Critical role for Epac1 in inflammatory pain controlled by GRK2-mediated phosphorylation of Epac1.

PubMed

Singhmar, Pooja; Huo, XiaoJiao; Eijkelkamp, Niels; Berciano, Susana Rojo; Baameur, Faiza; Mei, Fang C; Zhu, Yingmin; Cheng, Xiaodong; Hawke, David; Mayor, Federico; Murga, Cristina; Heijnen, Cobi J; Kavelaars, Annemieke

2016-03-15

cAMP signaling plays a key role in regulating pain sensitivity. Here, we uncover a previously unidentified molecular mechanism in which direct phosphorylation of the exchange protein directly activated by cAMP 1 (EPAC1) by G protein kinase 2 (GRK2) suppresses Epac1-to-Rap1 signaling, thereby inhibiting persistent inflammatory pain. Epac1(-/-) mice are protected against inflammatory hyperalgesia in the complete Freund's adjuvant (CFA) model. Moreover, the Epac-specific inhibitor ESI-09 inhibits established CFA-induced mechanical hyperalgesia without affecting normal mechanical sensitivity. At the mechanistic level, CFA increased activity of the Epac target Rap1 in dorsal root ganglia of WT, but not of Epac1(-/-), mice. Using sensory neuron-specific overexpression of GRK2 or its kinase-dead mutant in vivo, we demonstrate that GRK2 inhibits CFA-induced hyperalgesia in a kinase activity-dependent manner. In vitro, GRK2 inhibits Epac1-to-Rap1 signaling by phosphorylation of Epac1 at Ser-108 in the Disheveled/Egl-10/pleckstrin domain. This phosphorylation event inhibits agonist-induced translocation of Epac1 to the plasma membrane, thereby reducing Rap1 activation. Finally, we show that GRK2 inhibits Epac1-mediated sensitization of the mechanosensor Piezo2 and that Piezo2 contributes to inflammatory mechanical hyperalgesia. Collectively, these findings identify a key role of Epac1 in chronic inflammatory pain and a molecular mechanism for controlling Epac1 activity and chronic pain through phosphorylation of Epac1 at Ser-108. Importantly, using the Epac inhibitor ESI-09, we validate Epac1 as a potential therapeutic target for chronic pain.

Epac-protein kinase C alpha signaling in purinergic P2X3R-mediated hyperalgesia after inflammation.

PubMed

Gu, Yanping; Li, Guangwen; Chen, Yong; Huang, Li-Yen Mae

2016-07-01

Sensitization of purinergic P2X3 receptors (P2X3Rs) is a major mechanism contributing to injury-induced exaggerated pain responses. We showed in a previous study that cyclic adenosine monophosphate (cAMP)-dependent guanine nucleotide exchange factor 1 (Epac1) in rat sensory dorsal root ganglia (DRGs) is upregulated after inflammatory injury, and it plays a critical role in P2X3R sensitization by activating protein kinase C epsilon (PKCε) inside the cells. protein kinase C epsilon has been established as the major PKC isoform mediating injury-induced hyperalgesic responses. On the other hand, the role of PKCα in receptor sensitization was seldom considered. Here, we studied the participation of PKCα in Epac signaling in P2X3R-mediated hyperalgesia. The expression of both Epac1 and Epac2 and the level of cAMP in DRGs are greatly enhanced after complete Freund adjuvant (CFA)-induced inflammation. The expression of phosphorylated PKCα is also upregulated. Complete Freund adjuvant (CFA)-induced P2X3R-mediated hyperalgesia is not only blocked by Epac antagonists but also by the classical PKC isoform inhibitors, Go6976, and PKCα-siRNA. These CFA effects are mimicked by the application of the Epac agonist, 8-(4-chlorophenylthio)-2 -O-methyl-cAMP (CPT), in control rats, further confirming the involvement of Epacs. Because the application of Go6976 prior to CPT still reduces CPT-induced hyperalgesia, PKCα is downstream of Epacs to mediate the enhancement of P2X3R responses in DRGs. The pattern of translocation of PKCα inside DRG neurons in response to CPT or CFA stimulation is distinct from that of PKCε. Thus, in contrast to prevalent view, PKCα also plays an essential role in producing complex inflammation-induced receptor-mediated hyperalgesia.

Toll-like receptor 4-mediated cAMP production up-regulates B-cell activating factor expression in Raw264.7 macrophages.

PubMed

Moon, Eun-Yi; Lee, Yu-Sun; Choi, Wahn Soo; Lee, Mi-Hee

2011-10-15

B-cell activating factor (BAFF) plays a role in the generation and the maintenance of mature B cells. Lipopolysaccharide (LPS) increased BAFF expression through the activation of toll-like receptor 4 (TLR4)-dependent signal transduction. Here, we investigated the mechanism of action on mouse BAFF (mBAFF) expression by cAMP production in Raw264.7 mouse macrophages. mBAFF expression was increased by the treatment with a cAMP analogue, dibutyryl-cAMP which is the activator of protein kinase A (PKA), cAMP effector protein. PKA activation was measured by the phosphorylation of cAMP-response element binding protein (CREB) on serine 133 (S133). cAMP production and CREB (S133) phosphorylation were augmented by LPS-stimulation. While mBAFF promoter activity was enhanced by the co-transfection with pS6-RSV-CREB, it was reduced by siRNA-CREB. PKA inhibitor, H-89, reduced CREB (S133) phosphorylation and mBAFF expression in control and LPS-stimulated macrophages. Another principal cAMP effector protein is cAMP-responsive guanine nucleotide exchange factor (Epac), a Rap GDP exchange factor. Epac was activated by the treatment with 8-(4-chloro-phenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate (CPT), Epac activator, as judged by the measurement of Rap1 activation. Basal level of mBAFF expression was increased by CPT treatment. LPS-stimulated mBAFF expression was also slightly enhanced by co-treatment with CPT. In addition, dibutyryl-cAMP and CPT enhanced mBAFF expression in bone marrow-derived macrophages (BMDM). With these data, it suggests that the activation of PKA and cAMP/Epac1/Rap1 pathways could be required for basal mBAFF expression, as well as being up-regulated in the TLR4-induced mBAFF expression. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Phospholipase C-ε links Epac2 activation to the potentiation of glucose-stimulated insulin secretion from mouse islets of Langerhans

PubMed Central

Dzhura, Igor; Chepurny, Oleg G; Leech, Colin A; Roe, Michael W; Dzhura, Elvira; Xu, Xin; Lu, Youming; Schwede, Frank; Genieser, Hans-G; Smrcka, Alan V

2011-01-01

Glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells is potentiated by cAMP-elevating agents, such as the incretin hormone glucagon-like peptide-1 (GLP-1) and cAMP exerts its insulin secretagogue action by activating both protein kinase A (PKA) and the cAMP-regulated guanine nucleotide exchange factor designated as Epac2. Although prior studies of mouse islets demonstrated that Epac2 acts via Rap1 GTPase to potentiate GSIS, it is not understood which downstream targets of Rap1 promote the exocytosis of insulin. Here, we measured insulin secretion stimulated by a cAMP analog that is a selective activator of Epac proteins in order to demonstrate that a Rap1-regulated phospholipase C-epsilon (PLC-ε) links Epac2 activation to the potentiation of GSIS. Our analysis demonstrates that the Epac activator 8-pCPT-2′-O-Me-cAMP-AM potentiates GSIS from the islets of wild-type (WT) mice, whereas it has a greatly reduced insulin secretagogue action in the islets of Epac2 (−/−) and PLC-ε (−/−) knockout (KO) mice. Importantly, the insulin secretagogue action of 8-pCPT-2′-O-Me-cAMP-AM in WT mouse islets cannot be explained by an unexpected action of this cAMP analog to activate PKA, as verified through the use of a FRET-based A-kinase activity reporter (AKAR3) that reports PKA activation. Since the KO of PLC-ε disrupts the ability of 8-pCPT-2′-O-Me-cAMP-AM to potentiate GSIS, while also disrupting its ability to stimulate an increase of β-cell [Ca2+]i, the available evidence indicates that it is a Rap1-regulated PLC-ε that links Epac2 activation to Ca2+-dependent exocytosis of insulin. PMID:21478675

The Projection Analysis of NMR Chemical Shifts Reveals Extended EPAC Autoinhibition Determinants

PubMed Central

Selvaratnam, Rajeevan; VanSchouwen, Bryan; Fogolari, Federico; Mazhab-Jafari, Mohammad T.; Das, Rahul; Melacini, Giuseppe

2012-01-01

EPAC is a cAMP-dependent guanine nucleotide exchange factor that serves as a prototypical molecular switch for the regulation of essential cellular processes. Although EPAC activation by cAMP has been extensively investigated, the mechanism of EPAC autoinhibition is still not fully understood. The steric clash between the side chains of two conserved residues, L273 and F300 in EPAC1, has been previously shown to oppose the inactive-to-active conformational transition in the absence of cAMP. However, it has also been hypothesized that autoinhibition is assisted by entropic losses caused by quenching of dynamics that occurs if the inactive-to-active transition takes place in the absence of cAMP. Here, we test this hypothesis through the comparative NMR analysis of several EPAC1 mutants that target different allosteric sites of the cAMP-binding domain (CBD). Using what to our knowledge is a novel projection analysis of NMR chemical shifts to probe the effect of the mutations on the autoinhibition equilibrium of the CBD, we find that whenever the apo/active state is stabilized relative to the apo/inactive state, dynamics are consistently quenched in a conserved loop (β2-β3) and helix (α5) of the CBD. Overall, our results point to the presence of conserved and nondegenerate determinants of CBD autoinhibition that extends beyond the originally proposed L273/F300 residue pair, suggesting that complete activation necessitates the simultaneous suppression of multiple autoinhibitory mechanisms, which in turn confers added specificity for the cAMP allosteric effector. PMID:22325287

Orally active Epac inhibitor reverses mechanical allodynia and loss of intraepidermal nerve fibers in a mouse model of chemotherapy-induced peripheral neuropathy.

PubMed

Singhmar, Pooja; Huo, XiaoJiao; Li, Yan; Dougherty, Patrick M; Mei, Fang; Cheng, Xiaodong; Heijnen, Cobi J; Kavelaars, Annemieke

2018-05-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect of cancer treatment that significantly compromises quality of life of cancer patients and survivors. Identification of targets for pharmacological intervention to prevent or reverse CIPN is needed. We investigated exchange protein regulated by cAMP (Epac) as a potential target. Epacs are cAMP-binding proteins known to play a pivotal role in mechanical allodynia induced by nerve injury and inflammation. We demonstrate that global Epac1-knockout (Epac1-/-) male and female mice are protected against paclitaxel-induced mechanical allodynia. In addition, spinal cord astrocyte activation and intraepidermal nerve fiber (IENF) loss are significantly reduced in Epac1-/- mice as compared to wild-type mice. Moreover, Epac1-/- mice do not develop the paclitaxel-induced deficits in mitochondrial bioenergetics in the sciatic nerve that are a hallmark of CIPN. Notably, mice with cell-specific deletion of Epac1 in Nav1.8-positive neurons (N-Epac1-/-) also show reduced paclitaxel-induced mechanical allodynia, astrocyte activation, and IENF loss, indicating that CIPN develops downstream of Epac1 activation in nociceptors. The Epac-inhibitor ESI-09 reversed established paclitaxel-induced mechanical allodynia in wild-type mice even when dosing started 10 days after completion of paclitaxel treatment. In addition, oral administration of ESI-09 suppressed spinal cord astrocyte activation in the spinal cord and protected against IENF loss. Ex vivo, ESI-09 blocked paclitaxel-induced abnormal spontaneous discharges in dorsal root ganglion neurons. Collectively, these findings implicate Epac1 in nociceptors as a novel target for treatment of CIPN. This is clinically relevant because ESI-09 has the potential to reverse a debilitating and long-lasting side effect of cancer treatment.

Role of Dynamics in the Autoinhibition and Activation of the Exchange Protein Directly Activated by Cyclic AMP (EPAC)*

PubMed Central

VanSchouwen, Bryan; Selvaratnam, Rajeevan; Fogolari, Federico; Melacini, Giuseppe

2011-01-01

The exchange protein directly activated by cAMP (EPAC) is a key receptor of cAMP in eukaryotes and controls critical signaling pathways. Currently, no residue resolution information is available on the full-length EPAC dynamics, which are known to be pivotal determinants of allostery. In addition, no information is presently available on the intermediates for the classical induced fit and conformational selection activation pathways. Here these questions are addressed through molecular dynamics simulations on five key states along the thermodynamic cycle for the cAMP-dependent activation of a fully functional construct of EPAC2, which includes the cAMP-binding domain and the integral catalytic region. The simulations are not only validated by the agreement with the experimental trends in cAMP-binding domain dynamics determined by NMR, but they also reveal unanticipated dynamic attributes, rationalizing previously unexplained aspects of EPAC activation and autoinhibition. Specifically, the simulations show that cAMP binding causes an extensive perturbation of dynamics in the distal catalytic region, assisting the recognition of the Rap1b substrate. In addition, analysis of the activation intermediates points to a possible hybrid mechanism of EPAC allostery incorporating elements of both the induced fit and conformational selection models. In this mechanism an entropy compensation strategy results in a low free-energy pathway of activation. Furthermore, the simulations indicate that the autoinhibitory interactions of EPAC are more dynamic than previously anticipated, leading to a revised model of autoinhibition in which dynamics fine tune the stability of the autoinhibited state, optimally sensitizing it to cAMP while avoiding constitutive activation. PMID:21873431

Biochemical and Pharmacological Characterizations of ESI-09 Based EPAC Inhibitors: Defining the ESI-09 “Therapeutic Window”

PubMed Central

Zhu, Yingmin; Chen, Haijun; Boulton, Stephen; Mei, Fang; Ye, Na; Melacini, Giuseppe; Zhou, Jia; Cheng, Xiaodong

2015-01-01

The cAMP signaling cascade is one of the most frequently targeted pathways for the development of pharmaceutics. A plethora of recent genetic and pharmacological studies suggest that exchange proteins directly activated by cAMP (EPACs) are implicated in multiple pathologies. Selective EPAC inhibitors have been recently developed. One specific inhibitor, ESI-09, has been shown to block EPAC activity and functions, as well as to recapitulate genetic phenotypes of EPAC knockout mice when applied in vivo. However, a recent study raised concern that ESI-09 might act as a non-specific protein denaturant. Herein, we present a detailed biochemical and pharmacological characterization, as well as a structure-activity relationship (SAR) analysis of ESI-09. Our studies show that ESI-09 dose-dependently inhibits activity of both EPAC1 and EPAC2 with apparent IC50 values well below the concentrations shown to induce “protein denaturation”. Moreover, the ESI-09's action towards EPAC proteins is highly sensitive to minor modifications of the 3-chlorophenyl moiety. Taken together, these results demonstrate that ESI-09 indeed acts as an EPAC specific antagonist and does not significantly destabilize/denature proteins at pharmacological effective concentrations. This conclusion is further supported by NMR data showing that ESI-09 induces residue-dependent chemical shift changes at low concentrations, while preserving well dispersed peaks. PMID:25791905

Biochemical and pharmacological characterizations of ESI-09 based EPAC inhibitors: defining the ESI-09 "therapeutic window".

PubMed

Zhu, Yingmin; Chen, Haijun; Boulton, Stephen; Mei, Fang; Ye, Na; Melacini, Giuseppe; Zhou, Jia; Cheng, Xiaodong

2015-03-20

The cAMP signaling cascade is one of the most frequently targeted pathways for the development of pharmaceutics. A plethora of recent genetic and pharmacological studies suggest that exchange proteins directly activated by cAMP (EPACs) are implicated in multiple pathologies. Selective EPAC inhibitors have been recently developed. One specific inhibitor, ESI-09, has been shown to block EPAC activity and functions, as well as to recapitulate genetic phenotypes of EPAC knockout mice when applied in vivo. However, a recent study raised concern that ESI-09 might act as a non-specific protein denaturant. Herein, we present a detailed biochemical and pharmacological characterization, as well as a structure-activity relationship (SAR) analysis of ESI-09. Our studies show that ESI-09 dose-dependently inhibits activity of both EPAC1 and EPAC2 with apparent IC50 values well below the concentrations shown to induce "protein denaturation". Moreover, the ESI-09's action towards EPAC proteins is highly sensitive to minor modifications of the 3-chlorophenyl moiety. Taken together, these results demonstrate that ESI-09 indeed acts as an EPAC specific antagonist and does not significantly destabilize/denature proteins at pharmacological effective concentrations. This conclusion is further supported by NMR data showing that ESI-09 induces residue-dependent chemical shift changes at low concentrations, while preserving well dispersed peaks.

Role of cyclic AMP sensor Epac1 in masseter muscle hypertrophy and myosin heavy chain transition induced by β2-adrenoceptor stimulation.

PubMed

Ohnuki, Yoshiki; Umeki, Daisuke; Mototani, Yasumasa; Jin, Huiling; Cai, Wenqian; Shiozawa, Kouichi; Suita, Kenji; Saeki, Yasutake; Fujita, Takayuki; Ishikawa, Yoshihiro; Okumura, Satoshi

2014-12-15

The predominant isoform of β-adrenoceptor (β-AR) in skeletal muscle is β2-AR and that in the cardiac muscle is β1-AR. We have reported that Epac1 (exchange protein directly activated by cAMP 1), a new protein kinase A-independent cAMP sensor, does not affect cardiac hypertrophy in response to pressure overload or chronic isoproterenol (isoprenaline) infusion. However, the role of Epac1 in skeletal muscle hypertrophy remains poorly understood. We thus examined the effect of disruption of Epac1, the major Epac isoform in skeletal muscle, on masseter muscle hypertrophy induced by chronic β2-AR stimulation with clenbuterol (CB) in Epac1-null mice (Epac1KO). The masseter muscle weight/tibial length ratio was similar in wild-type (WT) and Epac1KO at baseline and was significantly increased in WT after CB infusion, but this increase was suppressed in Epac1KO. CB treatment significantly increased the proportion of myosin heavy chain (MHC) IIb at the expense of that of MHC IId/x in both WT and Epac1KO, indicating that Epac1 did not mediate the CB-induced MHC isoform transition towards the faster isoform. The mechanism of suppression of CB-mediated hypertrophy in Epac1KO is considered to involve decreased activation of Akt signalling. In addition, CB-induced histone deacetylase 4 (HDAC4) phosphorylation on serine 246 mediated by calmodulin kinase II (CaMKII), which plays a role in skeletal muscle hypertrophy, was suppressed in Epac1KO. Our findings suggest that Epac1 plays a role in β2-AR-mediated masseter muscle hypertrophy, probably through activation of both Akt signalling and CaMKII/HDAC4 signalling. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Juvenile Hormone Regulation of Drosophila Epac - A Guanine Nucleotide Exchange Factor for Rap1 Small GTPase

USDA-ARS?s Scientific Manuscript database

Previously, we utilized a microchip array encompassing probes for 14,010 genes of Drosophila melanogaster to analyze the effect of (10R) juvenile hormone III (JH) on genome-wide gene expression in Drosophila S2 cells. Treatment with JH yielded a collection of 32 gene transcripts that demonstrated a ...

Exchange protein activated by cAMP (Epac) mediates cAMP-dependent but protein kinase A-insensitive modulation of vascular ATP-sensitive potassium channels

PubMed Central

Purves, Gregor I; Kamishima, Tomoko; Davies, Lowri M; Quayle, John M; Dart, Caroline

2009-01-01

Exchange proteins directly activated by cyclic AMP (Epacs or cAMP-GEF) represent a family of novel cAMP-binding effector proteins. The identification of Epacs and the recent development of pharmacological tools that discriminate between cAMP-mediated pathways have revealed previously unrecognized roles for cAMP that are independent of its traditional target cAMP-dependent protein kinase (PKA). Here we show that Epac exists in a complex with vascular ATP-sensitive potassium (KATP) channel subunits and that cAMP-mediated activation of Epac modulates KATP channel activity via a Ca2+-dependent mechanism involving the activation of Ca2+-sensitive protein phosphatase 2B (PP-2B, calcineurin). Application of the Epac-specific cAMP analogue 8-pCPT-2′-O-Me-cAMP, at concentrations that activate Epac but not PKA, caused a 41.6 ± 4.7% inhibition (mean ±s.e.m.; n= 7) of pinacidil-evoked whole-cell KATP currents recorded in isolated rat aortic smooth muscle cells. Importantly, similar results were obtained when cAMP was elevated by addition of the adenylyl cyclase activator forskolin in the presence of the structurally distinct PKA inhibitors, Rp-cAMPS or KT5720. Activation of Epac by 8-pCPT-2′-O-Me-cAMP caused a transient 171.0 ± 18.0 nm (n= 5) increase in intracellular Ca2+ in Fura-2-loaded aortic myocytes, which persisted in the absence of extracellular Ca2+. Inclusion of the Ca2+-specific chelator BAPTA in the pipette-filling solution or preincubation with the calcineurin inhibitors, cyclosporin A or ascomycin, significantly reduced the ability of 8-pCPT-2′-O-Me-cAMP to inhibit whole-cell KATP currents. These results highlight a previously undescribed cAMP-dependent regulatory mechanism that may be essential for understanding the physiological and pathophysiological roles ascribed to arterial KATP channels in the control of vascular tone and blood flow. PMID:19491242

Kv7 Channel Activation Underpins EPAC-Dependent Relaxations of Rat Arteries.

PubMed

Stott, Jennifer B; Barrese, Vincenzo; Greenwood, Iain A

2016-12-01

To establish the role of Kv7 channels in EPAC (exchange protein directly activated by cAMP)-dependent relaxations of the rat vasculature and to investigate whether this contributes to β-adrenoceptor-mediated vasorelaxations. Isolated rat renal and mesenteric arteries (RA and MA, respectively) were used for isometric tension recording to study the relaxant effects of a specific EPAC activator and the β-adrenoceptor agonist isoproterenol in the presence of potassium channel inhibitors and cell signaling modulators. Isolated myocytes were used in proximity ligation assay studies to detect localization of signaling intermediaries with Kv7.4 before and after cell stimulation. Our studies showed that the EPAC activator (8-pCPT-2Me-cAMP-AM) produced relaxations and enhanced currents of MA and RA that were sensitive to linopirdine (Kv7 inhibitor). Linopirdine also inhibited isoproterenol-mediated relaxations in both RA and MA. In the MA, isoproterenol relaxations were sensitive to EPAC inhibition, but not protein kinase A inhibition. In contrast, isoproterenol relaxations in RA were attenuated by protein kinase A but not by EPAC inhibition. Proximity ligation assay showed a localization of Kv7.4 with A-kinase anchoring protein in both vessels in the basal state, which increased only in the RA with isoproterenol stimulation. In the MA, but not the RA, a localization of Kv7.4 with both Rap1a and Rap2 (downstream of EPAC) increased with isoproterenol stimulation. EPAC-dependent vasorelaxations occur in part via activation of Kv7 channels. This contributes to the isoproterenol-mediated relaxation in mesenteric, but not renal, arteries. © 2016 American Heart Association, Inc.

Exchange protein directly activated by cAMP mediates slow delayed-rectifier current remodeling by sustained β-adrenergic activation in guinea pig hearts.

PubMed

Aflaki, Mona; Qi, Xiao-Yan; Xiao, Ling; Ordog, Balazs; Tadevosyan, Artavazd; Luo, Xiaobin; Maguy, Ange; Shi, Yanfen; Tardif, Jean-Claude; Nattel, Stanley

2014-03-14

β-Adrenoceptor activation contributes to sudden death risk in heart failure. Chronic β-adrenergic stimulation, as occurs in patients with heart failure, causes potentially arrhythmogenic reductions in slow delayed-rectifier K(+) current (IKs). To assess the molecular mechanisms of IKs downregulation caused by chronic β-adrenergic activation, particularly the role of exchange protein directly activated by cAMP (Epac). Isolated guinea pig left ventricular cardiomyocytes were incubated in primary culture and exposed to isoproterenol (1 μmol/L) or vehicle for 30 hours. Sustained isoproterenol exposure decreased IKs density (whole cell patch clamp) by 58% (P<0.0001), with corresponding decreases in potassium voltage-gated channel subfamily E member 1 (KCNE1) mRNA and membrane protein expression (by 45% and 51%, respectively). Potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) mRNA expression was unchanged. The β1-adrenoceptor antagonist 1-[2-((3-Carbamoyl-4-hydroxy)phenoxy)ethylamino]-3-[4-(1-methyl-4-trifluoromethyl-2-imidazolyl)phenoxy]-2-propanol dihydrochloride (CGP-20712A) prevented isoproterenol-induced IKs downregulation, whereas the β2-antagonist ICI-118551 had no effect. The selective Epac activator 8-pCPT-2'-O-Me-cAMP decreased IKs density to an extent similar to isoproterenol exposure, and adenoviral-mediated knockdown of Epac1 prevented isoproterenol-induced IKs/KCNE1 downregulation. In contrast, protein kinase A inhibition with a cell-permeable highly selective peptide blocker did not affect IKs downregulation. 1,2-Bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetate-AM acetoxymethyl ester (BAPTA-AM), cyclosporine, and inhibitor of nuclear factor of activated T cell (NFAT)-calcineurin association-6 (INCA6) prevented IKs reduction by isoproterenol and INCA6 suppressed isoproterenol-induced KCNE1 downregulation, consistent with signal-transduction via the Ca(2+)/calcineurin/NFAT pathway. Isoproterenol induced nuclear NFATc3/c4 translocation (immunofluorescence), which was suppressed by Epac1 knockdown. Chronic in vivo administration of isoproterenol to guinea pigs reduced IKs density and KCNE1 mRNA and protein expression while inducing cardiac dysfunction and action potential prolongation. Selective in vivo activation of Epac via sp-8-pCPT-2'-O-Me-cAMP infusion decreased IKs density and KCNE1 mRNA/protein expression. Prolonged β1-adrenoceptor stimulation suppresses IKs by downregulating KCNE1 mRNA and protein via Epac-mediated Ca(2+)/calcineurin/NFAT signaling. These results provide new insights into the molecular basis of K(+) channel remodeling under sustained adrenergic stimulation.

Epac1, PDE4, and PKC protein expression and their association with AKAP95, Cx43, and cyclinD2/E1 in breast cancer tissues.

PubMed

Huang, Ping; Sun, Qian; Zhuang, Wenxin; Peng, Kuan; Wang, Dai; Yao, Youliang; Guo, Dongbei; Zhang, Lu; Shen, Chuhan; Sun, Mengyun; Tang, Chaoying; Teng, Bogang; Zhang, Yongxing

2017-09-01

This study was conducted to investigate the exchange protein directly activated by cAMP (Epac1), PDE4, and PKC expression in breast cancer tissues, and the correlation between these proteins and AKAP95, Cx43, cyclin D2, and cyclin E1. PV-9000 two-step immunohistochemistry was used to analyze protein expression. The positive rate of Epac1 protein expression in breast cancer tissues (58%) was higher than in para-carcinoma tissues (10%) (P < 0.05). There were no significant differences in the positive rates of PDE4 and PKC expression between breast cancer and para-carcinoma tissues (P > 0.05). The positive expression rate of PDE4 was higher in the P53 protein positive group compared to the P53 negative group (P < 0.05). Correlations between Epac1 and cyclin D2, PDE4 and cyclin D2, AKAP95 and PKC, Cx43 and PKC, and cyclin D2 and PKC proteins were observed (P < 0.05). Epac1 expression in breast cancer tissues was increased, suggesting that the protein may be involved in the development of breast cancer. Correlations between Epac1 and cyclin D2, PDE4 and cyclin D2, AKAP95 and PKC, Cx43 and PKC, and cyclin D2 and PKC proteins suggested synergistic effects among these proteins in the development of breast cancer. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Activation of Cyclic Adenosine Monophosphate Pathway Increases the Sensitivity of Cancer Cells to the Oncolytic Virus M1.

PubMed

Li, Kai; Zhang, Haipeng; Qiu, Jianguang; Lin, Yuan; Liang, Jiankai; Xiao, Xiao; Fu, Liwu; Wang, Fang; Cai, Jing; Tan, Yaqian; Zhu, Wenbo; Yin, Wei; Lu, Bingzheng; Xing, Fan; Tang, Lipeng; Yan, Min; Mai, Jialuo; Li, Yuan; Chen, Wenli; Qiu, Pengxin; Su, Xingwen; Gao, Guangping; Tai, Phillip W L; Hu, Jun; Yan, Guangmei

2016-02-01

Oncolytic virotherapy is a novel and emerging treatment modality that uses replication-competent viruses to destroy cancer cells. Although diverse cancer cell types are sensitive to oncolytic viruses, one of the major challenges of oncolytic virotherapy is that the sensitivity to oncolysis ranges among different cancer cell types. Furthermore, the underlying mechanism of action is not fully understood. Here, we report that activation of cyclic adenosine monophosphate (cAMP) signaling significantly sensitizes refractory cancer cells to alphavirus M1 in vitro, in vivo, and ex vivo. We find that activation of the cAMP signaling pathway inhibits M1-induced expression of antiviral factors in refractory cancer cells, leading to prolonged and severe endoplasmic reticulum (ER) stress, and cell apoptosis. We also demonstrate that M1-mediated oncolysis, which is enhanced by cAMP signaling, involves the factor, exchange protein directly activated by cAMP 1 (Epac1), but not the classical cAMP-dependent protein kinase A (PKA). Taken together, cAMP/Epac1 signaling pathway activation inhibits antiviral factors and improves responsiveness of refractory cancer cells to M1-mediated virotherapy.

Off-target effect of the Epac agonist 8-pCPT-2'-O-Me-cAMP on P2Y12 receptors in blood platelets.

PubMed

Herfindal, Lars; Nygaard, Gyrid; Kopperud, Reidun; Krakstad, Camilla; Døskeland, Stein Ove; Selheim, Frode

2013-08-09

The primary target of the cAMP analogue 8-pCPT-2'-O-Me-cAMP is exchange protein directly activated by cAMP (Epac). Here we tested potential off-target effects of the Epac activator on blood platelet activation signalling. We found that the Epac analogue 8-pCPT-2'-O-Me-cAMP inhibits agonist-induced-GPCR-stimulated, but not collagen-stimulated, P-selectin surface expression on Epac1 deficient platelets. In human platelets, 8-pCPT-2'-O-Me-cAMP inhibited P-selectin expression elicited by the PKC activator PMA. This effect was abolished in the presence of the extracellular ADP scavenger system CP/CPK. In silico modelling of 8-pCPT-2'O-Me-cAMP binding into the purinergic platelet receptor P2Y12 revealed that the analogue docks similar to the P2Y12 antagonist 2MeSAMP. The 8-pCPT-2'-O-Me-cAMP analogue per se, did not provoke Rap 1 (Rap 1-GTP) activation or phosphorylation on the vasodilator-stimulated phosphoprotein (VASP) at Ser-157. In addition, the protein kinase A (PKA) antagonists Rp-cAMPS and Rp-8-Br-cAMPS failed to block the inhibitory effect of 8-pCPT-2'-O-Me-cAMP on thrombin- and TRAP-induced Rap 1 activation, thus suggesting that PKA is not involved. We conclude that the 8-pCPT-2'-O-Me-cAMP analogue is able to inhibit agonist-induced-GPCR-stimulated P-selectin independent from Epac1; the off-target effect of the analogue appears to be mediated by antagonistic P2Y12 receptor binding. This has implications when using cAMP analogues on specialised system involving such receptors. We found, however that the Epac agonist 8-Br-2'-O-Me-cAMP did not affect platelet activation at similar concentrations. Copyright © 2013 Elsevier Inc. All rights reserved.

Activation of G protein-coupled bile acid receptor, TGR5, induces smooth muscle relaxation via both Epac- and PKA-mediated inhibition of RhoA/Rho kinase pathway.

PubMed

Rajagopal, Senthilkumar; Kumar, Divya P; Mahavadi, Sunila; Bhattacharya, Sayak; Zhou, Ruizhe; Corvera, Carlos U; Bunnett, Nigel W; Grider, John R; Murthy, Karnam S

2013-03-01

The present study characterized the TGR5 expression and the signaling pathways coupled to this receptor that mediates the relaxation of gastric smooth muscle. TGR5 was detected in gastric muscle cells by RT-PCR and Western blotting. Treatment of cells with the TGR5-selective ligand oleanolic acid (OA) activated Gαs, but not Gαq, Gαi1, Gαi2, or Gαi3, and increased cAMP levels. OA did not elicit contraction, but caused relaxation of carbachol-induced contraction of gastric muscle cells from wild-type mice, but not tgr5(-/-) mice. OA, but not a selective exchange protein activated by cAMP (Epac) ligand (8-pCPT-2'-O-Me-cAMP), caused phosphorylation of RhoA and the phosphorylation was blocked by the PKA inhibitor, myristoylated PKI, and by the expression of phosphorylation-deficient mutant RhoA (S188A). Both OA and Epac ligand stimulated Ras-related protein 1 (Rap1) and inhibited carbachol (CCh)-induced Rho kinase activity. Expression of RhoA (S188A) or PKI partly reversed the inhibition of Rho kinase activity by OA but had no effect on inhibition by Epac ligand. However, suppression of Rap1 with siRNA blocked the inhibition of Rho kinase by Epac ligand, and partly reversed the inhibition by OA; the residual inhibition was blocked by PKI. Muscle relaxation in response to OA, but not Epac ligand, was partly reversed by PKI. We conclude that activation of TGR5 causes relaxation of gastric smooth muscle and the relaxation is mediated through inhibition of RhoA/Rho kinase pathway via both cAMP/Epac-dependent stimulation of Rap1 and cAMP/PKA-dependent phosphorylation of RhoA at Ser(188). TGR5 receptor activation on smooth muscle reveals a novel mechanism for the regulation of gut motility by bile acids.

Activation of G protein-coupled bile acid receptor, TGR5, induces smooth muscle relaxation via both Epac- and PKA-mediated inhibition of RhoA/Rho kinase pathway

PubMed Central

Rajagopal, Senthilkumar; Kumar, Divya P.; Mahavadi, Sunila; Bhattacharya, Sayak; Zhou, Ruizhe; Corvera, Carlos U.; Bunnett, Nigel W.; Grider, John R.

2013-01-01

The present study characterized the TGR5 expression and the signaling pathways coupled to this receptor that mediates the relaxation of gastric smooth muscle. TGR5 was detected in gastric muscle cells by RT-PCR and Western blotting. Treatment of cells with the TGR5-selective ligand oleanolic acid (OA) activated Gαs, but not Gαq, Gαi1, Gαi2, or Gαi3, and increased cAMP levels. OA did not elicit contraction, but caused relaxation of carbachol-induced contraction of gastric muscle cells from wild-type mice, but not tgr5−/− mice. OA, but not a selective exchange protein activated by cAMP (Epac) ligand (8-pCPT-2′-O-Me-cAMP), caused phosphorylation of RhoA and the phosphorylation was blocked by the PKA inhibitor, myristoylated PKI, and by the expression of phosphorylation-deficient mutant RhoA (S188A). Both OA and Epac ligand stimulated Ras-related protein 1 (Rap1) and inhibited carbachol (CCh)-induced Rho kinase activity. Expression of RhoA (S188A) or PKI partly reversed the inhibition of Rho kinase activity by OA but had no effect on inhibition by Epac ligand. However, suppression of Rap1 with siRNA blocked the inhibition of Rho kinase by Epac ligand, and partly reversed the inhibition by OA; the residual inhibition was blocked by PKI. Muscle relaxation in response to OA, but not Epac ligand, was partly reversed by PKI. We conclude that activation of TGR5 causes relaxation of gastric smooth muscle and the relaxation is mediated through inhibition of RhoA/Rho kinase pathway via both cAMP/Epac-dependent stimulation of Rap1 and cAMP/PKA-dependent phosphorylation of RhoA at Ser188. TGR5 receptor activation on smooth muscle reveals a novel mechanism for the regulation of gut motility by bile acids. PMID:23275618

β-Adrenergic induced SR Ca2+ leak is mediated by an Epac-NOS pathway.

PubMed

Pereira, Laëtitia; Bare, Dan J; Galice, Samuel; Shannon, Thomas R; Bers, Donald M

2017-07-01

Cardiac β-adrenergic receptors (β-AR) and Ca 2+ -Calmodulin dependent protein kinase (CaMKII) regulate both physiological and pathophysiological Ca 2+ signaling. Elevated diastolic Ca 2+ leak from the sarcoplasmic reticulum (SR) contributes to contractile dysfunction in heart failure and to arrhythmogenesis. β-AR activation is known to increase SR Ca 2+ leak via CaMKII-dependent phosphorylation of the ryanodine receptor. Two independent and reportedly parallel pathways have been implicated in this β-AR-CaMKII cascade, one involving exchange protein directly activated by cAMP (Epac2) and another involving nitric oxide synthase 1 (NOS1). Here we tested whether Epac and NOS function in a single series pathway to increase β-AR induced and CaMKII-dependent SR Ca 2+ leak. Leak was measured as both Ca 2+ spark frequency and tetracaine-induced shifts in SR Ca 2+ , in mouse and rabbit ventricular myocytes. Direct Epac activation by 8-CPT (8-(4-chlorophenylthio)-2'-O-methyl-cAMP) mimicked β-AR-induced SR Ca 2+ leak, and both were blocked by NOS inhibition. The same was true for myocyte CaMKII activation (assessed via a FRET-based reporter) and ryanodine receptor phosphorylation. Inhibitor and phosphorylation studies also implicated phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) downstream of Epac and above NOS activation in this pathway. We conclude that these two independently characterized parallel pathways function mainly via a single series arrangement (β-AR-cAMP-Epac-PI3K-Akt-NOS1-CaMKII) to mediate increased SR Ca 2+ leak. Thus, for β-AR activation the cAMP-PKA branch effects inotropy and lusitropy (by effects on Ca 2+ current and SR Ca 2+ -ATPase), this cAMP-Epac-NOS pathway increases pathological diastolic SR Ca 2+ leak. This pathway distinction may allow novel SR Ca 2+ leak therapeutic targeting in treatment of arrhythmias in heart failure that spare the inotropic and lusitropic effects of the PKA branch. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lithium and an EPAC-specific inhibitor ESI-09 synergistically suppress pancreatic cancer cell proliferation and survival.

PubMed

Wang, Xinshuo; Luo, Cheng; Cheng, Xiaodong; Lu, Meiling

2017-07-01

Our previous studies showed that while lithium suppresses proliferation and induces apoptosis in pancreatic cancer cells, the inhibition of exchange proteins directly activated by cyclic adenosine monophosphate (cAMP) (EPAC)1 blocks pancreatic cancer cell migration and invasion. In this study, we further investigated the combinatory effects of lithium and EPAC-specific inhibitor (ESI)-09, an EPAC-specific inhibitor, on pancreatic cancer cell proliferation and viability, and explored whether lithium synergistically cooperates with EPAC inhibition in suppressing pancreatic cancer cell tumorigenicity. The cell viability of pancreatic cancer cell lines PANC-1 and MiaPaCa-2 was measured after 48 h of incubation with different dose combination of lithium and ESI-09. Flow cytometric analysis was carried out to further verify the impact of lithium and ESI-09 upon PANC-1 cell proliferation and apoptosis. To investigate the mechanism that the effects generated by lithium and ESI-09 on PANC-1 cells, the intracellular cAMP level was measured by an ELISA-based cAMP immunoassay. Our data showed that lithium and ESI-09 synergistically inhibit pancreatic cancer cell growth and survival. Furthermore, our results revealed a novel mechanism in which the synergism between lithium and ESI-09 is not mediated by the inhibitory effect of lithium toward GSK3β, but by lithium's ability to suppress cAMP/protein kinase A signaling. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Phosphodiesterase inhibitors suppress Lactobacillus casei cell-wall-induced NF-κB and MAPK activations and cell proliferation through protein kinase A--or exchange protein activated by cAMP-dependent signal pathway.

PubMed

Saito, Takekatsu; Sugimoto, Naotoshi; Ohta, Kunio; Shimizu, Tohru; Ohtani, Kaori; Nakayama, Yuko; Nakamura, Taichi; Hitomi, Yashiaki; Nakamura, Hiroyuki; Koizumi, Shoichi; Yachie, Akihiro

2012-01-01

Specific strains of Lactobacillus have been found to be beneficial in treating some types of diarrhea and vaginosis. However, a high mortality rate results from underlying immunosuppressive conditions in patients with Lactobacillus casei bacteremia. Cyclic AMP (cAMP) is a small second messenger molecule that mediates signal transduction. The onset and progression of inflammatory responses are sensitive to changes in steady-state cAMP levels. L. casei cell wall extract (LCWE) develops arteritis in mice through Toll-like receptor-2 signaling. The purpose of this study was to investigate whether intracellular cAMP affects LCWE-induced pathological signaling. LCWE was shown to induce phosphorylation of the nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways and cell proliferation in mice fibroblast cells. Theophylline and phosphodiesterase inhibitor increased intracellular cAMP and inhibited LCWE-induced cell proliferation as well as phosphorylation of NF-κB and MAPK. Protein kinase A inhibitor H89 prevented cAMP-induced MAPK inhibition, but not cAMP-induced NF-κB inhibition. An exchange protein activated by cAMP (Epac) agonist inhibited NF-κB activation but not MAPK activation. These results indicate that an increase in intracellular cAMP prevents LCWE induction of pathological signaling pathways dependent on PKA and Epac signaling.

Rasip1 regulates vertebrate vascular endothelial junction stability through Epac1-Rap1 signaling

PubMed Central

Wilson, Christopher W.; Parker, Leon H.; Hall, Christopher J.; Smyczek, Tanya; Mak, Judy; Crow, Ailey; Posthuma, George; De Mazière, Ann; Sagolla, Meredith; Chalouni, Cecile; Vitorino, Philip; Roose-Girma, Merone; Warming, Søren; Klumperman, Judith; Crosier, Philip S.

2013-01-01

Establishment and stabilization of endothelial tubes with patent lumens is vital during vertebrate development. Ras-interacting protein 1 (RASIP1) has been described as an essential regulator of de novo lumenogenesis through modulation of endothelial cell (EC) adhesion to the extracellular matrix (ECM). Here, we show that in mouse and zebrafish embryos, Rasip1-deficient vessels transition from an angioblast cord to a hollow tube, permit circulation of primitive erythrocytes, but ultimately collapse, leading to hemorrhage and embryonic lethality. Knockdown of RASIP1 does not alter EC-ECM adhesion, but causes cell-cell detachment and increases permeability of EC monolayers in vitro. We also found that endogenous RASIP1 in ECs binds Ras-related protein 1 (RAP1), but not Ras homolog gene family member A or cell division control protein 42 homolog. Using an exchange protein directly activated by cyclic adenosine monophosphate 1 (EPAC1)-RAP1–dependent model of nascent junction formation, we demonstrate that a fraction of the RASIP1 protein pool localizes to cell-cell contacts. Loss of RASIP1 phenocopies loss of RAP1 or EPAC1 in ECs by altering junctional actin organization, localization of the actin-bundling protein nonmuscle myosin heavy chain IIB, and junction remodeling. Our data show that RASIP1 regulates the integrity of newly formed blood vessels as an effector of EPAC1-RAP1 signaling. PMID:23886837

Forskolin increases angiogenesis through the coordinated cross-talk of PKA-dependent VEGF expression and Epac-mediated PI3K/Akt/eNOS signaling.

PubMed

Namkoong, Seung; Kim, Chun-Ki; Cho, Young-Lai; Kim, Ji-Hee; Lee, Hansoo; Ha, Kwon-Soo; Choe, Jongseon; Kim, Pyeung-Hyeun; Won, Moo-Ho; Kwon, Young-Geun; Shim, Eun Bo; Kim, Young-Myeong

2009-06-01

Forskolin, a potent activator of adenylyl cyclases, has been implicated in modulating angiogenesis, but the underlying mechanism has not been clearly elucidated. We investigated the signal mechanism by which forskolin regulates angiogenesis. Forskolin stimulated angiogenesis of human endothelial cells and in vivo neovascularization, which was accompanied by phosphorylation of CREB, ERK, Akt, and endothelial nitric oxide synthase (eNOS) as well as NO production and VEGF expression. Forskolin-induced CREB phosphorylation, VEGF promoter activity, and VEGF expression were blocked by the PKA inhibitor PKI.Moreover, phosphorylation of ERK by forskolin was inhibited by the MEK inhibitor PD98059, but not PKI. The forskolin-induced Akt/eNOS/NO pathway was completely inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, but not significantly suppressed by PKI. These inhibitors and a NOS inhibitor partially inhibited forskolin-induced angiogenesis. The exchange protein directly activated by cAMP (Epac) activator, 8CPT-2Me-cAMP, promoted the Akt/eNOS/NO pathway and ERK phosphorylation,but did not induce CREB phosphorylation and VEGF expression. The angiogenic effect of the Epac activator was diminished by the inhibition of PI3K and MEK, but not by the PKA inhibitor. Small interfering RNA-mediated knockdown of Epac1 suppressed forskolin-induced angiogenesis and phosphorylation of ERK, Akt, and eNOS, but not CREB phosphorylation and VEGF expression. These results suggest that forskolin stimulates angiogenesis through coordinated cross-talk between two distinct pathways, PKA-dependent VEGF expression and Epac-dependent ERKactivation and PI3K/Akt/eNOS/NO signaling.

cAMP signalling decreases p300 protein levels by promoting its ubiquitin/proteasome dependent degradation via Epac and p38 MAPK in lung cancer cells.

PubMed

Jeong, Min-Jae; Kim, Eui-Jun; Cho, Eun-Ah; Ye, Sang-Kyu; Kang, Gyeong Hoon; Juhnn, Yong-Sung

2013-05-02

The transcriptional coactivator p300 functions as a histone acetyltransferase and a scaffold for transcription factors. We investigated the effect of cAMP signalling on p300 expression. The activation of cAMP signalling by the expression of constitutively active Gαs or by treatment with isoproterenol decreased the p300 protein expression in lung cancer cells. Isoproterenol promoted the ubiquitination and subsequent proteasomal degradation of p300 in an Epac-dependent manner. Epac promoted p300 degradation by inhibiting the activity of p38 MAPK. It is concluded that cAMP signalling decreases the level of the p300 protein by promoting its ubiquitin-proteasome dependent degradation, which is mediated by Epac and p38 MAPK, in lung cancer cells. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Exchange Protein Activated by cAMP Enhances Long-Term Memory Formation Independent of Protein Kinase A

ERIC Educational Resources Information Center

Ma, Nan; Abel, Ted; Hernandez, Pepe J.

2009-01-01

It is well established that cAMP signaling within neurons plays a major role in the formation of long-term memories--signaling thought to proceed through protein kinase A (PKA). However, here we show that exchange protein activated by cAMP (Epac) is able to enhance the formation of long-term memory in the hippocampus and appears to do so…

Transcriptional activation of peroxisome proliferator-activated receptor-{gamma} requires activation of both protein kinase A and Akt during adipocyte differentiation

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

Kim, Sang-pil; Ha, Jung Min; Yun, Sung Ji

2010-08-13

Research highlights: {yields} Elevated cAMP activates both PKA and Epac. {yields} PKA activates CREB transcriptional factor and Epac activates PI3K/Akt pathway via Rap1. {yields} Akt modulates PPAR-{gamma} transcriptional activity in concert with CREB. -- Abstract: Peroxisome proliferator-activated receptor-{gamma} (PPAR-{gamma}) is required for the conversion of pre-adipocytes. However, the mechanism underlying activation of PPAR-{gamma} is unclear. Here we showed that cAMP-induced activation of protein kinase A (PKA) and Akt is essential for the transcriptional activation of PPAR-{gamma}. Hormonal induction of adipogenesis was blocked by a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002), by a protein kinase A (PKA) inhibitor (H89), and by amore » Rap1 inhibitor (GGTI-298). Transcriptional activity of PPAR-{gamma} was markedly enhanced by 3-isobutyl-1-methylxanthine (IBMX), but not insulin and dexamethasone. In addition, IBMX-induced PPAR-{gamma} transcriptional activity was blocked by PI3K/Akt, PKA, or Rap1 inhibitors. 8-(4-Chlorophenylthio)-2'-O-methyl-cAMP (8-pCPT-2'-O-Me-cAMP) which is a specific agonist for exchanger protein directly activated by cAMP (Epac) significantly induced the activation of Akt. Furthermore, knock-down of Akt1 markedly attenuated PPAR-{gamma} transcriptional activity. These results indicate that both PKA and Akt signaling pathways are required for transcriptional activation of PPAR-{gamma}, suggesting post-translational activation of PPAR-{gamma} might be critical step for adipogenic gene expression.« less

Epac2 Mediates cAMP-Dependent Potentiation of Neurotransmission in the Hippocampus

PubMed Central

Fernandes, Herman B.; Riordan, Sean; Nomura, Toshihiro; Remmers, Christine L.; Kraniotis, Stephen; Marshall, John J.; Kukreja, Lokesh; Vassar, Robert

2015-01-01

Presynaptic terminal cAMP elevation plays a central role in plasticity at the mossy fiber-CA3 synapse of the hippocampus. Prior studies have identified protein kinase A as a downstream effector of cAMP that contributes to mossy fiber LTP (MF-LTP), but the potential contribution of Epac2, another cAMP effector expressed in the MF synapse, has not been considered. We investigated the role of Epac2 in MF-CA3 neurotransmission using Epac2−/− mice. The deletion of Epac2 did not cause gross alterations in hippocampal neuroanatomy or basal synaptic transmission. Synaptic facilitation during short trains was not affected by loss of Epac2 activity; however, both long-term plasticity and forskolin-mediated potentiation of MFs were impaired, demonstrating that Epac2 contributes to cAMP-dependent potentiation of transmitter release. Examination of synaptic transmission during long sustained trains of activity suggested that the readily releasable pool of vesicles is reduced in Epac2−/− mice. These data suggest that cAMP elevation uses an Epac2-dependent pathway to promote transmitter release, and that Epac2 is required to maintain the readily releasable pool at MF synapses in the hippocampus. PMID:25904804

Microtubule-regulating proteins and cAMP-dependent signaling in neuroblastoma differentiation.

PubMed

Muñoz-Llancao, Pablo; de Gregorio, Cristian; Las Heras, Macarena; Meinohl, Christopher; Noorman, Kevin; Boddeke, Erik; Cheng, Xiaodong; Lezoualc'h, Frank; Schmidt, Martina; Gonzalez-Billault, Christian

2017-03-01

Neurons are highly differentiated cells responsible for the conduction and transmission of information in the nervous system. The proper function of a neuron relies on the compartmentalization of their intracellular domains. Differentiated neuroblastoma cells have been extensively used to study and understand the physiology and cell biology of neuronal cells. Here, we show that differentiation of N1E-115 neuroblastoma cells is more pronounced upon exposure of a chemical analog of cyclic AMP (cAMP), db-cAMP. We next analysed the expression of key microtubule-regulating proteins in differentiated cells and the expression and activation of key cAMP players such as EPAC, PKA and AKAP79/150. Most of the microtubule-promoting factors were up regulated during differentiation of N1E-115 cells, while microtubule-destabilizing proteins were down regulated. We observed an increase in tubulin post-translational modifications related to microtubule stability. As expected, db-cAMP increased PKA- and EPAC-dependent signalling. Consistently, pharmacological modulation of EPAC activity instructed cell differentiation, number of neurites, and neurite length in N1E-115 cells. Moreover, disruption of the PKA-AKAP interaction reduced these morphometric parameters. Interestingly, PKA and EPAC act synergistically to induce neuronal differentiation in N1E-115. Altogether these results show that the changes observed in the differentiation of N1E-115 cells proceed by regulating several microtubule-stabilizing factors, and the acquisition of a neuronal phenotype is a process involving concerted although independent functions of EPAC and PKA. © 2017 Wiley Periodicals, Inc.

β-Agonist-mediated Relaxation of Airway Smooth Muscle Is Protein Kinase A-dependent*

PubMed Central

Morgan, Sarah J.; Deshpande, Deepak A.; Tiegs, Brian C.; Misior, Anna M.; Yan, Huandong; Hershfeld, Alena V.; Rich, Thomas C.; Panettieri, Reynold A.; An, Steven S.; Penn, Raymond B.

2014-01-01

Inhaled β-agonists are effective at reversing bronchoconstriction in asthma, but the mechanism by which they exert this effect is unclear and controversial. PKA is the historically accepted effector, although this assumption is made on the basis of associative and not direct evidence. Recent studies have asserted that exchange protein activated by cAMP (Epac), not PKA, mediates the relaxation of airway smooth muscle (ASM) observed with β-agonist treatment. This study aims to clarify the role of PKA in the prorelaxant effects of β-agonists on ASM. Inhibition of PKA activity via expression of the PKI and RevAB peptides results in increased β-agonist-mediated cAMP release, abolishes the inhibitory effect of isoproterenol on histamine-induced intracellular calcium flux, and significantly attenuates histamine-stimulated MLC-20 phosphorylation. Analyses of ASM cell and tissue contraction demonstrate that PKA inhibition eliminates most, if not all, β-agonist-mediated relaxation of contracted smooth muscle. Conversely, Epac knockdown had no effect on the regulation of contraction or procontractile signaling by isoproterenol. These findings suggest that PKA, not Epac, is the predominant and physiologically relevant effector through which β-agonists exert their relaxant effects. PMID:24973219

Epac2 Mediates cAMP-Dependent Potentiation of Neurotransmission in the Hippocampus.

PubMed

Fernandes, Herman B; Riordan, Sean; Nomura, Toshihiro; Remmers, Christine L; Kraniotis, Stephen; Marshall, John J; Kukreja, Lokesh; Vassar, Robert; Contractor, Anis

2015-04-22

Presynaptic terminal cAMP elevation plays a central role in plasticity at the mossy fiber-CA3 synapse of the hippocampus. Prior studies have identified protein kinase A as a downstream effector of cAMP that contributes to mossy fiber LTP (MF-LTP), but the potential contribution of Epac2, another cAMP effector expressed in the MF synapse, has not been considered. We investigated the role of Epac2 in MF-CA3 neurotransmission using Epac2(-/-) mice. The deletion of Epac2 did not cause gross alterations in hippocampal neuroanatomy or basal synaptic transmission. Synaptic facilitation during short trains was not affected by loss of Epac2 activity; however, both long-term plasticity and forskolin-mediated potentiation of MFs were impaired, demonstrating that Epac2 contributes to cAMP-dependent potentiation of transmitter release. Examination of synaptic transmission during long sustained trains of activity suggested that the readily releasable pool of vesicles is reduced in Epac2(-/-) mice. These data suggest that cAMP elevation uses an Epac2-dependent pathway to promote transmitter release, and that Epac2 is required to maintain the readily releasable pool at MF synapses in the hippocampus. Copyright © 2015 the authors 0270-6474/15/356544-10$15.00/0.

Preparation of Enteromorpha prolifera-based cetyl trimethyl ammonium bromide-doped activated carbon and its application for nickel(II) removal.

PubMed

Wang, Man; Hao, Fang; Li, Gang; Huang, Ji; Bao, Nan; Huang, Lihui

2014-06-01

Activated carbon was prepared from Enteromorpha prolifera (EP) by H3PO4 activation in the presence of doped cetyl trimethyl ammonium bromide (CTAB), producing EPAC-CTAB. The thermal decomposition process of the activated carbon substrate was identified by thermo-gravimetric analysis. Scanning electron microscope (SEM), N2 adsorption/desorption, Fourier transform infrared spectroscopy (FTIR), Boehm titration, and X-ray Photoelectron Spectroscopy (XPS) were employed to characterize the physicochemical properties of native EPAC and EPAC-CTAB. EPAC-CTAB exhibited smaller surface area (689.0m(2)/g) and lower total pore volume (0.361cm(3)/g) than those of EPAC (1045.8m(2)/g and 1.048cm(3)/g), while the number of acidic groups, oxygen and nitrogen groups on the surface of EPAC-CTAB increased through CTAB doping. The batch kinetics and isotherm adsorption studies of nickel(II) onto the adsorbents were examined and agreed well with the pseudo-second-order model and the Langmuir model. The maximum adsorption capacity determined from the Langmuir model was 16.9mg/g for EPAC and 49.8mg/g for EPAC-CTAB. Under acidic condition, the adsorption of nickel(II) onto EPAC and EPAC-CTAB was hindered due to ion competition and electrostatic repulsion. The results indicated that using CTAB as a dopant for EPAC modification could markedly enhance the nickel(II) removal. Copyright © 2014. Published by Elsevier Inc.

Activation of G protein-coupled estrogen receptor 1 induces coronary artery relaxation via Epac/Rap1-mediated inhibition of RhoA/Rho kinase pathway in parallel with PKA.

PubMed

Yu, Xuan; Zhang, Qiao; Zhao, Yan; Schwarz, Benjamin J; Stallone, John N; Heaps, Cristine L; Han, Guichun

2017-01-01

Previously, we reported that cAMP/PKA signaling is involved in GPER-mediated coronary relaxation by activating MLCP via inhibition of RhoA pathway. In the current study, we tested the hypothesis that activation of GPER induces coronary artery relaxation via inhibition of RhoA/Rho kinase pathway by cAMP downstream targets, exchange proteins directly activated by cAMP (Epac) as well as PKA. Our results show that Epac inhibitors, brefeldin A (BFA, 50 μM), or ESI-09 (20 μM), or CE3F4 (100 μM), all partially inhibited porcine coronary artery relaxation response to the selective GPER agonist, G-1 (0.3-3 μM); while concurrent administration of BFA and PKI (5 μM), a PKA inhibitor, almost completely blocked the relaxation effect of G-1. The Epac specific agonist, 8-CPT-2Me-cAMP (007, 1-100 μM), induced a concentration-dependent relaxation response. Furthermore, the activity of Ras-related protein 1 (Rap1) was up regulated by G-1 (1 μM) treatment of porcine coronary artery smooth muscle cells (CASMCs). Phosphorylation of vasodilator-stimulated phosphoprotein (p-VASP) was elevated by G-1 (1 μM) treatment, but not by 007 (50 μM); and the effect of G-1 on p-VASP was blocked by PKI, but not by ESI-09, an Epac antagonist. RhoA activity was similarly down regulated by G-1 and 007, whereas ESI-09 restored most of the reduced RhoA activity by G-1 treatment. Furthermore, G-1 decreased PGF2α-induced p-MYPT1, which was partially reversed with either ESI-09 or PKI; whereas, concurrent administration of ESI-09 and PKI totally prevented the inhibitory effect of G-1. The inhibitory effects of G-1 on p- MLC levels in CASMCs were mostly restored by either ESI-09 or PKI. These results demonstrate that activation of GPER induces coronary artery relaxation via concurrent inhibition of RhoA/Rho kinase by Epac/Rap1 and PKA. GPER could be a potential drug target for preventing and treating cardiovascular diseases.

Activation of exchange protein activated by cAMP in the rat basolateral amygdala impairs reconsolidation of a memory associated with self-administered cocaine.

PubMed

Wan, Xun; Torregrossa, Mary M; Sanchez, Hayde; Nairn, Angus C; Taylor, Jane R

2014-01-01

The intracellular mechanisms underlying memory reconsolidation critically involve cAMP signaling. These events were originally attributed to PKA activation by cAMP, but the identification of Exchange Protein Activated by cAMP (Epac), as a distinct mediator of cAMP signaling, suggests that cAMP-regulated processes that subserve memory reconsolidation are more complex. Here we investigated how activation of Epac with 8-pCPT-cAMP (8-CPT) impacts reconsolidation of a memory that had been associated with cocaine self-administration. Rats were trained to lever press for cocaine on an FR-1 schedule, in which each cocaine delivery was paired with a tone+light cue. Lever pressing was then extinguished in the absence of cue presentations and cocaine delivery. Following the last day of extinction, rats were put in a novel context, in which the conditioned cue was presented to reactivate the cocaine-associated memory. Immediate bilateral infusions of 8-CPT into the basolateral amygdala (BLA) following reactivation disrupted subsequent cue-induced reinstatement in a dose-dependent manner, and modestly reduced responding for conditioned reinforcement. When 8-CPT infusions were delayed for 3 hours after the cue reactivation session or were given after a cue extinction session, no effect on cue-induced reinstatement was observed. Co-administration of 8-CPT and the PKA activator 6-Bnz-cAMP (10 nmol/side) rescued memory reconsolidation while 6-Bnz alone had no effect, suggesting an antagonizing interaction between the two cAMP signaling substrates. Taken together, these studies suggest that activation of Epac represents a parallel cAMP-dependent pathway that can inhibit reconsolidation of cocaine-cue memories and reduce the ability of the cue to produce reinstatement of cocaine-seeking behavior.

Activation of Exchange Protein Activated by cAMP in the Rat Basolateral Amygdala Impairs Reconsolidation of a Memory Associated with Self-Administered Cocaine

PubMed Central

Sanchez, Hayde; Nairn, Angus C.; Taylor, Jane R.

2014-01-01

The intracellular mechanisms underlying memory reconsolidation critically involve cAMP signaling. These events were originally attributed to PKA activation by cAMP, but the identification of Exchange Protein Activated by cAMP (Epac), as a distinct mediator of cAMP signaling, suggests that cAMP-regulated processes that subserve memory reconsolidation are more complex. Here we investigated how activation of Epac with 8-pCPT-cAMP (8-CPT) impacts reconsolidation of a memory that had been associated with cocaine self-administration. Rats were trained to lever press for cocaine on an FR-1 schedule, in which each cocaine delivery was paired with a tone+light cue. Lever pressing was then extinguished in the absence of cue presentations and cocaine delivery. Following the last day of extinction, rats were put in a novel context, in which the conditioned cue was presented to reactivate the cocaine-associated memory. Immediate bilateral infusions of 8-CPT into the basolateral amygdala (BLA) following reactivation disrupted subsequent cue-induced reinstatement in a dose-dependent manner, and modestly reduced responding for conditioned reinforcement. When 8-CPT infusions were delayed for 3 hours after the cue reactivation session or were given after a cue extinction session, no effect on cue-induced reinstatement was observed. Co-administration of 8-CPT and the PKA activator 6-Bnz-cAMP (10 nmol/side) rescued memory reconsolidation while 6-Bnz alone had no effect, suggesting an antagonizing interaction between the two cAMP signaling substrates. Taken together, these studies suggest that activation of Epac represents a parallel cAMP-dependent pathway that can inhibit reconsolidation of cocaine-cue memories and reduce the ability of the cue to produce reinstatement of cocaine-seeking behavior. PMID:25259911

β-Agonist-mediated relaxation of airway smooth muscle is protein kinase A-dependent.

PubMed

Morgan, Sarah J; Deshpande, Deepak A; Tiegs, Brian C; Misior, Anna M; Yan, Huandong; Hershfeld, Alena V; Rich, Thomas C; Panettieri, Reynold A; An, Steven S; Penn, Raymond B

2014-08-15

Inhaled β-agonists are effective at reversing bronchoconstriction in asthma, but the mechanism by which they exert this effect is unclear and controversial. PKA is the historically accepted effector, although this assumption is made on the basis of associative and not direct evidence. Recent studies have asserted that exchange protein activated by cAMP (Epac), not PKA, mediates the relaxation of airway smooth muscle (ASM) observed with β-agonist treatment. This study aims to clarify the role of PKA in the prorelaxant effects of β-agonists on ASM. Inhibition of PKA activity via expression of the PKI and RevAB peptides results in increased β-agonist-mediated cAMP release, abolishes the inhibitory effect of isoproterenol on histamine-induced intracellular calcium flux, and significantly attenuates histamine-stimulated MLC-20 phosphorylation. Analyses of ASM cell and tissue contraction demonstrate that PKA inhibition eliminates most, if not all, β-agonist-mediated relaxation of contracted smooth muscle. Conversely, Epac knockdown had no effect on the regulation of contraction or procontractile signaling by isoproterenol. These findings suggest that PKA, not Epac, is the predominant and physiologically relevant effector through which β-agonists exert their relaxant effects. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Null EPAC Mutants Reveal a Sequential Order of Versatile cAMP Effects during "Drosophila" Aversive Odor Learning

ERIC Educational Resources Information Center

Richlitzki, Antje; Latour, Philipp; Schwärzel, Martin

2017-01-01

Here, we define a role of the cAMP intermediate EPAC in "Drosophila" aversive odor learning by means of null epac mutants. Complementation analysis revealed that EPAC acts downstream from the "rutabaga" adenylyl cyclase and in parallel to protein kinase A. By means of targeted knockdown and genetic rescue we identified mushroom…

A role for Piezo2 in EPAC1-dependent mechanical allodynia

PubMed Central

Eijkelkamp, N; Linley, J.E.; Torres, J.M.; Bee, L.; Dickenson, A.H.; Gringhuis, M.; Minett, M.S.; Hong, G.S.; Lee, E.; Oh, U.; Ishikawa, Y.; Zwartkuis, F.J.; Cox, J.J.; Wood, J.N.

2013-01-01

Aberrant mechanosensation has an important role in different pain states. Here we show that Epac1 (cyclic AMP sensor) potentiation of Piezo2-mediated mechanotransduction contributes to mechanical allodynia. Dorsal root ganglia Epac1 mRNA levels increase during neuropathic pain, and nerve damage-induced allodynia is reduced in Epac1−/− mice. The Epac-selective cAMP analogue 8-pCPT sensitizes mechanically evoked currents in sensory neurons. Human Piezo2 produces large mechanically gated currents that are enhanced by the activation of the cAMP-sensor Epac1 or cytosolic calcium but are unaffected by protein kinase C or protein kinase A and depend on the integrity of the cytoskeleton. In vivo, 8-pCPT induces long-lasting allodynia that is prevented by the knockdown of Epac1 and attenuated by mouse Piezo2 knockdown. Piezo2 knockdown also enhanced thresholds for light touch. Finally, 8-pCPT sensitizes responses to innocuous mechanical stimuli without changing the electrical excitability of sensory fibres. These data indicate that the Epac1–Piezo2 axis has a role in the development of mechanical allodynia during neuropathic pain. PMID:23575686

The Orphan G Protein-coupled Receptor GPR17 Negatively Regulates Oligodendrocyte Differentiation via Gαi/o and Its Downstream Effector Molecules.

PubMed

Simon, Katharina; Hennen, Stephanie; Merten, Nicole; Blättermann, Stefanie; Gillard, Michel; Kostenis, Evi; Gomeza, Jesus

2016-01-08

Recent studies have recognized G protein-coupled receptors as important regulators of oligodendrocyte development. GPR17, in particular, is an orphan G protein-coupled receptor that has been identified as oligodendroglial maturation inhibitor because its stimulation arrests primary mouse oligodendrocytes at a less differentiated stage. However, the intracellular signaling effectors transducing its activation remain poorly understood. Here, we use Oli-neu cells, an immortalized cell line derived from primary murine oligodendrocytes, and primary rat oligodendrocyte cultures as model systems to identify molecular targets that link cell surface GPR17 to oligodendrocyte maturation blockade. We demonstrate that stimulation of GPR17 by the small molecule agonist MDL29,951 (2-carboxy-4,6-dichloro-1H-indole-3-propionic acid) decreases myelin basic protein expression levels mainly by triggering the Gαi/o signaling pathway, which in turn leads to reduced activity of the downstream cascade adenylyl cyclase-cAMP-PKA-cAMP response element-binding protein (CREB). In addition, we show that GPR17 activation also diminishes myelin basic protein abundance by lessening stimulation of the exchange protein directly activated by cAMP (EPAC), thus uncovering a previously unrecognized role for EPAC to regulate oligodendrocyte differentiation. Together, our data establish PKA and EPAC as key downstream effectors of GPR17 that inhibit oligodendrocyte maturation. We envisage that treatments augmenting PKA and/or EPAC activity represent a beneficial approach for therapeutic enhancement of remyelination in those demyelinating diseases where GPR17 is highly expressed, such as multiple sclerosis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Exchange protein activated by cAMP (Epac) induces vascular relaxation by activating Ca2+-sensitive K+ channels in rat mesenteric artery

PubMed Central

Roberts, Owain Llŷr; Kamishima, Tomoko; Barrett-Jolley, Richard; Quayle, John M; Dart, Caroline

2013-01-01

Vasodilator-induced elevation of intracellular cyclic AMP (cAMP) is a central mechanism governing arterial relaxation but is incompletely understood due to the diversity of cAMP effectors. Here we investigate the role of the novel cAMP effector exchange protein directly activated by cAMP (Epac) in mediating vasorelaxation in rat mesenteric arteries. In myography experiments, the Epac-selective cAMP analogue 8-pCPT-2′-O-Me-cAMP-AM (5 μm, subsequently referred to as 8-pCPT-AM) elicited a 77.6 ± 7.1% relaxation of phenylephrine-contracted arteries over a 5 min period (mean ± SEM; n= 6). 8-pCPT-AM induced only a 16.7 ± 2.4% relaxation in arteries pre-contracted with high extracellular K+ over the same time period (n= 10), suggesting that some of Epac's relaxant effect relies upon vascular cell hyperpolarization. This involves Ca2+-sensitive, large-conductance K+ (BKCa) channel opening as iberiotoxin (100 nm) significantly reduced the ability of 8-pCPT-AM to reverse phenylephrine-induced contraction (arteries relaxed by only 35.0 ± 8.5% over a 5 min exposure to 8-pCPT-AM, n= 5; P < 0.05). 8-pCPT-AM increased Ca2+ spark frequency in Fluo-4-AM-loaded mesenteric myocytes from 0.045 ± 0.008 to 0.103 ± 0.022 sparks s-1μm-1 (P < 0.05) and reversibly increased both the frequency (0.94 ± 0.25 to 2.30 ± 0.72 s−1) and amplitude (23.9 ± 3.3 to 35.8 ± 7.7 pA) of spontaneous transient outward currents (STOCs) recorded in isolated mesenteric myocytes (n= 7; P < 0.05). 8-pCPT-AM-activated STOCs were sensitive to iberiotoxin (100 nm) and to ryanodine (30 μm). Current clamp recordings of isolated myocytes showed a 7.9 ± 1.0 mV (n= 10) hyperpolarization in response to 8-pCPT-AM that was sensitive to iberiotoxin (n= 5). Endothelial disruption suppressed 8-pCPT-AM-mediated relaxation in phenylephrine-contracted arteries (24.8 ± 4.9% relaxation after 5 min of exposure, n= 5; P < 0.05), as did apamin and TRAM-34, blockers of Ca2+-sensitive, small- and intermediate-conductance K+ (SKCa and IKCa) channels, respectively, and NG-nitro-l-arginine methyl ester, an inhibitor of nitric oxide synthase (NOS). In Fluo-4-AM-loaded mesenteric endothelial cells, 8-pCPT-AM induced a sustained increase in global Ca2+. Our data suggest that Epac hyperpolarizes smooth muscle by (1) increasing localized Ca2+ release from ryanodine receptors (Ca2+ sparks) to activate BKCa channels, and (2) endothelial-dependent mechanisms involving the activation of SKCa/IKCa channels and NOS. Epac-mediated smooth muscle hyperpolarization will limit Ca2+ entry via voltage-sensitive Ca2+ channels and represents a novel mechanism of arterial relaxation. PMID:23959673

Calcium/calmodulin‐dependent kinase 2 mediates Epac‐induced spontaneous transient outward currents in rat vascular smooth muscle

PubMed Central

Humphries, Edward S. A.; Kamishima, Tomoko; Quayle, John M.

2017-01-01

Key points The Ca2+ and redox‐sensing enzyme Ca2+/calmodulin‐dependent kinase 2 (CaMKII) is a crucial and well‐established signalling molecule in the heart and brain.In vascular smooth muscle, which controls blood flow by contracting and relaxing in response to complex Ca2+ signals and oxidative stress, surprisingly little is known about the role of CaMKII.The vasodilator‐induced second messenger cAMP can relax vascular smooth muscle via its effector, exchange protein directly activated by cAMP (Epac), by activating spontaneous transient outward currents (STOCs) that hyperpolarize the cell membrane and reduce voltage‐dependent Ca2+ influx. How Epac activates STOCs is unknown.In the present study, we map the pathway by which Epac increases STOC activity in contractile vascular smooth muscle and show that a critical step is the activation of CaMKII.To our knowledge, this is the first report of CaMKII activation triggering cellular activity known to induce vasorelaxation. Abstract Activation of the major cAMP effector, exchange protein directly activated by cAMP (Epac), induces vascular smooth muscle relaxation by increasing the activity of ryanodine (RyR)‐sensitive release channels on the peripheral sarcoplasmic reticulum. Resultant Ca2+ sparks activate plasma membrane Ca2+‐activated K+ (BKCa) channels, evoking spontaneous transient outward currents (STOCs) that hyperpolarize the cell and reduce voltage‐dependent Ca2+ entry. In the present study, we investigate the mechanism by which Epac increases STOC activity. We show that the selective Epac activator 8‐(4‐chloro‐phenylthio)‐2′‐O‐methyladenosine‐3′, 5‐cyclic monophosphate‐AM (8‐pCPT‐AM) induces autophosphorylation (activation) of calcium/calmodulin‐dependent kinase 2 (CaMKII) and also that inhibition of CaMKII abolishes 8‐pCPT‐AM‐induced increases in STOC activity. Epac‐induced CaMKII activation is probably initiated by inositol 1,4,5‐trisphosphate (IP3)‐mobilized Ca2+: 8‐pCPT‐AM fails to induce CaMKII activation following intracellular Ca2+ store depletion and inhibition of IP3 receptors blocks both 8‐pCPT‐AM‐mediated CaMKII phosphorylation and STOC activity. 8‐pCPT‐AM does not directly activate BKCa channels, but STOCs cannot be generated by 8‐pCPT‐AM in the presence of ryanodine. Furthermore, exposure to 8‐pCPT‐AM significantly slows the initial rate of [Ca2+]i rise induced by the RyR activator caffeine without significantly affecting the caffeine‐induced Ca2+ transient amplitude, a measure of Ca2+ store content. We conclude that Epac‐mediated STOC activity (i) occurs via activation of CaMKII and (ii) is driven by changes in the underlying behaviour of RyR channels. To our knowledge, this is the first report of CaMKII initiating cellular activity linked to vasorelaxation and suggests novel roles for this Ca2+ and redox‐sensing enzyme in the regulation of vascular tone and blood flow. PMID:28731505

Hydrogen peroxide stimulation of CFTR reveals an Epac-mediated, soluble AC-dependent cAMP amplification pathway common to GPCR signalling

PubMed Central

Ivonnet, P; Salathe, M; Conner, G E

2015-01-01

BACKGROUND AND PURPOSE H2O2 is widely understood to regulate intracellular signalling. In airway epithelia, H2O2 stimulates anion secretion primarily by activating an autocrine PGE2 signalling pathway via EP4 and EP1 receptors to initiate cytic fibrosis transmembrane regulator (CFTR)-mediated Cl− secretion. This study investigated signalling downstream of the receptors activated by H2O2. EXPERIMENTAL APPROACH Anion secretion by differentiated bronchial epithelial cells was measured in Ussing chambers during stimulation with H2O2, an EP4 receptor agonist or β2-adrenoceptor agonist in the presence and absence of inhibitors of ACs and downstream effectors. Intracellular calcium ([Ca2+]I) changes were followed by microscopy using fura–2-loaded cells and PKA activation followed by FRET microscopy. KEY RESULTS Transmembrane adenylyl cyclase (tmAC) and soluble AC (sAC) were both necessary for H2O2 and EP4 receptor-mediated CFTR activation in bronchial epithelia. H2O2 and EP4 receptor agonist stimulated tmAC to increase exchange protein activated by cAMP (Epac) activity that drives PLC activation to raise [Ca2+]i via Ca2+ store release (and not entry). Increased [Ca2+]i led to sAC activation and further increases in CFTR activity. Stimulation of sAC did not depend on changes in [HCO3−]. Ca2+-activated apical KCa1.1 channels and cAMP-activated basolateral KV7.1 channels contributed to H2O2-stimulated anion currents. A similar Epac-mediated pathway was seen following β2-adrenoceptor or forskolin stimulation. CONCLUSIONS AND IMPLICATIONS H2O2 initiated a complex signalling cascade that used direct stimulation of tmACs by Gαs followed by Epac-mediated Ca2+ crosstalk to activate sAC. The Epac-mediated Ca2+ signal constituted a positive feedback loop that amplified CFTR anion secretion following stimulation of tmAC by a variety of stimuli. PMID:25220136

Rp-cAMPS Prodrugs Reveal the cAMP Dependence of First-Phase Glucose-Stimulated Insulin Secretion

PubMed Central

Schwede, Frank; Chepurny, Oleg G.; Kaufholz, Melanie; Bertinetti, Daniela; Leech, Colin A.; Cabrera, Over; Zhu, Yingmin; Mei, Fang; Cheng, Xiaodong; Manning Fox, Jocelyn E.; MacDonald, Patrick E.; Genieser, Hans-G.; Herberg, Friedrich W.

2015-01-01

cAMP-elevating agents such as the incretin hormone glucagon-like peptide-1 potentiate glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. However, a debate has existed since the 1970s concerning whether or not cAMP signaling is essential for glucose alone to stimulate insulin secretion. Here, we report that the first-phase kinetic component of GSIS is cAMP-dependent, as revealed through the use of a novel highly membrane permeable para-acetoxybenzyl (pAB) ester prodrug that is a bioactivatable derivative of the cAMP antagonist adenosine-3′,5′-cyclic monophosphorothioate, Rp-isomer (Rp-cAMPS). In dynamic perifusion assays of human or rat islets, a step-wise increase of glucose concentration leads to biphasic insulin secretion, and under these conditions, 8-bromoadenosine-3′,5′-cyclic monophosphorothioate, Rp-isomer, 4-acetoxybenzyl ester (Rp-8-Br-cAMPS-pAB) inhibits first-phase GSIS by up to 80%. Surprisingly, second-phase GSIS is inhibited to a much smaller extent (≤20%). Using luciferase, fluorescence resonance energy transfer, and bioluminescence resonance energy transfer assays performed in living cells, we validate that Rp-8-Br-cAMPS-pAB does in fact block cAMP-dependent protein kinase activation. Novel effects of Rp-8-Br-cAMPS-pAB to block the activation of cAMP-regulated guanine nucleotide exchange factors (Epac1, Epac2) are also validated using genetically encoded Epac biosensors, and are independently confirmed in an in vitro Rap1 activation assay using Rp-cAMPS and Rp-8-Br-cAMPS. Thus, in addition to revealing the cAMP dependence of first-phase GSIS from human and rat islets, these findings establish a pAB-based chemistry for the synthesis of highly membrane permeable prodrug derivatives of Rp-cAMPS that act with micromolar or even nanomolar potency to inhibit cAMP signaling in living cells. PMID:26061564

Protective Effect of Quercetin in LPS-Induced Murine Acute Lung Injury Mediated by cAMP-Epac Pathway.

PubMed

Wang, Xue-Feng; Song, Shun-de; Li, Ya-Jun; Hu, Zheng Qiang; Zhang, Zhe-Wen; Yan, Chun-Guang; Li, Zi-Gang; Tang, Hui-Fang

2018-06-01

Quercetin (Que) as an abundant flavonol element possesses potent antioxidative properties and has protective effect in lipopolysaccharide (LPS)-induced acute lung injury (ALI), but the specific mechanism is still unclear, so we investigated the effect of Que from in vivo and in vitro studies and the related mechanism of cAMP-PKA/Epac pathway. The results in mice suggested that Que can inhibit the release of inflammatory cytokine, block neutrophil recruitment, and decrease the albumin leakage in dose-dependent manners. At the same time, Que can increase the cAMP content of lung tissue, and Epac content, except PKA. The results in epithelial cell (MLE-12) suggested that Que also can inhibit the inflammatory mediators keratinocyte-derived chemokines release after LPS stimulation; Epac inhibitor ESI-09 functionally antagonizes the inhibitory effect of Que; meanwhile, PKA inhibitor H89 functionally enhances the inhibitory effect of Que. Overexpression of Epac1 in MLE-12 suggested that Epac1 enhance the effect of Que. All those results suggested that the protective effect of quercetin in ALI is involved in cAMP-Epac pathway.

PKA and Epac synergistically inhibit smooth muscle cell proliferation

PubMed Central

Hewer, Richard C.; Sala-Newby, Graciela B.; Wu, Yih-Jer; Newby, Andrew C.; Bond, Mark

2011-01-01

Cyclic AMP signalling promotes VSMC quiescence in healthy vessels and during vascular healing following injury. Cyclic AMP inhibits VSMC proliferation via mechanisms that are not fully understood. We investigated the role of PKA and Epac signalling on cAMP-induced inhibition of VSMC proliferation. cAMP-mediated growth arrest was PKA-dependent. However, selective PKA activation with 6-Benzoyl-cAMP did not inhibit VSMC proliferation, indicating a requirement for additional pathways. Epac activation using the selective cAMP analogue 8-CPT-2′-O-Me-cAMP, did not affect levels of hyperphosphorylated Retinoblastoma (Rb) protein, a marker of G1-S phase transition, or BrdU incorporation, despite activation of the Epac-effector Rap1. However, 6-Benzoyl-cAMP and 8-CPT-2′-O-Me-cAMP acted synergistically to inhibit Rb-hyperphosphorylation and BrdU incorporation, indicating that both pathways are required for growth inhibition. Consistent with this, constitutively active Epac increased Rap1 activity and synergised with 6-Benzoyl-cAMP to inhibit VSMC proliferation. PKA and Epac synergised to inhibit phosphorylation of ERK and JNK. Induction of stellate morphology, previously associated with cAMP-mediated growth arrest, was also dependent on activation of both PKA and Epac. Rap1 inhibition with Rap1GAP or siRNA silencing did not negate forskolin-induced inhibition of Rb-hyperphosphorylation, BrdU incorporation or stellate morphology. This data demonstrates for the first time that Epac synergises with PKA via a Rap1-independent mechanism to mediate cAMP-induced growth arrest in VSMC. This work highlights the role of Epac as a major player in cAMP-dependent growth arrest in VSMC. PMID:20971121

Simulation of the Intraseasonal Variability over the Eastern Pacific ITCZ in Climate Models

NASA Technical Reports Server (NTRS)

Jiang, Xianan; Waliser, Duane E.; Kim, Daehyun; Zhao, Ming; Sperber, Kenneth R.; Stern, W. F.; Schubert, Siegfried D.; Zhang, Guang J.; Wang, Wanqiu; Khairoutdinov, Marat;

Acute alcohol intoxication-induced microvascular leakage.

PubMed

Doggett, Travis M; Breslin, Jerome W

2014-09-01

Alcohol intoxication can increase inflammation and worsen injury, yet the mechanisms involved are not clear. We investigated whether acute alcohol intoxication increases microvascular permeability and investigated potential signaling mechanisms in endothelial cells that may be involved. Conscious rats received a 2.5 g/kg alcohol bolus via gastric catheters to produce acute intoxication. Microvascular leakage of intravenously administered fluorescein isothiocyanate (FITC)-conjugated albumin (FITC-albumin) from the mesenteric microcirculation was assessed by intravital microscopy. Endothelial-specific mechanisms were studied using cultured endothelial cell monolayers. Transendothelial electrical resistance (TER) served as an index of barrier function, before and after treatment with alcohol or its metabolite acetaldehyde. Pharmacologic agents were used to test the roles of alcohol metabolism, oxidative stress, p38 mitogen-activated protein kinase (MAPK), myosin light-chain kinase (MLCK), rho kinase (ROCK), and exchange protein activated by cAMP (Epac). VE-cadherin localization was investigated to assess junctional integrity. Rac1 and RhoA activation was assessed by ELISA assays. Alcohol significantly increased FITC-albumin extravasation from the mesenteric microcirculation. Alcohol also significantly decreased TER and disrupted VE-cadherin organization at junctions. Acetaldehyde significantly decreased TER, but inhibition of alcohol dehydrogenase or application of a superoxide dismutase mimetic failed to prevent alcohol-induced decreases in TER. Inhibition of p38 MAPK, but not MLCK or ROCK, significantly attenuated the alcohol-induced barrier dysfunction. Alcohol rapidly decreased GTP-bound Rac1 but not RhoA during the drop in TER. Activation of Epac increased TER, but did not prevent alcohol from decreasing TER. However, activation of Epac after initiation of alcohol-induced barrier dysfunction quickly resolved TER to baseline levels. Our results suggest that alcohol intoxication increases microvascular permeability to plasma proteins. The data also suggest the endothelial-specific mechanism involves the p38 MAPK, Rac1, and reorganization of VE-cadherin at junctions. Last, activation of Epac can quickly resolve alcohol-induced endothelial barrier dysfunction. Copyright © 2014 by the Research Society on Alcoholism.

The role of c-Jun in controlling the EPAC1-dependent induction of the SOCS3 gene in HUVECs

PubMed Central

Wiejak, Jolanta; Dunlop, Julia; Yarwood, Stephen J.

2014-01-01

The cyclic AMP sensor, EPAC1, activates AP1-mediated transcription in HUVECs. Correspondingly, induction of the SOCS3 minimal promoter by EPAC1 requires a single AP1 site that constitutively binds phosphorylated (Ser63) c-Jun in DNA-pull-down assays. c-Jun (Ser63) becomes further phosphorylated following cyclic AMP stimulation and specific activation of protein kinase A (PKA), but not through selective activation of EPAC1. Moreover, despite a requirement for c-Jun for SOCS3 induction in fibroblasts, phospho-null c-Jun (Ser63/73Ala) had little effect on SOCS3 induction by cyclic AMP in HUVECs. AP1 activation and SOCS3 induction by EPAC1 in HUVECs therefore occur independently of c-Jun phosphorylation on Ser63. PMID:24631457

Evidence for a Pro-Proliferative Feedback Loop in Prostate Cancer: The Role of Epac1 and COX-2-Dependent Pathways

PubMed Central

Misra, Uma Kant; Pizzo, Salvatore Vincent

2013-01-01

Objective In human prostate cancer cells, a selective Epac agonist, 8-CPT-2Me-cAMP, upregulates cell proliferation and survival via activation of Ras-MAPK and PI- 3-kinase-Akt-mTOR signaling cascades. Here we examine the role of inflammatory mediators in Epac1-induced cellular proliferation by determining the expression of the pro-inflammatory markers p-cPLA2, COX-2, and PGE2 in prostate cancer cells treated with 8-CPT-2Me-cAMP. Methods We employed inhibitors of COX-2, mTORC1, and mTORC2 to probe cyclic AMP-dependent pathways in human prostate cancer cells. RNAi targeting Epac1, Raptor, and Rictor was also employed in these studies. Results 8-CPT-2Me-cAMP treatment caused a 2–2.5-fold increase of p-cPLA2S505, COX-2, and PGE2 levels in human prostate cancer cell lines. Pretreatment of cells with the COX-2 inhibitor SC-58125 or the EP4 antagonist AH-23848, or with an inhibitor of mTORC1 and mTORC2, Torin1, significantly reduced the Epac1-dependent increase of p-cPLA2 and COX-2, p-S6-kinaseT389, and p-AKTS473. In addition, Epac1-induced protein and DNA synthesis were greatly reduced upon pretreatment of cells with either COX-2, EP4, or mTOR inhibitors. Transfection of prostate cancer cells with Epac1 dsRNA, Raptor dsRNA, or Rictor dsRNA profoundly reduced Epac1-dependent increases in p-cPLA2 and COX-2. Conclusion We show that Epac1, a downstream effector of cAMP, functions as a pro-inflammatory modulator in prostate cancer cells and promotes cell proliferation and survival by upregulating Ras-MAPK, and PI 3-kinase-Akt-mTOR signaling. PMID:23646189

The role of c-Jun in controlling the EPAC1-dependent induction of the SOCS3 gene in HUVECs.

PubMed

Wiejak, Jolanta; Dunlop, Julia; Yarwood, Stephen J

2014-05-02

The cyclic AMP sensor, EPAC1, activates AP1-mediated transcription in HUVECs. Correspondingly, induction of the SOCS3 minimal promoter by EPAC1 requires a single AP1 site that constitutively binds phosphorylated (Ser63) c-Jun in DNA-pull-down assays. c-Jun (Ser63) becomes further phosphorylated following cyclic AMP stimulation and specific activation of protein kinase A (PKA), but not through selective activation of EPAC1. Moreover, despite a requirement for c-Jun for SOCS3 induction in fibroblasts, phospho-null c-Jun (Ser63/73Ala) had little effect on SOCS3 induction by cyclic AMP in HUVECs. AP1 activation and SOCS3 induction by EPAC1 in HUVECs therefore occur independently of c-Jun phosphorylation on Ser63. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Actions of cAMP on calcium sensitization in human detrusor smooth muscle contraction.

PubMed

Hayashi, Maya; Kajioka, Shunichi; Itsumi, Momoe; Takahashi, Ryosuke; Shahab, Nouval; Ishigami, Takao; Takeda, Masahiro; Masuda, Noriyuki; Yamaguchi, Akito; Naito, Seiji

2016-01-01

To clarify the effect of cAMP on the Ca(2+) -sensitized smooth muscle contraction in human detrusor, as well as the role of novel exchange protein directly activated by cAMP (Epac) in cAMP-mediated relaxation. All experimental protocols to record isometric tension force were performed using α-toxin-permeabilized human detrusor smooth muscle strips. The mechanisms of cAMP-mediated suppression of Ca(2+) sensitization activated by 10 μm carbachol (CCh) and 100 μm GTP were studied using a selective rho kinase (ROK) inhibitor, Y-27632, and a selective protein kinase C (PKC) inhibitor, GF-109203X. The relaxation mechanisms were further probed using a selective protein kinase A (PKA) activator, 6-Bnz-cAMP and a selective Epac activator, 8-pCPT-2'-O-Me-cAMP. We observed that CCh-induced Ca(2+) sensitization was inhibited by cAMP in a concentration-dependent manner. GF-109203X (10 μm) but not Y-27632 (10 μm) significantly enhanced the relaxation effect induced by cAMP (100 μm). 6-Bnz-cAMP (100 μm) predominantly decreased the tension force in comparison with 8-pCPT-2'-O-Me-cAMP (100 μm). We showed that cAMP predominantly inhibited the ROK pathway but not the PKC pathway. The PKA-dependent pathway is dominant, while Epac plays a minor role in human detrusor smooth muscle Ca(2+) sensitization. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

PDE4 inhibition reduces neointima formation and inhibits VCAM-1 expression and histone methylation in an Epac-dependent manner.

PubMed

Lehrke, Michael; Kahles, Florian; Makowska, Anna; Tilstam, Pathricia V; Diebold, Sebastian; Marx, Judith; Stöhr, Robert; Hess, Katharina; Endorf, Elizabeth B; Bruemmer, Dennis; Marx, Nikolaus; Findeisen, Hannes M

2015-04-01

Phosphodiesterase 4 (PDE4) activity mediates cAMP-dependent smooth muscle cell (SMC) activation following vascular injury. In this study we have investigated the effects of specific PDE4 inhibition with roflumilast on SMC proliferation and inflammatory activation in vitro and neointima formation following guide wire-induced injury of the femoral artery in mice in vivo. In vitro, roflumilast did not affect SMC proliferation, but diminished TNF-α induced expression of the vascular cell adhesion molecule 1 (VCAM-1). Specific activation of the cAMP effector Epac, but not PKA activation mimicked the effects of roflumilast on VCAM-1 expression. Consistently, the reduction of VCAM-1 expression was rescued following inhibition of Epac. TNF-α induced NFκB p65 translocation and VCAM-1 promoter activity were not altered by roflumilast in SMCs. However, roflumilast treatment and Epac activation repressed the induction of the activating epigenetic histone mark H3K4me2 at the VCAM-1 promoter, while PKA activation showed no effect. Furthermore, HDAC inhibition blocked the inhibitory effect of roflumilast on VCAM-1 expression. Both, roflumilast and Epac activation reduced monocyte adhesion to SMCs in vitro. Finally, roflumilast treatment attenuated femoral artery intima-media ratio by more than 50% after 4weeks. In summary, PDE4 inhibition regulates VCAM-1 through a novel Epac-dependent mechanism, which involves regulatory epigenetic components and reduces neointima formation following vascular injury. PDE4 inhibition and Epac activation might represent novel approaches for the treatment of vascular diseases, including atherosclerosis and in-stent restenosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Differential and brain region-specific regulation of Rap-1 and Epac in depressed suicide victims.

PubMed

Dwivedi, Yogesh; Mondal, Amal C; Rizavi, Hooriyah S; Faludi, Gabor; Palkovits, Miklos; Sarosi, Andrea; Conley, Robert R; Pandey, Ghanshyam N

2006-06-01

Depression is a major public health problem. Despite many years of research, the molecular mechanisms associated with depression remain unclear. Rap-1, activated in response to many extracellular stimuli, is one of the major substrates of protein kinase A, which participates in myriad physiologic functions in the brain, including cell survival and synaptic plasticity. Rap-1 is also activated directly by cyclic adenosine monophosphate through Epac, and thus participates in mediating physiologic functions independent of protein kinase A. To examine whether the pathogenesis of depression is associated with altered activation and expression of Rap-1, as well as expression of Epac, in depressed suicide victims. Postmortem study. Tissues were obtained from the Lenhossek Human Brain Program, Semmelweis University, Budapest, Hungary, and the Brain Collection Program of the Maryland Psychiatric Research Center, Baltimore. Postmortem brains of 28 depressed suicide victims and 28 nonpsychiatric control subjects. Examination of brain tissues. Rap-1 activation as well as messenger RNA and protein levels of Rap-1 and Epac in prefrontal cortex, hippocampus, and cerebellum. Rap-1 activation was significantly reduced (P<.001) in prefrontal cortex and hippocampus in the suicide group. This was associated with significant reductions in Rap-1 messenger RNA and protein levels (P<.001). In contrast, protein level of only Epac-2 (P<.001) but not Epac-1 (P = .89) was significantly increased in prefrontal cortex and hippocampus of these subjects. These changes were present whether the 2 cohorts were analyzed together or separately. None of the measures showed any significant change in cerebellum in the suicide group. Given the importance of Rap-1 in neuroprotection and synaptic plasticity, our findings of differential regulation of Rap-1 and Epac between brain regions suggest the relevance of these molecules in the pathophysiology of depression.

Cortactin deficiency is associated with reduced neutrophil recruitment but increased vascular permeability in vivo.

PubMed

Schnoor, Michael; Lai, Frank P L; Zarbock, Alexander; Kläver, Ruth; Polaschegg, Christian; Schulte, Dörte; Weich, Herbert A; Oelkers, J Margit; Rottner, Klemens; Vestweber, Dietmar

2011-08-01

Neutrophil extravasation and the regulation of vascular permeability require dynamic actin rearrangements in the endothelium. In this study, we analyzed in vivo whether these processes require the function of the actin nucleation-promoting factor cortactin. Basal vascular permeability for high molecular weight substances was enhanced in cortactin-deficient mice. Despite this leakiness, neutrophil extravasation in the tumor necrosis factor-stimulated cremaster was inhibited by the loss of cortactin. The permeability defect was caused by reduced levels of activated Rap1 (Ras-related protein 1) in endothelial cells and could be rescued by activating Rap1 via the guanosine triphosphatase (GTPase) exchange factor EPAC (exchange protein directly activated by cAMP). The defect in neutrophil extravasation was caused by enhanced rolling velocity and reduced adhesion in postcapillary venules. Impaired rolling interactions were linked to contributions of β(2)-integrin ligands, and firm adhesion was compromised by reduced ICAM-1 (intercellular adhesion molecule 1) clustering around neutrophils. A signaling process known to be critical for the formation of ICAM-1-enriched contact areas and for transendothelial migration, the ICAM-1-mediated activation of the GTPase RhoG was blocked in cortactin-deficient endothelial cells. Our results represent the first physiological evidence that cortactin is crucial for orchestrating the molecular events leading to proper endothelial barrier function and leukocyte recruitment in vivo.

Ghrelin Induces Leptin Resistance by Activation of Suppressor of Cytokine Signaling 3 Expression in Male Rats: Implications in Satiety Regulation

PubMed Central

Heldsinger, Andrea; Grabauskas, Gintautas; Wu, Xiaoyin; Zhou, ShiYi; Lu, Yuanxu; Song, Il

2014-01-01

The anorexigenic adipocyte-derived hormone leptin and the orexigenic hormone ghrelin act in opposition to regulate feeding behavior via the vagal afferent pathways. The mechanisms by which ghrelin exerts its inhibitory effects on leptin are unknown. We hypothesized that ghrelin activates the exchange protein activated by cAMP (Epac), inducing increased SOCS3 expression, which negatively affects leptin signal transduction and neuronal firing in nodose ganglia (NG) neurons. We showed that 91 ± 3% of leptin receptor (LRb) –bearing neurons contained ghrelin receptors (GHS-R1a) and that ghrelin significantly inhibited leptin-stimulated STAT3 phosphorylation in rat NG neurons. Studies of the signaling cascades used by ghrelin showed that ghrelin caused a significant increase in Epac and suppressor of cytokine signaling 3 (SOCS3) expression in cultured rat NG neurons. Transient transfection of cultured NG neurons to silence SOCS3 and Epac genes reversed the inhibitory effects of ghrelin on leptin-stimulated STAT3 phosphorylation. Patch-clamp studies and recordings of single neuronal discharges of vagal primary afferent neurons showed that ghrelin markedly inhibited leptin-stimulated neuronal firing, an action abolished by silencing SOCS3 expression in NG. Plasma ghrelin levels increased significantly during fasting. This was accompanied by enhanced SOCS3 expression in the NG and prevented by treatment with a ghrelin antagonist. Feeding studies showed that silencing SOCS3 expression in the NG reduced food intake evoked by endogenous leptin. We conclude that ghrelin exerts its inhibitory effects on leptin-stimulated neuronal firing by increasing SOCS3 expression. The SOCS3 signaling pathway plays a pivotal role in ghrelin's inhibitory effect on STAT3 phosphorylation, neuronal firing, and feeding behavior. PMID:25060362

Anthrax edema toxin disrupts distinct steps in Rab11-dependent junctional transport

PubMed Central

Guichard, Annabel; Jain, Prashant; Moayeri, Mahtab; Cruz-Moreno, Beatriz; Leppla, Stephen H.; Nizet, Victor

2017-01-01

Various bacterial toxins circumvent host defenses through overproduction of cAMP. In a previous study, we showed that edema factor (EF), an adenylate cyclase from Bacillus anthracis, disrupts endocytic recycling mediated by the small GTPase Rab11. As a result, cargo proteins such as cadherins fail to reach inter-cellular junctions. In the present study, we provide further mechanistic dissection of Rab11 inhibition by EF using a combination of Drosophila and mammalian systems. EF blocks Rab11 trafficking after the GTP-loading step, preventing a constitutively active form of Rab11 from delivering cargo vesicles to the plasma membrane. Both of the primary cAMP effector pathways -PKA and Epac/Rap1- contribute to inhibition of Rab11-mediated trafficking, but act at distinct steps of the delivery process. PKA acts early, preventing Rab11 from associating with its effectors Rip11 and Sec15. In contrast, Epac functions subsequently via the small GTPase Rap1 to block fusion of recycling endosomes with the plasma membrane, and appears to be the primary effector of EF toxicity in this process. Similarly, experiments conducted in mammalian systems reveal that Epac, but not PKA, mediates the activity of EF both in cell culture and in vivo. The small GTPase Arf6, which initiates endocytic retrieval of cell adhesion components, also contributes to junctional homeostasis by counteracting Rab11-dependent delivery of cargo proteins at sites of cell-cell contact. These studies have potentially significant practical implications, since chemical inhibition of either Arf6 or Epac blocks the effect of EF in cell culture and in vivo, opening new potential therapeutic avenues for treating symptoms caused by cAMP-inducing toxins or related barrier-disrupting pathologies. PMID:28945820

Anthrax edema toxin disrupts distinct steps in Rab11-dependent junctional transport.

PubMed

Guichard, Annabel; Jain, Prashant; Moayeri, Mahtab; Schwartz, Ruth; Chin, Stephen; Zhu, Lin; Cruz-Moreno, Beatriz; Liu, Janet Z; Aguilar, Bernice; Hollands, Andrew; Leppla, Stephen H; Nizet, Victor; Bier, Ethan

2017-09-01

Various bacterial toxins circumvent host defenses through overproduction of cAMP. In a previous study, we showed that edema factor (EF), an adenylate cyclase from Bacillus anthracis, disrupts endocytic recycling mediated by the small GTPase Rab11. As a result, cargo proteins such as cadherins fail to reach inter-cellular junctions. In the present study, we provide further mechanistic dissection of Rab11 inhibition by EF using a combination of Drosophila and mammalian systems. EF blocks Rab11 trafficking after the GTP-loading step, preventing a constitutively active form of Rab11 from delivering cargo vesicles to the plasma membrane. Both of the primary cAMP effector pathways -PKA and Epac/Rap1- contribute to inhibition of Rab11-mediated trafficking, but act at distinct steps of the delivery process. PKA acts early, preventing Rab11 from associating with its effectors Rip11 and Sec15. In contrast, Epac functions subsequently via the small GTPase Rap1 to block fusion of recycling endosomes with the plasma membrane, and appears to be the primary effector of EF toxicity in this process. Similarly, experiments conducted in mammalian systems reveal that Epac, but not PKA, mediates the activity of EF both in cell culture and in vivo. The small GTPase Arf6, which initiates endocytic retrieval of cell adhesion components, also contributes to junctional homeostasis by counteracting Rab11-dependent delivery of cargo proteins at sites of cell-cell contact. These studies have potentially significant practical implications, since chemical inhibition of either Arf6 or Epac blocks the effect of EF in cell culture and in vivo, opening new potential therapeutic avenues for treating symptoms caused by cAMP-inducing toxins or related barrier-disrupting pathologies.

Epac-induced ryanodine receptor type 2 activation inhibits sodium currents in atrial and ventricular murine cardiomyocytes.

PubMed

Valli, Haseeb; Ahmad, Shiraz; Sriharan, Sujan; Dean, Lydia D; Grace, Andrew A; Jeevaratnam, Kamalan; Matthews, Hugh R; Huang, Christopher L-H

2018-03-01

Acute RyR2 activation by exchange protein directly activated by cAMP (Epac) reversibly perturbs myocyte Ca 2+ homeostasis, slows myocardial action potential conduction, and exerts pro-arrhythmic effects. Loose patch-clamp studies, preserving in vivo extracellular and intracellular conditions, investigated Na + current in intact cardiomyocytes in murine atrial and ventricular preparations following Epac activation. Depolarising steps to varying test voltages activated typical voltage-dependent Na + currents. Plots of peak current against depolarisation from resting potential gave pretreatment maximum atrial and ventricular currents of -20.23 ± 1.48 (17) and -29.8 ± 2.4 (10) pA/μm 2 (mean ± SEM [n]). Challenge by 8-CPT (1 μmol/L) reduced these currents to -11.21 ± 0.91 (12) (P < .004) and -19.3 ± 1.6 (11) pA/μm 2 (P < .04) respectively. Currents following further addition of the RyR2 inhibitor dantrolene (10 μmol/L) (-19.91 ± 2.84 (13) and -26.6 ± 1.7 (17)), and dantrolene whether alone (-19.53 ± 1.97 (8) and -27.6 ± 1.9 (14)) or combined with 8-CPT (-19.93 ± 2.59 (12) and -29.9 ± 2.5(11)), were indistinguishable from pretreatment values (all P > .05). Assessment of the inactivation that followed by applying subsequent steps to a fixed voltage 100 mV positive to resting potential gave concordant results. Half-maximal inactivation voltages and steepness factors, and time constants for Na + current recovery from inactivation in double-pulse experiments, were similar through all the pharmacological conditions. Intracellular sharp microelectrode membrane potential recordings in intact Langendorff-perfused preparations demonstrated concordant variations in maximum rates of atrial and ventricular action potential upstroke, (dV/dt) max . We thus demonstrate an acute, reversible, Na + channel inhibition offering a possible mechanism for previously reported pro-arrhythmic slowing of AP propagation following modifications of Ca 2+ homeostasis, complementing earlier findings from chronic alterations in Ca 2+ homeostasis in genetically-modified RyR2-P2328S hearts. © 2017 The Authors. Clinical and Experimental Pharmacology and Physiology Published by John Wiley & Sons Australia, Ltd.

cAMP-dependent activation of protein kinase A attenuates respiratory syncytial virus-induced human airway epithelial barrier disruption

PubMed Central

Harford, Terri J.; Linfield, Debra T.; Altawallbeh, Ghaith; Midura, Ronald J.; Ivanov, Andrei I.; Piedimonte, Giovanni

2017-01-01

Airway epithelium forms a barrier to the outside world and has a crucial role in susceptibility to viral infections. Cyclic adenosine monophosphate (cAMP) is an important second messenger acting via two intracellular signaling molecules: protein kinase A (PKA) and the guanidine nucleotide exchange factor, Epac. We sought to investigate effects of increased cAMP level on the disruption of model airway epithelial barrier caused by RSV infection and the molecular mechanisms underlying cAMP actions. Human bronchial epithelial cells were infected with RSV-A2 and treated with either cAMP releasing agent, forskolin, or cAMP analogs. Structure and functions of the Apical Junctional Complex (AJC) were evaluated by measuring transepithelial electrical resistance and permeability to FITC-dextran, and determining localization of AJC proteins by confocal microscopy. Increased intracellular cAMP level significantly attenuated RSV-induced disassembly of AJC. These barrier-protective effects of cAMP were due to the activation of PKA signaling and did not involve Epac activity. Increased cAMP level reduced RSV-induced reorganization of the actin cytoskeleton, including apical accumulation of an essential actin-binding protein, cortactin, and inhibited expression of the RSV F protein. These barrier-protective and antiviral-function of cAMP signaling were evident even when cAMP level was increased after the onset of RSV infection. Taken together, our study demonstrates that cAMP/PKA signaling attenuated RSV-induced disruption of structure and functions of the model airway epithelial barrier by mechanisms involving the stabilization of epithelial junctions and inhibition of viral biogenesis. Improving our understanding of the mechanisms involved in RSV-induced epithelial dysfunction and viral pathogenesis will help to develop novel anti-viral therapeutic approaches. PMID:28759570

Education in Pediatrics Across the Continuum (EPAC): First Steps Toward Realizing the Dream of Competency-Based Education.

PubMed

Andrews, John S; Bale, James F; Soep, Jennifer B; Long, Michele; Carraccio, Carol; Englander, Robert; Powell, Deborah

2018-03-01

The Education in Pediatrics Across the Continuum (EPAC) Study Group is developing the first competency-based, time-variable progression from undergraduate medical education (UME) to graduate medical education (GME) in the history of medical education in the United States. EPAC, an innovation project sponsored by the Association of American Medical Colleges and supported by the Josiah Macy Jr. Foundation, was developed through a collaboration between five medical schools and multiple professional organizations with an interest in undergraduate and graduate medical education. The planning and implementation process demanded cooperatively addressing practical barriers such as education requirements for licensure and developing approaches to learner assessment that provided meaningful information about competency. Each participating school now has at least three cohorts of learners participating, and the program is transitioning its first cohort of students from UME to GME based on achievement of predetermined competencies that allow this transition. Members of the first cohort of learners in this program have begun their pediatric residency training at different times beginning in late 2016, confirming the feasibility of competency-based advancement from UME to GME in pediatrics. Although there is still much to learn about the outcomes of EPAC learners' professional development in residency training and beyond, EPAC has defined an operational approach to a different path through medical school and into residency training, based on the attainment of competence.

Arrhythmic effects of Epac-mediated ryanodine receptor activation in Langendorff-perfused murine hearts are associated with reduced conduction velocity.

PubMed

Li, Mengye; Hothi, Sandeep S; Salvage, Samantha C; Jeevaratnam, Kamalan; Grace, Andrew A; Huang, Christopher L-H

2017-06-01

Recent papers have attributed arrhythmic substrate in murine RyR2-P2328S hearts to reduced action potential (AP) conduction velocities (CV), reflecting acute functional inhibition and/or reduced expression of sodium channels. We explored for acute effects of direct exchange protein directly activated by cAMP (Epac)-mediated ryanodine receptor-2 (RyR2) activation on arrhythmic substrate and CV. Monophasic action potential (MAP) recordings demonstrated that initial steady (8 Hz) extrinsic pacing elicited ventricular tachycardia (VT) in 0 of 18 Langendorff-perfused wild-type mouse ventricles before pharmacological intervention. The Epac activator 8-CPT (8-(4-chlorophenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate) (VT in 1 of 7 hearts), and the RyR2 blocker dantrolene, either alone (0 of 11) or with 8-CPT (0 of 9) did not then increase VT incidence (P>.05). Both progressively increased pacing rates and programmed extrasystolic (S2) stimuli similarly produced no VT in untreated hearts (n=20 and n=9 respectively). 8-CPT challenge then increased VT incidences (5 of 7 and 4 of 8 hearts respectively; P<.05). However, dantrolene, whether alone (0 of 10 and 1 of 13) or combined with 8-CPT (0 of 10 and 0 of 13) did not increase VT incidence relative to those observed in untreated hearts (P>.05). 8-CPT but not dantrolene, whether alone or combined with 8-CPT, correspondingly increased AP latencies (1.14±0.04 (n=7), 1.04±0.03 (n=10), 1.09±0.05 (n=8) relative to respective control values). In contrast, AP durations, conditions for 2:1 conduction block and ventricular effective refractory periods remained unchanged throughout. We thus demonstrate for the first time that acute RyR2 activation reversibly induces VT in specific association with reduced CV. © 2017 The Authors. Clinical and Experimental Pharmacology and Physiology Published by John Wiley & Sons Australia, Ltd.

Dual contradictory roles of cAMP signaling pathways in hydroxyl radical production in the rat striatum.

PubMed

Hara, Shuichi; Kobayashi, Masamune; Kuriiwa, Fumi; Mukai, Toshiji; Mizukami, Hajime

2012-03-15

Studies have suggested that cAMP signaling pathways may be associated with the production of reactive oxygen species. In this study, we examined how modifications in cAMP signaling affected the production of hydroxyl radicals in rat striatum using microdialysis to measure extracellular 2,3-dihydroxybenzoic acid (2,3-DHBA), which is a hydroxyl radical adduct of salicylate. Up to 50 nmol of the cell-permeative cAMP mimetic 8-bromo-cAMP (8-Br-cAMP) increased 2,3-DHBA in a dose-dependent manner (there was no additional increase in 2,3-DHBA at 100 nmol). Another cAMP mimetic, dibutyryl cAMP (db-cAMP), caused a nonsignificant increase in 2,3-DHBA at 50 nmol and a significant decrease at 100 nmol. Up to 20 nmol of forskolin, which is a direct activator of adenylyl cyclase, increased 2,3-DHBA, similar to the effect of 8-Br-cAMP; however, forskolin resulted in a much greater increase in 2,3-DHBA. A potent inhibitor of protein kinase A (PKA), H89 (500 μM), potentiated the 8-Br-cAMP- and forskolin-induced increases in 2,3-DHBA and antagonized the inhibitory effect of 100 nmol of db-cAMP. Interestingly, the administration of 100 nmol of 8-bromo-cGMP alone or in combination with H89 had no significant effect on 2,3-DHBA levels. Doses of 100 nmol of a preferential PKA activator (6-phenyl-cAMP) or a preferential PKA inhibitor (8-bromoadenosine-3',5'-cyclic monophosphorothionate, Rp-isomer; Rp-8-Br-cAMPS), which also inhibits the cAMP-mediated activation of Epac (the exchange protein directly activated by cAMP), suppressed or enhanced, respectively, the formation of 2,3-DHBA. Up to 100 nmol of 8-(4-chlorophenylthio)-2'-O-methyladenosine-cAMP, which is a selective activator of Epac, dose-dependently stimulated the formation of 2,3-DHBA. These findings suggest that cAMP signaling plays contradictory roles (stimulation and inhibition) in the production of hydroxyl radicals in rat striatum by differential actions of Epac and PKA. These roles might contribute to the production of hydroxyl radicals concomitant with cAMP in carbon monoxide poisoning, because the formation of 2,3-DHBA was potentiated by the PKA inhibitor H89 and suppressed by Rp-8-Br-cAMPS, which inhibits PKA and Epac. Copyright © 2012 Elsevier Inc. All rights reserved.

REVIEW: Role of cyclic AMP signaling in the production and function of the incretin hormone glucagon-like peptide-1

NASA Astrophysics Data System (ADS)

Yu, Zhiwen; Jin, Tianru

2008-01-01

Pancreatic cells express the proglucagon gene (gcg) and thereby produce the peptide hormone glucagon, which stimulates hepatic glucose production and thereby increases blood glucose levels. The same gcg gene is also expressed in the intestinal endocrine L cells and certain neural cells in the brain. In the gut, gcg expression leads to the production of glucagon-like peptide-1 (GLP-1). This incretin hormone stimulates insulin secretion when blood glucose level is high. In addition, GLP-1 stimulates pancreatic cell proliferation, inhibits cell apoptosis, and has been utilized in the trans-differentiation of insulin producing cells. Today, a long-term effective GLP-1 receptor agonist has been developed as a drug in treating diabetes and potentially other metabolic disorders. Extensive investigations have shown that the expression of gcg and the production of GLP-1 can be activated by the elevation of the second messenger cyclic AMP (cAMP). Recent studies suggest that in addition to protein kinase A (PKA), exchange protein activated by cAMP (Epac), another effector of cAMP signaling, and the crosstalk between PKA and Wnt signaling pathway, are also involved in cAMP-stimulated gcg expression and GLP-1 production. Furthermore, functions of GLP-1 in pancreatic cells are mainly mediated by cAMP-PKA, cAMP-Epac and Wnt signaling pathways as well.

Mechanical loading stimulates chondrogenesis via the PKA/CREB-Sox9 and PP2A pathways in chicken micromass cultures.

PubMed

Juhász, Tamás; Matta, Csaba; Somogyi, Csilla; Katona, Éva; Takács, Roland; Soha, Rudolf Ferenc; Szabó, István A; Cserháti, Csaba; Sződy, Róbert; Karácsonyi, Zoltán; Bakó, Eva; Gergely, Pál; Zákány, Róza

2014-03-01

Biomechanical stimuli play important roles in the formation of articular cartilage during early foetal life, and optimal mechanical load is a crucial regulatory factor of adult chondrocyte metabolism and function. In this study, we undertook to analyse mechanotransduction pathways during in vitro chondrogenesis. Chondroprogenitor cells isolated from limb buds of 4-day-old chicken embryos were cultivated as high density cell cultures for 6 days. Mechanical stimulation was carried out by a self-designed bioreactor that exerted uniaxial intermittent cyclic load transmitted by the culture medium as hydrostatic pressure and fluid shear to differentiating cells. The loading scheme (0.05 Hz, 600 Pa; for 30 min) was applied on culturing days 2 and 3, when final commitment and differentiation of chondroprogenitor cells occurred in this model. The applied mechanical load significantly augmented cartilage matrix production and elevated mRNA expression of several cartilage matrix constituents, including collagen type II and aggrecan core protein, as well as matrix-producing hyaluronan synthases through enhanced expression, phosphorylation and nuclear signals of the main chondrogenic transcription factor Sox9. Along with increased cAMP levels, a significantly enhanced protein kinase A (PKA) activity was also detected and CREB, the archetypal downstream transcription factor of PKA signalling, exhibited elevated phosphorylation levels and stronger nuclear signals in response to mechanical stimuli. All the above effects were diminished by the PKA-inhibitor H89. Inhibition of the PKA-independent cAMP-mediators Epac1 and Epac2 with HJC0197 resulted in enhanced cartilage formation, which was additive to that of the mechanical stimulation, implying that the chondrogenesis-promoting effect of mechanical load was independent of Epac. At the same time, PP2A activity was reduced following mechanical load and treatments with the PP2A-inhibitor okadaic acid were able to mimic the effects of the intervention. Our results indicate that proper mechanical stimuli augment in vitro cartilage formation via promoting both differentiation and matrix production of chondrogenic cells, and the opposing regulation of the PKA/CREB-Sox9 and the PP2A signalling pathways is crucial in this phenomenon. Copyright © 2014 Elsevier Inc. All rights reserved.

Epac2-dependent mobilization of intracellular Ca2+ by glucagon-like peptide-1 receptor agonist exendin-4 is disrupted in β-cells of phospholipase C-ɛ knockout mice

PubMed Central

Dzhura, Igor; Chepurny, Oleg G; Kelley, Grant G; Leech, Colin A; Roe, Michael W; Dzhura, Elvira; Afshari, Parisa; Malik, Sundeep; Rindler, Michael J; Xu, Xin; Lu, Youming; Smrcka, Alan V; Holz, George G

2010-01-01

Calcium can be mobilized in pancreatic β-cells via a mechanism of Ca2+-induced Ca2+ release (CICR), and cAMP-elevating agents such as exendin-4 facilitate CICR in β-cells by activating both protein kinase A and Epac2. Here we provide the first report that a novel phosphoinositide-specific phospholipase C-ɛ (PLC-ɛ) is expressed in the islets of Langerhans, and that the knockout (KO) of PLC-ɛ gene expression in mice disrupts the action of exendin-4 to facilitate CICR in the β-cells of these mice. Thus, in the present study, in which wild-type (WT) C57BL/6 mouse β-cells were loaded with the photolabile Ca2+ chelator NP-EGTA, the UV flash photolysis-catalysed uncaging of Ca2+ generated CICR in only 9% of the β-cells tested, whereas CICR was generated in 82% of the β-cells pretreated with exendin-4. This action of exendin-4 to facilitate CICR was reproduced by cAMP analogues that activate protein kinase A (6-Bnz-cAMP-AM) or Epac2 (8-pCPT-2′-O-Me-cAMP-AM) selectively. However, in β-cells of PLC-ɛ KO mice, and also Epac2 KO mice, these test substances exhibited differential efficacies in the CICR assay such that exendin-4 was partly effective, 6-Bnz-cAMP-AM was fully effective, and 8-pCPT-2′-O-Me-cAMP-AM was without significant effect. Importantly, transduction of PLC-ɛ KO β-cells with recombinant PLC-ɛ rescued the action of 8-pCPT-2′-O-Me-cAMP-AM to facilitate CICR, whereas a K2150E PLC-ɛ with a mutated Ras association (RA) domain, or a H1640L PLC-ɛ that is catalytically dead, were both ineffective. Since 8-pCPT-2′-O-Me-cAMP-AM failed to facilitate CICR in WT β-cells transduced with a GTPase activating protein (RapGAP) that downregulates Rap activity, the available evidence indicates that a signal transduction ‘module’ comprised of Epac2, Rap and PLC-ɛ exists in β-cells, and that the activities of Epac2 and PLC-ɛ are key determinants of CICR in this cell type. PMID:21041529

Statistical Characteristic of Global Tropical Cyclone Looping Motion

NASA Astrophysics Data System (ADS)

Shen, W.; Song, J.; Wang, Y.

2016-12-01

Statistical characteristic of looping motion of tropical cyclones (TCs) in the Western North Pacific (WPAC), North Atlantic (NATL), Eastern North Pacific (EPAC), Northern Indian Ocean (NIO), Southern Indian Ocean (SIO) and South Pacific (SPAC) basins are investigated by using IBTrACS archive maintained by NOAA. From global perspective, about ten percent TCs experience a looping motion in the above six basins. The southern hemisphere (SH) including SIO and SPAC basins have higher looping percentage than the northern hemisphere (NH), while the EPAC basin has the least looping percentage. The interannual variation of the number of looping TCs are significantly correlated with that of total TCs in the NATL, SIO and SPAC basins, while there are no correlations between the EPAC and NIO basins. The numbers of looping TCs have a higher percentage in the early and late cyclone season in the NH rather than the peak period of cyclone season, while the SIO and SPAC basins have the higher looping percentage in the early and late cyclone season, respectively. The looping motion of TCs mainly concentrates on the scale of tropical depression to category 2 and has its peak value on the scale of tropical storm. The looping motion appears more frequently and has a higher percentage at the pre-mature stage than the post-mature stage of TCs in most basins except EPAC. Comparing the intensity and intensity variation caused by the looping motion, the weaker TCs tend to intensify after looping, while the more intense ones weaken.

The Alternative Epac/cAMP Pathway and the MAPK Pathway Mediate hCG Induction of Leptin in Placental Cells

PubMed Central

Maymó, Julieta Lorena; Pérez Pérez, Antonio; Maskin, Bernardo; Dueñas, José Luis; Calvo, Juan Carlos; Sánchez Margalet, Víctor; Varone, Cecilia Laura

2012-01-01

Pleiotropic effects of leptin have been identified in reproduction and pregnancy, particularly in the placenta, where it works as an autocrine hormone. In this work, we demonstrated that human chorionic gonadotropin (hCG) added to JEG-3 cell line or to placental explants induces endogenous leptin expression. We also found that hCG increased cAMP intracellular levels in BeWo cells in a dose-dependent manner, stimulated cAMP response element (CRE) activity and the cotransfection with an expression plasmid of a dominant negative mutant of CREB caused a significant inhibition of hCG stimulation of leptin promoter activity. These results demonstrate that hCG indeed activates cAMP/PKA pathway, and that this pathway is involved in leptin expression. Nevertheless, we found leptin induction by hCG is dependent on cAMP levels. Treatment with (Bu)2cAMP in combination with low and non stimulatory hCG concentrations led to an increase in leptin expression, whereas stimulatory concentrations showed the opposite effect. We found that specific PKA inhibition by H89 caused a significant increase of hCG leptin induction, suggesting that probably high cAMP levels might inhibit hCG effect. It was found that hCG enhancement of leptin mRNA expression involved the MAPK pathway. In this work, we demonstrated that hCG leptin induction through the MAPK signaling pathway is inhibited by PKA. We observed that ERK1/2 phosphorylation increased when hCG treatment was combined with H89. In view of these results, the involvement of the alternative cAMP/Epac signaling pathway was studied. We observed that a cAMP analogue that specifically activates Epac (CPT-OMe) stimulated leptin expression by hCG. In addition, the overexpression of Epac and Rap1 proteins increased leptin promoter activity and enhanced hCG. In conclusion, we provide evidence suggesting that hCG induction of leptin gene expression in placenta is mediated not only by activation of the MAPK signaling pathway but also by the alternative cAMP/Epac signaling pathway. PMID:23056265

Cannabinoid Type 1 Receptors Transiently Silence Glutamatergic Nerve Terminals of Cultured Cerebellar Granule Cells

PubMed Central

Ramírez-Franco, Jorge; Bartolomé-Martín, David; Alonso, Beatris; Torres, Magdalena; Sánchez-Prieto, José

2014-01-01

Cannabinoid receptors are the most abundant G protein-coupled receptors in the brain and they mediate retrograde short-term inhibition of neurotransmitter release, as well as long-term depression of synaptic transmission at many excitatory synapses. The induction of presynaptically silent synapses is a means of modulating synaptic strength, which is important for synaptic plasticity. Persistent activation of cannabinoid type 1 receptors (CB1Rs) mutes GABAergic terminals, although it is unclear if CB1Rs can also induce silencing at glutamatergic synapses. Cerebellar granule cells were transfected with VGLUT1-pHluorin to visualise the exo-endocytotic cycle. We found that prolonged stimulation (10 min) of cannabinoid receptors with the agonist HU-210 induces the silencing of previously active synapses. However, the presynaptic silencing induced by HU-210 is transient as it reverses after 20 min. cAMP with forskolin prevented CB1R-induced synaptic silencing, via activation of the Exchange Protein directly Activated by cAMP (Epac). Furthermore, Epac activation accelerated awakening of already silent boutons. Electron microscopy revealed that silencing was associated with synaptic vesicle (SV) redistribution within the nerve terminal, which diminished the number of vesicles close to the active zone of the plasma membrane. Finally, by combining functional and immunocytochemical approaches, we observed a strong correlation between the release capacity of the nerve terminals and RIM1α protein content, but not that of Munc13-1 protein. These results suggest that prolonged stimulation of cannabinoid receptors can transiently silence glutamatergic nerve terminals. PMID:24533119

Intracellular ascorbate tightens the endothelial permeability barrier through Epac1 and the tubulin cytoskeleton

PubMed Central

Parker, William H.; Rhea, Elizabeth Meredith; Qu, Zhi-Chao; Hecker, Morgan R.

2016-01-01

Vitamin C, or ascorbic acid, both tightens the endothelial permeability barrier in basal cells and also prevents barrier leak induced by inflammatory agents. Barrier tightening by ascorbate in basal endothelial cells requires nitric oxide derived from activation of nitric oxide synthase. Although ascorbate did not affect cyclic AMP levels in our previous study, there remains a question of whether it might activate downstream cyclic AMP-dependent pathways. In this work, we found in both primary and immortalized cultured endothelial cells that ascorbate tightened the endothelial permeability barrier by ∼30%. In human umbilical vein endothelial cells, this occurred at what are likely physiologic intracellular ascorbate concentrations. In so doing, ascorbate decreased measures of oxidative stress and also flattened the cells to increase cell-to-cell contact. Inhibition of downstream cyclic AMP-dependent proteins via protein kinase A did not prevent ascorbate from tightening the endothelial permeability barrier, whereas inhibition of Epac1 did block the ascorbate effect. Although Epac1 was required, its mediator Rap1 was not activated. Furthermore, ascorbate acutely stabilized microtubules during depolymerization induced by colchicine and nocodazole. Over several days in culture, ascorbate also increased the amount of stable acetylated α-tubulin. Microtubule stabilization was further suggested by the finding that ascorbate increased the amount of Epac1 bound to α-tubulin. These results suggest that physiologic ascorbate concentrations tighten the endothelial permeability barrier in unstimulated cells by stabilizing microtubules in a manner downstream of cyclic AMP that might be due both to increasing nitric oxide availability and to scavenging of reactive oxygen or nitrogen species. PMID:27605450

Biochemical properties of urea transporters.

PubMed

Chen, Guangping

2014-01-01

Urea and urea transporters (UT) are critical to the production of concentrated urine and hence in maintaining body fluid balance. The UT-A1 urea transporter is the major and most important UT isoform in the kidney. Native UT-A1, expressed in the terminal inner medullary collecting duct (IMCD) epithelial cells, is a glycosylated protein with two glycoforms of 117 and 97 kDa. Vasopressin is the major hormone in vivo that rapidly increases urea permeability in the IMCD through increases in phosphorylation and apical plasma-membrane accumulation of UT-A1. The cell signaling pathway for vasopressin-mediated UT-A1 phosphorylation and activity involves two cAMP-dependent signaling pathways: protein kinase A (PKA) and exchange protein activated by cAMP (Epac). In this chapter, we will discuss UT-A1 regulation by phosphorylation, ubiquitination, and glycosylation.

The cAMP signaling system inhibits the repair of {gamma}-ray-induced DNA damage by promoting Epac1-mediated proteasomal degradation of XRCC1 protein in human lung cancer cells

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

Cho, Eun-Ah; Juhnn, Yong-Sung, E-mail: juhnn@snu.ac.kr

2012-06-01

Highlights: Black-Right-Pointing-Pointer cAMP signaling system inhibits repair of {gamma}-ray-induced DNA damage. Black-Right-Pointing-Pointer cAMP signaling system inhibits DNA damage repair by decreasing XRCC1 expression. Black-Right-Pointing-Pointer cAMP signaling system decreases XRCC1 expression by promoting its proteasomal degradation. Black-Right-Pointing-Pointer The promotion of XRCC1 degradation by cAMP signaling system is mediated by Epac1. -- Abstract: Cyclic AMP is involved in the regulation of metabolism, gene expression, cellular growth and proliferation. Recently, the cAMP signaling system was found to modulate DNA-damaging agent-induced apoptosis by regulating the expression of Bcl-2 family proteins and inhibitors of apoptosis. Thus, we hypothesized that the cAMP signaling may modulate DNAmore » repair activity, and we investigated the effects of the cAMP signaling system on {gamma}-ray-induced DNA damage repair in lung cancer cells. Transient expression of a constitutively active mutant of stimulatory G protein (G{alpha}sQL) or treatment with forskolin, an adenylyl cyclase activator, augmented radiation-induced DNA damage and inhibited repair of the damage in H1299 lung cancer cells. Expression of G{alpha}sQL or treatment with forskolin or isoproterenol inhibited the radiation-induced expression of the XRCC1 protein, and exogenous expression of XRCC1 abolished the DNA repair-inhibiting effect of forskolin. Forskolin treatment promoted the ubiquitin and proteasome-dependent degradation of the XRCC1 protein, resulting in a significant decrease in the half-life of the protein after {gamma}-ray irradiation. The effect of forskolin on XRCC1 expression was not inhibited by PKA inhibitor, but 8-pCPT-2 Prime -O-Me-cAMP, an Epac-selective cAMP analog, increased ubiquitination of XRCC1 protein and decreased XRCC1 expression. Knockdown of Epac1 abolished the effect of 8-pCPT-2 Prime -O-Me-cAMP and restored XRCC1 protein level following {gamma}-ray irradiation. From these results, we conclude that the cAMP signaling system inhibits the repair of {gamma}-ray-induced DNA damage by promoting the ubiquitin-proteasome dependent degradation of XRCC1 in an Epac-dependent pathway in lung cancer cells.« less

hCG activates Epac-Erk1/2 signaling regulating Progesterone Receptor expression and function in human endometrial stromal cells.

PubMed

Tapia-Pizarro, Alejandro; Archiles, Sebastián; Argandoña, Felipe; Valencia, Cecilia; Zavaleta, Keyla; Cecilia Johnson, M; González-Ramos, Reinaldo; Devoto, Luigi

2017-06-01

How does hCG signal in human endometrial stromal cells (ESCs) and what is its role in regulating ESC function? hCG signaling in ESCs activates the extracellular signal-regulated protein kinases 1 and 2 (Erk1/2) pathway through exchange protein activated by cyclic AMP (cAMP) (Epac) and transiently increases progesterone receptor (PR) transcript and protein expression and its transcriptional function. hCG is one of the earliest embryo-derived secreted signals in the endometrium, which abundantly expresses LH/hCG receptors. hCG signals through cAMP/protein kinase A (PKA) in gonadal cells, but in endometrial epithelial cells, hCG induces Erk1/2 activation independent of the cAMP/PKA pathway. Few data exist concerning the signal transduction pathways triggered by hCG in ESCs and their role in regulation of ESC function. This is an in vitro study comprising patients undergoing benign gynecological surgery (n = 46). Endometrial samples were collected from normal cycling women during the mid-secretory phase for ESCs isolation. The study conducted in an academic research laboratory within a tertiary-care hospital. The activation of the Erk1/2 signal transduction pathway elicited by hCG was evaluated in ESC. Signaling pathway inhibitors were used to examine the roles of PKA, PI3K, PKC, adenylyl cyclase and Epac on the hCG-stimulated up-regulation of phospho-Erk1/2 (pErk1/2). Erk1/2 phosphorylation was determined by immunoblot. siRNA targeting Epac was used to investigate the molecular mechanisms. To assess the role of Erk1/2 signaling induced by hCG on ESC function, gene expression regulation was examined by immunofluorescence and real-time quantitative PCR. The role of PR on the regulation of transcript levels was studied using progesterone and the PR antagonist RU486. All experiments were conducted using at least three different cell culture preparations in triplicate. Addition of hCG to ESCs in vitro induced the phosphorylation of Erk1/2 through cAMP accumulation. Such induction could not be blocked by inhibitors for PKA, PKC and PI3K. Epac inhibition and knockdown with siRNA prevented pErk1/2 induction by hCG. ESCs stimulated with hCG for up to 72 h showed a significant increase in PR mRNA and immunofluorescent label at 48 h only; an effect that was abrogated with the mitogen-activated protein kinase kinase inhibitor UO126. In addition, the hCG-activated Erk1/2 pathway significantly decreased the mRNA levels for secreted frizzled-related protein 4 (SFRP4) at 24 h, whereas it increased those for homeobox A10 (HOXA10) at 48 h (P = 0.041 and P = 0.022 versus control, respectively). Prolactin mRNA levels were not significantly modified. HOXA10 mRNA up-regulation by hCG was not enhanced by co-stimulation with progesterone; however, it was completely abolished in the presence of RU486 (P = 0.036 hCG versus hCG + RU486). N/A. This is an in vitro study utilizing stromal cell cultures from human endometrial tissues. Furthermore, results obtained should also be confirmed in vivo in the context of the whole human endometrial tissue and hormonal milieu. The in vitro experiments using hCG have been conducted without other hormones/factors that may also modulate the ESCs response to hCG. We have determined that hCG induces the PR through the Erk1/2 pathway in ESCs which may render them more sensitive to progesterone, increasing our understanding about the effects of hCG at the embryo-maternal interface. The activation of such a pathway in the context of the hormonal milieu during the window of implantation might contribute to a successful dialog between the embryo and the uterus, leading to appropriate endometrial function. Defective hCG signaling in the endometrial stromal tissue may lead to an incomplete uterine response, compromising embryo implantation and early pregnancy. This work was supported by the National Fund for Scientific and Technological Development, Government of Chile (FONDECYT) grants 11100443 and 1140614 (A.T.-P.). The authors have no conflicts of interest to declare. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

New kids on the block: The Popeye domain containing (POPDC) protein family acting as a novel class of cAMP effector proteins in striated muscle.

PubMed

Brand, Thomas; Schindler, Roland

2017-12-01

The cyclic 3',5'-adenosine monophosphate (cAMP) signalling pathway constitutes an ancient signal transduction pathway present in prokaryotes and eukaryotes. Previously, it was thought that in eukaryotes three effector proteins mediate cAMP signalling, namely protein kinase A (PKA), exchange factor directly activated by cAMP (EPAC) and the cyclic-nucleotide gated channels. However, recently a novel family of cAMP effector proteins emerged and was termed the Popeye domain containing (POPDC) family, which consists of three members POPDC1, POPDC2 and POPDC3. POPDC proteins are transmembrane proteins, which are abundantly present in striated and smooth muscle cells. POPDC proteins bind cAMP with high affinity comparable to PKA. Presently, their biochemical activity is poorly understood. However, mutational analysis in animal models as well as the disease phenotype observed in patients carrying missense mutations suggests that POPDC proteins are acting by modulating membrane trafficking of interacting proteins. In this review, we will describe the current knowledge about this gene family and also outline the apparent gaps in our understanding of their role in cAMP signalling and beyond. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A novel dimerization interface of cyclic nucleotide binding domain, which is disrupted in presence of cAMP: implications for CNG channels gating.

PubMed

Gushchin, Ivan Y; Gordeliy, Valentin I; Grudinin, Sergei

2012-09-01

Cyclic nucleotide binding domain (CNBD) is a ubiquitous domain of effector proteins involved in signalling cascades of prokaryota and eukaryota. CNBD activation by cyclic nucleotide monophosphate (cNMP) is studied well in the case of several proteins. However, this knowledge is hardly applicable to cNMP-modulated cation channels. Despite the availability of CNBD crystal structures of bacterial cyclic nucleotide-gated (CNG) and mammalian hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels in presence and absence of the cNMP, the full understanding of CNBD conformational changes during activation is lacking. Here, we describe a novel CNBD dimerization interface found in crystal structures of bacterial CNG channel MlotiK1 and mammalian cAMP-activated guanine nucleotide-exchange factor Epac2. Molecular dynamics simulations show that the found interface is stable on the studied timescale of 100 ns, in contrast to the dimerization interface, reported previously. Comparisons with cN-bound structures of CNBD show that the dimerization is incompatible with cAMP binding. Thus, the cAMP-dependent monomerization of CNBD may be an alternative mechanism of the cAMP sensing. Based on these findings, we propose a model of the bacterial CNG channel modulation by cAMP.

The cAMP signaling system inhibits the repair of γ-ray-induced DNA damage by promoting Epac1-mediated proteasomal degradation of XRCC1 protein in human lung cancer cells.

PubMed

Cho, Eun-Ah; Juhnn, Yong-Sung

2012-06-01

Cyclic AMP is involved in the regulation of metabolism, gene expression, cellular growth and proliferation. Recently, the cAMP signaling system was found to modulate DNA-damaging agent-induced apoptosis by regulating the expression of Bcl-2 family proteins and inhibitors of apoptosis. Thus, we hypothesized that the cAMP signaling may modulate DNA repair activity, and we investigated the effects of the cAMP signaling system on γ-ray-induced DNA damage repair in lung cancer cells. Transient expression of a constitutively active mutant of stimulatory G protein (GαsQL) or treatment with forskolin, an adenylyl cyclase activator, augmented radiation-induced DNA damage and inhibited repair of the damage in H1299 lung cancer cells. Expression of GαsQL or treatment with forskolin or isoproterenol inhibited the radiation-induced expression of the XRCC1 protein, and exogenous expression of XRCC1 abolished the DNA repair-inhibiting effect of forskolin. Forskolin treatment promoted the ubiquitin and proteasome-dependent degradation of the XRCC1 protein, resulting in a significant decrease in the half-life of the protein after γ-ray irradiation. The effect of forskolin on XRCC1 expression was not inhibited by PKA inhibitor, but 8-pCPT-2'-O-Me-cAMP, an Epac-selective cAMP analog, increased ubiquitination of XRCC1 protein and decreased XRCC1 expression. Knockdown of Epac1 abolished the effect of 8-pCPT-2'-O-Me-cAMP and restored XRCC1 protein level following γ-ray irradiation. From these results, we conclude that the cAMP signaling system inhibits the repair of γ-ray-induced DNA damage by promoting the ubiquitin-proteasome dependent degradation of XRCC1 in an Epac-dependent pathway in lung cancer cells. Copyright © 2012 Elsevier Inc. All rights reserved.

Compartmentalized cAMP Signaling Associated With Lipid Raft and Non-raft Membrane Domains in Adult Ventricular Myocytes.

PubMed

Agarwal, Shailesh R; Gratwohl, Jackson; Cozad, Mia; Yang, Pei-Chi; Clancy, Colleen E; Harvey, Robert D

2018-01-01

Aim: Confining cAMP production to discrete subcellular locations makes it possible for this ubiquitous second messenger to elicit unique functional responses. Yet, factors that determine how and where the production of this diffusible signaling molecule occurs are incompletely understood. The fluid mosaic model originally proposed that signal transduction occurs through random interactions between proteins diffusing freely throughout the plasma membrane. However, it is now known that the movement of membrane proteins is restricted, suggesting that the plasma membrane is segregated into distinct microdomains where different signaling proteins can be concentrated. In this study, we examined what role lipid raft and non-raft membrane domains play in compartmentation of cAMP signaling in adult ventricular myocytes. Methods and Results: The freely diffusible fluorescence resonance energy transfer-based biosensor Epac2-camps was used to measure global cytosolic cAMP responses, while versions of the probe targeted to lipid raft (Epac2-MyrPalm) and non-raft (Epac2-CAAX) domains were used to monitor local cAMP production near the plasma membrane. We found that β-adrenergic receptors, which are expressed in lipid raft and non-raft domains, produce cAMP responses near the plasma membrane that are distinctly different from those produced by E-type prostaglandin receptors, which are expressed exclusively in non-raft domains. We also found that there are differences in basal cAMP levels associated with lipid raft and non-raft domains, and that this can be explained by differences in basal adenylyl cyclase activity associated with each of these membrane environments. In addition, we found evidence that phosphodiesterases 2, 3, and 4 work together in regulating cAMP activity associated with both lipid raft and non-raft domains, while phosphodiesterase 3 plays a more prominent role in the bulk cytoplasmic compartment. Conclusion: These results suggest that different membrane domains contribute to the formation of distinct pools of cAMP under basal conditions as well as following receptor stimulation in adult ventricular myocytes.

Regulation of renal urea transport by vasopressin.

PubMed

Sands, Jeff M; Blount, Mitsi A; Klein, Janet D

2011-01-01

Terrestrial life would be miserable without the ability to concentrate urine. Production of concentrated urine requires complex interactions among the nephron segments and vasculature in the kidney medulla. In addition to water channels (aquaporins) and sodium transporters, urea transporters are critically important to the theories proposed to explain the physiologic processes occurring when urine is concentrated. Vasopressin (anti-diuretic hormone) is the key hormone regulating the production of concentrated urine. Vasopressin rapidly increases water and urea transport in the terminal inner medullary collecting duct (IMCD). Vasopressin rapidly increases urea permeability in the IMCD through increases in phosphorylation and apical plasma-membrane accumulation of the urea transporter A1 (UT-A1). Vasopressin acts through two cAMP-dependent signaling pathways in the IMCD: protein kinase A and exchange protein activated by cAMP Epac. Protein kinase A phosphorylates UT-A1 at serines 486 and 499. In summary, vasopressin regulates urea transport acutely by increasing UT-A1 phosphorylation and the apical plasma-membrane accumulation of UT-A1 through two cAMP-dependent pathways.

Design of 140 MW X-band Relativistic Klystron for Linear Collider

NASA Astrophysics Data System (ADS)

Dolbilov, G. V.; Azorsky, N. I.; Shvetsov, V. S.; Balakin, V. E.; Avrakhov, P. V.; Kazakov, S. Yu.; Teryaev, V. E.; Vogel, V. F.

1997-05-01

It has been reported at EPAC-96 on successful experimental results on achievement of 100 MW output rf power in a wide aperture (15 mm), high gain (80 dB) 14 GHz VLEPP klystron with distributed suppression of parasitic oscillations (G.V. Dolbilov et al., Proc. EPAC-96, Sitges (Barselona), 10-14 June, 1996, Vol. 3, p. 2143). This report presents design of an electrodynamic structure of the X-band klystron for linear collider with a higher efficiency up to 56 % which will be achieved at the same parameters of the electron beam (U = 1 MeV, I = 250 A, emittance 0.05 π cm\\cdotrad). Design rf output power of the klystron is 140 MW. Experimental investigations of electrodynamic structure of the klystron are planned to perform using the driving beam of the JINR LIA-3000 induction accelerator (E = 1 MeV, I = 250 A, τ = 250 ns).

The ceramide-1-phosphate analogue PCERA-1 modulates tumour necrosis factor-alpha and interleukin-10 production in macrophages via the cAMP-PKA-CREB pathway in a GTP-dependent manner.

PubMed

Avni, Dorit; Philosoph, Amir; Meijler, Michael M; Zor, Tsaffrir

2010-03-01

The synthetic phospho-ceramide analogue-1 (PCERA-1) down-regulates production of the pro-inflammatory cytokine tumour necrosis factor-alpha (TNF-alpha) and up-regulates production of the anti-inflammatory cytokine interleukin-10 (IL-10) in lipopolysaccharide (LPS) -stimulated macrophages. We have previously reported that PCERA-1 increases cyclic adenosine monophosphate (cAMP) levels. The objective of this study was to delineate the signalling pathway leading from PCERA-1 via cAMP to modulation of TNF-alpha and IL-10 production. We show here that PCERA-1 elevates intra-cellular cAMP level in a guanosine triphosphate-dependent manner in RAW264.7 macrophages. The cell-permeable dibutyryl cAMP was able to mimic the effects of PCERA-1 on cytokine production, whereas 8-chloro-phenylthio-methyladenosine-cAMP, which specifically activates the exchange protein directly activated by cAMP (EPAC) but not protein kinase A (PKA), failed to mimic PCERA-1 activities. Consistently, the PKA inhibitor H89 efficiently blocked PCERA-1-driven cytokine modulation as well as PCERA-1-stimulated phosphorylation of cAMP response element binding protein (CREB) on Ser-133. Finally, PCERA-1 activated cAMP-responsive transcription of a luciferase reporter, in synergism with the phosphodiesterase (PDE)-4 inhibitor rolipram. Our results suggest that PCERA-1 activates a G(s) protein-coupled receptor, leading to elevation of cAMP, which acts via the PKA-CREB pathway to promote TNF-alpha suppression and IL-10 induction in LPS-stimulated macrophages. Identification of the PCERA-1 receptor is expected to set up a new target for development of novel anti-inflammatory drugs.

Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial

PubMed Central

Bime, Christian; Wei, Christine Y; Holbrook, Janet; Smith, Lewis J; Wise, Robert A

2013-01-01

Background Broad dietary patterns have been linked to asthma but the relative contribution of specific nutrients is unclear. Soy genistein has important anti-inflammatory and other biological effects that might be beneficial in asthma. A positive association was previously reported between soy genistein intake and lung function but not with asthma exacerbations. Aims To conduct a post-hoc analysis of patients with inadequately controlled asthma enrolled in a prospective multicentre clinical trial to replicate this association. Methods A total of 300 study participants were included in the analysis. Dietary soy genistein intake was measured using the Block Soy Foods Screener. The level of soy genistein intake (little or no intake, moderate intake, or high intake) was compared with baseline lung function (pre-bronchodilator forced expiratory volume in 1 second (FEV1)) and asthma control (proportion of participants with an episode of poor asthma control (EPAC) and annualised rates of EPACs over a 6-month follow-up period. Results Participants with little or no genistein intake had a lower baseline FEV1 than those with a moderate or high intake (2.26L vs. 2.53L and 2.47L, respectively; p=0.01). EPACs were more common among those with no genistein intake than in those with a moderate or high intake (54% vs. 35% vs. 40%, respectively; p<0.001). These findings remained significant after adjustment for patient demographics and body mass index. Conclusions In patients with asthma, consumption of a diet with moderate to high amounts of soy genistein is associated with better lung function and better asthma control. PMID:22885561

Activation of GPR4 by Acidosis Increases Endothelial Cell Adhesion through the cAMP/Epac Pathway

PubMed Central

Leffler, Nancy R.; Asch, Adam S.; Witte, Owen N.; Yang, Li V.

2011-01-01

Endothelium-leukocyte interaction is critical for inflammatory responses. Whereas the tissue microenvironments are often acidic at inflammatory sites, the mechanisms by which cells respond to acidosis are not well understood. Using molecular, cellular and biochemical approaches, we demonstrate that activation of GPR4, a proton-sensing G protein-coupled receptor, by isocapnic acidosis increases the adhesiveness of human umbilical vein endothelial cells (HUVECs) that express GPR4 endogenously. Acidosis in combination with GPR4 overexpression further augments HUVEC adhesion with U937 monocytes. In contrast, overexpression of a G protein signaling-defective DRY motif mutant (R115A) of GPR4 does not elicit any increase of HUVEC adhesion, indicating the requirement of G protein signaling. Downregulation of GPR4 expression by RNA interference reduces the acidosis-induced HUVEC adhesion. To delineate downstream pathways, we show that inhibition of adenylate cyclase by inhibitors, 2′,5′-dideoxyadenosine (DDA) or SQ 22536, attenuates acidosis/GPR4-induced HUVEC adhesion. Consistently, treatment with a cAMP analog or a Gi signaling inhibitor increases HUVEC adhesiveness, suggesting a role of the Gs/cAMP signaling in this process. We further show that the cAMP downstream effector Epac is important for acidosis/GPR4-induced cell adhesion. Moreover, activation of GPR4 by acidosis increases the expression of vascular adhesion molecules E-selectin, VCAM-1 and ICAM-1, which are functionally involved in acidosis/GPR4-mediated HUVEC adhesion. Similarly, hypercapnic acidosis can also activate GPR4 to stimulate HUVEC adhesion molecule expression and adhesiveness. These results suggest that acidosis/GPR4 signaling regulates endothelial cell adhesion mainly through the Gs/cAMP/Epac pathway and may play a role in the inflammatory response of vascular endothelial cells. PMID:22110680

FIELD PERFORMANCE OF WOODBURNING STOVES IN CRESTED BUTTE, COLORADO

EPA Science Inventory

The paper discusses field emissions from woodstoves measured in Crested Butte, Colorado, during the winters of 1988-89 and 1989-90. Both particulate matter and carbon monoxide emissions were measured. The database from this work is large, including conventional stoves and EPA-cer...

Regulation of Renal Urea Transport by Vasopressin

PubMed Central

Sands, Jeff M.; Blount, Mitsi A.; Klein, Janet D.

2011-01-01

Terrestrial life would be miserable without the ability to concentrate urine. Production of concentrated urine requires complex interactions among the nephron segments and vasculature in the kidney medulla. In addition to water channels (aquaporins) and sodium transporters, urea transporters are critically important to the theories proposed to explain the physiologic processes occurring when urine is concentrated. Vasopressin (anti-diuretic hormone) is the key hormone regulating the production of concentrated urine. Vasopressin rapidly increases water and urea transport in the terminal inner medullary collecting duct (IMCD). Vasopressin rapidly increases urea permeability in the IMCD through increases in phosphorylation and apical plasma-membrane accumulation of the urea transporter A1 (UT-A1). Vasopressin acts through two cAMP-dependent signaling pathways in the IMCD: protein kinase A and exchange protein activated by cAMP Epac. Protein kinase A phosphorylates UT-A1 at serines 486 and 499. In summary, vasopressin regulates urea transport acutely by increasing UT-A1 phosphorylation and the apical plasma-membrane accumulation of UT-A1 through two cAMP-dependent pathways. PMID:21686211

Advanced Computing Tools and Models for Accelerator Physics

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

Ryne, Robert; Ryne, Robert D.

2008-06-11

This paper is based on a transcript of my EPAC'08 presentation on advanced computing tools for accelerator physics. Following an introduction I present several examples, provide a history of the development of beam dynamics capabilities, and conclude with thoughts on the future of large scale computing in accelerator physics.

Dynamics of β-adrenergic/cAMP signaling and morphological changes in cultured astrocytes.

PubMed

Vardjan, Nina; Kreft, Marko; Zorec, Robert

2014-04-01

The morphology of astrocytes, likely regulated by cAMP, determines the structural association between astrocytes and the synapse, consequently modulating synaptic function. β-Adrenergic receptors (β-AR), which increase cytosolic cAMP concentration ([cAMP]i ), may affect cell morphology. However, the real-time dynamics of β-AR-mediated cAMP signaling in single live astrocytes and its effect on cell morphology have not been studied. We used the fluorescence resonance energy transfer (FRET)-based cAMP biosensor Epac1-camps to study time-dependent changes in [cAMP]i ; morphological changes in primary rat astrocytes were monitored by real-time confocal microscopy. Stimulation of β-AR by adrenaline, noradrenaline, and isoprenaline, a specific agonist of β-AR, rapidly increased [cAMP]i (∼15 s). The FRET signal response, mediated via β-AR, was faster than in the presence of forskolin (twofold) and dibutyryl-cAMP (>35-fold), which directly activate adenylyl cyclase and Epac1-camps, respectively, likely due to slow entry of these agents into the cytosol. Oscillations in [cAMP]i have not been recorded, indicating that cAMP-dependent processes operate in a slow time domain. Most Epac1-camps expressing astrocytes revealed a morphological change upon β-AR activation and attained a stellate morphology within 1 h. The morphological changes exhibited a bell-shaped dependency on [cAMP]i . The 5-10% decrease in cell cross-sectional area and the 30-50% increase in cell perimeter are likely due to withdrawal of the cytoplasm to the perinuclear region and the appearance of protrusions on the surface of astrocytes. Because astrocyte processes ensheath neurons, β-AR/cAMP-mediated morphological changes can modify the geometry of the extracellular space, affecting synaptic, neuronal, and astrocyte functions in health and disease. Copyright © 2014 Wiley Periodicals, Inc.

The Bile Acid Receptor TGR5 Does Not Interact with β-Arrestins or Traffic to Endosomes but Transmits Sustained Signals from Plasma Membrane Rafts*

PubMed Central

Jensen, Dane D.; Godfrey, Cody B.; Niklas, Christian; Canals, Meritxell; Kocan, Martina; Poole, Daniel P.; Murphy, Jane E.; Alemi, Farzad; Cottrell, Graeme S.; Korbmacher, Christoph; Lambert, Nevin A.; Bunnett, Nigel W.; Corvera, Carlos U.

2013-01-01

TGR5 is a G protein-coupled receptor that mediates bile acid (BA) effects on energy balance, inflammation, digestion, and sensation. The mechanisms and spatiotemporal control of TGR5 signaling are poorly understood. We investigated TGR5 signaling and trafficking in transfected HEK293 cells and colonocytes (NCM460) that endogenously express TGR5. BAs (deoxycholic acid (DCA), taurolithocholic acid) and the selective agonists oleanolic acid and 3-(2-chlorophenyl)-N-(4-chlorophenyl)-N, 5-dimethylisoxazole-4-carboxamide stimulated cAMP formation but did not induce TGR5 endocytosis or recruitment of β-arrestins, as assessed by confocal microscopy. DCA, taurolithocholic acid, and oleanolic acid did not stimulate TGR5 association with β-arrestin 1/2 or G protein-coupled receptor kinase (GRK) 2/5/6, as determined by bioluminescence resonance energy transfer. 3-(2-chlorophenyl)-N-(4-chlorophenyl)-N, 5-dimethylisoxazole-4-carboxamide stimulated a low level of TGR5 interaction with β-arrestin 2 and GRK2. DCA induced cAMP formation at the plasma membrane and cytosol, as determined using exchange factor directly regulated by cAMP (Epac2)-based reporters, but cAMP signals did not desensitize. AG1478, an inhibitor of epidermal growth factor receptor tyrosine kinase, the metalloprotease inhibitor batimastat, and methyl-β-cyclodextrin and filipin, which block lipid raft formation, prevented DCA stimulation of ERK1/2. Bioluminescence resonance energy transfer analysis revealed TGR5 and EGFR interactions that were blocked by disruption of lipid rafts. DCA stimulated TGR5 redistribution to plasma membrane microdomains, as localized by immunogold electron microscopy. Thus, TGR5 does not interact with β-arrestins, desensitize, or traffic to endosomes. TGR5 signals from plasma membrane rafts that facilitate EGFR interaction and transactivation. An understanding of the spatiotemporal control of TGR5 signaling provides insights into the actions of BAs and therapeutic TGR5 agonists/antagonists. PMID:23818521

Rab3a Is Critical for Trapping Alpha-MSH Granules in the High Ca2+-Affinity Pool by Preventing Constitutive Exocytosis

PubMed Central

Sedej, Simon; Klemen, Maša Skelin; Schlüter, Oliver M.; Rupnik, Marjan Slak

2013-01-01

Rab3a is a small GTPase of the Rab3 subfamily that acts during late stages of Ca2+-regulated exocytosis. Previous functional analysis in pituitary melanotrophs described Rab3a as a positive regulator of Ca2+-dependent exocytosis. However, the precise role of the Rab3a isoform on the kinetics and intracellular [Ca2+] sensitivity of regulated exocytosis, which may affect the availability of two major peptide hormones, α-melanocyte stimulating hormone (α-MSH) and β-endorphin in plasma, remain elusive. We employed Rab3a knock-out mice (Rab3a KO) to explore the secretory phenotype in melanotrophs from fresh pituitary tissue slices. High resolution capacitance measurements showed that Rab3a KO melanotrophs possessed impaired Ca2+-triggered secretory activity as compared to wild-type cells. The hampered secretion was associated with the absence of cAMP-guanine exchange factor II/ Epac2-dependent secretory component. This component has been attributed to high Ca2+-sensitive release-ready vesicles as determined by slow photo-release of caged Ca2+. Radioimmunoassay revealed that α-MSH, but not β-endorphin, was elevated in the plasma of Rab3a KO mice, indicating increased constitutive exocytosis of α-MSH. Increased constitutive secretion of α-MSH from incubated tissue slices was associated with reduced α-MSH cellular content in Rab3a-deficient pituitary cells. Viral re-expression of the Rab3a protein in vitro rescued the secretory phenotype of melanotrophs from Rab3a KO mice. In conclusion, we suggest that Rab3a deficiency promotes constitutive secretion and underlies selective impairment of Ca2+-dependent release of α-MSH. PMID:24205339

Performance of bean bruchids Callosobruchus maculatus and Zabrotes subfasciatus (Coleoptera: Bruchidae) reared on resistant (IT81D-1045) and susceptible (Epace 10) Vigna unguiculata seeds: relationship with trypsin inhibitor and vicilin excretion.

PubMed

Sales, M P; Andrade, L B S; Ary, M B; Miranda, M R A; Teixeira, F M; Oliveira, A S; Fernandes, K V S; Xavier-Filho, J

2005-12-01

Callosobruchus maculatus (Cm) and Zabrotes subfasciatus (Zs) were reared on resistant (IT81D-1045) and on susceptible (Epace 10) cowpea seeds. The emergence of adult insects, total developmental period (TDP) and excretion of trypsin inhibitor and vicilin were determined for both bruchid populations. Parameter evaluation showed that the Zs populations emerged from both seeds had no significant differences in emergence and TDP. The Cm population raised from resistant seeds had lower emergence (5.6+/-1.3%) and delayed TDP (46+/-1.25 days) than those emerged from susceptible seeds. The excretion of defense proteins showed that Zs reared in resistant seeds excreted 1.7 times more trypsin inhibitor, but this did not affect emergence or TDP. Furthermore, Cm population emerged from resistant seeds excreted 7 times higher vicilin and 0.4 times less trypsin inhibitor than that emerged from susceptible seeds. These results indicate that vicilins from resistant seeds are involved to significantly longer TDP (46 days) and also drastic reduction of insect emergence ( approximately 5%) of C. maculatus.

2011 Precision Strike Annual Review Held in Fort Walton Beach, Florida on February 23-24, 2011

DTIC Science & Technology

2011-02-24

Captain Mike Flanagan, USN Annual Review Event Chair: Erik Ballinger | International Chairs: Jim Pennock & Earle Rudolph Annual Meeting Chair...Challenges (Go-Fasts) UNCLASSIFIED UNCLASSIFIED Targeting Challenges (SPSS) SPSS Interdiction EPAC JAN 2011 UNCLASSIFIED UNCLASSIFIED Targeting...by a near- peer , or global competitor. Yesterday Dr. Huessy talked about the need for EMP hardening, are these COTS components cyber-hardened

Exenatide exerts a PKA-dependent positive inotropic effect in human atrial myocardium: GLP-1R mediated effects in human myocardium.

PubMed

Wallner, Markus; Kolesnik, Ewald; Ablasser, Klemens; Khafaga, Mounir; Wakula, Paulina; Ljubojevic, Senka; Thon-Gutschi, Eva Maria; Sourij, Harald; Kapl, Martin; Edmunds, Nicholas J; Kuzmiski, J Brent; Griffith, David A; Knez, Igor; Pieske, Burkert; von Lewinski, Dirk

2015-12-01

Glucagon-like peptide-1 receptor (GLP-1R) agonists are a rapidly growing class of drugs developed for treating type-2 diabetes mellitus. Patients with diabetes carry an up to 5-fold greater mortality risk compared to non-diabetic patients, mainly as a result of cardiovascular diseases. Although beneficial cardiovascular effects have been reported, exact mechanisms of GLP-1R-agonist action in the heart, especially in human myocardium, are poorly understood. The effects of GLP-1R-agonists (exenatide, GLP-1(7-36)NH2, PF-06446009, PF-06446667) on cardiac contractility were tested in non-failing atrial and ventricular trabeculae from 72 patients. The GLP-1(7-36)NH2 metabolite, GLP-1(9-36)NH2, was also examined. In electrically stimulated trabeculae, the effects of compounds on isometric force were measured in the absence and presence of pharmacological inhibitors of signal transduction pathways. The role of β-arrestin signaling was examined using a β-arrestin partial agonist, PF-06446667. Expression levels were tested by immunoblots. Translocation of GLP-1R downstream molecular targets, Epac2, GLUT-1 and GLUT-4, were assessed by fluorescence microscopy. All tested GLP-1R-agonists significantly increased developed force in human atrial trabeculae, whereas GLP-1(9-36)NH2 had no effect. Exendin(9-39)NH2, a GLP-1R-antagonist, and H-89 blunted the inotropic effect of exenatide. In addition, exenatide increased PKA-dependent phosphorylation of phospholamban (PLB), GLUT-1 and Epac2 translocation, but not GLUT-4 translocation. Exenatide failed to enhance contractility in ventricular myocardium. Quantitative real-time PCR (qRT-PCR) revealed a significant higher GLP-1R expression in the atrium compared to ventricle. Exenatide increased contractility in a dose-dependent manner via GLP-1R/cAMP/PKA pathway and induced GLUT-1 and Epac2 translocation in human atrial myocardium, but had no effect in ventricular myocardium. Therapeutic use of GLP-1R-agonists may therefore impart beneficial effects on myocardial function and remodelling. Copyright © 2015 Elsevier Ltd. All rights reserved.

Energetic particle composition variations during the March 1991 events measured with the Ulysses EPAC instrument

NASA Technical Reports Server (NTRS)

Krupp, N.; Keppler, E.; Fraenz, M.; Korth, A.; Witte, M.; Moussas, X.; Blake, J. B.; Naidu, K.; Quenby, J. J.; Woch, J.

1992-01-01

Energetic particle measurements are reported which were obtained with the EPAC instrument on board the Ulysses spacecraft during March 1991 when a series of important flares occurred at the sun. The time interval March 22 through March 29 is studied in three periods with different ion compositions. At a quasi-perpendicular shock on March 23, shock-drift acceleration of protons, helium and electrons was observed. Thirteen hours after this shock the energetic ion composition changed dramatically by almost two orders of magnitude, signaling the arrival of a coronal mass ejection or driver gas. This driver gas was still present at the spacecraft when a second quasi-perpendicular shock passed the spacecraft. The ratio Fe/O increased from 0.6 to 1.0 indicative of a connection to solar particles for about six hours after the second shock. The second shock did not accelerate ions as well and electrons not at all. Six hours after this shock the same oxygen and ion composition was observed as before, indicating that the second shock did not alter the energetic ion composition. A third ion composition was observed before the driver gas disappeared which was significantly different from those observed before the first and between the two shocks.

Distinct pools of cAMP centre on different isoforms of adenylyl cyclase in pituitary-derived GH3B6 cells.

PubMed

Wachten, Sebastian; Masada, Nanako; Ayling, Laura-Jo; Ciruela, Antonio; Nikolaev, Viacheslav O; Lohse, Martin J; Cooper, Dermot M F

2010-01-01

Microdomains have been proposed to explain specificity in the myriad of possible cellular targets of cAMP. Local differences in cAMP levels can be generated by phosphodiesterases, which control the diffusion of cAMP. Here, we address the possibility that adenylyl cyclases, the source of cAMP, can be primary architects of such microdomains. Distinctly regulated adenylyl cyclases often contribute to total cAMP levels in endogenous cellular settings, making it virtually impossible to determine the contribution of a specific isoform. To investigate cAMP dynamics with high precision at the single-isoform level, we developed a targeted version of Epac2-camps, a cAMP sensor, in which the sensor was tagged to a catalytically inactive version of the Ca(2+)-stimulable adenylyl cyclase 8 (AC8). This sensor, and less stringently targeted versions of Epac2-camps, revealed opposite regulation of cAMP synthesis in response to Ca(2+) in GH(3)B(6) pituitary cells. Ca(2+) release triggered by thyrotropin-releasing hormone stimulated the minor endogenous AC8 species. cAMP levels were decreased by inhibition of AC5 and AC6, and simultaneous activation of phosphodiesterases, in different compartments of the same cell. These findings demonstrate the existence of distinct adenylyl-cyclase-centered cAMP microdomains in live cells and open the door to their molecular micro-dissection.

Multiple Rap1 effectors control Epac1-mediated tightening of endothelial junctions.

PubMed

Pannekoek, Willem-Jan; Vliem, Marjolein J; Bos, Johannes L

2018-02-17

Epac1 and Rap1 mediate cAMP-induced tightening of endothelial junctions. We have previously found that one of the mechanisms is the inhibition of Rho-mediated tension in radial stress fibers by recruiting the RhoGAP ArhGAP29 in a complex containing the Rap1 effectors Rasip1 and Radil. However, other mechanisms have been proposed as well, most notably the induction of tension in circumferential actin cables by Cdc42 and its GEF FGD5. Here, we have investigated how Rap1 controls FGD5/Cdc42 and how this interconnects with Radil/Rasip1/ArhGAP29. Using endothelial barrier measurements, we show that Rho inhibition is not sufficient to explain the barrier stimulating effect of Rap1. Indeed, Cdc42-mediated tension is induced at cell-cell contacts upon Rap1 activation and this is required for endothelial barrier function. Depletion of potential Rap1 effectors identifies AF6 to mediate Rap1 enhanced tension and concomitant Rho-independent barrier function. When overexpressed in HEK293T cells, AF6 is found in a complex with FGD5 and Radil. From these results we conclude that Rap1 utilizes multiple pathways to control tightening of endothelial junctions, possibly through a multiprotein effector complex, in which AF6 functions to induce tension in circumferential actin cables.

Purinergic A2b Receptor Activation by Extracellular Cues Affects Positioning of the Centrosome and Nucleus and Causes Reduced Cell Migration.

PubMed

Ou, Young; Chan, Gordon; Zuo, Jeremy; Rattner, Jerome B; van der Hoorn, Frans A

2016-07-15

The tight, relative positioning of the nucleus and centrosome in mammalian cells is important for the regulation of cell migration. Under pathophysiological conditions, the purinergic A2b receptor can regulate cell motility, but the underlying mechanism remains unknown. Expression of A2b, normally low, is increased in tissues experiencing adverse physiological conditions, including hypoxia and inflammation. ATP is released from such cells. We investigated whether extracellular cues can regulate centrosome-nucleus positioning and cell migration. We discovered that hypoxia as well as extracellular ATP cause a reversible increase in the distance between the centrosome and nucleus and reduced cell motility. We uncovered the underlying pathway: both treatments act through the A2b receptor and specifically activate the Epac1/RapGef3 pathway. We show that cells lacking A2b do not respond in this manner to hypoxia or ATP but transfection of A2b restores this response, that Epac1 is critically involved, and that Rap1B is important for the relative positioning of the centrosome and nucleus. Our results represent, to our knowledge, the first report demonstrating that pathophysiological conditions can impact the distance between the centrosome and nucleus. Furthermore, we identify the A2b receptor as a central player in this process. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Purinergic A2b Receptor Activation by Extracellular Cues Affects Positioning of the Centrosome and Nucleus and Causes Reduced Cell Migration*

PubMed Central

Ou, Young; Chan, Gordon; Zuo, Jeremy; Rattner, Jerome B.; van der Hoorn, Frans A.

2016-01-01

The tight, relative positioning of the nucleus and centrosome in mammalian cells is important for the regulation of cell migration. Under pathophysiological conditions, the purinergic A2b receptor can regulate cell motility, but the underlying mechanism remains unknown. Expression of A2b, normally low, is increased in tissues experiencing adverse physiological conditions, including hypoxia and inflammation. ATP is released from such cells. We investigated whether extracellular cues can regulate centrosome-nucleus positioning and cell migration. We discovered that hypoxia as well as extracellular ATP cause a reversible increase in the distance between the centrosome and nucleus and reduced cell motility. We uncovered the underlying pathway: both treatments act through the A2b receptor and specifically activate the Epac1/RapGef3 pathway. We show that cells lacking A2b do not respond in this manner to hypoxia or ATP but transfection of A2b restores this response, that Epac1 is critically involved, and that Rap1B is important for the relative positioning of the centrosome and nucleus. Our results represent, to our knowledge, the first report demonstrating that pathophysiological conditions can impact the distance between the centrosome and nucleus. Furthermore, we identify the A2b receptor as a central player in this process. PMID:27226580

Regulatory Evaluation of Petroleum Hydrocarbons in Dredged Material: Proceedings of a Workshop Held in Vicksburg, Mississippi on 15-17 March 1988

DTIC Science & Technology

1990-07-01

in Daphnia magna" 8909 Draft TN: Effects of Petroleum Hydrocarbon Bioaccumulation in Aquatic Animals 9009 Input to EPA/CE Implementation Manuals CONT...database for bioaccumulation of the 15 PAHs as indicative of levels of concern for petroleum hydrocarbons in marine and freshwater. ASSESSMENT OF THE PROBLEM...mc I LEIU OCy, JMISCELLANEOUS PAPER EL-90-11 of EREGULATORY EVALUATION OF PETROLEUM HYDROCARBONS IN DREDGED MATERIAL PROCEEDINGS OF A WORKSHOP

Role of CRF Receptor Signaling in Stress Vulnerability, Anxiety, and Depression

PubMed Central

Hauger, Richard L.; Risbrough, Victoria; Oakley, Robert H.; Olivares-Reyes, J. Alberto; Dautzenberg, Frank M.

2011-01-01

Markers of hyperactive central corticotropin releasing factor (CRF) systems and CRF-related single nucleotide polymorphisms (SNPs) have been identified in patients with anxiety and depressive disorders. Designing more effective antagonists may now be guided by data showing that small molecules bind to transmembrane domains. Specifically, CRF1 receptor antagonists have been developed as novel anxiolytic and antidepressant treatments. Because CRF1 receptors become rapidly desensitized by G protein-coupled receptor kinase (GRK) and β-arrestin mechanisms in the presence of high agonist concentrations, neuronal hypersecretion of synaptic CRF alone may be insufficient to account for excessive central CRF neurotransmission in stress-induced affective pathophysiology. In addition to desensitizing receptor function, GRK phosphorylation and β-arrestin binding can shift a G protein-coupled receptor (GPCR) to signal selectively via the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK-MAPK) or Akt pathways independent of G proteins. Also, Epac-dependent CRF1 receptor signaling via the ERK-MAPK pathway has been found to potentiate brain-derived neurotrophic factor (BDNF)-stimulated TrkB signaling. Thus, genetic or acquired abnormalities in GRK and β-arrestin function may be involved in the pathophysiology of stress-induced anxiety and depression. PMID:19906236

Vitexin exerts cardioprotective effect on chronic myocardial ischemia/reperfusion injury in rats via inhibiting myocardial apoptosis and lipid peroxidation.

PubMed

Che, Xia; Wang, Xin; Zhang, Junyan; Peng, Chengfeng; Zhen, Yilan; Shao, Xu; Zhang, Gongliang; Dong, Liuyi

2016-01-01

The aim of this study was to explore the cardioprotective effect of vitexin on chronic myocardial ischemia/reperfusion injury in rats and potential mechanisms. A chronic myocardial ischemia/reperfusion injury model was established by ligating left anterior descending coronary for 60 minutes, and followed by reperfusion for 14 days. After 2 weeks ischemia/reperfusion, cardiac function was measured to assess myocardial injury. The level of ST segment was recorded in different periods by electrocardiograph. The change of left ventricular function and myocardial reaction degree of fibrosis of heart was investigated by hematoxylin and eosin (HE) staining and Sirius red staining. Endothelium-dependent relaxations due to acetylcholine were observed in isolated rat thoracic aortic ring preparation. The blood samples were collected to measure the levels of MDA, the activities of SOD and NADPH in serum. Epac1, Rap1, Bax and Bcl-2 were examined by using Western Blotting. Vitexin exerted significant protective effect on chronic myocardial ischemia/reperfusion injury, improved obviously left ventricular diastolic function and reduced myocardial reactive fibrosis degree in rats of myocardial ischemia. Medium and high-dose vitexin groups presented a significant decrease in Bax, Epac1 and Rap1 production and increase in Bcl-2 compared to the I/R group. It may be related to preventing myocardial cells from apoptosis, improving myocardial diastolic function and inhibiting lipid peroxidation. Vitexin is a cardioprotective herb, which may be a promising useful complementary and alternative medicine for patients with coronary heart disease.

Resveratrol Influences Pancreatic Islets by Opposing Effects on Electrical Activity and Insulin Release.

PubMed

Brouwer, Simone; Hoffmeister, Theresa; Gresch, Anne; Schönhoff, Lisa; Düfer, Martina

2018-03-01

Resveratrol is suggested to improve glycemic control by activation of sirtuin 1 (SIRT1) and has already been tested clinically. Our investigation characterizes the targets of resveratrol in pancreatic beta cells and their contribution to short- and long-term effects on insulin secretion. Islets or beta cells are isolated from C57BL/6N mice. Electrophysiology is performed with microelectrode arrays and patch-clamp technique, insulin secretion and content are determined by radioimmunoassay, cAMP is measured by enzyme-linked immunosorbent assay, and cytosolic Ca 2+ concentration by fluorescence methods. Resveratrol (25 μmol L -1 ) elevates [Ca 2+ ] c and potentiates glucose-stimulated insulin secretion. These effects are associated with increased intracellular cAMP and are sensitive to the SIRT1 blocker Ex-527. Inhibition of EPAC1 by CE3F4 also abolishes the stimulatory effect of resveratrol. The underlying mechanism does not involve membrane depolarization as resveratrol even reduces electrical activity despite blocking K ATP channels. Importantly, after prolonged exposure to resveratrol (14 days), the beneficial influence of the polyphenol on insulin release is lost. Resveratrol addresses multiple targets in pancreatic islets. Potentiation of insulin secretion is mediated by SIRT1-dependent activation of cAMP/EPAC1. Considering resveratrol as therapeutic supplement for patients with type 2 diabetes mellitus, the inhibitory influence on electrical excitability attenuates positive effects. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An Overview of Energetic Particle Measurements in the Jovian Magnetosphere with the EPAC Sensor on Ulysses.

PubMed

Keppler, E; Blake, J B; Fränz, M; Korth, A; Krupp, N; Quenby, J J; Witte, M; Woch, J

1992-09-11

Observations of ions and electrons of probable Jovian origin upstream of Jupiter were observed after a corotating interplanetary particle event. During the passage of Ulysses through the Jovian bow shock, magnetopause, and outer magnetosphere, the fluxes of energetic particles were surprisingly low. During the passage through the "middle magnetosphere," corotating fluxes were observed within the current sheet near the jovimagnetic equato. During the outbound pass, fluxes were variably directed; in the later part of the flyby, they were probably related to high-latitude phenomena.

Investigation of Methods to Eliminate Voltage Delay in Li/SOCl2 Cells.

DTIC Science & Technology

1980-05-01

of storage at 550C the surface was completely covered with cubic crystals averaging about 8 pim on an edge (Figure 24). The lithium surface stored at...completely covered with cubic crystals, showing no smooth undercoating at all (Figure 25). The average crystal diameter was approximately 3.3 pim , with a...used. ithi timl acgu ire0d A Ci yst al I me surt ace, oil dr n torage at elevated temlper aI Ite t. T[he out lace, showed ch[ ott ine by EPAC except

Vitexin exerts cardioprotective effect on chronic myocardial ischemia/reperfusion injury in rats via inhibiting myocardial apoptosis and lipid peroxidation

PubMed Central

Che, Xia; Wang, Xin; Zhang, Junyan; Peng, Chengfeng; Zhen, Yilan; Shao, Xu; Zhang, Gongliang; Dong, Liuyi

2016-01-01

Purpose: The aim of this study was to explore the cardioprotective effect of vitexin on chronic myocardial ischemia/reperfusion injury in rats and potential mechanisms. Methods: A chronic myocardial ischemia/reperfusion injury model was established by ligating left anterior descending coronary for 60 minutes, and followed by reperfusion for 14 days. After 2 weeks ischemia/reperfusion, cardiac function was measured to assess myocardial injury. The level of ST segment was recorded in different periods by electrocardiograph. The change of left ventricular function and myocardial reaction degree of fibrosis of heart was investigated by hematoxylin and eosin (HE) staining and Sirius red staining. Endothelium-dependent relaxations due to acetylcholine were observed in isolated rat thoracic aortic ring preparation. The blood samples were collected to measure the levels of MDA, the activities of SOD and NADPH in serum. Epac1, Rap1, Bax and Bcl-2 were examined by using Western Blotting. Results: Vitexin exerted significant protective effect on chronic myocardial ischemia/reperfusion injury, improved obviously left ventricular diastolic function and reduced myocardial reactive fibrosis degree in rats of myocardial ischemia. Medium and high-dose vitexin groups presented a significant decrease in Bax, Epac1 and Rap1 production and increase in Bcl-2 compared to the I/R group. It may be related to preventing myocardial cells from apoptosis, improving myocardial diastolic function and inhibiting lipid peroxidation. Conclusions: Vitexin is a cardioprotective herb, which may be a promising useful complementary and alternative medicine for patients with coronary heart disease. PMID:27648122

First person - Gergő Szanda.

PubMed

2018-05-16

First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Gergő Szanda is the first author on 'Mitochondrial cAMP exerts positive feedback on mitochondrial Ca 2+ uptake via the recruitment of Epac1', published in Journal of Cell Science. Gergő is an assistant professor and leads a group at Semmelweis University, Budapest, Hungary, investigating Ca 2+ signaling and mitochondrial biology, and the role of endocannabinoids in metabolism. © 2018. Published by The Company of Biologists Ltd.

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

A novel approach to prevent endothelial hyperpermeability: the Crataegus extract WS® 1442 targets the cAMP/Rap1 pathway.

PubMed

Bubik, Martin F; Willer, Elisabeth A; Bihari, Peter; Jürgenliemk, Guido; Ammer, Hermann; Krombach, Fritz; Zahler, Stefan; Vollmar, Angelika M; Fürst, Robert

2012-01-01

Endothelial hyperpermeability followed by edema formation is a hallmark of many severe disorders. Effective drugs directly targeting endothelial barrier function are widely lacking. We hypothesized that the hawthorn (Crataegus spp.) extract WS® 1442, a proven multi-component drug against moderate forms of heart failure, would prevent vascular leakage by affecting endothelial barrier-regulating systems. In vivo, WS® 1442 inhibited the histamine-evoked extravasation of FITC-dextran from mouse cremaster muscle venules. In cultured human endothelial cells, WS® 1442 blocked the thrombin-induced FITC-dextran permeability. By applying biochemical and microscopic techniques, we revealed that WS® 1442 abrogates detrimental effects of thrombin on adherens junctions (vascular endothelial-cadherin), the F-actin cytoskeleton, and the contractile apparatus (myosin light chain). Mechanistically, WS® 1442 inhibited the thrombin-induced rise of intracellular calcium (ratiometric measurement), followed by an inactivation of PKC and RhoA (pulldown assay). Moreover, WS® 1442 increased endothelial cAMP levels (ELISA), which consequently activated PKA and Rap1 (pulldown assay). Utilizing pharmacological inhibitors or siRNA, we found that PKA is not involved in barrier protection, whereas Epac1, Rap1, and Rac1 play a crucial role in the WS® 1442-induced activation of cortactin, which triggers a strong cortical actin rearrangement. In summary, WS® 1442 effectively protects against endothelial barrier dysfunction in vitro and in vivo. It specifically interacts with endothelial permeability-regulating systems by blocking the Ca(2+)/PKC/RhoA and activating the cAMP/Epac1/Rap1 pathway. As a proven safe herbal drug, WS® 1442 opens a novel pharmacological approach to treat hyperpermeability-associated diseases. This in-depth mechanistic work contributes to a better acceptance of this herbal remedy. Copyright © 2011 Elsevier Ltd. All rights reserved.

Culture adaptation of malaria parasites selects for convergent loss-of-function mutants.

PubMed

Claessens, Antoine; Affara, Muna; Assefa, Samuel A; Kwiatkowski, Dominic P; Conway, David J

2017-01-24

Cultured human pathogens may differ significantly from source populations. To investigate the genetic basis of laboratory adaptation in malaria parasites, clinical Plasmodium falciparum isolates were sampled from patients and cultured in vitro for up to three months. Genome sequence analysis was performed on multiple culture time point samples from six monoclonal isolates, and single nucleotide polymorphism (SNP) variants emerging over time were detected. Out of a total of five positively selected SNPs, four represented nonsense mutations resulting in stop codons, three of these in a single ApiAP2 transcription factor gene, and one in SRPK1. To survey further for nonsense mutants associated with culture, genome sequences of eleven long-term laboratory-adapted parasite strains were examined, revealing four independently acquired nonsense mutations in two other ApiAP2 genes, and five in Epac. No mutants of these genes exist in a large database of parasite sequences from uncultured clinical samples. This implicates putative master regulator genes in which multiple independent stop codon mutations have convergently led to culture adaptation, affecting most laboratory lines of P. falciparum. Understanding the adaptive processes should guide development of experimental models, which could include targeted gene disruption to adapt fastidious malaria parasite species to culture.

Beta-Adrenoceptor Activation Reduces Both Dermal Microvascular Endothelial Cell Migration via a cAMP-Dependent Mechanism and Wound Angiogenesis.

PubMed

O'Leary, Andrew P; Fox, James M; Pullar, Christine E

2015-02-01

Angiogenesis is an essential process during tissue regeneration; however, the amount of angiogenesis directly correlates with the level of wound scarring. Angiogenesis is lower in scar-free foetal wounds while angiogenesis is raised and abnormal in pathophysiological scarring such as hypertrophic scars and keloids. Delineating the mechanisms that modulate angiogenesis and could reduce scarring would be clinically useful. Beta-adrenoceptors (β-AR) are G protein-coupled receptors (GPCRs) expressed on all skin cell-types. They play a role in wound repair but their specific role in angiogenesis is unknown. In this study, a range of in vitro assays (single cell migration, scratch wound healing, ELISAs for angiogenic growth factors and tubule formation) were performed with human dermal microvascular endothelial cells (HDMEC) to investigate and dissect mechanisms underpinning β-AR-mediated modulation of angiogenesis in chick chorioallantoic membranes (CAM) and murine excisional skin wounds. β-AR activation reduced HDMEC migration via cyclic adenosine monophosphate (cAMP)-dependent and protein kinase A (PKA)-independent mechanisms as demonstrated through use of an EPAC agonist that auto-inhibited the cAMP-mediated β-AR transduced reduction in HDMEC motility; a PKA inhibitor was, conversely, ineffective. ELISA studies demonstrated that β-AR activation reduced pro-angiogenic growth factor secretion from HDMECs (fibroblast growth factor 2) and keratinocytes (vascular endothelial growth factor A) revealing possible β-AR-mediated autocrine and paracrine anti-angiogenic mechanisms. In more complex environments, β-AR activation delayed HDMEC tubule formation and decreased angiogenesis both in the CAM assay and in murine excisional skin wounds in vivo. β-AR activation reduced HDMEC function in vitro and angiogenesis in vivo; therefore, β-AR agonists could be promising anti-angiogenic modulators in skin. © 2014 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

Phosphodiesterase 4 regulates the migration of B16-F10 melanoma cells.

PubMed

Watanabe, Yoshihiro; Murata, Taku; Shimizu, Kasumi; Morita, Hiroshi; Inui, Madoka; Tagawa, Toshiro

2012-08-01

Phosphodiesterases (PDEs) are important regulators of signal transduction processes. Eleven PDE gene families (PDE1-11) have been identified and several PDE isoforms are selectively expressed in various cell types. PDE4 family members specifically hydrolyze cyclic AMP (cAMP). Four genes (PDE4A-D) are known to encode PDE4 enzymes, with additional diversity generated by the use of alternative mRNA splicing and the use of different promoters. While PDE4 selective inhibitors show therapeutic potential for treating major diseases such as asthma and chronic obstructive pulmonary disease, little is known concerning the role of PDE4 in malignant melanoma. In this study, we examined the role of PDE4 in mouse B16-F10 melanoma cells. In these cells, PDE4 activity was found to be ∼60% of total PDE activity. RT-PCR detected only PDE4B and PDE4D mRNA. Cell growth was inhibited by the cAMP analog, 8-bromo-cAMP, but not by the specific PDE4 inhibitors, rolipram and denbufylline, which increased intracellular cAMP concentrations. Finally, migration of the B16-F10 cells was inhibited by the PDE4 inhibitors and 8-bromo-cAMP, while migration was increased by a protein kinase A (PKA) inhibitor, PKI(14-22), and was not affected by 8-pCPT-2'-O-Me-cAMP, which is an analog of exchange protein activated by cAMP (Epac). The inhibitory effect of rolipram on migration was reversed by PKI(14-22). Based on these results, PDE4 appears to play an important role in the migration of B16-F10 cells, and therefore may be a novel target for the treatment of malignant melanoma.

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

PubMed

Aungsumart, Saharat; Apiwattanakul, Metha

2017-04-01

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

Real-time monitoring of intracellular cAMP during acute ethanol exposure

PubMed Central

Gupta, Ratna; Qualls-Creekmore, Emily; Yoshimura, Masami

2013-01-01

Background In previous studies we have shown that ethanol enhances the activity of Gs-stimulated membrane-bound adenylyl cyclase (AC). The effect is AC isoform specific and the type 7 AC (AC7) is most responsive to ethanol. In this study, we employed a fluorescence resonance energy transfer (FRET) based cAMP sensor, Epac1-camps, to examine real-time temporal dynamics of ethanol effects on cAMP concentrations. To our knowledge, this is the first report on real-time detection of the ethanol effect on intracellular cAMP. Methods Hela cells were transfected with Epac1-camps, dopamine D1A receptor, and one isoform of AC (AC7 or AC3). Fluorescent images were captured using a specific filter set for cyan fluorescent protein (CFP), yellow fluorescent protein (YFP), and FRET, respectively and FRET intensity was calculated on a pixel-by-pixel basis to examine changes in cAMP. Results During 2-minute stimulation with dopamine (DA), the cytoplasmic cAMP level quickly increased, then decreased to a plateau, where the cAMP level was higher than the level prior to stimulation with DA. Ethanol concentration dependently increased cytoplasmic cAMP in cells transfected with AC7, while ethanol did not have effect on cells transfected with AC3. Similar trends were observed for cAMP at the plasma membrane and in the nucleus during 2-minute stimulation with DA. Unexpectedly, when cells expressing AC7 were stimulated with DA or other Gs protein-coupled receptor’s ligand plus ethanol for 5 seconds, ethanol reduced cAMP concentration. Conclusion These results suggest that ethanol has two opposing effects on the cAMP generating system in an AC isoform specific manner, the enhancing effect on AC activity and the short lived inhibitory effect. Thus, ethanol may have a different effect on cAMP depending on not only AC isoform but also the duration of exposure. PMID:23731206

The effector and scaffolding proteins AF6 and MUPP1 interact with connexin36 and localize at gap junctions that form electrical synapses in rodent brain.

PubMed

Li, X; Lynn, B D; Nagy, J I

2012-01-01

Electrical synapses formed by neuronal gap junctions composed of connexin36 (Cx36) occur in most major structures in the mammalian central nervous system. These synapses link ensembles of neurons and influence their network properties. Little is known about the macromolecular constituents of neuronal gap junctions or how transmission through electrical synapses is regulated at the level of channel conductance or gap junction assembly/disassembly. Such knowledge is a prerequisite to understanding the roles of gap junctions in neuronal circuitry. Gap junctions share similarities with tight and adhesion junctions in that all three reside at close plasma membrane appositions, and therefore may associate with similar structural and regulatory proteins. Previously, we reported that the tight junction-associated protein zonula occludens-1 (ZO-1) interacts with Cx36 and is localized at gap junctions. Here, we demonstrate that two proteins known to be associated with tight and adherens junctions, namely AF6 and MUPP1, are components of neuronal gap junctions in rodent brain. By immunofluorescence, AF6 and MUPP1 were co-localized with Cx36 in many brain areas. Co-immunoprecipitation and pull-down approaches revealed an association of Cx36 with AF6 and MUPP1, which required the C-terminus PDZ domain interaction motif of Cx36 for interaction with the single PDZ domain of AF6 and with the 10th PDZ domain of MUPP1. As AF6 is a target of the cAMP/Epac/Rap1 signalling pathway and MUPP1 is a scaffolding protein that interacts with CaMKII, the present results suggest that AF6 may be a target for cAMP/Epac/Rap1 signalling at electrical synapses, and that MUPP1 may contribute to anchoring CaMKII at these synapses. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

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

PubMed Central

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

2014-01-01

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

Stress peptide PACAP engages multiple signaling pathways within the carotid body to initiate excitatory responses in respiratory and sympathetic chemosensory afferents.

PubMed

Roy, Arijit; Derakhshan, Fatemeh; Wilson, Richard J A

2013-06-15

Consistent with a critical role in respiratory and autonomic stress responses, the carotid bodies are strongly excited by pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide implicated in stress responses throughout the sympathetic nervous system. PACAP excites isolated carotid body glomus cells via activation of PAC1 receptors, with one study suggesting PAC1-induced excitation is due entirely to protein kinase A (PKA)-mediated inhibition of TASK channels. However, in other systems, PAC1 is known to be coupled to multiple intracellular signaling pathways, including PKA, phospholipase C (PLC), phospholipase D (PLD), and protein kinase C (PKC), that trigger multiple downstream effectors including increased Ca²⁺ mobilization, inhibition of various K⁺ channels, and activation of nonselective cation channels. This study tests if non-PKA/TASK channel signaling helps mediate the stimulatory effects of PACAP on the carotid body. Using an ex vivo arterially perfused rat carotid body preparation, we show that PACAP-38 stimulates carotid sinus nerve activity in a biphasic manner (peak response, falling to plateau). PKA blocker H-89 only reduced the plateau response (~41%), whereas the TASK-1-like K⁺ channel blocker/transient receptor potential vanilloid 1 channel agonist anandamide only inhibited the peak response (~48%), suggesting involvement of additional pathways. The PLD blocker CAY10594 significantly inhibited both peak and plateau responses. The PLC blocker U73122 decimated both peak and plateau responses. Brefeldin A, a blocker of Epac (cAMP-activated guanine exchange factor, reported to link Gs-coupled receptors with PLC/PLD), also reduced both phases of the response, as did blocking signaling downstream of PLC/PLD with the PKC inhibitors chelerythrine chloride and GF109203X. Suggesting the involvement of non-TASK ion channels in the effects of PACAP, the A-type K⁺ channel blocker 4-aminopyridine, and the putative transient receptor potential channel (TRPC)/T-type calcium channel blocker SKF96365 each significantly inhibited the peak and steady-state responses. These data suggest the stimulatory effect of PACAP-38 on carotid body sensory activity is mediated through multiple signaling pathways: the PLC-PKC pathways predominates, with TRPC and/or T-type channel activation and Kv channel inactivation; only partial involvement is attributable to PKA and PLD activation.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-10

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

ERYTHROPOIETIC FACTOR PURIFICATION

DOEpatents

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

1962-05-01

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

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

PubMed

Feldman, Sue S

2018-04-30

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

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

ERIC Educational Resources Information Center

Lee, Jong-Yeon; Park, Sanghoon

2017-01-01

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

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

PubMed

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

2017-06-01

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

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

PubMed Central

2018-01-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2014-03-01

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

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

PubMed Central

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

2011-01-01

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

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

PubMed

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

2012-07-01

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

FRET-based binding assay between a fluorescent cAMP analogue and a cyclic nucleotide-binding domain tagged with a CFP.

PubMed

Romero, Francisco; Santana-Calvo, Carmen; Sánchez-Guevara, Yoloxochitl; Nishigaki, Takuya

2017-09-01

The cyclic nucleotide-binding domain (CNBD) functions as a regulatory domain of many proteins involved in cyclic nucleotide signalling. We developed a straightforward and reliable binding assay based on intermolecular fluorescence resonance energy transfer (FRET) between an adenosine-3', 5'-cyclic monophosphate analogue labelled with fluorescein and a recombinant CNBD of human EPAC1 tagged with a cyan fluorescence protein (CFP). The high FRET efficiency of this method (~ 80%) allowed us to perform several types of binding experiments with nanomolar range of sample using conventional equipment. In addition, the CFP tag on the CNBD enabled us to perform a specific binding experiment using an unpurified protein. Considering these advantages, this technique is useful to study poorly characterized CNBDs. © 2017 Federation of European Biochemical Societies.

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

PubMed

Vogtt, K; Winter, R

2005-08-01

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

Cyclic AMP is a key regulator of M1 to M2a phenotypic conversion of microglia in the presence of Th2 cytokines.

PubMed

Ghosh, Mousumi; Xu, Yong; Pearse, Damien D

2016-01-13

Microglia and macrophages play a central role in neuroinflammation. Pro-inflammatory cytokines trigger their conversion to a classically activated (M1) phenotype, sustaining inflammation and producing a cytotoxic environment. Conversely, anti-inflammatory cytokines polarize the cells towards an alternatively activated (M2), tissue reparative phenotype. Elucidation of the signal transduction pathways involved in M1 to M2 phenotypic conversion may provide insight into how the innate immune response can be harnessed during distinct phases of disease or injury to mediate neuroprotection and neurorepair. Microglial cells (cell line and primary) were subjected to combined cyclic adenosine monophosphate (cyclic AMP) and IL-4, or either alone, in the presence of pro-inflammatory mediators, lipopolysaccharide (LPS), or tumor necrosis factor-α (TNF-α). Their effects on the expression of characteristic markers for M1 and M2 microglia were assessed. Similarly, the M1 and M2 phenotypes of microglia and macrophages within the lesion site were then evaluated following a contusive spinal cord injury (SCI) to the thoracic (T8) spinal cord of rats and mice when the agents were administered systemically. It was demonstrated that cyclic AMP functions synergistically with IL-4 to promote M1 to M2 conversion of microglia in culture. The combination of cyclic AMP and IL-4, but neither alone, induced an Arg-1(+)/iNOS(-)cell phenotype with concomitant expression of other M2-specific markers including TG2 and RELM-α. M2-converted microglia showed ameliorated production of pro-inflammatory cytokines (TNF-α and IP-10) and reactive oxygen species, with no alteration in phagocytic properties. M2a conversion required protein kinase A (PKA), but not the exchange protein directly activated by cyclic AMP (EPAC). Systemic delivery of cyclic AMP and IL-4 after experimental SCI also promoted a significant M1 to M2a phenotypic change in microglia and macrophage population dynamics in the lesion. Using primary microglia, microglial cell lines, and experimental models of CNS injury, we demonstrate that cyclic AMP levels are a critical determinant in M1-M2 polarization. High levels of cyclic AMP promoted an Arg-1(+) M2a phenotype when microglia were activated with pro-inflammatory stimuli and Th2 cytokines. Th2 cytokines or cyclic AMP independently did not promote these changes. Phenotypic conversion of microglia provides a powerful new therapeutic approach for altering the balance of cytotoxic to reparative microglia in a diversity of neurological diseases and injury.

Protein kinase A-mediated cell proliferation in brown preadipocytes is independent of Erk1/2, PI{sub 3}K and mTOR

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

Wang, Yanling; Sato, Masaaki; Guo, Yuan

2014-10-15

The physiological agonist norepinephrine promotes cell proliferation of brown preadipocytes during the process of tissue recruitment. In a primary culture system, cAMP mediates these adrenergic effects. In the present study, we demonstrated that, in contrast to other systems where the mitogenic effect of cAMP requires the synergistic action of (serum) growth factors, especially insulin/IGF, the cAMP effect in brown preadipocytes was independent of serum and insulin. Protein kinase A, rather than Epac, mediated the cAMP mitogenic effect. The Erk 1/2 family of MAPK, the PI{sub 3}K system and the mTOR complexes were all activated by cAMP, but these activations weremore » not necessary for cAMP-induced cell proliferation; a protein kinase C isoform may be involved in mediating cAMP-activated cell proliferation. We conclude that the generally acknowledged cellular mediators for induction of cell proliferation are not involved in this process in the brown preadipocyte system; this conclusion may be of relevance both for examination of mechanisms for induction of brown adipose tissue recruitment but also for understanding the mechanism behind e.g. certain endocrine neoplasias. - Highlights: • cAMP can mimick norepinephrine-induced proliferation of brown preadipocytes. • The cAMP-induced proliferation can occur in the absence of serum, of any other growth factors, and of insulin. • Erk1/2, PI{sub 3}K and mTOR are cAMP activated but not involved in induction of proliferation. • A Protein Kinase C member may be in the signalling cascade. • This pathway analysis may also be of importance for certain endocrine hyper- and neoplasias.« less

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

PubMed Central

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

2014-01-01

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

Exendin-4 inhibits high-altitude cerebral edema by protecting against neurobiological dysfunction

PubMed Central

Sun, Zhong-Lei; Jiang, Xian-Feng; Cheng, Yuan-Chi; Liu, Ying-Fu; Yang, Kai; Zhu, Shuang-Long; Kong, Xian-Bin; Tu, Yue; Bian, Ke-Feng; Liu, Zhen-Lin; Chen, Xu-Yi

2018-01-01

The anti-inflammatory and antioxidant effects of exendin-4 (Ex-4) have been reported previously. However, whether (Ex-4) has anti-inflammatory and antioxidant effects on high-altitude cerebral edema (HACE) remains poorly understood. In this study, two rat models of HACE were established by placing rats in a hypoxic environment with a simulated altitude of either 6000- or 7000-m above sea level (MASL) for 72 hours. An altitude of 7000 MASL with 72-hours of hypoxia was found to be the optimized experimental paradigm for establishing HACE models. Then, in rats where a model of HACE was established by introducing them to a 7000 MASL environment with 72-hours of hypoxia treatment, 2, 10 and, 100 μg of Ex-4 was intraperitoneally administrated. The open field test and tail suspension test were used to test animal behavior. Routine methods were used to detect change in inflammatory cells. Hematoxylin-eosin staining was performed to determine pathological changes to brain tissue. Wet/dry weight ratios were used to measure brain water content. Evans blue leakage was used to determine blood-brain barrier integrity. Enzyme-linked immunosorbent assay (ELISA) was performed to measure markers of inflammation and oxidative stress including superoxide dismutase, glutathione, and malonaldehyde values, as well as interleukin-6, tumor necrosis factor-alpha, cyclic adenosine monophosphate levels in the brain tissue. Western blot analysis was performed to determine the levels of occludin, ZO-1, SOCS-3, vascular endothelial growth factor, EPAC1, nuclear factor-kappa B, and aquaporin-4. Our results demonstrate that Ex-4 preconditioning decreased brain water content, inhibited inflammation and oxidative stress, alleviated brain tissue injury, maintain blood-brain barrier integrity, and effectively improved motor function in rat models of HACE. These findings suggest that Ex-4 exhibits therapeutic potential in the treatment of HACE. PMID:29722317

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

ERIC Educational Resources Information Center

Daly, Amanda; Barker, Michelle

2010-01-01

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

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.

PubMed

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

2014-05-14

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

FPGA-based multi-channel fluorescence lifetime analysis of Fourier multiplexed frequency-sweeping lifetime imaging

PubMed Central

Zhao, Ming; Li, Yu; Peng, Leilei

2014-01-01

We report a fast non-iterative lifetime data analysis method for the Fourier multiplexed frequency-sweeping confocal FLIM (Fm-FLIM) system [ Opt. Express22, 10221 ( 2014)24921725]. The new method, named R-method, allows fast multi-channel lifetime image analysis in the system’s FPGA data processing board. Experimental tests proved that the performance of the R-method is equivalent to that of single-exponential iterative fitting, and its sensitivity is well suited for time-lapse FLIM-FRET imaging of live cells, for example cyclic adenosine monophosphate (cAMP) level imaging with GFP-Epac-mCherry sensors. With the R-method and its FPGA implementation, multi-channel lifetime images can now be generated in real time on the multi-channel frequency-sweeping FLIM system, and live readout of FRET sensors can be performed during time-lapse imaging. PMID:25321778

Ground Motion Studies for Large Future Accelerator

NASA Astrophysics Data System (ADS)

Takeda, Shigeru; Oide, Katsunobu

1997-05-01

The future large accelerator, such as TeV linear collider, should have extremely small emittance to perform the required luminosity. Precise alignment of machine components is essential to prevent emittance dilution. The ground motion spoils alignment of accelerator elements and results in emittance growth. The ground motion in the frequency range of seismic vibration is mostly coherent in the related accelerator. But the incoherent diffusive or Brownian like motion becomes dominant at frequency region less than seismic vibration [1, 2, 3]. Slow ground motion with respect to the machine performance is discussed including the method of tunnel construction. Our experimental results and recent excavated results clarify that application of TBMs is better excavating method than NATM (Drill + Blast) for accelerator tunnel to prevent emittance dilution. ([1] V. Shiltsev, Proc. of IWAA95 Tsukuba, 1995. [2] Shigeru Takeda et al., Proc. of EPAC96, 1996. [3] A. Sery, Proc. of LINAC96, 1996.)

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

PubMed

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

2012-04-04

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

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

PubMed

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

2015-07-01

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

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

NASA Astrophysics Data System (ADS)

Bojko, Marian; Kocich, Radim

2016-06-01

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

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

PubMed

Alexandrescu, A T

2001-01-01

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

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

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

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

Studies on Some Factors Affecting the Quantitative Estimation of the Exchange Capacity of Organic Matter

Treesearch

Walter M. Broadfoot; Edward H. Tyner

1939-01-01

Methods which are satisfactory for determining the base-exchange capacity of mineral soils can not be applied indiscriminately for determining the exchange capacity of fresh or decomposed plant residues.

USSR Report, Chemistry

DTIC Science & Technology

1985-08-19

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

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

DOE PAGES

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

2015-06-01

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

Physicians' acceptance of electronic medical records exchange: an extension of the decomposed TPB model with institutional trust and perceived risk.

PubMed

Hsieh, Pi-Jung

2015-01-01

Electronic medical records (EMRs) exchange improves clinical quality and reduces medical costs. However, few studies address the antecedent factors of physicians' intentions to use EMR exchange. Based on institutional trust and perceived risk integrated with the decomposed theory of planned behavior (TPB) model, we propose a theoretical model to explain the intention of physicians to use an EMR exchange system. We conducted a field survey in Taiwan to collect data from physicians who had experience using the EMR exchange systems. A valid sample of 191 responses was collected for data analysis. To test the proposed research model, we employed structural equation modeling using the partial least squares method. The study findings show that the following five factors have a significant influence on the physicians' intentions to use EMR exchange systems: (a) attitude; (b) subjective norm; (c) perceived behavior control; (d) institutional trust; and (e) perceived risk. These five factors are predictable by perceived usefulness, perceived ease of use, and compatibility, interpersonal and governmental influence, facilitating conditions and self-efficacy, situational normality and structural assurance, and institutional trust, respectively. The results also indicate that institutional trust and perceived risk integrated with the decomposed TPB model improve the prediction of physician's intentions to use EMR exchange. The results of this study indicate that our research model effectively predicts the intention of physicians to use EMR exchange, and provides valuable implications for academics and practitioners. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

EPA Science Inventory

Air exchange rate is critical to determining the relationship between indoor and outdoor concentrations of hazardous pollutants. Approximately 150 air exchange experiments were completed in two residences: a two-story detached house located in Redwood City, CA and a three-story...

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...

Knowledge exchange and integrated services: experiences from an integrated community intellectual (learning) disability service for adults.

PubMed

Farrington, C; Clare, I C H; Holland, A J; Barrett, M; Oborn, E

2015-03-01

This paper examines knowledge exchange dynamics in a specialist integrated intellectual (learning) disability service, comprising specialist healthcare provision with social care commissioning and management, and considers their significance in terms of integrated service delivery. A qualitative study focusing on knowledge exchange and integrated services. Semi-structured interviews (n = 25) were conducted with members of an integrated intellectual disability service in England regarding their perceptions of knowledge exchange within the service and the way in which knowledge exchange impinges on the operation of the integrated service. Exchange of 'explicit' (codifiable) knowledge between health and care management components of the service is problematic because of a lack of integrated clinical governance and related factors such as IT and care record systems and office arrangements. Team meetings and workplace interactions allowed for informal exchange of explicit and 'tacit' (non-codifiable) knowledge, but presented challenges in terms of knowledge exchange completeness and sustainability. Knowledge exchange processes play an important role in the functioning of integrated services incorporating health and care management components. Managers need to ensure that knowledge exchange processes facilitate both explicit and tacit knowledge exchange and do not rely excessively on informal, 'ad hoc' interactions. Research on integrated services should take account of micro-scale knowledge exchange dynamics and relationships between social dynamics and physical factors. © 2014 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Asparagine promotes cancer cell proliferation through use as an amino acid exchange factor

PubMed Central

Krall, Abigail S.; Xu, Shili; Graeber, Thomas G.; Braas, Daniel; Christofk, Heather R.

2016-01-01

Cellular amino acid uptake is critical for mTOR complex 1 (mTORC1) activation and cell proliferation. However, the regulation of amino acid uptake is not well-understood. Here we describe a role for asparagine as an amino acid exchange factor: intracellular asparagine exchanges with extracellular amino acids. Through asparagine synthetase knockdown and altering of media asparagine concentrations, we show that intracellular asparagine levels regulate uptake of amino acids, especially serine, arginine and histidine. Through its exchange factor role, asparagine regulates mTORC1 activity and protein synthesis. In addition, we show that asparagine regulation of serine uptake influences serine metabolism and nucleotide synthesis, suggesting that asparagine is involved in coordinating protein and nucleotide synthesis. Finally, we show that maintenance of intracellular asparagine levels is critical for cancer cell growth. Collectively, our results indicate that asparagine is an important regulator of cancer cell amino acid homeostasis, anabolic metabolism and proliferation. PMID:27126896

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

USGS Publications Warehouse

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

2011-01-01

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

Experimental study on heat transfer performance of fin-tube exchanger and PSHE for waste heat recovery

NASA Astrophysics Data System (ADS)

Chen, Ting; Bae, Kyung Jin; Kwon, Oh Kyung

2018-02-01

In this paper, heat transfer characteristics of fin-tube heat exchanger and primary surface heat exchanger (PSHE) used in waste heat recovery were investigated experimentally. The flow in the fin-tube heat exchanger is cross flow and in PSHE counter flow. The variations of friction factor and Colburn j factor with air mass flow rate, and Nu number with Re number are presented. Various comparison methods are used to evaluate heat transfer performance, and the results show that the heat transfer rate of the PSHE is on average 17.3% larger than that of fin-tube heat exchanger when air mass flow rate is ranging from 1.24 to 3.45 kg/min. However, the PSHE causes higher pressure drop, and the fin-tube heat exchanger has a wider application range which leads to a 31.7% higher value of maximum heat transfer rate compared to that of the PSHE. Besides, under the same fan power per unit frontal surface, a higher heat transfer rate value is given in the fin-tube heat exchanger.

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…

Coming to Canada to Study: Factors that Influence Student's Decisions to Participate in International Exchange

ERIC Educational Resources Information Center

Massey, Jennifer; Burrow, Jeff

2012-01-01

Increasing numbers of students are participating in study abroad programs. Outcomes associated with these programs have been studied extensively, but relatively little is known about what motivates and influences students to participate. This study investigated factors that motivate and influence students to study on exchange and explored how…

Multidimensional generalized-ensemble algorithms for complex systems.

PubMed

Mitsutake, Ayori; Okamoto, Yuko

2009-06-07

We give general formulations of the multidimensional multicanonical algorithm, simulated tempering, and replica-exchange method. We generalize the original potential energy function E(0) by adding any physical quantity V of interest as a new energy term. These multidimensional generalized-ensemble algorithms then perform a random walk not only in E(0) space but also in V space. Among the three algorithms, the replica-exchange method is the easiest to perform because the weight factor is just a product of regular Boltzmann-like factors, while the weight factors for the multicanonical algorithm and simulated tempering are not a priori known. We give a simple procedure for obtaining the weight factors for these two latter algorithms, which uses a short replica-exchange simulation and the multiple-histogram reweighting techniques. As an example of applications of these algorithms, we have performed a two-dimensional replica-exchange simulation and a two-dimensional simulated-tempering simulation using an alpha-helical peptide system. From these simulations, we study the helix-coil transitions of the peptide in gas phase and in aqueous solution.

Application of Monte Carlo techniques to transient thermal modeling of cavity radiometers having diffuse-specular surfaces

NASA Technical Reports Server (NTRS)

Mahan, J. R.; Eskin, L. D.

1981-01-01

A viable alternative to the net exchange method of radiative analysis which is equally applicable to diffuse and diffuse-specular enclosures is presented. It is particularly more advantageous to use than the net exchange method in the case of a transient thermal analysis involving conduction and storage of energy as well as radiative exchange. A new quantity, called the distribution factor is defined which replaces the angle factor and the configuration factor. Once obtained, the array of distribution factors for an ensemble of surface elements which define an enclosure permits the instantaneous net radiative heat fluxes to all of the surfaces to be computed directly in terms of the known surface temperatures at that instant. The formulation of the thermal model is described, as is the determination of distribution factors by application of a Monte Carlo analysis. The results show that when fewer than 10,000 packets are emitted, an unsatisfactory approximation for the distribution factors is obtained, but that 10,000 packets is sufficient.

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

PubMed Central

Hocker, Harrison J.; Cho, Kwang-Jin; Chen, Chung-Ying K.; Rambahal, Nandini; Sagineedu, Sreenivasa Rao; Shaari, Khozirah; Stanslas, Johnson; Hancock, John F.; Gorfe, Alemayehu A.

2013-01-01

Aberrant signaling by oncogenic mutant rat sarcoma (Ras) proteins occurs in ∼15% of all human tumors, yet direct inhibition of Ras by small molecules has remained elusive. Recently, several small-molecule ligands have been discovered that directly bind Ras and inhibit its function by interfering with exchange factor binding. However, it is unclear whether, or how, these ligands could lead to drugs that act against constitutively active oncogenic mutant Ras. Using a dynamics-based pocket identification scheme, ensemble docking, and innovative cell-based assays, here we show that andrographolide (AGP)—a bicyclic diterpenoid lactone isolated from Andrographis paniculata—and its benzylidene derivatives bind to transient pockets on Kirsten-Ras (K-Ras) and inhibit GDP–GTP exchange. As expected for inhibitors of exchange factor binding, AGP derivatives reduced GTP loading of wild-type K-Ras in response to acute EGF stimulation with a concomitant reduction in MAPK activation. Remarkably, however, prolonged treatment with AGP derivatives also reduced GTP loading of, and signal transmission by, oncogenic mutant K-RasG12V. In sum, the combined analysis of our computational and cell biology results show that AGP derivatives directly bind Ras, block GDP–GTP exchange, and inhibit both wild-type and oncogenic K-Ras signaling. Importantly, our findings not only show that nucleotide exchange factors are required for oncogenic Ras signaling but also demonstrate that inhibiting nucleotide exchange is a valid approach to abrogating the function of oncogenic mutant Ras. PMID:23737504

Divergent Label-free Cell Phenotypic Pharmacology of Ligands at the Overexpressed β2-Adrenergic Receptors

NASA Astrophysics Data System (ADS)

Ferrie, Ann M.; Sun, Haiyan; Zaytseva, Natalya; Fang, Ye

2014-01-01

We present subclone sensitive cell phenotypic pharmacology of ligands at the β2-adrenergic receptor (β2-AR) stably expressed in HEK-293 cells. The parental cell line was transfected with green fluorescent protein (GFP)-tagged β2-AR. Four stable subclones were established and used to profile a library of sixty-nine AR ligands. Dynamic mass redistribution (DMR) profiling resulted in a pharmacological activity map suggesting that HEK293 endogenously expresses functional Gi-coupled α2-AR and Gs-coupled β2-AR, and the label-free cell phenotypic activity of AR ligands are subclone dependent. Pathway deconvolution revealed that the DMR of epinephrine is originated mostly from the remodeling of actin microfilaments and adhesion complexes, to less extent from the microtubule networks and receptor trafficking, and certain agonists displayed different efficacy towards the cAMP-Epac pathway. We demonstrate that receptor signaling and ligand pharmacology is sensitive to the receptor expression level, and the organization of the receptor and its signaling circuitry.

Widespread receptivity to neuropeptide PDF throughout the neuronal circadian clock network of Drosophila revealed by real-time cyclic AMP imaging.

PubMed

Shafer, Orie T; Kim, Dong Jo; Dunbar-Yaffe, Richard; Nikolaev, Viacheslav O; Lohse, Martin J; Taghert, Paul H

2008-04-24

The neuropeptide PDF is released by sixteen clock neurons in Drosophila and helps maintain circadian activity rhythms by coordinating a network of approximately 150 neuronal clocks. Whether PDF acts directly on elements of this neural network remains unknown. We address this question by adapting Epac1-camps, a genetically encoded cAMP FRET sensor, for use in the living brain. We find that a subset of the PDF-expressing neurons respond to PDF with long-lasting cAMP increases and confirm that such responses require the PDF receptor. In contrast, an unrelated Drosophila neuropeptide, DH31, stimulates large cAMP increases in all PDF-expressing clock neurons. Thus, the network of approximately 150 clock neurons displays widespread, though not uniform, PDF receptivity. This work introduces a sensitive means of measuring cAMP changes in a living brain with subcellular resolution. Specifically, it experimentally confirms the longstanding hypothesis that PDF is a direct modulator of most neurons in the Drosophila clock network.

The Central Role of cAMP in Regulating Plasmodium falciparum Merozoite Invasion of Human Erythrocytes

PubMed Central

More, Kunal R.; Siddiqui, Faiza Amber; Pachikara, Niseema; Ramdani, Ghania; Langsley, Gordon; Chitnis, Chetan E.

2014-01-01

All pathogenesis and death associated with Plasmodium falciparum malaria is due to parasite-infected erythrocytes. Invasion of erythrocytes by P. falciparum merozoites requires specific interactions between host receptors and parasite ligands that are localized in apical organelles called micronemes. Here, we identify cAMP as a key regulator that triggers the timely secretion of microneme proteins enabling receptor-engagement and invasion. We demonstrate that exposure of merozoites to a low K+ environment, typical of blood plasma, activates a bicarbonate-sensitive cytoplasmic adenylyl cyclase to raise cytosolic cAMP levels and activate protein kinase A, which regulates microneme secretion. We also show that cAMP regulates merozoite cytosolic Ca2+ levels via induction of an Epac pathway and demonstrate that increases in both cAMP and Ca2+ are essential to trigger microneme secretion. Our identification of the different elements in cAMP-dependent signaling pathways that regulate microneme secretion during invasion provides novel targets to inhibit blood stage parasite growth and prevent malaria. PMID:25522250

Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases.

PubMed

Park, Sung-Jun; Ahmad, Faiyaz; Philp, Andrew; Baar, Keith; Williams, Tishan; Luo, Haibin; Ke, Hengming; Rehmann, Holger; Taussig, Ronald; Brown, Alexandra L; Kim, Myung K; Beaven, Michael A; Burgin, Alex B; Manganiello, Vincent; Chung, Jay H

2012-02-03

Resveratrol, a polyphenol in red wine, has been reported as a calorie restriction mimetic with potential antiaging and antidiabetogenic properties. It is widely consumed as a nutritional supplement, but its mechanism of action remains a mystery. Here, we report that the metabolic effects of resveratrol result from competitive inhibition of cAMP-degrading phosphodiesterases, leading to elevated cAMP levels. The resulting activation of Epac1, a cAMP effector protein, increases intracellular Ca(2+) levels and activates the CamKKβ-AMPK pathway via phospholipase C and the ryanodine receptor Ca(2+)-release channel. As a consequence, resveratrol increases NAD(+) and the activity of Sirt1. Inhibiting PDE4 with rolipram reproduces all of the metabolic benefits of resveratrol, including prevention of diet-induced obesity and an increase in mitochondrial function, physical stamina, and glucose tolerance in mice. Therefore, administration of PDE4 inhibitors may also protect against and ameliorate the symptoms of metabolic diseases associated with aging. Copyright © 2012 Elsevier Inc. All rights reserved.

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.

Process gas hear recovery

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

Anderson, W.M.; Thurner, R.P.

1977-01-01

In considering the use of regenerative and recuperative heat exchangers for process-gas heat recovery general information regarding heat-exchanger effectiveness versus initial capital investment and operating costs is discussed. Specific examples for preheating combustion air for process furnaces and for using primary and secondary heat exchangers in conjunction with an air-pollution-control system for drying and curing ovens cover basic heat-exchanger design and application considerations as well as investment-payback factors.

Raising the Curtain. A Report with Recommendations on Academic Exchanges with East Central Europe and the USSR. East Central Europe Information Exchange Report 1.

ERIC Educational Resources Information Center

Burn, Barbara B.

This report provides an overview of the changes in the development of academic exchange activity between the United States, the Soviet Union, and East Central Europe in the context of far-reaching reforms throughout the region. It also explores the factors which may facilitate or inhibit further growth in academic exchanges. The report begins with…

Influence of genome and bio-ecology on the prevalence of genome exchange in unisexuals of the Ambystoma complex.

PubMed

Beauregard, France; Angers, Bernard

2018-05-31

Unisexuals of the blue-spotted salamander complex are thought to reproduce by kleptogenesis. Genome exchanges associated with this sperm-dependent mode of reproduction are expected to result in a higher genetic variation and multiple ploidy levels compared to clonality. However, the existence of some populations exclusively formed of genetically identical individuals suggests that factors could prevent genome exchanges. This study aimed at assessing the prevalence of genome exchange among unisexuals of the Ambystoma laterale-jeffersonianum complex from 10 sites in the northern part of their distribution. A total of 235 individuals, including 207 unisexuals, were genotyped using microsatellite loci and AFLP. Unisexual individuals could be sorted in five genetically distinct groups, likely derived from the same paternal A. jeffersonianum haplome. One of these groups exclusively reproduced clonally, even when found in sympatry with lineages presenting signature of genome exchange. Genome exchange was site-dependent for another group. Genome exchange was detected at all sites for the three remaining groups. Prevalence of genome exchange appears to be associated with ecological conditions such as availability of effective sperm donors. Intrinsic genomic factors may also affect this process, since different lineages in sympatry present highly variable rate of genome exchange. The coexistence of clonal and genetically diversified lineages opens the door to further research on alternatives to genetic variation.

The C-terminal Helix of Pseudomonas aeruginosa Elongation Factor Ts Tunes EF-Tu Dynamics to Modulate Nucleotide Exchange.

PubMed

De Laurentiis, Evelina Ines; Mercier, Evan; Wieden, Hans-Joachim

2016-10-28

Little is known about the conservation of critical kinetic parameters and the mechanistic strategies of elongation factor (EF) Ts-catalyzed nucleotide exchange in EF-Tu in bacteria and particularly in clinically relevant pathogens. EF-Tu from the clinically relevant pathogen Pseudomonas aeruginosa shares over 84% sequence identity with the corresponding elongation factor from Escherichia coli Interestingly, the functionally closely linked EF-Ts only shares 55% sequence identity. To identify any differences in the nucleotide binding properties, as well as in the EF-Ts-mediated nucleotide exchange reaction, we performed a comparative rapid kinetics and mutagenesis analysis of the nucleotide exchange mechanism for both the E. coli and P. aeruginosa systems, identifying helix 13 of EF-Ts as a previously unnoticed regulatory element in the nucleotide exchange mechanism with species-specific elements. Our findings support the base side-first entry of the nucleotide into the binding pocket of the EF-Tu·EF-Ts binary complex, followed by displacement of helix 13 and rapid binding of the phosphate side of the nucleotide, ultimately leading to the release of EF-Ts. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

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

PubMed

Vedovato, Natascia; Rispoli, Giorgio

2007-09-01

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

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

PubMed Central

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

2004-01-01

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

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

PubMed

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

2016-01-01

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

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

PubMed Central

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

2016-01-01

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

Exchange nailing for nonunion of diaphyseal fractures of the tibia: our results and an analysis of the risk factors for failure.

PubMed

Tsang, S T J; Mills, L A; Frantzias, J; Baren, J P; Keating, J F; Simpson, A H R W

2016-04-01

The aim of this study was to identify risk factors for the failure of exchange nailing in nonunion of tibial diaphyseal fractures. A cohort of 102 tibial diaphyseal nonunions in 101 patients with a mean age of 36.9 years (15 to 74) were treated between January 1992 and December 2012 by exchange nailing. Of which 33 (32%) were initially open injuries. The median time from primary fixation to exchange nailing was 6.5 months (interquartile range (IQR) 4.3 to 9.8 months). The main outcome measures were union, number of secondary fixation procedures required to achieve union and time to union. Univariate analysis and multiple regression were used to identify risk factors for failure to achieve union. Multiple causes for the primary nonunion were found for 28 (27%) tibiae, with infection present in 32 (31%). Six patients were lost to follow-up. Further surgical procedures were required in 35 (36%) nonunions. Other fixation modalities were required in five fractures. A single nail exchange procedure achieved union in 60/96 (63%) of all nonunions. Only 11 out of 31 infected nonunions (35.4%) healed after one exchange nail procedure. Up to five repeated exchange nailings, with or without bone grafting, ultimately achieved union in 89 (93%) fractures. The median time to union after exchange nailing was 8.7 months (IQR 5.7 to 14.0 months). Univariate analysis confirmed that an oligotrophic/atrophic pattern of nonunion (p = 0.002), a bone gap of 5 mm or more (p = 0.04) and infection (p < 0.001), were predictive for failure of exchange nailing Multiple regression analysis found that infection was the strongest predictor of failure (p < 0.001). Exchange nailing is an effective treatment for aseptic tibial diaphyseal nonunion. However, in the presence of severe infection with a highly resistant organism, or extensive sclerosis of the bone, other fixation modalities, such as Ilizarov treatment, should be considered. Exchange nailing is an effective treatment for aseptic tibial diaphyseal nonunion. ©2016 The British Editorial Society of Bone & Joint Surgery.

Environment-Dependent Guest Exchange in Supramolecular Hosts

PubMed Central

2015-01-01

Dynamic exchange of guest molecules, encapsulated in host assemblies, is a phenomenon in supramolecular chemistry that has important implications in several applications. While the mechanism of exchange in micellar assemblies has been previously investigated, the effect of host and guest environment upon the guest-exchange dynamics has received little attention, if any. In this paper, we study the guest-exchange mechanism in pH-sensitive nanogels along with pH-insensitive nanogels as a control. By systematically comparing the behavior of these nanogels, we show that size, concentration, and hydrophobicity can all play a critical role in guest-exchange dynamics. More importantly, these studies reveal that the dominant mechanism of guest exchange can intimately depend on environmental factors. PMID:25244305

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.

PubMed

Truong, Hong-Ha M; Mehrotra, Megha; Montoya, Orlando; Lama, Javier R; Guanira, Juan V; Casapía, Martín; Veloso, Valdiléa G; Buchbinder, Susan P; Mayer, Kenneth H; Chariyalertsak, Suwat; Schechter, Mauro; Bekker, Linda-Gail; Kallás, Esper G; Grant, Robert M

2017-05-01

Exchange sex and higher education were associated with an increased likelihood of international sexual partnerships (ISPs). Exchange sex and older age were associated with an increased likelihood of condomless sex in ISPs. Educational and socioeconomic factors may create unbalanced power dynamics that influence exchange sex and condomless sex in ISPs.

Landscape determinants of exchangeable calcium and magnesium in Ozark Highland forest soils

Treesearch

John M. Kabrick; Keith W. Goyne; Zhaofei Fan; Dennis Meinert

2011-01-01

Exchangeable base cations, particularly Ca and Mg, largely govern soil acidity and, consequently, plant species composition in temperate forests. Although studies have identified soil and terrain characteristics affecting exchangeable Ca and Mg, few studies have identified the relative importance of factors affecting Ca and Mg distribution across landscapes. Objectives...

Triphenyltin impairs a protein kinase A (PKA)-dependent increase of cytosolic Na{sup +} and Ca{sup 2+} and PKA-independent increase of cytosolic Ca{sup 2+} associated with insulin secretion in hamster pancreatic {beta}-cells

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

Miura, Yoshikazu; Matsui, Hisao

2006-11-01

Oral administration of triphenyltin chloride (TPT) (60 mg/kg body weight) inhibits the insulin secretion by decreasing the cytoplasmic Ca{sup 2+} concentration ([Ca{sup 2+}] {sub i}) induced by glucose-dependent insulinotropic polypeptide (GIP) in pancreatic {beta}-cells of the hamster. To test the possibility that the abnormal level of [Ca{sup 2+}] {sub i} induced by TPT administration could be due to a defect in the cAMP-dependent cytoplasmic Na{sup +} concentration ([Na{sup +}] {sub i}) in the {beta}-cells, we investigated the effects of TPT administration on the changes of [Na{sup +}] {sub i} induced by GIP, glucagon-like peptide-1 (GLP-1), or forskolin, an activator ofmore » adenylyl cyclase, and on the changes of [Na{sup +}] {sub i} or [Ca{sup 2+}] {sub i} induced by 6-Bnz-cAMP, an activator of protein kinase A (PKA), and 8-pCPT-2'-O-Me-cAMP, an activator of Epac. The [Na{sup +}] {sub i} and [Ca{sup 2+}] {sub i} were measured in islet cells loaded with sodium-binding benzofuran isophthalate (SBFI) and fura-2, respectively. In the presence of 135 mM Na{sup +}, TPT administration significantly reduced the rise in [Na{sup +}] {sub i} by 10 nM GLP-1, 10 {mu}M forskolin, and 50 {mu}M 6-Bnz-cAMP, but had not effect in a Na{sup +}-free medium. In the presence of 135 mM Na{sup +}, TPT administration also reduced the rise in [Ca{sup 2+}] {sub i} by 8-pCPT-2'-O-Me-cAMP plus10 {mu}M H-89, a inhibitor of PKA, and 6-Bnz-cAMP. Moreover, TPT administration significantly reduced the insulin secretion by 2 mM db-cAMP, GLP-1, GIP, and 8-pCPT-2'-O-Me-cAMP with and without H-89, and that by 6-Bnz-cAMP and forskolin. Our study suggested that TPT has inhibitory effects on the cellular Ca{sup 2+} response due to a reduced Na{sup +} permeability through PKA-dependent mechanisms in hamster islet cells. Also TPT has the reduction of [Ca{sup 2+}] {sub i} related to Na{sup +}-dependent insulin secretion after an activation of Epac.« less

Predicting adolescents' disclosure of personal information in exchange for commercial incentives: an application of an extended theory of planned behavior.

PubMed

Heirman, Wannes; Walrave, Michel; Ponnet, Koen

2013-02-01

This study adopts a global theoretical framework to predict adolescents' disclosure of personal information in exchange for incentives offered by commercial Websites. The study postulates and tests the validity of a model based on the theory of planned behavior (TPB), including antecedent factors of attitude and perceived behavioral control (PBC). A survey was conducted among 1,042 respondents. Results from SEM analyses show that the hypothesized model fits the empirical data well. The model accounts for 61.9 percent of the variance in adolescents' intention to disclose and 43.7 percent of the variance in self-reported disclosure. Perceived social pressure exerted by significant others (subjective norm) is the most important TPB factor in predicting intention to disclose personal information in exchange for incentives. This finding suggests that in discussions of adolescents' information privacy, the importance of social factors outweighs the individually oriented TPB factors of attitude and PBC. Moreover, privacy concern and trust propensity are significant predictors of respondents' attitudes toward online disclosure in exchange for commercial incentives, whereas the frequency of Internet use significantly affects their level of PBC.

Factors influencing intentions to use social recommender systems: a social exchange perspective.

PubMed

Chang, Tsung-Sheng; Hsiao, Wei-Hung

2013-05-01

This study employs the perspective of social exchange theory and seeks to understand users' intentions to use social recommender systems (SRS) through three psychological factors: trust, shared values, and reputation. We use structural equation modeling to analyze 221 valid questionnaires. The results show that trust has a direct positive influence on the intention to use SRS, followed by shared values, whereas reputation has an indirect influence on SRS use. We further discuss specific recommendations concerning these factors for developing SRS.

On factors influencing air-water gas exchange in emergent wetlands

USGS Publications Warehouse

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

2018-01-01

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

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

PubMed

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

2012-12-01

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

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 %.

Analysis of Heat Transfers inside Counterflow Plate Heat Exchanger Augmented by an Auxiliary Fluid Flow

PubMed Central

Khaled, A.-R. A.

2014-01-01

Enhancement of heat transfers in counterflow plate heat exchanger due to presence of an intermediate auxiliary fluid flow is investigated. The intermediate auxiliary channel is supported by transverse conducting pins. The momentum and energy equations for the primary fluids are solved numerically and validated against a derived approximate analytical solution. A parametric study including the effect of the various plate heat exchanger, and auxiliary channel dimensionless parameters is conducted. Different enhancement performance indicators are computed. The various trends of parameters that can better enhance heat transfer rates above those for the conventional plate heat exchanger are identified. Large enhancement factors are obtained under fully developed flow conditions. The maximum enhancement factors can be increased by above 8.0- and 5.0-fold for the step and exponential distributions of the pins, respectively. Finally, counterflow plate heat exchangers with auxiliary fluid flows are recommended over the typical ones if these flows can be provided with the least cost. PMID:24719572

Analysis of heat transfers inside counterflow plate heat exchanger augmented by an auxiliary fluid flow.

PubMed

Khaled, A-R A

2014-01-01

Enhancement of heat transfers in counterflow plate heat exchanger due to presence of an intermediate auxiliary fluid flow is investigated. The intermediate auxiliary channel is supported by transverse conducting pins. The momentum and energy equations for the primary fluids are solved numerically and validated against a derived approximate analytical solution. A parametric study including the effect of the various plate heat exchanger, and auxiliary channel dimensionless parameters is conducted. Different enhancement performance indicators are computed. The various trends of parameters that can better enhance heat transfer rates above those for the conventional plate heat exchanger are identified. Large enhancement factors are obtained under fully developed flow conditions. The maximum enhancement factors can be increased by above 8.0- and 5.0-fold for the step and exponential distributions of the pins, respectively. Finally, counterflow plate heat exchangers with auxiliary fluid flows are recommended over the typical ones if these flows can be provided with the least cost.

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

Treesearch

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

1994-01-01

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

Measuring Collaboration and Communication to Increase Implementation of Evidence-Based Practices: The Cultural Exchange Inventory

ERIC Educational Resources Information Center

Palinkas, Lawrence A.; Garcia, Antonio; Aarons, Gregory; Finno-Velasquez, Megan; Fuentes, Dahlia; Holloway, Ian; Chamberlain, Patricia

2018-01-01

The Cultural Exchange Inventory (CEI) is a 15-item instrument designed to measure the process (7 items) and outcomes (8 items) of exchanges of knowledge, attitudes and practices between members of different organisations collaborating in implementing evidence-based practice. We conducted principal axis factor analyses and parallel analyses of data…

International Sexual Partnerships May Be Shaped by Sexual Histories and Socioeconomic Status

PubMed Central

Truong, Hong-Ha M.; Mehrotra, Megha; Montoya, Orlando; Lama, Javier R.; Guanira, Juan V.; Casapía, Martín; Veloso, Valdiléa G.; Buchbinder, Susan P.; Mayer, Kenneth H.; Chariyalertsak, Suwat; Schechter, Mauro; Bekker, Linda-Gail; Kallás, Esper G.; Grant, Robert M.

2017-01-01

Exchange sex and higher education were associated with an increased likelihood of international sexual partnerships (ISPs). Exchange sex and older age were associated with an increased likelihood of condomless sex in ISPs. Educational and socioeconomic factors may create unbalanced power dynamics that influence exchange sex and condomless sex in ISPs. PMID:28407648

75 FR 62137 - Notice of Public Meeting; Proposed Alluvial Valley Floor Coal Exchange Public Interest Factors...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-07

...; MTM-99236] Notice of Public Meeting; Proposed Alluvial Valley Floor Coal Exchange Public Interest... (SMCRA) of 1977. This exchange (serial number MTM-99236) has been proposed by Jay Nance, Brett A... Director. [FR Doc. 2010-25060 Filed 10-6-10; 8:45 am] BILLING CODE 4310-DN-P ...

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.

PubMed

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

2018-03-23

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

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.

A General Econometric Model of the Determinants of Library Subscription Prices of Scholarly Journals: The Role of Exchange Rate Risk and Other Factors.

ERIC Educational Resources Information Center

Chressanthis, George A.; Chressanthis, June D.

1994-01-01

Provides regression-based empirical evidence of the effects of variations in exchange rate risk on 1985 library prices of the top-ranked 99 journals in economics. The relationship between individual journal prices and library prices is shown, and other factors associated with increases and decreases in library journal prices are given. (Contains…

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

PubMed

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

2011-09-28

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

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.

Predictors of Adolescent Successful Development after an Exchange: The Importance of Activity Qualities and Youth Input

ERIC Educational Resources Information Center

Lawford, Heather L.; Ramey, Heather L.; Rose-Krasnor, Linda; Proctor, Andrea S.

2012-01-01

The purpose of this study is to examine the factors involved in predicting successful development after an intensive exchange experience in adolescence. Specifically, we considered the eight positive features, as conceptualized by Eccles and Gootman (2002), as well as the amount of input youth had into their exchange experience as predictors of…

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

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

PubMed

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

2013-01-01

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

Daily rhythms in locomotor circuits in Drosophila involve PDF

PubMed Central

Pírez, Nicolás; Christmann, Bethany L.

2013-01-01

The neuropeptide pigment-dispersing factor (PDF) has been studied extensively in Drosophila, and its role in circadian time-keeping has been firmly established. The role of PDF outside of the clock circuit, however, is poorly understood. A recent study suggested that PDF may act on the ellipsoid body (EB) to link the clock and sleep/activity circuits. We performed whole brain optical imaging with the fluorescence resonance energy transfer (FRET)-based cAMP sensor Epac1-camps expressed under control of the pdfR promoter to address how the clock and sleep deprivation affect the physiology of these cells. Basal cAMP levels in EB were regulated both by PDF and synaptic inputs that are controlled by the circadian clock. Acute application of PDF to the brain caused a significant, and PDF-receptor-dependent, increase in cAMP in EB cells. Application of TTX to block circuit-mediated effects of PDF increased the morning response but not the response at night, implying the existence of a temporally regulated, PDF-stimulated input that blocks cAMP generation. ACh produced both direct (TTX-insensitive) and indirect (TTX-sensitive) increases in cAMP during the day but was totally TTX-insensitive at night, indicating that ACh-stimulated inputs to the EB are suppressed at night. Sleep deprivation did not affect the cAMP responses of these cells to either PDF or ACh. These results suggest a novel role for PDF as a modulator of activity outside of the clock circuit. By elucidating the mechanisms by which the neuropeptide PDF act on its target cells, our work contributes to our understating of how the central clock coordinates activity and sleep. PMID:23678016

Daily rhythms in locomotor circuits in Drosophila involve PDF.

PubMed

Pírez, Nicolás; Christmann, Bethany L; Griffith, Leslie C

2013-08-01

The neuropeptide pigment-dispersing factor (PDF) has been studied extensively in Drosophila, and its role in circadian time-keeping has been firmly established. The role of PDF outside of the clock circuit, however, is poorly understood. A recent study suggested that PDF may act on the ellipsoid body (EB) to link the clock and sleep/activity circuits. We performed whole brain optical imaging with the fluorescence resonance energy transfer (FRET)-based cAMP sensor Epac1-camps expressed under control of the pdfR promoter to address how the clock and sleep deprivation affect the physiology of these cells. Basal cAMP levels in EB were regulated both by PDF and synaptic inputs that are controlled by the circadian clock. Acute application of PDF to the brain caused a significant, and PDF-receptor-dependent, increase in cAMP in EB cells. Application of TTX to block circuit-mediated effects of PDF increased the morning response but not the response at night, implying the existence of a temporally regulated, PDF-stimulated input that blocks cAMP generation. ACh produced both direct (TTX-insensitive) and indirect (TTX-sensitive) increases in cAMP during the day but was totally TTX-insensitive at night, indicating that ACh-stimulated inputs to the EB are suppressed at night. Sleep deprivation did not affect the cAMP responses of these cells to either PDF or ACh. These results suggest a novel role for PDF as a modulator of activity outside of the clock circuit. By elucidating the mechanisms by which the neuropeptide PDF act on its target cells, our work contributes to our understating of how the central clock coordinates activity and sleep.

Prostaglandin E2 inhibition of IL-27 production in murine dendritic cells: a novel mechanism which involves IRF1

PubMed Central

Hooper, Kirsten M; Yen, Jui-Hung; Kong, Weimin; Rahbari, Kate M; Kuo, Ping-Chang; Gamero, Ana M; Ganea, Doina

2016-01-01

IL-27, a multifunctional cytokine produced by antigen-presenting cells, antagonizes inflammation by affecting conventional dendritic cells (cDC), inducing IL-10, and promoting development of regulatory Tr1 cells. Although the mechanisms involved in IL-27 induction are well-studied, much less is known about the factors that negatively impact IL-27 expression. Prostaglandin E2 (PGE2), a major immunomodulatory prostanoid, acts as a pro-inflammatory agent in several models of inflammatory/autoimmune diseases, promoting primarily Th17 development and function. In this study, we report on a novel mechanism which promotes the pro-inflammatory function of PGE2. We showed previously that PGE2 inhibits IL-27 production in murine bone marrow derived DCs. Here, we show that, in addition to BMDCs, PGE2 inhibits IL-27 production in macrophages and in splenic cDC and we identify a novel pathway consisting of signaling through EP2/EP4→induction of cAMP→downregulation of IRF1 expression and binding to the p28 ISRE site. The inhibitory effect of PGE2 on p28 and irf1 expression does not involve endogenous IFNβ, STAT1 or STAT2, and inhibition of IL-27 does not appear to be mediated through PKA, EPAC, PI3K, or MAPKs. We observed similar inhibition of il27p28 expression in vivo in splenic DC following administration of dimethyl PGE2 in conjunction with LPS. Based on the anti-inflammatory role of IL-27 in cDC and through the generation of Tr1 cells, we propose that the PGE2-induced inhibition of IL-27 in activated cDC represents an important additional mechanism for its in vivo pro-inflammatory functions. PMID:28062696

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

NASA Astrophysics Data System (ADS)

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

2018-01-01

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

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…

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

PubMed Central

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

2013-01-01

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

Characteristics associated with regional health information organization viability.

PubMed

Adler-Milstein, Julia; Landefeld, John; Jha, Ashish K

2010-01-01

Regional Health Information Organizations (RHIOs) will likely play a key role in our nation's effort to catalyze health information exchange. Yet we know little about why some efforts succeed while others fail. We sought to identify factors associated with RHIO viability. Using data from a national survey of RHIOs that we conducted in mid-2008, we examined factors associated with becoming operational and factors associated with financial viability. We used multivariate logistic regression models to identify unique predictors. We classified RHIOs actively facilitating data exchange as operational and measured financial viability as the percent of operating costs covered by revenue from participants in data exchange (0-24%, 25-74%, 75-100%). Predictors included breadth of participants, breadth of data exchanged, whether the RHIO focused on a specific population, whether RHIO participants had a history of collaborating, and sources of revenue during the planning phase. Exchanging a narrow set of data and involving a broad group of stakeholders were independently associated with a higher likelihood of being operational. Involving hospitals and ambulatory physicians, and securing early funding from participants were associated with a higher likelihood of financial viability, while early grant funding seemed to diminish the likelihood. Finding ways to help RHIOs become operational and self-sustaining will bolster the current approach to nationwide health information exchange. Our work suggests that convening a broad coalition of stakeholders to focus on a narrow set of data is an important step in helping RHIOs become operational. Convincing stakeholders to financially commit early in the process may help RHIOs become self-sustaining.

Patient Protection and Affordable Care Act; establishment of exchanges and qualified health plans; exchange standards for employers. Final rule, Interim final rule.

PubMed

2012-03-27

This final rule will implement the new Affordable Insurance Exchanges ("Exchanges"), consistent with title I of the Patient Protection and Affordable Care Act of 2010 as amended by the Health Care and Education Reconciliation Act of 2010, referred to collectively as the Affordable Care Act. The Exchanges will provide competitive marketplaces for individuals and small employers to directly compare available private health insurance options on the basis of price, quality, and other factors. The Exchanges, which will become operational by January 1, 2014, will help enhance competition in the health insurance market, improve choice of affordable health insurance, and give small businesses the same purchasing clout as large businesses.

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

A simple electrostatic switch important in the activation of type I protein kinase A by cyclic AMP.

PubMed

Vigil, Dominico; Lin, Jung-Hsin; Sotriffer, Christoph A; Pennypacker, Juniper K; McCammon, J Andrew; Taylor, Susan S

2006-01-01

Cyclic AMP activates protein kinase A by binding to an inhibitory regulatory (R) subunit and releasing inhibition of the catalytic (C) subunit. Even though crystal structures of regulatory and catalytic subunits have been solved, the precise molecular mechanism by which cyclic AMP activates the kinase remains unknown. The dynamic properties of the cAMP binding domain in the absence of cAMP or C-subunit are also unknown. Here we report molecular-dynamics simulations and mutational studies of the RIalpha R-subunit that identify the C-helix as a highly dynamic switch which relays cAMP binding to the helical C-subunit binding regions. Furthermore, we identify an important salt bridge which links cAMP binding directly to the C-helix that is necessary for normal activation. Additional mutations show that a hydrophobic "hinge" region is not as critical for the cross-talk in PKA as it is in the homologous EPAC protein, illustrating how cAMP can control diverse functions using the evolutionarily conserved cAMP-binding domains.

Specific Sirt1 Activator-mediated Improvement in Glucose Homeostasis Requires Sirt1-Independent Activation of AMPK.

PubMed

Park, Sung-Jun; Ahmad, Faiyaz; Um, Jee-Hyun; Brown, Alexandra L; Xu, Xihui; Kang, Hyeog; Ke, Hengming; Feng, Xuesong; Ryall, James; Philp, Andrew; Schenk, Simon; Kim, Myung K; Sartorelli, Vittorio; Chung, Jay H

2017-04-01

The specific Sirt1 activator SRT1720 increases mitochondrial function in skeletal muscle, presumably by activating Sirt1. However, Sirt1 gain of function does not increase mitochondrial function, which raises a question about the central role of Sirt1 in SRT1720 action. Moreover, it is believed that the metabolic effects of SRT1720 occur independently of AMP-activated protein kinase (AMPK), an important metabolic regulator that increases mitochondrial function. Here, we show that SRT1720 activates AMPK in a Sirt1-independent manner and SRT1720 activates AMPK by inhibiting a cAMP degrading phosphodiesterase (PDE) in a competitive manner. Inhibiting the cAMP effector protein Epac prevents SRT1720 from activating AMPK or Sirt1 in myotubes. Moreover, SRT1720 does not increase mitochondrial function or improve glucose tolerance in AMPKα2 knockout mice. Interestingly, weight loss induced by SRT1720 is not sufficient to improve glucose tolerance. Therefore, contrary to current belief, the metabolic effects produced by SRT1720 require AMPK, which can be activated independently of Sirt1. Published by Elsevier B.V.

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

PubMed

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

2001-12-14

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

Ionic Control of the Reversal Response of Cilia in Paramecium caudatum

PubMed Central

Naitoh, Yutaka

1968-01-01

The duration of ciliary reversal of Paramecium caudatum in response to changes in external ionic factors was determined with various ionic compositions of both equilibration and stimulation media. The reversal response was found to occur when calcium ions bound by an inferred cellular cation exchange system were liberated in exchange for externally applied cations other than calcium. Factors which affect the duration of the response were (a) initial amount of calcium bound by the cation exchange system, (b) final amount of calcium bound by the system after equilibration with the stimulation medium, and (c) concentration of calcium ions in the stimulation medium. An empirical equation is presented which relates the duration of the response to these three factors. On the basis of these and previously published data, the following hypothesis is proposed for the mechanism underlying ciliary reversal in response to cationic stimulation: Ca++ liberated from the cellular cation exchange system activates a contractile system which is energized by ATP. Contraction of this component results in the reversal of effective beat direction of cilia by a mechanism not yet understood. The duration of reversal in live paramecia is related to the time course of bound calcium release. PMID:4966766

Contrasting dynamics of leaf potential and gas exchange during progressive drought cycles and recovery in Amorpha fruticosa and Robinia pseudoacacia.

PubMed

Yan, Weiming; Zheng, Shuxia; Zhong, Yangquanwei; Shangguan, Zhouping

2017-06-30

Leaf gas exchange is closely associated with water relations; however, less attention has been given to this relationship over successive drought events. Dynamic changes in gas exchange and water potential in the seedlings of two woody species, Amorpha fruticosa and Robinia pseudoacacia, were monitored during recurrent drought. The pre-dawn leaf water potential declined in parallel with gas exchange in both species, and sharp declines in gas exchange occurred with decreasing water potential. A significant correlation between pre-dawn water potential and gas exchange was observed in both species and showed a right shift in R. pseudoacacia in the second drought. The results suggested that stomatal closure in early drought was mediated mainly by elevated foliar abscisic acid (ABA) in R. pseudoacacia, while a shift from ABA-regulated to leaf-water-potential-driven stomatal closure was observed in A. fruticosa. After re-watering, the pre-dawn water potential recovered quickly, whereas stomatal conductance did not fully recover from drought in R. pseudoacacia, which affected the ability to tightly control transpiration post-drought. The dynamics of recovery from drought suggest that stomatal behavior post-drought may be restricted mainly by hydraulic factors, but non-hydraulic factors may also be involved in R. pseudoacacia.

77 FR 18309 - Patient Protection and Affordable Care Act; Establishment of Exchanges and Qualified Health Plans...

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.

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

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

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

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

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

DOE PAGES

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

2018-01-31

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

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.

PubMed

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.

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

NASA Astrophysics Data System (ADS)

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

2016-11-01

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

Understanding the drivers of interprofessional collaborative practice among HIV primary care providers and case managers in HIV care programmes.

PubMed

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

PubMed Central

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

Bronchial lumen is the safer route for an airway exchange catheter in double-lumen tube replacement: preventable complication in airway management for thoracic surgery.

PubMed

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.

Fuzzy forecasting based on two-factors second-order fuzzy-trend logical relationship groups and particle swarm optimization techniques.

PubMed

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.

The embodied nurse: Interdisciplinary knowledge exchange between compassionate nursing and recent developments in embodied leadership studies.

PubMed

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.

Supplemental Conceptual Design Study of an Integrated Voice/Data Switching and Multiplexing Technique for an Access Area Exchange

DTIC Science & Technology

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

Analysis of Radiation-natural Convection Interactions in 1-g and low-g Environments using the Discrete Exchange Factor Method

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.

Individual, network, and neighborhood correlates of exchange sex among female non-injection drug users in Baltimore, MD (2005–2007)

PubMed Central

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.

PubMed

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.

Role of protein kinase A and class II phosphatidylinositol 3-kinase C2β in the downregulation of KCa3.1 channel synthesis and membrane surface expression by lyso-globotriaosylceramide

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

Choi, Ju Yeon; Park, Seonghee, E-mail: sp@ewha.ac.kr

The intermediate conductance calcium-activated potassium channel (KCa3.1) mediates proliferation of many cell types including fibroblasts, and is a molecular target for intervention in various cell proliferative diseases. Our previous study showed that reduction of KCa3.1 channel expression by lyso-globotriaosylceramide (lyso-Gb3) inhibits differentiation into myofibroblasts and collagen synthesis, which might lead to development of ascending thoracic aortic aneurysm secondary to Fabry disease. However, how lyso-Gb3 downregulates KCa3.1 channel expression is unknown. Therefore, we aimed to investigate the underlying mechanisms of lyso-Gb3-mediated KCa3.1 channel downregulation, focusing on the cAMP signaling pathway. We found that lyso-Gb3 increased the intracellular cAMP concentration by upregulationmore » of adenylyl cyclase 6 and inhibited ERK 1/2 phosphorylation through the protein kinase A (PKA) pathway, leading to the inhibition of KCa3.1 channel synthesis, not the exchange protein directly activated by cAMP (Epac) pathway. Moreover, lyso-Gb3 suppressed expression of class II phosphatidylinositol 3-kinase C2β (PI3KC2β) by PKA activation, which reduces the production of phosphatidylinositol 3-phosphate [PI(3)P], and the reduced membrane surface expression of KCa3.1 channel was recovered by increasing the intracellular levels of PI(3)P. Consequently, our findings that lyso-Gb3 inhibited both KCa3.1 channel synthesis and surface expression by increasing intracellular cAMP, and controlled surface expression through changes in PI3KC2β-mediated PI(3)P production, suggest that modulation of PKA and PI3KC2β activity to control of KCa3.1 channel expression can be an alternative important target to attenuate ascending thoracic aortic aneurysms in Fabry disease. - Highlights: • Lyso-Gb3 causes elevation of intracellular cAMP. • Lyso-Gb3 inhibits the ERK 1/2 phosphorylation through PKA, thereby reducing KCa3.1 channel synthesis. • Lyso-Gb3 reduces PI3KC2β-mediated intracellular PI(3)P production. • Lyso-Gb3 reduces both surface and total expression of the KCa3.1 channel. • Increasing intracellular levels of PI(3)P only recovers the reduced surface expression.« less

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

PubMed Central

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

Exchange Sex Among Persons Who Inject Drugs in the New York Metropolitan Area: The Importance of Local Context, Gender and Sexual Identity.

PubMed

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.

Current issues and uncertainties in the measurement and modelling of air-vegetation exchange and within-plant processing of POPs.

PubMed

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…

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

PubMed Central

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

2010-01-01

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

DNA Strand Exchange and RecA Homologs in Meiosis

PubMed Central

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

The Moderating Role of Leader-Member Exchange in the Relationships Between Emotional Labor and Burnout in Clinical Nurses.

PubMed

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.

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

PubMed Central

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

2009-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2014-12-01

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

Functional Synergy between Rab5 Effector Rabaptin-5 and Exchange Factor Rabex-5 When Physically Associated in a Complex

PubMed Central

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

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

PubMed

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

2003-11-01

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

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.

Nurses' turnover intention: The impact of leader-member exchange, organizational identification and job embeddedness.

PubMed

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.

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

USGS Publications Warehouse

Han, Liang-Feng; Plummer, Niel

2013-01-01

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

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…

Spatiotemporally‐Resolved Air Exchange Rate as a Modifier of Acute Air Pollution‐Related Morbidity in AtlantaMorbidity in Atlanta

EPA Science Inventory

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...

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

USGS Publications Warehouse

Hartman, Blayne; Hammond, Douglas E.

1984-01-01

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

The Structure of RalF, an ADP-Ribosylation Factor Guanine Nucleotide Exchange Factor from Legionella pneumophila, Reveals the Presence of a Cap over the Active Site

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

PubMed Central

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.

PubMed

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.

PubMed

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

2014-01-01

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

Exchange-Mediated Contrast in CEST and Spin-Lock Imaging

PubMed Central

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

2014-01-01

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

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

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

PubMed Central

2012-01-01

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

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

PubMed

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

2014-06-27

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

Universal model for water costs of gas exchange by animals and plants

PubMed Central

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.

PubMed

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.

PubMed

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.

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

PubMed

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

2014-08-01

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

Cotton fiber properties: relative humidity and its effect on flat bundle strength, elongation, and fracture morphology

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...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-03

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

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

PubMed Central

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

Social organization influences the exchange and species richness of medicinal plants in Amazonian homegardens.

PubMed

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.

PubMed

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.

Perspectives of advanced thermal management in solar thermochemical syngas production using a counter-flow solid-solid heat exchanger

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.

PubMed

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.

The performance of ammonium exchanged zeolite for the biodegradation of petroleum hydrocarbons migrating in soil water.

PubMed

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.

PubMed

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.

Cardiotoxic and Cardioprotective Features of Chronic β-adrenergic Signaling

PubMed Central

Zhang, Xiaoying; Szeto, Christopher; Gao, Erhe; Tang, Mingxin; Jin, Jianguo; Fu, Qin; Makarewich, Catherine; Ai, Xiaojie; Li, Ying; Tang, Allen; Wang, Jenny; Gao, Hui; Wang, Fang; Ge, Xinyi Joy; Kunapuli, Satya P.; Zhou, Lin; Zeng, Chunyu; Xiang, Kevin Yang; Chen, Xiongwen

2012-01-01

Rationale In the failing heart, persistent β-adrenergic receptor (βAR) activation is thought to induce myocyte death by protein kinase A (PKA)-dependent and PKA-independent activation of calcium/calmodulin-dependent kinase II (CaMKII). β-Adrenergic signaling pathways are also capable of activating cardioprotective mechanisms. Objective This study used a novel PKA inhibitor peptide (PKI) to inhibit PKA activity to test the hypothesis that βAR signaling causes cell death through PKA-dependent pathways and cardioprotection through PKA-independent pathways. Methods and Results In PKI transgenic mice, chronic isoproterenol (ISO) failed to induce cardiac hypertrophy, fibrosis, myocyte apoptosis and depressed cardiac function. In cultured adult feline ventricular myocytes (AFVMs), PKA inhibition protected myocytes from death induced by β1-AR agonists by preventing cytosolic and SR Ca2+ overload and CaMKII activation. PKA inhibition revealed a cardioprotective role of β-adrenergic signaling via cAMP/EPAC /Rap1/Rac/ERK pathway. Selective PKA inhibition causes protection in the heart after myocardial infarction (MI) that was superior to β-blocker therapy. Conclusion These results suggest that selective block of PKA could be a novel heart failure therapy. PMID:23104882

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…

77 FR 76121 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing of Proposed Rule Change To List...

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...

77 FR 77160 - Self-Regulatory Organizations; Chicago Mercantile Exchange Inc.; Notice of Filing of Proposed...

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.

PubMed

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

2018-02-01

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

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

PubMed

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

2011-08-09

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

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

PubMed Central

2011-01-01

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

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

PubMed Central

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

PubMed Central

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.

PubMed

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

2017-10-15

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

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.

PubMed

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.

PubMed

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.

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

NASA Technical Reports Server (NTRS)

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

2000-01-01

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

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

PubMed

Tsonev, Latchezar I; Hirsh, Allen G

2008-07-25

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

[Characteristics of mercury exchange flux between soil and atmosphere under the snow retention and snow melting control].

PubMed

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

USGS Publications Warehouse

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

1987-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2016-08-01

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

Simple full micromagnetic model of exchange bias behavior in ferro/antiferromagnetic layered structures (abstract)

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

Treesearch

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...

Effect of pre-roast moisture content and post roast cooling parameters on oil migration during oil roasting of peanuts

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...

The Role of Community Trust and Altruism in Knowledge Sharing: An Investigation of a Virtual Community of Teacher Professionals

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…

Lack of motivation: a new modifiable risk factor for peritonitis in patients undergoing peritoneal dialysis?

PubMed

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.

Treesearch

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.

Factors Determining the Frequency of the Killer Trait within Populations of the Paramecium aurelia Complex

PubMed Central

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.

PubMed

Shunmugam, Manoharan; Shunmugam, Sudhakaran; Williamson, Tom H; Laidlaw, D Alistair

2011-10-21

The primary aim of this study was to evaluate the efficiency of air-gas exchange techniques and the factors that influence the final concentration of an intraocular gas tamponade. Parameters were varied to find the optimum method of performing an air-gas exchange in ideal circumstances. A computer model of the eye was designed using 3D software with fluid flow analysis capabilities. Factors such as angular distance between ports, gas infusion gauge, exhaust vent gauge and depth were varied in the model. Flow rate and axial length were also modulated to simulate faster injections and more myopic eyes, respectively. The flush volume of gas required to achieve a 97% intraocular gas fraction concentration were compared. Modulating individual factors did not reveal any clinically significant difference in the angular distance between ports, exhaust vent size, and depth or rate of gas injection. In combination, however, there was a 28% increase in air-gas exchange efficiency comparing the most efficient with the least efficient studied parameters in this model. The gas flush volume required to achieve a 97% gas fill also increased proportionately at a ratio of 5.5 to 6.2 times the volume of the eye. A 35-mL flush is adequate for eyes up to 25 mm in axial length; however, eyes longer than this would require a much greater flush volume, and surgeons should consider using two separate 50-mL gas syringes to ensure optimal gas concentration for eyes greater than 25 mm in axial length.

Effect of mobile phone reminder messages on adherence of stent removal or exchange in patients with benign pancreaticobiliary diseases: a prospectively randomized, controlled study.

PubMed

Gu, Yong; Wang, Limei; Zhao, Lina; Liu, Zhiguo; Luo, Hui; Tao, Qin; Zhang, Rongchun; He, Shuixiang; Wang, Xiangping; Huang, Rui; Zhang, Linhui; Pan, Yanglin; Guo, Xuegang

2016-08-26

Plastic and covered metal stents need to be removed or exchanged within appropriate time in case of undesirable complications. However, it is not uncommon that patients do not follow the recommendation for further stent management after Endoscopic Retrograde Cholangiopancreatography (ERCP). The effect of short message service (SMS) intervention monthly on the stent removal/exchange adherence in patients after ERCP is unknown at this time. A prospective, randomized controlled study was conducted. After receiving regular instructions, patients were randomly assigned to receive SMS reminding monthly (SMS group) for stent removal/exchange or not (control group). The primary outcome was stent removal/exchange adherence within appropriate time (4 months for plastic stent or 7 months for covered stent). Multivariate analysis was performed to assess factors associated with stent removal/exchange adherence within appropriate time. Intention-to-treat analysis was used. A total of 48 patients were randomized, 23 to the SMS group and 25 to the control. Adherence to stent removal/exchange was reported in 78.2 % (18/23) of patients receiving the SMS intervention compared with 40 % (10/25) in the control group (RR 1.98, 95 % CI 1.16-3.31; p = 0 · 010). Among patients with plastic stent insertion, the median interval time from stent implantation to stent removal/exchange were 90 days in the SMS group and 136 days in the control respectively (HR 0.36, 95 % CI 0.16-0.84, p = 0.018). No difference was found between the two groups regarding late-stage stent-related complications. The rate of recurrent abdominal pain tended to be lower in SMS group without significant difference (8.7 vs 28 %, p = 0.144). Multivariate logistic regression analyses revealed that SMS reminding was the only factor associated with adherence of stent removal/exchange (OR 6.73, 95 % CI 1.64-27.54, p = 0.008). This first effectiveness trial demonstrated that SMS reminding monthly could significantly increase the patient adherence to stent removal/exchange after ERCP. The study was respectively registered on July 10 in 2016 at ClinicalTrials.gov ( NCT02831127 ).

Discrepancy in reports of support exchanges between parents and adult offspring: within- and between-family differences.

PubMed

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.

Discrepancy in Reports of Support Exchanges between Parents and Adult Offspring: Within- and Between-Family Differences

PubMed Central

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

Empirical Correction for Differences in Chemical Exchange Rates in Hydrogen Exchange-Mass Spectrometry Measurements.

PubMed

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.

The load and release characteristics on a strong cationic ion-exchange fiber: kinetics, thermodynamics, and influences.

PubMed

Yuan, Jing; Gao, Yanan; Wang, Xinyu; Liu, Hongzhuo; Che, Xin; Xu, Lu; Yang, Yang; Wang, Qifang; Wang, Yan; Li, Sanming

2014-01-01

Ion-exchange fibers were different from conventional ion-exchange resins in their non-cross-linked structure. The exchange was located on the surface of the framework, and the transport resistance reduced significantly, which might mean that the exchange is controlled by an ionic reaction instead of diffusion. Therefore, this work aimed to investigate the load and release characteristics of five model drugs with the strong cationic ion-exchange fiber ZB-1. Drugs were loaded using a batch process and released in United States Pharmacopoeia (USP) dissolution apparatus 2. Opposing exchange kinetics, suitable for the special structure of the fiber, were developed for describing the exchange process with the help of thermodynamics, which illustrated that the load was controlled by an ionic reaction. The molecular weight was the most important factor to influence the drug load and release rate. Strong alkalinity and rings in the molecular structures made the affinity between the drug and fiber strong, while logP did not cause any profound differences. The drug-fiber complexes exhibited sustained release. Different kinds and concentrations of counter ions or different amounts of drug-fiber complexes in the release medium affected the release behavior, while the pH value was independent of it. The groundwork for in-depth exploration and further application of ion-exchange fibers has been laid.

Destabilizing Mutations Alter the Hydrogen Exchange Mechanism in Ribonuclease A

PubMed Central

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

2008-01-01

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

The load and release characteristics on a strong cationic ion-exchange fiber: kinetics, thermodynamics, and influences

PubMed Central

Yuan, Jing; Gao, Yanan; Wang, Xinyu; Liu, Hongzhuo; Che, Xin; Xu, Lu; Yang, Yang; Wang, Qifang; Wang, Yan; Li, Sanming

2014-01-01

Ion-exchange fibers were different from conventional ion-exchange resins in their non-cross-linked structure. The exchange was located on the surface of the framework, and the transport resistance reduced significantly, which might mean that the exchange is controlled by an ionic reaction instead of diffusion. Therefore, this work aimed to investigate the load and release characteristics of five model drugs with the strong cationic ion-exchange fiber ZB-1. Drugs were loaded using a batch process and released in United States Pharmacopoeia (USP) dissolution apparatus 2. Opposing exchange kinetics, suitable for the special structure of the fiber, were developed for describing the exchange process with the help of thermodynamics, which illustrated that the load was controlled by an ionic reaction. The molecular weight was the most important factor to influence the drug load and release rate. Strong alkalinity and rings in the molecular structures made the affinity between the drug and fiber strong, while logP did not cause any profound differences. The drug–fiber complexes exhibited sustained release. Different kinds and concentrations of counter ions or different amounts of drug–fiber complexes in the release medium affected the release behavior, while the pH value was independent of it. The groundwork for in-depth exploration and further application of ion-exchange fibers has been laid. PMID:25114504

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.

PubMed

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

PubMed Central

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

Potassium and the K+/H+ Exchanger Kha1p Promote Binding of Copper to ApoFet3p Multi-copper Ferroxidase*

PubMed Central

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

Multi-cell storage battery

DOEpatents

Brohm, Thomas; Bottcher, Friedhelm

2000-01-01

A multi-cell storage battery, in particular to a lithium storage battery, which contains a temperature control device and in which groups of one or more individual cells arranged alongside one another are separated from one another by a thermally insulating solid layer whose coefficient of thermal conductivity lies between 0.01 and 0.2 W/(m*K), the thermal resistance of the solid layer being greater by at least a factor .lambda. than the thermal resistance of the individual cell. The individual cell is connected, at least in a region free of insulating material, to a heat exchanger, the thermal resistance of the heat exchanger in the direction toward the neighboring cell being selected to be greater by at least a factor .lambda. than the thermal resistance of the individual cell and, in addition, the thermal resistance of the heat exchanger toward the temperature control medium being selected to be smaller by at least a factor of about 10 than the thermal resistance of the individual cell, and .lambda. being the ratio of the energy content of the individual cell to the amount of energy that is needed to trigger a thermally induced cell failure at a defined upper operating temperature limit.

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).

Transfer factors of natural radionuclides and (137)Cs from soil to plants used in traditional medicine in central Serbia.

PubMed

Djelic, Gorica; Krstic, Dragana; Stajic, Jelena M; Milenkovic, Biljana; Topuzovic, Marina; Nikezic, Dragoslav; Vucic, Dusica; Zeremski, Tijana; Stankovic, Milan; Kostic, Dragana

2016-07-01

Transfer factors of natural radionuclides and (137)Cs from soil to plants used in traditional medicine were determined. The transfer factors (TF) were calculated as Bq kg(-1) of dry plant per Bq kg(-1) of dry soil. Mass activity concentrations of (226)Ra, (232)Th, (40)K and (137)Cs in soil and plant samples were measured with high purity germanium detector (HPGe). The concentrations of As, Co, Cr, Cu, Mn, Ni, Pb and Zn were determined, as well as the cation exchange capacity (CEC) and the content of exchangeable cations (Ca, Mg, K, Na). Wide ranges of values were obtained for all the metals, especially for Cr and Ni. The Absalom model was used for determination of the amount of (137)Cs transferred from soil to plant based on soil characteristics such as pH, exchangeable potassium, humus and clay contents. The estimated transfer factors were in the range from 0.011 to 0.307 with an arithmetic mean of 0.071, median of 0.050, geometric mean of 0.053 and geometric standard deviation (GSD) of 2.08. This value agreed well with that calculated from the measurements of 0.069, geometric mean 0.040 and GSD 3.19. Correlations between radionuclides, metals, physicochemical properties and transfer factors were determined by Spearman correlation coefficient. There was a strong positive correlation between (137)Cs transfer factor and the ratio of transfer factor for K and (137)Cs. Principal Component Analysis (PCA) was performed in order to identify some pattern of data. Copyright © 2016. Published by Elsevier Ltd.

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

NASA Astrophysics Data System (ADS)

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

2014-12-01

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

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.

PubMed

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.

Light water detritiation

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

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

2015-03-15

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

High resolution main-ion charge exchange spectroscopy in the DIII-D H-mode pedestal.

PubMed

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.

Fuzzy forecasting based on two-factors second-order fuzzy-trend logical relationship groups and the probabilities of trends of fuzzy logical relationships.

PubMed

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.

Severe hypoglycemia and diabetic ketoacidosis among youth with type 1 diabetes in the T1D Exchange clinic registry

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...

JPRS Report, China

DTIC Science & Technology

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

Estimation of Hydrogen-Exchange Protection Factors from MD Simulation Based on Amide Hydrogen Bonding Analysis.

PubMed

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.

Estimation of Hydrogen-Exchange Protection Factors from MD Simulation Based on Amide Hydrogen Bonding Analysis

PubMed Central

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

Probing the rate-limiting step for intramolecular transfer of a transcription factor between specific sites on the same DNA molecule by (15)Nz-exchange NMR spectroscopy.

PubMed

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

PubMed Central

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...

78 FR 25116 - Self-Regulatory Organizations; Chicago Mercantile Exchange Inc.; Notice of Filing of Proposed...

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...

On-bead combinatorial synthesis and imaging of chemical exchange saturation transfer magnetic resonance imaging agents to identify factors that influence water exchange.

PubMed

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.

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

PubMed Central

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

2016-01-01

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

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.

Monitoring Ras Interactions with the Nucleotide Exchange Factor Son of Sevenless (Sos) Using Site-specific NMR Reporter Signals and Intrinsic Fluorescence*

PubMed Central

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.

Improving estimations of greenhouse gas transfer velocities by atmosphere-ocean couplers in Earth-System and regional models

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.

The dopamine D1 receptor is expressed and facilitates relaxation in airway smooth muscle.

PubMed

Mizuta, Kentaro; Zhang, Yi; Xu, Dingbang; Mizuta, Fumiko; D'Ovidio, Frank; Masaki, Eiji; Emala, Charles W

2013-09-02

Dopamine signaling is mediated by Gs protein-coupled "D1-like" receptors (D1 and D5) and Gi-coupled "D2-like" receptors (D2-4). In asthmatic patients, inhaled dopamine induces bronchodilation. Although the Gi-coupled dopamine D2 receptor is expressed and sensitizes adenylyl cyclase activity in airway smooth muscle (ASM) cells, the Gs-coupled dopamine D1-like receptor subtypes have never been identified on these cells. Activation of Gs-coupled receptors stimulates cyclic AMP (cAMP) production through the stimulation of adenylyl cyclase, which promotes ASM relaxation. We questioned whether the dopamine D1-like receptor is expressed on ASM, and modulates its function through Gs-coupling. The mRNA and protein expression of dopamine D1-like receptor subtypes in both native human and guinea pig ASM tissue and cultured human ASM (HASM) cells was measured. To characterize the stimulation of cAMP through the dopamine D1 receptor, HASM cells were treated with dopamine or the dopamine D1-like receptor agonists (A68930 or SKF38393) before cAMP measurements. To evaluate whether the activation of dopamine D1 receptor induces ASM relaxation, guinea pig tracheal rings suspended under isometric tension in organ baths were treated with cumulatively increasing concentrations of dopamine or A68930, following an acetylcholine-induced contraction with or without the cAMP-dependent protein kinase (PKA) inhibitor Rp-cAMPS, the large-conductance calcium-activated potassium (BKCa) channel blocker iberiotoxin, or the exchange proteins directly activated by cAMP (Epac) antagonist NSC45576. Messenger RNA encoding the dopamine D1 and D5 receptors were detected in native human ASM tissue and cultured HASM cells. Immunoblots confirmed the protein expression of the dopamine D1 receptor in both native human and guinea pig ASM tissue and cultured HASM cells. The dopamine D1 receptor was also immunohistochemically localized to both human and guinea pig ASM. The dopamine D1-like receptor agonists stimulated cAMP production in HASM cells, which was reversed by the selective dopamine D1-like receptor antagonists SCH23390 or SCH39166. A68930 relaxed acetylcholine-contracted guinea pig tracheal rings, which was attenuated by Rp-cAMPS but not by iberiotoxin or NSC45576. These results demonstrate that the dopamine D1 receptors are expressed on ASM and regulate smooth muscle force via cAMP activation of PKA, and offer a novel target for therapeutic relaxation of ASM.

The dopamine D1 receptor is expressed and facilitates relaxation in airway smooth muscle

PubMed Central

2013-01-01

Background Dopamine signaling is mediated by Gs protein-coupled “D1-like” receptors (D1 and D5) and Gi-coupled “D2-like” receptors (D2-4). In asthmatic patients, inhaled dopamine induces bronchodilation. Although the Gi-coupled dopamine D2 receptor is expressed and sensitizes adenylyl cyclase activity in airway smooth muscle (ASM) cells, the Gs-coupled dopamine D1-like receptor subtypes have never been identified on these cells. Activation of Gs-coupled receptors stimulates cyclic AMP (cAMP) production through the stimulation of adenylyl cyclase, which promotes ASM relaxation. We questioned whether the dopamine D1-like receptor is expressed on ASM, and modulates its function through Gs-coupling. Methods The mRNA and protein expression of dopamine D1-like receptor subtypes in both native human and guinea pig ASM tissue and cultured human ASM (HASM) cells was measured. To characterize the stimulation of cAMP through the dopamine D1 receptor, HASM cells were treated with dopamine or the dopamine D1-like receptor agonists (A68930 or SKF38393) before cAMP measurements. To evaluate whether the activation of dopamine D1 receptor induces ASM relaxation, guinea pig tracheal rings suspended under isometric tension in organ baths were treated with cumulatively increasing concentrations of dopamine or A68930, following an acetylcholine-induced contraction with or without the cAMP-dependent protein kinase (PKA) inhibitor Rp-cAMPS, the large-conductance calcium-activated potassium (BKCa) channel blocker iberiotoxin, or the exchange proteins directly activated by cAMP (Epac) antagonist NSC45576. Results Messenger RNA encoding the dopamine D1 and D5 receptors were detected in native human ASM tissue and cultured HASM cells. Immunoblots confirmed the protein expression of the dopamine D1 receptor in both native human and guinea pig ASM tissue and cultured HASM cells. The dopamine D1 receptor was also immunohistochemically localized to both human and guinea pig ASM. The dopamine D1-like receptor agonists stimulated cAMP production in HASM cells, which was reversed by the selective dopamine D1-like receptor antagonists SCH23390 or SCH39166. A68930 relaxed acetylcholine-contracted guinea pig tracheal rings, which was attenuated by Rp-cAMPS but not by iberiotoxin or NSC45576. Conclusions These results demonstrate that the dopamine D1 receptors are expressed on ASM and regulate smooth muscle force via cAMP activation of PKA, and offer a novel target for therapeutic relaxation of ASM. PMID:24004608

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

DOE PAGES

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

DOE PAGES

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

2016-06-04

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

Clinical usefulness of a functional assay for the von Willebrand factor cleaving protease (ADAMTS 13) and its inhibitor in a patient with thrombotic thrombocytopenic purpura.

PubMed

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.

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

DOT National Transportation Integrated Search

1990-11-01

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

The Effects of Supply Chain Orientation, Supply Chain Management, and Collaboration on Perceived Firm Performance

DTIC Science & Technology

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.

Heat transfer to and from vegetated surfaces - An analytical method for the bulk exchange coefficients

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

PubMed Central

Rawat, Naveen; Pan, Zhenwen; Lamarche, Cody J.; Wetherby, Anthony; Waterman, Rory; Tokumoto, Takahisa; Cherian, Judy G.; Headrick, Randall L.; McGill, Stephen A.; Furis, Madalina I.

2015-01-01

The origins of spin exchange in crystalline thin films of Copper Octabutoxy Phthalocyanine (Cu-OBPc) are investigated using Magnetic Circular Dichroism (MCD) spectroscopy. These studies are made possible by a solution deposition technique which produces highly ordered films with macroscopic grain sizes suitable for optical studies. For temperatures lower than 2 K, the contribution of a specific state in the valence band manifold originating from the hybridized lone pair in nitrogen orbitals of the Phthalocyanine ring, bears the Brillouin-like signature of an exchange interaction with the localized d-shell Cu spins. A comprehensive MCD spectral analysis coupled with a molecular field model of a σπ − d exchange analogous to sp-d interactions in Diluted Magnetic Semiconductors (DMS) renders an enhanced Zeeman splitting and a modified g-factor of −4 for the electrons that mediate the interaction. These studies define an experimental tool for identifying electronic states involved in spin-dependent exchange interactions in organic materials. PMID:26559337

Spin Exchange Interaction in Substituted Copper Phthalocyanine Crystalline Thin Films.

PubMed

Rawat, Naveen; Pan, Zhenwen; Lamarche, Cody J; Wetherby, Anthony; Waterman, Rory; Tokumoto, Takahisa; Cherian, Judy G; Headrick, Randall L; McGill, Stephen A; Furis, Madalina I

2015-11-12

The origins of spin exchange in crystalline thin films of Copper Octabutoxy Phthalocyanine (Cu-OBPc) are investigated using Magnetic Circular Dichroism (MCD) spectroscopy. These studies are made possible by a solution deposition technique which produces highly ordered films with macroscopic grain sizes suitable for optical studies. For temperatures lower than 2 K, the contribution of a specific state in the valence band manifold originating from the hybridized lone pair in nitrogen orbitals of the Phthalocyanine ring, bears the Brillouin-like signature of an exchange interaction with the localized d-shell Cu spins. A comprehensive MCD spectral analysis coupled with a molecular field model of a σπ - d exchange analogous to sp-d interactions in Diluted Magnetic Semiconductors (DMS) renders an enhanced Zeeman splitting and a modified g-factor of -4 for the electrons that mediate the interaction. These studies define an experimental tool for identifying electronic states involved in spin-dependent exchange interactions in organic materials.

Real-time observation of cation exchange kinetics and dynamics at the muscovite-water interface

PubMed Central

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*

PubMed Central

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.

PubMed

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

DTIC Science & Technology

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

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.

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

PubMed

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

2018-05-01

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

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

NASA Technical Reports Server (NTRS)

Jennings, Mallory; Quinn, Gregory; Strange, Jeremy

2012-01-01

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

Dynamics of T-Junction Solution Switching Aimed at Patch Clamp Experiments

PubMed Central

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

DOE PAGES

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

An Analysis of the Effect of Surface Heat Exchange on the Thermal Behavior of an Idealized Aquifer Thermal Energy Storage System

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.

Better band gaps for wide-gap semiconductors from a locally corrected exchange-correlation potential that nearly eliminates self-interaction errors

DOE PAGES

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

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-18

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

78 FR 12127 - Self-Regulatory Organizations; Chicago Mercantile Exchange Inc.; Notice of Designation of a...

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.

PubMed

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.

Factor H autoantibody is associated with atypical hemolytic uremic syndrome in children in the United Kingdom and Ireland.

PubMed

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.

Synergistic effects on enantioselectivity of zwitterionic chiral stationary phases for separations of chiral acids, bases, and amino acids by HPLC.

PubMed

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.

FRET Imaging in Three-dimensional Hydrogels

PubMed Central

Taboas, Juan M.

2016-01-01

Imaging of Förster resonance energy transfer (FRET) is a powerful tool for examining cell biology in real-time. Studies utilizing FRET commonly employ two-dimensional (2D) culture, which does not mimic the three-dimensional (3D) cellular microenvironment. A method to perform quenched emission FRET imaging using conventional widefield epifluorescence microscopy of cells within a 3D hydrogel environment is presented. Here an analysis method for ratiometric FRET probes that yields linear ratios over the probe activation range is described. Measurement of intracellular cyclic adenosine monophosphate (cAMP) levels is demonstrated in chondrocytes under forskolin stimulation using a probe for EPAC1 activation (ICUE1) and the ability to detect differences in cAMP signaling dependent on hydrogel material type, herein a photocrosslinking hydrogel (PC-gel, polyethylene glycol dimethacrylate) and a thermoresponsive hydrogel (TR-gel). Compared with 2D FRET methods, this method requires little additional work. Laboratories already utilizing FRET imaging in 2D can easily adopt this method to perform cellular studies in a 3D microenvironment. It can further be applied to high throughput drug screening in engineered 3D microtissues. Additionally, it is compatible with other forms of FRET imaging, such as anisotropy measurement and fluorescence lifetime imaging (FLIM), and with advanced microscopy platforms using confocal, pulsed, or modulated illumination. PMID:27500354

Combined Effects of Ozone and Drought on the Physiology and Membrane Lipids of Two Cowpea (Vigna unguiculata (L.) Walp) Cultivars.

PubMed

Rebouças, Deborah Moura; De Sousa, Yuri Maia; Bagard, Matthieu; Costa, Jose Helio; Jolivet, Yves; De Melo, Dirce Fernandes; Repellin, Anne

2017-03-03

The interactive effects of drought and ozone on the physiology and leaf membrane lipid content, composition and metabolism of cowpea (Vigna unguiculata (L.) Walp.) were investigated in two cultivars (EPACE-1 and IT83-D) grown under controlled conditions. The drought treatment (three-week water deprivation) did not cause leaf injury but restricted growth through stomatal closure. In contrast, the short-term ozone treatment (130 ppb 12 h daily during 14 day) had a limited impact at the whole-plant level but caused leaf injury, hydrogen peroxide accumulation and galactolipid degradation. These effects were stronger in the IT83-D cultivar, which also showed specific ozone responses such as a higher digalactosyl-diacylglycerol (DGDG):monogalactosyldiacylglycerol (MGDG) ratio and the coordinated up-regulation of DGDG synthase (VuDGD2) and ω-3 fatty acid desaturase 8 (VuFAD8) genes, suggesting that membrane remodeling occurred under ozone stress in the sensitive cultivar. When stresses were combined, ozone did not modify the stomatal response to drought and the observed effects on whole-plant physiology were essentially the same as when drought was applied alone. Conversely, the drought-induced stomatal closure appeared to alleviate ozone effects through the reduction of ozone uptake.

Combined Effects of Ozone and Drought on the Physiology and Membrane Lipids of Two Cowpea (Vigna unguiculata (L.) Walp) Cultivars

PubMed Central

Moura Rebouças, Deborah; Maia De Sousa, Yuri; Bagard, Matthieu; Costa, Jose Helio; Jolivet, Yves; Fernandes De Melo, Dirce; Repellin, Anne

2017-01-01

The interactive effects of drought and ozone on the physiology and leaf membrane lipid content, composition and metabolism of cowpea (Vigna unguiculata (L.) Walp.) were investigated in two cultivars (EPACE-1 and IT83-D) grown under controlled conditions. The drought treatment (three-week water deprivation) did not cause leaf injury but restricted growth through stomatal closure. In contrast, the short-term ozone treatment (130 ppb 12 h daily during 14 day) had a limited impact at the whole-plant level but caused leaf injury, hydrogen peroxide accumulation and galactolipid degradation. These effects were stronger in the IT83-D cultivar, which also showed specific ozone responses such as a higher digalactosyl-diacylglycerol (DGDG):monogalactosyl-diacylglycerol (MGDG) ratio and the coordinated up-regulation of DGDG synthase (VuDGD2) and ω-3 fatty acid desaturase 8 (VuFAD8) genes, suggesting that membrane remodeling occurred under ozone stress in the sensitive cultivar. When stresses were combined, ozone did not modify the stomatal response to drought and the observed effects on whole-plant physiology were essentially the same as when drought was applied alone. Conversely, the drought-induced stomatal closure appeared to alleviate ozone effects through the reduction of ozone uptake. PMID:28273829

Distance-Based Configurational Entropy of Proteins from Molecular Dynamics Simulations

PubMed Central

Fogolari, Federico; Corazza, Alessandra; Fortuna, Sara; Soler, Miguel Angel; VanSchouwen, Bryan; Brancolini, Giorgia; Corni, Stefano; Melacini, Giuseppe; Esposito, Gennaro

2015-01-01

Estimation of configurational entropy from molecular dynamics trajectories is a difficult task which is often performed using quasi-harmonic or histogram analysis. An entirely different approach, proposed recently, estimates local density distribution around each conformational sample by measuring the distance from its nearest neighbors. In this work we show this theoretically well grounded the method can be easily applied to estimate the entropy from conformational sampling. We consider a set of systems that are representative of important biomolecular processes. In particular: reference entropies for amino acids in unfolded proteins are obtained from a database of residues not participating in secondary structure elements;the conformational entropy of folding of β2-microglobulin is computed from molecular dynamics simulations using reference entropies for the unfolded state;backbone conformational entropy is computed from molecular dynamics simulations of four different states of the EPAC protein and compared with order parameters (often used as a measure of entropy);the conformational and rototranslational entropy of binding is computed from simulations of 20 tripeptides bound to the peptide binding protein OppA and of β2-microglobulin bound to a citrate coated gold surface. This work shows the potential of the method in the most representative biological processes involving proteins, and provides a valuable alternative, principally in the shown cases, where other approaches are problematic. PMID:26177039

Distance-Based Configurational Entropy of Proteins from Molecular Dynamics Simulations.

PubMed

Fogolari, Federico; Corazza, Alessandra; Fortuna, Sara; Soler, Miguel Angel; VanSchouwen, Bryan; Brancolini, Giorgia; Corni, Stefano; Melacini, Giuseppe; Esposito, Gennaro

2015-01-01

Estimation of configurational entropy from molecular dynamics trajectories is a difficult task which is often performed using quasi-harmonic or histogram analysis. An entirely different approach, proposed recently, estimates local density distribution around each conformational sample by measuring the distance from its nearest neighbors. In this work we show this theoretically well grounded the method can be easily applied to estimate the entropy from conformational sampling. We consider a set of systems that are representative of important biomolecular processes. In particular: reference entropies for amino acids in unfolded proteins are obtained from a database of residues not participating in secondary structure elements;the conformational entropy of folding of β2-microglobulin is computed from molecular dynamics simulations using reference entropies for the unfolded state;backbone conformational entropy is computed from molecular dynamics simulations of four different states of the EPAC protein and compared with order parameters (often used as a measure of entropy);the conformational and rototranslational entropy of binding is computed from simulations of 20 tripeptides bound to the peptide binding protein OppA and of β2-microglobulin bound to a citrate coated gold surface. This work shows the potential of the method in the most representative biological processes involving proteins, and provides a valuable alternative, principally in the shown cases, where other approaches are problematic.

cAMP Regulation of Airway Smooth Muscle Function

PubMed Central

Billington, Charlotte K.; Ojo, Oluwaseun O.; Penn, Raymond B.; Ito, Satoru

2013-01-01

Agonists activating β2-adrenoceptors (β2ARs) on airway smooth muscle (ASM) are the drug of choice for rescue from acute bronchoconstriction in patients with both asthma and chronic obstructive pulmonary disease (COPD). Moreover, the use of long-acting β-agonists combined with inhaled corticosteroids constitutes an important maintenance therapy for these diseases. β-Agonists are effective bronchodilators due primarily to their ability to antagonize ASM contraction. The presumed cellular mechanism of action involves the generation of intracellular cAMP, which in turn can activate the effector molecules cAMP-dependent protein kinase (PKA) and Epac. Other agents such as prostaglandin E2 and phosphodiesterase inhibitors that also increase intracellular cAMP levels in ASM, can also antagonize ASM contraction, and inhibit other ASM functions including proliferation and migration. Therefore, β2ARs and cAMP are key players in combating the pathophysiology of airway narrowing and remodeling. However, limitations of β-agonist therapy due to drug tachyphylaxis related to β2AR desensitization, and recent findings regarding the manner in which β2ARs and cAMP signal, have raised new and interesting questions about these well-studied molecules. In this review we discuss current concepts regarding β2ARs and cAMP in the regulation of ASM cell functions and their therapeutic roles in asthma and COPD. PMID:22634112

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

NASA Astrophysics Data System (ADS)

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

2016-04-01

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

Temporal and spatial distributions of nutrients under the influence of human activities in Sishili Bay, northern Yellow Sea of China.

PubMed

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

PubMed Central

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.

PubMed

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.

Monitoring Ras Interactions with the Nucleotide Exchange Factor Son of Sevenless (Sos) Using Site-specific NMR Reporter Signals and Intrinsic Fluorescence.

PubMed

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.

PubMed

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

PubMed Central

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.

PubMed

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.

Hydrogen/deuterium exchange, a unique and effective method for MS fragmentation behavior elucidation of ginkgolides and its application to systematic research in Ginkgo biloba.

PubMed

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.

PubMed

Winwood-Smith, Hugh S; White, Craig R

2018-06-07

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

Optimizing the parameters of heat transmission in a small heat exchanger with spiral tapes cut as triangles and Aluminum oxide nanofluid using central composite design method

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.

Optimizing the parameters of heat transmission in a small heat exchanger with spiral tapes cut as triangles and Aluminum oxide nanofluid using central composite design method

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.

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

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

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

PubMed Central

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

2014-01-01

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

Factors motivating and affecting health information exchange usage

PubMed Central

Zhao, Hongwei; Jaspserson, 'Jon; Gamm, Larry D; Ohsfeldt, Robert L

2011-01-01

Objective Health information exchange (HIE) is the process of electronically sharing patient-level information between providers. However, where implemented, reports indicate HIE system usage is low. The aim of this study was to determine the factors associated with different types of HIE usage. Design Cross-sectional analysis of clinical data from emergency room encounters included in an operational HIE effort linked to system user logs using crossed random-intercept logistic regression. Measurements Independent variables included factors indicative of information needs. System usage was measured as none, basic usage, or a novel pattern of usage. Results The system was accessed for 2.3% of all encounters (6142 out of 271 305). Novel usage patterns were more likely for more complex patients. The odds of HIE usage were lower in the face of time constraints. In contrast to expectations, system usage was lower when the patient was unfamiliar to the facility. Limitations Because of differences between HIE efforts and the fact that not all types of HIE usage (ie, public health) could be included in the analysis, results are limited in terms of generalizablity. Conclusions This study of actual HIE system usage identifies patients and circumstances in which HIE is more likely to be used and factors that are likely to discourage usage. The paper explores the implications of the findings for system redesign, information integration across exchange partners, and for meaningful usage criteria emerging from provisions of the Health Information Technology for Economic & Clinical Health Act. PMID:21262919

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...

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

PubMed

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

2016-11-08

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

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

DOE PAGES

Rothstein, Ira Z.; Stewart, Iain W.

2016-08-03

Starting with QCD, we derive an effective field theory description for forward scattering and factorization violation as part of the soft-collinear effective field theory (SCET) for high energy scattering. These phenomena are mediated by long distance Glauber gluon exchanges, which are static in time, localized in the longitudinal distance, and act as a kernel for forward scattering where |t| << s. In hard scattering, Glauber gluons can induce corrections which invalidate factorization. With SCET, Glauber exchange graphs can be calculated explicitly, and are distinct from graphs involving soft, collinear, or ultrasoft gluons. We derive a complete basis of operators whichmore » describe the leading power effects of Glauber exchange. Key ingredients include regulating light-cone rapidity singularities and subtractions which prevent double counting. Our results include a novel all orders gauge invariant pure glue soft operator which appears between two collinear rapidity sectors. The 1-gluon Feynman rule for the soft operator coincides with the Lipatov vertex, but it also contributes to emissions with ≥ 2 soft gluons. Our Glauber operator basis is derived using tree level and one-loop matching calculations from full QCD to both SCET II and SCET I. The one-loop amplitude’s rapidity renormalization involves mixing of color octet operators and yields gluon Reggeization at the amplitude level. The rapidity renormalization group equation for the leading soft and collinear functions in the forward scattering cross section are each given by the BFKL equation. Various properties of Glauber gluon exchange in the context of both forward scattering and hard scattering factorization are described. For example, we derive an explicit rule for when eikonalization is valid, and provide a direct connection to the picture of multiple Wilson lines crossing a shockwave. In hard scattering operators Glauber subtractions for soft and collinear loop diagrams ensure that we are not sensitive to the directions for soft and collinear Wilson lines. Conversely, certain Glauber interactions can be absorbed into these soft and collinear Wilson lines by taking them to be in specific directions. Finally, we also discuss criteria for factorization violation.« less

Configuration Factors for Exchange of Radiant Energy Between Axisymmetrical Sections of Cylinders, Cones, and Hemispheres and Their Bases

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.

78 FR 2571 - Special Access for Price Cap Local Exchange Carriers; AT&T Corporation Petition for Rulemaking To...

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.

PubMed

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

2018-02-01

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

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

PubMed

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

2016-01-01

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

Health information exchange policies of 11 diverse health systems and the associated impact on volume of exchange.

PubMed

Downing, N Lance; Adler-Milstein, Julia; Palma, Jonathan P; Lane, Steven; Eisenberg, Matthew; Sharp, Christopher; Longhurst, Christopher A

2017-01-01

Provider organizations increasingly have the ability to exchange patient health information electronically. Organizational health information exchange (HIE) policy decisions can impact the extent to which external information is readily available to providers, but this relationship has not been well studied. Our objective was to examine the relationship between electronic exchange of patient health information across organizations and organizational HIE policy decisions. We focused on 2 key decisions: whether to automatically search for information from other organizations and whether to require HIE-specific patient consent. We conducted a retrospective time series analysis of the effect of automatic querying and the patient consent requirement on the monthly volume of clinical summaries exchanged. We could not assess degree of use or usefulness of summaries, organizational decision-making processes, or generalizability to other vendors. Between 2013 and 2015, clinical summary exchange volume increased by 1349% across 11 organizations. Nine of the 11 systems were set up to enable auto-querying, and auto-querying was associated with a significant increase in the monthly rate of exchange (P = .006 for change in trend). Seven of the 11 organizations did not require patient consent specifically for HIE, and these organizations experienced a greater increase in volume of exchange over time compared to organizations that required consent. Automatic querying and limited consent requirements are organizational HIE policy decisions that impact the volume of exchange, and ultimately the information available to providers to support optimal care. Future efforts to ensure effective HIE may need to explicitly address these factors. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association.

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

PubMed Central

Dalmark, Mads; Wieth, Jens Otto

1972-01-01

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

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.

Influence of government controls over the currency exchange rate in the evolution of Hurst's exponent: An autonomous agent-based model

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

PubMed Central

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

PubMed Central

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.

PubMed

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.

PubMed

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.

Water exchange in manganese-based water-oxidizing catalysts in photosynthetic systems: from the water-oxidizing complex in photosystem II to nano-sized manganese oxides.

PubMed

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.

Dynamers: Polyacylhydrazone reversible covalent polymers, component exchange, and constitutional diversity

PubMed Central

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

Plasma exchange in the treatment of thyroid storm secondary to type II amiodarone-induced thyrotoxicosis.

PubMed

Zhu, Ling; Zainudin, Sueziani Binte; Kaushik, Manish; Khor, Li Yan; Chng, Chiaw Ling

2016-01-01

Type II amiodarone-induced thyrotoxicosis (AIT) is an uncommon cause of thyroid storm. Due to the rarity of the condition, little is known about the role of plasma exchange in the treatment of severe AIT. A 56-year-old male presented with thyroid storm 2months following cessation of amiodarone. Despite conventional treatment, his condition deteriorated. He underwent two cycles of plasma exchange, which successfully controlled the severe hyperthyroidism. The thyroid hormone levels continued to fall up to 10h following plasma exchange. He subsequently underwent emergency total thyroidectomy and the histology of thyroid gland confirmed type II AIT. Management of thyroid storm secondary to type II AIT can be challenging as patients may not respond to conventional treatments, and thyroid storm may be more harmful in AIT patients owing to the underlying cardiac disease. If used appropriately, plasma exchange can effectively reduce circulating hormones, to allow stabilisation of patients in preparation for emergency thyroidectomy. Type II AIT is an uncommon cause of thyroid storm and may not respond well to conventional thyroid storm treatment.Prompt diagnosis and therapy are important, as patients may deteriorate rapidly.Plasma exchange can be used as an effective bridging therapy to emergency thyroidectomy.This case shows that in type II AIT, each cycle of plasma exchange can potentially lower free triiodothyronine levels for 10h.Important factors to consider when planning plasma exchange as a treatment for thyroid storm include timing of each session, type of exchange fluid to be used and timing of surgery.

Food Exchange List and Dietary Management of Non-Communicable Diseases in Cultural Perspective.

PubMed

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.

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

USGS Publications Warehouse

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

2009-01-01

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

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

PubMed Central

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.

PubMed

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.

47 CFR 36.3 - Freezing of jurisdictional separations category relationships and/or allocation factors.

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

DOE PAGES

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

2017-12-06

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

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

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

Rimal, Dipak

2014-05-01

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

FACTORS INFLUENCING PHOTOREACTIONS OF DISSOLVED ORGANIC MATTER IN A COASTAL RIVER OF THE SOUTHEASTERN UNITED STATES

EPA Science Inventory

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

DTIC Science & Technology

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

Experiments to Evaluate and Implement Passive Tracer Gas Methods to Measure Ventilation Rates in Homes

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

Exploring the Context of Trafficking and Adolescent Sex Industry Involvement in Tijuana, Mexico: Consequences for HIV Risk and Prevention

PubMed Central

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

Exploring the context of trafficking and adolescent sex industry involvement in Tijuana, Mexico: consequences for HIV risk and prevention.

PubMed

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.

Precipitation-mediated responses of soil acid buffering capacity to long-term nitrogen addition in a semi-arid grassland

NASA Astrophysics Data System (ADS)

Cai, Jiangping; Luo, Wentao; Liu, Heyong; Feng, Xue; Zhang, Yongyong; Wang, Ruzhen; Xu, Zhuwen; Zhang, Yuge; Jiang, Yong

2017-12-01

Atmospheric nitrogen (N) deposition can result in soil acidification and reduce soil acid buffering capacity. However, it remains poorly understood how changes in precipitation regimes with elevated atmospheric N deposition affect soil acidification processes in a water-limited grassland. Here, we conducted a 9-year split-plot experiment with water addition as the main factor and N addition as the second factor. Results showed that soil acid buffering capacity significantly decreased with increased N inputs, mainly due to the decline of soil effective cation exchange capacity (ECEC) and exchangeable basic cations (especially Ca2+), indicating an acceleration of soil acidification status in this steppes. Significant interactive N and water effects were detected on the soil acid buffering capacity. Water addition enhanced the soil ECEC and exchangeable base cations and thus alleviated the decrease of soil acid buffering capacity under N addition. Our findings suggested that precipitation can mitigate the impact of increased N deposition on soil acidification in semi-arid grasslands. This knowledge should be used to improve models predicting soil acidification processes in terrestrial ecosystems under changing environmental conditions.

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.

Identification of a negative regulatory region for the exchange activity and characterization of T332I mutant of Rho guanine nucleotide exchange factor 10 (ARHGEF10).

PubMed

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.

Identification of a Negative Regulatory Region for the Exchange Activity and Characterization of T332I Mutant of Rho Guanine Nucleotide Exchange Factor 10 (ARHGEF10)*

PubMed Central

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

Subtle exchange model of flow depended on the blood cell shape to enhance the micro-circulation in capillary

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.

Discovery of Aminopiperidine Indoles That Activate the Guanine Nucleotide Exchange Factor SOS1 and Modulate RAS Signaling.

PubMed

Abbott, Jason R; Hodges, Timothy R; Daniels, R Nathan; Patel, Pratiq A; Kennedy, Jack Phillip; Howes, Jennifer E; Akan, Denis T; Burns, Michael C; Sai, Jiqing; Sobolik, Tammy; Beesetty, Yugandhar; Lee, Taekyu; Rossanese, Olivia W; Phan, Jason; Waterson, Alex G; Fesik, Stephen W

2018-06-01

Deregulated RAS activity, often the result of mutation, is implicated in approximately 30% of all human cancers. Despite this statistic, no clinically successful treatment for RAS-driven tumors has yet been developed. One approach for modulating RAS activity is to target and affect the activity of proteins that interact with RAS, such as the guanine nucleotide exchange factor (GEF) son of sevenless homologue 1 (SOS1). Here, we report on structure-activity relationships (SAR) in an indole series of compounds. Using structure-based design, we systematically explored substitution patterns on the indole nucleus, the pendant amino acid moiety, and the linker unit that connects these two fragments. Best-in-class compounds activate the nucleotide exchange process at sub-micromolar concentrations in vitro, increase levels of active RAS-GTP in HeLa cells, and elicit signaling changes in the mitogen-activated protein kinase/extracellular regulated kinase (MAPK/ERK) pathway, resulting in a decrease in pERK1/2 T202/Y204 protein levels at higher compound concentrations.

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.

Information exchange using a prescribed form and involvement of occupational health nurses promotes occupational physicians to collaborate with attending physicians for supporting workers with illness in Japan.

PubMed

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.

Small-GTPase-associated signaling by the guanine nucleotide exchange factors CpDock180 and CpCdc24, the GTPase effector CpSte20, and the scaffold protein CpBem1 in Claviceps purpurea.

PubMed

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.

PubMed

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.

Disruption of stomatal lineage signaling or transcriptional regulators has differential effects on mesophyll development, but maintains coordination of gas exchange.

PubMed

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.

PubMed

Côté, Jean-François; Vuori, Kristiina

2006-01-01

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

Pulmonary gas exchange in acute respiratory failure.

PubMed

Rodriguez-Roisin, R

1994-01-01

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

Neutrinoless ββ decay mediated by the exchange of light and heavy neutrinos: the role of nuclear structure correlations

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

DOE PAGES

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

Patients' support for health information exchange: a literature review and classification of key factors.

PubMed

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.

Defective Guanine Nucleotide Exchange in the Elongation Factor-like 1 (EFL1) GTPase by Mutations in the Shwachman-Diamond Syndrome Protein*

PubMed Central

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

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

PubMed

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

2008-01-01

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

ATP Dependence of Na+/H+ Exchange

PubMed Central

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

1997-01-01

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

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

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

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

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

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

Are BVOC exchanges in agricultural ecosystems overestimated? Insights from fluxes measured in a maize field over a whole growing season

NASA Astrophysics Data System (ADS)

Bachy, Aurélie; Aubinet, Marc; Schoon, Niels; Amelynck, Crist; Bodson, Bernard; Moureaux, Christine; Heinesch, Bernard

2016-04-01

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.

Regulation of protein multipoint adsorption on ion-exchange adsorbent and its application to the purification of macromolecules.

PubMed

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.

Exchange of Sex for Drugs or Money in Adolescents and Young Adults: An Examination of Sociodemographic Factors, HIV-Related Risk, and Community Context.

PubMed

Boyer, Cherrie B; Greenberg, Lauren; Chutuape, Kate; Walker, Bendu; Monte, Dina; Kirk, Jennifer; Ellen, Jonathan M

2017-02-01

The goal of this research was to examine associations among sociodemographic factors, HIV risk, and community context (e.g., economic insecurity, job training, housing instability, crime victimization, and perceived community norms) in adolescents and young adults who ever exchanged sex for drugs or money. Anonymous survey data were collected using ACASIs at community venues where adolescents and young adults congregate in resource-challenged, STI prevalent, urban, US neighborhoods. Conventional descriptive statistics, Fisher's exact tests, and generalized estimating equations approaches were used to examine associations. Participants (1818, 95.5 % of those screened eligible) were, on average, aged 21.0 years; 42.2 % were males, and 4.6 % were transgender. Almost one-third (32.1 %) identified as gay or lesbian, 18.1 % identified as bisexual; 66.2 % were Black and 21.0 % were Hispanic; 1.3 % was 'living on the street'. A sizeable proportion reported HIV-related risk: 16.3 % exchanged sex, 12.6 % had sex with someone they knew to be HIV-infected, 7.8 % had sex with someone who injected drugs, and 1.3 % injected drugs. Multivariate comparisons identified a number of variables (e.g., being male or transgender, homelessness, sex with a partner who has HIV, STI history, unemployment, job training access, housing instability, crime victimization, perceived community norms) that were significantly associated with exchange of sex (p < 0.05). This research contributes to the knowledge-base regarding exchange of sex among adolescents and young adults, particularly as it relates to community context. Longitudinal studies to describe the trajectory of social, health, and physical risks and consequences are needed for development of effective evidence-based prevention strategies.

Sequence variations and protein expression levels of the two immune evasion proteins Gpm1 and Pra1 influence virulence of clinical Candida albicans isolates.

PubMed

Luo, Shanshan; Hipler, Uta-Christina; Münzberg, Christin; Skerka, Christine; Zipfel, Peter F

2015-01-01

Candida albicans, the important human fungal pathogen uses multiple evasion strategies to control, modulate and inhibit host complement and innate immune attack. Clinical C. albicans strains vary in pathogenicity and in serum resistance, in this work we analyzed sequence polymorphisms and variations in the expression levels of two central fungal complement evasion proteins, Gpm1 (phosphoglycerate mutase 1) and Pra1 (pH-regulated antigen 1) in thirteen clinical C. albicans isolates. Four nucleotide (nt) exchanges, all representing synonymous exchanges, were identified within the 747-nt long GPM1 gene. For the 900-nt long PRA1 gene, sixteen nucleotide exchanges were identified, which represented synonymous, as well as non-synonymous exchanges. All thirteen clinical isolates had a homozygous exchange (A to G) at position 73 of the PRA1 gene. Surface levels of Gpm1 varied by 8.2, and Pra1 levels by 3.3 fold in thirteen tested isolates and these differences influenced fungal immune fitness. The high Gpm1/Pra1 expressing candida strains bound the three human immune regulators more efficiently, than the low expression strains. The difference was 44% for Factor H binding, 51% for C4BP binding and 23% for plasminogen binding. This higher Gpm1/Pra1 expressing strains result in enhanced survival upon challenge with complement active, Factor H depleted human serum (difference 40%). In addition adhesion to and infection of human endothelial cells was increased (difference 60%), and C3b surface deposition was less effective (difference 27%). Thus, variable expression levels of central immune evasion protein influences immune fitness of the human fungal pathogen C. albicans and thus contribute to fungal virulence.

Roles of Bacillus subtilis DprA and SsbA in RecA-mediated genetic recombination.

PubMed

Yadav, Tribhuwan; Carrasco, Begoña; Serrano, Ester; Alonso, Juan C

2014-10-03

Bacillus subtilis competence-induced RecA, SsbA, SsbB, and DprA are required to internalize and to recombine single-stranded (ss) DNA with homologous resident duplex. RecA, in the ATP · Mg(2+)-bound form (RecA · ATP), can nucleate and form filament onto ssDNA but is inactive to catalyze DNA recombination. We report that SsbA or SsbB bound to ssDNA blocks the RecA filament formation and fails to activate recombination. DprA facilitates RecA filamentation; however, the filaments cannot engage in DNA recombination. When ssDNA was preincubated with SsbA, but not SsbB, DprA was able to activate DNA strand exchange dependent on RecA · ATP. This work demonstrates that RecA · ATP, in concert with SsbA and DprA, catalyzes DNA strand exchange, and SsbB is an accessory factor in the reaction. In contrast, RecA · dATP efficiently catalyzes strand exchange even in the absence of single-stranded binding proteins or DprA, and addition of the accessory factors marginally improved it. We proposed that the RecA-bound nucleotide (ATP and to a lesser extent dATP) might dictate the requirement for accessory factors. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

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

Determination of Backbone Amide Hydrogen Exchange Rates of Cytochrome c Using Partially Scrambled Electron Transfer Dissociation Data

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.