wolf, Jutta M.
2014-01-01
Social relationships are generally thought of as beneficial. However, the present study set out to test the hypothesis that for individuals who perceive others to judge their appearance negatively, daily social interactions can also be a source of stress. Indeed when assessing 38 young adults, we found that both more incidences of negative exchanges reported during the past month as well as perceived negative appearance judgments by others were associated with more self-reported stress. Interestingly, however, for individuals with low attribution body esteem, higher numbers of positive social exchanges during the past month were related to health-relevant changes in biological markers of chronic stress as well. The same was true for individuals with high attribution body esteem who reported to experience only very few positive exchanges. As such, these findings go beyond the initial focus on low body esteem and negative social exchanges and introduce high body esteem as well as daily positive exchanges as potential health risk factors. PMID:25457637
Fifty Years of Research in ARDS. Gas Exchange in Acute Respiratory Distress Syndrome.
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.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Constantin, Lucian A.; Fabiano, Eduardo; Della Sala, Fabio
We introduce a novel non-local ingredient for the construction of exchange density functionals: the reduced Hartree parameter, which is invariant under the uniform scaling of the density and represents the exact exchange enhancement factor for one- and two-electron systems. The reduced Hartree parameter is used together with the conventional meta-generalized gradient approximation (meta-GGA) semilocal ingredients (i.e., the electron density, its gradient, and the kinetic energy density) to construct a new generation exchange functional, termed u-meta-GGA. This u-meta-GGA functional is exact for the exchange of any one- and two-electron systems, is size-consistent and non-empirical, satisfies the uniform density scaling relation, andmore » recovers the modified gradient expansion derived from the semiclassical atom theory. For atoms, ions, jellium spheres, and molecules, it shows a good accuracy, being often better than meta-GGA exchange functionals. Our construction validates the use of the reduced Hartree ingredient in exchange-correlation functional development, opening the way to an additional rung in the Jacob’s ladder classification of non-empirical density functionals.« less
Contributions of chemical exchange to T1ρ dispersion in a tissue model.
Cobb, Jared G; Xie, Jingping; Gore, John C
2011-12-01
Variations in T(1ρ) with locking-field strength (T(1ρ) dispersion) may be used to estimate proton exchange rates. We developed a novel approach utilizing the second derivative of the dispersion curve to measure exchange in a model system of cross-linked polyacrylamide gels. These gels were varied in relative composition of comonomers, increasing stiffness, and in pH, modifying exchange rates. Magnetic resonance images were recorded with a spin-locking sequence as described by Sepponen et al. These measurements were fit to a mono-exponential decay function yielding values for T(1ρ) at each locking-field measured. These values were then fit to a model by Chopra et al. for estimating exchange rates. For low stiffness gels, the calculated exchange values increased by a factor of 4 as pH increased, consistent with chemical exchange being the dominant contributor to T(1ρ) dispersion. Interestingly, calculated chemical exchange rates also increased with stiffness, likely due to modified side-chain exchange kinetics as the composition varied. This article demonstrates a new method to assess the structural and chemical effects on T(1ρ) relaxation dispersion with a suitable model. These phenomena may be exploited in an imaging context to emphasize the presence of nuclei of specific exchange rates, rather than chemical shifts. Copyright © 2011 Wiley Periodicals, Inc.
Human factors engineering: the next challenge.
Durand-Viel, Denys
2004-10-01
This fictional exchange between a General Manager, a Research and Development Officer and a Regulatory Affairs Manager after a near incident with a recently launched device explains how human factors engineering is the key to design success.
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.
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.
Zhang, Gang; Wang, Ning; Ai, Jian-Chao; Zhang, Lei; Yang, Jing; Liu, Zi-Qi
2013-02-01
Jiapigou gold mine, located in the upper Songhua River, was once the largest mine in China due to gold output, where gold extraction with algamation was widely applied to extract gold resulting in severe mercury pollution to ambient environmental medium. In order to study the characteristics of mercury exchange flux between soil (snow) and atmosphere under the snow retention and snow melting control, sampling sites were selected in equal distances along the slope which is situated in the typical hill-valley terrain unit. Mercury exchange flux between soil (snow) and atmosphere was determined with the method of dynamic flux chamber and in all sampling sites the atmosphere concentration from 0 to 150 cm near to the earth in the vertical direction was measured. Furthermore, the impact factors including synchronous meteorology, the surface characteristics under the snow retention and snow melting control and the mercury concentration in vertical direction were also investigated. The results are as follows: During the period of snow retention and melting the air mercury tends to gather towards valley bottom along the slope and an obvious deposit tendency process was found from air to the earth's surface under the control of thermal inversion due to the underlying surface of cold source (snow surface). However, during the period of snow melting, mercury exchange flux between the soil and atmosphere on the surface of the earth with the snow being melted demonstrates alternative deposit and release processes. As for the earth with snow covered, the deposit level of mercury exchange flux between soil and atmosphere is lower than that during the period of snow retention. The relationship between mercury exchange flux and impact factors shows that in snow retention there is a remarkable negative linear correlation between mercury exchange flux and air mercury concentration as well as between the former and the air temperature. In addition, in snow melting mercury exchange flux is remarkably negatively linearly correlated to air mercury concentration and positively linearly correlated to air temperature. Furthermore, there is a general positive linear correlation between mercury exchange flux and soil temperature on the surface of earth after snow melting.
Kinetic theory of oxygen isotopic exchange between minerals and water
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.
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.
NASA Astrophysics Data System (ADS)
Koon, Norman C.
1997-04-01
It is shown using full micromagnetic relaxation calculations that exchange bias behavior is predicted for single-crystal ferro/antiferromagnetic layers with a fully compensated interface. The particular example most fully studied has a bcc/bct lattice structure with a fully compensated (110) interface plane. Only bilinear Heisenberg exchange was assumed, with anisotropy only in the antiferromagnet. In spite of the intuitive notion that exchange coupling between a ferromagnet and an antiferromagnet across a fully compensated plane of the antiferromagnet should be zero, we find strong coupling, comparable to the bilinear exchange, with a 90° angle between the ferromagnetic and antiferromagnetic axes of layers far from the interface in absence of an applied field. Even though the 90° coupling has characteristics resembling "biquadratic" exchange, it originates entirely from frustrated bilinear exchange. The development of exchange bias is found to originate from the formation of a domain wall in the antiferromagnet via the strong 90° exchange coupling and pinning of the wall by the magnetocrystalline anisotropy in the antiferromagnet. Because the large demagnetizing factor of the ferromagnet tends to confine its magnetization to the plane, the exchange bias is found to depend mainly on the strength and the symmetry of the in-plane component of anisotropy. Although little effort was made to analyze specific systems, the model reproduces many of the qualitative features observed in real exchange bias systems and gives reasonable semiquantitative estimates for the bias field when exchange and anisotropy values consistent with real systems are used.
Bilateral foreign direct investment in forest industry between the U.S. and Canada
Rao V Nagubadi; Daowei Zhang
2011-01-01
In this study we examine the trends and various factors influencing bilateral foreign direct investment (FDI) in the U.S. and Canadian forest industry between 1989 and 2008. Using panel data analysis methods, we find that bilateral FDI is positively influenced by depreciation of host country's real exchange rates and exchange rate volatility, and home country...
USDA-ARS?s Scientific Manuscript database
Oil migration affects the quality and shelf-life of food products and consequently has an impact on overall consumer acceptance. Exchange of oil may occur during or after oil roasting of peanuts but little is known about the factors contributing to this exchange. This study examines the effect of p...
ERIC Educational Resources Information Center
Chen, Hsiu-Ling; Fan, Hsueh-Liang; Tsai, Chin-Chung
2014-01-01
The knowledge sharing process within a virtual community of teacher professionals is viewed as a social exchange process in that the knowledge sharing intention and behavior of individuals are influenced by the exchange relationship among members. However, relatively little research has focused on this approach to exploring the factors that…
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...
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...
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...
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...
HIV Risk Behavior among Amphetamine Injectors at U.S. Syringe Exchange Programs
ERIC Educational Resources Information Center
Braine, Naomi; Des Jarlais, Don C.; Goldblatt, Cullen; Zadoretzky, Cathy; Turner, Charles
2005-01-01
The goal of this study was to compare HIV risk behaviors of amphetamine and non-amphetamine injectors at syringe exchange programs (SEP) in the United States and to identify factors associated with injection risk. This analysis is based on data from a random cross-section of participants at 13 SEPs in different parts of the country. All interviews…
Paudel, Klara; Namagondlu, Girish; Samad, Nasreen; McKitty, Khadija; Fan, Stanley L
2015-03-01
Can we identify modifiable risk factors for peritonitis in patients undergoing peritoneal dialysis (PD)? We aimed to determine whether housing standard, PD exchange technique or patient motivation might be modifiable risks for peritonitis. We also explored the relationship between lack of motivation and depression. Nurse home visits assessed PD exchange technique, environment and patient motivation. Motivation scores were correlated separately with an Apathy Evaluation Score and a depression score using PHQ-9 questionnaires. Home hygiene, exchange technique and motivation were above average in 53%, 56% and 60%, respectively in 104 patients undergoing PD. After 15 months, 25.9% patients developed peritonitis but nurses' ratings of homes and exchange techniques were not predictive. Low patient motivation was predictive. Patients rated to have above or below median motivation had significantly different Apathy Scores (p = 0.0002). Unmotivated depressed patients were significantly more likely to develop peritonitis compared to motivated depressed patients. Lack of motivation predicted peritonitis particularly if associated with depression. Further studies are required focusing on specific motivation scoring schemes and the psychosocial support that might lead to better outcomes. © 2014 European Dialysis and Transplant Nurses Association/European Renal Care Association.
Tables and conversions for microclimatology.
James M. Brown
1973-01-01
A series of tables, charts, and conversion factors have been prepared for use in microclimatic and ecological studies. Included are: the solution to various equations of radiant energy exchange; solar radiation diagrams; psychometric and precipitation data; and unit conversion factors.
Landis, Wayne G.
1987-01-01
The factors maintaining the cytoplasmically inherited killer trait in populations of Paramecium tetraurelia and Paramecium biaurelia were examined using, in part, computer simulation. Frequency of the K and k alleles, infection and loss of the endosymbionts, recombination during conjugation and autogamy, cytoplasmic exchange and natural selection were incorporated in a model. Infection during cytoplasmic exchange at conjugation and natural selection were factors that would increase the proportion of killers in a population. Conversely, k alleles reduced the proportion of killers in a population, acting through conjugation and autogamy. Field studies indicate that the odd mating type is prevalent in P. tetraurelia isolated from nature. Conjugation and therefore transmission by cytoplasmic transfer would be rare. Competition studies indicate a strong selective disadvantage for sensitives at concentrations found in nature. Natural selection must therefore be the factor maintaining the killer trait in P. tetraurelia. PMID:3557112
Air-gas exchange reevaluated: clinically important results of a computer simulation.
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.
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 ).
Kim, Kyungmin; Zarit, Steven H; Birditt, Kira S; Fingerman, Karen L
2014-04-01
Using data from 929 parent-child dyads nested in 458 three-generation families (aged 76 for the oldest generation, 50 for the middle generation, and 24 for the youngest generation), this study investigated how discrepancies in reports of support that parents and their adult offspring exchanged with one another vary both within and between families, and what factors explain variations in dyadic discrepancies. We found substantial within- and between-family differences in dyadic discrepancies in reports of support exchanges. For downward exchanges (from parents to offspring), both dyad-specific characteristics within a family (e.g., gender composition, relative levels of relationship quality, and family obligation) and shared family characteristics (e.g., average levels of relationship quality) showed significant effects on dyadic discrepancies. For upward exchanges (from offspring to parents), however, only dyad-specific characteristics (e.g., gender composition, coresidence, relative levels of positive relationship quality, and family obligation) were significantly associated with discrepancies. Discrepancies in support exchanges were mainly associated with dyad-specific characteristics, but they also appeared to be influenced by family emotional environments. The use of multiple informants revealed that families differ in discrepancies in reports of exchanges, which has implications for quality of family life as well as future exchanges. PsycINFO Database Record (c) 2014 APA, all rights reserved.
Kim, Kyungmin; Zarit, Steven H.; Birditt, Kira S.; Fingerman, Karen L.
2014-01-01
Using data from 929 parent-child dyads nested in 458 three-generation families (aged 76 for the oldest generation, 50 for the middle generation, and 24 for the youngest generation), this study investigated how discrepancies in reports of support that parents and their adult offspring exchanged with one another vary both within and between families, and what factors explain variations in dyadic discrepancies. We found substantial within- and between-family differences in dyadic discrepancies in reports of support exchanges. For downward exchanges (from parents to offspring), both dyad-specific characteristics within a family (e.g., gender composition, relative levels of relationship quality, and family obligation) and shared family characteristics (e.g., average levels of relationship quality) showed significant effects on dyadic discrepancies. For upward exchanges (from offspring to parents), however, only dyad-specific characteristics (e.g., gender composition, coresidence, relative levels of positive relationship quality, and family obligation) were significantly associated with discrepancies. Discrepancies in support exchanges were mainly associated with dyad-specific characteristics, but they also appeared to be influenced by family emotional environments. The use of multiple informants revealed that families differ in discrepancies in reports of exchanges, which has implications for quality of family life as well as future exchanges. PMID:24548009
Toth, Ronald T; Mills, Brittney J; Joshi, Sangeeta B; Esfandiary, Reza; Bishop, Steven M; Middaugh, C Russell; Volkin, David B; Weis, David D
2017-09-05
A barrier to the use of hydrogen exchange-mass spectrometry (HX-MS) in many contexts, especially analytical characterization of various protein therapeutic candidates, is that differences in temperature, pH, ionic strength, buffering agent, or other additives can alter chemical exchange rates, making HX data gathered under differing solution conditions difficult to compare. Here, we present data demonstrating that HX chemical exchange rates can be substantially altered not only by the well-established variables of temperature and pH but also by additives including arginine, guanidine, methionine, and thiocyanate. To compensate for these additive effects, we have developed an empirical method to correct the hydrogen-exchange data for these differences. First, differences in chemical exchange rates are measured by use of an unstructured reporter peptide, YPI. An empirical chemical exchange correction factor, determined by use of the HX data from the reporter peptide, is then applied to the HX measurements obtained from a protein of interest under different solution conditions. We demonstrate that the correction is experimentally sound through simulation and in a proof-of-concept experiment using unstructured peptides under slow-exchange conditions (pD 4.5 at ambient temperature). To illustrate its utility, we applied the correction to HX-MS excipient screening data collected for a pharmaceutically relevant IgG4 mAb being characterized to determine the effects of different formulations on backbone dynamics.
Leakage and sweet spots in triple-quantum-dot spin qubits: A molecular-orbital study
NASA Astrophysics Data System (ADS)
Zhang, Chengxian; Yang, Xu-Chen; Wang, Xin
2018-04-01
A triple-quantum-dot system can be operated as either an exchange-only qubit or a resonant-exchange qubit. While it is generally believed that the decisive advantage of the resonant-exchange qubit is the suppression of charge noise because it is operated at a sweet spot, we show that the leakage is also an important factor. Through molecular-orbital-theoretic calculations, we show that when the system is operated in the exchange-only scheme, the leakage to states with double electron occupancy in quantum dots is severe when rotations around the axis 120∘ from z ̂ is performed. While this leakage can be reduced by either shrinking the dots or separating them further, the exchange interactions are also suppressed at the same time, making the gate operations unfavorably slow. When the system is operated as a resonant-exchange qubit, the leakage is three to five orders of magnitude smaller. We have also calculated the optimal detuning point which minimizes the leakage for the resonant-exchange qubit, and have found that although it does not coincide with the double sweet spot for the charge noise, they are rather close. Our results suggest that the resonant-exchange qubit has another advantage, that leakage can be greatly suppressed compared to the exchange-only qubit, and operating at the double sweet spot point should be optimal both for reducing charge noise and suppressing leakage.
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.
Destabilizing Mutations Alter the Hydrogen Exchange Mechanism in Ribonuclease A
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
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
Time-dependent spin-density-functional-theory description of He+-He collisions
NASA Astrophysics Data System (ADS)
Baxter, Matthew; Kirchner, Tom; Engel, Eberhard
2017-09-01
Theoretical total cross-section results for all ionization and capture processes in the He+-He collision system are presented in the approximate impact energy range of 10-1000 keV/amu. Calculations were performed within the framework of time-dependent spin-density functional theory. The Krieger-Li-Iafrate approximation was used to determine an accurate exchange-correlation potential in the exchange-only limit. The results of two models, one where electron translation factors in the orbitals used to calculate the potential are ignored and another where partial electron translation factors are included, are compared with available experimental data as well as a selection of previous theoretical calculations.
Prosocial coping and substance use during pregnancy.
Blechman, E A; Lowell, E S; Garrett, J
1999-01-01
In structured interviews of pregnant inner-city residents, 38 substance users reported more current liking of drugs and polysubstance use, disengagement coping, depressive symptoms, negative affect, and antisocial behavior than did 45 nonusers. During videotaped interviews, trained observers coded less warmth and less prosocial information exchange (e.g., self-disclosure, question asking) among users. Factor analysis of measures of coping and its concomitants yielded a three-factor (prosocial, antisocial, asocial) solution, with asocial and antisocial coping predominating among substance users. These results suggest that coping has emotional, social, and cognitive elements. This study is the first to demonstrate an association between a substance-using lifestyle and limited prosocial information exchange.
Rho-guanine nucleotide exchange factors during development
Mulinari, Shai
2010-01-01
The development of multicellular organisms is associated with extensive rearrangements of tissues and cell sheets. The driving force for these rearrangements is generated mostly by the actin cytoskeleton. In order to permit the reproducible development of a specific body plan, dynamic reorganization of the actin cytoskeleton must be precisely coordinated in space and time. GTP-exchange factors that activate small GTPases of the Rho family play an important role in this process. Here we review the role of this class of cytoskeletal regulators during important developmental processes such as epithelial morphogenesis, cytokinesis, cell migration, cell polarity, neuronal growth cone extension and phagocytosis in different model systems. PMID:21686118
Wu, Xiaobin; Kim, Heejeong; Seravalli, Javier; Barycki, Joseph J.; Hart, P. John; Gohara, David W.; Di Cera, Enrico; Jung, Won Hee; Kosman, Daniel J.; Lee, Jaekwon
2016-01-01
Acquisition and distribution of metal ions support a number of biological processes. Here we show that respiratory growth of and iron acquisition by the yeast Saccharomyces cerevisiae relies on potassium (K+) compartmentalization to the trans-Golgi network via Kha1p, a K+/H+ exchanger. K+ in the trans-Golgi network facilitates binding of copper to the Fet3p multi-copper ferroxidase. The effect of K+ is not dependent on stable binding with Fet3p or alteration of the characteristics of the secretory pathway. The data suggest that K+ acts as a chemical factor in Fet3p maturation, a role similar to that of cations in folding of nucleic acids. Up-regulation of KHA1 gene in response to iron limitation via iron-specific transcription factors indicates that K+ compartmentalization is linked to cellular iron homeostasis. Our study reveals a novel functional role of K+ in the binding of copper to apoFet3p and identifies a K+/H+ exchanger at the secretory pathway as a new molecular factor associated with iron uptake in yeast. PMID:26966178
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.
Factors contributing to attitude exchange amongst preservice elementary teachers
NASA Astrophysics Data System (ADS)
Palmer, David H.
2002-01-01
Previous research has shown that elementary education majors often dislike science and lack confidence in their ability to teach it. This is an important problem because students who hold these attitudes are likely to avoid teaching science, or teach it poorly, when they become teachers. It is therefore necessary to identify preservice elementary teachers who hold negative attitudes towards science, and attempt to convert these attitudes to positive before they become teachers. This study was designed to identify students whose attitudes had changed from negative to positive (i.e., attitude exchange had occurred) after participating in a one-semester elementary science education course, and to identify the course factors that were responsible. Four participants were individually interviewed. The transcripts indicated that attitude exchange had occurred for each of the four students. Each student described several features of the course that had a positive influence. These were of three main types: personal attributes of the tutor, specific teaching strategies, and external validation. It was proposed that many of the individual factors were effective because they represented either performance accomplishments or vicarious experience as defined by Bandura (Psychological Review, 84, 1977, 191-215).
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.
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.
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.
Exchange Sex and HIV Infection Among Men Who Have Sex with Men: 20 US Cities, 2011.
M Nerlander, Lina; Hess, Kristen L; Sionean, Catlainn; E Rose, Charles; Thorson, Anna; Broz, Dita; Paz-Bailey, Gabriela
2017-08-01
This study assessed the prevalence of exchanging sex for money or drugs among men who have sex with men (MSM) in the 2011 US National HIV Behavioral Surveillance system. Prevalence of HIV, being HIV-positive but unaware (HIV-positive-unaware), risk behaviors and use of services were compared between MSM who did and did not receive money or drugs from one or more casual male partners in exchange for oral or anal sex in the past 12 months. Among 8411 MSM, 7.0 % exchanged sex. MSM who exchanged sex were more likely to be non-Hispanic black, live in poverty, have injected drugs, have multiple condomless anal sex partners, be HIV-positive and be HIV-positive-unaware. In multivariable analysis, exchange sex was associated with being HIV-positive-unaware (aPR 1.34, 95 % CI 1.05-1.69) after adjusting for race/ethnicity, age, education, poverty, and injecting drugs. MSM who exchange sex represent an important group to reach with HIV prevention, testing, and care services as they were more likely to report behavioral risk factors that put them at risk of HIV.
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
PH motifs in PAR1&2 endow breast cancer growth.
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.
Functional hierarchy of the N-terminal tyrosines of SLP-76.
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.
Moreno, M A; Domínguez, L; Teshager, T; Herrero, I A; Porrero, M C
2000-05-01
Antimicrobial resistance is a problem in modern public health and antimicrobial use and especially misuse, the most important selecting force for bacterial antibiotic resistance. As this resistance must be monitored we have designed the Spanish network 'Red de Vigilancia de Resistencias Antibióticas en Bacterias de Origen Veterinario'. This network covers the three critical points of veterinary responsibility, bacteria from sick animals, bacteria from healthy animals and bacteria from food animals. Key bacteria, antimicrobials and animal species have been defined for each of these groups along with laboratory methods for testing antimicrobial susceptibility and for data analysis and reporting. Surveillance of sick animals was first implemented using Escherichia coli as the sentinel bacterium. Surveillance of E. coli and Enterococcus faecium from healthy pigs was implemented in 1998. In July 1999, data collection on Salmonella spp. was initiated in poultry slaughterhouses. Additionally, the prevalence of vancomycin resistant E. faecium was also monitored. This network has specific topics of interest related to methods of determining resistance, analysis and reporting of data, methods of use for veterinary practitioners and collaboration with public health authorities.
High resolution main-ion charge exchange spectroscopy in the DIII-D H-mode pedestal.
Grierson, B A; Burrell, K H; Chrystal, C; Groebner, R J; Haskey, S R; Kaplan, D H
2016-11-01
A new high spatial resolution main-ion (deuterium) charge-exchange spectroscopy system covering the tokamak boundary region has been installed on the DIII-D tokamak. Sixteen new edge main-ion charge-exchange recombination sightlines have been combined with nineteen impurity sightlines in a tangentially viewing geometry on the DIII-D midplane with an interleaving design that achieves 8 mm inter-channel radial resolution for detailed profiles of main-ion temperature, velocity, charge-exchange emission, and neutral beam emission. At the plasma boundary, we find a strong enhancement of the main-ion toroidal velocity that exceeds the impurity velocity by a factor of two. The unique combination of experimentally measured main-ion and impurity profiles provides a powerful quasi-neutrality constraint for reconstruction of tokamak H-mode pedestals.
Chen, Shyi-Ming; Chen, Shen-Wen
2015-03-01
In this paper, we present a new method for fuzzy forecasting based on two-factors second-order fuzzy-trend logical relationship groups and the probabilities of trends of fuzzy-trend logical relationships. Firstly, the proposed method fuzzifies the historical training data of the main factor and the secondary factor into fuzzy sets, respectively, to form two-factors second-order fuzzy logical relationships. Then, it groups the obtained two-factors second-order fuzzy logical relationships into two-factors second-order fuzzy-trend logical relationship groups. Then, it calculates the probability of the "down-trend," the probability of the "equal-trend" and the probability of the "up-trend" of the two-factors second-order fuzzy-trend logical relationships in each two-factors second-order fuzzy-trend logical relationship group, respectively. Finally, it performs the forecasting based on the probabilities of the down-trend, the equal-trend, and the up-trend of the two-factors second-order fuzzy-trend logical relationships in each two-factors second-order fuzzy-trend logical relationship group. We also apply the proposed method to forecast the Taiwan Stock Exchange Capitalization Weighted Stock Index (TAIEX) and the NTD/USD exchange rates. The experimental results show that the proposed method outperforms the existing methods.
USDA-ARS?s Scientific Manuscript database
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. The anal...
1987-09-14
prices are also affected by many other factors, for example, by the value of commodities, by supply and demand, by taxation, by foreign exchange rates and... exchange rates may directly or indirectly cause product value to fluctuate up or down. Thus, only by adjusting prices in a timely manner can we ensure...changes in materialized and live labor, improvements in production technology, changes in natural-resource supply and fluctuations in foreign
Park, In-Hee; Venable, John D; Steckler, Caitlin; Cellitti, Susan E; Lesley, Scott A; Spraggon, Glen; Brock, Ansgar
2015-09-28
Hydrogen exchange (HX) studies have provided critical insight into our understanding of protein folding, structure, and dynamics. More recently, hydrogen exchange mass spectrometry (HX-MS) has become a widely applicable tool for HX studies. The interpretation of the wealth of data generated by HX-MS experiments as well as other HX methods would greatly benefit from the availability of exchange predictions derived from structures or models for comparison with experiment. Most reported computational HX modeling studies have employed solvent-accessible-surface-area based metrics in attempts to interpret HX data on the basis of structures or models. In this study, a computational HX-MS prediction method based on classification of the amide hydrogen bonding modes mimicking the local unfolding model is demonstrated. Analysis of the NH bonding configurations from molecular dynamics (MD) simulation snapshots is used to determine partitioning over bonded and nonbonded NH states and is directly mapped into a protection factor (PF) using a logistics growth function. Predicted PFs are then used for calculating deuteration values of peptides and compared with experimental data. Hydrogen exchange MS data for fatty acid synthase thioesterase (FAS-TE) collected for a range of pHs and temperatures was used for detailed evaluation of the approach. High correlation between prediction and experiment for observable fragment peptides is observed in the FAS-TE and additional benchmarking systems that included various apo/holo proteins for which literature data were available. In addition, it is shown that HX modeling can improve experimental resolution through decomposition of in-exchange curves into rate classes, which correlate with prediction from MD. Successful rate class decompositions provide further evidence that the presented approach captures the underlying physical processes correctly at the single residue level. This assessment is further strengthened in a comparison of residue resolved protection factor predictions for staphylococcal nuclease with NMR data, which was also used to compare prediction performance with other algorithms described in the literature. The demonstrated transferable and scalable MD based HX prediction approach adds significantly to the available tools for HX-MS data interpretation based on available structures and models.
Park, In-Hee; Venable, John D.; Steckler, Caitlin; Cellitti, Susan E.; Lesley, Scott A.; Spraggon, Glen; Brock, Ansgar
2015-01-01
Hydrogen exchange (HX) studies have provided critical insight into our understanding of protein folding, structure and dynamics. More recently, Hydrogen Exchange Mass Spectrometry (HX-MS) has become a widely applicable tool for HX studies. The interpretation of the wealth of data generated by HX-MS experiments as well as other HX methods would greatly benefit from the availability of exchange predictions derived from structures or models for comparison with experiment. Most reported computational HX modeling studies have employed solvent-accessible-surface-area based metrics in attempts to interpret HX data on the basis of structures or models. In this study, a computational HX-MS prediction method based on classification of the amide hydrogen bonding modes mimicking the local unfolding model is demonstrated. Analysis of the NH bonding configurations from Molecular Dynamics (MD) simulation snapshots is used to determine partitioning over bonded and non-bonded NH states and is directly mapped into a protection factor (PF) using a logistics growth function. Predicted PFs are then used for calculating deuteration values of peptides and compared with experimental data. Hydrogen exchange MS data for Fatty acid synthase thioesterase (FAS-TE) collected for a range of pHs and temperatures was used for detailed evaluation of the approach. High correlation between prediction and experiment for observable fragment peptides is observed in the FAS-TE and additional benchmarking systems that included various apo/holo proteins for which literature data were available. In addition, it is shown that HX modeling can improve experimental resolution through decomposition of in-exchange curves into rate classes, which correlate with prediction from MD. Successful rate class decompositions provide further evidence that the presented approach captures the underlying physical processes correctly at the single residue level. This assessment is further strengthened in a comparison of residue resolved protection factor predictions for staphylococcal nuclease with NMR data, which was also used to compare prediction performance with other algorithms described in the literature. The demonstrated transferable and scalable MD based HX prediction approach adds significantly to the available tools for HX-MS data interpretation based on available structures and models. PMID:26241692
Ryu, Kyoung-Seok; Tugarinov, Vitali; Clore, G Marius
2014-10-15
The kinetics of translocation of the homeodomain transcription factor HoxD9 between specific sites of the same or opposite polarities on the same DNA molecule have been studied by (15)Nz-exchange NMR spectroscopy. We show that exchange occurs by two facilitated diffusion mechanisms: a second-order intermolecular exchange reaction between specific sites located on different DNA molecules without the protein dissociating into free solution that predominates at high concentrations of free DNA, and a first-order intramolecular process involving direct transfer between specific sites located on the same DNA molecule. Control experiments using a mixture of two DNA molecules, each possessing only a single specific site, indicate that transfer between specific sites by full dissociation of HoxD9 into solution followed by reassociation is too slow to measure by z-exchange spectroscopy. Intramolecular transfer with comparable rate constants occurs between sites of the same and opposing polarity, indicating that both rotation-coupled sliding and hopping/flipping (analogous to geminate recombination) occur. The half-life for intramolecular transfer (0.5-1 s) is many orders of magnitude larger than the calculated transfer time (1-100 μs) by sliding, leading us to conclude that the intramolecular transfer rates measured by z-exchange spectroscopy represent the rate-limiting step for a one-base-pair shift from the specific site to the immediately adjacent nonspecific site. At zero concentration of added salt, the intramolecular transfer rate constants between sites of opposing polarity are smaller than those between sites of the same polarity, suggesting that hopping/flipping may become rate-limiting at very low salt concentrations.
Contact Activation of Blood Plasma and Factor XII by Ion-exchange Resins
Yeh, Chyi-Huey Josh; Dimachkie, Ziad O.; Golas, Avantika; Cheng, Alice; Parhi, Purnendu; Vogler, Erwin A.
2011-01-01
Sepharose ion-exchange particles bearing strong Lewis acid/base functional groups (sulfopropyl, carboxymethyl, quarternary ammonium, dimethyl aminoethyl, and iminodiacetic acid) exhibiting high plasma protein adsorbent capacities are shown to be more efficient activators of blood factor XII in neat-buffer solution than either hydrophilic clean-glass particles or hydrophobic octyl sepharose particles ( FXII→surfaceactivatorFXIIa; a.k.a autoactivation, where FXII is the zymogen and FXIIa is a procoagulant protease). In sharp contrast to the clean-glass standard of comparison, ion-exchange activators are shown to be inefficient activators of blood plasma coagulation. These contrasting activation properties are proposed to be due to the moderating effect of plasma-protein adsorption on plasma coagulation. Efficient adsorption of blood plasma proteins unrelated to the coagulation cascade impedes FXII contacts with ion-exchange particles immersed in plasma, reducing autoactivation, and causing sluggish plasma coagulation. By contrast, plasma proteins do not adsorb to hydrophilic clean glass and efficient autoactivation leads directly to efficient activation of plasma coagulation. It is also shown that competitive-protein adsorption can displace FXIIa adsorbed to the surface of ion-exchange resins. As a consequence of highly-efficient autoactivation and FXIIa displacement by plasma proteins, ion-exchange particles are slightly more efficient activators of plasma coagulation than hydrophobic octyl sepharose particles that do not bear strong Lewis acid/base surface functionalities but to which plasma proteins adsorb efficiently. Plasma proteins thus play a dual role in moderating contact activation of the plasma coagulation cascade. The principal role is impeding FXII contact with activating surfaces but this same effect can displace FXIIa from an activating surface into solution where the protease can potentiate subsequent steps of the plasma coagulation cascade. PMID:21982294
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...
Federal Register 2010, 2011, 2012, 2013, 2014
2013-04-29
... Liquidity Factor of CME's CDS Margin Methodology April 23, 2013. Pursuant to Section 19(b)(1) of the... additions; bracketed text indicates deletions. * * * * * CME CDS Liquidity Margin Factor Calculation Methodology The Liquidity Factor will be calculated as the sum of two components: (1) A concentration charge...
Napolitano, Roberta; Soesbe, Todd C; De León-Rodríguez, Luis M; Sherry, A Dean; Udugamasooriya, D Gomika
2011-08-24
The sensitivity of magnetic resonance imaging (MRI) contrast agents is highly dependent on the rate of water exchange between the inner sphere of a paramagnetic ion and bulk water. Normally, identifying a paramagnetic complex that has optimal water exchange kinetics is done by synthesizing and testing one compound at a time. We report here a rapid, economical on-bead combinatorial synthesis of a library of imaging agents. Eighty different 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid (DOTA)-tetraamide peptoid derivatives were prepared on beads using a variety of charged, uncharged but polar, hydrophobic, and variably sized primary amines. A single chemical exchange saturation transfer image of the on-bead library easily distinguished those compounds having the most favorable water exchange kinetics. This combinatorial approach will allow rapid screening of libraries of imaging agents to identify the chemical characteristics of a ligand that yield the most sensitive imaging agents. This technique could be automated and readily adapted to other types of MRI or magnetic resonance/positron emission tomography agents as well.
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
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.
Vo, Uybach; Vajpai, Navratna; Flavell, Liz; Bobby, Romel; Breeze, Alexander L.; Embrey, Kevin J.; Golovanov, Alexander P.
2016-01-01
The activity of Ras is controlled by the interconversion between GTP- and GDP-bound forms partly regulated by the binding of the guanine nucleotide exchange factor Son of Sevenless (Sos). The details of Sos binding, leading to nucleotide exchange and subsequent dissociation of the complex, are not completely understood. Here, we used uniformly 15N-labeled Ras as well as [13C]methyl-Met,Ile-labeled Sos for observing site-specific details of Ras-Sos interactions in solution. Binding of various forms of Ras (loaded with GDP and mimics of GTP or nucleotide-free) at the allosteric and catalytic sites of Sos was comprehensively characterized by monitoring signal perturbations in the NMR spectra. The overall affinity of binding between these protein variants as well as their selected functional mutants was also investigated using intrinsic fluorescence. The data support a positive feedback activation of Sos by Ras·GTP with Ras·GTP binding as a substrate for the catalytic site of activated Sos more weakly than Ras·GDP, suggesting that Sos should actively promote unidirectional GDP → GTP exchange on Ras in preference of passive homonucleotide exchange. Ras·GDP weakly binds to the catalytic but not to the allosteric site of Sos. This confirms that Ras·GDP cannot properly activate Sos at the allosteric site. The novel site-specific assay described may be useful for design of drugs aimed at perturbing Ras-Sos interactions. PMID:26565026
Calculation of exchange interaction for modified Gaussian coupled quantum dots
NASA Astrophysics Data System (ADS)
Khordad, R.
2017-08-01
A system of two laterally coupled quantum dots with modified Gaussian potential has been considered. Each quantum dot has an electron under electric and magnetic field. The quantum dots have been considered as hydrogen-like atoms. The physical picture has translated into the Heisenberg spin Hamiltonian. The Schrödinger equation using finite element method has been numerically solved. The exchange energy factor has been calculated as a functions of electric field, magnetic field, and the separation distance between the centers of the dots ( d). According to the results, it is found that there is the transition from anti-ferromagnetic to ferromagnetic for constant electric field. Also, the transition occurs from ferromagnetic to anti-ferromagnetic for constant magnetic field (B>1 T). With decreasing the distance between the centers of the dots and increasing magnetic field, the transition occurs from anti-ferromagnetic to ferromagnetic. It is found that a switching of exchange energy factor is presented without canceling the interactions of the electric and magnetic fields on the system.
NASA Astrophysics Data System (ADS)
Vieira, V. M. N. C. S.; Sahlée, E.; Jurus, P.; Clementi, E.; Pettersson, H.; Mateus, M.
2015-09-01
Earth-System and regional models, forecasting climate change and its impacts, simulate atmosphere-ocean gas exchanges using classical yet too simple generalizations relying on wind speed as the sole mediator while neglecting factors as sea-surface agitation, atmospheric stability, current drag with the bottom, rain and surfactants. These were proved fundamental for accurate estimates, particularly in the coastal ocean, where a significant part of the atmosphere-ocean greenhouse gas exchanges occurs. We include several of these factors in a customizable algorithm proposed for the basis of novel couplers of the atmospheric and oceanographic model components. We tested performances with measured and simulated data from the European coastal ocean, having found our algorithm to forecast greenhouse gas exchanges largely different from the forecasted by the generalization currently in use. Our algorithm allows calculus vectorization and parallel processing, improving computational speed roughly 12× in a single cpu core, an essential feature for Earth-System models applications.
Structure-preserving and rank-revealing QR-factorizations
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bischof, C.H.; Hansen, P.C.
1991-11-01
The rank-revealing QR-factorization (RRQR-factorization) is a special QR-factorization that is guaranteed to reveal the numerical rank of the matrix under consideration. This makes the RRQR-factorization a useful tool in the numerical treatment of many rank-deficient problems in numerical linear algebra. In this paper, a framework is presented for the efficient implementation of RRQR algorithms, in particular, for sparse matrices. A sparse RRQR-algorithm should seek to preserve the structure and sparsity of the matrix as much as possible while retaining the ability to capture safely the numerical rank. To this end, the paper proposes to compute an initial QR-factorization using amore » restricted pivoting strategy guarded by incremental condition estimation (ICE), and then applies the algorithm suggested by Chan and Foster to this QR-factorization. The column exchange strategy used in the initial QR factorization will exploit the fact that certain column exchanges do not change the sparsity structure, and compute a sparse QR-factorization that is a good approximation of the sought-after RRQR-factorization. Due to quantities produced by ICE, the Chan/Foster RRQR algorithm can be implemented very cheaply, thus verifying that the sought-after RRQR-factorization has indeed been computed. Experimental results on a model problem show that the initial QR-factorization is indeed very likely to produce RRQR-factorization.« less
Dispersive approach to two-photon exchange in elastic electron-proton scattering
Blunden, P. G.; Melnitchouk, W.
2017-06-14
We examine the two-photon exchange corrections to elastic electron-nucleon scattering within a dispersive approach, including contributions from both nucleon and Δ intermediate states. The dispersive analysis avoids off-shell uncertainties inherent in traditional approaches based on direct evaluation of loop diagrams, and guarantees the correct unitary behavior in the high energy limit. Using empirical information on the electromagnetic nucleon elastic and NΔ transition form factors, we compute the two-photon exchange corrections both algebraically and numerically. Finally, results are compared with recent measurements of e + p to e - p cross section ratios from the CLAS, VEPP-3 and OLYMPUS experiments.
In-pore exchange and diffusion of carbonate solvent mixtures in nanoporous carbon
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.
Rick, M E; Austin, H; Leitman, S F; Krizek, D M; Aronson, D L
2004-02-01
Decreased von Willebrand factor cleaving protease activity (VWFCP, ADAMTS 13) leads to persistence of unusually large multimers of von Willebrand factor that bind to platelets, causing platelet aggregates, microangiopathic hemolysis, and thrombocytopenia in patients with thrombotic thrombocytopenic purpura (TTP). The clinical value of measuring ADAMTS 13 and its inhibitor is not fully defined; the case reported here illustrates the usefulness of the assay to help confirm the clinical diagnosis in a patient with other potential causes for thrombotic microangiopathy; the assay also helped in making treatment decisions. A patient with systemic lupus erythematosis (SLE) presented with fever and abdominal pain, thrombocytopenia, and anemia. Thrombotic microangiopathy was diagnosed by the appearance of schistocytes, decreasing platelet count, and evidence of hemolysis. ADAMTS 13 was decreased and an inhibitor was demonstrated in the patient's initial blood sample within 24 hr of admission. Plasma exchange was initiated, and serial assays showed increased ADAMTS 13 activity and decreased inhibitor after each plasma exchange; there was a rebound in inhibitor and a decrease in ADAMTS 13 activity prior to the next exchange that lessened over time. Increasing levels of protease activity correlated with clinical and laboratory improvement. Measurement of ADAMTS 13 activity and its inhibitor aided in the diagnosis of this complicated case of a patient with other potential causes for microangiopathic hemolysis. Subsequent levels correlated with the clinical course, and disappearance of the inhibitor indicated that long-term plasma exchange or other immunosuppressive treatment was not needed.
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...
2012-06-01
Communalities – Factor Analysis .................................................................... 30 Table 3. Total Variance Explained – Factor Analysis...43 Table 12. Pearson Correlation...standards of corporate values and allying oneself with exchange partners having similar values, (3) communicating valuable information, including
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.
Optimization of the Heat Exchangers of a Thermoelectric Generation System
NASA Astrophysics Data System (ADS)
Martínez, A.; Vián, J. G.; Astrain, D.; Rodríguez, A.; Berrio, I.
2010-09-01
The thermal resistances of the heat exchangers have a strong influence on the electric power produced by a thermoelectric generator. In this work, the heat exchangers of a thermoelectric generator have been optimized in order to maximize the electric power generated. This thermoelectric generator harnesses heat from the exhaust gas of a domestic gas boiler. Statistical design of experiments was used to assess the influence of five factors on both the electric power generated and the pressure drop in the chimney: height of the generator, number of modules per meter of generator height, length of the fins of the hot-side heat exchanger (HSHE), length of the gap between fins of the HSHE, and base thickness of the HSHE. The electric power has been calculated using a computational model, whereas Fluent computational fluid dynamics (CFD) has been used to obtain the thermal resistances of the heat exchangers and the pressure drop. Finally, the thermoelectric generator has been optimized, taking into account the restrictions on the pressure drop.
NASA Technical Reports Server (NTRS)
Massman, William J.
1987-01-01
The semianalytical model outlined in a previous study (Massman, 1987) to describe momentum exchange between the atmosphere and vegetated surfaces is extended to include the exchange of heat. The methods employed are based on one-dimensional turbulent diffusivities, and use analytical solutions to the steady-state diffusion equation. The model is used to assess the influence that the canopy foliage structure and density, the wind profile structure within the canopy, and the shelter factor can have upon the inverse surface Stanton number (kB exp -1), as well as to explore the consequences of introducing a scalar displacement height which can be different from the momentum displacement height. In general, the triangular foliage area density function gives results which agree more closely with observations than that for constant foliage area density. The intended application of this work is for parameterizing the bulk aerodynamic resistances for heat and momentum exchange for use within large-scale models of plant-atmosphere exchanges.
Spin Exchange Interaction in Substituted Copper Phthalocyanine Crystalline Thin Films
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
Spin Exchange Interaction in Substituted Copper Phthalocyanine Crystalline Thin Films.
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.
Real-time observation of cation exchange kinetics and dynamics at the muscovite-water interface
Lee, Sang Soo; Fenter, Paul; Nagy, Kathryn L.; Sturchio, Neil C.
2017-01-01
Ion exchange at charged solid–liquid interfaces is central to a broad range of chemical and transport phenomena. Real-time observations of adsorption/desorption at the molecular-scale elucidate exchange reaction pathways. Here we report temporal variation in the distribution of Rb+ species at the muscovite (001)–water interface during exchange with Na+. Time-resolved resonant anomalous X-ray reflectivity measurements at 25 °C reveal that Rb+ desorption occurs over several tens of seconds during which thermodynamically stable inner-sphere Rb+ slowly transforms to a less stable outer-sphere Rb+. In contrast, Rb+ adsorption is about twice as fast, proceeding from Rb+ in the bulk solution to the stable inner-sphere species. The Arrhenius plot of the adsorption/desorption rate constants measured from 9 to 55 °C shows that the pre-exponential factor for desorption is significantly smaller than that for adsorption, indicating that this reduced attempt frequency of cation detachment largely explains the slow cation exchange processes at the interface. PMID:28598428
Effect of ionophores on the rate of intramolecular cation exchange in durosemiquinone ion pairs
NASA Technical Reports Server (NTRS)
Eastman, M. P.; Bruno, G. V.; Mcguyer, C. A.; Gutierrez, A. R.; Shannon, J. M.
1979-01-01
The effects of the ionophores 15-crown-5 (15C5), 18-crown-6 (18C6), dibenzo-18-crown-6 (DBC) and cryptand 222 (C222) on intramolecular cation exchange in ion pairs of the sodium salt of the durosemiquinone anion in benzene solution are investigated. Electron paramagnetic resonance spectra of the 18C6 and 15C5 complexes with durosemiquinone reduced by contact with a sodium mirror show an alternating line width which indicates that the sodium ion is being exchanged between equivalent sites near the oxygens of the semiquinone with activation energies of 8.7 and 6.0 kcal/mole and Arrhenius preexponential factors of 9 x 10 to the 12th/sec and 10 to the 12th/sec, respectively. Spectra obtained for the DBC complexes show no evidence of exchange, while those of C222 indicate rapid exchange. It is also noted that the hyperfine splitting constants measured do not change over the 50-K temperature interval studied.
DAILY SOCIAL EXCHANGES AND AFFECT IN MIDDLE AND LATER ADULTHOOD: THE IMPACT OF LONELINESS AND AGE*
RUSSELL, ALISSA; BERGEMAN, C. S.; SCOTT, STACEY B.
2013-01-01
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 investigated whether loneliness or age moderate the relationship between daily affect and daily social exchanges with family and friends. Results indicated differences between events involving family and those involving friends. Furthermore, lonelier individuals benefitted more from positive events than less lonely adults but were not more negatively reactive to negative events. Moreover, results suggested that older adults’ affect is more independent of both positive and negative social events compared to younger people. Implications are discussed for the importance of daily social exchanges, daily social stress vulnerability, and the influences of loneliness across middle and later adulthood. PMID:22950350
Statistical approach to partial equilibrium analysis
NASA Astrophysics Data System (ADS)
Wang, Yougui; Stanley, H. E.
2009-04-01
A statistical approach to market equilibrium and efficiency analysis is proposed in this paper. One factor that governs the exchange decisions of traders in a market, named willingness price, is highlighted and constitutes the whole theory. The supply and demand functions are formulated as the distributions of corresponding willing exchange over the willingness price. The laws of supply and demand can be derived directly from these distributions. The characteristics of excess demand function are analyzed and the necessary conditions for the existence and uniqueness of equilibrium point of the market are specified. The rationing rates of buyers and sellers are introduced to describe the ratio of realized exchange to willing exchange, and their dependence on the market price is studied in the cases of shortage and surplus. The realized market surplus, which is the criterion of market efficiency, can be written as a function of the distributions of willing exchange and the rationing rates. With this approach we can strictly prove that a market is efficient in the state of equilibrium.
Acidity and hydrogen exchange dynamics of iron(II)-bound nitroxyl in aqueous solution.
Gao, Yin; Toubaei, Abouzar; Kong, Xianqi; Wu, Gang
2014-10-20
Nitroxyl-iron(II) (HNO-Fe(II)) complexes are often unstable in aqueous solution, thus making them very difficult to study. Consequently, many fundamental chemical properties of Fe(II)-bound HNO have remained unknown. Using a comprehensive multinuclear ((1)H, (15)N, (17)O) NMR approach, the acidity of the Fe(II)-bound HNO in [Fe(CN)5(HNO)](3-) was investigated and its pK(a) value was determined to be greater than 11. Additionally, HNO undergoes rapid hydrogen exchange with water in aqueous solution and this exchange process is catalyzed by both acid and base. The hydrogen exchange dynamics for the Fe(II)-bound HNO have been characterized and the obtained benchmark values, when combined with the literature data on proteins, reveal that the rate of hydrogen exchange for the Fe(II)-bound HNO in the interior of globin proteins is reduced by a factor of 10(6). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Multi-Resolution Rapid Prototyping of Vehicle Cooling Systems: Approach and Test Results
2014-08-01
where the A/C was working. Figure 21: Comparison model/experiment for condenser refrigerant power; heat transfer factor = 0.8 The figure...previously. To demonstrate stable interactions with a more realistic environment, we have connected the four heat exchangers (two radiators, condenser ...simulations of any vehicle (or other) cooling systems. It can be seen that the underHood heat exchangers (transaxle radiator, condenser and ICE
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
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.
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
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.
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.
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.
Dynamics of T-Junction Solution Switching Aimed at Patch Clamp Experiments
Auzmendi, Jerónimo A.; Smoler, Mariano; Moffatt, Luciano
2015-01-01
Solutions exchange systems are responsible for the timing of drug application on patch clamp experiments. There are two basic strategies for generating a solution exchange. When slow exchanges are bearable, it is easier to perform the exchange inside the tubing system upstream of the exit port. On the other hand, fast, reproducible, exchanges are usually performed downstream of the exit port. As both strategies are combinable, increasing the performance of upstream exchanges is desirable. We designed a simple method for manufacturing T-junctions (300 μm I.D.) and we measured the time profile of exchange of two saline solutions using a patch pipette with an open tip. Three factors were found to determine the timing of the solution switching: pressure, travelled distance and off-center distance. A linear relationship between the time delay and the travelled distance was found for each tested pressure, showing its dependence to the fluid velocity, which increased with pressure. The exchange time was found to increase quadratically with the delay, although a sizeable variability remains unexplained by this relationship. The delay and exchange times increased as the recording pipette moved away from the center of the stream. Those increases became dramatic as the pipette was moved close to the stream borders. Mass transport along the travelled distance between the slow fluid at the border and the fast fluid at the center seems to contribute to the time course of the solution exchange. This effect would be present in all tubing based devices. Present results might be of fundamental importance for the adequate design of serial compound exchangers which would be instrumental in the discovery of drugs that modulate the action of the physiological agonists of ion channels with the purpose of fine tuning their physiology. PMID:26177538
Long-range-corrected Rung 3.5 density functional approximations
NASA Astrophysics Data System (ADS)
Janesko, Benjamin G.; Proynov, Emil; Scalmani, Giovanni; Frisch, Michael J.
2018-03-01
Rung 3.5 functionals are a new class of approximations for density functional theory. They provide a flexible intermediate between exact (Hartree-Fock, HF) exchange and semilocal approximations for exchange. Existing Rung 3.5 functionals inherit semilocal functionals' limitations in atomic cores and density tails. Here we address those limitations using range-separated admixture of HF exchange. We present three new functionals. LRC-ωΠLDA combines long-range HF exchange with short-range Rung 3.5 ΠLDA exchange. SLC-ΠLDA combines short- and long-range HF exchange with middle-range ΠLDA exchange. LRC-ωΠLDA-AC incorporates a combination of HF, semilocal, and Rung 3.5 exchange in the short range, based on an adiabatic connection. We test these in a new Rung 3.5 implementation including up to analytic fourth derivatives. LRC-ωΠLDA and SLC-ΠLDA improve atomization energies and reaction barriers by a factor of 8 compared to the full-range ΠLDA. LRC-ωΠLDA-AC brings further improvement approaching the accuracy of standard long-range corrected schemes LC-ωPBE and SLC-PBE. The new functionals yield highest occupied orbital energies closer to experimental ionization potentials and describe correctly the weak charge-transfer complex of ethylene and dichlorine and the hole-spin distribution created by an Al defect in quartz. This study provides a framework for more flexible range-separated Rung 3.5 approximations.
Effect of market factors on the short-time pricing of stock-exchange metals
NASA Astrophysics Data System (ADS)
Bogdanov, S. V.; Shevelev, I. M.; Chernyi, S. A.
2016-12-01
The open trade on the world market is estimated using information of one-day exchange prices of nonferrous and precious metals, oil, reduced crude, and gasoline and the main world stock indices in the time period from January 1, 2009 to December 31, 2015. It is found that the short-term changes in the prices of nonferrous metals are determined by the prices on the metal market. The changes in the prices of energy carriers and the stock trade on the stock market weakly influence the pricing of nonferrous and precious metals. The prices of metals depend on the situation during trade on commodity exchanges, and the stock market indirectly influences the exchange prices of metals through changes in the share prices of the companies that produce copper, aluminum, and zinc.
High resolution main-ion charge exchange spectroscopy in the DIII-D H-mode pedestal
Grierson, B. A.; Burrell, K. H.; Chrystal, C.; ...
2016-09-12
A new high spatial resolution main-ion (deuterium) charge-exchange spectroscopy system covering the tokamak boundary region has been installed on the DIII-D tokamak. Sixteen new edge main-ion charge-exchange recombination sightlines have been combined with nineteen impurity sightlines in a tangentially viewing geometry on the DIII-D midplane with an interleaving design that achieves 8 mm inter-channel radial resolution for detailed profiles of main-ion temperature, velocity, charge-exchange emission, and neutral beam emission. At the plasma boundary, we find a strong enhancement of the main-ion toroidal velocity that exceeds the impurity velocity by a factor of two. Furthermore, the unique combination of experimentally measuredmore » main-ion and impurity profiles provides a powerful quasi-neutrality constraint for reconstruction of tokamak H-mode pedestals.« less
NASA Astrophysics Data System (ADS)
Güven, O.; Melville, J. G.; Molz, F. J.
1983-06-01
Analytical expressions are derived for the temperature distribution and the mean temperature of an idealized aquifer thermal energy storage (ATES) system, taking into account the heat exchange at the ground surface and the finite thickness of the overlying layer above the storage aquifer. The analytical expressions for the mean temperature may be used to obtain rough estimates of first-cycle recovery factors for preliminary evaluations of shallow confined or unconfined ATES systems. The results, which are presented in nondimensional plots, indicate that surface heat exchange may have a significant influence on the thermal behavior of shallow ATES systems. Thus it is suggested that the effects of surface heat exchange should be considered carefully and included in the detailed analyses of such ATES systems.
Singh, Prashant; Harbola, Manoj K.; Johnson, Duane D.
2017-09-08
Here, this work constitutes a comprehensive and improved account of electronic-structure and mechanical properties of silicon-nitride (more » $${\\rm Si}_{3}$$ $${\\rm N}_{4}$$ ) polymorphs via van Leeuwen and Baerends (LB) exchange-corrected local density approximation (LDA) that enforces the exact exchange potential asymptotic behavior. The calculated lattice constant, bulk modulus, and electronic band structure of $${\\rm Si}_{3}$$ $${\\rm N}_{4}$$ polymorphs are in good agreement with experimental results. We also show that, for a single electron in a hydrogen atom, spherical well, or harmonic oscillator, the LB-corrected LDA reduces the (self-interaction) error to exact total energy to ~10%, a factor of three to four lower than standard LDA, due to a dramatically improved representation of the exchange-potential.« less
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...
Federal Register 2010, 2011, 2012, 2013, 2014
2013-02-21
... risk factor component of its credit default swap (``CDS'') margin model. CME proposes to use an index... with the liquidity risk factor component. The proposed rule change was published for comment in the... on Proposed Rule Change Related to the Liquidity Factor of CME's CDS Margin Methodology February 14...
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.
Choice of the replacement fluid during large volume plasma-exchange.
Nydegger, U E
1983-01-01
The replacement fluid used during therapeutic large volume plasma-exchange can be seen as an important factor influencing the result of such treatment. The choice includes fluids such as electrolyte solutions, gelatin, hydroxyethyl-starch, albumin and fresh frozen plasma. By evaluating the pathophysiology of the underlying disease, it is possible to choose between merely replacing the removed volume by non-protein fluids or rather to introduce plasma protein components into the patient's circulation by substituting with purified or enriched proteins such as albumin, clotting factors, antithrombin III or fresh frozen plasma. This paper analyzes the rationale for the choice of the appropriate replacement fluid taking into account pathophysiologic, pharmacologic and logistic criteria.
Brocklebank, Vicky; Johnson, Sally; Sheerin, Thomas P; Marks, Stephen D; Gilbert, Rodney D; Tyerman, Kay; Kinoshita, Meredith; Awan, Atif; Kaur, Amrit; Webb, Nicholas; Hegde, Shivaram; Finlay, Eric; Fitzpatrick, Maggie; Walsh, Patrick R; Wong, Edwin K S; Booth, Caroline; Kerecuk, Larissa; Salama, Alan D; Almond, Mike; Inward, Carol; Goodship, Timothy H; Sheerin, Neil S; Marchbank, Kevin J; Kavanagh, David
2017-11-01
Factor H autoantibodies can impair complement regulation, resulting in atypical hemolytic uremic syndrome, predominantly in childhood. There are no trials investigating treatment, and clinical practice is only informed by retrospective cohort analysis. Here we examined 175 children presenting with atypical hemolytic uremic syndrome in the United Kingdom and Ireland for factor H autoantibodies that included 17 children with titers above the international standard. Of the 17, seven had a concomitant rare genetic variant in a gene encoding a complement pathway component or regulator. Two children received supportive treatment; both developed established renal failure. Plasma exchange was associated with a poor rate of renal recovery in seven of 11 treated. Six patients treated with eculizumab recovered renal function. Contrary to global practice, immunosuppressive therapy to prevent relapse in plasma exchange-treated patients was not adopted due to concerns over treatment-associated complications. Without immunosuppression, the relapse rate was high (five of seven). However, reintroduction of treatment resulted in recovery of renal function. All patients treated with eculizumab achieved sustained remission. Five patients received renal transplants without specific factor H autoantibody-targeted treatment with recurrence in one who also had a functionally significant CFI mutation. Thus, our current practice is to initiate eculizumab therapy for treatment of factor H autoantibody-mediated atypical hemolytic uremic syndrome rather than plasma exchange with or without immunosuppression. Based on this retrospective analysis we see no suggestion of inferior treatment, albeit the strength of our conclusions is limited by the small sample size. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
Hoffmann, Christian V; Pell, Reinhard; Lämmerhofer, Michael; Lindner, Wolfgang
2008-11-15
In an attempt to overcome the limited applicability scope of earlier proposed Cinchona alkaloid-based chiral weak anion exchangers (WAX) and recently reported aminosulfonic acid-based chiral strong cation exchangers (SCX), which are conceptionally restricted to oppositely charged solutes, their individual chiral selector (SO) subunits have been fused in a combinatorial synthesis approach into single, now zwitterionic, chiral SO motifs. The corresponding zwitterionic ion-exchange-type chiral stationary phases (CSPs) in fact combined the applicability spectra of the parent chiral ion exchangers allowing for enantioseparations of chiral acids and amine-type solutes in liquid chromatography using polar organic mode with largely rivaling separation factors as compared to the parent WAX and SCX CSPs. Furthermore, the application spectrum could be remarkably expanded to various zwitterionic analytes such as alpha- and beta-amino acids and peptides. A set of structurally related yet different CSPs consisting of either a quinine or quinidine alkaloid moiety as anion-exchange subunit and various chiral or achiral amino acids as cation-exchange subunits enabled us to derive structure-enantioselectivity relationships, which clearly provided strong unequivocal evidence for synergistic effects of the two oppositely charged ion-exchange subunits being involved in molecular recognition of zwitterionic analytes by zwitterionic SOs driven by double ionic coordination.
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.
Wang, Yujue; Liu, Dongyan; Dong, Zhijun; Di, Baoping; Shen, Xuhong
2012-12-01
The temporal and spatial distributions of dissolved inorganic nitrogen (DIN), dissolved organic nitrogen (DON), soluble reactive phosphorus (SRP) and dissolved reactive silica (DRSi) together with chlorophyll-a, temperature and salinity were analyzed monthly from December 2008 to March 2010 at four zones in Sishili Bay located in the northern Yellow Sea. The nutrient distribution was impacted by seasonal factors (biotic factors, temperature and wet deposition), physical factors (water exchange) and anthropogenic loadings. The seasonal variations of nutrients were mainly determined by the seasonal factors and the spatial distribution of nutrients was mainly related to water exchange. Anthropogenic loadings for DIN, SRP and DRSi were mainly from point sources, but for DON, non-point sources were also important. Nutrient limitation has changed from DIN in 1997 to SRP and DRSi in 2010, and this has resulted in changes in the dominant red tide species from diatom to dinoflagellates. Copyright © 2012 Elsevier Ltd. All rights reserved.
Respiratory gas exchange of high altitude adapted chick embryos
NASA Technical Reports Server (NTRS)
Wangensteen, O. D.; Rahn, H.; Burton, R. R.; Smith, A. H.
1974-01-01
Study of gas exchange by embryos from chickens acclimatized to an altitude of 3800 m. The oxygen partial pressure and carbon dioxide partial pressure differences across the egg shell were measured and found to be less than the values previously reported for sea-level eggs by about a factor of two. Further measurements of embryonic oxygen consumption and shell conductivity to oxygen indicated that, compared to eggs at sea level, oxygen consumption was reduced by a factor of 0.58 while conductivity to oxygen was increased only by a factor of 1.07 in the high-altitude eggs. These independent measurements predict the change in oxygen partial pressure across the egg shell of the high-altitude eggs to be only 0.54 times that of sea-level eggs; the directly measured factor was 0.53. The authors conclude that at high altitude, a major adaptation of the chick embryo is a reduced metabolism which decreases the change in oxygen partial pressure across the egg shell since its gas conductivity remains essentially unchanged.
Impacts of Changes of Indoor Air Pressure and Air Exchange Rate in Vapor Intrusion Scenarios
Shen, Rui; Suuberg, Eric M.
2016-01-01
There has, in recent years, been increasing interest in understanding the transport processes of relevance in vapor intrusion of volatile organic compounds (VOCs) into buildings on contaminated sites. These studies have included fate and transport modeling. Most such models have simplified the prediction of indoor air contaminant vapor concentrations by employing a steady state assumption, which often results in difficulties in reconciling these results with field measurements. This paper focuses on two major factors that may be subject to significant transients in vapor intrusion situations, including the indoor air pressure and the air exchange rate in the subject building. A three-dimensional finite element model was employed with consideration of daily and seasonal variations in these factors. From the results, the variations of indoor air pressure and air exchange rate are seen to contribute to significant variations in indoor air contaminant vapor concentrations. Depending upon the assumptions regarding the variations in these parameters, the results are only sometimes consistent with the reports of several orders of magnitude in indoor air concentration variations from field studies. The results point to the need to examine more carefully the interplay of these factors in order to quantitatively understand the variations in potential indoor air exposures. PMID:28090133
Impacts of Changes of Indoor Air Pressure and Air Exchange Rate in Vapor Intrusion Scenarios.
Shen, Rui; Suuberg, Eric M
2016-02-01
There has, in recent years, been increasing interest in understanding the transport processes of relevance in vapor intrusion of volatile organic compounds (VOCs) into buildings on contaminated sites. These studies have included fate and transport modeling. Most such models have simplified the prediction of indoor air contaminant vapor concentrations by employing a steady state assumption, which often results in difficulties in reconciling these results with field measurements. This paper focuses on two major factors that may be subject to significant transients in vapor intrusion situations, including the indoor air pressure and the air exchange rate in the subject building. A three-dimensional finite element model was employed with consideration of daily and seasonal variations in these factors. From the results, the variations of indoor air pressure and air exchange rate are seen to contribute to significant variations in indoor air contaminant vapor concentrations. Depending upon the assumptions regarding the variations in these parameters, the results are only sometimes consistent with the reports of several orders of magnitude in indoor air concentration variations from field studies. The results point to the need to examine more carefully the interplay of these factors in order to quantitatively understand the variations in potential indoor air exposures.
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.
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.
Vo, Uybach; Vajpai, Navratna; Flavell, Liz; Bobby, Romel; Breeze, Alexander L; Embrey, Kevin J; Golovanov, Alexander P
2016-01-22
The activity of Ras is controlled by the interconversion between GTP- and GDP-bound forms partly regulated by the binding of the guanine nucleotide exchange factor Son of Sevenless (Sos). The details of Sos binding, leading to nucleotide exchange and subsequent dissociation of the complex, are not completely understood. Here, we used uniformly (15)N-labeled Ras as well as [(13)C]methyl-Met,Ile-labeled Sos for observing site-specific details of Ras-Sos interactions in solution. Binding of various forms of Ras (loaded with GDP and mimics of GTP or nucleotide-free) at the allosteric and catalytic sites of Sos was comprehensively characterized by monitoring signal perturbations in the NMR spectra. The overall affinity of binding between these protein variants as well as their selected functional mutants was also investigated using intrinsic fluorescence. The data support a positive feedback activation of Sos by Ras·GTP with Ras·GTP binding as a substrate for the catalytic site of activated Sos more weakly than Ras·GDP, suggesting that Sos should actively promote unidirectional GDP → GTP exchange on Ras in preference of passive homonucleotide exchange. Ras·GDP weakly binds to the catalytic but not to the allosteric site of Sos. This confirms that Ras·GDP cannot properly activate Sos at the allosteric site. The novel site-specific assay described may be useful for design of drugs aimed at perturbing Ras-Sos interactions. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Building and strengthening infrastructure for data exchange: lessons from the beacon communities.
Torres, Gretchen W; Swietek, Karen; Ubri, Petry S; Singer, Rachel F; Lowell, Kristina H; Miller, Wilhelmine
2014-01-01
The Beacon Community Cooperative Agreement Program supports interventions, including care-delivery innovations, provider performance measurement and feedback initiatives, and tools for providers and consumers to enhance care. Using a learning health system framework, we examine the Beacon Communities' processes in building and strengthening health IT (HIT) infrastructures, specifically successes and challenges in sharing patient information to improve clinical care. In 2010, the Office of the National Coordinator for Health Information Technology (ONC) launched the three-year program, which provided $250 million to 17 Beacon Communities to invest in HIT and health information exchange (HIE) infrastructure. Beacon Communities used this funding to develop and disseminate HIT-enabled quality improvement practices found effective in particular community and practice environments. NORC conducted 7 site visits, November 2012-March 2013, selecting Communities to represent diverse program features. From August-October 2013, NORC held discussions with the remaining 10 Communities. Following each visit or discussion, NORC summarized the information gathered, including transcripts, team observations, and other documents the Community provided, to facilitate a within-Community analysis of context and stakeholders, intervention strategies, enabling factors, and challenges. Although each Community designed and implemented data-sharing strategies in a unique environment, similar challenges and enabling factors emerged across the Beacons. From a learning health system perspective, their strategies to build and strengthen data-sharing infrastructures address the following crosscutting priorities: promoting technical advances and innovations by helping providers adapt EHRs for data exchange and performance measurement with customizable IT and offering technical support to smaller, independent providers; engaging key stakeholders; and fostering transparent governance and stewardship of the infrastructure with neutral conveners. While all the Communities developed or strengthened data-exchange infrastructure, each did this in a unique environment of existing health care market and legal factors. The Communities, however, encountered similar challenges and enabling factors. Organizations undertaking collaborative data sharing, performance measurement and clinical transformation can learn from the Beacon Communities' experience.
Building and Strengthening Infrastructure for Data Exchange: Lessons from the Beacon Communities
Torres, Gretchen W.; Swietek, Karen; Ubri, Petry S.; Singer, Rachel F.; Lowell, Kristina H.; Miller, Wilhelmine
2014-01-01
Introduction: The Beacon Community Cooperative Agreement Program supports interventions, including care-delivery innovations, provider performance measurement and feedback initiatives, and tools for providers and consumers to enhance care. Using a learning health system framework, we examine the Beacon Communities’ processes in building and strengthening health IT (HIT) infrastructures, specifically successes and challenges in sharing patient information to improve clinical care. Background: In 2010, the Office of the National Coordinator for Health Information Technology (ONC) launched the three-year program, which provided $250 million to 17 Beacon Communities to invest in HIT and health information exchange (HIE) infrastructure. Beacon Communities used this funding to develop and disseminate HIT-enabled quality improvement practices found effective in particular community and practice environments. Methods: NORC conducted 7 site visits, November 2012–March 2013, selecting Communities to represent diverse program features. From August–October 2013, NORC held discussions with the remaining 10 Communities. Following each visit or discussion, NORC summarized the information gathered, including transcripts, team observations, and other documents the Community provided, to facilitate a within-Community analysis of context and stakeholders, intervention strategies, enabling factors, and challenges. Results: Although each Community designed and implemented data-sharing strategies in a unique environment, similar challenges and enabling factors emerged across the Beacons. From a learning health system perspective, their strategies to build and strengthen data-sharing infrastructures address the following crosscutting priorities: promoting technical advances and innovations by helping providers adapt EHRs for data exchange and performance measurement with customizable IT and offering technical support to smaller, independent providers; engaging key stakeholders; and fostering transparent governance and stewardship of the infrastructure with neutral conveners. Conclusion: While all the Communities developed or strengthened data-exchange infrastructure, each did this in a unique environment of existing health care market and legal factors. The Communities, however, encountered similar challenges and enabling factors. Organizations undertaking collaborative data sharing, performance measurement and clinical transformation can learn from the Beacon Communities’ experience. PMID:25848619
Gendered Pathways: Violent Childhood Maltreatment, Sex Exchange, and Drug Use.
Verona, Edelyn; Murphy, Brett; Javdani, Shabnam
2015-04-20
Recent work has emphasized the role of violent victimization, along with risky contexts like sex exchange, in pathways to problems of externalizing and substance use in women. Nonetheless, few studies have empirically tested gender differences involving the roles of adversity factors (e.g., childhood violent maltreatment, sex exchange) in drug use patterns. The present study tested a model of gender differences in relationships between childhood physical and sexual abuse, sex exchange, and two indicators of drug use: engagement and symptoms of disorder. We recruited an ethnically-diverse sample of 304 (130 women) adults with recent histories of violence and/or drug use, who completed a substance use diagnostic interview, the Childhood Trauma Questionnaire, and a sex exchange questionnaire. First, structural equation modeling revealed that childhood sexual and physical abuse were related to increased drug engagement in women and men, respectively, above the influence of early childhood contextual variables (e.g., neighborhood, family) and age. Second, sexual abuse was related to sex exchange, which in turn was related to drug use symptoms in women but not men. These data provide empirical support for distinct trauma-related pathways to drug use problems in men and women, which has implications for gendered explanations and prevention approaches.
Niu, Xingliang; Luo, Jun; Xu, Deran; Zou, Hongyan; Kong, Lingyi
2017-02-05
Ginkgolides, the main active constituents of Ginkgo biloba, possess significant selectively inhibition on platelet-activating factor and pancreatic lipase and attract wide attention in pharmacological research area. In our study, an effective hydrogen/deuterium (H/D) exchange method was developed by exchanging the α-Hs of lactone groups in ginkgolides with Ds, which was very useful for the elucidation of the fragmentation patterns of ginkgolides in Quadrupole Time-of-flight Mass Spectrometry (Q-TOF-MS), especially in accurately distinguishing the type and position of substituent in framework of ginkgolides. Then, a systematic research strategy for qualitative and quantitative analysis of ginkgolides, based on H/D exchange, tandem solid-phase extraction and LC-Q-TOF-MS, was developed, which was successfully applied in each medicinal part of G. biloba, which indicated that ginkgolide B was the most abundant ginkgolide in the seeds of G. biloba (60.6μg/g). This research was the successful application of H/D exchange in natural products, and proved that H/D exchange is a potential method for analysis research of complex TCMs active constituents. Copyright © 2016 Elsevier B.V. All rights reserved.
Short-duration respirometry underestimates metabolic rate for discontinuous breathers.
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.
NASA Astrophysics Data System (ADS)
Ghasemi, Nahid; Aghayari, Reza; Maddah, Heydar
2018-07-01
The present study aims at optimizing the heat transmission parameters such as Nusselt number and friction factor in a small double pipe heat exchanger equipped with rotating spiral tapes cut as triangles and filled with aluminum oxide nanofluid. The effects of Reynolds number, twist ratio (y/w), rotating twisted tape and concentration (w%) on the Nusselt number and friction factor are also investigated. The central composite design and the response surface methodology are used for evaluating the responses necessary for optimization. According to the optimal curves, the most optimized value obtained for Nusselt number and friction factor was 146.6675 and 0.06020, respectively. Finally, an appropriate correlation is also provided to achieve the optimal model of the minimum cost. Optimization results showed that the cost has decreased in the best case.
NASA Astrophysics Data System (ADS)
Ghasemi, Nahid; Aghayari, Reza; Maddah, Heydar
2018-02-01
The present study aims at optimizing the heat transmission parameters such as Nusselt number and friction factor in a small double pipe heat exchanger equipped with rotating spiral tapes cut as triangles and filled with aluminum oxide nanofluid. The effects of Reynolds number, twist ratio (y/w), rotating twisted tape and concentration (w%) on the Nusselt number and friction factor are also investigated. The central composite design and the response surface methodology are used for evaluating the responses necessary for optimization. According to the optimal curves, the most optimized value obtained for Nusselt number and friction factor was 146.6675 and 0.06020, respectively. Finally, an appropriate correlation is also provided to achieve the optimal model of the minimum cost. Optimization results showed that the cost has decreased in the best case.
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.
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
Factors motivating and affecting health information exchange usage
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
20 CFR 418.3125 - What are redeterminations?
Code of Federal Regulations, 2010 CFR
2010-04-01
... from data exchanges with Federal and State agencies that may affect whether you should receive a full... random sample of cases for quality assurance purposes. For each collection of sample cases, all factors... with primary repositories of information relevant to each individual factor (e.g., we may contact...
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.
Study of groundwater arsenic pollution in Lanyang Plain using multivariate statistical analysis
NASA Astrophysics Data System (ADS)
chan, S.
2013-12-01
The study area, Lanyang Plain in the eastern Taiwan, has highly developed agriculture and aquaculture, which consume over 70% of the water supplies. Groundwater is frequently considered as an alternative water source. However, the serious arsenic pollution of groundwater in Lanyan Plain should be well studied to ensure the safety of groundwater usage. In this study, 39 groundwater samples were collected. The results of hydrochemistry demonstrate two major trends in Piper diagram. The major trend with most of groundwater samples is determined with water type between Ca+Mg-HCO3 and Na+K-HCO3. This can be explained with cation exchange reaction. The minor trend is obviously corresponding to seawater intrusion, which has water type of Na+K-Cl, because the localities of these samples are all in the coastal area. The multivariate statistical analysis on hydrochemical data was conducted for further exploration on the mechanism of arsenic contamination. Two major factors can be extracted with factor analysis. The major factor includes Ca, Mg and Sr while the minor factor includes Na, K and As. This reconfirms that cation exchange reaction mainly control the groundwater hydrochemistry in the study area. It is worth to note that arsenic is positively related to Na and K. The result of cluster analysis shows that groundwater samples with high arsenic concentration can be grouped into that with high Na, K and HCO3. This supports that cation exchange would enhance the release of arsenic and exclude the effect of seawater intrusion. In other words, the water-rock reaction time is key to obtain higher arsenic content. In general, the major source of arsenic in sediments include exchangeable, reducible and oxidizable phases, which are adsorbed ions, Fe-Mn oxides and organic matters/pyrite, respectively. However, the results of factor analysis do not show apparent correlation between arsenic and Fe/Mn. This may exclude Fe-Mn oxides as a major source of arsenic. The other sources will be evaluated by more trace elements, such as rare earth elements.
An effective field theory for forward scattering and factorization violation
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
NASA Technical Reports Server (NTRS)
Buschman, Albert J., Jr.; Pittman, Claud M.
1961-01-01
Radiation-interchange configuration factors are derived for axisymmetrical sections of cylinders, cones, and hemispheres radiating internally to annular and circular sections of their bases and to other axisymmetrical sections. The general procedure of obtaining configuration factors is outlined and the results are presented in the form of equations, tables, and figures.
Federal Register 2010, 2011, 2012, 2013, 2014
2013-01-11
...., observed sales and purchases). This allows for an analysis that controls for factors that may vary widely... those factors that affect providers' decisions to expand existing networks, e.g., the non-price factors... Street SW., Room CY-A257, Washington, DC 20554. The complete text may be purchased from Best Copy and...
Therapeutic Plasma Exchange in Critically Ill Children Requiring Intensive Care.
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.
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.
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.
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
Modeling of sorption processes on solid-phase ion-exchangers
NASA Astrophysics Data System (ADS)
Dorofeeva, Ludmila; Kuan, Nguyen Anh
2018-03-01
Research of alkaline elements separation on solid-phase ion-exchangers is carried out to define the selectivity coefficients and height of an equivalent theoretical stage for both continuous and stepwise filling of column by ionite. On inorganic selective sorbents the increase in isotope enrichment factor up to 0.0127 is received. Also, parametrical models that are adequately describing dependence of the pressure difference and the magnitude expansion in the ion-exchange layer from the flow rate and temperature have been obtained. The concentration rate value under the optimum realization conditions of process and depending on type of a selective material changes in a range 1.021÷1.092. Calculated results show agreement with experimental data.
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.
NASA Astrophysics Data System (ADS)
Chávez Muñoz, Pablo; Fernandes da Silva, Marcus; Vivas Miranda, José; Claro, Francisco; Gomez Diniz, Raimundo
2007-12-01
We have studied the performance of the Hurst's index associated with the currency exchange rate in Brazil and Chile. It is shown that this index maps the degree of government control in the exchange rate. A model of supply and demand based in an autonomous agent is proposed, that simulates a virtual market of sale and purchase, where buyer or seller are forced to negotiate through an intermediary. According to this model, the average of the price of daily transactions correspond to the theoretical balance proposed by the law of supply and demand. The influence of an added tendency factor is also analyzed.
Multi-scale evaporator architectures for geothermal binary power plants
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sabau, Adrian S; Nejad, Ali; Klett, James William
2016-01-01
In this paper, novel geometries of heat exchanger architectures are proposed for evaporators that are used in Organic Rankine Cycles. A multi-scale heat exchanger concept was developed by employing successive plenums at several length-scale levels. Flow passages contain features at both macro-scale and micro-scale, which are designed from Constructal Theory principles. Aside from pumping power and overall thermal resistance, several factors were considered in order to fully assess the performance of the new heat exchangers, such as weight of metal structures, surface area per unit volume, and total footprint. Component simulations based on laminar flow correlations for supercritical R134a weremore » used to obtain performance indicators.« less
Regulating the Regulator: Post-Translational Modification of Ras
Ahearn, Ian M.; Haigis, Kevin; Bar-Sagi, Dafna; Philips, Mark R.
2013-01-01
Ras proteins are monomeric GTPases that act as binary molecular switches to regulate a wide range of cellular processes. The exchange of GTP for GDP on Ras is regulated by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), which regulate the activation state of Ras without covalently modifying it. In contrast, post-translational modifications (PTMs) of Ras proteins direct them to various cellular membranes and, in some cases, modulate GTP–GDP exchange. Important Ras PTMs include the constitutive and irreversible remodelling of its C-terminal CAAX motif by farnesylation, proteolysis and methylation, reversible palmitoylation, and conditional modifications including phosphorylation, peptidyl-proly isomerisation, mono- and di-ubiquitination, nitrosylation, ADP ribosylation and glucosylation. PMID:22189424
Atomic sites and stability of Cs+ captured within zeolitic nanocavities
Yoshida, Kaname; Toyoura, Kazuaki; Matsunaga, Katsuyuki; Nakahira, Atsushi; Kurata, Hiroki; Ikuhara, Yumi H.; Sasaki, Yukichi
2013-01-01
Zeolites have potential application as ion-exchangers, catalysts and molecular sieves. Zeolites are once again drawing attention in Japan as stable adsorbents and solidification materials of fission products, such as 137Cs+ from damaged nuclear-power plants. Although there is a long history of scientific studies on the crystal structures and ion-exchange properties of zeolites for practical application, there are still open questions, at the atomic-level, on the physical and chemical origins of selective ion-exchange abilities of different cations and detailed atomic structures of exchanged cations inside the nanoscale cavities of zeolites. Here, the precise locations of Cs+ ions captured within A-type zeolite were analyzed using high-resolution electron microscopy. Together with theoretical calculations, the stable positions of absorbed Cs+ ions in the nanocavities are identified, and the bonding environment within the zeolitic framework is revealed to be a key factor that influences the locations of absorbed cations. PMID:23949184
Access to Health Care Services among Young People Exchanging Sex in Detroit.
Knittel, Andrea K; Graham, Louis F; Peterson, Jerry; Lopez, William; Snow, Rachel C
2018-04-05
Within the related epidemics of sex exchange, drug use, and poverty, access to health care is shaped by intersecting identities, policy, and infrastructure. This study uses a unique survey sample of young adults in Detroit, who are exchanging sex on the street, in strip clubs, and at after-hours parties and other social clubs. Factors predicting access to free or affordable health care services, such as venue, patterns of sexual exchange influence, drug use and access to transportation, were examined using multivariable logistic regression and qualitative comparative analysis. The most significant predictors of low access to health care services were unstable housing and lack of access to reliable transportation. In addition, working on the street was associated with decreased access to services. Coordinated policy and programming changes are needed to increase health care access to this group, including improved access to transportation, housing, and employment, and integration of health care services.
Advances in quantifying air-sea gas exchange and environmental forcing.
Wanninkhof, Rik; Asher, William E; Ho, David T; Sweeney, Colm; McGillis, Wade R
2009-01-01
The past decade has seen a substantial amount of research on air-sea gas exchange and its environmental controls. These studies have significantly advanced the understanding of processes that control gas transfer, led to higher quality field measurements, and improved estimates of the flux of climate-relevant gases between the ocean and atmosphere. This review discusses the fundamental principles of air-sea gas transfer and recent developments in gas transfer theory, parameterizations, and measurement techniques in the context of the exchange of carbon dioxide. However, much of this discussion is applicable to any sparingly soluble, non-reactive gas. We show how the use of global variables of environmental forcing that have recently become available and gas exchange relationships that incorporate the main forcing factors will lead to improved estimates of global and regional air-sea gas fluxes based on better fundamental physical, chemical, and biological foundations.
Najafpour, Mohammad Mahdi; Isaloo, Mohsen Abbasi; Eaton-Rye, Julian J; Tomo, Tatsuya; Nishihara, Hiroshi; Satoh, Kimiyuki; Carpentier, Robert; Shen, Jian-Ren; Allakhverdiev, Suleyman I
2014-09-01
The water-oxidizing complex (WOC), also known as the oxygen-evolving complex (OEC), of photosystem II in oxygenic photosynthetic organisms efficiently catalyzes water oxidation. It is, therefore, responsible for the presence of oxygen in the Earth's atmosphere. The WOC is a manganese-calcium (Mn₄CaO₅(H₂O)₄) cluster housed in a protein complex. In this review, we focus on water exchange chemistry of metal hydrates and discuss the mechanisms and factors affecting this chemical process. Further, water exchange rates for both the biological cofactor and synthetic manganese water splitting are discussed. The importance of fully unveiling the water exchange mechanism to understand the chemistry of water oxidation is also emphasized here. This article is part of a special issue entitled: photosynthesis research for sustainability: keys to produce clean energy. Copyright © 2014 Elsevier B.V. All rights reserved.
Skene, Williams G.; Lehn, Jean-Marie P.
2004-01-01
Component exchange in reversible polymers allows the generation of dynamic constitutional diversity. The polycondensation of dihydrazides with dialdehydes generates polyacylhydrazones, to which the acylhydrazone functionality formed confers both hydrogen-bonding and reversibility features through the amide and imine groups, respectively. Polyacylhydrazones are thus dynamic polyamides. They are able to reversibly exchange either one or both of their repeating monomer units in the presence of different monomers, thus presenting constitutional dynamic diversity. The polymers subjected to monomer exchange/interchange may be brought to exhibit physical properties vastly different from those of the original polymer. The principle may be extended to other important classes of polymers, giving access, for instance, to dynamic polyureas or polycarbamates. These reversible polymers are therefore able to incorporate, decorporate, or reshuffle their constituting monomers, namely in response to environmental physical or chemical factors, an adaptability feature central to constitutional dynamic chemistry. PMID:15150411
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.
Food Exchange List and Dietary Management of Non-Communicable Diseases in Cultural Perspective.
Khan, Mahnaz Nasir; Kalsoom, Samia; Khan, Ayyaz Ali
2017-01-01
This review focuses at highlighting the importance of Food Exchange List in cultural perspective, as an effective dietary tool to help individuals' manage their dietary modifications in relation to non communicable diseases whilst specifying measures that can help improve the quality of Food Exchange Lists for combating various non communicable diseases and addressing adherence related issues to specialized diets. A search was done using PubMed & Google Scholar till June 2016. Search terms used were food exchange list AND disease, diet AND non-communicable diseases. We included only studies that discussed Food Exchange List (FEL) in relation to non-communicable diseases; in addition to factors like cultural relevance and adherence. Out of the 837 papers accessed 57 were identified as relevant to the Food Exchange List, out of which 39 papers were focused to the concept and development of the Food Exchange List. Only 18 discussed FEL in relation to non communicable diseases and were thus included in the review. Food exchange list is a user friendly tool for dietary modification due to disease. This tool may help to customize meals for people as it provides information regarding various food items in different groups. This tool is helpful in reducing blood & plasma glucose levels, maintaining lipid profile & effectively combating other diet related diseases & those ailments in which diet plays a significant role in maintenance & prevention from reoccurrences. However, better management and adherence to modified diets for non communicable diseases can be ensured by keeping cultural relevance under consideration before using Food Exchange Lists for such diseases.
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.
Acetone and Water on TiO₂(110): H/D Exchange
DOE Office of Scientific and Technical Information (OSTI.GOV)
Henderson, Michael A.
2005-04-12
Isotopic H/D exchange between coadsorbed acetone and water on the TiO?(110) surface was examined using temperature programmed desorption (TPD) as a function of coverage and two surface pretreatments (oxidation and reduction). Coadsorbed acetone and water interact repulsively on reduced TiO?(110) based on results from the companion paper to this study, with water exerting a greater influence in destabilizing acetone and acetone having only a nominal influence on water. Despite the repulsive interaction between these coadsorbates, about 0.02 ML of a 1 ML d6-acetone on the reduced surface exhibits H/D exchange with coadsorbed water, with the exchange occurring exclusively in themore » high temperature region of the d?-acetone TPD spectrum at {approx}340 K. The effect was confirmed with combinations of d?-acetone and D?O. The extent of exchange decreased on the reduced surface with water coverages above {approx}0.3 ML due to the ability of water to displace coadsorbed acetone from first layer sites to the multilayer. In contrast, the extent of exchange increased by a factor of 3 when the surface was pre-oxidized prior to coadsorption. In this case, there was no evidence for the negative influence of high water coverages on the extent of H/D exchange. Comparison of the TPD spectra from the exchange products (either d?- or d?-acetone depending on the coadsorption pairing) suggests that, in addition to the 340 K exchange process seen on the reduced surface, a second exchange process was observed on the oxidized surface at {approx}390 K. In both cases (oxidized and reduced), desorption of the H/D exchange products appeared to be reaction limited and to involve the influence of OH/OD groups (or water formed during recombinative desorption of OH/OD groups) instead of molecularly adsorbed water. The 340 K exchange process is assigned to reaction at step sites and the 390 K exchange process is attributed to the influence of oxygen adatoms deposited during surface oxidation. The H/D exchange mechanism likely involves an enolate or propenol surface intermediate formed transiently during the desorption of oxygen-stabilized acetone molecules.« less
Semilocal density functional obeying a strongly tightened bound for exchange
Sun, Jianwei; Perdew, John P.; Ruzsinszky, Adrienn
2015-01-01
Because of its useful accuracy and efficiency, density functional theory (DFT) is one of the most widely used electronic structure theories in physics, materials science, and chemistry. Only the exchange-correlation energy is unknown, and needs to be approximated in practice. Exact constraints provide useful information about this functional. The local spin-density approximation (LSDA) was the first constraint-based density functional. The Lieb–Oxford lower bound on the exchange-correlation energy for any density is another constraint that plays an important role in the development of generalized gradient approximations (GGAs) and meta-GGAs. Recently, a strongly and optimally tightened lower bound on the exchange energy was proved for one- and two-electron densities, and conjectured for all densities. In this article, we present a realistic “meta-GGA made very simple” (MGGA-MVS) for exchange that respects this optimal bound, which no previous beyond-LSDA approximation satisfies. This constraint might have been expected to worsen predicted thermochemical properties, but in fact they are improved over those of the Perdew–Burke–Ernzerhof GGA, which has nearly the same correlation part. MVS exchange is however radically different from that of other GGAs and meta-GGAs. Its exchange enhancement factor has a very strong dependence upon the orbital kinetic energy density, which permits accurate energies even with the drastically tightened bound. When this nonempirical MVS meta-GGA is hybridized with 25% of exact exchange, the resulting global hybrid gives excellent predictions for atomization energies, reaction barriers, and weak interactions of molecules. PMID:25561554
Extratropical Stratosphere-Troposphere Mass Exchange
NASA Technical Reports Server (NTRS)
Schoeberl, Mark R.
2004-01-01
Understanding the exchange of gases between the stratosphere and the troposphere is important for determining how pollutants enter the stratosphere and how they leave. This study does a global analysis of that the exchange of mass between the stratosphere and the troposphere. While the exchange of mass is not the same as the exchange of constituents, you can t get the constituent exchange right if you have the mass exchange wrong. Thus this kind of calculation is an important test for models which also compute trace gas transport. In this study I computed the mass exchange for two assimilated data sets and a GCM. The models all agree that amount of mass descending from the stratosphere to the troposphere in the Northern Hemisphere extra tropics is approx. 10(exp 10) kg/s averaged over a year. The value for the Southern Hemisphere by about a factor of two. ( 10(exp 10) kg of air is the amount of air in 100 km x 100 km area with a depth of 100 m - roughly the size of the D.C. metro area to a depth of 300 feet.) Most people have the idea that most of the mass enters the stratosphere through the tropics. But this study shows that almost 5 times more mass enters the stratosphere through the extra-tropics. This mass, however, is quickly recycled out again. Thus the lower most stratosphere is a mixture of upper stratospheric air and tropospheric air. This is an important result for understanding the chemistry of the lower stratosphere.
Semilocal density functional obeying a strongly tightened bound for exchange.
Sun, Jianwei; Perdew, John P; Ruzsinszky, Adrienn
2015-01-20
Because of its useful accuracy and efficiency, density functional theory (DFT) is one of the most widely used electronic structure theories in physics, materials science, and chemistry. Only the exchange-correlation energy is unknown, and needs to be approximated in practice. Exact constraints provide useful information about this functional. The local spin-density approximation (LSDA) was the first constraint-based density functional. The Lieb-Oxford lower bound on the exchange-correlation energy for any density is another constraint that plays an important role in the development of generalized gradient approximations (GGAs) and meta-GGAs. Recently, a strongly and optimally tightened lower bound on the exchange energy was proved for one- and two-electron densities, and conjectured for all densities. In this article, we present a realistic "meta-GGA made very simple" (MGGA-MVS) for exchange that respects this optimal bound, which no previous beyond-LSDA approximation satisfies. This constraint might have been expected to worsen predicted thermochemical properties, but in fact they are improved over those of the Perdew-Burke-Ernzerhof GGA, which has nearly the same correlation part. MVS exchange is however radically different from that of other GGAs and meta-GGAs. Its exchange enhancement factor has a very strong dependence upon the orbital kinetic energy density, which permits accurate energies even with the drastically tightened bound. When this nonempirical MVS meta-GGA is hybridized with 25% of exact exchange, the resulting global hybrid gives excellent predictions for atomization energies, reaction barriers, and weak interactions of molecules.
Code of Federal Regulations, 2010 CFR
2010-10-01
... relationships and/or allocation factors. 36.3 Section 36.3 Telecommunication FEDERAL COMMUNICATIONS COMMISSION... of the acquiring company, the acquiring carrier shall first sum its existing (pre-purchase) access... category relationships for the acquiring carrier's post-transfer study area. (e) Any local exchange carrier...
SLA before ABC: Factors Facilitating Second Language Acquisition in Irish-Medium Playgroups.
ERIC Educational Resources Information Center
Mhathuna, Maire Mhic
1995-01-01
This study investigated factors facilitating acquisition of Irish in Irish-medium playgroups designed for children who are native English-speakers. Data were gathered in four visits each to two such playgroups, each containing approximately 20 children. Four aspects of conversational exchanges were examined: understanding; code mixing; formulaic…
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.
Proton and neutron electromagnetic form factors and uncertainties
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.
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).
Photoreactions of dissolved organic matter can affect the oxidizing capacity, nutrient dynamics, trace gas exchange, and color of surface waters. This study focuses on factors that affect the photoreactions of the colored dissolved organic matter (CDOM) in the Satilla River, a co...
An Investigation of Factors Associated with Student Participation in Study Abroad
ERIC Educational Resources Information Center
Doyle, Stephanie; Gendall, Philip; Meyer, Luanna H.; Hoek, Janet; Tait, Carolyn; McKenzie, Lynanne; Loorparg, Avatar
2010-01-01
International student exchange programs are widely promoted in higher education as a means of developing desirable intercultural skills and understanding among students. This multimethod study employed data from student surveys, tertiary institution case studies, and interviews with key stakeholders to identify factors that inhibited or promoted…
THE CLIMATIC AND HYDROLOGIC FACTORS AFFECTING THE REDISTRIBUTION OF SR-90
leaching solution present and the chemical and cation exchange properties of the soil solution ; a mathematical model of movement was established...manual for using high speed computers to compute the factors of the daily water balance was prepared; the influence of the soil solution in
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lunden, Melissa; Faulkner, David; Heredia, Elizabeth
2012-10-01
This report documents experiments performed in three homes to assess the methodology used to determine air exchange rates using passive tracer techniques. The experiments used four different tracer gases emitted simultaneously but implemented with different spatial coverage in the home. Two different tracer gas sampling methods were used. The results characterize the factors of the execution and analysis of the passive tracer technique that affect the uncertainty in the calculated air exchange rates. These factors include uncertainties in tracer gas emission rates, differences in measured concentrations for different tracer gases, temporal and spatial variability of the concentrations, the comparison betweenmore » different gas sampling methods, and the effect of different ventilation conditions.« less
Goldenberg, Shira M.; Silverman, Jay G.; Engstrom, David; Bojorquez-Chapela, Ietza; Usita, Paula; Rolón, María Luisa; Strathdee, Steffanie A.
2015-01-01
Coerced and adolescent sex industry involvement are linked to serious health and social consequences, including enhanced risk of HIV infection. Using ethnographic fieldwork, including interviews with 30 female sex workers with a history of coerced or adolescent sex industry involvement, we describe contextual factors influencing vulnerability to coerced and adolescent sex industry entry and their impacts on HIV risk and prevention. Early gender-based violence and economic vulnerabilities perpetuated subsequent vulnerability to coercion and adolescent sex exchange, while HIV risk mitigation capacities improved with increased age, control over working conditions, and experience. Structural interventions addressing gender-based violence, economic factors, and HIV prevention among all females who exchange sex are needed. PMID:25648946
Goldenberg, Shira M; Silverman, Jay G; Engstrom, David; Bojorquez-Chapela, Ietza; Usita, Paula; Rolón, María Luisa; Strathdee, Steffanie A
2015-04-01
Coerced and adolescent sex industry involvement are linked to serious health and social consequences, including enhanced risk of HIV infection. Using ethnographic fieldwork, including interviews with 30 female sex workers with a history of coerced or adolescent sex industry involvement, we describe contextual factors influencing vulnerability to coerced and adolescent sex industry entry and their impacts on HIV risk and prevention. Early gender-based violence and economic vulnerability perpetuated vulnerability to coercion and adolescent sex exchange, while HIV risk mitigation capacities improved with increased age, control over working conditions, and experience. Structural interventions addressing gender-based violence, economic factors, and HIV prevention among all females who exchange sex are needed. © The Author(s) 2015.
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.
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.
Heat transfer in thin, compact heat exchangers with circular, rectangular, or pin-fin flow passages
NASA Technical Reports Server (NTRS)
Olson, D. A.
1992-01-01
Heat transfer and pressure drop have been measured of three thin, compact heat exchangers in helium gas at 3.5 MPa and higher, with Reynolds numbers of 450 to 36,000. The flow geometries for the three heat exchanger specimens were: circular tube, rectangular channel, and staggered pin fin with tapered pins. The specimens were heated radiatively at heat fluxes up to 77 W/sq cm. Correlations were developed for the isothermal friction factor as a function of Reynolds number, and for the Nusselt number as a function of Reynolds number and the ratio of wall temperature to fluid temperature. The specimen with the pin fin internal geometry had significantly better heat transfer than the other specimens, but it also had higher pressure drop. For certain conditions of helium flow and heating, the temperature more than doubled from the inlet to the outlet of the specimens, producing large changes in gas velocity, density, viscosity, and thermal conductivity. These changes in properties did not affect the correlations for friction factor and Nusselt number in turbulent flow.
Chaya, Taro; Shibata, Satoshi; Tokuhara, Yasunori; Yamaguchi, Wataru; Matsumoto, Hiroshi; Kawahara, Ichiro; Kogo, Mikihiko; Ohoka, Yoshiharu; Inagaki, Shinobu
2011-08-26
The T332I mutation in Rho guanine nucleotide exchange factor 10 (ARHGEF10) was previously found in persons with slowed nerve conduction velocities and thin myelination of peripheral nerves. However, the molecular and cellular basis of the T332I mutant is not understood. Here, we show that ARHGEF10 has a negative regulatory region in the N terminus, in which residue 332 is located, and the T332I mutant is constitutively active. An N-terminal truncated ARHGEF10 mutant, ARHGEF10 ΔN (lacking amino acids 1-332), induced cell contraction that was inhibited by a Rho kinase inhibitor Y27632 and had higher GEF activity for RhoA than the wild type. The T332I mutant also showed the phenotype similar to the N-terminal truncated mutant. These data suggest that the ARHGEF10 T332I mutation-associated phenotype observed in the peripheral nerves is due to activated GEF activity of the ARHGEF10 T332I mutant.
Chaya, Taro; Shibata, Satoshi; Tokuhara, Yasunori; Yamaguchi, Wataru; Matsumoto, Hiroshi; Kawahara, Ichiro; Kogo, Mikihiko; Ohoka, Yoshiharu; Inagaki, Shinobu
2011-01-01
The T332I mutation in Rho guanine nucleotide exchange factor 10 (ARHGEF10) was previously found in persons with slowed nerve conduction velocities and thin myelination of peripheral nerves. However, the molecular and cellular basis of the T332I mutant is not understood. Here, we show that ARHGEF10 has a negative regulatory region in the N terminus, in which residue 332 is located, and the T332I mutant is constitutively active. An N-terminal truncated ARHGEF10 mutant, ARHGEF10 ΔN (lacking amino acids 1–332), induced cell contraction that was inhibited by a Rho kinase inhibitor Y27632 and had higher GEF activity for RhoA than the wild type. The T332I mutant also showed the phenotype similar to the N-terminal truncated mutant. These data suggest that the ARHGEF10 T332I mutation-associated phenotype observed in the peripheral nerves is due to activated GEF activity of the ARHGEF10 T332I mutant. PMID:21719701
NASA Astrophysics Data System (ADS)
Chan, Iatneng
2012-02-01
In general the exchange of gases or other material in capillary system is conceptualized by the diffusion effect. But in this model, we investigate a micro-flow pattern by simulation and computation on a micro-exchange model in which the blood cell is a considered factor, especially on its shape. It shows that the cell benefits the circulation while it is moving in the capillary. In the study, the flow detail near the cell surface is mathematically analyzed, such that the Navier-Stokes equations are applied and the viscous factor is also briefly considered. For having a driven force to the motion of micro-circulation, a breathing mode is suggested to approximately compute on the flow rate in the blood capillary during the transfer of cell. The rate is also used to estimate the enhancement to the circulation in additional to the outcome of diffusion. Moreover in the research, the shape change of capillary wall under pressure influence is another element in the beginning calculation for the effect in the assistance to cell motion.
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.
Architecture Study for a Fuel Depot Supplied from Lunar Assets
NASA Technical Reports Server (NTRS)
Perrin, Thomas M.; Casler, James G.
2016-01-01
This architecture study sought to determine the optimum architecture for a fuel depot supplied from lunar assets. Four factors - the location of propellant processing (on the Moon or on the depot), the depot location (on the Moon, L1, GEO, or LEO), the propellant transfer location (L1, GEO, or LEO), and the propellant transfer method (bulk fuel or canister exchange) were combined to identify 18 candidate architectures. Two design reference missions (DRMs) - a commercial satellite servicing mission and a Government cargo mission to Mars - created demand for propellants, while a propellant delivery DRM examined supply issues. The study concluded Earth-Moon L1 is the best location for an orbiting depot. For all architectures, propellant boiloff was less than anticipated, and was far overshadowed by delta-v requirements and resulting fuel consumption. Bulk transfer is the most flexible for both the supplier and customer. However, since canister exchange bypasses the transfer of bulk cryogens and necessary chilldown losses, canister exchange shows promise and merits further investigation. Overall, this work indicates propellant consumption and loss is an essential factor in assessing fuel depot architectures.
Muto, Go; Nakamura, Rina Ishii; Yokoyama, Kazuhito; Kitamura, Fumihiko; Omori, Yuki; Saito, Masahiko; Endo, Motoki
2017-12-19
The maintenance of a balance between work and disease treatment is an important issue in Japan. This study explored factors that affect collaboration between occupational physicians (OPs) and attending physicians (APs). A questionnaire was mailed to 1,102 OPs. The questionnaire assessed the demographic characteristics of OPs; their opinions and behaviors related to collaboration, including the exchange of medical information with APs; and the occupational health service system at their establishments. In total, 275 OPs completed the questionnaire (25.0% response rate). Over 80% of respondents believed OPs should collaborate with APs. After adjusting for company size, collaboration >10 times/year (with regard to both returning to work following sick leave and annual health check-ups for employees) was significantly associated with environmental factors, such as the presence of occupational health nurses (odds ratio (OR): 5.56 and 5.01, respectively, p<0.05) and the use of prescribed forms for information exchange (OR: 4.21 and 3.63, respectively, p<0.05) but not with the demographic characteristics of the OPs (p>0.05). The majority of OPs believed that collaboration with APs is important for supporting workers with illnesses. Support systems including prescribed forms of information exchange and occupational health nurses, play pivotal roles in promoting this collaboration.
Herrmann, Andrea; Tillmann, Britta A M; Schürmann, Janine; Bölker, Michael; Tudzynski, Paul
2014-04-01
Monomeric GTPases of the Rho subfamily are important mediators of polar growth and NADPH (Nox) signaling in a variety of organisms. These pathways influence the ability of Claviceps purpurea to infect host plants. GTPase regulators contribute to the nucleotide loading cycle that is essential for proper functionality of the GTPases. Scaffold proteins gather GTPase complexes to facilitate proper function. The guanine nucleotide exchange factors (GEFs) CpCdc24 and CpDock180 activate GTPase signaling by triggering nucleotide exchange of the GTPases. Here we show that CpCdc24 harbors nucleotide exchange activity for both Rac and Cdc42 homologues. The GEFs partly share the cellular distribution of the GTPases and interact with the putative upstream GTPase CpRas1. Interaction studies show the formation of higher-order protein complexes, mediated by the scaffold protein CpBem1. Besides the GTPases and GEFs, these complexes also contain the GTPase effectors CpSte20 and CpCla4, as well as the regulatory protein CpNoxR. Functional characterizations suggest a role of CpCdc24 mainly in polarity, whereas CpDock180 is involved in stress tolerance mechanisms. These findings indicate the dynamic formation of small GTPase complexes and improve the model for GTPase-associated signaling in C. purpurea.
Isotopic fractionation of tritium in biological systems.
Le Goff, Pierre; Fromm, Michel; Vichot, Laurent; Badot, Pierre-Marie; Guétat, Philippe
2014-04-01
Isotopic fractionation of tritium is a highly relevant issue in radiation protection and requires certain radioecological considerations. Sound evaluation of this factor is indeed necessary to determine whether environmental compartments are enriched/depleted in tritium or if tritium is, on the contrary, isotopically well-distributed in a given system. The ubiquity of tritium and the standard analytical methods used to assay it may induce biases in both the measurement and the signification that is accorded to the so-called fractionation: based on an exhaustive review of the literature, we show how, sometimes large deviations may appear. It is shown that when comparing the non-exchangeable fraction of organically bound tritium (neOBT) to another fraction of tritium (e.g. tritiated water) the preparation of samples and the measurement of neOBT reported frequently led to underestimation of the ratio of tritium to hydrogen (T/H) in the non-exchangeable compartment by a factor of 5% to 50%. In the present study, corrections are proposed for most of the biological matrices studied so far. Nevertheless, the values of isotopic fractionation reported in the literature remain difficult to compare with each other, especially since the physical quantities and units often vary between authors. Some improvements are proposed to better define what should encompass the concepts of exchangeable and non-exchangeable fractions. Copyright © 2014 Elsevier Ltd. All rights reserved.
Dow, Graham J; Berry, Joseph A; Bergmann, Dominique C
2017-10-01
Stomata are simultaneously tasked with permitting the uptake of carbon dioxide for photosynthesis while limiting water loss from the plant. This process is mainly regulated by guard cell control of the stomatal aperture, but recent advancements have highlighted the importance of several genes that control stomatal development. Using targeted genetic manipulations of the stomatal lineage and a combination of gas exchange and microscopy techniques, we show that changes in stomatal development of the epidermal layer lead to coupled changes in the underlying mesophyll tissues. This coordinated response tends to match leaf photosynthetic potential (V cmax ) with gas-exchange capacity (g smax ), and hence the uptake of carbon dioxide for water lost. We found that different genetic regulators systematically altered tissue coordination in separate ways: the transcription factor SPEECHLESS (SPCH) primarily affected leaf size and thickness, whereas peptides in the EPIDERMAL PATTERNING FACTOR (EPF) family altered cell density in the mesophyll. It was also determined that interlayer coordination required the cell-surface receptor TOO MANY MOUTHS (TMM). These results demonstrate that stomata-specific regulators can alter mesophyll properties, which provides insight into how molecular pathways can organize leaf tissues to coordinate gas exchange and suggests new strategies for improving plant water-use efficiency. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.
In vitro guanine nucleotide exchange activity of DHR-2/DOCKER/CZH2 domains.
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.
Pulmonary gas exchange in acute respiratory failure.
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.
NASA Astrophysics Data System (ADS)
Menéndez, J.
2018-01-01
Neutrinoless β β decay nuclear matrix elements calculated with the shell model and energy-density functional theory typically disagree by more than a factor of two in the standard scenario of light-neutrino exchange. In contrast, for a decay mediated by sterile heavy neutrinos the deviations are reduced to about 50%, an uncertainty similar to the one due to short-range effects. We compare matrix elements in the light- and heavy-neutrino-exchange channels, exploring the radial, momentum transfer and angular momentum-parity matrix element distributions, and considering transitions that involve correlated and uncorrelated nuclear states. We argue that the shorter-range heavy-neutrino exchange is less sensitive to collective nuclear correlations, and that discrepancies in matrix elements are mostly due to the treatment of long-range correlations in many-body calculations. Our analysis supports previous studies suggesting that isoscalar pairing correlations, which affect mostly the longer-range part of the neutrinoless β β decay operator, are partially responsible for the differences between nuclear matrix elements in the standard light-neutrino-exchange mechanism.
Real-time observation of cation exchange kinetics and dynamics at the muscovite-water interface
Lee, Sang Soo; Fenter, Paul; Nagy, Kathryn L.; ...
2017-06-09
Here, ion exchange at charged solid–liquid interfaces is central to a broad range of chemical and transport phenomena. Real-time observations of adsorption/desorption at the molecular-scale elucidate exchange reaction pathways. Here, we report temporal variation in the distribution of Rb + species at the muscovite (001)–water interface during exchange with Na +. Time-resolved resonant anomalous X-ray reflectivity measurements reveal that Rb + desorption occurs over several tens of seconds during which thermodynamically stable inner-sphere Rb + slowly transforms to less stable outer-sphere Rb + at 25°C. In contrast, Rb + adsorption is about twice as fast, proceeding quickly from Rb +more » in the bulk solution to the stable inner-sphere species. The Arrhenius plot of the adsorption/desorption rate constants measured from 9 to 55°C shows that the pre-exponential factor for desorption is significantly smaller than for adsorption, indicating that this reduced attempt frequency of cation detachment largely explains the slow cation exchange processes at the interface.« less
Esmaeilzadeh, Pouyan; Sambasivan, Murali
2017-04-04
Literature indicates that one of the most important factors affecting the widespread adoption of Health Information Exchange (HIE) is patient support and endorsement. In order to reap all the expected benefits of HIE, patients' acceptance of technology is a challenge that is not fully studied. There are a few studies which have focused on requirements of electronic medical information exchange from consumers' views and expectations. This study is aimed at reviewing the literature to articulate factors that affect patients to support HIE efforts. A literature review of current studies addressing patients' views on HIE from 2005 was undertaken. Five electronic research databases (Science Direct, PubMed, Web of Science, CINAHL, and Academic Search Premiere) were searched to retrieve articles reporting pros and cons of HIE from patients' opinion. One hundred and ninety six articles were initially retrieved from the databases. Out of 196, 36 studies met the inclusion criteria and were fully reviewed. Our findings indicate that patient's attitude toward HIE is affected by seven main factors: perceived benefits, perceived concerns, patient characteristics, patient participation level in HIE, type of health information, identity of recipients, and patient preferences regarding consent and features. The findings provide useful theoretical implications for research by developing a classification of significant factors and a framework based on the lessons learned from the literature to help guide HIE efforts. Our results also have fundamental practical implications for policy makers, current and potential organizers of HIEs by highlighting the role of patients in the widespread implementation of HIE. The study indicates that new approaches should be applied to completely underline HIE benefits for patients and also address their concerns.
García-Márquez, Adrián; Gijsbers, Abril; de la Mora, Eugenio; Sánchez-Puig, Nuria
2015-01-01
Ribosome biogenesis is orchestrated by the action of several accessory factors that provide time and directionality to the process. One such accessory factor is the GTPase EFL1 involved in the cytoplasmic maturation of the ribosomal 60S subunit. EFL1 and SBDS, the protein mutated in the Shwachman-Diamond syndrome (SBDS), release the anti-association factor eIF6 from the surface of the ribosomal subunit 60S. Here we report a kinetic analysis of fluorescent guanine nucleotides binding to EFL1 alone and in the presence of SBDS using fluorescence stopped-flow spectroscopy. Binding kinetics of EFL1 to both GDP and GTP suggests a two-step mechanism with an initial binding event followed by a conformational change of the complex. Furthermore, the same behavior was observed in the presence of the SBDS protein irrespective of the guanine nucleotide evaluated. The affinity of EFL1 for GTP is 10-fold lower than that calculated for GDP. Association of EFL1 to SBDS did not modify the affinity for GTP but dramatically decreased that for GDP by increasing the dissociation rate of the nucleotide. Thus, SBDS acts as a guanine nucleotide exchange factor (GEF) for EFL1 promoting its activation by the release of GDP. Finally, fluorescence anisotropy measurements showed that the S143L mutation present in the Shwachman-Diamond syndrome altered a surface epitope for EFL1 and largely decreased the affinity for it. These results suggest that loss of interaction between these proteins due to mutations in the disease consequently prevents the nucleotide exchange regulation the SBDS exerts on EFL1. PMID:25991726
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
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.
ATP Dependence of Na+/H+ Exchange
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
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
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
NASA Astrophysics Data System (ADS)
Bachy, Aurélie; Aubinet, Marc; Schoon, Niels; Amelynck, Crist; Bodson, Bernard; Moureaux, Christine; Heinesch, Bernard
2016-04-01
Maize is the most important C4 crop worldwide. It is also the second most important crop worldwide (C3 and C4 mixed), and is a dominant crop in some world regions. Therefore, it can potentially influence local climate and air quality through its exchanges of gases with the atmosphere. Among others, biogenic volatile organic compounds (BVOC) are known to influence the atmospheric composition and thereby modify greenhouse gases lifetime and pollutant formation in the atmosphere. However, so far, only two studies have dealt with BVOC exchanges from maize. Moreover, these studies were conducted on a limited range of meteorological and phenological conditions, so that the knowledge of BVOC exchanges by this crop remains poor. Here, we present the first BVOC measurement campaign performed at ecosystem-scale on a maize field during a whole growing season. It was carried out in the Lonzée Terrestrial Observatory (LTO), an ICOS site. BVOC fluxes were measured by the disjunct by mass-scanning eddy covariance technique with a proton transfer reaction mass spectrometer for BVOC mixing ratios measurements. Outstanding results are (i) BVOC exchanges from soil were as important as BVOC exchanges from maize itself; (ii) BVOC exchanges observed on our site were much lower than exchanges observed by other maize studies, even under normalized temperature and light conditions, (iii) they were also lower than those observed on other crops grown in Europe. Lastly (iv), BVOC exchanges observed on our site under standard environmental conditions, i.e., standard emission factors SEF, were much lower than those currently considered by BVOC exchange up-scaling models. From those observations, we deduced that (i) soil BVOC exchanges should be better understood and should be incorporated in terrestrial BVOC exchanges models, and that (ii) SEF for the C4 crop plant functional type cannot be evaluated at global scale but should be determined for each important agronomic and pedo-climatic region. Moreover, as in our region (i.e., temperate climate, silty-loam soils), SEF observed on maize were much lower than SEF currently considered by models, our results tend to lower the impact of agricultural ecosystems on BVOC exchanges.
Huang, Yongdong; Bi, Jingxiu; Zhao, Lan; Ma, Guanghui; Su, Zhiguo
2010-12-01
Ion-exchange chromatography (IEC) using commercial ionic absorbents is a widely used technique for protein purification. Protein adsorption onto ion-exchange adsorbents often involves a multipoint adsorption. In IEC of multimeric proteins or "soft" proteins, the intense multipoint binding would make the further desorption difficult, even lead to the destruction of protein structure and the loss of its biological activity. In this paper, DEAE Sepharose FF adsorbents with controllable ligand densities from 0.020 to 0.183 mmol/ml were synthesized, and then the effect of ligand density on the static ion-exchange adsorption of bovine serum albumin (BSA) onto DEAE Sepharose FF was studied by batch adsorption technique. Steric mass-action (SMA) model was employed to analyze the static adsorption behavior. The results showed that the SMA model parameters, equilibrium constant (K(a)), characteristic number of binding sites (υ) and steric factor (σ), increased gradually with ligand density. Thus, it was feasible to regulate BSA multipoint adsorption by modulating the ligand density of ion-exchange adsorbent. Furthermore, IEC of hepatitis B surface antigen (HBsAg) using DEAE Sepharose FF adsorbents with different ligand densities was carried out, and the activity recovery of HBsAg was improved from 42% to 67% when the ligand density was decreased from 0.183 to 0.020 mmol/ml. Taking the activity recovery of HBsAg, the purification factor and the binding capacity into account, DEAE Sepharose FF with a ligand density of 0.041 mmol/ml was most effective for the purification of HBsAg. Such a strategy may also be beneficial for the purification of macromolecules and multimeric proteins. Copyright © 2010 Elsevier Inc. All rights reserved.
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.
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.
Roles of Bacillus subtilis DprA and SsbA in RecA-mediated genetic recombination.
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.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Almasbahi, M.S.
In a world of generalized floating exchange rates, it is not enough to solve the problem of exchange rate policy by determining whether to peg or float the currency under consideration. It is also necessary to choose to what major currency to peg. The main purpose of this study is to investigate and determine empirically the optimum currency peg for the Saudi riyal. To accomplish this goal, a simple conventional trade model, that includes variables found in many other studies of import and export demand, was used. In addition, an exchange rate term was added as a separate independent variablemore » in the import and export demand equations in order to assess the effect of exchange rate on the trade flows. The criteria for the optimal currency peg in this study were based on two factors. First, the error statistics for projected imports and exports using alternative exchange rate regimes. Second, variances of projected imports, exports and trade balance using alternative exchange rate regimes. The exchange rate has a significant impact on the Saudia Arabian trade flows which implies that changes in the riyals value affect the Saudi trade deficit. Moreover, the exchange rate has a more powerful effect on its aggregate imports than on the world demand for its exports. There is also a strong support for the hypothesis that the exchange rate affects the value of the Saudi bilateral trade with its five major trade partners. On the aggregate level, the SDR peg seems to be the best currency peg for the Saudi riyal since it provides the best prediction errors and the lowest variance for the trade balance. Finally, on the disaggregate level, the US dollar provides the best performance and yields the best results among all the six currency pegs considered in this study.« less
NASA Astrophysics Data System (ADS)
Hamuro, Yoshitomo; E, Sook Yen
2018-05-01
The technological goal of hydrogen/deuterium exchange-mass spectrometry (HDX-MS) is to determine backbone amide hydrogen exchange rates. The most critical challenge to achieve this goal is obtaining the deuterium incorporation in single-amide resolution, and gas-phase fragmentation may provide a universal solution. The gas-phase fragmentation may generate the daughter ions which differ by a single amino acid and the difference in deuterium incorporations in the two analogous ions can yield the deuterium incorporation at the sub-localized site. Following the pioneering works by Jørgensen and Rand, several papers utilized the electron transfer dissociation (ETD) to determine the location of deuterium in single-amide resolution. This paper demonstrates further advancement of the strategy by determining backbone amide hydrogen exchange rates, instead of just determining deuterium incorporation at a single time point, in combination with a wide time window monitoring. A method to evaluate the effects of scrambling and to determine the exchange rates from partially scrambled HDX-ETD-MS data is described. All parent ions for ETD fragmentation were regio-selectively scrambled: The deuterium in some regions of a peptide ion was scrambled while that in the other regions was not scrambled. The method determined 31 backbone amide hydrogen exchange rates of cytochrome c in the non-scrambled regions. Good fragmentation of a parent ion, a low degree of scrambling, and a low number of exchangeable hydrogens in the preceding side chain are the important factors to determine the exchange rate. The exchange rates determined by the HDX-MS are in good agreement with those determined by NMR. [Figure not available: see fulltext.
Hamuro, Yoshitomo; E, Sook Yen
2018-05-01
The technological goal of hydrogen/deuterium exchange-mass spectrometry (HDX-MS) is to determine backbone amide hydrogen exchange rates. The most critical challenge to achieve this goal is obtaining the deuterium incorporation in single-amide resolution, and gas-phase fragmentation may provide a universal solution. The gas-phase fragmentation may generate the daughter ions which differ by a single amino acid and the difference in deuterium incorporations in the two analogous ions can yield the deuterium incorporation at the sub-localized site. Following the pioneering works by Jørgensen and Rand, several papers utilized the electron transfer dissociation (ETD) to determine the location of deuterium in single-amide resolution. This paper demonstrates further advancement of the strategy by determining backbone amide hydrogen exchange rates, instead of just determining deuterium incorporation at a single time point, in combination with a wide time window monitoring. A method to evaluate the effects of scrambling and to determine the exchange rates from partially scrambled HDX-ETD-MS data is described. All parent ions for ETD fragmentation were regio-selectively scrambled: The deuterium in some regions of a peptide ion was scrambled while that in the other regions was not scrambled. The method determined 31 backbone amide hydrogen exchange rates of cytochrome c in the non-scrambled regions. Good fragmentation of a parent ion, a low degree of scrambling, and a low number of exchangeable hydrogens in the preceding side chain are the important factors to determine the exchange rate. The exchange rates determined by the HDX-MS are in good agreement with those determined by NMR. Graphical Abstract ᅟ.
Escobar, Carlos; Moniz, Marta; Nunes, Pedro; Abadesso, Clara; Ferreira, Teresa; Barra, António; Lichtner, Anabela; Loureiro, Helena; Dias, Alexandra; Almeida, Helena
2017-10-31
The benefits of manual versus automated red blood cell exchange have rarely been documented and studies in young sickle cell disease patients are scarce. We aim to describe and compare our experience in these two procedures. Young patients (≤ 21 years old) who underwent manual- or automated-red blood cell exchange for prevention or treatment of sickle cell disease complications were included. Clinical, technical and hematological data were prospectively recorded and analyzed. Ninety-four red blood cell exchange sessions were performed over a period of 68 months, including 57 manual and 37 automated, 63 for chronic complications prevention, 30 for acute complications and one in the pre-operative setting. Mean decrease in sickle hemoglobin levels was higher in automated-red blood cell exchange (p < 0.001) and permitted a higher sickle hemoglobin level decrease per volume removed (p < 0.001), while hemoglobin and hematocrit remained stable. Ferritin levels on chronic patients decreased 54%. Most frequent concern was catheter outflow obstruction on manual-red blood cell exchange and access alarm on automated-red blood cell exchange. No major complication or alloimunization was recorded. Automated-red blood cell exchange decreased sickle hemoglobin levels more efficiently than manual procedure in the setting of acute and chronic complications of sickle cell disease, with minor technical concerns mainly due to vascular access. The threshold of sickle hemoglobin should be individualized for clinical and hematological goals. In our cohort of young patients, the need for an acceptable venous access was a limiting factor, but iron-overload was avoided. Automated red blood cell exchange is safe and well tolerated. It permits a higher sickle hemoglobin removal efficacy, better volume status control and iron-overload avoidance.
NASA Astrophysics Data System (ADS)
Hamuro, Yoshitomo; E, Sook Yen
2018-03-01
The technological goal of hydrogen/deuterium exchange-mass spectrometry (HDX-MS) is to determine backbone amide hydrogen exchange rates. The most critical challenge to achieve this goal is obtaining the deuterium incorporation in single-amide resolution, and gas-phase fragmentation may provide a universal solution. The gas-phase fragmentation may generate the daughter ions which differ by a single amino acid and the difference in deuterium incorporations in the two analogous ions can yield the deuterium incorporation at the sub-localized site. Following the pioneering works by Jørgensen and Rand, several papers utilized the electron transfer dissociation (ETD) to determine the location of deuterium in single-amide resolution. This paper demonstrates further advancement of the strategy by determining backbone amide hydrogen exchange rates, instead of just determining deuterium incorporation at a single time point, in combination with a wide time window monitoring. A method to evaluate the effects of scrambling and to determine the exchange rates from partially scrambled HDX-ETD-MS data is described. All parent ions for ETD fragmentation were regio-selectively scrambled: The deuterium in some regions of a peptide ion was scrambled while that in the other regions was not scrambled. The method determined 31 backbone amide hydrogen exchange rates of cytochrome c in the non-scrambled regions. Good fragmentation of a parent ion, a low degree of scrambling, and a low number of exchangeable hydrogens in the preceding side chain are the important factors to determine the exchange rate. The exchange rates determined by the HDX-MS are in good agreement with those determined by NMR. [Figure not available: see fulltext.
Rachek, I. A.; Arrington, J.; Dmitriev, V. F.; ...
2015-02-12
The ratio of the elastic e +p to e –p scattering cross sections has been measured precisely, allowing the determination of the two-photon exchange contribution to these processes. This neglected contribution is believed to be the cause of the discrepancy between the Rosenbluth and polarization transfer methods of measuring the proton electromagnetic form factors. The experiment was performed at the VEPP-3 storage ring at beam energies of 1.6 and 1.0 GeV and at lepton scattering angles between 15° and 105°. The data obtained show evidence of a significant two-photon exchange effect. Furthermore, the results are compared with several theoretical predictions.
Hu, Jiangping; Ding, Hong
2012-01-01
Cuprates, ferropnictides and ferrochalcogenides are three classes of unconventional high temperature superconductors, who share similar phase diagrams in which superconductivity develops after a magnetic order is suppressed, suggesting a strong interplay between superconductivity and magnetism, although the exact picture of this interplay remains elusive. Here we show that there is a direct bridge connecting antiferromagnetic exchange interactions determined in the parent compounds of these materials to the superconducting gap functions observed in the corresponding superconducting materials: in all high temperature superconductors, the Fermi surface topology matches the form factor of the pairing symmetry favored by local magnetic exchange interactions. We suggest that this match offers a principle guide to search for new high temperature superconductors. PMID:22536479
DOE Office of Scientific and Technical Information (OSTI.GOV)
Singh, Prashant; Harbola, Manoj K.; Johnson, Duane D.
Here, this work constitutes a comprehensive and improved account of electronic-structure and mechanical properties of silicon-nitride (more » $${\\rm Si}_{3}$$ $${\\rm N}_{4}$$ ) polymorphs via van Leeuwen and Baerends (LB) exchange-corrected local density approximation (LDA) that enforces the exact exchange potential asymptotic behavior. The calculated lattice constant, bulk modulus, and electronic band structure of $${\\rm Si}_{3}$$ $${\\rm N}_{4}$$ polymorphs are in good agreement with experimental results. We also show that, for a single electron in a hydrogen atom, spherical well, or harmonic oscillator, the LB-corrected LDA reduces the (self-interaction) error to exact total energy to ~10%, a factor of three to four lower than standard LDA, due to a dramatically improved representation of the exchange-potential.« less
Sampling of Protein Folding Transitions: Multicanonical Versus Replica Exchange Molecular Dynamics.
Jiang, Ping; Yaşar, Fatih; Hansmann, Ulrich H E
2013-08-13
We compare the efficiency of multicanonical and replica exchange molecular dynamics for the sampling of folding/unfolding events in simulations of proteins with end-to-end β -sheet. In Go-model simulations of the 75-residue MNK6, we observe improvement factors of 30 in the number of folding/unfolding events of multicanonical molecular dynamics over replica exchange molecular dynamics. As an application, we use this enhanced sampling to study the folding landscape of the 36-residue DS119 with an all-atom physical force field and implicit solvent. Here, we find that the rate-limiting step is the formation of the central helix that then provides a scaffold for the parallel β -sheet formed by the two chain ends.