Regulation of ENaC and CFTR expression with K+ channel modulators and effect on fluid absorption across alveolar epithelial cells.

PubMed

Leroy, Claudie; Privé, Anik; Bourret, Jean-Charles; Berthiaume, Yves; Ferraro, Pasquale; Brochiero, Emmanuelle

2006-12-01

In a recent study (Leroy C, Dagenais A, Berthiaume Y, and Brochiero E. Am J Physiol Lung Cell Mol Physiol 286: L1027-L1037, 2004), we identified an ATP-sensitive K(+) (K(ATP)) channel in alveolar epithelial cells, formed by inwardly rectifying K(+) channel Kir6.1/sulfonylurea receptor (SUR)2B subunits. We found that short applications of K(ATP), voltage-dependent K(+) channel KvLQT1, and calcium-activated K(+) (K(Ca)) channel modulators modified Na(+) and Cl(-) currents in alveolar monolayers. In addition, it was shown previously that a K(ATP) opener increased alveolar liquid clearance in human lungs by a mechanism possibly related to epithelial sodium channels (ENaC). We therefore hypothesized that prolonged treatment with K(+) channel modulators could induce a sustained regulation of ENaC activity and/or expression. Alveolar monolayers were treated for 24 h with inhibitors of K(ATP), KvLQT1, and K(Ca) channels identified by PCR. Glibenclamide and clofilium (K(ATP) and KvLQT1 inhibitors) strongly reduced basal transepithelial current, amiloride-sensitive Na(+) current, and forskolin-activated Cl(-) currents, whereas pinacidil, a K(ATP) activator, increased them. Interestingly, K(+) inhibitors or membrane depolarization (induced by valinomycin in high-K(+) medium) decreased alpha-, beta-, and gamma-ENaC and CFTR mRNA. alpha-ENaC and CFTR proteins also declined after glibenclamide or clofilium treatment. Conversely, pinacidil augmented ENaC and CFTR mRNAs and proteins. Since alveolar fluid transport was found to be driven, at least in part, by Na(+) transport through ENaC, we tested the impact of K(+) channel modulators on fluid absorption across alveolar monolayers. We found that glibenclamide and clofilium reduced fluid absorption to a level similar to that seen in the presence of amiloride, whereas pinacidil slightly enhanced it. Long-term regulation of ENaC and CFTR expression by K(+) channel activity could benefit patients with pulmonary diseases affecting ion transport and fluid clearance.

Renal intercalated cells and blood pressure regulation.

PubMed

Wall, Susan M

2017-12-01

Type B and non-A, non-B intercalated cells are found within the connecting tubule and the cortical collecting duct. Of these cell types, type B intercalated cells are known to mediate Cl - absorption and HCO 3 - secretion largely through pendrin-dependent Cl - /HCO 3 - exchange. This exchange is stimulated by angiotensin II administration and is also stimulated in models of metabolic alkalosis, for instance after aldosterone or NaHCO 3 administration. In some rodent models, pendrin-mediated HCO 3 - secretion modulates acid-base balance. However, the role of pendrin in blood pressure regulation is likely of more physiological or clinical significance. Pendrin regulates blood pressure not only by mediating aldosterone-sensitive Cl - absorption, but also by modulating the aldosterone response for epithelial Na + channel (ENaC)-mediated Na + absorption. Pendrin regulates ENaC through changes in open channel of probability, channel surface density, and channels subunit total protein abundance. Thus, aldosterone stimulates ENaC activity through both direct and indirect effects, the latter occurring through its stimulation of pendrin expression and function. Therefore, pendrin contributes to the aldosterone pressor response. Pendrin may also modulate blood pressure in part through its action in the adrenal medulla, where it modulates the release of catecholamines, or through an indirect effect on vascular contractile force. This review describes how aldosterone and angiotensin II-induced signaling regulate pendrin and the contributory role of pendrin in distal nephron function and blood pressure.

Endothelial epithelial sodium channel inhibition activates endothelial nitric oxide synthase via phosphoinositide 3-kinase/Akt in small-diameter mesenteric arteries.

PubMed

Pérez, Francisco R; Venegas, Fabiola; González, Magdalena; Andrés, Sergio; Vallejos, Catalina; Riquelme, Gloria; Sierralta, Jimena; Michea, Luis

2009-06-01

Recent studies have shown that the epithelial sodium channel (ENaC) is expressed in vascular tissue. However, the role that ENaC may play in the responses to vasoconstrictors and NO production has yet to be addressed. In this study, the contractile responses of perfused pressurized small-diameter rat mesenteric arteries to phenylephrine and serotonin were reduced by ENaC blockade with amiloride (75.1+/-3.2% and 16.9+/-2.3% of control values, respectively; P<0.01) that was dose dependent (EC(50)=88.9+/-1.6 nmol/L). Incubation with benzamil, another ENaC blocker, had similar effects. alpha, beta, and gamma ENaC were identified in small-diameter rat mesenteric arteries using RT-PCR and Western blot with specific antibodies. In situ hybridization and immunohistochemistry localized ENaC expression to the tunica media and endothelium of small-diameter rat mesenteric arteries. Patch-clamp experiments demonstrated that primary cultures of mesenteric artery endothelial cells expressed amiloride-sensitive sodium currents. Mechanical ablation of the endothelium or inhibition of eNOS with N(omega)-nitro-L-arginine inhibited the reduction in contractility caused by ENaC blockers. ENaC inhibitors increased eNOS phosphorylation (Ser 1177) and Akt phosphorylation (Ser 473). The presence of the phosphoinositide 3-kinase inhibitor LY294002 blunted Akt phosphorylation and eNOS phosphorylation and the decrease in the response to phenylephrine caused by blockers of ENaC, indicating that the phosphoinositide 3-kinase/Akt pathway was activated after ENaC inhibition. Finally, we observed that the effects of blockers of ENaC were flow dependent and that the vasodilatory response to shear stress was enhanced by ENaC blockade. Our results identify a previously unappreciated role for ENaC as a negative modulator of eNOS and NO production in resistance arteries.

Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue distribution, and associated inherited diseases

PubMed Central

Hanukoglu, Israel; Hanukoglu, Aaron

2016-01-01

The epithelial sodium channel (ENaC) is composed of three homologous subunits and allows the flow of Na+ ions across high resistance epithelia, maintaining body salt and water homeostasis. ENaC dependent reabsorption of Na+ in the kidney tubules regulates extracellular fluid (ECF) volume and blood pressure by modulating osmolarity. In multi-ciliated cells, ENaC is located in cilia and plays an essential role in the regulation of epithelial surface liquid volume necessary for cilial transport of mucus and gametes in the respiratory and reproductive tracts respectively. The subunits that form ENaC (named as alpha, beta, gamma and delta, encoded by genes SCNN1A, SCNN1B, SCNN1G, and SCNN1D) are members of the ENaC/Degenerin superfamily. The earliest appearance of ENaC orthologs is in the genomes of the most ancient vertebrate taxon, Cyclostomata (jawless vertebrates) including lampreys, followed by earliest representatives of Gnathostomata (jawed vertebrates) including cartilaginous sharks. Among Euteleostomi (bony vertebrates), Actinopterygii (ray finned-fishes) branch has lost ENaC genes. Yet, most animals in the Sarcopterygii (lobe-finned fish) branch including Tetrapoda, amphibians and amniotes (lizards, crocodiles, birds, and mammals), have four ENaC paralogs. We compared the sequences of ENaC orthologs from 20 species and established criteria for the identification of ENaC orthologs and paralogs, and their distinction from other members of the ENaC/Degenerin superfamily, especially ASIC family. Differences between ENaCs and ASICs are summarized in view of their physiological functions and tissue distributions. Structural motifs that are conserved throughout vertebrate ENaCs are highlighted. We also present a comparative overview of the genotype-phenotype relationships in inherited diseases associated with ENaC mutations, including multisystem pseudohypoaldosteronism (PHA1B), Liddle syndrome, cystic fibrosis-like disease and essential hypertension. PMID:26772908

Renal intercalated cells and blood pressure regulation

PubMed Central

Wall, Susan M.

2017-01-01

Type B and non-A, non-B intercalated cells are found within the connecting tubule and the cortical collecting duct. Of these cell types, type B intercalated cells are known to mediate Cl− absorption and HCO3− secretion largely through pendrin-dependent Cl−/HCO3− exchange. This exchange is stimulated by angiotensin II administration and is also stimulated in models of metabolic alkalosis, for instance after aldosterone or NaHCO3 administration. In some rodent models, pendrin-mediated HCO3− secretion modulates acid-base balance. However, the role of pendrin in blood pressure regulation is likely of more physiological or clinical significance. Pendrin regulates blood pressure not only by mediating aldosterone-sensitive Cl− absorption, but also by modulating the aldosterone response for epithelial Na+ channel (ENaC)-mediated Na+ absorption. Pendrin regulates ENaC through changes in open channel of probability, channel surface density, and channels subunit total protein abundance. Thus, aldosterone stimulates ENaC activity through both direct and indirect effects, the latter occurring through its stimulation of pendrin expression and function. Therefore, pendrin contributes to the aldosterone pressor response. Pendrin may also modulate blood pressure in part through its action in the adrenal medulla, where it modulates the release of catecholamines, or through an indirect effect on vascular contractile force. This review describes how aldosterone and angiotensin II-induced signaling regulate pendrin and the contributory role of pendrin in distal nephron function and blood pressure. PMID:29285423

The function and regulation of acid‐sensing ion channels (ASICs) and the epithelial Na+ channel (ENaC): IUPHAR Review 19

PubMed Central

Boscardin, Emilie; Alijevic, Omar; Hummler, Edith

2016-01-01

Acid‐sensing ion channels (ASICs) and the epithelial Na+ channel (ENaC) are both members of the ENaC/degenerin family of amiloride‐sensitive Na+ channels. ASICs act as proton sensors in the nervous system where they contribute, besides other roles, to fear behaviour, learning and pain sensation. ENaC mediates Na+ reabsorption across epithelia of the distal kidney and colon and of the airways. ENaC is a clinically used drug target in the context of hypertension and cystic fibrosis, while ASIC is an interesting potential target. Following a brief introduction, here we will review selected aspects of ASIC and ENaC function. We discuss the origin and nature of pH changes in the brain and the involvement of ASICs in synaptic signalling. We expose how in the peripheral nervous system, ASICs cover together with other ion channels a wide pH range as proton sensors. We introduce the mechanisms of aldosterone‐dependent ENaC regulation and the evidence for an aldosterone‐independent control of ENaC activity, such as regulation by dietary K+. We then provide an overview of the regulation of ENaC by proteases, a topic of increasing interest over the past few years. In spite of the profound differences in the physiological and pathological roles of ASICs and ENaC, these channels share many basic functional and structural properties. It is likely that further research will identify physiological contexts in which ASICs and ENaC have similar or overlapping roles. PMID:27278329

Modulation of epithelial sodium channel trafficking and function by sodium 4-phenylbutyrate in human nasal epithelial cells.

PubMed

Prulière-Escabasse, Virginie; Planès, Carole; Escudier, Estelle; Fanen, Pascale; Coste, André; Clerici, Christine

2007-11-23

Sodium 4-phenylbutyrate (4-PBA) has been shown to correct the cellular trafficking of several mutant or nonmutant plasma membrane proteins such as cystic fibrosis transmembrane conductance regulator through the expression of 70-kDa heat shock proteins. The objective of the study was to determine whether 4-PBA may influence the functional expression of epithelial sodium channels (ENaC) in human nasal epithelial cells (HNEC). Using primary cultures of HNEC, we demonstrate that 4-PBA (5 mm for 6 h) markedly stimulated amiloride-sensitive sodium channel activity and that this was related to an increased abundance of alpha-, beta-, and gamma-ENaC subunits in the apical membrane. The increase in ENaC cell surface expression (i) was due to insertion of newly ENaC subunits as determined by brefeldin A experiments and (ii) was not associated with cell surface retention of ENaC subunits because endocytosis of ENaC subunits was unchanged. In addition, we find that ENaC co-immunoprecipitated with the heat shock protein constitutively expressed Hsc70, that has been reported to modulate ENaC trafficking, and that 4-PBA decreased Hsc70 protein level. Finally, we report that in cystic fibrosis HNEC obtained from two cystic fibrosis patients, 4-PBA increased functional expression of ENaC as demonstrated by the increase in amiloride-sensitive sodium transport and in alpha-, beta-, and gamma-ENaC subunit expression in the apical membrane. Our results suggest that in HNEC, 4-PBA increases the functional expression of ENaC through the insertion of new alpha-, beta-, and gamma-ENaC subunits into the apical membrane and also suggest that 4-PBA could modify ENaC trafficking by reducing Hsc70 protein expression.

Regulation of Epithelial Sodium Transport via Epithelial Na+ Channel

PubMed Central

Marunaka, Yoshinori; Niisato, Naomi; Taruno, Akiyuki; Ohta, Mariko; Miyazaki, Hiroaki; Hosogi, Shigekuni; Nakajima, Ken-ichi; Kusuzaki, Katsuyuki; Ashihara, Eishi; Nishio, Kyosuke; Iwasaki, Yoshinobu; Nakahari, Takashi; Kubota, Takahiro

2011-01-01

Renal epithelial Na+ transport plays an important role in homeostasis of our body fluid content and blood pressure. Further, the Na+ transport in alveolar epithelial cells essentially controls the amount of alveolar fluid that should be kept at an appropriate level for normal gas exchange. The epithelial Na+ transport is generally mediated through two steps: (1) the entry step of Na+ via epithelial Na+ channel (ENaC) at the apical membrane and (2) the extrusion step of Na+ via the Na+, K+-ATPase at the basolateral membrane. In general, the Na+ entry via ENaC is the rate-limiting step. Therefore, the regulation of ENaC plays an essential role in control of blood pressure and normal gas exchange. In this paper, we discuss two major factors in ENaC regulation: (1) activity of individual ENaC and (2) number of ENaC located at the apical membrane. PMID:22028593

Effect of dietary salt intake on epithelial Na+ channels (ENaC) in vasopressin magnocellular neurosecretory neurons in the rat supraoptic nucleus.

PubMed

Sharma, Kaustubh; Haque, Masudul; Guidry, Richard; Ueta, Yoichi; Teruyama, Ryoichi

2017-09-01

A growing body of evidence suggests that epithelial Na + channels (ENaCs) in the brain play a significant role in the regulation of blood pressure; however, the brain structures that mediate the effect are not well understood. Because vasopressin (VP) neurons play a pivotal role in coordinating neuroendocrine and autonomic responses to maintain cardiovascular homeostasis, a basic understanding of the regulation and activity of ENaC in VP neurons is of great interest. We show that high dietary salt intake caused an increase in the expression and activity of ENaC which resulted in the steady state depolarization of VP neurons. The results help us understand one of the mechanisms underlying how dietary salt intake affects the activity of VP neurons via ENaC activity. All three epithelial Na + channel (ENaC) subunits (α, β and γ) are located in vasopressin (VP) magnocellular neurons in the hypothalamic supraoptic (SON) and paraventricular nuclei. Our previous study demonstrated that ENaC mediates a Na + leak current that affects the steady state membrane potential in VP neurons. In the present study, we evaluated the effect of dietary salt intake on ENaC regulation and activity in VP neurons. High dietary salt intake for 7 days caused an increase in expression of β- and γENaC subunits in the SON and the translocation of αENaC immunoreactivity towards the plasma membrane. Patch clamp experiments on hypothalamic slices showed that the mean amplitude of the putative ENaC currents was significantly greater in VP neurons from animals that were fed a high salt diet compared with controls. The enhanced ENaC current contributed to the more depolarized basal membrane potential observed in VP neurons in the high salt diet group. These findings indicate that high dietary NaCl intake enhances the expression and activity of ENaCs, which augments synaptic drive by depolarizing the basal membrane potential close to the action potential threshold during hormonal demand. However, ENaCs appear to have only a minor role in the regulation of the firing activity of VP neurons in the absence of synaptic inputs as neither the mean intraburst frequency, burst duration, nor interspike interval variability of phasic bursting activity was affected. Moreover, ENaC activity did not affect the initiation, sustention, or termination of the phasic bursting generated in an intrinsic manner without synaptic inputs. © 2017 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Increased renal alpha-epithelial sodium channel (ENAC) protein and increased ENAC activity in normal pregnancy.

PubMed

West, Crystal; Zhang, Zheng; Ecker, Geoffrey; Masilamani, Shyama M E

2010-11-01

Pregnancy-mediated sodium (Na) retention is required to provide an increase in plasma volume for the growing fetus. The mechanisms responsible for this Na retention are not clear. We first used a targeted proteomics approach and found that there were no changes in the protein abundance compared with virgin rats of the β or γ ENaC, type 3 Na(+)/H(+) exchanger (NHE3), bumetanide-sensitive cotransporter (NKCC2), or NaCl cotransporter (NCC) in mid- or late pregnancy. In contrast, we observed marked increases in the abundance of the α-ENaC subunit. The plasma volume increased progressively during pregnancy with the greatest plasma volume being evident in late pregnancy. ENaC inhibition abolished the difference in plasma volume status between virgin and pregnant rats. To determine the in vivo activity of ENaC, we conducted in vivo studies of rats in late pregnancy (days 18-20) and virgin rats to measure the natriuretic response to ENaC blockade (with benzamil). The in vivo activity of ENaC (U(Na)V postbenzamil-U(Na)V postvehicle) was markedly increased in late pregnancy, and this difference was abolished by pretreatment with the mineralocorticoid receptor antagonist, eplerenone. These findings demonstrate that the increased α-ENaC subunit of pregnancy is associated with an mineralocorticoid-dependent increase in ENaC activity. Further, we show that ENaC activity is a major contributor of plasma volume status in late pregnancy. These changes are likely to contribute to the renal sodium retention and plasma volume expansion required for an optimal pregnancy.

Derlin-1 promotes ubiquitylation and degradation of the epithelial Na+ channel, ENaC.

PubMed

You, Hui; Ge, Yamei; Zhang, Jian; Cao, Yizhi; Xing, Jing; Su, Dongming; Huang, Yujie; Li, Min; Qu, Shen; Sun, Fei; Liang, Xiubin

2017-03-15

Ubiquitylation of the epithelial Na + channel (ENaC) plays a critical role in cellular functions, including transmembrane transport of Na + , Na + and water balance, and blood pressure stabilization. Published studies have suggested that ENaC subunits are targets of ER-related degradation (ERAD) in yeast systems. However, the molecular mechanism underlying proteasome-mediated degradation of ENaC subunits remains to be established. Derlin-1, an E3 ligase mediator, links recognized target proteins to ubiquitin-mediated proteasomal degradation in the cytosol. In the present study, we found that derlin-1 suppressed the expression of ENaC at the protein level and that the subunit α-ENaC (also known as SCNN1A) physically interacted with derlin-1 at the membrane-anchored domains or the loop regions, and that derlin-1 initiated α-ENaC retrotranslocation. In addition, HUWE1, an endoplasmic reticulum (ER)-resident E3 ubiquitin ligase, was recruited and promoted K11-linked polyubiquitylation of α-ENaC and, hence, formation of an α-ENaC ubiquitin-mediated degradation complex. These findings suggest that derlin-1 promotes ENaC ubiquitylation and enhances ENaC ubiquitin- mediated proteasome degradation. The derlin-1 pathway therefore may represent a significant early checkpoint in the recognition and degradation of ENaC in mammalian cells. © 2017. Published by The Company of Biologists Ltd.

Blood pressure regulation via the epithelial sodium channel: from gene to kidney and beyond.

PubMed

Büsst, Cara J

2013-08-01

The epithelial sodium channel (ENaC) has long been recognized as playing a vital role in blood pressure (BP) regulation due to its involvement in fluid balance. The genes encoding the three ENaC subunits are likewise important contributors to hypertension, both in rare monogenic diseases and in the general population. The unusually high numbers of genetic variants associated with complex traits, including BP, that are located in non-coding areas suggest an involvement of these variants in regulatory functions. This may involve differential regulation of expression in different tissues. Emerging evidence indicates that the ENaC plays an important role in BP determination not only via its actions in the kidney, but also in other tissues commonly involved in BP regulation. The ENaC in the central nervous system is proposed to regulate BP via sympathetic nervous system activity. Recent evidence suggests that the ENaC contributes to vascular function and the myogenic response. Additional roles potentially include initiation of the baroreceptor reflex via ENaC in the baroreceptors and driving high salt intake with a 'taste for salt' via ENaC in the tongue. The present review describes the involvement of the ENaC in the determination of BP at a genetic and physiological level, detailing recent evidence for its role in the kidney and in other pertinent tissues. © 2013 Wiley Publishing Asia Pty Ltd.

Gain-of-Function Mutation W493R in the Epithelial Sodium Channel Allosterically Reconfigures Intersubunit Coupling*♦

PubMed Central

Shobair, Mahmoud; Dagliyan, Onur; Kota, Pradeep; Dang, Yan L.; He, Hong; Stutts, M. Jackson; Dokholyan, Nikolay V.

2016-01-01

Sodium absorption in epithelial cells is rate-limited by the epithelial sodium channel (ENaC) activity in lung, kidney, and the distal colon. Pathophysiological conditions, such as cystic fibrosis and Liddle syndrome, result from water-electrolyte imbalance partly due to malfunction of ENaC regulation. Because the quaternary structure of ENaC is yet undetermined, the bases of pathologically linked mutations in ENaC subunits α, β, and γ are largely unknown. Here, we present a structural model of heterotetrameric ENaC α1βα2γ that is consistent with previous cross-linking results and site-directed mutagenesis experiments. By using this model, we show that the disease-causing mutation αW493R rewires structural dynamics of the intersubunit interfaces α1β and α2γ. Changes in dynamics can allosterically propagate to the channel gate. We demonstrate that cleavage of the γ-subunit, which is critical for full channel activation, does not mediate activation of ENaC by αW493R. Our molecular dynamics simulations led us to identify a channel-activating electrostatic interaction between α2Arg-493 and γGlu-348 at the α2γ interface. By neutralizing a sodium-binding acidic patch at the α1β interface, we reduced ENaC activation of αW493R by more than 2-fold. By combining homology modeling, molecular dynamics, cysteine cross-linking, and voltage clamp experiments, we propose a dynamics-driven model for the gain-of-function in ENaC by αW493R. Our integrated computational and experimental approach advances our understanding of structure, dynamics, and function of ENaC in its disease-causing state. PMID:26668308

Interaction of Serum- and Glucocorticoid Regulated Kinase 1 (SGK1) with the WW-Domains of Nedd4-2 Is Required for Epithelial Sodium Channel Regulation

PubMed Central

Wiemuth, Dominik; Lott, J. Shaun; Ly, Kevin; Ke, Ying; Teesdale-Spittle, Paul; Snyder, Peter M.; McDonald, Fiona J.

2010-01-01

Background The epithelial sodium channel (ENaC) is an integral component of the pathway for Na+ absorption in epithelial cells. The ubiquitin ligases Nedd4 and Nedd4-2 bind to ENaC and decrease its activity. Conversely, Serum- and Glucocorticoid regulated Kinase-1 (SGK1), a downstream mediator of aldosterone, increases ENaC activity. This effect is at least partly mediated by direct interaction between SGK and Nedd4-2. SGK binds both Nedd4 and Nedd4-2, but it is only able to phosphorylate Nedd4-2. Phosphorylation of Nedd4-2 reduces its ability to bind to ENaC, due to the interaction of phosphorylated Nedd4-2 with 14-3-3 proteins, and hence increases ENaC activity. WW-domains in Nedd4-like proteins bind PY-motifs (PPXY) present in ENaC subunits, and SGK also has a PY-motif. Principal Finding Here we show that single or tandem WW-domains of Nedd4 and Nedd4-2 mediate binding to SGK and that different WW-domains of Nedd4 and Nedd4-2 are involved. Our data also show that WW-domains 2 and 3 of Nedd4-2 mediate the interaction with SGK in a cooperative manner, that activated SGK has increased affinity for the WW-domains of Nedd4-2 in vitro, and a greater stimulatory effect on ENaC Na+ transport compared to wildtype SGK. Further, SGK lacking a PY motif failed to stimulate ENaC activity in the presence of Nedd4-2. Conclusions Binding of Nedd4-2 WW-domains to SGK is necessary for SGK-induced ENaC activity. PMID:20730100

Salt-Induced Hypertension in a Mouse Model of Liddle's Syndrome is Mediated by Epithelial Sodium Channels in the Brain

PubMed Central

Van Huysse, James W.; Amin, Md. Shahrier; Yang, Baoli; Leenen, Frans H. H.

2012-01-01

Neural precursor cell expressed and developmentally downregulated 4-2 protein (Nedd4-2) facilitates the endocytosis of epithelial Na channels (ENaC). Both mice and humans with a loss of regulation of ENaC by Nedd4-2 have salt-induced hypertension. ENaC is also expressed in the brain, where it is critical for hypertension on high salt diet in salt-sensitive rats. In the present studies we assessed whether Nedd4-2 knockout (−/−) mice have: 1) increased brain ENaC; 2) elevated CSF sodium on high salt diet; and 3) enhanced pressor responses to CSF sodium and hypertension on high salt diet, both mediated by brain ENaC. Prominent choroid plexus and neuronal ENaC staining was present in −/− but not in wild-type (W/T) mice. In chronically instrumented mice, intracerebroventricular (icv) infusion of Na-rich aCSF increased MAP 3-fold higher in −/− than W/T. Icv infusion of the ENaC blocker benzamil abolished this enhancement. In telemetered −/− mice on high salt diet (8% NaCl), CSF [Na+], MAP and HR increased significantly, MAP by 30-35 mmHg. These MAP and HR responses were largely prevented by icv benzamil, but only to a minor extent by sc benzamil at the icv rate. We conclude that increased ENaC expression in the brain of Nedd 4-2 −/− mice mediates their hypertensive response to high salt diet, by causing increased sodium levels in the CSF as well as hyper-responsiveness to CSF sodium. These findings highlight the possible causative contribution of CNS ENaC in the etiology of salt-induced hypertension. PMID:22802227

Epithelial Sodium and Acid-Sensing Ion Channels

NASA Astrophysics Data System (ADS)

Kellenberger, Stephan

The epithelial Na+ channel (ENaC) and acid-sensing ion channels (ASICs) are non-voltage-gated Na+ channels that form their own subfamilies within the ENaC/degenerin ion channel family. ASICs are sensors of extracellular pH, and ENaC, whose main function is trans-epithelial Na+ transport, can sense extra- and intra-cellular Na+. In aldosterone-responsive epithelial cells of the kidney, ENaC plays a critical role in the control of sodium balance, blood volume and blood pressure. In airway epithelia, ENaC has a distinct role in controlling fluid reabsorption at the air-liquid interface, thereby determining the rate of mucociliary transport. In taste receptor cells of the tongue, ENaC is involved in salt taste sensation. ASICs have emerged as key sensors for extracellular protons in central and peripheral neurons. Although not all of their physiological and pathological functions are firmly established yet, there is good evidence for a role of ASICs in the brain in learning, expression of fear, and in neurodegeneration after ischaemic stroke. In sensory neurons, ASICs are involved in nociception and mechanosensation. ENaC and ASIC subunits share substantial sequence homology and the conservation of several functional domains. This chapter summarises our current understanding of the physiological functions and of the mechanisms of ion permeation, gating and regulation of ENaC and ASICs.

Acute ENaC Stimulation by cAMP in a Kidney Cell Line is Mediated by Exocytic Insertion from a Recycling Channel Pool

PubMed Central

Butterworth, Michael B.; Edinger, Robert S.; Johnson, John P.; Frizzell, Raymond A.

2005-01-01

Acute hormonal regulation of the epithelial sodium channel (ENaC) in tight epithelia increases transcellular Na+ transport via trafficking of intracellular channels to the apical surface. The fate of the channels removed from the apical surface following agonist washout is less clear. By repetitively stimulating polarized mouse cortical collecting duct (mCCD, MPKCCD14) epithelia, we evaluated the hypothesis that ENaC recycles through an intracellular pool to be available for reinsertion into the apical membrane. Short circuit current (ISC), membrane capacitance (CT), and conductance (GT) were recorded from mCCD epithelia mounted in modified Ussing chambers. Surface biotinylation of ENaC demonstrated an increase in channel number in the apical membrane following cAMP stimulation. This increase was accompanied by a 83 ± 6% (n = 31) increase in ISC and a 15.3 ± 1.5% (n = 15) increase in CT. Selective membrane permeabilization demonstrated that the CT increase was due to an increase in apical membrane capacitance. ISC and CT declined to basal levels on stimulus washout. Repetitive cAMP stimulation and washout (∼1 h each cycle) resulted in response fatigue; ΔISC decreased ∼10% per stimulation–recovery cycle. When channel production was blocked by cycloheximide, ΔISC decreased ∼15% per stimulation cycle, indicating that newly synthesized ENaC contributed a relatively small fraction of the channels mobilized to the apical membrane. Selective block of surface ENaC by benzamil demonstrated that channels inserted from a subapical pool made up >90% of the stimulated ISC, and that on restimulation a large proportion of channels retrieved from the apical surface were reinserted into the apical membrane. Channel recycling was disrupted by brefeldin A, which inhibited ENaC exocytosis, by chloroquine, which inhibited ENaC endocytosis and recycling, and by latrunculin A, which blocked ENaC exocytosis. A compartment model featuring channel populations in the apical membrane and intracellular recycling pool provided an adequate kinetic description of the ISC responses to repetitive stimulation. The model supports the concept of ENaC recycling in response to repetitive cAMP stimulation. PMID:15623897

Acute ENaC stimulation by cAMP in a kidney cell line is mediated by exocytic insertion from a recycling channel pool.

PubMed

Butterworth, Michael B; Edinger, Robert S; Johnson, John P; Frizzell, Raymond A

2005-01-01

Acute hormonal regulation of the epithelial sodium channel (ENaC) in tight epithelia increases transcellular Na(+) transport via trafficking of intracellular channels to the apical surface. The fate of the channels removed from the apical surface following agonist washout is less clear. By repetitively stimulating polarized mouse cortical collecting duct (mCCD, (MPK)CCD(14)) epithelia, we evaluated the hypothesis that ENaC recycles through an intracellular pool to be available for reinsertion into the apical membrane. Short circuit current (I(SC)), membrane capacitance (C(T)), and conductance (G(T)) were recorded from mCCD epithelia mounted in modified Ussing chambers. Surface biotinylation of ENaC demonstrated an increase in channel number in the apical membrane following cAMP stimulation. This increase was accompanied by a 83 +/- 6% (n = 31) increase in I(SC) and a 15.3 +/- 1.5% (n = 15) increase in C(T). Selective membrane permeabilization demonstrated that the C(T) increase was due to an increase in apical membrane capacitance. I(SC) and C(T) declined to basal levels on stimulus washout. Repetitive cAMP stimulation and washout (approximately 1 h each cycle) resulted in response fatigue; DeltaI(SC) decreased approximately 10% per stimulation-recovery cycle. When channel production was blocked by cycloheximide, DeltaI(SC) decreased approximately 15% per stimulation cycle, indicating that newly synthesized ENaC contributed a relatively small fraction of the channels mobilized to the apical membrane. Selective block of surface ENaC by benzamil demonstrated that channels inserted from a subapical pool made up >90% of the stimulated I(SC), and that on restimulation a large proportion of channels retrieved from the apical surface were reinserted into the apical membrane. Channel recycling was disrupted by brefeldin A, which inhibited ENaC exocytosis, by chloroquine, which inhibited ENaC endocytosis and recycling, and by latrunculin A, which blocked ENaC exocytosis. A compartment model featuring channel populations in the apical membrane and intracellular recycling pool provided an adequate kinetic description of the I(SC) responses to repetitive stimulation. The model supports the concept of ENaC recycling in response to repetitive cAMP stimulation.

Plasma Potassium Determines NCC Abundance in Adult Kidney-Specific γENaC Knockout.

PubMed

Boscardin, Emilie; Perrier, Romain; Sergi, Chloé; Maillard, Marc P; Loffing, Johannes; Loffing-Cueni, Dominique; Koesters, Robert; Rossier, Bernard C; Hummler, Edith

2018-03-01

The amiloride-sensitive epithelial sodium channel (ENaC) and the thiazide-sensitive sodium chloride cotransporter (NCC) are key regulators of sodium and potassium and colocalize in the late distal convoluted tubule of the kidney. Loss of the α ENaC subunit leads to a perinatal lethal phenotype characterized by sodium loss and hyperkalemia resembling the human syndrome pseudohypoaldosteronism type 1 (PHA-I). In adulthood, inducible nephron-specific deletion of α ENaC in mice mimics the lethal phenotype observed in neonates, and as in humans, this phenotype is prevented by a high sodium (HNa + )/low potassium (LK + ) rescue diet. Rescue reflects activation of NCC, which is suppressed at baseline by elevated plasma potassium concentration. In this study, we investigated the role of the γ ENaC subunit in the PHA-I phenotype. Nephron-specific γ ENaC knockout mice also presented with salt-wasting syndrome and severe hyperkalemia. Unlike mice lacking α ENaC or β ΕΝaC, an HNa + /LK + diet did not normalize plasma potassium (K + ) concentration or increase NCC activation. However, when K + was eliminated from the diet at the time that γ ENaC was deleted, plasma K + concentration and NCC activity remained normal, and progressive weight loss was prevented. Loss of the late distal convoluted tubule, as well as overall reduced β ENaC subunit expression, may be responsible for the more severe hyperkalemia. We conclude that plasma K + concentration becomes the determining and limiting factor in regulating NCC activity, regardless of Na + balance in γ ENaC-deficient mice. Copyright © 2018 by the American Society of Nephrology.

Inhaled ENaC antisense oligonucleotide ameliorates cystic fibrosis-like lung disease in mice.

PubMed

Crosby, Jeff R; Zhao, Chenguang; Jiang, Chong; Bai, Dong; Katz, Melanie; Greenlee, Sarah; Kawabe, Hiroshi; McCaleb, Michael; Rotin, Daniela; Guo, Shuling; Monia, Brett P

2017-11-01

Epithelial sodium channel (ENaC, Scnn1) hyperactivity in the lung leads to airway surface dehydration and mucus accumulation in cystic fibrosis (CF) patients and in mice with CF-like lung disease. We identified several potent ENaC specific antisense oligonucleotides (ASOs) and tested them by inhalation in mouse models of CF-like lung disease. The inhaled ASOs distributed into lung airway epithelial cells and decreased ENaC expression by inducing RNase H1-dependent degradation of the targeted Scnn1a mRNA. Aerosol delivered ENaC ASO down-regulated mucus marker expression and ameliorated goblet cell metaplasia, inflammation, and airway hyper-responsiveness. Lack of systemic activity of ASOs delivered via the aerosol route ensures the safety of this approach. Our results demonstrate that antisense inhibition of ENaC in airway epithelial cells could be an effective and safe approach for the prevention and reversal of lung symptoms in CF and potentially other inflammatory diseases of the lung. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Sodium 4-phenylbutyrate upregulates ENaC and sodium absorption in T84 cells.

PubMed

Iordache, Claudiu; Duszyk, Marek

2007-01-15

Butyrate and other short-chain fatty acids (SCFA), produced by colonic bacterial flora, affect numerous epithelial cell functions. To better understand how SCFA regulate ion transport, we investigated the effects of 4-phenylbutyrate (4-PBA) on Na(+) absorption in T84 cells. Under standard cell culture conditions, the short circuit current did not display any amiloride-sensitive Na(+) absorption and was wholly representative of Cl(-) secretion. However, when T84 cells were grown in the presence of 5 mM 4-PBA, a gradual appearance of amiloride-sensitive Na(+) channel (ENaC) activity was observed that reached a plateau after 24 h. Quantitative RT-PCR and Western blot studies of ENaC subunit expression indicated that 4-PBA stimulated alpha and gamma subunits. Trichostatin A, an inhibitor of histone deacetylase, mimicked the effects of 4-PBA, suggesting that 4-PBA affects ENaC expression by inhibiting deacetylases. 4-PBA had no effect on ENaC expression in airway epithelial cells indicating tissue-specific effect. We conclude that butyrate plays an important role in regulating colonic Na(+) absorption by increasing ENaC transcription and activity.

NVP-QBE170: an inhaled blocker of the epithelial sodium channel with a reduced potential to induce hyperkalaemia

PubMed Central

Coote, K J; Paisley, D; Czarnecki, S; Tweed, M; Watson, H; Young, A; Sugar, R; Vyas, M; Smith, N J; Baettig, U; Groot-Kormelink, P J; Gosling, M; Lock, R; Ethell, B; Williams, G; Schumacher, A; Harris, J; Abraham, W M; Sabater, J; Poll, C T; Faller, T; Collingwood, S P; Danahay, H

2015-01-01

Background and Purpose Inhaled amiloride, a blocker of the epithelial sodium channel (ENaC), enhances mucociliary clearance (MCC) in cystic fibrosis (CF) patients. However, the dose of amiloride is limited by the mechanism-based side effect of hyperkalaemia resulting from renal ENaC blockade. Inhaled ENaC blockers with a reduced potential to induce hyperkalaemia provide a therapeutic strategy to improve mucosal hydration and MCC in the lungs of CF patients. The present study describes the preclinical profile of a novel ENaC blocker, NVP-QBE170, designed for inhaled delivery, with a reduced potential to induce hyperkalaemia. Experimental Approach The in vitro potency and duration of action of NVP-QBE170 were compared with amiloride and a newer ENaC blocker, P552-02, in primary human bronchial epithelial cells (HBECs) by short-circuit current. In vivo efficacy and safety were assessed in guinea pig (tracheal potential difference/hyperkalaemia), rat (hyperkalaemia) and sheep (MCC). Key Results In vitro, NVP-QBE170 potently inhibited ENaC function in HBEC and showed a longer duration of action to comparator molecules. In vivo, intratracheal (i.t.) instillation of NVP-QBE170 attenuated ENaC activity in the guinea pig airways with greater potency and duration of action than that of amiloride without inducing hyperkalaemia in either guinea pig or rat. Dry powder inhalation of NVP-QBE170 by conscious sheep increased MCC and was better than inhaled hypertonic saline in terms of efficacy and duration of action. Conclusions and Implications NVP-QBE170 highlights the potential for inhaled ENaC blockers to exhibit efficacy in the airways with a reduced risk of hyperkalaemia, relative to existing compounds. PMID:25573195

NVP-QBE170: an inhaled blocker of the epithelial sodium channel with a reduced potential to induce hyperkalaemia.

PubMed

Coote, K J; Paisley, D; Czarnecki, S; Tweed, M; Watson, H; Young, A; Sugar, R; Vyas, M; Smith, N J; Baettig, U; Groot-Kormelink, P J; Gosling, M; Lock, R; Ethell, B; Williams, G; Schumacher, A; Harris, J; Abraham, W M; Sabater, J; Poll, C T; Faller, T; Collingwood, S P; Danahay, H

2015-06-01

Inhaled amiloride, a blocker of the epithelial sodium channel (ENaC), enhances mucociliary clearance (MCC) in cystic fibrosis (CF) patients. However, the dose of amiloride is limited by the mechanism-based side effect of hyperkalaemia resulting from renal ENaC blockade. Inhaled ENaC blockers with a reduced potential to induce hyperkalaemia provide a therapeutic strategy to improve mucosal hydration and MCC in the lungs of CF patients. The present study describes the preclinical profile of a novel ENaC blocker, NVP-QBE170, designed for inhaled delivery, with a reduced potential to induce hyperkalaemia. The in vitro potency and duration of action of NVP-QBE170 were compared with amiloride and a newer ENaC blocker, P552-02, in primary human bronchial epithelial cells (HBECs) by short-circuit current. In vivo efficacy and safety were assessed in guinea pig (tracheal potential difference/hyperkalaemia), rat (hyperkalaemia) and sheep (MCC). In vitro, NVP-QBE170 potently inhibited ENaC function in HBEC and showed a longer duration of action to comparator molecules. In vivo, intratracheal (i.t.) instillation of NVP-QBE170 attenuated ENaC activity in the guinea pig airways with greater potency and duration of action than that of amiloride without inducing hyperkalaemia in either guinea pig or rat. Dry powder inhalation of NVP-QBE170 by conscious sheep increased MCC and was better than inhaled hypertonic saline in terms of efficacy and duration of action. NVP-QBE170 highlights the potential for inhaled ENaC blockers to exhibit efficacy in the airways with a reduced risk of hyperkalaemia, relative to existing compounds. © 2015 The British Pharmacological Society.

CFTR fails to inhibit the epithelial sodium channel ENaC expressed in Xenopus laevis oocytes

PubMed Central

Nagel, G; Barbry, P; Chabot, H; Brochiero, E; Hartung, K; Grygorczyk, R

2005-01-01

The cystic fibrosis transmembrane conductance regulator (CFTR) plays a crucial role in regulating fluid secretion by the airways, intestines, sweat glands and other epithelial tissues. It is well established that the CFTR is a cAMP-activated, nucleotide-dependent anion channel, but additional functions are often attributed to it, including regulation of the epithelial sodium channel (ENaC). The absence of CFTR-dependent ENaC inhibition and the resulting sodium hyperabsorption were postulated to be a major electrolyte transport abnormality in cystic fibrosis (CF)-affected epithelia. Several ex vivo studies, including those that used the Xenopus oocyte expression system, have reported ENaC inhibition by activated CFTR, but contradictory results have also been obtained. Because CFTR–ENaC interactions have important implications in the pathogenesis of CF, the present investigation was undertaken by our three independent laboratories to resolve whether CFTR regulates ENaC in oocytes and to clarify potential sources of previously reported dissimilar observations. Using different experimental protocols and a wide range of channel expression levels, we found no evidence that activated CFTR regulates ENaC when oocyte membrane potential was carefully clamped. We determined that an apparent CFTR-dependent ENaC inhibition could be observed when resistance in series with the oocyte membrane was not low enough or the feedback voltage gain was not high enough. We suggest that the inhibitory effect of CFTR on ENaC reported in some earlier oocyte studies could be attributed to problems arising from high levels of channel expression and suboptimal recording conditions, that is, large series resistance and/or insufficient feedback voltage gain. PMID:15746174

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

Jeggle, Pia; Smith, Ewan St. J.; Stewart, Andrew P.

ASIC and ENaC are co-expressed in various cell types, and there is evidence for a close association between them. Here, we used atomic force microscopy (AFM) to determine whether ASIC1a and ENaC subunits are able to form cross-clade hybrid ion channels. ASIC1a and ENaC could be co-isolated from detergent extracts of tsA 201 cells co-expressing the two subunits. Isolated proteins were incubated with antibodies against ENaC and Fab fragments against ASIC1a. AFM imaging revealed proteins that were decorated by both an antibody and a Fab fragment with an angle of ∼120° between them, indicating the formation of ASIC1a/ENaC heterotrimers. -more » Highlights: • There is evidence for a close association between ASIC and ENaC. • We used AFM to test whether ASIC1a and ENaC subunits form cross-clade ion channels. • Isolated proteins were incubated with subunit-specific antibodies and Fab fragments. • Some proteins were doubly decorated at ∼120° by an antibody and a Fab fragment. • Our results indicate the formation of ASIC1a/ENaC heterotrimers.« less

Novel small molecule epithelial sodium channel inhibitors as potential therapeutics in cystic fibrosis - a patent evaluation.

PubMed

Schoenberger, Matthias; Althaus, Mike

2013-10-01

Novel molecular platforms for epithelial sodium channel (ENaC) modulators are claimed in the following six patents: WO2012035158(A1); WO2009074575(A2); WO2011028740(A1); WO2009150137(A2); WO2011079087(A1); WO2008135557(A1). These ENaC inhibitors may be used in blocking transepithelial sodium and consequently water absorption across airway epithelia. This may result in airway rehydration and enhanced mucociliary clearance in patients with cystic fibrosis (CF) lung disease. All inhibitors resemble the classical ENaC blocker amiloride but follow different strategies to increase structural diversity in a sterically tolerant region. These substitutions can be modified to i) enhance potency of ENaC inhibition; ii) reduce epithelial permeability; and iii) broaden applicability in order to be used as potential drugs for CF therapy. Most of the claims and patent data are supported by the currently available literature. The patents deliver a solid chemical basis for a variety of chemical modifications of the ENaC inhibitor amiloride. These modifications may result in the development of a novel, applicable ENaC inhibitors which may have lasting effects on diseased airways and may achieve airway rehydration and enhanced mucociliary clearance in CF lung disease.

Regulation of the epithelial Na+ channel by membrane tension.

PubMed

Awayda, M S; Subramanyam, M

1998-08-01

The sensitivity of alphabetagamma rat epithelial Na+ channel (rENaC) to osmotically or mechanically induced changes of membrane tension was investigated in the Xenopus oocyte expression system, using both dual electrode voltage clamp and cell-attached patch clamp methodologies. ENaC whole-cell currents were insensitive to mechanical cell swelling caused by direct injection of 90 or 180 nl of 100-mM KCl. Similarly, ENaC whole-cell currents were insensitive to osmotic cell swelling caused by a 33% decrease of bathing solution osmolarity. The lack of an effect of cell swelling on ENaC was independent of the status of the actin cytoskeleton, as ENaC remained insensitive to osmotic and mechanical cell swelling in oocytes pretreated with cytochalasin B for 2-5 h. This apparent insensitivity of ENaC to increased cell volume and changes of membrane tension was also observed at the single channel level in membrane patches subjected to negative or positive pressures of 5 or 10 in. of water. However, and contrary to the lack of an effect of cell swelling, ENaC currents were inhibited by cell shrinking. A 45-min incubation in a 260-mosmol solution (a 25% increase of solution osmolarity) caused a decrease of ENaC currents (at -100 mV) from -3.42 +/- 0.34 to -2.02 +/- 0.23 microA (n = 6). This decrease of current with cell shrinking was completely blocked by pretreatment of oocytes with cytochalasin B, indicating that these changes of current are not likely related to a direct effect of cell shrinking. We conclude that alpha beta gamma rENaC is not directly mechanosensitive when expressed in a system that can produce a channel with identical properties to those found in native epithelia.

ENaC activity in collecting ducts modulates NCC in cirrhotic mice.

PubMed

Mordasini, David; Loffing-Cueni, Dominique; Loffing, Johannes; Beatrice, Rohrbach; Maillard, Marc P; Hummler, Edith; Burnier, Michel; Escher, Geneviève; Vogt, Bruno

2015-12-01

Cirrhosis is a frequent and severe disease, complicated by renal sodium retention leading to ascites and oedema. A better understanding of the complex mechanisms responsible for renal sodium handling could improve clinical management of sodium retention. Our aim was to determine the importance of the amiloride-sensitive epithelial sodium channel (ENaC) in collecting ducts in compensate and decompensate cirrhosis. Bile duct ligation was performed in control mice (CTL) and collecting duct-specific αENaC knockout (KO) mice, and ascites development, aldosterone plasma concentration, urinary sodium/potassium ratio and sodium transporter expression were compared. Disruption of ENaC in collecting ducts (CDs) did not alter ascites development, urinary sodium/potassium ratio, plasma aldosterone concentrations or Na,K-ATPase abundance in CCDs. Total αENaC abundance in whole kidney increased in cirrhotic mice of both genotypes and cleaved forms of α and γ ENaC increased only in ascitic mice of both genotypes. The sodium chloride cotransporter (NCC) abundance was lower in non-ascitic KO, compared to non-ascitic CTL, and increased when ascites appeared. In ascitic mice, the lack of αENaC in CDs induced an upregulation of total ENaC and NCC and correlated with the cleavage of ENaC subunits. This revealed compensatory mechanisms which could also take place when treating the patients with diuretics. These compensatory mechanisms should be considered for future development of therapeutic strategies.

Gadolinium released by the linear gadolinium-based contrast-agent Gd-DTPA decreases the activity of human epithelial Na+ channels (ENaCs).

PubMed

Knoepp, Fenja; Bettmer, Joerg; Fronius, Martin

2017-05-01

Gadolinium-based-contrast-agents (GBCAs) are used for magnetic-resonance-imaging and associated with renal and cardiovascular adverse reactions caused by released Gd 3+ ions. Gd 3+ is also a modulator of mechano-gated ion channels, including the epithelial Na + channel (ENaC) that is expressed in kidney epithelium and the vasculature. ENaC is important for salt-/water homeostasis and blood pressure regulation and a likely target of released Gd 3+ from GBCAs causing the above-mentioned adverse reactions. Therefore this study examined the effect of Gd 3+ and GBCAs on ENaC's activity. Human αβγENaC was expressed in Xenopus laevis oocytes and exposed to Gd 3+ , linear (Gd-DTPA, Magnevist) or cyclic (Dotarem) GBCAs. Transmembrane ion-currents (I M ) were recorded by the two-electrode-voltage-clamp technique and Gd 3+ -release by Gd-DTPA was confirmed by inductively coupled plasma-mass spectrometry. Gd 3+ exerts biphasic effects on ENaC's activity: ≤0.3mmol/l decreased I M which was preventable by DEPC (modifies histidines). Strikingly Gd 3+ ≥0.4mmol/l increased I M and this effect was prevented by cysteine-modifying MTSEA. Linear Gd-DTPA and Magnevist mimicked the effect of ≤0.3mmol/l Gd 3+ , whereas the chelator DTPA showed no effect. Gd 3+ and Gd-DTPA increased the IC 50 for amiloride, but did not affect ENaC's self-inhibition. Interestingly, cyclic Gd-DOTA (Dotarem) increased I M to a similar extent as its chelator DOTA, suggesting that the chelator rather than released Gd 3+ is responsible for this effect. These results confirm Gd 3+ -release from linear Gd-DTPA and indicate that the released Gd 3+ amount is sufficient to interfere with ENaC's activity to provide putative explanations for GBCA-related adverse effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Regulation of blood pressure and renal function by NCC and ENaC: lessons from genetically engineered mice.

PubMed

Verouti, Sophia N; Boscardin, Emilie; Hummler, Edith; Frateschi, Simona

2015-04-01

The activity of the thiazide-sensitive Na(+)/Cl(-) cotransporter (NCC) and of the amiloride-sensitive epithelial Na(+) channel (ENaC) is pivotal for blood pressure regulation. NCC is responsible for Na(+) reabsorption in the distal convoluted tubule (DCT) of the nephron, while ENaC reabsorbs the filtered Na(+) in the late DCT and in the cortical collecting ducts (CCD) providing the final renal adjustment to Na(+) balance. Here, we aim to highlight the recent advances made using transgenic mouse models towards the understanding of the regulation of NCC and ENaC function relevant to the control of sodium balance and blood pressure. We thus like to pave the way for common mechanisms regulating these two sodium-transporting proteins and their potential implication in structural remodeling of the nephron segments and Na(+) and Cl(-) reabsorption. Copyright © 2015 Elsevier Ltd. All rights reserved.

Identification of Extracellular Domain Residues Required for Epithelial Na+ Channel Activation by Acidic pH

PubMed Central

Collier, Daniel M.; Peterson, Zerubbabel J.; Blokhin, Ilya O.; Benson, Christopher J.; Snyder, Peter M.

2012-01-01

A growing body of evidence suggests that the extracellular domain of the epithelial Na+ channel (ENaC) functions as a sensor that fine tunes channel activity in response to changes in the extracellular environment. We previously found that acidic pH increases the activity of human ENaC, which results from a decrease in Na+ self-inhibition. In the current work, we identified extracellular domain residues responsible for this regulation. We found that rat ENaC is less sensitive to pH than human ENaC, an effect mediated in part by the γ subunit. We identified a group of seven residues in the extracellular domain of γENaC (Asp-164, Gln-165, Asp-166, Glu-292, Asp-335, His-439, and Glu-455) that, when individually mutated to Ala, decreased proton activation of ENaC. γE455 is conserved in βENaC (Glu-446); mutation of this residue to neutral amino acids (Ala, Cys) reduced ENaC stimulation by acidic pH, whereas reintroduction of a negative charge (by MTSES modification of Cys) restored pH regulation. Combination of the seven γENaC mutations with βE446A generated a channel that was not activated by acidic pH, but inhibition by alkaline pH was intact. Moreover, these mutations reduced the effect of pH on Na+ self-inhibition. Together, the data identify eight extracellular domain residues in human β- and γENaC that are required for regulation by acidic pH. PMID:23060445

Scoring of predicted GRK2 phosphorylation sites in Nedd4-2.

PubMed

Arthur, Jonathan W; Sanchez-Perez, Angeles; Cook, David I

2006-09-15

Epithelial Na(+) channels (ENaC) mediate the transport of sodium (Na) across epithelia in the kidney, gut and lungs and are required for blood pressure regulation. They are inhibited by ubiquitin protein ligases, such as Nedd4-2. These ligases bind to proline-rich motifs (PY motifs) present in the C-termini of ENaC subunits. Loss of this inhibition leads to hypertension. We have previously reported that ENaC channels are maintained in the active state by the G protein coupled receptor kinase, GRK2. The enzyme has been implicated in the development of essential hypertension [R. D. Feldman (2002) Mol. Pharmacol., 61, 707-709]. Additional findings in our lab pointed towards a possible role for GRK2 in the phosphorylation and inactivation of Nedd4-2. We have predicted GRK2 phosphorylation sites on Nedd4-2 by combining sequence analysis, homology modeling and surface accessibility calculations. A total of 24 potential phosphorylation sites were predicted by sequence analysis. Of these, 16 could be modeled using homology modeling and 6 of these were found to have sufficient surface exposure to be accessible to the GRK2 enzyme responsible for the phosphorylation of Nedd4-2. The method provides an ordered list of the most probable GRK2 phosphorylation sites on Nedd4-2 providing invaluable guidance to future experimental studies aimed at mutating certain Nedd4-2 residues in order to prevent phosphorylation by GRK2. The method developed could be applied in a wide variety of biological applications involving the binding of one molecule to a protein. The relative effectiveness of the technique is determined mainly by the quality of the homology model built for the protein of interest. jarthur@med.usyd.edu.au

Hydration status regulates sodium flux and inflammatory pathways through epithelial sodium channel (ENaC) in the skin.

PubMed

Xu, Wei; Hong, Seok Jong; Zeitchek, Michael; Cooper, Garry; Jia, Shengxian; Xie, Ping; Qureshi, Hannan A; Zhong, Aimei; Porterfield, Marshall D; Galiano, Robert D; Surmeier, D James; Mustoe, Thomas A

2015-03-01

Although it is known that the inflammatory response that results from disruption of epithelial barrier function after injury results in excessive scarring, the upstream signals remain unknown. It has also been observed that epithelial disruption results in reduced hydration status and that the use of occlusive dressings that prevent water loss from wounds decreases scar formation. We hypothesized that hydration status changes sodium homeostasis and induces sodium flux in keratinocytes, which result in activation of pathways responsible for keratinocyte-fibroblast signaling and ultimately lead to activation of fibroblasts. Here, we demonstrate that perturbations in epithelial barrier function lead to increased sodium flux in keratinocytes. We identified that sodium flux in keratinocytes is mediated by epithelial sodium channels (ENaCs) and causes increased secretion of proinflammatory cytokines, which activate fibroblast via the cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) pathway. Similar changes in signal transduction and sodium flux occur by increased sodium concentration, which simulates reduced hydration, in the media in epithelial cultures or human ex vivo skin cultures. Blockade of ENaC, prostaglandin synthesis, or PGE2 receptors all reduce markers of fibroblast activation and collagen synthesis. In addition, employing a validated in vivo excessive scar model in the rabbit ear, we demonstrate that utilization of either an ENaC blocker or a COX-2 inhibitor results in a marked reduction in scarring. Other experiments demonstrate that the activation of COX-2 in response to increased sodium flux is mediated through the PIK3/Akt pathway. Our results indicate that ENaC responds to small changes in sodium concentration with inflammatory mediators and suggest that the ENaC pathway is a potential target for a strategy to prevent fibrosis.

TGF-β directs trafficking of the epithelial sodium channel ENaC which has implications for ion and fluid transport in acute lung injury.

PubMed

Peters, Dorothea M; Vadász, István; Wujak, Lukasz; Wygrecka, Malgorzata; Olschewski, Andrea; Becker, Christin; Herold, Susanne; Papp, Rita; Mayer, Konstantin; Rummel, Sebastian; Brandes, Ralph P; Günther, Andreas; Waldegger, Siegfried; Eickelberg, Oliver; Seeger, Werner; Morty, Rory E

2014-01-21

TGF-β is a pathogenic factor in patients with acute respiratory distress syndrome (ARDS), a condition characterized by alveolar edema. A unique TGF-β pathway is described, which rapidly promoted internalization of the αβγ epithelial sodium channel (ENaC) complex from the alveolar epithelial cell surface, leading to persistence of pulmonary edema. TGF-β applied to the alveolar airspaces of live rabbits or isolated rabbit lungs blocked sodium transport and caused fluid retention, which--together with patch-clamp and flow cytometry studies--identified ENaC as the target of TGF-β. TGF-β rapidly and sequentially activated phospholipase D1, phosphatidylinositol-4-phosphate 5-kinase 1α, and NADPH oxidase 4 (NOX4) to produce reactive oxygen species, driving internalization of βENaC, the subunit responsible for cell-surface stability of the αβγENaC complex. ENaC internalization was dependent on oxidation of βENaC Cys(43). Treatment of alveolar epithelial cells with bronchoalveolar lavage fluids from ARDS patients drove βENaC internalization, which was inhibited by a TGF-β neutralizing antibody and a Tgfbr1 inhibitor. Pharmacological inhibition of TGF-β signaling in vivo in mice, and genetic ablation of the nox4 gene in mice, protected against perturbed lung fluid balance in a bleomycin model of lung injury, highlighting a role for both proximal and distal components of this unique ENaC regulatory pathway in lung fluid balance. These data describe a unique TGF-β-dependent mechanism that regulates ion and fluid transport in the lung, which is not only relevant to the pathological mechanisms of ARDS, but might also represent a physiological means of acutely regulating ENaC activity in the lung and other organs.

Aldosterone Modulates the Association between NCC and ENaC.

PubMed

Wynne, Brandi M; Mistry, Abinash C; Al-Khalili, Otor; Mallick, Rickta; Theilig, Franziska; Eaton, Douglas C; Hoover, Robert S

2017-06-23

Distal sodium transport is a final step in the regulation of blood pressure. As such, understanding how the two main sodium transport proteins, the thiazide-sensitive sodium chloride cotransporter (NCC) and the epithelial sodium channel (ENaC), are regulated is paramount. Both are expressed in the late distal nephron; however, no evidence has suggested that these two sodium transport proteins interact. Recently, we established that these two sodium transport proteins functionally interact in the second part of the distal nephron (DCT2). Given their co-localization within the DCT2, we hypothesized that NCC and ENaC interactions might be modulated by aldosterone (Aldo). Aldo treatment increased NCC and αENaC colocalization (electron microscopy) and interaction (coimmunoprecipitation). Finally, with co-expression of the Aldo-induced protein serum- and glucocorticoid-inducible kinase 1 (SGK1), NCC and αENaC interactions were increased. These data demonstrate that Aldo promotes increased interaction of NCC and ENaC, within the DCT2 revealing a novel method of regulation for distal sodium reabsorption.

Molecular genetics of Liddle's syndrome.

PubMed

Yang, Kun-Qi; Xiao, Yan; Tian, Tao; Gao, Ling-Gen; Zhou, Xian-Liang

2014-09-25

Liddle's syndrome, an autosomal dominant form of monogenic hypertension, is characterized by salt-sensitive hypertension with early penetrance, hypokalemia, metabolic alkalosis, suppression of plasma rennin activity and aldosterone secretion, and a clear-cut response to epithelial sodium channel (ENaC) blockers but not spironolactone therapy. Our understanding of ENaCs and Na(+) transport defects has expanded greatly over the past two decades and provides detailed insight into the molecular basis of Liddle's syndrome. In this review, we offer an overview of recent advances in understanding the molecular genetics of Liddle's syndrome, involving mutation analysis, molecular mechanisms and genetic testing. The ENaC in the distal nephron is composed of α, β and γ subunits that share similar structures. Mutations associated with Liddle's syndrome are positioned in either β or γ subunits and disturb or truncate a conserved proline-rich sequence (i.e., PY motif), leading to constitutive activation of the ENaC. Genetic testing has made it possible to make accurate diagnoses and develop tailored therapies for mutation carriers. Copyright © 2014 Elsevier B.V. All rights reserved.

Scaffold Protein Connector Enhancer of Kinase Suppressor of Ras Isoform 3 (CNK3) Coordinates Assembly of a Multiprotein Epithelial Sodium Channel (ENaC)-regulatory Complex*

PubMed Central

Soundararajan, Rama; Ziera, Tim; Koo, Eric; Ling, Karen; Wang, Jian; Borden, Steffen A.; Pearce, David

2012-01-01

Hormone regulation of ion transport in the kidney tubules is essential for fluid and electrolyte homeostasis in vertebrates. A large body of evidence has suggested that transporters and channels exist in multiprotein regulatory complexes; however, relatively little is known about the composition of these complexes or their assembly. The epithelial sodium channel (ENaC) in particular is tightly regulated by the salt-regulatory hormone aldosterone, which acts at least in part by increasing expression of the serine-threonine kinase SGK1. Here we show that aldosterone induces the formation of a 1.0–1.2-MDa plasma membrane complex, which includes ENaC, SGK1, and the ENaC inhibitor Nedd4-2, a key target of SGK1. We further show that this complex contains the PDZ domain-containing protein connector enhancer of kinase suppressor of Ras isoform 3 (CNK3). CNK3 physically interacts with ENaC, Nedd4-2, and SGK1; enhances the interactions among them; and stimulates ENaC function in a PDZ domain-dependent, aldosterone-induced manner. These results strongly suggest that CNK3 is a molecular scaffold, which coordinates the assembly of a multiprotein ENaC-regulatory complex and hence plays a central role in Na+ homeostasis. PMID:22851176

The role of lung inflation and sodium transport in airway liquid clearance during lung aeration in newborn rabbits.

PubMed

Siew, Melissa L; Wallace, Megan J; Allison, Beth J; Kitchen, Marcus J; te Pas, Arjan B; Islam, M Sirajul; Lewis, Robert A; Fouras, Andreas; Yagi, Naoto; Uesugi, Kentaro; Hooper, Stuart B

2013-04-01

Recent phase-contrast X-ray imaging studies suggest that inspiration primarily drives lung aeration and airway liquid clearance at birth, which questions the role of adrenaline-induced activation of epithelial sodium channels (ENaCs). We hypothesized that pressures generated by inspiration have a greater role in airway liquid clearance than do ENaCs after birth. Rabbit pups (30 d of gestation) were delivered and sedated, and 0.1 ml of saline (S) or amiloride (Am; an ENaC inhibitor) was instilled into the lungs before mechanical ventilation. Two other groups (30 d of gestation) were treated similarly but were also given adrenaline (S/Ad and Am/Ad) before mechanical ventilation. Amiloride and adrenaline did not affect functional residual capacity (FRC) recruitment (P > 0.05). Amiloride increased the rate of FRC loss between inflations (Am: -5.2 ± 0.6 ml/kg/s), whereas adrenaline reduced the rate of FRC loss (S/Ad: -1.9 ± 0.3 ml/kg/s) as compared with saline-treated controls (S: -3.5 ± -0.6 ml/kg/s; P < 0.05). These data indicate that inspiration is a major determinant of airway liquid clearance and FRC development during positive pressure ventilation. Although ENaC inhibition and adrenaline administration had no detectable effect on FRC development, ENaC may help to prevent liquid from re-entering the airways during expiration.

The sodium chloride cotransporter (NCC) and epithelial sodium channel (ENaC) associate.

PubMed

Mistry, Abinash C; Wynne, Brandi M; Yu, Ling; Tomilin, Viktor; Yue, Qiang; Zhou, Yiqun; Al-Khalili, Otor; Mallick, Rickta; Cai, Hui; Alli, Abdel A; Ko, Benjamin; Mattheyses, Alexa; Bao, Hui-Fang; Pochynyuk, Oleh; Theilig, Franziska; Eaton, Douglas C; Hoover, Robert S

2016-10-01

The thiazide-sensitive sodium chloride cotransporter (NCC) and the epithelial sodium channel (ENaC) are two of the most important determinants of salt balance and thus systemic blood pressure. Abnormalities in either result in profound changes in blood pressure. There is one segment of the nephron where these two sodium transporters are coexpressed, the second part of the distal convoluted tubule. This is a key part of the aldosterone-sensitive distal nephron, the final regulator of salt handling in the kidney. Aldosterone is the key hormonal regulator for both of these proteins. Despite these shared regulators and coexpression in a key nephron segment, associations between these proteins have not been investigated. After confirming apical localization of these proteins, we demonstrated the presence of functional transport proteins and native association by blue native PAGE. Extensive coimmunoprecipitation experiments demonstrated a consistent interaction of NCC with α- and γ-ENaC. Mammalian two-hybrid studies demonstrated direct binding of NCC to ENaC subunits. Fluorescence resonance energy transfer and immunogold EM studies confirmed that these transport proteins are within appropriate proximity for direct binding. Additionally, we demonstrate that there are functional consequences of this interaction, with inhibition of NCC affecting the function of ENaC. This novel finding of an association between ENaC and NCC could alter our understanding of salt transport in the distal tubule. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Rab27a regulates epithelial sodium channel (ENaC) activity through synaptotagmin-like protein (SLP-5) and Munc13-4 effector mechanism

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

Saxena, Sunil K.; Horiuchi, Hisanori; Fukuda, Mitsunori

Liddle's syndrome (excessive absorption of sodium ions) and PHA-1 (pseudohypoaldosteronism type 1) with decreased sodium absorption are caused by the mutations in the amiloride-sensitive epithelial sodium channel ENaC. Rab proteins are small GTPases involved in vesicle transport, docking, and fusion. Earlier, we reported that Rab27a inhibits ENaC-mediated currents through protein-protein interaction in HT-29 cells. We hereby report that Rab27a-dependent inhibition is associated with the GTP/GDP status as constitutively active or GTPase-deficient mutant Q78L inhibits amiloride-sensitive currents whereas GDP-locked inactive mutant T23N showed no effect. In order to further explore the molecular mechanism of this regulation, we performed competitive assays withmore » two Rab27a-binding proteins: synaptotagmin-like protein (SLP-5) and Munc13-4 (a putative priming factor for exocytosis). Both proteins eliminate negative modulation of Rab27a on ENaC function. The SLP-5 reversal of Rab27a effect was restricted to C-terminal C2A/C2B domains assigned for putative phospholipids-binding function while the Rab27a-binding SHD motif imparted higher inhibition. The ENaC-mediated currents remain unaffected by Rab27a though SLP-5 appears to strongly bind it. The immunoprecipitation experiments suggest that in the presence of excessive Munc13-4 and SLP-5 proteins, Rab27a interaction with ENaC is diminished. Munc13-4 and SLP-5 limit the Rab27a availability to ENaC, thus minimizing its effect on channel function. These observations decisively prove that Rab27a inhibits ENaC function through a complex mechanism that involves GTP/GDP status, and protein-protein interactions involving Munc13-4 and SLP-5 effector proteins.« less

Cyp2c44 epoxygenase is essential for preventing the renal sodium absorption during increasing dietary potassium intake.

PubMed

Sun, Peng; Antoun, Joseph; Lin, Dao-Hong; Yue, Peng; Gotlinger, Katherine H; Capdevila, Jorge; Wang, Wen-Hui

2012-02-01

The aim of this study is to test whether the Cyp2c44 epoxygenase-dependent metabolism of arachidonic acid prevents the hypertensive effect of a high K (HK) intake by inhibiting the epithelial sodium channel (ENaC) activity. A HK intake elevated Cyp2c44 mRNA expression and 11,12-epoxyeicosatrienoic acid levels in the cortical collecting duct in Cyp2c44(+/+) mice (wild-type [wt]). However, an HK intake failed to increase 11,12-epoxyeicosatrienoic acid formation in the cortical collecting ducts of Cyp2c44(-/-) mice. Moreover, increasing K intake enhanced arachidonic acid-induced inhibition of ENaC in the wt but not in Cyp2c44(-/-) mice. In contrast, 11,12-epoxyeicosatrienoic acid, a Cyp2c44 metabolite, inhibited ENaC in the wt and Cyp2c44(-/-) mice. The notion that Cyp2c44 is the epoxygenase responsible for mediating the inhibitory effects of arachidonic acid on ENaC is further suggested by the observation that inhibiting Cyp-epoxygenase increased the whole-cell Na currents in principal cells of wt but not in Cyp2c44(-/-) mice. Feeding mice with an HK diet raised the systemic blood pressures of Cyp2c44(-/-) mice but was without an effect on wt mice. Moreover, application of amiloride abolished the HK-induced hypertension in Cyp2c44(-/-) mice. The HK-induced hypertension of Cyp2c44(-/-) mice was accompanied by decreasing 24-hour urinary Na excretion and increasing the plasma Na concentration, and the effects were absent in wt mice. In contrast, disruption of the Cyp2c44 gene did not alter K excretion. We conclude that Cyp2c44 epoxygenase mediates the inhibitory effect of arachidonic acid on ENaC and that Cyp2c44 functions as an HK-inducible antihypertensive enzyme responsible for inhibiting ENaC activity and Na absorption in the aldosterone-sensitive distal nephron.

Effective silencing of ENaC by siRNA delivered with epithelial-targeted nanocomplexes in human cystic fibrosis cells and in mouse lung.

PubMed

Tagalakis, Aristides D; Munye, Mustafa M; Ivanova, Rositsa; Chen, Hanpeng; Smith, Claire M; Aldossary, Ahmad M; Rosa, Luca Z; Moulding, Dale; Barnes, Josephine L; Kafetzis, Konstantinos N; Jones, Stuart A; Baines, Deborah L; Moss, Guy W J; O'Callaghan, Christopher; McAnulty, Robin J; Hart, Stephen L

2018-05-10

Loss of the cystic fibrosis transmembrane conductance regulator in cystic fibrosis (CF) leads to hyperabsorption of sodium and fluid from the airway due to upregulation of the epithelial sodium channel (ENaC). Thickened mucus and depleted airway surface liquid (ASL) then lead to impaired mucociliary clearance. ENaC regulation is thus a promising target for CF therapy. Our aim was to develop siRNA nanocomplexes that mediate effective silencing of airway epithelial ENaC in vitro and in vivo with functional correction of epithelial ion and fluid transport. We investigated translocation of nanocomplexes through mucus and their transfection efficiency in primary CF epithelial cells grown at air-liquid interface (ALI).Short interfering RNA (SiRNA)-mediated silencing was examined by quantitative RT-PCR and western analysis of ENaC. Transepithelial potential (V t ), short circuit current (I sc ), ASL depth and ciliary beat frequency (CBF) were measured for functional analysis. Inflammation was analysed by histological analysis of normal mouse lung tissue sections. Nanocomplexes translocated more rapidly than siRNA alone through mucus. Transfections of primary CF epithelial cells with nanocomplexes targeting αENaC siRNA, reduced αENaC and βENaC mRNA by 30%. Transfections reduced V t , the amiloride-sensitive I sc and mucus protein concentration while increasing ASL depth and CBF to normal levels. A single dose of siRNA in mouse lung silenced ENaC by approximately 30%, which persisted for at least 7 days. Three doses of siRNA increased silencing to approximately 50%. Nanoparticle-mediated delivery of ENaCsiRNA to ALI cultures corrected aspects of the mucociliary defect in human CF cells and offers effective delivery and silencing in vivo. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

TGF-β directs trafficking of the epithelial sodium channel ENaC which has implications for ion and fluid transport in acute lung injury

PubMed Central

Peters, Dorothea M.; Vadász, István; Wujak, Łukasz; Wygrecka, Małgorzata; Olschewski, Andrea; Becker, Christin; Herold, Susanne; Papp, Rita; Mayer, Konstantin; Rummel, Sebastian; Brandes, Ralph P.; Günther, Andreas; Waldegger, Siegfried; Eickelberg, Oliver; Seeger, Werner; Morty, Rory E.

2014-01-01

TGF-β is a pathogenic factor in patients with acute respiratory distress syndrome (ARDS), a condition characterized by alveolar edema. A unique TGF-β pathway is described, which rapidly promoted internalization of the αβγ epithelial sodium channel (ENaC) complex from the alveolar epithelial cell surface, leading to persistence of pulmonary edema. TGF-β applied to the alveolar airspaces of live rabbits or isolated rabbit lungs blocked sodium transport and caused fluid retention, which—together with patch-clamp and flow cytometry studies—identified ENaC as the target of TGF-β. TGF-β rapidly and sequentially activated phospholipase D1, phosphatidylinositol-4-phosphate 5-kinase 1α, and NADPH oxidase 4 (NOX4) to produce reactive oxygen species, driving internalization of βENaC, the subunit responsible for cell-surface stability of the αβγENaC complex. ENaC internalization was dependent on oxidation of βENaC Cys43. Treatment of alveolar epithelial cells with bronchoalveolar lavage fluids from ARDS patients drove βENaC internalization, which was inhibited by a TGF-β neutralizing antibody and a Tgfbr1 inhibitor. Pharmacological inhibition of TGF-β signaling in vivo in mice, and genetic ablation of the nox4 gene in mice, protected against perturbed lung fluid balance in a bleomycin model of lung injury, highlighting a role for both proximal and distal components of this unique ENaC regulatory pathway in lung fluid balance. These data describe a unique TGF-β–dependent mechanism that regulates ion and fluid transport in the lung, which is not only relevant to the pathological mechanisms of ARDS, but might also represent a physiological means of acutely regulating ENaC activity in the lung and other organs. PMID:24324142

Affinity and specificity of interactions between Nedd4 isoforms and the epithelial Na+ channel.

PubMed

Henry, Pauline C; Kanelis, Voula; O'Brien, M Christine; Kim, Brian; Gautschi, Ivan; Forman-Kay, Julie; Schild, Laurent; Rotin, Daniela

2003-05-30

The epithelial Na+ channel (alphabetagammaENaC) regulates salt and fluid homeostasis and blood pressure. Each ENaC subunit contains a PY motif (PPXY) that binds to the WW domains of Nedd4, a Hect family ubiquitin ligase containing 3-4 WW domains and usually a C2 domain. It has been proposed that Nedd4-2, but not Nedd4-1, isoforms can bind to and suppress ENaC activity. Here we challenge this notion and show that, instead, the presence of a unique WW domain (WW3*) in either Nedd4-2 or Nedd4-1 determines high affinity interactions and the ability to suppress ENaC. WW3* from either Nedd4-2 or Nedd4-1 binds ENaC-PY motifs equally well (e.g. Kd approximately 10 microm for alpha- or betaENaC, 3-6-fold higher affinity than WW4), as determined by intrinsic tryptophan fluorescence. Moreover, dNedd4-1, which naturally contains a WW3* instead of WW2, is able to suppress ENaC function equally well as Nedd4-2. Homology models of the WW3*.betaENaC-PY complex revealed that a Pro and Ala conserved in all WW3*, but not other Nedd4-WW domains, help form the binding pocket for PY motif prolines. Extensive contacts are formed between the betaENaC-PY motif and the Pro in WW3*, and the small Ala creates a large pocket to accommodate the peptide. Indeed, mutating the conserved Pro and Ala in WW3* reduces binding affinity 2-3-fold. Additionally, we demonstrate that mutations in PY motif residues that form contacts with the WW domain based on our previously solved structure either abolish or severely reduce binding affinity to the WW domain and that the extent of binding correlates with the level of ENaC suppression. Independently, we show that a peptide encompassing the PY motif of sgk1, previously proposed to bind to Nedd4-2 and alter its ability to regulate ENaC, does not bind (or binds poorly) the WW domains of Nedd4-2. Collectively, these results suggest that high affinity of WW domain-PY-motif interactions rather than affiliation with Nedd4-1/Nedd-2 is critical for ENaC suppression by Nedd4 proteins.

Regulation of ENaC-mediated alveolar fluid clearance by insulin via PI3K/Akt pathway in LPS-induced acute lung injury.

PubMed

Deng, Wang; Li, Chang-Yi; Tong, Jin; Zhang, Wei; Wang, Dao-Xin

2012-03-30

Stimulation of epithelial sodium channel (ENaC) increases Na(+) transport, a driving force of alveolar fluid clearance (AFC) to keep alveolar spaces free of edema fluid that is beneficial for acute lung injury (ALI). It is well recognized that regulation of ENaC by insulin via PI3K pathway, but the mechanism of this signaling pathway to regulate AFC and ENaC in ALI remains unclear. The aim of this study was to investigate the effect of insulin on AFC in ALI and clarify the pathway in which insulin regulates the expression of ENaC in vitro and in vivo. A model of ALI (LPS at a dose of 5.0 mg/kg) with non-hyperglycemia was established in Sprague-Dawley rats receiving continuous exogenous insulin by micro-osmotic pumps and wortmannin. The lungs were isolated for measurement of bronchoalveolar lavage fluid(BALF), total lung water content(TLW), and AFC after ALI for 8 hours. Alveolar epithelial type II cells were pre-incubated with LY294002, Akt inhibitor and SGK1 inhibitor 30 minutes before insulin treatment for 2 hours. The expressions of α-,β-, and γ-ENaC were detected by immunocytochemistry, reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting. In vivo, insulin decreased TLW, enchanced AFC, increased the expressions of α-,β-, and γ-ENaC and the level of phosphorylated Akt, attenuated lung injury and improved the survival rate in LPS-induced ALI, the effects of which were blocked by wortmannin. Amiloride, a sodium channel inhibitor, significantly reduced insulin-induced increase in AFC. In vitro, insulin increased the expressions of α-,β-, and γ-ENaC as well as the level of phosphorylated Akt but LY294002 and Akt inhibitor significantly prevented insulin-induced increase in the expression of ENaC and the level of phosphorylated Akt respectively. Immunoprecipitation studies showed that levels of Nedd4-2 binding to ENaC were decreased by insulin via PI3K/Akt pathway. Our study demonstrated that insulin alleviated pulmonary edema and enhanced AFC by increasing the expression of ENaC that dependent upon PI3K/Akt pathway by inhibition of Nedd4-2.

JPRS Report, Science & Technology, Europe & Latin America, Argentina: Specifications of ARGOS 380 MW Reactor.

DTIC Science & Technology

1988-02-18

programme. It has a licensing agreement with Siemens AG’s Kraftwerk Union AG, which is its minor shareholder. Under this agreement, ENACE has the...Argentine nuclear programme. It has a licensing agreement with Siemens AG’s Kraftwerk Union AG, which is its minor shareholder. Under this agreement, ENACE

Urinary Proteolytic Activation of Renal Epithelial Na+ Channels in Chronic Heart Failure.

PubMed

Zheng, Hong; Liu, Xuefei; Sharma, Neeru M; Li, Yulong; Pliquett, Rainer U; Patel, Kaushik P

2016-01-01

One of the key mechanisms involved in renal Na(+) retention in chronic heart failure (CHF) is activation of epithelial Na(+) channels (ENaC) in collecting tubules. Proteolytic cleavage has an important role in activating ENaC. We hypothesized that enhanced levels of proteases in renal tubular fluid activate ENaC, resulting in renal Na(+) retention in rats with CHF. CHF was produced by left coronary artery ligation in rats. By immunoblotting, we found that several urinary serine proteases were significantly increased in CHF rats compared with sham rats (fold increases: furin 6.7, prostasin 23.6, plasminogen 2.06, and plasmin 3.57 versus sham). Similar increases were observed in urinary samples from patients with CHF. Whole-cell patch clamp was conducted in cultured renal collecting duct M-1 cells to record Na(+) currents. Protease-rich urine (from rats and patients with CHF) significantly increased the Na(+) inward current in M-1 cells. Two weeks of protease inhibitor treatment significantly abrogated the enhanced diuretic and natriuretic responses to ENaC inhibitor benzamil in rats with CHF. Increased podocyte lesions were observed in the kidneys of rats with CHF by transmission electron microscopy. Consistent with these results, podocyte damage markers desmin and podocin expressions were also increased in rats with CHF (increased ≈2-folds). These findings suggest that podocyte damage may lead to increased proteases in the tubular fluid, which in turn contributes to the enhanced renal ENaC activity, providing a novel mechanistic insight for Na(+) retention commonly observed in CHF. © 2015 American Heart Association, Inc.

Urinary proteolytic activation of renal epithelial Na+ channels in chronic heart failure

PubMed Central

Zheng, Hong; Liu, Xuefei; Sharma, Neeru M.; Li, Yulong; Pliquett, Rainer U; Patel, Kaushik P.

2015-01-01

One of the key mechanisms involved in renal Na+ retention in chronic heart failure (CHF) is activation of epithelial Na+ channels (ENaC) in collecting tubules. Proteolytic cleavage has an important role in activating ENaC. We hypothesized that enhanced levels of proteases in renal tubular fluid activate ENaC resulting in renal Na+ retention in rats with CHF. CHF was produced by left coronary artery ligation in rats. By immunoblotting, we found that several urinary serine proteases were significantly increased in CHF rats compared to sham rats (fold increases: furin 6.7, prostasin 23.6, plasminogen 2.06 and plasmin 3.57 vs. sham). Similar increases were observed in urinary samples from patients with CHF. Whole-cell patch-clamp was conducted in cultured renal collecting duct M-1 cells to record Na+ currents. Protease-rich urine (from rats and patients with CHF) significantly increased the Na+ inward current in M-1 cells. Two weeks of protease inhibitor treatment significantly abrogated the enhanced diuretic and natriuretic responses to ENaC inhibitor benzamil in rats with CHF. Increased podocyte lesions were observed in the kidneys of rats with CHF by transmission electron microscopy. Consistent with these results, podocyte damage markers desmin and podocin expressions were also increased in rats with CHF (increased ~2 folds). These findings suggest that podocyte damage may lead to increased proteases in the tubular fluid which in turn contributes to the enhanced renal ENaC activity, providing a novel mechanistic insight for Na+ retention commonly observed in CHF. PMID:26628676

Ethanol Alters Alveolar Fluid Balance via Nadph Oxidase (NOX) Signaling to Epithelial Sodium Channels (ENaC) in the Lung

PubMed Central

Downs, Charles A.; Kreiner, Lisa H.; Eaton, Amity F.; Johnson, Nicholle M.; Brown, Lou Ann

2013-01-01

Chronic alcohol consumption is associated with increased incidence of ICU-related morbidity and mortality, primarily from acute respiratory distress syndrome (ARDS). However, the mechanisms involved are unknown. One explanation is that alcohol regulates epithelial sodium channels (ENaC) via oxidant signaling to promote a pro- injury environment. We used small rodent models to mimic acute and chronic alcohol consumption and tested the hypothesis that ethanol (EtOH) would affect lung fluid clearance by up-regulating ENaC activity in the lung. Fluorescence labeling of rat lung slices and in vivo mouse lung revealed an increase in ROS production in response to acute EtOH exposure. Using western blots and fluorescein-5-maleimide labeling, we conclude that EtOH exposure modifies cysteines of α-ENaC while data from single channel patch clamp analysis confirm that 0.16% EtOH increased ENaC activity in rat alveolar cells. In vivo lung fluid clearance demonstrated a latent increase in fluid clearance in mice receiving EtOH diet. Ethanol mice given a tracheal instillation of LPS demonstrated early lung fluid clearance compared to caloric control mice and C57Bl/6 mice. Standard biochemical techniques reveal that chronic EtOH consumption resulted in greater protein expression of the catalytic gp91phox subunit and the obligate Rac1 protein. Collectively these data suggest that chronic EtOH consumption may lead to altered regulation of ENaC, contributing to a ‘pro-injury’ environment in the alcohol lung. PMID:23382956

WNK4 regulates activity of the epithelial Na+ channel in vitro and in vivo

PubMed Central

Ring, Aaron M.; Cheng, Sam X.; Leng, Qiang; Kahle, Kristopher T.; Rinehart, Jesse; Lalioti, Maria D.; Volkman, Heather M.; Wilson, Frederick H.; Hebert, Steven C.; Lifton, Richard P.

2007-01-01

Homeostasis of intravascular volume, Na+, Cl−, and K+ is interdependent and determined by the coordinated activities of structurally diverse mediators in the distal nephron and the distal colon. The behavior of these flux pathways is regulated by the renin–angiotensin–aldosterone system; however, the mechanisms that allow independent modulation of individual elements have been obscure. Previous work has shown that mutations in WNK4 cause pseudohypoaldosteronism type II (PHAII), a disease featuring hypertension with hyperkalemia, due to altered activity of specific Na-Cl cotransporters, K+ channels, and paracellular Cl− flux mediators of the distal nephron. By coexpression studies in Xenopus oocytes, we now demonstrate that WNK4 also inhibits the epithelial Na+ channel (ENaC), the major mediator of aldosterone-sensitive Na+ (re)absorption, via a mechanism that is independent of WNK4's kinase activity. This inhibition requires intact C termini in ENaC β- and γ-subunits, which contain PY motifs used to target ENaC for clearance from the plasma membrane. Importantly, PHAII-causing mutations eliminate WNK4's inhibition of ENaC, thereby paralleling other effects of PHAII to increase sodium balance. The relevance of these findings in vivo was studied in mice harboring PHAII-mutant WNK4. The colonic epithelium of these mice demonstrates markedly increased amiloride-sensitive Na+ flux compared with wild-type littermates. These studies identify ENaC as a previously unrecognized downstream target of WNK4 and demonstrate a functional role for WNK4 in the regulation of colonic Na+ absorption. These findings support a key role for WNK4 in coordinating the activities of diverse flux pathways to achieve integrated fluid and electrolyte homeostasis. PMID:17360470

Potential Roles of Amiloride-Sensitive Sodium Channels in Cancer Development.

PubMed

Xu, Siguang; Liu, Cui; Ma, Yana; Ji, Hong-Long; Li, Xiumin

2016-01-01

The ENaC/degenerin ion channel superfamily includes the amiloride-sensitive epithelial sodium channel (ENaC) and acid sensitive ionic channel (ASIC). ENaC is a multimeric ion channel formed by heteromultimeric membrane glycoproteins, which participate in a multitude of biological processes by mediating the transport of sodium (Na(+)) across epithelial tissues such as the kidney, lungs, bladder, and gut. Aberrant ENaC functions contribute to several human disease states including pseudohypoaldosteronism, Liddle syndrome, cystic fibrosis, and salt-sensitive hypertension. Increasing evidence suggests that ion channels not only regulate ion homeostasis and electric signaling in excitable cells but also play important roles in cancer cell behaviors such as proliferation, apoptosis, invasion, and migration. Indeed, ENaCs/ASICs had been reported to be associated with cancer characteristics. Given their cell surface localization and pharmacology, pharmacological strategies to target ENaC/ASIC family members may be promising cancer therapeutics.

Increased apical Na+ permeability in cystic fibrosis is supported by a quantitative model of epithelial ion transport

PubMed Central

O’Donoghue, Donal L; Dua, Vivek; Moss, Guy W J; Vergani, Paola

2013-01-01

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes an anion channel. In the human lung CFTR loss causes abnormal ion transport across airway epithelial cells. As a result CF individuals produce thick mucus, suffer persistent bacterial infections and have a much reduced life expectancy. Trans-epithelial potential difference (Vt) measurements are routinely carried out on nasal epithelia of CF patients in the clinic. CF epithelia exhibit a hyperpolarised basal Vt and a larger Vt change in response to amiloride (a blocker of the epithelial Na+ channel, ENaC). Are these altered bioelectric properties solely a result of electrical coupling between the ENaC and CFTR currents, or are they due to an increased ENaC permeability associated with CFTR loss? To examine these issues we have developed a quantitative mathematical model of human nasal epithelial ion transport. We find that while the loss of CFTR permeability hyperpolarises Vt and also increases amiloride-sensitive Vt, these effects are too small to account for the magnitude of change observed in CF epithelia. Instead, a parallel increase in ENaC permeability is required to adequately fit observed experimental data. Our study provides quantitative predictions for the complex relationships between ionic permeabilities and nasal Vt, giving insights into the physiology of CF disease that have important implications for CF therapy. PMID:23732645

Expression and localization of taste receptor genes in the vallate papillae of rats: effect of zinc deficiency.

PubMed

Ikeda, Atsuo; Sekine, Hiroki; Takao, Kyoichi; Ikeda, Minoru

2013-09-01

We found a difference in expression sites between TAS2Rs and ENaC (epithelial sodium channels). The number of TAS2R-positive cells and ENaC-positive cells were decreased in zinc-deficient diet rats. These findings suggest that decreased expression of taste receptor genes may play an important role in the onset of zinc deficiency-associated taste disorder. The present study was aimed at histologically investigating the expression and localization of TAS2Rs and ENaC in the vallate taste buds of rats. Changes in expression of the taste receptor genes in zinc-deficient rats were also investigated. The vallate papillae of five rats fed a normal diet and five rats fed a zinc-deficient diet were used. In situ hybridization was performed to investigate the expression and localization of TAS2Rs and ENaC. TAS2R-positive cells per taste bud were counted, and differences in number between the normal and zinc-deficient diet rats were investigated. In the normal rats, expression of TAS2Rs was observed specifically in the taste bud cells. In contrast, ENaC-positive cells were observed in a part of the taste bud cells and a large number of epithelial cells. Fewer cells were positive for TAS2Rs and ENaC in the zinc-deficient diet rats.

Delivery of ENaC siRNA to epithelial cells mediated by a targeted nanocomplex: a therapeutic strategy for cystic fibrosis.

PubMed

Manunta, Maria D I; Tagalakis, Aristides D; Attwood, Martin; Aldossary, Ahmad M; Barnes, Josephine L; Munye, Mustafa M; Weng, Alexander; McAnulty, Robin J; Hart, Stephen L

2017-04-06

The inhibition of ENaC may have therapeutic potential in CF airways by reducing sodium hyperabsorption, restoring lung epithelial surface fluid levels, airway hydration and mucociliary function. The challenge has been to deliver siRNA to the lung with sufficient efficacy for a sustained therapeutic effect. We have developed a self-assembling nanocomplex formulation for siRNA delivery to the airways that consists of a liposome (DOTMA/DOPE; L), an epithelial targeting peptide (P) and siRNA (R). LPR formulations were assessed for their ability to silence expression of the transcript of the gene encoding the α-subunit of the sodium channel ENaC in cell lines and primary epithelial cells, in submerged cultures or grown in air-liquid interface conditions. LPRs, containing 50 nM or 100 nM siRNA, showed high levels of silencing, particularly in primary airway epithelial cells. When nebulised these nanocomplexes still retained their biophysical properties and transfection efficiencies. The silencing ability was determined at protein level by confocal microscopy and western blotting. In vivo data demonstrated that these nanoparticles had the ability to silence expression of the α-ENaC subunit gene. In conclusion, these findings show that LPRs can modulate the activity of ENaC and this approach might be promising as co-adjuvant therapy for cystic fibrosis.

Inhibition of airway surface fluid absorption by cholinergic stimulation

PubMed Central

Joo, Nam Soo; Krouse, Mauri E.; Choi, Jae Young; Cho, Hyung-Ju; Wine, Jeffrey J.

2016-01-01

In upper airways airway surface liquid (ASL) depth and clearance rates are both increased by fluid secretion. Secretion is opposed by fluid absorption, mainly via the epithelial sodium channel, ENaC. In static systems, increased fluid depth activates ENaC and decreased depth inhibits it, suggesting that secretion indirectly activates ENaC to reduce ASL depth. We propose an alternate mechanism in which cholinergic input, which causes copious airway gland secretion, also inhibits ENaC-mediated absorption. The conjoint action accelerates clearance, and the increased transport of mucus out of the airways restores ASL depth while cleansing the airways. We were intrigued by early reports of cholinergic inhibition of absorption by airways in some species. To reinvestigate this phenomenon, we studied inward short-circuit currents (Isc) in tracheal mucosa from human, sheep, pig, ferret, and rabbit and in two types of cultured cells. Basal Isc was inhibited 20–70% by the ENaC inhibitor, benzamil. Long-lasting inhibition of ENaC-dependent Isc was also produced by basolateral carbachol in all preparations except rabbit and the H441 cell line. Atropine inhibition produced a slow recovery or prevented inhibition if added before carbachol. The mechanism for inhibition was not determined and is most likely multi-factorial. However, its physiological significance is expected to be increased mucus clearance rates in cholinergically stimulated airways. PMID:26846701

Genetic variation in CYP4A11 and blood pressure response to mineralocorticoid receptor antagonism or ENaC inhibition: an exploratory pilot study in African Americans.

PubMed

Laffer, Cheryl L; Elijovich, Fernando; Eckert, George J; Tu, Wanzhu; Pratt, J Howard; Brown, Nancy J

2014-07-01

An rs3890011 variant of CYP4A11, which is in linkage disequilibrium with the loss-of-function variant rs1126742, is associated with hypertension in humans. In mice, Cyp4a deficiency results in salt-sensitive hypertension through activation of ENaC. We tested the hypothesis that the rs3890011 variant is associated with blood pressure response to drugs acting via the ENaC pathway. African Americans with volume-dependent, resistant hypertension were randomized to treatment with placebo, spironolactone, amiloride, or combination. Blood pressure responses were analyzed by CYP4A11 genotypes. Rs3890011 (GG:GC:CC = 20:35:28) and rs1126742 (TT:TC:CC = 45:31:7) were in linkage disequilibrium (D' = 1, r = 0.561). Expected small number of rs1126742 CC homozygotes precluded analysis of the effect of this genotype on treatment responses. Spironolactone reduced blood pressure in rs3890011 GG and GC individuals, but not in CC homozygotes (P = .002), whereas amiloride reduced blood pressure similarly in all rs3890011 genotypes. The antihypertensive effects of spironolactone and amiloride were comparable in GG and GC participants, but only amiloride reduced pressure in CC homozygotes (-6.3 ± 7.3/-3.2 ± 4.0 vs. +6.8 ± 7.9/+4.8 ± 8.6 mm Hg, P < .01/<.05). The aldosterone response to spironolactone was also blunted in the CC genotype. In individuals homozygous for the CYP4A11 rs3890011 C allele, blood pressure is resistant to mineralocorticoid receptor antagonism, but sensitive to ENaC inhibition, consistent with ENaC activation. Studies in a larger population are needed to replicate these findings. Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Controlling epithelial sodium channels with light using photoswitchable amilorides

NASA Astrophysics Data System (ADS)

Schönberger, Matthias; Althaus, Mike; Fronius, Martin; Clauss, Wolfgang; Trauner, Dirk

2014-08-01

Amiloride is a widely used diuretic that blocks epithelial sodium channels (ENaCs). These heterotrimeric transmembrane proteins, assembled from β, γ and α or δ subunits, effectively control water transport across epithelia and sodium influx into non-epithelial cells. The functional role of δβγENaC in various organs, including the human brain, is still poorly understood and no pharmacological tools are available for the functional differentiation between α- and δ-containing ENaCs. Here we report several photoswitchable versions of amiloride. One compound, termed PA1, enables the optical control of ENaC channels, in particular the δβγ isoform, by switching between blue and green light, or by turning on and off blue light. PA1 was used to modify functionally δβγENaC in amphibian and mammalian cells. We also show that PA1 can be used to differentiate between δβγENaC and αβγENaC in a model for the human lung epithelium.

Cross-talk between insulin and IGF-1 receptors in the cortical collecting duct principal cells: implication for ENaC-mediated Na+ reabsorption

PubMed Central

Ilatovskaya, Daria V.; Levchenko, Vladislav; Brands, Michael W.; Pavlov, Tengis S.

2015-01-01

Insulin and IGF-1 are recognized as powerful regulators of the epithelial Na+ channel (ENaC) in the aldosterone-sensitive distal nephron. As previously described, these hormones both acutely increase ENaC activity in freshly isolated split open tubules and cultured principal cortical collecting duct cells. The present study was aimed at differentiating the effects of insulin and IGF-1 on Na+ transport in immortalized mpkCCDcl4 cells and defining their interrelations. We have shown that both insulin and IGF-1 applied basolaterally, but not apically, enhanced transepithelial Na+ transport in the mpkCCDcl4 cell line with EC50 values of 8.8 and 14.5 nM, respectively. Insulin treatment evoked phosphorylation of both insulin and IGF-1 receptors, whereas the effects of IGF-1 were more profound on its own receptor rather than the insulin receptor. AG-1024 and PPP, inhibitors of IGF-1 and insulin receptor tyrosine kinase activity, diminished insulin- and IGF-1-stimulated Na+ transport in mpkCCDcl4 cells. The effects of insulin and IGF-1 on ENaC-mediated currents were found to be additive, with insulin likely stimulating both IGF-1 and insulin receptors. We hypothesize that insulin activates IGF-1 receptors in addition to its own receptors, making the effects of these hormones interconnected. PMID:25651558

Bumetanide increases Cl--dependent short-circuit current in late distal colon: Evidence for the presence of active electrogenic Cl- absorption.

PubMed

Tang, Lieqi; Fang, Xiefan; Winesett, Steven P; Cheng, Catherine Y; Binder, Henry J; Rivkees, Scott A; Cheng, Sam X

2017-01-01

Mammalian colonic epithelia consist of cells that are capable of both absorbing and secreting Cl-. The present studies employing Ussing chamber technique identified two opposing short-circuit current (Isc) responses to basolateral bumetanide in rat distal colon. Apart from the transepithelial Cl--secretory Isc in early distal colon that was inhibited by bumetanide, bumetanide also stimulated Isc in late distal colon that had not previously been identified. Since bumetanide inhibits basolateral Na+-K+-2Cl- cotransporter (NKCC) in crypt cells and basolateral K+-Cl- cotransporter (KCC) in surface epithelium, we proposed this stimulatory Isc could represent a KCC-mediated Cl- absorptive current. In support of this hypothesis, ion substitution experiments established Cl- dependency of this absorptive Isc and transport inhibitor studies demonstrated the involvement of an apical Cl- conductance. Current distribution and RNA sequencing analyses revealed that this Cl- absorptive Isc is closely associated with epithelial Na+ channel (ENaC) but is not dependent on ENaC activity. Thus, inhibition of ENaC by 10 μM amiloride or benzamil neither altered the direction nor its activity. Physiological studies suggested that this Cl- absorptive Isc senses dietary Cl- content; thus when dietary Cl- was low, Cl- absorptive Isc was up-regulated. In contrast, when dietary Cl- was increased, Cl- absorptive Isc was down-regulated. We conclude that an active Cl- extrusion mechanism exists in ENaC-expressing late distal colon and likely operates in parallel with ENaC to facilitate NaCl absorption.

The mineralocorticoid receptor (MR) regulates ENaC but not NCC in mice with random MR deletion.

PubMed

Czogalla, Jan; Vohra, Twinkle; Penton, David; Kirschmann, Moritz; Craigie, Eilidh; Loffing, Johannes

2016-05-01

Aldosterone binds to the mineralocorticoid receptor (MR) and increases renal Na(+) reabsorption via up-regulation of the epithelial Na(+) channel (ENaC) and the Na(+)-K(+)-ATPase in the collecting system (CS) and possibly also via the NaCl cotransporter (NCC) in the distal convoluted tubule (DCT). However, whether aldosterone directly regulates NCC via MR or indirectly through systemic alterations remains controversial. We used mice with deletion of MR in ∼20 % of renal tubule cells (MR/X mice), in which MR-positive (MR(wt)) and -negative (MR(ko)) cells can be studied side-by-side in the same physiological context. Adult MR/X mice showed similar mRNA and protein levels of renal ion transport proteins to control mice. In MR/X mice, no differences in NCC abundance and phosphorylation was seen between MR(wt) and MR(ko) cells and dietary Na(+) restriction up-regulated NCC to similar extent in both groups of cells. In contrast, MR(ko) cells in the CS did not show any detectable alpha-ENaC abundance or apical targeting of ENaC neither on control diet nor in response to dietary Na(+) restriction. Furthermore, Na(+)-K(+)-ATPase expression was unaffected in MR(ko) cells of the DCT, while it was lost in MR(ko) cells of the CS. In conclusion, MR is crucial for ENaC and Na(+)-K(+)-ATPase regulation in the CS, but is dispensable for NCC and Na(+)-K(+)-ATPase regulation in the DCT.

Assessment of epithelial sodium channel variants in nonwhite cystic fibrosis patients with non-diagnostic CFTR genotypes.

PubMed

Brennan, Marie-Luise; Pique, Lynn M; Schrijver, Iris

2016-01-01

Several lines of evidence suggest a role for the epithelial sodium channel (ENaC) in cystic fibrosis (CF). The purpose of our study was to assess the contribution of genetic variants in the ENaC subunits (α, β, γ) in nonwhite CF patients in whom CFTR molecular testing has been non-diagnostic. Samples were obtained from patients who were nonwhite and whose molecular CFTR testing did not identify two mutations. Sequencing of the SCNN1A, B, and G genes was performed and variants assessed for pathogenicity and association with CF using databases, protein and splice site mutation analysis software, and literature review. We identified four nonsynonymous amino acid variants in SCNN1A, three in SCNN1B and one in SCNN1G. There was no convincing evidence of pathogenicity. Whereas all have been reported in the dbSNP database, only p.Ala334Thr, p.Val573Ile, and p.Thr663Ala in SCNN1A, p.Gly442Val in SCNN1B and p.Gly183Ser in SCNN1G were previously reported in ENaC genetic studies of CF or CF-like patients. Synonymous substitutions were also observed but novel synonymous variants were not detected. There is no conclusive association of ENaC genetic variants with CF in nonwhite CF patients. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Feedforward activation of endothelial ENaC by high sodium

PubMed Central

Korte, Stefanie; Sträter, Alexandra S.; Drüppel, Verena; Oberleithner, Hans; Jeggle, Pia; Grossmann, Claudia; Fobker, Manfred; Nofer, Jerzy-Roch; Brand, Eva; Kusche-Vihrog, Kristina

2014-01-01

Kidney epithelial sodium channels (ENaCs) are known to be inactivated by high sodium concentrations (feedback inhibition). Recently, the endothelial sodium channel (EnNaC) was identified to control the nanomechanical properties of the endothelium. EnNaC-dependent endothelial stiffening reduces the release of nitric oxide, the hallmark of endothelial dysfunction. To study the regulatory impact of sodium on EnNaC, endothelial cells (EA.hy926 and ex vivo mouse endothelium) were incubated in aldosterone-free solutions containing either low (130 mM) or high (150 mM) sodium concentrations. By applying atomic force microscopy-based nanoindentation, an unexpected positive correlation between increasing sodium concentrations and cortical endothelial stiffness was observed, which can be attributed to functional EnNaC. In particular, an acute rise in sodium concentration (+20 mM) was sufficient to increase EnNaC membrane abundance by 90% and stiffening of the endothelial cortex by 18%. Despite the absence of exogenous aldosterone, these effects were prevented by the aldosterone synthase inhibitor FAD286 (100 nM) or the mineralocorticoid receptor (MR)-antagonist spironolactone (100 nM), indicating endogenous aldosterone synthesis and MR-dependent signaling. Interestingly, in the presence of high-sodium concentrations, FAD286 increased the transcription of the MR by 69%. Taken together, a novel feedforward activation of EnNaC by sodium is proposed that contrasts ENaC feedback inhibition in kidney.—Korte, S., Sträter, A. S., Drüppel, V., Oberleithner, H., Jeggle, P., Grossmann, C., Fobker, M., Nofer, J.-R., Brand, E., Kusche-Vihrog, K. Feedforward activation of endothelial ENaC by high sodium. PMID:24868010

Acute inhibition of NCC does not activate distal electrogenic Na+ reabsorption or kaliuresis.

PubMed

Hunter, Robert W; Craigie, Eilidh; Homer, Natalie Z M; Mullins, John J; Bailey, Matthew A

2014-02-15

Na(+) reabsorption from the distal renal tubule involves electroneutral and electrogenic pathways, with the latter promoting K(+) excretion. The relative activities of these two pathways are tightly controlled, participating in the minute-to-minute regulation of systemic K(+) balance. The pathways are interdependent: the activity of the NaCl cotransporter (NCC) in the distal convoluted tubule influences the activity of the epithelial Na(+) channel (ENaC) downstream. This effect might be mediated by changes in distal Na(+) delivery per se or by molecular and structural adaptations in the connecting tubule and collecting ducts. We hypothesized that acute inhibition of NCC activity would cause an immediate increase in Na(+) flux through ENaC, with a concomitant increase in renal K(+) excretion. We tested this using renal clearance methodology in anesthetized mice, by the administration of hydrochlorothiazide (HCTZ) and/or benzamil (BZM) to exert specific blockade of NCC and ENaC, respectively. Bolus HCTZ elicited a natriuresis that was sustained for up to 110 min; urinary K(+) excretion was not affected. Furthermore, the magnitude of the natriuresis was no greater during concomitant BZM administration. This suggests that ENaC-mediated Na(+) reabsorption was not normally limited by Na(+) delivery, accounting for the absence of thiazide-induced kaliuresis. After dietary Na(+) restriction, HCTZ elicited a kaliuresis, but the natiuretic effect of HCTZ was not enhanced by BZM. Our findings support a model in which inhibition of NCC activity does not increase Na(+) reabsorption through ENaC solely by increasing distal Na(+) delivery but rather by inducing a molecular and structural adaptation in downstream nephron segments.

Hypotonic Shock Modulates Na+ Current via a Cl- and Ca2+/Calmodulin Dependent Mechanism in Alveolar Epithelial Cells

PubMed Central

Tatur, Sabina; Brochiero, Emmanuelle; Grygorczyk, Ryszard; Berthiaume, Yves

2013-01-01

Alveolar epithelial cells are involved in Na+ absorption via the epithelial Na+ channel (ENaC), an important process for maintaining an appropriate volume of liquid lining the respiratory epithelium and for lung oedema clearance. Here, we investigated how a 20% hypotonic shock modulates the ionic current in these cells. Polarized alveolar epithelial cells isolated from rat lungs were cultured on permeant filters and their electrophysiological properties recorded. A 20% bilateral hypotonic shock induced an immediate, but transient 52% rise in total transepithelial current and a 67% increase in the amiloride-sensitive current mediated by ENaC. Amiloride pre-treatment decreased the current rise after hypotonic shock, showing that ENaC current is involved in this response. Since Cl- transport is modulated by hypotonic shock, its contribution to the basal and hypotonic-induced transepithelial current was also assessed. Apical NPPB, a broad Cl- channel inhibitor and basolateral DIOA a potassium chloride co-transporter (KCC) inhibitor reduced the total and ENaC currents, showing that transcellular Cl- transport plays a major role in that process. During hypotonic shock, a basolateral Cl- influx, partly inhibited by NPPB is essential for the hypotonic-induced current rise. Hypotonic shock promoted apical ATP secretion and increased intracellular Ca2+. While apyrase, an ATP scavenger, did not inhibit the hypotonic shock current response, W7 a calmodulin antagonist completely prevented the hypotonic current rise. These results indicate that a basolateral Cl- influx as well as Ca2+/calmodulin, but not ATP, are involved in the acute transepithelial current rise elicited by hypotonic shock. PMID:24019969

Redox regulation of epithelial sodium channels examined in alveolar type 1 and 2 cells patch-clamped in lung slice tissue.

PubMed

Helms, My N; Jain, Lucky; Self, Julie L; Eaton, Douglas C

2008-08-15

The alveolar surface of the lung is lined by alveolar type 1 (AT1) and type 2 (AT2) cells. Using single channel patch clamp analysis in lung slice preparations, we are able to uniquely study AT1 and AT2 cells separately from intact lung. We report for the first time the Na+ transport properties of type 2 cells accessed in live lung tissue (as we have done in type 1 cells). Type 2 cells in lung tissue slices express both highly selective cation and nonselective cation channels with average conductances of 8.8 +/- 3.2 and 22.5 +/- 6.3 picosiemens, respectively. Anion channels with 10-picosiemen conductance are also present in the apical membrane of type 2 cells. Our lung slice studies importantly verify the use of cultured cell model systems commonly used in lung epithelial sodium channel (ENaC) studies. Furthermore, we identify novel functional differences between the cells that make up the alveolar epithelium. One important difference is that exposure to the nitric oxide (NO) donor, PAPA-NONOate (1.5 microm), significantly decreases average ENaC NPo in type 2 cells (from 1.38 +/- 0.26 to 0.82 +/- 0.16; p < 0.05 and n = 18) but failed to alter ENaC activity in alveolar type 1 cells. Elevating endogenous superoxide (O2.) levels with Ethiolat, a superoxide dismutase inhibitor, prevented NO inhibition of ENaC activity in type 2 cells, supporting the novel hypothesis that O2. and NO signaling plays an important role in maintaining lung fluid balance.

Renal sodium transport in renin-deficient Dahl salt-sensitive rats

PubMed Central

Pavlov, Tengis S; Levchenko, Vladislav; Ilatovskaya, Daria V; Moreno, Carol; Staruschenko, Alexander

2016-01-01

Objective: The Dahl salt-sensitive rat is a well-established model of salt-sensitive hypertension. The goal of this study was to assess the expression and activity of renal sodium channels and transporters in the renin-deficient salt-sensitive rat. Methods: Renin knockout (Ren−/−) rats created on the salt-sensitive rat background were used to investigate the role of renin in the regulation of ion transport in salt-sensitive hypertension. Western blotting and patch-clamp analyses were utilized to assess the expression level and activity of Na+ transporters. Results: It has been described previously that Ren−/− rats exhibit severe kidney underdevelopment, polyuria, and lower body weight and blood pressure compared to their wild-type littermates. Here we found that renin deficiency led to decreased expression of sodium-hydrogen antiporter (NHE3), the Na+/H+ exchanger involved in Na+ absorption in the proximal tubules, but did not affect the expression of Na-K-Cl cotransporter (NKCC2), the main transporter in the loop of Henle. In the distal nephron, the expression of sodium chloride cotransporter (NCC) was lower in Ren−/− rats. Single-channel patch clamp analysis detected decreased ENaC activity in Ren−/− rats which was mediated via changes in the channel open probability. Conclusion: These data illustrate that renin deficiency leads to significant dysregulation of ion transporters. PMID:27443990

Inhibition of Protease-Epithelial Sodium Channel Signaling Improves Mucociliary Function in Cystic Fibrosis Airways.

PubMed

Reihill, James A; Walker, Brian; Hamilton, Robert A; Ferguson, Timothy E G; Elborn, J Stuart; Stutts, M Jackson; Harvey, Brian J; Saint-Criq, Vinciane; Hendrick, Siobhan M; Martin, S Lorraine

2016-09-15

In cystic fibrosis (CF) a reduction in airway surface liquid (ASL) height compromises mucociliary clearance, favoring mucus plugging and chronic bacterial infection. Inhibitors of the epithelial sodium channel (ENaC) have therapeutic potential in CF airways to reduce hyperstimulated sodium and fluid absorption to levels that can restore airway hydration. To determine whether a novel compound (QUB-TL1) designed to inhibit protease/ENaC signaling in CF airways restores ASL volume and mucociliary function. Protease activity was measured using fluorogenic activity assays. Differentiated primary airway epithelial cell cultures (F508del homozygotes) were used to determined ENaC activity (Ussing chamber recordings), ASL height (confocal microscopy), and mucociliary function (by tracking the surface flow of apically applied microbeads). Cell toxicity was measured using a lactate dehydrogenase assay. QUB-TL1 inhibits extracellularly located channel activating proteases (CAPs), including prostasin, matriptase, and furin, the activities of which are observed at excessive levels at the apical surface of CF airway epithelial cells. QUB-TL1-mediated CAP inhibition results in diminished ENaC-mediated Na(+) absorption in CF airway epithelial cells caused by internalization of a prominent pool of cleaved (active) ENaCγ from the cell surface. Importantly, diminished ENaC activity correlates with improved airway hydration status and mucociliary clearance. We further demonstrate QUB-TL1-mediated furin inhibition, which is in contrast to other serine protease inhibitors (camostat mesylate and aprotinin), affords protection against neutrophil elastase-mediated ENaC activation and Pseudomonas aeruginosa exotoxin A-induced cell death. QUB-TL1 corrects aberrant CAP activities, providing a mechanism to delay or prevent the development of CF lung disease in a manner independent of CF transmembrane conductance regulator mutation.

Optimizing nasal potential difference analysis for CFTR modulator development: assessment of ivacaftor in CF subjects with the G551D-CFTR mutation.

PubMed

Rowe, Steven M; Liu, Bo; Hill, Aubrey; Hathorne, Heather; Cohen, Morty; Beamer, John R; Accurso, Frank J; Dong, Qunming; Ordoñez, Claudia L; Stone, Anne J; Olson, Eric R; Clancy, John P

2013-01-01

Nasal potential difference (NPD) is used as a biomarker of the cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial sodium channel (ENaC) activity. We evaluated methods to detect changes in chloride and sodium transport by NPD based on a secondary analysis of a Phase II CFTR-modulator study. Thirty-nine subjects with CF who also had the G551D-CFTR mutation were randomized to receive ivacaftor (Kalydeco™; also known as VX-770) in four doses or placebo twice daily for at least 14 days. All data were analyzed by a single investigator who was blinded to treatment assignment. We compared three analysis methods to determine the best approach to quantify changes in chloride and sodium transport: (1) the average of both nostrils; (2) the most-polarized nostril at each visit; and (3) the most-polarized nostril at screening carried forward. Parameters of ion transport included the PD change with zero chloride plus isoproterenol (CFTR activity), the basal PD, Ringer's PD, and change in PD with amiloride (measurements of ENaC activity), and the delta NPD (measuring CFTR and ENaC activity). The average and most-polarized nostril at each visit were most sensitive to changes in chloride and sodium transport, whereas the most-polarized nostril at screening carried forward was less discriminatory. Based on our findings, NPD studies should assess both nostrils rather than a single nostril. We also found that changes in CFTR activity were more readily detected than changes in ENaC activity, and that rigorous standardization was associated with relatively good within-subject reproducibility in placebo-treated subjects (± 2.8 mV). Therefore, we have confirmed an assay of reasonable reproducibility for detecting chloride-transport improvements in response to CFTR modulation.

Complex Evolutionary Dynamics of Massively Expanded Chemosensory Receptor Families in an Extreme Generalist Chelicerate Herbivore.

PubMed

Ngoc, Phuong Cao Thi; Greenhalgh, Robert; Dermauw, Wannes; Rombauts, Stephane; Bajda, Sabina; Zhurov, Vladimir; Grbić, Miodrag; Van de Peer, Yves; Van Leeuwen, Thomas; Rouzé, Pierre; Clark, Richard M

2016-12-14

While mechanisms to detoxify plant produced, anti-herbivore compounds have been associated with plant host use by herbivores, less is known about the role of chemosensory perception in their life histories. This is especially true for generalists, including chelicerate herbivores that evolved herbivory independently from the more studied insect lineages. To shed light on chemosensory perception in a generalist herbivore, we characterized the chemosensory receptors (CRs) of the chelicerate two-spotted spider mite, Tetranychus urticae, an extreme generalist. Strikingly, T. urticae has more CRs than reported in any other arthropod to date. Including pseudogenes, 689 gustatory receptors were identified, as were 136 degenerin/Epithelial Na+ Channels (ENaCs) that have also been implicated as CRs in insects. The genomic distribution of T. urticae gustatory receptors indicates recurring bursts of lineage-specific proliferations, with the extent of receptor clusters reminiscent of those observed in the CR-rich genomes of vertebrates or C. elegans Although pseudogenization of many gustatory receptors within clusters suggests relaxed selection, a subset of receptors is expressed. Consistent with functions as CRs, the genomic distribution and expression of ENaCs in lineage-specific T. urticae expansions mirrors that observed for gustatory receptors. The expansion of ENaCs in T. urticae to > 3-fold that reported in other animals was unexpected, raising the possibility that ENaCs in T. urticae have been co-opted to fulfill a major role performed by unrelated CRs in other animals. More broadly, our findings suggest an elaborate role for chemosensory perception in generalist herbivores that are of key ecological and agricultural importance. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Potassium Supplementation Prevents Sodium Chloride Cotransporter Stimulation during Angiotensin II Hypertension

PubMed Central

Veiras, Luciana C.; Han, Jiyang; Ralph, Donna L.; McDonough, Alicia A.

2016-01-01

Ang II hypertension increases distal tubule Na-Cl cotransporter (NCC) abundance and phosphorylation (NCCp), as well as epithelial Na+ channel (ENaC) abundance and activating cleavage. Acutely raising plasma [K+] by infusion or ingestion provokes a rapid decrease in NCCp that drives a compensatory kaliuresis. The first aim tested whether acutely raising plasma [K+] with a single 3 hr 2% potassium meal would lower NCCp in Sprague Dawley rats after 14 days of AngII (400 ng/kg/min). The potassium-rich meal neither decreased NCCp nor increased K+ excretion. AngII infused rats exhibited lower plasma [K+] versus controls (3.6 ± 0.2 vs. 4.5 ± 0.1 mmol/L, p < 0.05) suggesting that Ang II mediated ENaC activation provokes K+ depletion. The second aim tested whether doubling dietary potassium intake from 1% (A1K) to 2% (A2K) would prevent K+ depletion during AngII infusion and, thus, prevent NCC accumulation. A2K fed rats exhibited normal plasma [K+] and 2-fold higher K+ excretion and plasma [aldosterone] versus A1K. In A1K rats, NCC, NCCpS71, and NCCpT53 abundance increased 1.5- to 3-fold versus controls (p< 0.05). The rise in NCC and NCCp abundance was prevented in the A2K rats, yet blood pressure did not significantly decrease. ENaC subunit abundance and cleavage increased 1.5- to 3-fold in both A1K and A2K; ROMK abundance was unaffected by Ang II or dietary K+. In summary, the accumulation and phosphorylation of NCC seen during chronic AngII infusion hypertension is likely secondary to potassium deficiency driven by ENaC stimulation. PMID:27600183

Nedd4-2 Modulates Renal Na+-Cl− Cotransporter via the Aldosterone-SGK1-Nedd4-2 Pathway

PubMed Central

Arroyo, Juan Pablo; Lagnaz, Dagmara; Ronzaud, Caroline; Vázquez, Norma; Ko, Benjamin S.; Moddes, Lauren; Ruffieux-Daidié, Dorothée; Hausel, Pierrette; Koesters, Robert; Yang, Baoli; Stokes, John B.; Hoover, Robert S.

2011-01-01

Regulation of renal Na+ transport is essential for controlling blood pressure, as well as Na+ and K+ homeostasis. Aldosterone stimulates Na+ reabsorption by the Na+-Cl− cotransporter (NCC) in the distal convoluted tubule (DCT) and by the epithelial Na+ channel (ENaC) in the late DCT, connecting tubule, and collecting duct. Aldosterone increases ENaC expression by inhibiting the channel's ubiquitylation and degradation; aldosterone promotes serum-glucocorticoid-regulated kinase SGK1-mediated phosphorylation of the ubiquitin-protein ligase Nedd4-2 on serine 328, which prevents the Nedd4-2/ENaC interaction. It is important to note that aldosterone increases NCC protein expression by an unknown post-translational mechanism. Here, we present evidence that Nedd4-2 coimmunoprecipitated with NCC and stimulated NCC ubiquitylation at the surface of transfected HEK293 cells. In Xenopus laevis oocytes, coexpression of NCC with wild-type Nedd4-2, but not its catalytically inactive mutant, strongly decreased NCC activity and surface expression. SGK1 prevented this inhibition in a kinase-dependent manner. Furthermore, deficiency of Nedd4-2 in the renal tubules of mice and in cultured mDCT15 cells upregulated NCC. In contrast to ENaC, Nedd4-2-mediated inhibition of NCC did not require the PY-like motif of NCC. Moreover, the mutation of Nedd4-2 at either serine 328 or 222 did not affect SGK1 action, and mutation at both sites enhanced Nedd4-2 activity and abolished SGK1-dependent inhibition. Taken together, these results suggest that aldosterone modulates NCC protein expression via a pathway involving SGK1 and Nedd4-2 and provides an explanation for the well-known aldosterone-induced increase in NCC protein expression. PMID:21852580

The Role of Epithelial Sodium Channel ENaC and the Apical Cl-/HCO3- Exchanger Pendrin in Compensatory Salt Reabsorption in the Setting of Na-Cl Cotransporter (NCC) Inactivation.

PubMed

Patel-Chamberlin, Mina; Varasteh Kia, Mujan; Xu, Jie; Barone, Sharon; Zahedi, Kamyar; Soleimani, Manoocher

2016-01-01

The absence of NCC does not cause significant salt wasting in NCC deficient mice under basal conditions. We hypothesized that ENaC and pendrin play important roles in compensatory salt absorption in the setting of NCC inactivation, and their inhibition and/or downregulation can cause significant salt wasting in NCC KO mice. WT and NCC KO mice were treated with a daily injection of either amiloride, an inhibitor of ENaC, or acetazolamide (ACTZ), a blocker of salt and bicarbonate reabsorption in the proximal tubule and an inhibitor of carbonic anhydrases in proximal tubule and intercalated cells, or a combination of acetazolamide plus amiloride for defined durations. Animals were subjected to daily balance studies. At the end of treatment, kidneys were harvested and examined. Blood samples were collected for electrolytes and acid base analysis. Amiloride injection significantly increased the urine output (UO) in NCC KO mice (from 1.3 ml/day before to 2.5 ml/day after amiloride, p<0.03, n = 4) but caused only a slight change in UO in WT mice (p>0.05). The increase in UO in NCC KO mice was associated with a significant increase in sodium excretion (from 0.25 mmol/24 hrs at baseline to 0.35 mmol/24 hrs after amiloride injection, p<0.05, n = 4). Daily treatment with ACTZ for 6 days resulted in >80% reduction of kidney pendrin expression in both WT and NCC KO mice. However, ACTZ treatment noticeably increased urine output and salt excretion only in NCC KO mice (with urine output increasing from a baseline of 1.1 ml/day to 2.3 ml/day and sodium excretion increasing from 0.22 mmole/day before to 0.31 mmole/day after ACTZ) in NCC KO mice; both parameters were significantly higher than in WT mice. Western blot analysis demonstrated significant enhancement in ENaC expression in medulla and cortex of NCC KO and WT mice in response to ACTZ injection for 6 days, and treatment with amiloride in ACTZ-pretreated mice caused a robust increase in salt excretion in both NCC KO and WT mice. Pendrin KO mice did not display a significant increase in urine output or salt excretion after treatment with amiloride or ACTZ. 1. ENaC plays an important role in salt reabsorption in NCC KO mice. 2. NCC contributes to compensatory salt reabsorption in the setting of carbonic anhydrase inhibition, which is associated with increased delivery of salt from the proximal tubule and the down regulation of pendrin. 3. ENaC is upregulated by ACTZ treatment and its inhibition by amiloride causes significant diuresis in NCC KO and WT mice. Despite being considered mild agents individually, we propose that the combination of acetazolamide and amiloride in the setting of NCC inhibition (i.e., hydrochlorothiazide) will be a powerful diuretic regimen.

Decreased ENaC expression compensates the increased NCC activity following inactivation of the kidney-specific isoform of WNK1 and prevents hypertension.

PubMed

Hadchouel, Juliette; Soukaseum, Christelle; Büsst, Cara; Zhou, Xiao-ou; Baudrie, Véronique; Zürrer, Tany; Cambillau, Michelle; Elghozi, Jean-Luc; Lifton, Richard P; Loffing, Johannes; Jeunemaitre, Xavier

2010-10-19

Mutations in WNK1 and WNK4 lead to familial hyperkalemic hypertension (FHHt). Because FHHt associates net positive Na(+) balance together with K(+) and H(+) renal retention, the identification of WNK1 and WNK4 led to a new paradigm to explain how aldosterone can promote either Na(+) reabsorption or K(+) secretion in a hypovolemic or hyperkalemic state, respectively. WNK1 gives rise to L-WNK1, an ubiquitous kinase, and KS-WNK1, a kinase-defective isoform expressed in the distal convoluted tubule. By inactivating KS-WNK1 in mice, we show here that this isoform is an important regulator of sodium transport. KS-WNK1(-/-) mice display an increased activity of the Na-Cl cotransporter NCC, expressed specifically in the distal convoluted tubule, where it participates in the fine tuning of sodium reabsorption. Moreover, the expression of the ROMK and BKCa potassium channels was modified in KS-WNK1(-/-) mice, indicating that KS-WNK1 is also a regulator of potassium transport in the distal nephron. Finally, we provide an alternative model for FHHt. Previous studies suggested that the activation of NCC plays a central role in the development of hypertension and hyperkalemia. Even though the increase in NCC activity in KS-WNK1(-/-) mice was less pronounced than in mice overexpressing a mutant form of WNK4, our study suggests that the activation of Na-Cl cotransporter is not sufficient by itself to induce a hyperkalemic hypertension and that the deregulation of other channels, such as the Epithelial Na(+) channel (ENaC), is probably required.

Caffeine intake antagonizes salt sensitive hypertension through improvement of renal sodium handling

PubMed Central

Yu, Hao; Yang, Tao; Gao, Peng; Wei, Xing; Zhang, Hexuan; Xiong, Shiqiang; Lu, Zongshi; Li, Li; Wei, Xiao; Chen, Jing; Zhao, Yu; Arendshorst, William J.; Shang, Qianhui; Liu, Daoyan; Zhu, Zhiming

2016-01-01

High salt intake is a major risk factor for hypertension. Although acute caffeine intake produces moderate diuresis and natriuresis, caffeine increases the blood pressure (BP) through activating sympathetic activity. However, the long-term effects of caffeine on urinary sodium excretion and blood pressure are rarely investigated. Here, we investigated whether chronic caffeine administration antagonizes salt sensitive hypertension by promoting urinary sodium excretion. Dahl salt-sensitive (Dahl-S) rats were fed with high salt diet with or without 0.1% caffeine in drinking water for 15 days. The BP, heart rate and locomotor activity of rats was analyzed and urinary sodium excretion was determined. The renal epithelial Na+ channel (ENaC) expression and function were measured by in vivo and in vitro experiments. Chronic consumption of caffeine attenuates hypertension induced by high salt without affecting sympathetic nerve activity in Dahl-S rats. The renal α-ENaC expression and ENaC activity of rats decreased after chronic caffeine administration. Caffeine increased phosphorylation of AMPK and decrease α-ENaC expression in cortical collecting duct cells. Inhibiting AMPK abolished the effect of caffeine on α-ENaC. Chronic caffeine intake prevented the development of salt-sensitive hypertension through promoting urinary sodium excretion, which was associated with activation of renal AMPK and inhibition of renal tubular ENaC. PMID:27173481

The Role of Epithelial Sodium Channel ENaC and the Apical Cl-/HCO3- Exchanger Pendrin in Compensatory Salt Reabsorption in the Setting of Na-Cl Cotransporter (NCC) Inactivation

PubMed Central

Patel-Chamberlin, Mina; Varasteh Kia, Mujan; Xu, Jie; Barone, Sharon; Zahedi, Kamyar; Soleimani, Manoocher

2016-01-01

Background The absence of NCC does not cause significant salt wasting in NCC deficient mice under basal conditions. We hypothesized that ENaC and pendrin play important roles in compensatory salt absorption in the setting of NCC inactivation, and their inhibition and/or downregulation can cause significant salt wasting in NCC KO mice. Methods WT and NCC KO mice were treated with a daily injection of either amiloride, an inhibitor of ENaC, or acetazolamide (ACTZ), a blocker of salt and bicarbonate reabsorption in the proximal tubule and an inhibitor of carbonic anhydrases in proximal tubule and intercalated cells, or a combination of acetazolamide plus amiloride for defined durations. Animals were subjected to daily balance studies. At the end of treatment, kidneys were harvested and examined. Blood samples were collected for electrolytes and acid base analysis. Results Amiloride injection significantly increased the urine output (UO) in NCC KO mice (from 1.3 ml/day before to 2.5 ml/day after amiloride, p<0.03, n = 4) but caused only a slight change in UO in WT mice (p>0.05). The increase in UO in NCC KO mice was associated with a significant increase in sodium excretion (from 0.25 mmol/24 hrs at baseline to 0.35 mmol/24 hrs after amiloride injection, p<0.05, n = 4). Daily treatment with ACTZ for 6 days resulted in >80% reduction of kidney pendrin expression in both WT and NCC KO mice. However, ACTZ treatment noticeably increased urine output and salt excretion only in NCC KO mice (with urine output increasing from a baseline of 1.1 ml/day to 2.3 ml/day and sodium excretion increasing from 0.22 mmole/day before to 0.31 mmole/day after ACTZ) in NCC KO mice; both parameters were significantly higher than in WT mice. Western blot analysis demonstrated significant enhancement in ENaC expression in medulla and cortex of NCC KO and WT mice in response to ACTZ injection for 6 days, and treatment with amiloride in ACTZ-pretreated mice caused a robust increase in salt excretion in both NCC KO and WT mice. Pendrin KO mice did not display a significant increase in urine output or salt excretion after treatment with amiloride or ACTZ. Conclusion 1. ENaC plays an important role in salt reabsorption in NCC KO mice. 2. NCC contributes to compensatory salt reabsorption in the setting of carbonic anhydrase inhibition, which is associated with increased delivery of salt from the proximal tubule and the down regulation of pendrin. 3. ENaC is upregulated by ACTZ treatment and its inhibition by amiloride causes significant diuresis in NCC KO and WT mice. Despite being considered mild agents individually, we propose that the combination of acetazolamide and amiloride in the setting of NCC inhibition (i.e., hydrochlorothiazide) will be a powerful diuretic regimen. PMID:26963391

Study of the Effect of Lubricant Emulsion Percentage and Tool Material on Surface Roughness in Machining of EN-AC 48000 Alloy

NASA Astrophysics Data System (ADS)

Soltani, E.; Shahali, H.; Zarepour, H.

2011-01-01

In this paper, the effect of machining parameters, namely, lubricant emulsion percentage and tool material on surface roughness has been studied in machining process of EN-AC 48000 aluminum alloy. EN-AC 48000 aluminum alloy is an important alloy in industries. Machining of this alloy is of vital importance due to built-up edge and tool wear. A L9 Taguchi standard orthogonal array has been applied as experimental design to investigate the effect of the factors and their interaction. Nine machining tests have been carried out with three random replications resulting in 27 experiments. Three type of cutting tools including coated carbide (CD1810), uncoated carbide (H10), and polycrystalline diamond (CD10) have been used in this research. Emulsion percentage of lubricant is selected at three levels including 3%, 5% and 10%. Statistical analysis has been employed to study the effect of factors and their interactions using ANOVA method. Moreover, the optimal factors level has been achieved through signal to noise ratio (S/N) analysis. Also, a regression model has been provided to predict the surface roughness. Finally, the results of the confirmation tests have been presented to verify the adequacy of the predictive model. In this research, surface quality was improved by 9% using lubricant and statistical optimization method.

Redox Regulation of Epithelial Sodium Channels Examined in Alveolar Type 1 and 2 Cells Patch-clamped in Lung Slice Tissue*

PubMed Central

Helms, My N.; Jain, Lucky; Self, Julie L.; Eaton, Douglas C.

2008-01-01

The alveolar surface of the lung is lined by alveolar type 1 (AT1) and type 2 (AT2) cells. Using single channel patch clamp analysis in lung slice preparations, we are able to uniquely study AT1 and AT2 cells separately from intact lung. We report for the first time the Na+ transport properties of type 2 cells accessed in live lung tissue (as we have done in type 1 cells). Type 2 cells in lung tissue slices express both highly selective cation and nonselective cation channels with average conductances of 8.8 ± 3.2 and 22.5 ± 6.3 picosiemens, respectively. Anion channels with 10-picosiemen conductance are also present in the apical membrane of type 2 cells. Our lung slice studies importantly verify the use of cultured cell model systems commonly used in lung epithelial sodium channel (ENaC) studies. Furthermore, we identify novel functional differences between the cells that make up the alveolar epithelium. One important difference is that exposure to the nitric oxide (NO) donor, PAPA-NONOate (1.5 μm), significantly decreases average ENaC NPo in type 2 cells (from 1.38 ± 0.26 to 0.82 ± 0.16; p < 0.05 and n = 18) but failed to alter ENaC activity in alveolar type 1 cells. Elevating endogenous superoxide (\\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}{\\mathrm{O}}_{2}^{\\overline{.}}\\end{equation*}\\end{document}) levels with Ethiolat, a superoxide dismutase inhibitor, prevented NO inhibition of ENaC activity in type 2 cells, supporting the novel hypothesis that \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}{\\mathrm{O}}_{2}^{\\overline{.}}\\end{equation*}\\end{document} and NO signaling plays an important role in maintaining lung fluid balance. PMID:18541535

Whole-exome sequencing reveals an inherited R566X mutation of the epithelial sodium channel β-subunit in a case of early-onset phenotype of Liddle syndrome.

PubMed

Polfus, Linda M; Boerwinkle, Eric; Gibbs, Richard A; Metcalf, Ginger; Muzny, Donna; Veeraraghavan, Narayanan; Grove, Megan; Shete, Sanjay; Wallace, Stephanie; Milewicz, Dianna; Hanchard, Neil; Lupski, James R; Hashmi, Syed Shahrukh; Gupta-Malhotra, Monesha

2016-11-01

To comprehensively evaluate a European-American child with severe hypertension, whole-exome sequencing (WES) was performed on the child and parents, which identified causal variation of the proband's early-onset disease. The proband's hypertension was resistant to treatment, requiring a multiple drug regimen including amiloride, spironolactone, and hydrochlorothiazide. We suspected a monogenic form of hypertension because of the persistent hypokalemia with low plasma levels of renin and aldosterone. To address this, we focused on rare functional variants and indels, and performed gene-based tests incorporating linkage scores and allele frequency and filtered on deleterious functional mutations. Drawing upon clinical presentation, 27 genes were selected evidenced to cause monogenic hypertension and matched to the gene-based results. This resulted in the identification of a stop-gain mutation in an epithelial sodium channel (ENaC), SCNN1B , an established Liddle syndrome gene, shared by the child and her father. Interestingly, the father also harbored a missense mutation (p.Trp552Arg) in the α-subunit of the ENaC trimer, SCNN1A , possibly pointing to pseudohypoaldosteronism type I. This case is unique in that we present the early-onset disease and treatment response caused by a canonical stop-gain mutation (p.Arg566*) as well as ENaC digenic hits in the father, emphasizing the utility of WES informing precision medicine.

Characterization of interactions between Nedd4 and beta and gammaENaC using surface plasmon resonance.

PubMed

Asher, C; Chigaev, A; Garty, H

2001-09-07

Cell surface expression of the epithelial Na(+) channel ENaC is regulated by the ubiquitin ligase Nedd4. Binding of the WW domains of Nedd4 to the PY region in the carboxy tails of beta and gammaENaC, results in channel ubiquitination and degradation. Kinetic analysis of these interactions has been done using surface plasmon resonance. Synthetic peptides corresponding to the PY regions of beta and gammaENaC were immobilized on a sensor chip and "real-time" kinetics of their binding to recombinant WW proteins was determined. Specificity of the interactions was established by competition experiment, as well as by monitoring effects of a point mutation known to impair Nedd4/ENaC binding. These data provides the first determination of association, dissociation and equilibrium constants for the interactions between WW2 and beta or gammaENaC. Copyright 2001 Academic Press.

A MicroRNA Cluster miR-23-24-27 Is Upregulated by Aldosterone in the Distal Kidney Nephron Where it Alters Sodium Transport.

PubMed

Liu, Xiaoning; Edinger, Robert S; Klemens, Christine A; Phua, Yu L; Bodnar, Andrew J; LaFramboise, William A; Ho, Jacqueline; Butterworth, Michael B

2017-06-01

The epithelial sodium channel (ENaC) is expressed in the epithelial cells of the distal convoluted tubules, connecting tubules, and cortical collecting duct (CCD) in the kidney nephron. Under the regulation of the steroid hormone aldosterone, ENaC is a major determinant of sodium (Na + ) and water balance. The ability of aldosterone to regulate microRNAs (miRs) in the kidney has recently been realized, but the role of miRs in Na + regulation has not been well established. Here we demonstrate that expression of a miR cluster mmu-miR-23-24-27, is upregulated in the CCD by aldosterone stimulation both in vitro and in vivo. Increasing the expression of these miRs increased Na + transport in the absence of aldosterone stimulation. Potential miR targets were evaluated and miR-27a/b was verified to bind to the 3'-untranslated region of intersectin-2, a multi-domain protein expressed in the distal kidney nephron and involved in the regulation of membrane trafficking. Expression of Itsn2 mRNA and protein was decreased after aldosterone stimulation. Depletion of Itsn2 expression, mimicking aldosterone regulation, increased ENaC-mediated Na + transport, while Itsn2 overexpression reduced ENaC's function. These findings reinforce a role for miRs in aldosterone regulation of Na + transport, and implicate miR-27 in aldosterone's action via a novel target. J. Cell. Physiol. 232: 1306-1317, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Chloride transport-driven alveolar fluid secretion is a major contributor to cardiogenic lung edema

PubMed Central

Solymosi, Esther A.; Kaestle-Gembardt, Stefanie M.; Vadász, István; Wang, Liming; Neye, Nils; Chupin, Cécile Julie Adrienne; Rozowsky, Simon; Ruehl, Ramona; Tabuchi, Arata; Schulz, Holger; Kapus, Andras; Morty, Rory E.; Kuebler, Wolfgang M.

2013-01-01

Alveolar fluid clearance driven by active epithelial Na+ and secondary Cl− absorption counteracts edema formation in the intact lung. Recently, we showed that impairment of alveolar fluid clearance because of inhibition of epithelial Na+ channels (ENaCs) promotes cardiogenic lung edema. Concomitantly, we observed a reversal of alveolar fluid clearance, suggesting that reversed transepithelial ion transport may promote lung edema by driving active alveolar fluid secretion. We, therefore, hypothesized that alveolar ion and fluid secretion may constitute a pathomechanism in lung edema and aimed to identify underlying molecular pathways. In isolated perfused lungs, alveolar fluid clearance and secretion were determined by a double-indicator dilution technique. Transepithelial Cl− secretion and alveolar Cl− influx were quantified by radionuclide tracing and alveolar Cl− imaging, respectively. Elevated hydrostatic pressure induced ouabain-sensitive alveolar fluid secretion that coincided with transepithelial Cl− secretion and alveolar Cl− influx. Inhibition of either cystic fibrosis transmembrane conductance regulator (CFTR) or Na+-K+-Cl− cotransporters (NKCC) blocked alveolar fluid secretion, and lungs of CFTR−/− mice were protected from hydrostatic edema. Inhibition of ENaC by amiloride reproduced alveolar fluid and Cl− secretion that were again CFTR-, NKCC-, and Na+-K+-ATPase–dependent. Our findings show a reversal of transepithelial Cl− and fluid flux from absorptive to secretory mode at hydrostatic stress. Alveolar Cl− and fluid secretion are triggered by ENaC inhibition and mediated by NKCC and CFTR. Our results characterize an innovative mechanism of cardiogenic edema formation and identify NKCC1 as a unique therapeutic target in cardiogenic lung edema. PMID:23645634

Nonantibiotic macrolides prevent human neutrophil elastase-induced mucus stasis and airway surface liquid volume depletion.

PubMed

Tarran, Robert; Sabater, Juan R; Clarke, Tainya C; Tan, Chong D; Davies, Catrin M; Liu, Jia; Yeung, Arthur; Garland, Alaina L; Stutts, M Jackson; Abraham, William M; Phillips, Gary; Baker, William R; Wright, Clifford D; Wilbert, Sibylle

2013-06-01

Mucus clearance is an important component of the lung's innate defense system. A failure of this system brought on by mucus dehydration is common to both cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Mucus clearance rates are regulated by the volume of airway surface liquid (ASL) and by ciliary beat frequency (CBF). Chronic treatment with macrolide antibiotics is known to be beneficial to both CF and COPD patients. However, chronic macrolide usage may induce bacterial resistance. We have developed a novel macrolide, 2'-desoxy-9-(S)-erythromycylamine (GS-459755), that has significantly diminished antibiotic activity against Staphylococcus aureus, Streptococcus pneumonia, Moraxella catarrhalis, and Haemophilus influenzae. Since neutrophilia frequently occurs in chronic lung disease and human neutrophil elastase (HNE) induces mucus stasis by activating the epithelial sodium channel (ENaC), we tested the ability of GS-459755 to protect against HNE-induced mucus stasis. GS-459755 had no effect on HNE activity. However, GS-459755 pretreatment protected against HNE-induced ASL volume depletion in human bronchial epithelial cells (HBECs). The effect of GS-459755 on ASL volume was dose dependent (IC₅₀ ~3.9 μM) and comparable to the antibacterial macrolide azithromycin (IC₅₀ ~2.4 μM). Macrolides had no significant effect on CBF or on transepithelial water permeability. However, the amiloride-sensitive transepithelial voltage, a marker of ENaC activity, was diminished by macrolide pretreatment. We conclude that GS-459755 may limit HNE-induced activation of ENaC and may be useful for the treatment of mucus dehydration in CF and COPD without inducing bacterial resistance.

Altered ion transport by thyroid epithelia from CFTR−/− pigs suggests mechanisms for hypothyroidism in Cystic Fibrosis

PubMed Central

Li, Hui; Ganta, Suhasini; Fong, Peying

2010-01-01

Subclinical hypothyroidism has been linked to Cystic Fibrosis (CF), and the cystic fibrosis transmembrane conductance regulator (CFTR) shown to be expressed in the thyroid. The thyroid epithelium secretes Cl− and absorbs Na+ in response to cAMP. Chloride secretion may provide a counter-ion for the SLC26A4 (Pendrin)-mediated I− secretion which is required for the first step of thyroid hormonogenesis, thyroglobulin iodination. In contrast, few models exist to explain a role for Na+ absorption. Whether CFTR mediates the secretory Cl− current in thyroid epithelium has not been directly addressed. We used thyroids from a novel pig CFTR−/− model, generated primary pig thyroid epithelial cell cultures (pThECs), analyzed these cultures for preservation of thyroid-specific transcripts and proteins, and monitored 1) the Cl− secretory response to the cAMP agonist, isoproterenol and 2) the amiloride-sensitive Na+ current. Baseline short-circuit current (Isc) did not differ between CFTR+/+ and CFTR−/− cultures. Serosal isoproterenol increased Isc in CFTR+/+, but not CFTR−/−, monolayers. Compared to CFTR+/+ thyroid cultures, amiloride-sensitive Na+ absorption measured in CFTR−/− pThECs represented a greater fraction of the resting Isc. However, levels of transcripts encoding ENaC subunits did not differ between CFTR+/+ and CFTR−/− pThECs. Immunoblot analysis verified ENaC subunit protein expression, but quantification indicated no difference in expression levels. Our studies definitively demonstrate that CFTR mediates cAMP-stimulated Cl− secretion in a well-differentiated thyroid culture model, and that knockout of CFTR promotes increased Na+ absorption by a mechanism other than increased ENaC expression. These findings suggest several models for the mechanism of CF-associated hypothyroidism. PMID:20729267

Regional differences in rat conjunctival ion transport activities

PubMed Central

Yu, Dongfang; Thelin, William R.; Rogers, Troy D.; Stutts, M. Jackson; Randell, Scott H.; Grubb, Barbara R.

2012-01-01

Active ion transport and coupled osmotic water flow are essential to maintain ocular surface health. We investigated regional differences in the ion transport activities of the rat conjunctivas and compared these activities with those of cornea and lacrimal gland. The epithelial sodium channel (ENaC), sodium/glucose cotransporter 1 (Slc5a1), transmembrane protein 16 (Tmem16a, b, f, and g), cystic fibrosis transmembrane conductance regulator (Cftr), and mucin (Muc4, 5ac, and 5b) mRNA expression was characterized by RT-PCR. ENaC proteins were measured by Western blot. Prespecified regions (palpebral, fornical, and bulbar) of freshly isolated conjunctival tissues and cell cultures were studied electrophysiologically with Ussing chambers. The transepithelial electrical potential difference (PD) of the ocular surface was also measured in vivo. The effect of amiloride and UTP on the tear volume was evaluated in lacrimal gland excised rats. All selected genes were detected but with different expression patterns. We detected αENaC protein in all tissues, βENaC in palpebral and fornical conjunctiva, and γENaC in all tissues except lacrimal glands. Electrophysiological studies of conjunctival tissues and cell cultures identified functional ENaC, SLC5A1, CFTR, and TMEM16. Fornical conjunctiva exhibited the most active ion transport under basal conditions amongst conjunctival regions. PD measurements confirmed functional ENaC-mediated Na+ transport on the ocular surface. Amiloride and UTP increased tear volume in lacrimal gland excised rats. This study demonstrated that the different regions of the conjunctiva exhibited a spectrum of ion transport activities. Understanding the specific functions of distinct regions of the conjunctiva may foster a better understanding of the physiology maintaining hydration of the ocular surface. PMID:22814399

Mineralocorticoid effects in the late gestation ovine fetal lung

PubMed Central

McCartney, Jarret; Richards, Elaine M.; Wood, Charles E.; Keller‐Wood, Maureen

2014-01-01

Abstract This study was designed to determine the effects of corticosteroids at MR in the late‐gestation fetal lung. Since both the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) are expressed at relatively high levels in the fetal lung, endogenous corticosteroids may act at MR as well as GR in the preterm fetal lung. The GR agonist, betamethasone, the MR agonist, aldosterone, or both were infused intravenously for 48 h in ovine fetuses of approximately 130 days gestation. Effects on airway pressures during stepwise inflation of the in situ lung, expression of ENaC alpha (SCNN1A), ENaC beta (SCNN1B), and Na,K ATPase (ATP1A1), and elastin and collagen content were determined after the infusions. We found that aldosterone significantly reduced the airway pressure measured during the initial step in inflation of the lung, although aldosterone had no overall effect on lung compliance, nor did aldosterone induce expression of ENaCα, ENaCβ or Na,K ATPaseα1. Betamethasone significantly increased expression of the epithelial sodium channel (ENaC) subunit mRNAs, and collagen and elastin content in the lungs, although this dose of betamethasone also had no effect on lung compliance. There was no synergy between effects of the MR and GR agonists. Transcriptomic analysis suggested that although aldosterone did not alter genes in pathways related to epithelial sodium transport, aldosterone did alter genes in pathways involved in cell proliferation in the lungs. The results are consistent with corticosteroid‐induced fluid reabsorption at birth through GR rather than MR, but suggest that MR facilitates lung maturation, and may contribute to inflation with the first breaths via mechanisms distinct from known aldosterone effects in other epithelia. PMID:25347852

Thirst Increases Chorda Tympani Responses to Sodium Chloride.

PubMed

Mast, Thomas G; Breza, Joseph M; Contreras, Robert J

2017-10-01

In nature, water is present as a low-salt solution, thus we hypothesized that thirst would increase taste responses to low-salt solutions. We investigated the effect of thirst on the 2 different salt detection mechanisms present in the rat chorda tympani (CT) nerve. The first mechanism is dependent upon the epithelial sodium channel (ENaC), is blocked by benzamil, and is specific to the cation sodium. The second mechanism, while undefined, is independent of ENaC, and detects multiple cations. We expected thirst to increase benzamil-sensitive sodium responses due to mechanistically increasing the benzamil-sensitive ENaC. We recorded CT whole-nerve electrophysiological responses to lingual application of NaCl, KCl (30, 75, 150, 300, 500, and 600 mM), and imitation rainwater in both control and 24-h water-restricted male rats. NaCl solutions were presented in artificial saliva before and after lingual application of 5µM benzamil. Water restriction significantly increased the integrated CT responses to NaCl but not to KCl or imitation rainwater. Consistent with our hypothesis, only the benzamil-sensitive, and not the benzamil-insensitive, CT sodium response significantly increased. Additionally, CT responses to salt were recorded following induction of either osmotic or volemic thirst. Both thirsts significantly enhanced the integrated CT responses to NaCl and KCl, but not imitation rainwater. Interestingly, osmotic and volemic thirsts increased CT responses by increasing both the benzamil-sensitive and benzamil-insensitive CT sodium responses. We propose that thirst increases the sensitivity of the CT nerve to sodium. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Mechanisms of renal control of potassium homeostasis in complete aldosterone deficiency.

PubMed

Todkar, Abhijeet; Picard, Nicolas; Loffing-Cueni, Dominique; Sorensen, Mads V; Mihailova, Marija; Nesterov, Viatcheslav; Makhanova, Natalia; Korbmacher, Christoph; Wagner, Carsten A; Loffing, Johannes

2015-02-01

Aldosterone-independent mechanisms may contribute to K(+) homeostasis. We studied aldosterone synthase knockout (AS(-/-)) mice to define renal control mechanisms of K(+) homeostasis in complete aldosterone deficiency. AS(-/-) mice were normokalemic and tolerated a physiologic dietary K(+) load (2% K(+), 2 days) without signs of illness, except some degree of polyuria. With supraphysiologic K(+) intake (5% K(+)), AS(-/-) mice decompensated and became hyperkalemic. High-K(+) diets induced upregulation of the renal outer medullary K(+) channel in AS(-/-) mice, whereas upregulation of the epithelial sodium channel (ENaC) sufficient to increase the electrochemical driving force for K(+) excretion was detected only with a 2% K(+) diet. Phosphorylation of the thiazide-sensitive NaCl cotransporter was consistently lower in AS(-/-) mice than in AS(+/+) mice and was downregulated in mice of both genotypes in response to increased K(+) intake. Inhibition of the angiotensin II type 1 receptor reduced renal creatinine clearance and apical ENaC localization, and caused severe hyperkalemia in AS(-/-) mice. In contrast with the kidney, the distal colon of AS(-/-) mice did not respond to dietary K(+) loading, as indicated by Ussing-type chamber experiments. Thus, renal adaptation to a physiologic, but not supraphysiologic, K(+) load can be achieved in aldosterone deficiency by aldosterone-independent activation of the renal outer medullary K(+) channel and ENaC, to which angiotensin II may contribute. Enhanced urinary flow and reduced activity of the thiazide-sensitive NaCl cotransporter may support renal adaptation by activation of flow-dependent K(+) secretion and increased intratubular availability of Na(+) that can be reabsorbed in exchange for K(+) secreted. Copyright © 2015 by the American Society of Nephrology.

CFTR/ENaC dependent regulation of membrane potential during human sperm capacitation is initiated by bicarbonate uptake through NBC.

PubMed

Puga Molina, Lis C; Pinto, Nicolas A; Torres, Nicolás I; Gonzalez-Cota, Ana L; Luque, Guillermina M; Balestrini, Paula A; Romarowski, Ana; Krapf, Dario; Santi, Celia M; Trevino, Claudia L; Darszon, Alberto; Buffone, Mariano G

2018-05-09

To fertilize an egg, sperm must reside in the female reproductive tract to undergo several maturational changes that are collectively referred to as capacitation. From a molecular point of view, the HCO3--dependent activation of the atypical soluble adenylyl cyclase (ADCY10) is one of the first events that occurs during capacitation and leads to the subsequent cAMP-dependent activation of protein kinase A (PKA). Capacitation is also accompanied by hyperpolarization of the sperm plasma membrane. We previously reported that PKA activation is necessary for CFTR (Cystic Fibrosis Transmembrane Conductance Regulator Channel) activity and for the modulation of membrane potential (Em). However, the main HCO3- transporters involved in the initial transport and the PKA-dependent Em changes are not well known nor characterized. Here, we analyzed how the activity of CFTR regulates Em during capacitation and examined its relationship with an electrogenic Na+/HCO3- cotransporter (NBC) and epithelial Na+ channels (ENaCs). We observed that inhibition of both CFTR and NBC decreased HCO3- influx, resulting in lower PKA activity, and that events downstream the cAMP-activation of PKA are essential for the regulation of Em. Addition of a permeable cAMP analog partially rescued the inhibitory effects caused by these inhibitors. HCO3-  also produced a rapid membrane hyperpolarization mediated by ENaC channels, which contribute to the regulation of Em during capacitation. Altogether, we demonstrate for the first time, that NBC cotransporters and ENaC channels are essential in the CFTR-dependent activation of the cAMP/PKA signaling pathway and Em regulation during human sperm capacitation. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

The central mechanism underlying hypertension: a review of the roles of sodium ions, epithelial sodium channels, the renin–angiotensin–aldosterone system, oxidative stress and endogenous digitalis in the brain

PubMed Central

Takahashi, Hakuo; Yoshika, Masamichi; Komiyama, Yutaka; Nishimura, Masato

2011-01-01

The central nervous system has a key role in regulating the circulatory system by modulating the sympathetic and parasympathetic nervous systems, pituitary hormone release, and the baroreceptor reflex. Digoxin- and ouabain-like immunoreactive materials were found >20 years ago in the hypothalamic nuclei. These factors appeared to localize to the paraventricular and supraoptic nuclei and the nerve fibers at the circumventricular organs and supposed to affect electrolyte balance and blood pressure. The turnover rate of these materials increases with increasing sodium intake. As intracerebroventricular injection of ouabain increases blood pressure via sympathetic activation, an endogenous digitalis-like factor (EDLF) was thought to regulate cardiovascular system-related functions in the brain, particularly after sodium loading. Experiments conducted mainly in rats revealed that the mechanism of action of ouabain in the brain involves sodium ions, epithelial sodium channels (ENaCs) and the renin–angiotensin–aldosterone system (RAAS), all of which are affected by sodium loading. Rats fed a high-sodium diet develop elevated sodium levels in their cerebrospinal fluid, which activates ENaCs. Activated ENaCs and/or increased intracellular sodium in neurons activate the RAAS; this releases EDLF in the brain, activating the sympathetic nervous system. The RAAS promotes oxidative stress in the brain, further activating the RAAS and augmenting sympathetic outflow. Angiotensin II and aldosterone of peripheral origin act in the brain to activate this cascade, increasing sympathetic outflow and leading to hypertension. Thus, the brain Na+–ENaC–RAAS–EDLF axis activates sympathetic outflow and has a crucial role in essential and secondary hypertension. This report provides an overview of the central mechanism underlying hypertension and discusses the use of antihypertensive agents. PMID:21814209

NaCl responsive taste cells in the mouse fungiform taste buds.

PubMed

Yoshida, R; Horio, N; Murata, Y; Yasumatsu, K; Shigemura, N; Ninomiya, Y

2009-03-17

Previous studies have demonstrated that rodents' chorda tympani (CT) nerve fibers responding to NaCl can be classified according to their sensitivities to the epithelial sodium channel (ENaC) blocker amiloride into two groups: amiloride-sensitive (AS) and -insensitive (AI). The AS fibers were shown to respond specifically to NaCl, whereas AI fibers broadly respond to various electrolytes, including NaCl. These data suggest that salt taste transduction in taste cells may be composed of at least two different systems; AS and AI ones. To further address this issue, we investigated the responses to NaCl, KCl and HCl and the amiloride sensitivity of mouse fungiform papilla taste bud cells which are innervated by the CT nerve. Comparable with the CT data, the results indicated that 56 NaCl-responsive cells tested were classified into two groups; 25 cells ( approximately 44%) narrowly responded to NaCl and their NaCl response were inhibited by amiloride (AS cells), whereas the remaining 31 cells ( approximately 56%) responded not only to NaCl, but to KCl and/or HCl and showed no amiloride inhibition of NaCl responses (AI cells). Amiloride applied to the basolateral side of taste cells had no effect on NaCl responses in the AS and AI cells. Single cell reverse transcription-polymerase chain reaction (RT-PCR) experiments indicated that ENaC subunit mRNA was expressed in a subset of AS cells. These findings suggest that the mouse fungiform taste bud is composed of AS and AI cells that can transmit taste information differently to their corresponding types of CT fibers, and apical ENaCs may be involved in the NaCl responses of AS cells.

Rapid elevation of sodium transport through insulin is mediated by AKT in alveolar cells

PubMed Central

Mattes, Charlott; Laube, Mandy; Thome, Ulrich H.

2014-01-01

Abstract Alveolar fluid clearance is driven by vectorial Na+ transport and promotes postnatal lung adaptation. The effect of insulin on alveolar epithelial Na+ transport was studied in isolated alveolar cells from 18–19‐day gestational age rat fetuses. Equivalent short‐circuit currents (ISC) were measured in Ussing chambers and different kinase inhibitors were used to determine the pathway of insulin stimulation. In Western Blot measurements the activation of mediators stimulated by insulin was analyzed. The ISC showed a fast dose‐dependent increase by insulin, which could be attributed to an increased ENaC (epithelial Na+ channel) activity in experiments with permeabilized apical or basolateral membrane. 5‐(N‐Ethyl‐N‐isopropyl)amiloride inhibition of ISC was not affected, however, benzamil‐sensitive ISC was increased in insulin‐stimulated monolayers. The application of LY‐294002 and Akti1/2 both completely blocked the stimulating effect of insulin on ISC. PP242 partly blocked the effect of insulin, whereas Rapamycin evoked no inhibition. Western Blot measurements revealed an increased phosphorylation of AKT after insulin stimulation. SGK1 activity was also increased by insulin as shown by Western Blot of pNDRG1. However, in Ussing chamber measurements, GSK650394, an inhibitor of SGK1 did not prevent the increase in ISC induced by insulin. The application of IGF‐1 mimicked the effect of insulin and increased the ENaC activity. In addition, an increased autophosphorylation of the IGF‐1R/IR was observed after insulin stimulation. We conclude that insulin rapidly increases epithelial Na+ transport by enhancing the activity of endogenous ENaC through activation of PI3K/AKT in alveolar cells. PMID:24760523

Nonantibiotic macrolides prevent human neutrophil elastase-induced mucus stasis and airway surface liquid volume depletion

PubMed Central

Sabater, Juan R.; Clarke, Tainya C.; Tan, Chong D.; Davies, Catrin M.; Liu, Jia; Yeung, Arthur; Garland, Alaina L.; Stutts, M. Jackson; Abraham, William M.; Phillips, Gary; Baker, William R.; Wright, Clifford D.; Wilbert, Sibylle

2013-01-01

Mucus clearance is an important component of the lung's innate defense system. A failure of this system brought on by mucus dehydration is common to both cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Mucus clearance rates are regulated by the volume of airway surface liquid (ASL) and by ciliary beat frequency (CBF). Chronic treatment with macrolide antibiotics is known to be beneficial to both CF and COPD patients. However, chronic macrolide usage may induce bacterial resistance. We have developed a novel macrolide, 2′-desoxy-9-(S)-erythromycylamine (GS-459755), that has significantly diminished antibiotic activity against Staphylococcus aureus, Streptococcus pneumonia, Moraxella catarrhalis, and Haemophilus influenzae. Since neutrophilia frequently occurs in chronic lung disease and human neutrophil elastase (HNE) induces mucus stasis by activating the epithelial sodium channel (ENaC), we tested the ability of GS-459755 to protect against HNE-induced mucus stasis. GS-459755 had no effect on HNE activity. However, GS-459755 pretreatment protected against HNE-induced ASL volume depletion in human bronchial epithelial cells (HBECs). The effect of GS-459755 on ASL volume was dose dependent (IC50 ∼3.9 μM) and comparable to the antibacterial macrolide azithromycin (IC50 ∼2.4 μM). Macrolides had no significant effect on CBF or on transepithelial water permeability. However, the amiloride-sensitive transepithelial voltage, a marker of ENaC activity, was diminished by macrolide pretreatment. We conclude that GS-459755 may limit HNE-induced activation of ENaC and may be useful for the treatment of mucus dehydration in CF and COPD without inducing bacterial resistance. PMID:23542952

β-Liddle mutation of the epithelial sodium channel increases alveolar fluid clearance and reduces the severity of hydrostatic pulmonary oedema in mice

PubMed Central

Randrianarison, Nadia; Escoubet, Brigitte; Ferreira, Chrystophe; Fontayne, Alexandre; Fowler-Jaeger, Nicole; Clerici, Christine; Hummler, Edith; Rossier, Bernard C; Planès, Carole

2007-01-01

Transepithelial sodium transport via alveolar epithelial Na+ channels and Na+,K+-ATPase constitutes the driving force for removal of alveolar oedema fluid. Decreased activity of the amiloride-sensitive epithelial Na+ channel (ENaC) in the apical membrane of alveolar epithelial cells impairs sodium-driven alveolar fluid clearance (AFC) and predisposes to pulmonary oedema. We hypothesized that hyperactivity of ENaC in the distal lung could improve AFC and facilitate the resolution of pulmonary oedema. AFC and lung fluid balance were studied at baseline and under conditions of hydrostatic pulmonary oedema in the β-Liddle (L) mouse strain harbouring a gain-of-function mutation (R566stop) within the Scnn1b gene. As compared with wild-type (+/+), baseline AFC was increased by 2- and 3-fold in heterozygous (+/L) and homozygous mutated (L/L) mice, respectively, mainly due to increased amiloride-sensitive AFC. The β2-agonist terbutaline stimulated AFC in +/+ and +/L mice, but not in L/L mice. Acute volume overload induced by saline infusion (40% of body weight over 2 h) significantly increased extravascular (i.e. interstitial and alveolar) lung water as assessed by the bloodless wet-to-dry lung weight ratio in +/+ and L/L mice, as compared with baseline. However, the increase was significantly larger in +/+ than in L/L groups (P= 0.01). Volume overload also increased the volume of the alveolar epithelial lining fluid in +/+ mice, indicating the presence of alveolar oedema, but not in L/L mice. Cardiac function as evaluated by echocardiography was comparable in both groups. These data show that constitutive ENaC activation improved sodium-driven AFC in the mouse lung, and attenuated the severity of hydrostatic pulmonary oedema. PMID:17430990

Regional differences in rat conjunctival ion transport activities.

PubMed

Yu, Dongfang; Thelin, William R; Rogers, Troy D; Stutts, M Jackson; Randell, Scott H; Grubb, Barbara R; Boucher, Richard C

2012-10-01

Active ion transport and coupled osmotic water flow are essential to maintain ocular surface health. We investigated regional differences in the ion transport activities of the rat conjunctivas and compared these activities with those of cornea and lacrimal gland. The epithelial sodium channel (ENaC), sodium/glucose cotransporter 1 (Slc5a1), transmembrane protein 16 (Tmem16a, b, f, and g), cystic fibrosis transmembrane conductance regulator (Cftr), and mucin (Muc4, 5ac, and 5b) mRNA expression was characterized by RT-PCR. ENaC proteins were measured by Western blot. Prespecified regions (palpebral, fornical, and bulbar) of freshly isolated conjunctival tissues and cell cultures were studied electrophysiologically with Ussing chambers. The transepithelial electrical potential difference (PD) of the ocular surface was also measured in vivo. The effect of amiloride and UTP on the tear volume was evaluated in lacrimal gland excised rats. All selected genes were detected but with different expression patterns. We detected αENaC protein in all tissues, βENaC in palpebral and fornical conjunctiva, and γENaC in all tissues except lacrimal glands. Electrophysiological studies of conjunctival tissues and cell cultures identified functional ENaC, SLC5A1, CFTR, and TMEM16. Fornical conjunctiva exhibited the most active ion transport under basal conditions amongst conjunctival regions. PD measurements confirmed functional ENaC-mediated Na(+) transport on the ocular surface. Amiloride and UTP increased tear volume in lacrimal gland excised rats. This study demonstrated that the different regions of the conjunctiva exhibited a spectrum of ion transport activities. Understanding the specific functions of distinct regions of the conjunctiva may foster a better understanding of the physiology maintaining hydration of the ocular surface.

Channel-transporter complexes: an emerging theme in cell signaling.

PubMed

Abbott, Geoffrey W

2016-11-01

In a recent edition of Biochemical Journal, Mistry et al. described the discovery of a novel protein complex, formed from the epithelial sodium channel (ENaC) and the sodium chloride cotransporter (NCC) [Mistry et al. (2016) Biochem. J. 473, 3237–3252]. The importance of these two proteins in the regulation of salt balance and blood pressure has long been known, as has their overlapping expression in the distal convoluted tubule of the kidney. The new study by Mistry et al. now demonstrates their physical interaction in the kidney and when heterologously co-expressed. Furthermore, the authors demonstrate some degree of functional co-dependence between ENaC and NCC, with pharmacological inhibition of the latter diminishing activity of the former when the two are co-assembled. This novel and potentially important interaction adds to a growing number of recently identified channel-transporter ('chansporter') complexes, which together constitute an emerging theme in cell signaling. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Exploring Nontraditional Participation as an Approach to Make Water Quality Trading Markets More Effective

EPA Science Inventory

Water quality trading (WQT) under the Clean Water Act is a compliance option for water quality based effluent limitations in a National Pollutant Discharge Elimination System (NPDES) permit (i.e., the requirements for discharging, monitoring, and reporting). States that have enac...

Cryptosporidium Off-The-Slide Genotyping: Recovery of Oocysts Extracted from Slides Examined by Method 1623

EPA Science Inventory

Cryptosporidium has been found world wide and is an important waterborne parasite causing a self-limiting diarrhea; however, in the immunocompromised it may become chronic and can even lead to death. To characterize the risk of exposure to Cryptosporidium in water the USEPA enac...

Multiresidue method for pesticide residue analysis in food of animal and plant origin based on GC or LC and MS or MS/MS.

PubMed

Muñoz, Eva; Muñoz, Gloria; Pineda, Laura; Serrahima, Eulalia; Centrich, Francesc

2012-01-01

A multiresidue method based on GC or LC and MS or MS/MS for the determination of 204 pesticides in diverse food matrixes of animal and plant origin is described. The method can include different stages of cleanup according to the chemical characteristics of each sample. Samples were extracted using accelerated solvent extraction. Those with a high fat content or that contained chlorophyll required further purification by gel permeation chromatography and/or SPE (ENVI-Carb). The methodology developed here was fully validated; the LOQs for the 204 pesticides are presented. The LOQ values lie between 0.01 to 0.02 mg/kg. However, in some cases, mainly in baby food, they were as low as 0.003 mg/kg, thereby meeting European Union requirements on maximum residue levels for pesticides, as outlined in European regulation 396/2005 and the Commission Directive 2003/13/EC. The procedure has been accredited for a wide scope of pesticides and matrixes by the Spanish Accreditation Body (ENAC) following ISO/IEC 17025:2005, as outlined in ENAC technical note NT-19.

Localization of beta and gamma subunits of ENaC in sensory nerve endings in the rat foot pad.

PubMed

Drummond, H A; Abboud, F M; Welsh, M J

2000-11-24

The molecular mechanisms underlying mechanoelectrical transduction and the receptors that detect light touch remain uncertain. Studies in Caenorhabditis elegans suggest that members of the DEG/ENaC cation channel family may be mechanoreceptors. Therefore, we tested the hypothesis that subunits of the mammalian epithelial Na(+) channel (ENaC) family are expressed in touch receptors in rat hairless skin. We detected betaENaC and gammaENaC, but not alphaENaC transcripts in cervical and lumbar dorsal root ganglia (DRG). Using immunofluorescence, we found betaENaC and gammaENaC expressed in medium to large lumbar DRG neurons. Moreover, we detected these two subunits in Merkel cell-neurite complexes, Meissner-like corpuscles, and small lamellated corpuscles, specialized mechanosensory structures of the skin. Within these structures, betaENaC and gammaENaC were localized in the nerve fibers believed to contain the sensors responsive to mechanical stress. Thus beta and gammaENaC subunits are good candidates as components of the molecular sensor that detects touch.

Prenatal programming of rat cortical collecting tubule sodium transport.

PubMed

Cheng, Chih-Jen; Lozano, German; Baum, Michel

2012-03-15

Prenatal insults have been shown to lead to elevated blood pressure in offspring when they are studied as adults. Prenatal administration of dexamethasone and dietary protein deprivation have demonstrated that there is an increase in transporter abundance for a number of nephron segments but not the subunits of the epithelial sodium channel (ENaC) in the cortical collecting duct. Recent studies have shown that aldosterone is elevated in offspring of protein-deprived mothers when studied as adults, but the physiological importance of the increase in serum aldosterone is unknown. As an indirect measure of ENaC activity, we compared the natriuretic response to benzamil in offspring of mothers who ate a low-protein diet (6%) with those who ate a normal diet (20%) for the last half of pregnancy. The natriuretic response to benzamil was greater in the 6% group (821.1 ± 161.0 μmol/24 h) compared with the 20% group (279.1 ± 137.0 μmol/24 h), consistent with greater ENaC activity in vivo (P < 0.05). In this study, we also directly studied cortical collecting tubule function from adult rats using in vitro microperfusion. There was no difference in basal or vasopressin-stimulated osmotic water permeability. However, while cortical collecting ducts of adult offspring whose mothers ate a 20% protein diet had no sodium transport (-1.9 ± 3.1 pmol·mm(-1)·min(-1)), the offspring of rats that ate a 6% protein diet during the last half of pregnancy had a net sodium flux of 10.7 ± 2.6 pmol·mm(-1)·min(-1) (P = 0.01) in tubules perfused in vitro. Sodium transport was measured using ion-selective electrodes, a novel technique allowing measurement of sodium in nanoliter quantities of fluid. Thus we directly demonstrate that there is prenatal programming of cortical collecting duct sodium transport.

Go with the Flow: Cerebrospinal Fluid Flow Regulates Neural Stem Cell Proliferation.

PubMed

Kaneko, Naoko; Sawamoto, Kazunobu

2018-06-01

Adult neural stem cells in the wall of brain ventricles make direct contact with cerebrospinal fluid. In this issue of Cell Stem Cell, Petrik et al. (2018) demonstrate that these neural stem cells sense the flow of cerebrospinal fluid through a transmembrane sodium channel, ENaC, which regulates their proliferation. Copyright © 2018 Elsevier Inc. All rights reserved.

The carboxyl terminus of the alpha-subunit of the amiloride-sensitive epithelial sodium channel binds to F-actin.

PubMed

Mazzochi, Christopher; Bubien, James K; Smith, Peter R; Benos, Dale J

2006-03-10

The activity of the amiloride-sensitive epithelial sodium channel (ENaC) is modulated by F-actin. However, it is unknown if there is a direct interaction between alpha-ENaC and actin. We have investigated the hypothesis that the actin cytoskeleton directly binds to the carboxyl terminus of alpha-ENaC using a combination of confocal microscopy, co-immunoprecipitation, and protein binding studies. Confocal microscopy of Madin-Darby canine kidney cell monolayers stably transfected with wild type, rat isoforms of alpha-, beta-, and gamma-ENaC revealed co-localization of alpha-ENaC with the cortical F-actin cytoskeleton both at the apical membrane and within the subapical cytoplasm. F-actin was found to co-immunoprecipitate with alpha-ENaC from whole cell lysates of this cell line. Gel overlay assays demonstrated that F-actin specifically binds to the carboxyl terminus of alpha-ENaC. A direct interaction between F-actin and the COOH terminus of alpha-ENaC was further corroborated by F-actin co-sedimentation studies. This is the first study to report a direct and specific biochemical interaction between F-actin and ENaC.

Pyrethroid stimulation of ion transport across frog skin.

PubMed

Cassano, Giuseppe; Bellantuono, Vito; Ardizzone, Concetta; Lippe, Claudio

2003-06-01

Pyrethroids are grouped into two classes (types I and II) because of the absence or presence of an alpha-cyano substituent and the production of a different intoxication syndrome in rodents. In this study, we investigated the effect of pyrethroids on the ion transport across frog skin (Rana esculenta). The short-circuit current value (estimate of ion transport) was increased by each of the eight pyrethroids tested, with the following order of potency: lambda-cyhalothrin > deltamethrin > alpha-cypermethrin = beta-cyfluthrin > bioallethrin > permethrin > bioresmethrin > phenothrin. The first four compounds are type II pyrethroids. Therefore, ion transport is stimulated more by type II pyrethroids than by type I. Experiments performed in the presence of amiloride support the conclusion that pyrethroids mainly increase Na+ absorption and to a lesser extent Cl- secretion. In these experiments, no systematic difference between type I and II pyrethroids was found. Finally, the stimulation by pyrethroids was inhibited by indomethacin and W7 (inhibitors of cyclooxygenases and the Ca2+/calmodulin system, respectively). These observations suggest that pyrethroids do not directly affect the epithelial Na+ channel (ENaC) but indirectly influence an intracellular event involved in ENaC modulation and linked to the Ca2+ signaling cascade.

Neural precursor cell-expressed developmentally down-regulated protein 4-2 (Nedd4-2) regulation by 14-3-3 protein binding at canonical serum and glucocorticoid kinase 1 (SGK1) phosphorylation sites.

PubMed

Chandran, Sindhu; Li, Hui; Dong, Wuxing; Krasinska, Karolina; Adams, Chris; Alexandrova, Ludmila; Chien, Allis; Hallows, Kenneth R; Bhalla, Vivek

2011-10-28

Regulation of epithelial Na(+) channel (ENaC)-mediated transport in the distal nephron is a critical determinant of blood pressure in humans. Aldosterone via serum and glucocorticoid kinase 1 (SGK1) stimulates ENaC by phosphorylation of the E3 ubiquitin ligase Nedd4-2, which induces interaction with 14-3-3 proteins. However, the mechanisms of SGK1- and 14-3-3-mediated regulation of Nedd4-2 are unclear. There are three canonical SGK1 target sites on Nedd4-2 that overlap phosphorylation-dependent 14-3-3 interaction motifs. Two of these are termed "minor," and one is termed "major," based on weak or strong binding to 14-3-3 proteins, respectively. By mass spectrometry, we found that aldosterone significantly stimulates phosphorylation of a minor, relative to the major, 14-3-3 binding site on Nedd4-2. Phosphorylation-deficient minor site Nedd4-2 mutants bound less 14-3-3 than did wild-type (WT) Nedd4-2, and minor site Nedd4-2 mutations were sufficient to inhibit SGK1 stimulation of ENaC cell surface expression. As measured by pulse-chase and cycloheximide chase assays, a major binding site Nedd4-2 mutant had a shorter cellular half-life than WT Nedd4-2, but this property was not dependent on binding to 14-3-3. Additionally, a dimerization-deficient 14-3-3ε mutant failed to bind Nedd4-2. We conclude that whereas phosphorylation at the Nedd4-2 major site is important for interaction with 14-3-3 dimers, minor site phosphorylation by SGK1 may be the relevant molecular switch that stabilizes Nedd4-2 interaction with 14-3-3 and thus promotes ENaC cell surface expression. We also propose that major site phosphorylation promotes cellular Nedd4-2 protein stability, which potentially represents a novel form of regulation for turnover of E3 ubiquitin ligases.

Hybrid Lipid/Polymer Nanoparticles for Pulmonary Delivery of siRNA: Development and Fate Upon In Vitro Deposition on the Human Epithelial Airway Barrier.

PubMed

d'Angelo, Ivana; Costabile, Gabriella; Durantie, Estelle; Brocca, Paola; Rondelli, Valeria; Russo, Annapina; Russo, Giulia; Miro, Agnese; Quaglia, Fabiana; Petri-Fink, Alke; Rothen-Rutishauser, Barbara; Ungaro, Francesca

2017-10-16

Nowadays, the downregulation of genes involved in the pathogenesis of severe lung diseases through local siRNA delivery appears an interesting therapeutic approach. In this study, we propose novel hybrid lipid-polymer nanoparticles (hNPs) consisting of poly(lactic-co-glycolic) acid (PLGA) and dipalmitoyl phosphatidylcholine (DPPC) as siRNA inhalation system. A panel of DPPC/PLGA hNPs was prepared by emulsion/solvent diffusion and fully characterized. A combination of model siRNAs against the sodium transepithelial channel (ENaC) was entrapped in optimized hNPs comprising or not poly(ethylenimine) (PEI) as third component. siRNA-loaded hNPs were characterized for encapsulation efficiency, release kinetics, aerodynamic properties, and stability in artificial mucus (AM). The fate and cytotoxicity of hNPs upon aerosolization on a triple cell co-culture model (TCCC) mimicking human epithelial airway barrier were assessed. Finally, the effect of siRNA-loaded hNPs on ENaC protein expression at 72 hours was evaluated in A549 cells. Optimized muco-inert hNPs encapsulating model siRNA with high efficiency were produced. The developed hNPs displayed a hydrodynamic diameter of ∼150 nm, a low polydispersity index, a negative ζ potential close to -25 mV, and a peculiar triphasic siRNA release lasting for 5 days, which slowed down in the presence of PEI. siRNA formulations showed optimal in vitro aerosol performance after delivery with a vibrating mesh nebulizer. Furthermore, small-angle X-ray scattering analyses highlighted an excellent stability upon incubation with AM, confirming the potential of hNPs for direct aerosolization on mucus-lined airways. Studies in TCCC confirmed that fluorescent hNPs are internalized inside airway epithelial cells and do not exert any cytotoxic or acute proinflammatory effect. Finally, a prolonged inhibition of ENaC protein expression was observed in A549 cells upon treatment with siRNA-loaded hNPs. Results demonstrate the great potential of hNPs as carriers for pulmonary delivery of siRNA, prompting toward investigation of their therapeutic effectiveness in severe lung diseases.

Open Markov Processes and Reaction Networks

NASA Astrophysics Data System (ADS)

Swistock Pollard, Blake Stephen

We begin by defining the concept of `open' Markov processes, which are continuous-time Markov chains where probability can flow in and out through certain `boundary' states. We study open Markov processes which in the absence of such boundary flows admit equilibrium states satisfying detailed balance, meaning that the net flow of probability vanishes between all pairs of states. External couplings which fix the probabilities of boundary states can maintain such systems in non-equilibrium steady states in which non-zero probability currents flow. We show that these non-equilibrium steady states minimize a quadratic form which we call 'dissipation.' This is closely related to Prigogine's principle of minimum entropy production. We bound the rate of change of the entropy of a driven non-equilibrium steady state relative to the underlying equilibrium state in terms of the flow of probability through the boundary of the process. We then consider open Markov processes as morphisms in a symmetric monoidal category by splitting up their boundary states into certain sets of `inputs' and `outputs.' Composition corresponds to gluing the outputs of one such open Markov process onto the inputs of another so that the probability flowing out of the first process is equal to the probability flowing into the second. Tensoring in this category corresponds to placing two such systems side by side. We construct a `black-box' functor characterizing the behavior of an open Markov process in terms of the space of possible steady state probabilities and probability currents along the boundary. The fact that this is a functor means that the behavior of a composite open Markov process can be computed by composing the behaviors of the open Markov processes from which it is composed. We prove a similar black-boxing theorem for reaction networks whose dynamics are given by the non-linear rate equation. Along the way we describe a more general category of open dynamical systems where composition corresponds to gluing together open dynamical systems.

Net Surface Flux Budget Over Tropical Oceans Estimated from the Tropical Rainfall Measuring Mission (TRMM)

NASA Astrophysics Data System (ADS)

Fan, Tai-Fang

We begin by defining the concept of `open' Markov processes, which are continuous-time Markov chains where probability can flow in and out through certain `boundary' states. We study open Markov processes which in the absence of such boundary flows admit equilibrium states satisfying detailed balance, meaning that the net flow of probability vanishes between all pairs of states. External couplings which fix the probabilities of boundary states can maintain such systems in non-equilibrium steady states in which non-zero probability currents flow. We show that these non-equilibrium steady states minimize a quadratic form which we call 'dissipation.' This is closely related to Prigogine's principle of minimum entropy production. We bound the rate of change of the entropy of a driven non-equilibrium steady state relative to the underlying equilibrium state in terms of the flow of probability through the boundary of the process. We then consider open Markov processes as morphisms in a symmetric monoidal category by splitting up their boundary states into certain sets of `inputs' and `outputs.' Composition corresponds to gluing the outputs of one such open Markov process onto the inputs of another so that the probability flowing out of the first process is equal to the probability flowing into the second. Tensoring in this category corresponds to placing two such systems side by side. We construct a `black-box' functor characterizing the behavior of an open Markov process in terms of the space of possible steady state probabilities and probability currents along the boundary. The fact that this is a functor means that the behavior of a composite open Markov process can be computed by composing the behaviors of the open Markov processes from which it is composed. We prove a similar black-boxing theorem for reaction networks whose dynamics are given by the non-linear rate equation. Along the way we describe a more general category of open dynamical systems where composition corresponds to gluing together open dynamical systems.

Magneto - Optical Imaging of Superconducting MgB2 Thin Films

NASA Astrophysics Data System (ADS)

Hummert, Stephanie Maria

We begin by defining the concept of `open' Markov processes, which are continuous-time Markov chains where probability can flow in and out through certain `boundary' states. We study open Markov processes which in the absence of such boundary flows admit equilibrium states satisfying detailed balance, meaning that the net flow of probability vanishes between all pairs of states. External couplings which fix the probabilities of boundary states can maintain such systems in non-equilibrium steady states in which non-zero probability currents flow. We show that these non-equilibrium steady states minimize a quadratic form which we call 'dissipation.' This is closely related to Prigogine's principle of minimum entropy production. We bound the rate of change of the entropy of a driven non-equilibrium steady state relative to the underlying equilibrium state in terms of the flow of probability through the boundary of the process. We then consider open Markov processes as morphisms in a symmetric monoidal category by splitting up their boundary states into certain sets of `inputs' and `outputs.' Composition corresponds to gluing the outputs of one such open Markov process onto the inputs of another so that the probability flowing out of the first process is equal to the probability flowing into the second. Tensoring in this category corresponds to placing two such systems side by side. We construct a `black-box' functor characterizing the behavior of an open Markov process in terms of the space of possible steady state probabilities and probability currents along the boundary. The fact that this is a functor means that the behavior of a composite open Markov process can be computed by composing the behaviors of the open Markov processes from which it is composed. We prove a similar black-boxing theorem for reaction networks whose dynamics are given by the non-linear rate equation. Along the way we describe a more general category of open dynamical systems where composition corresponds to gluing together open dynamical systems.

Boron Carbide Filled Neutron Shielding Textile Polymers

NASA Astrophysics Data System (ADS)

Manzlak, Derrick Anthony

We begin by defining the concept of `open' Markov processes, which are continuous-time Markov chains where probability can flow in and out through certain `boundary' states. We study open Markov processes which in the absence of such boundary flows admit equilibrium states satisfying detailed balance, meaning that the net flow of probability vanishes between all pairs of states. External couplings which fix the probabilities of boundary states can maintain such systems in non-equilibrium steady states in which non-zero probability currents flow. We show that these non-equilibrium steady states minimize a quadratic form which we call 'dissipation.' This is closely related to Prigogine's principle of minimum entropy production. We bound the rate of change of the entropy of a driven non-equilibrium steady state relative to the underlying equilibrium state in terms of the flow of probability through the boundary of the process. We then consider open Markov processes as morphisms in a symmetric monoidal category by splitting up their boundary states into certain sets of `inputs' and `outputs.' Composition corresponds to gluing the outputs of one such open Markov process onto the inputs of another so that the probability flowing out of the first process is equal to the probability flowing into the second. Tensoring in this category corresponds to placing two such systems side by side. We construct a `black-box' functor characterizing the behavior of an open Markov process in terms of the space of possible steady state probabilities and probability currents along the boundary. The fact that this is a functor means that the behavior of a composite open Markov process can be computed by composing the behaviors of the open Markov processes from which it is composed. We prove a similar black-boxing theorem for reaction networks whose dynamics are given by the non-linear rate equation. Along the way we describe a more general category of open dynamical systems where composition corresponds to gluing together open dynamical systems.

Parallel Unstructured Grid Generation for Complex Real-World Aerodynamic Simulations

NASA Astrophysics Data System (ADS)

Zagaris, George

We begin by defining the concept of `open' Markov processes, which are continuous-time Markov chains where probability can flow in and out through certain `boundary' states. We study open Markov processes which in the absence of such boundary flows admit equilibrium states satisfying detailed balance, meaning that the net flow of probability vanishes between all pairs of states. External couplings which fix the probabilities of boundary states can maintain such systems in non-equilibrium steady states in which non-zero probability currents flow. We show that these non-equilibrium steady states minimize a quadratic form which we call 'dissipation.' This is closely related to Prigogine's principle of minimum entropy production. We bound the rate of change of the entropy of a driven non-equilibrium steady state relative to the underlying equilibrium state in terms of the flow of probability through the boundary of the process. We then consider open Markov processes as morphisms in a symmetric monoidal category by splitting up their boundary states into certain sets of `inputs' and `outputs.' Composition corresponds to gluing the outputs of one such open Markov process onto the inputs of another so that the probability flowing out of the first process is equal to the probability flowing into the second. Tensoring in this category corresponds to placing two such systems side by side. We construct a `black-box' functor characterizing the behavior of an open Markov process in terms of the space of possible steady state probabilities and probability currents along the boundary. The fact that this is a functor means that the behavior of a composite open Markov process can be computed by composing the behaviors of the open Markov processes from which it is composed. We prove a similar black-boxing theorem for reaction networks whose dynamics are given by the non-linear rate equation. Along the way we describe a more general category of open dynamical systems where composition corresponds to gluing together open dynamical systems.

Polymeric Radiation Shielding for Applications in Space: Polyimide Synthesis and Modeling of Multi-Layered Polymeric Shields

NASA Astrophysics Data System (ADS)

Schiavone, Clinton Cleveland

We begin by defining the concept of `open' Markov processes, which are continuous-time Markov chains where probability can flow in and out through certain `boundary' states. We study open Markov processes which in the absence of such boundary flows admit equilibrium states satisfying detailed balance, meaning that the net flow of probability vanishes between all pairs of states. External couplings which fix the probabilities of boundary states can maintain such systems in non-equilibrium steady states in which non-zero probability currents flow. We show that these non-equilibrium steady states minimize a quadratic form which we call 'dissipation.' This is closely related to Prigogine's principle of minimum entropy production. We bound the rate of change of the entropy of a driven non-equilibrium steady state relative to the underlying equilibrium state in terms of the flow of probability through the boundary of the process. We then consider open Markov processes as morphisms in a symmetric monoidal category by splitting up their boundary states into certain sets of `inputs' and `outputs.' Composition corresponds to gluing the outputs of one such open Markov process onto the inputs of another so that the probability flowing out of the first process is equal to the probability flowing into the second. Tensoring in this category corresponds to placing two such systems side by side. We construct a `black-box' functor characterizing the behavior of an open Markov process in terms of the space of possible steady state probabilities and probability currents along the boundary. The fact that this is a functor means that the behavior of a composite open Markov process can be computed by composing the behaviors of the open Markov processes from which it is composed. We prove a similar black-boxing theorem for reaction networks whose dynamics are given by the non-linear rate equation. Along the way we describe a more general category of open dynamical systems where composition corresponds to gluing together open dynamical systems.

Processing and Conversion of Algae to Bioethanol

NASA Astrophysics Data System (ADS)

Kampfe, Sara Katherine

We begin by defining the concept of `open' Markov processes, which are continuous-time Markov chains where probability can flow in and out through certain `boundary' states. We study open Markov processes which in the absence of such boundary flows admit equilibrium states satisfying detailed balance, meaning that the net flow of probability vanishes between all pairs of states. External couplings which fix the probabilities of boundary states can maintain such systems in non-equilibrium steady states in which non-zero probability currents flow. We show that these non-equilibrium steady states minimize a quadratic form which we call 'dissipation.' This is closely related to Prigogine's principle of minimum entropy production. We bound the rate of change of the entropy of a driven non-equilibrium steady state relative to the underlying equilibrium state in terms of the flow of probability through the boundary of the process. We then consider open Markov processes as morphisms in a symmetric monoidal category by splitting up their boundary states into certain sets of `inputs' and `outputs.' Composition corresponds to gluing the outputs of one such open Markov process onto the inputs of another so that the probability flowing out of the first process is equal to the probability flowing into the second. Tensoring in this category corresponds to placing two such systems side by side. We construct a `black-box' functor characterizing the behavior of an open Markov process in terms of the space of possible steady state probabilities and probability currents along the boundary. The fact that this is a functor means that the behavior of a composite open Markov process can be computed by composing the behaviors of the open Markov processes from which it is composed. We prove a similar black-boxing theorem for reaction networks whose dynamics are given by the non-linear rate equation. Along the way we describe a more general category of open dynamical systems where composition corresponds to gluing together open dynamical systems.

The Development of the CALIPSO LiDAR Simulator

NASA Astrophysics Data System (ADS)

Powell, Kathleen A.

We begin by defining the concept of `open' Markov processes, which are continuous-time Markov chains where probability can flow in and out through certain `boundary' states. We study open Markov processes which in the absence of such boundary flows admit equilibrium states satisfying detailed balance, meaning that the net flow of probability vanishes between all pairs of states. External couplings which fix the probabilities of boundary states can maintain such systems in non-equilibrium steady states in which non-zero probability currents flow. We show that these non-equilibrium steady states minimize a quadratic form which we call 'dissipation.' This is closely related to Prigogine's principle of minimum entropy production. We bound the rate of change of the entropy of a driven non-equilibrium steady state relative to the underlying equilibrium state in terms of the flow of probability through the boundary of the process. We then consider open Markov processes as morphisms in a symmetric monoidal category by splitting up their boundary states into certain sets of `inputs' and `outputs.' Composition corresponds to gluing the outputs of one such open Markov process onto the inputs of another so that the probability flowing out of the first process is equal to the probability flowing into the second. Tensoring in this category corresponds to placing two such systems side by side. We construct a `black-box' functor characterizing the behavior of an open Markov process in terms of the space of possible steady state probabilities and probability currents along the boundary. The fact that this is a functor means that the behavior of a composite open Markov process can be computed by composing the behaviors of the open Markov processes from which it is composed. We prove a similar black-boxing theorem for reaction networks whose dynamics are given by the non-linear rate equation. Along the way we describe a more general category of open dynamical systems where composition corresponds to gluing together open dynamical systems.

Exploring a Novel Approach to Technical Nuclear Forensics Utilizing Atomic Force Microscopy

NASA Astrophysics Data System (ADS)

Peeke, Richard Scot

We begin by defining the concept of `open' Markov processes, which are continuous-time Markov chains where probability can flow in and out through certain `boundary' states. We study open Markov processes which in the absence of such boundary flows admit equilibrium states satisfying detailed balance, meaning that the net flow of probability vanishes between all pairs of states. External couplings which fix the probabilities of boundary states can maintain such systems in non-equilibrium steady states in which non-zero probability currents flow. We show that these non-equilibrium steady states minimize a quadratic form which we call 'dissipation.' This is closely related to Prigogine's principle of minimum entropy production. We bound the rate of change of the entropy of a driven non-equilibrium steady state relative to the underlying equilibrium state in terms of the flow of probability through the boundary of the process. We then consider open Markov processes as morphisms in a symmetric monoidal category by splitting up their boundary states into certain sets of `inputs' and `outputs.' Composition corresponds to gluing the outputs of one such open Markov process onto the inputs of another so that the probability flowing out of the first process is equal to the probability flowing into the second. Tensoring in this category corresponds to placing two such systems side by side. We construct a `black-box' functor characterizing the behavior of an open Markov process in terms of the space of possible steady state probabilities and probability currents along the boundary. The fact that this is a functor means that the behavior of a composite open Markov process can be computed by composing the behaviors of the open Markov processes from which it is composed. We prove a similar black-boxing theorem for reaction networks whose dynamics are given by the non-linear rate equation. Along the way we describe a more general category of open dynamical systems where composition corresponds to gluing together open dynamical systems.

Modeling of Critically-Stratified Gravity Flows: Application to the Eel River Continental Shelf, Northern California

NASA Astrophysics Data System (ADS)

Scully, Malcolm E.

We begin by defining the concept of `open' Markov processes, which are continuous-time Markov chains where probability can flow in and out through certain `boundary' states. We study open Markov processes which in the absence of such boundary flows admit equilibrium states satisfying detailed balance, meaning that the net flow of probability vanishes between all pairs of states. External couplings which fix the probabilities of boundary states can maintain such systems in non-equilibrium steady states in which non-zero probability currents flow. We show that these non-equilibrium steady states minimize a quadratic form which we call 'dissipation.' This is closely related to Prigogine's principle of minimum entropy production. We bound the rate of change of the entropy of a driven non-equilibrium steady state relative to the underlying equilibrium state in terms of the flow of probability through the boundary of the process. We then consider open Markov processes as morphisms in a symmetric monoidal category by splitting up their boundary states into certain sets of `inputs' and `outputs.' Composition corresponds to gluing the outputs of one such open Markov process onto the inputs of another so that the probability flowing out of the first process is equal to the probability flowing into the second. Tensoring in this category corresponds to placing two such systems side by side. We construct a `black-box' functor characterizing the behavior of an open Markov process in terms of the space of possible steady state probabilities and probability currents along the boundary. The fact that this is a functor means that the behavior of a composite open Markov process can be computed by composing the behaviors of the open Markov processes from which it is composed. We prove a similar black-boxing theorem for reaction networks whose dynamics are given by the non-linear rate equation. Along the way we describe a more general category of open dynamical systems where composition corresponds to gluing together open dynamical systems.

Production of Cyclohexylene-Containing Diamines in Pursuit of Novel Radiation Shielding Materials

NASA Astrophysics Data System (ADS)

Bate, Norah G.

We begin by defining the concept of `open' Markov processes, which are continuous-time Markov chains where probability can flow in and out through certain `boundary' states. We study open Markov processes which in the absence of such boundary flows admit equilibrium states satisfying detailed balance, meaning that the net flow of probability vanishes between all pairs of states. External couplings which fix the probabilities of boundary states can maintain such systems in non-equilibrium steady states in which non-zero probability currents flow. We show that these non-equilibrium steady states minimize a quadratic form which we call 'dissipation.' This is closely related to Prigogine's principle of minimum entropy production. We bound the rate of change of the entropy of a driven non-equilibrium steady state relative to the underlying equilibrium state in terms of the flow of probability through the boundary of the process. We then consider open Markov processes as morphisms in a symmetric monoidal category by splitting up their boundary states into certain sets of `inputs' and `outputs.' Composition corresponds to gluing the outputs of one such open Markov process onto the inputs of another so that the probability flowing out of the first process is equal to the probability flowing into the second. Tensoring in this category corresponds to placing two such systems side by side. We construct a `black-box' functor characterizing the behavior of an open Markov process in terms of the space of possible steady state probabilities and probability currents along the boundary. The fact that this is a functor means that the behavior of a composite open Markov process can be computed by composing the behaviors of the open Markov processes from which it is composed. We prove a similar black-boxing theorem for reaction networks whose dynamics are given by the non-linear rate equation. Along the way we describe a more general category of open dynamical systems where composition corresponds to gluing together open dynamical systems.

Development of Boron-Containing Polyimide Materials and Poly(arylene Ether)s for Radiation Shielding

NASA Astrophysics Data System (ADS)

Collins, Brittani May

We begin by defining the concept of `open' Markov processes, which are continuous-time Markov chains where probability can flow in and out through certain `boundary' states. We study open Markov processes which in the absence of such boundary flows admit equilibrium states satisfying detailed balance, meaning that the net flow of probability vanishes between all pairs of states. External couplings which fix the probabilities of boundary states can maintain such systems in non-equilibrium steady states in which non-zero probability currents flow. We show that these non-equilibrium steady states minimize a quadratic form which we call 'dissipation.' This is closely related to Prigogine's principle of minimum entropy production. We bound the rate of change of the entropy of a driven non-equilibrium steady state relative to the underlying equilibrium state in terms of the flow of probability through the boundary of the process. We then consider open Markov processes as morphisms in a symmetric monoidal category by splitting up their boundary states into certain sets of `inputs' and `outputs.' Composition corresponds to gluing the outputs of one such open Markov process onto the inputs of another so that the probability flowing out of the first process is equal to the probability flowing into the second. Tensoring in this category corresponds to placing two such systems side by side. We construct a `black-box' functor characterizing the behavior of an open Markov process in terms of the space of possible steady state probabilities and probability currents along the boundary. The fact that this is a functor means that the behavior of a composite open Markov process can be computed by composing the behaviors of the open Markov processes from which it is composed. We prove a similar black-boxing theorem for reaction networks whose dynamics are given by the non-linear rate equation. Along the way we describe a more general category of open dynamical systems where composition corresponds to gluing together open dynamical systems.

Magnetization Dynamics and Anisotropy in Ferromagnetic/Antiferromagnetic Ni/NiO Bilayers

NASA Astrophysics Data System (ADS)

Petersen, Andreas

We begin by defining the concept of `open' Markov processes, which are continuous-time Markov chains where probability can flow in and out through certain `boundary' states. We study open Markov processes which in the absence of such boundary flows admit equilibrium states satisfying detailed balance, meaning that the net flow of probability vanishes between all pairs of states. External couplings which fix the probabilities of boundary states can maintain such systems in non-equilibrium steady states in which non-zero probability currents flow. We show that these non-equilibrium steady states minimize a quadratic form which we call 'dissipation.' This is closely related to Prigogine's principle of minimum entropy production. We bound the rate of change of the entropy of a driven non-equilibrium steady state relative to the underlying equilibrium state in terms of the flow of probability through the boundary of the process. We then consider open Markov processes as morphisms in a symmetric monoidal category by splitting up their boundary states into certain sets of `inputs' and `outputs.' Composition corresponds to gluing the outputs of one such open Markov process onto the inputs of another so that the probability flowing out of the first process is equal to the probability flowing into the second. Tensoring in this category corresponds to placing two such systems side by side. We construct a `black-box' functor characterizing the behavior of an open Markov process in terms of the space of possible steady state probabilities and probability currents along the boundary. The fact that this is a functor means that the behavior of a composite open Markov process can be computed by composing the behaviors of the open Markov processes from which it is composed. We prove a similar black-boxing theorem for reaction networks whose dynamics are given by the non-linear rate equation. Along the way we describe a more general category of open dynamical systems where composition corresponds to gluing together open dynamical systems.

Assessing future vent opening locations at the Somma-Vesuvio volcanic complex: 2. Probability maps of the caldera for a future Plinian/sub-Plinian event with uncertainty quantification

NASA Astrophysics Data System (ADS)

Tadini, A.; Bevilacqua, A.; Neri, A.; Cioni, R.; Aspinall, W. P.; Bisson, M.; Isaia, R.; Mazzarini, F.; Valentine, G. A.; Vitale, S.; Baxter, P. J.; Bertagnini, A.; Cerminara, M.; de Michieli Vitturi, M.; Di Roberto, A.; Engwell, S.; Esposti Ongaro, T.; Flandoli, F.; Pistolesi, M.

2017-06-01

In this study, we combine reconstructions of volcanological data sets and inputs from a structured expert judgment to produce a first long-term probability map for vent opening location for the next Plinian or sub-Plinian eruption of Somma-Vesuvio. In the past, the volcano has exhibited significant spatial variability in vent location; this can exert a significant control on where hazards materialize (particularly of pyroclastic density currents). The new vent opening probability mapping has been performed through (i) development of spatial probability density maps with Gaussian kernel functions for different data sets and (ii) weighted linear combination of these spatial density maps. The epistemic uncertainties affecting these data sets were quantified explicitly with expert judgments and implemented following a doubly stochastic approach. Various elicitation pooling metrics and subgroupings of experts and target questions were tested to evaluate the robustness of outcomes. Our findings indicate that (a) Somma-Vesuvio vent opening probabilities are distributed inside the whole caldera, with a peak corresponding to the area of the present crater, but with more than 50% probability that the next vent could open elsewhere within the caldera; (b) there is a mean probability of about 30% that the next vent will open west of the present edifice; (c) there is a mean probability of about 9.5% that the next medium-large eruption will enlarge the present Somma-Vesuvio caldera, and (d) there is a nonnegligible probability (mean value of 6-10%) that the next Plinian or sub-Plinian eruption will have its initial vent opening outside the present Somma-Vesuvio caldera.

Enacs Survey of Southern Galaxies Indicates Open Universe

NASA Astrophysics Data System (ADS)

1996-02-01

New Light on Rich Clusters of Galaxies and their Formation History In the context of a comprehensive Key-Programme , carried out with telescopes at the ESO La Silla Observatory, a team of European astronomers [1]. has recently obtained radial velocities for more than 5600 galaxies in about 100 rich clusters of galaxies. With this programme the amount of information about the motions of galaxies (the kinematical data) in such clusters has almost been doubled. This has allowed the team to study the distribution of the cluster masses, and also the dynamical state of clusters in new and interesting ways. An important result of this programme is that the derived masses of the investigated clusters of galaxies indicate that the mean density of the Universe is insufficient to halt the current expansion; we may therefore be living in an open Universe that will expand forever. Clusters of galaxies as tracers of large-scale structure About 40 years ago, American astronomer George Abell, working at the Palomar Observatory in California, was the first to perform a systematic study of rich clusters of galaxies , that is clusters with particularly many member galaxies located within a relatively restricted region in the sky. He identified several thousands of such clusters, and he numbered and described them; they are now known to astronomers as `Abell clusters'. More than twenty years earlier, Swiss-American astronomer Fritz Zwicky, using the famous 100-inch Mount Wilson telescope above Los Angeles, concluded that the total mass of a rich cluster of galaxies is probably much larger than the combined mass of the individual galaxies we can observe in it. This phenomenon is now known as the `Missing Dark Matter' , and many attempts have since been made to understand its true nature. Although the existence of this Dark Matter is generally accepted, it has been very difficult to prove its existence in a direct way. Rich clusters have several components: in addition to several hundreds, in some cases even thousands of galaxies (each with many billions of stars and much interstellar matter), they also contain hot gas (with a temperature of several million degrees) which is best visible in X-rays, as well as the invisible dark matter just mentioned. In fact, these clusters are the largest and most massive objects that are known today, and a detailed study of their properties can therefore provide insight into the way in which large-scale structures in the Universe have formed. This unique information is encoded into the distribution of the clusters' total masses, of their physical shapes, and not the least in the way they are distributed in space. The need for a `complete' cluster sample Several of these fundamental questions can be studied by observing a few, or at the most several tens of well-chosen clusters. However, if the goal is to discriminate between the various proposed theories of formation of their spatial distribution and thus the Universe's large-scale structure, it is essential that uniform data is collected for a sample of clusters that is complete in a statistical sense. Only then will it be possible to determine reliably the distribution of cluster masses and shapes, etc. For such comprehensive investigations, `complete' samples of clusters (that is, brighter than a certain magnitude and located within a given area in the sky) can be compiled either by means of catalogues like the one published by Abell and his collaborators and based on the distribution of optically selected galaxies, or from large-scale surveys of X-ray sources. However, in both cases, it is of paramount importance to verify the physical reality of the presumed clusters. Sometimes several galaxies are seen in nearly the same direction and therefore appear to form a cluster, but it later turns out that they are at very different distances and do not form a physical entity. This control must be performed through spectroscopic observations of the galaxies in the candidate clusters. Such observations are crucial, as they not only prove the existence of a cluster, but also determine its distance and provide information about the motion of the individual galaxies within the cluster. The ESO Nearby Abell Cluster Survey (ENACS) Until recently, there existed no large cluster sample with extensive and uniform data on the motions of the individual galaxies. But now, in the context of an ESO Key-Programme known as the ESO Nearby Abell Cluster Survey or ENACS , the team of European astronomers has collected spectroscopic and photometric data for a substantial sample of more than one-hundred, rich and relatively nearby southern clusters from the Abell catalogue [2]. The extensive observations were carried out with the OPTOPUS multi-fibre spectrograph attached to the ESO 3.6-metre telescope at the La Silla Observatory, during 35 nights in the period from September 1989 to October 1993. With this very efficient spectrograph, the spectra of about 50 galaxies could be recorded simultaneously, dramatically reducing the necessary observing time. In total, the programme has yielded reliable radial velocities for more than 5600 galaxies in the direction of about 100 rich clusters. The velocities were derived from a comparison of the observed wavelengths of absorption and emission lines with their rest wavelengths (the galaxy `redshifts'). Assuming a particular value of the `Hubble constant' (the proportionality factor between the velocity of a galaxy and its distance, due to the general expansion of the Universe), the distances of the galaxies can then be derived directly from the measured velocities. The new observations approximately double the amount of data available for rich clusters of galaxies. In combination with earlier data, the ENACS has produced a `complete' sample of 128 rich Abell clusters in a region centered near the south galactic pole (the direction which is perpendicular to the main plane of the Milky Way galaxy), and comprising about one-fifth of the entire sky. The sample extends out to a cluster distance of almost 1,000 million light-years (300 Mpc) The space density of the 128 clusters is constant within the investigated volume, so that this sample is well suited to study, among others, the distribution of cluster masses. For a representative subset of 80 clusters, accurate information on the internal motions of galaxies in the clusters is available. Most nearby and rich Abell clusters are real In their pioneering work, Abell and his collaborators identified the clusters from visual inspection of photographic plates obtained with the Palomar telescopes [3]. Some concern has frequently been expressed that an important fraction of the rich Abell clusters may not be real, but rather the result of chance superpositions in the sky of several smaller groups of galaxies. However, the data of the ENACS now prove conclusively that 90 percent of the rich, nearby Abell clusters are real: i.e. many of the galaxies observed in each of these clusters are indeed at the same distance and they form a physical entity. Nevertheless, about one-quarter of the galaxies in the ENACS do not belong to the main clusters and reside in much smaller galaxy groups or are located in the vast space in between. This can be clearly seen in the distribution of the radial velocities in the direction of each of the clusters, shown in the diagramme (click here to get the [GIF,35k] or [Postscript,544k] version and the caption ) attached to this Press Release. When studying this distribution, it must be kept in mind, that the velocities of the galaxies in the clusters contain two components. The first is due to the general expansion of the Universe and depends only on the distance of the cluster; it is therefore the same for all galaxies in the cluster. The other reflects the individual motions of the galaxies within the cluster. Cluster masses and the mean density of the Universe The motions of the galaxies within a cluster makes it possible to estimate the total mass of the cluster: the greater the mass, the faster the motions must be in order to prevent the cluster from collapsing [4]. Using the data for the full sample of 128 clusters, the distribution of cluster masses has been derived. This distribution has been compared with predictions based on several models for the formation of large-scale structures in the Universe. A very important result of the current work is that the observations do not support scenarios which are based on the assumption that the mean density of the Universe is equal to the `critical' value, i.e. the one which would correspond to a so-called `flat' Universe. The observed cluster masses are systematically smaller than those predicted in such models. Instead, the observed distribution of cluster masses seems to indicate that the mean density of the Universe is probably only a fairly small fraction of the critical value. This points to the Universe being `open' and ever-expanding. Cluster formation may still be going on The galaxies observed during the ENACS programme may be divided into two groups on the basis of their optical spectra, those that show clear emission lines and those that do not. The former are almost all late-type galaxies, that is spiral galaxies with ionized gas in their disks which gives rise to the emission lines. It appears that both the distribution within the cluster, as well as the velocities, of the galaxies with emission lines are significantly different from those of the galaxies without emission lines. It seems that the emission-line galaxies have a tendency to avoid the central regions of their clusters, and their average radial velocities are about 20 percent larger than those of the non-emission galaxies. A plausible interpretation of these results is that a large part of the emission-line galaxies have not yet `mixed' with the other galaxies, and that they are approaching the central regions of their respective clusters for the first time. This may imply that the formation of at least a good fraction of the nearby, rich clusters is still going on. If the mean density of the Universe is indeed much smaller than the critical density, as indicated by the cluster masses determined during this survey, then this is a quite unexpected result. One explanation may be that many clusters have only started to form fairly recently. Notes: [1] The team is headed by Peter Katgert (Leiden Observatory, The Netherlands) and Alain Mazure (Laboratoire d'Astronomie Spatiale, Marseille, France); other members are Andrea Biviano and Roland den Hartog (Leiden Observatory, The Netherlands), Pierre Dubath (Observatoire de Geneve, Switzerland), Eric Escalera (SISSA, Trieste, Italy), Paola Focardi (Bologna University, Italy), Daniel Gerbal (Institut d'Astrophysique, Paris, France), Guilano Giuricin (SISSA, Trieste, Italy), Bernard Jones (Theoretical Astrophysics Centre, Copenhagen, Denmark), Olivier Le Fevre (Meudon Observatory, Paris, France), Mariano Moles and Jaime Perea (Astrophysics Institute of Andalucia, Granada, Spain), and George Rhee (University of Nevada, Las Vegas, U.S.A.). [2] The detailed results will soon be published in two comprehensive articles to appear in the European journal Astronomy & Astrophysics. [3] This Press Release is accompanied by ESO Press Photo 07/96, (click here to get the image [GIF,45k] and caption ) showing one of the rich clusters, as observed with the ESO 1-metre Schmidt telescope. [4] The masses of the planets in the solar system are determined in a similar way from the motions of their moons. The faster the moon moves around the planet at a given distance, the heavier is the planet.

High-Performance Nanocomposites Designed for Radiation Shielding in Space and an Application of GIS for Analyzing Nanopowder Dispersion in Polymer Matrixes

NASA Astrophysics Data System (ADS)

Auslander, Joseph Simcha

We begin by defining the concept of `open' Markov processes, which are continuous-time Markov chains where probability can flow in and out through certain `boundary' states. We study open Markov processes which in the absence of such boundary flows admit equilibrium states satisfying detailed balance, meaning that the net flow of probability vanishes between all pairs of states. External couplings which fix the probabilities of boundary states can maintain such systems in non-equilibrium steady states in which non-zero probability currents flow. We show that these non-equilibrium steady states minimize a quadratic form which we call 'dissipation.' This is closely related to Prigogine's principle of minimum entropy production. We bound the rate of change of the entropy of a driven non-equilibrium steady state relative to the underlying equilibrium state in terms of the flow of probability through the boundary of the process. We then consider open Markov processes as morphisms in a symmetric monoidal category by splitting up their boundary states into certain sets of `inputs' and `outputs.' Composition corresponds to gluing the outputs of one such open Markov process onto the inputs of another so that the probability flowing out of the first process is equal to the probability flowing into the second. Tensoring in this category corresponds to placing two such systems side by side. We construct a `black-box' functor characterizing the behavior of an open Markov process in terms of the space of possible steady state probabilities and probability currents along the boundary. The fact that this is a functor means that the behavior of a composite open Markov process can be computed by composing the behaviors of the open Markov processes from which it is composed. We prove a similar black-boxing theorem for reaction networks whose dynamics are given by the non-linear rate equation. Along the way we describe a more general category of open dynamical systems where composition corresponds to gluing together open dynamical systems.

Time-Resolved Magneto-Optical Imaging of Superconducting YBCO Thin Films in the High-Frequency AC Current Regime

NASA Astrophysics Data System (ADS)

Frey, Alexander

We begin by defining the concept of `open' Markov processes, which are continuous-time Markov chains where probability can flow in and out through certain `boundary' states. We study open Markov processes which in the absence of such boundary flows admit equilibrium states satisfying detailed balance, meaning that the net flow of probability vanishes between all pairs of states. External couplings which fix the probabilities of boundary states can maintain such systems in non-equilibrium steady states in which non-zero probability currents flow. We show that these non-equilibrium steady states minimize a quadratic form which we call 'dissipation.' This is closely related to Prigogine's principle of minimum entropy production. We bound the rate of change of the entropy of a driven non-equilibrium steady state relative to the underlying equilibrium state in terms of the flow of probability through the boundary of the process. We then consider open Markov processes as morphisms in a symmetric monoidal category by splitting up their boundary states into certain sets of `inputs' and `outputs.' Composition corresponds to gluing the outputs of one such open Markov process onto the inputs of another so that the probability flowing out of the first process is equal to the probability flowing into the second. Tensoring in this category corresponds to placing two such systems side by side. We construct a `black-box' functor characterizing the behavior of an open Markov process in terms of the space of possible steady state probabilities and probability currents along the boundary. The fact that this is a functor means that the behavior of a composite open Markov process can be computed by composing the behaviors of the open Markov processes from which it is composed. We prove a similar black-boxing theorem for reaction networks whose dynamics are given by the non-linear rate equation. Along the way we describe a more general category of open dynamical systems where composition corresponds to gluing together open dynamical systems.

Use of Remote Sensing to Identify Essential Habitat for Aeschynomene virginica (L.) BSP, a Threatened Tidal Freshwater Wetland Plant

NASA Astrophysics Data System (ADS)

Mountz, Elizabeth M.

We begin by defining the concept of `open' Markov processes, which are continuous-time Markov chains where probability can flow in and out through certain `boundary' states. We study open Markov processes which in the absence of such boundary flows admit equilibrium states satisfying detailed balance, meaning that the net flow of probability vanishes between all pairs of states. External couplings which fix the probabilities of boundary states can maintain such systems in non-equilibrium steady states in which non-zero probability currents flow. We show that these non-equilibrium steady states minimize a quadratic form which we call 'dissipation.' This is closely related to Prigogine's principle of minimum entropy production. We bound the rate of change of the entropy of a driven non-equilibrium steady state relative to the underlying equilibrium state in terms of the flow of probability through the boundary of the process. We then consider open Markov processes as morphisms in a symmetric monoidal category by splitting up their boundary states into certain sets of `inputs' and `outputs.' Composition corresponds to gluing the outputs of one such open Markov process onto the inputs of another so that the probability flowing out of the first process is equal to the probability flowing into the second. Tensoring in this category corresponds to placing two such systems side by side. We construct a `black-box' functor characterizing the behavior of an open Markov process in terms of the space of possible steady state probabilities and probability currents along the boundary. The fact that this is a functor means that the behavior of a composite open Markov process can be computed by composing the behaviors of the open Markov processes from which it is composed. We prove a similar black-boxing theorem for reaction networks whose dynamics are given by the non-linear rate equation. Along the way we describe a more general category of open dynamical systems where composition corresponds to gluing together open dynamical systems.

Silver-Polyimide Nanocomposite Films: Single-Stage Synthesis and Analysis of Metalized Partially-Fluorinated Polyimide BTDA/4-BDAF Prepared from Silver(I) Complexes

NASA Astrophysics Data System (ADS)

Abelard, Joshua Erold Robert

We begin by defining the concept of `open' Markov processes, which are continuous-time Markov chains where probability can flow in and out through certain `boundary' states. We study open Markov processes which in the absence of such boundary flows admit equilibrium states satisfying detailed balance, meaning that the net flow of probability vanishes between all pairs of states. External couplings which fix the probabilities of boundary states can maintain such systems in non-equilibrium steady states in which non-zero probability currents flow. We show that these non-equilibrium steady states minimize a quadratic form which we call 'dissipation.' This is closely related to Prigogine's principle of minimum entropy production. We bound the rate of change of the entropy of a driven non-equilibrium steady state relative to the underlying equilibrium state in terms of the flow of probability through the boundary of the process. We then consider open Markov processes as morphisms in a symmetric monoidal category by splitting up their boundary states into certain sets of `inputs' and `outputs.' Composition corresponds to gluing the outputs of one such open Markov process onto the inputs of another so that the probability flowing out of the first process is equal to the probability flowing into the second. Tensoring in this category corresponds to placing two such systems side by side. We construct a `black-box' functor characterizing the behavior of an open Markov process in terms of the space of possible steady state probabilities and probability currents along the boundary. The fact that this is a functor means that the behavior of a composite open Markov process can be computed by composing the behaviors of the open Markov processes from which it is composed. We prove a similar black-boxing theorem for reaction networks whose dynamics are given by the non-linear rate equation. Along the way we describe a more general category of open dynamical systems where composition corresponds to gluing together open dynamical systems.

Multifunctional Polymer Synthesis and Incorporation of Gadolinium Compounds and Modified Tungsten Nanoparticles for Improvement of Radiation Shielding for use in Outer Space

NASA Astrophysics Data System (ADS)

Harbert, Emily Grace

We begin by defining the concept of `open' Markov processes, which are continuous-time Markov chains where probability can flow in and out through certain `boundary' states. We study open Markov processes which in the absence of such boundary flows admit equilibrium states satisfying detailed balance, meaning that the net flow of probability vanishes between all pairs of states. External couplings which fix the probabilities of boundary states can maintain such systems in non-equilibrium steady states in which non-zero probability currents flow. We show that these non-equilibrium steady states minimize a quadratic form which we call 'dissipation.' This is closely related to Prigogine's principle of minimum entropy production. We bound the rate of change of the entropy of a driven non-equilibrium steady state relative to the underlying equilibrium state in terms of the flow of probability through the boundary of the process. We then consider open Markov processes as morphisms in a symmetric monoidal category by splitting up their boundary states into certain sets of `inputs' and `outputs.' Composition corresponds to gluing the outputs of one such open Markov process onto the inputs of another so that the probability flowing out of the first process is equal to the probability flowing into the second. Tensoring in this category corresponds to placing two such systems side by side. We construct a `black-box' functor characterizing the behavior of an open Markov process in terms of the space of possible steady state probabilities and probability currents along the boundary. The fact that this is a functor means that the behavior of a composite open Markov process can be computed by composing the behaviors of the open Markov processes from which it is composed. We prove a similar black-boxing theorem for reaction networks whose dynamics are given by the non-linear rate equation. Along the way we describe a more general category of open dynamical systems where composition corresponds to gluing together open dynamical systems.

Maintenance of Mouse Gustatory Terminal Field Organization Is Disrupted following Selective Removal of Peripheral Sodium Salt Taste Activity at Adulthood

PubMed Central

Sun, Chengsan

2017-01-01

Neural activity plays a critical role in the development of central circuits in sensory systems. However, the maintenance of these circuits at adulthood is usually not dependent on sensory-elicited neural activity. Recent work in the mouse gustatory system showed that selectively deleting the primary transduction channel for sodium taste, the epithelial sodium channel (ENaC), throughout development dramatically impacted the organization of the central terminal fields of three nerves that carry taste information to the nucleus of the solitary tract. More specifically, deleting ENaCs during development prevented the normal maturation of the fields. The present study was designed to extend these findings by testing the hypothesis that the loss of sodium taste activity impacts the maintenance of the normal adult terminal field organization in male and female mice. To do this, we used an inducible Cre-dependent genetic recombination strategy to delete ENaC function after terminal field maturation occurred. We found that removal of sodium taste neural activity at adulthood resulted in significant reorganization of mature gustatory afferent terminal fields in the nucleus of the solitary tract. Specifically, the chorda tympani and greater superficial petrosal nerve terminal fields were 1.4× and 1.6× larger than age-matched controls, respectively. By contrast, the glossopharyngeal nerve, which is not highly sensitive to sodium taste stimulation, did not undergo terminal field reorganization. These surprising results suggest that gustatory nerve terminal fields remain plastic well into adulthood, which likely impacts central coding of taste information and taste-related behaviors with altered taste experience. SIGNIFICANCE STATEMENT Neural activity plays a major role in the development of sensory circuits in the mammalian brain. However, the importance of sensory-driven activity in maintaining these circuits at adulthood, especially in subcortical structures, appears to be much less. Here, we tested whether the loss of sodium taste activity in adult mice impacts the maintenance of how taste nerves project to the first central relay. We found that specific loss of sodium-elicited taste activity at adulthood produced dramatic and selective reorganization of terminal fields in the brainstem. This demonstrates, for the first time, that taste-elicited activity is necessary for the normal maintenance of central gustatory circuits at adulthood and highlights a level of plasticity not seen in other sensory system subcortical circuits. PMID:28676575

The effect of NO-donors on chloride efflux, intracellular Ca(2+) concentration and mRNA expression of CFTR and ENaC in cystic fibrosis airway epithelial cells.

PubMed

Oliynyk, Igor; Hussain, Rashida; Amin, Ahmad; Johannesson, Marie; Roomans, Godfried M

2013-06-01

Since previous studies showed that the endogenous bronchodilator, S-nitrosglutathione (GSNO), caused a marked increase in CFTR-mediated chloride (Cl(-)) efflux and improved the trafficking of CFTR to the plasma membrane, and that also the nitric oxide (NO)-donor GEA3162 had a similar, but smaller, effect on Cl(-) efflux, it was investigated whether the NO-donor properties of GSNO were relevant for its effect on Cl(-) efflux from airway epithelial cells. Hence, the effect of a number of other NO-donors, sodium nitroprusside (SNP), S-nitroso-N-acetyl-DL-penicillamine (SNAP), diethylenetriamine/nitric oxide adduct (DETA-NO), and diethylenetriamine/nitric oxide adduct (DEA-NONOate) on Cl(-) efflux from CFBE (∆F508/∆F508-CFTR) airway epithelial cells was tested. Cl(-) efflux was determined using the fluorescent N-(ethoxycarbonylmethyl)-6-methoxyquinoliniu bromide (MQAE)-technique. Possible changes in the intracellular Ca(2+) concentration were tested by the fluorescent fluo-4 method in a confocal microscope system. Like previously with GSNO, after 4 h incubation with the NO-donor, an increased Cl(-) efflux was found (in the order SNAP>DETA-NO>SNP). The effect of DEA-NONOate on Cl(-) efflux was not significant, and the compound may have (unspecific) deleterious effects on the cells. Again, as with GSNO, after a short (5 min) incubation, SNP had no significant effect on Cl(-) efflux. None of the NO-donors that had a significant effect on Cl(-) efflux caused significant changes in the intracellular Ca(2+) concentration. After 4 h preincubation, SNP caused a significant increase in the mRNA expression of CFTR. SNAP and DEA-NONOate decreased the mRNA expression of all ENaC subunits significantly. DETA-NO caused a significant decrease only in α-ENaC expression. After a short preincubation, none of the NO-donors had a significant effect, neither on the expression of CFTR, nor on that of the ENaC subunits in the presence and absence of L-cysteine. It can be concluded that the effect of GSNO on Cl(-) efflux is, at least in part, due to its properties as an NO-donor, and the effect is likely to be mediated by CFTR, not by Ca(2+)-activated Cl(-) channels. Copyright © 2013. Published by Elsevier Inc.

Combinatorial effects of quercetin and sex-steroids on fluid and electrolytes’ (Na+, Cl-, HCO3-) secretory mechanisms in the uterus of ovariectomised female Sprague-Dawley rats

PubMed Central

Shahzad, Huma; Giribabu, Nelli; Karim, Kamarulzaman; Kassim, Normadiah M.; Muniandy, Sekaran

2017-01-01

Dysregulation of uterine fluid environment could impair successful reproduction and this could be due to the effect of environmental estrogens. Therefore, in this study, effect of quercetin, an environmental estrogen on uterine fluid and electrolytes concentrations were investigated under sex-steroid influence. Ovariectomised adult female Sprague-Dawley rats were given 10, 50 or 100mg/kg/day quercetin subcutaneously with 17-β estradiol (E) for seven days or three days E, then three days E plus progesterone (P) (E+P) treatment. Uterine fluid secretion rate, Na+, Cl- and HCO3- concentrations were determined by in-vivo perfusion. Following sacrifice, uteri were harvested and levels of the proteins of interest were identified by Western blotting and Realtime PCR. Distribution of these proteins in the uterus was observed by immunofluorescence. Levels of uterine cAMP were measured by enzyme-linked immunoassay (EIA). Administration of quercetin at increasing doses increased uterine fluid secretion rate, Na+, Cl- and HCO3- concentrations, but to the levels lesser than that of E. In concordant, levels of CFTR, SLC4A4, ENaC (α, β and γ), Na+/K+-ATPase, GPα/β, AC and cAMP in the uterus increased following increased in the doses of quercetin. Co-administration of quercetin with E caused uterine fluid secretion rate, Na+, Cl- and HCO3- concentrations to decrease. In concordant, uterine CFTR, SLC26A6, SLC4A4, ENaC (α, β and γ), Na+/K+-ATPase, GPα/β, AC and cAMP decreased. Greatest effects were observed following co-administration of 10mg/kg/day quercetin with E. Co-administration of quercetin with E+P caused uterine fluid Na+ and HCO3- concentrations to increase but no changes in fluid secretion rate and Cl- concentration were observed. Co-administration of high dose quercetin (100 mg/kg/day) with E+P caused uterine CFTR, SLC26A6, AC, GPα/β and ENaC (α, β and γ) to increase. Quercetin-induced changes in the uterine fluid secretion rate and electrolytes concentrations could potentially affect the uterine reproductive functions under female sex-steroid influence. PMID:28253299

Endothelin-1 mediates natriuresis but not polyuria during vitamin D-induced acute hypercalcaemia.

PubMed

Tokonami, Natsuko; Cheval, Lydie; Monnay, Isabelle; Meurice, Guillaume; Loffing, Johannes; Feraille, Eric; Houillier, Pascal

2017-04-15

Hypercalcaemia can occur under various pathological conditions, such as primary hyperparathyroidism, malignancy or granulomatosis, and it induces natriuresis and polyuria in various species via an unknown mechanism. A previous study demonstrated that hypercalcaemia induced by vitamin D in rats increased endothelin (ET)-1 expression in the distal nephron, which suggests the involvement of the ET system in hypercalcaemia-induced effects. In the present study, we demonstrate that, during vitamin D-induced hypercalcaemia, the activation of ET system by increased ET-1 is responsible for natriuresis but not for polyuria. Vitamin D-treated hypercalcaemic mice showed a blunted response to amiloride, suggesting that epithelial sodium channel function is inhibited. We have identified an original pathway that specifically mediates the effects of vitamin D-induced hypercalcaemia on sodium handling in the distal nephron without affecting water handling. Acute hypercalcaemia increases urinary sodium and water excretion; however, the underlying molecular mechanism remains unclear. Because vitamin D-induced hypercalcaemia increases the renal expression of endothelin (ET)-1, we hypothesized that ET-1 mediates the effects of hypercalcaemia on renal sodium and water handling. Hypercalcaemia was induced in 8-week-old, parathyroid hormone-supplemented, male mice by oral administration of dihydrotachysterol (DHT) for 3 days. DHT-treated mice became hypercalcaemic and displayed increased urinary water and sodium excretion compared to controls. mRNA levels of ET-1 and the transcription factors CCAAT-enhancer binding protein β and δ were specifically increased in the distal convoluted tubule and downstream segments in DHT-treated mice. To examine the role of the ET system in hypercalcaemia-induced natriuresis and polyuria, mice were treated with the ET-1 receptor antagonist macitentan, with or without DHT. Mice treated with both macitentan and DHT displayed hypercalcaemia and polyuria similar to that in mice treated with DHT alone; however, no increase in urinary sodium excretion was observed. To identify the affected sodium transport mechanism, we assessed the response to various diuretics in control and DHT-treated hypercalcaemic mice. Amiloride, an inhibitor of the epithelial sodium channel (ENaC), increased sodium excretion to a lesser extent in DHT-treated mice compared to control mice. Mice treated with either macitentan+DHT or macitentan alone had a similar response to amiloride. In summary, vitamin D-induced hypercalcaemia increases the renal production of ET-1 and decreases ENaC activity, which is probably responsible for the rise in urinary sodium excretion but not for polyuria. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Endothelin‐1 mediates natriuresis but not polyuria during vitamin D‐induced acute hypercalcaemia

PubMed Central

Tokonami, Natsuko; Cheval, Lydie; Monnay, Isabelle; Meurice, Guillaume; Loffing, Johannes; Feraille, Eric

2017-01-01

Key points Hypercalcaemia can occur under various pathological conditions, such as primary hyperparathyroidism, malignancy or granulomatosis, and it induces natriuresis and polyuria in various species via an unknown mechanism.A previous study demonstrated that hypercalcaemia induced by vitamin D in rats increased endothelin (ET)‐1 expression in the distal nephron, which suggests the involvement of the ET system in hypercalcaemia‐induced effects.In the present study, we demonstrate that, during vitamin D‐induced hypercalcaemia, the activation of ET system by increased ET‐1 is responsible for natriuresis but not for polyuria.Vitamin D‐treated hypercalcaemic mice showed a blunted response to amiloride, suggesting that epithelial sodium channel function is inhibited.We have identified an original pathway that specifically mediates the effects of vitamin D‐induced hypercalcaemia on sodium handling in the distal nephron without affecting water handling. Abstract Acute hypercalcaemia increases urinary sodium and water excretion; however, the underlying molecular mechanism remains unclear. Because vitamin D‐induced hypercalcaemia increases the renal expression of endothelin (ET)‐1, we hypothesized that ET‐1 mediates the effects of hypercalcaemia on renal sodium and water handling. Hypercalcaemia was induced in 8‐week‐old, parathyroid hormone‐supplemented, male mice by oral administration of dihydrotachysterol (DHT) for 3 days. DHT‐treated mice became hypercalcaemic and displayed increased urinary water and sodium excretion compared to controls. mRNA levels of ET‐1 and the transcription factors CCAAT‐enhancer binding protein β and δ were specifically increased in the distal convoluted tubule and downstream segments in DHT‐treated mice. To examine the role of the ET system in hypercalcaemia‐induced natriuresis and polyuria, mice were treated with the ET‐1 receptor antagonist macitentan, with or without DHT. Mice treated with both macitentan and DHT displayed hypercalcaemia and polyuria similar to that in mice treated with DHT alone; however, no increase in urinary sodium excretion was observed. To identify the affected sodium transport mechanism, we assessed the response to various diuretics in control and DHT‐treated hypercalcaemic mice. Amiloride, an inhibitor of the epithelial sodium channel (ENaC), increased sodium excretion to a lesser extent in DHT‐treated mice compared to control mice. Mice treated with either macitentan+DHT or macitentan alone had a similar response to amiloride. In summary, vitamin D‐induced hypercalcaemia increases the renal production of ET‐1 and decreases ENaC activity, which is probably responsible for the rise in urinary sodium excretion but not for polyuria. PMID:28120456

Salt restriction induces pseudohypoaldosteronism type 1 in mice expressing low levels of the β-subunit of the amiloride-sensitive epithelial sodium channel

PubMed Central

Pradervand, Sylvain; Barker, Pierre M.; Wang, Qing; Ernst, Stephen A.; Beermann, Friedrich; Grubb, Barbara R.; Burnier, Michel; Schmidt, Andrea; Bindels, Rene J. M.; Gatzy, John T.; Rossier, Bernard C.; Hummler, Edith

1999-01-01

The amiloride-sensitive epithelial sodium channel (ENaC) is a heteromultimer of three homologous subunits (α-, β-, and γ-subunits). To study the role of the β-subunit in vivo, we analyzed mice in which the βENaC gene locus was disrupted. These mice showed low levels of βENaC mRNA expression in kidney (≈1%), lung (≈1%), and colon (≈4%). In homozygous mutant βENaC mice, no βENaC protein could be detected with immunofluorescent staining. At birth, there was a small delay in lung-liquid clearance that paralleled diminished amiloride-sensitive Na+ absorption in tracheal explants. With normal salt intake, these mice showed a normal growth rate. However, in vivo, adult βENaC m/m mice exhibited a significantly reduced ENaC activity in colon and elevated plasma aldosterone levels, suggesting hypovolemia and pseudohypoaldosteronism type 1. This phenotype was clinically silent, as βENaC m/m mice showed no weight loss, normal plasma Na+ and K+ concentrations, normal blood pressure, and a compensated metabolic acidosis. On low-salt diets, βENaC-mutant mice developed clinical symptoms of an acute pseudohypoaldosteronism type 1 (weight loss, hyperkalemia, and decreased blood pressure), indicating that βENaC is required for Na+ conservation during salt deprivation. PMID:9990093

The ESO Nearby Abell Cluster Survey. VI. Spatial distribution and kinematics of early- and late-type galaxies

NASA Astrophysics Data System (ADS)

de Theije, P. A. M.; Katgert, P.

1999-01-01

Analysis of the data obtained in the ESO Nearby Abell Cluster Survey (ENACS) has shown that the space distribution and kinematics of galaxies with detectable emission lines in their spectra differ significantly from those of galaxies without emission lines. This result, and details of the kinematics, were considered as support for the idea that at least the spirals with emission lines are on orbits that are not isotropic. This might indicate that this subset of late-type galaxies either has `first approach'-orbits towards the dense core of their respective clusters, or has orbits that `avoid' the core. The galaxies with emission lines are essentially all late-type galaxies. On the other hand, the emission-line galaxies represent only about a third of the late-type galaxies, the majority of which do not show detectable emission lines. The galaxies without emission lines are therefore a mix of early- and late-type galaxies. In this paper we attempt to separate early- and late-type galaxies, and we study possible differences in distribution and kinematics of the two galaxy classes. For only about 10% of the galaxies in the ENACS, the morphology is known from imaging. Here, we describe our classification on the basis of the ENACS spectrum. The significant information in each spectrum is compressed into 15 Principal Components, which are used as input for an Artificial Neural Network. The latter is `trained' with 150 of the 270 galaxies for which a morphological type is available from Dressler, and subsequently used to classify each galaxy. This yields a classification for two-thirds of the ENACS galaxies. The Artificial Neural Network has two output classes: early-type (E+S0) and late-type (S+I) galaxies. We do not distinguish E and S0 galaxies, because these cannot be separated very robustly on the basis of the spectrum. The success rate of the classification is estimated from the sample of 120 galaxies with Dressler morphologies which were not used to train the ANN. The success rate is higher for early-type than for late-type galaxies (78+/-6% vs. {63+/-6%}). The weighted average success rate, irrespective of type, is {73+/-4%}. The success rate is somewhat larger for the training set, and highest for the galaxies with emission lines. Of the 3798 galaxies that were classified from their spectrum {57+/-7%} are of early type, and {43+/-7%} of late type. Using a subset of these 3798 galaxies, we constructed a composite cluster of 2594 galaxies, 399 of which have emission lines and are therefore almost exclusively spirals and irregulars. The kinematics and spatial distribution of the late-type galaxies without emission lines resemble much more those of the early-type galaxies than those of the late-type galaxies with emission lines. Yet, the late-type galaxies without emission lines may have a somewhat larger velocity dispersion and a slightly less centrally concentrated distribution than the early-type galaxies. Only the late-type galaxies with emission lines appear to have a considerably larger global velocity dispersion and a much less concentrated projected density profile than the other galaxies. Thus, the suggestion of fairly radial, and possibly `first approach' orbits applies only to spirals with emission lines. The early-type galaxies with emission lines (among which the AGN), may also have a large velocity dispersion and be concentrated towards the cluster centre. Based on observations collected at the European Southern Observatory (La Silla, Chile)

Systematic review and meta-analysis of nasal potential difference in hypoxia-induced lung injury.

PubMed

Su, Zhenlei; Zhu, Lili; Wu, Jing; Zhao, Runzhen; Ji, Hong-Long

2016-08-04

Nasal potential difference (NPD), a well-established in vivo clinical test for cystic fibrosis, reflects transepithelial cation and anion transport in the respiratory epithelium. To analyze whether NPD can be applied to diagnose hypoxic lung injury, we searched PubMed, EMBASE, Scopus, Web of Science, Ovid MEDLINE, and Google Scholar, and analyzed data retrieved from eleven unbiased studies for high altitude pulmonary edema (HAPE) and respiratory distress syndrome (RDS) using the software RevMan and R. There was a significant reduction in overall basal (WMD -5.27 mV, 95% CI: -6.03 to -4.52, P < 0.00001, I(2) = 42%), amiloride-sensitive (ENaC) (-2.87 mV, 95% CI: -4.02 to -1.72, P < 0.00001, I(2) = 51%), and -resistant fractions (-3.91 mV, 95% CI: -7.64 to -0.18, P = 0.04, I(2) = 95%) in lung injury patients. Further analysis of HAPE and RDS separately corroborated these observations. Moreover, SpO2 correlated with ENaC-associated NPD positively in patients only, but apparently related to CFTR-contributed NPD level inversely. These correlations were confirmed by the opposite associations between NPD values and altitude, which had a negative regression with SpO2 level. Basal NPD was significantly associated with amiloride-resistant but not ENaC fraction. Our analyses demonstrate that acute lung injury associated with systemic hypoxia is characterized by dysfunctional NPD.

Renal tubular NEDD4-2 deficiency causes NCC-mediated salt-dependent hypertension.

PubMed

Ronzaud, Caroline; Loffing-Cueni, Dominique; Hausel, Pierrette; Debonneville, Anne; Malsure, Sumedha Ram; Fowler-Jaeger, Nicole; Boase, Natasha A; Perrier, Romain; Maillard, Marc; Yang, Baoli; Stokes, John B; Koesters, Robert; Kumar, Sharad; Hummler, Edith; Loffing, Johannes; Staub, Olivier

2013-02-01

The E3 ubiquitin ligase NEDD4-2 (encoded by the Nedd4L gene) regulates the amiloride-sensitive epithelial Na+ channel (ENaC/SCNN1) to mediate Na+ homeostasis. Mutations in the human β/γENaC subunits that block NEDD4-2 binding or constitutive ablation of exons 6-8 of Nedd4L in mice both result in salt-sensitive hypertension and elevated ENaC activity (Liddle syndrome). To determine the role of renal tubular NEDD4-2 in adult mice, we generated tetracycline-inducible, nephron-specific Nedd4L KO mice. Under standard and high-Na+ diets, conditional KO mice displayed decreased plasma aldosterone but normal Na+/K+ balance. Under a high-Na+ diet, KO mice exhibited hypercalciuria and increased blood pressure, which were reversed by thiazide treatment. Protein expression of βENaC, γENaC, the renal outer medullary K+ channel (ROMK), and total and phosphorylated thiazide-sensitive Na+Cl- cotransporter (NCC) levels were increased in KO kidneys. Unexpectedly, Scnn1a mRNA, which encodes the αENaC subunit, was reduced and proteolytic cleavage of αENaC decreased. Taken together, these results demonstrate that loss of NEDD4-2 in adult renal tubules causes a new form of mild, salt-sensitive hypertension without hyperkalemia that is characterized by upregulation of NCC, elevation of β/γENaC, but not αENaC, and a normal Na+/K+ balance maintained by downregulation of ENaC activity and upregulation of ROMK.

VizieR Online Data Catalog: Proper motions of PM2000 open clusters (Krone-Martins+, 2010)

NASA Astrophysics Data System (ADS)

Krone-Martins, A.; Soubiran, C.; Ducourant, C.; Teixeira, R.; Le Campion, J. F.

2010-04-01

We present lists of proper-motions and kinematic membership probabilities in the region of 49 open clusters or possible open clusters. The stellar proper motions were taken from the Bordeaux PM2000 catalogue. The segregation between cluster and field stars and the assignment of membership probabilities was accomplished by applying a fully automated method based on parametrisations for the probability distribution functions and genetic algorithm optimisation heuristics associated with a derivative-based hill climbing algorithm for the likelihood optimization. (3 data files).

Maintenance of Mouse Gustatory Terminal Field Organization Is Disrupted following Selective Removal of Peripheral Sodium Salt Taste Activity at Adulthood.

PubMed

Skyberg, Rolf; Sun, Chengsan; Hill, David L

2017-08-09

Neural activity plays a critical role in the development of central circuits in sensory systems. However, the maintenance of these circuits at adulthood is usually not dependent on sensory-elicited neural activity. Recent work in the mouse gustatory system showed that selectively deleting the primary transduction channel for sodium taste, the epithelial sodium channel (ENaC), throughout development dramatically impacted the organization of the central terminal fields of three nerves that carry taste information to the nucleus of the solitary tract. More specifically, deleting ENaCs during development prevented the normal maturation of the fields. The present study was designed to extend these findings by testing the hypothesis that the loss of sodium taste activity impacts the maintenance of the normal adult terminal field organization in male and female mice. To do this, we used an inducible Cre-dependent genetic recombination strategy to delete ENaC function after terminal field maturation occurred. We found that removal of sodium taste neural activity at adulthood resulted in significant reorganization of mature gustatory afferent terminal fields in the nucleus of the solitary tract. Specifically, the chorda tympani and greater superficial petrosal nerve terminal fields were 1.4× and 1.6× larger than age-matched controls, respectively. By contrast, the glossopharyngeal nerve, which is not highly sensitive to sodium taste stimulation, did not undergo terminal field reorganization. These surprising results suggest that gustatory nerve terminal fields remain plastic well into adulthood, which likely impacts central coding of taste information and taste-related behaviors with altered taste experience. SIGNIFICANCE STATEMENT Neural activity plays a major role in the development of sensory circuits in the mammalian brain. However, the importance of sensory-driven activity in maintaining these circuits at adulthood, especially in subcortical structures, appears to be much less. Here, we tested whether the loss of sodium taste activity in adult mice impacts the maintenance of how taste nerves project to the first central relay. We found that specific loss of sodium-elicited taste activity at adulthood produced dramatic and selective reorganization of terminal fields in the brainstem. This demonstrates, for the first time, that taste-elicited activity is necessary for the normal maintenance of central gustatory circuits at adulthood and highlights a level of plasticity not seen in other sensory system subcortical circuits. Copyright © 2017 the authors 0270-6474/17/377619-12$15.00/0.

Open quantum random walk in terms of quantum Bernoulli noise

NASA Astrophysics Data System (ADS)

Wang, Caishi; Wang, Ce; Ren, Suling; Tang, Yuling

2018-03-01

In this paper, we introduce an open quantum random walk, which we call the QBN-based open walk, by means of quantum Bernoulli noise, and study its properties from a random walk point of view. We prove that, with the localized ground state as its initial state, the QBN-based open walk has the same limit probability distribution as the classical random walk. We also show that the probability distributions of the QBN-based open walk include those of the unitary quantum walk recently introduced by Wang and Ye (Quantum Inf Process 15:1897-1908, 2016) as a special case.

Regulation of Sodium Transport in the Inner Ear

PubMed Central

Kim, Sung Huhn; Marcus, Daniel C.

2011-01-01

Na+ concentrations in endolymph must be controlled to maintain hair cell function since the transduction channels of hair cells are cation-permeable, but not K+-selective. Flooding or fluctuations of the hair cell cytosol with Na+ would be expected to lead to cellular dysfunction, hearing loss and vertigo. This review briefly describes cellular mechanisms known to be responsible for Na+homeostasis in each compartment of the inner ear, including the cochlea, saccule, semicircular canals and endolymphatic sac. The influx of Na+into endolymph of each of the organs is likely via passive diffusion, but these pathways have not yet been identified or characterized. Na+ absorption is controlled by gate -keeper channels in the apical (endolymphatic) membrane of the transporting cells. Highly Na+-selective epithelial sodium channels (ENaC) control absorption by Reissner’s membrane, saccular extramacular epithelium, semicircular canal duct epithelium and endolymphatic sac. ENaC activity is controlled by a number of signal pathways, but most notably by genomic regulation of channel numbers in the membrane via glucocorticoid signaling. Nonselective cation channels in the apical membrane of outer sulcus epithelial cells and vestibular transitional cells mediate Na+ and parasensory K+ absorption. The K+-mediated transduction current in hair cells is also accompanied by a Na+ flux since the transduction channels are nonselective cation channels. Cation absorption by all of these cells is regulated by extracellular ATP via apical nonselective cation channels (P2X receptors). The heterogeneous population of epithelial cells in the endolymphatic sac is thought to have multiple absorptive pathways for Na+ with regulatory pathways that include glucocorticoids and purinergic agonists. PMID:21620939

Mineralocorticoid-induced sodium appetite and renal salt retention: Evidence for common signaling and effector mechanisms

PubMed Central

Fu, Yiling; Vallon, Volker

2014-01-01

An increase in renal sodium chloride (salt) retention and an increase in sodium appetite is the body's response to salt restriction or depletion in order to restore salt balance. Renal salt retention and increased sodium appetite can also be maladaptive and sustain the pathophysiology in conditions like salt-sensitive hypertension and chronic heart failure. Here we review the central role of the mineralocorticoid aldosterone in both the increase in renal salt reabsorption and sodium appetite. We discuss the working hypothesis that aldosterone activates similar signaling and effector mechanisms in the kidney and brain, including the mineralocorticoid receptor, the serum-and-glucocorticoid-induced kinase SGK1, the ubiquitin ligase NEDD4-2, and the epithelial sodium channel ENaC. The latter also mediates the gustatory salt sensing in the tongue, which is required for the manifestation of increased salt intake. Effects of aldosterone on both brain and kidney synergize with the effects of angiotensin II. Thus, mineralocorticoids appear to induce similar molecular pathways in the kidney, brain, and possibly tongue, which could provide opportunities for more effective therapeutic interventions. Inhibition of renal salt reabsorption is compensated by stimulation of salt appetite and vice versa; targeting both mechanisms should be more effective. Inhibiting the arousal to consume salty food may improve a patient's compliance to reducing salt intake. While a better understanding of the molecular mechanisms is needed and will provide new options, current pharmacological interventions that target both salt retention and sodium appetite include mineralocorticoid receptor antagonists and potentially inhibitors of angiotensin II and ENaC. PMID:25376899

ROMK inhibitor actions in the nephron probed with diuretics

PubMed Central

Kharade, Sujay V.; Flores, Daniel; Lindsley, Craig W.; Satlin, Lisa M.

2015-01-01

Diuretics acting on specific nephron segments to inhibit Na+ reabsorption have been used clinically for decades; however, drug interactions, tolerance, and derangements in serum K+ complicate their use to achieve target blood pressure. ROMK is an attractive diuretic target, in part, because its inhibition is postulated to indirectly inhibit the bumetanide-sensitive Na+-K+-2Cl− cotransporter (NKCC2) and the amiloride- and benzamil-sensitive epithelial Na+ channel (ENaC). The development of small-molecule ROMK inhibitors has created opportunities for exploring the physiological responses to ROMK inhibition. The present study evaluated how inhibition of ROMK alone or in combination with NKCC2, ENaC, or the hydrochlorothiazide (HCTZ) target NCC alter fluid and electrolyte transport in the nephron. The ROMK inhibitor VU591 failed to induce diuresis when administered orally to rats. However, another ROMK inhibitor, termed compound A, induced a robust natriuretic diuresis without kaliuresis. Compound A produced additive effects on urine output and Na+ excretion when combined with HCTZ, amiloride, or benzamil, but not when coadministered with bumetanide, suggesting that the major diuretic target site is the thick ascending limb (TAL). Interestingly, compound A inhibited the kaliuretic response induced by bumetanide and HCTZ, an effect we attribute to inhibition of ROMK-mediated K+ secretion in the TAL and CD. Compound A had no effect on heterologously expressed flow-sensitive large-conductance Ca2+-activated K+ channels (Slo1/β1). In conclusion, compound A represents an important new pharmacological tool for investigating the renal consequences of ROMK inhibition and therapeutic potential of ROMK as a diuretic target. PMID:26661652

ROMK inhibitor actions in the nephron probed with diuretics.

PubMed

Kharade, Sujay V; Flores, Daniel; Lindsley, Craig W; Satlin, Lisa M; Denton, Jerod S

2016-04-15

Diuretics acting on specific nephron segments to inhibit Na + reabsorption have been used clinically for decades; however, drug interactions, tolerance, and derangements in serum K + complicate their use to achieve target blood pressure. ROMK is an attractive diuretic target, in part, because its inhibition is postulated to indirectly inhibit the bumetanide-sensitive Na + -K + -2Cl - cotransporter (NKCC2) and the amiloride- and benzamil-sensitive epithelial Na + channel (ENaC). The development of small-molecule ROMK inhibitors has created opportunities for exploring the physiological responses to ROMK inhibition. The present study evaluated how inhibition of ROMK alone or in combination with NKCC2, ENaC, or the hydrochlorothiazide (HCTZ) target NCC alter fluid and electrolyte transport in the nephron. The ROMK inhibitor VU591 failed to induce diuresis when administered orally to rats. However, another ROMK inhibitor, termed compound A, induced a robust natriuretic diuresis without kaliuresis. Compound A produced additive effects on urine output and Na + excretion when combined with HCTZ, amiloride, or benzamil, but not when coadministered with bumetanide, suggesting that the major diuretic target site is the thick ascending limb (TAL). Interestingly, compound A inhibited the kaliuretic response induced by bumetanide and HCTZ, an effect we attribute to inhibition of ROMK-mediated K + secretion in the TAL and CD. Compound A had no effect on heterologously expressed flow-sensitive large-conductance Ca 2+ -activated K + channels (Slo1/β1). In conclusion, compound A represents an important new pharmacological tool for investigating the renal consequences of ROMK inhibition and therapeutic potential of ROMK as a diuretic target. Copyright © 2016 the American Physiological Society.

Point mutations in the post-M2 region of human alpha-ENaC regulate cation selectivity.

PubMed

Ji, H L; Parker, S; Langloh, A L; Fuller, C M; Benos, D J

2001-07-01

We tested the hypothesis that an arginine-rich region immediately following the second transmembrane domain may constitute part of the inner mouth of the epithelial Na+ channel (ENaC) pore and, hence, influence conduction and/or selectivity properties of the channel by expressing double point mutants in Xenopus oocytes. Double point mutations of arginines in this post-M2 region of the human alpha-ENaC (alpha-hENaC) led to a decrease and increase in the macroscopic conductance of alphaR586E,R587Ebetagamma- and alphaR589E,R591Ebetagamma-hENaC, respectively, but had no effect on the single-channel conductance of either double point mutant. However, the apparent equilibrium dissociation constant for Na+ was decreased for both alphaR586E,R587Ebetagamma- and alphaR589E,R591Ebetagamma-hENaC, and the maximum amiloride-sensitive Na+ current was decreased for alphaR586E,R587Ebetagamma-hENaC and increased for alphaR589E,R591Ebetagamma-hENaC. The relative permeabilities of Li+ and K+ vs. Na+ were increased 11.25- to 27.57-fold for alphaR586E,R587Ebetagamma-hENaC compared with wild type. The relative ion permeability of these double mutants and wild-type ENaC was inversely related to the crystal diameter of the permeant ions. Thus the region of positive charge is important for the ion permeation properties of the channel and may form part of the pore itself.

Caveolin-1 siRNA increases the pulmonary microvascular and alveolar epithelial permeability in rats.

PubMed

Gao, Chengjin; Li, Rongrong; Huan, Jingning; Li, Wei

2011-01-01

Increased pulmonary microvascular and epithelial permeability are important contributors to pulmonary edema in acute lung injury. In this study, we used small interfering RNA (siRNA) to knock down caveolin-1 expression in rat lungs and to confirm the important role of caveolin-1 in regulating pulmonary edema. After pulmonary injection of siRNA against caveolin-1 messenger RNA incorporated in liposomes with three concentrations of 0.4, 0.8, and 1.2 mg/kg, the gene silencing rate and the effects of caveolin-1 siRNA on aquaporin (AQP)-1, AQP-5, and epithelial sodium channel (ENaC) were detected. For pulmonary permeability analysis, Evans blue fluorimetry, ratios of albumin concentrations between blood and bronchoalveolar lavage, and wet/dry weight ratios were measured. The impacts of caveolin-1 suppression on interendothelial junctions were evaluated by the performance of electron microscopy and the analysis of vascular endothelial (VE)-cadherin Western blot. Alveolar wall thickness analysis and chest fluoroscopy were performed to determine the pulmonary edema degree. After 72 hours of injection, the gene silencing rate of caveolin-1 siRNA is about 87%. AQP-1, AQP-5, ENaC-α, ENaC-β, ENaC-γ, and VE-cadherin protein levels were decreased by 63%, 66%, 80%, 90%, 89%, and 50%, respectively. Caveolin-1 siRNA also resulted in increasing microvascular and epithelial permeability and pulmonary edema. These data suggest that caveolin-1 plays an important part in regulating the pulmonary permeability by modifying AQP-1, AQP-5, ENaC, and VE-cadherin.

Living with a leaky skin: upregulation of ion transport proteins during sloughing.

PubMed

Wu, Nicholas C; Cramp, Rebecca L; Franklin, Craig E

2017-06-01

Amphibian skin is a multifunctional organ providing protection from the external environment and facilitating the physiological exchange of gases, water and salts with the environment. In order to maintain these functions, the outer layer of skin is regularly replaced in a process called sloughing. During sloughing, the outermost layer of the skin is removed in its entirety, which has the potential to interfere with skin permeability and ion transport, disrupting homeostasis. In this study, we measured, in vivo , the effects of sloughing on the cutaneous efflux of ions in toads Rhinella marina kept in freshwater conditions. We also measured transepithelial potential, cutaneous resistance, active ion transport and the distribution, abundance and gene expression of the key ion transport proteins sodium-potassium ATPase (NKA) and epithelial sodium channel (ENaC) during sloughing. We hypothesised that the increase in transepithelial efflux of ions during sloughing is a consequence of increased permeability and/or a reduction in the abundance or expression of cutaneous ion transport proteins, resulting in disruption of internal ion homeostasis. There was a significant increase in sodium and chloride efflux during sloughing in R. marina However, although in vitro skin resistance decreased after sloughing, active sodium transport increased commensurate with an increase in NKA and ENaC protein abundance in the skin. These changes in skin function associated with sloughing did not affect the maintenance of internal electrolyte homeostasis. These results suggest that during sloughing, amphibians actively maintain internal homeostasis by increasing cutaneous rates of ion uptake. © 2017. Published by The Company of Biologists Ltd.

Constitutively Active SPAK Causes Hyperkalemia by Activating NCC and Remodeling Distal Tubules.

PubMed

Grimm, P Richard; Coleman, Richard; Delpire, Eric; Welling, Paul A

2017-09-01

Aberrant activation of with no lysine (WNK) kinases causes familial hyperkalemic hypertension (FHHt). Thiazide diuretics treat the disease, fostering the view that hyperactivation of the thiazide-sensitive sodium-chloride cotransporter (NCC) in the distal convoluted tubule (DCT) is solely responsible. However, aberrant signaling in the aldosterone-sensitive distal nephron (ASDN) and inhibition of the potassium-excretory renal outer medullary potassium (ROMK) channel have also been implicated. To test these ideas, we introduced kinase-activating mutations after Lox-P sites in the mouse Stk39 gene, which encodes the terminal kinase in the WNK signaling pathway, Ste20-related proline-alanine-rich kinase (SPAK). Renal expression of the constitutively active (CA)-SPAK mutant was specifically targeted to the early DCT using a DCT-driven Cre recombinase. CA-SPAK mice displayed thiazide-treatable hypertension and hyperkalemia, concurrent with NCC hyperphosphorylation. However, thiazide-mediated inhibition of NCC and consequent restoration of sodium excretion did not immediately restore urinary potassium excretion in CA-SPAK mice. Notably, CA-SPAK mice exhibited ASDN remodeling, involving a reduction in connecting tubule mass and attenuation of epithelial sodium channel (ENaC) and ROMK expression and apical localization. Blocking hyperactive NCC in the DCT gradually restored ASDN structure and ENaC and ROMK expression, concurrent with the restoration of urinary potassium excretion. These findings verify that NCC hyperactivity underlies FHHt but also reveal that NCC-dependent changes in the driving force for potassium secretion are not sufficient to explain hyperkalemia. Instead, a DCT-ASDN coupling process controls potassium balance in health and becomes aberrantly activated in FHHt. Copyright © 2017 by the American Society of Nephrology.

CNS sites activated by renal pelvic epithelial sodium channels (ENaCs) in response to hypertonic saline in awake rats.

PubMed

Goodwill, Vanessa S; Terrill, Christopher; Hopewood, Ian; Loewy, Arthur D; Knuepfer, Mark M

2017-05-01

In some patients, renal nerve denervation has been reported to be an effective treatment for essential hypertension. Considerable evidence suggests that afferent renal nerves (ARN) and sodium balance play important roles in the development and maintenance of high blood pressure. ARN are sensitive to sodium concentrations in the renal pelvis. To better understand the role of ARN, we infused isotonic or hypertonic NaCl (308 or 500mOsm) into the left renal pelvis of conscious rats for two 2hours while recording arterial pressure and heart rate. Subsequently, brain tissue was analyzed for immunohistochemical detection of the protein Fos, a marker for neuronal activation. Fos-immunoreactive neurons were identified in numerous sites in the forebrain and brainstem. These areas included the nucleus tractus solitarius (NTS), the lateral parabrachial nucleus, the paraventricular nucleus of the hypothalamus (PVH) and the supraoptic nucleus (SON). The most effective stimulus was 500mOsm NaCl. Activation of these sites was attenuated or prevented by administration of benzamil (1μM) or amiloride (10μM) into the renal pelvis concomitantly with hypertonic saline. In anesthetized rats, infusion of hypertonic saline but not isotonic saline into the renal pelvis elevated ARN activity and this increase was attenuated by simultaneous infusion of benzamil or amiloride. We propose that renal pelvic epithelial sodium channels (ENaCs) play a role in activation of ARN and, via central visceral afferent circuits, this system modulates fluid volume and peripheral blood pressure. These pathways may contribute to the development of hypertension. Copyright © 2016 Elsevier B.V. All rights reserved.

The Everett-Wheeler interpretation and the open future

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

Sudbery, Anthony

2011-03-28

I discuss the meaning of probability in the Everett-Wheeler interpretation of quantum mechanics, together with the problem of defining histories. To resolve these, I propose an understanding of probability arising from a form of temporal logic: the probability of a future-tense proposition is identified with its truth value in a many-valued and context-dependent logic. In short, probability is degree of truth. These ideas relate to traditional naive ideas of time and chance. Indeed, I argue that Everettian quantum mechanics is the only form of scientific theory that truly incorporates the perception that the future is open.

Time‐dependent renewal‐model probabilities when date of last earthquake is unknown

USGS Publications Warehouse

Field, Edward H.; Jordan, Thomas H.

2015-01-01

We derive time-dependent, renewal-model earthquake probabilities for the case in which the date of the last event is completely unknown, and compare these with the time-independent Poisson probabilities that are customarily used as an approximation in this situation. For typical parameter values, the renewal-model probabilities exceed Poisson results by more than 10% when the forecast duration exceeds ~20% of the mean recurrence interval. We also derive probabilities for the case in which the last event is further constrained to have occurred before historical record keeping began (the historic open interval), which can only serve to increase earthquake probabilities for typically applied renewal models.We conclude that accounting for the historic open interval can improve long-term earthquake rupture forecasts for California and elsewhere.

Activation of the Endogenous Renin-Angiotensin-Aldosterone System or Aldosterone Administration Increases Urinary Exosomal Sodium Channel Excretion.

PubMed

Qi, Ying; Wang, Xiaojing; Rose, Kristie L; MacDonald, W Hayes; Zhang, Bing; Schey, Kevin L; Luther, James M

2016-02-01

Urinary exosomes secreted by multiple cell types in the kidney may participate in intercellular signaling and provide an enriched source of kidney-specific proteins for biomarker discovery. Factors that alter the exosomal protein content remain unknown. To determine whether endogenous and exogenous hormones modify urinary exosomal protein content, we analyzed samples from 14 mildly hypertensive patients in a crossover study during a high-sodium (HS, 160 mmol/d) diet and low-sodium (LS, 20 mmol/d) diet to activate the endogenous renin-angiotensin-aldosterone system. We further analyzed selected exosomal protein content in a separate cohort of healthy persons receiving intravenous aldosterone (0.7 μg/kg per hour for 10 hours) versus vehicle infusion. The LS diet increased plasma renin activity and aldosterone concentration, whereas aldosterone infusion increased only aldosterone concentration. Protein analysis of paired urine exosome samples by liquid chromatography-tandem mass spectrometry-based multidimensional protein identification technology detected 2775 unique proteins, of which 316 exhibited significantly altered abundance during LS diet. Sodium chloride cotransporter (NCC) and α- and γ-epithelial sodium channel (ENaC) subunits from the discovery set were verified using targeted multiple reaction monitoring mass spectrometry quantified with isotope-labeled peptide standards. Dietary sodium restriction or acute aldosterone infusion similarly increased urine exosomal γENaC[112-122] peptide concentrations nearly 20-fold, which correlated with plasma aldosterone concentration and urinary Na/K ratio. Urine exosomal NCC and αENaC concentrations were relatively unchanged during these interventions. We conclude that urinary exosome content is altered by renin-angiotensin-aldosterone system activation. Urinary measurement of exosomal γENaC[112-122] concentration may provide a useful biomarker of ENaC activation in future clinical studies. Copyright © 2016 by the American Society of Nephrology.

Activation of the Endogenous Renin-Angiotensin-Aldosterone System or Aldosterone Administration Increases Urinary Exosomal Sodium Channel Excretion

PubMed Central

Qi, Ying; Wang, Xiaojing; Rose, Kristie L.; MacDonald, W. Hayes; Zhang, Bing; Schey, Kevin L.

2016-01-01

Urinary exosomes secreted by multiple cell types in the kidney may participate in intercellular signaling and provide an enriched source of kidney-specific proteins for biomarker discovery. Factors that alter the exosomal protein content remain unknown. To determine whether endogenous and exogenous hormones modify urinary exosomal protein content, we analyzed samples from 14 mildly hypertensive patients in a crossover study during a high-sodium (HS, 160 mmol/d) diet and low-sodium (LS, 20 mmol/d) diet to activate the endogenous renin-angiotensin-aldosterone system. We further analyzed selected exosomal protein content in a separate cohort of healthy persons receiving intravenous aldosterone (0.7 μg/kg per hour for 10 hours) versus vehicle infusion. The LS diet increased plasma renin activity and aldosterone concentration, whereas aldosterone infusion increased only aldosterone concentration. Protein analysis of paired urine exosome samples by liquid chromatography-tandem mass spectrometry–based multidimensional protein identification technology detected 2775 unique proteins, of which 316 exhibited significantly altered abundance during LS diet. Sodium chloride cotransporter (NCC) and α- and γ-epithelial sodium channel (ENaC) subunits from the discovery set were verified using targeted multiple reaction monitoring mass spectrometry quantified with isotope-labeled peptide standards. Dietary sodium restriction or acute aldosterone infusion similarly increased urine exosomal γENaC[112–122] peptide concentrations nearly 20-fold, which correlated with plasma aldosterone concentration and urinary Na/K ratio. Urine exosomal NCC and αENaC concentrations were relatively unchanged during these interventions. We conclude that urinary exosome content is altered by renin-angiotensin-aldosterone system activation. Urinary measurement of exosomal γENaC[112–122] concentration may provide a useful biomarker of ENaC activation in future clinical studies. PMID:26113616

Calcium Homeostasis Modulator 1-Like Currents in Rat Fungiform Taste Cells Expressing Amiloride-Sensitive Sodium Currents.

PubMed

Bigiani, Albertino

2017-05-01

Salt reception by taste cells is still the less understood transduction process occurring in taste buds, the peripheral sensory organs for the detection of food chemicals. Although there is evidence suggesting that the epithelial sodium channel (ENaC) works as sodium receptor, yet it is not clear how salt-detecting cells signal the relevant information to nerve endings. Taste cells responding to sweet, bitter, and umami substances release ATP as neurotransmitter through a nonvesicular mechanism. Three different channel proteins have been proposed as conduit for ATP secretion: pannexin channels, connexin hemichannels, and calcium homeostasis modulator 1 (CALHM1) channels. In heterologous expression systems, these channels mediate outwardly rectifying membrane currents with distinct biophysical and pharmacological properties. I therefore tested whether also salt-detecting taste cells were endowed with these currents. To this aim, I applied the patch-clamp techniques to single cells in isolated taste buds from rat fungiform papillae. Salt-detecting cells were functionally identified by exploiting the effect of amiloride, which induces a current response by shutting down ENaCs. I looked for the presence of outwardly rectifying currents by using appropriate voltage-clamp protocols and specific pharmacological tools. I found that indeed salt-detecting cells possessed these currents with properties consistent with the presence, at least in part, of CALHM1 channels. Unexpectedly, CALHM1-like currents in taste cells were potentiated by known blockers of pannexin, suggesting a possible inhibitory action of this protein on CALMH1. These findings indicate that communication between salt-detecting cells and nerve endings might involve ATP release by CALMH1 channels. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Double knockout of carbonic anhydrase II (CAII) and Na(+)-Cl(-) cotransporter (NCC) causes salt wasting and volume depletion.

PubMed

Xu, Jie; Barone, Sharon; Brooks, Mary-Beth; Soleimani, Manoocher

2013-01-01

The thiazide-sensitive Na(+)-Cl(-) cotransporter NCC and the Cl(-)/HCO3(-)exchanger pendrin are expressed on apical membranes of distal cortical nephron segments and mediate salt absorption, with pendrin working in tandem with the epithelial Na(+) channel (ENaC) and the Na(+)-dependent chloride/bicarbonate exchanger (NDCBE), whereas NCC is working by itself. A recent study showed that NCC and pendrin compensate for loss of each other under basal conditions, therefore masking the role that each plays in salt reabsorption. Carbonic anhydrase II (CAII, CA2 or CAR2) plays an important role in acid-base transport and salt reabsorption in the proximal convoluted tubule and acid-base transport in the collecting duct. Animals with CAII deletion show remodeling of intercalated cells along with the downregulation of pendrin. NCC KO mice on the other hand show significant upregulation of pendrin and ENaC. Neither model shows any significant salt wasting under baseline conditions. We hypothesized that the up-regulation of pendrin is essential for the prevention of salt wasting in NCC KO mice. To test this hypothesis, we generated NCC/CAII double KO (dKO) mice by crossing mice with single deletion of NCC and CAII. The NCC/CAII dKO mice displayed significant downregulation of pendrin, along with polyuria and salt wasting. As a result, the dKO mice developed volume depletion, which was associated with the inability to concentrate urine. We conclude that the upregulation of pendrin is essential for the prevention of salt and water wasting in NCC deficient animals and its downregulation or inactivation will result in salt wasting, impaired water conservation and volume depletion in the setting of NCC inactivation or inhibition. © 2014 S. Karger AG, Basel.

Nerve growth factor reduces amiloride‐sensitive Na+ transport in human airway epithelial cells

PubMed Central

Shimko, Michael J.; Zaccone, Eric J.; Thompson, Janet A.; Schwegler‐Berry, Diane; Kashon, Michael L.; Fedan, Jeffrey S.

2014-01-01

Abstract Nerve growth factor (NGF) is overexpressed in patients with inflammatory lung diseases, including virus infections. Airway surface liquid (ASL), which is regulated by epithelial cell ion transport, is essential for normal lung function. No information is available regarding the effect of NGF on ion transport of airway epithelium. To investigate whether NGF can affect ion transport, human primary air‐interface cultured epithelial cells were placed in Ussing chambers to obtain transepithelial voltage (−7.1 ± 3.4 mV), short‐circuit current (Isc, 5.9 ± 1.0 μA), and transepithelial resistance (750 Ω·cm2), and to measure responses to ion transport inhibitors. Amiloride (apical, 3.5 × 10−5 mol/L) decreased Isc by 55.3%. Apically applied NGF (1 ng/mL) reduced Isc by 5.3% in 5 min; basolaterally applied NGF had no effect. The response to amiloride was reduced (41.6%) in the presence of NGF. K‐252a (10 nmol/L, apical) did not itself affect Na+ transport, but it attenuated the NGF‐induced reduction in Na+ transport, indicating the participation of the trkA receptor in the NGF‐induced reduction in Na+ transport. PD‐98059 (30 μmol/L, apical and basolateral) did not itself affect Na+ transport, but attenuated the NGF‐induced reduction in Na+ transport, indicating that trkA activated the Erk 1/2 signaling cascade. NGF stimulated phosphorylation of Erk 1/2 and the β‐subunit of ENaC. K‐252a and PD‐98059 inhibited these responses. NGF had no effect on Isc in the presence of apical nystatin (50 μmol/L). These results indicate that NGF inhibits Na+ transport through a trkA‐Erk 1/2‐activated signaling pathway linked to ENaC phosphorylation. PMID:25347857

Increasing plasma [K+] by intravenous potassium infusion reduces NCC phosphorylation and drives kaliuresis and natriuresis.

PubMed

Rengarajan, Srinivas; Lee, Donna H; Oh, Young Taek; Delpire, Eric; Youn, Jang H; McDonough, Alicia A

2014-05-01

Dietary potassium loading results in rapid kaliuresis, natriuresis, and diuresis associated with reduced phosphorylation (p) of the distal tubule Na(+)-Cl(-) cotransporter (NCC). Decreased NCC-p inhibits NCC-mediated Na(+) reabsorption and shifts Na(+) downstream for reabsorption by epithelial Na(+) channels (ENaC), which can drive K(+) secretion. Whether the signal is initiated by ingesting potassium or a rise in plasma K(+) concentration ([K(+)]) is not understood. We tested the hypothesis, in male rats, that an increase in plasma [K(+)] is sufficient to reduce NCC-p and drive kaliuresis. After an overnight fast, a single 3-h 2% potassium (2%K) containing meal increased plasma [K(+)] from 4.0 ± 0.1 to 5.2 ± 0.2 mM; increased urinary K(+), Na(+), and volume excretion; decreased NCC-p by 60%; and marginally reduced cortical Na(+)-K(+)-2Cl(-) cotransporter (NKCC) phosphorylation 25% (P = 0.055). When plasma [K(+)] was increased by tail vein infusion of KCl to 5.5 ± 0.1 mM over 3 h, significant kaliuresis and natriuresis ensued, NCC-p decreased by 60%, and STE20/SPS1-related proline alanine-rich kinase (SPAK) phosphorylation was marginally reduced 35% (P = 0.052). The following were unchanged at 3 h by either the potassium-rich meal or KCl infusion: Na(+)/H(+) exchanger 3 (NHE3), NHE3-p, NKCC, ENaC subunits, and renal outer medullary K(+) channel. In summary, raising plasma [K(+)] by intravenous infusion to a level equivalent to that observed after a single potassium-rich meal triggers renal kaliuretic and natriuretic responses, independent of K(+) ingestion, likely driven by decreased NCC-p and activity sufficient to shift sodium reabsorption downstream to where Na(+) reabsorption and flow drive K(+) secretion.

Pharmacological activators of AMP-activated protein kinase have different effects on Na+ transport processes across human lung epithelial cells.

PubMed

Woollhead, A M; Sivagnanasundaram, J; Kalsi, K K; Pucovsky, V; Pellatt, L J; Scott, J W; Mustard, K J; Hardie, D G; Baines, D L

2007-08-01

AMP-activated protein kinase (AMPK) is activated by metformin, phenformin, and the AMP mimetic, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR). We have completed an extensive study of the pharmacological effects of these drugs on AMPK activation, adenine nucleotide concentration, transepithelial amiloride-sensitive (I(amiloride)) and ouabain-sensitive basolateral (I(ouabain)) short circuit current in H441 lung epithelial cells. H441 cells were grown on permeable filters at air interface. I(amiloride), I(ouabain) and transepithelial resistance were measured in Ussing chambers. AMPK activity was measured as the amount of radiolabelled phosphate transferred to the SAMS peptide. Adenine nucleotide concentration was analysed by reverse phase HPLC and NAD(P)H autofluorescence was measured using confocal microscopy. Phenformin, AICAR and metformin increased AMPK (alpha1) activity and decreased I(amiloride). The AMPK inhibitor Compound C prevented the action of metformin and AICAR but not phenformin. Phenformin and AICAR decreased I(ouabain) across H441 monolayers and decreased monolayer resistance. The decrease in I(amiloride) was closely related to I(ouabain) with phenformin, but not in AICAR treated monolayers. Metformin and phenformin increased the cellular AMP:ATP ratio but only phenformin and AICAR decreased cellular ATP. Activation of alpha1-AMPK is associated with inhibition of apical amiloride-sensitive Na(+) channels (ENaC), which has important implications for the clinical use of metformin. Additional pharmacological effects evoked by AICAR and phenformin on I(ouabain), with potential secondary effects on apical Na+ conductance, ENaC activity and monolayer resistance, have important consequences for their use as pharmacological activators of AMPK in cell systems where Na+K+ATPase is an important component.

Pharmacological activators of AMP-activated protein kinase have different effects on Na+ transport processes across human lung epithelial cells

PubMed Central

Woollhead, A M; Sivagnanasundaram, J; Kalsi, K K; Pucovsky, V; Pellatt, L J; Scott, J W; Mustard, K J; Hardie, D G; Baines, D L

2007-01-01

Background and purpose: AMP-activated protein kinase (AMPK) is activated by metformin, phenformin, and the AMP mimetic, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR). We have completed an extensive study of the pharmacological effects of these drugs on AMPK activation, adenine nucleotide concentration, transepithelial amiloride-sensitive (Iamiloride) and ouabain-sensitive basolateral (Iouabain) short circuit current in H441 lung epithelial cells. Experimental approach: H441 cells were grown on permeable filters at air interface. Iamiloride, Iouabain and transepithelial resistance were measured in Ussing chambers. AMPK activity was measured as the amount of radiolabelled phosphate transferred to the SAMS peptide. Adenine nucleotide concentration was analysed by reverse phase HPLC and NAD(P)H autofluorescence was measured using confocal microscopy. Key results: Phenformin, AICAR and metformin increased AMPK (α1) activity and decreased Iamiloride. The AMPK inhibitor Compound C prevented the action of metformin and AICAR but not phenformin. Phenformin and AICAR decreased Iouabain across H441 monolayers and decreased monolayer resistance. The decrease in Iamiloride was closely related to Iouabain with phenformin, but not in AICAR treated monolayers. Metformin and phenformin increased the cellular AMP:ATP ratio but only phenformin and AICAR decreased cellular ATP. Conclusions and implications: Activation of α1-AMPK is associated with inhibition of apical amiloride-sensitive Na+ channels (ENaC), which has important implications for the clinical use of metformin. Additional pharmacological effects evoked by AICAR and phenformin on Iouabain, with potential secondary effects on apical Na+ conductance, ENaC activity and monolayer resistance, have important consequences for their use as pharmacological activators of AMPK in cell systems where Na+K+ATPase is an important component. PMID:17603555

Altered lipid and salt taste responsivity in ghrelin and GOAT null mice.

PubMed

Cai, Huan; Cong, Wei-Na; Daimon, Caitlin M; Wang, Rui; Tschöp, Matthias H; Sévigny, Jean; Martin, Bronwen; Maudsley, Stuart

2013-01-01

Taste perception plays an important role in regulating food preference, eating behavior and energy homeostasis. Taste perception is modulated by a variety of factors, including gastric hormones such as ghrelin. Ghrelin can regulate growth hormone release, food intake, adiposity, and energy metabolism. Octanoylation of ghrelin by ghrelin O-acyltransferase (GOAT) is a specific post-translational modification which is essential for many biological activities of ghrelin. Ghrelin and GOAT are both widely expressed in many organs including the gustatory system. In the current study, overall metabolic profiles were assessed in wild-type (WT), ghrelin knockout (ghrelin(-/-)), and GOAT knockout (GOAT(-/-)) mice. Ghrelin(-/-) mice exhibited decreased food intake, increased plasma triglycerides and increased ketone bodies compared to WT mice while demonstrating WT-like body weight, fat composition and glucose control. In contrast GOAT(-/-) mice exhibited reduced body weight, adiposity, resting glucose and insulin levels compared to WT mice. Brief access taste behavioral tests were performed to determine taste responsivity in WT, ghrelin(-/-) and GOAT(-/-) mice. Ghrelin and GOAT null mice possessed reduced lipid taste responsivity. Furthermore, we found that salty taste responsivity was attenuated in ghrelin(-/-) mice, yet potentiated in GOAT(-/-) mice compared to WT mice. Expression of the potential lipid taste regulators Cd36 and Gpr120 were reduced in the taste buds of ghrelin and GOAT null mice, while the salt-sensitive ENaC subunit was increased in GOAT(-/-) mice compared with WT mice. The altered expression of Cd36, Gpr120 and ENaC may be responsible for the altered lipid and salt taste perception in ghrelin(-/-) and GOAT(-/-) mice. The data presented in the current study potentially implicates ghrelin signaling activity in the modulation of both lipid and salt taste modalities.

Phase Transition for the Large-Dimensional Contact Process with Random Recovery Rates on Open Clusters

NASA Astrophysics Data System (ADS)

Xue, Xiaofeng

2016-12-01

In this paper we are concerned with the contact process with random recovery rates on open clusters of bond percolation on Z^d. Let ξ be a random variable such that P(ξ ≥ 1)=1, which ensures E1/ξ <+∞, then we assign i. i. d. copies of ξ on the vertices as the random recovery rates. Assuming that each edge is open with probability p and the infection can only spread through the open edges, then we obtain that limsup _{d→ +∞}λ _d≤ λ _c=1/pE{1}/{ξ}, where λ _d is the critical value of the process on Z^d, i.e., the maximum of the infection rates with which the infection dies out with probability one when only the origin is infected at t=0. To prove the above main result, we show that the following phase transition occurs. Assuming that lceil log drceil vertices are infected at t=0, where these vertices can be located anywhere, then when the infection rate λ >λ _c, the process survives with high probability as d→ +∞ while when λ <λ _c, the process dies out at time O(log d) with high probability.

Emergence and stability of intermediate open vesicles in disk-to-vesicle transitions.

PubMed

Li, Jianfeng; Zhang, Hongdong; Qiu, Feng; Shi, An-Chang

2013-07-01

The transition between two basic structures, a disk and an enclosed vesicle, of a finite membrane is studied by examining the minimum energy path (MEP) connecting these two states. The MEP is constructed using the string method applied to continuum elastic membrane models. The results reveal that, besides the commonly observed disk and vesicle, open vesicles (bowl-shaped vesicles or vesicles with a pore) can become stable or metastable shapes. The emergence, stability, and probability distribution of these open vesicles are analyzed. It is demonstrated that open vesicles can be stabilized by higher-order elastic energies. The estimated probability distribution of the different structures is in good agreement with available experiments.

Calculation of transmission probability by solving an eigenvalue problem

NASA Astrophysics Data System (ADS)

Bubin, Sergiy; Varga, Kálmán

2010-11-01

The electron transmission probability in nanodevices is calculated by solving an eigenvalue problem. The eigenvalues are the transmission probabilities and the number of nonzero eigenvalues is equal to the number of open quantum transmission eigenchannels. The number of open eigenchannels is typically a few dozen at most, thus the computational cost amounts to the calculation of a few outer eigenvalues of a complex Hermitian matrix (the transmission matrix). The method is implemented on a real space grid basis providing an alternative to localized atomic orbital based quantum transport calculations. Numerical examples are presented to illustrate the efficiency of the method.

Airway mucus, inflammation and remodeling: emerging links in the pathogenesis of chronic lung diseases.

PubMed

Zhou-Suckow, Zhe; Duerr, Julia; Hagner, Matthias; Agrawal, Raman; Mall, Marcus A

2017-03-01

Airway mucus obstruction is a hallmark of many chronic lung diseases including rare genetic disorders such as cystic fibrosis (CF) and primary ciliary dyskinesia, as well as common lung diseases such as asthma and chronic obstructive pulmonary disease (COPD), which have emerged as a leading cause of morbidity and mortality worldwide. However, the role of excess airway mucus in the in vivo pathogenesis of these diseases remains poorly understood. The generation of mice with airway-specific overexpression of epithelial Na + channels (ENaC), exhibiting airway surface dehydration (mucus hyperconcentration), impaired mucociliary clearance (MCC) and mucus plugging, led to a model of muco-obstructive lung disease that shares key features of CF and COPD. In this review, we summarize recent progress in the understanding of causes of impaired MCC and in vivo consequences of airway mucus obstruction that can be inferred from studies in βENaC-overexpressing mice. These studies confirm that mucus hyperconcentration on airway surfaces plays a critical role in the pathophysiology of impaired MCC, mucus adhesion and airway plugging that cause airflow obstruction and provide a nidus for bacterial infection. In addition, these studies support the emerging concept that excess airway mucus per se, probably via several mechanisms including hypoxic epithelial necrosis, retention of inhaled irritants or allergens, and potential immunomodulatory effects, is a potent trigger of chronic airway inflammation and associated lung damage, even in the absence of bacterial infection. Finally, these studies suggest that improvement of mucus clearance may be a promising therapeutic strategy for a spectrum of muco-obstructive lung diseases.

Inhibition of the calcium channel by intracellular protons in single ventricular myocytes of the guinea-pig.

PubMed Central

Kaibara, M; Kameyama, M

1988-01-01

1. The inhibitory effects of intracellular protons (Hi+) on the L-type Ca2+ channel activity were investigated in single ventricular myocytes of guinea-pigs by using the patch-clamp method in the open-cell-attached patch configuration, where 'run down' of the channel was partially prevented. 2. Hi+ reduced the unitary Ba2+ current of the Ca2+ channel by 10-20% without changing the maximum slope conductance. 3. Hi+ did not alter the number of channels in patches containing one or two channels. 4. Hi+ markedly reduced the mean current normalized by the unitary current, which gave the open-state probability multiplied by the number of channels in the patch. The dose-response curve between Hi+ and the open-state probability indicated half-maximum inhibition at pHi 6.6 and an apparent Hill coefficient of 1. 5. Hi+ shifted both the steady-state activation and inactivation curves in a negative direction by 10-15 mV, and the effects were reversible. 6. Hi+ did not affect the fast open-closed kinetics represented by the C-C-O scheme, apart from increasing the slow time constant of the closed time. 7. Hi+ increased the percentage of blank sweeps and reduced that of non-blank sweeps resulting in a decreased probability of channel opening. 8. Photo-oxidation with Rose Bengal abolished the reducing effect of Hi+ on the open-state probability (Po) in two out of ten experiments, suggesting the possible involvement of histidine residues in the Hi+ effect. 9. The above results indicate that Hi+ inhibits the Ba2+ current mainly by affecting the slow gating mechanism of the channel. PMID:2855346

ENaC/DEG in Tumor Development and Progression

PubMed Central

Liu, Cui; Zhu, Li-Li; Xu, Si-Guang; Ji, Hong-Long; Li, Xiu-Min

2016-01-01

The epithelial Na+ channel/degenerin (ENaC/DEG) superfamily, including the acid-sensing ion channels (ASICs), is characterized by a high degree of similarity in structure but highly diverse in physiological functions. These ion channels have been shown to be important in several physiological functions of normal epithelial cells, including salt homeostasis, fluid transportation and cell mobility. There is increasing evidence suggesting that ENaC/DEG channels are critically engaged in cancer cell biology, such as proliferation, migration, invasion and apoptosis, playing a role in tumor development and progression. In this review, we will discuss recent studies showing the role of ENaC and ASIC channels in epithelial cells and its relationship to the oncogenesis. PMID:27698929

Risky Business: Do Native Rodents Use Habitat and Odor Cues to Manage Predation Risk in Australian Deserts?

PubMed Central

Spencer, Emma E.; Crowther, Mathew S.; Dickman, Christopher R.

2014-01-01

In open, arid environments with limited shelter there may be strong selection on small prey species to develop behaviors that facilitate predator avoidance. Here, we predicted that rodents should avoid predator odor and open habitats to reduce their probability of encounter with potential predators, and tested our predictions using a native Australian desert rodent, the spinifex hopping-mouse (Notomys alexis). We tested the foraging and movement responses of N. alexis to non-native predator (fox and cat) odor, in sheltered and open macro- and microhabitats. Rodents did not respond to predator odor, perhaps reflecting the inconsistent selection pressure that is imposed on prey species in the desert environment due to the transience of predator-presence. However, they foraged primarily in the open and moved preferentially across open sand. The results suggest that N. alexis relies on escape rather than avoidance behavior when managing predation risk, with its bipedal movement probably allowing it to exploit open environments most effectively. PMID:24587396

Risky business: do native rodents use habitat and odor cues to manage predation risk in Australian deserts?

PubMed

Spencer, Emma E; Crowther, Mathew S; Dickman, Christopher R

2014-01-01

In open, arid environments with limited shelter there may be strong selection on small prey species to develop behaviors that facilitate predator avoidance. Here, we predicted that rodents should avoid predator odor and open habitats to reduce their probability of encounter with potential predators, and tested our predictions using a native Australian desert rodent, the spinifex hopping-mouse (Notomys alexis). We tested the foraging and movement responses of N. alexis to non-native predator (fox and cat) odor, in sheltered and open macro- and microhabitats. Rodents did not respond to predator odor, perhaps reflecting the inconsistent selection pressure that is imposed on prey species in the desert environment due to the transience of predator-presence. However, they foraged primarily in the open and moved preferentially across open sand. The results suggest that N. alexis relies on escape rather than avoidance behavior when managing predation risk, with its bipedal movement probably allowing it to exploit open environments most effectively.

The Best of Two Open Worlds at the National Open University of Nigeria

ERIC Educational Resources Information Center

Agbu, Jane-frances Obiageli; Mulder, Fred; de Vries, Fred; Tenebe, Vincent; Caine, Abel

2016-01-01

It will be wise for educational institutions, from primary to tertiary level, globally, to reflect on their position and profile with respect to the new concepts of Open Educational Resources (OER) and Massive Open Online Courses (MOOCs). Responses will be diverse of course but the potential is so manifest that many institutions probably will…

Automated measurement of spatial preference in the open field test with transmitted lighting.

PubMed

Kulikov, Alexander V; Tikhonova, Maria A; Kulikov, Victor A

2008-05-30

New modification of the open field was designed to improve automation of the test. The main innovations were: (1) transmitted lighting and (2) estimation of probability to find pixels associated with an animal in the selected region of arena as an objective index of spatial preference. Transmitted (inverted) lighting significantly ameliorated the contrast between an animal and arena and allowed to track white animals with similar efficacy as colored ones. Probability as a measure of preference of selected region was mathematically proved and experimentally verified. A good correlation between probability and classic indices of spatial preference (number of region entries and time spent therein) was shown. The algorithm of calculation of probability to find pixels associated with an animal in the selected region was implemented in the EthoStudio software. Significant interstrain differences in locomotion and the central zone preference (index of anxiety) were shown using the inverted lighting and the EthoStudio software in mice of six inbred strains. The effects of arena shape (circle or square) and a novel object presence in the center of arena on the open field behavior in mice were studied.

Temperature Influences Chorda Tympani Nerve Responses to Sweet, Salty, Sour, Umami, and Bitter Stimuli in Mice.

PubMed

Lu, Bo; Breza, Joseph M; Contreras, Robert J

2016-08-06

Temperature profoundly affects the perceived intensity of taste, yet we know little of the extent of temperature's effect on taste in the peripheral nervous system. Accordingly, we investigated the influence of temperature from 23 °C to 43 °C in 4 °C intervals on the integrated responses of the chorda tympani (CT) nerve to a large series of chemical stimuli representing sweet, salty, sour, bitter, and umami tastes in C57BL/J6 mice. We also measured neural responses to NaCl, Na-gluconate, Na-acetate, Na-sulfate, and MSG with and without 5 µM benzamil, an epithelial sodium channel (ENaC) antagonist, to assess the influence of temperature on ENaC-dependent and ENaC-independent response components. Our results showed that for most stimuli (0.5M sucrose, glucose, fructose, and maltose; 0.02M saccharin and sucralose; 0.5M NaCl, Na-gluconate, Na-acetate, Na-sulfate, KCl, K-gluconate, K-acetate, and K-sulfate; 0.05M citric acid, acetic acid, and HCl; 0.1M MSG and 0.05M quinine hydrochloride: QHCl), CT response magnitudes were maximal between 35 °C and 39 °C and progressively smaller at cooler or warmer temperatures. In contrast, the weakest responses to NH 4 Cl, (NH 4 ) 2 SO4, and K-sulfate were at the lowest temperature, with response magnitude increasing monotonically with increasing temperature, while the largest responses to acetic acid were at the lowest temperature, with response magnitude decreasing with increasing temperature. The response to sweet and umami stimuli across temperatures were similar reflecting the involvement of TRPM5 activity, in contrast to bitter stimuli, which were weakly affected by temperature. Temperature-modulated responses to salts and acids most likely operate through mechanisms independent of ENaC and TRPM5. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cellular distribution and function of ion channels involved in transport processes in rat tracheal epithelium.

PubMed

Hahn, Anne; Faulhaber, Johannes; Srisawang, Lalita; Stortz, Andreas; Salomon, Johanna J; Mall, Marcus A; Frings, Stephan; Möhrlen, Frank

2017-06-01

Transport of water and electrolytes in airway epithelia involves chloride-selective ion channels, which are controlled either by cytosolic Ca 2+ or by cAMP The contributions of the two pathways to chloride transport differ among vertebrate species. Because rats are becoming more important as animal model for cystic fibrosis, we have examined how Ca 2+ - dependent and cAMP- dependent Cl - secretion is organized in the rat tracheal epithelium. We examined the expression of the Ca 2+ -gated Cl - channel anoctamin 1 (ANO1), the cystic fibrosis transmembrane conductance regulator (CFTR) Cl - channel, the epithelial Na + channel ENaC, and the water channel aquaporin 5 (AQP5) in rat tracheal epithelium. The contribution of ANO1 channels to nucleotide-stimulated Cl - secretion was determined using the channel blocker Ani9 in short-circuit current recordings obtained from primary cultures of rat tracheal epithelial cells in Ussing chambers. We found that ANO1, CFTR and AQP5 proteins were expressed in nonciliated cells of the tracheal epithelium, whereas ENaC was expressed in ciliated cells. Among nonciliated cells, ANO1 occurred together with CFTR and Muc5b and, in addition, in a different cell type without CFTR and Muc5b. Bioelectrical studies with the ANO1-blocker Ani9 indicated that ANO1 mediated the secretory response to the nucleotide uridine-5'-triphosphate. Our data demonstrate that, in rat tracheal epithelium, Cl - secretion and Na + absorption are routed through different cell types, and that ANO1 channels form the molecular basis of Ca 2+ -dependent Cl - secretion in this tissue. These characteristic features of Cl - -dependent secretion reveal similarities and distinct differences to secretory processes in human airways. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Temperature Influences Chorda Tympani Nerve Responses to Sweet, Salty, Sour, Umami, and Bitter Stimuli in Mice

PubMed Central

Lu, Bo; Breza, Joseph M.

2016-01-01

Temperature profoundly affects the perceived intensity of taste, yet we know little of the extent of temperature’s effect on taste in the peripheral nervous system. Accordingly, we investigated the influence of temperature from 23 °C to 43 °C in 4 °C intervals on the integrated responses of the chorda tympani (CT) nerve to a large series of chemical stimuli representing sweet, salty, sour, bitter, and umami tastes in C57BL/J6 mice. We also measured neural responses to NaCl, Na-gluconate, Na-acetate, Na-sulfate, and MSG with and without 5 µM benzamil, an epithelial sodium channel (ENaC) antagonist, to assess the influence of temperature on ENaC-dependent and ENaC-independent response components. Our results showed that for most stimuli (0.5M sucrose, glucose, fructose, and maltose; 0.02M saccharin and sucralose; 0.5M NaCl, Na-gluconate, Na-acetate, Na-sulfate, KCl, K-gluconate, K-acetate, and K-sulfate; 0.05M citric acid, acetic acid, and HCl; 0.1M MSG and 0.05M quinine hydrochloride: QHCl), CT response magnitudes were maximal between 35 °C and 39 °C and progressively smaller at cooler or warmer temperatures. In contrast, the weakest responses to NH4Cl, (NH4)2SO4, and K-sulfate were at the lowest temperature, with response magnitude increasing monotonically with increasing temperature, while the largest responses to acetic acid were at the lowest temperature, with response magnitude decreasing with increasing temperature. The response to sweet and umami stimuli across temperatures were similar reflecting the involvement of TRPM5 activity, in contrast to bitter stimuli, which were weakly affected by temperature. Temperature-modulated responses to salts and acids most likely operate through mechanisms independent of ENaC and TRPM5. PMID:27497433

Sodium glucose transporter 2 (SGLT2) inhibition with empagliflozin improves cardiac diastolic function in a female rodent model of diabetes.

PubMed

Habibi, Javad; Aroor, Annayya R; Sowers, James R; Jia, Guanghong; Hayden, Melvin R; Garro, Mona; Barron, Brady; Mayoux, Eric; Rector, R Scott; Whaley-Connell, Adam; DeMarco, Vincent G

2017-01-13

Obese and diabetic individuals are at increased risk for impairments in diastolic relaxation and heart failure with preserved ejection fraction. The impairments in diastolic relaxation are especially pronounced in obese and diabetic women and predict future cardiovascular disease (CVD) events in this population. Recent clinical data suggest sodium glucose transporter-2 (SGLT2) inhibition reduces CVD events in diabetic individuals, but the mechanisms of this CVD protection are unknown. To determine whether targeting SGLT2 improves diastolic relaxation, we utilized empagliflozin (EMPA) in female db/db mice. Eleven week old female db/db mice were fed normal mouse chow, with or without EMPA, for 5 weeks. Blood pressure (BP), HbA1c and fasting glucose were significantly increased in untreated db/db mice (DbC) (P < 0.01). EMPA treatment (DbE) improved glycemic indices (P < 0.05), but not BP (P > 0.05). At baseline, DbC and DbE had already established impaired diastolic relaxation as indicated by impaired septal wall motion (>tissue Doppler derived E'/A' ratio) and increased left ventricular (LV) filling pressure (

Open Markov Processes and Reaction Networks

ERIC Educational Resources Information Center

Swistock Pollard, Blake Stephen

2017-01-01

We begin by defining the concept of "open" Markov processes, which are continuous-time Markov chains where probability can flow in and out through certain "boundary" states. We study open Markov processes which in the absence of such boundary flows admit equilibrium states satisfying detailed balance, meaning that the net flow…

Computing under-ice discharge: A proof-of-concept using hydroacoustics and the Probability Concept

NASA Astrophysics Data System (ADS)

Fulton, John W.; Henneberg, Mark F.; Mills, Taylor J.; Kohn, Michael S.; Epstein, Brian; Hittle, Elizabeth A.; Damschen, William C.; Laveau, Christopher D.; Lambrecht, Jason M.; Farmer, William H.

2018-07-01

Under-ice discharge is estimated using open-water reference hydrographs; however, the ratings for ice-affected sites are generally qualified as poor. The U.S. Geological Survey (USGS), in collaboration with the Colorado Water Conservation Board, conducted a proof-of-concept to develop an alternative method for computing under-ice discharge using hydroacoustics and the Probability Concept. The study site was located south of Minturn, Colorado (CO), USA, and was selected because of (1) its proximity to the existing USGS streamgage 09064600 Eagle River near Minturn, CO, and (2) its ease-of-access to verify discharge using a variety of conventional methods. From late September 2014 to early March 2015, hydraulic conditions varied from open water to under ice. These temporal changes led to variations in water depth and velocity. Hydroacoustics (tethered and uplooking acoustic Doppler current profilers and acoustic Doppler velocimeters) were deployed to measure the vertical-velocity profile at a singularly important vertical of the channel-cross section. Because the velocity profile was non-standard and cannot be characterized using a Power Law or Log Law, velocity data were analyzed using the Probability Concept, which is a probabilistic formulation of the velocity distribution. The Probability Concept-derived discharge was compared to conventional methods including stage-discharge and index-velocity ratings and concurrent field measurements; each is complicated by the dynamics of ice formation, pressure influences on stage measurements, and variations in cross-sectional area due to ice formation. No particular discharge method was assigned as truth. Rather one statistical metric (Kolmogorov-Smirnov; KS), agreement plots, and concurrent measurements provided a measure of comparability between various methods. Regardless of the method employed, comparisons between each method revealed encouraging results depending on the flow conditions and the absence or presence of ice cover. For example, during lower discharges dominated by under-ice and transition (intermittent open-water and under-ice) conditions, the KS metric suggests there is not sufficient information to reject the null hypothesis and implies that the Probability Concept and index-velocity rating represent similar distributions. During high-flow, open-water conditions, the comparisons are less definitive; therefore, it is important that the appropriate analytical method and instrumentation be selected. Six conventional discharge measurements were collected concurrently with Probability Concept-derived discharges with percent differences (%) of -9.0%, -21%, -8.6%, 17.8%, 3.6%, and -2.3%. This proof-of-concept demonstrates that riverine discharges can be computed using the Probability Concept for a range of hydraulic extremes (variations in discharge, open-water and under-ice conditions) immediately after the siting phase is complete, which typically requires one day. Computing real-time discharges is particularly important at sites, where (1) new streamgages are planned, (2) river hydraulics are complex, and (3) shifts in the stage-discharge rating are needed to correct the streamflow record. Use of the Probability Concept does not preclude the need to maintain a stage-area relation. Both the Probability Concept and index-velocity rating offer water-resource managers and decision makers alternatives for computing real-time discharge for open-water and under-ice conditions.

Computing under-ice discharge: A proof-of-concept using hydroacoustics and the Probability Concept

USGS Publications Warehouse

Fulton, John W.; Henneberg, Mark F.; Mills, Taylor J.; Kohn, Michael S.; Epstein, Brian; Hittle, Elizabeth A.; Damschen, William C.; Laveau, Christopher D.; Lambrecht, Jason M.; Farmer, William H.

2018-01-01

Under-ice discharge is estimated using open-water reference hydrographs; however, the ratings for ice-affected sites are generally qualified as poor. The U.S. Geological Survey (USGS), in collaboration with the Colorado Water Conservation Board, conducted a proof-of-concept to develop an alternative method for computing under-ice discharge using hydroacoustics and the Probability Concept.The study site was located south of Minturn, Colorado (CO), USA, and was selected because of (1) its proximity to the existing USGS streamgage 09064600 Eagle River near Minturn, CO, and (2) its ease-of-access to verify discharge using a variety of conventional methods. From late September 2014 to early March 2015, hydraulic conditions varied from open water to under ice. These temporal changes led to variations in water depth and velocity. Hydroacoustics (tethered and uplooking acoustic Doppler current profilers and acoustic Doppler velocimeters) were deployed to measure the vertical-velocity profile at a singularly important vertical of the channel-cross section. Because the velocity profile was non-standard and cannot be characterized using a Power Law or Log Law, velocity data were analyzed using the Probability Concept, which is a probabilistic formulation of the velocity distribution. The Probability Concept-derived discharge was compared to conventional methods including stage-discharge and index-velocity ratings and concurrent field measurements; each is complicated by the dynamics of ice formation, pressure influences on stage measurements, and variations in cross-sectional area due to ice formation.No particular discharge method was assigned as truth. Rather one statistical metric (Kolmogorov-Smirnov; KS), agreement plots, and concurrent measurements provided a measure of comparability between various methods. Regardless of the method employed, comparisons between each method revealed encouraging results depending on the flow conditions and the absence or presence of ice cover.For example, during lower discharges dominated by under-ice and transition (intermittent open-water and under-ice) conditions, the KS metric suggests there is not sufficient information to reject the null hypothesis and implies that the Probability Concept and index-velocity rating represent similar distributions. During high-flow, open-water conditions, the comparisons are less definitive; therefore, it is important that the appropriate analytical method and instrumentation be selected. Six conventional discharge measurements were collected concurrently with Probability Concept-derived discharges with percent differences (%) of −9.0%, −21%, −8.6%, 17.8%, 3.6%, and −2.3%.This proof-of-concept demonstrates that riverine discharges can be computed using the Probability Concept for a range of hydraulic extremes (variations in discharge, open-water and under-ice conditions) immediately after the siting phase is complete, which typically requires one day. Computing real-time discharges is particularly important at sites, where (1) new streamgages are planned, (2) river hydraulics are complex, and (3) shifts in the stage-discharge rating are needed to correct the streamflow record. Use of the Probability Concept does not preclude the need to maintain a stage-area relation. Both the Probability Concept and index-velocity rating offer water-resource managers and decision makers alternatives for computing real-time discharge for open-water and under-ice conditions.

Single-Pixel Optical Fluctuation Analysis of Calcium Channel Function in Active Zones of Motor Nerve Terminals

PubMed Central

Luo, Fujun; Dittrich, Markus; Stiles, Joel R.; Meriney, Stephen D.

2011-01-01

We used high-resolution fluorescence imaging and single-pixel optical fluctuation analysis to estimate the opening probability of individual voltage-gated calcium (Ca2+) channels during an action potential and the number of such Ca2+ channels within active zones of frog neuromuscular junctions. Analysis revealed ~36 Ca2+ channels within each active zone, similar to the number of docked synaptic vesicles but far less than the total number of transmembrane particles reported based on freeze-fracture analysis (~200–250). The probability that each channel opened during an action potential was only ~0.2. These results suggest why each active zone averages only one quantal release event during every other action potential, despite a substantial number of docked vesicles. With sparse Ca2+ channels and low opening probability, triggering of fusion for each vesicle is primarily controlled by Ca2+ influx through individual Ca2+ channels. In contrast, the entire synapse is highly reliable because it contains hundreds of active zones. PMID:21813687

Lithium: a versatile tool for understanding renal physiology

PubMed Central

Ecelbarger, Carolyn M.

2013-01-01

By virtue of its unique interactions with kidney cells, lithium became an important research tool in renal physiology and pathophysiology. Investigators have uncovered the intricate relationships of lithium with the vasopressin and aldosterone systems, and the membrane channels or transporters regulated by them. While doing so, their work has also led to 1) questioning the role of adenylyl cyclase activity and prostaglandins in lithium-induced suppression of aquaporin-2 gene transcription; 2) unraveling the role of purinergic signaling in lithium-induced polyuria; and 3) highlighting the importance of the epithelial sodium channel (ENaC) in lithium-induced nephrogenic diabetes insipidus (NDI). Lithium-induced remodeling of the collecting duct has the potential to shed new light on collecting duct remodeling in disease conditions, such as diabetes insipidus. The finding that lithium inhibits glycogen synthase kinase-3β (GSK3β) has opened an avenue for studies on the role of GSK3β in urinary concentration, and GSK isoforms in renal development. Finally, proteomic and metabolomic profiling of the kidney and urine in rats treated with lithium is providing insights into how the kidney adapts its metabolism in conditions such as acquired NDI and the multifactorial nature of lithium-induced NDI. This review provides state-of-the-art knowledge of lithium as a versatile tool for understanding the molecular physiology of the kidney, and a comprehensive view of how this tool is challenging some of our long-standing concepts in renal physiology, often with paradigm shifts, and presenting paradoxical situations in renal pathophysiology. In addition, this review points to future directions in research where lithium can lead the renal community. PMID:23408166

Dropout rates in medical students at one school before and after the installation of admission tests in Austria.

PubMed

Reibnegger, Gilbert; Caluba, Hans-Christian; Ithaler, Daniel; Manhal, Simone; Neges, Heide Maria; Smolle, Josef

2011-08-01

Admission to medical studies in Austria since academic year 2005-2006 has been regulated by admission tests. At the Medical University of Graz, an admission test focusing on secondary-school-level knowledge in natural sciences has been used for this purpose. The impact of this important change on dropout rates of female versus male students and older versus younger students is reported. All 2,860 students admitted to the human medicine diploma program at the Medical University of Graz from academic years 2002-2003 to 2008-2009 were included. Nonparametric and semiparametric survival analysis techniques were employed to compare cumulative probability of dropout between demographic groups. Cumulative probability of dropout was significantly reduced in students selected by active admission procedure versus those admitted openly (P < .0001). Relative hazard ratio of selected versus openly admitted students was only 0.145 (95% CI, 0.106-0.198). Among openly admitted students, but not for selected ones, the cumulative probabilities for dropout were higher for females (P < .0001) and for older students (P < .0001). Generally, dropout hazard is highest during the second year of study. The introduction of admission testing significantly decreased the cumulative probability for dropout. In openly admitted students a significantly higher risk for dropout was found in female students and in older students, whereas no such effects can be detected after admission testing. Future research should focus on the sex dependence, with the aim of improving success rates among female applicants on the admission tests.

A compositional framework for Markov processes

NASA Astrophysics Data System (ADS)

Baez, John C.; Fong, Brendan; Pollard, Blake S.

2016-03-01

We define the concept of an "open" Markov process, or more precisely, continuous-time Markov chain, which is one where probability can flow in or out of certain states called "inputs" and "outputs." One can build up a Markov process from smaller open pieces. This process is formalized by making open Markov processes into the morphisms of a dagger compact category. We show that the behavior of a detailed balanced open Markov process is determined by a principle of minimum dissipation, closely related to Prigogine's principle of minimum entropy production. Using this fact, we set up a functor mapping open detailed balanced Markov processes to open circuits made of linear resistors. We also describe how to "black box" an open Markov process, obtaining the linear relation between input and output data that holds in any steady state, including nonequilibrium steady states with a nonzero flow of probability through the system. We prove that black boxing gives a symmetric monoidal dagger functor sending open detailed balanced Markov processes to Lagrangian relations between symplectic vector spaces. This allows us to compute the steady state behavior of an open detailed balanced Markov process from the behaviors of smaller pieces from which it is built. We relate this black box functor to a previously constructed black box functor for circuits.

A Few Meters Matter: Local Habitats Drive Reproductive Cycles in a Tropical Lizard.

PubMed

Otero, Luisa M; Huey, Raymond B; Gorman, George C

2015-09-01

Reproductive phenology often varies geographically within species, driven by environmental gradients that alter growth and reproduction. However, environments can differ between adjacent habitats at single localities. In lowland Puerto Rico, both open (sunny, warm) and forested (shady, cool) habitats may be only meters apart. The lizard Anolis cristatellus lives in both habitats: it thermoregulates carefully in the open but is a thermoconformer in the forest. To determine whether reproduction differs between habitats, we compared reproductive cycles of females in open versus forest habitats at two localities for over 2 years. Open females were more likely than forest females to be reproductive throughout the year, probably because open females were able to bask and thereby achieve warmer body temperatures. These between-habitat differences in reproduction were especially marked in cool months and are equivalent in magnitude to those between populations separated by elevation. Thus, environmental differences (even on a microlandscape scale) matter to reproduction and probably to demography.

Dynamic Equilibrium of Cardiac Troponin C's Hydrophobic Cleft and Its Modulation by Ca2+ Sensitizers and a Ca2+ Sensitivity Blunting Phosphomimic, cTnT(T204E).

PubMed

Schlecht, William; Dong, Wen-Ji

2017-10-18

Several studies have suggested that conformational dynamics are important in the regulation of thin filament activation in cardiac troponin C (cTnC); however, little direct evidence has been offered to support these claims. In this study, a dye homodimerization approach is developed and implemented that allows the determination of the dynamic equilibrium between open and closed conformations in cTnC's hydrophobic cleft. Modulation of this equilibrium by Ca 2+ , cardiac troponin I (cTnI), cardiac troponin T (cTnT), Ca 2+ -sensitizers, and a Ca 2+ -desensitizing phosphomimic of cTnT (cTnT(T204E) is characterized. Isolated cTnC contained a small open conformation population in the absence of Ca 2+ that increased significantly upon the addition of saturating levels of Ca 2+ . This suggests that the Ca 2+ -induced activation of thin filament arises from an increase in the probability of hydrophobic cleft opening. The inclusion of cTnI increased the population of open cTnC, and the inclusion of cTnT had the opposite effect. Samples containing Ca 2+ -desensitizing cTnT(T204E) showed a slight but insignificant decrease in open conformation probability compared to samples with cardiac troponin T, wild type [cTnT(wt)], while Ca 2+ sensitizer treated samples generally increased open conformation probability. These findings show that an equilibrium between the open and closed conformations of cTnC's hydrophobic cleft play a significant role in tuning the Ca 2+ sensitivity of the heart.

Probabilistic Open Set Recognition

NASA Astrophysics Data System (ADS)

Jain, Lalit Prithviraj

Real-world tasks in computer vision, pattern recognition and machine learning often touch upon the open set recognition problem: multi-class recognition with incomplete knowledge of the world and many unknown inputs. An obvious way to approach such problems is to develop a recognition system that thresholds probabilities to reject unknown classes. Traditional rejection techniques are not about the unknown; they are about the uncertain boundary and rejection around that boundary. Thus traditional techniques only represent the "known unknowns". However, a proper open set recognition algorithm is needed to reduce the risk from the "unknown unknowns". This dissertation examines this concept and finds existing probabilistic multi-class recognition approaches are ineffective for true open set recognition. We hypothesize the cause is due to weak adhoc assumptions combined with closed-world assumptions made by existing calibration techniques. Intuitively, if we could accurately model just the positive data for any known class without overfitting, we could reject the large set of unknown classes even under this assumption of incomplete class knowledge. For this, we formulate the problem as one of modeling positive training data by invoking statistical extreme value theory (EVT) near the decision boundary of positive data with respect to negative data. We provide a new algorithm called the PI-SVM for estimating the unnormalized posterior probability of class inclusion. This dissertation also introduces a new open set recognition model called Compact Abating Probability (CAP), where the probability of class membership decreases in value (abates) as points move from known data toward open space. We show that CAP models improve open set recognition for multiple algorithms. Leveraging the CAP formulation, we go on to describe the novel Weibull-calibrated SVM (W-SVM) algorithm, which combines the useful properties of statistical EVT for score calibration with one-class and binary support vector machines. Building from the success of statistical EVT based recognition methods such as PI-SVM and W-SVM on the open set problem, we present a new general supervised learning algorithm for multi-class classification and multi-class open set recognition called the Extreme Value Local Basis (EVLB). The design of this algorithm is motivated by the observation that extrema from known negative class distributions are the closest negative points to any positive sample during training, and thus should be used to define the parameters of a probabilistic decision model. In the EVLB, the kernel distribution for each positive training sample is estimated via an EVT distribution fit over the distances to the separating hyperplane between positive training sample and closest negative samples, with a subset of the overall positive training data retained to form a probabilistic decision boundary. Using this subset as a frame of reference, the probability of a sample at test time decreases as it moves away from the positive class. Possessing this property, the EVLB is well-suited to open set recognition problems where samples from unknown or novel classes are encountered at test. Our experimental evaluation shows that the EVLB provides a substantial improvement in scalability compared to standard radial basis function kernel machines, as well as P I-SVM and W-SVM, with improved accuracy in many cases. We evaluate our algorithm on open set variations of the standard visual learning benchmarks, as well as with an open subset of classes from Caltech 256 and ImageNet. Our experiments show that PI-SVM, WSVM and EVLB provide significant advances over the previous state-of-the-art solutions for the same tasks.

Open-loop frequency acquisition for suppressed-carrier biphase signals using one-pole arm filters

NASA Technical Reports Server (NTRS)

Shah, B.; Holmes, J. K.

1991-01-01

Open loop frequency acquisition performance is discussed for suppressed carrier binary phase shift keyed signals in terms of the probability of detecting the carrier frequency offset when the arms of the Costas loop detector have one pole filters. The approach, which does not require symbol timing, uses fast Fourier transforms (FFTs) to detect the carrier frequency offset. The detection probability, which depends on both the 3 dB arm filter bandwidth and the received symbol signal to noise ratio, is derived and is shown to be independent of symbol timing. It is shown that the performance of this technique is slightly better that other open loop acquisition techniques which use integrators in the arms and whose detection performance varies with symbol timing.

Open WorldCat and Its Impact on Academic Libraries

ERIC Educational Resources Information Center

El-Sherbini, Magda

2007-01-01

This paper analyzes librarians' reactions to the Open OCLC WorldCat. A detailed survey was sent to ARL libraries to explore what, if anything, the libraries are currently doing to prepare for these changes and how they plan to cope with the probability of having all their records open to the whole world. Survey findings indicate that most of the…

Sudden transition and sudden change from open spin environments

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

Hu, Zheng-Da; School of Science, Jiangnan University, Wuxi 214122; Xu, Jing-Bo, E-mail: xujb@zju.edu.cn

2014-11-15

We investigate the necessary conditions for the existence of sudden transition or sudden change phenomenon for appropriate initial states under dephasing. As illustrative examples, we study the behaviors of quantum correlation dynamics of two noninteracting qubits in independent and common open spin environments, respectively. For the independent environments case, we find that the quantum correlation dynamics is closely related to the Loschmidt echo and the dynamics exhibits a sudden transition from classical to quantum correlation decay. It is also shown that the sudden change phenomenon may occur for the common environment case and stationary quantum discord is found at themore » high temperature region of the environment. Finally, we investigate the quantum criticality of the open spin environment by exploring the probability distribution of the Loschmidt echo and the scaling transformation behavior of quantum discord, respectively. - Highlights: • Sudden transition or sudden change from open spin baths are studied. • Quantum discord is related to the Loschmidt echo in independent open spin baths. • Steady quantum discord is found in a common open spin bath. • The probability distribution of the Loschmidt echo is analyzed. • The scaling transformation behavior of quantum discord is displayed.« less

VizieR Online Data Catalog: Shape parameters for 154 Galactic open clusters (Zhai+, 2017)

NASA Astrophysics Data System (ADS)

Zhai, M.; Abt, H.; Zhao, G.; Li, C.

2017-06-01

The data used are from database WEBDA (http://www.univie.ac.at/webda/). We have found 946 open clusters with equatorial coordinates for each cluster member. Since cluster members are easily contaminated by field stars, we have only adopted stars with membership probabilities higher than 70% as cluster members. It is rarely possible to determine a cluster's shape with a small number of members, so we have only considered relatively richer clusters, which host more than 20 of the most probable member stars. After these selections, there are 154 clusters left. (1 data file).

Electron-conformational transformations govern the temperature dependence of the cardiac ryanodine receptor gating

NASA Astrophysics Data System (ADS)

Moskvin, A. S.; Iaparov, B. I.; Ryvkin, A. M.; Solovyova, O. E.; Markhasin, V. S.

2015-07-01

Temperature influences many aspects of cardiac excitation-contraction coupling, in particular, hypothermia increases the open probability ( P open) of cardiac sarcoplasmic reticulum (SR) Ca2+-release channels (ryanodine-sensitive RyR channels) rising the SR Ca2+ load in mammalian myocytes. However, to the best of our knowledge, no theoretical models are available for that effect. Traditional Markov chain models do not provide a reasonable molecular mechanistic insight on the origin of the temperature effects. Here in the paper we address a simple physically clear electron-conformational model to describe the RyR gating and argue that a synergetic effect of external thermal fluctuation forces (Gaussian-Markovian noise) and internal friction via the temperature stimulation/suppression of the open-close RyR tunneling probability can be considered as a main contributor to temperature effects on the RyR gating. Results of the computer modeling allowed us to successfully reproduce all the temperature effects observed for an isolated RyR gating in vitro under reducing the temperature: increase in P open and mean open time without any significant effect on mean closed

Excluding joint probabilities from quantum theory

NASA Astrophysics Data System (ADS)

Allahverdyan, Armen E.; Danageozian, Arshag

2018-03-01

Quantum theory does not provide a unique definition for the joint probability of two noncommuting observables, which is the next important question after the Born's probability for a single observable. Instead, various definitions were suggested, e.g., via quasiprobabilities or via hidden-variable theories. After reviewing open issues of the joint probability, we relate it to quantum imprecise probabilities, which are noncontextual and are consistent with all constraints expected from a quantum probability. We study two noncommuting observables in a two-dimensional Hilbert space and show that there is no precise joint probability that applies for any quantum state and is consistent with imprecise probabilities. This contrasts with theorems by Bell and Kochen-Specker that exclude joint probabilities for more than two noncommuting observables, in Hilbert space with dimension larger than two. If measurement contexts are included into the definition, joint probabilities are not excluded anymore, but they are still constrained by imprecise probabilities.

Cluster membership probability: polarimetric approach

NASA Astrophysics Data System (ADS)

Medhi, Biman J.; Tamura, Motohide

2013-04-01

Interstellar polarimetric data of the six open clusters Hogg 15, NGC 6611, NGC 5606, NGC 6231, NGC 5749 and NGC 6250 have been used to estimate the membership probability for the stars within them. For proper-motion member stars, the membership probability estimated using the polarimetric data is in good agreement with the proper-motion cluster membership probability. However, for proper-motion non-member stars, the membership probability estimated by the polarimetric method is in total disagreement with the proper-motion cluster membership probability. The inconsistencies in the determined memberships may be because of the fundamental differences between the two methods of determination: one is based on stellar proper motion in space and the other is based on selective extinction of the stellar output by the asymmetric aligned dust grains present in the interstellar medium. The results and analysis suggest that the scatter of the Stokes vectors q (per cent) and u (per cent) for the proper-motion member stars depends on the interstellar and intracluster differential reddening in the open cluster. It is found that this method could be used to estimate the cluster membership probability if we have additional polarimetric and photometric information for a star to identify it as a probable member/non-member of a particular cluster, such as the maximum wavelength value (λmax), the unit weight error of the fit (σ1), the dispersion in the polarimetric position angles (overline{ɛ }), reddening (E(B - V)) or the differential intracluster reddening (ΔE(B - V)). This method could also be used to estimate the membership probability of known member stars having no membership probability as well as to resolve disagreements about membership among different proper-motion surveys.

Open Quantum Random Walks on the Half-Line: The Karlin-McGregor Formula, Path Counting and Foster's Theorem

NASA Astrophysics Data System (ADS)

Jacq, Thomas S.; Lardizabal, Carlos F.

2017-11-01

In this work we consider open quantum random walks on the non-negative integers. By considering orthogonal matrix polynomials we are able to describe transition probability expressions for classes of walks via a matrix version of the Karlin-McGregor formula. We focus on absorbing boundary conditions and, for simpler classes of examples, we consider path counting and the corresponding combinatorial tools. A non-commutative version of the gambler's ruin is studied by obtaining the probability of reaching a certain fortune and the mean time to reach a fortune or ruin in terms of generating functions. In the case of the Hadamard coin, a counting technique for boundary restricted paths in a lattice is also presented. We discuss an open quantum version of Foster's Theorem for the expected return time together with applications.

Open Mess Management Career Ladder AFS 742X0 and CEM Code 74200.

DTIC Science & Technology

1980-12-01

I. OPEN MESS MANAGERS (SPC049, N=187) 11. FOOD / BEVERAGE OPERATIONS ASSISTANI MANAGERS ’LUSTER (GRP076, N=92) a. Bar and Operations Managers (GKP085...said they will or probably will reenlist. 1I. FOOD / BEVERAGE OPERATIONS ASSISTANT MANAGERS CLUSTER (GRP076).- This cluster of 9-2 reslpo nrts-(23...operation of open mess food and beverage functions. The majority of these airmen identify themselves as Assistant Managers of open mess facilities and are

Computational modeling of epithelial fluid and ion transport in the parotid duct after transfection of human aquaporin-1

PubMed Central

Chiorini, John A; Sneyd, James; Suresh, Vinod

2017-01-01

Previous studies have shown that localized delivery of the aquaporin-1 (AQP1) gene to the parotid duct can restore saliva flow in minipigs following irradiation-induced salivary hypofunction. The resulting flow rate and electrochemistry of secreted saliva contradicts current understanding of ductal fluid transport. We hypothesized that changes in expression of ion transport proteins have occurred following AQP1 transfection. We use a mathematical model of ion and fluid transport across the parotid duct epithelial cells to predict the expression profile of ion transporters that are consistent with the experimental measurements of saliva composition and secretion rates. Using a baseline set of parameters, the model reproduces the data for the irradiated, non-AQP1-transfected case. We propose three scenarios which may have occurred after transfection, which differ in the location of the AQP1 gene. The first scenario places AQP1 within nonsecretory cells, and requires that epithelial sodium channel (ENaC) expression is greatly reduced (1.3% of baseline), and ductal bicarbonate concentration is increased from 40.6 to 137.0 mM, to drive water secretion into the duct. The second scenario introduces the AQP1 gene into all ductal cells. The final scenario has AQP1 primarily in the proximal duct cells which secrete water under baseline conditions. We find the change in the remaining cells includes a 95.8% reduction in ENaC expression, enabling us to reproduce all experimental ionic concentrations within 9 mM. These findings provide a mechanistic basis for the observations and will guide the further development of gene transfer therapy for salivary hypofunction. NEW & NOTEWORTHY Following transfection of aquaporin into the parotid ducts of minipigs with salivary hypofunction, the resulting increase in salivary flow rates contradicts current understanding of ductal fluid transport. We show that the change in saliva electrochemistry and flow rate can be explained by changes in expression of ion transporters in the ductal cell membranes, using a mathematical model replicating a single parotid duct. PMID:27932503

Aldosterone sensitizes connecting tubule glomerular feedback via the aldosterone receptor GPR30

PubMed Central

Ren, YiLin; D'Ambrosio, Martin A.; Garvin, Jeffrey L.; Leung, Pablo; Kutskill, Kristopher; Wang, Hong; Peterson, Edward L.

2014-01-01

Increasing Na delivery to epithelial Na channels (ENaC) in the connecting tubule (CNT) dilates the afferent arteriole (Af-Art), a process we call connecting tubule glomerular feedback (CTGF). We hypothesize that aldosterone sensitizes CTGF via a nongenomic mechanism that stimulates CNT ENaC via the aldosterone receptor GPR30. Rabbit Af-Arts and their adherent CNTs were microdissected and simultaneously perfused. Two consecutive CTGF curves were elicited by increasing luminal NaCl in the CNT. During the control period, the concentration of NaCl that elicited a half-maximal response (EC50) was 37.0 ± 2.0 mmol/l; addition of aldosterone 10−8 mol/l to the CNT lumen caused a left-shift (decrease) in EC50 to 19.3 ± 1.3 mmol/l (P = 0.001 vs. control; n = 6). Neither the transcription inhibitor actinomycin D nor the translation inhibitor cycloheximide prevented the effect of aldosterone (control EC50 = 34.7 ± 1.9 mmol/l; aldosterone+actinomycin D EC50 = 22.6 ± 1.6 mmol/l; P < 0.001 and control EC50 = 32.4 ± 4.3 mmol/l; aldosterone+cycloheximide EC50 = 17.4 ± 3.3 mmol/l; P < 0.001). The aldosterone antagonist eplerenone prevented the sensitization of CTGF by aldosterone (control EC50 = 33.2 ± 1.7 mmol/l; aldosterone+eplerenone EC50 = 33.5 ± 1.3 mmol/l; n = 7). The GPR30 receptor blocker G-36 blocked the sensitization of CTGF by aldosterone (aldosterone EC50 = 16.5 ± 1.9 mmol/l; aldosterone+G-36 EC50 = 29.0 ± 2.1 mmol/l; n = 7; P < 0.001). Finally, we found that the sensitization of CTGF by aldosterone was mediated, at least in part, by the sodium/hydrogen exchanger (NHE). We conclude that aldosterone in the CNT lumen sensitizes CTGF via a nongenomic effect involving GPR30 receptors and NHE. Sensitized CTGF induced by aldosterone may contribute to renal damage by increasing Af-Art dilation and glomerular capillary pressure (glomerular barotrauma). PMID:24966088

Computational modeling of epithelial fluid and ion transport in the parotid duct after transfection of human aquaporin-1.

PubMed

Fong, Shelley; Chiorini, John A; Sneyd, James; Suresh, Vinod

2017-02-01

Previous studies have shown that localized delivery of the aquaporin-1 (AQP1) gene to the parotid duct can restore saliva flow in minipigs following irradiation-induced salivary hypofunction. The resulting flow rate and electrochemistry of secreted saliva contradicts current understanding of ductal fluid transport. We hypothesized that changes in expression of ion transport proteins have occurred following AQP1 transfection. We use a mathematical model of ion and fluid transport across the parotid duct epithelial cells to predict the expression profile of ion transporters that are consistent with the experimental measurements of saliva composition and secretion rates. Using a baseline set of parameters, the model reproduces the data for the irradiated, non-AQP1-transfected case. We propose three scenarios which may have occurred after transfection, which differ in the location of the AQP1 gene. The first scenario places AQP1 within nonsecretory cells, and requires that epithelial sodium channel (ENaC) expression is greatly reduced (1.3% of baseline), and ductal bicarbonate concentration is increased from 40.6 to 137.0 mM, to drive water secretion into the duct. The second scenario introduces the AQP1 gene into all ductal cells. The final scenario has AQP1 primarily in the proximal duct cells which secrete water under baseline conditions. We find the change in the remaining cells includes a 95.8% reduction in ENaC expression, enabling us to reproduce all experimental ionic concentrations within 9 mM. These findings provide a mechanistic basis for the observations and will guide the further development of gene transfer therapy for salivary hypofunction. Following transfection of aquaporin into the parotid ducts of minipigs with salivary hypofunction, the resulting increase in salivary flow rates contradicts current understanding of ductal fluid transport. We show that the change in saliva electrochemistry and flow rate can be explained by changes in expression of ion transporters in the ductal cell membranes, using a mathematical model replicating a single parotid duct. Copyright © 2017 the American Physiological Society.

Synergistic interplay of Gβγ and phosphatidylinositol 4,5-bisphosphate dictates Kv7.4 channel activity.

PubMed

Povstyan, Oleksandr V; Barrese, Vincenzo; Stott, Jennifer B; Greenwood, Iain A

2017-02-01

Kv7.4 channels are key determinants of arterial contractility and cochlear mechanosensation that, like all Kv7 channels, have an obligatory requirement for phosphatidylinositol 4,5-bisphosphate (PIP 2 ). βγ G proteins (Gβγ) have been identified as novel positive regulators of Kv7.4. The present study ascertained whether Gβγ increased Kv7.4 open probability through an increased sensitivity to PIP 2 . In HEK cells stably expressing Kv7.4, PIP 2 or Gβγ increased open probability in a concentration dependent manner. Depleting PIP 2 prevented any Gβγ-mediated stimulation whilst an array of Gβγ inhibitors prohibited any PIP 2 -induced current enhancement. A combination of PIP 2 and Gβγ at sub-efficacious concentrations increased channel open probability considerably. The stimulatory effects of three Kv7.2-7.5 channel activators were also lost by PIP 2 depletion or Gβγ inhibitors. This study alters substantially our understanding of the fundamental processes that dictate Kv7.4 activity, revealing a more complex and subtle paradigm where the reliance on local phosphoinositide is dictated by interaction with Gβγ.

Fluctuation relation for heat exchange in Markovian open quantum systems

NASA Astrophysics Data System (ADS)

Ramezani, M.; Golshani, M.; Rezakhani, A. T.

2018-04-01

A fluctuation relation for the heat exchange of an open quantum system under a thermalizing Markovian dynamics is derived. We show that the probability that the system absorbs an amount of heat from its bath, at a given time interval, divided by the probability of the reverse process (releasing the same amount of heat to the bath) is given by an exponential factor which depends on the amount of heat and the difference between the temperatures of the system and the bath. Interestingly, this relation is akin to the standard form of the fluctuation relation (for forward-backward dynamics). We also argue that the probability of the violation of the second law of thermodynamics in the form of the Clausius statement (i.e., net heat transfer from a cold system to its hot bath) drops exponentially with both the amount of heat and the temperature differences of the baths.

Fluctuation relation for heat exchange in Markovian open quantum systems.

PubMed

Ramezani, M; Golshani, M; Rezakhani, A T

2018-04-01

A fluctuation relation for the heat exchange of an open quantum system under a thermalizing Markovian dynamics is derived. We show that the probability that the system absorbs an amount of heat from its bath, at a given time interval, divided by the probability of the reverse process (releasing the same amount of heat to the bath) is given by an exponential factor which depends on the amount of heat and the difference between the temperatures of the system and the bath. Interestingly, this relation is akin to the standard form of the fluctuation relation (for forward-backward dynamics). We also argue that the probability of the violation of the second law of thermodynamics in the form of the Clausius statement (i.e., net heat transfer from a cold system to its hot bath) drops exponentially with both the amount of heat and the temperature differences of the baths.

Determining open cluster membership. A Bayesian framework for quantitative member classification

NASA Astrophysics Data System (ADS)

Stott, Jonathan J.

2018-01-01

Aims: My goal is to develop a quantitative algorithm for assessing open cluster membership probabilities. The algorithm is designed to work with single-epoch observations. In its simplest form, only one set of program images and one set of reference images are required. Methods: The algorithm is based on a two-stage joint astrometric and photometric assessment of cluster membership probabilities. The probabilities were computed within a Bayesian framework using any available prior information. Where possible, the algorithm emphasizes simplicity over mathematical sophistication. Results: The algorithm was implemented and tested against three observational fields using published survey data. M 67 and NGC 654 were selected as cluster examples while a third, cluster-free, field was used for the final test data set. The algorithm shows good quantitative agreement with the existing surveys and has a false-positive rate significantly lower than the astrometric or photometric methods used individually.

Understanding the Thermodynamics of Biological Order

ERIC Educational Resources Information Center

Peterson, Jacob

2012-01-01

By growth in size and complexity (i.e., changing from more probable to less probable states), plants and animals appear to defy the second law of thermodynamics. The usual explanation describes the input of nutrient and sunlight energy into open thermodynamic systems. However, energy input alone does not address the ability to organize and create…

Resonances in the cumulative reaction probability for a model electronically nonadiabatic reaction

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

Qi, J.; Bowman, J.M.

1996-05-01

The cumulative reaction probability, flux{endash}flux correlation function, and rate constant are calculated for a model, two-state, electronically nonadiabatic reaction, given by Shin and Light [S. Shin and J. C. Light, J. Chem. Phys. {bold 101}, 2836 (1994)]. We apply straightforward generalizations of the flux matrix/absorbing boundary condition approach of Miller and co-workers to obtain these quantities. The upper adiabatic electronic potential supports bound states, and these manifest themselves as {open_quote}{open_quote}recrossing{close_quote}{close_quote} resonances in the cumulative reaction probability, at total energies above the barrier to reaction on the lower adiabatic potential. At energies below the barrier, the cumulative reaction probability for themore » coupled system is shifted to higher energies relative to the one obtained for the ground state potential. This is due to the effect of an additional effective barrier caused by the nuclear kinetic operator acting on the ground state, adiabatic electronic wave function, as discussed earlier by Shin and Light. Calculations are reported for five sets of electronically nonadiabatic coupling parameters. {copyright} {ital 1996 American Institute of Physics.}« less

Redescription of Spirodentalium Walcott ( Gastropoda: Late Cambrian) from Wisconsin ( USA).

USGS Publications Warehouse

Yochelson, E.L.

1987-01-01

Spirodentalium Walcott, 1890, was originally described as a scaphopod. A reinterpretation of the type lot suggests that its overall shape is that of an open-coiled gastropod. If so, this is probably the earliest known open-coiled form and it is sinistral in coiling direction. -Author

College Students' Openness toward Autism Spectrum Disorders: Improving Peer Acceptance

ERIC Educational Resources Information Center

Nevill, Rose E. A.; White, Susan W.

2011-01-01

One probable consequence of rising rates of autism spectrum disorder diagnosis in individuals without co-occurring intellectual disability is that more young adults with diagnoses or traits of ASD will attend college and require appropriate supports. This study sought to explore college students' openness to peers who demonstrate…

Alternative probability theories for cognitive psychology.

PubMed

Narens, Louis

2014-01-01

Various proposals for generalizing event spaces for probability functions have been put forth in the mathematical, scientific, and philosophic literatures. In cognitive psychology such generalizations are used for explaining puzzling results in decision theory and for modeling the influence of context effects. This commentary discusses proposals for generalizing probability theory to event spaces that are not necessarily boolean algebras. Two prominent examples are quantum probability theory, which is based on the set of closed subspaces of a Hilbert space, and topological probability theory, which is based on the set of open sets of a topology. Both have been applied to a variety of cognitive situations. This commentary focuses on how event space properties can influence probability concepts and impact cognitive modeling. Copyright © 2013 Cognitive Science Society, Inc.

Cardiac sodium channel Markov model with temperature dependence and recovery from inactivation.

PubMed Central

Irvine, L A; Jafri, M S; Winslow, R L

1999-01-01

A Markov model of the cardiac sodium channel is presented. The model is similar to the CA1 hippocampal neuron sodium channel model developed by Kuo and Bean (1994. Neuron. 12:819-829) with the following modifications: 1) an additional open state is added; 2) open-inactivated transitions are made voltage-dependent; and 3) channel rate constants are exponential functions of enthalpy, entropy, and voltage and have explicit temperature dependence. Model parameters are determined using a simulated annealing algorithm to minimize the error between model responses and various experimental data sets. The model reproduces a wide range of experimental data including ionic currents, gating currents, tail currents, steady-state inactivation, recovery from inactivation, and open time distributions over a temperature range of 10 degrees C to 25 degrees C. The model also predicts measures of single channel activity such as first latency, probability of a null sweep, and probability of reopening. PMID:10096885

The probability of quantal secretion near a single calcium channel of an active zone.

PubMed Central

Bennett, M R; Farnell, L; Gibson, W G

2000-01-01

A Monte Carlo analysis has been made of calcium dynamics and quantal secretion at microdomains in which the calcium reaches very high concentrations over distances of <50 nm from a channel and for which calcium dynamics are dominated by diffusion. The kinetics of calcium ions in microdomains due to either the spontaneous or evoked opening of a calcium channel, both of which are stochastic events, are described in the presence of endogenous fixed and mobile buffers. Fluctuations in the number of calcium ions within 50 nm of a channel are considerable, with the standard deviation about half the mean. Within 10 nm of a channel these numbers of ions can give rise to calcium concentrations of the order of 100 microM. The temporal changes in free calcium and calcium bound to different affinity indicators in the volume of an entire varicosity or bouton following the opening of a single channel are also determined. A Monte Carlo analysis is also presented of how the dynamics of calcium ions at active zones, after the arrival of an action potential and the stochastic opening of a calcium channel, determine the probability of exocytosis from docked vesicles near the channel. The synaptic vesicles in active zones are found docked in a complex with their calcium-sensor associated proteins and a voltage-sensitive calcium channel, forming a secretory unit. The probability of quantal secretion from an isolated secretory unit has been determined for different distances of an open calcium channel from the calcium sensor within an individual unit: a threefold decrease in the probability of secretion of a quantum occurs with a doubling of the distance from 25 to 50 nm. The Monte Carlo analysis also shows that the probability of secretion of a quantum is most sensitive to the size of the single-channel current compared with its sensitivity to either the binding rates of the sites on the calcium-sensor protein or to the number of these sites that must bind a calcium ion to trigger exocytosis of a vesicle. PMID:10777721

Ensemble modeling of stochastic unsteady open-channel flow in terms of its time-space evolutionary probability distribution - Part 2: numerical application

NASA Astrophysics Data System (ADS)

Dib, Alain; Kavvas, M. Levent

2018-03-01

The characteristic form of the Saint-Venant equations is solved in a stochastic setting by using a newly proposed Fokker-Planck Equation (FPE) methodology. This methodology computes the ensemble behavior and variability of the unsteady flow in open channels by directly solving for the flow variables' time-space evolutionary probability distribution. The new methodology is tested on a stochastic unsteady open-channel flow problem, with an uncertainty arising from the channel's roughness coefficient. The computed statistical descriptions of the flow variables are compared to the results obtained through Monte Carlo (MC) simulations in order to evaluate the performance of the FPE methodology. The comparisons show that the proposed methodology can adequately predict the results of the considered stochastic flow problem, including the ensemble averages, variances, and probability density functions in time and space. Unlike the large number of simulations performed by the MC approach, only one simulation is required by the FPE methodology. Moreover, the total computational time of the FPE methodology is smaller than that of the MC approach, which could prove to be a particularly crucial advantage in systems with a large number of uncertain parameters. As such, the results obtained in this study indicate that the proposed FPE methodology is a powerful and time-efficient approach for predicting the ensemble average and variance behavior, in both space and time, for an open-channel flow process under an uncertain roughness coefficient.

Open star clusters in the Milky Way. Comparison of photometric and trigonometric distance scales based on Gaia TGAS data

NASA Astrophysics Data System (ADS)

Kovaleva, Dana A.; Piskunov, Anatoly E.; Kharchenko, Nina V.; Röser, Siegfried; Schilbach, Elena; Scholz, Ralf-Dieter; Reffert, Sabine; Yen, Steffi X.

2017-10-01

Context. The global survey of star clusters in the Milky Way (MWSC) is a comprehensive list of 3061 objects that provides, among other parameters, distances to clusters based on isochrone fitting. The Tycho-Gaia Astrometric Solution (TGAS) catalogue, which is a part of Gaia data release 1 (Gaia DR1), delivers accurate trigonometric parallax measurements for more than 2 million stars, including those in star clusters. Aims: We compare the open cluster photometric distance scale with the measurements given by the trigonometric parallaxes from TGAS to evaluate the consistency between these values. Methods: The average parallaxes of probable cluster members available in TGAS provide the trigonometric distance scale of open clusters, while the photometric scale is given by the distances published in the MWSC. Sixty-four clusters are suited for comparison as they have more than 16 probable members with parallax measurements in TGAS. We computed the average parallaxes of the probable members and compared these to the photometric parallaxes derived within the MWSC. Results: We find a good agreement between the trigonometric TGAS-based and the photometric MWSC-based distance scales of open clusters, which for distances less than 2.3 kpc coincide at a level of about 0.1 mas with no dependence on the distance. If at all, there is a slight systematic offset along the Galactic equator between 30° and 160° galactic longitude.

Voting for a personality: Do first impressions and self-evaluations affect voting decisions?

PubMed

Koppensteiner, Markus; Stephan, Pia

2014-08-01

Participants were asked to assess their own personality (i.e. Big Five scales), the personality of politicians shown in brief silent video clips, and the probability that they would vote for these politicians. Response surface analyses (RSA) revealed noteworthy effects of self-ratings and observer-ratings of openness, agreeableness, and emotional stability on voting probability. Furthermore, the participants perceived themselves as being more open, more agreeable, more emotionally stable, and more extraverted than the average politician. The study supports previous findings that first impressions affect decision making on important issues. Results also indicate that when only nonverbal information is available people prefer political candidates they perceive as having personality traits they value in themselves.

BOOK REVIEW: OPENING SCIENCE, THE EVOLVING GUIDE ...

EPA Pesticide Factsheets

The way we get our funding, collaborate, do our research, and get the word out has evolved over hundreds of years but we can imagine a more open science world, largely facilitated by the internet. The movement towards this more open way of doing and presenting science is coming, and it is not taking hundreds of years. If you are interested in these trends, and would like to find out more about where this is all headed and what it means to you, consider downloding Opening Science, edited by Sönke Bartling and Sascha Friesike, subtitled The Evolving Guide on How the Internet is Changing Research, Collaboration, and Scholarly Publishing. In 26 chapters by various authors from a range of disciplines the book explores the developing world of open science, starting from the first scientific revolution and bringing us to the next scientific revolution, sometimes referred to as “Science 2.0”. Some of the articles deal with the impact of the changing landscape of how science is done, looking at the impact of open science on Academia, or journal publishing, or medical research. Many of the articles look at the uses, pitfalls, and impact of specific tools, like microblogging (think Twitter), social networking, and reference management. There is lots of discussion and definition of terms you might use or misuse like “altmetrics” and “impact factor”. Science will probably never be completely open, and Twitter will probably never replace the journal article,

Insulin activates single amiloride-blockable Na channels in a distal nephron cell line (A6).

PubMed

Marunaka, Y; Hagiwara, N; Tohda, H

1992-09-01

Using the patch-clamp technique, we studied the effect of insulin on an amiloride-blockable Na channel in the apical membrane of a distal nephron cell line (A6) cultured on permeable collagen films for 10-14 days. NPo (N, number of channels per patch membrane; Po, average value of open probability of individual channels in the patch) under baseline conditions was 0.88 +/- 0.12 (SE)(n = 17). After making cell-attached patches on the apical membrane which contained Na channels, insulin (1 mU/ml) was applied to the serosal bath. While maintaining the cell-attached patch, NPo significantly increased to 1.48 +/- 0.19 (n = 17; P less than 0.001) after 5-10 min of insulin application. The open probability of Na channels was 0.39 +/- 0.01 (n = 38) under baseline condition, and increased to 0.66 +/- 0.03 (n = 38, P less than 0.001) after addition of insulin. The baseline single-channel conductance was 4pS, and neither the single-channel conductance nor the current-voltage relationship was significantly changed by insulin. These results indicate that insulin increases Na absorption in the distal nephron by increasing the open probability of the amiloride-blockable Na channel.

Developing a Model and Applications for Probabilities of Student Success: A Case Study of Predictive Analytics

ERIC Educational Resources Information Center

Calvert, Carol Elaine

2014-01-01

This case study relates to distance learning students on open access courses. It demonstrates the use of predictive analytics to generate a model of the probabilities of success and retention at different points, or milestones, in a student journey. A core set of explanatory variables has been established and their varying relative importance at…

Gravity and decoherence: the double slit experiment revisited

NASA Astrophysics Data System (ADS)

Samuel, Joseph

2018-02-01

The double slit experiment is iconic and widely used in classrooms to demonstrate the fundamental mystery of quantum physics. The puzzling feature is that the probability of an electron arriving at the detector when both slits are open is not the sum of the probabilities when the slits are open separately. The superposition principle of quantum mechanics tells us to add amplitudes rather than probabilities and this results in interference. This experiment defies our classical intuition that the probabilities of exclusive events add. In understanding the emergence of the classical world from the quantum one, there have been suggestions by Feynman, Diosi and Penrose that gravity is responsible for suppressing interference. This idea has been pursued in many different forms ever since, predominantly within Newtonian approaches to gravity. In this paper, we propose and theoretically analyse two ‘gedanken’ or thought experiments which lend strong support to the idea that gravity is responsible for decoherence. The first makes the point that thermal radiation can suppress interference. The second shows that in an accelerating frame, Unruh radiation does the same. Invoking the Einstein equivalence principle to relate acceleration to gravity, we support the view that gravity is responsible for decoherence.

Answer to Question {number_sign}21 [{open_quote}{open_quote}Snell{close_quote}s law in quantum mechanics,{close_quote}{close_quote} Steve Blau and Brad Halfpap, Am. J. Phys. {bold 63} (7), 583 (1995)

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

Milonni, P.W.

1996-07-01

The quantum mechanical description of reflection and refraction in terms of photons is further extrapolated. The probability amplitude for a photon to be found inside or outside the medium is derived.

Late quaternary environments, Denali National Park and Preserve, Alaska

USGS Publications Warehouse

Elias, S.A.; Short, S.K.; Waythomas, C.F.

1996-01-01

Late Quaternary pollen, plant macrofossils, and insect fossils were studied from sites along three rivers in the foothills north of the Alaska Range in Denali National Park and Preserve. The aim was to carry out a reconaissance of late Quaternary organic sediments in the region, emphasizing the mid-Wisconsin, or Boutellier interstadial interval. Samples of probable early- to mid-Boutellier age (ca. 60 000 to 40 000 B.P.) from Unit 2 at the Toklat High Bluffs site indicate open boreal woodland with dense alder shrub vegetation. Organic Unit 1 at the Foraker River Slump site indicates open taiga with shrubs of probable Boutellier age. Fossil evidence from the youngest horizon in this unit indicates graminoid tundra environments, marking the transition from interstadial to late Wisconsin glacial environments. Early Holocene samples from the Foraker exposures suggest birch shrub tundra; coniferous forest apparently became established only alter 6500 B.P. Local variations in forest composition at the Foraker and Sushana sites were probably the result of disturbances, such as fire.

A novel approach to estimate the eruptive potential and probability in open conduit volcanoes

PubMed Central

De Gregorio, Sofia; Camarda, Marco

2016-01-01

In open conduit volcanoes, volatile-rich magma continuously enters into the feeding system nevertheless the eruptive activity occurs intermittently. From a practical perspective, the continuous steady input of magma in the feeding system is not able to produce eruptive events alone, but rather surplus of magma inputs are required to trigger the eruptive activity. The greater the amount of surplus of magma within the feeding system, the higher is the eruptive probability.Despite this observation, eruptive potential evaluations are commonly based on the regular magma supply, and in eruptive probability evaluations, generally any magma input has the same weight. Conversely, herein we present a novel approach based on the quantification of surplus of magma progressively intruded in the feeding system. To quantify the surplus of magma, we suggest to process temporal series of measurable parameters linked to the magma supply. We successfully performed a practical application on Mt Etna using the soil CO2 flux recorded over ten years. PMID:27456812

A novel approach to estimate the eruptive potential and probability in open conduit volcanoes.

PubMed

De Gregorio, Sofia; Camarda, Marco

2016-07-26

In open conduit volcanoes, volatile-rich magma continuously enters into the feeding system nevertheless the eruptive activity occurs intermittently. From a practical perspective, the continuous steady input of magma in the feeding system is not able to produce eruptive events alone, but rather surplus of magma inputs are required to trigger the eruptive activity. The greater the amount of surplus of magma within the feeding system, the higher is the eruptive probability.Despite this observation, eruptive potential evaluations are commonly based on the regular magma supply, and in eruptive probability evaluations, generally any magma input has the same weight. Conversely, herein we present a novel approach based on the quantification of surplus of magma progressively intruded in the feeding system. To quantify the surplus of magma, we suggest to process temporal series of measurable parameters linked to the magma supply. We successfully performed a practical application on Mt Etna using the soil CO2 flux recorded over ten years.

[OPEN FIELD BEHAVIOR AS A PREDICTIVE CRITERIA REFLECTING RATS CORTICOSTERONELEVEL BEFORE AND AFTER STRESS].

PubMed

Umriukhin, P E; Grigorchuk, O S

2015-12-01

In the presented study we investigated the possibility to use the open field behavior data for prediction of corticosterone level in rat blood plasma before and after stress. It is shown that the most reliable open field behavior parameters, reflecting high probability of significant upregulation of corticosterone after 3 hours of immobilization, are the short latency of first movement and low locomotor activity during the test. Rats with high corticosterone at normal non-stress conditions are characterized by low locomotor activity and on the contrary long latency period for the entrance of open field center.

Voting for a personality: Do first impressions and self-evaluations affect voting decisions?

PubMed Central

Koppensteiner, Markus; Stephan, Pia

2014-01-01

Participants were asked to assess their own personality (i.e. Big Five scales), the personality of politicians shown in brief silent video clips, and the probability that they would vote for these politicians. Response surface analyses (RSA) revealed noteworthy effects of self-ratings and observer-ratings of openness, agreeableness, and emotional stability on voting probability. Furthermore, the participants perceived themselves as being more open, more agreeable, more emotionally stable, and more extraverted than the average politician. The study supports previous findings that first impressions affect decision making on important issues. Results also indicate that when only nonverbal information is available people prefer political candidates they perceive as having personality traits they value in themselves. PMID:25089064

Wildlife strike risk assessment in several Italian airports: lessons from BRI and a new methodology implementation.

PubMed

Soldatini, Cecilia; Albores-Barajas, Yuri Vladimir; Lovato, Tomas; Andreon, Adriano; Torricelli, Patrizia; Montemaggiori, Alessandro; Corsa, Cosimo; Georgalas, Vyron

2011-01-01

The presence of wildlife in airport areas poses substantial hazards to aviation. Wildlife aircraft collisions (hereafter wildlife strikes) cause losses in terms of human lives and direct monetary losses for the aviation industry. In recent years, wildlife strikes have increased in parallel with air traffic increase and species habituation to anthropic areas. In this paper, we used an ecological approach to wildlife strike risk assessment to eight Italian international airports. The main achievement is a site-specific analysis that avoids flattening wildlife strike events on a large scale while maintaining comparable airport risk assessments. This second version of the Birdstrike Risk Index (BRI2) is a sensitive tool that provides different time scale results allowing appropriate management planning. The methodology applied has been developed in accordance with the Italian Civil Aviation Authority, which recognizes it as a national standard implemented in the advisory circular ENAC APT-01B.

Wildlife Strike Risk Assessment in Several Italian Airports: Lessons from BRI and a New Methodology Implementation

PubMed Central

Soldatini, Cecilia; Albores-Barajas, Yuri Vladimir; Lovato, Tomas; Andreon, Adriano; Torricelli, Patrizia; Montemaggiori, Alessandro; Corsa, Cosimo; Georgalas, Vyron

2011-01-01

The presence of wildlife in airport areas poses substantial hazards to aviation. Wildlife aircraft collisions (hereafter wildlife strikes) cause losses in terms of human lives and direct monetary losses for the aviation industry. In recent years, wildlife strikes have increased in parallel with air traffic increase and species habituation to anthropic areas. In this paper, we used an ecological approach to wildlife strike risk assessment to eight Italian international airports. The main achievement is a site-specific analysis that avoids flattening wildlife strike events on a large scale while maintaining comparable airport risk assessments. This second version of the Birdstrike Risk Index (BRI2) is a sensitive tool that provides different time scale results allowing appropriate management planning. The methodology applied has been developed in accordance with the Italian Civil Aviation Authority, which recognizes it as a national standard implemented in the advisory circular ENAC APT-01B. PMID:22194950

Comparison of Traditional and Open-Access Appointment Scheduling for Exponentially Distributed Service Time.

PubMed

Yan, Chongjun; Tang, Jiafu; Jiang, Bowen; Fung, Richard Y K

2015-01-01

This paper compares the performance measures of traditional appointment scheduling (AS) with those of an open-access appointment scheduling (OA-AS) system with exponentially distributed service time. A queueing model is formulated for the traditional AS system with no-show probability. The OA-AS models assume that all patients who call before the session begins will show up for the appointment on time. Two types of OA-AS systems are considered: with a same-session policy and with a same-or-next-session policy. Numerical results indicate that the superiority of OA-AS systems is not as obvious as those under deterministic scenarios. The same-session system has a threshold of relative waiting cost, after which the traditional system always has higher total costs, and the same-or-next-session system is always preferable, except when the no-show probability or the weight of patients' waiting is low. It is concluded that open-access policies can be viewed as alternative approaches to mitigate the negative effects of no-show patients.

Stochastic Sznajd Model in Open Community

NASA Astrophysics Data System (ADS)

Emmert-Streib, Frank

We extend the Sznajd Model for opinion formation by introducing persuasion probabilities for opinions. Moreover, we couple the system to an environment which mimics the application of the opinion. This results in a feedback, representing single-state opinion transitions in opposite to the two-state opinion transitions for persuading other people. We call this model opinion formation in an open community (OFOC). It can be seen as a stochastic extension of the Sznajd model for an open community, because it allows for a special choice of parameters to recover the original Sznajd model. We demonstrate the effect of feedback in the OFOC model by applying it to a scenario in which, e.g., opinion B is worse then opinion A but easier explained to other people. Casually formulated we analyzed the question, how much better one has to be, in order to persuade other people, provided the opinion is worse. Our results reveal a linear relation between the transition probability for opinion B and the influence of the environment on B.

Spatial and Temporal Analysis of Eruption Locations, Compositions, and Styles in Northern Harrat Rahat, Kingdom of Saudi Arabia

NASA Astrophysics Data System (ADS)

Dietterich, H. R.; Stelten, M. E.; Downs, D. T.; Champion, D. E.

2017-12-01

Harrat Rahat is a predominantly mafic, 20,000 km2 volcanic field in western Saudi Arabia with an elongate volcanic axis extending 310 km north-south. Prior mapping suggests that the youngest eruptions were concentrated in northernmost Harrat Rahat, where our new geologic mapping and geochronology reveal >300 eruptive vents with ages ranging from 1.2 Ma to a historic eruption in 1256 CE. Eruption compositions and styles vary spatially and temporally within the volcanic field, where extensive alkali basaltic lavas dominate, but more evolved compositions erupted episodically as clusters of trachytic domes and small-volume pyroclastic flows. Analysis of vent locations, compositions, and eruption styles shows the evolution of the volcanic field and allows assessment of the spatio-temporal probabilities of vent opening and eruption styles. We link individual vents and fissures to eruptions and their deposits using field relations, petrography, geochemistry, paleomagnetism, and 40Ar/39Ar and 36Cl geochronology. Eruption volumes and deposit extents are derived from geologic mapping and topographic analysis. Spatial density analysis with kernel density estimation captures vent densities of up to 0.2 %/km2 along the north-south running volcanic axis, decaying quickly away to the east but reaching a second, lower high along a secondary axis to the west. Temporal trends show slight younging of mafic eruption ages to the north in the past 300 ka, as well as clustered eruptions of trachytes over the past 150 ka. Vent locations, timing, and composition are integrated through spatial probability weighted by eruption age for each compositional range to produce spatio-temporal models of vent opening probability. These show that the next mafic eruption is most probable within the north end of the main (eastern) volcanic axis, whereas more evolved compositions are most likely to erupt within the trachytic centers further to the south. These vent opening probabilities, combined with corresponding eruption properties, can be used as the basis for lava flow and tephra fall hazard maps.

Quantifying the origins of life on a planetary scale.

PubMed

Scharf, Caleb; Cronin, Leroy

2016-07-19

A simple, heuristic formula with parallels to the Drake Equation is introduced to help focus discussion on open questions for the origins of life in a planetary context. This approach indicates a number of areas where quantitative progress can be made on parameter estimation for determining origins of life probabilities, based on constraints from Bayesian approaches. We discuss a variety of "microscale" factors and their role in determining "macroscale" abiogenesis probabilities on suitable planets. We also propose that impact ejecta exchange between planets with parallel chemistries and chemical evolution could in principle amplify the development of molecular complexity and abiogenesis probabilities. This amplification could be very significant, and both bias our conclusions about abiogenesis probabilities based on the Earth and provide a major source of variance in the probability of life arising in planetary systems. We use our heuristic formula to suggest a number of observational routes for improving constraints on origins of life probabilities.

How Inhomogeneous Site Percolation Works on Bethe Lattices: Theory and Application

NASA Astrophysics Data System (ADS)

Ren, Jingli; Zhang, Liying; Siegmund, Stefan

2016-03-01

Inhomogeneous percolation, for its closer relationship with real-life, can be more useful and reasonable than homogeneous percolation to illustrate the critical phenomena and dynamical behaviour of complex networks. However, due to its intricacy, the theoretical framework of inhomogeneous percolation is far from being complete and many challenging problems are still open. In this paper, we first investigate inhomogeneous site percolation on Bethe Lattices with two occupation probabilities, and then extend the result to percolation with m occupation probabilities. The critical behaviour of this inhomogeneous percolation is shown clearly by formulating the percolation probability with given occupation probability p, the critical occupation probability , and the average cluster size where p is subject to . Moreover, using the above theory, we discuss in detail the diffusion behaviour of an infectious disease (SARS) and present specific disease-control strategies in consideration of groups with different infection probabilities.

Quantifying the origins of life on a planetary scale

NASA Astrophysics Data System (ADS)

Scharf, Caleb; Cronin, Leroy

2016-07-01

A simple, heuristic formula with parallels to the Drake Equation is introduced to help focus discussion on open questions for the origins of life in a planetary context. This approach indicates a number of areas where quantitative progress can be made on parameter estimation for determining origins of life probabilities, based on constraints from Bayesian approaches. We discuss a variety of “microscale” factors and their role in determining “macroscale” abiogenesis probabilities on suitable planets. We also propose that impact ejecta exchange between planets with parallel chemistries and chemical evolution could in principle amplify the development of molecular complexity and abiogenesis probabilities. This amplification could be very significant, and both bias our conclusions about abiogenesis probabilities based on the Earth and provide a major source of variance in the probability of life arising in planetary systems. We use our heuristic formula to suggest a number of observational routes for improving constraints on origins of life probabilities.

De-identification Methods for Open Health Data: The Case of the Heritage Health Prize Claims Dataset

PubMed Central

Arbuckle, Luk; Koru, Gunes; Eze, Benjamin; Gaudette, Lisa; Neri, Emilio; Rose, Sean; Howard, Jeremy; Gluck, Jonathan

2012-01-01

Background There are many benefits to open datasets. However, privacy concerns have hampered the widespread creation of open health data. There is a dearth of documented methods and case studies for the creation of public-use health data. We describe a new methodology for creating a longitudinal public health dataset in the context of the Heritage Health Prize (HHP). The HHP is a global data mining competition to predict, by using claims data, the number of days patients will be hospitalized in a subsequent year. The winner will be the team or individual with the most accurate model past a threshold accuracy, and will receive a US $3 million cash prize. HHP began on April 4, 2011, and ends on April 3, 2013. Objective To de-identify the claims data used in the HHP competition and ensure that it meets the requirements in the US Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule. Methods We defined a threshold risk consistent with the HIPAA Privacy Rule Safe Harbor standard for disclosing the competition dataset. Three plausible re-identification attacks that can be executed on these data were identified. For each attack the re-identification probability was evaluated. If it was deemed too high then a new de-identification algorithm was applied to reduce the risk to an acceptable level. We performed an actual evaluation of re-identification risk using simulated attacks and matching experiments to confirm the results of the de-identification and to test sensitivity to assumptions. The main metric used to evaluate re-identification risk was the probability that a record in the HHP data can be re-identified given an attempted attack. Results An evaluation of the de-identified dataset estimated that the probability of re-identifying an individual was .0084, below the .05 probability threshold specified for the competition. The risk was robust to violations of our initial assumptions. Conclusions It was possible to ensure that the probability of re-identification for a large longitudinal dataset was acceptably low when it was released for a global user community in support of an analytics competition. This is an example of, and methodology for, achieving open data principles for longitudinal health data. PMID:22370452

An open source multivariate framework for n-tissue segmentation with evaluation on public data.

PubMed

Avants, Brian B; Tustison, Nicholas J; Wu, Jue; Cook, Philip A; Gee, James C

2011-12-01

We introduce Atropos, an ITK-based multivariate n-class open source segmentation algorithm distributed with ANTs ( http://www.picsl.upenn.edu/ANTs). The Bayesian formulation of the segmentation problem is solved using the Expectation Maximization (EM) algorithm with the modeling of the class intensities based on either parametric or non-parametric finite mixtures. Atropos is capable of incorporating spatial prior probability maps (sparse), prior label maps and/or Markov Random Field (MRF) modeling. Atropos has also been efficiently implemented to handle large quantities of possible labelings (in the experimental section, we use up to 69 classes) with a minimal memory footprint. This work describes the technical and implementation aspects of Atropos and evaluates its performance on two different ground-truth datasets. First, we use the BrainWeb dataset from Montreal Neurological Institute to evaluate three-tissue segmentation performance via (1) K-means segmentation without use of template data; (2) MRF segmentation with initialization by prior probability maps derived from a group template; (3) Prior-based segmentation with use of spatial prior probability maps derived from a group template. We also evaluate Atropos performance by using spatial priors to drive a 69-class EM segmentation problem derived from the Hammers atlas from University College London. These evaluation studies, combined with illustrative examples that exercise Atropos options, demonstrate both performance and wide applicability of this new platform-independent open source segmentation tool.

An Open Source Multivariate Framework for n-Tissue Segmentation with Evaluation on Public Data

PubMed Central

Tustison, Nicholas J.; Wu, Jue; Cook, Philip A.; Gee, James C.

2012-01-01

We introduce Atropos, an ITK-based multivariate n-class open source segmentation algorithm distributed with ANTs (http://www.picsl.upenn.edu/ANTs). The Bayesian formulation of the segmentation problem is solved using the Expectation Maximization (EM) algorithm with the modeling of the class intensities based on either parametric or non-parametric finite mixtures. Atropos is capable of incorporating spatial prior probability maps (sparse), prior label maps and/or Markov Random Field (MRF) modeling. Atropos has also been efficiently implemented to handle large quantities of possible labelings (in the experimental section, we use up to 69 classes) with a minimal memory footprint. This work describes the technical and implementation aspects of Atropos and evaluates its performance on two different ground-truth datasets. First, we use the BrainWeb dataset from Montreal Neurological Institute to evaluate three-tissue segmentation performance via (1) K-means segmentation without use of template data; (2) MRF segmentation with initialization by prior probability maps derived from a group template; (3) Prior-based segmentation with use of spatial prior probability maps derived from a group template. We also evaluate Atropos performance by using spatial priors to drive a 69-class EM segmentation problem derived from the Hammers atlas from University College London. These evaluation studies, combined with illustrative examples that exercise Atropos options, demonstrate both performance and wide applicability of this new platform-independent open source segmentation tool. PMID:21373993

Gating kinetics of batrachotoxin-modified Na+ channels in the squid giant axon. Voltage and temperature effects.

PubMed Central

Correa, A M; Bezanilla, F; Latorre, R

1992-01-01

The gating kinetics of batrachotoxin-modified Na+ channels were studied in outside-out patches of axolemma from the squid giant axon by means of the cut-open axon technique. Single channel kinetics were characterized at different membrane voltages and temperatures. The probability of channel opening (Po) as a function of voltage was well described by a Boltzmann distribution with an equivalent number of gating particles of 3.58. The voltage at which the channel was open 50% of the time was a function of [Na+] and temperature. A decrease in the internal [Na+] induced a shift to the right of the Po vs. V curve, suggesting the presence of an integral negative fixed charge near the activation gate. An increase in temperature decreased Po, indicating a stabilization of the closed configuration of the channel and also a decrease in entropy upon channel opening. Probability density analysis of dwell times in the closed and open states of the channel at 0 degrees C revealed the presence of three closed and three open states. The slowest open kinetic component constituted only a small fraction of the total number of transitions and became negligible at voltages greater than -65 mV. Adjacent interval analysis showed that there is no correlation in the duration of successive open and closed events. Consistent with this analysis, maximum likelihood estimation of the rate constants for nine different single-channel models produced a preferred model (model 1) having a linear sequence of closed states and two open states emerging from the last closed state. The effect of temperature on the rate constants of model 1 was studied. An increase in temperature increased all rate constants; the shift in Po would be the result of an increase in the closing rates predominant over the change in the opening rates. The temperature study also provided the basis for building an energy diagram for the transitions between channel states. PMID:1318096

Phenformin and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) activation of AMP-activated protein kinase inhibits transepithelial Na+ transport across H441 lung cells.

PubMed

Woollhead, Alison M; Scott, John W; Hardie, D Grahame; Baines, Deborah L

2005-08-01

Active re-absorption of Na+ across the alveolar epithelium is essential to maintain lung fluid balance. Na+ entry at the luminal membrane is predominantly via the amiloride-sensitive Na+ channel (ENaC) down its electrochemical gradient. This gradient is generated and maintained by basolateral Na+ extrusion via Na+,K+-ATPase an energy-dependent process. Several kinases and factors that activate them are known to regulate these processes; however, the role of AMP-activated protein kinase (AMPK) in the lung is unknown. AMPK is an ultra-sensitive cellular energy sensor that monitors energy consumption and down-regulates ATP-consuming processes when activated. The biguanide phenformin has been shown to independently decrease ion transport processes, influence cellular metabolism and activate AMPK. The AMP mimetic drug 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) also activates AMPK in intact cells. Western blotting revealed that both the alpha1 and alpha2 catalytic subunits of AMPK are present in Na+ transporting H441 human lung epithelial cells. Phenformin and AICAR increased AMPK activity in H441 cells in a dose-dependent fashion, stimulating the kinase maximally at 5-10 mm (P = 0.001, n = 3) and 2 mm (P < 0.005, n = 3), respectively. Both agents significantly decreased basal ion transport (measured as short circuit current) across H441 monolayers by approximately 50% compared with that of controls (P < 0.05, n = 4). Neither treatment altered the resistance of the monolayers. Phenformin and AICAR significantly reduced amiloride-sensitive transepithelial Na+ transport compared with controls (P < 0.05, n = 4). This was a result of both decreased Na+,K+-ATPase activity and amiloride-sensitive apical Na+ conductance. Transepithelial Na+ transport decreased with increasing concentrations of phenformin (0.1-10 mm) and showed a significant correlation with AMPK activity. Taken together, these results show that phenformin and AICAR suppress amiloride-sensitive Na+ transport across H441 cells via a pathway that includes activation of AMPK and inhibition of both apical Na+ entry through ENaC and basolateral Na+ extrusion via the Na+,K+-ATPase. These are the first studies to provide a cellular signalling mechanism for the action of phenformin on ion transport processes, and also the first studies showing AMPK as a regulator of Na+ absorption in the lung.

Phenformin and 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) activation of AMP-activated protein kinase inhibits transepithelial Na+ transport across H441 lung cells

PubMed Central

Woollhead, Alison M; Scott, John W; Hardie, D Grahame; Baines, Deborah L

2005-01-01

Active re-absorption of Na+ across the alveolar epithelium is essential to maintain lung fluid balance. Na+ entry at the luminal membrane is predominantly via the amiloride-sensitive Na+ channel (ENaC) down its electrochemical gradient. This gradient is generated and maintained by basolateral Na+ extrusion via Na+,K+-ATPase an energy-dependent process. Several kinases and factors that activate them are known to regulate these processes; however, the role of AMP-activated protein kinase (AMPK) in the lung is unknown. AMPK is an ultra-sensitive cellular energy sensor that monitors energy consumption and down-regulates ATP-consuming processes when activated. The biguanide phenformin has been shown to independently decrease ion transport processes, influence cellular metabolism and activate AMPK. The AMP mimetic drug 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) also activates AMPK in intact cells. Western blotting revealed that both the α1 and α2 catalytic subunits of AMPK are present in Na+ transporting H441 human lung epithelial cells. Phenformin and AICAR increased AMPK activity in H441 cells in a dose-dependent fashion, stimulating the kinase maximally at 5–10 mm (P = 0.001, n = 3) and 2 mm (P < 0.005, n = 3), respectively. Both agents significantly decreased basal ion transport (measured as short circuit current) across H441 monolayers by approximately 50% compared with that of controls (P < 0.05, n = 4). Neither treatment altered the resistance of the monolayers. Phenformin and AICAR significantly reduced amiloride-sensitive transepithelial Na+ transport compared with controls (P < 0.05, n = 4). This was a result of both decreased Na+,K+-ATPase activity and amiloride-sensitive apical Na+ conductance. Transepithelial Na+ transport decreased with increasing concentrations of phenformin (0.1–10 mm) and showed a significant correlation with AMPK activity. Taken together, these results show that phenformin and AICAR suppress amiloride-sensitive Na+ transport across H441 cells via a pathway that includes activation of AMPK and inhibition of both apical Na+ entry through ENaC and basolateral Na+ extrusion via the Na+,K+-ATPase. These are the first studies to provide a cellular signalling mechanism for the action of phenformin on ion transport processes, and also the first studies showing AMPK as a regulator of Na+ absorption in the lung. PMID:15919715

A Seakeeping Performance and Affordability Tradeoff Study for the Coast Guard Offshore Patrol Cutter

DTIC Science & Technology

2016-06-01

Index Polar Plot for Sea State 4, All Headings Are Relative to the Wave Motion and Velocity is Given in Meters per Second...40 Figure 15. Probability and Cumulative Density Functions of Annual Sea State Occurrences in the Open Ocean, North Pacific...criteria at a given sea state. Probability distribution functions are available that describe the likelihood that an operational area will experience

How to Recognize and Avoid Potential, Possible, or Probable Predatory Open-Access Publishers, Standalone, and Hijacked Journals.

PubMed

Danevska, Lenche; Spiroski, Mirko; Donev, Doncho; Pop-Jordanova, Nada; Polenakovic, Momir

2016-11-01

The Internet has enabled an easy method to search through the vast majority of publications and has improved the impact of scholarly journals. However, it can also pose threats to the quality of published articles. New publishers and journals have emerged so-called open-access potential, possible, or probable predatory publishers and journals, and so-called hijacked journals. It was our aim to increase the awareness and warn scholars, especially young researchers, how to recognize these journals and how to avoid submission of their papers to these journals. Review and critical analysis of the relevant published literature, Internet sources and personal experience, thoughts, and observations of the authors. The web blog of Jeffrey Beall, University of Colorado, was greatly consulted. Jeffrey Beall is a Denver academic librarian who regularly maintains two lists: the first one, of potential, possible, or probable predatory publishers and the second one, of potential, possible, or probable predatory standalone journals. Aspects related to this topic presented by other authors have been discussed as well. Academics should bear in mind how to differentiate between trustworthy and reliable journals and predatory ones, considering: publication ethics, peer-review process, international academic standards, indexing and abstracting, preservation in digital repositories, metrics, sustainability, etc.

Truncated Long-Range Percolation on Oriented Graphs

NASA Astrophysics Data System (ADS)

van Enter, A. C. D.; de Lima, B. N. B.; Valesin, D.

2016-07-01

We consider different problems within the general theme of long-range percolation on oriented graphs. Our aim is to settle the so-called truncation question, described as follows. We are given probabilities that certain long-range oriented bonds are open; assuming that the sum of these probabilities is infinite, we ask if the probability of percolation is positive when we truncate the graph, disallowing bonds of range above a possibly large but finite threshold. We give some conditions in which the answer is affirmative. We also translate some of our results on oriented percolation to the context of a long-range contact process.

Shannon entropy and avoided crossings in closed and open quantum billiards

NASA Astrophysics Data System (ADS)

Park, Kyu-Won; Moon, Songky; Shin, Younghoon; Kim, Jinuk; Jeong, Kabgyun; An, Kyungwon

2018-06-01

The relation between Shannon entropy and avoided crossings is investigated in dielectric microcavities. The Shannon entropy of the probability density for eigenfunctions in an open elliptic billiard as well as a closed quadrupole billiard increases as the center of the avoided crossing is approached. These results are opposite to those of atomic physics for electrons. It is found that the collective Lamb shift of the open quantum system and the symmetry breaking in the closed chaotic quantum system have equivalent effects on the Shannon entropy.

Disease-causing mutations C277R and C277Y modify gating of human ClC-1 chloride channels in myotonia congenita

PubMed Central

Weinberger, Sebastian; Wojciechowski, Daniel; Sternberg, Damien; Lehmann-Horn, Frank; Jurkat-Rott, Karin; Becher, Toni; Begemann, Birgit; Fahlke, Christoph; Fischer, Martin

2012-01-01

Myotonia congenita is a genetic condition that is caused by mutations in the muscle chloride channel gene CLCN1 and characterized by delayed muscle relaxation and muscle stiffness. We here investigate the functional consequences of two novel disease-causing missense mutations, C277R and C277Y, using heterologous expression in HEK293T cells and patch clamp recording. Both mutations reduce macroscopic anion currents in transfected cells. Since hClC-1 is a double-barrelled anion channel, this reduction in current amplitude might be caused by altered gating of individual protopores or of joint openings and closing of both protopores. We used non-stationary noise analysis and single channel recordings to separate the mutants’ effects on individual and common gating processes. We found that C277Y inverts the voltage dependence and reduces the open probabilities of protopore and common gates resulting in decreases of absolute open probabilities of homodimeric channels to values below 3%. In heterodimeric channels, C277R and C277Y also reduce open probabilities and shift the common gate activation curve towards positive potentials. Moreover, C277Y modifies pore properties of hClC-1. It reduces single protopore current amplitudes to about two-thirds of wild-type values, and inverts the anion permeability sequence to I− = NO3− > Br− > Cl−. Our findings predict a dramatic reduction of the muscle fibre resting chloride conductance and thus fully explain the disease-causing effects of mutations C277R and C277Y. Moreover, they provide additional insights into the function of C277, a residue recently implicated in common gating of ClC channels. PMID:22641783

[Lifestyle and probabilty of dementia in the elderly].

PubMed

León-Ortiz, Pablo; Ruiz-Flores, Manuel Leonardo; Ramírez-Bermúdez, Jesús; Sosa-Ortiz, Ana Luisa

2013-01-01

there is evidence of a relationship between physical and cognitive activity and the development of dementia, although this hypothesis has not been tested in Mexican population. analyze the association between an increased participation in physical and cognitive activities and the probability of having dementia, using a Mexican open population sample. we made a cross sectional survey in open Mexican population of residents in urban and rural areas of 65 of age and older; we performed cognitive assessments to identify subjects with dementia, as well as questionnaires to assess the level of participation in physical and cognitive activities. We performed a binary logistic regression analysis to establish the association between participation and the probability of having dementia. we included 2003 subjects, 180 with diagnosis of dementia. Subjects with dementia were older, had less education and higher prevalence of some chronic diseases. The low participation in cognitive activities was associated with a higher probability of developing dementia. Patients with dementia had significantly lower scores on physical activity scales. this study supports the hypothesis of a relationship between low cognitive and physical activity and the presentation of dementia.

Estimating temporary emigration and breeding proportions using capture-recapture data with Pollock's robust design

USGS Publications Warehouse

Kendall, W.L.; Nichols, J.D.; Hines, J.E.

1997-01-01

Statistical inference for capture-recapture studies of open animal populations typically relies on the assumption that all emigration from the studied population is permanent. However, there are many instances in which this assumption is unlikely to be met. We define two general models for the process of temporary emigration, completely random and Markovian. We then consider effects of these two types of temporary emigration on Jolly-Seber (Seber 1982) estimators and on estimators arising from the full-likelihood approach of Kendall et al. (1995) to robust design data. Capture-recapture data arising from Pollock's (1982) robust design provide the basis for obtaining unbiased estimates of demographic parameters in the presence of temporary emigration and for estimating the probability of temporary emigration. We present a likelihood-based approach to dealing with temporary emigration that permits estimation under different models of temporary emigration and yields tests for completely random and Markovian emigration. In addition, we use the relationship between capture probability estimates based on closed and open models under completely random temporary emigration to derive three ad hoc estimators for the probability of temporary emigration, two of which should be especially useful in situations where capture probabilities are heterogeneous among individual animals. Ad hoc and full-likelihood estimators are illustrated for small mammal capture-recapture data sets. We believe that these models and estimators will be useful for testing hypotheses about the process of temporary emigration, for estimating demographic parameters in the presence of temporary emigration, and for estimating probabilities of temporary emigration. These latter estimates are frequently of ecological interest as indicators of animal movement and, in some sampling situations, as direct estimates of breeding probabilities and proportions.

Does the probability of developing ocular trauma-related visual deficiency differ between genders?

PubMed

Blanco-Hernández, Dulce Milagros Razo; Valencia-Aguirre, Jessica Daniela; Lima-Gómez, Virgilio

2011-01-01

Ocular trauma affects males more often than females, but the impact of this condition regarding visual prognosis is unknown. We undertook this study to compare the probability of developing ocular trauma-related visual deficiency between genders, as estimated by the ocular trauma score (OTS). We designed an observational, retrospective, comparative, cross-sectional and open-label study. Female patients aged ≥6 years with ocular trauma were included and matched by age and ocular wall status with male patients at a 1:2 male/female ratio. Initial trauma features and the probability of developing visual deficiency (best corrected visual acuity <20/40) 6 months after the injury, as estimated by the OTS, were compared between genders. The proportion and 95% confidence intervals (95% CI) of visual deficiency 6 months after the injury were estimated. Ocular trauma features and the probability of developing visual deficiency were compared between genders (χ(2) and Fisher's exact test); p value <0.05 was considered significant. Included were 399 eyes (133 from females and 266 from males). Mean age of patients was 25.7 ± 14.6 years. Statistical differences existed in the proportion of zone III in closed globe trauma (p = 0.01) and types A (p = 0.04) and type B (p = 0.02) in open globe trauma. The distribution of the OTS categories was similar for both genders (category 5: p = 0.9); the probability of developing visual deficiency was 32.6% (95% CI = 24.6 to 40.5) in females and 33.2% (95% CI = 27.6 to 38.9) in males (p = 0.9). The probability of developing ocular trauma-related visual deficiency was similar for both genders. The same standard is required.

Connexin and Pannexin hemichannels are regulated by redox potential

PubMed Central

Retamal, Mauricio A.

2014-01-01

Connexins (Cxs) and Pannexins (Panxs) are two non-related protein families, having both the property to form hemichannels at the plasma membrane. There are 21 genes coding for different Cx based proteins and only 3 for Panx. Under physiological conditions, these hemichannels (Cxs and Panxs) present a low open probability, but when open, they allow the release of signaling molecules to the extracellular space. However, under pathological conditions, these hemichannels increase their open probability, inducing important lysis of metabolites, and ionic imbalance, which in turn induce the massive entry of Ca+2 to the cell. Actually, it is well recognized that Cxs and Panxs based channels play an important role in several diseases and -in many cases- this is associated with an aberrant hemichannel opening. Hemichannel opening and closing are controlled by a plethora of signaling including changes of the voltage plasma membrane, protein-protein interactions, and several posttranslational modifications, including protein cleavage, phosphorylation, glycosylation, hydroxylation and S-nitrosylation, among others. In particular, it has been recently shown that the cellular redox status modulates the opening/closing and permeability of at least Cx43, Cx46, and Panx1 hemichannels. Thus, for example, the gaseous transmitter nitric oxide (NO) can induce the S-nitrosylation of these proteins modulating in turn several of their properties. The reason is that the redox status of a cell is fundamental to set their response to the environment and also plays an important role in several pathologies. In this review, I will discuss how NO and other molecules associated with redox signaling modulate Cxs and Panx hemichannels properties. PMID:24611056

Temperature and Voltage Coupling to Channel Opening in Transient Receptor Potential Melastatin 8 (TRPM8)*♦

PubMed Central

Raddatz, Natalia; Castillo, Juan P.; Gonzalez, Carlos; Alvarez, Osvaldo; Latorre, Ramon

2014-01-01

Expressed in somatosensory neurons of the dorsal root and trigeminal ganglion, the transient receptor potential melastatin 8 (TRPM8) channel is a Ca2+-permeable cation channel activated by cold, voltage, phosphatidylinositol 4,5-bisphosphate, and menthol. Although TRPM8 channel gating has been characterized at the single channel and macroscopic current levels, there is currently no consensus regarding the extent to which temperature and voltage sensors couple to the conduction gate. In this study, we extended the range of voltages where TRPM8-induced ionic currents were measured and made careful measurements of the maximum open probability the channel can attain at different temperatures by means of fluctuation analysis. The first direct measurements of TRPM8 channel temperature-driven conformational rearrangements provided here suggest that temperature alone is able to open the channel and that the opening reaction is voltage-independent. Voltage is a partial activator of TRPM8 channels, because absolute open probability values measured with fully activated voltage sensors are less than 1, and they decrease as temperature rises. By unveiling the fast temperature-dependent deactivation process, we show that TRPM8 channel deactivation is well described by a double exponential time course. The fast and slow deactivation processes are temperature-dependent with enthalpy changes of 27.2 and 30.8 kcal mol−1. The overall Q10 for the closing reaction is about 33. A three-tiered allosteric model containing four voltage sensors and four temperature sensors can account for the complex deactivation kinetics and coupling between voltage and temperature sensor activation and channel opening. PMID:25352597

Differences in compassion fatigue, symptoms of posttraumatic stress disorder and relationship satisfaction, including sexual desire and functioning, between male and female detectives who investigate sexual offenses against children: a pilot study.

PubMed

Lane, Eric J; Lating, Jeffrey M; Lowry, Jenny L; Martino, Traci P

2010-01-01

Law enforcement detectives who work with traumatized individuals, especially children who were victims of sexual abuse or assault, are likely to experience job-related emotional distress. The purpose of this study was to examine the relations among compassion fatigue, probable PTSD symptoms, and personal relationship satisfaction, including communication and sexual satisfaction, in a sample of 47 male and female detectives. Responses to the administered questionnaires indicated a relation between compassion fatigue symptoms and probable PTSD symptoms. There also were compelling gender differences. For example, for male detectives, open communication with their spouse or significant other was negatively correlated with burnout, indicating the more open the communication, the lower the reported burnout. However for female detectives there was a negative correlation between open communication with spouse or significant other and compassion satisfaction, suggesting that more open communication was related to lower levels of satisfaction with their ability to be a professional caregiver Furthermore, although stepwise regression analysis indicated that years of service as a detective is independently associated with sexual desire, female detectives evidenced less sexual desire and more difficulty with sexual functioning than did male detectives. Implications of these preliminary findings are discussed and limitations addressed.

Voltage-dependent K+ channel gating and voltage sensor toxin sensitivity depend on the mechanical state of the lipid membrane.

PubMed

Schmidt, Daniel; MacKinnon, Roderick

2008-12-09

Voltage-dependent K(+) (Kv) channels underlie action potentials through gating conformational changes that are driven by membrane voltage. In this study of the paddle chimera Kv channel, we demonstrate that the rate of channel opening, the voltage dependence of the open probability, and the maximum achievable open probability depend on the lipid membrane environment. The activity of the voltage sensor toxin VsTx1, which interferes with voltage-dependent gating by partitioning into the membrane and binding to the channel, also depends on the membrane. Membrane environmental factors that influence channel function are divisible into two general categories: lipid compositional and mechanical state. The mechanical state can have a surprisingly large effect on the function of a voltage-dependent K(+) channel, including its pharmacological interaction with voltage sensor toxins. The dependence of VSTx1 activity on the mechanical state of the membrane leads us to hypothesize that voltage sensor toxins exert their effect by perturbing the interaction forces that exist between the channel and the membrane.

Voltage-dependent K+ channel gating and voltage sensor toxin sensitivity depend on the mechanical state of the lipid membrane

PubMed Central

Schmidt, Daniel; MacKinnon, Roderick

2008-01-01

Voltage-dependent K+ (Kv) channels underlie action potentials through gating conformational changes that are driven by membrane voltage. In this study of the paddle chimera Kv channel, we demonstrate that the rate of channel opening, the voltage dependence of the open probability, and the maximum achievable open probability depend on the lipid membrane environment. The activity of the voltage sensor toxin VsTx1, which interferes with voltage-dependent gating by partitioning into the membrane and binding to the channel, also depends on the membrane. Membrane environmental factors that influence channel function are divisible into two general categories: lipid compositional and mechanical state. The mechanical state can have a surprisingly large effect on the function of a voltage-dependent K+ channel, including its pharmacological interaction with voltage sensor toxins. The dependence of VSTx1 activity on the mechanical state of the membrane leads us to hypothesize that voltage sensor toxins exert their effect by perturbing the interaction forces that exist between the channel and the membrane. PMID:19050073

Simultaneous profiling of the Arctic Atmospheric Boundary Layer

NASA Astrophysics Data System (ADS)

Mayer, S.; Jonassen, M.; Reuder, J.

2009-09-01

The structure of the Arctic atmospheric boundary layer (AABL) and the heat and moisture fluxes between relatively warm water and cold air above non-sea-ice-covered water (such as fjords, leads and polynyas) are of great importance for the sensitive Arctic climate system (e.g. Andreas and Cash, 1999). So far, such processes are not sufficiently resolved in numerical weather prediction (NWP) and climate models (e.g. Tjernström et al., 2005). Especially for regions with complex topography as the Svalbard mountains and fjords the state and diurnal evolution of the AABL is not well known yet. Knowledge can be gained by novel and flexible measurement techniques such as the use of an unmanned aerial vehicle (UAV). An UAV can perform vertical profiles as well as horizontal surveys of the mean meteorological parameters: temperature, relative humidity, pressure and wind. A corresponding UAV, called Small Unmanned Meteorological Observer (SUMO), has been developed at the Geophysical Institute at the University of Bergen in cooperation with Müller Engineering (www.pfump.org) and the Paparazzi Project (http://paparazzi.enac.fr). SUMO has been used under Arctic conditions at Longyear airport, Spitsbergen in March/April 2009. Besides vertical profiles up to 1500 m and horizontal surveys at flight levels of 100 and 200 m, SUMO could measure vertical profiles for the first time simultaneously in a horizontal distance of 1 km; one over the ice and snow-covered land surface and the other one above the open water of Isfjorden. This has been the first step of future multiple UAV operations in so called "swarms” or "flocks”. With this, corresponding measurements of the diurnal evolution of the AABL can be achieved with minimum technical efforts and costs. In addition, the Advanced Research Weather Forecasting model (AR-WRF version 3.1) has been run in high resolution (grid size: 1 km). First results of a sensitivity study where ABL schemes have been tested and compared with respect to the measured SUMO profiles are presented.

Land-Surface Subsidence and Open Bedrock Fractures in the Tully Valley, Onondaga County, New York

USGS Publications Warehouse

Hackett, William R.; Gleason, Gayle C.; Kappel, William M.

2009-01-01

Open bedrock fractures were mapped in and near two brine field areas in Tully Valley, New York. More than 400 open fractures and closed joints were mapped for dimension, orientation, and distribution along the east and west valley walls adjacent to two former brine fields. The bedrock fractures are as much as 2 feet wide and over 50 feet deep, while linear depressions in the soil, which are 3 to 10 feet wide and 3 to 6 feet deep, indicate the presence of open bedrock fractures below the soil. The fractures are probably the result of solution mining of halite deposits about 1,200 feet below the land surface.

The effect of activity-based instruction on conceptual development of seventh grade students in probability

NASA Astrophysics Data System (ADS)

Gürbüz, Ramazan

2010-09-01

The purpose of this study is to investigate and compare the effects of activity-based and traditional instructions on students' conceptual development of certain probability concepts. The study was conducted using a pretest-posttest control group design with 80 seventh graders. A developed 'Conceptual Development Test' comprising 12 open-ended questions was administered on both groups of students before and after the intervention. The data were analysed using analysis of covariance, with the pretest as covariate. The results revealed that activity-based instruction (ABI) outperformed the traditional counterpart in the development of probability concepts. Furthermore, ABI was found to contribute students' conceptual development of the concept of 'Probability of an Event' the most, whereas to the concept of 'Sample Space' the least. As a consequence, it can be deduced that the designed instructional process was effective in the instruction of probability concepts.

Quantifying the origins of life on a planetary scale

PubMed Central

Scharf, Caleb; Cronin, Leroy

2016-01-01

A simple, heuristic formula with parallels to the Drake Equation is introduced to help focus discussion on open questions for the origins of life in a planetary context. This approach indicates a number of areas where quantitative progress can be made on parameter estimation for determining origins of life probabilities, based on constraints from Bayesian approaches. We discuss a variety of “microscale” factors and their role in determining “macroscale” abiogenesis probabilities on suitable planets. We also propose that impact ejecta exchange between planets with parallel chemistries and chemical evolution could in principle amplify the development of molecular complexity and abiogenesis probabilities. This amplification could be very significant, and both bias our conclusions about abiogenesis probabilities based on the Earth and provide a major source of variance in the probability of life arising in planetary systems. We use our heuristic formula to suggest a number of observational routes for improving constraints on origins of life probabilities. PMID:27382156

Hydrophobic interaction between contiguous residues in the S6 transmembrane segment acts as a stimuli integration node in the BK channel

PubMed Central

Carrasquel-Ursulaez, Willy; Contreras, Gustavo F.; Sepúlveda, Romina V.; Aguayo, Daniel; González-Nilo, Fernando

2015-01-01

Large-conductance Ca2+- and voltage-activated K+ channel (BK) open probability is enhanced by depolarization, increasing Ca2+ concentration, or both. These stimuli activate modular voltage and Ca2+ sensors that are allosterically coupled to channel gating. Here, we report a point mutation of a phenylalanine (F380A) in the S6 transmembrane helix that, in the absence of internal Ca2+, profoundly hinders channel opening while showing only minor effects on the voltage sensor active–resting equilibrium. Interpretation of these results using an allosteric model suggests that the F380A mutation greatly increases the free energy difference between open and closed states and uncouples Ca2+ binding from voltage sensor activation and voltage sensor activation from channel opening. However, the presence of a bulky and more hydrophobic amino acid in the F380 position (F380W) increases the intrinsic open–closed equilibrium, weakening the coupling between both sensors with the pore domain. Based on these functional experiments and molecular dynamics simulations, we propose that F380 interacts with another S6 hydrophobic residue (L377) in contiguous subunits. This pair forms a hydrophobic ring important in determining the open–closed equilibrium and, like an integration node, participates in the communication between sensors and between the sensors and pore. Moreover, because of its effects on open probabilities, the F380A mutant can be used for detailed voltage sensor experiments in the presence of permeant cations. PMID:25548136

Slow relaxation in weakly open rational polygons.

PubMed

Kokshenev, Valery B; Vicentini, Eduardo

2003-07-01

The interplay between the regular (piecewise-linear) and irregular (vertex-angle) boundary effects in nonintegrable rational polygonal billiards (of m equal sides) is discussed. Decay dynamics in polygons (of perimeter P(m) and small opening Delta) is analyzed through the late-time survival probability S(m) approximately equal t(-delta). Two distinct slow relaxation channels are established. The primary universal channel exhibits relaxation of regular sliding orbits, with delta=1. The secondary channel is given by delta>1 and becomes open when m>P(m)/Delta. It originates from vertex order-disorder dual effects and is due to relaxation of chaoticlike excitations.

Habituating to handling: factors affecting preorbital gland opening in red deer calves.

PubMed

Ceacero, F; Landete-Castillejos, T; Bartošová, J; García, A J; Bartoš, L; Komárková, M; Gallego, L

2014-09-01

The preorbital gland plays not only an olfactory role in cervids but also a visual one. Opening this gland is an easy way for the calf to communicate with the mother, indicating hunger/satiety, stress, pain, fear, or excitement. This information can be also useful for farm operators to assess how fast the calves habituate to handling routines and to detect those calves that do not habituate and may suffer chronic stress in the future. Thirty-one calves were subjected to 2 consecutive experiments to clarify if observing preorbital gland opening is related to habituation to handling in red deer calves (Cervus elaphus). Calves were born in 3 different paddocks, handled as newborns (Exp. 1), and then subjected to the same routine handling but with different periodicity: every 1, 2, or 3 wk (Exp. 2). In Exp. 1, preorbital gland opening was recorded in newborns during an initial handling (including weighing, ear tagging, and sex determination). Preorbital gland opening occurred in 93% of calves during this procedure and was not affected by sex, time since birth, or birth weight. Experiment 2 consisted of measuring preorbital opening during the same routine handling (weighing, blood sampling, and rump touching to assess body condition) when calves were 1, 3, and 5 mo old. Binary logistic regression showed that gland opening was associated with habituation to handling, since at 1 and 3 mo the probability of opening the gland decreased with the number of handlings that a calf experienced before (P = 0.008 and P = 0.028, respectively). However, there were no further changes in preorbital gland opening rate in the 5-mo-old calves (P = 0.182). The significant influence of the number of previous handlings on the probability of opening the preorbital gland was confirmed through generalized linear model with repeated measures (P = 0.007). Preorbital gland opening decreased along the phases of the study. Nevertheless, we found a significant trend in individuals to keep similar opening patterns (intraclass correlation coefficient = 0.807, P < 0.001), which suggests that the more stressed individuals can be detected with this method. Therefore, we conclude that preorbital gland opening during routine handlings is related to the number of previous handlings, and thus it can be used as an indicator of lack of habituation to handling in farmed cervids.

Should we use closed or open infusion containers for prevention of bloodstream infections?

PubMed

Rangel-Frausto, Manuel S; Higuera-Ramirez, Francisco; Martinez-Soto, Jose; Rosenthal, Victor D

2010-02-02

Hospitalized patients in critical care settings are at risk for bloodstream infections (BSI). Most BSIs originate from a central line (CL), and they increase length of stay, cost, and mortality. Open infusion containers may increase the risk of contamination and administration-related (CLAB) because they allow the entry of air into the system, thereby also providing an opportunity for microbial entry. Closed infusion containers were designed to overcome this flaw. However, open infusion containers are still widely used throughout the world.The objective of the study was to determine the effect of switching from open (glass, burettes, and semi-rigid) infusion containers to closed, fully collapsible, plastic infusion containers (Viaflex) on the rate and time to onset of central line-associated bloodstream infections CLABs. An open label, prospective cohort, active healthcare-associated infection surveillance, sequential study was conducted in four ICUs in Mexico. Centers for Disease Control National Nosocomial Infections Surveillance Systems definitions were used to define device-associated infections. A total of 1,096 adult patients who had a central line in place for >24 hours were enrolled. The CLAB rate was significantly higher during the open versus the closed container period (16.1 versus 3.2 CLAB/1000 central line days; RR = 0.20, 95% CI = 0.11-0.36, P < 0.0001). The probability of developing CLAB remained relatively constant in the closed container period (1.4% Days 2-4 to 0.5% Days 8-10), but increased in the open container period (4.9% Days 2-4 to 5.4% Days 8-10). The chance of acquiring a CLAB was significantly decreased (81%) in the closed container period (Cox proportional hazard ratio 0.19, P < 0.0001). Mortality was statistically significantly lower during the closed versus the open container period (23.4% versus 16.1%; RR = 0.69, 95% CI = 0.54-0.88, P < 0.01). Closed infusion containers significantly reduced CLAB rate, the probability of acquiring CLAB, and mortality.

Modeling Drosophila Positional Preferences in Open Field Arenas with Directional Persistence and Wall Attraction

PubMed Central

Soibam, Benjamin; Goldfeder, Rachel L.; Manson-Bishop, Claire; Gamblin, Rachel; Pletcher, Scott D.; Shah, Shishir; Gunaratne, Gemunu H.; Roman, Gregg W.

2012-01-01

In open field arenas, Drosophila adults exhibit a preference for arena boundaries over internal walls and open regions. Herein, we investigate the nature of this preference using phenomenological modeling of locomotion to determine whether local arena features and constraints on movement alone are sufficient to drive positional preferences within open field arenas of different shapes and with different internal features. Our model has two components: directional persistence and local wall force. In regions far away from walls, the trajectory is entirely characterized by a directional persistence probability, , for each movement defined by the step size, , and the turn angle, . In close proximity to walls, motion is computed from and a local attractive force which depends on the distance between the fly and points on the walls. The directional persistence probability was obtained experimentally from trajectories of wild type Drosophila in a circular open field arena and the wall force was computed to minimize the difference between the radial distributions from the model and Drosophila in the same circular arena. The two-component model for fly movement was challenged by comparing the positional preferences from the two-component model to wild type Drosophila in a variety of open field arenas. In most arenas there was a strong concordance between the two-component model and Drosophila. In more complex arenas, the model exhibits similar trends, but some significant differences were found. These differences suggest that there are emergent features within these complex arenas that have significance for the fly, such as potential shelter. Hence, the two-component model is an important step in defining how Drosophila interact with their environment. PMID:23071591

Nonidentifiability of population size from capture-recapture data with heterogeneous detection probabilities

USGS Publications Warehouse

Link, W.A.

2003-01-01

Heterogeneity in detection probabilities has long been recognized as problematic in mark-recapture studies, and numerous models developed to accommodate its effects. Individual heterogeneity is especially problematic, in that reasonable alternative models may predict essentially identical observations from populations of substantially different sizes. Thus even with very large samples, the analyst will not be able to distinguish among reasonable models of heterogeneity, even though these yield quite distinct inferences about population size. The problem is illustrated with models for closed and open populations.

Genetics of Taste Receptors

PubMed Central

Bachmanov, Alexander A.; Bosak, Natalia P.; Lin, Cailu; Matsumoto, Ichiro; Ohmoto, Makoto; Reed, Danielle R.; Nelson, Theodore M.

2016-01-01

Taste receptors function as one of the interfaces between internal and external milieus. Taste receptors for sweet and umami (T1R [taste receptor, type 1]), bitter (T2R [taste receptor, type 2]), and salty (ENaC [epithelial sodium channel]) have been discovered in the recent years, but transduction mechanisms of sour taste and ENaC-independent salt taste are still poorly understood. In addition to these five main taste qualities, the taste system detects such noncanonical “tastes” as water, fat, and complex carbohydrates, but their reception mechanisms require further research. Variations in taste receptor genes between and within vertebrate species contribute to individual and species differences in taste-related behaviors. These variations are shaped by evolutionary forces and reflect species adaptations to their chemical environments and feeding ecology. Principles of drug discovery can be applied to taste receptors as targets in order to develop novel taste compounds to satisfy demand in better artificial sweeteners, enhancers of sugar and sodium taste, and blockers of bitterness of food ingredients and oral medications. PMID:23886383

Experimental Damage Criterion for Static and Fatigue Life Assessment of Commercial Aluminum Alloy Die Castings

NASA Astrophysics Data System (ADS)

Battaglia, Eleonora; Bonollo, Franco; Ferro, Paolo

2017-05-01

Defects, particularly porosity and oxides, in high-pressure die casting can seriously compromise the in-service behavior and durability of products subjected to static or cyclic loadings. In this study, the influence of dimension, orientation, and position of casting defects on the mechanical properties of an AlSi12(b) (EN-AC 44100) aluminum alloy commercial component has been studied. A finite element model has been carried out in order to calculate the stress distribution induced by service loads and identify the crack initiation zones. Castings were qualitatively classified on the basis of porosities distribution detected by X-ray technique and oxides observed on fracture surfaces of specimens coming from fatigue and tensile tests. A damage criterion has been formulated which considers the influence of defects position and orientation on the mechanical strength of the components. Using the proposed damage criterion, it was possible to describe the mechanical behavior of the castings with good accuracy.

Serum and Glucocorticoid Regulated Kinase 1 in Sodium Homeostasis

PubMed Central

Lou, Yiyun; Zhang, Fan; Luo, Yuqin; Wang, Liya; Huang, Shisi; Jin, Fan

2016-01-01

The ubiquitously expressed serum and glucocorticoid regulated kinase 1 (SGK1) is tightly regulated by osmotic and hormonal signals, including glucocorticoids and mineralocorticoids. Recently, SGK1 has been implicated as a signal hub for the regulation of sodium transport. SGK1 modulates the activities of multiple ion channels and carriers, such as epithelial sodium channel (ENaC), voltage-gated sodium channel (Nav1.5), sodium hydrogen exchangers 1 and 3 (NHE1 and NHE3), sodium-chloride symporter (NCC), and sodium-potassium-chloride cotransporter 2 (NKCC2); as well as the sodium-potassium adenosine triphosphatase (Na+/K+-ATPase) and type A natriuretic peptide receptor (NPR-A). Accordingly, SGK1 is implicated in the physiology and pathophysiology of Na+ homeostasis. Here, we focus particularly on recent findings of SGK1’s involvement in Na+ transport in renal sodium reabsorption, hormone-stimulated salt appetite and fluid balance and discuss the abnormal SGK1-mediated Na+ reabsorption in hypertension, heart disease, edema with diabetes, and embryo implantation failure. PMID:27517916

Role of aquaporin and sodium channel in pleural water movement.

PubMed

Jiang, Jinjun; Hu, Jie; Bai, Chunxue

2003-12-16

The role of the ENaC sodium channel and aquaporin-1 (AQP1) water channel on pleural fluid dynamics in mice was investigated. 0.25 ml of hypertonic or isosmolar fluid was infused into the pleural space in anesthetized wildtype and AQP1 null mice. Pleural fluid was sampled at specified times to quantify the osmolality and volume. The sodium channel activator terbutaline increased isosmolar fluid clearance by 90% while the sodium channel inhibitor amiloride decreased it by 15%, but had no effect on osmotically driven water transport. AQP1 deletion significantly decreased osmotic water transport in pleural space by twofold, but it had no effect on isosmolar fluid clearance. Pretreatment with dexamethasone increased pleural osmotic fluid entry by 25%, while intravenous injection of HgCl2 decreased osmotic pleural water movement by 43%. These results provided evidence for a role of a sodium channel in pleural fluid absorption; AQP1 plays a major role in osmotic liquid transport but it does not affect isosmolar fluid clearance.

Diffusive flux in a model of stochastically gated oxygen transport in insect respiration

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

Berezhkovskii, Alexander M.; Shvartsman, Stanislav Y.

Oxygen delivery to insect tissues is controlled by transport through a branched tubular network that is connected to the atmosphere by valve-like gates, known as spiracles. In certain physiological regimes, the spiracles appear to be randomly switching between open and closed states. Quantitative analysis of this regime leads a reaction-diffusion problem with stochastically switching boundary condition. We derive an expression for the diffusive flux at long times in this problem. Our approach starts with the derivation of the passage probability for a single particle that diffuses between a stochastically gated boundary, which models the opening and closing spiracle, and themore » perfectly absorbing boundary, which models oxygen absorption by the tissue. This passage probability is then used to derive an expression giving the diffusive flux as a function of the geometric parameters of the tube and characteristic time scales of diffusion and gate dynamics.« less

Turning Oscillations Into Opportunities: Lessons from a Bacterial Decision Gate

NASA Astrophysics Data System (ADS)

Schultz, Daniel; Lu, Mingyang; Stavropoulos, Trevor; Onuchic, Jose'; Ben-Jacob, Eshel

2013-04-01

Sporulation vs. competence provides a prototypic example of collective cell fate determination. The decision is performed by the action of three modules: 1) A stochastic competence switch whose transition probability is regulated by population density, population stress and cell stress. 2) A sporulation timer whose clock rate is regulated by cell stress and population stress. 3) A decision gate that is coupled to the timer via a special repressilator-like loop. We show that the distinct circuit architecture of this gate leads to special dynamics and noise management characteristics: The gate opens a time-window of opportunity for competence transitions during which it generates oscillations that are turned into a chain of transition opportunities - each oscillation opens a short interval with high transition probability. The special architecture of the gate also leads to filtering of external noise and robustness against internal noise and variations in the circuit parameters.

Diffusive flux in a model of stochastically gated oxygen transport in insect respiration.

PubMed

Berezhkovskii, Alexander M; Shvartsman, Stanislav Y

2016-05-28

Oxygen delivery to insect tissues is controlled by transport through a branched tubular network that is connected to the atmosphere by valve-like gates, known as spiracles. In certain physiological regimes, the spiracles appear to be randomly switching between open and closed states. Quantitative analysis of this regime leads a reaction-diffusion problem with stochastically switching boundary condition. We derive an expression for the diffusive flux at long times in this problem. Our approach starts with the derivation of the passage probability for a single particle that diffuses between a stochastically gated boundary, which models the opening and closing spiracle, and the perfectly absorbing boundary, which models oxygen absorption by the tissue. This passage probability is then used to derive an expression giving the diffusive flux as a function of the geometric parameters of the tube and characteristic time scales of diffusion and gate dynamics.

Opinion evolution and rare events in an open community

NASA Astrophysics Data System (ADS)

Ye, Yusong; Yang, Zhuoqin; Zhang, Zili

2016-11-01

There are many multi-stable phenomena in society. To explain these multi-stable phenomena, we have studied opinion evolution in an open community. We focus on probability of transition (or the mean transition time) that the system transfer from one state to another. We suggest a bistable model to provide an interpretation of these phenomena. The quasi-potential method that we used is the most important method to calculate the transition time and it can be used to determine the whole probability density. We study the condition of bistability and then discuss rare events in a multi-stable system. In our model, we find that two parameters, ;temperature; and ;persuading intensity,; influence the behavior of the system; a suitable ;persuading intensity; and low ;temperature; make the system more stable. This means that the transition rarely happens. The asymmetric phenomenon caused by ;public-opinion; is also discussed.

Turning Oscillations Into Opportunities: Lessons from a Bacterial Decision Gate

PubMed Central

Schultz, Daniel; Lu, Mingyang; Stavropoulos, Trevor; Onuchic, Jose'; Ben-Jacob, Eshel

2013-01-01

Sporulation vs. competence provides a prototypic example of collective cell fate determination. The decision is performed by the action of three modules: 1) A stochastic competence switch whose transition probability is regulated by population density, population stress and cell stress. 2) A sporulation timer whose clock rate is regulated by cell stress and population stress. 3) A decision gate that is coupled to the timer via a special repressilator-like loop. We show that the distinct circuit architecture of this gate leads to special dynamics and noise management characteristics: The gate opens a time-window of opportunity for competence transitions during which it generates oscillations that are turned into a chain of transition opportunities – each oscillation opens a short interval with high transition probability. The special architecture of the gate also leads to filtering of external noise and robustness against internal noise and variations in the circuit parameters. PMID:23591544

Multimode delta Scuti stars in the open cluster NGC 7062

NASA Astrophysics Data System (ADS)

Freyhammer, L. M.; Arentoft, T.; Sterken, C.

2001-03-01

The central field of NGC 7062 was observed intensively with the main goal of finding delta Scuti stars suitable for use in asteroseismological tests of stellar structure and evolution theory. BV time series photometry was obtained for this northern open cluster, which has a large population of stars inside the delta Scuti instability strip, making it a probable host of several such variables. We report findings of 15 pulsating stars, including at least 13 delta Scuti stars. Ten variables oscillate in two or more frequencies. Only one of these variables was known before, for which we detected 9 frequencies. Five probable variables are mentioned, and period analysis is given for all 20 stars. Based on observations obtained at the Nordic Optical Telescope, operated on the island of La Palma jointly by Denmark, Finland, Iceland, Norway, and Sweden, in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisíca de Canarias.

Occupancy and abundance of Eleutherodactylus frogs in coffee plantations in Puerto Rico

USGS Publications Warehouse

Monroe, Kelen D.; Collazo, Jaime A.; Pacifici, Krishna; Reich, Brian J.; Puente-Rolón, Alberto R.; Terando, Adam J.

2017-01-01

Shaded coffee plantations are of conservation value for many taxa, particularly for resident avifauna in the face of extensive landscape changes. Yet, little is known about the value of coffee plantations for amphibians because there are scant demographic data to index their value among species with different habitat preferences. We estimated the probability of occupancy of three frog species: Eleutherodactylus wightmanae, a forest species; E. brittoni, a grassland species; and E. antillensis, an open habitat species. Occupancy was estimated in sun and shaded plantations, and in secondary forest, in the west-central mountains of Puerto Rico. We also estimated the probability that a survey station was occupied by no individuals, one, or >1 individual, as a proxy of abundance. The aforementioned parameters, and local colonization and extinction probability, were modeled as a function of weather conditions (temperature, humidity) and vegetation cover at the sampling station (5 m) and contextual (100 m) scales. Encounter histories were obtained with passive acoustic recorders between February and July in 2015. Consistent with known habitat preferences, the highest occupancies were associated with secondary forests for E. wightmanae and sun plantations for E. brittoni. Occupancy probability for E. antillensis was similar across habitat types, indicating no aversion to shaded–forested habitats. Shaded plantations harbored moderate levels of occupancy for all species, indicating their potential value for multispecies conservation. Local colonization rates increased with forest cover for E. wightmanae, and with open habitats for E. brittoni and E. antillensis. Open habitats harbored a higher abundance of E. brittoni and E antillensis, but lower values for E. wightmanae. Sun and shaded plantations could provide quality habitat for Eleutherodactylus spp. if managed for features that promote local colonization and abundance.

Voltage-Gated Lipid Ion Channels

PubMed Central

Blicher, Andreas; Heimburg, Thomas

2013-01-01

Synthetic lipid membranes can display channel-like ion conduction events even in the absence of proteins. We show here that these events are voltage-gated with a quadratic voltage dependence as expected from electrostatic theory of capacitors. To this end, we recorded channel traces and current histograms in patch-experiments on lipid membranes. We derived a theoretical current-voltage relationship for pores in lipid membranes that describes the experimental data very well when assuming an asymmetric membrane. We determined the equilibrium constant between closed and open state and the open probability as a function of voltage. The voltage-dependence of the lipid pores is found comparable to that of protein channels. Lifetime distributions of open and closed events indicate that the channel open distribution does not follow exponential statistics but rather power law behavior for long open times. PMID:23823188

The complexity of divisibility.

PubMed

Bausch, Johannes; Cubitt, Toby

2016-09-01

We address two sets of long-standing open questions in linear algebra and probability theory, from a computational complexity perspective: stochastic matrix divisibility, and divisibility and decomposability of probability distributions. We prove that finite divisibility of stochastic matrices is an NP-complete problem, and extend this result to nonnegative matrices, and completely-positive trace-preserving maps, i.e. the quantum analogue of stochastic matrices. We further prove a complexity hierarchy for the divisibility and decomposability of probability distributions, showing that finite distribution divisibility is in P, but decomposability is NP-hard. For the former, we give an explicit polynomial-time algorithm. All results on distributions extend to weak-membership formulations, proving that the complexity of these problems is robust to perturbations.

Fingerprints of exceptional points in the survival probability of resonances in atomic spectra

NASA Astrophysics Data System (ADS)

Cartarius, Holger; Moiseyev, Nimrod

2011-07-01

The unique time signature of the survival probability exactly at the exceptional point parameters is studied here for the hydrogen atom in strong static magnetic and electric fields. We show that indeed the survival probability S(t)=|<ψ(0)|ψ(t)>|2 decays exactly as |1-at|2e-ΓEPt/ℏ, where ΓEP is associated with the decay rate at the exceptional point and a is a complex constant depending solely on the initial wave packet that populates exclusively the two almost degenerate states of the non-Hermitian Hamiltonian. This may open the possibility for a first experimental detection of exceptional points in a quantum system.

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

Goldstein, Adam; Connaughton, Valerie; Briggs, Michael S.

We present a method to estimate the jet opening angles of long duration gamma-ray bursts (GRBs) using the prompt gamma-ray energetics and an inversion of the Ghirlanda relation, which is a correlation between the time-integrated peak energy of the GRB prompt spectrum and the collimation-corrected energy in gamma-rays. The derived jet opening angles using this method and detailed assumptions match well with the corresponding inferred jet opening angles obtained when a break in the afterglow is observed. Furthermore, using a model of the predicted long GRB redshift probability distribution observable by the Fermi Gamma-ray Burst Monitor (GBM), we estimate themore » probability distributions for the jet opening angle and rest-frame energetics for a large sample of GBM GRBs for which the redshifts have not been observed. Previous studies have only used a handful of GRBs to estimate these properties due to the paucity of observed afterglow jet breaks, spectroscopic redshifts, and comprehensive prompt gamma-ray observations, and we potentially expand the number of GRBs that can be used in this analysis by more than an order of magnitude. In this analysis, we also present an inferred distribution of jet breaks which indicates that a large fraction of jet breaks are not observable with current instrumentation and observing strategies. We present simple parameterizations for the jet angle, energetics, and jet break distributions so that they may be used in future studies.« less

Estimation of population size using open capture-recapture models

USGS Publications Warehouse

McDonald, T.L.; Amstrup, Steven C.

2001-01-01

One of the most important needs for wildlife managers is an accurate estimate of population size. Yet, for many species, including most marine species and large mammals, accurate and precise estimation of numbers is one of the most difficult of all research challenges. Open-population capture-recapture models have proven useful in many situations to estimate survival probabilities but typically have not been used to estimate population size. We show that open-population models can be used to estimate population size by developing a Horvitz-Thompson-type estimate of population size and an estimator of its variance. Our population size estimate keys on the probability of capture at each trap occasion and therefore is quite general and can be made a function of external covariates measured during the study. Here we define the estimator and investigate its bias, variance, and variance estimator via computer simulation. Computer simulations make extensive use of real data taken from a study of polar bears (Ursus maritimus) in the Beaufort Sea. The population size estimator is shown to be useful because it was negligibly biased in all situations studied. The variance estimator is shown to be useful in all situations, but caution is warranted in cases of extreme capture heterogeneity.

Environmental Health Risks and Housing Values: Evidence from 1,600 Toxic Plant Openings and Closings.

PubMed

Currie, Janet; Davis, Lucas; Greenstone, Michael; Walker, Reed

2015-02-01

Regulatory oversight of toxic emissions from industrial plants and understanding about these emissions' impacts are in their infancy. Applying a research design based on the openings and closings of 1,600 industrial plants to rich data on housing markets and infant health, we find that: toxic air emissions affect air quality only within 1 mile of the plant; plant openings lead to 11 percent declines in housing values within 0.5 mile or a loss of about $4.25 million for these households; and a plant's operation is associated with a roughly 3 percent increase in the probability of low birthweight within 1 mile.

Impacts of savanna trees on forage quality for a large African herbivore

PubMed Central

De Kroon, Hans; Prins, Herbert H. T.

2008-01-01

Recently, cover of large trees in African savannas has rapidly declined due to elephant pressure, frequent fires and charcoal production. The reduction in large trees could have consequences for large herbivores through a change in forage quality. In Tarangire National Park, in Northern Tanzania, we studied the impact of large savanna trees on forage quality for wildebeest by collecting samples of dominant grass species in open grassland and under and around large Acacia tortilis trees. Grasses growing under trees had a much higher forage quality than grasses from the open field indicated by a more favourable leaf/stem ratio and higher protein and lower fibre concentrations. Analysing the grass leaf data with a linear programming model indicated that large savanna trees could be essential for the survival of wildebeest, the dominant herbivore in Tarangire. Due to the high fibre content and low nutrient and protein concentrations of grasses from the open field, maximum fibre intake is reached before nutrient requirements are satisfied. All requirements can only be satisfied by combining forage from open grassland with either forage from under or around tree canopies. Forage quality was also higher around dead trees than in the open field. So forage quality does not reduce immediately after trees die which explains why negative effects of reduced tree numbers probably go initially unnoticed. In conclusion our results suggest that continued destruction of large trees could affect future numbers of large herbivores in African savannas and better protection of large trees is probably necessary to sustain high animal densities in these ecosystems. PMID:18309522

An evaluation of open set recognition for FLIR images

NASA Astrophysics Data System (ADS)

Scherreik, Matthew; Rigling, Brian

2015-05-01

Typical supervised classification algorithms label inputs according to what was learned in a training phase. Thus, test inputs that were not seen in training are always given incorrect labels. Open set recognition algorithms address this issue by accounting for inputs that are not present in training and providing the classifier with an option to reject" unknown samples. A number of such techniques have been developed in the literature, many of which are based on support vector machines (SVMs). One approach, the 1-vs-set machine, constructs a slab" in feature space using the SVM hyperplane. Inputs falling on one side of the slab or within the slab belong to a training class, while inputs falling on the far side of the slab are rejected. We note that rejection of unknown inputs can be achieved by thresholding class posterior probabilities. Another recently developed approach, the Probabilistic Open Set SVM (POS-SVM), empirically determines good probability thresholds. We apply the 1-vs-set machine, POS-SVM, and closed set SVMs to FLIR images taken from the Comanche SIG dataset. Vehicles in the dataset are divided into three general classes: wheeled, armored personnel carrier (APC), and tank. For each class, a coarse pose estimate (front, rear, left, right) is taken. In a closed set sense, we analyze these algorithms for prediction of vehicle class and pose. To test open set performance, one or more vehicle classes are held out from training. By considering closed and open set performance separately, we may closely analyze both inter-class discrimination and threshold effectiveness.

Estimating survival and breeding probability for pond-breeding amphibians: a modified robust design

USGS Publications Warehouse

Bailey, L.L.; Kendall, W.L.; Church, D.R.; Wilbur, H.M.

2004-01-01

Many studies of pond-breeding amphibians involve sampling individuals during migration to and from breeding habitats. Interpreting population processes and dynamics from these studies is difficult because (1) only a proportion of the population is observable each season, while an unknown proportion remains unobservable (e.g., non-breeding adults) and (2) not all observable animals are captured. Imperfect capture probability can be easily accommodated in capture?recapture models, but temporary transitions between observable and unobservable states, often referred to as temporary emigration, is known to cause problems in both open- and closed-population models. We develop a multistate mark?recapture (MSMR) model, using an open-robust design that permits one entry and one exit from the study area per season. Our method extends previous temporary emigration models (MSMR with an unobservable state) in two ways. First, we relax the assumption of demographic closure (no mortality) between consecutive (secondary) samples, allowing estimation of within-pond survival. Also, we add the flexibility to express survival probability of unobservable individuals (e.g., ?non-breeders?) as a function of the survival probability of observable animals while in the same, terrestrial habitat. This allows for potentially different annual survival probabilities for observable and unobservable animals. We apply our model to a relictual population of eastern tiger salamanders (Ambystoma tigrinum tigrinum). Despite small sample sizes, demographic parameters were estimated with reasonable precision. We tested several a priori biological hypotheses and found evidence for seasonal differences in pond survival. Our methods could be applied to a variety of pond-breeding species and other taxa where individuals are captured entering or exiting a common area (e.g., spawning or roosting area, hibernacula).

Probabilistic mapping of flood-induced backscatter changes in SAR time series

NASA Astrophysics Data System (ADS)

Schlaffer, Stefan; Chini, Marco; Giustarini, Laura; Matgen, Patrick

2017-04-01

The information content of flood extent maps can be increased considerably by including information on the uncertainty of the flood area delineation. This additional information can be of benefit in flood forecasting and monitoring. Furthermore, flood probability maps can be converted to binary maps showing flooded and non-flooded areas by applying a threshold probability value pF = 0.5. In this study, a probabilistic change detection approach for flood mapping based on synthetic aperture radar (SAR) time series is proposed. For this purpose, conditional probability density functions (PDFs) for land and open water surfaces were estimated from ENVISAT ASAR Wide Swath (WS) time series containing >600 images using a reference mask of permanent water bodies. A pixel-wise harmonic model was used to account for seasonality in backscatter from land areas caused by soil moisture and vegetation dynamics. The approach was evaluated for a large-scale flood event along the River Severn, United Kingdom. The retrieved flood probability maps were compared to a reference flood mask derived from high-resolution aerial imagery by means of reliability diagrams. The obtained performance measures indicate both high reliability and confidence although there was a slight under-estimation of the flood extent, which may in part be attributed to topographically induced radar shadows along the edges of the floodplain. Furthermore, the results highlight the importance of local incidence angle for the separability between flooded and non-flooded areas as specular reflection properties of open water surfaces increase with a more oblique viewing geometry.

Spatial vent opening probability map of El Hierro Island (Canary Islands, Spain)

NASA Astrophysics Data System (ADS)

Becerril, Laura; Cappello, Annalisa; Galindo, Inés; Neri, Marco; Del Negro, Ciro

2013-04-01

The assessment of the probable spatial distribution of new eruptions is useful to manage and reduce the volcanic risk. It can be achieved in different ways, but it becomes especially hard when dealing with volcanic areas less studied, poorly monitored and characterized by a low frequent activity, as El Hierro. Even though it is the youngest of the Canary Islands, before the 2011 eruption in the "Las Calmas Sea", El Hierro had been the least studied volcanic Island of the Canaries, with more historically devoted attention to La Palma, Tenerife and Lanzarote. We propose a probabilistic method to build the susceptibility map of El Hierro, i.e. the spatial distribution of vent opening for future eruptions, based on the mathematical analysis of the volcano-structural data collected mostly on the Island and, secondly, on the submerged part of the volcano, up to a distance of ~10-20 km from the coast. The volcano-structural data were collected through new fieldwork measurements, bathymetric information, and analysis of geological maps, orthophotos and aerial photographs. They have been divided in different datasets and converted into separate and weighted probability density functions, which were then included in a non-homogeneous Poisson process to produce the volcanic susceptibility map. Future eruptive events on El Hierro is mainly concentrated on the rifts zones, extending also beyond the shoreline. The major probabilities to host new eruptions are located on the distal parts of the South and West rifts, with the highest probability reached in the south-western area of the West rift. High probabilities are also observed in the Northeast and South rifts, and the submarine parts of the rifts. This map represents the first effort to deal with the volcanic hazard at El Hierro and can be a support tool for decision makers in land planning, emergency plans and civil defence actions.

Microcracks, micropores, and their petrologic interpretation for 72415 and 15418

NASA Technical Reports Server (NTRS)

Richter, D.; Simmons, G.; Siegfried, R.

1976-01-01

Lunar samples 72415 and 15418 have complex microstructures that indicate a series of fracturing and healing events. Both samples contain relatively few open microcracks but many sealed and healed microcracks. Dunite 72415 contains abundant healed cracks that formed tectonically, symplectic intergrowths spatially and probably genetically related to microcracks, and a cataclastic matrix that has been extensively sintered. Metamorphosed breccia 15418 contains many post-metamorphic healed cracks, large shock induced cracks that have been sealed with glass, and a few younger, thin, open shock induced cracks.

Fixedwing UAV soundings of the boundary layer during the ScaleX 2015 summer campaign in southern Germany

NASA Astrophysics Data System (ADS)

Philipp, Andreas; Groos, Alexander; Petersen, Erik; Bischoff, Julian; Szogs, Sebastian; Beck, Christoph; Hähner, Jörg; Jacobeit, Jucundus

2016-04-01

In order to examine the potential to close the local water cycle budget and to evaluate models on different scales (among other aims) a fleet of 6 fixed wing UAVs has been operated by the Institute for Geography and the Institute for Informatics of the University of Augsburg during the ScaleX measurement campaign of the KIT/IMK-IFU (Karlsruher Institut für Technologie/Institut für Meteorologie und Klimatologie, Garmisch Partenkirchen). The site is located in southern Germany in a rural, hilly landscape at a small catchment tributing to the Ammersee and equipped with several ground based and remote sensing hydrological instruments. In order to complement these instruments by in situ measurements of the boundary layer, three intensive observation periods (IOPs) for taking temperature and humidity profiles took place, each with a different set up in order to evaluate optimal operation modes. The UAVs are all operated by the open hardware Apogee autopilot and sensor controller developed by ENAC (Ecole Nationale de l'Aviation Civile, Toulouse) operated by the PPRZ open source software package. The first IOP (30.06.-01.07.2015) was an experiment to cover a small site of 500 by 500 meters (well-apointed with hydrological instruments) in a 24 hours period as dense as possible. Thus three simultaneous helical profile flights (radius 70 m) have been run at each full hour around three different centres with heights ranging up to 1000 m above ground level (with special permissions). During a second IOP (15.07.2015) it has been tried to increase the frequence of profile flights up to 2 flights per hours between 7:30 and 14:00 CEST. These soundings have been accompanied by flyovers of a manned ultra light aircraft of the IMK-IFU. Finally a third experiment (06.08.2015) tried to evaluate longer flights (up to 55 minutes) of two UAVs at constant levels of 300 and 500 m above ground level between 6:00 and 14:00 CEST in order to cover the early diurnal cycle even more constantly by the in situ measurements. A midnight profile for measuring the staring conditions of the development has been measured up to a hight of 1600 m, which was the permitted limit for this campaign. Data analysis using a newly developed 3D software showed that these flight experiments are able to reveal several distinct meteorological processes developing during the diurnal cycle which are shortly discussed on the poster.

Case Study: OpenSSL 2012 Validation

DTIC Science & Technology

2013-08-01

there are probably millions of users who are impacted directly, and hundreds of millions who are indirectly affected. Cryptographic libraries are...UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESSES 8. PERFORMING ORGANIZATION REPORT NUMBER D-4991 H13 -001174 Institute for Defense

Long‐term time‐dependent probabilities for the third Uniform California Earthquake Rupture Forecast (UCERF3)

USGS Publications Warehouse

Field, Edward; Biasi, Glenn P.; Bird, Peter; Dawson, Timothy E.; Felzer, Karen R.; Jackson, David A.; Johnson, Kaj M.; Jordan, Thomas H.; Madden, Christopher; Michael, Andrew J.; Milner, Kevin; Page, Morgan T.; Parsons, Thomas E.; Powers, Peter; Shaw, Bruce E.; Thatcher, Wayne R.; Weldon, Ray J.; Zeng, Yuehua

2015-01-01

The 2014 Working Group on California Earthquake Probabilities (WGCEP 2014) presents time-dependent earthquake probabilities for the third Uniform California Earthquake Rupture Forecast (UCERF3). Building on the UCERF3 time-independent model, published previously, renewal models are utilized to represent elastic-rebound-implied probabilities. A new methodology has been developed that solves applicability issues in the previous approach for un-segmented models. The new methodology also supports magnitude-dependent aperiodicity and accounts for the historic open interval on faults that lack a date-of-last-event constraint. Epistemic uncertainties are represented with a logic tree, producing 5,760 different forecasts. Results for a variety of evaluation metrics are presented, including logic-tree sensitivity analyses and comparisons to the previous model (UCERF2). For 30-year M≥6.7 probabilities, the most significant changes from UCERF2 are a threefold increase on the Calaveras fault and a threefold decrease on the San Jacinto fault. Such changes are due mostly to differences in the time-independent models (e.g., fault slip rates), with relaxation of segmentation and inclusion of multi-fault ruptures being particularly influential. In fact, some UCERF2 faults were simply too long to produce M 6.7 sized events given the segmentation assumptions in that study. Probability model differences are also influential, with the implied gains (relative to a Poisson model) being generally higher in UCERF3. Accounting for the historic open interval is one reason. Another is an effective 27% increase in the total elastic-rebound-model weight. The exact factors influencing differences between UCERF2 and UCERF3, as well as the relative importance of logic-tree branches, vary throughout the region, and depend on the evaluation metric of interest. For example, M≥6.7 probabilities may not be a good proxy for other hazard or loss measures. This sensitivity, coupled with the approximate nature of the model and known limitations, means the applicability of UCERF3 should be evaluated on a case-by-case basis.

Using open robust design models to estimate temporary emigration from capture-recapture data.

PubMed

Kendall, W L; Bjorkland, R

2001-12-01

Capture-recapture studies are crucial in many circumstances for estimating demographic parameters for wildlife and fish populations. Pollock's robust design, involving multiple sampling occasions per period of interest, provides several advantages over classical approaches. This includes the ability to estimate the probability of being present and available for detection, which in some situations is equivalent to breeding probability. We present a model for estimating availability for detection that relaxes two assumptions required in previous approaches. The first is that the sampled population is closed to additions and deletions across samples within a period of interest. The second is that each member of the population has the same probability of being available for detection in a given period. We apply our model to estimate survival and breeding probability in a study of hawksbill sea turtles (Eretmochelys imbricata), where previous approaches are not appropriate.

Using open robust design models to estimate temporary emigration from capture-recapture data

USGS Publications Warehouse

Kendall, W.L.; Bjorkland, R.

2001-01-01

Capture-recapture studies are crucial in many circumstances for estimating demographic parameters for wildlife and fish populations. Pollock's robust design, involving multiple sampling occasions per period of interest, provides several advantages over classical approaches. This includes the ability to estimate the probability of being present and available for detection, which in some situations is equivalent to breeding probability. We present a model for estimating availability for detection that relaxes two assumptions required in previous approaches. The first is that the sampled population is closed to additions and deletions across samples within a period of interest. The second is that each member of the population has the same probability of being available for detection in a given period. We apply our model to estimate survival and breeding probability in a study of hawksbill sea turtles (Eretmochelys imbricata), where previous approaches are not appropriate.

Computer simulation of random variables and vectors with arbitrary probability distribution laws

NASA Technical Reports Server (NTRS)

Bogdan, V. M.

1981-01-01

Assume that there is given an arbitrary n-dimensional probability distribution F. A recursive construction is found for a sequence of functions x sub 1 = f sub 1 (U sub 1, ..., U sub n), ..., x sub n = f sub n (U sub 1, ..., U sub n) such that if U sub 1, ..., U sub n are independent random variables having uniform distribution over the open interval (0,1), then the joint distribution of the variables x sub 1, ..., x sub n coincides with the distribution F. Since uniform independent random variables can be well simulated by means of a computer, this result allows one to simulate arbitrary n-random variables if their joint probability distribution is known.

Study of recreational land and open space using Skylab imagery

NASA Technical Reports Server (NTRS)

Sattinger, I. J. (Principal Investigator)

1975-01-01

The author has identified the following significant results. An analysis of the statistical uniqueness of each of the signatures of the Gratiot-Saginaw State Game Area was made by computing a matrix of probabilities of misclassification for all possible signature pairs. Within each data set, the 35 signatures were then aggregated into a smaller set of composite signatures by combining groups of signatures having high probabilities of misclassification. Computer separation of forest denisty classes was poor with multispectral scanner data collected on 5 August 1973. Signatures from the scanner data were further analyzed to determine the ranking of spectral channels for computer separation of the scene classes. Probabilities of misclassification were computed for composite signatures using four separate combinations of data source and channel selection.

Technology-enhanced Interactive Teaching of Marginal, Joint and Conditional Probabilities: The Special Case of Bivariate Normal Distribution

PubMed Central

Dinov, Ivo D.; Kamino, Scott; Bhakhrani, Bilal; Christou, Nicolas

2014-01-01

Summary Data analysis requires subtle probability reasoning to answer questions like What is the chance of event A occurring, given that event B was observed? This generic question arises in discussions of many intriguing scientific questions such as What is the probability that an adolescent weighs between 120 and 140 pounds given that they are of average height? and What is the probability of (monetary) inflation exceeding 4% and housing price index below 110? To address such problems, learning some applied, theoretical or cross-disciplinary probability concepts is necessary. Teaching such courses can be improved by utilizing modern information technology resources. Students’ understanding of multivariate distributions, conditional probabilities, correlation and causation can be significantly strengthened by employing interactive web-based science educational resources. Independent of the type of a probability course (e.g. majors, minors or service probability course, rigorous measure-theoretic, applied or statistics course) student motivation, learning experiences and knowledge retention may be enhanced by blending modern technological tools within the classical conceptual pedagogical models. We have designed, implemented and disseminated a portable open-source web-application for teaching multivariate distributions, marginal, joint and conditional probabilities using the special case of bivariate Normal distribution. A real adolescent height and weight dataset is used to demonstrate the classroom utilization of the new web-application to address problems of parameter estimation, univariate and multivariate inference. PMID:25419016

Technology-enhanced Interactive Teaching of Marginal, Joint and Conditional Probabilities: The Special Case of Bivariate Normal Distribution.

PubMed

Dinov, Ivo D; Kamino, Scott; Bhakhrani, Bilal; Christou, Nicolas

2013-01-01

Data analysis requires subtle probability reasoning to answer questions like What is the chance of event A occurring, given that event B was observed? This generic question arises in discussions of many intriguing scientific questions such as What is the probability that an adolescent weighs between 120 and 140 pounds given that they are of average height? and What is the probability of (monetary) inflation exceeding 4% and housing price index below 110? To address such problems, learning some applied, theoretical or cross-disciplinary probability concepts is necessary. Teaching such courses can be improved by utilizing modern information technology resources. Students' understanding of multivariate distributions, conditional probabilities, correlation and causation can be significantly strengthened by employing interactive web-based science educational resources. Independent of the type of a probability course (e.g. majors, minors or service probability course, rigorous measure-theoretic, applied or statistics course) student motivation, learning experiences and knowledge retention may be enhanced by blending modern technological tools within the classical conceptual pedagogical models. We have designed, implemented and disseminated a portable open-source web-application for teaching multivariate distributions, marginal, joint and conditional probabilities using the special case of bivariate Normal distribution. A real adolescent height and weight dataset is used to demonstrate the classroom utilization of the new web-application to address problems of parameter estimation, univariate and multivariate inference.

The luminal K+ channel of the thick ascending limb of Henle's loop.

PubMed

Bleich, M; Schlatter, E; Greger, R

1990-01-01

In vitro perfused rat thick ascending limbs of Henle's loop (TAL) were used (n = 260) to analyse the conductance properties of the luminal membrane applying the patch-clamp technique. Medullary (mTAL) and cortical (cTAL) tubule segments were dissected and perfused in vitro. The free end of the tubule was held and immobilized at one edge by a holding pipette kept under continuous suction. A micropositioner was used to insert a patch pipette into the lumen, and a gigaohm seal with the luminal membrane was achieved in 455 instances out of considerably more trials. In approximately 20% of all gigaohm seals recordings of single ionic channels were obtained. We have identified only one single type of K+ channel in these cell-attached and cell-excised recordings. In the cell-attached configuration with KCl or NaCl in the pipette, the channel had a conductance of 60 +/- 6 pS (n = 24) and 31 +/- 7 pS (n = 4) respectively. In cell-free patches with KCl either in the patch pipette or in the bath and with a Ringer-type solution (NaCl) on the opposite side the conductance was 72 +/- 4 pS (n = 37) at a clamp voltage of 0 mV. The permeability was 0.33 +/- 0.02 . 10(-12) cm3/s. The selectivity sequence of this channel was: K+ = Rb+ = NH4+ = Cs+ greater than Li+ much greater than Na+ = 0; the conductance sequence was K+ much greater than Li+ much greater than Rb+ = Cs+ = NH4+ = Na+ = 0. In excised patches Rb+, Cs+ and NH4+ when present in the bath at 145 mmol/l all inhibited K+ currents out of the pipette. The channel kinetics were described by one open (9.5 +/- 1.5 ms, n = 18) and by two closed (1.4 +/- 0.1 and 14 +/- 2 ms) time constants. The open probability of this channel was increased by depolarization. The channel open probability was reduced voltage dependently by Ba2+ (half maximal inhibition at 0 mV: 0.07 mmol/l) from the cytosolic side. Verapamil, diltiazem, quinine and quinidine inhibited at approximately 1 mumol/l -0.1 mmol/l from either side. Similarly, the amino cations lidocaine, tetraethylammonium and choline inhibited at 10-100 mmol/l. The channel was downregulated in its open probability by cytosolic Ca2+ activities greater than 10(-7) mol/l and by adenosine triphosphate greater than or equal to 10(-4) mol/l. The open probability was downregulated by decreasing cytosolic pH (2-fold by a decrease in pH by less than or equal to 0.2 units).(ABSTRACT TRUNCATED AT 400 WORDS)

78 FR 55775 - Pipeline Safety: Information Collection Activities

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-11

...'' is open to wide interpretation and suggests that ``awareness'' be replaced with ``discovery'', which... conditions characterize ``discovery'' as ``when an operator's representative has adequate information from... ``adequate'' and ``probable'' in the definition of ``discovery'' provides additional clarity. Part A18 of the...

Hidden Markov analysis of mechanosensitive ion channel gating.

PubMed

Khan, R Nazim; Martinac, Boris; Madsen, Barry W; Milne, Robin K; Yeo, Geoffrey F; Edeson, Robert O

2005-02-01

Patch clamp data from the large conductance mechanosensitive channel (MscL) in E. coli was studied with the aim of developing a strategy for statistical analysis based on hidden Markov models (HMMs) and determining the number of conductance levels of the channel, together with mean current, mean dwell time and equilibrium probability of occupancy for each level. The models incorporated state-dependent white noise and moving average adjustment for filtering, with maximum likelihood parameter estimates obtained using an EM (expectation-maximisation) based iteration. Adjustment for filtering was included as it could be expected that the electronic filter used in recording would have a major effect on obviously brief intermediate conductance level sojourns. Preliminary data analysis revealed that the brevity of intermediate level sojourns caused difficulties in assignment of data points to levels as a result of over-estimation of noise variances. When reasonable constraints were placed on these variances using the better determined noise variances for the closed and fully open levels, idealisation anomalies were eliminated. Nevertheless, simulations suggested that mean sojourn times for the intermediate levels were still considerably over-estimated, and that recording bandwidth was a major limitation; improved results were obtained with higher bandwidth data (10 kHz sampled at 25 kHz). The simplest model consistent with these data had four open conductance levels, intermediate levels being approximately 20%, 51% and 74% of fully open. The mean lifetime at the fully open level was about 1 ms; estimates for the three intermediate levels were 54-92 micros, probably still over-estimates.

Long-term survival in laparoscopic vs open resection for colorectal liver metastases: inverse probability of treatment weighting using propensity scores.

PubMed

Lewin, Joel W; O'Rourke, Nicholas A; Chiow, Adrian K H; Bryant, Richard; Martin, Ian; Nathanson, Leslie K; Cavallucci, David J

2016-02-01

This study compares long-term outcomes between intention-to-treat laparoscopic and open approaches to colorectal liver metastases (CLM), using inverse probability of treatment weighting (IPTW) based on propensity scores to control for selection bias. Patients undergoing liver resection for CLM by 5 surgeons at 3 institutions from 2000 to early 2014 were analysed. IPTW based on propensity scores were generated and used to assess the marginal treatment effect of the laparoscopic approach via a weighted Cox proportional hazards model. A total of 298 operations were performed in 256 patients. 7 patients with planned two-stage resections were excluded leaving 284 operations in 249 patients for analysis. After IPTW, the population was well balanced. With a median follow up of 36 months, 5-year overall survival (OS) and recurrence-free survival (RFS) for the cohort were 59% and 38%. 146 laparoscopic procedures were performed in 140 patients, with weighted 5-year OS and RFS of 54% and 36% respectively. In the open group, 138 procedures were performed in 122 patients, with a weighted 5-year OS and RFS of 63% and 38% respectively. There was no significant difference between the two groups in terms of OS or RFS. In the Brisbane experience, after accounting for bias in treatment assignment, long term survival after LLR for CLM is equivalent to outcomes in open surgery. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Long-term survival in laparoscopic vs open resection for colorectal liver metastases: inverse probability of treatment weighting using propensity scores

PubMed Central

Lewin, Joel W.; O'Rourke, Nicholas A.; Chiow, Adrian K.H.; Bryant, Richard; Martin, Ian; Nathanson, Leslie K.; Cavallucci, David J.

2015-01-01

Background This study compares long-term outcomes between intention-to-treat laparoscopic and open approaches to colorectal liver metastases (CLM), using inverse probability of treatment weighting (IPTW) based on propensity scores to control for selection bias. Method Patients undergoing liver resection for CLM by 5 surgeons at 3 institutions from 2000 to early 2014 were analysed. IPTW based on propensity scores were generated and used to assess the marginal treatment effect of the laparoscopic approach via a weighted Cox proportional hazards model. Results A total of 298 operations were performed in 256 patients. 7 patients with planned two-stage resections were excluded leaving 284 operations in 249 patients for analysis. After IPTW, the population was well balanced. With a median follow up of 36 months, 5-year overall survival (OS) and recurrence-free survival (RFS) for the cohort were 59% and 38%. 146 laparoscopic procedures were performed in 140 patients, with weighted 5-year OS and RFS of 54% and 36% respectively. In the open group, 138 procedures were performed in 122 patients, with a weighted 5-year OS and RFS of 63% and 38% respectively. There was no significant difference between the two groups in terms of OS or RFS. Conclusion In the Brisbane experience, after accounting for bias in treatment assignment, long term survival after LLR for CLM is equivalent to outcomes in open surgery. PMID:26902138

Open-loop-feedback control of serum drug concentrations: pharmacokinetic approaches to drug therapy.

PubMed

Jelliffe, R W

1983-01-01

Recent developments to optimize open-loop-feedback control of drug dosage regimens, generally applicable to pharmacokinetically oriented therapy with many drugs, involve computation of patient-individualized strategies for obtaining desired serum drug concentrations. Analyses of past therapy are performed by least squares, extended least squares, and maximum a posteriori probability Bayesian methods of fitting pharmacokinetic models to serum level data. Future possibilities for truly optimal open-loop-feedback therapy with full Bayesian methods, and conceivably for optimal closed-loop therapy in such data-poor clinical situations, are also discussed. Implementation of these various therapeutic strategies, using automated, locally controlled infusion devices, has also been achieved in prototype form.

The germicidal effect of the open air in different parts of The Netherlands.

PubMed Central

de Mik, G.; de Groot, I.

1977-01-01

Using the microthread technique the survival of Escherichia coli MRE 162 in open air was measured in different parts of The Netherlands. The presence of bactericidal compounds (open air factor = OAF) could be demonstrated on several days and quantitated in relative units of OAF concentration. In the absence of ozone the OAF concentration was always low. In the presence of ozone the OAF concentration was dependent on wind direction. At the selected microthread exposure sites air from areas with high traffic intensity contributed more to OAF production than air from industrial areas. OAF production is probably related to the nature of hydrocarbons in the air. Images Fig. 4 Fig. 5 PMID:321676

Environmental Health Risks and Housing Values: Evidence from 1,600 Toxic Plant Openings and Closings†

PubMed Central

Currie, Janet; Davis, Lucas; Greenstone, Michael

2016-01-01

Regulatory oversight of toxic emissions from industrial plants and understanding about these emissions’ impacts are in their infancy. Applying a research design based on the openings and closings of 1,600 industrial plants to rich data on housing markets and infant health, we find that: toxic air emissions affect air quality only within 1 mile of the plant; plant openings lead to 11 percent declines in housing values within 0.5 mile or a loss of about $4.25 million for these households; and a plant’s operation is associated with a roughly 3 percent increase in the probability of low birthweight within 1 mile. PMID:27134284

Dual regulation of the native ClC-K2 chloride channel in the distal nephron by voltage and pH

PubMed Central

Pinelli, Laurent; Nissant, Antoine; Edwards, Aurélie; Paulais, Marc

2016-01-01

ClC-K2, a member of the ClC family of Cl− channels and transporters, forms the major basolateral Cl− conductance in distal nephron epithelial cells and therefore plays a central role in renal Cl− absorption. However, its regulation remains largely unknown because of the fact that recombinant ClC-K2 has not yet been studied at the single-channel level. In the present study, we investigate the effects of voltage, pH, Cl−, and Ca2+ on native ClC-K2 in the basolateral membrane of intercalated cells from the mouse connecting tubule. The ∼10-pS channel shows a steep voltage dependence such that channel activity increases with membrane depolarization. Intracellular pH (pHi) and extracellular pH (pHo) differentially modulate the voltage dependence curve: alkaline pHi flattens the curve by causing an increase in activity at negative voltages, whereas alkaline pHo shifts the curve toward negative voltages. In addition, pHi, pHo, and extracellular Ca2+ strongly increase activity, mainly because of an increase in the number of active channels with a comparatively minor effect on channel open probability. Furthermore, voltage alters both the number of active channels and their open probability, whereas intracellular Cl− has little influence. We propose that changes in the number of active channels correspond to them entering or leaving an inactivated state, whereas modulation of open probability corresponds to common gating by these channels. We suggest that pH, through the combined effects of pHi and pHo on ClC-K2, might be a key regulator of NaCl absorption and Cl−/HCO3− exchange in type B intercalated cells. PMID:27574292

Dual regulation of the native ClC-K2 chloride channel in the distal nephron by voltage and pH.

PubMed

Pinelli, Laurent; Nissant, Antoine; Edwards, Aurélie; Lourdel, Stéphane; Teulon, Jacques; Paulais, Marc

2016-09-01

ClC-K2, a member of the ClC family of Cl(-) channels and transporters, forms the major basolateral Cl(-) conductance in distal nephron epithelial cells and therefore plays a central role in renal Cl(-) absorption. However, its regulation remains largely unknown because of the fact that recombinant ClC-K2 has not yet been studied at the single-channel level. In the present study, we investigate the effects of voltage, pH, Cl(-), and Ca(2+) on native ClC-K2 in the basolateral membrane of intercalated cells from the mouse connecting tubule. The ∼10-pS channel shows a steep voltage dependence such that channel activity increases with membrane depolarization. Intracellular pH (pHi) and extracellular pH (pHo) differentially modulate the voltage dependence curve: alkaline pHi flattens the curve by causing an increase in activity at negative voltages, whereas alkaline pHo shifts the curve toward negative voltages. In addition, pHi, pHo, and extracellular Ca(2+) strongly increase activity, mainly because of an increase in the number of active channels with a comparatively minor effect on channel open probability. Furthermore, voltage alters both the number of active channels and their open probability, whereas intracellular Cl(-) has little influence. We propose that changes in the number of active channels correspond to them entering or leaving an inactivated state, whereas modulation of open probability corresponds to common gating by these channels. We suggest that pH, through the combined effects of pHi and pHo on ClC-K2, might be a key regulator of NaCl absorption and Cl(-)/HCO3 (-) exchange in type B intercalated cells. © 2016 Pinelli et al.

From axiomatics of quantum probability to modelling geological uncertainty and management of intelligent hydrocarbon reservoirs with the theory of open quantum systems.

PubMed

Lozada Aguilar, Miguel Ángel; Khrennikov, Andrei; Oleschko, Klaudia

2018-04-28

As was recently shown by the authors, quantum probability theory can be used for the modelling of the process of decision-making (e.g. probabilistic risk analysis) for macroscopic geophysical structures such as hydrocarbon reservoirs. This approach can be considered as a geophysical realization of Hilbert's programme on axiomatization of statistical models in physics (the famous sixth Hilbert problem). In this conceptual paper , we continue development of this approach to decision-making under uncertainty which is generated by complexity, variability, heterogeneity, anisotropy, as well as the restrictions to accessibility of subsurface structures. The belief state of a geological expert about the potential of exploring a hydrocarbon reservoir is continuously updated by outputs of measurements, and selection of mathematical models and scales of numerical simulation. These outputs can be treated as signals from the information environment E The dynamics of the belief state can be modelled with the aid of the theory of open quantum systems: a quantum state (representing uncertainty in beliefs) is dynamically modified through coupling with E ; stabilization to a steady state determines a decision strategy. In this paper, the process of decision-making about hydrocarbon reservoirs (e.g. 'explore or not?'; 'open new well or not?'; 'contaminated by water or not?'; 'double or triple porosity medium?') is modelled by using the Gorini-Kossakowski-Sudarshan-Lindblad equation. In our model, this equation describes the evolution of experts' predictions about a geophysical structure. We proceed with the information approach to quantum theory and the subjective interpretation of quantum probabilities (due to quantum Bayesianism).This article is part of the theme issue 'Hilbert's sixth problem'. © 2018 The Author(s).

From axiomatics of quantum probability to modelling geological uncertainty and management of intelligent hydrocarbon reservoirs with the theory of open quantum systems

NASA Astrophysics Data System (ADS)

Lozada Aguilar, Miguel Ángel; Khrennikov, Andrei; Oleschko, Klaudia

2018-04-01

As was recently shown by the authors, quantum probability theory can be used for the modelling of the process of decision-making (e.g. probabilistic risk analysis) for macroscopic geophysical structures such as hydrocarbon reservoirs. This approach can be considered as a geophysical realization of Hilbert's programme on axiomatization of statistical models in physics (the famous sixth Hilbert problem). In this conceptual paper, we continue development of this approach to decision-making under uncertainty which is generated by complexity, variability, heterogeneity, anisotropy, as well as the restrictions to accessibility of subsurface structures. The belief state of a geological expert about the potential of exploring a hydrocarbon reservoir is continuously updated by outputs of measurements, and selection of mathematical models and scales of numerical simulation. These outputs can be treated as signals from the information environment E. The dynamics of the belief state can be modelled with the aid of the theory of open quantum systems: a quantum state (representing uncertainty in beliefs) is dynamically modified through coupling with E; stabilization to a steady state determines a decision strategy. In this paper, the process of decision-making about hydrocarbon reservoirs (e.g. `explore or not?'; `open new well or not?'; `contaminated by water or not?'; `double or triple porosity medium?') is modelled by using the Gorini-Kossakowski-Sudarshan-Lindblad equation. In our model, this equation describes the evolution of experts' predictions about a geophysical structure. We proceed with the information approach to quantum theory and the subjective interpretation of quantum probabilities (due to quantum Bayesianism). This article is part of the theme issue `Hilbert's sixth problem'.

Properties of the Open Cluster Tombaugh 1 from High-resolution Spectroscopy and uvbyCaHβ Photometry

NASA Astrophysics Data System (ADS)

Sales Silva, João V.; Carraro, Giovanni; Anthony-Twarog, Barbara J.; Moni Bidin, Christian; Costa, Edgardo; Twarog, Bruce A.

2016-01-01

Open clusters can be the key to deepening our knowledge on various issues involving the structure and evolution of the Galactic disk and details of stellar evolution because a cluster’s properties are applicable to all its members. However, the number of open clusters with detailed analysis from high-resolution spectroscopy or precision photometry imposes severe limitations on studies of these objects. To expand the number of open clusters with well-defined chemical abundances and fundamental parameters, we investigate the poorly studied, anticenter open cluster Tombaugh 1. Using precision uvbyCaHβ photometry and high-resolution spectroscopy, we derive the cluster’s reddening, obtain photometric metallicity estimates, and, for the first time, present a detailed abundance analysis of 10 potential cluster stars (nine clump stars and one Cepheid). Using the radial position from the cluster center and multiple color indices, we have isolated a sample of unevolved, probable single-star members of Tombaugh 1. From 51 stars, the cluster reddening is found to be E(b-y) = 0.221 ± 0.006 or E(B-V) = 0.303 ± 0.008, where the errors refer to the internal standard errors of the mean. The weighted photometric metallicity from m1 and hk is [Fe/H] = -0.10 ± 0.02, while a match to the Victoria-Regina Strömgren isochrones leads to an age of 0.95 ± 0.10 Gyr and an apparent modulus of (m-M) = 13.10 ± 0.10. Radial velocities identify six giants as probable cluster members, and the elemental abundances of Fe, Na, Mg, Al, Si, Ca, Ti, Cr, Ni, Y, Ba, Ce, and Nd have been derived for both the cluster and the field stars. Tombaugh 1 appears to be a typical inner thin disk, intermediate-age open cluster of slightly subsolar metallicity, located just beyond the solar circle, with solar elemental abundance ratios except for the heavy s-process elements, which are a factor of two above solar. Its metallicity is consistent with a steep metallicity gradient in the galactocentric region between 9.5 and 12 kpc. Our study also shows that Cepheid XZ CMa is not a member of Tombaugh 1 and reveals that this Cepheid presents signs of barium enrichment, making it a probable binary star. Based on observations carried out at Las Campanas Observatory (program ID: CN2009B-042) and Cerro Tololo Inter-American Observatory.

Just War Theory Applied to US Policy in Pakistan and Yemen

DTIC Science & Technology

2014-05-12

cause, proper authority, right intention, last resort, probability of success, proportionality, discrimination . 16. SECURITY CLASSIFICATION OF: 17...21 Discrimination ...theater of conflict opened up. Whether or not the United States made wise decisions in handicapping itself by limiting offensive operations to airstrikes

Update of membership and mean proper motion of open clusters from UCAC5 catalog

NASA Astrophysics Data System (ADS)

Dias, W. S.; Monteiro, H.; Assafin, M.

2018-06-01

We present mean proper motions and membership probabilities of individual stars for optically visible open clusters, which have been determined using data from the UCAC5 catalog. This follows our previous studies with the UCAC2 and UCAC4 catalogs, but now using improved proper motions in the GAIA reference frame. In the present study results were obtained for a sample of 1108 open clusters. For five clusters, this is the first determination of mean proper motion, and for the whole sample, we present results with a much larger number of identified astrometric member stars than on previous studies. It is the last update of our Open cluster Catalog based on proper motion data only. Future updates will count on astrometric, photometric and spectroscopic GAIA data as input for analyses.

The optimisation of occupational potential exposures - preliminary considerations

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

Crouail, P.; Guimaraes, L.

1995-03-01

One of the major innovation brought about the ICRP 60 recommendations and emphasized by the ICRP 64 publication, is the introduction of the concept of potential exposures into the system of radiological protection. Potential exposures are characterized by {open_quotes}probability of occurrence lesser than unity{close_quotes} and {open_quotes}radiological risks exceeding normal levels{close_quotes} where normal must be interpreted as not exceeding the planned routine exposures. It is then necessary to develop consensual methods to look for and choose the optimum scenarios (i.e. those for which probability of events and possible consequences have been reduced as low as reasonably achievable). Moreover, the boundaries formore » the unacceptable levels of risks for workers should be defined, as well as reasonable risk indicators. The aim of this paper is to discuss the actual changes in the field of occupational radiological protection, induced by the potential exposure concept with particular emphasize on the optimization of protection.« less

A QUANTITATIVE ANALYSIS OF DISTANT OPEN CLUSTERS

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

Janes, Kenneth A.; Hoq, Sadia

2011-03-15

The oldest open star clusters are important for tracing the history of the Galactic disk, but many of the more distant clusters are heavily reddened and projected against the rich stellar background of the Galaxy. We have undertaken an investigation of several distant clusters (Berkeley 19, Berkeley 44, King 25, NGC 6802, NGC 6827, Berkeley 52, Berkeley 56, NGC 7142, NGC 7245, and King 9) to develop procedures for separating probable cluster members from the background field. We next created a simple quantitative approach for finding approximate cluster distances, reddenings, and ages. We first conclude that with the possible exceptionmore » of King 25 they are probably all physical clusters. We also find that for these distant clusters our typical errors are about {+-}0.07 in E(B - V), {+-}0.15 in log(age), and {+-}0.25 in (m - M){sub o}. The clusters range in age from 470 Myr to 7 Gyr and range from 7.1 to 16.4 kpc from the Galactic center.« less

Point of data saturation was assessed using resampling methods in a survey with open-ended questions.

PubMed

Tran, Viet-Thi; Porcher, Raphael; Falissard, Bruno; Ravaud, Philippe

2016-12-01

To describe methods to determine sample sizes in surveys using open-ended questions and to assess how resampling methods can be used to determine data saturation in these surveys. We searched the literature for surveys with open-ended questions and assessed the methods used to determine sample size in 100 studies selected at random. Then, we used Monte Carlo simulations on data from a previous study on the burden of treatment to assess the probability of identifying new themes as a function of the number of patients recruited. In the literature, 85% of researchers used a convenience sample, with a median size of 167 participants (interquartile range [IQR] = 69-406). In our simulation study, the probability of identifying at least one new theme for the next included subject was 32%, 24%, and 12% after the inclusion of 30, 50, and 100 subjects, respectively. The inclusion of 150 participants at random resulted in the identification of 92% themes (IQR = 91-93%) identified in the original study. In our study, data saturation was most certainly reached for samples >150 participants. Our method may be used to determine when to continue the study to find new themes or stop because of futility. Copyright © 2016 Elsevier Inc. All rights reserved.

Deep sediment resuspension and thick nepheloid layer generation by open-ocean convection

NASA Astrophysics Data System (ADS)

Durrieu de Madron, X.; Ramondenc, S.; Berline, L.; Houpert, L.; Bosse, A.; Martini, S.; Guidi, L.; Conan, P.; Curtil, C.; Delsaut, N.; Kunesch, S.; Ghiglione, J. F.; Marsaleix, P.; Pujo-Pay, M.; Séverin, T.; Testor, P.; Tamburini, C.

2017-03-01

The Gulf of Lions in the northwestern Mediterranean is one of the few sites around the world ocean exhibiting deep open-ocean convection. Based on 6 year long (2009-2015) time series from a mooring in the convection region, shipborne measurements from repeated cruises, from 2012 to 2015, and glider measurements, we report evidence of bottom thick nepheloid layer formation, which is coincident with deep sediment resuspension induced by bottom-reaching convection events. This bottom nepheloid layer, which presents a maximum thickness of more than 2000 m in the center of the convection region, probably results from the action of cyclonic eddies that are formed during the convection period and can persist within their core while they travel through the basin. The residence time of this bottom nepheloid layer appears to be less than a year. In situ measurements of suspended particle size further indicate that the bottom nepheloid layer is primarily composed of aggregates between 100 and 1000 µm in diameter, probably constituted of fine silts. Bottom-reaching open ocean convection, as well as deep dense shelf water cascading that occurred concurrently some years, lead to recurring deep sediments resuspension episodes. They are key mechanisms that control the concentration and characteristics of the suspended particulate matter in the basin, and in turn affect the bathypelagic biological activity.

Solid rocket propellant waste disposal/ingredient recovery study

NASA Technical Reports Server (NTRS)

Mcintosh, M. J.

1976-01-01

A comparison of facility and operating costs of alternate methods shows open burning to be the lowest cost incineration method of waste propellant disposal. The selection, development, and implementation of an acceptable alternate is recommended. The recovery of ingredients from waste propellant has the probability of being able to pay its way, and even show a profit, when large consistent quantities of composite propellant are available. Ingredients recovered from space shuttle waste propellant would be worth over $1.5 million. Open and controlled burning are both energy wasteful.

Aquatic Plant Control Research Program. Large-Scale Operations Management Test of Use of the White Amur for Control of Problem Aquatic Plants. The Herpetofauna of Lake Conway: Species Accounts.

DTIC Science & Technology

1983-07-01

complex suite of physiological and 39 respiratory adaptations (Ultch 1976) enable this species to occupy both open water and littoral zone environments...be an adaptation to avoid fish predation on juveniles in open water and may explain the spring peak in funnel trap captures near shore (Fig. 10). 79...population of C. picta probably is not established on Lake Conway. The one collected individual 103 defecated gastropod (Viviparous sp.) shells and

Irreversible temperature gating in trpv1 sheds light on channel activation

PubMed Central

Sánchez-Moreno, Ana; Guevara-Hernández, Eduardo; Contreras-Cervera, Ricardo; Rangel-Yescas, Gisela; Ladrón-de-Guevara, Ernesto; Rosenbaum, Tamara

2018-01-01

Temperature-activated TRP channels or thermoTRPs are among the only proteins that can directly convert temperature changes into changes in channel open probability. In spite of a wealth of functional and structural information, the mechanism of temperature activation remains unknown. We have carefully characterized the repeated activation of TRPV1 by thermal stimuli and discovered a previously unknown inactivation process, which is irreversible. We propose that this form of gating in TRPV1 channels is a consequence of the heat absorption process that leads to channel opening. PMID:29869983

Detection of Sea Ice and Open Water from RADARSAT-2 Images for Data Assimilation

NASA Astrophysics Data System (ADS)

Komarov, A.; Buehner, M.

2016-12-01

Automated detection of sea ice and open water from SAR data is very important for further assimilation into coupled ocean-sea ice-atmosphere numerical models, such as the Regional Ice-Ocean Prediction System being implemented at the Environment and Climate Change Canada. Conventional classification approaches based on various learning techniques are found to be limited by the fact that they typically do not indicate the level of confidence for ice and water retrievals. Meanwhile, only ice/water retrievals with a very high level of confidence are allowed to be assimilated into the sea ice model to avoid propagating and magnifying errors into the numerical prediction system. In this study we developed a new technique for ice and water detection from dual-polarization RADARSAT-2 HH-HV images which provides the probability of ice/water at a given location. We collected many hundreds of thousands of SAR signatures over various sea ice types (i.e. new, grey, first-year, and multi-year ice) and open water from all available RADARSAT-2 images and the corresponding Canadian Ice Service Image Analysis products over the period from November 2010 to May 2016. Our analysis of the dataset revealed that ice/water separation can be effectively performed in the space of SAR-based variables independent of the incidence angle and noise floor (such as texture measures) and auxiliary Global Environmental Multiscale Model parameters (such as surface wind speed). Choice of the parameters will be specifically discussed in the presentation. An ice probability empirical model as a function of the selected predictors was built in a form of logistic regression, based on the training dataset from 2012 to 2016. The developed ice probability model showed very good performance on the independent testing subset (year 2011). With the ice/water probability threshold of 0.95 reflecting a very high level of confidence, 79% of the testing ice and water samples were classified with the accuracy of 99%. These results are particularly important in light of the upcoming RADARSAT Constellation mission which will drastically increase the amount of SAR data over the Arctic region.

Simulation study of traffic car accidents at a single lane roundabout

NASA Astrophysics Data System (ADS)

Echab, H.; Lakouari, N.; Ez-Zahraouy, H.; Benyoussef, A.

2016-07-01

In this paper, using the Nagel-Schreckenberg model, we numerically investigate the probability Pac of entering/circulating car accidents to occur at single-lane roundabout under the expanded open boundary. The roundabout consists of N on-ramps (respectively, off-ramps). The boundary is controlled by the injecting rates α1,α2 and the extracting rate β. The simulation results show that, depending on the injecting rates, the car accidents are more likely to happen when the capacity of the rotary is set to its maximum. Moreover, we found that the large values of rotary size L and the probability of preferential Pexit are reliable to improve safety and reduce accidents. However, the usage of indicator, the increase of β and/or N provokes an increase of car accident probability.

Persistence and extinction for a class of stochastic SIS epidemic models with nonlinear incidence rate

NASA Astrophysics Data System (ADS)

Teng, Zhidong; Wang, Lei

2016-06-01

In this paper, a class of stochastic SIS epidemic models with nonlinear incidence rate is investigated. It is shown that the extinction and persistence of the disease in probability are determined by a threshold value R˜0. That is, if R˜0 < 1 and an additional condition holds then disease dies out, and if R˜0 > 1 then disease is weak permanent with probability one. To obtain the permanence in the mean of the disease, a new quantity R̂0 is introduced, and it is proved that if R̂0 > 1 the disease is permanent in the mean with probability one. Furthermore, the numerical simulations are presented to illustrate some open problems given in Remarks 1-3 and 5 of this paper.

Exact Maximum-Entropy Estimation with Feynman Diagrams

NASA Astrophysics Data System (ADS)

Netser Zernik, Amitai; Schlank, Tomer M.; Tessler, Ran J.

2018-02-01

A longstanding open problem in statistics is finding an explicit expression for the probability measure which maximizes entropy with respect to given constraints. In this paper a solution to this problem is found, using perturbative Feynman calculus. The explicit expression is given as a sum over weighted trees.

Evidence for a separate mechanism of toxicity for the Type I and the Type II pyrethroid insecticides.

PubMed

Breckenridge, Charles B; Holden, Larry; Sturgess, Nicholas; Weiner, Myra; Sheets, Larry; Sargent, Dana; Soderlund, David M; Choi, Jin-Sung; Symington, Steve; Clark, J Marshall; Burr, Steve; Ray, David

2009-11-01

Neurotoxicity and mechanistic data were collected for six alpha-cyano pyrethroids (beta-cyfluthrin, cypermethrin, deltamethrin, esfenvalerate, fenpropathrin and lambda-cyhalothrin) and up to six non-cyano containing pyrethroids (bifenthrin, S-bioallethrin [or allethrin], permethrin, pyrethrins, resmethrin [or its cis-isomer, cismethrin] and tefluthrin under standard conditions. Factor analysis and multivariate dissimilarity analysis were employed to evaluate four independent data sets comprised of (1) fifty-six behavioral and physiological parameters from an acute neurotoxicity functional observatory battery (FOB), (2) eight electrophysiological parameters from voltage clamp experiments conducted on the Na(v)1.8 sodium channel expressed in Xenopus oocytes, (3) indices of efficacy, potency and binding calculated for calcium ion influx across neuronal membranes, membrane depolarization and glutamate released from rat brain synaptosomes and (4) changes in chloride channel open state probability using a patch voltage clamp technique for membranes isolated from mouse neuroblastoma cells. The pyrethroids segregated into Type I (T--syndrome-tremors) and Type II (CS syndrome--choreoathetosis with salivation) groups based on FOB data. Of the alpha-cyano pyrethroids, deltamethrin, lambda-cyhalothrin, cyfluthrin and cypermethrin arrayed themselves strongly in a dose-dependent manner along two factors that characterize the CS syndrome. Esfenvalerate and fenpropathrin displayed weaker response profiles compared to the non-cyano pyrethroids. Visual clustering on multidimensional scaling (MDS) maps based upon sodium ion channel and calcium influx and glutamate release dissimilarities gave similar groupings. The non-cyano containing pyrethroids were arrayed in a dose-dependent manner along two different factors that characterize the T-syndrome. Bifenthrin was an outlier when MDS maps of the non-cyano pyrethroids were based on sodium ion channel characteristics and permethrin was an outlier when the MDS maps were based on calcium influx/glutamate release potency. Four of six alpha-cyano pyrethroids (lambda-cyfluthrin, cypermethrin, deltamethrin and fenpropathrin) reduced open chloride channel probability. The R-isomers of lambda-l-cyhalothrin reduced open channel probability whereas the S-isomers, antagonized the action of the R-isomers. None of the non-cyano pyrethroids reduced open channel probability, except bioallethrin, which gave a weak response. Overall, based upon neurotoxicity data and the effect of pyrethroids on sodium, calcium and chloride ion channels, it is proposed that bioallethrin, cismethrin, tefluthrin, bifenthrin and permethrin belong to one common mechanism group and deltamethrin, lambda-cyhalothrin, cyfluthrin and cypermethrin belong to a second. Fenpropathrin and esfenvalerate occupy an intermediate position between these two groups.

Higher-dimensional attractors with absolutely continuous invariant probability

NASA Astrophysics Data System (ADS)

Bocker, Carlos; Bortolotti, Ricardo

2018-05-01

Consider a dynamical system given by , where E is a linear expanding map of , C is a linear contracting map of and f is in . We provide sufficient conditions for E that imply the existence of an open set of pairs for which the corresponding dynamic T admits a unique absolutely continuous invariant probability. A geometrical characteristic of transversality between self-intersections of images of is present in the dynamic of the maps in . In addition, we give a condition between E and C under which it is possible to perturb f to obtain a pair in .

Exact joint density-current probability function for the asymmetric exclusion process.

PubMed

Depken, Martin; Stinchcombe, Robin

2004-07-23

We study the asymmetric simple exclusion process with open boundaries and derive the exact form of the joint probability function for the occupation number and the current through the system. We further consider the thermodynamic limit, showing that the resulting distribution is non-Gaussian and that the density fluctuations have a discontinuity at the continuous phase transition, while the current fluctuations are continuous. The derivations are performed by using the standard operator algebraic approach and by the introduction of new operators satisfying a modified version of the original algebra. Copyright 2004 The American Physical Society

The β1 Subunit Enhances Oxidative Regulation of Large-Conductance Calcium-activated K+ Channels

PubMed Central

Santarelli, Lindsey Ciali; Chen, Jianguo; Heinemann, Stefan H.; Hoshi, Toshinori

2004-01-01

Oxidative stress may alter the functions of many proteins including the Slo1 large conductance calcium-activated potassium channel (BKCa). Previous results demonstrated that in the virtual absence of Ca2+, the oxidant chloramine-T (Ch-T), without the involvement of cysteine oxidation, increases the open probability and slows the deactivation of BKCa channels formed by human Slo1 (hSlo1) α subunits alone. Because native BKCa channel complexes may include the auxiliary subunit β1, we investigated whether β1 influences the oxidative regulation of hSlo1. Oxidation by Ch-T with β1 present shifted the half-activation voltage much further in the hyperpolarizing direction (−75 mV) as compared with that with α alone (−30 mV). This shift was eliminated in the presence of high [Ca2+]i, but the increase in open probability in the virtual absence of Ca2+ remained significant at physiologically relevant voltages. Furthermore, the slowing of channel deactivation after oxidation was even more dramatic in the presence of β1. Oxidation of cysteine and methionine residues within β1 was not involved in these potentiated effects because expression of mutant β1 subunits lacking cysteine or methionine residues produced results similar to those with wild-type β1. Unlike the results with α alone, oxidation by Ch-T caused a significant acceleration of channel activation only when β1 was present. The β1 M177 mutation disrupted normal channel activation and prevented the Ch-T–induced acceleration of activation. Overall, the functional effects of oxidation of the hSlo1 pore-forming α subunit are greatly amplified by the presence of β1, which leads to the additional increase in channel open probability and the slowing of deactivation. Furthermore, M177 within β1 is a critical structural determinant of channel activation and oxidative sensitivity. Together, the oxidized BKCa channel complex with β1 has a considerable chance of being open within the physiological voltage range even at low [Ca2+]i. PMID:15452197

Holocene environmental and climatic changes at Gorgo Basso, a coastal lake in southern Sicily, Italy

NASA Astrophysics Data System (ADS)

Tinner, Willy; van Leeuwen, Jacqueline F. N.; Colombaroli, Daniele; Vescovi, Elisa; van der Knaap, W. O.; Henne, Paul D.; Pasta, Salvatore; D'Angelo, Stefania; La Mantia, Tommaso

2009-07-01

We used a new sedimentary record to reconstruct the Holocene vegetation and fire history of Gorgo Basso, a coastal lake in south-western Sicily (Italy). Pollen and charcoal data suggest a fire-prone open grassland near the site until ca 10,000 cal yr BP (8050 cal BC), when Pistacia shrubland expanded and fire activity declined, probably in response to increased moisture availability. Evergreen Olea europaea woods expanded ca 8400 to decline abruptly at 8200 cal yr BP, when climatic conditions became drier at other sites in the Mediterranean region. Around 7000 cal yr BP evergreen broadleaved forests ( Quercus ilex, Quercus suber and O. europaea) expanded at the cost of open communities. The expansion of evergreen broadleaved forests was associated with a decline of fire and of local Neolithic ( Ficus carica-Cerealia based) agriculture that had initiated ca 500 years earlier. Vegetational, fire and land-use changes ca 7000 cal yr BP were probably caused by increased precipitation that resulted from (insolation-forced) weakening of the monsoon and Hadley circulation ca 8000-6000 cal yr BP. Low fire activity and dense coastal evergreen forests persisted until renewed human activity (probably Greek, respectively Roman colonists) disrupted the forest ca 2700 cal yr BP (750 BC) and 2100 cal yr BP (150 BC) to gain open land for agriculture. The intense use of fire for this purpose induced the expansion of open maquis, garrigue, and grassland-prairie environments (with an increasing abundance of the native palm Chamaerops humilis). Prehistoric land-use phases after the Bronze Age seem synchronous with those at other sites in southern and central Europe, possibly as a result of climatic forcing. Considering the response of vegetation to Holocene climatic variability as well as human impact we conclude that under (semi-)natural conditions evergreen broadleaved Q. ilex- O. europaea (s.l.) forests would still dominate near Gorgo Basso. However, forecasted climate change and aridification may lead to a situation similar to that before 7000 cal yr BP and thus trigger a rapid collapse of the few relict evergreen broadleaved woodlands in coastal Sicily and elsewhere in the southern Mediterranean region.

Multistate and multihypothesis discrimination with open quantum systems

NASA Astrophysics Data System (ADS)

Kiilerich, Alexander Holm; Mølmer, Klaus

2018-05-01

We show how an upper bound for the ability to discriminate any number N of candidates for the Hamiltonian governing the evolution of an open quantum system may be calculated by numerically efficient means. Our method applies an effective master-equation analysis to evaluate the pairwise overlaps between candidate full states of the system and its environment pertaining to the Hamiltonians. These overlaps are then used to construct an N -dimensional representation of the states. The optimal positive-operator valued measure (POVM) and the corresponding probability of assigning a false hypothesis may subsequently be evaluated by phrasing optimal discrimination of multiple nonorthogonal quantum states as a semidefinite programming problem. We provide three realistic examples of multihypothesis testing with open quantum systems.

Disc displacement without reduction: a retrospective study of a clinical diagnostic sign.

PubMed

Giraudeau, Anne; Jeany, Marion; Ehrmann, Elodie; Déjou, Jacques; Ouni, Imed; Orthlieb, Jean-Daniel

2017-03-01

The purpose of this retrospective study is to evaluate a clinical diagnostic sign for disc displacement without reduction (DDWR), the absence of additional condylar translation during opening compared with protrusion. Thirty-eight electronic axiographic and magnetic resonance imaging (MRI) examinations of the TMJ were analyzed in order to compare the opening/protrusion ratio of condylar translation between non-painful DDWR and non-DDWR. According to the Mann-Whitney U test, the opening/protrusion ratio in non-painful DDWR differs significantly from non-DDWR (p < 0.0001). Among non-painful DDWR, there is no additional condylar translation during opening in comparison with protrusion, and this is probably also the case for DDWR without limited opening, which is a subtype that has not been validated by the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). Comparative condylar palpation can analyze this sign, and therefore, further comparative investigations between MRI and clinical examination are needed to validate the corresponding clinical test.

InSAR analysis for detecting the route of hydrothermal fluid to the surface during the 2015 phreatic eruption of Hakone Volcano, Japan

NASA Astrophysics Data System (ADS)

Doke, Ryosuke; Harada, Masatake; Mannen, Kazutaka; Itadera, Kazuhiro; Takenaka, Jun

2018-04-01

Although the 2015 Hakone Volcano eruption was a small-scale phreatic eruption with a discharged mass of only about 100 tons, interferometric synthetic aperture radar successfully detected surface deformations related to the eruption. Inversion model of the underground hydrothermal system based on measured ground displacements by ALOS-2/PALSAR-2 images showed that a crack opened at an elevation of about 530-830 m, probably at the time of the eruption. A geomorphological analysis detected several old NW-SE trending fissures, and the open crack was located just beneath one of the fissures. Thus, the crack that opened during the 2015 eruption could have been a preexisting crack that formed during a more voluminous hydrothermal eruption. In addition, the inversion model implies that a sill deflation occurred at an elevation of about 225 m, probably at the time of the eruption. The deflation of sill-like body represents a preexisting hydrothermal reservoir at an elevation of 100-400 m, which intruded fluid in the open crack prior to eruption. The volume changes of the open crack and the sill were calculated to be 1.14 × 105 m3 (inflation) and 0.49 × 105 m3 (deflation), respectively. A very local swelling (about 200 m in diameter) was also detected at the eruption center 2 months before the eruption. The local swelling, whose rate in satellite line-of-sight was 0.7-0.9 cm/day during May 2015 and declined in June, had been monitored until the time of the eruption, when its uplift halted. This was modeled as a point pressure source at an elevation of about 900 m (at a depth of about 80-90 m from the ground surface) and is considered to be a minor hydrothermal reservoir just beneath the fumarolic field. Our analysis shows that the northernmost tip of the open crack reached within 200 m of the surface. Thus, it is reasonable to assume that the hydrothermal fluid in the open crack found a way to the surface and formed the eruption.[Figure not available: see fulltext.

Steady-state kinetics of solitary batrachotoxin-treated sodium channels. Kinetics on a bounded continuum of polymer conformations.

PubMed Central

Rubinson, K A

1992-01-01

The underlying principles of the kinetics and equilibrium of a solitary sodium channel in the steady state are examined. Both the open and closed kinetics are postulated to result from round-trip excursions from a transition region that separates the openable and closed forms. Exponential behavior of the kinetics can have origins different from small-molecule systems. These differences suggest that the probability density functions (PDFs) that describe the time dependences of the open and closed forms arise from a distribution of rate constants. The distribution is likely to arise from a thermal modulation of the channel structure, and this provides a physical basis for the following three-variable equation: [formula; see text] Here, A0 is a scaling term, k is the mean rate constant, and sigma quantifies the Gaussian spread for the contributions of a range of effective rate constants. The maximum contribution is made by k, with rates faster and slower contributing less. (When sigma, the standard deviation of the spread, goes to zero, then p(f) = A0 e-kt.) The equation is applied to the single-channel steady-state probability density functions for batrachotoxin-treated sodium channels (1986. Keller et al. J. Gen. Physiol. 88: 1-23). The following characteristics are found: (a) The data for both open and closed forms of the channel are fit well with the above equation, which represents a Gaussian distribution of first-order rate processes. (b) The simple relationship [formula; see text] holds for the mean effective rat constants. Or, equivalently stated, the values of P open calculated from the k values closely agree with the P open values found directly from the PDF data. (c) In agreement with the known behavior of voltage-dependent rate constants, the voltage dependences of the mean effective rate constants for the opening and closing of the channel are equal and opposite over the voltage range studied. That is, [formula; see text] "Bursts" are related to the well-known cage effect of solution chemistry. PMID:1312365

Selective interference with pacemaker activity by electrical dental devices.

PubMed

Miller, C S; Leonelli, F M; Latham, E

1998-01-01

We sought to determine whether electromagnetic interference with cardiac pacemakers occurs during the operation of contemporary electrical dental equipment. Fourteen electrical dental devices were tested in vitro for their ability to interfere with the function of two Medtronics cardiac pacemakers (one a dual-chamber, bipolar Thera 7942 pacemaker, the other a single-chamber, unipolar Minix 8340 pacemaker). Atrial and ventricular pacemaker output and electrocardiographic activity were monitored by means of telemetry with the use of a Medtronics 9760/90 programmer. Atrial and ventricular pacing were inhibited by electromagnetic interference produced by the electrosurgical unit up to a distance of 10 cm, by the ultrasonic bath cleaner up to 30 cm, and by the magnetorestrictive ultrasonic scalers up to 37.5 cm. In contrast, operation of the amalgamator, electric pulp tester, composite curing light, dental handpieces, electric toothbrush, microwave oven, dental chair and light, ENAC ultrasonic instrument, radiography unit, and sonic scaler did not alter pacing rate or rhythm. These results suggest that certain electrosurgical and ultrasonic instruments may produce deleterious effects in medically fragile patients with cardiac pacemakers.

Mammalian short palate lung and nasal epithelial clone 1 (SPLUNC1) in pH-dependent airway hydration✩

PubMed Central

Tarran, Robert; Redinbo, Matthew R.

2014-01-01

The epithelia that line the conducting airways are the lung’s first point of contact with inhaled pathogens and toxicants. As such, they are known to play an important role in the lung’s innate defense system, which includes (i) the production of airway surface liquid (ASL) that helps cleanse the airways through the physical removal of pathogens and toxicants on the mucociliary escalator and (ii) the secretion of anti-microbial proteins into the ASL to kill inhaled pathogens. Interestingly, the recently crystallized short palate lung and nasal epithelial clone 1 (SPLUNC1) protein appears to be a multi-functional protein. That is, it not only acts as an anti-microbial agent, but also modulates ASL homeostasis by acting as an endogenous inhibitor of the epithelial Na+ channel (ENaC). This review will focus on the latter function of SPLUNC1, and will discuss new structural and physiological data regarding SPLUNC1’s failure to function as a regulator of ASL hydration in CF airways. PMID:24631954

VACUUM TRAP AND VALVE COMBINATION

DOEpatents

Milleron, N.; Levenson, L.

1963-02-19

This patent relates to a vacuum trap and valve combination suitable for use in large ultra-high vacuum systems. The vacuum trap is a chamber having an inlet and outlet opening which may be made to communicate with a chamber to be evacuated and a diffusion pump, respectively. A valve is designed to hermeticaliy seal with inlet opening and, when opened, block the line-of- sight'' between the inlet and outlet openings, while allowing a large flow path between the opened vaive and the side walls of the trap. The interior of the trap and the side of the valve facing the inlet opening are covered with an impurity absorbent, such as Zeolite or activated aluminum. Besides the advantage of combining two components of a vacuum system into one, the present invention removes the need for a baffle between the pump and the chamber to be evacuated. In one use of a specific embodiment of this invention, the transmission probability was 45 and the partial pressure of the pump fluid vapor in the vacuum chamber was at least 100 times lower than its vapor pressure. (AEC)

Detection of the nipple in automated 3D breast ultrasound using coronal slab-average-projection and cumulative probability map

NASA Astrophysics Data System (ADS)

Kim, Hannah; Hong, Helen

2014-03-01

We propose an automatic method for nipple detection on 3D automated breast ultrasound (3D ABUS) images using coronal slab-average-projection and cumulative probability map. First, to identify coronal images that appeared remarkable distinction between nipple-areola region and skin, skewness of each coronal image is measured and the negatively skewed images are selected. Then, coronal slab-average-projection image is reformatted from selected images. Second, to localize nipple-areola region, elliptical ROI covering nipple-areola region is detected using Hough ellipse transform in coronal slab-average-projection image. Finally, to separate the nipple from areola region, 3D Otsu's thresholding is applied to the elliptical ROI and cumulative probability map in the elliptical ROI is generated by assigning high probability to low intensity region. False detected small components are eliminated using morphological opening and the center point of detected nipple region is calculated. Experimental results show that our method provides 94.4% nipple detection rate.

Integrating geological uncertainty in long-term open pit mine production planning by ant colony optimization

NASA Astrophysics Data System (ADS)

Gilani, Seyed-Omid; Sattarvand, Javad

2016-02-01

Meeting production targets in terms of ore quantity and quality is critical for a successful mining operation. In-situ grade uncertainty causes both deviations from production targets and general financial deficits. A new stochastic optimization algorithm based on ant colony optimization (ACO) approach is developed herein to integrate geological uncertainty described through a series of the simulated ore bodies. Two different strategies were developed based on a single predefined probability value (Prob) and multiple probability values (Pro bnt) , respectively in order to improve the initial solutions that created by deterministic ACO procedure. Application at the Sungun copper mine in the northwest of Iran demonstrate the abilities of the stochastic approach to create a single schedule and control the risk of deviating from production targets over time and also increase the project value. A comparison between two strategies and traditional approach illustrates that the multiple probability strategy is able to produce better schedules, however, the single predefined probability is more practical in projects requiring of high flexibility degree.

An Untapped Talent Pool

ERIC Educational Resources Information Center

Weinstein, Margery

2011-01-01

An organization probably prides itself on its openness in finding new talent. It is eager to add people with diverse backgrounds and skills to its roster of employees. Yet, like many companies, it might be hesitant to actively recruit persons with disabilities. Recruiting and integrating these individuals may require greater care, but what an…

Primary Blast Injuries in the Open and in Foxholes Resulting from Nuclear Type Detonations

DTIC Science & Technology

1991-07-01

within a few hours after blast are probably caused by suffocation from blood and fluids obstructing the airways and from intra- abdominal...ATT’N: _-COMIPAQ •.. • - i .• :_ ... . - ARMED FORCES RADIOBIOLOGY RSCH INST ATTN: DEPT OF RADIATION BIOCHEMISTRY INTERSERVICE NUCLEAR WEAPONS SCHOOL

Quantum Information Biology: From Theory of Open Quantum Systems to Adaptive Dynamics

NASA Astrophysics Data System (ADS)

Asano, Masanari; Basieva, Irina; Khrennikov, Andrei; Ohya, Masanori; Tanaka, Yoshiharu; Yamato, Ichiro

This chapter reviews quantum(-like) information biology (QIB). Here biology is treated widely as even covering cognition and its derivatives: psychology and decision making, sociology, and behavioral economics and finances. QIB provides an integrative description of information processing by bio-systems at all scales of life: from proteins and cells to cognition, ecological and social systems. Mathematically QIB is based on the theory of adaptive quantum systems (which covers also open quantum systems). Ideologically QIB is based on the quantum-like (QL) paradigm: complex bio-systems process information in accordance with the laws of quantum information and probability. This paradigm is supported by plenty of statistical bio-data collected at all bio-scales. QIB re ects the two fundamental principles: a) adaptivity; and, b) openness (bio-systems are fundamentally open). In addition, quantum adaptive dynamics provides the most generally possible mathematical representation of these principles.

Velocity and size of droplets in dense region of diesel fuel spray on transient needle opening condition

NASA Astrophysics Data System (ADS)

Ueki, Hironobu; Ishida, Masahiro; Sakaguchi, Daisaku

2005-06-01

In order to investigate the effect of transient needle opening on early stage of spray behavior, simultaneous measurements of velocity and size of droplet were conducted by a newly developed laser 2-focus velocimeter (L2F). The micro-scale probe of the L2F was consisted of two foci with a distance of 36 µm. The tested nozzle had a single hole with a diameter of 0.2 mm. The measurements of injection pressure, needle lift, and crank angle were synchronized with the spray measurement by the L2F at the position 10 mm downstream from the nozzle exit. It has been clearly shown that the velocity and size of droplet increase with needle valve opening and that the probability density distribution of droplet size can be fitted to the Nukiyama-Tanasawa distribution under the transient needle opening condition.

Open magnetic fields in active regions

NASA Technical Reports Server (NTRS)

Svestka, Z.; Solodyna, C. V.; Howard, R.; Levine, R. H.

1977-01-01

Soft X-ray images and magnetograms of several active regions and coronal holes are examined which support the interpretation that some of the dark X-ray gaps seen between interconnecting loops and inner cores of active regions are foot points of open field lines inside the active regions. Characteristics of the investigated dark gaps are summarized. All the active regions with dark X-ray gaps at the proper place and with the correct polarity predicted by global potential extrapolation of photospheric magnetic fields are shown to be old active regions, indicating that field opening is accomplished only in a late phase of active-region development. It is noted that some of the observed dark gaps probably have nothing in common with open fields, but are either due to the decreased temperature in low-lying portions of interconnecting loops or are the roots of higher and less dense or cooler loops.

"An estimate of the probability of vesicle exocytosis in a Monte Carlo model of buffered diffusion of calcium channel currents"

NASA Astrophysics Data System (ADS)

Dimcovic, Z. M.; Eagan, T. P.; Kidane, T. K.; Brown, R. W.; Petschek, R. G.; McEnery, M. W.

2001-10-01

The opening of voltage-dependent calcium channels results in an influx of calcium ions promoting the fusion of synaptic vesicles. The fusion leads to release of neurotransmitters, which in turn allow the propagation of nerve impulses. A Monte Carlo model of the diffusion of calcium following its surge into the cell is used to estimate the probability for exocytosis. Besides the calcium absorption by fixed and mobile buffers, key ingredients are the physical size and position of the tethered vesicle and a sensing model for the interaction of the vesicle and calcium. The release probability is compared to previously published studies where the finite vesicle size was not considered. (Supported by NIH MH55747, AHA 96001250, NSF0086643, and a CWRU Presidential Research Initiative grant.)

The double slit experiment and the time reversed fire alarm

NASA Astrophysics Data System (ADS)

Halabi, Tarek

2011-03-01

When both slits of the double slit experiment are open, closing one paradoxically increases the detection rate at some points on the detection screen. Feynman famously warned that temptation to "understand" such a puzzling feature only draws us into blind alleys. Nevertheless, we gain insight into this feature by drawing an analogy between the double slit experiment and a time reversed fire alarm. Much as closing the slit increases probability of a future detection, ruling out fire drill scenarios, having heard the fire alarm, increases probability of a past fire (using Bayesian inference). Classically, Bayesian inference is associated with computing probabilities of past events. We therefore identify this feature of the double slit experiment with a time reversed thermodynamic arrow. We believe that much of the enigma of quantum mechanics is simply due to some variation of time's arrow.

Cell membrane organization is important for inner hair cell MET-channel gating

NASA Astrophysics Data System (ADS)

Effertz, Thomas; Scharr, Alexandra L.; Ricci, Anthony J.

2018-05-01

Specialized sensory cells, hair cells, translate mechanical stimuli into electro/chemical responses. This process, termed mechano-electrical transduction (MET), is localized to the hair cell's sensory organelle, the hair bundle. The mature hair bundle comprises three rows of actin filled stereocilia, arranged in a staircase pattern. Deflections towards the tallest row of stereocilia activate MET channels, residing at the top of stereocilia. While other MET channels can be activated or modulated by changes to their lipid environment, this remains unknown for the mammalian auditory MET channel. We show here that the effect of lipid and cholesterol depletion from the cell membrane affect the MET current as well. We used γ-cyclodextrin to extract lipids form the membrane, reversibly reducing the peak MET current, current adaptation, and decreasing the channels resting open probability. The recovery after γ-cyclodextrin treatment was slower than the initial peak current reduction, suggesting that a specific lipid organization is required for normal MET channel function, which requires time reestablish. Extraction of cholesterol, using Mβ-cyclodextrin, irreversibly reduces the peak MET current and reversibly increases the channel resting open probability, suggesting that cholesterol restricts MET channel opening. This restriction could be useful to increase the channel's signal to noise ratio. Together this data suggests that the cell membrane is part of the force relay machinery to the MET channel and could possibly restrict gating associated conformational changes of the MET channel.

Irreversible temperature gating in trpv1 sheds light on channel activation.

PubMed

Sánchez-Moreno, Ana; Guevara-Hernández, Eduardo; Contreras-Cervera, Ricardo; Rangel-Yescas, Gisela; Ladrón-de-Guevara, Ernesto; Rosenbaum, Tamara; Islas, León D

2018-06-05

Temperature-activated TRP channels or thermoTRPs are among the only proteins that can directly convert temperature changes into changes in channel open probability. In spite of a wealth of functional and structural information, the mechanism of temperature activation remains unknown. We have carefully characterized the repeated activation of TRPV1 by thermal stimuli and discovered a previously unknown inactivation process, which is irreversible. We propose that this form of gating in TRPV1 channels is a consequence of the heat absorption process that leads to channel opening. © 2018, Sánchez-Moreno et al.

Mechanisms of anionic detergent-induced hemolysis.

PubMed

Chernitsky, E; Senkovich, O

1998-09-01

The effect of osmotic protectors (sucrose and polyethylene glycols) and of a decrease in the detergent concentration at different points of hemolysis of human erythrocytes by sodium dodecyl sulphate on the shape of kinetic curves of hemolysis were studied. It is shown that slow detergent-induced hemolysis follows the colloid-osmotic mechanisms. Evidence is provided that rapid hemolysis by sodium dodecyl sulphate is caused by opening of large pores sufficient for the release of hemoglobin molecules rather than by the colloid-osmotic mechanism, and that the kinetics of hemolysis is mainly determined by time dependence of the opening probability of these pores.

The N253F mutant structure of trehalose synthase from Deinococcus radiodurans reveals an open active-site topology.

PubMed

Chow, Sih Yao; Wang, Yung Lin; Hsieh, Yu Chiao; Lee, Guan Chiun; Liaw, Shwu Huey

2017-11-01

Trehalose synthase (TS) catalyzes the reversible conversion of maltose to trehalose and belongs to glycoside hydrolase family 13 (GH13). Previous mechanistic analysis suggested a rate-limiting protein conformational change, which is probably the opening and closing of the active site. Consistently, crystal structures of Deinococcus radiodurans TS (DrTS) in complex with the inhibitor Tris displayed an enclosed active site for catalysis of the intramoleular isomerization. In this study, the apo structure of the DrTS N253F mutant displays a new open conformation with an empty active site. Analysis of these structures suggests that substrate binding induces a domain rotation to close the active site. Such a substrate-induced domain rotation has also been observed in some other GH13 enzymes.

Effects of selective attention on continuous opinions and discrete decisions

NASA Astrophysics Data System (ADS)

Si, Xia-Meng; Liu, Yun; Xiong, Fei; Zhang, Yan-Chao; Ding, Fei; Cheng, Hui

2010-09-01

Selective attention describes that individuals have a preference on information according to their involving motivation. Based on achievements of social psychology, we propose an opinion interacting model to improve the modeling of individuals’ interacting behaviors. There are two parameters governing the probability of agents interacting with opponents, i.e. individual relevance and time-openness. It is found that, large individual relevance and large time-openness advance the appearance of large clusters, but large individual relevance and small time-openness favor the lessening of extremism. We also put this new model into application to work out some factor leading to a successful product. Numerical simulations show that selective attention, especially individual relevance, cannot be ignored by launcher firms and information spreaders so as to attain the most successful promotion.

[Single channel analysis of aconitine blockade of calcium channels in rat myocardiocytes].

PubMed

Chen, L; Ma, C; Cai, B C; Lu, Y M; Wu, H

1995-01-01

Ventricular myocardiocytes from neonatal Wistar rats were isolated and cultured. Aconitine, Ca2+ channel blocker verapamil or Ca2+ channel activator BAY K8644 were added to the bath solution separately. Using the cell-attached configuration of the patch clamp technique, the single channel activities of L type Ca2+ channel were recorded before and after addition of all three drugs. The results showed the blocking effect of aconitine (50 micrograms.ml-1) on L type Ca2+ channels. Its mechanism may be relevant to the decrease in both open state probability and the mean open time of Ca2+ channel. The difference was statistically significant compared with control group (P < 0.01). The amplitude of Ba2+ currents, which flow through open L type Ca2+ channel was unchanged.

Stacking Oxygen-Separation Cells

NASA Technical Reports Server (NTRS)

Schroeder, James E.

1991-01-01

Simplified configuration and procedure developed for assembly of stacks of solid-electrolyte cells separating oxygen from air electrochemically. Reduces number of components and thus reduces probability of such failures as gas leaks, breakdown of sensitive parts, and electrical open or short circuits. Previous, more complicated version of cell described in "Improved Zirconia Oxygen-Separation Cell" (NPO-16161).

When Using the Mean is Meaningless: Examples from Probability Theory and Cardiology.

ERIC Educational Resources Information Center

Liebovitch, Larry S.; Todorov, Angelo T.; Wood, Mark A.; Ellenbogen, Kenneth A.

This chapter describes how the mean of fractal processes does not exist and is not a meaningful measure of some data. It discusses how important it is to stay open to the possibility that sometimes analytic techniques fail to satisfy some assumptions on which the mean is based. (KHR)

Drupal Done Right

ERIC Educational Resources Information Center

Coombs, Karen

2009-01-01

Drupal is a PHP-and MySQL-based system for managing web sites, developed in 2000 and released in 2001 under the open GNU General Public License (GPL). It is modular, extensible, and scalable. In recent years, Drupal has gained a huge following within libraries as a content management system (CMS). Probably the best-known extension of Drupal in the…

TEACHING COMPOSITION. WHAT RESEARCH SAYS TO THE TEACHER, NUMBER 18.

ERIC Educational Resources Information Center

BURROWS, ALVINA T.

ALTHOUGH CHILDREN'S NEEDS FOR WRITTEN EXPRESSION PROBABLY PARALLEL THOSE OF ADULTS, THE REASON BEHIND CHILDREN'S CHOICE OF WRITING OVER SPEAKING IN GIVEN INSTANCES IS OPEN TO CONJECTURE. MOREOVER, THE COMMON ASSUMPTION BY TEACHERS THAT CHILDREN CAN AND SHOULD WRITE ABOUT PERSONAL INTERESTS OUGHT TO BE TEMPERED BY THE IDEA THAT MANY INTERESTS ARE…

Giant desiccation fissures on the Black Rock and Smoke Creek Deserts, Nevada

USGS Publications Warehouse

Willden, R.; Mabey, D.R.

1961-01-01

Open fissures, from 100 to several hundred feet apart, that have produced polygonal patterns on the Black Rock Desert, Nevada, are believed to be giant desiccation cracks resulting from a secular trend toward aridity in the last few decades. Similar features on the Smoke Creek Desert probably have the same origin.

Using Technology to Support Statistical Reasoning: Birds, Eggs and Times to Hatch

ERIC Educational Resources Information Center

Reeve, Elizabeth; Beswick, Kim

2013-01-01

This article by Elizabeth Reeve and Kim Beswick illustrates how primary children may engage with the Statistics and Probability content contained in the Australian Curriculum. Technology has opened up many possibilities for young children to engage with statistics. In the process the children learned a great deal more than just mathematics.

Lithium acts as a potentiator of AMPAR currents in hippocampal CA1 cells by selectively increasing channel open probability

PubMed Central

Gebhardt, Christine; Cull-Candy, Stuart G

2010-01-01

Recent evidence suggests that lithium, which is used in the treatment of bipolar disorders, may act by influencing AMPAR properties at central glutamatergic synapses. While it is clear that lithium potentiates recombinant AMPAR responses in a subunit specific way, the origin of this potentiation is not known. We examined the effects of lithium on native AMPAR channels in CA1 pyramidal cells in hippocampal slices where AMPARs are expected to be associated with auxiliary subunits. We found that lithium produced a selective increase in single-channel open probability (Popen), with little effect on single-channel conductance or burst length. From the present and previous finding it is likely that lithium causes a reduction in the time to recovery from desensitization, resulting in the observed increase in Popen. This would be consistent with the view that lithium acts like certain other allosteric AMPAR modulators to reduce the time spent in the desensitized state, but differs from those that act by slowing dissociation of glutamate. PMID:20807790

A test of flushing procedures to control salt-water intrusion at the W. P. Franklin Dam near Ft. Myers, Florida and The magnitude and extent of salt-water contamination in the Caloosahatchee River between La Belle and Olga, Florida

USGS Publications Warehouse

Boggess, Durward H.

1970-01-01

During low-flow periods, salty water from the tidal part of the Caloosahatchee River moves upstream during boat lockages at the W. P. Franklin Darn near Ft. Myers, Florida, as shown on figure L Salty water enters the lock chamber through openings of the downstream sector gates which separate tidal and fresh water; when the upstream gates open, some of the salty water moves into the upper pool, probably as a density current. Repeated injections of salty water cause a progressive increase in the salinity of the upstream water. The salty water moves upstream within the deeper parts of the river channel as far as 5 or more miles above the lock. Some mixing of the high-chloride deeper water and the fresher shallow water occurs in the affected reach above the lock, probably as a result of wind and waves, and turbulence created by boat traffic.

Effect of inclusions on heterogeneous crack nucleation in nanocomposites

NASA Astrophysics Data System (ADS)

Gutkin, M. Yu.; Ovid'Ko, I. A.; Skiba, N. V.

2007-02-01

A two-dimensional theoretical model is proposed for the heterogeneous nucleation of a grain-boundary nanocrack in a nanocomposite consisting of a nanocrystalline matrix and nanoinclusions whose elastic moduli are identical to those of the matrix. The inclusions have the form of rods with a rectangular cross section and undergo dilatation eigenstrain induced by the differences in the lattice parameters and thermal expansion coefficients of the matrix and inclusions. In terms of the model, a mode-I-II nanocrack nucleates at the negative disclination of a biaxial dipole consisting of wedge grain-boundary (or junction) disclinations; then, the nanocrack opens along a grain boundary and reaches an inclusion boundary. Depending on the relative positions and orientations of the initial segment of the nanocrack and the inclusion, the nanocrack can either penetrate into the inclusion or bypass it along the matrix-inclusion interface. The nanocrack nucleation probability increases near an inclusion with negative (compressive) dilatation eigenstrain. A decrease in the inclusion size decreases (increases) the probability of a crack opening along the interface if the dilatation eigenstrain is negative (positive).

Multi-GPU parallel algorithm design and analysis for improved inversion of probability tomography with gravity gradiometry data

NASA Astrophysics Data System (ADS)

Hou, Zhenlong; Huang, Danian

2017-09-01

In this paper, we make a study on the inversion of probability tomography (IPT) with gravity gradiometry data at first. The space resolution of the results is improved by multi-tensor joint inversion, depth weighting matrix and the other methods. Aiming at solving the problems brought by the big data in the exploration, we present the parallel algorithm and the performance analysis combining Compute Unified Device Architecture (CUDA) with Open Multi-Processing (OpenMP) based on Graphics Processing Unit (GPU) accelerating. In the test of the synthetic model and real data from Vinton Dome, we get the improved results. It is also proved that the improved inversion algorithm is effective and feasible. The performance of parallel algorithm we designed is better than the other ones with CUDA. The maximum speedup could be more than 200. In the performance analysis, multi-GPU speedup and multi-GPU efficiency are applied to analyze the scalability of the multi-GPU programs. The designed parallel algorithm is demonstrated to be able to process larger scale of data and the new analysis method is practical.

A quantum measure of the multiverse

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

Vilenkin, Alexander, E-mail: vilenkin@cosmos.phy.tufts.edu

2014-05-01

It has been recently suggested that probabilities of different events in the multiverse are given by the frequencies at which these events are encountered along the worldline of a geodesic observer (the ''watcher''). Here I discuss an extension of this probability measure to quantum theory. The proposed extension is gauge-invariant, as is the classical version of this measure. Observations of the watcher are described by a reduced density matrix, and the frequencies of events can be found using the decoherent histories formalism of Quantum Mechanics (adapted to open systems). The quantum watcher measure makes predictions in agreement with the standardmore » Born rule of QM.« less

Public opinion by a poll process: model study and Bayesian view

NASA Astrophysics Data System (ADS)

Lee, Hyun Keun; Kim, Yong Woon

2018-05-01

We study the formation of public opinion in a poll process where the current score is open to the public. The voters are assumed to vote probabilistically for or against their own preference considering the group opinion collected up to then in the score. The poll-score probability is found to follow the beta distribution in the large polls limit. We demonstrate that various poll results, even those contradictory to the population preference, are possible with non-zero probability density and that such deviations are readily triggered by initial bias. It is mentioned that our poll model can be understood in the Bayesian viewpoint.

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

Cartarius, Holger; Moiseyev, Nimrod; Department of Physics and Minerva Center for Nonlinear Physics of Complex Systems, Technion-Israel Institute of Technology, Haifa, 32000

The unique time signature of the survival probability exactly at the exceptional point parameters is studied here for the hydrogen atom in strong static magnetic and electric fields. We show that indeed the survival probability S(t)=|<{psi}(0)|{psi}(t)>|{sup 2} decays exactly as |1-at|{sup 2}e{sup -{Gamma}{sub E}{sub P}t/({Dirac_h}/2{pi})}, where {Gamma}{sub EP} is associated with the decay rate at the exceptional point and a is a complex constant depending solely on the initial wave packet that populates exclusively the two almost degenerate states of the non-Hermitian Hamiltonian. This may open the possibility for a first experimental detection of exceptional points in a quantum system.

Defining the Lower Limit of a "Critical Bone Defect" in Open Diaphyseal Tibial Fractures.

PubMed

Haines, Nikkole M; Lack, William D; Seymour, Rachel B; Bosse, Michael J

2016-05-01

To determine healing outcomes of open diaphyseal tibial shaft fractures treated with reamed intramedullary nailing (IMN) with a bone gap of 10-50 mm on ≥50% of the cortical circumference and to better define a "critical bone defect" based on healing outcome. Retrospective cohort study. Forty patients, age 18-65, with open diaphyseal tibial fractures with a bone gap of 10-50 mm on ≥50% of the circumference as measured on standard anteroposterior and lateral postoperative radiographs treated with IMN. IMN of an open diaphyseal tibial fracture with a bone gap. Level-1 trauma center. Healing outcomes, union or nonunion. Forty patients were analyzed. Twenty-one (52.5%) went on to nonunion and nineteen (47.5%) achieved union. Radiographic apparent bone gap (RABG) and infection were the only 2 covariates predicting nonunion outcome (P = 0.046 for infection). The RABG was determined by measuring the bone gap on each cortex and averaging over 4 cortices. Fractures achieving union had a RABG of 12 ± 1 mm versus 20 ± 2 mm in those going on to nonunion (P < 0.01). This remained significant when patients with infection were removed. Receiver operator characteristic analysis demonstrated that RABG was predictive of outcome (area under the curve of 0.79). A RABG of 25 mm was the statistically optimal threshold for prediction of healing outcome. Patients with open diaphyseal tibial fractures treated with IMN and a <25 mm RABG have a reasonable probability of achieving union without additional intervention, whereas those with larger gaps have a higher probability of nonunion. Research investigating interventions for RABGs should use a predictive threshold for defining a critical bone defect that is associated with greater than 50% risk of nonunion without supplementary treatment. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

A bursting potassium channel in isolated cholinergic synaptosomes of Torpedo electric organ.

PubMed Central

Edry-Schiller, J; Ginsburg, S; Rahamimoff, R

1991-01-01

1. Pinched-off cholinergic nerve terminals (synaptosomes) prepared from the electric organ of Torpedo ocelata were fused into large structures (greater than 20 microns) using dimethyl sulphoxide and polyethylene glycol 1500, as previously described for synaptic vesicles from the same organ. 2. The giant fused synaptosomes were easily amenable to the patch clamp technique and 293 seals with a resistance greater than 4 G omega were obtained in the 'cell-attached' configuration. In a large fraction of the experiments, an 'inside-out' patch configuration was achieved. 3. Several types of unitary ionic currents were observed. This study describes the most frequently observed single-channel activity which was found in 247 out of the 293 membrane patches (84.3%). 4. The single-channel current-voltage relation was linear between -60 and 20 mV and showed a slope conductance of 23.8 +/- 1.3 pS when the pipette contained 350-390 mM-Na+ and the bath facing the inside of the synaptosomal membrane contained 390 mM-K+. 5. From extrapolated reversal potential measurements, it was concluded that this channel has a large selectivity for K+ over Na+ (70.4 +/- 11.5, mean +/- S.E.M.). Chloride ions are not transported significantly through this potassium channel. 6. This potassium channel has a low probability of opening. The probability of being in the open state increases upon depolarization and reaches about 1% when the inside of the patch is 20 mV positive compared to the pipette side. 7. The mean channel open time increases with depolarization; thus the product current x time (= charge) also increases upon depolarization, showing properties of an outward rectifier. 8. The potassium channel in the giant synaptosome membrane has a bursting behaviour. Open-time distribution, closed-time distribution and a Poisson analysis indicate that the minimal kinetic scheme requires one open state and three closed states. PMID:1654418

A Comparison of Grizzly Bear Demographic Parameters Estimated from Non-Spatial and Spatial Open Population Capture-Recapture Models.

PubMed

Whittington, Jesse; Sawaya, Michael A

2015-01-01

Capture-recapture studies are frequently used to monitor the status and trends of wildlife populations. Detection histories from individual animals are used to estimate probability of detection and abundance or density. The accuracy of abundance and density estimates depends on the ability to model factors affecting detection probability. Non-spatial capture-recapture models have recently evolved into spatial capture-recapture models that directly include the effect of distances between an animal's home range centre and trap locations on detection probability. Most studies comparing non-spatial and spatial capture-recapture biases focussed on single year models and no studies have compared the accuracy of demographic parameter estimates from open population models. We applied open population non-spatial and spatial capture-recapture models to three years of grizzly bear DNA-based data from Banff National Park and simulated data sets. The two models produced similar estimates of grizzly bear apparent survival, per capita recruitment, and population growth rates but the spatial capture-recapture models had better fit. Simulations showed that spatial capture-recapture models produced more accurate parameter estimates with better credible interval coverage than non-spatial capture-recapture models. Non-spatial capture-recapture models produced negatively biased estimates of apparent survival and positively biased estimates of per capita recruitment. The spatial capture-recapture grizzly bear population growth rates and 95% highest posterior density averaged across the three years were 0.925 (0.786-1.071) for females, 0.844 (0.703-0.975) for males, and 0.882 (0.779-0.981) for females and males combined. The non-spatial capture-recapture population growth rates were 0.894 (0.758-1.024) for females, 0.825 (0.700-0.948) for males, and 0.863 (0.771-0.957) for both sexes. The combination of low densities, low reproductive rates, and predominantly negative population growth rates suggest that Banff National Park's population of grizzly bears requires continued conservation-oriented management actions.

Turbulent aerosol fluxes over the Arctic Ocean: 2. Wind-driven sources from the sea

NASA Astrophysics Data System (ADS)

Nilsson, E. D.; Rannik, Ü.; Swietlicki, E.; Leck, C.; Aalto, P. P.; Zhou, J.; Norman, M.

2001-12-01

An eddy-covariance flux system was successfully applied over open sea, leads and ice floes during the Arctic Ocean Expedition in July-August 1996. Wind-driven upward aerosol number fluxes were observed over open sea and leads in the pack ice. These particles must originate from droplets ejected into the air at the bursting of small air bubbles at the water surface. The source flux F (in 106 m-2 s-1) had a strong dependency on wind speed, log>(F>)=0.20U¯-1.71 and 0.11U¯-1.93, over the open sea and leads, respectively (where U¯ is the local wind speed at about 10 m height). Over the open sea the wind-driven aerosol source flux consisted of a film drop mode centered at ˜100 nm diameter and a jet drop mode centered at ˜1 μm diameter. Over the leads in the pack ice, a jet drop mode at ˜2 μm diameter dominated. The jet drop mode consisted of sea-salt, but oxalate indicated an organic contribution, and bacterias and other biogenic particles were identified by single particle analysis. Particles with diameters less than -100 nm appear to have contributed to the flux, but their chemical composition is unknown. Whitecaps were probably the bubble source at open sea and on the leads at high wind speed, but a different bubble source is needed in the leads owing to their small fetch. Melting of ice in the leads is probably the best candidate. The flux over the open sea was of such a magnitude that it could give a significant contribution to the condensation nuclei (CCN) population. Although the flux from the leads were roughly an order of magnitude smaller and the leads cover only a small fraction of the pack ice, the local source may till be important for the CCN population in Arctic fogs. The primary marine aerosol source will increase both with increased wind speed and with decreased ice fraction and extent. The local CCN production may therefore increase and influence cloud or fog albedo and lifetime in response to greenhouse warming in the Arctic Ocean region.

Matrix product representation of the stationary state of the open zero range process

NASA Astrophysics Data System (ADS)

Bertin, Eric; Vanicat, Matthieu

2018-06-01

Many one-dimensional lattice particle models with open boundaries, like the paradigmatic asymmetric simple exclusion process (ASEP), have their stationary states represented in the form of a matrix product, with matrices that do not explicitly depend on the lattice site. In contrast, the stationary state of the open 1D zero-range process (ZRP) takes an inhomogeneous factorized form, with site-dependent probability weights. We show that in spite of the absence of correlations, the stationary state of the open ZRP can also be represented in a matrix product form, where the matrices are site-independent, non-commuting and determined from algebraic relations resulting from the master equation. We recover the known distribution of the open ZRP in two different ways: first, using an explicit representation of the matrices and boundary vectors; second, from the sole knowledge of the algebraic relations satisfied by these matrices and vectors. Finally, an interpretation of the relation between the matrix product form and the inhomogeneous factorized form is proposed within the framework of hidden Markov chains.

Segregation analysis of Alzheimer pedigrees: Rare Mendelian dominant mutation(s) explain a minority of early-onset cases

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

Martinez, M.; Campion, D.; Babron, M.C.

1996-02-16

Segregation analysis of Alzheimer disease (AD) in 92 families ascertained through early-onset ({le}age 60 years) AD (EOAD) probands has been carried out, allowing for a mixture in AD inheritance among probands. The goal was to quantify the proportion of probands that could be explained by autosomal inheritance of a rare disease allele {open_quotes}a{close_quotes} at a Mendelian dominant gene (MDG). Our data provide strong evidence for a mixture of two distributions; AD transmission is fully explained by MDG inheritance in <20% of probands. Male and female age-of-onset distributions are significantly different for {open_quotes}AA{close_quote} but not for {open_quotes}aA{close_quote} subjects. For {open_quotes}aA{close_quote} subjectsmore » the estimated penetrance value was close to 1 by age 60. For {open_quotes}AA{close_quotes} subjects, it reaches, by age 90, 10% (males) and 30% (females). We show a clear cutoff in the posterior probability of being an MDG case. 10 refs., 1 tab.« less

Predictors of death and production performance of layer chickens in opened and sealed pens in a tropical savannah environment.

PubMed

Shittu, Aminu; Raji, Abdullahi Abdullahi; Madugu, Shuaibu A; Hassan, Akinola Waheed; Fasina, Folorunso Oludayo

2014-09-12

Layer chickens are exposed to high risks of production losses and mortality with impact on farm profitability. The harsh tropical climate and severe disease outbreaks, poor biosecurity, sub-minimal vaccination and treatment protocols, poor management practices, poor chick quality, feed-associated causes, and unintended accidents oftentimes aggravate mortality and negatively affect egg production. The objectives of this study were to estimate the probability of survival and evaluate risk factors for death under different intensive housing conditions in a tropical climate, and to assess the production performance in the housing systems. Daily mean mortality percentages and egg production figures were significantly lower and higher in the sealed pens and open houses (P < 0. 001) respectively. The total mean feed consumption/bird/day was similar for the open sided and sealed pens but the mean feed quantity per egg produce was significantly lower in the sealed pens ((P < 0.005). Seasons differently impacted on mortality with the hot-dry season producing significantly higher risk of mortality (61 times) and reduced egg production. Other parameters also differed except the egg production during the cold-dry season. Layers in sealed pens appear to have higher probability of survival and the Kaplan-Meir survival curves differed for each pen; ≥ 78 weeks old layer have higher probability of survival compared with the younger chickens and the 19-38 weeks age category are at highest risk of death (P < 0.001). The hazard-ratio for mortality of layers raised in sealed pens was 0.568 (56.8%). Reasons for spiked mortality in layer chickens may not always be associated with disease. Hot-dry climatic environment is associated with heat stress, waning immunity and inefficient feed usage and increase probability of death with reduced egg production; usage of environmentally controlled building in conditions where environmental temperature may rise significantly above 25°C will reduce this impact. Since younger birds (19-38 weeks) are at higher risk of death due to stress of coming into production, management changes and diseases, critical implementation of protocols that will reduce death at this precarious period becomes mandatory. Whether older chickens' better protection from death is associated with many prophylactic and metaphylactic regimen of medications/vaccination will need further investigation.

The statistics of Pearce element diagrams and the Chayes closure problem

NASA Astrophysics Data System (ADS)

Nicholls, J.

1988-05-01

Pearce element ratios are defined as having a constituent in their denominator that is conserved in a system undergoing change. The presence of a conserved element in the denominator simplifies the statistics of such ratios and renders them subject to statistical tests, especially tests of significance of the correlation coefficient between Pearce element ratios. Pearce element ratio diagrams provide unambigous tests of petrologic hypotheses because they are based on the stoichiometry of rock-forming minerals. There are three ways to recognize a conserved element: 1. The petrologic behavior of the element can be used to select conserved ones. They are usually the incompatible elements. 2. The ratio of two conserved elements will be constant in a comagmatic suite. 3. An element ratio diagram that is not constructed with a conserved element in the denominator will have a trend with a near zero intercept. The last two criteria can be tested statistically. The significance of the slope, intercept and correlation coefficient can be tested by estimating the probability of obtaining the observed values from a random population of arrays. This population of arrays must satisfy two criteria: 1. The population must contain at least one array that has the means and variances of the array of analytical data for the rock suite. 2. Arrays with the means and variances of the data must not be so abundant in the population that nearly every array selected at random has the properties of the data. The population of random closed arrays can be obtained from a population of open arrays whose elements are randomly selected from probability distributions. The means and variances of these probability distributions are themselves selected from probability distributions which have means and variances equal to a hypothetical open array that would give the means and variances of the data on closure. This hypothetical open array is called the Chayes array. Alternatively, the population of random closed arrays can be drawn from the compositional space available to rock-forming processes. The minerals comprising the available space can be described with one additive component per mineral phase and a small number of exchange components. This space is called Thompson space. Statistics based on either space lead to the conclusion that Pearce element ratios are statistically valid and that Pearce element diagrams depict the processes that create chemical inhomogeneities in igneous rock suites.

Probability Distributome: A Web Computational Infrastructure for Exploring the Properties, Interrelations, and Applications of Probability Distributions.

PubMed

Dinov, Ivo D; Siegrist, Kyle; Pearl, Dennis K; Kalinin, Alexandr; Christou, Nicolas

2016-06-01

Probability distributions are useful for modeling, simulation, analysis, and inference on varieties of natural processes and physical phenomena. There are uncountably many probability distributions. However, a few dozen families of distributions are commonly defined and are frequently used in practice for problem solving, experimental applications, and theoretical studies. In this paper, we present a new computational and graphical infrastructure, the Distributome , which facilitates the discovery, exploration and application of diverse spectra of probability distributions. The extensible Distributome infrastructure provides interfaces for (human and machine) traversal, search, and navigation of all common probability distributions. It also enables distribution modeling, applications, investigation of inter-distribution relations, as well as their analytical representations and computational utilization. The entire Distributome framework is designed and implemented as an open-source, community-built, and Internet-accessible infrastructure. It is portable, extensible and compatible with HTML5 and Web2.0 standards (http://Distributome.org). We demonstrate two types of applications of the probability Distributome resources: computational research and science education. The Distributome tools may be employed to address five complementary computational modeling applications (simulation, data-analysis and inference, model-fitting, examination of the analytical, mathematical and computational properties of specific probability distributions, and exploration of the inter-distributional relations). Many high school and college science, technology, engineering and mathematics (STEM) courses may be enriched by the use of modern pedagogical approaches and technology-enhanced methods. The Distributome resources provide enhancements for blended STEM education by improving student motivation, augmenting the classical curriculum with interactive webapps, and overhauling the learning assessment protocols.

Probability Distributome: A Web Computational Infrastructure for Exploring the Properties, Interrelations, and Applications of Probability Distributions

PubMed Central

Dinov, Ivo D.; Siegrist, Kyle; Pearl, Dennis K.; Kalinin, Alexandr; Christou, Nicolas

2015-01-01

Probability distributions are useful for modeling, simulation, analysis, and inference on varieties of natural processes and physical phenomena. There are uncountably many probability distributions. However, a few dozen families of distributions are commonly defined and are frequently used in practice for problem solving, experimental applications, and theoretical studies. In this paper, we present a new computational and graphical infrastructure, the Distributome, which facilitates the discovery, exploration and application of diverse spectra of probability distributions. The extensible Distributome infrastructure provides interfaces for (human and machine) traversal, search, and navigation of all common probability distributions. It also enables distribution modeling, applications, investigation of inter-distribution relations, as well as their analytical representations and computational utilization. The entire Distributome framework is designed and implemented as an open-source, community-built, and Internet-accessible infrastructure. It is portable, extensible and compatible with HTML5 and Web2.0 standards (http://Distributome.org). We demonstrate two types of applications of the probability Distributome resources: computational research and science education. The Distributome tools may be employed to address five complementary computational modeling applications (simulation, data-analysis and inference, model-fitting, examination of the analytical, mathematical and computational properties of specific probability distributions, and exploration of the inter-distributional relations). Many high school and college science, technology, engineering and mathematics (STEM) courses may be enriched by the use of modern pedagogical approaches and technology-enhanced methods. The Distributome resources provide enhancements for blended STEM education by improving student motivation, augmenting the classical curriculum with interactive webapps, and overhauling the learning assessment protocols. PMID:27158191

Combining band recovery data and Pollock's robust design to model temporary and permanent emigration

USGS Publications Warehouse

Lindberg, M.S.; Kendall, W.L.; Hines, J.E.; Anderson, M.G.

2001-01-01

Capture-recapture models are widely used to estimate demographic parameters of marked populations. Recently, this statistical theory has been extended to modeling dispersal of open populations. Multistate models can be used to estimate movement probabilities among subdivided populations if multiple sites are sampled. Frequently, however, sampling is limited to a single site. Models described by Burnham (1993, in Marked Individuals in the Study of Bird Populations, 199-213), which combined open population capture-recapture and band-recovery models, can be used to estimate permanent emigration when sampling is limited to a single population. Similarly, Kendall, Nichols, and Hines (1997, Ecology 51, 563-578) developed models to estimate temporary emigration under Pollock's (1982, Journal of Wildlife Management 46, 757-760) robust design. We describe a likelihood-based approach to simultaneously estimate temporary and permanent emigration when sampling is limited to a single population. We use a sampling design that combines the robust design and recoveries of individuals obtained immediately following each sampling period. We present a general form for our model where temporary emigration is a first-order Markov process, and we discuss more restrictive models. We illustrate these models with analysis of data on marked Canvasback ducks. Our analysis indicates that probability of permanent emigration for adult female Canvasbacks was 0.193 (SE = 0.082) and that birds that were present at the study area in year i - 1 had a higher probability of presence in year i than birds that were not present in year i - 1.

Modeling the effect of toe clipping on treefrog survival: Beyond the return rate

USGS Publications Warehouse

Waddle, J.H.; Rice, K.G.; Mazzotti, F.J.; Percival, H.F.

2008-01-01

Some studies have described a negative effect of toe clipping on return rates of marked anurans, but the return rate is limited in that it does not account for heterogeneity of capture probabilities. We used open population mark-recapture models to estimate both apparent survival (ϕ) and the recapture probability (p) of two treefrog species individually marked by clipping 2–4 toes. We used information-theoretic model selection to examine the effect of toe clipping on survival while accounting for variation in capture probability. The model selection results indicate strong support for an effect of toe clipping on survival of Green Treefrogs (Hyla cinerea) and only limited support for an effect of toe clipping on capture probability. We estimate there was a mean absolute decrease in survival of 5.02% and 11.16% for Green Treefrogs with three and four toes removed, respectively, compared to individuals with just two toes removed. Results for Squirrel Treefrogs (Hyla squirella) indicate little support for an effect of toe clipping on survival but may indicate some support for a negative effect on capture probability. We believe that the return rate alone should not be used to examine survival of marked animals because constant capture probability must be assumed, and our examples demonstrate how capture probability may vary over time and among groups. Mark-recapture models provide a method for estimating the effect of toe clipping on anuran survival in situations where unique marks are applied.

Heterogeneous detection probabilities for imperiled Missouri River fishes: implications for large-river monitoring programs

USGS Publications Warehouse

Schloesser, J.T.; Paukert, Craig P.; Doyle, W.J.; Hill, Tracy D.; Steffensen, K.D.; Travnichek, Vincent H.

2012-01-01

Occupancy modeling was used to determine (1) if detection probabilities (p) for 7 regionally imperiled Missouri River fishes (Scaphirhynchus albus, Scaphirhynchus platorynchus, Cycleptus elongatus, Sander canadensis, Macrhybopsis aestivalis, Macrhybopsis gelida, and Macrhybopsis meeki) differed among gear types (i.e. stationary gill nets, drifted trammel nets, and otter trawls), and (2) how detection probabilities were affected by habitat (i.e. pool, bar, and open water), longitudinal position (five 189 to 367 rkm long segments), sampling year (2003 to 2006), and season (July 1 to October 30 and October 31 to June 30). Adult, large-bodied fishes were best detected with gill nets (p: 0.02–0.74), but most juvenile large-bodied and all small-bodied species were best detected with otter trawls (p: 0.02–0.58). Trammel nets may be a redundant sampling gear for imperiled fishes in the lower Missouri River because most species had greater detection probabilities with gill nets or otter trawls. Detection probabilities varied with river segment for S. platorynchus, C. elongatus, and all small-bodied fishes, suggesting that changes in habitat influenced gear efficiency or abundance changes among river segments. Detection probabilities varied by habitat for adult S. albus and S. canadensis, year for juvenile S. albus, C. elongatus, and S. canadensis, and season for adult S. albus. Concentrating sampling effort on gears with the greatest detection probabilities may increase species detections to better monitor a population's response to environmental change and the effects of management actions on large-river fishes.

Li-Ion Battery By-Pass Removal Qualification

NASA Astrophysics Data System (ADS)

Borthomieu, Y.; Pasquier, E.

2005-05-01

The reasons of the by-pass use on Space batteries is to avoid open circuit, short-circuit and dramatic performances drift on the power system. By-pass diodes are currently used in NiH2 batteries due to the high probability of open circuit at cell level. This probability is mainly linked to the possibility to have a hydrogen leak within the pressure vessel due to the high operating pressure (70 bars) that can induce cell open circuit.For the Lithium-Ion batteries, first items had bypass implemented by similarity, but:All the cell failure cases have been analyzed at battery level:- Cell Open circuit:In contrast to NiCd and NiH2 cells, Li-Ion cells can be put in parallel due to the fact the open circuit voltage (OCV) is linked to the State Of Charge (SOC).With cells in parallel, a battery open circuit failure can never be encountered even with a cell in open circuit.- Cell Short circuit:In case of cell short, the entire cells within the module will be shorted.- Cell capacity spread:If the capacities of cells in series are strongly diverging, the worst module limits the battery. In case the battery is no more able to deliver the requested power for which it was designed, the worst module has to be reversed. In reversal, a Li-Ion cell is self-shorted. So, the strong capacity decrease in one module leads to the short of this module.These three failure cases cover all the possible Li-Ion failure root causes.Considering these three events, the analysis demonstrates that the Li-Ion battery still functions in any case without any by-pass system because the design of the battery size always takes into account the loss of one module.Nevertheless, the by-pass removal should allow to:- Improve the battery reliability as each bypass unit represents a single - Reduce by at least 30 % of the total price of the battery,- Reduce significant weight at battery level,- Shorten the battery manufacturing lead time (at least8 months for by-pass purchasing), - Avoid US export licenses.A formal qualification of a Li-Ion battery without by- pass system is on going in the frame of an ESA ARTES 3 contract.

An MDI (Minimum Discrimination Information) Model and an Algorithm for Composite Hypotheses Testing and Estimation in Marketing. Revision 2.

DTIC Science & Technology

1982-09-01

considered to be Markovian and the fact that Ehrenberg has been openly critical of the use of first-order Markov processes in describing consumer ... behavior -/ disinclines us to treating these data in this manner. We Shall therefore interpret the p (i,i) as joint rather than conditional probabilities

Construction of a polyhedron decorated MOF with a unique network through the combination of two classic secondary building units.

PubMed

Ren, Guo-Jian; Chang, Ze; Xu, Jian; Hu, Zhenpeng; Liu, Yan-Qing; Xu, Yue-Ling; Bu, Xian-He

2016-02-04

A novel decorated metal-organic polyhedron (MOP) based metal-organic framework with a unique 4,9-connected network is successfully constructed, which displays a relatively strong interaction toward H2 and CO2 probably due to the existence of open metal sites in the secondary building units.

A Computer Simulation Using Spreadsheets for Learning Concept of Steady-State Equilibrium

ERIC Educational Resources Information Center

Sharda, Vandana; Sastri, O. S. K. S.; Bhardwaj, Jyoti; Jha, Arbind K.

2016-01-01

In this paper, we present a simple spreadsheet based simulation activity that can be performed by students at the undergraduate level. This simulation is implemented in free open source software (FOSS) LibreOffice Calc, which is available for both Windows and Linux platform. This activity aims at building the probability distribution for the…

Deriving the Regression Equation without Using Calculus

ERIC Educational Resources Information Center

Gordon, Sheldon P.; Gordon, Florence S.

2004-01-01

Probably the one "new" mathematical topic that is most responsible for modernizing courses in college algebra and precalculus over the last few years is the idea of fitting a function to a set of data in the sense of a least squares fit. Whether it be simple linear regression or nonlinear regression, this topic opens the door to applying the…

Jimmy Carter, Palestinian Art, and Brandeis

ERIC Educational Resources Information Center

Jankowski, Paul

2007-01-01

The principle, in the author's mind, is simple enough--to allow expression on campus when it is not hateful or defamatory or threatening, and to encourage it when it is civil and open-minded and of probable interest to some members of the community. The devil lies in the practice. In this article, the author discusses various issues that have…

Post-hit dynamics of price limit hits in the Chinese stock markets

NASA Astrophysics Data System (ADS)

Wu, Ting; Wang, Yue; Li, Ming-Xia

2017-01-01

Price limit trading rules are useful to cool off traders short-term trading mania on individual stocks. The price dynamics approaching the limit boards are known as the magnet effect. However, the price dynamics after opening price limit hits are not well investigated. Here, we provide a detailed analysis on the price dynamics after the hits of up-limit or down-limit is open based on all A-share stocks traded in the Chinese stock markets. A "W" shape is found in the expected return, which reveals high probability of a continuous price limit hit on the following day. We also find that price dynamics after opening limit hits are dependent on the market trends. The time span of continuously hitting the price limit is found to an influence factor of the expected profit after the limit hit is open. Our analysis provides a better understanding of the price dynamics around the limit boards and contributes potential practical values for investors.

Are voluntary wheel running and open-field behavior correlated in mice? Different answers from comparative and artificial selection approaches.

PubMed

Careau, Vincent; Bininda-Emonds, Olaf R P; Ordonez, Genesis; Garland, Theodore

2012-09-01

Voluntary wheel running and open-field behavior are probably the two most widely used measures of locomotion in laboratory rodents. We tested whether these two behaviors are correlated in mice using two approaches: the phylogenetic comparative method using inbred strains of mice and an ongoing artificial selection experiment on voluntary wheel running. After taking into account the measurement error and phylogenetic relationships among inbred strains, we obtained a significant positive correlation between distance run on wheels and distance moved in the open-field for both sexes. Thigmotaxis was negatively correlated with distance run on wheels in females but not in males. By contrast, mice from four replicate lines bred for high wheel running did not differ in either distance covered or thigmotaxis in the open field as compared with mice from four non-selected control lines. Overall, results obtained in the selection experiment were generally opposite to those observed among inbred strains. Possible reasons for this discrepancy are discussed.

Opening of K+ channels by capacitive stimulation from silicon chip

NASA Astrophysics Data System (ADS)

Ulbrich, M. H.; Fromherz, P.

2005-10-01

The development of stable neuroelectronic systems requires a stimulation of nerve cells from semiconductor devices without electrochemical effects at the electrolyte/solid interface and without damage of the cell membrane. The interaction must rely on a reversible opening of voltage-gated ion channels by capacitive coupling. In a proof-of-principle experiment, we demonstrate that Kv1.3 potassium channels expressed in HEK293 cells can be opened from an electrolyte/oxide/silicon (EOS) capacitor. A sufficient strength of electrical coupling is achieved by insulating silicon with a thin film of TiO2 to achieve a high capacitance and by removing NaCl from the electrolyte to enhance the resistance of the cell-chip contact. When a decaying voltage ramp is applied to the EOS capacitor, an outward current through the attached cell membrane is observed that is specific for Kv1.3 channels. An open probability up to fifty percent is estimated by comparison with a numerical simulation of the cell-chip contact.

Effect of stochastic gating on channel-facilitated transport of non-interacting and strongly repelling solutes.

PubMed

Berezhkovskii, Alexander M; Bezrukov, Sergey M

2017-08-28

Ligand- or voltage-driven stochastic gating-the structural rearrangements by which the channel switches between its open and closed states-is a fundamental property of biological membrane channels. Gating underlies the channel's ability to respond to different stimuli and, therefore, to be functionally regulated by the changing environment. The accepted understanding of the gating effect on the solute flux through the channel is that the mean flux is the product of the flux through the open channel and the probability of finding the channel in the open state. Here, using a diffusion model of channel-facilitated transport, we show that this is true only when the gating is much slower than the dynamics of solute translocation through the channel. If this condition breaks, the mean flux could differ from this simple estimate by orders of magnitude.

Effect of stochastic gating on channel-facilitated transport of non-interacting and strongly repelling solutes

NASA Astrophysics Data System (ADS)

Berezhkovskii, Alexander M.; Bezrukov, Sergey M.

2017-08-01

Ligand- or voltage-driven stochastic gating—the structural rearrangements by which the channel switches between its open and closed states—is a fundamental property of biological membrane channels. Gating underlies the channel's ability to respond to different stimuli and, therefore, to be functionally regulated by the changing environment. The accepted understanding of the gating effect on the solute flux through the channel is that the mean flux is the product of the flux through the open channel and the probability of finding the channel in the open state. Here, using a diffusion model of channel-facilitated transport, we show that this is true only when the gating is much slower than the dynamics of solute translocation through the channel. If this condition breaks, the mean flux could differ from this simple estimate by orders of magnitude.

Camouflage of a high-angle skeletal Class II open-bite malocclusion in an adult after mini-implant failure during treatment.

PubMed

Franzotti Sant'Anna, Eduardo; Carneiro da Cunha, Amanda; Paludo Brunetto, Daniel; Franzotti Sant'Anna, Claudia

2017-03-01

The treatment of skeletal anterior open-bite malocclusion requires complex orthodontic planning that considers its multifactorial etiology, treatment limitations, and high relapse rates. This case report illustrates a successful treatment approach for a skeletal high-angle Class II malocclusion in an adult with a severe open bite. The treatment consisted of a high-pull headgear therapy after mini-implants failure during fixed orthodontic therapy. Adequate esthetics and function were achieved. Despite its low probability, the unexpected event of mini-implant loosening during complex treatments should be considered. Therefore, classic orthodontic mechanics should be established, especially when treating patients for whom invasive procedures such as miniplates or orthognathic surgery are not available options. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Bethe/Gauge correspondence in odd dimension: modular double, non-perturbative corrections and open topological strings

NASA Astrophysics Data System (ADS)

Sciarappa, Antonio

2016-10-01

Bethe/Gauge correspondence as it is usually stated is ill-defined in five dimensions and needs a "non-perturbative" completion; a related problem also appears in three dimensions. It has been suggested that this problem, probably due to incompleteness of Omega background regularization in odd dimension, may be solved if we consider gauge theory on compact S 5 and S 3 geometries. We will develop this idea further by giving a full Bethe/Gauge correspondence dictionary on S 5 and S 3 focussing mainly on the eigenfunctions of (open and closed) relativistic 2-particle Toda chain and its quantized spectral curve: these are most properly written in terms of non-perturbatively completed NS open topological strings. A key ingredient is Faddeev's modular double structure which is naturally implemented by the S 5 and S 3 geometries.

A Stigmergy Approach for Open Source Software Developer Community Simulation

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

Cui, Xiaohui; Beaver, Justin M; Potok, Thomas E

2009-01-01

The stigmergy collaboration approach provides a hypothesized explanation about how online groups work together. In this research, we presented a stigmergy approach for building an agent based open source software (OSS) developer community collaboration simulation. We used group of actors who collaborate on OSS projects as our frame of reference and investigated how the choices actors make in contribution their work on the projects determinate the global status of the whole OSS projects. In our simulation, the forum posts and project codes served as the digital pheromone and the modified Pierre-Paul Grasse pheromone model is used for computing developer agentmore » behaviors selection probability.« less

Modelling the transport of oil after a proposed oil spill accident in Barents Sea and its environmental impact on Alke species

NASA Astrophysics Data System (ADS)

Lu, J.; Yuan, F.; Mikkelsen, J. D.; Ohm, C.; Stange, E.; Holand, M.

2017-08-01

Accidental oil spills can have significant effect on the coastal and marine environment. As the oil extraction and exploration activities increase in the Barents Sea, it is of increasingly importance to investigate the potential oil spill incidents associated with these activities. In this study, the transport and fate of oil after a proposed oil spill incident in Barents Sea was modelled by oil spill contingency and response model OSCAR. The possibility that the spilled oil reach the open sea and the strand area was calculated respectively. The influence area of the incident was calculated by combining the results from 200 simulations. The possibility that the spilled oil reach Alke species, a vulnerable species and on the National Red List of birds in Barents Sea, was analyzed by combining oil spill modelling results and the Alke species distribution data. The results showed that oil is dominated with a probability of 70-100% in the open sea to reach an area in a radius of 20km from the release location after 14 days of release. The probability reduces with the increasing distances from the release location. It is higher possibility that the spilled oil will reach the Alke species in the strand area than in the open sea in the summer. The total influence area of the release is 11 429 km2 for the surface water and 1528 km2 for the coastal area.

Factors influencing message dissemination through social media

NASA Astrophysics Data System (ADS)

Zheng, Zeyu; Yang, Huancheng; Fu, Yang; Fu, Dianzheng; Podobnik, Boris; Stanley, H. Eugene

2018-06-01

Online social networks strongly impact our daily lives. An internet user (a "Netizen") wants messages to be efficiently disseminated. The susceptible-infected-recovered (SIR) dissemination model is the traditional tool for exploring the spreading mechanism of information diffusion. We here test our SIR-based dissemination model on open and real-world data collected from Twitter. We locate and identify phase transitions in the message dissemination process. We find that message content is a stronger factor than the popularity of the sender. We also find that the probability that a message will be forwarded has a threshold that affects its ability to spread, and when the probability is above the threshold the message quickly achieves mass dissemination.

Three-dimensional atom localization via electromagnetically induced transparency in a three-level atomic system.

PubMed

Wang, Zhiping; Cao, Dewei; Yu, Benli

2016-05-01

We present a new scheme for three-dimensional (3D) atom localization in a three-level atomic system via measuring the absorption of a weak probe field. Owing to the space-dependent atom-field interaction, the position probability distribution of the atom can be directly determined by measuring the probe absorption. It is found that, by properly varying the parameters of the system, the probability of finding the atom in 3D space can be almost 100%. Our scheme opens a promising way to achieve high-precision and high-efficiency 3D atom localization, which provides some potential applications in laser cooling or atom nano-lithography via atom localization.

Trending in Probability of Collision Measurements

NASA Technical Reports Server (NTRS)

Vallejo, J. J.; Hejduk, M. D.; Stamey, J. D.

2015-01-01

A simple model is proposed to predict the behavior of Probabilities of Collision (P(sub c)) for conjunction events. The model attempts to predict the location and magnitude of the peak P(sub c) value for an event by assuming the progression of P(sub c) values can be modeled to first order by a downward-opening parabola. To incorporate prior information from a large database of past conjunctions, the Bayes paradigm is utilized; and the operating characteristics of the model are established through a large simulation study. Though the model is simple, it performs well in predicting the temporal location of the peak (P(sub c)) and thus shows promise as a decision aid in operational conjunction assessment risk analysis.

Mice take calculated risks.

PubMed

Kheifets, Aaron; Gallistel, C R

2012-05-29

Animals successfully navigate the world despite having only incomplete information about behaviorally important contingencies. It is an open question to what degree this behavior is driven by estimates of stochastic parameters (brain-constructed models of the experienced world) and to what degree it is directed by reinforcement-driven processes that optimize behavior in the limit without estimating stochastic parameters (model-free adaptation processes, such as associative learning). We find that mice adjust their behavior in response to a change in probability more quickly and abruptly than can be explained by differential reinforcement. Our results imply that mice represent probabilities and perform calculations over them to optimize their behavior, even when the optimization produces negligible material gain.

Mice take calculated risks

PubMed Central

Kheifets, Aaron; Gallistel, C. R.

2012-01-01

Animals successfully navigate the world despite having only incomplete information about behaviorally important contingencies. It is an open question to what degree this behavior is driven by estimates of stochastic parameters (brain-constructed models of the experienced world) and to what degree it is directed by reinforcement-driven processes that optimize behavior in the limit without estimating stochastic parameters (model-free adaptation processes, such as associative learning). We find that mice adjust their behavior in response to a change in probability more quickly and abruptly than can be explained by differential reinforcement. Our results imply that mice represent probabilities and perform calculations over them to optimize their behavior, even when the optimization produces negligible material gain. PMID:22592792

Bipartite discrimination of independently prepared quantum states as a counterexample to a parallel repetition conjecture

NASA Astrophysics Data System (ADS)

Akibue, Seiseki; Kato, Go

2018-04-01

For distinguishing quantum states sampled from a fixed ensemble, the gap in bipartite and single-party distinguishability can be interpreted as a nonlocality of the ensemble. In this paper, we consider bipartite state discrimination in a composite system consisting of N subsystems, where each subsystem is shared between two parties and the state of each subsystem is randomly sampled from a particular ensemble comprising the Bell states. We show that the success probability of perfectly identifying the state converges to 1 as N →∞ if the entropy of the probability distribution associated with the ensemble is less than 1, even if the success probability is less than 1 for any finite N . In other words, the nonlocality of the N -fold ensemble asymptotically disappears if the probability distribution associated with each ensemble is concentrated. Furthermore, we show that the disappearance of the nonlocality can be regarded as a remarkable counterexample of a fundamental open question in theoretical computer science, called a parallel repetition conjecture of interactive games with two classically communicating players. Measurements for the discrimination task include a projective measurement of one party represented by stabilizer states, which enable the other party to perfectly distinguish states that are sampled with high probability.

Survival estimates for Florida manatees from the photo-identification of individuals

USGS Publications Warehouse

Langtimm, C.A.; Beck, C.A.; Edwards, H.H.; Fick-Child, K. J.; Ackerman, B.B.; Barton, S.L.; Hartley, W.C.

2004-01-01

We estimated adult survival probabilities for the endangered Florida manatee (Trichechus manatus latirostris) in four regional populations using photo-identification data and open-population capture-recapture statistical models. The mean annual adult survival probability over the most recent 10-yr period of available estimates was as follows: Northwest - 0.956 (SE 0.007), Upper St. Johns River - 0.960 (0.011), Atlantic Coast - 0.937 (0.008), and Southwest - 0.908 (0.019). Estimates of temporal variance independent of sampling error, calculated from the survival estimates, indicated constant survival in the Upper St. Johns River, true temporal variability in the Northwest and Atlantic Coast, and large sampling variability obscuring estimates for the Southwest. Calf and subadult survival probabilities were estimated for the Upper St. Johns River from the only available data for known-aged individuals: 0.810 (95% CI 0.727-0.873) for 1st year calves, 0.915 (0.827-0.960) for 2nd year calves, and 0.969 (0.946-0.982) for manatee 3 yr or older. These estimates of survival probabilities and temporal variance, in conjunction with estimates of reproduction probabilities from photoidentification data can be used to model manatee population dynamics, estimate population growth rates, and provide an integrated measure of regional status.

Airway Hydration and COPD

PubMed Central

Ghosh, Arunava; Boucher, R.C.; Tarran, Robert

2015-01-01

Chronic obstructive pulmonary disease (COPD) is one of the prevalent causes of worldwide mortality and encompasses two major clinical phenotypes, i.e., chronic bronchitis (CB) and emphysema. The most common cause of COPD is chronic tobacco inhalation. Research focused on the chronic bronchitic phenotype of COPD has identified several pathological processes that drive disease initiation and progression. For example, the lung’s mucociliary clearance (MCC) system performs the critical task of clearing inhaled pathogens and toxic materials from the lung. MCC efficiency is dependent on: (i) the ability of apical plasma membrane ion channels such as the cystic fibrosis transmembrane conductance regulator (CFTR) and the epithelial Na+ channel (ENaC) to maintain airway hydration; (ii) ciliary beating; and, (iii) appropriate rates of mucin secretion. Each of these components is impaired in CB and likely contributes to the mucus stasis/accumulation seen in CB patients. This review highlights the cellular components responsible for maintaining MCC and how this process is disrupted following tobacco exposure and with CB. We shall also discuss existing therapeutic strategies for the treatment of chronic bronchitis and how components of the MCC can be used as biomarkers for the evaluation of tobacco or tobacco-like-product exposure. PMID:26068443

The absence of intrarenal ACE protects against hypertension

PubMed Central

Gonzalez-Villalobos, Romer A.; Janjoulia, Tea; Fletcher, Nicholas K.; Giani, Jorge F.; Nguyen, Mien T.X.; Riquier-Brison, Anne D.; Seth, Dale M.; Fuchs, Sebastien; Eladari, Dominique; Picard, Nicolas; Bachmann, Sebastian; Delpire, Eric; Peti-Peterdi, Janos; Navar, L. Gabriel; Bernstein, Kenneth E.; McDonough, Alicia A.

2013-01-01

Activation of the intrarenal renin-angiotensin system (RAS) can elicit hypertension independently from the systemic RAS. However, the precise mechanisms by which intrarenal Ang II increases blood pressure have never been identified. To this end, we studied the responses of mice specifically lacking kidney angiotensin-converting enzyme (ACE) to experimental hypertension. Here, we show that the absence of kidney ACE substantially blunts the hypertension induced by Ang II infusion (a model of high serum Ang II) or by nitric oxide synthesis inhibition (a model of low serum Ang II). Moreover, the renal responses to high serum Ang II observed in wild-type mice, including intrarenal Ang II accumulation, sodium and water retention, and activation of ion transporters in the loop of Henle (NKCC2) and distal nephron (NCC, ENaC, and pendrin) as well as the transporter activating kinases SPAK and OSR1, were effectively prevented in mice that lack kidney ACE. These findings demonstrate that ACE metabolism plays a fundamental role in the responses of the kidney to hypertensive stimuli. In particular, renal ACE activity is required to increase local Ang II, to stimulate sodium transport in loop of Henle and the distal nephron, and to induce hypertension. PMID:23619363

Questions in the Answers to Primary School Educational Reconstruction in Sierra Leone

ERIC Educational Resources Information Center

Hinton, Samuel

2009-01-01

The purpose of this paper is to review current issues in pre- and primary school reform and to pose questions on the long-term implications of present day solutions. Such an exercise will open up discussion on the probable effects of educational policy decisions with a view to minimize negative effects brought on by new policies. Because data…

Qualitative aspects of the effectiveness of Culpeo foxes (Lycalopex culpaeus) as dispersers of Prosopis alba (Fabaceae) in a Bolivian dry valley

NASA Astrophysics Data System (ADS)

Maldonado, D. E.; Loayza, A. P.; Garcia, E.; Pacheco, L. F.

2018-02-01

Foxes disperse several plant species in arid and semi-arid environments, but their effectiveness as dispersal agents still remains unclear. In this study, we examined qualitative components of the effectiveness of L. culpaeus as a disperser of P. alba seeds in an inter-Andean dry valley of La Paz, Bolivia. Specifically, we determined seed deposition microhabitats, and the probabilities of germination, seed removal and seedling recruitment in these microhabitats. Additionally, we assessed the effect of gut-passage on P. alba germination. We collected 159 scats, which contained a total of 3402 endocarps fragments. Foxes dispersed seeds into two microhabitats: open areas and under woody vegetation, but more frequently in the former. The probability of germination did not differ between gut-passed and control seeds, but control seeds germinated faster than gut-passed ones. The likelihood of removal was greater for endocarps fragments in open microhabitats than under woody vegetation. Only a small percentage of the seeds in each microhabitat germinated, but none survived more than a week. We conclude that although the Culpeo fox can defecate intact P. alba seeds, it does not provide effective dispersal services.

Cataloging the Praesepe Cluster: Identifying Interlopers and Binary Systems

NASA Astrophysics Data System (ADS)

Lucey, Madeline R.; Gosnell, Natalie M.; Mann, Andrew; Douglas, Stephanie

2018-01-01

We present radial velocity measurements from an ongoing survey of the Praesepe open cluster using the WIYN 3.5m Telescope. Our target stars include 229 early-K to mid-M dwarfs with proper motion memberships that have been observed by the repurposed Kepler mission, K2. With this survey, we will provide a well-constrained membership list of the cluster. By removing interloping stars and determining the cluster binary frequency we can avoid systematic errors in our analysis of the K2 findings and more accurately determine exoplanet properties in the Praesepe cluster. Obtaining accurate exoplanet parameters in open clusters allows us to study the temporal dimension of exoplanet parameter space. We find Praesepe to have a mean radial velocity of 34.09 km/s and a velocity dispersion of 1.13 km/s, which is consistent with previous studies. We derive radial velocity membership probabilities for stars with ≥3 radial velocity measurements and compare against published membership probabilities. We also identify radial velocity variables and potential double-lined spectroscopic binaries. We plan to obtain more observations to determine the radial velocity membership of all the stars in our sample, as well as follow up on radial velocity variables to determine binary orbital solutions.

Validation of individual and aggregate global flood hazard models for two major floods in Africa.

NASA Astrophysics Data System (ADS)

Trigg, M.; Bernhofen, M.; Whyman, C.

2017-12-01

A recent intercomparison of global flood hazard models undertaken by the Global Flood Partnership shows that there is an urgent requirement to undertake more validation of the models against flood observations. As part of the intercomparison, the aggregated model dataset resulting from the project was provided as open access data. We compare the individual and aggregated flood extent output from the six global models and test these against two major floods in the African Continent within the last decade, namely severe flooding on the Niger River in Nigeria in 2012, and on the Zambezi River in Mozambique in 2007. We test if aggregating different number and combination of models increases model fit to the observations compared with the individual model outputs. We present results that illustrate some of the challenges of comparing imperfect models with imperfect observations and also that of defining the probability of a real event in order to test standard model output probabilities. Finally, we propose a collective set of open access validation flood events, with associated observational data and descriptions that provide a standard set of tests across different climates and hydraulic conditions.

Photographic mark-recapture analysis of local dynamics within an open population of dolphins.

PubMed

Fearnbach, H; Durban, J; Parsons, K; Claridge, D

2012-07-01

Identifying demographic changes is important for understanding population dynamics. However, this requires long-term studies of definable populations of distinct individuals, which can be particularly challenging when studying mobile cetaceans in the marine environment. We collected photo-identification data from 19 years (1992-2010) to assess the dynamics of a population of bottlenose dolphins (Tursiops truncatus) restricted to the shallow (<7 m) waters of Little Bahama Bank, northern Bahamas. This population was known to range beyond our study area, so we adopted a Bayesian mixture modeling approach to mark-recapture to identify clusters of individuals that used the area to different extents, and we specifically estimated trends in survival, recruitment, and abundance of a "resident" population with high probabilities of identification. There was a high probability (p= 0.97) of a long-term decrease in the size of this resident population from a maximum of 47 dolphins (95% highest posterior density intervals, HPDI = 29-61) in 1996 to a minimum of just 24 dolphins (95% HPDI = 14-37) in 2009, a decline of 49% (95% HPDI = approximately 5% to approximately 75%). This was driven by low per capita recruitment (average approximately 0.02) that could not compensate for relatively low apparent survival rates (average approximately 0.94). Notably, there was a significant increase in apparent mortality (approximately 5 apparent mortalities vs. approximately 2 on average) in 1999 when two intense hurricanes passed over the study area, with a high probability (p = 0.83) of a drop below the average survival probability (approximately 0.91 in 1999; approximately 0.94, on average). As such, our mark-recapture approach enabled us to make useful inference about local dynamics within an open population of bottlenose dolphins; this should be applicable to other studies challenged by sampling highly mobile individuals with heterogeneous space use.

EMISSIONS OF ORGANIC AIR TOXICS FROM OPEN ...

EPA Pesticide Factsheets

A detailed literature search was performed to collect and collate available data reporting emissions of toxic organic substances into the air from open burning sources. Availability of data varied according to the source and the class of air toxics of interest. Volatile organic compound (VOC) and polycyclic aromatic hydrocarbon (PAH) data were available for many of the sources. Data on semivolatile organic compounds (SVOCs) that are not PAHs were available for several sources. Carbonyl and polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofuran (PCDD/F) data were available for only a few sources. There were several sources for which no emissions data were available at all. Several observations were made including: 1) Biomass open burning sources typically emitted less VOCs than open burning sources with anthropogenic fuels on a mass emitted per mass burned basis, particularly those where polymers were concerned; 2) Biomass open burning sources typically emitted less SVOCs and PAHs than anthropogenic sources on a mass emitted per mass burned basis. Burning pools of crude oil and diesel fuel produced significant amounts of PAHs relative to other types of open burning. PAH emissions were highest when combustion of polymers was taking place; and 3) Based on very limited data, biomass open burning sources typically produced higher levels of carbonyls than anthropogenic sources on a mass emitted per mass burned basis, probably due to oxygenated structures r

The Research and Implementation of MUSER CLEAN Algorithm Based on OpenCL

NASA Astrophysics Data System (ADS)

Feng, Y.; Chen, K.; Deng, H.; Wang, F.; Mei, Y.; Wei, S. L.; Dai, W.; Yang, Q. P.; Liu, Y. B.; Wu, J. P.

2017-03-01

It's urgent to carry out high-performance data processing with a single machine in the development of astronomical software. However, due to the different configuration of the machine, traditional programming techniques such as multi-threading, and CUDA (Compute Unified Device Architecture)+GPU (Graphic Processing Unit) have obvious limitations in portability and seamlessness between different operation systems. The OpenCL (Open Computing Language) used in the development of MUSER (MingantU SpEctral Radioheliograph) data processing system is introduced. And the Högbom CLEAN algorithm is re-implemented into parallel CLEAN algorithm by the Python language and PyOpenCL extended package. The experimental results show that the CLEAN algorithm based on OpenCL has approximately equally operating efficiency compared with the former CLEAN algorithm based on CUDA. More important, the data processing in merely CPU (Central Processing Unit) environment of this system can also achieve high performance, which has solved the problem of environmental dependence of CUDA+GPU. Overall, the research improves the adaptability of the system with emphasis on performance of MUSER image clean computing. In the meanwhile, the realization of OpenCL in MUSER proves its availability in scientific data processing. In view of the high-performance computing features of OpenCL in heterogeneous environment, it will probably become the preferred technology in the future high-performance astronomical software development.

Ligament-induced sacral fractures of the pelvis are possible.

PubMed

Steinke, Hanno; Hammer, Niels; Lingslebe, Uwe; Höch, Andreas; Klink, Thomas; Böhme, Jörg

2014-07-01

Pelvic ring stability is maintained passively by both the osseous and the ligamentous apparatus. Therapeutic approaches focus mainly on fracture patterns, so ligaments are often neglected. When they rupture along with the bone after pelvic ring fractures, disrupting stability, ligaments need to be considered during reconstruction and rehabilitation. Our aim was to determine the influence of ligaments on open-book injury using two experimental models with body donors. Mechanisms of bone avulsion related to open-book injury were investigated. Open-book injuries were induced in human pelves and subsequently investigated by anatomical dissection and endoscopy. The findings were compared to CT and MRI scans of open-book injuries. Relevant structures were further analyzed using plastinated cross-sections of the posterior pelvic ring. A fragment of the distal sacrum was observed, related to open-book injury. Two ligaments were found to be responsible for this avulsion phenomenon: the caudal portion of the anterior sacroiliac ligament and another ligament running along the ventral surface of the third sacral vertebra. The sacral fragment remained attached to the coxal bone by this second ligament after open-book injury. These results were validated using plastination and the structures were identified. Pelvic ligaments are probably involved in sacral avulsion caused by lateral traction. Therefore, ligaments should to be taken into account in diagnosis of open-book injury and subsequent therapy. Copyright © 2014 Wiley Periodicals, Inc.

Sill intrusion in volcanic calderas: implications for vent opening probability

NASA Astrophysics Data System (ADS)

Giudicepietro, Flora; Macedonio, Giovanni; Martini, Marcello; D'Auria, Luca

2017-04-01

Calderas show peculiar behaviors with remarkable dynamic processes, which do not often culminate in eruptions. Observations and studies conducted in recent decades have shown that the most common cause of unrest in the calderas is due to magma intrusion; in particular, the intrusion of sills at shallow depths. Monogenic cones, with large areal dispersion, are quite common in the calderas, suggesting that the susceptibility analysis based on geological features, is not strictly suitable for estimating the vent opening probability in calderas. In general, the opening of a new eruptive vent can be regarded as a rock failure process. The stress field in the rocks that surrounds and tops the magmatic reservoirs plays an important role in causing the rock failure and creating the path that magma can follow towards the surface. In this conceptual framework, we approach the problem of getting clues about the probability of vent opening in volcanic calderas through the study of the stress field produced by the intrusion of magma, in particular, by the intrusion of a sill. We simulate the intrusion of a sill free to expand radially, with shape and dimensions which vary with time. The intrusion process is controlled by the elastic response of the rock plate above the sill, which bends because of the intrusion, and by gravity, that drives the magma towards the zones where the thickness of the sill is smaller. We calculated the stress field in the plate rock above the sill. We found that at the bottom of the rock plate above the sill the maximum intensity of tensile stress is concentrated at the front of the sill and spreads radially with it, over time. For this reason, we think that the front of the spreading sill is prone to open for eruptive vents. Even in the central area of the sill the intensity of stress is relatively high, but at the base of the rock plate stress is compressive. Under isothermal conditions, the stress soon reaches its maximum value (time interval depending on the model parameters) and then decreases over time during the intrusion. However, if we consider the effect of the cooling of magma, with the temperature which decreases with time and the viscosity that increases, we'll find that the stress in the rock above the sill gradually increases with time and becomes higher than in isothermal case. In order to investigate the role of the physical properties of magma and rock above the sill in the generation of the stress field we have carried out different simulations by varying the viscosity of magma and the rigidity of the rock and found that high viscosity magma produces a relatively high stress intensity, as well as a high rock rigidity does.

Understanding Hawking radiation in the framework of open quantum systems

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

Yu Hongwei; Zhang Jialin

2008-01-15

We study the Hawking radiation in the framework of open quantum systems by examining the time evolution of a detector (modeled by a two-level atom) interacting with vacuum massless scalar fields. The dynamics of the detector is governed by a master equation obtained by tracing over the field degrees of freedom from the complete system. The nonunitary effects are studied by analyzing the time behavior of a particular observable of the detector, i.e., its admissible state, in the Unruh, Hartle-Hawking, as well as Boulware vacua outside a Schwarzschild black hole. We find that the detector in both the Unruh andmore » Hartle-Hawking vacua would spontaneously excite with a nonvanishing probability the same as what one would obtain if there is thermal radiation at the Hawking temperature from the black hole, thus reproducing the basic results concerning the Hawking effect in the framework of open quantum systems.« less

Coupling of activation and inactivation gate in a K+-channel: potassium and ligand sensitivity

PubMed Central

Ader, Christian; Schneider, Robert; Hornig, Sönke; Velisetty, Phanindra; Vardanyan, Vitya; Giller, Karin; Ohmert, Iris; Becker, Stefan; Pongs, Olaf; Baldus, Marc

2009-01-01

Potassium (K+)-channel gating is choreographed by a complex interplay between external stimuli, K+ concentration and lipidic environment. We combined solid-state NMR and electrophysiological experiments on a chimeric KcsA–Kv1.3 channel to delineate K+, pH and blocker effects on channel structure and function in a membrane setting. Our data show that pH-induced activation is correlated with protonation of glutamate residues at or near the activation gate. Moreover, K+ and channel blockers distinctly affect the open probability of both the inactivation gate comprising the selectivity filter of the channel and the activation gate. The results indicate that the two gates are coupled and that effects of the permeant K+ ion on the inactivation gate modulate activation-gate opening. Our data suggest a mechanism for controlling coordinated and sequential opening and closing of activation and inactivation gates in the K+-channel pore. PMID:19661921

A preliminary comparison of photometric (MWSC) and trigonometric (TGAS) distances of open cluster stars

NASA Astrophysics Data System (ADS)

Kovaleva, Dana; Piskunov, Anatoly; Kharchenko, Nina; Scholz, Ralf-Dieter

2017-12-01

The goal of this researchwas to compare the open cluster photometric distance scale of the global survey of star clusters in the MilkyWay (MWSC) with the distances derived fromtrigonometric parallaxes fromthe Gaia DR1/TGAS catalogue and to investigate towhich degree and extent both scales agree.We compared the parallax-based and photometrybased distances of 5743 cluster stars selected as members of 1118 clusters based on their kinematic and photometric MWSC membership probabilities. We found good overall agreement between trigonometric and photometric distances of open cluster stars. The residuals between them were small and unbiased up to log(d, [pc]) ≈ 2.8. If we considered only the most populated clusters and used cluster distances obtained from the mean trigonometric parallax of their MWSC members, the good agreement of the distance scales continued up to log(d, [pc]) ≈ 3.3.

Organic micropollutants in marine plastics debris from the open ocean and remote and urban beaches.

PubMed

Hirai, Hisashi; Takada, Hideshige; Ogata, Yuko; Yamashita, Rei; Mizukawa, Kaoruko; Saha, Mahua; Kwan, Charita; Moore, Charles; Gray, Holly; Laursen, Duane; Zettler, Erik R; Farrington, John W; Reddy, Christopher M; Peacock, Emily E; Ward, Marc W

2011-08-01

To understand the spatial variation in concentrations and compositions of organic micropollutants in marine plastic debris and their sources, we analyzed plastic fragments (∼10 mm) from the open ocean and from remote and urban beaches. Polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), dichloro-diphenyl-trichloroethane and its metabolites (DDTs), polybrominated diphenyl ethers (PBDEs), alkylphenols and bisphenol A were detected in the fragments at concentrations from 1 to 10,000 ng/g. Concentrations showed large piece-to-piece variability. Hydrophobic organic compounds such as PCBs and PAHs were sorbed from seawater to the plastic fragments. PCBs are most probably derived from legacy pollution. PAHs showed a petrogenic signature, suggesting the sorption of PAHs from oil slicks. Nonylphenol, bisphenol A, and PBDEs came mainly from additives and were detected at high concentrations in some fragments both from remote and urban beaches and the open ocean. Copyright © 2011 Elsevier Ltd. All rights reserved.

Biophysical Properties of ATP-sensitive Potassium Channels in CA3 Hippocampal Neurons

NASA Astrophysics Data System (ADS)

Obregón-Herrera, Armando; Márquez-Gamiño, Sergio; Onetti, Carlos G.

2004-09-01

Single-channel activity of glucose-sensitive channels from CA3 neurons of the rat hippocampus, was studied in cell-attached membrane patches. Single-channel activity was totally abolished at 20 mM external glucose. Glucose-sensitive channels were selective to K+ ions; the unitary conductance was 170 pS in 140 mM K+, and the K+ permeability was 3.86×10-13 cmṡs-1. The open-state probability (PO) increased with membrane depolarization as a result of mean open time enhancement and shortening of the closure periods. The activation midpoint was -79 mV. Glucose-sensitive K+ channel of CA3 neurons could be considered as an ATP-sensitive potassium channel.

Quasibound states in a triple Gaussian potential

NASA Astrophysics Data System (ADS)

Reichl, L. E.; Porter, Max D.

2018-04-01

We derive the transmission probabilities and delay times, and identify quasibound state structures in an open quantum system consisting of three Gaussian potential energy peaks, a system whose classical scattering dynamics we show to be chaotic. Such open quantum systems can serve as models for nanoscale quantum devices and their wave dynamics are similar to electromagnetic wave dynamics in optical microcavities. We use a quantum web to determine energy regimes for which the system exhibits the quantum manifestations of chaos, and we show that the classical scattering dynamics contains a significant amount of chaos. We also derive an exact expression for the non-Hermitian Hamiltonian whose eigenvalues give quasibound state energies and lifetimes of the system.

Piston manometer as an absolute standard for vacuum-gage calibration in the range 2 to 500 millitorr

NASA Technical Reports Server (NTRS)

Warshawsky, I.

1972-01-01

A thin disk is suspended, with very small annular clearance, in a cylindrical opening in the base plate of a calibration chamber. A continuous flow of calibration gas passes through the chamber and annular opening to a downstream high vacuum pump. The ratio of pressures on the two faces of the disk is very large, so that the upstream pressure is substantially equal to net force on the disk divided by disk area. This force is measured with a dynamometer that is calibrated in place with dead weights. A probable error of + or - (0.2 millitorr plus 0.2 percent) is attainable when downstream pressure is known to 10 percent.

The investigation of the lateral interaction effect's on traffic flow behavior under open boundaries

NASA Astrophysics Data System (ADS)

Bouadi, M.; Jetto, K.; Benyoussef, A.; El Kenz, A.

2017-11-01

In this paper, an open boundaries traffic flow system is studied by taking into account the lateral interaction with spatial defects. For a random defects distribution, if the vehicles velocities are weakly correlated, the traffic phases can be predicted by considering the corresponding inflow and outflow functions. Conversely, if the vehicles velocities are strongly correlated, a phase segregation appears inside the system's bulk which induces the maximum current appearance. Such velocity correlation depends mainly on the defects densities and the probabilities of lateral deceleration. However, for a compact defects distribution, the traffic phases are predictable by using the inflow in the system beginning, the inflow entering the defects zone and the outflow function.

Are Birds Smarter Than Mathematicians? Pigeons (Columba livia) Perform Optimally on a Version of the Monty Hall Dilemma

PubMed Central

Herbranson, Walter T.; Schroeder, Julia

2011-01-01

The “Monty Hall Dilemma” (MHD) is a well known probability puzzle in which a player tries to guess which of three doors conceals a desirable prize. After an initial choice is made, one of the remaining doors is opened, revealing no prize. The player is then given the option of staying with their initial guess or switching to the other unopened door. Most people opt to stay with their initial guess, despite the fact that switching doubles the probability of winning. A series of experiments investigated whether pigeons (Columba livia), like most humans, would fail to maximize their expected winnings in a version of the MHD. Birds completed multiple trials of a standard MHD, with the three response keys in an operant chamber serving as the three doors and access to mixed grain as the prize. Across experiments, the probability of gaining reinforcement for switching and staying was manipulated, and birds adjusted their probability of switching and staying to approximate the optimal strategy. Replication of the procedure with human participants showed that humans failed to adopt optimal strategies, even with extensive training. PMID:20175592

Comparison of three versions of Partin tables to predict final pathologic stage in a Chinese cohort: a decision curve analysis.

PubMed

Xiao, Wen-Jun; Ye, Ding-Wei; Yao, Xu-Dong; Zhang, Shi-Lin; Dai, Bo

2013-01-01

To compare Partin tables (PTs) 1997, 2001, and 2007 for their clinical applicability in a Chinese cohort based upon a decision curve analysis (DCA). Clinical and pathologic data of 264 consecutive Chinese patients with clinically localized prostate cancer were used. These patients underwent open radical prostatectomy between 2005 and 2011. DCA quantified the net benefit of different PT versions relating to specific threshold probabilities of established capsular penetration (ECP), seminal vesicle involvement (SVI), and lymph node involvement (LNI). Overall, ECP, SVI, and LNI were recorded in 23.1, 10.2, and 6.1%, respectively. When the threshold probability was below the prevalence for LNI and ECP predictions, the DCA favored the 2007 version versus the 1997 version for SVI. DCA indicates that for low threshold probability, decision models are useful to discriminate the performance differences of three PT versions, although net benefit differences were not apparent. For high threshold probability, there may not be an important benefit from the use of PTs and the current analysis cannot translate into meaningful net gains differences. Copyright © 2013 S. Karger AG, Basel.

Quantum stochastic walks on networks for decision-making.

PubMed

Martínez-Martínez, Ismael; Sánchez-Burillo, Eduardo

2016-03-31

Recent experiments report violations of the classical law of total probability and incompatibility of certain mental representations when humans process and react to information. Evidence shows promise of a more general quantum theory providing a better explanation of the dynamics and structure of real decision-making processes than classical probability theory. Inspired by this, we show how the behavioral choice-probabilities can arise as the unique stationary distribution of quantum stochastic walkers on the classical network defined from Luce's response probabilities. This work is relevant because (i) we provide a very general framework integrating the positive characteristics of both quantum and classical approaches previously in confrontation, and (ii) we define a cognitive network which can be used to bring other connectivist approaches to decision-making into the quantum stochastic realm. We model the decision-maker as an open system in contact with her surrounding environment, and the time-length of the decision-making process reveals to be also a measure of the process' degree of interplay between the unitary and irreversible dynamics. Implementing quantum coherence on classical networks may be a door to better integrate human-like reasoning biases in stochastic models for decision-making.

Quantum stochastic walks on networks for decision-making

NASA Astrophysics Data System (ADS)

Martínez-Martínez, Ismael; Sánchez-Burillo, Eduardo

2016-03-01

Recent experiments report violations of the classical law of total probability and incompatibility of certain mental representations when humans process and react to information. Evidence shows promise of a more general quantum theory providing a better explanation of the dynamics and structure of real decision-making processes than classical probability theory. Inspired by this, we show how the behavioral choice-probabilities can arise as the unique stationary distribution of quantum stochastic walkers on the classical network defined from Luce’s response probabilities. This work is relevant because (i) we provide a very general framework integrating the positive characteristics of both quantum and classical approaches previously in confrontation, and (ii) we define a cognitive network which can be used to bring other connectivist approaches to decision-making into the quantum stochastic realm. We model the decision-maker as an open system in contact with her surrounding environment, and the time-length of the decision-making process reveals to be also a measure of the process’ degree of interplay between the unitary and irreversible dynamics. Implementing quantum coherence on classical networks may be a door to better integrate human-like reasoning biases in stochastic models for decision-making.

Quantum stochastic walks on networks for decision-making

PubMed Central

Martínez-Martínez, Ismael; Sánchez-Burillo, Eduardo

2016-01-01

Recent experiments report violations of the classical law of total probability and incompatibility of certain mental representations when humans process and react to information. Evidence shows promise of a more general quantum theory providing a better explanation of the dynamics and structure of real decision-making processes than classical probability theory. Inspired by this, we show how the behavioral choice-probabilities can arise as the unique stationary distribution of quantum stochastic walkers on the classical network defined from Luce’s response probabilities. This work is relevant because (i) we provide a very general framework integrating the positive characteristics of both quantum and classical approaches previously in confrontation, and (ii) we define a cognitive network which can be used to bring other connectivist approaches to decision-making into the quantum stochastic realm. We model the decision-maker as an open system in contact with her surrounding environment, and the time-length of the decision-making process reveals to be also a measure of the process’ degree of interplay between the unitary and irreversible dynamics. Implementing quantum coherence on classical networks may be a door to better integrate human-like reasoning biases in stochastic models for decision-making. PMID:27030372

Are birds smarter than mathematicians? Pigeons (Columba livia) perform optimally on a version of the Monty Hall Dilemma.

PubMed

Herbranson, Walter T; Schroeder, Julia

2010-02-01

The "Monty Hall Dilemma" (MHD) is a well known probability puzzle in which a player tries to guess which of three doors conceals a desirable prize. After an initial choice is made, one of the remaining doors is opened, revealing no prize. The player is then given the option of staying with their initial guess or switching to the other unopened door. Most people opt to stay with their initial guess, despite the fact that switching doubles the probability of winning. A series of experiments investigated whether pigeons (Columba livia), like most humans, would fail to maximize their expected winnings in a version of the MHD. Birds completed multiple trials of a standard MHD, with the three response keys in an operant chamber serving as the three doors and access to mixed grain as the prize. Across experiments, the probability of gaining reinforcement for switching and staying was manipulated, and birds adjusted their probability of switching and staying to approximate the optimal strategy. Replication of the procedure with human participants showed that humans failed to adopt optimal strategies, even with extensive training.

Discovering Peripheral Arterial Disease Cases from Radiology Notes Using Natural Language Processing

PubMed Central

Savova, Guergana K.; Fan, Jin; Ye, Zi; Murphy, Sean P.; Zheng, Jiaping; Chute, Christopher G.; Kullo, Iftikhar J.

2010-01-01

As part of the Electronic Medical Records and Genomics Network, we applied, extended and evaluated an open source clinical Natural Language Processing system, Mayo’s Clinical Text Analysis and Knowledge Extraction System, for the discovery of peripheral arterial disease cases from radiology reports. The manually created gold standard consisted of 223 positive, 19 negative, 63 probable and 150 unknown cases. Overall accuracy agreement between the system and the gold standard was 0.93 as compared to a named entity recognition baseline of 0.46. Sensitivity for the positive, probable and unknown cases was 0.93–0.96, and for the negative cases was 0.72. Specificity and negative predictive value for all categories were in the 90’s. The positive predictive value for the positive and unknown categories was in the high 90’s, for the negative category was 0.84, and for the probable category was 0.63. We outline the main sources of errors and suggest improvements. PMID:21347073

A model of VDAC structural rearrangement in the presence of a salt activity gradient

NASA Astrophysics Data System (ADS)

Levadny, Victor; Colombini, Marco; Aguilella, Vicente M.

2001-11-01

We have considered the structural transformations of a voltage dependent anion-selective channel (VDAC) known as `gating'. We analysed the redistribution of VDAC among its states. The difference in electrostatic energy between the trans-closed and cis-closed states of VDAC is shown to be the cause of changes in the voltage dependence of the gating in the presence of a salt activity gradient. The asymmetry in the voltage dependence of the open probability about zero millivolts was connected with the apparent location of the voltage sensor. The theory describes the experimental data satisfactorily and explains the nature of the shift of the probability curve as well as the differences found in the asymmetry of the curve for different salts.

Double-survey estimates of bald eagle populations in Oregon

USGS Publications Warehouse

Anthony, R.G.; Garrett, Monte G.; Isaacs, F.B.

1999-01-01

The literature on abundance of birds of prey is almost devoid of population estimates with statistical rigor. Therefore, we surveyed bald eagle (Haliaeetus leucocephalus) populations on the Crooked and lower Columbia rivers of Oregon and used the double-survey method to estimate populations and sighting probabilities for different survey methods (aerial, boat, vehicle) and bald eagle ages (adults vs. subadults). Sighting probabilities were consistently 20%. The results revealed variable and negative bias (percent relative bias = -9 to -70%) of direct counts and emphasized the importance of estimating populations where some measure of precision and ability to conduct inference tests are available. We recommend use of the double-survey method to estimate abundance of bald eagle populations and other raptors in open habitats.

Calmodulin kinase II and protein kinase C mediate the effect of increased intracellular calcium to augment late sodium current in rabbit ventricular myocytes.

PubMed

Ma, Jihua; Luo, Antao; Wu, Lin; Wan, Wei; Zhang, Peihua; Ren, Zhiqiang; Zhang, Shuo; Qian, Chunping; Shryock, John C; Belardinelli, Luiz

2012-04-15

An increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) augments late sodium current (I(Na.L)) in cardiomyocytes. This study tests the hypothesis that both Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) and protein kinase C (PKC) mediate the effect of increased [Ca(2+)](i) to increase I(Na.L). Whole cell and open cell-attached patch clamp techniques were used to record I(Na.L) in rabbit ventricular myocytes dialyzed with solutions containing various concentrations of [Ca(2+)](i). Dialysis of cells with [Ca(2+)](i) from 0.1 to 0.3, 0.6, and 1.0 μM increased I(Na.L) in a concentration-dependent manner from 0.221 ± 0.038 to 0.554 ± 0.045 pA/pF (n = 10, P < 0.01) and was associated with an increase in mean Na(+) channel open probability and prolongation of channel mean open-time (n = 7, P < 0.01). In the presence of 0.6 μM [Ca(2+)](i), KN-93 (10 μM) and bisindolylmaleimide (BIM, 2 μM) decreased I(Na.L) by 45.2 and 54.8%, respectively. The effects of KN-93 and autocamtide-2-related inhibitory peptide II (2 μM) were not different. A combination of KN-93 and BIM completely reversed the increase in I(Na.L) as well as the Ca(2+)-induced changes in Na(+) channel mean open probability and mean open-time induced by 0.6 μM [Ca(2+)](i). Phorbol myristoyl acetate increased I(Na.L) in myocytes dialyzed with 0.1 μM [Ca(2+)](i); the effect was abolished by Gö-6976. In summary, both CaMKII and PKC are involved in [Ca(2+)](i)-mediated augmentation of I(Na.L) in ventricular myocytes. Inhibition of CaMKII and/or PKC pathways may be a therapeutic target to reduce myocardial dysfunction and cardiac arrhythmias caused by calcium overload.

Analysis of Spectral-type A/B Stars in Five Open Clusters

NASA Astrophysics Data System (ADS)

Wilhelm, Ronald J.; Rafuil Islam, M.

2014-01-01

We have obtained low resolution (R = 1000) spectroscopy of N=68, spectral-type A/B stars in five nearby open star clusters using the McDonald Observatory, 2.1m telescope. The sample of blue stars in various clusters were selected to test our new technique for determining interstellar reddening and distances in areas where interstellar reddening is high. We use a Bayesian approach to find the posterior distribution for Teff, Logg and [Fe/H] from a combination of reddened, photometric colors and spectroscopic line strengths. We will present calibration results for this technique using open cluster star data with known reddening and distances. Preliminary results suggest our technique can produce both reddening and distance determinations to within 10% of cluster values. Our technique opens the possibility of determining distances for blue stars at low Galactic latitudes where extinction can be large and differential. We will also compare our stellar parameter determinations to previously reported MK spectral classifications and discuss the probability that some of our stars are not members of their reported clusters.

Automatic threshold selection for multi-class open set recognition

NASA Astrophysics Data System (ADS)

Scherreik, Matthew; Rigling, Brian

2017-05-01

Multi-class open set recognition is the problem of supervised classification with additional unknown classes encountered after a model has been trained. An open set classifer often has two core components. The first component is a base classifier which estimates the most likely class of a given example. The second component consists of open set logic which estimates if the example is truly a member of the candidate class. Such a system is operated in a feed-forward fashion. That is, a candidate label is first estimated by the base classifier, and the true membership of the example to the candidate class is estimated afterward. Previous works have developed an iterative threshold selection algorithm for rejecting examples from classes which were not present at training time. In those studies, a Platt-calibrated SVM was used as the base classifier, and the thresholds were applied to class posterior probabilities for rejection. In this work, we investigate the effectiveness of other base classifiers when paired with the threshold selection algorithm and compare their performance with the original SVM solution.

Influence of light and plant size on the reproduction and growth of small palm tree species: Comparing two methods for measuring canopy openness.

PubMed

Amadeu, Luã S N; Sampaio, Mauricio B; Dos Santos, Flavio A M

2016-09-01

The reproduction and growth of large palms are influenced by many factors, including light and plant size, but few studies have examined smaller species (up to 2 m tall). We examined the effect of incident light and individual size on growth rates, the probability of reproduction, and the number of inflorescences of three small palm species and compared two methods for estimating canopy openness. We measured canopy openness above the crowns of 132 adult plants and in the centers of 72 subplots (10 × 10 m) where individuals were sampled. We also recorded individual size and the number of leaves and inflorescences produced in two years. Reproductive individuals of Butia paraguayensis tend to occur in illuminated microhabitats. Reproduction of Acrocomia emensis was correlated with stem diameter, but not with light. Reproduction was inversely related to individual size and light in Syagrus petraea, probably because this clonal palm invests heavily in sexual reproduction during its younger stages and clonal activity in older stages and may be adapted to the low-light conditions of the woodland understory. Growth was not predicted by light or individual size. Stronger correlations were found when incident light was measured directly above the crown, as opposed to the subplot center. The influences of light on reproduction are dependent on plant life histories, even among related and sympatric species. Light measurements directly above individual crowns provide better understanding of the reproductive effort rather than in subplot center. © 2016 Botanical Society of America.

Risk models for mortality following elective open and endovascular abdominal aortic aneurysm repair: a single institution experience.

PubMed

Choke, E; Lee, K; McCarthy, M; Nasim, A; Naylor, A R; Bown, M; Sayers, R

2012-12-01

To develop and validate an "in house" risk model for predicting perioperative mortality following elective AAA repair and to compare this with other models. Multivariate logistics regression analysis was used to identify risk factors for perioperative-day mortality from one tertiary institution's prospectively maintained database. Consecutive elective open (564) and endovascular (589) AAA repairs (2000-2010) were split randomly into development (810) and validation (343) data sets. The resultant model was compared to Glasgow Aneurysm Score (GAS), Modified Customised Probability Index (m-CPI), CPI, the Vascular Governance North West (VGNW) model and the Medicare model. Variables associated with perioperative mortality included: increasing age (P = 0.034), myocardial infarct within last 10 years (P = 0.0008), raised serum creatinine (P = 0.005) and open surgery (P = 0.0001). The areas under the receiver operating characteristic curve (AUC) for predicted probability of 30-day mortality in development and validation data sets were 0.79 and 0.82 respectively. AUCs for GAS, m-CPI and CPI were poor (0.63, 0.58 and 0.58 respectively), whilst VGNW and Medicare model were fair (0.73 and 0.79 respectively). In this study, an "in-house" developed and validated risk model has the most accurate discriminative value in predicting perioperative mortality after elective AAA repair. For purposes of comparative audit with case mix adjustments, national models such as the VGNW or Medicare models should be used. Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Single-Transverse-Spin-Asymmetry studies with a fixed-target experiment using the LHC beams (AFTER@LHC)

DOE PAGES

Lansberg, J. P.; Anselmino, M.; Arnaldi, R.; ...

2016-11-19

Here we discuss the potential of AFTER@LHC to measure single-transverse-spin asymmetries in open-charm and bottomonium production. With a HERMES-like hydrogen polarised target, such measurements over a year can reach precisions close to the per cent level. This is particularly remarkable since these analyses can probably not be carried out anywhere else.

Bear damage to young Douglas-fir.

Treesearch

Thomas W. Childs; Norman P. Worthington

1955-01-01

Newly-formed sapwood of young conifers has probably been a food for bears since time immemorial, but damage to trees has only recently attracted the attention of foresters. In many localities, all stages of bear-caused wounds can be found, from fresh ones to those covered with callus, On a 3-acre clear-cut, made in 1950 in a rather open part of the 110-year-old stand...

A Comparison of Grizzly Bear Demographic Parameters Estimated from Non-Spatial and Spatial Open Population Capture-Recapture Models

PubMed Central

Whittington, Jesse; Sawaya, Michael A.

2015-01-01

Capture-recapture studies are frequently used to monitor the status and trends of wildlife populations. Detection histories from individual animals are used to estimate probability of detection and abundance or density. The accuracy of abundance and density estimates depends on the ability to model factors affecting detection probability. Non-spatial capture-recapture models have recently evolved into spatial capture-recapture models that directly include the effect of distances between an animal’s home range centre and trap locations on detection probability. Most studies comparing non-spatial and spatial capture-recapture biases focussed on single year models and no studies have compared the accuracy of demographic parameter estimates from open population models. We applied open population non-spatial and spatial capture-recapture models to three years of grizzly bear DNA-based data from Banff National Park and simulated data sets. The two models produced similar estimates of grizzly bear apparent survival, per capita recruitment, and population growth rates but the spatial capture-recapture models had better fit. Simulations showed that spatial capture-recapture models produced more accurate parameter estimates with better credible interval coverage than non-spatial capture-recapture models. Non-spatial capture-recapture models produced negatively biased estimates of apparent survival and positively biased estimates of per capita recruitment. The spatial capture-recapture grizzly bear population growth rates and 95% highest posterior density averaged across the three years were 0.925 (0.786–1.071) for females, 0.844 (0.703–0.975) for males, and 0.882 (0.779–0.981) for females and males combined. The non-spatial capture-recapture population growth rates were 0.894 (0.758–1.024) for females, 0.825 (0.700–0.948) for males, and 0.863 (0.771–0.957) for both sexes. The combination of low densities, low reproductive rates, and predominantly negative population growth rates suggest that Banff National Park’s population of grizzly bears requires continued conservation-oriented management actions. PMID:26230262

The Cost-Effectiveness of Surgical Fixation of Distal Radial Fractures: A Computer Model-Based Evaluation of Three Operative Modalities.

PubMed

Rajan, Prashant V; Qudsi, Rameez A; Dyer, George S M; Losina, Elena

2018-02-07

There is no consensus on the optimal fixation method for patients who require a surgical procedure for distal radial fractures. We used cost-effectiveness analyses to determine which of 3 modalities offers the best value: closed reduction and percutaneous pinning, open reduction and internal fixation, or external fixation. We developed a Markov model that projected short-term and long-term health benefits and costs in patients undergoing a surgical procedure for a distal radial fracture. Simulations began at the patient age of 50 years and were run over the patient's lifetime. The analysis was conducted from health-care payer and societal perspectives. We estimated transition probabilities and quality-of-life values from the literature and determined costs from Medicare reimbursement schedules in 2016 U.S. dollars. Suboptimal postoperative outcomes were determined by rates of reduction loss (4% for closed reduction and percutaneous pinning, 1% for open reduction and internal fixation, and 11% for external fixation) and rates of orthopaedic complications. Procedural costs were $7,638 for closed reduction and percutaneous pinning, $10,170 for open reduction and internal fixation, and $9,886 for external fixation. Outputs were total costs and quality-adjusted life-years (QALYs), discounted at 3% per year. We considered willingness-to-pay thresholds of $50,000 and $100,000. We conducted deterministic and probabilistic sensitivity analyses to evaluate the impact of data uncertainty. From the health-care payer perspective, closed reduction and percutaneous pinning dominated (i.e., produced greater QALYs at lower costs than) open reduction and internal fixation and dominated external fixation. From the societal perspective, the incremental cost-effectiveness ratio for closed reduction and percutaneous pinning compared with open reduction and internal fixation was $21,058 per QALY and external fixation was dominated. In probabilistic sensitivity analysis, open reduction and internal fixation was cost-effective roughly 50% of the time compared with roughly 45% for closed reduction and percutaneous pinning. When considering data uncertainty, there is only a 5% to 10% difference in the frequency of probability combinations that find open reduction and internal fixation to be more cost-effective. The current degree of uncertainty in the data produces difficulty in distinguishing either strategy as being more cost-effective overall and thus it may be left to surgeon and patient shared decision-making. Economic Level III. See Instructions for Authors for a complete description of levels of evidence.

Phosphorylation of rat brain purified mitochondrial Voltage-Dependent Anion Channel by c-Jun N-terminal kinase-3 modifies open-channel noise.

PubMed

Gupta, Rajeev

2017-09-02

The drift kinetic energy of ionic flow through single ion channels cause vibrations of the pore walls which are observed as open-state current fluctuations (open-channel noise) during single-channel recordings. Vibration of the pore wall leads to transitions among different conformational sub-states of the channel protein in the open-state. Open-channel noise analysis can provide important information about the different conformational sub-state transitions and how biochemical modifications of ion channels would affect their transport properties. It has been shown that c-Jun N-terminal kinase-3 (JNK3) becomes activated by phosphorylation in various neurodegenerative diseases and phosphorylates outer mitochondrion associated proteins leading to neuronal apoptosis. In our earlier work, JNK3 has been reported to phosphorylate purified rat brain mitochondrial voltage-dependent anion channel (VDAC) in vitro and modify its conductance and opening probability. In this article we have compared the open-state noise profile of the native and the JNK3 phosphorylated VDAC using Power Spectral Density vs frequency plots. Power spectral density analysis of open-state noise indicated power law with average slope value α ≈1 for native VDAC at both positive and negative voltage whereas average α value < 0.5 for JNK3 phosphorylated VDAC at both positive and negative voltage. It is proposed that 1/f 1 power law in native VDAC open-state noise arises due to coupling of ionic transport and conformational sub-states transitions in open-state and this coupling is perturbed as a result of channel phosphorylation. Copyright © 2017 Elsevier Inc. All rights reserved.

Reliability analysis for determining performance of barrage based on gates operation

NASA Astrophysics Data System (ADS)

Adiningrum, C.; Hadihardaja, I. K.

2017-06-01

Some rivers located on a flat slope topography such as Cilemahabang river and Ciherang river in Cilemahabang watershed, Bekasi regency, West Java are susceptible to flooding. The inundation mostly happens near a barrage in the middle and downstream of the Cilemahabang watershed, namely the Cilemahabang and Caringin barrages. Barrages or gated weirs are difficult to exploit since the gate must be kept and operated properly under any circumstances. Therefore, a reliability analysis of the gates operation is necessary to determine the performance of the barrage with respect to the number of gates opened and the gates opening heights. The First Order Second Moment (FOSM) method was used to determine the performance by the reliability index (β) and the probability of failure (risk). It was found that for Cilemahabang Barrage, the number of gates opened with load (L) represents the peak discharge derived from various rainfall (P) respectively one gate with opening height (h=1m) for Preal, two gates (h=1m and h=1,5m) for P50, and three gates (each gate with h=2,5m) for P100. For Caringin Barrage, the results are minimum three gates opened (each gate with h=2,5 m) for Preal, five gates opened (each gate with h=2,5m) for P50, and six gates opened (each gate with h=2,5m) for P100. It can be concluded that a greater load (L) needs greater resistance (R) to counterbalance. Resistance can be added by increasing the number of gates opened and the gate opening height. A higher number of gates opened will lead to the decrease of water level in the upstream of barrage and less risk of overflow.

Estimating the empirical probability of submarine landslide occurrence

USGS Publications Warehouse

Geist, Eric L.; Parsons, Thomas E.; Mosher, David C.; Shipp, Craig; Moscardelli, Lorena; Chaytor, Jason D.; Baxter, Christopher D. P.; Lee, Homa J.; Urgeles, Roger

2010-01-01

The empirical probability for the occurrence of submarine landslides at a given location can be estimated from age dates of past landslides. In this study, tools developed to estimate earthquake probability from paleoseismic horizons are adapted to estimate submarine landslide probability. In both types of estimates, one has to account for the uncertainty associated with age-dating individual events as well as the open time intervals before and after the observed sequence of landslides. For observed sequences of submarine landslides, we typically only have the age date of the youngest event and possibly of a seismic horizon that lies below the oldest event in a landslide sequence. We use an empirical Bayes analysis based on the Poisson-Gamma conjugate prior model specifically applied to the landslide probability problem. This model assumes that landslide events as imaged in geophysical data are independent and occur in time according to a Poisson distribution characterized by a rate parameter λ. With this method, we are able to estimate the most likely value of λ and, importantly, the range of uncertainty in this estimate. Examples considered include landslide sequences observed in the Santa Barbara Channel, California, and in Port Valdez, Alaska. We confirm that given the uncertainties of age dating that landslide complexes can be treated as single events by performing statistical test of age dates representing the main failure episode of the Holocene Storegga landslide complex.

[Predicting the probability of development and progression of primary open angle glaucoma by regression modeling].

PubMed

Likhvantseva, V G; Sokolov, V A; Levanova, O N; Kovelenova, I V

2018-01-01

Prediction of the clinical course of primary open-angle glaucoma (POAG) is one of the main directions in solving the problem of vision loss prevention and stabilization of the pathological process. Simple statistical methods of correlation analysis show the extent of each risk factor's impact, but do not indicate the total impact of these factors in personalized combinations. The relationships between the risk factors is subject to correlation and regression analysis. The regression equation represents the dependence of the mathematical expectation of the resulting sign on the combination of factor signs. To develop a technique for predicting the probability of development and progression of primary open-angle glaucoma based on a personalized combination of risk factors by linear multivariate regression analysis. The study included 66 patients (23 female and 43 male; 132 eyes) with newly diagnosed primary open-angle glaucoma. The control group consisted of 14 patients (8 male and 6 female). Standard ophthalmic examination was supplemented with biochemical study of lacrimal fluid. Concentration of matrix metalloproteinase MMP-2 and MMP-9 in tear fluid in both eyes was determined using 'sandwich' enzyme-linked immunosorbent assay (ELISA) method. The study resulted in the development of regression equations and step-by-step multivariate logistic models that can help calculate the risk of development and progression of POAG. Those models are based on expert evaluation of clinical and instrumental indicators of hydrodynamic disturbances (coefficient of outflow ease - C, volume of intraocular fluid secretion - F, fluctuation of intraocular pressure), as well as personalized morphometric parameters of the retina (central retinal thickness in the macular area) and concentration of MMP-2 and MMP-9 in the tear film. The newly developed regression equations are highly informative and can be a reliable tool for studying of the influence vector and assessment of pathogenic potential of the independent risk factors in specific personalized combinations.

Uniform California earthquake rupture forecast, version 2 (UCERF 2)

USGS Publications Warehouse

Field, E.H.; Dawson, T.E.; Felzer, K.R.; Frankel, A.D.; Gupta, V.; Jordan, T.H.; Parsons, T.; Petersen, M.D.; Stein, R.S.; Weldon, R.J.; Wills, C.J.

2009-01-01

The 2007 Working Group on California Earthquake Probabilities (WGCEP, 2007) presents the Uniform California Earthquake Rupture Forecast, Version 2 (UCERF 2). This model comprises a time-independent (Poisson-process) earthquake rate model, developed jointly with the National Seismic Hazard Mapping Program and a time-dependent earthquake-probability model, based on recent earthquake rates and stress-renewal statistics conditioned on the date of last event. The models were developed from updated statewide earthquake catalogs and fault deformation databases using a uniform methodology across all regions and implemented in the modular, extensible Open Seismic Hazard Analysis framework. The rate model satisfies integrating measures of deformation across the plate-boundary zone and is consistent with historical seismicity data. An overprediction of earthquake rates found at intermediate magnitudes (6.5 ??? M ???7.0) in previous models has been reduced to within the 95% confidence bounds of the historical earthquake catalog. A logic tree with 480 branches represents the epistemic uncertainties of the full time-dependent model. The mean UCERF 2 time-dependent probability of one or more M ???6.7 earthquakes in the California region during the next 30 yr is 99.7%; this probability decreases to 46% for M ???7.5 and to 4.5% for M ???8.0. These probabilities do not include the Cascadia subduction zone, largely north of California, for which the estimated 30 yr, M ???8.0 time-dependent probability is 10%. The M ???6.7 probabilities on major strike-slip faults are consistent with the WGCEP (2003) study in the San Francisco Bay Area and the WGCEP (1995) study in southern California, except for significantly lower estimates along the San Jacinto and Elsinore faults, owing to provisions for larger multisegment ruptures. Important model limitations are discussed.

A hydroclimatological approach to predicting regional landslide probability using Landlab

NASA Astrophysics Data System (ADS)

Strauch, Ronda; Istanbulluoglu, Erkan; Nudurupati, Sai Siddhartha; Bandaragoda, Christina; Gasparini, Nicole M.; Tucker, Gregory E.

2018-02-01

We develop a hydroclimatological approach to the modeling of regional shallow landslide initiation that integrates spatial and temporal dimensions of parameter uncertainty to estimate an annual probability of landslide initiation based on Monte Carlo simulations. The physically based model couples the infinite-slope stability model with a steady-state subsurface flow representation and operates in a digital elevation model. Spatially distributed gridded data for soil properties and vegetation classification are used for parameter estimation of probability distributions that characterize model input uncertainty. Hydrologic forcing to the model is through annual maximum daily recharge to subsurface flow obtained from a macroscale hydrologic model. We demonstrate the model in a steep mountainous region in northern Washington, USA, over 2700 km2. The influence of soil depth on the probability of landslide initiation is investigated through comparisons among model output produced using three different soil depth scenarios reflecting the uncertainty of soil depth and its potential long-term variability. We found elevation-dependent patterns in probability of landslide initiation that showed the stabilizing effects of forests at low elevations, an increased landslide probability with forest decline at mid-elevations (1400 to 2400 m), and soil limitation and steep topographic controls at high alpine elevations and in post-glacial landscapes. These dominant controls manifest themselves in a bimodal distribution of spatial annual landslide probability. Model testing with limited observations revealed similarly moderate model confidence for the three hazard maps, suggesting suitable use as relative hazard products. The model is available as a component in Landlab, an open-source, Python-based landscape earth systems modeling environment, and is designed to be easily reproduced utilizing HydroShare cyberinfrastructure.

Cholesterol modulates open probability and desensitization of NMDA receptors

PubMed Central

Korinek, Miloslav; Vyklicky, Vojtech; Borovska, Jirina; Lichnerova, Katarina; Kaniakova, Martina; Krausova, Barbora; Krusek, Jan; Balik, Ales; Smejkalova, Tereza; Horak, Martin; Vyklicky, Ladislav

2015-01-01

NMDA receptors (NMDARs) are glutamate-gated ion channels that mediate excitatory neurotransmission in the CNS. Although these receptors are in direct contact with plasma membrane, lipid–NMDAR interactions are little understood. In the present study, we aimed at characterizing the effect of cholesterol on the ionotropic glutamate receptors. Whole-cell current responses induced by fast application of NMDA in cultured rat cerebellar granule cells (CGCs) were almost abolished (reduced to 3%) and the relative degree of receptor desensitization was increased (by seven-fold) after acute cholesterol depletion by methyl-β-cyclodextrin. Both of these effects were fully reversible by cholesterol repletion. By contrast, the responses mediated by AMPA/kainate receptors were not affected by cholesterol depletion. Similar results were obtained in CGCs after chronic inhibition of cholesterol biosynthesis by simvastatin and acute enzymatic cholesterol degradation to 4-cholesten-3-one by cholesterol oxidase. Fluorescence anisotropy measurements showed that membrane fluidity increased after methyl-β-cyclodextrin pretreatment. However, no change in fluidity was observed after cholesterol enzymatic degradation, suggesting that the effect of cholesterol on NMDARs is not mediated by changes in membrane fluidity. Our data show that diminution of NMDAR responses by cholesterol depletion is the result of a reduction of the open probability, whereas the increase in receptor desensitization is the result of an increase in the rate constant of entry into the desensitized state. Surface NMDAR population, agonist affinity, single-channel conductance and open time were not altered in cholesterol-depleted CGCs. The results of our experiments show that cholesterol is a strong endogenous modulator of NMDARs. Key points NMDA receptors (NMDARs) are tetrameric cation channels permeable to calcium; they mediate excitatory synaptic transmission in the CNS and their excessive activation can lead to neurodegeneration. Although these receptors are in direct contact with plasma membrane, lipid–NMDAR interactions are little understood. Using cultured rat cerebellar granule cells, we show that acute and chronic pretreatments resulting in cell cholesterol depletion profoundly diminish NMDAR responses and increase NMDAR desensitization, and also that cholesterol enrichment potentiates NMDAR responses; however, cholesterol manipulation has no effect on the amplitude of AMPA/kainate receptor responses. Diminution of NMDAR responses by cholesterol depletion is the result of a reduction of the ion channel open probability, whereas the increase in receptor desensitization is the result of an increase in the rate constant of entry into the desensitized state. These results demonstrate the physiological role of membrane lipids in the modulation of NMDAR activity. PMID:25651798

Costs, quality of life and cost-effectiveness of arthroscopic and open repair for rotator cuff tears: an economic evaluation alongside the UKUFF trial.

PubMed

Murphy, J; Gray, A; Cooper, C; Cooper, D; Ramsay, C; Carr, A

2016-12-01

A trial-based comparison of the use of resources, costs and quality of life outcomes of arthroscopic and open surgical management for rotator cuff tears in the United Kingdom NHS was performed using data from the United Kingdom Rotator Cuff Study (UKUFF) randomised controlled trial. Using data from 273 patients, healthcare-related use of resources, costs and quality-adjusted life years (QALYs) were estimated at 12 months and 24 months after surgery on an intention-to-treat basis with adjustment for covariates. Uncertainty about the incremental cost-effectiveness ratio for arthroscopic versus open management at 24 months of follow-up was incorporated using bootstrapping. Multiple imputation methods were used to deal with missing data. There were no significant differences between the arthroscopic and open groups in terms of total mean use and cost of resources or QALYs at any time post-operatively. Open management dominated arthroscopic management in 59.8% of bootstrapped cost and effect differences. The probability that arthroscopic management was cost-effective compared with open management at a willingness-to-pay threshold of £20 000 per QALY gained was 20.9%. There was no significant overall difference in the use or cost of resources or quality of life between arthroscopic and open management in the trial. There was uncertainty about which strategy was most cost-effective. Cite this article: Bone Joint J 2016;98-B:1648-55. ©2016 Gray et al.

A prospective study of the impact of opening a casino on gambling behaviours: 2- and 4-year follow-ups.

PubMed

Jacques, Christian; Ladouceur, Robert

2006-10-01

It is widely believed that the rate of pathological gambling is related to the accessibility and availability of gambling activities. Few empirical studies have yet been conducted to evaluate this hypothesis. Using a longitudinal prospective design, the current study evaluates the impact of a casino in Canada's Hull, Quebec region. A random sample of respondents from Hull (experimental group) and from Quebec City (comparison group) completed the South Oaks Gambling Screen (SOGS) and gambling- related questions before the opening of the Hull Casino (pretest), 1 year after the opening (posttest), and on follow-up at Years 2 and 4. Although, 1 year after the opening of the casino, we did observe an increase in playing casino games and in the maximum amount of money lost in 1 day's gambling, this trend was not maintained over time (2- and 4-year follow-ups). In the Hull cohort, the rate of at-risk and probable pathological gamblers and the number of criteria on the SOGS did not increase at the 2- and 4-year follow-ups. The residents' reluctance to open a local casino was generally stable over time following the casino's opening. The discussion raises different explanatory factors and focuses on the context of the Regional Exposure Model as a potentially more applicable measure of studying the expansion of gambling.

Understanding interaction effects of climate change and fire management on bird distributions through combined process and habitat models

USGS Publications Warehouse

White, Joseph D.; Gutzwiller, Kevin J.; Barrow, Wylie C.; Johnson-Randall, Lori; Zygo, Lisa; Swint, Pamela

2011-01-01

Avian conservation efforts must account for changes in vegetation composition and structure associated with climate change. We modeled vegetation change and the probability of occurrence of birds to project changes in winter bird distributions associated with climate change and fire management in the northern Chihuahuan Desert (southwestern U.S.A.). We simulated vegetation change in a process-based model (Landscape and Fire Simulator) in which anticipated climate change was associated with doubling of current atmospheric carbon dioxide over the next 50 years. We estimated the relative probability of bird occurrence on the basis of statistical models derived from field observations of birds and data on vegetation type, topography, and roads. We selected 3 focal species, Scaled Quail (Callipepla squamata), Loggerhead Shrike (Lanius ludovicianus), and Rock Wren (Salpinctes obsoletus), that had a range of probabilities of occurrence for our study area. Our simulations projected increases in relative probability of bird occurrence in shrubland and decreases in grassland and Yucca spp. and ocotillo (Fouquieria splendens) vegetation. Generally, the relative probability of occurrence of all 3 species was highest in shrubland because leaf-area index values were lower in shrubland. This high probability of occurrence likely is related to the species' use of open vegetation for foraging. Fire suppression had little effect on projected vegetation composition because as climate changed there was less fuel and burned area. Our results show that if future water limits on plant type are considered, models that incorporate spatial data may suggest how and where different species of birds may respond to vegetation changes.

Understanding interaction effects of climate change and fire management on bird distributions through combined process and habitat models

USGS Publications Warehouse

White, Joseph D.; Gutzwiller, Kevin J.; Barrow, Wylie C.; Johnson-Randall, Lori; Zygo, Lisa; Swint, Pamela

2011-01-01

Avian conservation efforts must account for changes in vegetation composition and structure associated with climate change. We modeled vegetation change and the probability of occurrence of birds to project changes in winter bird distributions associated with climate change and fire management in the northern Chihuahuan Desert (southwestern U.S.A.). We simulated vegetation change in a process-based model (Landscape and Fire Simulator) in which anticipated climate change was associated with doubling of current atmospheric carbon dioxide over the next 50 years. We estimated the relative probability of bird occurrence on the basis of statistical models derived from field observations of birds and data on vegetation type, topography, and roads. We selected 3 focal species, Scaled Quail (Callipepla squamata), Loggerhead Shrike (Lanius ludovicianus), and Rock Wren (Salpinctes obsoletus), that had a range of probabilities of occurrence for our study area. Our simulations projected increases in relative probability of bird occurrence in shrubland and decreases in grassland and Yucca spp. and ocotillo (Fouquieria splendens) vegetation. Generally, the relative probability of occurrence of all 3 species was highest in shrubland because leaf-area index values were lower in shrubland. This high probability of occurrence likely is related to the species' use of open vegetation for foraging. Fire suppression had little effect on projected vegetation composition because as climate changed there was less fuel and burned area. Our results show that if future water limits on plant type are considered, models that incorporate spatial data may suggest how and where different species of birds may respond to vegetation changes. ??2011 Society for Conservation Biology.

Automated detection of submerged navigational obstructions in freshwater impoundments with hull mounted sidescan sonar

NASA Astrophysics Data System (ADS)

Morris, Phillip A.

The prevalence of low-cost side scanning sonar systems mounted on small recreational vessels has created improved opportunities to identify and map submerged navigational hazards in freshwater impoundments. However, these economical sensors also present unique challenges for automated techniques. This research explores related literature in automated sonar imagery processing and mapping technology, proposes and implements a framework derived from these sources, and evaluates the approach with video collected from a recreational grade sonar system. Image analysis techniques including optical character recognition and an unsupervised computer automated detection (CAD) algorithm are employed to extract the transducer GPS coordinates and slant range distance of objects protruding from the lake bottom. The retrieved information is formatted for inclusion into a spatial mapping model. Specific attributes of the sonar sensors are modeled such that probability profiles may be projected onto a three dimensional gridded map. These profiles are computed from multiple points of view as sonar traces crisscross or come near each other. As lake levels fluctuate over time so do the elevation points of view. With each sonar record, the probability of a hazard existing at certain elevations at the respective grid points is updated with Bayesian mechanics. As reinforcing data is collected, the confidence of the map improves. Given a lake's current elevation and a vessel draft, a final generated map can identify areas of the lake that have a high probability of containing hazards that threaten navigation. The approach is implemented in C/C++ utilizing OpenCV, Tesseract OCR, and QGIS open source software and evaluated in a designated test area at Lake Lavon, Collin County, Texas.

MOSES: A Matlab-based open-source stochastic epidemic simulator.

PubMed

Varol, Huseyin Atakan

2016-08-01

This paper presents an open-source stochastic epidemic simulator. Discrete Time Markov Chain based simulator is implemented in Matlab. The simulator capable of simulating SEQIJR (susceptible, exposed, quarantined, infected, isolated and recovered) model can be reduced to simpler models by setting some of the parameters (transition probabilities) to zero. Similarly, it can be extended to more complicated models by editing the source code. It is designed to be used for testing different control algorithms to contain epidemics. The simulator is also designed to be compatible with a network based epidemic simulator and can be used in the network based scheme for the simulation of a node. Simulations show the capability of reproducing different epidemic model behaviors successfully in a computationally efficient manner.

CSMP Mathematics for the Intermediate Grades. Part V. Teacher's Guide. The Languages of Strings and Arrows. Geometry and Measurement. Probability and Statistics. Experimental Version.

ERIC Educational Resources Information Center

CEMREL, Inc., St. Louis, MO.

This Comprehensive School Mathematics Program (CSMP) guide is divided into three major parts. The first, the Languages of Strings and Arrows, opens with a suggested lesson order. Major sections cover instructional approaches for: (1) Games with Strings, (2) Necklaces, and (3) The Table Game. A Series of appendices is included. Part 2, Geometry and…

Semi-Markov Approach to the Shipping Safety Modelling

NASA Astrophysics Data System (ADS)

Guze, Sambor; Smolarek, Leszek

2012-02-01

In the paper the navigational safety model of a ship on the open area has been studied under conditions of incomplete information. Moreover the structure of semi-Markov processes is used to analyse the stochastic ship safety according to the subjective acceptance of risk by the navigator. In addition, the navigator’s behaviour can be analysed by using the numerical simulation to estimate the probability of collision in the safety model.

Beyond quantum probability: another formalism shared by quantum physics and psychology.

PubMed

Dzhafarov, Ehtibar N; Kujala, Janne V

2013-06-01

There is another meeting place for quantum physics and psychology, both within and outside of cognitive modeling. In physics it is known as the issue of classical (probabilistic) determinism, and in psychology it is known as the issue of selective influences. The formalisms independently developed in the two areas for dealing with these issues turn out to be identical, opening ways for mutually beneficial interactions.

Interaction between Antagonist of Cannabinoid Receptor and Antagonist of Adrenergic Receptor on Anxiety in Male Rat.

PubMed

Komaki, Alireza; Abdollahzadeh, Fatemeh; Sarihi, Abdolrahman; Shahidi, Siamak; Salehi, Iraj

2014-01-01

Anxiety is among the most common and treatable mental disorders. Adrenergic and cannabinoid systems have an important role in the neurobiology of anxiety. The elevated plus-maze (EPM) has broadly been used to investigate anxiolytic and anxiogenic compounds. The present study investigated the effects of intraperitoneal (IP) injection of cannabinoid CB1 receptor antagonist (AM251) in the presence of alpha-1 adrenergic antagonist (Prazosin) on rat behavior in the EPM. In this study, the data were obtained from male Wistar rat, which weighing 200- 250 g. Animal behavior in EPM were videotaped and saved in computer for 10 min after IP injection of saline, AM251 (0.3 mg/kg), Prazosin (0.3 mg/kg) and AM251 + Prazosin, subsequently scored for conventional indices of anxiety. During the test period, the number of open and closed arms entries, the percentage of entries into the open arms of the EPM, and the spent time in open and closed arms were recorded. Diazepam was considered as a positive control drug with anxiolytic effect (0.3, 0.6, 1.2 mg/kg). Diazepam increased the number of open arm entries and the percentage of spent time on the open arms. IP injection of AM251 before EPM trial decreased open arms exploration and open arm entry. Whereas, Prazosin increased open arms exploration and open arm entry. This study showed that both substances in simultaneous injection have conflicting effects on the responses of each of these two compounds in a single injection. Injection of CB1 receptor antagonist may have an anxiogenic profile in rat, whereas adrenergic antagonist has an anxiolytic effect. Further investigations are essential for better understanding of anxiolytic and anxiogenic properties and neurobiological mechanisms of action and probable interactions of the two systems.

Probabilistic pipe fracture evaluations for leak-rate-detection applications

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

Rahman, S.; Ghadiali, N.; Paul, D.

1995-04-01

Regulatory Guide 1.45, {open_quotes}Reactor Coolant Pressure Boundary Leakage Detection Systems,{close_quotes} was published by the U.S. Nuclear Regulatory Commission (NRC) in May 1973, and provides guidance on leak detection methods and system requirements for Light Water Reactors. Additionally, leak detection limits are specified in plant Technical Specifications and are different for Boiling Water Reactors (BWRs) and Pressurized Water Reactors (PWRs). These leak detection limits are also used in leak-before-break evaluations performed in accordance with Draft Standard Review Plan, Section 3.6.3, {open_quotes}Leak Before Break Evaluation Procedures{close_quotes} where a margin of 10 on the leak detection limit is used in determining the crackmore » size considered in subsequent fracture analyses. This study was requested by the NRC to: (1) evaluate the conditional failure probability for BWR and PWR piping for pipes that were leaking at the allowable leak detection limit, and (2) evaluate the margin of 10 to determine if it was unnecessarily large. A probabilistic approach was undertaken to conduct fracture evaluations of circumferentially cracked pipes for leak-rate-detection applications. Sixteen nuclear piping systems in BWR and PWR plants were analyzed to evaluate conditional failure probability and effects of crack-morphology variability on the current margins used in leak rate detection for leak-before-break.« less

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

Ullah, Ghanim; Demuro, Angelo; Parker, Ian

Amyloid beta (Aβ) oligomers associated with Alzheimer’s disease (AD) form Ca 2+-permeable plasma membrane pores, leading to a disruption of the otherwise well-controlled intracellular calcium (Ca 2+) homeostasis. The resultant up-regulation of intracellular Ca 2+ concentration has detrimental implications for memory formation and cell survival. The gating kinetics and Ca 2+ permeability of Aβ pores are not well understood. We have used computational modeling in conjunction with the ability of optical patch-clamping for massively parallel imaging of Ca 2+ flux through thousands of pores in the cell membrane of Xenopus oocytes to elucidate the kinetic properties of Aβ pores. Themore » fluorescence time-series data from individual pores were idealized and used to develop data-driven Markov chain models for the kinetics of the Aβ pore at different stages of its evolution. Our study provides the first demonstration of developing Markov chain models for ion channel gating that are driven by optical-patch clamp data with the advantage of experiments being performed under close to physiological conditions. As a result, we demonstrate the up-regulation of gating of various Ca 2+ release channels due to Aβ pores and show that the extent and spatial range of such up-regulation increases as Aβ pores with low open probability and Ca 2+ permeability transition into those with high open probability and Ca 2+ permeability.« less

Baseline concentrations of biliary PAH metabolites in perch (Perca fluviatilis) in the open Gulf of Finland and in two coastal areas

NASA Astrophysics Data System (ADS)

Vuorinen, Pekka J.; Saulamo, Kari; Lecklin, Tiina; Rahikainen, Mika; Koivisto, Pertti; Keinänen, Marja

2017-07-01

Female perch (Perca fluviatilis) were sampled annually in late summer from 2006 to 2009 from the open sea of the eastern Gulf of Finland off Haapasaari island to monitor baseline biliary PAH metabolite concentrations. In addition, two coastal locations were sampled in 2008. PAH metabolite concentrations were compared between the open sea and coastal samples and between the sampling years and examined in relation to the body characteristics of perch. Of the PAH metabolites, only 1-hydroxypyrene (1-OH pyrene) was detected at quantifiable levels in the bile of nearly all perch individuals. There were some annual differences but no temporal trend in the concentration of biliary 1-OH pyrene in perch from Haapasaari. At the coastal locations, 1-OH pyrene concentrations in the bile of perch were significantly higher than in the open sea Haapasaari area, probably due to greater contamination of the coastal sites and differences in feeding behaviour. No correlations between the body characteristics of perch and 1-OH pyrene concentrations were detected. It is concluded that PAH metabolites in the bile of fish could be measured in the Gulf of Finland to detect oil spills in the open sea, and the cost-effective total fluorescence method could be used in such monitoring programmes.

Mechanism-Based Mathematical Model for Gating of Ionotropic Glutamate Receptors.

PubMed

Dai, Jian; Wollmuth, Lonnie P; Zhou, Huan-Xiang

2015-08-27

We present a mathematical model for ionotropic glutamate receptors (iGluR's) that is built on mechanistic understanding and yields a number of thermodynamic and kinetic properties of channel gating. iGluR's are ligand-gated ion channels responsible for the vast majority of fast excitatory neurotransmission in the central nervous system. The effects of agonist-induced closure of the ligand-binding domain (LBD) are transmitted to the transmembrane channel (TMC) via interdomain linkers. Our model demonstrates that, relative to full agonists, partial agonists may reduce either the degree of LBD closure or the curvature of the LBD free energy basin, leading to less stabilization of the channel open state and hence lower channel open probability. A rigorous relation is derived between the channel closed-to-open free energy difference and the tension within the linker. Finally, by treating LBD closure and TMC opening as diffusive motions, we obtain gating trajectories that resemble stochastic current traces from single-channel recordings and calculate the rate constants for transitions between the channel open and closed states. Our model can be implemented by molecular dynamics simulations to realistically depict iGluR gating and may guide functional experiments in gaining deeper insight into this essential family of channel proteins.

Direct detection of a single photon by humans

PubMed Central

Tinsley, Jonathan N.; Molodtsov, Maxim I.; Prevedel, Robert; Wartmann, David; Espigulé-Pons, Jofre; Lauwers, Mattias; Vaziri, Alipasha

2016-01-01

Despite investigations for over 70 years, the absolute limits of human vision have remained unclear. Rod cells respond to individual photons, yet whether a single-photon incident on the eye can be perceived by a human subject has remained a fundamental open question. Here we report that humans can detect a single-photon incident on the cornea with a probability significantly above chance. This was achieved by implementing a combination of a psychophysics procedure with a quantum light source that can generate single-photon states of light. We further discover that the probability of reporting a single photon is modulated by the presence of an earlier photon, suggesting a priming process that temporarily enhances the effective gain of the visual system on the timescale of seconds. PMID:27434854

Electron-beam generated porous dextran gels: experimental and quantum chemical studies.

PubMed

Naumov, Sergej; Knolle, Wolfgang; Becher, Jana; Schnabelrauch, Matthias; Reichelt, Senta

2014-06-01

The aim of this work was to investigate the reaction mechanism of electron-beam generated macroporous dextran cryogels by quantum chemical calculation and electron paramagnetic resonance measurements. Electron-beam radiation was used to initiate the cross-linking reaction of methacrylated dextran in semifrozen aqueous solutions. The pore morphology of the resulting cryogels was visualized by scanning electron microscopy. Quantum chemical calculations and electron paramagnetic resonance studies provided information on the most probable reaction pathway and the chain growth radicals. The most probable reaction pathway was a ring opening reaction and the addition of a C-atom to the double-bond of the methacrylated dextran molecule. First detailed quantum chemical calculation on the reaction mechanism of electron-beam initiated cross-linking reaction of methacrylated dextran are presented.

Variables associated with detection probability, detection latency, and behavioral responses of Golden-winged Warblers (Vermivora chrysoptera)

USGS Publications Warehouse

Aldinger, Kyle R.; Wood, Petra B.

2015-01-01

Detection probability during point counts and its associated variables are important considerations for bird population monitoring and have implications for conservation planning by influencing population estimates. During 2008–2009, we evaluated variables hypothesized to be associated with detection probability, detection latency, and behavioral responses of male Golden-winged Warblers in pastures in the Monongahela National Forest, West Virginia, USA. This is the first study of male Golden-winged Warbler detection probability, detection latency, or behavioral response based on point-count sampling with known territory locations and identities for all males. During 3-min passive point counts, detection probability decreased as distance to a male's territory and time since sunrise increased. During 3-min point counts with playback, detection probability decreased as distance to a male's territory increased, but remained constant as time since sunrise increased. Detection probability was greater when point counts included type 2 compared with type 1 song playback, particularly during the first 2 min of type 2 song playback. Golden-winged Warblers primarily use type 1 songs (often zee bee bee bee with a higher-pitched first note) in intersexual contexts and type 2 songs (strident, rapid stutter ending with a lower-pitched buzzy note) in intrasexual contexts. Distance to a male's territory, ordinal date, and song playback type were associated with the type of behavioral response to song playback. Overall, ~2 min of type 2 song playback may increase the efficacy of point counts for monitoring populations of Golden-winged Warblers by increasing the conspicuousness of males for visual identification and offsetting the consequences of surveying later in the morning. Because playback may interfere with the ability to detect distant males, it is important to follow playback with a period of passive listening. Our results indicate that even in relatively open pasture vegetation, detection probability of male Golden-winged Warblers is imperfect and highly variable.

Compensating for geographic variation in detection probability with water depth improves abundance estimates of coastal marine megafauna.

PubMed

Hagihara, Rie; Jones, Rhondda E; Sobtzick, Susan; Cleguer, Christophe; Garrigue, Claire; Marsh, Helene

2018-01-01

The probability of an aquatic animal being available for detection is typically <1. Accounting for covariates that reduce the probability of detection is important for obtaining robust estimates of the population abundance and determining its status and trends. The dugong (Dugong dugon) is a bottom-feeding marine mammal and a seagrass community specialist. We hypothesized that the probability of a dugong being available for detection is dependent on water depth and that dugongs spend more time underwater in deep-water seagrass habitats than in shallow-water seagrass habitats. We tested this hypothesis by quantifying the depth use of 28 wild dugongs fitted with GPS satellite transmitters and time-depth recorders (TDRs) at three sites with distinct seagrass depth distributions: 1) open waters supporting extensive seagrass meadows to 40 m deep (Torres Strait, 6 dugongs, 2015); 2) a protected bay (average water depth 6.8 m) with extensive shallow seagrass beds (Moreton Bay, 13 dugongs, 2011 and 2012); and 3) a mixture of lagoon, coral and seagrass habitats to 60 m deep (New Caledonia, 9 dugongs, 2013). The fitted instruments were used to measure the times the dugongs spent in the experimentally determined detection zones under various environmental conditions. The estimated probability of detection was applied to aerial survey data previously collected at each location. In general, dugongs were least available for detection in Torres Strait, and the population estimates increased 6-7 fold using depth-specific availability correction factors compared with earlier estimates that assumed homogeneous detection probability across water depth and location. Detection probabilities were higher in Moreton Bay and New Caledonia than Torres Strait because the water transparency in these two locations was much greater than in Torres Strait and the effect of correcting for depth-specific detection probability much less. The methodology has application to visual survey of coastal megafauna including surveys using Unmanned Aerial Vehicles.

Combined statistical analysis of landslide release and propagation

NASA Astrophysics Data System (ADS)

Mergili, Martin; Rohmaneo, Mohammad; Chu, Hone-Jay

2016-04-01

Statistical methods - often coupled with stochastic concepts - are commonly employed to relate areas affected by landslides with environmental layers, and to estimate spatial landslide probabilities by applying these relationships. However, such methods only concern the release of landslides, disregarding their motion. Conceptual models for mass flow routing are used for estimating landslide travel distances and possible impact areas. Automated approaches combining release and impact probabilities are rare. The present work attempts to fill this gap by a fully automated procedure combining statistical and stochastic elements, building on the open source GRASS GIS software: (1) The landslide inventory is subset into release and deposition zones. (2) We employ a traditional statistical approach to estimate the spatial release probability of landslides. (3) We back-calculate the probability distribution of the angle of reach of the observed landslides, employing the software tool r.randomwalk. One set of random walks is routed downslope from each pixel defined as release area. Each random walk stops when leaving the observed impact area of the landslide. (4) The cumulative probability function (cdf) derived in (3) is used as input to route a set of random walks downslope from each pixel in the study area through the DEM, assigning the probability gained from the cdf to each pixel along the path (impact probability). The impact probability of a pixel is defined as the average impact probability of all sets of random walks impacting a pixel. Further, the average release probabilities of the release pixels of all sets of random walks impacting a given pixel are stored along with the area of the possible release zone. (5) We compute the zonal release probability by increasing the release probability according to the size of the release zone - the larger the zone, the larger the probability that a landslide will originate from at least one pixel within this zone. We quantify this relationship by a set of empirical curves. (6) Finally, we multiply the zonal release probability with the impact probability in order to estimate the combined impact probability for each pixel. We demonstrate the model with a 167 km² study area in Taiwan, using an inventory of landslides triggered by the typhoon Morakot. Analyzing the model results leads us to a set of key conclusions: (i) The average composite impact probability over the entire study area corresponds well to the density of observed landside pixels. Therefore we conclude that the method is valid in general, even though the concept of the zonal release probability bears some conceptual issues that have to be kept in mind. (ii) The parameters used as predictors cannot fully explain the observed distribution of landslides. The size of the release zone influences the composite impact probability to a larger degree than the pixel-based release probability. (iii) The prediction rate increases considerably when excluding the largest, deep-seated, landslides from the analysis. We conclude that such landslides are mainly related to geological features hardly reflected in the predictor layers used.

Self-organised criticality and 1/f noise in single-channel current of voltage-dependent anion channel

NASA Astrophysics Data System (ADS)

Banerjee, J.; Verma, M. K.; Manna, S.; Ghosh, S.

2006-02-01

Noise profile of Voltage Dependent Anion Channel (VDAC) is investigated in open channel state. Single-channel currents through VDAC from mitochondria of rat brain reconstituted into a planar lipid bilayer are recorded under different voltage clamped conditions across the membrane. Power spectrum analysis of current indicates power law noise of 1/f nature. Moreover, this 1/f nature of the open channel noise is seen throughout the range of applied membrane potential from -30 to +30 mV. It is being proposed that 1/f noise in open ion channel arises out of obstruction in the passage of ions across the membrane. The process is recognised as a phenomenon of self-organized criticality (SOC) like sandpile avalanche and other physical systems. Based on SOC it has been theoretically established that the system of ion channel follows power law noise as observed in our experiments. We also show that the first-time return probability of current fluctuations obeys a power law distribution.

Vegetation Response to Upper Pliocene Glacial/Interglacial Cyclicity in the Central Mediterranean

NASA Astrophysics Data System (ADS)

Combourieu-Nebout, Nathalie

1993-09-01

New detailed pollen analysis of the lower part of the Upper Pliocene Semaforo section (Crotone, Italy) documents cyclic behavior of vegetation at the beginning of the Northern Hemisphere glaciations. The competition between four vegetation units (subtropical humid forest, deciduous temperate forest, altitudinal coniferous forest, and open xeric assemblage) probably reflects modifications of vegetation belts at this montane site. Several increases in herbaceous open vegetation regularly alternate with subtropical humid forest, which expresses rapid climatic oscillations. The complete temporal succession—deciduous forest (rich in Quercus), followed by subtropical humid forest (Taxodiaceae and Cathaya), then altitudinal coniferous forest ( Tsuga, Cedrus, Abies, and Picea), and finally herbaceous open vegetation (Graminae, Compositae, and Artemisia )—displays the climatic evolution from warm and humid interglaciation to cold and dry glaciation. It also suggests an independent variation of temperature and humidity, the two main climatic parameters. The vegetation history of southern Calabria recorded in the Semaforo section have been correlated with the ∂ 18O signal established in the Atlantic Ocean.

Edaravone protects osteoblastic cells from dexamethasone through inhibiting oxidative stress and mPTP opening.

PubMed

Sun, Wen-xiao; Zheng, Hai-ya; Lan, Jun

2015-11-01

Existing evidences have emphasized an important role of oxidative stress in dexamethasone (Dex)-induced osteoblastic cell damages. Here, we investigated the possible anti-Dex activity of edaravone in osteoblastic cells, and studied the underlying mechanisms. We showed that edaravone dose-dependently attenuated Dex-induced death and apoptosis of established human or murine osteoblastic cells. Further, Dex-mediated damages to primary murine osteoblasts were also alleviated by edaravone. In osteoblastic cells/osteoblasts, Dex induced significant oxidative stresses, tested by increased levels of reactive oxygen species and lipid peroxidation, which were remarkably inhibited by edaravone. Meanwhile, edaravone repressed Dex-induced mitochondrial permeability transition pore (mPTP) opening, or mitochondrial membrane potential reduction, in osteoblastic cells/osteoblasts. Significantly, edaravone-induced osteoblast-protective activity against Dex was alleviated with mPTP inhibition through cyclosporin A or cyclophilin-D siRNA. Together, we demonstrate that edaravone protects osteoblasts from Dex-induced damages probably through inhibiting oxidative stresses and following mPTP opening.

Tomograms for open quantum systems: In(finite) dimensional optical and spin systems

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

Thapliyal, Kishore, E-mail: tkishore36@yahoo.com; Banerjee, Subhashish, E-mail: subhashish@iitj.ac.in; Pathak, Anirban, E-mail: anirban.pathak@gmail.com

Tomograms are obtained as probability distributions and are used to reconstruct a quantum state from experimentally measured values. We study the evolution of tomograms for different quantum systems, both finite and infinite dimensional. In realistic experimental conditions, quantum states are exposed to the ambient environment and hence subject to effects like decoherence and dissipation, which are dealt with here, consistently, using the formalism of open quantum systems. This is extremely relevant from the perspective of experimental implementation and issues related to state reconstruction in quantum computation and communication. These considerations are also expected to affect the quasiprobability distribution obtained frommore » experimentally generated tomograms and nonclassicality observed from them. -- Highlights: •Tomograms are constructed for open quantum systems. •Finite and infinite dimensional quantum systems are studied. •Finite dimensional systems (phase states, single & two qubit spin states) are studied. •A dissipative harmonic oscillator is considered as an infinite dimensional system. •Both pure dephasing as well as dissipation effects are studied.« less

AtALMT9 is a malate-activated vacuolar chloride channel required for stomatal opening in Arabidopsis

PubMed Central

De Angeli, Alexis; Zhang, Jingbo; Meyer, Stefan; Martinoia, Enrico

2013-01-01

Water deficit strongly affects crop productivity. Plants control water loss and CO2 uptake by regulating the aperture of the stomatal pores within the leaf epidermis. Stomata aperture is regulated by the two guard cells forming the pore and changing their size in response to ion uptake and release. While our knowledge about potassium and chloride fluxes across the plasma membrane of guard cells is advanced, little is known about fluxes across the vacuolar membrane. Here we present the molecular identification of the long-sought-after vacuolar chloride channel. AtALMT9 is a chloride channel activated by physiological concentrations of cytosolic malate. Single-channel measurements demonstrate that this activation is due to a malate-dependent increase in the channel open probability. Arabidopsis thaliana atalmt9 knockout mutants exhibited impaired stomatal opening and wilt more slowly than the wild type. Our findings show that AtALMT9 is a vacuolar chloride channel having a major role in controlling stomata aperture. PMID:23653216

Entropy generation in biophysical systems

NASA Astrophysics Data System (ADS)

Lucia, U.; Maino, G.

2013-03-01

Recently, in theoretical biology and in biophysical engineering the entropy production has been verified to approach asymptotically its maximum rate, by using the probability of individual elementary modes distributed in accordance with the Boltzmann distribution. The basis of this approach is the hypothesis that the entropy production rate is maximum at the stationary state. In the present work, this hypothesis is explained and motivated, starting from the entropy generation analysis. This latter quantity is obtained from the entropy balance for open systems considering the lifetime of the natural real process. The Lagrangian formalism is introduced in order to develop an analytical approach to the thermodynamic analysis of the open irreversible systems. The stationary conditions of the open systems are thus obtained in relation to the entropy generation and the least action principle. Consequently, the considered hypothesis is analytically proved and it represents an original basic approach in theoretical and mathematical biology and also in biophysical engineering. It is worth remarking that the present results show that entropy generation not only increases but increases as fast as possible.

A 21.7 kb DNA segment on the left arm of yeast chromosome XIV carries WHI3, GCR2, SPX18, SPX19, an homologue to the heat shock gene SSB1 and 8 new open reading frames of unknown function.

PubMed

Jonniaux, J L; Coster, F; Purnelle, B; Goffeau, A

1994-12-01

We report the amino acid sequence of 13 open reading frames (ORF > 299 bp) located on a 21.7 kb DNA segment from the left arm of chromosome XIV of Saccharomyces cerevisiae. Five open reading frames had been entirely or partially sequenced previously: WHI3, GCR2, SPX19, SPX18 and a heat shock gene similar to SSB1. The products of 8 other ORFs are new putative proteins among which N1394 is probably a membrane protein. N1346 contains a leucine zipper pattern and the corresponding ORF presents an HAP (global regulator of respiratory genes) upstream activating sequence in the promoting region. N1386 shares homologies with the DNA structure-specific recognition protein family SSRPs and the corresponding ORF is preceded by an MCB (MluI cell cycle box) upstream activating factor.

Nicotine is a potent blocker of the cardiac A-type K(+) channels. Effects on cloned Kv4.3 channels and native transient outward current.

PubMed

Wang, H; Shi, H; Zhang, L; Pourrier, M; Yang, B; Nattel, S; Wang, Z

2000-09-05

Nicotine is a main constituent of cigarette smoke and smokeless tobacco, known to increase the risk of sudden cardiac death. This study aimed at establishing ionic mechanisms underlying potential electrophysiological effects of nicotine. Effects of nicotine on Kv4.3 and Kv4.2 channels expressed in Xenopus oocytes were studied at the whole-cell and single-channel levels. The effects of nicotine on the transient outward K(+) current (I:(to)) were studied by use of whole-cell patch-clamp techniques in canine ventricular myocytes. Nicotine potently inhibited Kv4 current. The concentration for half-maximal inhibition (IC(50)) was 40+/-4 nmol/L, and the current was abolished by 100 micromol/L nicotine. The IC(50) for block of native I:(to) was 270+/-43 nmol/L. The steady-state activation properties of Kv4.3 and I:(to) were unaltered by nicotine, whereas positive shifts of the inactivation curves were observed. Of the total inhibition of Kv4.3 and I:(to) by nicotine, 40% was due to tonic block and 60% was attributable to use-dependent block. Activation, inactivation, and reactivation kinetics were not significantly changed by nicotine. Nicotine reduced single-channel conductance, open probability, and open time but increased the closed time of Kv4.3. The effects of nicotine were not altered by antagonists to various neurotransmitter receptors, indicating direct effects on I:(to) channels. Nicotine is a potent inhibitor of cardiac A-type K(+) channels, with blockade probably due to block of closed and open channels. This action may contribute to the ability of nicotine to affect cardiac electrophysiology and induce arrhythmias.

A search for peculiar stars in the open cluster Hogg 16

NASA Astrophysics Data System (ADS)

Cariddi, Stefano; Azatyan, Naira M.; Kurfürst, Petr; Štofanová, Lýdia; Netopil, Martin; Paunzen, Ernst; Pintado, Olga I.; Aidelman, Yael J.

2018-01-01

The study of chemically peculiar (CP) stars in open clusters provides valuable information about their evolutionary status. Their detection can be performed using the Δa photometric system, which maps a characteristic flux depression at λ ∼ 5200 Å. This paper aims at studying the occurrence of CP stars in the earliest stages of evolution of a stellar population by applying this technique to Hogg 16, a very young Galactic open cluster ( ∼ 25 Myr). We identified several peculiar candidates: two B-type stars with a negative Δa index (CD - 60 4701, CPD - 60 4706) are likely emission-line (Be) stars, even though spectral measurements are necessary for a proper classification of the second one; a third object (CD - 60 4703), identified as a Be candidate in literature, appears to be a background B-type supergiant with no significant Δa index, which does not rule out the possibility that it is indeed peculiar as the normality line of Δa for supergiants has not been studied in detail yet. A fourth object (CD - 60 4699) appears to be a magnetic CP star of 8 M⊙, but obtained spectral data seem to rule out this hypothesis. Three more magnetic CP star candidates are found in the domain of early F-type stars. One is a probable nonmember and close to the border of significance, but the other two are probably pre-main sequence cluster objects. This is very promising, as it can lead to very strong constraints to the diffusion theory. Finally, we derived the fundamental parameters of Hogg 16 and provide for the first time an estimate of its metal content.

Membership and Dynamical Parameters of the Open Cluster NGC 1039

NASA Astrophysics Data System (ADS)

Wang, Jiaxin; Ma, Jun; Wu, Zhenyu; Zhou, Xu

2017-11-01

In this paper, we analyze the open cluster NGC 1039. This young open cluster is observed as a part of Beijing-Arizona-Taiwan-Connecticut Multicolor Sky Survey. Combining our observations with the Sloan Digital Sky Survey photometric data, we employ the Padova stellar model and the zero-age main-sequence curve to the data to derive a reddening, E(B-V)=0.10+/- 0.02, and a distance modulus, {(m-M)}0=8.4+/- 0.2, for NGC 1039. The photometric membership probabilities of stars in the region of NGC 1039 are derived using the spectral energy distribution-fitting method. According to the membership probabilities ({P}{SED}) obtained here, 582 stars are cluster members with {P}{SED} larger than 60%. In addition, we determine the structural parameters of NGC 1039 by fitting its radial density profile with the King model. These parameters are a core radius, {R}{{c}}=4.44+/- 1.31 {pc}; a tidal radius, {R}{{t}}=13.57+/- 4.85 {pc}; and a concentration parameter of {C}0={log}({R}{{t}}/{R}{{c}})=0.49+/- 0.20. We also fit the observed mass function of NGC 1039 with masses from 0.3 {M}⊙ to 1.65 {M}⊙ with a power-law function {{Φ }}(m)\\propto {m}α to derive its slopes of mass functions of different spatial regions. The results obtained here show that the slope of the mass function of NGC 1039 is flatter in the central regions (α = 0.117), becomes steeper at larger radii (α = -2.878), and breaks at {m}{break}≈ 0.80 {M}⊙ . In particular, for the first time, our results show that the mass segregation appears in NGC 1039.

Methods for stable recording of short-circuit current in a Na+-transporting epithelium.

PubMed

Gondzik, Veronika; Awayda, Mouhamed S

2011-07-01

Epithelial Na(+) transport as measured by a variety of techniques, including the short-circuit current technique, has been described to exhibit a "rundown" phenomenon. This phenomenon manifests as time-dependent decrease of current and resistance and precludes the ability to carry out prolonged experiments aimed at examining the regulation of this transport. We developed methods for prolonged stable recordings of epithelial Na(+) transport using modifications of the short-circuit current technique and commercial Ussing-type chambers. We utilize the polarized MDCK cell line expressing the epithelial Na(+) channel (ENaC) to describe these methods. Briefly, existing commercial chambers were modified to allow continuous flow of Ringer solution and precise control of such flow. Chamber manifolds and associated plumbing were modified to allow precise temperature clamp preventing temperature oscillations. Recording electrodes were modified to eliminate the use of KCl and prevent membrane depolarization from KCl leakage. Solutions utilized standard bicarbonate-based buffers, but all gasses were prehydrated to clamp buffer osmolarity. We demonstrate that these modifications result in measurements of current and resistance that are stable for at least 2 h. We further demonstrate that drifts in osmolarity similar to those obtained before prior to our modifications can lead to a decrease of current and resistance similar to those attributed to rundown.

In-vitro evaluation of Er:YAG laser irradiation in apicoectomy and retrofilling cavity preparation compared to two other techniques

NASA Astrophysics Data System (ADS)

Camargo, Selma C. C.; Gavini, Giulio; Eduardo, Carlos d. P.; Aun, Carlos E.; Coil, Jeffrey M.

1998-04-01

The aim of this research was to evaluate under SEM observation, the apical cut surface and retrofilling cavity prepared with Er:YAG laser and two other conventional techniques. Thirty extracted human teeth were divided into two groups of 15 teeth each. For Group 1 apicoectomy was performed using high speed handpiece and diamond burs. For Group 2 Er:YAG* laser irradiation (wavelength of 2.94 micrometer, pulse width of 250 - 500 microseconds) was used in 400 mJ of energy, frequency of 6 Hz, on focus mode under destiled water refrigeration. Each group was divided into 3 subgroups. For groups G1A and G2A, retrofilling cavity preparations were performed using low speed handpiece and burs, for groups G1B and G2B Enac technique was indicated. Groups G1C and G2C Er:YAG laser irradiation was used under same energy level previously described. All specimens were prepared for SEM observations. Pictures were taken under 30x and 600x magnification. Two different observers analyzed the smoothness and morphological appearance of those preparations. Data's were collected showing a smoothness surface, no debries or smear layer on group 2 (Laser irradiation) compared to group 1. Differences were also noted when retrofiling cavities were analyzed.

Autosomal recessive hyponatremia due to isolated salt wasting in sweat associated with a mutation in the active site of Carbonic Anhydrase 12.

PubMed

Muhammad, Emad; Leventhal, Neta; Parvari, Galit; Hanukoglu, Aaron; Hanukoglu, Israel; Chalifa-Caspi, Vered; Feinstein, Yael; Weinbrand, Jenny; Jacoby, Harel; Manor, Esther; Nagar, Tal; Beck, John C; Sheffield, Val C; Hershkovitz, Eli; Parvari, Ruti

2011-04-01

Genetic disorders of excessive salt loss from sweat glands have been observed in pseudohypoaldosteronism type I (PHA) and cystic fibrosis that result from mutations in genes encoding epithelial Na+ channel (ENaC) subunits and the transmembrane conductance regulator (CFTR), respectively. We identified a novel autosomal recessive form of isolated salt wasting in sweat, which leads to severe infantile hyponatremic dehydration. Three affected individuals from a small Bedouin clan presented with failure to thrive, hyponatremic dehydration and hyperkalemia with isolated sweat salt wasting. Using positional cloning, we identified the association of a Glu143Lys mutation in carbonic anhydrase 12 (CA12) with the disease. Carbonic anhydrase is a zinc metalloenzyme that catalyzes the reversible hydration of carbon dioxide to form a bicarbonate anion and a proton. Glu143 in CA12 is essential for zinc coordination in this metalloenzyme and lowering of the protein-metal affinity reduces its catalytic activity. This is the first presentation of an isolated loss of salt from sweat gland mimicking PHA, associated with a mutation in the CA12 gene not previously implicated in human disorders. Our data demonstrate the importance of bicarbonate anion and proton production on salt concentration in sweat and its significance for sodium homeostasis.

Abort Trigger False Positive and False Negative Analysis Methodology for Threshold-Based Abort Detection

NASA Technical Reports Server (NTRS)

Melcher, Kevin J.; Cruz, Jose A.; Johnson Stephen B.; Lo, Yunnhon

2015-01-01

This paper describes a quantitative methodology for bounding the false positive (FP) and false negative (FN) probabilities associated with a human-rated launch vehicle abort trigger (AT) that includes sensor data qualification (SDQ). In this context, an AT is a hardware and software mechanism designed to detect the existence of a specific abort condition. Also, SDQ is an algorithmic approach used to identify sensor data suspected of being corrupt so that suspect data does not adversely affect an AT's detection capability. The FP and FN methodologies presented here were developed to support estimation of the probabilities of loss of crew and loss of mission for the Space Launch System (SLS) which is being developed by the National Aeronautics and Space Administration (NASA). The paper provides a brief overview of system health management as being an extension of control theory; and describes how ATs and the calculation of FP and FN probabilities relate to this theory. The discussion leads to a detailed presentation of the FP and FN methodology and an example showing how the FP and FN calculations are performed. This detailed presentation includes a methodology for calculating the change in FP and FN probabilities that result from including SDQ in the AT architecture. To avoid proprietary and sensitive data issues, the example incorporates a mixture of open literature and fictitious reliability data. Results presented in the paper demonstrate the effectiveness of the approach in providing quantitative estimates that bound the probability of a FP or FN abort determination.

Strong lensing probability in TeVeS (tensor-vector-scalar) theory

NASA Astrophysics Data System (ADS)

Chen, Da-Ming

2008-01-01

We recalculate the strong lensing probability as a function of the image separation in TeVeS (tensor-vector-scalar) cosmology, which is a relativistic version of MOND (MOdified Newtonian Dynamics). The lens is modeled by the Hernquist profile. We assume an open cosmology with Ωb = 0.04 and ΩΛ = 0.5 and three different kinds of interpolating functions. Two different galaxy stellar mass functions (GSMF) are adopted: PHJ (Panter, Heavens and Jimenez 2004 Mon. Not. R. Astron. Soc. 355 764) determined from SDSS data release 1 and Fontana (Fontana et al 2006 Astron. Astrophys. 459 745) from GOODS-MUSIC catalog. We compare our results with both the predicted probabilities for lenses from singular isothermal sphere galaxy halos in LCDM (Lambda cold dark matter) with a Schechter-fit velocity function, and the observational results for the well defined combined sample of the Cosmic Lens All-Sky Survey (CLASS) and Jodrell Bank/Very Large Array Astrometric Survey (JVAS). It turns out that the interpolating function μ(x) = x/(1+x) combined with Fontana GSMF matches the results from CLASS/JVAS quite well.

Preliminary appraisal of the geohydrologic aspects of drainage wells, Orlando area, central Florida

USGS Publications Warehouse

Kimrey, Joel O.

1978-01-01

The Floridan aquifer contains two highly transmissive cavernous zones in the Orlando area: an upper producing zone about 150-600 feet below land surface; and a lower producing zone about 1,100-1,500 feet below land surface. Natural head differences are downward and there is hydraulic connection between the two producing zones. Drainage wells are finished open-end into the upper producing zone and emplace surface waters directly into that zone by gravity. Quantitatively, their use constitutes an effective method of artificial recharge. Their negative aspects relate to the probably poor, but unknown, quality of the recharge water. Caution is suggested in drawing definite and final conclusions on the overall geohydrologic and environmental effects of drainage wells prior to the collection and interpretation of a considerable quantity of new data. Though few ground-water pollution problems have been documented to date, the potential for such pollution should be seriously considered in light of the prob-able continuing need to use drainage wells; the probable volumes and quality of water involved; and the hydraulic relations between the two producing zones.

Universal scheme for finite-probability perfect transfer of arbitrary multispin states through spin chains

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

Man, Zhong-Xiao, E-mail: zxman@mail.qfnu.edu.cn; An, Nguyen Ba, E-mail: nban@iop.vast.ac.vn; Xia, Yun-Jie, E-mail: yjxia@mail.qfnu.edu.cn

In combination with the theories of open system and quantum recovering measurement, we propose a quantum state transfer scheme using spin chains by performing two sequential operations: a projective measurement on the spins of ‘environment’ followed by suitably designed quantum recovering measurements on the spins of interest. The scheme allows perfect transfer of arbitrary multispin states through multiple parallel spin chains with finite probability. Our scheme is universal in the sense that it is state-independent and applicable to any model possessing spin–spin interactions. We also present possible methods to implement the required measurements taking into account the current experimental technologies.more » As applications, we consider two typical models for which the probabilities of perfect state transfer are found to be reasonably high at optimally chosen moments during the time evolution. - Highlights: • Scheme that can achieve perfect quantum state transfer is devised. • The scheme is state-independent and applicable to any spin-interaction models. • The scheme allows perfect transfer of arbitrary multispin states. • Applications to two typical models are considered in detail.« less

Stent thrombosis and major clinical events at 3 years after zotarolimus-eluting or sirolimus-eluting coronary stent implantation: a randomised, multicentre, open-label, controlled trial.

PubMed

Camenzind, Edoardo; Wijns, William; Mauri, Laura; Kurowski, Volkhard; Parikh, Keyur; Gao, Runlin; Bode, Christoph; Greenwood, John P; Boersma, Eric; Vranckx, Pascal; McFadden, Eugene; Serruys, Patrick W; O'Neil, William W; Jorissen, Brenda; Van Leeuwen, Frank; Steg, Ph Gabriel

2012-10-20

We sought to compare the long-term safety of two devices with different antiproliferative properties: the Endeavor zotarolimus-eluting stent (E-ZES; Medtronic, Inc) and the Cypher sirolimus-eluting stent (C-SES; Cordis, Johnson & Johnson) in a broad group of patients and lesions. Between May 21, 2007 and Dec 22, 2008, we recruited 8791 patients from 36 recruiting countries to participate in this open-label, multicentre, randomised, superiority trial. Eligible patients were those aged 18 years or older undergoing elective, unplanned, or emergency procedures in native coronary arteries. Patients were randomly assigned to either receive E-ZES and C-SES (ratio 1:1). Randomisation was stratified per centre with varying block sizes of four, six, or eight patients, and concealed with a central telephone-based or web-based allocation service. The primary outcome was definite or probable stent thrombosis at 3 years and was analysed by intention to treat. Patients and investigators were aware of treatment assignment. This trial is registered with ClinicalTrials.gov, number NCT00476957. PROTECT randomised 8791 patients, of whom 8709 provided consent to participate and were eligible: 4357 were allocated to the E-ZES group and 4352 patients to the C-SES group. At 3 years, rates of definite or probable stent thrombosis did not differ between groups (1·4% for E-ZES [predicted: 1·5%] vs 1·8% [predicted: 2·5%] for C-SES; hazard ratio [HR] 0·81, 95% CI 0·58-1·14, p=0·22). Dual antiplatelet therapy was used in 8402 (96%) patients at discharge, 7456 (88%) at 1 year, 3041 (37%) at 2 years, and 2364 (30%) at 3 years. No evidence of superiority of E-ZES compared with C-SES in definite or probable stent thrombosis rates was noted at 3 years. Time analysis suggests a difference in definite or probable stent thrombosis between groups is emerging over time, and a longer follow-up is therefore needed given the clinical relevance of stent thrombosis. Medtronic, Inc. Copyright © 2012 Elsevier Ltd. All rights reserved.

Probability hazard map for future vent opening at Etna volcano (Sicily, Italy).

NASA Astrophysics Data System (ADS)

Brancato, Alfonso; Tusa, Giuseppina; Coltelli, Mauro; Proietti, Cristina

2014-05-01

Mount Etna is a composite stratovolcano located along the Ionian coast of eastern Sicily. The frequent flank eruptions occurrence (at an interval of years, mostly concentrated along the NE, S and W rift zones) lead to a high volcanic hazard that, linked with intense urbanization, poses a high volcanic risk. A long-term volcanic hazard assessment, mainly based on the past behaviour of the Etna volcano, is the basic tool for the evaluation of this risk. Then, a reliable forecast where the next eruption will occur is needed. A computer-assisted analysis and probabilistic evaluations will provide the relative map, thus allowing identification of the areas prone to the highest hazard. Based on these grounds, the use of a code such BET_EF (Bayesian Event Tree_Eruption Forecasting) showed that a suitable analysis can be explored (Selva et al., 2012). Following an analysis we are performing, a total of 6886 point-vents referring to the last 4.0 ka of Etna flank activity, and spread over an area of 744 km2 (divided into N=2976 squared cell, with side of 500 m), allowed us to estimate a pdf by applying a Gaussian kernel. The probability values represent a complete set of outcomes mutually exclusive and the relative sum is normalized to one over the investigated area; then, the basic assumptions of a Dirichlet distribution (the prior distribution set in the BET_EF code (Marzocchi et al., 2004, 2008)) still hold. One fundamental parameter is the the equivalent number of data, that depicts our confidence on the best guess probability. The BET_EF code also works with a likelihood function. This is modelled by a Multinomial distribution, with parameters representing the number of vents in each cell and the total number of past data (i.e. the 6886 point-vents). Given the grid of N cells, the final posterior distribution will be evaluated by multiplying the a priori Dirichlet probability distribution with the past data in each cell through the likelihood. The probability hazard map shows a tendency to concentrate along the NE and S rifts, as well as Valle del Bove, increasing the difference in probability between these areas and the rest of the volcano edifice. It is worthy notice that a higher significance is still evident along the W rift, even if not comparable with the ones of the above mentioned areas. References Marzocchi W., Sandri L., Gasparini P., Newhall C. and Boschi E.; 2004: Quantifying probabilities of volcanic events: The example of volcanic hazard at Mount Vesuvius, J. Geophys. Res., 109, B11201, doi:10.1029/2004JB00315U. Marzocchi W., Sandri, L. and Selva, J.; 2008: BET_EF: a probabilistic tool for long- and short-term eruption forecasting, Bull. Volcanol., 70, 623 - 632, doi: 10.1007/s00445-007-0157-y. Selva J., Orsi G., Di Vito M.A., Marzocchi W. And Sandri L.; 2012: Probability hazard mapfor future vent opening atthe Campi Flegrei caldera, Italy, Bull. Volcanol., 74, 497 - 510, doi: 10.1007/s00445-011-0528-2.

Optical simulation of a Popescu-Rohrlich Box

PubMed Central

Chu, Wen-Jing; Zong, Xiao-Lan; Yang, Ming; Pan, Guo-Zhu; Cao, Zhuo-Liang

2016-01-01

It is well known that the fair-sampling loophole in Bell test opened by the selection of the state to be measured can lead to post-quantum correlations. In this paper, we make the selection of the results after measurement, which opens the fair- sampling loophole too, and thus can lead to post-quantum correlations. This kind of result-selection loophole can be realized by pre- and post-selection processes within the “two-state vector formalism”, and a physical simulation of Popescu-Rohrlich (PR) box is designed in linear optical system. The probability distribution of the PR has a maximal CHSH value 4, i.e. it can maximally violate CHSH inequality. Because the “two-state vector formalism” violates the information causality, it opens the locality loophole too, which means that this kind of results selection within “two-state vector formalism” leads to both fair- sampling loophole and locality loophole, so we call it a comprehensive loophole in Bell test. The comprehensive loophole opened by the results selection within “two-state vector formalism” may be another possible explanation of why post-quantum correlations are incompatible with quantum mechanics and seem not to exist in nature. PMID:27329203

Optical simulation of a Popescu-Rohrlich Box.

PubMed

Chu, Wen-Jing; Zong, Xiao-Lan; Yang, Ming; Pan, Guo-Zhu; Cao, Zhuo-Liang

2016-06-22

It is well known that the fair-sampling loophole in Bell test opened by the selection of the state to be measured can lead to post-quantum correlations. In this paper, we make the selection of the results after measurement, which opens the fair- sampling loophole too, and thus can lead to post-quantum correlations. This kind of result-selection loophole can be realized by pre- and post-selection processes within the "two-state vector formalism", and a physical simulation of Popescu-Rohrlich (PR) box is designed in linear optical system. The probability distribution of the PR has a maximal CHSH value 4, i.e. it can maximally violate CHSH inequality. Because the "two-state vector formalism" violates the information causality, it opens the locality loophole too, which means that this kind of results selection within "two-state vector formalism" leads to both fair- sampling loophole and locality loophole, so we call it a comprehensive loophole in Bell test. The comprehensive loophole opened by the results selection within "two-state vector formalism" may be another possible explanation of why post-quantum correlations are incompatible with quantum mechanics and seem not to exist in nature.

Daily Report East Europe Supplement

DTIC Science & Technology

1993-03-24

indicative of tolerant or intolerant atti- tudes, open-mindedness or a parochial way of thinking. Real difficulties with classification into the... teleology . We must realize this; we should not succumb to the complications imputed on us. I think that this is probably the only time in modern...history that the hunger for metaphysics and teleology is as great as it had been in the times of Christ. I may be wrong, but it seems to me that this

The Shock and Vibration Bulletin. Part 2. Opening Session, Panel Sessions, Seismic, Special Problems

DTIC Science & Technology

1975-06-01

Probability of spinal injury pre- dicted from cadaver data compared to op- erational experiences with various US Air Force ejection systems. (From...total inventory quantity is being pro- duced by Air Force personnel at Newark AFS. • n>4l OUTA Fig. 5 - Rivet Gyro- Phase I ability Assessment...decoupling occurred leading to oscillation . These experiments were accomplished during the initial checkout phase of the facility. Since these

Open Relationships, Nonconsensual Nonmonogamy, and Monogamy Among U.S. Adults: Findings from the 2012 National Survey of Sexual Health and Behavior.

PubMed

Levine, Ethan Czuy; Herbenick, Debby; Martinez, Omar; Fu, Tsung-Chieh; Dodge, Brian

2018-07-01

People in open and other consensually nonmonogamous partnerships have been historically underserved by researchers and providers. Many studies group such partnerships together with nonconsensual nonmonogamy (NCNM) under the banner of "concurrent sexual partnerships." Discrimination from service providers poses a substantial barrier to care. Responding to such concerns, this investigation explored sociodemographic correlates with open relationships and associations between relationship structure and sexual risk, HIV/STI testing, and relationship satisfaction in a nationally representative probability sample. Data were drawn from the 2012 National Survey of Sexual Health and Behavior (n = 2270). We used multinomial logistic regression to identify correlates with relationship structure, and linear and logistic regression to investigate associations between relationship structure and testing, condom use, and relationship satisfaction. Eighty-nine percent of participants reported monogamy, 4% reported open relationships, and 8% reported NCNM. Males, gay/lesbian individuals, bisexual individuals, and those who identified as "Other, Non-Hispanic" were more likely to report open relationships. Bisexual individuals and Black, Non-Hispanic participants were more likely to report NCNM; older participants were less likely to do so. Participants in open relationships reported more frequent condom use for anal intercourse and lower relationship satisfaction than monogamous participants. NCNM participants reported more HIV testing and lower satisfaction. Identities, experiences, and behaviors within open and other consensually nonmonogamous populations should be regarded as unique and diverse, rather than conflated with those common to other relationship structures. There is a need for greater awareness of diverse relationship structures among researchers and providers, and incorporation of related content into educational programming.

Single K ATP channel opening in response to action potential firing in mouse dentate granule neurons.

PubMed

Tanner, Geoffrey R; Lutas, Andrew; Martínez-François, Juan Ramón; Yellen, Gary

2011-06-08

ATP-sensitive potassium channels (K(ATP) channels) are important sensors of cellular metabolic state that link metabolism and excitability in neuroendocrine cells, but their role in nonglucosensing central neurons is less well understood. To examine a possible role for K(ATP) channels in modulating excitability in hippocampal circuits, we recorded the activity of single K(ATP) channels in cell-attached patches of granule cells in the mouse dentate gyrus during bursts of action potentials generated by antidromic stimulation of the mossy fibers. Ensemble averages of the open probability (p(open)) of single K(ATP) channels over repeated trials of stimulated spike activity showed a transient increase in p(open) in response to action potential firing. Channel currents were identified as K(ATP) channels through blockade with glibenclamide and by comparison with recordings from Kir6.2 knock-out mice. The transient elevation in K(ATP) p(open) may arise from submembrane ATP depletion by the Na(+)-K(+) ATPase, as the pump blocker strophanthidin reduced the magnitude of the elevation. Both the steady-state and stimulus-elevated p(open) of the recorded channels were higher in the presence of the ketone body R-β-hydroxybutyrate, consistent with earlier findings that ketone bodies can affect K(ATP) activity. Using perforated-patch recording, we also found that K(ATP) channels contribute to the slow afterhyperpolarization following an evoked burst of action potentials. We propose that activity-dependent opening of K(ATP) channels may help granule cells act as a seizure gate in the hippocampus and that ketone-body-mediated augmentation of the activity-dependent opening could in part explain the effect of the ketogenic diet in reducing epileptic seizures.

Dissociation in decision bias mechanism between probabilistic information and previous decision

PubMed Central

Kaneko, Yoshiyuki; Sakai, Katsuyuki

2015-01-01

Target detection performance is known to be influenced by events in the previous trials. It has not been clear, however, whether this bias effect is due to the previous sensory stimulus, motor response, or decision. Also it remains open whether or not the previous trial effect emerges via the same mechanism as the effect of knowledge about the target probability. In the present study, we asked normal human subjects to make a decision about the presence or absence of a visual target. We presented a pre-cue indicating the target probability before the stimulus, and also a decision-response mapping cue after the stimulus so as to tease apart the effect of decision from that of motor response. We found that the target detection performance was significantly affected by the probability cue in the current trial and also by the decision in the previous trial. While the information about the target probability modulated the decision criteria, the previous decision modulated the sensitivity to target-relevant sensory signals (d-prime). Using functional magnetic resonance imaging (fMRI), we also found that activation in the left intraparietal sulcus (IPS) was decreased when the probability cue indicated a high probability of the target. By contrast, activation in the right inferior frontal gyrus (IFG) was increased when the subjects made a target-present decision in the previous trial, but this change was observed specifically when the target was present in the current trial. Activation in these regions was associated with individual-difference in the decision computation parameters. We argue that the previous decision biases the target detection performance by modulating the processing of target-selective information, and this mechanism is distinct from modulation of decision criteria due to expectation of a target. PMID:25999844

A microcomputer program for energy assessment and aggregation using the triangular probability distribution

USGS Publications Warehouse

Crovelli, R.A.; Balay, R.H.

1991-01-01

A general risk-analysis method was developed for petroleum-resource assessment and other applications. The triangular probability distribution is used as a model with an analytic aggregation methodology based on probability theory rather than Monte-Carlo simulation. Among the advantages of the analytic method are its computational speed and flexibility, and the saving of time and cost on a microcomputer. The input into the model consists of a set of components (e.g. geologic provinces) and, for each component, three potential resource estimates: minimum, most likely (mode), and maximum. Assuming a triangular probability distribution, the mean, standard deviation, and seven fractiles (F100, F95, F75, F50, F25, F5, and F0) are computed for each component, where for example, the probability of more than F95 is equal to 0.95. The components are aggregated by combining the means, standard deviations, and respective fractiles under three possible siutations (1) perfect positive correlation, (2) complete independence, and (3) any degree of dependence between these two polar situations. A package of computer programs named the TRIAGG system was written in the Turbo Pascal 4.0 language for performing the analytic probabilistic methodology. The system consists of a program for processing triangular probability distribution assessments and aggregations, and a separate aggregation routine for aggregating aggregations. The user's documentation and program diskette of the TRIAGG system are available from USGS Open File Services. TRIAGG requires an IBM-PC/XT/AT compatible microcomputer with 256kbyte of main memory, MS-DOS 3.1 or later, either two diskette drives or a fixed disk, and a 132 column printer. A graphics adapter and color display are optional. ?? 1991.

Modeling of site occupancy dynamics for northern spotted owls, with emphasis on the effects of barred owls

USGS Publications Warehouse

Olson, Gail S.; Anthony, Robert G.; Forsman, Eric D.; Ackers, Steven H.; Loschl, Peter J.; Reid, Janice A.; Dugger, Katie M.; Glenn, Elizabeth M.; Ripple, William J.

2005-01-01

Northern spotted owls (Strix occidentalis caurina) have been studied intensively since their listing as a threatened species by the U.S. Fish and Wildlife Service in 1990. Studies of spotted owl site occupancy have used various binary response measures, but most of these studies have made the assumption that detectability is perfect, or at least high and not variable. Further, previous studies did not consider temporal variation in site occupancy. We used relatively new methods for open population modeling of site occupancy that incorporated imperfect and variable detectability of spotted owls and allowed modeling of temporal variation in site occupancy, extinction, and colonization probabilities. We also examined the effects of barred owl (S. varia) presence on these parameters. We used spotted owl survey data from 1990 to 2002 for 3 study areas in Oregon, USA, and we used program MARK to develop and analyze site occupancy models. We found per visit detection probabilities averaged <0.70 and were highly variable among study years and study areas. Site occupancy probabilities for owl pairs declined greatly on 1 study area and slightly on the other 2 areas. For all owls, including singles and pairs, site occupancy was mostly stable through time. Barred owl presence had a negative effect on spotted owl detection probabilities, and it had either a positive effect on local-extinction probabilities or a negative effect on colonization probabilities. We conclude that further analyses of spotted owls must account for imperfect and variable detectability and barred owl presence to properly interpret results. Further, because barred owl presence is increasing within the range of northern spotted owls, we expect to see further declines in the proportion of sites occupied by spotted owls.

Aerosol distribution during open suctioning and long-term surveillance of air quality in a respiratory care center within a medical center.

PubMed

Chung, Fen-Fang; Lin, Hui-Ling; Liu, Hsueh-Erh; Lien, Angela Shin-Yu; Hsiao, Hsiu-Feng; Chou, Lan-Ti; Wan, Gwo-Hwa

2015-01-01

The investigation of hospital air quality has been conducted in wards, ICUs, operating theaters, and public areas. Few studies have assessed air quality in respiratory care centers (RCCs), especially in mechanically ventilated patients with open suctioning. The RCC air quality indices (temperature, relative humidity, levels of CO2, total volatile organic compounds, particulate matter [PM], bacteria, and fungi) were monitored over 1 y. The air around the patient's head was sampled during open suctioning to examine the probability of bioaerosol exposure affecting health-care workers. This investigation found that the levels of indoor air pollutants (CO2, PM, bacteria, and fungi) were below the indoor air quality standard set by the Taiwan Environmental Protection Agency. Meanwhile, the levels of total volatile organic compounds sometimes exceeded the indoor air quality standard, particularly in August. The identified bacterial genera included Micrococcus species, Corynebacterium species, and Staphylococcus species, and the predominant fungal genera included yeast, Aspergillus species, Scopulariopsis species, and Trichoderma species. Additionally, airborne PM2.5, PM1, and bacteria were clearly raised during open suctioning in mechanically ventilated patients. This phenomenon demonstrated that open suctioning may increase the bacterial exposure risk of health-care workers. RCC air quality deserves long-term monitoring and evaluation. Health-care workers must implement self-protection strategies during open suctioning to ensure their occupational health and safety in health-care settings. Copyright © 2015 by Daedalus Enterprises.

The role of national regulations in RPAS-based mapping projects in the monitoring of natural hazards that could involve infrastructures: the example of the Val Venosta Railway (Northern Italy - Bolzano).

NASA Astrophysics Data System (ADS)

Gandolfo, Luca; Busnardo, Enrico; Castellarin, Nicola; Canella, Claudio; Canella, Federico; Stabile, Marco; Curci, Francesco; Petrillo, Giovanni

2016-04-01

Italy has adopted National Regulations for the use of RPAS in its country's airspace in December 2013, issued by the Italian Civil Aviation Authority (ENAC). Despite the issued regulations, over the past months an increasing number of unauthorized and unsafe operations have been performed and the attention to safety is growing quickly in the public opinion. For this reason "Critical Operations" is permitted only to those RPAS Operators which have received special authorization by ENAC after a very demanding Aeronautical procedure. According to the Regulations, the flight close to-over urban areas, industrial plants, highways and railways, implies that only authorized RPAS Operators may perform such activities. An example of a "Critical" operation were the RPAS flights performed along the Venosta railway line to evaluate the current situation of two areas affected by geological instability and laid the basis for a future high accurate monitoring. The Venosta Valley is located in the western part of South Tyrol (Norhtern Italy). The valley possesses some unique features compared to the entire Alps, the particularly dry climate and the presence of huge alluvional fans, which give rise to different levels of altitude in the valley. From geological point of view, the Venosta Valley is characterized by the presence of the Austroalpine domain. In particular, there are two different geological units in this area: (i) the crystalline schists of the basement, which includes paragneiss, gneiss, granitoid pegmatites, garnet micaschists, quartzites and phyllites. (ii) The Mesozoic coverage divided into various complexes with successions of phyllites, volcanics and magmatiti. The railway line that runs through the Venosta Valley (Merano - Malles) unfolds along a path of 59,8 kilometers and covers an altitude difference of about 700 meters. In particular, three tunnels characterized the first section, including the M. Giuseppe tunnel, which required extensive consolidations both inside and outside. The mission's scope was to achieve high precision photogrammetry data to reconstruct sub-centimetric 3D models of the retaining wall and the unstable rock mass. Flights have been performed with two different RPAS, a multicopter and an helicopter, controlled by a crew composed by three members: two pilots (Command and Backup Pilot) operating redundant data links for flight control and a payload operator and Aeronautical Flight procedures have been applied. The payload operated the camera to achieve the best images for the data acquisition and 3D model reconstruction. The flights have been conducted with manual piloting flight procedures because of the RPAS on board GPS is significantly affected by the mountain slope proximity. For this reason, for the georeferencing procedure, ground control points have been acquired by using an high precision GPS. Finally, using RPAS data it has been possible to assess the lateral earth pressure on the retaining wall of the railway embankment, while in the second case the aim was to accurately reconstruct the volumes of an unstable rock mass.