A review of channel selection algorithms for EEG signal processing

NASA Astrophysics Data System (ADS)

Alotaiby, Turky; El-Samie, Fathi E. Abd; Alshebeili, Saleh A.; Ahmad, Ishtiaq

2015-12-01

Digital processing of electroencephalography (EEG) signals has now been popularly used in a wide variety of applications such as seizure detection/prediction, motor imagery classification, mental task classification, emotion classification, sleep state classification, and drug effects diagnosis. With the large number of EEG channels acquired, it has become apparent that efficient channel selection algorithms are needed with varying importance from one application to another. The main purpose of the channel selection process is threefold: (i) to reduce the computational complexity of any processing task performed on EEG signals by selecting the relevant channels and hence extracting the features of major importance, (ii) to reduce the amount of overfitting that may arise due to the utilization of unnecessary channels, for the purpose of improving the performance, and (iii) to reduce the setup time in some applications. Signal processing tools such as time-domain analysis, power spectral estimation, and wavelet transform have been used for feature extraction and hence for channel selection in most of channel selection algorithms. In addition, different evaluation approaches such as filtering, wrapper, embedded, hybrid, and human-based techniques have been widely used for the evaluation of the selected subset of channels. In this paper, we survey the recent developments in the field of EEG channel selection methods along with their applications and classify these methods according to the evaluation approach.

Data-Adaptive Bias-Reduced Doubly Robust Estimation.

PubMed

Vermeulen, Karel; Vansteelandt, Stijn

2016-05-01

Doubly robust estimators have now been proposed for a variety of target parameters in the causal inference and missing data literature. These consistently estimate the parameter of interest under a semiparametric model when one of two nuisance working models is correctly specified, regardless of which. The recently proposed bias-reduced doubly robust estimation procedure aims to partially retain this robustness in more realistic settings where both working models are misspecified. These so-called bias-reduced doubly robust estimators make use of special (finite-dimensional) nuisance parameter estimators that are designed to locally minimize the squared asymptotic bias of the doubly robust estimator in certain directions of these finite-dimensional nuisance parameters under misspecification of both parametric working models. In this article, we extend this idea to incorporate the use of data-adaptive estimators (infinite-dimensional nuisance parameters), by exploiting the bias reduction estimation principle in the direction of only one nuisance parameter. We additionally provide an asymptotic linearity theorem which gives the influence function of the proposed doubly robust estimator under correct specification of a parametric nuisance working model for the missingness mechanism/propensity score but a possibly misspecified (finite- or infinite-dimensional) outcome working model. Simulation studies confirm the desirable finite-sample performance of the proposed estimators relative to a variety of other doubly robust estimators.

Is {sup 276}U a doubly magic nucleus?

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

Liliani, N., E-mail: netta.liliani@gmail.com; Sulaksono, A.

2016-04-19

We investigate a possible new doubly magic heavy nucleus by using a relativistic mean-field (RMF) model with the addition of a cross interaction term of omega-rho mesons and an electromagnetic exchange term. We propose that {sup 276}U is a doubly magic nucleus. The evidence for {sup 276}U being a doubly magic nucleus is shown through the two-nucleon gaps, the single-particle energies, and the neutron skin thickness of the nucleus. We have also found that the prediction of {sup 276}U as a doubly magic nucleus by the RMF model is not affected by the inclusion of isoscalar-isovector and electromagnetic exchange couplings.

Establishing low-lying doubly charmed baryons

NASA Astrophysics Data System (ADS)

Chen, Hua-Xing; Mao, Qiang; Chen, Wei; Liu, Xiang; Zhu, Shi-Lin

2017-08-01

We systematically study the S -wave doubly charmed baryons using the method of QCD sum rules. Our results suggest that the Ξcc ++ recently observed by LHCb can be well identified as the S -wave Ξc c state of JP=1 /2+. We study its relevant Ωc c state, the mass of which is predicted to be around 3.7 GeV. We also systematically study the P -wave doubly charmed baryons, the masses of which are predicted to be around 4.1 GeV. Especially, there can be several excited doubly charmed baryons in this energy region, and we suggest searching for them in order to study the fine structure of the strong interaction.

Image Discrimination Models With Stochastic Channel Selection

NASA Technical Reports Server (NTRS)

Ahumada, Albert J., Jr.; Beard, Bettina L.; Null, Cynthia H. (Technical Monitor)

1995-01-01

Many models of human image processing feature a large fixed number of channels representing cortical units varying in spatial position (visual field direction and eccentricity) and spatial frequency (radial frequency and orientation). The values of these parameters are usually sampled at fixed values selected to ensure adequate overlap considering the bandwidth and/or spread parameters, which are usually fixed. Even high levels of overlap does not always ensure that the performance of the model will vary smoothly with image translation or scale changes. Physiological measurements of bandwidth and/or spread parameters result in a broad distribution of estimated parameter values and the prediction of some psychophysical results are facilitated by the assumption that these parameters also take on a range of values. Selecting a sample of channels from a continuum of channels rather than using a fixed set can make model performance vary smoothly with changes in image position, scale, and orientation. It also facilitates the addition of spatial inhomogeneity, nonlinear feature channels, and focus of attention to channel models.

Theory of Alike Selectivity in Biological Channels

NASA Technical Reports Server (NTRS)

Luchinsky, Dmitry G.; Gibby, Will A. T.; Kaufman, Igor Kh.; Eisenberg, Robert S.; McClintock, Peter V. E.

2016-01-01

We introduce a statistical mechanical model of the selectivity filter that accounts for the interaction between ions within the channel and derive Eisenman equation of the filter selectivity directly from the condition of barrier-less conduction.

HCN Channels Modulators: The Need for Selectivity

PubMed Central

Romanelli, Maria Novella; Sartiani, Laura; Masi, Alessio; Mannaioni, Guido; Manetti, Dina; Mugelli, Alessandro; Cerbai, Elisabetta

2016-01-01

Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, the molecular correlate of the hyperpolarization-activated current (If/Ih), are membrane proteins which play an important role in several physiological processes and various pathological conditions. In the Sino Atrial Node (SAN) HCN4 is the target of ivabradine, a bradycardic agent that is, at the moment, the only drug which specifically blocks If. Nevertheless, several other pharmacological agents have been shown to modulate HCN channels, a property that may contribute to their therapeutic activity and/or to their side effects. HCN channels are considered potential targets for developing drugs to treat several important pathologies, but a major issue in this field is the discovery of isoform-selective compounds, owing to the wide distribution of these proteins into the central and peripheral nervous systems, heart and other peripheral tissues. This survey is focused on the compounds that have been shown, or have been designed, to interact with HCN channels and on their binding sites, with the aim to summarize current knowledge and possibly to unveil useful information to design new potent and selective modulators. PMID:26975509

An evolutionarily conserved gene family encodes proton-selective ion channels.

PubMed

Tu, Yu-Hsiang; Cooper, Alexander J; Teng, Bochuan; Chang, Rui B; Artiga, Daniel J; Turner, Heather N; Mulhall, Eric M; Ye, Wenlei; Smith, Andrew D; Liman, Emily R

2018-03-02

Ion channels form the basis for cellular electrical signaling. Despite the scores of genetically identified ion channels selective for other monatomic ions, only one type of proton-selective ion channel has been found in eukaryotic cells. By comparative transcriptome analysis of mouse taste receptor cells, we identified Otopetrin1 (OTOP1), a protein required for development of gravity-sensing otoconia in the vestibular system, as forming a proton-selective ion channel. We found that murine OTOP1 is enriched in acid-detecting taste receptor cells and is required for their zinc-sensitive proton conductance. Two related murine genes, Otop2 and Otop3 , and a Drosophila ortholog also encode proton channels. Evolutionary conservation of the gene family and its widespread tissue distribution suggest a broad role for proton channels in physiology and pathophysiology. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Initial steps of inactivation at the K+ channel selectivity filter

PubMed Central

Thomson, Andrew S.; Heer, Florian T.; Smith, Frank J.; Hendron, Eunan; Bernèche, Simon; Rothberg, Brad S.

2014-01-01

K+ efflux through K+ channels can be controlled by C-type inactivation, which is thought to arise from a conformational change near the channel’s selectivity filter. Inactivation is modulated by ion binding near the selectivity filter; however, the molecular forces that initiate inactivation remain unclear. We probe these driving forces by electrophysiology and molecular simulation of MthK, a prototypical K+ channel. Either Mg2+ or Ca2+ can reduce K+ efflux through MthK channels. However, Ca2+, but not Mg2+, can enhance entry to the inactivated state. Molecular simulations illustrate that, in the MthK pore, Ca2+ ions can partially dehydrate, enabling selective accessibility of Ca2+ to a site at the entry to the selectivity filter. Ca2+ binding at the site interacts with K+ ions in the selectivity filter, facilitating a conformational change within the filter and subsequent inactivation. These results support an ionic mechanism that precedes changes in channel conformation to initiate inactivation. PMID:24733889

Ion-binding properties of a K+ channel selectivity filter in different conformations.

PubMed

Liu, Shian; Focke, Paul J; Matulef, Kimberly; Bian, Xuelin; Moënne-Loccoz, Pierre; Valiyaveetil, Francis I; Lockless, Steve W

2015-12-08

K(+) channels are membrane proteins that selectively conduct K(+) ions across lipid bilayers. Many voltage-gated K(+) (KV) channels contain two gates, one at the bundle crossing on the intracellular side of the membrane and another in the selectivity filter. The gate at the bundle crossing is responsible for channel opening in response to a voltage stimulus, whereas the gate at the selectivity filter is responsible for C-type inactivation. Together, these regions determine when the channel conducts ions. The K(+) channel from Streptomyces lividians (KcsA) undergoes an inactivation process that is functionally similar to KV channels, which has led to its use as a practical system to study inactivation. Crystal structures of KcsA channels with an open intracellular gate revealed a selectivity filter in a constricted conformation similar to the structure observed in closed KcsA containing only Na(+) or low [K(+)]. However, recent work using a semisynthetic channel that is unable to adopt a constricted filter but inactivates like WT channels challenges this idea. In this study, we measured the equilibrium ion-binding properties of channels with conductive, inactivated, and constricted filters using isothermal titration calorimetry (ITC). EPR spectroscopy was used to determine the state of the intracellular gate of the channel, which we found can depend on the presence or absence of a lipid bilayer. Overall, we discovered that K(+) ion binding to channels with an inactivated or conductive selectivity filter is different from K(+) ion binding to channels with a constricted filter, suggesting that the structures of these channels are different.

Non-Equilibrium Dynamics Contribute to Ion Selectivity in the KcsA Channel

PubMed Central

Haas, Stephan; Farley, Robert A.

2014-01-01

The ability of biological ion channels to conduct selected ions across cell membranes is critical for the survival of both animal and bacterial cells. Numerous investigations of ion selectivity have been conducted over more than 50 years, yet the mechanisms whereby the channels select certain ions and reject others are not well understood. Here we report a new application of Jarzynski’s Equality to investigate the mechanism of ion selectivity using non-equilibrium molecular dynamics simulations of Na+ and K+ ions moving through the KcsA channel. The simulations show that the selectivity filter of KcsA adapts and responds to the presence of the ions with structural rearrangements that are different for Na+ and K+. These structural rearrangements facilitate entry of K+ ions into the selectivity filter and permeation through the channel, and rejection of Na+ ions. A mechanistic model of ion selectivity by this channel based on the results of the simulations relates the structural rearrangement of the selectivity filter to the differential dehydration of ions and multiple-ion occupancy and describes a mechanism to efficiently select and conduct K+. Estimates of the K+/Na+ selectivity ratio and steady state ion conductance for KcsA from the simulations are in good quantitative agreement with experimental measurements. This model also accurately describes experimental observations of channel block by cytoplasmic Na+ ions, the “punch through” relief of channel block by cytoplasmic positive voltages, and is consistent with the knock-on mechanism of ion permeation. PMID:24465882

Spectroscopy of singly, doubly, and triply bottom baryons

NASA Astrophysics Data System (ADS)

Wei, Ke-Wei; Chen, Bing; Liu, Na; Wang, Qian-Qian; Guo, Xin-Heng

2017-06-01

Recently, some singly bottom baryons have been established experimentally, but none of the doubly or triply bottom baryons have been observed. Under the Regge phenomenology, the mass of an unobserved ground-state doubly or triply bottom baryon is expressed as a function of masses of the well-established light baryons and singly bottom baryons. Then, the values of Regge slopes and Regge intercepts for baryons containing one, two, or three bottom quarks are calculated. After that, the masses of the orbitally excited singly, doubly, and triply bottom baryons are estimated. Our predictions may be useful for the discovery of these baryons and their JP assignments.

Doubly anharmonic oscillator under the topological effects of a screw dislocation

NASA Astrophysics Data System (ADS)

Bakke, Knut

2018-05-01

We consider an elastic medium with the distortion of a circular curve into a vertical spiral, and investigate the influence of this topological defect on the doubly anharmonic oscillator. We show that the Schrödinger equation for the doubly anharmonic oscillator in the presence of this linear topological defect can be solved analytically. We also obtain the exact expressions for the permitted energies of the ground state of the doubly anharmonic oscillator, and show that the topology of the screw dislocation modifies the spectrum of energy of the doubly anharmonic oscillator.

Theory of pure rotational transitions in doubly degenerate torsional states of ethane

NASA Technical Reports Server (NTRS)

Rosenberg, A.; Susskind, J.

1979-01-01

It is shown that pure rotational transitions in doubly degenerate torsional states of C2H6 (with selection rules Delta K = 0, plus or minus 1) are made allowed by Coriolis interaction between torsion and dipole-allowed vibrations. Expressions are presented for integrated intensities from which strengths of lines in the millimeter region can be calculated.

Sniffer Channel Selection for Monitoring Wireless LANs

NASA Astrophysics Data System (ADS)

Song, Yuan; Chen, Xian; Kim, Yoo-Ah; Wang, Bing; Chen, Guanling

Wireless sniffers are often used to monitor APs in wireless LANs (WLANs) for network management, fault detection, traffic characterization, and optimizing deployment. It is cost effective to deploy single-radio sniffers that can monitor multiple nearby APs. However, since nearby APs often operate on orthogonal channels, a sniffer needs to switch among multiple channels to monitor its nearby APs. In this paper, we formulate and solve two optimization problems on sniffer channel selection. Both problems require that each AP be monitored by at least one sniffer. In addition, one optimization problem requires minimizing the maximum number of channels that a sniffer listens to, and the other requires minimizing the total number of channels that the sniffers listen to. We propose a novel LP-relaxation based algorithm, and two simple greedy heuristics for the above two optimization problems. Through simulation, we demonstrate that all the algorithms are effective in achieving their optimization goals, and the LP-based algorithm outperforms the greedy heuristics.

Sodium channel selectivity and conduction: Prokaryotes have devised their own molecular strategy

PubMed Central

Finol-Urdaneta, Rocio K.; Wang, Yibo; Al-Sabi, Ahmed; Zhao, Chunfeng

2014-01-01

Striking structural differences between voltage-gated sodium (Nav) channels from prokaryotes (homotetramers) and eukaryotes (asymmetric, four-domain proteins) suggest the likelihood of different molecular mechanisms for common functions. For these two channel families, our data show similar selectivity sequences among alkali cations (relative permeability, Pion/PNa) and asymmetric, bi-ionic reversal potentials when the Na/K gradient is reversed. We performed coordinated experimental and computational studies, respectively, on the prokaryotic Nav channels NaChBac and NavAb. NaChBac shows an “anomalous,” nonmonotonic mole-fraction dependence in the presence of certain sodium–potassium mixtures; to our knowledge, no comparable observation has been reported for eukaryotic Nav channels. NaChBac’s preferential selectivity for sodium is reduced either by partial titration of its highly charged selectivity filter, when extracellular pH is lowered from 7.4 to 5.8, or by perturbation—likely steric—associated with a nominally electro-neutral substitution in the selectivity filter (E191D). Although no single molecular feature or energetic parameter appears to dominate, our atomistic simulations, based on the published NavAb crystal structure, revealed factors that may contribute to the normally observed selectivity for Na over K. These include: (a) a thermodynamic penalty to exchange one K+ for one Na+ in the wild-type (WT) channel, increasing the relative likelihood of Na+ occupying the binding site; (b) a small tendency toward weaker ion binding to the selectivity filter in Na–K mixtures, consistent with the higher conductance observed with both sodium and potassium present; and (c) integrated 1-D potentials of mean force for sodium or potassium movement that show less separation for the less selective E/D mutant than for WT. Overall, tight binding of a single favored ion to the selectivity filter, together with crucial inter-ion interactions within the pore

A novel channel selection method for optimal classification in different motor imagery BCI paradigms.

PubMed

Shan, Haijun; Xu, Haojie; Zhu, Shanan; He, Bin

2015-10-21

For sensorimotor rhythms based brain-computer interface (BCI) systems, classification of different motor imageries (MIs) remains a crucial problem. An important aspect is how many scalp electrodes (channels) should be used in order to reach optimal performance classifying motor imaginations. While the previous researches on channel selection mainly focus on MI tasks paradigms without feedback, the present work aims to investigate the optimal channel selection in MI tasks paradigms with real-time feedback (two-class control and four-class control paradigms). In the present study, three datasets respectively recorded from MI tasks experiment, two-class control and four-class control experiments were analyzed offline. Multiple frequency-spatial synthesized features were comprehensively extracted from every channel, and a new enhanced method IterRelCen was proposed to perform channel selection. IterRelCen was constructed based on Relief algorithm, but was enhanced from two aspects: change of target sample selection strategy and adoption of the idea of iterative computation, and thus performed more robust in feature selection. Finally, a multiclass support vector machine was applied as the classifier. The least number of channels that yield the best classification accuracy were considered as the optimal channels. One-way ANOVA was employed to test the significance of performance improvement among using optimal channels, all the channels and three typical MI channels (C3, C4, Cz). The results show that the proposed method outperformed other channel selection methods by achieving average classification accuracies of 85.2, 94.1, and 83.2 % for the three datasets, respectively. Moreover, the channel selection results reveal that the average numbers of optimal channels were significantly different among the three MI paradigms. It is demonstrated that IterRelCen has a strong ability for feature selection. In addition, the results have shown that the numbers of optimal

Doubly robust nonparametric inference on the average treatment effect.

PubMed

Benkeser, D; Carone, M; Laan, M J Van Der; Gilbert, P B

2017-12-01

Doubly robust estimators are widely used to draw inference about the average effect of a treatment. Such estimators are consistent for the effect of interest if either one of two nuisance parameters is consistently estimated. However, if flexible, data-adaptive estimators of these nuisance parameters are used, double robustness does not readily extend to inference. We present a general theoretical study of the behaviour of doubly robust estimators of an average treatment effect when one of the nuisance parameters is inconsistently estimated. We contrast different methods for constructing such estimators and investigate the extent to which they may be modified to also allow doubly robust inference. We find that while targeted minimum loss-based estimation can be used to solve this problem very naturally, common alternative frameworks appear to be inappropriate for this purpose. We provide a theoretical study and a numerical evaluation of the alternatives considered. Our simulations highlight the need for and usefulness of these approaches in practice, while our theoretical developments have broad implications for the construction of estimators that permit doubly robust inference in other problems.

Channels selection using independent component analysis and scalp map projection for EEG-based driver fatigue classification.

PubMed

Rifai Chai; Naik, Ganesh R; Sai Ho Ling; Tran, Yvonne; Craig, Ashley; Nguyen, Hung T

2017-07-01

This paper presents a classification of driver fatigue with electroencephalography (EEG) channels selection analysis. The system employs independent component analysis (ICA) with scalp map back projection to select the dominant of EEG channels. After channel selection, the features of the selected EEG channels were extracted based on power spectral density (PSD), and then classified using a Bayesian neural network. The results of the ICA decomposition with the back-projected scalp map and a threshold showed that the EEG channels can be reduced from 32 channels into 16 dominants channels involved in fatigue assessment as chosen channels, which included AF3, F3, FC1, FC5, T7, CP5, P3, O1, P4, P8, CP6, T8, FC2, F8, AF4, FP2. The result of fatigue vs. alert classification of the selected 16 channels yielded a sensitivity of 76.8%, specificity of 74.3% and an accuracy of 75.5%. Also, the classification results of the selected 16 channels are comparable to those using the original 32 channels. So, the selected 16 channels is preferable for ergonomics improvement of EEG-based fatigue classification system.

Lysine and the Na+/K+ Selectivity in Mammalian Voltage-Gated Sodium Channels.

PubMed

Li, Yang; Liu, Huihui; Xia, Mengdie; Gong, Haipeng

2016-01-01

Voltage-gated sodium (Nav) channels are critical in the generation and transmission of neuronal signals in mammals. The crystal structures of several prokaryotic Nav channels determined in recent years inspire the mechanistic studies on their selection upon the permeable cations (especially between Na+ and K+ ions), a property that is proposed to be mainly determined by residues in the selectivity filter. However, the mechanism of cation selection in mammalian Nav channels lacks direct explanation at atomic level due to the difference in amino acid sequences between mammalian and prokaryotic Nav homologues, especially at the constriction site where the DEKA motif has been identified to determine the Na+/K+ selectivity in mammalian Nav channels but is completely absent in the prokaryotic counterparts. Among the DEKA residues, Lys is of the most importance since its mutation to Arg abolishes the Na+/K+ selectivity. In this work, we modeled the pore domain of mammalian Nav channels by mutating the four residues at the constriction site of a prokaryotic Nav channel (NavRh) to DEKA, and then mechanistically investigated the contribution of Lys in cation selection using molecular dynamics simulations. The DERA mutant was generated as a comparison to understand the loss of ion selectivity caused by the K-to-R mutation. Simulations and free energy calculations on the mutants indicate that Lys facilitates Na+/K+ selection by electrostatically repelling the cation to a highly Na+-selective location sandwiched by the carboxylate groups of Asp and Glu at the constriction site. In contrast, the electrostatic repulsion is substantially weakened when Lys is mutated to Arg, because of two intrinsic properties of the Arg side chain: the planar geometric design and the sparse charge distribution of the guanidine group.

Selection of Inhibitor-Resistant Viral Potassium Channels Identifies a Selectivity Filter Site that Affects Barium and Amantadine Block

PubMed Central

Fujiwara, Yuichiro; Arrigoni, Cristina; Domigan, Courtney; Ferrara, Giuseppina; Pantoja, Carlos; Thiel, Gerhard; Moroni, Anna; Minor, Daniel L.

2009-01-01

Background Understanding the interactions between ion channels and blockers remains an important goal that has implications for delineating the basic mechanisms of ion channel function and for the discovery and development of ion channel directed drugs. Methodology/Principal Findings We used genetic selection methods to probe the interaction of two ion channel blockers, barium and amantadine, with the miniature viral potassium channel Kcv. Selection for Kcv mutants that were resistant to either blocker identified a mutant bearing multiple changes that was resistant to both. Implementation of a PCR shuffling and backcrossing procedure uncovered that the blocker resistance could be attributed to a single change, T63S, at a position that is likely to form the binding site for the inner ion in the selectivity filter (site 4). A combination of electrophysiological and biochemical assays revealed a distinct difference in the ability of the mutant channel to interact with the blockers. Studies of the analogous mutation in the mammalian inward rectifier Kir2.1 show that the T→S mutation affects barium block as well as the stability of the conductive state. Comparison of the effects of similar barium resistant mutations in Kcv and Kir2.1 shows that neighboring amino acids in the Kcv selectivity filter affect blocker binding. Conclusions/Significance The data support the idea that permeant ions have an integral role in stabilizing potassium channel structure, suggest that both barium and amantadine act at a similar site, and demonstrate how genetic selections can be used to map blocker binding sites and reveal mechanistic features. PMID:19834614

Structure and selectivity in bestrophin ion channels

DOE PAGES

Yang, Tingting; Liu, Qun; Kloss, Brian; ...

2014-09-25

Human bestrophin 1 (hBest1) is a calcium-activated chloride channel from the retinal pigment epithelium, where it can suffer mutations associated with vitelliform macular degeneration, or Best disease. We describe the structure of a bacterial homolog (KpBest) of hBest1 and functional characterizations of both channels. KpBest is a pentamer that forms a five-helix transmembrane pore, closed by three rings of conserved hydrophobic residues, and has a cytoplasmic cavern with a restricted exit. From electrophysiological analysis of structure-inspired mutations in KpBest and hBest1, we find a subtle control of ion selectivity in the bestrophins, including reversal of anion/cation selectivity, and dramatic activationmore » by mutations at the exit restriction. Lastly, a homology model of hBest1 shows the locations of disease-causing mutations and suggests possible roles in regulation.« less

Tuning the ion selectivity of tetrameric cation channels by changing the number of ion binding sites

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

Derebe, Mehabaw G.; Sauer, David B.; Zeng, Weizhong

2015-11-30

Selective ion conduction across ion channel pores is central to cellular physiology. To understand the underlying principles of ion selectivity in tetrameric cation channels, we engineered a set of cation channel pores based on the nonselective NaK channel and determined their structures to high resolution. These structures showcase an ensemble of selectivity filters with a various number of contiguous ion binding sites ranging from 2 to 4, with each individual site maintaining a geometry and ligand environment virtually identical to that of equivalent sites in K{sup +} channel selectivity filters. Combined with single channel electrophysiology, we show that only themore » channel with four ion binding sites is K{sup +} selective, whereas those with two or three are nonselective and permeate Na{sup +} and K{sup +} equally well. These observations strongly suggest that the number of contiguous ion binding sites in a single file is the key determinant of the channel's selectivity properties and the presence of four sites in K{sup +} channels is essential for highly selective and efficient permeation of K{sup +} ions.« less

Electrostatics of aquaporin and aquaglyceroporin channels correlates with their transport selectivity

PubMed Central

Oliva, Romina; Calamita, Giuseppe; Thornton, Janet M.; Pellegrini-Calace, Marialuisa

2010-01-01

Aquaporins are homotetrameric channel proteins, which allow the diffusion of water and small solutes across biological membranes. According to their transport function, aquaporins can be divided into “orthodox aquaporins”, which allow the flux of water molecules only, and “aquaglyceroporins”, which facilitate the diffusion of glycerol and other small solutes in addition to water. The contribution of individual residues in the pore to the selectivity of orthodox aquaporins and aquaglyceroporins is not yet fully understood. To gain insights into aquaporin selectivity, we focused on the sequence variation and electrostatics of their channels. The continuum Poisson-Boltzmann electrostatic potential along the channel was calculated and compared for ten three-dimensional-structures which are representatives of different aquaporin subfamilies, and a panel of functionally characterized mutants, for which high-accuracy three-dimensional-models could be derived. Interestingly, specific electrostatic profiles associated with the main selectivity to water or glycerol could be identified. In particular: (i) orthodox aquaporins showed a distinctive electrostatic potential maximum at the periplasmic side of the channel around the aromatic/Arg (ar/R) constriction site; (ii) aquaporin-0 (AQP0), a mammalian aquaporin with considerably low water permeability, had an additional deep minimum at the cytoplasmic side; (iii) aquaglyceroporins showed a rather flat potential all along the channel; and (iv) the bifunctional protozoan PfAQP had an unusual all negative profile. Evaluation of electrostatics of the mutants, along with a thorough sequence analysis of the aquaporin pore-lining residues, illuminated the contribution of specific residues to the electrostatics of the channels and possibly to their selectivity. PMID:20147624

Mechanism of activation at the selectivity filter of the KcsA K+ channel

PubMed Central

Heer, Florian T; Posson, David J; Wojtas-Niziurski, Wojciech

2017-01-01

Potassium channels are opened by ligands and/or membrane potential. In voltage-gated K+ channels and the prokaryotic KcsA channel, conduction is believed to result from opening of an intracellular constriction that prevents ion entry into the pore. On the other hand, numerous ligand-gated K+ channels lack such gate, suggesting that they may be activated by a change within the selectivity filter, a narrow region at the extracellular side of the pore. Using molecular dynamics simulations and electrophysiology measurements, we show that ligand-induced conformational changes in the KcsA channel removes steric restraints at the selectivity filter, thus resulting in structural fluctuations, reduced K+ affinity, and increased ion permeation. Such activation of the selectivity filter may be a universal gating mechanism within K+ channels. The occlusion of the pore at the level of the intracellular gate appears to be secondary. PMID:28994652

Streaming potentials in gramicidin channels measured with ion-selective microelectrodes.

PubMed Central

Tripathi, S; Hladky, S B

1998-01-01

Streaming potentials have been measured for gramicidin channels with a new method employing ion-selective microelectrodes. It is shown that ideally ion-selective electrodes placed at the membrane surface record the true streaming potential. Using this method for ion concentrations below 100 mM, approximately seven water molecules are transported whenever a sodium, potassium, or cesium ion, passes through the channel. This new method confirms earlier measurements (Rosenberg, P.A., and A. Finkelstein. 1978. Interaction of ions and water in gramicidin A channels. J. Gen. Physiol. 72:327-340) in which the streaming potentials were calculated as the difference between electrical potentials measured in the presence of gramicidin and in the presence of the ion carriers valinomycin and nonactin. PMID:9635745

Energetics of discrete selectivity bands and mutation-induced transitions in the calcium-sodium ion channels family

NASA Astrophysics Data System (ADS)

Kaufman, I.; Luchinsky, D. G.; Tindjong, R.; McClintock, P. V. E.; Eisenberg, R. S.

2013-11-01

We use Brownian dynamics (BD) simulations to study the ionic conduction and valence selectivity of a generic electrostatic model of a biological ion channel as functions of the fixed charge Qf at its selectivity filter. We are thus able to reconcile the discrete calcium conduction bands recently revealed in our BD simulations, M0 (Qf=1e), M1 (3e), M2 (5e), with a set of sodium conduction bands L0 (0.5e), L1 (1.5e), thereby obtaining a completed pattern of conduction and selectivity bands vs Qf for the sodium-calcium channels family. An increase of Qf leads to an increase of calcium selectivity: L0 (sodium-selective, nonblocking channel) → M0 (nonselective channel) → L1 (sodium-selective channel with divalent block) → M1 (calcium-selective channel exhibiting the anomalous mole fraction effect). We create a consistent identification scheme where the L0 band is putatively identified with the eukaryotic sodium channel The scheme created is able to account for the experimentally observed mutation-induced transformations between nonselective channels, sodium-selective channels, and calcium-selective channels, which we interpret as transitions between different rows of the identification table. By considering the potential energy changes during permeation, we show explicitly that the multi-ion conduction bands of calcium and sodium channels arise as the result of resonant barrierless conduction. The pattern of periodic conduction bands is explained on the basis of sequential neutralization taking account of self-energy, as Qf(z,i)=ze(1/2+i), where i is the order of the band and z is the valence of the ion. Our results confirm the crucial influence of electrostatic interactions on conduction and on the Ca2+/Na+ valence selectivity of calcium and sodium ion channels. The model and results could be also applicable to biomimetic nanopores with charged walls.

Use of color-coded sleeve shutters accelerates oscillograph channel selection

NASA Technical Reports Server (NTRS)

Bouchlas, T.; Bowden, F. W.

1967-01-01

Sleeve-type shutters mechanically adjust individual galvanometer light beams onto or away from selected channels on oscillograph papers. In complex test setups, the sleeve-type shutters are color coded to separately identify each oscillograph channel. This technique could be used on any equipment using tubular galvanometer light sources.

Unraveling the mechanism of selective ion transport in hydrophobic subnanometer channels

PubMed Central

Li, Hui; Francisco, Joseph S.; Zeng, Xiao Cheng

2015-01-01

Recently reported synthetic organic nanopore (SONP) can mimic a key feature of natural ion channels, i.e., selective ion transport. However, the physical mechanism underlying the K+/Na+ selectivity for the SONPs is dramatically different from that of natural ion channels. To achieve a better understanding of the selective ion transport in hydrophobic subnanometer channels in general and SONPs in particular, we perform a series of ab initio molecular dynamics simulations to investigate the diffusivity of aqua Na+ and K+ ions in two prototype hydrophobic nanochannels: (i) an SONP with radius of 3.2 Å, and (ii) single-walled carbon nanotubes (CNTs) with radii of 3–5 Å (these radii are comparable to those of the biological potassium K+ channels). We find that the hydration shell of aqua Na+ ion is smaller than that of aqua K+ ion but notably more structured and less yielding. The aqua ions do not lower the diffusivity of water molecules in CNTs, but in SONP the diffusivity of aqua ions (Na+ in particular) is strongly suppressed due to the rugged inner surface. Moreover, the aqua Na+ ion requires higher formation energy than aqua K+ ion in the hydrophobic nanochannels. As such, we find that the ion (K+ vs. Na+) selectivity of the (8, 8) CNT is ∼20× higher than that of SONP. Hence, the (8, 8) CNT is likely the most efficient artificial K+ channel due in part to its special interior environment in which Na+ can be fully solvated, whereas K+ cannot. This work provides deeper insights into the physical chemistry behind selective ion transport in nanochannels. PMID:26283377

Unraveling the mechanism of selective ion transport in hydrophobic subnanometer channels.

PubMed

Li, Hui; Francisco, Joseph S; Zeng, Xiao Cheng

2015-09-01

Recently reported synthetic organic nanopore (SONP) can mimic a key feature of natural ion channels, i.e., selective ion transport. However, the physical mechanism underlying the K(+)/Na(+) selectivity for the SONPs is dramatically different from that of natural ion channels. To achieve a better understanding of the selective ion transport in hydrophobic subnanometer channels in general and SONPs in particular, we perform a series of ab initio molecular dynamics simulations to investigate the diffusivity of aqua Na(+) and K(+) ions in two prototype hydrophobic nanochannels: (i) an SONP with radius of 3.2 Å, and (ii) single-walled carbon nanotubes (CNTs) with radii of 3-5 Å (these radii are comparable to those of the biological potassium K(+) channels). We find that the hydration shell of aqua Na(+) ion is smaller than that of aqua K(+) ion but notably more structured and less yielding. The aqua ions do not lower the diffusivity of water molecules in CNTs, but in SONP the diffusivity of aqua ions (Na(+) in particular) is strongly suppressed due to the rugged inner surface. Moreover, the aqua Na(+) ion requires higher formation energy than aqua K(+) ion in the hydrophobic nanochannels. As such, we find that the ion (K(+) vs. Na(+)) selectivity of the (8, 8) CNT is ∼20× higher than that of SONP. Hence, the (8, 8) CNT is likely the most efficient artificial K(+) channel due in part to its special interior environment in which Na(+) can be fully solvated, whereas K(+) cannot. This work provides deeper insights into the physical chemistry behind selective ion transport in nanochannels.

A Wearable Channel Selection-Based Brain-Computer Interface for Motor Imagery Detection.

PubMed

Lo, Chi-Chun; Chien, Tsung-Yi; Chen, Yu-Chun; Tsai, Shang-Ho; Fang, Wai-Chi; Lin, Bor-Shyh

2016-02-06

Motor imagery-based brain-computer interface (BCI) is a communication interface between an external machine and the brain. Many kinds of spatial filters are used in BCIs to enhance the electroencephalography (EEG) features related to motor imagery. The approach of channel selection, developed to reserve meaningful EEG channels, is also an important technique for the development of BCIs. However, current BCI systems require a conventional EEG machine and EEG electrodes with conductive gel to acquire multi-channel EEG signals and then transmit these EEG signals to the back-end computer to perform the approach of channel selection. This reduces the convenience of use in daily life and increases the limitations of BCI applications. In order to improve the above issues, a novel wearable channel selection-based brain-computer interface is proposed. Here, retractable comb-shaped active dry electrodes are designed to measure the EEG signals on a hairy site, without conductive gel. By the design of analog CAR spatial filters and the firmware of EEG acquisition module, the function of spatial filters could be performed without any calculation, and channel selection could be performed in the front-end device to improve the practicability of detecting motor imagery in the wearable EEG device directly or in commercial mobile phones or tablets, which may have relatively low system specifications. Finally, the performance of the proposed BCI is investigated, and the experimental results show that the proposed system is a good wearable BCI system prototype.

Energetics of discrete selectivity bands and mutation-induced transitions in the calcium-sodium ion channels family.

PubMed

Kaufman, I; Luchinsky, D G; Tindjong, R; McClintock, P V E; Eisenberg, R S

2013-11-01

We use Brownian dynamics (BD) simulations to study the ionic conduction and valence selectivity of a generic electrostatic model of a biological ion channel as functions of the fixed charge Q(f) at its selectivity filter. We are thus able to reconcile the discrete calcium conduction bands recently revealed in our BD simulations, M0 (Q(f)=1e), M1 (3e), M2 (5e), with a set of sodium conduction bands L0 (0.5e), L1 (1.5e), thereby obtaining a completed pattern of conduction and selectivity bands vs Q(f) for the sodium-calcium channels family. An increase of Q(f) leads to an increase of calcium selectivity: L0 (sodium-selective, nonblocking channel) → M0 (nonselective channel) → L1 (sodium-selective channel with divalent block) → M1 (calcium-selective channel exhibiting the anomalous mole fraction effect). We create a consistent identification scheme where the L0 band is putatively identified with the eukaryotic sodium channel The scheme created is able to account for the experimentally observed mutation-induced transformations between nonselective channels, sodium-selective channels, and calcium-selective channels, which we interpret as transitions between different rows of the identification table. By considering the potential energy changes during permeation, we show explicitly that the multi-ion conduction bands of calcium and sodium channels arise as the result of resonant barrierless conduction. The pattern of periodic conduction bands is explained on the basis of sequential neutralization taking account of self-energy, as Q(f)(z,i)=ze(1/2+i), where i is the order of the band and z is the valence of the ion. Our results confirm the crucial influence of electrostatic interactions on conduction and on the Ca(2+)/Na(+) valence selectivity of calcium and sodium ion channels. The model and results could be also applicable to biomimetic nanopores with charged walls.

Influence of the Selectivity Filter Properties on Proton Selectivity in the Influenza A M2 Channel.

PubMed

Dudev, Todor; Grauffel, Cédric; Lim, Carmay

2016-10-05

The homotetrameric M2 proton channel of influenza A plays a crucial role in the viral life cycle and is thus an important therapeutic target. It selectively conducts protons against a background of other competing cations whose concentrations are up to a million times greater than the proton concentration. Its selectivity is largely determined by a constricted region of its open pore known as the selectivity filter, which is lined by four absolutely conserved histidines. While the mechanism of proton transport through the channel has been studied, the physical principles underlying the selectivity for protons over other cations in the channel's His 4 selectivity filter remain elusive. Furthermore, it is not known if proton selectivity absolutely requires all four histidines with two of the four histidines protonated and if other titratable amino acid residues in lieu of the histidines could bind protons and how they affect proton selectivity. Here, we elucidate how the competition between protons and rival cations such as Na + depends on the selectivity filter's (1) histidine protonation state, (2) solvent exposure, (3) oligomeric state (the number of protein chains and thus the number of His ligands), and (4) ligand composition by evaluating the free energies for replacing monovalent Na + with H 3 O + in various model selectivity filters. We show that tetrameric His 4 filters are more proton-selective than their trimeric His 3 counterparts, and a dicationic His 4 filter where two of the four histidines are protonated is more proton-selective than tetrameric filters with other charge states/composition (different combinations of His protonation states or different metal-ligating ligands). The [His 4 ] 2+ filter achieves proton selectivity by providing suboptimal binding conditions for rival cations such as Na + , which prefers a neutral or negatively charged filter instead of a dicationic one, and three rather than four ligands with oxygen-ligating atoms.

A new Infrared Atmospheric Sounding Interferometer channel selection and assessment of its impact on Met Office NWP forecasts

NASA Astrophysics Data System (ADS)

Noh, Young-Chan; Sohn, Byung-Ju; Kim, Yoonjae; Joo, Sangwon; Bell, William; Saunders, Roger

2017-11-01

A new set of Infrared Atmospheric Sounding Interferometer (IASI) channels was re-selected from 314 EUMETSAT channels. In selecting channels, we calculated the impact of the individually added channel on the improvement in the analysis outputs from a one-dimensional variational analysis (1D-Var) for the Unified Model (UM) data assimilation system at the Met Office, using the channel score index (CSI) as a figure of merit. Then, 200 channels were selected in order by counting each individual channel's CSI contribution. Compared with the operationally used 183 channels for the UM at the Met Office, the new set shares 149 channels, while the other 51 channels are new. Also examined is the selection from the entropy reduction method with the same 1D-Var approach. Results suggest that channel selection can be made in a more objective fashion using the proposed CSI method. This is because the most important channels can be selected across the whole IASI observation spectrum. In the experimental trial runs using the UM global assimilation system, the new channels had an overall neutral impact in terms of improvement in forecasts, as compared with results from the operational channels. However, upper-tropospheric moist biases shown in the control run with operational channels were significantly reduced in the experimental trial with the newly selected channels. The reduction of moist biases was mainly due to the additional water vapor channels, which are sensitive to the upper-tropospheric water vapor.

Nonparametric methods for doubly robust estimation of continuous treatment effects.

PubMed

Kennedy, Edward H; Ma, Zongming; McHugh, Matthew D; Small, Dylan S

2017-09-01

Continuous treatments (e.g., doses) arise often in practice, but many available causal effect estimators are limited by either requiring parametric models for the effect curve, or by not allowing doubly robust covariate adjustment. We develop a novel kernel smoothing approach that requires only mild smoothness assumptions on the effect curve, and still allows for misspecification of either the treatment density or outcome regression. We derive asymptotic properties and give a procedure for data-driven bandwidth selection. The methods are illustrated via simulation and in a study of the effect of nurse staffing on hospital readmissions penalties.

Signatures of doubly-charged Higgsinos at colliders

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

Demir, D. A.; Deutsches Elektronen-Synchrotron, DESY, D-22603 Hamburg; Frank, M.

2008-11-23

Several supersymmetric models with extended gauge structures predict light doubly-charged Higgsinos. Their distinctive signature at the large hadron collider is highlighted by studying its production and decay characteristics.

Doubly charged coronene clusters—Much smaller than previously observed

NASA Astrophysics Data System (ADS)

Mahmoodi-Darian, Masoomeh; Raggl, Stefan; Renzler, Michael; Goulart, Marcelo; Huber, Stefan E.; Mauracher, Andreas; Scheier, Paul; Echt, Olof

2018-05-01

The smallest doubly charged coronene cluster ions reported so far, Cor152+, were produced by charge exchange between bare coronene clusters and He2+ [H. A. B. Johansson et al., Phys. Rev. A 84, 043201 (2011)]. These dications are at least five times larger than the estimated Rayleigh limit, i.e., the size at which the activation barrier for charge separation vanishes. Such a large discrepancy is unheard of for doubly charged atomic or molecular clusters. Here we report the mass spectrometric observation of doubly charged coronene trimers, produced by electron ionization of helium nanodroplets doped with coronene. The observation implies that Cor32+ features a non-zero fission barrier too large to overcome under the present experimental conditions. The height of the barriers for the dimer and trimer has been estimated by means of density functional theory calculations. A sizeable barrier for the trimer has been revealed in agreement with the experimental findings.

Modulation of mechanosensitive calcium-selective cation channels by temperature

NASA Technical Reports Server (NTRS)

Ding, J. P.; Pickard, B. G.

1993-01-01

Gating of associations of mechanosensitive Ca(2+)-selective cation co-channels in the plasmalemma of onion epidermis has a strong and unusual temperature dependence. Tension-dependent activity rises steeply as temperature is lowered from 25 degrees C to about 6 degrees C, but drops to a low level at about 5 degrees C. Under the conditions tested (with Mg2+ and K+ at the cytosolic face of outside-out membrane patches), promotion results both from more bursting at all observed linkage levels and from longer duration of bursts of co-channels linked as quadruplets and quintuplets. Co-channel conductance decreases linearly, but only modestly, with declining temperature. It is proposed that these and related mechanosensitive channels may participate in a variety of responses to temperature, including thermonasty, thermotropism, hydrotropism, and both cold damage and cold acclimation.

The regulation of transient receptor potential canonical 4 (TRPC4) channel by phosphodiesterase 5 inhibitor via the cyclic guanosine 3'5'-monophosphate.

PubMed

Wie, Jinhong; Jeong, SeungJoo; Kwak, Misun; Myeong, Jongyun; Chae, MeeRee; Park, Jong Kwan; Lee, Sung Won; So, Insuk

2017-06-01

The transient receptor potential (TRP) protein superfamily consists of a diverse group of cation channels that bear structural similarities to the fruit fly Drosophila TRP. The TRP superfamily is distinct from other groups of ion channels in displaying a large diversity in ion selectivity, modes of activation, and physiological functions. Classical TRP (transient receptor potential canonical (TRPC)) channels are activated by stimulation of Gq-PLC-coupled receptors and modulated by phosphorylation. The cyclic guanosine monophosphate (cGMP)-PKG pathway is involved in the regulation of TRPC3 and TRPC6 channels. Phosphodiesterase (PDE) 5 inhibitor induced muscle relaxation in corporal smooth muscle cells and was used to treat erectile dysfunction by inhibiting cGMP degradation. Here, we report the functional relationship between TRPC4 and cGMP. In human embryonic kidney (HEK) 293 cells overexpressing TRPC4, cGMP selectively activated TRPC4 channels and increased cytosolic calcium level through TRPC4 channel. We investigated phosphorylation sites in TRPC4 channels and identified S688 as an important phosphorylation site for the cGMP-PKG pathway. Cyclic GMP also activated TRPC4-like current with doubly rectifying current-voltage relationship in prostate smooth muscle cell lines. Taken together, these results show that TRPC4 is phosphorylated by the cGMP-PKG pathway and might be an important target for modulating prostate function by PDE5 inhibitors.

Implications of heavy quark-diquark symmetry for excited doubly heavy baryons and tetraquarks

NASA Astrophysics Data System (ADS)

Mehen, Thomas

2017-11-01

We give heavy quark-diquark symmetry predictions for doubly heavy baryons and tetraquarks in light of the recent discovery of the Ξcc ++ by LHCb. For five excited doubly charm baryons that are predicted to lie below the ΛcD threshold, we give predictions for their electromagnetic and strong decays using a previously developed chiral Lagrangian with heavy quark-diquark symmetry. Based on the mass of the Ξcc ++, the existence of a doubly heavy bottom I =0 tetraquark that is stable to strong and electromagnetic decays has been predicted. If the mass of this state is below 10405 MeV, as predicted in some models, we argue using heavy quark-diquark symmetry that the JP=1+ I =1 doubly bottom tetraquark state will lie just below the open bottom threshold and likely be a narrow state as well. In this scenario, we compute strong decay width for this state using a new Lagrangian for doubly heavy tetraquarks which is related to the singly heavy baryon Lagrangian by heavy quark-diquark symmetry.

Cation Selectivity in Biological Cation Channels Using Experimental Structural Information and Statistical Mechanical Simulation.

PubMed

Finnerty, Justin John; Peyser, Alexander; Carloni, Paolo

2015-01-01

Cation selective channels constitute the gate for ion currents through the cell membrane. Here we present an improved statistical mechanical model based on atomistic structural information, cation hydration state and without tuned parameters that reproduces the selectivity of biological Na+ and Ca2+ ion channels. The importance of the inclusion of step-wise cation hydration in these results confirms the essential role partial dehydration plays in the bacterial Na+ channels. The model, proven reliable against experimental data, could be straightforwardly used for designing Na+ and Ca2+ selective nanopores.

Cation Selectivity in Biological Cation Channels Using Experimental Structural Information and Statistical Mechanical Simulation

PubMed Central

Finnerty, Justin John

2015-01-01

Cation selective channels constitute the gate for ion currents through the cell membrane. Here we present an improved statistical mechanical model based on atomistic structural information, cation hydration state and without tuned parameters that reproduces the selectivity of biological Na+ and Ca2+ ion channels. The importance of the inclusion of step-wise cation hydration in these results confirms the essential role partial dehydration plays in the bacterial Na+ channels. The model, proven reliable against experimental data, could be straightforwardly used for designing Na+ and Ca2+ selective nanopores. PMID:26460827

Ion Selectivity Mechanism in a Bacterial Pentameric Ligand-Gated Ion Channel

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

Fritsch, Sebastian; Ivanov, Ivaylo; Wang, Hailong

2010-01-01

The proton-gated ion channel from Gloeobacter violaceus (GLIC) is a prokaryotic homolog of the eukaryotic nicotinic acetylcholine receptor that responds to the binding of neurotransmitter acetylcholine and mediates fast signal transmission. Recent emergence of a high-resolution crystal structure of GLIC captured in a potentially open state allowed detailed, atomic-level insight into ion conduction and selectivity mechanisms in these channels. Herein, we have examined the barriers to ion conduction and origins of ion selectivity in the GLIC channel by the construction of potential-of-mean-force profiles for sodium and chloride ions inside the transmembrane region. Our calculations reveal that the GLIC channel ismore » open for a sodium ion to transport, but presents a 11 kcal/mol free energy barrier for a chloride ion. Our collective findings identify three distinct contributions to the observed preference for the permeant ions. First, there is a substantial contribution due to a ring of negatively charged glutamate residues (E-2 ) at the narrow intracellular end of the channel. The negative electrostatics of this region and the ability of the glutamate side chains to directly bind cations would strongly favor the passage of sodium ions while hindering translocation of chloride ions. Second, our results imply a significant hydrophobic contribution to selectivity linked to differences in the desolvation penalty for the sodium versus chloride ions in the central hydrophobic region of the pore. This hydrophobic contribution is evidenced by the large free energy barriers experienced by Cl in the middle of the pore for both GLIC and the E-2 A mutant. Finally, there is a distinct contribution arising from the overall negative electrostatics of the channel.« less

Structural plasticity and dynamic selectivity of acid-sensing ion channel-spider toxin complexes

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

Baconguis, Isabelle; Gouaux, Eric

2012-07-29

Acid-sensing ion channels (ASICs) are voltage-independent, amiloride-sensitive channels involved in diverse physiological processes ranging from nociception to taste. Despite the importance of ASICs in physiology, we know little about the mechanism of channel activation. Here we show that psalmotoxin activates non-selective and Na +-selective currents in chicken ASIC1a at pH7.25 and 5.5, respectively. Crystal structures of ASIC1a–psalmotoxin complexes map the toxin binding site to the extracellular domain and show how toxin binding triggers an expansion of the extracellular vestibule and stabilization of the open channel pore. At pH7.25 the pore is approximately 10Å in diameter, whereas at pH5.5 the poremore » is largely hydrophobic and elliptical in cross-section with dimensions of approximately 5 by 7Å, consistent with a barrier mechanism for ion selectivity. These studies define mechanisms for activation of ASICs, illuminate the basis for dynamic ion selectivity and provide the blueprints for new therapeutic agents.« less

Non-selective cation channels in plasma and vacuolar membranes and their contribution to K+ transport.

PubMed

Pottosin, Igor; Dobrovinskaya, Oxana

2014-05-15

Both in vacuolar and plasma membranes, in addition to truly K(+)-selective channels there is a variety of non-selective channels, which conduct K(+) and other ions with little preference. Many non-selective channels in the plasma membrane are active at depolarized potentials, thus, contributing to K(+) efflux rather than to K(+) uptake. They may play important roles in xylem loading or contribute to a K(+) leak, induced by salt or oxidative stress. Here, three currents, expressed in root cells, are considered: voltage-insensitive cation current, non-selective outwardly rectifying current, and low-selective conductance, activated by reactive oxygen species. The latter two do not only poorly discriminate between different cations (like K(+)vs Na(+)), but also conduct anions. Such solute channels may mediate massive electroneutral transport of salts and might be involved in osmotic adjustment or volume decrease, associated with cell death. In the tonoplast two major currents are mediated by SV (slow) and FV (fast) vacuolar channels, respectively, which are virtually impermeable for anions. SV channels conduct mono- and divalent cations indiscriminately and are activated by high cytosolic Ca(2+) and depolarized voltages. FV channels are inhibited by micromolar cytosolic Ca(2+), Mg(2+), and polyamines, and conduct a variety of monovalent cations, including K(+). Strikingly, both SV and FV channels sense the K(+) content of vacuoles, which modulates their voltage dependence, and in case of SV, also alleviates channel's inhibition by luminal Ca(2+). Therefore, SV and FV channels may operate as K(+)-sensing valves, controlling K(+) distribution between the vacuole and the cytosol. Copyright © 2014 Elsevier GmbH. All rights reserved.

Selectivity Mechanism of the Voltage-gated Proton Channel, HV1

NASA Astrophysics Data System (ADS)

Dudev, Todor; Musset, Boris; Morgan, Deri; Cherny, Vladimir V.; Smith, Susan M. E.; Mazmanian, Karine; Decoursey, Thomas E.; Lim, Carmay

2015-05-01

Voltage-gated proton channels, HV1, trigger bioluminescence in dinoflagellates, enable calcification in coccolithophores, and play multifarious roles in human health. Because the proton concentration is minuscule, exquisite selectivity for protons over other ions is critical to HV1 function. The selectivity of the open HV1 channel requires an aspartate near an arginine in the selectivity filter (SF), a narrow region that dictates proton selectivity, but the mechanism of proton selectivity is unknown. Here we use a reduced quantum model to elucidate how the Asp-Arg SF selects protons but excludes other ions. Attached to a ring scaffold, the Asp and Arg side chains formed bidentate hydrogen bonds that occlude the pore. Introducing H3O+ protonated the SF, breaking the Asp-Arg linkage and opening the conduction pathway, whereas Na+ or Cl- was trapped by the SF residue of opposite charge, leaving the linkage intact, thus preventing permeation. An Asp-Lys SF behaved like the Asp-Arg one and was experimentally verified to be proton-selective, as predicted. Hence, interacting acidic and basic residues form favorable AspH0-H2O0-Arg+ interactions with hydronium but unfavorable Asp--X-/X+-Arg+ interactions with anions/cations. This proposed mechanism may apply to other proton-selective molecules engaged in bioenergetics, homeostasis, and signaling.

Nuclear spectroscopy of doubly-even130,132Ba

NASA Astrophysics Data System (ADS)

Gupta, Anuradha; Gupta, Surbhi; Singh, Suram; Bharti, Arun

2018-05-01

A comparative study of some high-spin characteristic nuclear structure properties of doubly-even 130,132Ba nuclei has been made using two microscopic frameworks - CHFB and PSM. The yrast spectra, intrinsic quadrupole moment and deformation systematics of these nuclei have been successfully calculated. Further, the calculated data from both the frameworks is also compared with the available experimental data and a good agreement has been obtained. The present CHFB calculations describes very well the low spin structure of even-even 130,132Ba nuclei whereas PSM calculations provide a qualitative description of the high-spin band structure of doubly-even 130,132Ba nuclei.

Channel and feature selection in multifunction myoelectric control.

PubMed

Khushaba, Rami N; Al-Jumaily, Adel

2007-01-01

Real time controlling devices based on myoelectric singles (MES) is one of the challenging research problems. This paper presents a new approach to reduce the computational cost of real time systems driven by Myoelectric signals (MES) (a.k.a Electromyography--EMG). The new approach evaluates the significance of feature/channel selection on MES pattern recognition. Particle Swarm Optimization (PSO), an evolutionary computational technique, is employed to search the feature/channel space for important subsets. These important subsets will be evaluated using a multilayer perceptron trained with back propagation neural network (BPNN). Practical results acquired from tests done on six subjects' datasets of MES signals measured in a noninvasive manner using surface electrodes are presented. It is proved that minimum error rates can be achieved by considering the correct combination of features/channels, thus providing a feasible system for practical implementation purpose for rehabilitation of patients.

Quantifying the causal effects of 20mph zones on road casualties in London via doubly robust estimation.

PubMed

Li, Haojie; Graham, Daniel J

2016-08-01

This paper estimates the causal effect of 20mph zones on road casualties in London. Potential confounders in the key relationship of interest are included within outcome regression and propensity score models, and the models are then combined to form a doubly robust estimator. A total of 234 treated zones and 2844 potential control zones are included in the data sample. The propensity score model is used to select a viable control group which has common support in the covariate distributions. We compare the doubly robust estimates with those obtained using three other methods: inverse probability weighting, regression adjustment, and propensity score matching. The results indicate that 20mph zones have had a significant causal impact on road casualty reduction in both absolute and proportional terms. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of doubly labeled water with respirometry at low- and high-activity levels

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

Westerterp, K.R.; Brouns, F.; Saris, W.H.

1988-07-01

In previous studies the doubly labeled water method for measuring energy expenditure in free-living humans has been validated against respirometry under sedentary conditions. In the present investigation, energy expenditure is measured simultaneously with doubly labeled water and respirometry at low- and high-activity levels. Over 6 days, five subjects were measured doing mainly sedentary activities like desk work; their average daily metabolic rate was 1.40 +/- 0.09 (SD) times sleeping metabolic rate. Four subjects were measured twice over 3.5 days, including 2 days with heavy bicycle ergometer work, resulting in an average daily metabolic rate of 2.61 +/- 0.25 (SD) timesmore » sleeping metabolic rate. At the low-activity level, energy expenditures from the doubly labeled water method were on the average 1.4 +/- 3.9% (SD) larger than those from respirometry. At the high-activity level, the doubly labeled water method yielded values that were 1.0 +/- 7.0% (SD) lower than those from respirometry. Results demonstrate the utility of the doubly labeled water method for the determination of energy expenditure in the range of activity levels in daily life.« less

Mechanosensory calcium-selective cation channels in epidermal cells

NASA Technical Reports Server (NTRS)

Ding, J. P.; Pickard, B. G.

1993-01-01

This paper explores the properties and likely functions of an epidermal Ca(2+)-selective cation channel complex activated by tension. As many as eight or nine linked or linkable equivalent conductance units or co-channels can open together. Open time for co-channel quadruplets and quintuplets tends to be relatively long with millimolar Mg2+ (but not millimolar Ca2+) at the cytosolic face of excised plasma membrane. Sensitivity to tension is regulated by transmembrane voltage and temperature. Under some circumstances channel activity is sychronized in rhythmic pulses. Certain lanthanides and a cytoskeleton-disturbing herbicide that inhibit gravitropic reception act on the channel system at low concentrations. Specifically, ethyl-N-phenylcarbamate promotes tension-dependent activity at micromolar levels. With moderate suction, Gd3+ provided at about 0.5 micromole at the extracellular face of the membrane promotes for several seconds but may then become inhibitory. Provision at 1-2 micromoles promotes and subsequently inhibits more vigorously (often abruptly and totally), and at high levels inhibits immediately. La3+, a poor gravitropic inhibitor, acts similarly but much more gradually and only at much higher concentrations. These properties, particularly these susceptibilities to modulation, indicate that in vivo the mechanosensitive channel must be mechanosensory and mechanoregulatory. It could serve to transduce the shear forces generated in the integrated wall-membrane-cytoskeleton system during turgor changes and cell expansion as well as transducing the stresses induced by gravity, touch and flexure. In so far as such transduction is modulated by voltage and temperature, the channels would also be sensors for these modalities as long as the wall-membrane-cytoskeleton system experiences mechanical stress.

Voltage-Gated Potassium Channels: A Structural Examination of Selectivity and Gating

PubMed Central

Kim, Dorothy M.; Nimigean, Crina M.

2016-01-01

Voltage-gated potassium channels play a fundamental role in the generation and propagation of the action potential. The discovery of these channels began with predictions made by early pioneers, and has culminated in their extensive functional and structural characterization by electrophysiological, spectroscopic, and crystallographic studies. With the aid of a variety of crystal structures of these channels, a highly detailed picture emerges of how the voltage-sensing domain reports changes in the membrane electric field and couples this to conformational changes in the activation gate. In addition, high-resolution structural and functional studies of K+ channel pores, such as KcsA and MthK, offer a comprehensive picture on how selectivity is achieved in K+ channels. Here, we illustrate the remarkable features of voltage-gated potassium channels and explain the mechanisms used by these machines with experimental data. PMID:27141052

X-ray structure of acid-sensing ion channel 1-snake toxin complex reveals open state of a Na(+)-selective channel.

PubMed

Baconguis, Isabelle; Bohlen, Christopher J; Goehring, April; Julius, David; Gouaux, Eric

2014-02-13

Acid-sensing ion channels (ASICs) detect extracellular protons produced during inflammation or ischemic injury and belong to the superfamily of degenerin/epithelial sodium channels. Here, we determine the cocrystal structure of chicken ASIC1a with MitTx, a pain-inducing toxin from the Texas coral snake, to define the structure of the open state of ASIC1a. In the MitTx-bound open state and in the previously determined low-pH desensitized state, TM2 is a discontinuous α helix in which the Gly-Ala-Ser selectivity filter adopts an extended, belt-like conformation, swapping the cytoplasmic one-third of TM2 with an adjacent subunit. Gly 443 residues of the selectivity filter provide a ring of three carbonyl oxygen atoms with a radius of ∼3.6 Å, presenting an energetic barrier for hydrated ions. The ASIC1a-MitTx complex illuminates the mechanism of MitTx action, defines the structure of the selectivity filter of voltage-independent, sodium-selective ion channels, and captures the open state of an ASIC. Copyright © 2014 Elsevier Inc. All rights reserved.

Measurement of Doubly Charged Ions in Ion Thruster Plumes

NASA Technical Reports Server (NTRS)

Williams, George J., Jr.; Domonkos, Matthew T.; Chavez, Joy M.

2002-01-01

The ratio of doubly to singly charged ions was measured in the plumes of a 30 cm and of a 40 cm ion thruster. The measured ratio was correlated with observed erosion rates and thruster operating conditions. The measured and calculated erosion rates paralleled variation in the j(sup ++)/j(sup +) ratio and indicated that the erosion was dominated by Xe III. Simple models of cathode potential surfaces which were developed in support of this work were in agreement with this conclusion and provided a predictive capability of the erosion given the ratio of doubly to singly charged ion currents.

Selectivity filters and cysteine-rich extracellular loops in voltage-gated sodium, calcium, and NALCN channels

PubMed Central

Stephens, Robert F.; Guan, W.; Zhorov, Boris S.; Spafford, J. David

2015-01-01

How nature discriminates sodium from calcium ions in eukaryotic channels has been difficult to resolve because they contain four homologous, but markedly different repeat domains. We glean clues from analyzing the changing pore region in sodium, calcium and NALCN channels, from single-cell eukaryotes to mammals. Alternative splicing in invertebrate homologs provides insights into different structural features underlying calcium and sodium selectivity. NALCN generates alternative ion selectivity with splicing that changes the high field strength (HFS) site at the narrowest level of the hourglass shaped pore where the selectivity filter is located. Alternative splicing creates NALCN isoforms, in which the HFS site has a ring of glutamates contributed by all four repeat domains (EEEE), or three glutamates and a lysine residue in the third (EEKE) or second (EKEE) position. Alternative splicing provides sodium and/or calcium selectivity in T-type channels with extracellular loops between S5 and P-helices (S5P) of different lengths that contain three or five cysteines. All eukaryotic channels have a set of eight core cysteines in extracellular regions, but the T-type channels have an infusion of 4–12 extra cysteines in extracellular regions. The pattern of conservation suggests a possible pairing of long loops in Domains I and III, which are bridged with core cysteines in NALCN, Cav, and Nav channels, and pairing of shorter loops in Domains II and IV in T-type channel through disulfide bonds involving T-type specific cysteines. Extracellular turrets of increasing lengths in potassium channels (Kir2.2, hERG, and K2P1) contribute to a changing landscape above the pore selectivity filter that can limit drug access and serve as an ion pre-filter before ions reach the pore selectivity filter below. Pairing of extended loops likely contributes to the large extracellular appendage as seen in single particle electron cryo-microscopy images of the eel Nav1 channel. PMID

Distinct regions that control ion selectivity and calcium-dependent activation in the bestrophin ion channel.

PubMed

Vaisey, George; Miller, Alexandria N; Long, Stephen B

2016-11-22

Cytoplasmic calcium (Ca 2+ ) activates the bestrophin anion channel, allowing chloride ions to flow down their electrochemical gradient. Mutations in bestrophin 1 (BEST1) cause macular degenerative disorders. Previously, we determined an X-ray structure of chicken BEST1 that revealed the architecture of the channel. Here, we present electrophysiological studies of purified wild-type and mutant BEST1 channels and an X-ray structure of a Ca 2+ -independent mutant. From these experiments, we identify regions of BEST1 responsible for Ca 2+ activation and ion selectivity. A "Ca 2+ clasp" within the channel's intracellular region acts as a sensor of cytoplasmic Ca 2+ . Alanine substitutions within a hydrophobic "neck" of the pore, which widen it, cause the channel to be constitutively active, irrespective of Ca 2+ . We conclude that the primary function of the neck is as a "gate" that controls chloride permeation in a Ca 2+ -dependent manner. In contrast to what others have proposed, we find that the neck is not a major contributor to the channel's ion selectivity. We find that mutation of a cytosolic "aperture" of the pore does not perturb the Ca 2+ dependence of the channel or its preference for anions over cations, but its mutation dramatically alters relative permeabilities among anions. The data suggest that the aperture functions as a size-selective filter that permits the passage of small entities such as partially dehydrated chloride ions while excluding larger molecules such as amino acids. Thus, unlike ion channels that have a single "selectivity filter," in bestrophin, distinct regions of the pore govern anion-vs.-cation selectivity and the relative permeabilities among anions.

Ion Selectivity Mechanism in a Bacterial Pentameric Ligand-Gated Ion Channel

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

Fritsch, Sebastian M; Ivanov, Ivaylo N; Wang, Hailong

2011-01-01

The proton-gated ion channel from Gloeobacter violaceus (GLIC) is a prokaryotic homolog of the eukaryotic nicotinic acetylcholine receptor (nAChR) that responds to the binding of neurotransmitter acetylcholine and mediates fast signal transmission. Recent emergence of a high resolution crystal structure of GLIC captured in a potentially open state allowed detailed, atomic-level insight into ion conduction and selectivity mechanisms in these channels. Herein, we have examined the barriers to ion conduction and origins of ion selectivity in the GLIC channel by the construction of potential of mean force (PMF) profiles for sodium and chloride ions inside the transmembrane region. Our calculationsmore » reveal that the GLIC channel is open for a sodium ion to transport, but presents a ~10 kcal/mol free energy barrier for a chloride ion, which arises primarily from the unfavorable interactions with a ring of negatively charged glutamate residues (E-2 ) at the intracellular end and a ring of hydrophobic residues (I9 ) in the middle of the transmembrane domain. Our collective findings further suggest that the charge selection mechanism can, to a large extent, be attributed to the narrow intracellular end and a ring of glutamate residues in this position their strong negative electrostatics and ability to bind cations. By contrast, E19 at the extracellular entrance only plays a minor role in ion selectivity of GLIC. In addition to electrostatics, both ion hydration and protein dynamics are found to be crucial for ion conduction as well, which explains why a chloride ion experiences a much greater barrier than a sodium ion in the hydrophobic region of the pore.« less

Electrode channel selection based on backtracking search optimization in motor imagery brain-computer interfaces.

PubMed

Dai, Shengfa; Wei, Qingguo

2017-01-01

Common spatial pattern algorithm is widely used to estimate spatial filters in motor imagery based brain-computer interfaces. However, use of a large number of channels will make common spatial pattern tend to over-fitting and the classification of electroencephalographic signals time-consuming. To overcome these problems, it is necessary to choose an optimal subset of the whole channels to save computational time and improve the classification accuracy. In this paper, a novel method named backtracking search optimization algorithm is proposed to automatically select the optimal channel set for common spatial pattern. Each individual in the population is a N-dimensional vector, with each component representing one channel. A population of binary codes generate randomly in the beginning, and then channels are selected according to the evolution of these codes. The number and positions of 1's in the code denote the number and positions of chosen channels. The objective function of backtracking search optimization algorithm is defined as the combination of classification error rate and relative number of channels. Experimental results suggest that higher classification accuracy can be achieved with much fewer channels compared to standard common spatial pattern with whole channels.

Doubly Selective Multiple Quantum Chemical Shift Imaging and T1 Relaxation Time Measurement of Glutathione (GSH) in the Human Brain In Vivo

PubMed Central

Choi, In-Young; Lee, Phil

2012-01-01

Mapping of a major antioxidant, glutathione (GSH), was achieved in the human brain in vivo using a doubly selective multiple quantum filtering based chemical shift imaging (CSI) of GSH at 3 T. Both in vivo and phantom tests in CSI and single voxel measurements were consistent with excellent suppression of overlapping signals from creatine, γ-Amino butyric acid (GABA) and macromolecules. The GSH concentration in the fronto-parietal region was 1.20 ± 0.16 µmol/g (mean ± SD, n = 7). The longitudinal relaxation time (T1) of GSH in the human brain was 397 ± 44 ms (mean ± SD, n = 5), which was substantially shorter than those of other metabolites. This GSH CSI method permits us to address regional differences of GSH in the human brain with conditions where oxidative stress has been implicated, including multiple sclerosis, aging and neurodegenerative diseases. PMID:22730142

Surgery for doubly committed ventricular septal defects.

PubMed

Shamsuddin, Ahmad Mahir; Chen, Yen Chuan; Wong, Abdul Rahim; Le, Trong-Phi; Anderson, Robert H; Corno, Antonio F

2016-08-01

Doubly committed ventricular septal defects (VSDs) account for up to almost one-third of isolated ventricular septal defects in Asian countries, compared with only 1/20th in western populations. In our surgical experience, this type of defect accounted for almost three-quarters of our practice. To date, patch closure has been considered the gold standard for surgical treatment of these lesions. Our objectives are to evaluate the indications and examine the outcomes of surgery for doubly committed VSDs. Between October 2013, when our service of paediatric cardiac surgery was opened, and December 2014, 24 patients were referred for surgical closure of VSDs. Among them, 17 patients (71%), with the median age of 6 years, ranging from 2 to 9 years, and with a median body weight of 19 kg, ranging from 11 to 56 kg, underwent surgical repair for doubly committed defects. In terms of size, the defect was considered moderate in 4 and large in 13. Aortic valvular regurgitation (AoVR) was present in 11 patients (65%) preoperatively, with associated malformations found in 14 (82%), with 5 patients (29%) having two or more associated defects. After surgery, there was trivial residual shunting in 2 patients (12%). AoVR persisted in 6 (35%), reducing to trivial in 5 (29%) and mild in 1 (6%). Mean stays in the intensive care unit and hospital were 2.6 ± 1.2 days, ranging from 2 to 7 days, and 6.8 ± 0.8 days, ranging from 6 to 9 days, respectively. The mean follow-up was 14 ± 4 months, ranging from 6 to 20 months, with no early or late deaths and without clinical deterioration. The incidence of doubly committed lesions is high in our experience, frequently associated with AoVR and other associated malformation. Early detection is crucial to prevent further progression of the disease. Patch closure remains the gold standard in management, not least since it allows simultaneous repair of associated intracardiac defects. © The Author 2016. Published by Oxford University Press on

Doubly stochastic Poisson processes in artificial neural learning.

PubMed

Card, H C

1998-01-01

This paper investigates neuron activation statistics in artificial neural networks employing stochastic arithmetic. It is shown that a doubly stochastic Poisson process is an appropriate model for the signals in these circuits.

Noseleaf pit in Egyptian slit-faced bat as a doubly curved reflector

NASA Astrophysics Data System (ADS)

Zhuang, Qiao; Wang, Xiao-Min; Li, Ming-Xuan; Mao, Jie; Wang, Fu-Xun

2012-02-01

Noseleaves in slit-faced bats have been hypothesized to affect the sonar beam. Using numerical methods, we show that the pit in the noseleaf of an Egyptian slit-faced bat has an effect on focusing the acoustic near field as well as shaping the radiation patterns and hence enhancing the directionality. The underlying physical mechanism suggested by the properties of the effect is that the pit acts as a doubly curved reflector. Thanks to the pit the beam shape is overall directional and more selectively widened at the high end of the biosonar frequency range to improve spatial coverage and detectability of targets.

Mechanism for phosphoinositide selectivity and activation of TRPV1 ion channels

PubMed Central

Ufret-Vincenty, Carmen A.; Klein, Rebecca M.; Collins, Marcus D.; Rosasco, Mario G.; Martinez, Gilbert Q.

2015-01-01

Although PI(4,5)P2 is believed to play an essential role in regulating the activity of numerous ion channels and transporters, the mechanisms by which it does so are unknown. Here, we used the ability of the TRPV1 ion channel to discriminate between PI(4,5)P2 and PI(4)P to localize the region of TRPV1 sequence that interacts directly with the phosphoinositide. We identified a point mutation in the proximal C-terminal region after the TRP box, R721A, that inverted the selectivity of TRPV1. Although the R721A mutation produced only a 30% increase in the EC50 for activation by PI(4,5)P2, it decreased the EC50 for activation by PI(4)P by more than two orders of magnitude. We used chemically induced and voltage-activated phosphatases to determine that PI(4)P continued to support TRPV1 activity even after depletion of PI(4,5)P2 from the plasma membrane. Our data cannot be explained by a purely electrostatic mechanism for interaction between the phosphoinositide and the protein, similar to that of the MARCKS (myristoylated alanine-rich C kinase substrate) effector domain or the EGF receptor. Rather, conversion of a PI(4,5)P2-selective channel to a PI(4)P-selective channel indicates that a structured phosphoinositide-binding site mediates the regulation of TRPV1 activity and that the amino acid at position 721 likely interacts directly with the moiety at the 5′ position of the phosphoinositide. PMID:25918361

Selectivity and permeation of alkali metal ions in K+-channels.

PubMed

Furini, Simone; Domene, Carmen

2011-06-24

Ion conduction in K(+)-channels is usually described in terms of concerted movements of K(+) progressing in a single file through a narrow pore. Permeation is driven by an incoming ion knocking on those ions already inside the protein. A fine-tuned balance between high-affinity binding and electrostatic repulsive forces between permeant ions is needed to achieve efficient conduction. While K(+)-channels are known to be highly selective for K(+) over Na(+), some K(+) channels conduct Na(+) in the absence of K(+). Other ions are known to permeate K(+)-channels with a more moderate preference and unusual conduction features. We describe an extensive computational study on ion conduction in K(+)-channels rendering free energy profiles for the translocation of three different alkali ions and some of their mixtures. The free energy maps for Rb(+) translocation show at atomic level why experimental Rb(+) conductance is slightly lower than that of K(+). In contrast to K(+) or Rb(+), external Na(+) block K(+) currents, and the sites where Na(+) transport is hindered are characterized. Translocation of K(+)/Na(+) mixtures is energetically unfavorable owing to the absence of equally spaced ion-binding sites for Na(+), excluding Na(+) from a channel already loaded with K(+). Copyright © 2011 Elsevier Ltd. All rights reserved.

The Doubly Labeled Water Method for Measuring Human Energy Expenditure: Adaptations for Spaceflight

NASA Technical Reports Server (NTRS)

Schulz, Leslie O.

1991-01-01

It is essential to determine human energy requirements in space, and the doubly labeled water method has been identified as the most appropriate means of indirect calorimetry to meet this need. The method employs naturally occurring, stable isotopes of hydrogen (H-2, deuterium) and oxygen (O-18) which, after dosing, mix with body water. The deuterium is lost from the body as water while the O-18 is eliminated as both water and CO2. The difference between the two isotope elimination rates is therefore a measure of CO2 production and hence energy expenditure. Spaceflight will present a unique challenge to the application of the doubly labeled water method. Specifically, interpretation of doubly labeled water results assumes that the natural abundance or 'background' levels of the isotopes remain constant during the measurement interval. To address this issue, an equilibration model will be developed in an ongoing ground-based study. As energy requirements of women matched to counterparts in the Astronauts Corps are being determined by doubly labeled water, the baseline isotope concentration will be changed by consumption of 'simulated Shuttle water' which is artificially enriched. One group of subjects will be equilibrated on simulated Shuttle water prior to energy determinations by doubly labeled water while the others will consume simulated Shuttle water after dosing. This process will allow us to derive a prediction equation to mathematically model the effect of changing background isotope concentrations.

Evoked potential correlates of selective attention with multi-channel auditory inputs

NASA Technical Reports Server (NTRS)

Schwent, V. L.; Hillyard, S. A.

1975-01-01

Ten subjects were presented with random, rapid sequences of four auditory tones which were separated in pitch and apparent spatial position. The N1 component of the auditory vertex evoked potential (EP) measured relative to a baseline was observed to increase with attention. It was concluded that the N1 enhancement reflects a finely tuned selective attention to one stimulus channel among several concurrent, competing channels. This EP enhancement probably increases with increased information load on the subject.

Aluminium and hydrogen ions inhibit a mechanosensory calcium-selective cation channel

NASA Technical Reports Server (NTRS)

Ding, J. P.; Pickard, B. G.

1993-01-01

The tension-dependent activity of mechanosensory calcium-selective cation channels in excised plasmalemmal patches from onion bulb scale epidermis is modulated by pH in the physiologically meaningful range between 4.5 and 7.2. It is rapidly lowered by lowering pH and rapidly raised by raising pH. Channel activity is effectively inhibited by low levels of aluminium ions and activity can be partially restored by washing for a few minutes. We suggest that under normal conditions the sensitivity of the mechanosensory channels to pH of the wall free space plays important roles in regulation of plant activities such as growth. We further suggest that, when levels of acid and aluminium ions in the soil solution are high, they might inhibit similar sensory channels in cells of the root tip, thus contributing critically to the acid soil syndrome.

Wavelet Packet Feature Assessment for High-Density Myoelectric Pattern Recognition and Channel Selection toward Stroke Rehabilitation.

PubMed

Wang, Dongqing; Zhang, Xu; Gao, Xiaoping; Chen, Xiang; Zhou, Ping

2016-01-01

This study presents wavelet packet feature assessment of neural control information in paretic upper limb muscles of stroke survivors for myoelectric pattern recognition, taking advantage of high-resolution time-frequency representations of surface electromyogram (EMG) signals. On this basis, a novel channel selection method was developed by combining the Fisher's class separability index and the sequential feedforward selection analyses, in order to determine a small number of appropriate EMG channels from original high-density EMG electrode array. The advantages of the wavelet packet features and the channel selection analyses were further illustrated by comparing with previous conventional approaches, in terms of classification performance when identifying 20 functional arm/hand movements implemented by 12 stroke survivors. This study offers a practical approach including paretic EMG feature extraction and channel selection that enables active myoelectric control of multiple degrees of freedom with paretic muscles. All these efforts will facilitate upper limb dexterity restoration and improved stroke rehabilitation.

Experimental and Theoretical Investigations of Doubly-excited Sextet States in

NASA Astrophysics Data System (ADS)

Lin, Bin; Berry, H. Gordon; Livingston, A. Eugene; Garnir, Henri-Pierre; Bastin, Thierry; Désesquelles, J.

2002-05-01

The energies and wave functions of the highly doubly-excited sextet states of boron-like O IV, F V and Ne VI are calculated with the Multi-Configuration Hartree-Fock (MCHF) plus the hydrogen-like QED effects and higher-order corrections method. The highly doubly-excited sextet states of boron-like O IV, F V and Ne VI are well above several ionization levels and metastable, and possible candidates for XUV- and soft x-ray laser and energy storage. Three doubly-excited sextet configurations (1s2s2p3 6So, 1s2s2p23s 6P and 1s2p33s 6So) are studied. The wavelengths of electric dipole transitions from the inner-shell excited terms 1s2s2p23s 6P-1s2p33s 6So are investigated by the beam-foil spectroscopy in the XUV spectral region. The predicted transition wavelengths agree with the experiment to 0.08Å. The higher-order corrections and fine structures are found to be critically important in these comparisons.

Centrifugal sedimentation for selectively packing channels with silica microbeads in three-dimensional micro/nanofluidic devices.

PubMed

Gong, Maojun; Bohn, Paul W; Sweedler, Jonathan V

2009-03-01

Incorporation of nanofluidic elements into microfluidic channels is one approach for adding filtration and partition functionality to planar microfluidic devices, as well as providing enhanced biomolecular separations. Here we introduce a strategy to pack microfluidic channels with silica nanoparticles and microbeads, thereby indirectly producing functional nanostructures; the method allows selected channels to be packed, here demonstrated so that a separation channel is packed while keeping an injection channel unpacked. A nanocapillary array membrane is integrated between two patterned microfluidic channels that cross each other in vertically separated layers. The membrane serves both as a frit for bead packing and as a fluid communication conduit between microfluidic channels. Centrifugal force-assisted sedimentation is then used to selectively pack the microfluidic channels using an aqueous silica bead suspension loaded into the appropriate inlet reservoirs. This packing approach may be used to simultaneously pack multiple channels with silica microbeads having different sizes and surface properties. The chip design and packing method introduced here are suitable for packing silica particles in sizes ranging from nanometers to micrometers and allow rapid (approximately 10 min) packing with high quality. The liquid/analyte transport characteristics of these packed micro/nanofluidic devices have potential utility in a wide range of applications, including electroosmotic pumping, liquid chromatographic separations, and electrochromatography.

Atrial-selective K+ channel blockers: potential antiarrhythmic drugs in atrial fibrillation?

PubMed

Ravens, Ursula

2017-11-01

In the wake of demographic change in Western countries, atrial fibrillation has reached an epidemiological scale, yet current strategies for drug treatment of the arrhythmia lack sufficient efficacy and safety. In search of novel medications, atrial-selective drugs that specifically target atrial over other cardiac functions have been developed. Here, I will address drugs acting on potassium (K + ) channels that are either predominantly expressed in atria or possess electrophysiological properties distinct in atria from ventricles. These channels include the ultra-rapidly activating, delayed outward-rectifying Kv1.5 channel conducting I Kur , the acetylcholine-activated inward-rectifying Kir3.1/Kir3.4 channel conducting I K,ACh , the Ca 2+ -activated K + channels of small conductance (SK) conducting I SK , and the two-pore domain K + (K2P) channels (tandem of P domains, weak inward-rectifying K + channels (TWIK-1), TWIK-related acid-sensitive K + channels (TASK-1 and TASK-3)) that are responsible for voltage-independent background currents I TWIK-1 , I TASK-1 , and I TASK-3 . Direct drug effects on these channels are described and their putative value in treatment of atrial fibrillation is discussed. Although many potential drug targets have emerged in the process of unravelling details of the pathophysiological mechanisms responsible for atrial fibrillation, we do not know whether novel antiarrhythmic drugs will be more successful when modulating many targets or a single specific one. The answer to this riddle can only be solved in a clinical context.

A mapping from the unitary to doubly stochastic matrices and symbols on a finite set

NASA Astrophysics Data System (ADS)

Karabegov, Alexander V.

2008-11-01

We prove that the mapping from the unitary to doubly stochastic matrices that maps a unitary matrix (ukl) to the doubly stochastic matrix (|ukl|2) is a submersion at a generic unitary matrix. The proof uses the framework of operator symbols on a finite set.

Locating the Anion-selectivity Filter of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Chloride Channel

PubMed Central

Cheung, Min; Akabas, Myles H.

1997-01-01

The cystic fibrosis transmembrane conductance regulator forms an anion-selective channel; the site and mechanism of charge selectivity is unknown. We previously reported that cysteines substituted, one at a time, for Ile331, Leu333, Arg334, Lys335, Phe337, Ser341, Ile344, Arg347, Thr351, Arg352, and Gln353, in and flanking the sixth membrane-spanning segment (M6), reacted with charged, sulfhydryl-specific, methanethiosulfonate (MTS) reagents. We inferred that these residues are on the water-accessible surface of the protein and may line the ion channel. We have now measured the voltage-dependence of the reaction rates of the MTS reagents with the accessible, engineered cysteines. By comparing the reaction rates of negatively and positively charged MTS reagents with these cysteines, we measured the extent of anion selectivity from the extracellular end of the channel to eight of the accessible residues. We show that the major site determining anion vs. cation selectivity is near the cytoplasmic end of the channel; it favors anions by ∼25-fold and may involve the residues Arg347 and Arg352. From the voltage dependence of the reaction rates, we calculated the electrical distance to the accessible residues. For the residues from Leu333 to Ser341 the electrical distance is not significantly different than zero; it is significantly different than zero for the residues Thr351 to Gln353. The maximum electrical distance measured was 0.6 suggesting that the channel extends more cytoplasmically and may include residues flanking the cytoplasmic end of the M6 segment. Furthermore, the electrical distance calculations indicate that R352C is closer to the extracellular end of the channel than either of the adjacent residues. We speculate that the cytoplasmic end of the M6 segment may loop back into the channel narrowing the lumen and thereby forming both the major resistance to current flow and the anion-selectivity filter. PMID:9089437

Evaluation of a doubly-swept blade tip for rotorcraft noise reduction

NASA Technical Reports Server (NTRS)

Wake, Brian E.; Egolf, T. Alan

1992-01-01

A computational study was performed for a doubly-swept rotor blade tip to determine its benefit for high-speed impulsive (HSI) and blade-vortex interaction (BVI) noise. This design consists of aft and forward sweep. For the HSI-noise computations, unsteady Euler calculations were performed for several variations to a rotor blade geometry. A doubly-swept planform was predicted to increase the delocalizing Mach number to 0.94 (representative of a 200+ kt helicopter). For the BVI-noise problem, it had been hypothesized that the doubly-swept blade tip, by producing a leading-edge vortex, would reduce the tip-vortex effect on BVI noise. A procedure was used in which the tip vortex velocity profile computed by a Navier-Stokes solver was used to compute the inflow associated with BVI. This inflow was used by a Euler solver to compute the unsteady pressures for an acoustic analysis. The results of this study were inconclusive due to the difficulty in accurately predicting the viscous tip vortex downstream of the blade. Also, for the condition studied, no leading-edge vortex formed at the tip.

Projective interpretation of some doubly special relativity theories

NASA Astrophysics Data System (ADS)

Jafari, N.; Shariati, A.

2011-09-01

A class of projective actions of the orthogonal group on the projective space is being studied. It is shown that the Fock-Lorentz and Magueijo-Smolin transformations known as doubly special relativity are such transformations. The formalism easily leads to new types of transformations.

Doubly labelled water assessment of energy expenditure: principle, practice, and promise.

PubMed

Westerterp, Klaas R

2017-07-01

The doubly labelled water method for the assessment of energy expenditure was first published in 1955, application in humans started in 1982, and it has become the gold standard for human energy requirement under daily living conditions. The method involves enriching the body water of a subject with heavy hydrogen ( 2 H) and heavy oxygen ( 18 O), and then determining the difference in washout kinetics between both isotopes, being a function of carbon dioxide production. In practice, subjects get a measured amount of doubly labelled water ( 2 H 2 18 O) to increase background enrichment of body water for 18 O of 2000 ppm with at least 180 ppm and background enrichment of body water for 2 H of 150 ppm with 120 ppm. Subsequently, the difference between the apparent turnover rates of the hydrogen and oxygen of body water is assessed from blood-, saliva-, or urine samples, collected at the start and end of the observation interval of 1-3 weeks. Samples are analyzed for 18 O and 2 H with isotope ratio mass spectrometry. The doubly labelled water method is the indicated method to measure energy expenditure in any environment, especially with regard to activity energy expenditure, without interference with the behavior of the subjects. Applications include the assessment of energy requirement from total energy expenditure, validation of dietary assessment methods and validation of physical activity assessment methods with doubly labelled water measured energy expenditure as reference, and studies on body mass regulation with energy expenditure as a determinant of energy balance.

Splitting Times of Doubly Quantized Vortices in Dilute Bose-Einstein Condensates

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

Huhtamaeki, J. A. M.; Pietilae, V.; Virtanen, S. M. M.

2006-09-15

Recently, the splitting of a topologically created doubly quantized vortex into two singly quantized vortices was experimentally investigated in dilute atomic cigar-shaped Bose-Einstein condensates [Y. Shin et al., Phys. Rev. Lett. 93, 160406 (2004)]. In particular, the dependency of the splitting time on the peak particle density was studied. We present results of theoretical simulations which closely mimic the experimental setup. We show that the combination of gravitational sag and time dependency of the trapping potential alone suffices to split the doubly quantized vortex in time scales which are in good agreement with the experiments.

Identification of Intracellular β-Barrel Residues Involved in Ion Selectivity in the Mechanosensitive Channel of Thermoanaerobacter tengcongensis

PubMed Central

Song, Yingcai; Zhang, Bing; Guo, Fei; Yang, Maojun; Li, Yang; Liu, Zhi-Qiang

2017-01-01

The mechanosensitive channel of small conductance (MscS) is a bacterial membrane pore that senses membrane tension and protects cells from lysis by releasing osmolytes. MscS is a homoheptameric channel with a cytoplasmic domain with seven portals and a β-barrel opening to the cytoplasm. TtMscS, an MscS channel from Thermoanaerobacter tengcongensis, is an anion-selective channel. A previous study from our laboratory has defined the crucial role of β-barrel in the anion selectivity of TtMscS (Zhang et al., 2012). However, the mechanistic details by which the β-barrel determines anion selectivity remain unclear. Here, using mutagenesis and patch-clamp recordings, we investigated the function and structural correlations between β-barrels and the anion selectivity of TtMscS at the atomic level. Our results indicated that mutation of V274, a residue at the center of the inner wall of the β-barrel in TtMscS, caused the anion selectivity of TtMscS reverse to cation selectivity. Moreover, the electrostatic potential (T272) and physical size (L276) of residues in the inner wall of β-barrel also determine the anion selectivity of TtMscS. In summary, the present study confirmed that the β-barrel region of TtMscS acts as a “selective filter” that renders TtMscS anion selectivity. PMID:29118717

Improved Doubly Robust Estimation when Data are Monotonely Coarsened, with Application to Longitudinal Studies with Dropout

PubMed Central

Tsiatis, Anastasios A.; Davidian, Marie; Cao, Weihua

2010-01-01

Summary A routine challenge is that of making inference on parameters in a statistical model of interest from longitudinal data subject to drop out, which are a special case of the more general setting of monotonely coarsened data. Considerable recent attention has focused on doubly robust estimators, which in this context involve positing models for both the missingness (more generally, coarsening) mechanism and aspects of the distribution of the full data, that have the appealing property of yielding consistent inferences if only one of these models is correctly specified. Doubly robust estimators have been criticized for potentially disastrous performance when both of these models are even only mildly misspecified. We propose a doubly robust estimator applicable in general monotone coarsening problems that achieves comparable or improved performance relative to existing doubly robust methods, which we demonstrate via simulation studies and by application to data from an AIDS clinical trial. PMID:20731640

Nonparametric Inference of Doubly Stochastic Poisson Process Data via the Kernel Method

PubMed Central

Zhang, Tingting; Kou, S. C.

2010-01-01

Doubly stochastic Poisson processes, also known as the Cox processes, frequently occur in various scientific fields. In this article, motivated primarily by analyzing Cox process data in biophysics, we propose a nonparametric kernel-based inference method. We conduct a detailed study, including an asymptotic analysis, of the proposed method, and provide guidelines for its practical use, introducing a fast and stable regression method for bandwidth selection. We apply our method to real photon arrival data from recent single-molecule biophysical experiments, investigating proteins' conformational dynamics. Our result shows that conformational fluctuation is widely present in protein systems, and that the fluctuation covers a broad range of time scales, highlighting the dynamic and complex nature of proteins' structure. PMID:21258615

Nonparametric Inference of Doubly Stochastic Poisson Process Data via the Kernel Method.

PubMed

Zhang, Tingting; Kou, S C

2010-01-01

Doubly stochastic Poisson processes, also known as the Cox processes, frequently occur in various scientific fields. In this article, motivated primarily by analyzing Cox process data in biophysics, we propose a nonparametric kernel-based inference method. We conduct a detailed study, including an asymptotic analysis, of the proposed method, and provide guidelines for its practical use, introducing a fast and stable regression method for bandwidth selection. We apply our method to real photon arrival data from recent single-molecule biophysical experiments, investigating proteins' conformational dynamics. Our result shows that conformational fluctuation is widely present in protein systems, and that the fluctuation covers a broad range of time scales, highlighting the dynamic and complex nature of proteins' structure.

Highly conducting and crystalline doubly doped tin oxide films fabricated using a low-cost and simplified spray technique

NASA Astrophysics Data System (ADS)

Ravichandran, K.; Muruganantham, G.; Sakthivel, B.

2009-11-01

Doubly doped (simultaneous doping of antimony and fluorine) tin oxide films (SnO 2:Sb:F) have been fabricated by employing an inexpensive and simplified spray technique using perfume atomizer from aqueous solution of SnCl 2 precursor. The structural studies revealed that the films are highly crystalline in nature with preferential orientation along the (2 0 0) plane. It is found that the size of the crystallites of the doubly doped tin oxide films is larger (69 nm) than that (27 nm) of their undoped counterparts. The dislocation density of the doubly doped film is lesser (2.08×10 14 lines/m 2) when compared with that of the undoped film (13.2×10 14 lines/m 2), indicating the higher degree of crystallinity of the doubly doped films. The SEM images depict that the films are homogeneous and uniform. The optical transmittance in the visible range and the optical band gap of the doubly doped films are 71% and 3.56 eV respectively. The sheet resistance (4.13 Ω/□) attained for the doubly doped film in this study is lower than the values reported for spray deposited fluorine or antimony doped tin oxide films prepared from aqueous solution of SnCl 2 precursor (without using methanol or ethanol).

Conformational plasticity in the selectivity filter of the TRPV2 ion channel.

PubMed

Zubcevic, Lejla; Le, Son; Yang, Huanghe; Lee, Seok-Yong

2018-05-01

Transient receptor potential vanilloid (TRPV) channels are activated by ligands and heat and are involved in various physiological processes. In contrast to the architecturally related voltage-gated cation channels, TRPV1 and TRPV2 subtypes possess another activation gate at the selectivity filter that can open widely enough to permeate large organic cations. Despite recent structural advances, the mechanism of selectivity filter gating and permeation for both metal ions and large molecules by TRPV1 or TRPV2 is not well known. Here, we determined two crystal structures of rabbit TRPV2 in its Ca 2+ -bound and resiniferatoxin (RTx)- and Ca 2+ -bound forms, to 3.9 Å and 3.1 Å, respectively. Notably, our structures show that RTx binding leads to two-fold symmetric opening of the selectivity filter of TRPV2 that is wide enough for large organic cation permeation. Combined with functional characterizations, our studies reveal a structural basis for permeation of Ca 2+ and large organic cations in TRPV2.

Ion Trapping with Fast-Response Ion-Selective Microelectrodes Enhances Detection of Extracellular Ion Channel Gradients

PubMed Central

Messerli, Mark A.; Collis, Leon P.; Smith, Peter J.S.

2009-01-01

Previously, functional mapping of channels has been achieved by measuring the passage of net charge and of specific ions with electrophysiological and intracellular fluorescence imaging techniques. However, functional mapping of ion channels using extracellular ion-selective microelectrodes has distinct advantages over the former methods. We have developed this method through measurement of extracellular K+ gradients caused by efflux through Ca2+-activated K+ channels expressed in Chinese hamster ovary cells. We report that electrodes constructed with short columns of a mechanically stable K+-selective liquid membrane respond quickly and measure changes in local [K+] consistent with a diffusion model. When used in close proximity to the plasma membrane (<4 μm), the ISMs pose a barrier to simple diffusion, creating an ion trap. The ion trap amplifies the local change in [K+] without dramatically changing the rise or fall time of the [K+] profile. Measurement of extracellular K+ gradients from activated rSlo channels shows that rapid events, 10–55 ms, can be characterized. This method provides a noninvasive means for functional mapping of channel location and density as well as for characterizing the properties of ion channels in the plasma membrane. PMID:19217875

Evolutionary insights into T-type Ca2+ channel structure, function, and ion selectivity from the Trichoplax adhaerens homologue

PubMed Central

Smith, Carolyn L.; Abdallah, Salsabil; Le, Phuong; Harracksingh, Alicia N.; Artinian, Liana; Tamvacakis, Arianna N.; Rehder, Vincent; Reese, Thomas S.

2017-01-01

Four-domain voltage-gated Ca2+ (Cav) channels play fundamental roles in the nervous system, but little is known about when or how their unique properties and cellular roles evolved. Of the three types of metazoan Cav channels, Cav1 (L-type), Cav2 (P/Q-, N- and R-type) and Cav3 (T-type), Cav3 channels are optimized for regulating cellular excitability because of their fast kinetics and low activation voltages. These same properties permit Cav3 channels to drive low-threshold exocytosis in select neurons and neurosecretory cells. Here, we characterize the single T-type calcium channel from Trichoplax adhaerens (TCav3), an early diverging animal that lacks muscle, neurons, and synapses. Co-immunolocalization using antibodies against TCav3 and neurosecretory cell marker complexin labeled gland cells, which are hypothesized to play roles in paracrine signaling. Cloning and in vitro expression of TCav3 reveals that, despite roughly 600 million years of divergence from other T-type channels, it bears the defining structural and biophysical features of the Cav3 family. We also characterize the channel’s cation permeation properties and find that its pore is less selective for Ca2+ over Na+ compared with the human homologue Cav3.1, yet it exhibits a similar potent block of inward Na+ current by low external Ca2+ concentrations (i.e., the Ca2+ block effect). A comparison of the permeability features of TCav3 with other cloned channels suggests that Ca2+ block is a locus of evolutionary change in T-type channel cation permeation properties and that mammalian channels distinguish themselves from invertebrate ones by bearing both stronger Ca2+ block and higher Ca2+ selectivity. TCav3 is the most divergent metazoan T-type calcium channel and thus provides an evolutionary perspective on Cav3 channel structure–function properties, ion selectivity, and cellular physiology. PMID:28330839

Search for doubly charged Higgs bosons in like-sign dilepton final states at √s¯= 7 TeV with the ATLAS detector

DOE PAGES

Aad, G.

2012-12-04

A search for doubly-charged Higgs bosons decaying to pairs of electrons and/or muons is presented. The search is performed using a data sample corresponding to an integrated luminosity of 4.7 fb -1 of pp collisions at √s¯ = 7 TeV collected by the ATLAS detector at the LHC. Pairs of prompt, isolated, high-p T leptons with the same electric charge (e ±e ±, e ±μ ±, μ ±μ ±) are selected, and their invariant mass distribution is searched for a narrow resonance. No significant excess over Standard Model background expectations is observed, and limits are placed on the cross sectionmore » times branching ratio for pair production of doubly-charged Higgs bosons. The masses of doubly-charged Higgs bosons are constrained depending on the branching ratio into these leptonic final states. Assuming pair production, coupling to left-handed fermions, and a branching ratio of 100% for each final state, masses below 409 GeV, 375 GeV, and 398 GeV are excluded for e ±e ±, e ±μ ±, and μ ±μ ±, respectively.« less

Use of doubly labeled water technique in soldiers training for jungle warfare

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

Forbes-Ewan, C.H.; Morrissey, B.L.; Gregg, G.C.

1989-07-01

The doubly labeled water method was used to estimate the energy expended by four members of an Australian Army platoon (34 soldiers) engaged in training for jungle warfare. Each subject received an oral isotope dose sufficient to raise isotope levels by 200-250 ({sup 18}O) and 100-120 ppm ({sup 2}H). The experimental period was 7 days. Concurrently, a factorial estimate of the energy expenditure of the platoon was conducted. Also, a food intake-energy balance study was conducted for the platoon. Mean daily energy expenditure by the doubly labeled water method was 4,750 kcal (range 4,152-5,394 kcal). The factorial estimate of meanmore » daily energy expenditure was 4,535 kcal. Because of inherent inaccuracies in the food intake-energy balance technique, we were able to conclude only that energy expenditure, as measured by this method, was greater than the estimated mean daily intake of 4,040 kcal. The doubly labeled water technique was well tolerated, is noninvasive, and appears to be suitable in a wide range of field applications.« less

AVHRR channel selection for land cover classification

USGS Publications Warehouse

Maxwell, S.K.; Hoffer, R.M.; Chapman, P.L.

2002-01-01

Mapping land cover of large regions often requires processing of satellite images collected from several time periods at many spectral wavelength channels. However, manipulating and processing large amounts of image data increases the complexity and time, and hence the cost, that it takes to produce a land cover map. Very few studies have evaluated the importance of individual Advanced Very High Resolution Radiometer (AVHRR) channels for discriminating cover types, especially the thermal channels (channels 3, 4 and 5). Studies rarely perform a multi-year analysis to determine the impact of inter-annual variability on the classification results. We evaluated 5 years of AVHRR data using combinations of the original AVHRR spectral channels (1-5) to determine which channels are most important for cover type discrimination, yet stabilize inter-annual variability. Particular attention was placed on the channels in the thermal portion of the spectrum. Fourteen cover types over the entire state of Colorado were evaluated using a supervised classification approach on all two-, three-, four- and five-channel combinations for seven AVHRR biweekly composite datasets covering the entire growing season for each of 5 years. Results show that all three of the major portions of the electromagnetic spectrum represented by the AVHRR sensor are required to discriminate cover types effectively and stabilize inter-annual variability. Of the two-channel combinations, channels 1 (red visible) and 2 (near-infrared) had, by far, the highest average overall accuracy (72.2%), yet the inter-annual classification accuracies were highly variable. Including a thermal channel (channel 4) significantly increased the average overall classification accuracy by 5.5% and stabilized interannual variability. Each of the thermal channels gave similar classification accuracies; however, because of the problems in consistently interpreting channel 3 data, either channel 4 or 5 was found to be a more

Low-Complexity User Selection for Rate Maximization in MIMO Broadcast Channels with Downlink Beamforming

PubMed Central

Silva, Adão; Gameiro, Atílio

2014-01-01

We present in this work a low-complexity algorithm to solve the sum rate maximization problem in multiuser MIMO broadcast channels with downlink beamforming. Our approach decouples the user selection problem from the resource allocation problem and its main goal is to create a set of quasiorthogonal users. The proposed algorithm exploits physical metrics of the wireless channels that can be easily computed in such a way that a null space projection power can be approximated efficiently. Based on the derived metrics we present a mathematical model that describes the dynamics of the user selection process which renders the user selection problem into an integer linear program. Numerical results show that our approach is highly efficient to form groups of quasiorthogonal users when compared to previously proposed algorithms in the literature. Our user selection algorithm achieves a large portion of the optimum user selection sum rate (90%) for a moderate number of active users. PMID:24574928

Estimating Mass Parameters of Doubly Synchronous Binary Asteroids

NASA Astrophysics Data System (ADS)

Davis, Alex; Scheeres, Daniel J.

2017-10-01

The non-spherical mass distributions of binary asteroid systems lead to coupled mutual gravitational forces and torques. Observations of the coupled attitude and orbital dynamics can be leveraged to provide information about the mass parameters of the binary system. The full 3-dimensional motion has 9 degrees of freedom, and coupled dynamics require the use of numerical investigation only. In the current study we simplify the system to a planar ellipsoid-ellipsoid binary system in a doubly synchronous orbit. Three modes are identified for the system, which has 4 degrees of freedom, with one degree of freedom corresponding to an ignorable coordinate. The three modes correspond to the three major librational modes of the system when it is in a doubly synchronous orbit. The linearized periods of each mode are a function of the mass parameters of the two asteroids, enabling measurement of these parameters based on observations of the librational motion. Here we implement estimation techniques to evaluate the capabilities of this mass measurement method. We apply this methodology to the Trojan binary asteroid system 617 Patroclus and Menoetius (1906 VY), the final flyby target of the recently announced LUCY Discovery mission. This system is of interest because a stellar occultation campaign of the Patroclus and Menoetius system has suggested that the asteroids are similarly sized oblate ellipsoids moving in a doubly-synchronous orbit, making the system an ideal test for this investigation. A number of missed observations during the campaign also suggested the possibility of a crater on the southern limb of Menoetius, the presence of which could be evaluated by our mass estimation method. This presentation will review the methodology and potential accuracy of our approach in addition to evaluating how the dynamical coupling can be used to help understand light curve and stellar occultation observations for librating binary systems.

Neutron star merger GW170817 strongly constrains doubly coupled bigravity

NASA Astrophysics Data System (ADS)

Akrami, Yashar; Brax, Philippe; Davis, Anne-Christine; Vardanyan, Valeri

2018-06-01

We study the implications of the recent detection of gravitational waves emitted by a pair of merging neutron stars and their electromagnetic counterpart, events GW170817 and GRB170817A, on the viability of the doubly coupled bimetric models of cosmic evolution, where the two metrics couple directly to matter through a composite, effective metric. We demonstrate that the bounds on the speed of gravitational waves place strong constraints on the doubly coupled models, forcing either the two metrics to be proportional at the background level or the models to become singly coupled. Proportional backgrounds are particularly interesting as they provide stable cosmological solutions with phenomenologies equivalent to that of Λ CDM at the background level as well as for linear perturbations, while nonlinearities are expected to show deviations from the standard model.

Stress state of a piecewise uniform layered space with doubly periodic internal cracks

NASA Astrophysics Data System (ADS)

Hakobyan, V. N.; Dashtoyan, L. L.

2018-04-01

The present paper deals with the stress state of a piecewise homogeneous plane formed by alternation junction of two distinct strips of equal height manufactured of different materials. There is a doubly periodic system of cracks on the plane. The governing system of singular integral equations of the first kind for the density of the crack dislocation is derived. The solution of the problem in the case where only one of the repeated strips contains one doubly-periodic crack is obtained by the method of mechanical quadratures.

Discriminating leptonic Yukawa interactions with doubly charged scalar at the ILC

NASA Astrophysics Data System (ADS)

Nomura, Takaaki; Okada, Hiroshi; Yokoya, Hiroshi

2018-04-01

We explore discrimination of two types of leptonic Yukawa interactions associated with Higgs triplet, LbarLc ΔLL, and with SU (2) singlet doubly charged scalar, ebarRc k++eR. These interactions can be distinguished by measuring the effects of doubly charged scalar boson exchange in the e+e- →ℓ+ℓ- processes at polarized electron-positron colliders. We study a forward-backward asymmetry of scattering angular distribution to estimate the sensitivity for these effects at the ILC. In addition, we investigate prospects of upper bounds on the Yukawa couplings by combining the constraints of lepton flavor violation processes and the e+e- →ℓ+ℓ- processes at the LEP and the ILC.

Signals of doubly-charged Higgsinos at the CERN Large Hadron Collider

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

Demir, Durmus A.; Deutsches Elektronen--Synchrotron, DESY, D-22603 Hamburg; Frank, Mariana

2008-08-01

Several supersymmetric models with extended gauge structures, motivated by either grand unification or by neutrino mass generation, predict light doubly-charged Higgsinos. In this work we study productions and decays of doubly-charged Higgsinos present in left-right supersymmetric models, and show that they invariably lead to novel collider signals not found in the minimal supersymmetric model or in any of its extensions motivated by the {mu} problem or even in extra dimensional theories. We investigate their distinctive signatures at the Large Hadron Collider in both pair- and single-production modes, and show that they are powerful tools in determining the underlying model viamore » the measurements at the Large Hadron Collider experiments.« less

Adaptive evolution of insect selective excitatory β-type sodium channel neurotoxins from scorpion venom.

PubMed

Wu, Wenlan; Li, Zhongjie; Ma, Yibao

2017-06-01

Insect selective excitatory β-type sodium channel neurotoxins from scorpion venom (β-NaScTxs) are composed of about 70-76 amino acid residues and share a common scaffold stabilized by four unique disulfide bonds. The phylogenetic analysis of these toxins was hindered by limited sequence data. In our recent study, two new insect selective excitatory β-NaScTxs, LmIT and ImIT, were isolated from Lychas mucronatus and Isometrus maculatus, respectively. With the sequences previously reported, we examined the adaptive molecular evolution of insect selective excitatory β-NaScTxs by estimating the nonsynonymous-to-synonymous rate ratio (ω=d N /d S ). The results revealed 12 positively selected sites in the genes of insect selective excitatory β-NaScTxs. Moreover, these positively selected sites match well with the sites important for interacting with sodium channels, as demonstrated in previous mutagenesis study. These results reveal that adaptive evolution after gene duplication is one of the most important genetic mechanisms of scorpion neurotoxin diversification. Copyright © 2017 Elsevier Inc. All rights reserved.

A Change in the Ion Selectivity of Ligand-Gated Ion Channels Provides a Mechanism to Switch Behavior.

PubMed

Pirri, Jennifer K; Rayes, Diego; Alkema, Mark J

2015-01-01

Behavioral output of neural networks depends on a delicate balance between excitatory and inhibitory synaptic connections. However, it is not known whether network formation and stability is constrained by the sign of synaptic connections between neurons within the network. Here we show that switching the sign of a synapse within a neural circuit can reverse the behavioral output. The inhibitory tyramine-gated chloride channel, LGC-55, induces head relaxation and inhibits forward locomotion during the Caenorhabditis elegans escape response. We switched the ion selectivity of an inhibitory LGC-55 anion channel to an excitatory LGC-55 cation channel. The engineered cation channel is properly trafficked in the native neural circuit and results in behavioral responses that are opposite to those produced by activation of the LGC-55 anion channel. Our findings indicate that switches in ion selectivity of ligand-gated ion channels (LGICs) do not affect network connectivity or stability and may provide an evolutionary and a synthetic mechanism to change behavior.

Sub-micron resolution selected area electron channeling patterns.

PubMed

Guyon, J; Mansour, H; Gey, N; Crimp, M A; Chalal, S; Maloufi, N

2015-02-01

Collection of selected area channeling patterns (SACPs) on a high resolution FEG-SEM is essential to carry out quantitative electron channeling contrast imaging (ECCI) studies, as it facilitates accurate determination of the crystal plane normal with respect to the incident beam direction and thus allows control the electron channeling conditions. Unfortunately commercial SACP modes developed in the past were limited in spatial resolution and are often no longer offered. In this contribution we present a novel approach for collecting high resolution SACPs (HR-SACPs) developed on a Gemini column. This HR-SACP technique combines the first demonstrated sub-micron spatial resolution with high angular accuracy of about 0.1°, at a convenient working distance of 10mm. This innovative approach integrates the use of aperture alignment coils to rock the beam with a digitally calibrated beam shift procedure to ensure the rocking beam is maintained on a point of interest. Moreover a new methodology to accurately measure SACP spatial resolution is proposed. While column considerations limit the rocking angle to 4°, this range is adequate to index the HR-SACP in conjunction with the pattern simulated from the approximate orientation deduced by EBSD. This new technique facilitates Accurate ECCI (A-ECCI) studies from very fine grained and/or highly strained materials. It offers also new insights for developing HR-SACP modes on new generation high-resolution electron columns. Copyright © 2014 Elsevier B.V. All rights reserved.

Three-Space Interaction in Doubly Sinusoidal Periodic Media

NASA Astrophysics Data System (ADS)

Tian-Lin, Dong; Ping, Chen

2006-06-01

Three-space-harmonic (3SH) interaction in doubly sinusoidal periodic (DSP) medium is investigated. Associated physical effects such as additional gap, defect state, and indirect gaps, are theoretically and numerically revealed. This simple DSP model can facilitate the understanding and utilizing of a series of effects in rather complicated periodic structures with additional defect or modulation.

Vortex motion in doubly connected domains

NASA Astrophysics Data System (ADS)

Zannetti, L.; Gallizio, F.; Ottino, G. M.

The unsteady two-dimensional rotational flow past doubly connected domains is analytically addressed. By concentrating the vorticity in point vortices, the flow is modelled as a potential flow with point singularities. The dependence of the complex potential on time is defined according to the Kelvin theorem. The general case of non-null circulations around the solid bodies is discussed. Vortex shedding and time evolution of the circulation past a two-element airfoil and past a two-bladed Darrieus turbine are presented as physically coherent examples.

Identification of ML204, a Novel Potent Antagonist That Selectively Modulates Native TRPC4/C5 Ion Channels*

PubMed Central

Miller, Melissa; Shi, Jie; Zhu, Yingmin; Kustov, Maksym; Tian, Jin-bin; Stevens, Amy; Wu, Meng; Xu, Jia; Long, Shunyou; Yang, Pu; Zholos, Alexander V.; Salovich, James M.; Weaver, C. David; Hopkins, Corey R.; Lindsley, Craig W.; McManus, Owen; Li, Min; Zhu, Michael X.

2011-01-01

Transient receptor potential canonical (TRPC) channels are Ca2+-permeable nonselective cation channels implicated in diverse physiological functions, including smooth muscle contractility and synaptic transmission. However, lack of potent selective pharmacological inhibitors for TRPC channels has limited delineation of the roles of these channels in physiological systems. Here we report the identification and characterization of ML204 as a novel, potent, and selective TRPC4 channel inhibitor. A high throughput fluorescent screen of 305,000 compounds of the Molecular Libraries Small Molecule Repository was performed for inhibitors that blocked intracellular Ca2+ rise in response to stimulation of mouse TRPC4β by μ-opioid receptors. ML204 inhibited TRPC4β-mediated intracellular Ca2+ rise with an IC50 value of 0.96 μm and exhibited 19-fold selectivity against muscarinic receptor-coupled TRPC6 channel activation. In whole-cell patch clamp recordings, ML204 blocked TRPC4β currents activated through either μ-opioid receptor stimulation or intracellular dialysis of guanosine 5′-3-O-(thio)triphosphate (GTPγS), suggesting a direct interaction of ML204 with TRPC4 channels rather than any interference with the signal transduction pathways. Selectivity studies showed no appreciable block by 10–20 μm ML204 of TRPV1, TRPV3, TRPA1, and TRPM8, as well as KCNQ2 and native voltage-gated sodium, potassium, and calcium channels in mouse dorsal root ganglion neurons. In isolated guinea pig ileal myocytes, ML204 blocked muscarinic cation currents activated by bath application of carbachol or intracellular infusion of GTPγS, demonstrating its effectiveness on native TRPC4 currents. Therefore, ML204 represents an excellent novel tool for investigation of TRPC4 channel function and may facilitate the development of therapeutics targeted to TRPC4. PMID:21795696

Altered ion channel conductance and ionic selectivity induced by large imposed membrane potential pulse.

PubMed Central

Chen, W; Lee, R C

1994-01-01

The effects of large magnitude transmembrane potential pulses on voltage-gated Na and K channel behavior in frog skeletal muscle membrane were studied using a modified double vaseline-gap voltage clamp. The effects of electroconformational damage to ionic channels were separated from damage to lipid bilayer (electroporation). A 4 ms transmembrane potential pulse of -600 mV resulted in a reduction of both Na and K channel conductivities. The supraphysiologic pulses also reduced ionic selectivity of the K channels against Na+ ions, resulting in a depolarization of the membrane resting potential. However, TTX and TEA binding effects were unaltered. The kinetics of spontaneous reversal of the electroconformational damage of channel proteins was found to be dependent on the magnitude of imposed membrane potential pulse. These results suggest that muscle and nerve dysfunction after electrical shock may be in part caused by electroconformational damage to voltage-gated ion channels. PMID:7948676

Mass spectra and radiative transitions of doubly heavy baryons in a relativized quark model

NASA Astrophysics Data System (ADS)

Lü, Qi-Fang; Wang, Kai-Lei; Xiao, Li-Ye; Zhong, Xian-Hui

2017-12-01

We study the mass spectra and radiative decays of doubly heavy baryons within the diquark picture in a relativized quark model. The mass of the JP=1 /2+ Ξc c ground state is predicted to be 3606 MeV, which is consistent with the mass of Ξcc ++(3621 ) newly observed by the LHCb Collaboration. The predicted mass gap between two S -wave states, Ξcc * (JP=3 /2+) and Ξc c (JP=1 /2+), is 69 MeV. Furthermore, the radiative transitions of doubly heavy baryons are also estimated by using the realistic wave functions obtained from relativized quark model. The radiative decay widths of Ξcc *++→Ξcc ++γ and Ξcc *+→Ξcc +γ are predicted to be about 7 and 4 keV, respectively. These predictions of doubly heavy baryons can provide helpful information for future experimental searches.

Apparent phosphorus availabilities of selected traditional and alternative feedstuffs for channel catfish

USDA-ARS?s Scientific Manuscript database

A digestibility trial with channel catfish Ictalurus punctatus was conducted to determine apparent availability coefficients (AACs) of phosphorus for selected common feedstuffs: soybean meal, cottonseed meal, wheat middlings, corn gluten feed (CGF), and corn distillers dried grains with solubles (DD...

Full Two-Body Problem Mass Parameter Observability Explored Through Doubly Synchronous Systems

NASA Astrophysics Data System (ADS)

Davis, Alex Benjamin; Scheeres, Daniel

2018-04-01

The full two-body problem (F2BP) is often used to model binary asteroid systems, representing the bodies as two finite mass distributions whose dynamics are influenced by their mutual gravity potential. The emergent behavior of the F2BP is highly coupled translational and rotational mutual motion of the mass distributions. For these systems the doubly synchronous equilibrium occurs when both bodies are tidally-locked and in a circular co-orbit. Stable oscillations about this equilibrium can be shown, for the nonplanar system, to be combinations of seven fundamental frequencies of the system and the mutual orbit rate. The fundamental frequencies arise as the linear periods of center manifolds identified about the equilibrium which are heavily influenced by each body’s mass parameters. We leverage these eight dynamical constraints to investigate the observability of binary asteroid mass parameters via dynamical observations. This is accomplished by proving the nonsingularity of the relationship between the frequencies and mass parameters for doubly synchronous systems. Thus we can invert the relationship to show that given observations of the frequencies, we can solve for the mass parameters of a target system. In so doing we are able to predict the estimation covariance of the mass parameters based on observation quality and define necessary observation accuracies for desired mass parameter certainties. We apply these tools to 617 Patroclus, a doubly synchronous Trojan binary and flyby target of the LUCY mission, as well as the Pluto and Charon system in order to predict mutual behaviors of these doubly synchronous systems and to provide observational requirements for these systems’ mass parameters

Efficient photocatalytic degradation of gaseous N,N-dimethylformamide in tannery waste gas using doubly open-ended Ag/TiO2 nanotube array membranes

NASA Astrophysics Data System (ADS)

Zhao, Yang; Ma, Lin; Chang, Wenkai; Huang, Zhiding; Feng, Xugen; Qi, Xiaoxia; Li, Zenghe

2018-06-01

Gaseous N,N-dimethylformamide (DMF), typical volatile organic compound exhausted from manufacturing factories, may damage the health of workers under long-term exposure even at low levels. The defined geometry, porous surface and highly ordered channels make the free-standing anodic TiO2 nanotube (TiNT) arrays particularly suitable for applications of practical air purification by flow-through photocatalysis. In the present work, crystallized doubly open-ended Ag/TiNT array membranes were designed and prepared by employing a lift-off process based on an anodization-annealing-anodization-etching sequence, followed by uniform Ag nanoparticles decoration. For the photocatalytic degradation of gaseous DMF at low concentration levels close to that found in realistic pollutant air, an analytical methodology for the monitoring and determination of degradation process was developed based on the coupling of headspace sampling with gas chromatography mass spectrometry (HS-GC-MS). The doubly open-ended Ag/TiNT arrays exhibited higher removal efficiency of gaseous DMF from air compared with conventional bottom-closed Ag/TiNT arrays and pure bottomless TiNT arrays. These results indicated that the photocatalytic properties of TiNT arrays were improved with the open-bottom morphology and the Ag nanoparticles decoration. Based on the analysis with GC-MS and high performance ion chromatography (HPIC), it was found that demethylation is the main pathway of DMF degradation in photocatalytic reactions. Furthermore, decontamination of actual polluted tannery waste gas collected in leather factory proved that the photocatalysis on doubly open-ended Ag/TiNT array membrane is an efficient way and a promising application to treat air contaminated by DMF despite the complexity of various volatile organic compounds.

Membrane-tethered peptides patterned after the TRP domain (TRPducins) selectively inhibit TRPV1 channel activity.

PubMed

Valente, Pierluigi; Fernández-Carvajal, Asia; Camprubí-Robles, María; Gomis, Ana; Quirce, Susana; Viana, Félix; Fernández-Ballester, Gregorio; González-Ros, José M; Belmonte, Carlos; Planells-Cases, Rosa; Ferrer-Montiel, Antonio

2011-05-01

The transient receptor potential vanilloid 1 (TRPV1) channel is a thermosensory receptor implicated in diverse physiological and pathological processes. The TRP domain, a highly conserved region in the C terminus adjacent to the internal channel gate, is critical for subunit tetramerization and channel gating. Here, we show that cell-penetrating, membrane-anchored peptides patterned after this protein domain are moderate and selective TRPV1 antagonists both in vitro and in vivo, blocking receptor activity in intact rat primary sensory neurons and their peripheral axons with mean decline time of 30 min. The most potent lipopeptide, TRP-p5, blocked all modes of TRPV1 gating with micromolar efficacy (IC(50)<10 μM), without significantly affecting other thermoTRP channels. In contrast, its retrosequence or the corresponding sequences of other TRPV channels did not alter TRPV1 channel activity (IC(50)>100 μM). TRP-p5 did not affect the capsaicin sensitivity of the vanilloid receptor. Our data suggest that TRP-p5 interferes with protein-protein interactions at the level of the TRP domain that are essential for the "conformational" change that leads to gate opening. Therefore, these palmitoylated peptides, which we termed TRPducins, are noncompetitive, voltage-independent, sequence-specific TRPV1 blockers. Our findings indicate that TRPducin-like peptides may embody a novel molecular strategy that can be exploited to generate a selective pharmacological arsenal for the TRP superfamily of ion channels.

Isotope shifts from collinear laser spectroscopy of doubly charged yttrium isotopes

NASA Astrophysics Data System (ADS)

Vormawah, L. J.; Vilén, M.; Beerwerth, R.; Campbell, P.; Cheal, B.; Dicker, A.; Eronen, T.; Fritzsche, S.; Geldhof, S.; Jokinen, A.; Kelly, S.; Moore, I. D.; Reponen, M.; Rinta-Antila, S.; Stock, S. O.; Voss, A.

2018-04-01

Collinear laser spectroscopy has been performed on doubly charged ions of radioactive yttrium in order to study the isotope shifts of the 294.6-nm 5 s 1/2 2S →5 p 1/2 2P line. The potential of such an alkali-metal-like transition to improve the reliability of atomic-field-shift and mass-shift factor calculations, and hence the extraction of nuclear mean-square radii, is discussed. Production of yttrium ion beams for such studies is available at the IGISOL IV Accelerator Laboratory, Jyväskylä, Finland. This newly recommissioned facility is described here in relation to the on-line study of accelerator-produced short-lived isotopes using collinear laser spectroscopy and application of the technique to doubly charged ions.

Doubly fed induction generator wind turbines with fuzzy controller: a survey.

PubMed

Sathiyanarayanan, J S; Kumar, A Senthil

2014-01-01

Wind energy is one of the extraordinary sources of renewable energy due to its clean character and free availability. With the increasing wind power penetration, the wind farms are directly influencing the power systems. The majority of wind farms are using variable speed wind turbines equipped with doubly fed induction generators (DFIG) due to their advantages over other wind turbine generators (WTGs). Therefore, the analysis of wind power dynamics with the DFIG wind turbines has become a very important research issue, especially during transient faults. This paper presents fuzzy logic control of doubly fed induction generator (DFIG) wind turbine in a sample power system. Fuzzy logic controller is applied to rotor side converter for active power control and voltage regulation of wind turbine.

Doubly Fed Induction Generator Wind Turbines with Fuzzy Controller: A Survey

PubMed Central

Sathiyanarayanan, J. S.; Senthil Kumar, A.

2014-01-01

Wind energy is one of the extraordinary sources of renewable energy due to its clean character and free availability. With the increasing wind power penetration, the wind farms are directly influencing the power systems. The majority of wind farms are using variable speed wind turbines equipped with doubly fed induction generators (DFIG) due to their advantages over other wind turbine generators (WTGs). Therefore, the analysis of wind power dynamics with the DFIG wind turbines has become a very important research issue, especially during transient faults. This paper presents fuzzy logic control of doubly fed induction generator (DFIG) wind turbine in a sample power system. Fuzzy logic controller is applied to rotor side converter for active power control and voltage regulation of wind turbine. PMID:25028677

Interplay between collective and single particle excitations around neutron-rich doubly-magic nuclei

NASA Astrophysics Data System (ADS)

Leoni, S.

2016-05-01

The excitation spectra of nuclei with one or two particles outside a doubly-magic core are expected to be dominated, at low energy, by the couplings between phonon excitations of the core and valence particles. A survey of the experimental situation is given for some nuclei lying in close proximity of neutron-rich doubly-magic systems, such as 47,49Ca, 133Sb and 210Bi. Data are obtained with various types of reactions (multinucleon transfer with heavy ions, cold neutron capture and neutron induced fission of 235U and 241Pu targets), with the employment of complex detection systems based on HPGe arrays. A comparison with theoretical calculations is also presented, in terms of large shell model calculations and of a phenomenological particle-phonon model. In the case of 133Sb, a new microscopic "hybrid" model is introduced: it is based on the coupling between core excitations (both collective and non-collective) of the doubly-magic core and the valence nucleon, using the Skyrme effective interaction in a consistent way.

Mapping of Residues Forming the Voltage Sensor of the Voltage-Dependent Anion-Selective Channel

NASA Astrophysics Data System (ADS)

Thomas, Lorie; Blachly-Dyson, Elizabeth; Colombini, Marco; Forte, Michael

1993-06-01

Voltage-gated ion-channel proteins contain "voltage-sensing" domains that drive the conformational transitions between open and closed states in response to changes in transmembrane voltage. We have used site-directed mutagenesis to identify residues affecting the voltage sensitivity of a mitochondrial channel, the voltage-dependent anion-selective channel (VDAC). Although charge changes at many sites had no effect, at other sites substitutions that increased positive charge also increased the steepness of voltage dependance and substitutions that decreased positive charge decreased voltage dependance by an appropriate amount. In contrast to the plasma membrane K^+ and Na^+ channels, these residues are distributed over large parts of the VDAC protein. These results have been used to define the conformational transitions that accompany voltage gating of an ion channel. This gating mechanism requires the movement of large portions of the VDAC protein through the membrane.

Ultrahigh Frequency Nanomechanical Piezoresistive Amplifiers for Direct Channel-Selective Receiver Front-Ends.

PubMed

Ramezany, Alireza; Pourkamali, Siavash

2018-04-11

Channel-selective filtering and amplification in ultrahigh frequency (UHF) receiver front-ends are crucial for realization of cognitive radio systems and the future of wireless communication. In the past decade, there have been significant advances in the performance of microscale electromechanical resonant devices. However, such devices have not yet been able to meet the requirements for direct channel selection at RF. They also occupy a relatively large area on the chip making implementation of large arrays to cover several frequency bands challenging. On the other hand, electromechanical piezoresistive resonant devices are active devices that have recently shown the possibility of simultaneous signal amplification and channel-select filtering at lower frequencies. It has been theoretically predicted that if scaled down into the nanoscale, they can operate in the UHF range with a very low power consumption. Here, for the first time nanomechanical piezoresistive amplifiers with active element dimensions as small as 50 nm × 200 nm are demonstrated. With a device area of less than 1.5 μm 2 a piezoresistive amplifier operating at 730 MHz shows effective quality factor ( Q) of 89,000 for a 50Ω load and gains as high as 10 dB and Q of 330,000 for a 250Ω load while consuming 189 μW of power. On the basis of the measurement results, it is shown that for piezoresistor dimensions of 30 nm × 100 nm it is possible to get a similar performance at 2.4 GHz with device footprint of less than 0.2 μm 2 .

Doubly charmed baryon production in heavy ion collisions

NASA Astrophysics Data System (ADS)

Yao, Xiaojun; Müller, Berndt

2018-04-01

We give an estimate of Ξcc ++ production rate and transverse momentum spectra in relativistic heavy ion collisions. We use Boltzmann transport equations to describe the dynamical evolution of charm quarks and diquarks inside quark-gluon plasma. In-medium formation and dissociation rates of charm diquarks are calculated from potential nonrelativistic QCD for the diquark sector. We solve the transport equations by Monte Carlo simulations. For 2.76 TeV Pb-Pb collisions with 0-10% centrality, the number of Ξcc ++ produced in the transverse momentum range 0-5 GeV and rapidity from -1 to 1 is roughly 0.02 per collision. We repeat the calculation with a melting temperature 250 MeV above which no diquarks can be formed. The number of Ξcc ++ produced in the same kinematic region is about 0.0125 per collision. We discuss how to study diquarks at finite temperature on a lattice and construct the antitriplet free energy in a gauge invariant but path dependent way. We also comment on extensions of the calculation to other doubly heavy baryons and doubly heavy tetraquarks and the feasibility of experimental measurements.

Apparatus and method for selectively channeling a fluid

DOEpatents

Rightley, Michael Joseph [Albuquerque, NM

2008-01-01

An apparatus for selectively channeling a high temperature fluid without chemically reacting with the fluid. The apparatus includes an inlet and a membrane positioned adjacent to the inlet, each composed of a chemically inert material. The membrane is formed by compressive preloading techniques. The apparatus further includes a seat disposed on the inlet adjacent to the membrane. The seat is composed of a heat resistant and chemically inert material. Operation of the apparatus requires that the temperature of the fluid remains below the chemical characteristic melting point of the seat. The apparatus further includes an actuator coupled to the membrane for rendering the membrane in an open and a closed position with respect to the seat. Specifically, the actuator supplies a load in the normal direction to the membrane to selectively engage the membrane in a plurality of predetermined configurations. Operatively, the apparatus receives the fluid at the inlet. The fluid is received at a high temperature and is directed from the inlet to the membrane. In the closed position, the actuator engages the membrane to prevent the fluid from flowing from the inlet between the membrane and the seat. Alternatively, in the open position, the actuator engages the membrane to permit fluid flow from the inlet between the membrane and the seat to at least one outlet provided by the apparatus. In one exemplary embodiment, the fluid may be discharged from the at least one outlet to a sensor in fluid communication with the at least one outlet. Accordingly, the sensor may measure the fluid channeled through the heat resistant and chemically inert environment provided by the apparatus.

A Search for Long-Lived Doubly-Charged Higgs Boson Production in anti-p p Collisions at sqrt(s)=1.96 TeV using RunII CDF

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

Tuttle, Joshua P.; /Duke U.

2005-01-01

We present a search for a quasi-stable doubly-charged Higgs particle at CDF using the Fermilab Tevatron for {radical}s = 1.96 TeV. The data presented are from approximately 290 pb{sup -1} of integrated luminosity collected using the upgraded Run 2 Collider Detector at Fermilab. These data were taken between February, 2002 and February, 2004. The long-lived decay products of Z's are selected in the central detector region (|{eta}| < 1.0). They select events triggered on a muon candidate having p{sub T} > 18 GeV in the event. After offline reconstruction, they require two isolated tracks (p{sub T} > 20 GeV) inmore » the event, one of which points to a stub in a muon detector. Since the search is based on the increased ionization a doubly-charged particle would produce as it passes through the detector, they require that both tracks be highly ionizing for an event to be selected as a H{sup {+-}{+-}} candidate. No such candidates are observed in the data. They set a lower mass limit of 146 GeV on a quasi-stable H{sup {+-}{+-}} boson.« less

Positrons vs electrons channeling in silicon crystal: energy levels, wave functions and quantum chaos manifestations

NASA Astrophysics Data System (ADS)

Shul'ga, N. F.; Syshchenko, V. V.; Tarnovsky, A. I.; Solovyev, I. I.; Isupov, A. Yu.

2018-01-01

The motion of fast electrons through the crystal during axial channeling could be regular and chaotic. The dynamical chaos in quantum systems manifests itself in both statistical properties of energy spectra and morphology of wave functions of the individual stationary states. In this report, we investigate the axial channeling of high and low energy electrons and positrons near [100] direction of a silicon crystal. This case is particularly interesting because of the fact that the chaotic motion domain occupies only a small part of the phase space for the channeling electrons whereas the motion of the channeling positrons is substantially chaotic for the almost all initial conditions. The energy levels of transverse motion, as well as the wave functions of the stationary states, have been computed numerically. The group theory methods had been used for classification of the computed eigenfunctions and identification of the non-degenerate and doubly degenerate energy levels. The channeling radiation spectrum for the low energy electrons has been also computed.

A New Equivalence Theory Method for Treating Doubly Heterogeneous Fuel - II. Verifications

DOE PAGES

Choi, Sooyoung; Kong, Chidong; Lee, Deokjung; ...

2015-03-09

A new methodology has been developed recently to treat resonance self-shielding in systems for which the fuel compact region of a reactor lattice consists of small fuel grains dispersed in a graphite matrix. The theoretical development adopts equivalence theory in both micro- and macro-level heterogeneities to provide approximate analytical expressions for the shielded cross sections, which may be interpolated from a table of resonance integrals or Bondarenko factors using a modified background cross section as the interpolation parameter. This paper describes the first implementation of the theoretical equations in a reactor analysis code. In order to reduce discrepancies caused bymore » use of the rational approximation for collision probabilities in the original derivation, a new formulation for a doubly heterogeneous Bell factor is developed in this paper to improve the accuracy of doubly heterogeneous expressions. This methodology is applied to a wide range of pin cell and assembly test problems with varying geometry parameters, material compositions, and temperatures, and the results are compared with continuous-energy Monte Carlo simulations to establish the accuracy and range of applicability of the new approach. It is shown that the new doubly heterogeneous self-shielding method including the Bell factor correction gives good agreement with reference Monte Carlo results.« less

A structural, functional, and computational analysis suggests pore flexibility as the base for the poor selectivity of CNG channels

PubMed Central

Napolitano, Luisa Maria Rosaria; Bisha, Ina; De March, Matteo; Marchesi, Arin; Arcangeletti, Manuel; Demitri, Nicola; Mazzolini, Monica; Rodriguez, Alex; Magistrato, Alessandra; Onesti, Silvia; Laio, Alessandro; Torre, Vincent

2015-01-01

Cyclic nucleotide-gated (CNG) ion channels, despite a significant homology with the highly selective K+ channels, do not discriminate among monovalent alkali cations and are permeable also to several organic cations. We combined electrophysiology, molecular dynamics (MD) simulations, and X-ray crystallography to demonstrate that the pore of CNG channels is highly flexible. When a CNG mimic is crystallized in the presence of a variety of monovalent cations, including Na+, Cs+, and dimethylammonium (DMA+), the side chain of Glu66 in the selectivity filter shows multiple conformations and the diameter of the pore changes significantly. MD simulations indicate that Glu66 and the prolines in the outer vestibule undergo large fluctuations, which are modulated by the ionic species and the voltage. This flexibility underlies the coupling between gating and permeation and the poor ionic selectivity of CNG channels. PMID:26100907

A structural, functional, and computational analysis suggests pore flexibility as the base for the poor selectivity of CNG channels.

PubMed

Napolitano, Luisa Maria Rosaria; Bisha, Ina; De March, Matteo; Marchesi, Arin; Arcangeletti, Manuel; Demitri, Nicola; Mazzolini, Monica; Rodriguez, Alex; Magistrato, Alessandra; Onesti, Silvia; Laio, Alessandro; Torre, Vincent

2015-07-07

Cyclic nucleotide-gated (CNG) ion channels, despite a significant homology with the highly selective K(+) channels, do not discriminate among monovalent alkali cations and are permeable also to several organic cations. We combined electrophysiology, molecular dynamics (MD) simulations, and X-ray crystallography to demonstrate that the pore of CNG channels is highly flexible. When a CNG mimic is crystallized in the presence of a variety of monovalent cations, including Na(+), Cs(+), and dimethylammonium (DMA(+)), the side chain of Glu66 in the selectivity filter shows multiple conformations and the diameter of the pore changes significantly. MD simulations indicate that Glu66 and the prolines in the outer vestibule undergo large fluctuations, which are modulated by the ionic species and the voltage. This flexibility underlies the coupling between gating and permeation and the poor ionic selectivity of CNG channels.

Detection of singly- and doubly-charged quaternary ammonium drugs in equine urine by liquid chromatography/tandem mass spectrometry.

PubMed

Ho, Emmie N M; Kwok, W H; Wong, April S Y; Wan, Terence S M

2012-01-13

Quaternary ammonium drugs (QADs) are anticholinergic agents some of which are known to have been abused or misused in equine sports. A recent review of literature shows that the screening methods reported thus far for QADs mainly cover singly-charged QADs. Doubly-charged QADs are extremely polar substances which are difficult to be extracted and poorly retained on reversed-phase columns. It would be ideal if a comprehensive method can be developed which can detect both singly- and doubly-charged QADs. This paper describes an efficient liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the simultaneous detection and confirmation of 38 singly- and doubly-charged QADs at sub-parts-per-billion (ppb) to low-ppb levels in equine urine after solid-phase extraction. Quaternary ammonium drugs were extracted from equine urine by solid-phase extraction (SPE) using an ISOLUTE(®) CBA SPE column and analysed by LC/MS/MS in the positive electrospray ionisation mode. Separation of the 38 QADs was achieved on a polar group embedded C18 LC column with a mixture of aqueous ammonium formate (pH 3.0, 10 mM) and acetonitrile as the mobile phase. Detection and confirmation of the 38 QADs at sub-ppb to low-ppb levels in equine urine could be achieved within 16 min using selected reaction monitoring (SRM). Matrix interference of the target transitions at the expected retention times was not observed. Other method validation data, including precision and recovery, were acceptable. The method was successfully applied to the analyses of drug-administration samples. Copyright © 2011 Elsevier B.V. All rights reserved.

Doubly robust matching estimators for high dimensional confounding adjustment.

PubMed

Antonelli, Joseph; Cefalu, Matthew; Palmer, Nathan; Agniel, Denis

2018-05-11

Valid estimation of treatment effects from observational data requires proper control of confounding. If the number of covariates is large relative to the number of observations, then controlling for all available covariates is infeasible. In cases where a sparsity condition holds, variable selection or penalization can reduce the dimension of the covariate space in a manner that allows for valid estimation of treatment effects. In this article, we propose matching on both the estimated propensity score and the estimated prognostic scores when the number of covariates is large relative to the number of observations. We derive asymptotic results for the matching estimator and show that it is doubly robust in the sense that only one of the two score models need be correct to obtain a consistent estimator. We show via simulation its effectiveness in controlling for confounding and highlight its potential to address nonlinear confounding. Finally, we apply the proposed procedure to analyze the effect of gender on prescription opioid use using insurance claims data. © 2018, The International Biometric Society.

Orientation of doubly rotated quartz plates.

PubMed

Sherman, J R

1989-01-01

A derivation from classical spherical trigonometry of equations to compute the orientation of doubly-rotated quartz blanks from Bragg X-ray data is discussed. These are usually derived by compact and efficient vector methods, which are reviewed briefly. They are solved by generating a quadratic equation with numerical coefficients. Two methods exist for performing the computation from measurements against two planes: a direct solution by a quadratic equation and a process of convergent iteration. Both have a spurious solution. Measurement against three lattice planes yields a set of three linear equations the solution of which is an unambiguous result.

Characterization of a C-type natriuretic peptide (CNP-39)-formed cation-selective channel from platypus (Ornithorhynchus anatinus) venom

PubMed Central

Kourie, Joseph I

1999-01-01

The lipid bilayer technique is used to characterize the biophysical and pharmacological properties of a novel, fast, cation-selective channel formed by incorporating platypus (Ornithorhynchus anatinus) venom (OaV) into lipid membranes.A synthetic C-type natriuretic peptide OaCNP-39, which is identical to that present in platypus venom, mimics the conductance, kinetics, selectivity and pharmacological properties of the OaV-formed fast cation-selective channel. The N-terminal fragment containing residues 1-17, i.e. OaCNP-39(1-17), induces the channel activity.The current amplitude of the TEACl-insensitive fast cation-selective channel is dependent on cytoplasmic K+, [K+]cis. The increase in the current amplitude, as a function of increasing [K+]cis, is non-linear and can be described by the Michaelis-Menten equation. At +140 mV, the values of γmax and KS are 63·1 pS and 169 mM, respectively, whereas at 0 mV the values of γmax and KS are 21·1 pS and 307 mM, respectively. γmax and KS are maximal single channel conductance and concentration for half-maximal γ, respectively. The calculated permeability ratios, PK:PRb:PNa: PCs:PLi, were 1:0·76:0·21:0·09:0·03, respectively.The probability of the fast channel being open, Po, increases from 0·15 at 0 mV to 0·75 at +140 mV. In contrast, the channel frequency, Fo, decreases from 400 to 180 events per second for voltages between 0 mV and +140. The mean open time, To, increases as the bilayer is made more positive, between 0 and +140 mV. The mean values of the voltage-dependent kinetic parameters, Po, Fo, To and mean closed time (Tc), are independent of [KCl]cis between 50 and 750 mM (P > 0·05).It is proposed that some of the symptoms of envenomation by platypus venom may be caused partly by changes in cellular functions mediated via the OaCNP-39-formed fast cation-selective channel, which affects signal transduction. PMID:10381585

Overcharging below the nanoscale: Multivalent cations reverse the ion selectivity of a biological channel

NASA Astrophysics Data System (ADS)

García-Giménez, Elena; Alcaraz, Antonio; Aguilella, Vicente M.

2010-02-01

We report charge inversion within a nanoscopic biological protein ion channel in salts of multivalent ions. The presence of positive divalent and trivalent counterions reverses the cationic selectivity of the OmpF channel, a general diffusion porin located in the outer membrane of E. coli. We discuss the conditions under which charge inversion can be inferred from the change in sign of the measured quantity, the channel zero current potential. By comparing experimental results in protein channels whose charge has been modified after site-directed mutagenesis, the predictions of current theories of charge inversion are critically examined. It is emphasized that charge inversion does not necessarily increase with the bare surface charge density of the interface and that even this concept of surface charge density may become meaningless in some biological ion channels. Thus, any theory based on electrostatic correlations or chemical binding should explicitly take into account the particular structure of the charged interface.

Synthesis of γ-Phosphate-Labeled and Doubly Labeled Adenosine Triphosphate Analogs.

PubMed

Hacker, Stephan M; Welter, Moritz; Marx, Andreas

2015-03-09

This unit describes the synthesis of γ-phosphate-labeled and doubly labeled adenosine triphosphate (ATP) analogs and their characterization using the phosphodiesterase I from Crotalus adamanteus (snake venom phosphodiesterase; SVPD). In the key step of the synthesis, ATP or an ATP analog, bearing a linker containing a trifluoroacetamide group attached to the nucleoside, are modified with an azide-containing linker at the terminal phosphate using an alkylation reaction. Subsequently, different labels are introduced to the linkers by transformation of one functional group to an amine and coupling to an N-hydroxysuccinimide ester. Specifically, the Staudinger reaction of the azide is employed as a straightforward means to obtain an amine in the presence of various labels. Furthermore, the fluorescence characteristics of a fluorogenic, doubly labeled ATP analog are investigated following enzymatic cleavage by SVPD. Copyright © 2015 John Wiley & Sons, Inc.

The calcium-permeable non-selective cation channel TRPM2 is modulated by cellular acidification

PubMed Central

Starkus, John G; Fleig, Andrea; Penner, Reinhold

2010-01-01

TRPM2 is a calcium-permeable non-selective cation channel expressed in the plasma membrane and in lysosomes that is critically involved in aggravating reactive oxygen species (ROS)-induced inflammatory processes and has been implicated in cell death. TRPM2 is gated by ADP-ribose (ADPR) and modulated by physiological processes that produce peroxide, cyclic ADP-ribose (cADPR), nicotinamide adenine dinucleotide phosphate (NAADP) and Ca2+. We investigated the role of extra- and intracellular acidification on heterologously expressed TRPM2 in HEK293 cells. Our results show that TRPM2 is inhibited by external acidification with an IC50 of pH 6.5 and is completely suppressed by internal pH of 6. Current inhibition requires channel opening and is strongly voltage dependent, being most effective at negative potentials. In addition, increased cytosolic pH buffering capacity or elevated [Ca2+]i reduces the rate of current inactivation elicited by extracellular acidification, and Na+ and Ca2+ influence the efficacy of proton-induced inactivation. Together, these results suggest that external protons permeate TRPM2 channels to gain access to an intracellular site that regulates channel activity. Consistent with this notion, single-channel measurements in HEK293 cells reveal that internal protons induce channel closure without affecting single-channel conductance, whereas external protons affect channel open probability as well as single-channel conductance of native TRPM2 in neutrophils. We conclude that protons compete with Na+ and Ca2+ for channel permeation and channel closure results from a competitive antagonism of protons at an intracellular Ca2+ binding site. PMID:20194125

The calcium-permeable non-selective cation channel TRPM2 is modulated by cellular acidification.

PubMed

Starkus, John G; Fleig, Andrea; Penner, Reinhold

2010-04-15

TRPM2 is a calcium-permeable non-selective cation channel expressed in the plasma membrane and in lysosomes that is critically involved in aggravating reactive oxygen species (ROS)-induced inflammatory processes and has been implicated in cell death. TRPM2 is gated by ADP-ribose (ADPR) and modulated by physiological processes that produce peroxide, cyclic ADP-ribose (cADPR), nicotinamide adenine dinucleotide phosphate (NAADP) and Ca(2+). We investigated the role of extra- and intracellular acidification on heterologously expressed TRPM2 in HEK293 cells. Our results show that TRPM2 is inhibited by external acidification with an IC(50) of pH 6.5 and is completely suppressed by internal pH of 6. Current inhibition requires channel opening and is strongly voltage dependent, being most effective at negative potentials. In addition, increased cytosolic pH buffering capacity or elevated [Ca(2+)](i) reduces the rate of current inactivation elicited by extracellular acidification, and Na(+) and Ca(2+) influence the efficacy of proton-induced inactivation. Together, these results suggest that external protons permeate TRPM2 channels to gain access to an intracellular site that regulates channel activity. Consistent with this notion, single-channel measurements in HEK293 cells reveal that internal protons induce channel closure without affecting single-channel conductance, whereas external protons affect channel open probability as well as single-channel conductance of native TRPM2 in neutrophils. We conclude that protons compete with Na(+) and Ca(2+) for channel permeation and channel closure results from a competitive antagonism of protons at an intracellular Ca(2+) binding site.

Psychosocial predictors of energy underreporting in a large doubly labeled water study.

PubMed

Tooze, Janet A; Subar, Amy F; Thompson, Frances E; Troiano, Richard; Schatzkin, Arthur; Kipnis, Victor

2004-05-01

Underreporting of energy intake is associated with self-reported diet measures and appears to be selective according to personal characteristics. Doubly labeled water is an unbiased reference biomarker for energy intake that may be used to assess underreporting. Our objective was to determine which factors are associated with underreporting of energy intake on food-frequency questionnaires (FFQs) and 24-h dietary recalls (24HRs). The study participants were 484 men and women aged 40-69 y who resided in Montgomery County, MD. Using the doubly labeled water method to measure total energy expenditure, we considered numerous psychosocial, lifestyle, and sociodemographic factors in multiple logistic regression models for prediction of the probability of underreporting on the FFQ and 24HR. In the FFQ models, fear of negative evaluation, weight-loss history, and percentage of energy from fat were the best predictors of underreporting in women (R(2) = 0.09); body mass index, comparison of activity level with that of others of the same sex and age, and eating frequency were the best predictors in men (R(2) = 0.10). In the 24HR models, social desirability, fear of negative evaluation, body mass index, percentage of energy from fat, usual activity, and variability in number of meals per day were the best predictors of underreporting in women (R(2) = 0.22); social desirability, dietary restraint, body mass index, eating frequency, dieting history, and education were the best predictors in men (R(2) = 0.25). Although the final models were significantly related to underreporting on both the FFQ and the 24HR, the amount of variation explained by these models was relatively low, especially for the FFQ.

TPC Proteins Are Phosphoinositide-activated Sodium-selective Ion Channels in Endosomes and Lysosomes

PubMed Central

Wang, Xiang; Zhang, Xiaoli; Dong, Xian-ping; Samie, Mohammad; Li, Xinran; Cheng, Xiping; Goschka, Andrew; Shen, Dongbiao; Zhou, Yandong; Harlow, Janice; Zhu, Michael X.; Clapham, David E.; Ren, Dejian; Xu, Haoxing

2012-01-01

Summary Mammalian Two-Pore Channels (TPC1, 2; TPCN1, TPCN2) encode ion channels in intracellular endosomes and lysosomes and were proposed to mediate endolysosomal calcium release triggered by the second messenger, nicotinic acid adenine dinucleotide phosphate (NAADP). By directly recording TPCs in endolysosomes from wild-type and TPC double knockout mice, here we show that, in contrast to previous conclusions, TPCs are in fact sodium-selective channels activated by PI(3,5)P2, and are not activated by NAADP. Moreover, the primary endolysosomal ion is Na+, not K+, as had been previously assumed. These findings suggest that the organellar membrane potential may undergo large regulatory changes, and may explain the specificity of PI(3,5)P2 in regulating the fusogenic potential of intracellular organelles. PMID:23063126

Possible roles of exceptionally conserved residues around the selectivity filters of sodium and calcium channels.

PubMed

Tikhonov, Denis B; Zhorov, Boris S

2011-01-28

In the absence of x-ray structures of sodium and calcium channels their homology models are used to rationalize experimental data and design new experiments. A challenge is to model the outer-pore region that folds differently from potassium channels. Here we report a new model of the outer-pore region of the NaV1.4 channel, which suggests roles of highly conserved residues around the selectivity filter. The model takes from our previous study (Tikhonov, D. B., and Zhorov, B. S. (2005) Biophys. J. 88, 184-197) the general disposition of the P-helices, selectivity filter residues, and the outer carboxylates, but proposes new intra- and inter-domain contacts that support structural stability of the outer pore. Glycine residues downstream from the selectivity filter are proposed to participate in knob-into-hole contacts with the P-helices and S6s. These contacts explain the adapted tetrodotoxin resistance of snakes that feed on toxic prey through valine substitution of isoleucine in the P-helix of repeat IV. Polar residues five positions upstream from the selectivity filter residues form H-bonds with the ascending-limb backbones. Exceptionally conserved tryptophans are engaged in inter-repeat H-bonds to form a ring whose π-electrons would facilitate passage of ions from the outer carboxylates to the selectivity filter. The outer-pore model of CaV1.2 derived from the NaV1.4 model is also stabilized by the ring of exceptionally conservative tryptophans and H-bonds between the P-helices and ascending limbs. In this model, the exceptionally conserved aspartate downstream from the selectivity-filter glutamate in repeat II facilitates passage of calcium ions to the selectivity-filter ring through the tryptophan ring. Available experimental data are discussed in view of the models.

The mechanosensory calcium-selective ion channel: key component of a plasmalemmal control centre?

NASA Technical Reports Server (NTRS)

Pickard, B. G.; Ding, J. P.

1993-01-01

Mechanosensory calcium-selective ion channels probably serve to detect not only mechanical stress but also electrical, thermal, and diverse chemical stimuli. Because all stimuli result in a common output, most notably a shift in second messenger calcium concentration, the channels are presumed to serve as signal integrators. Further, insofar as second messenger calcium in turn gives rise to mechanical, electrical, and diverse chemical changes, the channels are postulated to initiate regulatory feedbacks. It is proposed that the channels and the feedback loops play a wide range of roles in regulating normal plant function, as well as in mediating disturbance of normal function by environmental stressors and various pathogens. In developing evidence for the physiological performance of the channel, a model for a cluster of regulatory plasmalemmal proteins and cytoskeletal elements grouped around a set of wall-to-membrane and transmembrane linkers has proved useful. An illustration of how the model might operate is presented. It is founded on the demonstration that several xenobiotics interfere both with normal channel behaviour and with gravitropic reception. Accordingly, the first part of the illustration deals with how the channels and the control system within which they putatively operate might initiate gravitropism. Assuming that gravitropism is an asymmetric expression of growth, the activities of the channels and the plasmalemmal control system are extrapolated to account for regulation of both rate and allometry of cell expansion. Finally, it is discussed how light, hormones, redox agents and herbicides could in principle affect growth via the putative plasmalemmal control cluster or centre.

The Human Mitochondrial DNA Depletion Syndrome Gene MPV17 Encodes a Non-selective Channel That Modulates Membrane Potential.

PubMed

Antonenkov, Vasily D; Isomursu, Antti; Mennerich, Daniela; Vapola, Miia H; Weiher, Hans; Kietzmann, Thomas; Hiltunen, J Kalervo

2015-05-29

The human MPV17-related mitochondrial DNA depletion syndrome is an inherited autosomal recessive disease caused by mutations in the inner mitochondrial membrane protein MPV17. Although more than 30 MPV17 gene mutations were shown to be associated with mitochondrial DNA depletion syndrome, the function of MPV17 is still unknown. Mice deficient in Mpv17 show signs of premature aging. In the present study, we used electrophysiological measurements with recombinant MPV17 to reveal that this protein forms a non-selective channel with a pore diameter of 1.8 nm and located the channel's selectivity filter. The channel was weakly cation-selective and showed several subconductance states. Voltage-dependent gating of the channel was regulated by redox conditions and pH and was affected also in mutants mimicking a phosphorylated state. Likewise, the mitochondrial membrane potential (Δψm) and the cellular production of reactive oxygen species were higher in embryonic fibroblasts from Mpv17(-/-) mice. However, despite the elevated Δψm, the Mpv17-deficient mitochondria showed signs of accelerated fission. Together, these observations uncover the role of MPV17 as a Δψm-modulating channel that apparently contributes to mitochondrial homeostasis under different conditions. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

The Human Mitochondrial DNA Depletion Syndrome Gene MPV17 Encodes a Non-selective Channel That Modulates Membrane Potential*

PubMed Central

Antonenkov, Vasily D.; Isomursu, Antti; Mennerich, Daniela; Vapola, Miia H.; Weiher, Hans; Kietzmann, Thomas; Hiltunen, J. Kalervo

2015-01-01

The human MPV17-related mitochondrial DNA depletion syndrome is an inherited autosomal recessive disease caused by mutations in the inner mitochondrial membrane protein MPV17. Although more than 30 MPV17 gene mutations were shown to be associated with mitochondrial DNA depletion syndrome, the function of MPV17 is still unknown. Mice deficient in Mpv17 show signs of premature aging. In the present study, we used electrophysiological measurements with recombinant MPV17 to reveal that this protein forms a non-selective channel with a pore diameter of 1.8 nm and located the channel's selectivity filter. The channel was weakly cation-selective and showed several subconductance states. Voltage-dependent gating of the channel was regulated by redox conditions and pH and was affected also in mutants mimicking a phosphorylated state. Likewise, the mitochondrial membrane potential (Δψm) and the cellular production of reactive oxygen species were higher in embryonic fibroblasts from Mpv17−/− mice. However, despite the elevated Δψm, the Mpv17-deficient mitochondria showed signs of accelerated fission. Together, these observations uncover the role of MPV17 as a Δψm-modulating channel that apparently contributes to mitochondrial homeostasis under different conditions. PMID:25861990

Electron Transfer Dissociation with Supplemental Activation to Differentiate Aspartic and Isoaspartic Residues in Doubly Charged Peptide Cations

PubMed Central

Chan, Wai Yi Kelly; Chan, T. W. Dominic; O’Connor, Peter B.

2011-01-01

Electron-transfer dissociation (ETD) with supplemental activation of the doubly charged deamidated tryptic digested peptide ions allows differentiation of isoaspartic acid and aspartic acid residues using c + 57 or z• − 57 peaks. The diagnostic peak clearly localizes and characterizes the isoaspartic acid residue. Supplemental activation in ETD of the doubly charged peptide ions involves resonant excitation of the charge reduced precursor radical cations and leads to further dissociation, including extra backbone cleavages and secondary fragmentation. Supplemental activation is essential to obtain a high quality ETD spectrum (especially for doubly charged peptide ions) with sequence information. Unfortunately, the low-resolution of the ion trap mass spectrometer makes detection of the diagnostic peak for the aspartic acid residue difficult due to interference with side-chain loss from arginine and glutamic acid residues. PMID:20304674

Chloride channels as tools for developing selective insecticides.

PubMed

Bloomquist, Jeffrey R

2003-12-01

Ligand-gated chloride channels underlie inhibition in excitable membranes and are proven target sites for insecticides. The gamma-aminobutyric acid (GABA(1)) receptor/chloride ionophore complex is the primary site of action for a number of currently used insecticides, such as lindane, endosulfan, and fipronil. These compounds act as antagonists by stabilizing nonconducting conformations of the chloride channel. Blockage of the GABA-gated chloride channel reduces neuronal inhibition, which leads to hyperexcitation of the central nervous system, convulsions, and death. We recently investigated the mode of action of the silphinenes, plant-derived natural compounds that structurally resemble picrotoxinin. These materials antagonize the action of GABA on insect neurons and block GABA-mediated chloride uptake into mouse brain synaptoneurosomes in a noncompetitive manner. In mammals, avermectins have a blocking action on the GABA-gated chloride channel consistent with a coarse tremor, whereas at longer times and higher concentrations, activation of the channel suppresses neuronal activity. Invertebrates display ataxia, paralysis, and death as the predominant signs of poisoning, with a glutamate-gated chloride channel playing a major role. Additional target sites for the avermectins or other chloride channel-directed compounds might include receptors gated by histamine, serotonin, or acetylcholine.The voltage-sensitive chloride channels form another large gene family of chloride channels. Voltage-dependent chloride channels are involved in a number of physiological processes including: maintenance of electrical excitability, chloride ion secretion and resorption, intravesicular acidification, and cell volume regulation. A subset of these channels is affected by convulsants and insecticides in mammals, although the role they play in acute lethality in insects is unclear. Given the wide range of functions that they mediate, these channels are also potential targets for

Selective activation of vascular Kv7.4/Kv7.5 K+ channels by fasudil contributes to its vasorelaxant effect

PubMed Central

Zhang, Xuan; An, Hailong; Li, Junwei; Zhang, Yuanyuan; Liu, Yang; Jia, Zhanfeng; Zhang, Wei

2016-01-01

Background and Purpose Kv7 (Kv7.1–7.5) channels play an important role in the regulation of neuronal excitability and the cardiac action potential. Growing evidence suggests Kv7.4/Kv7.5 channels play a crucial role in regulating vascular smooth muscle contractility. Most of the reported Kv7 openers have shown poor selectivity across these five subtypes. In this study, fasudil – a drug used for cerebral vasospasm – has been found to be a selective opener of Kv7.4/Kv7.5 channels. Experimental Approach A perforated whole‐cell patch technique was used to record the currents and membrane potential. Homology modelling and a docking technique were used to investigate the interaction between fasudil and the Kv7.4 channel. An isometric tension recording technique was used to assess the vascular tension. Key Results Fasudil selectively and potently enhanced Kv7.4 and Kv7.4/Kv7.5 currents expressed in HEK293 cells, and shifted the voltage‐dependent activation curve in a more negative direction. Fasudil did not affect either Kv7.2 and Kv7.2/Kv7.3 currents expressed in HEK293 cells, the native neuronal M‐type K+ currents, or the resting membrane potential in small rat dorsal root ganglia neurons. The Val248 in S5 and Ile308 in S6 segment of Kv7.4 were critical for this activating effect of fasudil. Fasudil relaxed precontracted rat small arteries in a concentration‐dependent fashion; this effect was antagonized by the Kv7 channel blocker XE991. Conclusions and Implications These results suggest that fasudil is a selective Kv7.4/Kv7.5 channel opener and provide a new dimension for developing selective Kv7 modulators and a new prospective for the use, action and mechanism of fasudil. PMID:27677924

Coulomb-repulsion-assisted double ionization from doubly excited states of argon

NASA Astrophysics Data System (ADS)

Liao, Qing; Winney, Alexander H.; Lee, Suk Kyoung; Lin, Yun Fei; Adhikari, Pradip; Li, Wen

2017-08-01

We report a combined experimental and theoretical study to elucidate nonsequential double-ionization dynamics of argon atoms at laser intensities near and below the recollision-induced ionization threshold. Three-dimensional momentum measurements of two electrons arising from strong-field nonsequential double ionization are achieved with a custom-built electron-electron-ion coincidence apparatus, showing laser intensity-dependent Coulomb repulsion effect between the two outgoing electrons. Furthermore, a previously predicted feature of double ionization from doubly excited states is confirmed in the distributions of sum of two-electron momenta. A classical ensemble simulation suggests that Coulomb-repulsion-assisted double ionization from doubly excited states is at play at low laser intensity. This mechanism can explain the dependence of Coulomb repulsion effect on the laser intensity, as well as the transition from side-by-side to back-to-back dominant emission along the laser polarization direction.

Identifying the elusive link between amino acid sequence and charge selectivity in pentameric ligand-gated ion channels.

PubMed

Cymes, Gisela D; Grosman, Claudio

2016-10-10

Among neurotransmitter-gated ion channels, the superfamily of pentameric ligand-gated ion channels (pLGICs) is unique in that its members display opposite permeant-ion charge selectivities despite sharing the same structural fold. Although much effort has been devoted to the identification of the mechanism underlying the cation-versus-anion selectivity of these channels, a careful analysis of past work reveals that discrepancies exist, that different explanations for the same phenomenon have often been put forth, and that no consensus view has yet been reached. To elucidate the molecular basis of charge selectivity for the superfamily as a whole, we performed extensive mutagenesis and electrophysiological recordings on six different cation-selective and anion-selective homologs from vertebrate, invertebrate, and bacterial origin. We present compelling evidence for the critical involvement of ionized side chains-whether pore-facing or buried-rather than backbone atoms and propose a mechanism whereby not only their charge sign but also their conformation determines charge selectivity. Insertions, deletions, and residue-to-residue mutations involving nonionizable residues in the intracellular end of the pore seem to affect charge selectivity by changing the rotamer preferences of the ionized side chains in the first turn of the M2 α-helices. We also found that, upon neutralization of the charged residues in the first turn of M2, the control of charge selectivity is handed over to the many other ionized side chains that decorate the pore. This explains the long-standing puzzle as to why the neutralization of the intracellular-mouth glutamates affects charge selectivity to markedly different extents in different cation-selective pLGICs.

Molecular Dynamics Simulations of Orai Reveal How the Third Transmembrane Segment Contributes to Hydration and Ca2+ Selectivity in Calcium Release-Activated Calcium Channels.

PubMed

Alavizargar, Azadeh; Berti, Claudio; Ejtehadi, Mohammad Reza; Furini, Simone

2018-04-26

Calcium release-activated calcium (CRAC) channels open upon depletion of Ca 2+ from the endoplasmic reticulum, and when open, they are permeable to a selective flux of calcium ions. The atomic structure of Orai, the pore domain of CRAC channels, from Drosophila melanogaster has revealed many details about conduction and selectivity in this family of ion channels. However, it is still unclear how residues on the third transmembrane helix can affect the conduction properties of the channel. Here, molecular dynamics and Brownian dynamics simulations were employed to analyze how a conserved glutamate residue on the third transmembrane helix (E262) contributes to selectivity. The comparison between the wild-type and mutated channels revealed a severe impact of the mutation on the hydration pattern of the pore domain and on the dynamics of residues K270, and Brownian dynamics simulations proved that the altered configuration of residues K270 in the mutated channel impairs selectivity to Ca 2+ over Na + . The crevices of water molecules, revealed by molecular dynamics simulations, are perfectly located to contribute to the dynamics of the hydrophobic gate and the basic gate, suggesting a possible role in channel opening and in selectivity function.

The food dye FD&C Blue No. 1 is a selective inhibitor of the ATP release channel Panx1.

PubMed

Wang, Junjie; Jackson, David George; Dahl, Gerhard

2013-05-01

The food dye FD&C Blue No. 1 (Brilliant Blue FCF [BB FCF]) is structurally similar to the purinergic receptor antagonist Brilliant Blue G (BBG), which is a well-known inhibitor of the ionotropic P2X7 receptor (P2X7R). The P2X7R functionally interacts with the membrane channel protein pannexin 1 (Panx1) in inflammasome signaling. Intriguingly, ligands to the P2X7R, regardless of whether they are acting as agonists or antagonists at the receptor, inhibit Panx1 channels. Thus, because both P2X7R and Panx1 are inhibited by BBG, the diagnostic value of the drug is limited. Here, we show that the food dye BB FCF is a selective inhibitor of Panx1 channels, with an IC50 of 0.27 µM. No significant effect was observed with concentrations as high as 100 µM of BB FCF on P2X7R. Differing by just one hydroxyl group from BB FCF, the food dye FD&C Green No. 3 exhibited similar selective inhibition of Panx1 channels. A reverse selectivity was observed for the P2X7R antagonist, oxidized ATP, which in contrast to other P2X7R antagonists had no significant inhibitory effect on Panx1 channels. Based on its selective action, BB FCF can be added to the repertoire of drugs to study the physiology of Panx1 channels. Furthermore, because Panx1 channels appear to be involved directly or indirectly through P2X7Rs in several disorders, BB FCF and derivatives of this "safe" food dye should be given serious consideration for pharmacological intervention of conditions such as acute Crohn's disease, stroke, and injuries to the central nervous system.

Discrimination of correlated and entangling quantum channels with selective process tomography

DOE PAGES

Dumitrescu, Eugene; Humble, Travis S.

2016-10-10

The accurate and reliable characterization of quantum dynamical processes underlies efforts to validate quantum technologies, where discrimination between competing models of observed behaviors inform efforts to fabricate and operate qubit devices. We present a protocol for quantum channel discrimination that leverages advances in direct characterization of quantum dynamics (DCQD) codes. We demonstrate that DCQD codes enable selective process tomography to improve discrimination between entangling and correlated quantum dynamics. Numerical simulations show selective process tomography requires only a few measurement configurations to achieve a low false alarm rate and that the DCQD encoding improves the resilience of the protocol to hiddenmore » sources of noise. Lastly, our results show that selective process tomography with DCQD codes is useful for efficiently distinguishing sources of correlated crosstalk from uncorrelated noise in current and future experimental platforms.« less

Main-channel slopes of selected streams in Iowa for estimation of flood-frequency discharges.

DOT National Transportation Integrated Search

2003-01-01

This report describes a statewide study : conducted to develop main-channel slope (MCS) : curves for 138 selected streams in Iowa with : drainage areas greater than 100 square miles. : MCS values determined from the curves can be : used in regression...

Gating transitions in the selectivity filter region of a sodium channel are coupled to the domain IV voltage sensor.

PubMed

Capes, Deborah L; Arcisio-Miranda, Manoel; Jarecki, Brian W; French, Robert J; Chanda, Baron

2012-02-14

Voltage-dependent ion channels are crucial for generation and propagation of electrical activity in biological systems. The primary mechanism for voltage transduction in these proteins involves the movement of a voltage-sensing domain (D), which opens a gate located on the cytoplasmic side. A distinct conformational change in the selectivity filter near the extracellular side has been implicated in slow inactivation gating, which is important for spike frequency adaptation in neural circuits. However, it remains an open question whether gating transitions in the selectivity filter region are also actuated by voltage sensors. Here, we examine conformational coupling between each of the four voltage sensors and the outer pore of a eukaryotic voltage-dependent sodium channel. The voltage sensors of these sodium channels are not structurally symmetric and exhibit functional specialization. To track the conformational rearrangements of individual voltage-sensing domains, we recorded domain-specific gating pore currents. Our data show that, of the four voltage sensors, only the domain IV voltage sensor is coupled to the conformation of the selectivity filter region of the sodium channel. Trapping the outer pore in a particular conformation with a high-affinity toxin or disulphide crossbridge impedes the return of this voltage sensor to its resting conformation. Our findings directly establish that, in addition to the canonical electromechanical coupling between voltage sensor and inner pore gates of a sodium channel, gating transitions in the selectivity filter region are also coupled to the movement of a voltage sensor. Furthermore, our results also imply that the voltage sensor of domain IV is unique in this linkage and in the ability to initiate slow inactivation in sodium channels.

Voltage activation and hysteresis of the non-selective voltage-dependent channel in the intact human red cell.

PubMed

Bennekou, Poul; Barksmann, Trine L; Jensen, Lars R; Kristensen, Berit I; Christophersen, Palle

2004-05-01

Suspension of intact human red cells in media with low chloride and sodium concentrations (isotonic sucrose substitution) results in strongly inside positive membrane potentials, which activate the voltage-dependent non-selective cation (NSVDC) channel. By systematic variation of the initial Nernst potentials for chloride (degree of ion substitution) as well as the chloride conductance (block by NS1652), and by exploiting the interplay between the Ca(2+)-permeable NSVDC channel, the Ca(2+)-activated K+ channel (the Gárdos channel) and the Ca(2+)-pump, a graded activation of the NSVDC channel was achieved. Under these conditions, it was shown that the NSVDC channels exist in two states of activation depending on the initial conditions for the activation. The hysteretic behaviour, which in patch clamp experiments has been found for the individual channel unit, is thus retained at the cellular level and can be demonstrated with red cells in suspension.

Study of Internal Channel Surface Roughnesses Manufactured by Selective Laser Melting in Aluminum and Titanium Alloys

NASA Astrophysics Data System (ADS)

Pakkanen, Jukka; Calignano, Flaviana; Trevisan, Francesco; Lorusso, Massimo; Ambrosio, Elisa Paola; Manfredi, Diego; Fino, Paolo

2016-08-01

Interest in additive manufacturing (AM) has gained considerable impetus over the past decade. One of the driving factors for AM success is the ability to create unique designs with intrinsic characteristics as, e.g., internal channels used for hydraulic components, cooling channels, and heat exchangers. However, a couple of the main problems in internal channels manufactured by AM technologies are the high surface roughness obtained and the distortion of the channel shape. There is still much to understand in these design aspects. In this study, a cylindrical geometry for internal channels to be built with different angles with respect to the building plane in AlSi10Mg and Ti6Al4V alloys by selective laser melting was considered. The internal surfaces of the channels produced in both materials were analyzed by means of a surface roughness tester and by optical and electron microscopy to evaluate the effects of the material and design choices.

Doubly stochastic radial basis function methods

NASA Astrophysics Data System (ADS)

Yang, Fenglian; Yan, Liang; Ling, Leevan

2018-06-01

We propose a doubly stochastic radial basis function (DSRBF) method for function recoveries. Instead of a constant, we treat the RBF shape parameters as stochastic variables whose distribution were determined by a stochastic leave-one-out cross validation (LOOCV) estimation. A careful operation count is provided in order to determine the ranges of all the parameters in our methods. The overhead cost for setting up the proposed DSRBF method is O (n2) for function recovery problems with n basis. Numerical experiments confirm that the proposed method not only outperforms constant shape parameter formulation (in terms of accuracy with comparable computational cost) but also the optimal LOOCV formulation (in terms of both accuracy and computational cost).

New positive Ca2+-activated K+ channel gating modulators with selectivity for KCa3.1.

PubMed

Coleman, Nichole; Brown, Brandon M; Oliván-Viguera, Aida; Singh, Vikrant; Olmstead, Marilyn M; Valero, Marta Sofia; Köhler, Ralf; Wulff, Heike

2014-09-01

Small-conductance (KCa2) and intermediate-conductance (KCa3.1) calcium-activated K(+) channels are voltage-independent and share a common calcium/calmodulin-mediated gating mechanism. Existing positive gating modulators like EBIO, NS309, or SKA-31 activate both KCa2 and KCa3.1 channels with similar potency or, as in the case of CyPPA and NS13001, selectively activate KCa2.2 and KCa2.3 channels. We performed a structure-activity relationship (SAR) study with the aim of optimizing the benzothiazole pharmacophore of SKA-31 toward KCa3.1 selectivity. We identified SKA-111 (5-methylnaphtho[1,2-d]thiazol-2-amine), which displays 123-fold selectivity for KCa3.1 (EC50 111 ± 27 nM) over KCa2.3 (EC50 13.7 ± 6.9 μM), and SKA-121 (5-methylnaphtho[2,1-d]oxazol-2-amine), which displays 41-fold selectivity for KCa3.1 (EC50 109 nM ± 14 nM) over KCa2.3 (EC50 4.4 ± 1.6 μM). Both compounds are 200- to 400-fold selective over representative KV (KV1.3, KV2.1, KV3.1, and KV11.1), NaV (NaV1.2, NaV1.4, NaV1.5, and NaV1.7), as well as CaV1.2 channels. SKA-121 is a typical positive-gating modulator and shifts the calcium-concentration response curve of KCa3.1 to the left. In blood pressure telemetry experiments, SKA-121 (100 mg/kg i.p.) significantly lowered mean arterial blood pressure in normotensive and hypertensive wild-type but not in KCa3.1(-/-) mice. SKA-111, which was found in pharmacokinetic experiments to have a much longer half-life and to be much more brain penetrant than SKA-121, not only lowered blood pressure but also drastically reduced heart rate, presumably through cardiac and neuronal KCa2 activation when dosed at 100 mg/kg. In conclusion, with SKA-121, we generated a KCa3.1-specific positive gating modulator suitable for further exploring the therapeutical potential of KCa3.1 activation. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Channel-morphology data for the Tongue River and selected tributaries, southeastern Montana, 2001-02

USGS Publications Warehouse

Chase, Katherine J.

2004-01-01

Coal-bed methane exploration and production have begun within the Tongue River watershed in southeastern Montana. The development of coal-bed methane requires production of large volumes of ground water, some of which may be discharged to streams, potentially increasing stream discharge and sediment load. Changes in stream discharge or sediment load may result in changes to channel morphology through changes in erosion and vegetation. These changes might be subtle and difficult to detect without baseline data that indicate stream-channel conditions before extensive coal-bed methane development began. In order to provide this baseline channel-morphology data, the U.S. Geological Survey, in cooperation with the Bureau of Land Management, collected channel-morphology data in 2001-02 to document baseline conditions for several reaches along the Tongue River and selected tributaries. This report presents channel-morphology data for five sites on the mainstem Tongue River and four sites on its tributaries. Bankfull, water-surface, and thalweg elevations, channel sections, and streambed-particle sizes were measured along reaches near streamflow-gaging stations. At each site, the channel was classified using methods described by Rosgen. For six sites, bankfull discharge was determined from the stage- discharge relation at the gage for the stage corresponding to the bankfull elevation. For three sites, the step-backwater computer model HEC-RAS was used to estimate bankfull discharge. Recurrence intervals for the bankfull discharge also were estimated for eight of the nine sites. Channel-morphology data for each site are presented in maps, tables, graphs, and photographs.

Doubly Robust Additive Hazards Models to Estimate Effects of a Continuous Exposure on Survival.

PubMed

Wang, Yan; Lee, Mihye; Liu, Pengfei; Shi, Liuhua; Yu, Zhi; Abu Awad, Yara; Zanobetti, Antonella; Schwartz, Joel D

2017-11-01

The effect of an exposure on survival can be biased when the regression model is misspecified. Hazard difference is easier to use in risk assessment than hazard ratio and has a clearer interpretation in the assessment of effect modifications. We proposed two doubly robust additive hazards models to estimate the causal hazard difference of a continuous exposure on survival. The first model is an inverse probability-weighted additive hazards regression. The second model is an extension of the doubly robust estimator for binary exposures by categorizing the continuous exposure. We compared these with the marginal structural model and outcome regression with correct and incorrect model specifications using simulations. We applied doubly robust additive hazard models to the estimation of hazard difference of long-term exposure to PM2.5 (particulate matter with an aerodynamic diameter less than or equal to 2.5 microns) on survival using a large cohort of 13 million older adults residing in seven states of the Southeastern United States. We showed that the proposed approaches are doubly robust. We found that each 1 μg m increase in annual PM2.5 exposure was associated with a causal hazard difference in mortality of 8.0 × 10 (95% confidence interval 7.4 × 10, 8.7 × 10), which was modified by age, medical history, socioeconomic status, and urbanicity. The overall hazard difference translates to approximately 5.5 (5.1, 6.0) thousand deaths per year in the study population. The proposed approaches improve the robustness of the additive hazards model and produce a novel additive causal estimate of PM2.5 on survival and several additive effect modifications, including social inequality.

Robust doubly charged nodal lines and nodal surfaces in centrosymmetric systems

NASA Astrophysics Data System (ADS)

Bzdušek, Tomáš; Sigrist, Manfred

2017-10-01

Weyl points in three spatial dimensions are characterized by a Z -valued charge—the Chern number—which makes them stable against a wide range of perturbations. A set of Weyl points can mutually annihilate only if their net charge vanishes, a property we refer to as robustness. While nodal loops are usually not robust in this sense, it has recently been shown using homotopy arguments that in the centrosymmetric extension of the AI symmetry class they nevertheless develop a Z2 charge analogous to the Chern number. Nodal loops carrying a nontrivial value of this Z2 charge are robust, i.e., they can be gapped out only by a pairwise annihilation and not on their own. As this is an additional charge independent of the Berry π -phase flowing along the band degeneracy, such nodal loops are, in fact, doubly charged. In this manuscript, we generalize the homotopy discussion to the centrosymmetric extensions of all Atland-Zirnbauer classes. We develop a tailored mathematical framework dubbed the AZ +I classification and show that in three spatial dimensions such robust and multiply charged nodes appear in four of such centrosymmetric extensions, namely, AZ +I classes CI and AI lead to doubly charged nodal lines, while D and BDI support doubly charged nodal surfaces. We remark that no further crystalline symmetries apart from the spatial inversion are necessary for their stability. We provide a description of the corresponding topological charges, and develop simple tight-binding models of various semimetallic and superconducting phases that exhibit these nodes. We also indicate how the concept of robust and multiply charged nodes generalizes to other spatial dimensions.

Selective blockade of TRPA1 channel attenuates pathological pain without altering noxious cold sensation or body temperature regulation.

PubMed

Chen, Jun; Joshi, Shailen K; DiDomenico, Stanley; Perner, Richard J; Mikusa, Joe P; Gauvin, Donna M; Segreti, Jason A; Han, Ping; Zhang, Xu-Feng; Niforatos, Wende; Bianchi, Bruce R; Baker, Scott J; Zhong, Chengmin; Simler, Gricelda H; McDonald, Heath A; Schmidt, Robert G; McGaraughty, Steve P; Chu, Katharine L; Faltynek, Connie R; Kort, Michael E; Reilly, Regina M; Kym, Philip R

2011-05-01

Despite the increasing interest in TRPA1 channel as a pain target, its role in cold sensation and body temperature regulation is not clear; the efficacy and particularly side effects resulting from channel blockade remain poorly understood. Here we use a potent, selective, and bioavailable antagonist to address these issues. A-967079 potently blocks human (IC(50): 51 nmol/L, electrophysiology, 67 nmol/L, Ca(2+) assay) and rat TRPA1 (IC(50): 101 nmol/L, electrophysiology, 289 nmol/L, Ca(2+) assay). It is >1000-fold selective over other TRP channels, and is >150-fold selective over 75 other ion channels, enzymes, and G-protein-coupled receptors. Oral dosing of A-967079 produces robust drug exposure in rodents, and exhibits analgesic efficacy in allyl isothiocyanate-induced nocifensive response and osteoarthritic pain in rats (ED(50): 23.2 mg/kg, p.o.). A-967079 attenuates cold allodynia produced by nerve injury but does not alter noxious cold sensation in naive animals, suggesting distinct roles of TRPA1 in physiological and pathological states. Unlike TRPV1 antagonists, A-967079 does not alter body temperature. It also does not produce locomotor or cardiovascular side effects. Collectively, these data provide novel insights into TRPA1 function and suggest that the selective TRPA1 blockade may present a viable strategy for alleviating pain without untoward side effects. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Gas phase reactions of doubly charged alkaline earth and transition metal(II)-ligand complexes generated by electrospray ionization

NASA Astrophysics Data System (ADS)

Kohler, Martin; Leary, Julie A.

1997-03-01

Doubly charged metal(II)-complexes of [alpha] 1-3, [alpha] 1-6 mannotriose and the conserved trimannosyl core pentasaccharide as well as doubly charged complexes of Co(II), Mn(II), Ca(II) and Sr(II) with acetonitrile generated by electrospray ionization were studied by low energy collision induced dissociation (CID). Two main fragmentation pathways were observed for the metal(II)-oligosaccharide complexes. Regardless of the coordinating metal, loss of a neutral dehydrohexose residue (162 Da) from the doubly charged precursor ion is observed, forming a doubly charged product ion. However, if the oligosaccharide is coordinated to Co(II) or Mn(II), loss of a dehydroxyhexose cation is also observed. Investigation of the low mass region of the mass spectra of the metal coordinated oligosaccharides revealed intense signals corresponding to [metal(II) + (CH3CN)n2+ (where n = 1-6) species which were being formed by the metal(II) ions and the acetonitrile present in the sample. Analysis of these metal(II)-acetonitrile complexes provided further insight into the processes occurring upon low energy CID of doubly charged metal complexes. The metal(II)-acetonitrile system showed neutral loss and ligand cleavage as observed with the oligosaccharide complexes, as well as a series of six different dissociation mechanisms, most notable among them reduction from [metal(II) + (CH3CN)n2+ to the bare [metal(I)]+ species by electron transfer. Depending on the metal and collision gas chosen, one observes electron transfer from the ligand to the metal, electron transfer from the collision gas to the metal, proton transfer between ligands, heterolytic cleavage of the ligands, reactive collisions and loss of neutral ligands.

Drainage basins, channels, and flow characteristics of selected streams in central Pennsylvania

USGS Publications Warehouse

Brush, Lucien M.

1961-01-01

The hydraulic, basin, and geologic characteristics of 16 selected streams in central Pennsylvania were measured for the purpose of studying the relations among these general characteristics and their process of development. The basic parameters which were measured include bankfull width and depth, channel slope, bed material size and shape, length of stream from drainage divide, and size of drainage area. The kinds of bedrock over which the streams flow were noted. In these streams the bankfull channel is filled by flows approximating the 2.3-year flood. By measuring the breadth and mean depth of the channel, it was possible to compute the bankfull mean velocity for each of the 119 sampling stations. These data were then used to compute the downstream changes in hydraulic geometry of the streams studied. This method has been called an indirect computation of the hydraulic geometry. The results obtained by the indirect method are similar to those of the direct method of other workers. The basins were studied by examining the relations of drainage area, discharge, and length of stream from drainage divide. For the streams investigated, excellent correlations were found to exist between drainage area and the 2.3-year flood, as well as between length of stream from the basin divide and drainage area. From these correlations it is possible to predict the discharge for the 2.3-year flood at any arbitrary point along the length of the stream. The long, intermediate, and short axes of pebbles sampled from the bed of the stream were recorded to study both size and sphericity changes along individual streams and among the streams studied. No systematic downstream changes in sphericity were found. Particle size changes are erratic and show no consistent relation to channel slope. Particle size decreases downstream in many streams but remains constant or increases in others. Addition of material by tributaries is one factor affecting particle size and another is the parent

Control Demonstration of Multiple Doubly-Fed Induction Motors for Hybrid Electric Propulsion

NASA Technical Reports Server (NTRS)

Sadey, David J.; Bodson, Marc; Csank, Jeffrey T.; Hunker, Keith R.; Theman, Casey J.; Taylor, Linda M.

2017-01-01

The Convergent Aeronautics Solutions (CAS) High Voltage-Hybrid Electric Propulsion (HVHEP) task was formulated to support the move into future hybrid-electric aircraft. The goal of this project is to develop a new AC power architecture to support the needs of higher efficiency and lower emissions. This proposed architecture will adopt the use of the doubly-fed induction machine (DFIM) for propulsor drive motor application.The Convergent Aeronautics Solutions (CAS) High Voltage-Hybrid Electric Propulsion (HVHEP) task was formulated to support the move into future hybrid-electric aircraft. The goal of this project is to develop a new AC power architecture to support the needs of higher efficiency and lower emissions. This proposed architecture will adopt the use of the doubly-fed induction machine (DFIM) for propulsor drive motor application. DFIMs are attractive for several reasons, including but not limited to the ability to self-start, ability to operate sub- and super-synchronously, and requiring only fractionally rated power converters on a per-unit basis depending on the required range of operation. The focus of this paper is based specifically on the presentation and analysis of a novel strategy which allows for independent operation of each of the aforementioned doubly-fed induction motors. This strategy includes synchronization, soft-start, and closed loop speed control of each motor as a means of controlling output thrust; be it concurrently or differentially. The demonstration of this strategy has recently been proven out on a low power test bed using fractional horsepower machines. Simulation and hardware test results are presented in the paper.

Design-Based Intervention Research as the Science of the Doubly Artificial

ERIC Educational Resources Information Center

Cole, Michael; Packer, Martin

2016-01-01

This article uses a variety of principles of cultural-historical activity theory to extend Herbert Simon's (1996) insight into the inherent linkage between the creation of artifacts and design. We argue that design research must grapple with the doubly artificial, as the classrooms in which many educational designs are implemented are themselves…

Selective spider toxins reveal a role for Nav1.1 channel in mechanical pain

PubMed Central

Osteen, Jeremiah D.; Herzig, Volker; Gilchrist, John; Emrick, Joshua J.; Zhang, Chuchu; Wang, Xidao; Castro, Joel; Garcia-Caraballo, Sonia; Grundy, Luke; Rychkov, Grigori Y.; Weyer, Andy D.; Dekan, Zoltan; Undheim, Eivind A. B.; Alewood, Paul; Stucky, Cheryl L.; Brierley, Stuart M.; Basbaum, Allan I.; Bosmans, Frank; King, Glenn F.; Julius, David

2016-01-01

Voltage-gated sodium (Nav) channels initiate action potentials in most neurons, including primary afferent nerve fibers of the pain pathway. Local anesthetics block pain through non-specific actions at all Nav channels, but the discovery of selective modulators would facilitate the analysis of individual subtypes and their contributions to chemical, mechanical, or thermal pain. Here, we identify and characterize spider toxins that selectively activate the Nav1.1 subtype, whose role in nociception and pain has not been explored. We exploit these probes to demonstrate that Nav1.1-expressing fibers are modality-specific nociceptors: their activation elicits robust pain behaviors without neurogenic inflammation and produces profound hypersensitivity to mechanical, but not thermal, stimuli. In the gut, high-threshold mechanosensitive fibers also express Nav1.1 and show enhanced toxin sensitivity in a model of irritable bowel syndrome. Altogether, these findings establish an unexpected role for Nav1.1 in regulating the excitability of sensory nerve fibers that underlie mechanical pain. PMID:27281198

Finite-SNR analysis for partial relaying cooperation with channel coding and opportunistic relay selection

NASA Astrophysics Data System (ADS)

Vu, Thang X.; Duhamel, Pierre; Chatzinotas, Symeon; Ottersten, Bjorn

2017-12-01

This work studies the performance of a cooperative network which consists of two channel-coded sources, multiple relays, and one destination. To achieve high spectral efficiency, we assume that a single time slot is dedicated to relaying. Conventional network-coded-based cooperation (NCC) selects the best relay which uses network coding to serve the two sources simultaneously. The bit error rate (BER) performance of NCC with channel coding, however, is still unknown. In this paper, we firstly study the BER of NCC via a closed-form expression and analytically show that NCC only achieves diversity of order two regardless of the number of available relays and the channel code. Secondly, we propose a novel partial relaying-based cooperation (PARC) scheme to improve the system diversity in the finite signal-to-noise ratio (SNR) regime. In particular, closed-form expressions for the system BER and diversity order of PARC are derived as a function of the operating SNR value and the minimum distance of the channel code. We analytically show that the proposed PARC achieves full (instantaneous) diversity order in the finite SNR regime, given that an appropriate channel code is used. Finally, numerical results verify our analysis and demonstrate a large SNR gain of PARC over NCC in the SNR region of interest.

Chemical substitutions in the selectivity filter of potassium channels do not rule out constricted-like conformations for C-type inactivation

PubMed Central

Li, Jing; Boulanger, Eliot; Rui, Huan; Perozo, Eduardo; Roux, Benoît

2017-01-01

In many K+ channels, prolonged activating stimuli lead to a time-dependent reduction in ion conduction, a phenomenon known as C-type inactivation. X-ray structures of the KcsA channel suggest that this inactivated state corresponds to a “constricted” conformation of the selectivity filter. However, the functional significance of the constricted conformation has become a matter of debate. Functional and structural studies based on chemically modified semisynthetic KcsA channels along the selectivity filter led to the conclusion that the constricted conformation does not correspond to the C-type inactivated state. The main results supporting this view include the observation that C-type inactivation is not suppressed by a substitution of D-alanine at Gly77, even though this modification is believed to lock the selectivity filter into its conductive conformation, whereas it is suppressed following amide-to-ester backbone substitutions at Gly77 and Tyr78, even though these structure-conserving modifications are not believed to prevent the selectivity filter from adopting the constricted conformation. However, several untested assumptions about the structural and functional impact of these chemical modifications underlie these arguments. To make progress, molecular dynamics simulations based on atomic models of the KcsA channel were performed. The computational results support the notion that the constricted conformation of the selectivity filter corresponds to the functional C-type inactivated state of the KcsA. Importantly, MD simulations reveal that the semisynthetic KcsAD-ala77 channel can adopt an asymmetrical constricted-like nonconductive conformation and that the amide-to-ester backbone substitutions at Gly77 and Tyr78 perturb the hydrogen bonding involving the buried water molecules stabilizing the constricted conformation. PMID:28973956

An embryo of protocells: The capsule of graphene with selective ion channels

PubMed Central

Li, Zhan; Wang, Chunmei; Tian, Longlong; Bai, Jing; Yao, Huijun; Zhao, Yang; Zhang, Xin; Cao, Shiwei; Qi, Wei; Wang, Suomin; Shi, Keliang; Xu, Youwen; Mingliang, Zhang; Liu, Bo; Qiu, Hongdeng; Liu, Jie; Wu, Wangsuo; Wang, Xiaoli; Wenzhen, An

2015-01-01

The synthesis of artificial cell is a route for searching the origin of protocell. Here, we create a novel cell model of graphene capsules with selective ion channels, indicating that graphene might be an embryo of protocell membrane. Firstly, we found that the highly oxidized graphene and phospholipid-graphene oxide composite would curl into capsules under a strongly acidic saturated solution of heavy metallic salt solution at low temperature. Secondly, L-amino acids exhibited higher reactivity than D-amino acids on graphene oxides to form peptides, and the formed peptides in the influence of graphene would be transformed into a secondary structure, promoting the formation of left-handed proteins. Lastly, monolayer nanoporous graphene, prepared by unfocused 84Kr25+, has a high selectivity for permeation of the monovalent metal ions ( Rb+ > K+ > Cs+ > Na+ > Li+, based on permeation concentration), but does not allow Cl- go through. It is similar to K+ channels, which would cause an influx of K+ into capsule of graphene with the increase of pH in the primitive ocean, creating a suitable inner condition for the origin of life. Therefore, we built a model cell of graphene, which would provide a route for reproducing the origin of life. PMID:25989440

An embryo of protocells: The capsule of graphene with selective ion channels

DOE PAGES

Li, Zhan; Wang, Chunmei; Tian, Longlong; ...

2015-05-19

In this study, the synthesis of artificial cell is a route for searching the origin of protocell. Here, we create a novel cell model of graphene capsules with selective ion channels, indicating that graphene might be an embryo of protocell membrane. Firstly, we found that the highly oxidized graphene and phospholipid-graphene oxide composite would curl into capsules under a strongly acidic saturated solution of heavy metallic salt solution at low temperature. Secondly, L-amino acids exhibited higher reactivity than D-amino acids on graphene oxides to form peptides, and the formed peptides in the influence of graphene would be transformed into amore » secondary structure, promoting the formation of left-handed proteins. Lastly, monolayer nanoporous graphene, prepared by unfocused 84Kr 25+, has a high selectivity for permeation of the monovalent metal ions ( Rb + > K + > Cs + > Na + > Li +, based on permeation concentration), but does not allow Cl- go through. It is similar to K+ channels, which would cause an influx of K + into capsule of graphene with the increase of pH in the primitive ocean, creating a suitable inner condition for the origin of life. Therefore, we built a model cell of graphene, which would provide a route for reproducing the origin of life.« less

Neural network based control of Doubly Fed Induction Generator in wind power generation

NASA Astrophysics Data System (ADS)

Barbade, Swati A.; Kasliwal, Prabha

2012-07-01

To complement the other types of pollution-free generation wind energy is a viable option. Previously wind turbines were operated at constant speed. The evolution of technology related to wind systems industry leaded to the development of a generation of variable speed wind turbines that present many advantages compared to the fixed speed wind turbines. In this paper the phasor model of DFIG is used. This paper presents a study of a doubly fed induction generator driven by a wind turbine connected to the grid, and controlled by artificial neural network ANN controller. The behaviour of the system is shown with PI control, and then as controlled by ANN. The effectiveness of the artificial neural network controller is compared to that of a PI controller. The SIMULINK/MATLAB simulation for Doubly Fed Induction Generator and corresponding results and waveforms are displayed.

Validation of doubly labeled water method using a ruminant

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

Fancy, S.G.; Blanchard, J.M.; Holleman, D.F.

1986-07-01

CO/sub 2/ production (CDP, ml CO/sub 2/ . g-1 . h-1) by captive caribou and reindeer (Rangifer tarandus) was measured using the doubly labeled water method (/sup 3/H/sub 2/O and H2(18)O) and compared with CO/sub 2/ expiration rates (VCO/sub 2/), adjusted for CO/sub 2/ losses in CH4 and urine, as determined by open-circuit respirometry. CDP calculated from samples of blood or urine from a reindeer in winter was 1-3% higher than the adjusted VCO/sub 2/. Differences between values derived by the two methods of 5-20% were found in summer trials with caribou. None of these differences were statistically significant (Pmore » greater than 0.05). Differences in summer could in part be explained by the net deposition of /sup 3/H, 18O, and unlabeled CO/sub 2/ in antlers and other growing tissues. Total body water volumes calculated from /sup 3/H/sub 2/O dilution were up to 15% higher than those calculated from H/sub 2/(18)O dilution. The doubly labeled water method appears to be a reasonably accurate method for measuring CDP by caribou and reindeer in winter when growth rates are low, but the method may overestimate CDP by rapidly growing and/or fattening animals.« less

Optimized Energy Harvesting, Cluster-Head Selection and Channel Allocation for IoTs in Smart Cities

PubMed Central

Aslam, Saleem; Hasan, Najam Ul; Jang, Ju Wook; Lee, Kyung-Geun

2016-01-01

This paper highlights three critical aspects of the internet of things (IoTs), namely (1) energy efficiency, (2) energy balancing and (3) quality of service (QoS) and presents three novel schemes for addressing these aspects. For energy efficiency, a novel radio frequency (RF) energy-harvesting scheme is presented in which each IoT device is associated with the best possible RF source in order to maximize the overall energy that the IoT devices harvest. For energy balancing, the IoT devices in close proximity are clustered together and then an IoT device with the highest residual energy is selected as a cluster head (CH) on a rotational basis. Once the CH is selected, it assigns channels to the IoT devices to report their data using a novel integer linear program (ILP)-based channel allocation scheme by satisfying their desired QoS. To evaluate the presented schemes, exhaustive simulations are carried out by varying different parameters, including the number of IoT devices, the number of harvesting sources, the distance between RF sources and IoT devices and the primary user (PU) activity of different channels. The simulation results demonstrate that our proposed schemes perform better than the existing ones. PMID:27918424

Optimized Energy Harvesting, Cluster-Head Selection and Channel Allocation for IoTs in Smart Cities.

PubMed

Aslam, Saleem; Hasan, Najam Ul; Jang, Ju Wook; Lee, Kyung-Geun

2016-12-02

This paper highlights three critical aspects of the internet of things (IoTs), namely (1) energy efficiency, (2) energy balancing and (3) quality of service (QoS) and presents three novel schemes for addressing these aspects. For energy efficiency, a novel radio frequency (RF) energy-harvesting scheme is presented in which each IoT device is associated with the best possible RF source in order to maximize the overall energy that the IoT devices harvest. For energy balancing, the IoT devices in close proximity are clustered together and then an IoT device with the highest residual energy is selected as a cluster head (CH) on a rotational basis. Once the CH is selected, it assigns channels to the IoT devices to report their data using a novel integer linear program (ILP)-based channel allocation scheme by satisfying their desired QoS. To evaluate the presented schemes, exhaustive simulations are carried out by varying different parameters, including the number of IoT devices, the number of harvesting sources, the distance between RF sources and IoT devices and the primary user (PU) activity of different channels. The simulation results demonstrate that our proposed schemes perform better than the existing ones.

Inversion of membrane surface charge by trivalent cations probed with a cation-selective channel

PubMed Central

Gurnev, Philip A.; Bezrukov, Sergey M.

2014-01-01

We demonstrate that the cation-selective channel formed by gramicidin A can be used as a reliable sensor for studying the multivalent ion accumulation at the surfaces of charged lipid membranes and the “charge inversion” phenomenon. In asymmetrically charged membranes with the individual leaflets formed from pure negative and positive lipids bathed by 0.1 M CsCl solutions the channel exhibits current rectification which is comparable to that of a typical n/p semiconductor diode. We show that even at these highly asymmetrical conditions the channel conductance can be satisfactorily described by the electrodiffusion equation in the constant field approximation but, due to predictable limitations, only when the applied voltages do not exceed 50 mV. Analysis of the changes in the voltage-dependent channel conductance upon addition of trivalent cations allows us to gauge their interactions with the membrane surface. The inversion of the sign of the effective surface charge takes place at the concentrations which correlate with the cation size. Specifically, these concentrations are close to 0.05 mM for lanthanum, 0.25 mM for hexaamminecobalt, and 4 mM for spermidine. PMID:23088396

Inversion of membrane surface charge by trivalent cations probed with a cation-selective channel.

PubMed

Gurnev, Philip A; Bezrukov, Sergey M

2012-11-13

We demonstrate that the cation-selective channel formed by gramicidin A can be used as a reliable sensor for studying the multivalent ion accumulation at the surfaces of charged lipid membranes and the "charge inversion" phenomenon. In asymmetrically charged membranes with the individual leaflets formed from pure negative and positive lipids bathed by 0.1 M CsCl solutions the channel exhibits current rectification, which is comparable to that of a typical n/p semiconductor diode. We show that even at these highly asymmetrical conditions the channel conductance can be satisfactorily described by the electrodiffusion equation in the constant field approximation but, due to predictable limitations, only when the applied voltages do not exceed 50 mV. Analysis of the changes in the voltage-dependent channel conductance upon addition of trivalent cations allows us to gauge their interactions with the membrane surface. The inversion of the sign of the effective surface charge takes place at the concentrations, which correlate with the cation size. Specifically, these concentrations are close to 0.05 mM for lanthanum, 0.25 mM for hexaamminecobalt, and 4 mM for spermidine.

The transport kinetics and selectivity of HpUreI, the urea channel from Helicobacter pylori†

PubMed Central

Gray, Lawrence R; Gu, Sean X; Quick, Matthias; Khademi, Shahram

2017-01-01

Helicobacter pylori’s unique ability to colonize and survive in the acidic environment of the stomach is critically dependent on uptake of urea through the urea channel, HpUreI. Hence, HpUreI may represent a promising target for the development of specific drugs against this human pathogen. To obtain insight into the structure/function relationship of this channel, we have developed conditions for the high-yield expression and purification of stable recombinant HpUreI that allowed its detailed kinetic characterization in solubilized form and reconstituted into liposomes. Detergent-solubilized HpUreI forms homo-trimer, as determined by chemical cross-linking. Urea dissociation kinetics of purified HpUreI were determined by means of the scintillation proximity assay (SPA), whereas urea efflux was measured in HpUreI-containing proteoliposomes using stopped-flow spectrometry to determine the kinetics and selectivity of the urea channel. The kinetic analyses revealed that urea conduction in HpUreI is pH sensitive and saturable with a half-saturation concentration (or K0.5) of ~163 mM. Binding of urea by HpUreI was increased at lower pH; however, the apparent affinity of urea binding (~150 mM) was not significantly pH dependent. The solute selectivity analysis indicated that HpUreI is highly selective for urea and hydroxyurea. Removing either amino group of urea molecules diminishes their permeability through HpUreI. Similar to urea conduction, water diffusion through HpUreI is pH-dependent with low water permeability at neutral pH. PMID:21877689

Use of navigation channels by Lake Sturgeon: Does channelization increase vulnerability of fish to ship strikes?

PubMed

Hondorp, Darryl W; Bennion, David H; Roseman, Edward F; Holbrook, Christopher M; Boase, James C; Chiotti, Justin A; Thomas, Michael V; Wills, Todd C; Drouin, Richard G; Kessel, Steven T; Krueger, Charles C

2017-01-01

Channelization for navigation and flood control has altered the hydrology and bathymetry of many large rivers with unknown consequences for fish species that undergo riverine migrations. In this study, we investigated whether altered flow distributions and bathymetry associated with channelization attracted migrating Lake Sturgeon (Acipenser fulvescens) into commercial navigation channels, potentially increasing their exposure to ship strikes. To address this question, we quantified and compared Lake Sturgeon selection for navigation channels vs. alternative pathways in two multi-channel rivers differentially affected by channelization, but free of barriers to sturgeon movement. Acoustic telemetry was used to quantify Lake Sturgeon movements. Under the assumption that Lake Sturgeon navigate by following primary flow paths, acoustic-tagged Lake Sturgeon in the more-channelized lower Detroit River were expected to choose navigation channels over alternative pathways and to exhibit greater selection for navigation channels than conspecifics in the less-channelized lower St. Clair River. Consistent with these predictions, acoustic-tagged Lake Sturgeon in the more-channelized lower Detroit River selected the higher-flow and deeper navigation channels over alternative migration pathways, whereas in the less-channelized lower St. Clair River, individuals primarily used pathways alternative to navigation channels. Lake Sturgeon selection for navigation channels as migratory pathways also was significantly higher in the more-channelized lower Detroit River than in the less-channelized lower St. Clair River. We speculated that use of navigation channels over alternative pathways would increase the spatial overlap of commercial vessels and migrating Lake Sturgeon, potentially enhancing their vulnerability to ship strikes. Results of our study thus demonstrated an association between channelization and the path use of migrating Lake Sturgeon that could prove important for

Use of navigation channels by Lake Sturgeon: Does channelization increase vulnerability of fish to ship strikes?

PubMed Central

Bennion, David H.; Roseman, Edward F.; Holbrook, Christopher M.; Boase, James C.; Chiotti, Justin A.; Thomas, Michael V.; Wills, Todd C.; Drouin, Richard G.; Kessel, Steven T.; Krueger, Charles C.

2017-01-01

Channelization for navigation and flood control has altered the hydrology and bathymetry of many large rivers with unknown consequences for fish species that undergo riverine migrations. In this study, we investigated whether altered flow distributions and bathymetry associated with channelization attracted migrating Lake Sturgeon (Acipenser fulvescens) into commercial navigation channels, potentially increasing their exposure to ship strikes. To address this question, we quantified and compared Lake Sturgeon selection for navigation channels vs. alternative pathways in two multi-channel rivers differentially affected by channelization, but free of barriers to sturgeon movement. Acoustic telemetry was used to quantify Lake Sturgeon movements. Under the assumption that Lake Sturgeon navigate by following primary flow paths, acoustic-tagged Lake Sturgeon in the more-channelized lower Detroit River were expected to choose navigation channels over alternative pathways and to exhibit greater selection for navigation channels than conspecifics in the less-channelized lower St. Clair River. Consistent with these predictions, acoustic-tagged Lake Sturgeon in the more-channelized lower Detroit River selected the higher-flow and deeper navigation channels over alternative migration pathways, whereas in the less-channelized lower St. Clair River, individuals primarily used pathways alternative to navigation channels. Lake Sturgeon selection for navigation channels as migratory pathways also was significantly higher in the more-channelized lower Detroit River than in the less-channelized lower St. Clair River. We speculated that use of navigation channels over alternative pathways would increase the spatial overlap of commercial vessels and migrating Lake Sturgeon, potentially enhancing their vulnerability to ship strikes. Results of our study thus demonstrated an association between channelization and the path use of migrating Lake Sturgeon that could prove important for

ProTx-II, a selective inhibitor of NaV1.7 sodium channels, blocks action potential propagation in nociceptors.

PubMed

Schmalhofer, William A; Calhoun, Jeffrey; Burrows, Rachel; Bailey, Timothy; Kohler, Martin G; Weinglass, Adam B; Kaczorowski, Gregory J; Garcia, Maria L; Koltzenburg, Martin; Priest, Birgit T

2008-11-01

Voltage-gated sodium (Na(V)1) channels play a critical role in modulating the excitability of sensory neurons, and human genetic evidence points to Na(V)1.7 as an essential contributor to pain signaling. Human loss-of-function mutations in SCN9A, the gene encoding Na(V)1.7, cause channelopathy-associated indifference to pain (CIP), whereas gain-of-function mutations are associated with two inherited painful neuropathies. Although the human genetic data make Na(V)1.7 an attractive target for the development of analgesics, pharmacological proof-of-concept in experimental pain models requires Na(V)1.7-selective channel blockers. Here, we show that the tarantula venom peptide ProTx-II selectively interacts with Na(V)1.7 channels, inhibiting Na(V)1.7 with an IC(50) value of 0.3 nM, compared with IC(50) values of 30 to 150 nM for other heterologously expressed Na(V)1 subtypes. This subtype selectivity was abolished by a point mutation in DIIS3. It is interesting that application of ProTx-II to desheathed cutaneous nerves completely blocked the C-fiber compound action potential at concentrations that had little effect on Abeta-fiber conduction. ProTx-II application had little effect on action potential propagation of the intact nerve, which may explain why ProTx-II was not efficacious in rodent models of acute and inflammatory pain. Mono-iodo-ProTx-II ((125)I-ProTx-II) binds with high affinity (K(d) = 0.3 nM) to recombinant hNa(V)1.7 channels. Binding of (125)I-ProTx-II is insensitive to the presence of other well characterized Na(V)1 channel modulators, suggesting that ProTx-II binds to a novel site, which may be more conducive to conferring subtype selectivity than the site occupied by traditional local anesthetics and anticonvulsants. Thus, the (125)I-ProTx-II binding assay, described here, offers a new tool in the search for novel Na(V)1.7-selective blockers.

Message passing with queues and channels

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

Dozsa, Gabor J; Heidelberger, Philip; Kumar, Sameer

In an embodiment, a send thread receives an identifier that identifies a destination node and a pointer to data. The send thread creates a first send request in response to the receipt of the identifier and the data pointer. The send thread selects a selected channel from among a plurality of channels. The selected channel comprises a selected hand-off queue and an identification of a selected message unit. Each of the channels identifies a different message unit. The selected hand-off queue is randomly accessible. If the selected hand-off queue contains an available entry, the send thread adds the first sendmore » request to the selected hand-off queue. If the selected hand-off queue does not contain an available entry, the send thread removes a second send request from the selected hand-off queue and sends the second send request to the selected message unit.« less

Enhancement of the NMSU Channel Error Simulator to Provide User-Selectable Link Delays

NASA Technical Reports Server (NTRS)

Horan, Stephen; Wang, Ru-Hai

2000-01-01

This is the third in a continuing series of reports describing the development of the Space-to-Ground Link Simulator (SGLS) to be used for testing data transfers under simulated space channel conditions. The SGLS is based upon Virtual Instrument (VI) software techniques for managing the error generation, link data rate configuration, and, now, selection of the link delay value. In this report we detail the changes that needed to be made to the SGLS VI configuration to permit link delays to be added to the basic error generation and link data rate control capabilities. This was accomplished by modifying the rate-splitting VIs to include a buffer the hold the incoming data for the duration selected by the user to emulate the channel link delay. In sample tests of this configuration, the TCP/IP(sub ftp) service and the SCPS(sub fp) service were used to transmit 10-KB data files using both symmetric (both forward and return links set to 115200 bps) and unsymmetric (forward link set at 2400 bps and a return link set at 115200 bps) link configurations. Transmission times were recorded at bit error rates of 0 through 10(exp -5) to give an indication of the link performance. In these tests. we noted separate timings for the protocol setup time to initiate the file transfer and the variation in the actual file transfer time caused by channel errors. Both protocols showed similar performance to that seen earlier for the symmetric and unsymmetric channels. This time, the delays in establishing the file protocol also showed that these delays could double the transmission time and need to be accounted for in mission planning. Both protocols also showed a difficulty in transmitting large data files over large link delays. In these tests, there was no clear favorite between the TCP/IP(sub ftp) and the SCPS(sub fp). Based upon these tests, further testing is recommended to extend the results to different file transfer configurations.

Quark-level analogue of nuclear fusion with doubly heavy baryons.

PubMed

Karliner, Marek; Rosner, Jonathan L

2017-11-01

The essence of nuclear fusion is that energy can be released by the rearrangement of nucleons between the initial- and final-state nuclei. The recent discovery of the first doubly charmed baryon , which contains two charm quarks (c) and one up quark (u) and has a mass of about 3,621 megaelectronvolts (MeV) (the mass of the proton is 938 MeV) also revealed a large binding energy of about 130 MeV between the two charm quarks. Here we report that this strong binding enables a quark-rearrangement, exothermic reaction in which two heavy baryons (Λ c ) undergo fusion to produce the doubly charmed baryon and a neutron n (), resulting in an energy release of 12 MeV. This reaction is a quark-level analogue of the deuterium-tritium nuclear fusion reaction (DT → 4 He n). The much larger binding energy (approximately 280 MeV) between two bottom quarks (b) causes the analogous reaction with bottom quarks () to have a much larger energy release of about 138 MeV. We suggest some experimental setups in which the highly exothermic nature of the fusion of two heavy-quark baryons might manifest itself. At present, however, the very short lifetimes of the heavy bottom and charm quarks preclude any practical applications of such reactions.

Quark-level analogue of nuclear fusion with doubly heavy baryons

NASA Astrophysics Data System (ADS)

Karliner, Marek; Rosner, Jonathan L.

2017-11-01

The essence of nuclear fusion is that energy can be released by the rearrangement of nucleons between the initial- and final-state nuclei. The recent discovery of the first doubly charmed baryon , which contains two charm quarks (c) and one up quark (u) and has a mass of about 3,621 megaelectronvolts (MeV) (the mass of the proton is 938 MeV) also revealed a large binding energy of about 130 MeV between the two charm quarks. Here we report that this strong binding enables a quark-rearrangement, exothermic reaction in which two heavy baryons (Λc) undergo fusion to produce the doubly charmed baryon and a neutron n (), resulting in an energy release of 12 MeV. This reaction is a quark-level analogue of the deuterium-tritium nuclear fusion reaction (DT → 4He n). The much larger binding energy (approximately 280 MeV) between two bottom quarks (b) causes the analogous reaction with bottom quarks () to have a much larger energy release of about 138 MeV. We suggest some experimental setups in which the highly exothermic nature of the fusion of two heavy-quark baryons might manifest itself. At present, however, the very short lifetimes of the heavy bottom and charm quarks preclude any practical applications of such reactions.

Bit error rate performance of pi/4-DQPSK in a frequency-selective fast Rayleigh fading channel

NASA Technical Reports Server (NTRS)

Liu, Chia-Liang; Feher, Kamilo

1991-01-01

The bit error rate (BER) performance of pi/4-differential quadrature phase shift keying (DQPSK) modems in cellular mobile communication systems is derived and analyzed. The system is modeled as a frequency-selective fast Rayleigh fading channel corrupted by additive white Gaussian noise (AWGN) and co-channel interference (CCI). The probability density function of the phase difference between two consecutive symbols of M-ary differential phase shift keying (DPSK) signals is first derived. In M-ary DPSK systems, the information is completely contained in this phase difference. For pi/4-DQPSK, the BER is derived in a closed form and calculated directly. Numerical results show that for the 24 kBd (48 kb/s) pi/4-DQPSK operated at a carrier frequency of 850 MHz and C/I less than 20 dB, the BER will be dominated by CCI if the vehicular speed is below 100 mi/h. In this derivation, frequency-selective fading is modeled by two independent Rayleigh signal paths. Only one co-channel is assumed in this derivation. The results obtained are also shown to be valid for discriminator detection of M-ary DPSK signals.

Expression and purification of native and functional influenza A virus matrix 2 proton selective ion channel.

PubMed

Desuzinges Mandon, Elodie; Traversier, Aurélien; Champagne, Anne; Benier, Lorraine; Audebert, Stéphane; Balme, Sébastien; Dejean, Emmanuel; Rosa Calatrava, Manuel; Jawhari, Anass

2017-03-01

Influenza A virus displays one of the highest infection rates of all human viruses and therefore represents a severe human health threat associated with an important economical challenge. Influenza matrix protein 2 (M2) is a membrane protein of the viral envelope that forms a proton selective ion channel. Here we report the expression and native isolation of full length active M2 without mutations or fusions. The ability of the influenza virus to efficiently infect MDCK cells was used to express native M2 protein. Using a Calixarene detergents/surfactants based approach; we were able to solubilize most of M2 from the plasma membrane and purify it. The tetrameric form of native M2 was maintained during the protein preparation. Mass spectrometry shows that M2 was phosphorylated in its cytoplasmic tail (serine 64) and newly identifies an acetylation of the highly conserved Lysine 60. ELISA shows that solubilized and purified M2 was specifically recognized by M2 antibody MAB65 and was able to displace the antibody from M2 MDCK membranes. Using a bilayer voltage clamp measurement assay, we demonstrate a pH dependent proton selective ion channel activity. The addition of the M2 ion channel blocker amantadine allows a total inhibition of the channel activity, illustrating therefore the specificity of purified M2 activity. Taken together, this work shows the production and isolation of a tetrameric and functional native M2 ion channel that will pave the way to structural and functional characterization of native M2, conformational antibody development, small molecules compounds screening towards vaccine treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Macrolides selectively inhibit mutant KCNJ5 potassium channels that cause aldosterone-producing adenoma

PubMed Central

Scholl, Ute I.; Abriola, Laura; Zhang, Chengbiao; Reimer, Esther N.; Plummer, Mark; Zhang, Junhui; Hoyer, Denton; Merkel, Jane S.; Wang, Wenhui; Lifton, Richard P.

2017-01-01

Aldosterone-producing adenomas (APAs) are benign tumors of the adrenal gland that constitutively produce the salt-retaining steroid hormone aldosterone and cause millions of cases of severe hypertension worldwide. Either of 2 somatic mutations in the potassium channel KCNJ5 (G151R and L168R, hereafter referred to as KCNJ5MUT) in adrenocortical cells account for half of APAs worldwide. These mutations alter channel selectivity to allow abnormal Na+ conductance, resulting in membrane depolarization, calcium influx, aldosterone production, and cell proliferation. Because APA diagnosis requires a difficult invasive procedure, patients often remain undiagnosed and inadequately treated. Inhibitors of KCNJ5MUT could allow noninvasive diagnosis and therapy of APAs carrying KCNJ5 mutations. Here, we developed a high-throughput screen for rescue of KCNJ5MUT-induced lethality and identified a series of macrolide antibiotics, including roxithromycin, that potently inhibit KCNJ5MUT, but not KCNJ5WT. Electrophysiology demonstrated direct KCNJ5MUT inhibition. In human aldosterone-producing adrenocortical cancer cell lines, roxithromycin inhibited KCNJ5MUT-induced induction of CYP11B2 (encoding aldosterone synthase) expression and aldosterone production. Further exploration of macrolides showed that KCNJ5MUT was similarly selectively inhibited by idremcinal, a macrolide motilin receptor agonist, and by synthesized macrolide derivatives lacking antibiotic or motilide activity. Macrolide-derived selective KCNJ5MUT inhibitors thus have the potential to advance the diagnosis and treatment of APAs harboring KCNJ5MUT. PMID:28604387

Macrolides selectively inhibit mutant KCNJ5 potassium channels that cause aldosterone-producing adenoma.

PubMed

Scholl, Ute I; Abriola, Laura; Zhang, Chengbiao; Reimer, Esther N; Plummer, Mark; Kazmierczak, Barbara I; Zhang, Junhui; Hoyer, Denton; Merkel, Jane S; Wang, Wenhui; Lifton, Richard P

2017-06-30

Aldosterone-producing adenomas (APAs) are benign tumors of the adrenal gland that constitutively produce the salt-retaining steroid hormone aldosterone and cause millions of cases of severe hypertension worldwide. Either of 2 somatic mutations in the potassium channel KCNJ5 (G151R and L168R, hereafter referred to as KCNJ5MUT) in adrenocortical cells account for half of APAs worldwide. These mutations alter channel selectivity to allow abnormal Na+ conductance, resulting in membrane depolarization, calcium influx, aldosterone production, and cell proliferation. Because APA diagnosis requires a difficult invasive procedure, patients often remain undiagnosed and inadequately treated. Inhibitors of KCNJ5MUT could allow noninvasive diagnosis and therapy of APAs carrying KCNJ5 mutations. Here, we developed a high-throughput screen for rescue of KCNJ5MUT-induced lethality and identified a series of macrolide antibiotics, including roxithromycin, that potently inhibit KCNJ5MUT, but not KCNJ5WT. Electrophysiology demonstrated direct KCNJ5MUT inhibition. In human aldosterone-producing adrenocortical cancer cell lines, roxithromycin inhibited KCNJ5MUT-induced induction of CYP11B2 (encoding aldosterone synthase) expression and aldosterone production. Further exploration of macrolides showed that KCNJ5MUT was similarly selectively inhibited by idremcinal, a macrolide motilin receptor agonist, and by synthesized macrolide derivatives lacking antibiotic or motilide activity. Macrolide-derived selective KCNJ5MUT inhibitors thus have the potential to advance the diagnosis and treatment of APAs harboring KCNJ5MUT.

Adaptive real time selection for quantum key distribution in lossy and turbulent free-space channels

NASA Astrophysics Data System (ADS)

Vallone, Giuseppe; Marangon, Davide G.; Canale, Matteo; Savorgnan, Ilaria; Bacco, Davide; Barbieri, Mauro; Calimani, Simon; Barbieri, Cesare; Laurenti, Nicola; Villoresi, Paolo

2015-04-01

The unconditional security in the creation of cryptographic keys obtained by quantum key distribution (QKD) protocols will induce a quantum leap in free-space communication privacy in the same way that we are beginning to realize secure optical fiber connections. However, free-space channels, in particular those with long links and the presence of atmospheric turbulence, are affected by losses, fluctuating transmissivity, and background light that impair the conditions for secure QKD. Here we introduce a method to contrast the atmospheric turbulence in QKD experiments. Our adaptive real time selection (ARTS) technique at the receiver is based on the selection of the intervals with higher channel transmissivity. We demonstrate, using data from the Canary Island 143-km free-space link, that conditions with unacceptable average quantum bit error rate which would prevent the generation of a secure key can be used once parsed according to the instantaneous scintillation using the ARTS technique.

Terbinafine is a novel and selective activator of the two-pore domain potassium channel TASK3.

PubMed

Wright, Paul D; Veale, Emma L; McCoull, David; Tickle, David C; Large, Jonathan M; Ococks, Emma; Gothard, Gemma; Kettleborough, Catherine; Mathie, Alistair; Jerman, Jeffrey

2017-11-04

Two-pore domain potassium channels (K2Ps) are characterized by their four transmembrane domain and two-pore topology. They carry background (or leak) potassium current in a variety of cell types. Despite a number of important roles there is currently a lack of pharmacological tools with which to further probe K2P function. We have developed a cell-based thallium flux assay, using baculovirus delivered TASK3 (TWIK-related acid-sensitive K + channel 3, KCNK9, K2P9.1) with the aim of identifying novel, selective TASK3 activators. After screening a library of 1000 compounds, including drug-like and FDA approved molecules, we identified Terbinafine as an activator of TASK3. In a thallium flux assay a pEC50 of 6.2 ( ±0.12) was observed. When Terbinafine was screened against TASK2, TREK2, THIK1, TWIK1 and TRESK no activation was observed in thallium flux assays. Several analogues of Terbinafine were also purchased and structure activity relationships examined. To confirm Terbinafine's activation of TASK3 whole cell patch clamp electrophysiology was carried out and clear potentiation observed in both the wild type channel and the pathophysiological, Birk-Barel syndrome associated, G236R TASK3 mutant. No activity at TASK1 was observed in electrophysiology studies. In conclusion, we have identified the first selective activator of the two-pore domain potassium channel TASK3. Copyright © 2017 Elsevier Inc. All rights reserved.

Energy expenditure in space flight (doubly labelled water method) (8-IML-1)

NASA Technical Reports Server (NTRS)

Parsons, Howard G.

1992-01-01

The objective of the Energy Expenditure in Space Flight (ESS) experiment is to demonstrate and evaluate the doubly labeled water method of measuring the energy expended by crew members during approximately 7 days in microgravity. The doubly labeled water technique determines carbon dioxide production which is then used to calculate energy expenditure. The method relies on the equilibrium between oxygen in respiratory carbon dioxide and oxygen in body water. Because of this equilibrium, the kinetic of water turnover and respiration are interdependent. Under normal conditions, man contains small but significant amounts of deuterium and oxygen 18. Deuterium is eliminated from the body as water while oxygen 18 is eliminated as water and carbon dioxide. The difference in the turnover rates in the two isotopes is proportional to the carbon dioxide production. Deliberately enriching the total body water with both of these isotopes allows the isotope turnovers to be accurately measured in urine, plasma, or saliva samples. The samples are taken to the laboratory for analysis using an ion-ratio spectrometer.

Isotachophoresis system having larger-diameter channels flowing into channels with reduced diameter and with selectable counter-flow

DOEpatents

Mariella, Jr., Raymond P.

2018-03-06

An isotachophoresis system for separating a sample containing particles into discrete packets including a flow channel, the flow channel having a large diameter section and a small diameter section; a negative electrode operably connected to the flow channel; a positive electrode operably connected to the flow channel; a leading carrier fluid in the flow channel; a trailing carrier fluid in the flow channel; and a control for separating the particles in the sample into discrete packets using the leading carrier fluid, the trailing carrier fluid, the large diameter section, and the small diameter section.

Doubly robust estimation of generalized partial linear models for longitudinal data with dropouts.

PubMed

Lin, Huiming; Fu, Bo; Qin, Guoyou; Zhu, Zhongyi

2017-12-01

We develop a doubly robust estimation of generalized partial linear models for longitudinal data with dropouts. Our method extends the highly efficient aggregate unbiased estimating function approach proposed in Qu et al. (2010) to a doubly robust one in the sense that under missing at random (MAR), our estimator is consistent when either the linear conditional mean condition is satisfied or a model for the dropout process is correctly specified. We begin with a generalized linear model for the marginal mean, and then move forward to a generalized partial linear model, allowing for nonparametric covariate effect by using the regression spline smoothing approximation. We establish the asymptotic theory for the proposed method and use simulation studies to compare its finite sample performance with that of Qu's method, the complete-case generalized estimating equation (GEE) and the inverse-probability weighted GEE. The proposed method is finally illustrated using data from a longitudinal cohort study. © 2017, The International Biometric Society.

On the Structural Basis for Size-selective Permeation of Organic Cations through the Voltage-gated Sodium Channel

PubMed Central

Sun, Ye-Ming; Favre, Isabelle; Schild, Laurent; Moczydlowski, Edward

1997-01-01

Recent evidence indicates that ionic selectivity in voltage-gated Na+ channels is mediated by a small number of residues in P-region segments that link transmembrane elements S5 and S6 in each of four homologous domains denoted I, II, III, and IV. Important determinants for this function appear to be a set of conserved charged residues in the first three homologous domains, Asp(I), Glu(II), and Lys(III), located in a region of the pore called the DEKA locus. In this study, we examined several Ala-substitution mutations of these residues for alterations in ionic selectivity, inhibition of macroscopic current by external Ca2+ and H+, and molecular sieving behavior using a series of organic cations ranging in size from ammonium to tetraethylammonium. Whole-cell recording of wild-type and mutant channels of the rat muscle μ1 Na+ channel stably expressed in HEK293 cells was used to compare macroscopic current–voltage behavior in the presence of various external cations and an intracellular reference solution containing Cs+ and very low Ca2+. In particular, we tested the hypothesis that the Lys residue in domain III of the DEKA locus is responsible for restricting the permeation of large organic cations. Mutation of Lys(III) to Ala largely eliminated selectivity among the group IA monovalent alkali cations (Li+, Na+, K+, Rb+, Cs+) and permitted inward current of group IIA divalent cations (Mg2+, Ca2+, Sr2+, Ba2+). This same mutation also resulted in the acquisition of permeability to many large organic cations such as methylammonium, tetramethylammonium, and tetraethylammonium, all of which are impermeant in the native channel. The results lead to the conclusion that charged residues of the DEKA locus play an important role in molecular sieving behavior of the Na+ channel pore, a function that has been previously attributed to a hypothetical region of the channel called the “selectivity filter.” A detailed examination of individual contributions of the Asp(I), Glu

Laser-induced breakup of helium 3S 1s2s with intermediate doubly excited states

NASA Astrophysics Data System (ADS)

Simonsen, A. S.; Bachau, H.; Førre, M.

2014-02-01

Solving the time-dependent Schrödinger equation in full dimensionality for two electrons, it is found that in the XUV regime the two-photon double ionization dynamics of He(1s2s) is predominantly dictated by the process of resonance enhanced multiphoton ionization via doubly excited states (DESs). We have studied a pump-probe scenario where the full laser-driven breakup of the 3S 1s2s metastable state is dominated by intermediate quasiresonant excitation to doubly excited (autoionizing) states in the 3Po series. Clear evidence of multipath interference effects is revealed in the resulting angular distributions of the ejected electrons in cases where more than one intermediate DES is populated in the process.

Selective filling for patterning in microfluidic channels and integration of chromatography in "lab-on-a-chip" devices using sol-gel technology

NASA Astrophysics Data System (ADS)

Jindal, Rohit

The last decade has seen tremendous advancement in the development of miniaturized chemical analysis system also known as "lab-on-a-chip". It is believed that the true potential of these devices will be achieved by integrating various functions such as separation, reaction, sensing, mixing, pumping, injection and detection onto a single chip. The ability to pattern different functionalities is indispensable for the development of highly integrated devices. In this work, a simple method based on the concept of selective filling is described for patterning in the microfluidic channels. It is based on the difference in the free energy of filling between an open and a covered part of the channel. This method was used for the integration of chromatography in the microfluidic devices. A chromatographic column was realized by utilizing sol-gel as an immobilization matrix for entrapping reversed phase chromatographic particles. Localization of the stationary phase was achieved using the selective filling technique. Channels were fabricated in quartz using photolithography and wet etching. Electroosmotic flow was used for manipulating fluid movement in the channels. Cross channel design was used for making a pulse injection of the solutes in the separation channel. An optical fiber setup was developed for carrying out on-chip UV absorbance detection. Stationary phase was created under different sol-gel synthesis conditions. It was established that the sol-gel synthesis carried out under acidic conditions provides the optimum synthesis conditions for creating separation column. Chromatographic performance of the stationary phase material was demonstrated by separating peptides present in a mixture. The sol-gel immobilization method was extended for the integration of micropump in the chip. The micropump enables pumping of the fluid in field free channels. Preliminary results, demonstrating the potential of carbon nanotubes as a support material in the microfluidic channels

Receptor model for the molecular basis of tissue selectivity of 1,4-dihydropyridine calcium channel drugs

NASA Astrophysics Data System (ADS)

Langs, David A.; Strong, Phyllis D.; Triggle, David J.

1990-09-01

Our analysis of the solid state conformations of nifedipine [dimethyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinecarboxylate] and its 1,4-dihydropyridine (1,4-DHP) analogues produced a cartoon description of the important interactions between these drugs and their voltage-dependent calcium channel receptor. In the present study a molecular-level detailed model of the 1,4-DHP receptor binding site has been built from the published amino acid sequence of the 215-1 subunit of the voltage-dependent calcium channel isolated from rabbit skeletal muscle transverse tubule membranes. The voltage-sensing component of the channel described in this work differs from others reported for the homologous sodium channel in that it incorporates a water structure and a staggered, rather than eclipsed, hydrogen bonded S4 helix conformation. The major recognition surfaces of the receptor lie in helical grooves on the S4 or voltagesensing α-helix that is positioned in the center of the bundle of transmembrane helices that define each of the four calcium channel domains. Multiple binding clefts defined by Arg-X-X-Arg-P-X-X-S `reading frames' exist on the S4 strand. The tissue selectivity of nifedipine and its analogues may arise, in part, from conservative changes in the amino acid residues at the P and S positions of the reading frame that define the ester-binding regions of receptors from different tissues. The crystal structures of two tissue-selective nifedipine analogues, nimodipine [isopropyl (2-methoxyethyl) 1,4-dihydro-2,6- dimethyl-4-(3-nitrophenyl)-3,5-pyridinecarboxylate] and nitrendipine [ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinecarboxylate] are reported. Nimodipine was observed to have an unusual ester side chain conformation that enhances the fit to the proposed ester-sensing region of the receptor.

Advantages of reaction cell ICP-MS on doubly charged interferences for arsenic and selenium analysis in foods

PubMed Central

Jackson, Brian; Liba, Amir; Nelson, Jenny

2014-01-01

Recent reports of As concentrations in certain food and drinks have garnered public concern and led to a lowering of the US guideline maximum concentration for inorganic As in apple juice and proposed limits for As in rice products. In contrast Se is an essential micro-nutrient that can be limiting when Se-poor soils yield Se-poor food crops. Rare earth element (REE) doubly charged interferences on As and Se can be significant even when initial ICP-MS tuning minimizes doubly charged formation. We analyzed NIST 1547 (peach leaves) and 1515 (apple leaves), which contain high levels of REEs, by quadrupole ICP-MS with (He) collision mode, H2 reaction mode or triple quadrupole ICP-MS (ICP-QQQ) in mass-shift mode (O2 and O2/H2). Analysis by collision cell ICP-MS significantly over-estimated As and Se concentration due to REE doubly charged formation; mathematical correction increased the accuracy of analysis but is prone to error when analyte concentration and sensitivity is low and interferent is high. For Se, H2 reaction mode was effective in suppressing Gd2+ leading to accurate determination of Se in both SRMs without the need for mathematical correction. ICP-QQQ using mass-shift mode for As+ from m/z 75 to AsO+ at m/z 91 and Se+ from m/z 78 to SeO+ at m/z 94 alleviated doubly charged effects and resulted in accurate determination of As and Se in both SRMs without the need for correction equations. Zr and Mo isobars at 91 and 94 were shown to be effectively rejected by the MS/MS capability of the ICP-QQQ. PMID:25609851

Recent (circa 1998 to 2011) channel-migration rates of selected streams in Indiana

USGS Publications Warehouse

Robinson, Bret A.

2013-01-01

An investigation was completed to document recent (circa 1998 to 2011) channel-migration rates at 970 meander bends along 38 of the largest streams in Indiana. Data collection was completed by using the Google Earth™ platform and, for each selected site, identifying two images with capture dates separated by multiple years. Within each image, the position of the meander-bend cutbank was measured relative to a fixed local landscape feature visible in both images, and an average channel-migration rate was calculated at the point of maximum cutbank displacement. From these data it was determined that 65 percent of the measured sites have recently been migrating at a rate less than 1 ft/yr, 75 percent of the sites have been migrating at a rate less than 10 ft/yr, and while some sites are migrating in excess of 20 ft/yr, these occurrences are rare. In addition, it is shown that recent channel-migration activity is not evenly distributed across Indiana. For the stream reaches studied, far northern and much of far southern Indiana are drained by streams that recently have been relatively stationary. At the same time, this study shows that most of the largest streams in west-central Indiana and many of the largest streams in east-central Indiana have shown significant channel-migration activity during the recent past. It is anticipated that these results will support several fluvial-erosion-hazard mitigation activities currently being undertaken in Indiana.

Experience of superheat of solutions: doubly metastable systems

NASA Astrophysics Data System (ADS)

Skripov, P. V.

2017-11-01

The phenomenon of attainable superheat of two-component mixtures has been studied experimentally by the method of pulse heating of a wire probe. Special attention was called to the appearance of double metastability in the course of heating. Besides the usual superheating with respect to the liquid-vapor equilibrium temperature, the objects under study turn out to be supersaturated with respect to the carbon dioxide content. Preliminary experiments were carried out in the region of instability located above the diffusion spinodal. The results obtained lead to the choice of the program of further research on doubly metastable and unstable systems with different degrees of component compatibility.

Doubly Vinylogous Aldol Reaction of Furoate Esters with Aldehydes and Ketones.

PubMed

Hartwig, William T; Sammakia, Tarek

2017-01-06

The use of bulky Lewis acids, aluminum tris(2,6-diphenylphenoxide) (ATPH) and aluminum tris(2,6-di-2-naphthylphenoxide) (ATNP), in the doubly vinylogous aldol reaction between methyl-5-methyl-2-furoate and aldehydes or ketones is described. These reactions proceed smoothly and in high yields with both enolizable and non-enolizable substrates. This C-C bond-forming reaction enables a new bond construction for the synthesis of functionalized furans.

Baseline Channel Geometry and Aquatic Habitat Data for Selected Streams in the Matanuska-Susitna Valley, Alaska

USGS Publications Warehouse

Curran, Janet H.; Rice, William J.

2009-01-01

Small streams in the rapidly developing Matanuska-Susitna Valley in south-central Alaska are known to support anadromous and resident fish but little is known about their hydrologic and riparian conditions, or their sensitivity to the rapid development of the area or climate variability. To help address this need, channel geometry and aquatic habitat data were collected in 2005 as a baseline of stream conditions for selected streams. Three streams were selected as representative of various stream types, and one drainage network, the Big Lake drainage basin, was selected for a systematic assessment. Streams in the Big Lake basin were drawn in a Geographic Information System (GIS), and 55 reaches along 16 miles of Meadow Creek and its primary tributary Little Meadow Creek were identified from orthoimagery and field observations on the basis of distinctive physical and habitat parameters, most commonly gradient, substrate, and vegetation. Data-collection methods for sites at the three representative reaches and the 55 systematically studied reaches consisted of a field survey of channel and flood-plain geometry and collection of 14 habitat attributes using published protocols or slight modifications. Width/depth and entrenchment ratios along the Meadow-Little Meadow Creek corridor were large and highly variable upstream of Parks Highway and lower and more consistent downstream of Parks Highway. Channel width was strongly correlated with distance, increasing downstream in a log-linear relation. Runs formed the most common habitat type, and instream vegetation dominated the habitat cover types, which collectively covered 53 percent of the channel. Gravel suitable for spawning covered isolated areas along Meadow Creek and about 29 percent of Little Meadow Creek. Broad wetlands were common along both streams. For a comprehensive assessment of small streams in the Mat-Su Valley, critical additional data needs include hydrologic, geologic and geomorphic, and biologic data

Novel ion channel targets in atrial fibrillation.

PubMed

Hancox, Jules C; James, Andrew F; Marrion, Neil V; Zhang, Henggui; Thomas, Dierk

2016-08-01

Atrial fibrillation (AF) is the most common arrhythmia in humans. It is progressive and the development of electrical and structural remodeling makes early intervention desirable. Existing antiarrhythmic pharmacological approaches are not always effective and can produce unwanted side effects. Additional atrial-selective antiarrhythmic strategies are therefore desirable. Evidence for three novel ion channel atrial-selective therapeutic targets is evaluated: atrial-selective fast sodium channel current (INa) inhibition; small conductance calcium-activated potassium (SK) channels; and two-pore (K2P) potassium channels. Data from animal models support atrial-ventricular differences in INa kinetics and also suggest atrial-ventricular differences in sodium channel β subunit expression. Further work is required to determine whether intrinsic atrial-ventricular differences in human INa exist or whether functional differences occur due to distinct atrial and ventricular action and resting potentials. SK and K2P channels (particularly K2P 3.1) offer potentially attractive atrial-selective targets. Work is needed to identify the underlying basis of SK current that contributes to (patho)physiological atrial repolarization and settings in which SK inhibition is anti- versus pro-arrhythmic. Although K2P3.1 appears to be a promising target with comparatively selective drugs for experimental use, a lack of selective pharmacology hinders evaluation of other K2P channels as potential atrial-selective targets.

Achieving high permeability and enhanced selectivity for Angstrom-scale separations using artificial water channel membranes.

PubMed

Shen, Yue-Xiao; Song, Woochul C; Barden, D Ryan; Ren, Tingwei; Lang, Chao; Feroz, Hasin; Henderson, Codey B; Saboe, Patrick O; Tsai, Daniel; Yan, Hengjing; Butler, Peter J; Bazan, Guillermo C; Phillip, William A; Hickey, Robert J; Cremer, Paul S; Vashisth, Harish; Kumar, Manish

2018-06-12

Synthetic polymer membranes, critical to diverse energy-efficient separations, are subject to permeability-selectivity trade-offs that decrease their overall efficacy. These trade-offs are due to structural variations (e.g., broad pore size distributions) in both nonporous membranes used for Angstrom-scale separations and porous membranes used for nano to micron-scale separations. Biological membranes utilize well-defined Angstrom-scale pores to provide exceptional transport properties and can be used as inspiration to overcome this trade-off. Here, we present a comprehensive demonstration of such a bioinspired approach based on pillar[5]arene artificial water channels, resulting in artificial water channel-based block copolymer membranes. These membranes have a sharp selectivity profile with a molecular weight cutoff of ~ 500 Da, a size range challenging to achieve with current membranes, while achieving a large improvement in permeability (~65 L m -2  h -1  bar -1  compared with 4-7 L m -2  h -1  bar -1 ) over similarly rated commercial membranes.

Doubly distributing special obligations: what professional practice can learn from parenting

PubMed Central

Tilburt, Jon; Brody, Baruch

2018-01-01

A traditional ethic of medicine asserts that physicians have special obligations to individual patients with whom they have a clinical relationship. Contemporary trends in US healthcare financing like bundled payments seem to threaten traditional conceptions of special obligations of individual physicians to individual patients because their population-based focus sets a tone that seems to emphasise responsibilities for groups of patients by groups of physicians in an organisation. Prior to undertaking a cogent debate about the fate and normative weight of special obligations and a traditional ethic for contemporary healthcare, we need a deeper examination of what the traditional ethic of special obligations really means. Here we offer a conception of ‘doubly distributed’ special obligations. Physicians and similarly minded healing professionals abiding by a traditional ethic have always spread their devotion and attention across multiple patients and have shared responsibilities with physician and non-physician colleagues in much the same way devoted parents have frequently distributed their special obligations across multiple children and across multiple parents. By taking up the extended analogy of parent we argue that doubly distributing special obligations need not contradict the possibility of special obligations in restructured collective forms of healthcare delivery and financing. PMID:27125989

α-SNAP regulates dynamic, on-site assembly and calcium selectivity of Orai1 channels

PubMed Central

Li, Peiyao; Miao, Yong; Dani, Adish; Vig, Monika

2016-01-01

Orai1 forms a highly calcium-selective pore of the calcium release activated channel, and α-SNAP is necessary for its function. Here we show that α-SNAP regulates on-site assembly of Orai1 dimers into calcium-selective multimers. We find that Orai1 is a dimer in resting primary mouse embryonic fibroblasts but displays variable stoichiometry in the plasma membrane of store-depleted cells. Remarkably, α-SNAP depletion induces formation of higher-order Orai1 oligomers, which permeate significant levels of sodium via Orai1 channels. Sodium permeation in α-SNAP–deficient cells cannot be corrected by tethering multiple Stim1 domains to Orai1 C-terminal tail, demonstrating that α-SNAP regulates functional assembly and calcium selectivity of Orai1 multimers independently of Stim1 levels. Fluorescence nanoscopy reveals sustained coassociation of α-SNAP with Stim1 and Orai1, and α-SNAP–depleted cells show faster and less constrained mobility of Orai1 within ER-PM junctions, suggesting Orai1 and Stim1 coentrapment without stable contacts. Furthermore, α-SNAP depletion significantly reduces fluorescence resonance energy transfer between Stim1 and Orai1 N-terminus but not C-terminus. Taken together, these data reveal a unique role of α-SNAP in the on-site functional assembly of Orai1 subunits and suggest that this process may, in part, involve enabling crucial low-affinity interactions between Orai1 N-terminus and Stim1. PMID:27335124

Maitotoxin Is a Potential Selective Activator of the Endogenous Transient Receptor Potential Canonical Type 1 Channel in Xenopus laevis Oocytes

PubMed Central

Flores, Pedro L.; Rodríguez, Emma; Zapata, Estrella; Carbó, Roxana; Farías, José María; Martínez, Martín

2017-01-01

Maitotoxin (MTX) is the most potent marine toxin known to date. It is responsible for a particular human intoxication syndrome called ciguatera fish poisoning (CFP). Several reports indicate that MTX is an activator of non-selective cation channels (NSCC) in different cell types. The molecular identity of these channels is still an unresolved topic, and it has been proposed that the transient receptor potential (TRP) channels are involved in this effect. In Xenopus laevis oocytes, MTX at picomolar (pM) concentrations induces the activation of NSCC with functional and pharmacological properties that resemble the activity of TRP channels. The purpose of this study was to characterize the molecular identity of the TRP channel involved in the MTX response, using the small interference RNA (siRNA) approach and the two-electrode voltage-clamp technique (TEVC). The injection of a specifically designed siRNA to silence the transient receptor potential canonical type 1 (TRPC1) protein expression abolished the MTX response. MTX had no effect on oocytes, even at doses 20-fold higher compared to cells without injection. Total mRNA and protein levels of TRPC1 were notably diminished. The TRPC4 siRNA did not change the MTX effect, even though it was important to note that the protein level was reduced by the silencing of TRPC4. Our results suggest that MTX could be a selective activator of TRPC1 channels in X. laevis oocytes and a useful pharmacological tool for further studies on these TRP channels. PMID:28672825

Maitotoxin Is a Potential Selective Activator of the Endogenous Transient Receptor Potential Canonical Type 1 Channel in Xenopus laevis Oocytes.

PubMed

Flores, Pedro L; Rodríguez, Emma; Zapata, Estrella; Carbó, Roxana; Farías, José María; Martínez, Martín

2017-06-25

Maitotoxin (MTX) is the most potent marine toxin known to date. It is responsible for a particular human intoxication syndrome called ciguatera fish poisoning (CFP). Several reports indicate that MTX is an activator of non-selective cation channels (NSCC) in different cell types. The molecular identity of these channels is still an unresolved topic, and it has been proposed that the transient receptor potential (TRP) channels are involved in this effect. In Xenopus laevis oocytes, MTX at picomolar (pM) concentrations induces the activation of NSCC with functional and pharmacological properties that resemble the activity of TRP channels. The purpose of this study was to characterize the molecular identity of the TRP channel involved in the MTX response, using the small interference RNA (siRNA) approach and the two-electrode voltage-clamp technique (TEVC). The injection of a specifically designed siRNA to silence the transient receptor potential canonical type 1 (TRPC1) protein expression abolished the MTX response. MTX had no effect on oocytes, even at doses 20-fold higher compared to cells without injection. Total mRNA and protein levels of TRPC1 were notably diminished. The TRPC4 siRNA did not change the MTX effect, even though it was important to note that the protein level was reduced by the silencing of TRPC4. Our results suggest that MTX could be a selective activator of TRPC1 channels in X. laevis oocytes and a useful pharmacological tool for further studies on these TRP channels.

Fragmentation Patterns and Mechanisms of Singly and Doubly Protonated Peptoids Studied by Collision Induced Dissociation

NASA Astrophysics Data System (ADS)

Ren, Jianhua; Tian, Yuan; Hossain, Ekram; Connolly, Michael D.

2016-04-01

Peptoids are peptide-mimicking oligomers consisting of N-alkylated glycine units. The fragmentation patterns for six singly and doubly protonated model peptoids were studied via collision-induced dissociation tandem mass spectrometry. The experiments were carried out on a triple quadrupole mass spectrometer with an electrospray ionization source. Both singly and doubly protonated peptoids were found to fragment mainly at the backbone amide bonds to produce peptoid B-type N-terminal fragment ions and Y-type C-terminal fragment ions. However, the relative abundances of B- versus Y-ions were significantly different. The singly protonated peptoids fragmented by producing highly abundant Y-ions and lesser abundant B-ions. The Y-ion formation mechanism was studied through calculating the energetics of truncated peptoid fragment ions using density functional theory and by controlled experiments. The results indicated that Y-ions were likely formed by transferring a proton from the C-H bond of the N-terminal fragments to the secondary amine of the C-terminal fragments. This proton transfer is energetically favored, and is in accord with the observation of abundant Y-ions. The calculations also indicated that doubly protonated peptoids would fragment at an amide bond close to the N-terminus to yield a high abundance of low-mass B-ions and high-mass Y-ions. The results of this study provide further understanding of the mechanisms of peptoid fragmentation and, therefore, are a valuable guide for de novo sequencing of peptoid libraries synthesized via combinatorial chemistry.

Extracting Effective Higgs Couplings in the Golden Channel

DOE PAGES

Chen, Yi; Vega-Morales, Roberto

2014-04-08

Kinematic distributions in Higgs decays to four charged leptons, the so called ‘golden channel, are a powerful probe of the tensor structure of its couplings to neutral electroweak gauge bosons. In this study we construct the first part of a comprehensive analysis framework designed to maximize the information contained in this channel in order to perform direct extraction of the various possible Higgs couplings. We first complete an earlier analytic calculation of the leading order fully differential cross sections for the golden channel signal and background to include the 4e and 4μ final states with interference between identical final states.more » We also examine the relative fractions of the different possible combinations of scalar-tensor couplings by integrating the fully differential cross section over all kinematic variables as well as show various doubly differential spectra for both the signal and background. From these analytic expressions we then construct a ‘generator level’ analysis framework based on the maximum likelihood method. Then, we demonstrate the ability of our framework to perform multi-parameter extractions of all the possible effective couplings of a spin-0 scalar to pairs of neutral electroweak gauge bosons including any correlations. Furthermore, this framework provides a powerful method for study of these couplings and can be readily adapted to include the relevant detector and systematic effects which we demonstrate in an accompanying study to follow.« less

On Applications of Pyramid Doubly Joint Bilateral Filtering in Dense Disparity Propagation

NASA Astrophysics Data System (ADS)

Abadpour, Arash

2014-06-01

Stereopsis is the basis for numerous tasks in machine vision, robotics, and 3D data acquisition and processing. In order for the subsequent algorithms to function properly, it is important that an affordable method exists that, given a pair of images taken by two cameras, can produce a representation of disparity or depth. This topic has been an active research field since the early days of work on image processing problems and rich literature is available on the topic. Joint bilateral filters have been recently proposed as a more affordable alternative to anisotropic diffusion. This class of image operators utilizes correlation in multiple modalities for purposes such as interpolation and upscaling. In this work, we develop the application of bilateral filtering for converting a large set of sparse disparity measurements into a dense disparity map. This paper develops novel methods for utilizing bilateral filters in joint, pyramid, and doubly joint settings, for purposes including missing value estimation and upscaling. We utilize images of natural and man-made scenes in order to exhibit the possibilities offered through the use of pyramid doubly joint bilateral filtering for stereopsis.

STATIC ANALYSIS OF SHELLS OF REVOLUTION USING DOUBLY-CURVED QUADRILATERAL ELEMENTS DERIVED FROM ALTERNATE VARIATIONAL MODELS.

DTIC Science & Technology

geometrical shape of the finite element in both of the models is a doubly-curved quadrilateral element whose edge curves are the lines-of-curvature coordinates employed to define the shell midsurface . (Author)

Doubly differential star-16-QAM for fast wavelength switching coherent optical packet transceiver.

PubMed

Liu, Fan; Lin, Yi; Walsh, Anthony J; Yu, Yonglin; Barry, Liam P

2018-04-02

A coherent optical packet transceiver based on doubly differential star 16-ary quadrature amplitude modulation (DD-star-16-QAM) is presented for spectrally and energy efficient reconfigurable networks. The coding and decoding processes for this new modulation format are presented, simulations and experiments are then performed to investigate the performance of the DD-star-16-QAM in static and dynamic scenarios. The static results show that the influence of frequency offset (FO) can be cancelled out by doubly differential (DD) coding and the correction range is only limited by the electronic bandwidth of the receivers. In the dynamic scenario with a time-varying FO and linewidth, the DD-star-16-QAM can overcome the time-varying FO, and the switching time of around 70 ns is determined by the time it takes the dynamic linewidth to reach the requisite level. This format can thus achieve a shorter waiting time after switching tunable lasers than the commonly used square-16-QAM, in which the transmission performance is limited by the frequency transients after the wavelength switch.

Design of a doubly-hydrophilic block copolypeptide that directs the formation of calcium carbonate microspheres.

PubMed

Euliss, Larken E; Trnka, Tina M; Deming, Timothy J; Stucky, Galen D

2004-08-07

The crystallization of calcium carbonate into microspheres has been accomplished using the rationally-designed, doubly-hydrophilic block copolypeptide poly(Nepsilon-2[2-(2-methoxyethoxy)ethoxy]acetyl-L-lysine)(100)-b-poly(L-aspartate sodium salt)30 as a structure-directing agent.

P/Q-type calcium channel modulators

PubMed Central

Nimmrich, V; Gross, G

2012-01-01

P/Q-type calcium channels are high-voltage-gated calcium channels contributing to vesicle release at synaptic terminals. A number of neurological diseases have been attributed to malfunctioning of P/Q channels, including ataxia, migraine and Alzheimer's disease. To date, only two specific P/Q-type blockers are known: both are peptides deriving from the spider venom of Agelenopsis aperta, ω-agatoxins. Other peptidic calcium channel blockers with activity at P/Q channels are available, albeit with less selectivity. A number of low molecular weight compounds modulate P/Q-type currents with different characteristics, and some exhibit a peculiar bidirectional pattern of modulation. Interestingly, there are a number of therapeutics in clinical use, which also show P/Q channel activity. Because selectivity as well as the exact mode of action is different between all P/Q-type channel modulators, the interpretation of clinical and experimental data is complicated and needs a comprehensive understanding of their target profile. The situation is further complicated by the fact that information on potency varies vastly in the literature, which may be the result of different experimental systems, conditions or the splice variants of the P/Q channel. This review attempts to provide a comprehensive overview of the compounds available that affect the P/Q-type channel and should help with the interpretation of results of in vitro experiments and animal models. It also aims to explain some clinical observations by implementing current knowledge about P/Q channel modulation of therapeutically used non-selective drugs. Chances and challenges of the development of P/Q channel-selective molecules are discussed. PMID:22670568

Discovery of four doubly imaged quasar lenses from the Sloan digital sky survey

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

Inada, Naohisa; Oguri, Masamune; Rusu, Cristian E.

2014-06-01

We report the discovery of four doubly imaged quasar lenses. All the four systems are selected as lensed quasar candidates from the Sloan Digital Sky Survey data. We confirm their lensing hypothesis with additional imaging and spectroscopic follow-up observations. The discovered lenses are SDSS J0743+2457 with the source redshift z{sub s} = 2.165, the lens redshift z{sub l} = 0.381, and the image separation θ = 1.''034, SDSS J1128+2402 with z{sub s} = 1.608 and θ = 0.''844, SDSS J1405+0959 with z{sub s} = 1.810, z{sub l} ≈ 0.66, and θ = 1.''978, and SDSS J1515+1511 with z{sub s} =more » 2.054, z{sub l} = 0.742, and θ = 1.''989. It is difficult to estimate the lens redshift of SDSS J1128+2402 from the current data. Two of the four systems (SDSS J1405+0959 and SDSS J1515+1511) are included in our final statistical lens sample to derive constraints on dark energy and the evolution of massive galaxies.« less

Dynamics of the EAG1 K+ channel selectivity filter assessed by molecular dynamics simulations.

PubMed

Bernsteiner, Harald; Bründl, Michael; Stary-Weinzinger, Anna

2017-02-26

EAG1 channels belong to the KCNH family of voltage gated potassium channels. They are expressed in several brain regions and increased expression is linked to certain cancer types. Recent cryo-EM structure determination finally revealed the structure of these channels in atomic detail, allowing computational investigations. In this study, we performed molecular dynamics simulations to investigate the ion binding sites and the dynamical behavior of the selectivity filter. Our simulations suggest that sites S2 and S4 form stable ion binding sites, while ions placed at sites S1 and S3 rapidly switched to sites S2 and S4. Further, ions tended to dissociate away from S0 within less than 20 ns, due to increased filter flexibility. This was followed by water influx from the extracellular side, leading to a widening of the filter in this region, and likely non-conductive filter configurations. Simulations with the inactivation-enhancing mutant Y464A or Na + ions lead to trapped water molecules behind the SF, suggesting that these simulations captured early conformational changes linked to C-type inactivation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Use of an automated chromium reduction system for hydrogen isotope ratio analysis of physiological fluids applied to doubly labeled water analysis.

PubMed

Schoeller, D A; Colligan, A S; Shriver, T; Avak, H; Bartok-Olson, C

2000-09-01

The doubly labeled water method is commonly used to measure total energy expenditure in free-living subjects. The method, however, requires accurate and precise deuterium abundance determinations, which can be laborious. The aim of this study was to evaluate a fully automated, high-throughput, chromium reduction technique for the measurement of deuterium abundances in physiological fluids. The chromium technique was compared with an off-line zinc bomb reduction technique and also subjected to test-retest analysis. Analysis of international water standards demonstrated that the chromium technique was accurate and had a within-day precision of <1 per thousand. Addition of organic matter to water samples demonstrated that the technique was sensitive to interference at levels between 2 and 5 g l(-1). Physiological samples could be analyzed without this interference, plasma by 10000 Da exclusion filtration, saliva by sedimentation and urine by decolorizing with carbon black. Chromium reduction of urine specimens from doubly labeled water studies indicated no bias relative to zinc reduction with a mean difference in calculated energy expenditure of -0.2 +/- 3.9%. Blinded reanalysis of urine specimens from a second doubly labeled water study demonstrated a test-retest coefficient of variation of 4%. The chromium reduction method was found to be a rapid, accurate and precise method for the analysis of urine specimens from doubly labeled water. Copyright 2000 John Wiley & Sons, Ltd.

Reduction of the pectoral spine and girdle in domesticated Channel catfish is likely caused by changes in selection pressure.

PubMed

Fine, Michael L; Lahiri, Shweta; Sullivan, Amanda D H; Mayo, Mark; Newton, Scott H; Sismour, Edward N

2014-07-01

Locked pectoral spines of the Channel Catfish Ictalurus punctatus more than double the fish's width and complicate ingestion by gape-limited predators. The spine mates with the pectoral girdle, a robust structure that anchors the spine. This study demonstrates that both spine and girdle exhibit negative allometric growth and that pectoral spines and girdles are lighter in domesticated than in wild Channel Catfish. This finding could be explained by changes in selection pressure for spine growth during domestication or by an epigenetic effect in which exposure to predators in wild fish stimulates pectoral growth. We tested the epigenetic hypothesis by exposing domesticated Channel Catfish fingerlings to Largemouth Bass Micropterus salmoides predators for 13 weeks. Spines and girdles grow isometrically in the fingerlings, and regression analysis indicates no difference in proportional pectoral growth between control and predator-exposed fish. Therefore a change in selection pressure likely accounts for smaller pectoral growth in domesticated Channel Catfish. Decreasing spine growth in older fish suggests anti-predator functions are most important in smaller fish. Additionally, growth of the appendicular and axial skeleton is controlled differentially, and mechanical properties of the spine and not just its length are an important component of this defensive adaptation. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Validity of the remote food photography method against doubly labeled water among minority preschoolers

USDA-ARS?s Scientific Manuscript database

The aim of this study was to determine the validity of energy intake (EI) estimations made using the remote food photography method (RFPM) compared to the doubly labeled water (DLW) method in minority preschool children in a free-living environment. Seven days of food intake and spot urine samples...

Holographic recording in a doubly doped lithium niobate crystal with two wavelengths: a blue laser diode and a green laser

NASA Astrophysics Data System (ADS)

Komori, Yuichi; Ishii, Yukihiro

2010-08-01

A doubly-doped LiNbO3 (LN) crystal has been well used as a nonvolatile two-wavelength recording material. By using two levels of the crystal, two-kind holograms can be recorded on one crystal; a hologram is recorded with a 405-nm blue laser diode (LD) for a deep Mn level, and another hologram is with a 532-nm green laser for a shallow Fe level. The recording capacity doubles. A 780-nm LD is non-volatile reconstructing source since the LD line is insensitive to both levels. Multiplexed reconstructed images are demonstrated by using a sharp angular selectivity of a volume LN crystal keeping Bragg condition with spherical reconstructions.

Isolation of homoleptic platinum oxyanionic complexes with doubly protonated diazacrown cation

NASA Astrophysics Data System (ADS)

Vasilchenko, Danila; Tkachev, Sergey; Baidina, Iraida; Romanenko, Galina; Korenev, Sergey

2017-02-01

Doubly protonated diazacrown ether cation (1,4,10,13-tetraoxa-7,16-diazoniacyclooctadecane DCH22+) was used for the efficient isolation of the homoleptic platinum complexes [Pt(NO3)6]2- and [Pt(C2O4)2]2- to crystalline solid phases from solutions containing mixtures of related platinum complexes. DCH22+ molecules in nitric acid solution were shown to prevent the condensation of mononuclear [Pt(H2O)n(NO3)6-n]n-2 species.

Riparian vegetation patterns in relation to fluvial landforms and channel evolution along selected rivers of Tuscany (Central Italy)

USGS Publications Warehouse

Hupp, C.R.; Rinaldi, M.

2007-01-01

Riparian vegetation distribution patterns and diversity relative to various fluvial geomorphic channel patterns, landforms, and processes are described and interpreted for selected rivers of Tuscany, Central Italy; with emphasis on channel evolution following human impacts. Field surveys were conducted along thirteen gauged reaches for species presence, fluvial landforms, and the type and amount of channel/riparian zone change. Inundation frequency of different geomorphic surfaces was determined, and vegetation data were analyzed using BDA (binary discriminate analysis) and DCA (detrended correspondence analysis) and related to hydrogeomorphology. Multivariate analyses revealed distinct quantitative vegetation patterns relative to six major fluvial geomorphic surfaces. DCA of the vegetation data also showed distinct associations of plants to processes of adjustment that are related to stage of channel evolution, and clearly separated plants along disturbance/landform/soil moisture gradients. Species richness increases from the channel bed to the terrace and on heterogeneous riparian areas, whereas species richness decreases from moderate to intense incision and from low to intense narrowing. ?? 2007 by Association of American Geographers.

Mechanism underlying selective regulation of G protein-gated inwardly rectifying potassium channels by the psychostimulant-sensitive sorting nexin 27

PubMed Central

Balana, Bartosz; Maslennikov, Innokentiy; Kwiatkowski, Witek; Stern, Kalyn M.; Bahima, Laia; Choe, Senyon; Slesinger, Paul A.

2011-01-01

G protein-gated inwardly rectifying potassium (GIRK) channels are important gatekeepers of neuronal excitability. The surface expression of neuronal GIRK channels is regulated by the psychostimulant-sensitive sorting nexin 27 (SNX27) protein through a class I (-X-Ser/Thr-X-Φ, where X is any residue and Φ is a hydrophobic amino acid) PDZ-binding interaction. The G protein-insensitive inward rectifier channel (IRK1) contains the same class I PDZ-binding motif but associates with a different synaptic PDZ protein, postsynaptic density protein 95 (PSD95). The mechanism by which SNX27 and PSD95 discriminate these channels was previously unclear. Using high-resolution structures coupled with biochemical and functional analyses, we identified key amino acids upstream of the channel's canonical PDZ-binding motif that associate electrostatically with a unique structural pocket in the SNX27-PDZ domain. Changing specific charged residues in the channel's carboxyl terminus or in the PDZ domain converts the selective association and functional regulation by SNX27. Elucidation of this unique interaction site between ion channels and PDZ-containing proteins could provide a therapeutic target for treating brain diseases. PMID:21422294

TRP Channels

NASA Astrophysics Data System (ADS)

Voets, Thomas; Owsianik, Grzegorz; Nilius, Bernd

The TRP superfamily represents a highly diverse group of cation-permeable ion channels related to the product of the Drosophila trp (transient receptor potential) gene. The cloning and characterization of members of this cation channel family has experienced a remarkable growth during the last decade, uncovering a wealth of information concerning the role of TRP channels in a variety of cell types, tissues, and species. Initially, TRP channels were mainly considered as phospholipase C (PLC)-dependent and/or store-operated Ca2+-permeable cation channels. More recent research has highlighted the sensitivity of TRP channels to a broad array of chemical and physical stimuli, allowing them to function as dedicated biological sensors involved in processes ranging from vision to taste, tactile sensation, and hearing. Moreover, the tailored selectivity of certain TRP channels enables them to play key roles in the cellular uptake and/or transepithelial transport of Ca2+, Mg2+, and trace metal ions. In this chapter we give a brief overview of the TRP channel superfamily followed by a survey of current knowledge concerning their structure and activation mechanisms.

Reversal of Ion Charge Selectivity Renders the Pentameric Ligand-Gated Ion Channel GLIC Insensitive to Anesthetics

PubMed Central

Tillman, Tommy; Cheng, Mary H.; Chen, Qiang; Tang, Pei; Xu, Yan

2014-01-01

Pentameric ligand gated ion channels (pLGICs) are a family of structurally homologous cationic and anionic channels involved in neurotransmission. Cationic members of the pLGIC family are typically inhibited by general anesthetics, while anionic members are potentiated. GLIC is a prokaryotic cationic pLGIC and can be inhibited by clinical concentrations of general anesthetics. The introduction of three mutations, Y221A (Y–3′A), E222P (E–2′P) and N224R (N0′R), at the selectivity filter and one, A237T (A13′T), at the hydrophobic gate, converted GLIC to an anion channel. The mutated GLIC (GLIC4) became insensitive to the anesthetics propofol and etomidate as well as the channel blocker picrotoxin. Molecular dynamics (MD) simulations revealed changes in the structure and dynamics of GLIC4 in comparison to GLIC, particularly in the tilting angles of the pore-lining helix (TM2) that consequently resulted in different pore radius and hydration profiles. Propofol binding to an intra-subunit site of GLIC shifted the tilting angles of TM2 towards closure at the hydrophobic gate region, consistent with propofol inhibition of GLIC. In contrast, the pore of GLIC4 was much more resilient to perturbation from propofol binding. This study underscores the importance of pore dynamics and conformation to anesthetic effects on channel functions. PMID:22978431

Divalent ions are potential permeating blockers of the non-selective NaK ion channel: combined QM and MD based investigations.

PubMed

Sadhu, Biswajit; Sundararajan, Mahesh; Bandyopadhyay, Tusar

2017-10-18

The bacterial NaK ion channel is distinctly different from other known ion channels due to its inherent non-selective feature. One of the unexplored and rather interesting features is its ability to permeate divalent metal ions (such as Ca 2+ and Ba 2+ ) and not monovalent alkali metal ions. Several intriguing questions about the energetics and structural aspects still remain unanswered. For instance, what causes Ca 2+ to permeate as well as block the selectivity filter (SF) of the NaK ion channel and act as a "permeating blocker"? How and at what energetic cost does another chemical congener, Sr 2+ , as well as Ba 2+ , a potent blocker of the K + ion channel, permeate through the SF of the NaK ion channel? Finally, how do their translocation energetics differ from those of monovalent ions such as K + ? Here, in an attempt to address these outstanding issues, we elucidate the structure, binding and selectivity of divalent ions (Ca 2+ , Sr 2+ and Ba 2+ ) as they permeate through the SF of the NaK ion channel using all-atom molecular dynamics simulations and density functional theory based calculations. We unveil mechanistic insight into this translocation event using well-tempered metadynamics simulations in a polarizable environment using the mean-field model of water and incorporating electronic continuum corrections for ions via charge rescaling. The results show that, akin to K + coordination, Sr 2+ and Ba 2+ bind at the SF in a very similar fashion and remain octa-coordinated at all sites. Interestingly, differing from its local hydration structure, Ca 2+ interacts with eight carbonyls to remain at the middle of the S3 site. Furthermore, the binding of divalent metals at SF binding sites is more favorable than the binding of K + . However, their permeation through the extracellular entrance faces a considerably higher energetic barrier compared to that for K + , which eventually manifests their inherent blocking feature.

Dissociation of doubly charged clusters of lithium acetate: Asymmetric fission and breakdown of the liquid drop model: Dissociation of doubly charged clusters of lithium acetate

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

Shukla, Anil

2016-06-08

Unimolecular and collision-induced dissociation of doubly charged lithium acetate clusters, (CH3COOLi)nLi22+, demonstrated that Coulomb fission via charge separation is the dominant dissociation process with no contribution from the neutral evaporation processes for all such ions from the critical limit to larger cluster ions, although latter process have normally been observed in all earlier studies. These results are clearly in disagreement with the Rayleigh’s liquid drop model that has been used successfully to predict the critical size and explain the fragmentation behavior of multiply charged clusters.

Doubly 15N-substituted diazenylium: THz laboratory spectra and fractionation models

NASA Astrophysics Data System (ADS)

Dore, L.; Bizzocchi, L.; Wirström, E. S.; Degli Esposti, C.; Tamassia, F.; Charnley, S. B.

2017-07-01

Context. Isotopic fractionation in dense molecular cores has been suggested as a possible origin of large 14N/15N ratio variations in solar system materials. While chemical models can explain some observed variations with different fractionation patterns for molecules with -NH or -CN functional groups, they fail to reproduce the observed ratios in diazenylium (N2H+). Aims: Observations of doubly 15N-substituted species could provide important constraints and insights for theoretical chemical models of isotopic fractionation. However, spectroscopic data are very scarce. Methods: The rotational spectra of the fully 15N-substituted isopologues of the diazenylium ion, 15N2H+ and 15N2D+, have been investigated in the laboratory well into the THz region by using a source-modulation microwave spectrometer equipped with a negative glow discharge cell. An extended chemical reaction network has been used to estimate what ranges of 15N fractionation in doubly 15N-substituted species could be expected in the interstellar medium (ISM). Results: For each isotopologue of the H- and D-containing pair, nine rotational transitions were accurately measured in the frequency region 88 GHz-1.2 THz. The analysis of the spectrum provided very precise rest frequencies at millimeter and sub-millimeter wavelengths, useful for the radioastronomical identification of the rotational lines of 15N2H+ and 15N2D+ in the ISM.

Electrophysiological characterization of 14-benzoyltalatisamine, a selective blocker of the delayed rectifier K+ channel found in virtual screening.

PubMed

Song, Ming-Ke; Liu, Hong; Jiang, Hua-Liang; Yue, Jian-Min; Hu, Guo-Yuan

2006-02-15

14-Benzoyltalatisamine is a potent and selective blocker of the delayed rectifier K+ channel found in a computational virtual screening study. The compound was found to block the K+ channel from the extracellular side. However, it is unclear whether 14-benzoyltalatisamine shares the same block mechanism with tetraethylammonium (TEA). In order to elucidate how the hit compound found by the virtual screening interacts with the outer vestibule of the K+ channel, the effects of 14-benzoyltalatisamine and TEA on the delayed rectifier K+ current of rat dissociated hippocampal neurons were compared using whole-cell voltage-clamp recording. External application of 14-benzoyltalatisamine and TEA reversibly inhibited the current with IC50 values of 10.1+/-2.2 microM and 1.05+/-0.21 mM, respectively. 14-Benzoyltalatisamine exerted voltage-dependent inhibition, markedly accelerated the decay of the current, and caused a significant hyperpolarizing shift of the steady-state activation curve, whereas TEA caused voltage-independent inhibition, without affecting the kinetic parameters of the current. The blockade by 14-benzoyltalatisamine, but not by TEA, was significantly diminished in a high K+ (60 mM) external solution. The potency of 14-benzoyltalatisamine was markedly reduced in the presence of 15 mM TEA. The results suggest that 14-benzoyltalatisamine bind to the external pore entry of the delayed rectifier K+ channel with partial insertion into the selectivity filter, which is in conformity with that predicted by the molecular docking model in the virtual screening.

Selective Modulation of K+ Channel Kv7.4 Significantly Affects the Excitability of DRN 5-HT Neurons.

PubMed

Zhao, Chen; Su, Min; Wang, Yingzi; Li, Xinmeng; Zhang, Yongxue; Du, Xiaona; Zhang, Hailin

2017-01-01

The serotonin (5-HT) system originating in the dorsal raphe nucleus (DRN) is implicated in various mood- and emotion-related disorders, such as anxiety, fear and stress. Abnormal activity of DRN 5-HT neurons is the key factor in the development of these disorders. Here, we describe a crucial role for the Kv7.4 potassium channel in modulating DRN 5-HT neuronal excitability. We demonstrate that Kv7.4 is selectively expressed in 5-HT neurons of the DRN. Using selective Kv7.4 opener fasudil and Kv7.4 knock-out mice, we demonstrate that Kv7.4 is a potent modulator of DRN 5-HT neuronal excitability. Furthermore, we demonstrate that the cellular redox signaling mechanism is involved in this 5-HT activation of Kv7.4. The current study suggests a new strategy for treating psychiatric disorders related to altered activity of DRN 5-HT neurons using K + channel modulators.

Selective Modulation of K+ Channel Kv7.4 Significantly Affects the Excitability of DRN 5-HT Neurons

PubMed Central

Zhao, Chen; Su, Min; Wang, Yingzi; Li, Xinmeng; Zhang, Yongxue; Du, Xiaona; Zhang, Hailin

2017-01-01

The serotonin (5-HT) system originating in the dorsal raphe nucleus (DRN) is implicated in various mood- and emotion-related disorders, such as anxiety, fear and stress. Abnormal activity of DRN 5-HT neurons is the key factor in the development of these disorders. Here, we describe a crucial role for the Kv7.4 potassium channel in modulating DRN 5-HT neuronal excitability. We demonstrate that Kv7.4 is selectively expressed in 5-HT neurons of the DRN. Using selective Kv7.4 opener fasudil and Kv7.4 knock-out mice, we demonstrate that Kv7.4 is a potent modulator of DRN 5-HT neuronal excitability. Furthermore, we demonstrate that the cellular redox signaling mechanism is involved in this 5-HT activation of Kv7.4. The current study suggests a new strategy for treating psychiatric disorders related to altered activity of DRN 5-HT neurons using K+ channel modulators. PMID:29311835

Attosecond XUV absorption spectroscopy of doubly excited states in helium atoms dressed by a time-delayed femtosecond infrared laser

NASA Astrophysics Data System (ADS)

Yang, Z. Q.; Ye, D. F.; Ding, Thomas; Pfeifer, Thomas; Fu, L. B.

2015-01-01

In the present paper, we investigate the time-resolved transient absorption spectroscopy of doubly excited states of helium atoms by solving the time-dependent two-electron Schrödinger equation numerically based on a one-dimensional model. The helium atoms are subjected to an extreme ultraviolet (XUV) attosecond pulse and a time-delayed infrared (IR) few-cycle laser pulse. A superposition of doubly excited states populated by the XUV pulse is identified, which interferes with the direct ionization pathway leading to Fano resonance profiles in the photoabsorption spectrum. In the presence of an IR laser, however, the Fano line profiles are strongly modified: A shifting, splitting, and broadening of the original absorption lines is observed when the XUV attosecond pulse and infrared few-cycle laser pulse overlap in time, which is in good agreement with recent experimental results. At certain time delays, we observe symmetric Lorentz, inverted Fano profiles, and even negative absorption cross sections indicating that the XUV light can be amplified during the interaction with atoms. We further prove that the above pictures are general for different doubly excited states by suitably varying the frequency of the IR field to coherently couple the corresponding states.

Vibration and bending behavior of functionally graded nanocomposite doubly-curved shallow shells reinforced by graphene nanoplatelets

NASA Astrophysics Data System (ADS)

Wang, Aiwen; Chen, Hongyan; Hao, Yuxin; Zhang, Wei

2018-06-01

Free vibration and static bending of functionally graded (FG) graphene nanoplatelet (GPL) reinforced composite doubly-curved shallow shells with three distinguished distributions are analyzed. Material properties with gradient variation in the thickness aspect are evaluated by the modified Halpin-Tsai model. Mathematical model of the simply supported doubly-curved shallow shells rests upon Hamilton Principle and a higher order shear deformation theory (HSDT). The free vibration frequencies and bending deflections are gained by taking into account Navier technique. The agreement between the obtained results and ANSYS as well as the prior results in the open literature verifies the accuracy of the theory in this article. Further, parametric studies are accomplished to highlight the significant influence of GPL distribution patterns and weight fraction, stratification number, dimensions of GPLs and shells on the mechanical behavior of the system.

Program scheme using common source lines in channel stacked NAND flash memory with layer selection by multilevel operation

NASA Astrophysics Data System (ADS)

Kim, Do-Bin; Kwon, Dae Woong; Kim, Seunghyun; Lee, Sang-Ho; Park, Byung-Gook

2018-02-01

To obtain high channel boosting potential and reduce a program disturbance in channel stacked NAND flash memory with layer selection by multilevel (LSM) operation, a new program scheme using boosted common source line (CSL) is proposed. The proposed scheme can be achieved by applying proper bias to each layer through its own CSL. Technology computer-aided design (TCAD) simulations are performed to verify the validity of the new method in LSM. Through TCAD simulation, it is revealed that the program disturbance characteristics is effectively improved by the proposed scheme.

Selective Ablation of GIRK Channels in Dopamine Neurons Alters Behavioral Effects of Cocaine in Mice.

PubMed

McCall, Nora M; Kotecki, Lydia; Dominguez-Lopez, Sergio; Marron Fernandez de Velasco, Ezequiel; Carlblom, Nicholas; Sharpe, Amanda L; Beckstead, Michael J; Wickman, Kevin

2017-02-01

The increase in dopamine (DA) neurotransmission stimulated by in vivo cocaine exposure is tempered by G protein-dependent inhibitory feedback mechanisms in DA neurons of the ventral tegmental area (VTA). G protein-gated inwardly rectifying K + (GIRK/Kir3) channels mediate the direct inhibitory effect of GABA B receptor (GABA B R) and D 2 DA receptor (D 2 R) activation in VTA DA neurons. Here we examined the effect of the DA neuron-specific loss of GIRK channels on D 2 R-dependent regulation of VTA DA neuron excitability and on cocaine-induced, reward-related behaviors. Selective ablation of Girk2 in DA neurons did not alter the baseline excitability of VTA DA neurons but significantly reduced the magnitude of D 2 R-dependent inhibitory somatodendritic currents and blunted the impact of D 2 R activation on spontaneous activity and neuronal excitability. Mice lacking GIRK channels in DA neurons exhibited increased locomotor activation in response to acute cocaine administration and an altered locomotor sensitization profile, as well as increased responding for and intake of cocaine in an intravenous self-administration test. These mice, however, showed unaltered cocaine-induced conditioned place preference. Collectively, our data suggest that feedback inhibition to VTA DA neurons, mediated by GIRK channel activation, tempers the locomotor stimulatory effect of cocaine while also modulating the reinforcing effect of cocaine in an operant-based self-administration task.

Review of the If selective channel inhibitor ivabradine in the treatment of chronic stable angina.

PubMed

Prasad, Usha K; Gray, David; Purcell, Henry

2009-02-01

Coronary heart disease is the major cause of morbidity and mortality in industrialized countries, and its prevalence is predicted to grow as the population ages. Current drugs for chronic stable angina (such as beta-blockers, calcium-channel blockers, long- and short-acting nitrates, and potassium-channel activators) are often effective, either as monotherapy or in combination, but side effects and contraindications may limit their use. The "I(f)" (for "funny") channel, discovered in 1979, is expressed mainly in the membrane of pacemaker cells present in the sinus node, the atrioventricular node, the ventricular conduction pathways, and ventricular myocytes. By determining the slope of diastolic depolarization, which in turn controls action potential frequency, it is a key determinant of heart rate and so provides a new therapeutic target for controlling angina symptoms. A new antiangina drug, ivabradine, has been developed and licensed for clinical use. It exclusively reduces the heart rate by selectively blocking the I(f) channel of the sino-atrial node. As clinical trials have shown it to be remarkably well-tolerated, ivabradine offers an alternative for patients who cannot take, or are intolerant of, beta blockade. This review provides an insight into this new agent, its historical background, mechanism of action, and pathophysiologic basis, and provides up-to-date evidence-based information on its optimum use in stable angina.

Bathymetric survey of the Cayuga Inlet flood-control channel and selected tributaries in Ithaca, New York, 2016

USGS Publications Warehouse

Wernly, John F.; Nystrom, Elizabeth A.; Coon, William F.

2017-09-08

From July 14 to July 20, 2016, the U.S. Geological Survey, in cooperation with the City of Ithaca, New York, and the New York State Department of State, surveyed the bathymetry of the Cayuga Inlet flood-control channel and the mouths of selected tributaries to Cayuga Inlet and Cayuga Lake in Ithaca, N.Y. The flood-control channel, built by the U.S. Army Corps of Engineers between 1965 and 1970, was designed to convey flood flows from the Cayuga Inlet watershed through the City of Ithaca and minimize possible flood damages. Since that time, the channel has infrequently been maintained by dredging, and sediment accumulation and resultant shoaling have greatly decreased the conveyance of the channel and its navigational capability.U.S. Geological Survey personnel collected bathymetric data by using an acoustic Doppler current profiler. The survey produced a dense dataset of water depths that were converted to bottom elevations. These elevations were then used to generate a geographic information system bathymetric surface. The bathymetric data and resultant bathymetric surface show the current condition of the channel and provide the information that governmental agencies charged with maintaining the Cayuga Inlet for flood-control and navigational purposes need to make informed decisions regarding future maintenance measures.

Analysis of channel confined selective area growth in evolutionary growth of GaN on SiO 2

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

Leung, Benjamin; Tsai, Miao-Chan; Song, Jie

2015-09-01

Here, we analyze the chemical vapor deposition of semiconductor crystals by selective area growth in a non-planar geometry. Specifically, the growth process in laterally and vertically confined masks forming single-crystal GaN on SiO2 by metal-organic chemical vapor deposition is considered in detail. A textured AlN seed is used to initiate growth of oriented GaN selectively through the mask, allowing the reduction of degrees of freedom by the evolutionary grain selection process. As shown by measurements of growth rates within the mask, the sub micron length scale of the channel opening is comparable to the mean free path of precursors inmore » the gas phase, resulting in transport characteristics that can be described by an intermediate flow regime between continuum and free-molecular. Mass transport is modeled through kinetic theory to explain the growth rate enhancements of more than a factor of two by changes in reactor pressure. The growth conditions that enable the modification of nucleation density within the channel are then discussed, and are measured by electron-back scatter diffraction of the nucleated grains on the AlN seed. Finally, the selectivity behavior using the low fill factor masks needed in these configurations has been optimized by control of precursor flow rates and the H2 enhanced etching of the polycrystalline GaN nuclei.« less

SEMIPARAMETRIC EFFICIENT ESTIMATION FOR SHARED-FRAILTY MODELS WITH DOUBLY-CENSORED CLUSTERED DATA

PubMed Central

Wang, Jane-Ling

2018-01-01

In this paper, we investigate frailty models for clustered survival data that are subject to both left- and right-censoring, termed “doubly-censored data”. This model extends current survival literature by broadening the application of frailty models from right-censoring to a more complicated situation with additional left censoring. Our approach is motivated by a recent Hepatitis B study where the sample consists of families. We adopt a likelihood approach that aims at the nonparametric maximum likelihood estimators (NPMLE). A new algorithm is proposed, which not only works well for clustered data but also improve over existing algorithm for independent and doubly-censored data, a special case when the frailty variable is a constant equal to one. This special case is well known to be a computational challenge due to the left censoring feature of the data. The new algorithm not only resolves this challenge but also accommodate the additional frailty variable effectively. Asymptotic properties of the NPMLE are established along with semi-parametric efficiency of the NPMLE for the finite-dimensional parameters. The consistency of Bootstrap estimators for the standard errors of the NPMLE is also discussed. We conducted some simulations to illustrate the numerical performance and robustness of the proposed algorithm, which is also applied to the Hepatitis B data. PMID:29527068

Incorporating Born solvation energy into the three-dimensional Poisson-Nernst-Planck model to study ion selectivity in KcsA K+ channels

NASA Astrophysics Data System (ADS)

Liu, Xuejiao; Lu, Benzhuo

2017-12-01

Potassium channels are much more permeable to potassium than sodium ions, although potassium ions are larger and both carry the same positive charge. This puzzle cannot be solved based on the traditional Poisson-Nernst-Planck (PNP) theory of electrodiffusion because the PNP model treats all ions as point charges, does not incorporate ion size information, and therefore cannot discriminate potassium from sodium ions. The PNP model can qualitatively capture some macroscopic properties of certain channel systems such as current-voltage characteristics, conductance rectification, and inverse membrane potential. However, the traditional PNP model is a continuum mean-field model and has no or underestimates the discrete ion effects, in particular the ion solvation or self-energy (which can be described by Born model). It is known that the dehydration effect (closely related to ion size) is crucial to selective permeation in potassium channels. Therefore, we incorporated Born solvation energy into the PNP model to account for ion hydration and dehydration effects when passing through inhomogeneous dielectric channel environments. A variational approach was adopted to derive a Born-energy-modified PNP (BPNP) model. The model was applied to study a cylindrical nanopore and a realistic KcsA channel, and three-dimensional finite element simulations were performed. The BPNP model can distinguish different ion species by ion radius and predict selectivity for K+ over Na+ in KcsA channels. Furthermore, ion current rectification in the KcsA channel was observed by both the PNP and BPNP models. The I -V curve of the BPNP model for the KcsA channel indicated an inward rectifier effect for K+ (rectification ratio of ˜3 /2 ) but indicated an outward rectifier effect for Na+ (rectification ratio of ˜1 /6 ) .

KV7 channels in the human detrusor: channel modulator effects and gene and protein expression.

PubMed

Bientinesi, Riccardo; Mancuso, Cesare; Martire, Maria; Bassi, Pier Francesco; Sacco, Emilio; Currò, Diego

2017-02-01

Voltage-gated type 7 K + (K V 7 or KCNQ) channels regulate the contractility of various smooth muscles. With this study, we aimed to assess the role of K V 7 channels in the regulation of human detrusor contractility, as well as the gene and protein expression of K V 7 channels in this tissue. For these purposes, the isolated organ technique, RT-qPCR, and Western blot were used, respectively. XE-991, a selective K V 7 channel blocker, concentration-dependently contracted the human detrusor; mean EC 50 and E max of XE-991-induced concentration-response curve were 14.1 μM and 28.8 % of the maximal bethanechol-induced contraction, respectively. Flupirtine and retigabine, selective K V 7.2-7.5 channel activators, induced concentration-dependent relaxations of bethanechol-precontracted strips, with maximal relaxations of 51.6 and 51.8 % of the precontraction, respectively. XE-991 blocked the relaxations induced by flupirtine and retigabine. All five KCNQ genes were found to be expressed in the detrusor with KCNQ4 being the most expressed among them. Different bands, having sizes similar to some of reported K V 7.1, 7.4, and 7.5 channel subunit isoforms, were detected in the detrusor by Western blot with the K V 7.4 band being the most intense among them. In conclusion, K V 7 channels contribute to set the basal tone of the human detrusor. In addition, K V 7 channel activators significantly relax the detrusor. The K V 7.4 channels are probably the most important K V 7 channels expressed in the human detrusor. These data suggest that selective K V 7.4 channel activators might represent new pharmacological tools for inducing therapeutic relaxation of the detrusor.

Physical activity levels from a meta-analysis of doubly labeled water studies for validating energy intake as measured by dietary assessment.

PubMed

Black, A E

1996-06-01

Studies using doubly labeled water have identified underreporting of food intake as a problem of dietary surveys. However, reported energy intakes may be evaluated by comparison with energy requirements expressed as multiples of the basal metabolic rate, and a formula for calculating the value below which reported intake cannot be either a valid measure of habitual intake or a true low intake obtained by chance is presented. The energy requirements of different age-sex groups needed for the comparison with energy intakes have been obtained from a meta-analysis of doubly labeled water data.

Ionization Efficiency of Doubly Charged Ions Formed from Polyprotic Acids in Electrospray Negative Mode

NASA Astrophysics Data System (ADS)

Liigand, Piia; Kaupmees, Karl; Kruve, Anneli

2016-07-01

The ability of polyprotic acids to give doubly charged ions in negative mode electrospray was studied and related to physicochemical properties of the acids via linear discriminant analysis (LDA). It was discovered that the compound has to be strongly acidic (low p K a1 and p K a2) and to have high hydrophobicity (log P ow) to become multiply charged. Ability to give multiply charged ions in ESI/MS cannot be directly predicted from the solution phase acidities. Therefore, for the first time, a quantitative model to predict the charge state of the analyte in ESI/MS is proposed and validated for small anions. Also, a model to predict ionization efficiencies of these analytes was developed. Results indicate that acidity of the analyte, its octanol-water partition coefficient, and charge delocalization are important factors that influence ionization efficiencies as well as charge states of the analytes. The pH of the solvent was also found to be an important factor influencing the ionization efficiency of doubly charged ions.

Structural Heterogeneity of Doubly-Charged Peptide b-Ions

PubMed Central

Li, Xiaojuan; Huang, Yiqun; O’Connor, Peter B.; Lin, Cheng

2011-01-01

Performing collisionally activated dissociation (CAD) and electron capture dissociation (ECD) in tandem has shown great promise in providing comprehensive sequence information that was otherwise unobtainable by using either fragmentation method alone or in duet. However, the general applicability of this MS3 approach in peptide sequencing may be undermined by the formation of non-direct sequence ions, as sometimes observed under CAD, particularly when multiple stages of CAD are involved. In this study, varied-sized doubly-charged b-ions from three tachykinin peptides were investigated by ECD. Sequence scrambling was observed in ECD of all b-ions from neurokinin A (HKTDSFVGLM-NH2), suggesting the presence of N- and C-termini linked macro-cyclic conformers. On the contrary, none of the b-ions from eledoisin (pEPSKDAFIGLM-NH2) produced non-direct sequence ions under ECD, as it does not contain a free N-terminal amino group. ECD of several b-ions from Substance P (RPKPQQFFGLM-NH2) showed series of cm-Lys fragment ions which suggested that the macro-cyclic structure may also be formed by connecting the C-terminal carbonyl group and the ε-amino group of the lysine side chain. Theoretical investigation of selected Substance P b-ions revealed several low energy conformers, including both linear oxazolones and macro-ring structures, in corroboration with the experimental observation. This study showed that a b-ion may exist as a mixture of several forms, with their propensities influenced by its N-terminus, length, and certain side-chain groups. Further, the presence of several macro-cyclic structures may result in erroneous sequence assignment when the combined CAD and ECD methods are used in peptide sequencing. PMID:21472584

Structural Heterogeneity of Doubly-Charged Peptide b-Ions

NASA Astrophysics Data System (ADS)

Li, Xiaojuan; Huang, Yiqun; O'Connor, Peter B.; Lin, Cheng

2011-02-01

Performing collisionally activated dissociation (CAD) and electron capture dissociation (ECD) in tandem has shown great promise in providing comprehensive sequence information that was otherwise unobtainable by using either fragmentation method alone or in duet. However, the general applicability of this MS3 approach in peptide sequencing may be undermined by the formation of non-direct sequence ions, as sometimes observed under CAD, particularly when multiple stages of CAD are involved. In this study, varied-sized doubly-charged b-ions from three tachykinin peptides were investigated by ECD. Sequence scrambling was observed in ECD of all b-ions from neurokinin A (HKTDSFVGLM-NH2), suggesting the presence of N- and C-termini linked macro-cyclic conformers. On the contrary, none of the b-ions from eledoisin (pEPSKDAFIGLM-NH2) produced non-direct sequence ions under ECD, as it does not contain a free N-terminal amino group. ECD of several b-ions from Substance P (RPKPQQFFGLM-NH2) showed series of cm-Lys fragment ions which suggested that the macro-cyclic structure may also be formed by connecting the C-terminal carbonyl group and the ɛ-amino group of the lysine side chain. Theoretical investigation of selected Substance P b-ions revealed several low energy conformers, including both linear oxazolones and macro-ring structures, in corroboration with the experimental observation. This study showed that a b-ion may exist as a mixture of several forms, with their propensities influenced by its N-terminus, length, and certain side-chain groups. Further, the presence of several macro-cyclic structures may result in erroneous sequence assignment when the combined CAD and ECD methods are used in peptide sequencing.

Human HDAC isoform selectivity achieved via exploitation of the acetate release channel with structurally unique small molecule inhibitors

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

Whitehead, Lewis; Dobler, Markus R.; Radetich, Branko

2013-11-20

Herein we report the discovery of a family of novel yet simple, amino-acid derived class I HDAC inhibitors that demonstrate isoform selectivity via access to the internal acetate release channel. Isoform selectivity criteria is discussed on the basis of X-ray crystallography and molecular modeling of these novel inhibitors bound to HDAC8, potentially revealing insights into the mechanism of enzymatic function through novel structural features revealed at the atomic level.

Neurological perspectives on voltage-gated sodium channels

PubMed Central

Linley, John E.; Baker, Mark D.; Minett, Michael S.; Cregg, Roman; Werdehausen, Robert; Rugiero, François

2012-01-01

The activity of voltage-gated sodium channels has long been linked to disorders of neuronal excitability such as epilepsy and chronic pain. Recent genetic studies have now expanded the role of sodium channels in health and disease, to include autism, migraine, multiple sclerosis, cancer as well as muscle and immune system disorders. Transgenic mouse models have proved useful in understanding the physiological role of individual sodium channels, and there has been significant progress in the development of subtype selective inhibitors of sodium channels. This review will outline the functions and roles of specific sodium channels in electrical signalling and disease, focusing on neurological aspects. We also discuss recent advances in the development of selective sodium channel inhibitors. PMID:22961543

Pd/Cu-Oxide Nanoconjugate at Zeolite-Y Crystallite Crafting the Mesoporous Channels for Selective Oxidation of Benzyl-Alcohols.

PubMed

Sharma, Mukesh; Das, Biraj; Sharma, Mitu; Deka, Biplab K; Park, Young-Bin; Bhargava, Suresh K; Bania, Kusum K

2017-10-11

Solid-state grinding of palladium and copper salts allowed the growth of palladium/copper oxide interface at the zeolite-Y surface. The hybrid nanostructured material was used as reusable heterogeneous catalyst for selective oxidation of various benzyl alcohols. The large surface area provided by the zeolite-Y matrix highly influenced the catalytic activity, as well as the recyclability of the synthesized catalyst. Impregnation of PdO-CuO nanoparticles on zeolite crystallite leads to the generation of mesoporous channel that probably prevented the leaching of the metal-oxide nanoparticles and endorsed high mass transfer. Formation of mesoporous channel at the external surface of zeolite-Y was evident from transmission electron microscopy and surface area analysis. PdO-CuO nanoparticles were found to be within the range of 2-5 nm. The surface area of PdO-CuO-Y catalyst was found to be much lower than parent zeolite-Y. The decrease in surface area as well as the presence of hysteresis loop in the N 2 -adsoprtion isotherm further suggested successful encapsulation of PdO-CuO nanoparticles via the mesoporous channel formation. The high positive shifting in binding energy in both Pd and Cu was attributed to the influence of zeolite-Y framework on lattice contraction of metal oxides via confinement effect. PdO-CuO-Y catalyst was found to oxidize benzyl alcohol with 99% selectivity. On subjecting to microwave irradiation the same oxidation reaction was found to occur at ambient condition giving same conversion and selectivity.

Possibility of synthesizing a doubly magic superheavy nucleus

NASA Astrophysics Data System (ADS)

Aritomo, Y.

2007-02-01

The possibility of synthesizing a doubly magic superheavy nucleus, 298114184, is investigated on the basis of fluctuation-dissipation dynamics. In order to synthesize this nucleus, we must generate more neutron-rich compound nuclei because of the neutron emissions from excited compound nuclei. The compound nucleus 304114 has two advantages to achieving a high survival probability. First, because of low neutron separation energy and rapid cooling, the shell correction energy recovers quickly. Secondly, owing to neutron emissions, the neutron number in the nucleus approaches that of the double closed shell and the nucleus attains a large fission barrier. Because of these two effects, the survival probability of 304114 does not decrease until the excitation energy E*=50 MeV. These properties lead to a rather high evaporation residue cross section.

In pursuit of small molecule chemistry for calcium-permeable non-selective TRPC channels – mirage or pot of gold?

PubMed Central

Bon, Robin S; Beech, David J

2013-01-01

The primary purpose of this review is to address the progress towards small molecule modulators of human Transient Receptor Potential Canonical proteins (TRPC1, TRPC3, TRPC4, TRPC5, TRPC6 and TRPC7). These proteins generate channels for calcium and sodium ion entry. They are relevant to many mammalian cell types including acinar gland cells, adipocytes, astrocytes, cardiac myocytes, cochlea hair cells, endothelial cells, epithelial cells, fibroblasts, hepatocytes, keratinocytes, leukocytes, mast cells, mesangial cells, neurones, osteoblasts, osteoclasts, platelets, podocytes, smooth muscle cells, skeletal muscle and tumour cells. There are broad-ranging positive roles of the channels in cell adhesion, migration, proliferation, survival and turning, vascular permeability, hypertrophy, wound-healing, hypo-adiponectinaemia, angiogenesis, neointimal hyperplasia, oedema, thrombosis, muscle endurance, lung hyper-responsiveness, glomerular filtration, gastrointestinal motility, pancreatitis, seizure, innate fear, motor coordination, saliva secretion, mast cell degranulation, cancer cell drug resistance, survival after myocardial infarction, efferocytosis, hypo-matrix metalloproteinase, vasoconstriction and vasodilatation. Known small molecule stimulators of the channels include hyperforin, genistein and rosiglitazone, but there is more progress with inhibitors, some of which have promising potency and selectivity. The inhibitors include 2-aminoethoxydiphenyl borate, 2-aminoquinolines, 2-aminothiazoles, fatty acids, isothiourea derivatives, naphthalene sulfonamides, N-phenylanthranilic acids, phenylethylimidazoles, piperazine/piperidine analogues, polyphenols, pyrazoles and steroids. A few of these agents are starting to be useful as tools for determining the physiological and pathophysiological functions of TRPC channels. We suggest that the pursuit of small molecule modulators for TRPC channels is important but that it requires substantial additional effort and

A distinct sodium channel voltage-sensor locus determines insect selectivity of the spider toxin Dc1a.

PubMed

Bende, Niraj S; Dziemborowicz, Sławomir; Mobli, Mehdi; Herzig, Volker; Gilchrist, John; Wagner, Jordan; Nicholson, Graham M; King, Glenn F; Bosmans, Frank

2014-07-11

β-Diguetoxin-Dc1a (Dc1a) is a toxin from the desert bush spider Diguetia canities that incapacitates insects at concentrations that are non-toxic to mammals. Dc1a promotes opening of German cockroach voltage-gated sodium (Nav) channels (BgNav1), whereas human Nav channels are insensitive. Here, by transplanting commonly targeted S3b-S4 paddle motifs within BgNav1 voltage sensors into Kv2.1, we find that Dc1a interacts with the domain II voltage sensor. In contrast, Dc1a has little effect on sodium currents mediated by PaNav1 channels from the American cockroach even though their domain II paddle motifs are identical. When exploring regions responsible for PaNav1 resistance to Dc1a, we identified two residues within the BgNav1 domain II S1-S2 loop that when mutated to their PaNav1 counterparts drastically reduce toxin susceptibility. Overall, our results reveal a distinct region within insect Nav channels that helps determine Dc1a sensitivity, a concept that will be valuable for the design of insect-selective insecticides.

Radiative Rates for Forbidden Transitions in Doubly-Ionized Fe-Peak Elements

NASA Astrophysics Data System (ADS)

Fivet, Vanessa; Quinet, P.; Bautista, M.

2012-05-01

Accurate and reliable atomic data for lowly-ionized Fe-peak species (Sc, Ti, V, Cr, Mn, Fe, Co, Ni and Cu) are of paramount importance for the analysis of the high resolution astrophysical spectra currently available. The third spectra of several iron group elements have been observed in different galactic sources like Herbig-Haro objects in the Orion Nebula [1] and stars like Eta Carinae [2]. However, forbidden transitions between low-lying metastable levels of doubly-ionized iron-peak ions have been very little investigated so far and radiative rates for those lines remain sparse or inexistent. We are carrying out a systematic study of the electronic structure of doubly-ionized iron-peak elements. The magnetic dipole (M1) and electric quadrupole (E2) transition probabilities are computed using the pseudo-relativistic Hartree-Fock (HFR) code of Cowan [3] and the central Thomas-Fermi-Dirac potential approximation implemented in AUTOSTRUCTURE [4]. This multi-platform approach allows for consistency checks and intercomparison and has proven very successful in the study of the complex Fe-peak species where many different effects contribute [5]. References [1] A. Mesa-Delgado et al., MNRAS 395 (2009) 855 [2] S. Johansson et al., A&A 361 (2000) 977 [3] R.D. Cowan, The Theory of Atomic Structure and Spectra, Berkeley: Univ. California Press (1981) [4] N.R. Badnell, J. Phys. B: At. Mol. Opt. Phys. 30 (1997) 1 [5] M. Bautista et al., ApJ 718 (2010) L189

Integration of collinear-type doubly unresolved counterterms in NNLO jet cross sections

NASA Astrophysics Data System (ADS)

Del Duca, Vittorio; Somogyi, Gábor; Trócsányi, Zoltán

2013-06-01

In the context of a subtraction method for jet cross sections at NNLO accuracy in the strong coupling, we perform the integration over the two-particle factorised phase space of the collinear-type contributions to the doubly unresolved counterterms. We present the final result as a convolution in colour space of the Born cross section and of an insertion operator, which is written in terms of master integrals that we expand in the dimensional regularisation parameter.

Doubly stochastic Poisson process models for precipitation at fine time-scales

NASA Astrophysics Data System (ADS)

Ramesh, Nadarajah I.; Onof, Christian; Xie, Dichao

2012-09-01

This paper considers a class of stochastic point process models, based on doubly stochastic Poisson processes, in the modelling of rainfall. We examine the application of this class of models, a neglected alternative to the widely-known Poisson cluster models, in the analysis of fine time-scale rainfall intensity. These models are mainly used to analyse tipping-bucket raingauge data from a single site but an extension to multiple sites is illustrated which reveals the potential of this class of models to study the temporal and spatial variability of precipitation at fine time-scales.

Fabrication and Analysis of a Selectively Contacted Dual Channel High Electron Mobility Field-Effect Transistor

NASA Astrophysics Data System (ADS)

Khanna, Ravi

1992-01-01

A selectively contacted dual-channel high electron mobility transistor (SCD-CHEMT) has been designed, fabricated, and electrically characterized, in order to better understand the properties of two layers of two-dimensional electron gases (2DEGs) confined within a quantum well. The 2DEGs are placed under a Schottky barrier control gate which modulates their sheet charge densities, and by use of auxiliary Schottky barrier gates and two levels of ohmic contacts, electrical contacts to the individual channels in which each 2DEG resides is achieved. The design of the dual channel FET structure, and its practical realization by recourse to process development and fabrication are described, as are the techniques, results, and interpretations of electrical characterizations used to analyze the completed device. Critical fabrication procedures involving photolithography, etching, deposition, shallow and deep ohmic contact formation, and gate formation are developed, and a simple technique to reduce gate leakage by photo-oxidation is demonstrated. Analysis of the completed device is performed using one-dimensional band diagram simulations, magnetotransport and electrical measurements. Magnetotransport studies establish the existence of two 2DEGs within the quantum well at 4K. Drain current vs. drain voltage, and transconductance vs. gate voltage characteristics at room temperature confirm the presence of two 2DEGs and show that current flow between them occurs easily at room temperature. Carrier electron mobility profiles are taken of the 2DEGs and show that the lower 2DEG has a mobility comparable to that of a 2DEG formed at a normal interface, indicating that the "inverted interface problem" has been overcome. Capacitance vs. gate voltage measurements are taken, which are consistent with a simple device model consisting of gate depletion and interelectrode parasitic capacitances. It is concluded from the analysis that the dual channel system resides in three basic states

Selective block of KATP channels: why the anti-diabetic sulphonylureas and rosiglitazone have more in common than we thought

PubMed Central

Dart, Caroline

2012-01-01

Rosiglitazone, the thiazolidinedione class anti-diabetic withdrawn from Europe in 2010 amid reports of adverse cardiovascular effects, is revealed by Yu et al. in this issue of the British Journal of Pharmacology to be a selective blocker of ATP-sensitive potassium (KATP) channels. This seems little cause for excitement given that the closure of pancreatic KATP channels is integral to insulin secretion; and sulphonylureas, which inhibit KATP channels, are widely used to treat type II diabetes. However, rosiglitazone, whose primary targets are nuclear transcription factors that regulate genes involved in lipid metabolism, blocks KATP channels by a novel mechanism different to that of the sulphonylureas and has a worrying preference for blood flow–regulating vascular KATP channels. Identification of a new molecule that modulates KATP channel gating will not only tell us more about how these complex metabolic sensors work but also raises questions as to whether rosiglitazone suppresses the cardiovascular system's ability to cope with metabolic stress – a claim that has dogged the sulphonylureas for many years. LINKED ARTICLE This article is a commentary on Yu et al., pp. 26–36 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2012.01934.x PMID:22506686

α-SNAP regulates dynamic, on-site assembly and calcium selectivity of Orai1 channels.

PubMed

Li, Peiyao; Miao, Yong; Dani, Adish; Vig, Monika

2016-08-15

Orai1 forms a highly calcium-selective pore of the calcium release activated channel, and α-SNAP is necessary for its function. Here we show that α-SNAP regulates on-site assembly of Orai1 dimers into calcium-selective multimers. We find that Orai1 is a dimer in resting primary mouse embryonic fibroblasts but displays variable stoichiometry in the plasma membrane of store-depleted cells. Remarkably, α-SNAP depletion induces formation of higher-order Orai1 oligomers, which permeate significant levels of sodium via Orai1 channels. Sodium permeation in α-SNAP-deficient cells cannot be corrected by tethering multiple Stim1 domains to Orai1 C-terminal tail, demonstrating that α-SNAP regulates functional assembly and calcium selectivity of Orai1 multimers independently of Stim1 levels. Fluorescence nanoscopy reveals sustained coassociation of α-SNAP with Stim1 and Orai1, and α-SNAP-depleted cells show faster and less constrained mobility of Orai1 within ER-PM junctions, suggesting Orai1 and Stim1 coentrapment without stable contacts. Furthermore, α-SNAP depletion significantly reduces fluorescence resonance energy transfer between Stim1 and Orai1 N-terminus but not C-terminus. Taken together, these data reveal a unique role of α-SNAP in the on-site functional assembly of Orai1 subunits and suggest that this process may, in part, involve enabling crucial low-affinity interactions between Orai1 N-terminus and Stim1. © 2016 Li, Miao, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Cd(2+) sensitivity and permeability of a low voltage-activated Ca(2+) channel with CatSper-like selectivity filter.

PubMed

Garza-López, Edgar; Chávez, Julio César; Santana-Calvo, Carmen; López-González, Ignacio; Nishigaki, Takuya

2016-07-01

CatSper is a sperm-specific Ca(2+) channel that plays an essential role in the male fertility. However, its biophysical properties have been poorly characterized mainly due to its deficient heterologous expression. As other voltage-gated Ca(2+) channels (CaVs), CatSper possesses a conserved Ca(2+)-selective filter motif ([T/S]x[D/E]xW) in the pore region. Interestingly, CatSper conserves four aspartic acids (DDDD) as the negatively charged residues in this motif while high voltage-activated CaVs have four glutamic acids (EEEE) and low voltage-activated CaVs possess two glutamic acids and two aspartic acids (EEDD). Previous studies based on site-directed mutagenesis of L- and T-type channels showed that the number of D seems to have a negative correlation with their cadmium (Cd(2+)) sensitivity. These results suggest that CatSper (DDDD) would have low sensitivity to Cd(2+). To explore Cd(2+)-sensitivity and -permeability of CatSper, we performed two types of experiments: 1) Electrophysiological analysis of heterologously expressed human CaV3.1 channel and three pore mutants (DEDD, EDDD and DDDD), 2) Cd(2+) imaging of human spermatozoa with FluoZin-1. Electrophysiological studies showed a significant increase in Cd(2+) and manganese (Mn(2+)) currents through the CaV3.1 mutants as well as a reduction in the inhibitory effect of Cd(2+) on the Ca(2+) current. In fluorescence imaging with human sperm, we observed an increase in Cd(2+) influx potentiated by progesterone, a potent activator of CatSper. These results support our hypothesis, namely that Cd(2+)-sensitivity and -permeability are related to the absolute number of D in the Ca(2+)-selective filter independently to the type of the Cav channels. Copyright © 2016 Elsevier Ltd. All rights reserved.

Select α-arrestins control cell-surface abundance of the mammalian Kir2.1 potassium channel in a yeast model.

PubMed

Hager, Natalie A; Krasowski, Collin J; Mackie, Timothy D; Kolb, Alexander R; Needham, Patrick G; Augustine, Andrew A; Dempsey, Alison; Szent-Gyorgyi, Christopher; Bruchez, Marcel P; Bain, Daniel J; Kwiatkowski, Adam V; O'Donnell, Allyson F; Brodsky, Jeffrey L

2018-05-21

Protein composition at the plasma membrane is tightly regulated, with rapid protein internalization and selective targeting to the cell surface occurring in response to environmental changes. For example, ion channels are dynamically relocalized to or from the plasma membrane in response to physiological alterations, allowing cells and organisms to maintain osmotic and salt homeostasis. To identify additional factors that regulate the selective trafficking of a specific ion channel, we used a yeast model for a mammalian potassium channel, the K+ inwardly rectifying channel Kir2.1. Kir2.1 maintains potassium homeostasis in heart muscle cells, and Kir2.1 defects lead to human disease. By examining the ability of Kir2.1 to rescue the growth of yeast cells lacking endogenous potassium channels, we discovered that specific α-arrestins regulate Kir2.1 localization. Specifically, we found that the Ldb19/Art1, Aly1/Art6, and Aly2/Art3 α-arrestin adaptor proteins promote Kir2.1 trafficking to the cell surface, increase Kir2.1 activity at the plasma membrane, and raise intracellular potassium levels. To better quantify the intracellular and cell-surface populations of Kir2.1, we created fluorescence-activating protein fusions and for the first time used this technique to measure the cell-surface residency of a plasma membrane protein in yeast. Our experiments revealed that two α-arrestin effectors also control Kir2.1 localization. In particular, both the Rsp5 ubiquitin ligase and the protein phosphatase calcineurin facilitated the α-arrestin-mediated trafficking of Kir2.1. Together, our findings implicate α-arrestins in regulating an additional class of plasma membrane proteins and establish a new tool for dissecting the trafficking itinerary of any membrane protein in yeast. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Historical Channel Adjustment and Estimates of Selected Hydraulic Values in the Lower Sabine River and Lower Brazos River Basins, Texas and Louisiana

USGS Publications Warehouse

Heitmuller, Franklin T.; Greene, Lauren E.

2009-01-01

The U.S. Geological Survey, in cooperation with the Texas Water Development Board, evaluated historical channel adjustment and estimated selected hydraulic values at U.S. Geological Survey streamflow-gaging stations in the lower Sabine River Basin in Texas and Louisiana and lower Brazos River Basin in Texas to support geomorphic assessments of the Texas Instream Flow Program. Channel attributes including cross-section geometry, slope, and planform change were evaluated to learn how each river's morphology changed over the years in response to natural and anthropogenic disturbances. Historical and contemporary cross-sectional channel geometries at several gaging stations on each river were compared, planform changes were assessed, and hydraulic values were estimated including mean flow velocity, bed shear stress, Froude numbers, and hydraulic depth. The primary sources of historical channel morphology information were U.S. Geological Survey hard-copy discharge-measurement field notes. Additional analyses were done using computations of selected flow hydraulics, comparisons of historical and contemporary aerial photographs, comparisons of historical and contemporary ground photographs, evaluations of how frequently stage-discharge rating curves were updated, reviews of stage-discharge relations for field measurements, and considerations of bridge and reservoir construction activities. Based on historical cross sections at three gaging stations downstream from Toledo Bend Reservoir, the lower Sabine River is relatively stable, but is subject to substantial temporary scour-and-fill processes during floods. Exceptions to this characterization of relative stability include an episode of channel aggradation at the Sabine River near Bon Wier, Texas, during the 1930s, and about 2 to 3 feet of channel incision at the Sabine River near Burkeville, Texas, since the late 1950s. The Brazos River, at gaging stations downstream from Waco, Texas, has adjusted to a combination of

Binding Energy of 79Cu: Probing the Structure of the Doubly Magic 78Ni from Only One Proton Away

NASA Astrophysics Data System (ADS)

Welker, A.; Althubiti, N. A. S.; Atanasov, D.; Blaum, K.; Cocolios, T. E.; Herfurth, F.; Kreim, S.; Lunney, D.; Manea, V.; Mougeot, M.; Neidherr, D.; Nowacki, F.; Poves, A.; Rosenbusch, M.; Schweikhard, L.; Wienholtz, F.; Wolf, R. N.; Zuber, K.

2017-11-01

The masses of the neutron-rich copper isotopes 75-79Cu are determined using the precision mass spectrometer ISOLTRAP at the CERN-ISOLDE facility. The trend from the new data differs significantly from that of previous results, offering a first accurate view of the mass surface adjacent to the Z =28 , N =50 nuclide 78Ni and supporting a doubly magic character. The new masses compare very well with large-scale shell-model calculations that predict shape coexistence in a doubly magic 78Ni and a new island of inversion for Z <28 . A coherent picture of this important exotic region begins to emerge where excitations across Z =28 and N =50 form a delicate equilibrium with a spherical mean field.

Fluorescence correlation spectroscopy analysis for accurate determination of proportion of doubly labeled DNA in fluorescent DNA pool for quantitative biochemical assays.

PubMed

Hou, Sen; Sun, Lili; Wieczorek, Stefan A; Kalwarczyk, Tomasz; Kaminski, Tomasz S; Holyst, Robert

2014-01-15

Fluorescent double-stranded DNA (dsDNA) molecules labeled at both ends are commonly produced by annealing of complementary single-stranded DNA (ssDNA) molecules, labeled with fluorescent dyes at the same (3' or 5') end. Because the labeling efficiency of ssDNA is smaller than 100%, the resulting dsDNA have two, one or are without a dye. Existing methods are insufficient to measure the percentage of the doubly-labeled dsDNA component in the fluorescent DNA sample and it is even difficult to distinguish the doubly-labeled DNA component from the singly-labeled component. Accurate measurement of the percentage of such doubly labeled dsDNA component is a critical prerequisite for quantitative biochemical measurements, which has puzzled scientists for decades. We established a fluorescence correlation spectroscopy (FCS) system to measure the percentage of doubly labeled dsDNA (PDL) in the total fluorescent dsDNA pool. The method is based on comparative analysis of the given sample and a reference dsDNA sample prepared by adding certain amount of unlabeled ssDNA into the original ssDNA solution. From FCS autocorrelation functions, we obtain the number of fluorescent dsDNA molecules in the focal volume of the confocal microscope and PDL. We also calculate the labeling efficiency of ssDNA. The method requires minimal amount of material. The samples have the concentration of DNA in the nano-molar/L range and the volume of tens of microliters. We verify our method by using restriction enzyme Hind III to cleave the fluorescent dsDNA. The kinetics of the reaction depends strongly on PDL, a critical parameter for quantitative biochemical measurements. Copyright © 2013 Elsevier B.V. All rights reserved.

From pan-reactive KV7 channel opener to subtype selective opener/inhibitor by addition of a methyl group.

PubMed

Blom, Sigrid Marie; Rottländer, Mario; Kehler, Jan; Bundgaard, Christoffer; Schmitt, Nicole; Jensen, Henrik Sindal

2014-01-01

The voltage-gated potassium channels of the KV7 family (KV7.1-5) play important roles in controlling neuronal excitability and are therefore attractive targets for treatment of CNS disorders linked to hyperexcitability. One of the main challenges in developing KV7 channel active drugs has been to identify compounds capable of discriminating between the neuronally expressed subtypes (KV7.2-5), aiding the identification of the subunit composition of KV7 currents in various tissues, and possessing better therapeutic potential for particular indications. By taking advantage of the structure-activity relationship of acrylamide KV7 channel openers and the effects of these compounds on mutant KV7 channels, we have designed and synthesized a novel KV7 channel modulator with a unique profile. The compound, named SMB-1, is an inhibitor of KV7.2 and an activator of KV7.4. SMB-1 inhibits KV7.2 by reducing the current amplitude and increasing the time constant for the slow component of the activation kinetics. The activation of KV7.4 is seen as an increase in the current amplitude and a slowing of the deactivation kinetics. Experiments studying mutant channels with a compromised binding site for the KV7.2-5 opener retigabine indicate that SMB-1 binds within the same pocket as retigabine for both inhibition of KV7.2 and activation of KV7.4. SMB-1 may serve as a valuable tool for KV7 channel research and may be used as a template for further design of better subtype selective KV7 channel modulators. A compound with this profile could hold novel therapeutic potential such as the treatment of both positive and cognitive symptoms in schizophrenia.

Non-Selective Calcium Channel Blocker Bepridil Decreases Secondary Pathology in Mice after Photothrombotic Cortical Lesion

PubMed Central

Lipsanen, Anu; Flunkert, Stefanie; Kuptsova, Kristina; Hiltunen, Mikko; Windisch, Manfred; Hutter-Paier, Birgit; Jolkkonen, Jukka

2013-01-01

Experimental studies have identified a complex link between neurodegeneration, β-amyloid (Aβ) and calcium homeostasis. Here we asked whether early phase β-amyloid pathology in transgenic hAPPSL mice exaggerates the ischemic lesion and remote secondary pathology in the thalamus, and whether a non-selective calcium channel blocker reduces these pathologies. Transgenic hAPPSL (n = 33) and non-transgenic (n = 30) male mice (4–5 months) were subjected to unilateral cortical photothrombosis and treated with the non-selective calcium channel blocker bepridil (50 mg/kg, p.o., once a day) or vehicle for 28 days, starting administration 2 days after the operation. Animals were then perfused for histological analysis of infarct size, Aβ and calcium accumulation in the thalamus. Cortical photothrombosis resulted in a small infarct, which was associated with atypical Aβ and calcium accumulation in the ipsilateral thalamus. Transgenic mice had significantly smaller infarct volumes than non-transgenic littermates (P<0.05) and ischemia-induced rodent Aβ accumulation in the thalamus was lower in transgenic mice compared to non-transgenic mice (P<0.01). Bepridil decreased calcium load in the thalamus (P<0.01). The present data suggest less pronounced primary and secondary pathology in hAPPSL transgenic mice after ischemic cortical injury. Bepridil particularly decreased calcium pathology in the thalamus following ischemia. PMID:23555933

Synthesis, structural characterization and selectively catalytic properties of metal-organic frameworks with nano-sized channels: A modular design strategy

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

Qiu Lingguang; Gu Lina; Hu Gang

2009-03-15

Modular design method for designing and synthesizing microporous metal-organic frameworks (MOFs) with selective catalytical activity was described. MOFs with both nano-sized channels and potential catalytic activities could be obtained through self-assembly of a framework unit and a catalyst unit. By selecting hexaaquo metal complexes and the ligand BTC (BTC=1,3,5-benzenetricarboxylate) as framework-building blocks and using the metal complex [M(phen){sub 2}(H{sub 2}O){sub 2}]{sup 2+} (phen=1,10-phenanthroline) as a catalyst unit, a series of supramolecular MOFs 1-7 with three-dimensional nano-sized channels, i.e. [M{sup 1}(H{sub 2}O){sub 6}].[M{sup 2}(phen){sub 2}(H{sub 2}O){sub 2}]{sub 2}.2(BTC).xH{sub 2}O (M{sup 1}, M{sup 2}=Co(II), Ni(II), Cu(II), Zn(II), or Mn(II), phen=1,10-phenanthroline, BTC=1,3,5-benzenetricarboxylate, x=22-24),more » were synthesized through self-assembly, and their structures were characterized by IR, elemental analysis, and single-crystal X-ray diffraction. These supramolecular microporous MOFs showed significant size and shape selectivity in the catalyzed oxidation of phenols, which is due to catalytic reactions taking place in the channels of the framework. Design strategy, synthesis, and self-assembly mechanism for the construction of these porous MOFs were discussed. - Grapical abstract: A modular design strategy has been developed to synthesize microporous metal-organic frameworks with potential catalytic activity by self-assembly of the framework-building blocks and the catalyst unit.« less

G protein-gated K+ channel ablation in forebrain pyramidal neurons selectively impairs fear learning

PubMed Central

Victoria, Nicole C.; de Velasco, Ezequiel Marron Fernandez; Ostrovskaya, Olga; Metzger, Stefania; Xia, Zhilian; Kotecki, Lydia; Benneyworth, Michael A.; Zink, Anastasia N.; Martemyanov, Kirill A.; Wickman, Kevin

2015-01-01

Background Cognitive dysfunction occurs in many debilitating conditions including Alzheimer’s disease, Down syndrome, schizophrenia, and mood disorders. The dorsal hippocampus is a critical locus of cognitive processes linked to spatial and contextual learning. G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels, which mediate the postsynaptic inhibitory effect of many neurotransmitters, have been implicated in hippocampal-dependent cognition. Available evidence, however, derives primarily from constitutive gain-of-function models that lack cellular specificity. Methods We used constitutive and neuron-specific gene ablation models targeting an integral subunit of neuronal GIRK channels (GIRK2) to probe the impact of GIRK channels on associative learning and memory. Results Constitutive Girk2−/− mice exhibited a striking deficit in hippocampal-dependent (contextual) and hippocampal-independent (cue) fear conditioning. Mice lacking GIRK2 in GABA neurons (GAD-Cre:Girk2flox/flox mice) exhibited a clear deficit in GIRK-dependent signaling in dorsal hippocampal GABA neurons, but no evident behavioral phenotype. Mice lacking GIRK2 in forebrain pyramidal neurons (CaMKII-Cre(+):Girk2flox/flox mice) exhibited diminished GIRK-dependent signaling in dorsal, but not ventral, hippocampal pyramidal neurons. CaMKII-Cre(+):Girk2flox/flox mice also displayed a selective impairment in contextual fear conditioning, as both cue-fear and spatial learning were intact in these mice. Finally, loss of GIRK2 in forebrain pyramidal neurons correlated with enhanced long-term depression and blunted depotentiation of long-term potentiation at the Schaffer collateral/CA1 synapse in the dorsal hippocampus. Conclusions Our data suggest that GIRK channels in dorsal hippocampal pyramidal neurons are necessary for normal learning involving aversive stimuli, and support the contention that dysregulation of GIRK-dependent signaling may underlie cognitive dysfunction in some disorders. PMID

The formation of the doubly stable stratification in the Mediterranean Outflow

NASA Astrophysics Data System (ADS)

Bormans, M.; Turner, J. S.

1990-11-01

The Mediterranean Outflow as it exits from the Strait of Gibraltar can be seen as a gravity current flowing down the slope and mixing with Atlantic Water until it reaches its own density level. Typical salinity and temperature profiles through the core region of a Meddy show that the bottom of the core is colder and saltier than the top, leading to a stably stratified core with respect to double-diffusive processes. The bottom of the core is also more enriched with Mediterranean Water than the top, and this behaviour can be explained by a reduced mixing of the source water with the environment close to the rigid bottom. Although the mechanism involved is different from the actual case, we have successfully produced these doubly stable gradient in some laboratory experiments which incorporate the "filling-box" mechanism. Salt and sugar were used as laboratory analogues of temperature and salt, respectively. The laboratory experiments consisted of supplying a dense input fluid at the surface of a linearly salt stratified environment. We suggest that req, the ratio of the initial volume flux at the source to the volume flux at the equilibrium level, is an important parameter, and that in our experiments this must be in general smaller than 0.1 in order to produce a doubly stable region of salt and sugar. The most relevant experiments had a mixed sugar/salt input which is the analogue of the Mediterranean Outflow as it mixes with Atlantic Water outside the Strait of Gibraltar.

Selective disruption of high sensitivity heat activation but not capsaicin activation of TRPV1 channels by pore turret mutations

PubMed Central

Cui, Yuanyuan; Yang, Fan; Cao, Xu; Yarov-Yarovoy, Vladimir

2012-01-01

The capsaicin receptor transient receptor potential vanilloid (TRPV)1 is a highly heat-sensitive ion channel. Although chemical activation and heat activation of TRPV1 elicit similar pungent, painful sensation, the molecular mechanism underlying synergistic activation remains mysterious. In particular, where the temperature sensor is located and whether heat and capsaicin share a common activation pathway are debated. To address these fundamental issues, we searched for channel mutations that selectively affected one form of activation. We found that deletion of the first 10 amino acids of the pore turret significantly reduced the heat response amplitude and shifted the heat activation threshold, whereas capsaicin activation remained unchanged. Removing larger portions of the turret disrupted channel function. Introducing an artificial sequence to replace the deleted region restored sensitive capsaicin activation in these nonfunctional channels. The heat activation, however, remained significantly impaired, with the current exhibiting diminishing heat sensitivity to a level indistinguishable from that of a voltage-gated potassium channel, Kv7.4. Our results demonstrate that heat and capsaicin activation of TRPV1 are structurally and mechanistically distinct processes, and the pore turret is an indispensible channel structure involved in the heat activation process but is not part of the capsaicin activation pathway. Synergistic effect of heat and capsaicin on TRPV1 activation may originate from convergence of the two pathways on a common activation gate. PMID:22412190

Determination of channel change for selected streams, Maricopa County, Arizona

USGS Publications Warehouse

Capesius, Joseph P.; Lehman, Ted W.

2002-01-01

In Maricopa County, Arizona, 10 sites on seven streams were studied to determine the lateral and vertical change of the channel. Channel change was studied over time scales ranging from individual floods to decades using cross-section surveys, discharge measurements, changes in the point of zero flow, and repeat photography. All of the channels showed some change in cross-section area or hydraulic radius over the time scales studied, but the direction and mag-nitude of change varied considerably from one flow, or series of flows, to another. The documentation of cross-section geometry for streams in Maricopa County for long-term monitoring was begun in this study.

Pore size matters for potassium channel conductance

PubMed Central

Moldenhauer, Hans; Pincuntureo, Matías

2016-01-01

Ion channels are membrane proteins that mediate efficient ion transport across the hydrophobic core of cell membranes, an unlikely process in their absence. K+ channels discriminate K+ over cations with similar radii with extraordinary selectivity and display a wide diversity of ion transport rates, covering differences of two orders of magnitude in unitary conductance. The pore domains of large- and small-conductance K+ channels share a general architectural design comprising a conserved narrow selectivity filter, which forms intimate interactions with permeant ions, flanked by two wider vestibules toward the internal and external openings. In large-conductance K+ channels, the inner vestibule is wide, whereas in small-conductance channels it is narrow. Here we raise the idea that the physical dimensions of the hydrophobic internal vestibule limit ion transport in K+ channels, accounting for their diversity in unitary conductance. PMID:27619418

A Newborn Asteroid Family of Likely Rotational Origin Harboring a Doubly-Synchronous Binary

NASA Astrophysics Data System (ADS)

Drahus, Michal; Waniak, Waclaw

2016-10-01

From the total number of about twenty active asteroids identified to date, one of the most intriguing is P/2012 F5. The 2-km sized object has a short rotation period of 3.24 hr - the shortest known among main-belt active asteroids and comets - and is trailed by several fragments recently separated from the main nucleus (Drahus et al. 2015, ApJL 802, L8). Our extensive observations with Hubble in late 2015 and early 2016 have revealed that the fragments are real and stable "baby asteroids", still cocooned in their birth dust trail. Consequently, P/2012 F5 is the first known asteroid family forming in the present-day epoch. Given the rapid spin of the main nucleus, the system is also the best candidate for the first "rotational" asteroid family originating from rotational fission (as opposed to the long-known "collisional" families), extending the recently identified class of asteroid pairs (Pravec et al. 2010, Nature 466, 1085). Furthermore, the HST data allowed us to measure a light curve of the brightest fragment of P/2012 F5, several magnitudes fainter than the main nucleus. The light curve has all the characteristics of a close binary with significantly elongated, roughly equal sized components, having equal rotation and orbital periods of about 9 hr. The existence of a doubly-synchronous binary in an ultra-young asteroid family is seemingly inconsistent with the established "slow" binary formation path, in which YORP torques first lead to rotational fission and then tides lead to synchronization (Jacobson & Scheeres 2011, Icarus 214, 161). Instead, we believe that the object fissioned while orbiting the main nucleus and drawing its angular momentum, and was subsequently ejected from the system as a finished doubly-synchronous binary. This scenario is consistent with computer simulations in that the timescales for secondary fission and ejection from the system are indeed very short (Jacobson & Scheeres 2011, Icarus 214, 161). But the empirical evidence that

Developing a Comparative Docking Protocol for the Prediction of Peptide Selectivity Profiles: Investigation of Potassium Channel Toxins

PubMed Central

Chen, Po-Chia; Kuyucak, Serdar

2012-01-01

During the development of selective peptides against highly homologous targets, a reliable tool is sought that can predict information on both mechanisms of binding and relative affinities. These tools must first be tested on known profiles before application on novel therapeutic candidates. We therefore present a comparative docking protocol in HADDOCK using critical motifs, and use it to “predict” the various selectivity profiles of several major αKTX scorpion toxin families versus Kv1.1, Kv1.2 and Kv1.3. By correlating results across toxins of similar profiles, a comprehensive set of functional residues can be identified. Reasonable models of channel-toxin interactions can be then drawn that are consistent with known affinity and mutagenesis. Without biological information on the interaction, HADDOCK reproduces mechanisms underlying the universal binding of αKTX-2 toxins, and Kv1.3 selectivity of αKTX-3 toxins. The addition of constraints encouraging the critical lysine insertion confirms these findings, and gives analogous explanations for other families, including models of partial pore-block in αKTX-6. While qualitatively informative, the HADDOCK scoring function is not yet sufficient for accurate affinity-ranking. False minima in low-affinity complexes often resemble true binding in high-affinity complexes, despite steric/conformational penalties apparent from visual inspection. This contamination significantly complicates energetic analysis, although it is usually possible to obtain correct ranking via careful interpretation of binding-well characteristics and elimination of false positives. Aside from adaptations to the broader potassium channel family, we suggest that this strategy of comparative docking can be extended to other channels of interest with known structure, especially in cases where a critical motif exists to improve docking effectiveness. PMID:22474570

Search for doubly-charged Higgs Boson production in the decay H ++ H -- → μ +μ +μ -μ - with the D0 detector at √s = 1.96-TeV

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

Zdrazil, Marian

2004-08-01

This work presents a search for the pair production of doubly-charged Higgs Bosons in the process pmore » $$\\bar{p}$$ → H ++H -- → μ +μ +μ -μ - using inclusive dimuon events. These data correspond to an integrated luminosity of about 113 pb 1 and were recorded by the D0 experiment between August 2002 and June 2003. In the absence of a signal, 95% confidence level mass limits of M(H$$±±\\atop{L}$$) > 118.6 GeV/c 2 and M(H R ±±) > 98.1 GeV/c 2 are set for left-handed and right-handed doubly-charged Higgs boson, assuming 100% branching into muons and hypercharge |Y| = 2 and Yukawa coupling h μμ > 10 -7. This is the first search for doubly-charged Higgs bosons at hadron colliders. It significantly extends the previous mass limit of 100.5 GeV/c 2 for a left-handed doubly-charged Higgs boson measured in the muon final states by the OPAL collaboration.« less

A New Equivalence Theory Method for Treating Doubly Heterogeneous Fuel - I. Theory

DOE PAGES

Williams, Mark L.; Lee, Deokjung; Choi, Sooyoung

2015-03-04

A new methodology has been developed to treat resonance self-shielding in doubly heterogeneous very high temperature gas-cooled reactor systems in which the fuel compact region of a reactor lattice consists of small fuel grains dispersed in a graphite matrix. This new method first homogenizes the fuel grain and matrix materials using an analytically derived disadvantage factor from a two-region problem with equivalence theory and intermediate resonance method. This disadvantage factor accounts for spatial self-shielding effects inside each grain within the framework of an infinite array of grains. Then the homogenized fuel compact is self-shielded using a Bondarenko method to accountmore » for interactions between the fuel compact regions in the fuel lattice. In the final form of the equations for actual implementations, the double-heterogeneity effects are accounted for by simply using a modified definition of a background cross section, which includes geometry parameters and cross sections for both the grain and fuel compact regions. With the new method, the doubly heterogeneous resonance self-shielding effect can be treated easily even with legacy codes programmed only for a singly heterogeneous system by simple modifications in the background cross section for resonance integral interpolations. This paper presents a detailed derivation of the new method and a sensitivity study of double-heterogeneity parameters introduced during the derivation. The implementation of the method and verification results for various test cases are presented in the companion paper.« less

Roughness characteristics of natural channels

USGS Publications Warehouse

Barnes, Harry Hawthorne

1967-01-01

Color photographs and descriptive data are presented for 50 stream channels for which roughness coefficients have been determined. All hydraulic computations involving flow in open channels require an evaluation of the roughness characteristics of the channel. In the absence of a satisfactory quantitative procedure this evaluation remains chiefly an art. The ability to evaluate roughness coefficients must be developed through experience. One means of gaining this experience is by examining and becoming acquainted with the appearance of some typical channels whose roughness coefficients are known. The photographs and data contained in this report represent a wide range of channel conditions. Familiarity with the appearance, geometry, and roughness characteristics of these channels will improve the engineer's ability to select roughness coefficients for other channels .

Refined hierarchical kinematics quasi-3D Ritz models for free vibration analysis of doubly curved FGM shells and sandwich shells with FGM core

NASA Astrophysics Data System (ADS)

Fazzolari, Fiorenzo A.; Carrera, Erasmo

2014-02-01

In this paper, the Ritz minimum energy method, based on the use of the Principle of Virtual Displacements (PVD), is combined with refined Equivalent Single Layer (ESL) and Zig Zag (ZZ) shell models hierarchically generated by exploiting the use of Carrera's Unified Formulation (CUF), in order to engender the Hierarchical Trigonometric Ritz Formulation (HTRF). The HTRF is then employed to carry out the free vibration analysis of doubly curved shallow and deep functionally graded material (FGM) shells. The PVD is further used in conjunction with the Gauss theorem to derive the governing differential equations and related natural boundary conditions. Donnell-Mushtari's shallow shell-type equations are given as a particular case. Doubly curved FGM shells and doubly curved sandwich shells made up of isotropic face sheets and FGM core are investigated. The proposed shell models are widely assessed by comparison with the literature results. Two benchmarks are provided and the effects of significant parameters such as stacking sequence, boundary conditions, length-to-thickness ratio, radius-to-length ratio and volume fraction index on the circular frequency parameters and modal displacements are discussed.

Techniques for analyzing frequency selective surfaces - A review

NASA Technical Reports Server (NTRS)

Mittra, Raj; Chan, Chi H.; Cwik, Tom

1988-01-01

A number of representative techniques for analyzing frequency-selective surfaces (FSSs), which comprise periodic arrays of patches or apertures in a conducting screen and find important applications as filters in microwaves and optics, are discussed. The basic properties of the FSSs are reviewed and several different approaches to predicting their frequency-response characteristics are described. Some recent developments in the treatment of truncated, curved, and doubly periodic screens are mentioned and representative experimental results are included.

On the intermolecular Coulombic decay of singly and doubly ionized states of water dimer.

PubMed

Stoychev, Spas D; Kuleff, Alexander I; Cederbaum, Lorenz S

2010-10-21

A semiquantitative study of the intermolecular Coulombic decay (ICD) of singly and doubly ionized water dimer has been carried out with the help of ab initio computed ionization spectra and potential energy curves (PECs). These PECs are particular cuts through the (H(2)O)(2), (H(2)O)(2) (+), and (H(2)O)(2) (++) hypersurfaces along the distance between the two oxygen atoms. A comparison with the recently published experimental data for the ICD in singly ionized water dimers [T. Jahnke, H. Sann, T. Havermeier et al., Nat. Phys. 6, 139 (2010)] and in large water clusters [M. Mucke, M. Braune, S. Barth et al., Nat. Phys. 6, 143 (2010)] shows that such a simplified description in which the internal degrees of freedom of the water molecules are frozen gives surprisingly useful results. Other possible decay channels of the singly ionized water dimer are also investigated and the influence of the H-atom participating in the hydrogen bond on the spectra of the proton-donor and proton-acceptor molecules in the dimer is discussed. Importantly, the decay processes of one-site dicationic states of water dimer are discussed and an estimate of the ICD-electron spectra is made. More than 33% of the dications produced by Auger decay are found to undergo ICD. The qualitative results show that the ICD following Auger decay in water is also expected to be an additional source of low-energy electrons proven to be extremely important for causing damages to living tissues.

Triple differential cross sections of magnesium in doubly symmetric geometry

NASA Astrophysics Data System (ADS)

S, Y. Sun; X, Y. Miao; Xiang-Fu, Jia

2016-01-01

A dynamically screened three-Coulomb-wave (DS3C) method is applied to study the single ionization of magnesium by electron impact. Triple differential cross sections (TDCS) are calculated in doubly symmetric geometry at incident energies of 13.65, 17.65, 22.65, 27.65, 37.65, 47.65, 57.65, and 67.65 eV. Comparisons are made with experimental data and theoretical predictions from a three-Coulomb-wave function (3C) approach and distorted-wave Born approximation (DWBA). The overall agreement between the predictions of the DS3C model and the DWBA approach with the experimental data is satisfactory. Project supported by the National Natural Science Foundation of China (Grant No. 11274215).

A Study on Segmented Multiple-Step Forming of Doubly Curved Thick Plate by Reconfigurable Multi-Punch Dies

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

Ko, Young Ho; Han, Myoung Soo; Han, Jong Man

2007-05-17

Doubly curved thick plate forming in shipbuilding industries is currently performed by a thermal forming process, called as Line Heating by using gas flame torches. Due to the empirical manual work of it, the industries are eager for an alternative way to manufacture curved thick plates for ships. It was envisaged in this study to manufacture doubly curved thick plates by the multi-punch die forming. Experiments and finite element analyses were conducted to evaluate the feasibility of the reconfigurable discrete die forming to the thick plates. Single and segmented multiple step forming procedures were considered from both forming efficiency andmore » accuracy. Configuration of the multi-punch dies suitable for the segmented multiple step forming was also explored. As a result, Segmented multiple step forming with matched dies had a limited formability when the objective shapes become complicate, while a unmatched die configuration provided better possibility to manufacture large curved plates for ships.« less

The Minimum Binding Energy and Size of Doubly Muonic D3 Molecule

NASA Astrophysics Data System (ADS)

Eskandari, M. R.; Faghihi, F.; Mahdavi, M.

The minimum energy and size of doubly muonic D3 molecule, which two of the electrons are replaced by the much heavier muons, are calculated by the well-known variational method. The calculations show that the system possesses two minimum positions, one at typically muonic distance and the second at the atomic distance. It is shown that at the muonic distance, the effective charge, zeff is 2.9. We assumed a symmetric planar vibrational model between two minima and an oscillation potential energy is approximated in this region.

First Spectroscopic Studies and Detection in SgrB2 of 13C-DOUBLY Substitued Ethyl Cyanide

NASA Astrophysics Data System (ADS)

Margulès, L.; Motiyenko, R. A.; Guillemin, J.-C.; Müller, Holger S. P.; Belloche, Arnaud

2015-06-01

Ethyl cyanide (CH_3CH_2CN) is one of the most abundant complex organic molecules in the interstellar medium firstly detected in OMC-1 and Sgr B2 in 1977. The vibrationally excited states are enough populated under ISM conditions and could be detected. Apart from the deuterated ones, all mono-substituted isotopologues of ethyl cyanide (13C and 15N have been detected in the ISM. The detection of isotopologues in the ISM is important: it can give information about the formation process of complex organic molecules, and it is essential to clean the ISM spectra from the lines of known molecules in order to detect new ones. The 12C/13C ratio found in SgrB2: 20-30 suggests that the doubly 13C could be present in the spectral line survey recently obtained with ALMA (EMoCA), but no spectroscopic studies exist up to now. We measured and analyzed the spectra of the 13C-doubly-substitued species up to 1 THz with the Lille solid-state based spectrometer. The spectroscopic results and and the detection of the doubly 13C species in SgrB2 will be presented. This work was supported by the CNES and the Action sur Projets de l'INSU, PCMI. This work was also done under ANR-13-BS05-0008-02 IMOLABS. Support by the Deutsche Forschungsgemeinschaft via SFB 956, project B3 is acknowledged D.~R.~Johnson, et al., Astrophys.~J. 1977, 218, L370 A.~Belloche, et al., A&A 2013, 559, A47 A.M.~Daly, et al., Astrophys.~J. 2013, 768, 81 K.~Demyk, et al. A&A 2007 466, 255 Margulès, et al. A&A 2009, 493, 565 Belloche et al. 2014, Science, 345, 1584

Dynamic mass exchange in doubly degenerate binaries. I - 0.9 and 1.2 solar mass stars

NASA Technical Reports Server (NTRS)

Benz, W.; Cameron, A. G. W.; Press, W. H.; Bowers, R. L.

1990-01-01

The dynamic mass exchange process in doubly degenerate binaries was investigated using a three-dimensional numerical simulation of the evolution of a doubly degenerate binary system in which the primary is a 1.2-solar-mass white dwarf and the Roche lobe filling secondary is a 0.9-solar-mass dwarf. The results show that, in a little more than two orbital periods, the secondary is completely destroyed and transformed into a thick disk orbiting about the primary. Since only a very small fraction of the mass (0.0063 solar mass) escapes the system, the evolution of the binary results in the formation of a massive object. This object is composed of three parts, the initial white dwarf primary, a very hot pressure-supported spherical envelope, and a rotationally supported outer disk. The evolution of the system can be understood in terms of a simple analytical model where it is shown that the angular momentum carried by the mass during the transfer and stored in the disk determines the evolution of the system.

New Atomic Data for Doubly Ionized Iron Group Atoms by High Resolution UV Fourier Transform Spectroscopy

NASA Technical Reports Server (NTRS)

Smith, Peter L.; Pickering, Juliet C.; Thorne, A. P.

2002-01-01

Currently available laboratory spectroscopic data of doubly ionized iron-group element were obtained about 50 years ago using spectrographs of modest dispersion, photographic plates, and eye estimates of intensities. The accuracy of the older wavelength data is about 10 mAngstroms at best, whereas wavelengths are now needed to an accuracy of 1 part in 10(exp 6) to 10(exp 7) (0.2 to 2 mAngstroms at 2000 Angstroms). The Fourier transform (FT) spectroscopy group at Imperial College, London, and collaborators at the Harvard College Observatory have used a unique VUV FT spectrometer in a program focussed on improving knowledge of spectra of many neutral and singly and doubly ionized, astrophysically important, iron group elements. Spectra of Fe II and Fe III have been recorded at UV and VUV wavelengths with signal-to-noise ratios of several hundred for the stronger lines. Wavelengths and energy levels for Fe III are an order of magnitude more accurate than previous work; analysis is close to completion. f-values for Fe II have been published.

Applications of Ko Displacement Theory to the Deformed Shape Predictions of the Doubly-Tapered Ikhana Wing

NASA Technical Reports Server (NTRS)

Ko, William L.; Richards, W. Lance; Fleischer, Van Tran

2009-01-01

The Ko displacement theory, formulated for weak nonuniform (slowly changing cross sections) cantilever beams, was applied to the deformed shape analysis of the doubly-tapered wings of the Ikhana unmanned aircraft. The two-line strain-sensing system (along the wingspan) was used for sensing the bending strains needed for the wing-deformed shapes (deflections and cross-sectional twist) analysis. The deflection equation for each strain-sensing line was expressed in terms of the bending strains evaluated at multiple numbers of strain-sensing stations equally spaced along the strain-sensing line. For the preflight shape analysis of the Ikhana wing, the strain data needed for input to the displacement equations for the shape analysis were obtained from the nodal-stress output of the finite-element analysis. The wing deflections and cross-sectional twist angles calculated from the displacement equations were then compared with those computed from the finite-element computer program. The Ko displacement theory formulated for weak nonlinear cantilever beams was found to be highly accurate in the deformed shape predictions of the doubly-tapered Ikhana wing.

Characterization of selective Calcium-Release Activated Calcium channel blockers in mast cells and T-cells from human, rat, mouse and guinea-pig preparations.

PubMed

Rice, Louise V; Bax, Heather J; Russell, Linda J; Barrett, Victoria J; Walton, Sarah E; Deakin, Angela M; Thomson, Sally A; Lucas, Fiona; Solari, Roberto; House, David; Begg, Malcolm

2013-03-15

Loss of function mutations in the two key proteins which constitute Calcium-Release Activated Calcium (CRAC) channels demonstrate the critical role of this ion channel in immune cell function. The aim of this study was to demonstrate that inhibition of immune cell activation could be achieved with highly selective inhibitors of CRAC channels in vitro using cell preparations from human, rat, mouse and guinea-pig. Two selective small molecule blockers of CRAC channels; GSK-5498A and GSK-7975A were tested to demonstrate their ability to inhibit mediator release from mast cells, and pro-inflammatory cytokine release from T-cells in a variety of species. Both GSK-5498A and GSK-7975A completely inhibited calcium influx through CRAC channels. This led to inhibition of the release of mast cell mediators and T-cell cytokines from multiple human and rat preparations. Mast cells from guinea-pig and mouse preparations were not inhibited by GSK-5498A or GSK-7975A; however cytokine release was fully blocked from T-cells in a mouse preparation. GSK-5498A and GSK-7975A confirm the critical role of CRAC channels in human mast cell and T-cell function, and that inhibition can be achieved in vitro. The rat displays a similar pharmacology to human, promoting this species for future in vivo research with this series of molecules. Together these observations provide a critical forward step in the identification of CRAC blockers suitable for clinical development in the treatment of inflammatory disorders. Copyright © 2013 Elsevier B.V. All rights reserved.

State reference design and saturated control of doubly-fed induction generators under voltage dips

NASA Astrophysics Data System (ADS)

Tilli, Andrea; Conficoni, Christian; Hashemi, Ahmad

2017-04-01

In this paper, the stator/rotor currents control problem of doubly-fed induction generator under faulty line voltage is carried out. Common grid faults cause a steep decline in the line voltage profile, commonly denoted as voltage dip. This point is critical for such kind of machines, having their stator windings directly connected to the grid. In this respect, solid methodological nonlinear control theory arguments are exploited and applied to design a novel controller, whose main goal is to improve the system behaviour during voltage dips, endowing it with low voltage ride through capability, a fundamental feature required by modern Grid Codes. The proposed solution exploits both feedforward and feedback actions. The feedforward part relies on suitable reference trajectories for the system internal dynamics, which are designed to prevent large oscillations in the rotor currents and command voltages, excited by line perturbations. The feedback part uses state measurements and is designed according to Linear Matrix Inequalities (LMI) based saturated control techniques to further reduce oscillations, while explicitly accounting for the system constraints. Numerical simulations verify the benefits of the internal dynamics trajectory planning, and the saturated state feedback action, in crucially improving the Doubly-Fed Induction Machine response under severe grid faults.

Discovery of a Potent, Selective T-type Calcium Channel Blocker as a Drug Candidate for the Treatment of Generalized Epilepsies.

PubMed

Bezençon, Olivier; Heidmann, Bibia; Siegrist, Romain; Stamm, Simon; Richard, Sylvia; Pozzi, Davide; Corminboeuf, Olivier; Roch, Catherine; Kessler, Melanie; Ertel, Eric A; Reymond, Isabelle; Pfeifer, Thomas; de Kanter, Ruben; Toeroek-Schafroth, Michael; Moccia, Luca G; Mawet, Jacques; Moon, Richard; Rey, Markus; Capeleto, Bruno; Fournier, Elvire

2017-12-14

We report here the discovery and pharmacological characterization of N-(1-benzyl-1H-pyrazol-3-yl)-2-phenylacetamide derivatives as potent, selective, brain-penetrating T-type calcium channel blockers. Optimization focused mainly on solubility, brain penetration, and the search for an aminopyrazole metabolite that would be negative in an Ames test. This resulted in the preparation and complete characterization of compound 66b (ACT-709478), which has been selected as a clinical candidate.

Language Planning, Channel Management, and ESP.

ERIC Educational Resources Information Center

Kennedy, Chris

Channel management, a concept developed in marketing to refer to the process by which a product is moved from production to consumption, uses a channel of distribution operating at several levels, each responsible for one or more of the activities of moving the product forward to the consumer. The function of channel management is to select the…

Fabrication of nanowire channels with unidirectional alignment and controlled length by a simple, gas-blowing-assisted, selective-transfer-printing technique.

PubMed

Kim, Yong-Kwan; Kang, Pil Soo; Kim, Dae-Il; Shin, Gunchul; Kim, Gyu Tae; Ha, Jeong Sook

2009-03-01

A printing-based lithographic technique for the patterning of V(2)O(5) nanowire channels with unidirectional orientation and controlled length is introduced. The simple, directional blowing of a patterned polymer stamp with N(2) gas, inked with randomly distributed V(2)O(5) nanowires, induces alignment of the nanowires perpendicular to the long axis of the line patterns. Subsequent stamping on the amine-terminated surface results in the selective transfer of the aligned nanowires with a controlled length corresponding to the width of the relief region of the polymer stamp. By employing such a gas-blowing-assisted, selective-transfer-printing technique, two kinds of device structures consisting of nanowire channels and two metal electrodes with top contact, whereby the nanowires were aligned either parallel (parallel device) or perpendicular (serial device) to the current flow in the conduction channel, are fabricated. The electrical properties demonstrate a noticeable difference between the two devices, with a large hysteresis in the parallel device but none in the serial device. Systematic analysis of the hysteresis and the electrical stability account for the observed hysteresis in terms of the proton diffusion in the water layer of the V(2)O(5) nanowires, induced by the application of an external bias voltage higher than a certain threshold voltage.

Inhibition of G-Protein-Activated Inwardly Rectifying K+ Channels by the Selective Norepinephrine Reuptake Inhibitors Atomoxetine and Reboxetine

PubMed Central

Kobayashi, Toru; Washiyama, Kazuo; Ikeda, Kazutaka

2010-01-01

Atomoxetine and reboxetine are commonly used as selective norepinephrine reuptake inhibitors (NRIs) for the treatment of attention-deficit/hyperactivity disorder and depression, respectively. Furthermore, recent studies have suggested that NRIs may be useful for the treatment of several other psychiatric disorders. However, the molecular mechanisms underlying the various effects of NRIs have not yet been sufficiently clarified. G-protein-activated inwardly rectifying K+ (GIRK or Kir3) channels have an important function in regulating neuronal excitability and heart rate, and GIRK channel modulation has been suggested to be a potential treatment for several neuropsychiatric disorders and cardiac arrhythmias. In this study, we investigated the effects of atomoxetine and reboxetine on GIRK channels using the Xenopus oocyte expression assay. In oocytes injected with mRNA for GIRK1/GIRK2, GIRK2, or GIRK1/GIRK4 subunits, extracellular application of atomoxetine or reboxetine reversibly reduced GIRK currents. The inhibitory effects were concentration-dependent, but voltage-independent, and time-independent during each voltage pulse. However, Kir1.1 and Kir2.1 channels were insensitive to atomoxetine and reboxetine. Atomoxetine and reboxetine also inhibited GIRK currents induced by activation of cloned A1 adenosine receptors or by intracellularly applied GTPγS, a nonhydrolyzable GTP analogue. Furthermore, the GIRK currents induced by ethanol were concentration-dependently inhibited by extracellularly applied atomoxetine but not by intracellularly applied atomoxetine. The present results suggest that atomoxetine and reboxetine inhibit brain- and cardiac-type GIRK channels, revealing a novel characteristic of clinically used NRIs. GIRK channel inhibition may contribute to some of the therapeutic effects of NRIs and adverse side effects related to nervous system and heart function. PMID:20393461

Localized traveling pulses in natural doubly diffusive convection

NASA Astrophysics Data System (ADS)

Lo Jacono, D.; Bergeon, A.; Knobloch, E.

2017-09-01

Two-dimensional natural doubly diffusive convection in a vertical slot driven by an imposed temperature difference in the horizontal is studied using numerical continuation and direct numerical simulation. Two cases are considered and compared. In the first a concentration difference that balances thermal buoyancy is imposed in the horizontal and stationary localized structures are found to be organized in a standard snakes-and-ladders bifurcation diagram. Disconnected branches of traveling pulses TPn consisting of n ,n =1 ,2 ,⋯ , corotating cells are identified and shown to accumulate on a tertiary branch of traveling waves. With Robin or mixed concentration boundary conditions on one wall all localized states travel and the hitherto stationary localized states may connect up with the traveling pulses. The stability of the TPn states is determined and unstable TPn shown to evolve into spatio-temporal chaos. The calculations are done with no-slip boundary conditions in the horizontal and periodic boundary conditions in the vertical.

Electron Transfer Ion/Ion Reactions in a Three-Dimensional Quadrupole Ion Trap: Reactions of Doubly and Triply Protonated Peptides with SO2·−

PubMed Central

Pitteri, Sharon J.; Chrisman, Paul A.; Hogan, Jason M.; McLuckey, Scott A.

2005-01-01

Ion–ion reactions between a variety of peptide cations (doubly and triply charged) and SO2 anions have been studied in a 3-D quadrupole ion trap, resulting in proton and electron transfer. Electron transfer dissociation (ETD) gives many c- and z-type fragments, resulting in extensive sequence coverage in the case of triply protonated peptides with SO2·−. For triply charged neurotensin, in which a direct comparison can be made between 3-D and linear ion trap results, abundances of ETD fragments relative to one another appear to be similar. Reactions of doubly protonated peptides with SO2·− give much less structural information from ETD than triply protonated peptides. Collision-induced dissociation (CID) of singly charged ions formed in reactions with SO2·− shows a combination of proton and electron transfer products. CID of the singly charged species gives more structural information than ETD of the doubly protonated peptide, but not as much information as ETD of the triply protonated peptide. PMID:15762593

Diphtheria toxin-induced channels in Vero cells selective for monovalent cations

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

Sandvig, K.; Olsnes, S.

1988-09-05

Ion fluxes associated with translocation of diphtheria toxin across the surface membrane of Vero cells were studied. When cells with surface-bound toxin were exposed to low pH to induce toxin entry, the cells became permeable to Na+, K+, H+, choline+, and glucosamine+. There was no increased permeability to Cl-, SO4(-2), glucose, or sucrose, whereas the uptake of /sup 45/Ca2+ was slightly increased. The influx of Ca2+, which appears to be different from that of monovalent cations, was reduced by several inhibitors of anion transport and by verapamil, Mn2+, Co2+, and Ca2+, but not by Mg2+. The toxin-induced fluxes of N+,more » K+, and protons were inhibited by Cd2+. Cd2+ also protected the cells against intoxication by diphtheria toxin, suggesting that the open cation-selective channel is required for toxin translocation. The involvement of the toxin receptor is discussed.« less

Bovine chromaffin cells possess FTX-sensitive calcium channels.

PubMed

Gandía, L; Albillos, A; García, A G

1993-07-30

The effects of the synthetic analogue of the toxin from the venom of the funnel-web spider Agenelopsis aperta (sFTX) on whole-cell Ba2+ currents through Ca2+ channels were studied in cultured bovine chromaffin cells. sFTX selectively and reversibly blocked a significant component (55 +/- 3%) of the whole-cell IBa. Effects of sFTX were additive to those of omega-conotoxin GVIA, a selective blocker of N-type Ca2+ channels, and those of furnidipine, a novel dihydropyridine L-type Ca2+ channel blocker. We conclude that the cultured bovine chromaffin cells, in addition to N- and L-type Ca2+ channels, possess a P-type component in their whole-cell currents through their Ca2+ channels.

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

Fifth-order superintegrable quantum systems separating in Cartesian coordinates: Doubly exotic potentials

NASA Astrophysics Data System (ADS)

Abouamal, Ismail; Winternitz, Pavel

2018-02-01

We consider a two-dimensional quantum Hamiltonian separable in Cartesian coordinates and allowing a fifth-order integral of motion. We impose the superintegrablity condition and find all doubly exotic superintegrable potentials (i.e., potentials V(x, y) = V1(x) + V2(y), where neither V1(x) nor V2(y) satisfy a linear ordinary differential equation), allowing the existence of such an integral. All of these potentials are found to have the Painlevé property. Most of them are expressed in terms of known Painlevé transcendents or elliptic functions but some may represent new higher order Painlevé transcendents.

Study of transitional doubly-odd /sup 186/Ir and /sup 184/Ir

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

Ben Braham, A.; Bourgeois, C.; Kilcher, P.

1987-12-10

The transitional doubly-odd iridium nuclei with A = 184 and 186 have been studied from the ..beta../sup +//EC decay of the corresponding platinum isotopes using the on-line mass separator ISOCELE. Configurations can be reasonably Attributed to the low-lying states of /sup 184/Ir in agreement with results already known. On the other hand an E3 transition observed in /sup 186/Ir suggests that the known long-lived 1.7h 2/sup -/ state is located at 137.5 keV above the 16h 5/sup +/ state, raising questions about structure of this latter state.

Investigations into the tensile failure of doubly-convex cylindrical tablets under diametral loading using finite element methodology.

PubMed

Podczeck, Fridrun; Drake, Kevin R; Newton, J Michael

2013-09-15

In the literature various solutions exist for the calculation of the diametral compression tensile strength of doubly-convex tablets and each approach is based on experimental data obtained from single materials (gypsum, microcrystalline cellulose) only. The solutions are represented by complex equations and further differ for elastic and elasto-plastic behaviour of the compacts. The aim of this work was to develop a general equation that is applicable independently of deformation behaviour and which is based on simple tablet dimensions such as diameter and total tablet thickness only. With the help of 3D-FEM analysis the tensile failure stress of doubly-convex tables with central cylinder to total tablet thickness ratios W/D between 0.06 and 0.50 and face-curvature ratios D/R between 0.25 and 1.85 were evaluated. Both elastic and elasto-plastic deformation behaviour were considered. The results of 80 individual simulations were combined and showed that the tensile failure stress σt of doubly-convex tablets can be calculated from σt=(2P/πDW)(W/T)=2P/πDT with P being the failure load, D the diameter, W the central cylinder thickness, and T the total thickness of the tablet. This equation converts into the standard Brazilian equation (σt=2P/πDW) when W equals T, i.e. is equally valid for flat cylindrical tablets. In practice, the use of this new equation removes the need for complex measurements of tablet dimensions, because it only requires values for diameter and total tablet thickness. It also allows setting of standards for the mechanical strength of doubly-convex tablets. The new equation holds both for elastic and elasto-plastic deformation behaviour of the tablets under load. It is valid for all combinations of W/D-ratios between 0.06 and 0.50 with D/R-ratios between 0.00 and 1.85 except for W/D=0.50 in combination with D/R-ratios of 1.85 and 1.43 and for W/D-ratios of 0.40 and 0.30 in combination with D/R=1.85. FEM-analysis indicated a tendency to

Lipid microdomains and the regulation of ion channel function

PubMed Central

Dart, Caroline

2010-01-01

Many types of ion channel localize to cholesterol and sphingolipid-enriched regions of the plasma membrane known as lipid microdomains or ‘rafts’. The precise physiological role of these unique lipid microenvironments remains elusive due largely to difficulties associated with studying these potentially extremely small and dynamic domains. Nevertheless, increasing evidence suggests that membrane rafts regulate channel function in a number of different ways. Raft-enriched lipids such as cholesterol and sphingolipids exert effects on channel activity either through direct protein–lipid interactions or by influencing the physical properties of the bilayer. Rafts also appear to selectively recruit interacting signalling molecules to generate subcellular compartments that may be important for efficient and selective signal transduction. Direct interaction with raft-associated scaffold proteins such as caveolin can also influence channel function by altering gating kinetics or by affecting trafficking and surface expression. Selective association of ion channels with specific lipid microenvironments within the membrane is thus likely to be an important and fundamental regulatory aspect of channel physiology. This brief review highlights some of the existing evidence for raft modulation of channel function. PMID:20519314

The lysosomal potassium channel TMEM175 adopts a novel tetrameric architecture.

PubMed

Lee, Changkeun; Guo, Jiangtao; Zeng, Weizhong; Kim, Sunghoon; She, Ji; Cang, Chunlei; Ren, Dejian; Jiang, Youxing

2017-07-27

TMEM175 is a lysosomal K + channel that is important for maintaining the membrane potential and pH stability in lysosomes. It contains two homologous copies of a six-transmembrane-helix (6-TM) domain, which has no sequence homology to the canonical tetrameric K + channels and lacks the TVGYG selectivity filter motif found in these channels. The prokaryotic TMEM175 channel, which is present in a subset of bacteria and archaea, contains only a single 6-TM domain and functions as a tetramer. Here, we present the crystal structure of a prokaryotic TMEM175 channel from Chamaesiphon minutus, CmTMEM175, the architecture of which represents a completely different fold from that of canonical K + channels. All six transmembrane helices of CmTMEM175 are tightly packed within each subunit without undergoing domain swapping. The highly conserved TM1 helix acts as the pore-lining inner helix, creating an hourglass-shaped ion permeation pathway in the channel tetramer. Three layers of hydrophobic residues on the carboxy-terminal half of the TM1 helices form a bottleneck along the ion conduction pathway and serve as the selectivity filter of the channel. Mutagenesis analysis suggests that the first layer of the highly conserved isoleucine residues in the filter is primarily responsible for channel selectivity. Thus, the structure of CmTMEM175 represents a novel architecture of a tetrameric cation channel whose ion selectivity mechanism appears to be distinct from that of the classical K + channel family.

Design and analysis of a novel doubly salient permanent- magnet generator

NASA Astrophysics Data System (ADS)

Sarlioglu, Bulent

Improvements in permanent magnets and power electronics technologies have made it possible to devise different configurations of electrical machines which were not previously possible to implement. In this dissertation, a novel Doubly Salient Permanent Magnet (DSPM) generator has been designed, analyzed, and tested. The DSPM generator has four stator poles and six rotor poles. Two high density permanent magnets are located in the stator yoke. Since there are no windings or permanent magnets in the rotor, the DSPM generator has several advantages: the rotor has low inertia, no copper loss, no PM attachments, no brushes, and no slip rings. This type of rotor can be manufactured easily, and can be run at very high speeds as in the case of a switched reluctance machine. Compared to induction and switched reluctance machines, the DSPM generator can produce more power from the same geometry. Moreover, the efficiency of the DSPM generator is higher, since there is no copper loss associated with excitation of the machine. Another advantage of the DSPM generator is that the output AC voltage can easily be rectified by a diode bridge rectifier, while in the case of the switched reluctance machine one needs to use active semiconductor switches for power generation. If greater utilization and control of power production capability are desired, the AC output of the DSPM generator can be rectified using an active converter. In this dissertation, a novel doubly salient permanent magnet generator is introduced. First, the theory of the DSPM generator is given. Later, this novel generator is investigated using conventional magnetic circuits, nonlinear finite element analysis, and simulations with first order approximations and nonlinear modeling. It is compared with other generators. Static and no-load testing of the prototype DSPM generator are presented, and generator performance is evaluated with various power electronic circuits.

Selective inhibition of KCa3.1 channels mediates adenosine regulation of the motility of human T cells.

PubMed

Chimote, Ameet A; Hajdu, Peter; Kucher, Vladimir; Boiko, Nina; Kuras, Zerrin; Szilagyi, Orsolya; Yun, Yeo-Heung; Conforti, Laura

2013-12-15

Adenosine, a purine nucleoside, is present at high concentrations in tumors, where it contributes to the failure of immune cells to eliminate cancer cells. The mechanisms responsible for the immunosuppressive properties of adenosine are not fully understood. We tested the hypothesis that adenosine's immunosuppressive functions in human T lymphocytes are in part mediated via modulation of ion channels. The activity of T lymphocytes relies on ion channels. KCa3.1 and Kv1.3 channels control cytokine release and, together with TRPM7, regulate T cell motility. Adenosine selectively inhibited KCa3.1, but not Kv1.3 and TRPM7, in activated human T cells. This effect of adenosine was mainly mediated by A2A receptors, as KCa3.1 inhibition was reversed by SCH58261 (selective A2A receptor antagonist), but not by MRS1754 (A2B receptor antagonist), and it was mimicked by the A2A receptor agonist CGS21680. Furthermore, it was mediated by the cAMP/protein kinase A isoform (PKAI) signaling pathway, as adenylyl-cyclase and PKAI inhibition prevented adenosine effect on KCa3.1. The functional implication of the effect of adenosine on KCa3.1 was determined by measuring T cell motility on ICAM-1 surfaces. Adenosine and CGS21680 inhibited T cell migration. Comparable effects were obtained by KCa3.1 blockade with TRAM-34. Furthermore, the effect of adenosine on cell migration was abolished by pre-exposure to TRAM-34. Additionally, adenosine suppresses IL-2 secretion via KCa3.1 inhibition. Our data indicate that adenosine inhibits KCa3.1 in human T cells via A2A receptor and PKAI, thereby resulting in decreased T cell motility and cytokine release. This mechanism is likely to contribute to decreased immune surveillance in solid tumors.

Channel function reconstitution and re-animation: a single-channel strategy in the postcrystal age

PubMed Central

Oiki, Shigetoshi

2015-01-01

The most essential properties of ion channels for their physiologically relevant functions are ion-selective permeation and gating. Among the channel species, the potassium channel is primordial and the most ubiquitous in the biological world, and knowledge of this channel underlies the understanding of features of other ion channels. The strategy applied to studying channels changed dramatically after the crystal structure of the potassium channel was resolved. Given the abundant structural information available, we exploited the bacterial KcsA potassium channel as a simple model channel. In the postcrystal age, there are two effective frameworks with which to decipher the functional codes present in the channel structure, namely reconstitution and re-animation. Complex channel proteins are decomposed into essential functional components, and well-examined parts are rebuilt for integrating channel function in the membrane (reconstitution). Permeation and gating are dynamic operations, and one imagines the active channel by breathing life into the ‘frozen’ crystal (re-animation). Capturing the motion of channels at the single-molecule level is necessary to characterize the behaviour of functioning channels. Advanced techniques, including diffracted X-ray tracking, lipid bilayer methods and high-speed atomic force microscopy, have been used. Here, I present dynamic pictures of the KcsA potassium channel from the submolecular conformational changes to the supramolecular collective behaviour of channels in the membrane. These results form an integrated picture of the active channel and offer insights into the processes underlying the physiological function of the channel in the cell membrane. PMID:25833254

Channel function reconstitution and re-animation: a single-channel strategy in the postcrystal age.

PubMed

Oiki, Shigetoshi

2015-06-15

The most essential properties of ion channels for their physiologically relevant functions are ion-selective permeation and gating. Among the channel species, the potassium channel is primordial and the most ubiquitous in the biological world, and knowledge of this channel underlies the understanding of features of other ion channels. The strategy applied to studying channels changed dramatically after the crystal structure of the potassium channel was resolved. Given the abundant structural information available, we exploited the bacterial KcsA potassium channel as a simple model channel. In the postcrystal age, there are two effective frameworks with which to decipher the functional codes present in the channel structure, namely reconstitution and re-animation. Complex channel proteins are decomposed into essential functional components, and well-examined parts are rebuilt for integrating channel function in the membrane (reconstitution). Permeation and gating are dynamic operations, and one imagines the active channel by breathing life into the 'frozen' crystal (re-animation). Capturing the motion of channels at the single-molecule level is necessary to characterize the behaviour of functioning channels. Advanced techniques, including diffracted X-ray tracking, lipid bilayer methods and high-speed atomic force microscopy, have been used. Here, I present dynamic pictures of the KcsA potassium channel from the submolecular conformational changes to the supramolecular collective behaviour of channels in the membrane. These results form an integrated picture of the active channel and offer insights into the processes underlying the physiological function of the channel in the cell membrane. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Dynamical Evolution of a Doubly Quantized Vortex Imprinted in a Bose-Einstein Condensate

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

Mateo, A. Munoz; Delgado, V.

2006-11-03

The recent experiment by Shin et al. [Phys. Rev. Lett. 93, 160406 (2004)] on the decay of a doubly quantized vortex is analyzed by numerically solving the Gross-Pitaevskii equation. Our results demonstrate that the vortex decay is mainly a consequence of dynamical instability. The monotonic increase observed in the vortex lifetimes is a consequence of the fact that the measured lifetimes incorporate the time it takes for the initial perturbation to reach the central slice. When considered locally, the splitting occurs approximately at the same time in every condensate.

Chaotic behavior of channeling particles.

PubMed

Chen, Ling; Kaloyeros, Alain E.; Wang, Guang-Hou

1994-03-01

Channeling describes the collimated motion of energetic charged particles along the lattice plane or axis in a crystal. The energetic particles are steered through the channels formed by strings of atomic constituents in the lattice. In the case of planar channeling, the motion of a charged particle between the atomic planes can be periodic or quasiperiodic, such as a simple oscillatory motion in the transverse direction. In practice, however, the periodic motion of the channeling particles can be accompanied by an irregular, chaotic behavior. In this paper, the Moliere potential, which is considered as a good analytical approximation for the interaction of channeling particles with the rows of atoms in the lattice, is used to simulate the channeling behavior of positively charged particles in a tungsten (100) crystal plane. By appropriate selection of channeling parameters, such as the projectile energy E(0) and incident angle psi(0), the transition of channeling particles from regular to chaotic motion is demonstrated. It is argued that the fine structures that appear in the angular scan channeling experiments are due to the particles' chaotic motion.

General and mechanistic optimal relationships for tensile strength of doubly convex tablets under diametrical compression.

PubMed

Razavi, Sonia M; Gonzalez, Marcial; Cuitiño, Alberto M

2015-04-30

We propose a general framework for determining optimal relationships for tensile strength of doubly convex tablets under diametrical compression. This approach is based on the observation that tensile strength is directly proportional to the breaking force and inversely proportional to a non-linear function of geometric parameters and materials properties. This generalization reduces to the analytical expression commonly used for flat faced tablets, i.e., Hertz solution, and to the empirical relationship currently used in the pharmaceutical industry for convex-faced tablets, i.e., Pitt's equation. Under proper parametrization, optimal tensile strength relationship can be determined from experimental results by minimizing a figure of merit of choice. This optimization is performed under the first-order approximation that a flat faced tablet and a doubly curved tablet have the same tensile strength if they have the same relative density and are made of the same powder, under equivalent manufacturing conditions. Furthermore, we provide a set of recommendations and best practices for assessing the performance of optimal tensile strength relationships in general. Based on these guidelines, we identify two new models, namely the general and mechanistic models, which are effective and predictive alternatives to the tensile strength relationship currently used in the pharmaceutical industry. Copyright © 2015 Elsevier B.V. All rights reserved.

Validation of energy intake estimated from a food frequency questionnaire: a doubly labelled water study.

PubMed

Andersen, L Frost; Tomten, H; Haggarty, P; Løvø, A; Hustvedt, B-E

2003-02-01

The validation of dietary assessment methods is critical in the evaluation of the relation between dietary intake and health. The aim of this study was to assess the validity of a food frequency questionnaire by comparing energy intake with energy expenditure measured with the doubly labelled water method. Total energy expenditure was measured with the doubly labelled water (DLW) method during a 10 day period. Furthermore, the subjects filled in the food frequency questionnaire about 18-35 days after the DLW phase of the study was completed. Twenty-one healthy, non-pregnant females volunteered to participate in the study; only 17 subjects completed the study. The group energy intake was on average 10% lower than the energy expenditure, but the difference was not statistically significant. However, there was a wide range in reporting accuracy: seven subjects were identified as acceptable reporters, eight as under-reporters and two were identified as over-reporters. The width of the 95% confidence limits of agreement in a Bland and Altman plot for energy intake and energy expenditure varied from -5 to 3 MJ. The data showed that there was substantial variability in the accuracy of the food frequency questionnaire at the individual level. Furthermore, the results showed that the questionnaire was more accurate for groups than individuals.

Theoretical and experimental evidence of non-symmetric doubly localized rogue waves.

PubMed

He, Jingsong; Guo, Lijuan; Zhang, Yongshuai; Chabchoub, Amin

2014-11-08

We present determinant expressions for vector rogue wave (RW) solutions of the Manakov system, a two-component coupled nonlinear Schrödinger (NLS) equation. As a special case, we generate a family of exact and non-symmetric RW solutions of the NLS equation up to third order, localized in both space and time. The derived non-symmetric doubly localized second-order solution is generated experimentally in a water wave flume for deep-water conditions. Experimental results, confirming the characteristic non-symmetric pattern of the solution, are in very good agreement with theory as well as with numerical simulations, based on the modified NLS equation, known to model accurately the dynamics of weakly nonlinear wave packets in deep water.

Highly selective water channel activity measured by voltage clamp: analysis of planar lipid bilayers reconstituted with purified AqpZ.

PubMed

Pohl, P; Saparov, S M; Borgnia, M J; Agre, P

2001-08-14

Aquaporins are membrane channels selectively permeated by water or water plus glycerol. Conflicting reports have described ion conductance associated with some water channels, raising the question of whether ion conductance is a general property of the aquaporin family. To clarify this question, a defined system was developed to simultaneously measure water permeability and ion conductance. The Escherichia coli water channel aquaporin-Z (AqpZ) was studied, because it is a highly stable tetramer. Planar lipid bilayers were formed from unilamellar vesicles containing purified AqpZ. The hydraulic conductivity of bilayers made from the total extract of E. coli lipids increased 3-fold if reconstituted with AqpZ, but electric conductance was unchanged. No channel activity was detected under voltage-clamp conditions, indicating that less than one in 10(9) transport events is electrogenic. Microelectrode measurements were simultaneously undertaken adjacent to the membrane. Changes in sodium concentration profiles accompanying transmembrane water flow permitted calculation of the activation energies: 14 kcal/mol for protein-free lipid bilayers and 4 kcal/mol for lipid bilayers containing AqpZ. Neither the water permeability nor the electric conductivity exhibited voltage dependence. This sensitive system demonstrated that AqpZ is permeated by water but not charged ions and should permit direct analyses of putative electrogenic properties of other aquaporins.

β-adrenergic Receptor Blocker ICI 118,551 Selectively Increases Intermediate-Conductance Calcium-Activated Potassium Channel (IKCa )-Mediated Relaxations in Rat Main Mesenteric Artery.

PubMed

Ozkan, Melike Hacer; Uma, Serdar

2018-06-01

Endothelial IK C a and/or SK C a channels play an important role in the control of vascular tone by participating in endothelium-dependent relaxation. Whether β-AR antagonists, mainly used in hypertension, affect endothelial K C a channel function is unknown. In this study, we examined the effect of the β2-AR antagonist and inverse agonist ICI 118,551 on the IK C a /SK C a channel activity by assessing functional relaxation responses to several agonists that stimulate these channels. Mesenteric arterial rings isolated from male Sprague Dawley mounted to organ baths. Acetylcholine elicited IK C a - and SK C a -mediated relaxations that were abolished by TRAM-34 and apamin, respectively. ICI 118,551, which did not dilate the arteries per se, increased the IK C a -mediated relaxations, whereas SK C a -mediated relaxations remained unaltered. Same potentiating effect was also detected on the IK C a -mediated relaxations to carbachol and A23187, but not to NS309. Neither acetylcholine-induced nitric oxide-mediated relaxations nor SNP relaxations changed with ICI 118,551. The PKA inhibitor KT-5720, the selective β2-AR agonist salbutamol, the selective β2-AR antagonist butoxamine, the non-selective β-AR antagonist propranolol, and the inverse agonists carvedilol or nadolol failed to affect the IK C a -mediated relaxations. ICI 118,551-induced increase was not reversed by salbutamol or propranolol as well. Besides, low potassium-induced relaxations in endothelium-removed arteries remained the same in the presence of ICI 118,551. These data demonstrate a previously unrecognized action of ICI 118,551, the ability to potentiate endothelial IK C a channel-mediated vasodilation, through a mechanism independent of β2-AR antagonistic or inverse agonistic action. Instead, the enhancement of acetylcholine relaxation seems likely to occur by a mechanism secondary to endothelial calcium increase. © 2017 Nordic Association for the Publication of BCPT (former Nordic

Communication: Determining the structure of the N{sub 2}Ar van der Waals complex with laser-based channel-selected Coulomb explosion

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

Wu, Chengyin, E-mail: cywu@pku.edu.cn; Liu, Yunquan; Gong, Qihuang

2014-04-14

We experimentally reconstructed the structure of the N{sub 2}Ar van der Waals complex with the technique of laser-based channel-selected Coulomb explosion imaging. The internuclear distance between the N{sub 2} center of mass and the Ar atom, i.e., the length of the van der Waals bond, was determined to be 3.88 Å from the two-body explosion channels. The angle between the van der Waals bond and the N{sub 2} principal axis was determined to be 90° from the three-body explosion channels. The reconstructed structure was contrasted with our high level ab initio calculations. The agreement demonstrated the potential application of laser-basedmore » Coulomb explosion in imaging transient molecular structure, particularly for floppy van der Waals complexes, whose structures remain difficult to be determined by conventional spectroscopic methods.« less

C-Terminal residues in small potassium channel blockers OdK1 and OSK3 from scorpion venom fine-tune the selectivity.

PubMed

Kuzmenkov, Alexey I; Peigneur, Steve; Chugunov, Anton O; Tabakmakher, Valentin M; Efremov, Roman G; Tytgat, Jan; Grishin, Eugene V; Vassilevski, Alexander A

2017-05-01

We report isolation, sequencing, and electrophysiological characterization of OSK3 (α-KTx 8.8 in Kalium and Uniprot databases), a potassium channel blocker from the scorpion Orthochirus scrobiculosus venom. Using the voltage clamp technique, OSK3 was tested on a wide panel of 11 voltage-gated potassium channels expressed in Xenopus oocytes, and was found to potently inhibit Kv1.2 and Kv1.3 with IC 50 values of ~331nM and ~503nM, respectively. OdK1 produced by the scorpion Odontobuthus doriae differs by just two C-terminal residues from OSK3, but shows marked preference to Kv1.2. Based on the charybdotoxin-potassium channel complex crystal structure, a model was built to explain the role of the variable residues in OdK1 and OSK3 selectivity. Copyright © 2017 Elsevier B.V. All rights reserved.

Voltage-gated proton channels: what' next?

PubMed Central

DeCoursey, Thomas E

2008-01-01

This review is an attempt to identify and place in context some of the many questions about voltage-gated proton channels that remain unsolved. As the gene was identified only 2 years ago, the situation is very different than in fields where the gene has been known for decades. For the proton channel, most of the obvious and less obvious structure–function questions are still wide open. Remarkably, the proton channel protein strongly resembles the voltage-sensing domain of many voltage-gated ion channels, and thus offers a novel approach to study gating mechanisms. Another surprise is that the proton channel appears to function as a dimer, with two separate conduction pathways. A number of significant biological questions remain in dispute, unanswered, or in some cases, not yet asked. This latter deficit is ascribable to the intrinsic difficulty in evaluating the importance of one component in a complex system, and in addition, to the lack, until recently, of a means of performing an unambiguous lesion experiment, that is, of selectively eliminating the molecule in question. We still lack a potent, selective pharmacological inhibitor, but the identification of the gene has allowed the development of powerful new tools including proton channel antibodies, siRNA and knockout mice. PMID:18801839

Multilevel Concatenated Block Modulation Codes for the Frequency Non-selective Rayleigh Fading Channel

NASA Technical Reports Server (NTRS)

Lin, Shu; Rhee, Dojun

1996-01-01

This paper is concerned with construction of multilevel concatenated block modulation codes using a multi-level concatenation scheme for the frequency non-selective Rayleigh fading channel. In the construction of multilevel concatenated modulation code, block modulation codes are used as the inner codes. Various types of codes (block or convolutional, binary or nonbinary) are being considered as the outer codes. In particular, we focus on the special case for which Reed-Solomon (RS) codes are used as the outer codes. For this special case, a systematic algebraic technique for constructing q-level concatenated block modulation codes is proposed. Codes have been constructed for certain specific values of q and compared with the single-level concatenated block modulation codes using the same inner codes. A multilevel closest coset decoding scheme for these codes is proposed.

The lysosomal potassium channel TMEM175 adopts a novel tetrameric architecture

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

Lee, Changkeun; Guo, Jiangtao; Zeng, Weizhong

TMEM175 is a lysosomal K+ channel that is important for maintaining the membrane potential and pH stability in lysosomes1. It contains two homologous copies of a six-transmembrane-helix (6-TM) domain, which has no sequence homology to the canonical tetrameric K+ channels and lacks the TVGYG selectivity filter motif found in these channels2, 3, 4. The prokaryotic TMEM175 channel, which is present in a subset of bacteria and archaea, contains only a single 6-TM domain and functions as a tetramer. Here, we present the crystal structure of a prokaryotic TMEM175 channel from Chamaesiphon minutus, CmTMEM175, the architecture of which represents a completelymore » different fold from that of canonical K+ channels. All six transmembrane helices of CmTMEM175 are tightly packed within each subunit without undergoing domain swapping. The highly conserved TM1 helix acts as the pore-lining inner helix, creating an hourglass-shaped ion permeation pathway in the channel tetramer. Three layers of hydrophobic residues on the carboxy-terminal half of the TM1 helices form a bottleneck along the ion conduction pathway and serve as the selectivity filter of the channel. Mutagenesis analysis suggests that the first layer of the highly conserved isoleucine residues in the filter is primarily responsible for channel selectivity. Thus, the structure of CmTMEM175 represents a novel architecture of a tetrameric cation channel whose ion selectivity mechanism appears to be distinct from that of the classical K+ channel family.« less

Analysis of cylindrical wrap-around and doubly conformal patch antennas by way of the finite element-artificial absorber method

NASA Technical Reports Server (NTRS)

Volakis, J. L.; Kempel, L. C.; Sliva, R.; Wang, H. T. G.; Woo, A. G.

1994-01-01

The goal of this project was to develop analysis codes for computing the scattering and radiation of antennas on cylindrically and doubly conformal platforms. The finite element-boundary integral (FE-BI) method has been shown to accurately model the scattering and radiation of cavity-backed patch antennas. Unfortunately extension of this rigorous technique to coated or doubly curved platforms is cumbersome and inefficient. An alternative approximate approach is to employ an absorbing boundary condition (ABC) for terminating the finite element mesh thus avoiding use of a Green's function. A FE-ABC method is used to calculate the radar cross section (RCS) and radiation pattern of a cavity-backed patch antenna which is recessed within a metallic surface. It is shown that this approach is accurate for RCS and antenna pattern calculations with an ABC surface displaced as little as 0.3 lambda from the cavity aperture. These patch antennas may have a dielectric overlay which may also be modeled with this technique.

Roughness coefficients for stream channels in Arizona

USGS Publications Warehouse

Aldridge, B.N.; Garrett, J.M.

1973-01-01

       n in which V = mean cross-sectional velocity of flow, in feet per second; R = hydraulic radius at a cross section, which is the cross-sectional area divided by the wetter perimeter, in feet; Se = energy slope; and n = coefficient of roughness. Many research studies have been made to determine "n" values for open-channel flow (Carter and others, 1963). Guidelines for selecting coefficient of roughness for stream channels are given in most of the literature of stream-channel hydraulics, but few of the data relate directly to streams of Arizona, The U.S> Geological Survey, at the request of the Arizona Highway Department, assembled the color photographs and tables of the Manning "n" values in this report to aid highway engineers in the selection of roughness coefficients for Arizona streams. Most of the photographs show channel reaches for which values of "n" have been assigned by experienced Survey personnel; a few photographs are included for reaches where "n" values have been verified. Verified "n" values are computed from a known discharge and measured channel geometry. Selected photographs of stream channels for which "n" values have been verified are included in U.S. Geological Survey Water-Supply Paper 1849 (Barnes, 1967); stereoscopic slides of Barnes' (1967) photographs and additional photographs can be inspected at U.S> Geological Survey offices in: 2555 E. First Street, Tucson; and 5017 Federal Building, 230 N. First Avenue, Phoenix.

Coulomb- and Antiferromagnetic-Induced Fission in Doubly Charged Cubelike Fe-S Clusters

NASA Astrophysics Data System (ADS)

Yang, Xin; Wang, Xue-Bin; Niu, Shuqiang; Pickett, Chris J.; Ichiye, Toshiko; Wang, Lai-Sheng

2002-09-01

We report the observation of symmetric fission in doubly charged Fe-S cluster anions, [Fe4S4X4]2- -->2[Fe2S2X2]- (X=Cl,Br), owing to both Coulomb repulsion and antiferromagnetic coupling. Photoelectron spectroscopy shows that both the parent and the fission fragments have similar electronic structures and confirms the inverted energy schemes due to the strong spin polarization of the Fe 3d levels. The current observation provides direct confirmation for the unusual spin couplings in the [Fe4S4X4]2- clusters, which contain two valent-delocalized and ferromagnetically coupled Fe2S2 subunits.

Observation of the Doubly Charmed Baryon Ξ_{cc}^{++}.

PubMed

Aaij, R; Adeva, B; Adinolfi, M; Ajaltouni, Z; Akar, S; Albrecht, J; Alessio, F; Alexander, M; Alfonso Albero, A; Ali, S; Alkhazov, G; Alvarez Cartelle, P; Alves, A A; Amato, S; Amerio, S; Amhis, Y; An, L; Anderlini, L; Andreassi, G; Andreotti, M; Andrews, J E; Appleby, R B; Archilli, F; d'Argent, P; Arnau Romeu, J; Artamonov, A; Artuso, M; Aslanides, E; Auriemma, G; Baalouch, M; Babuschkin, I; Bachmann, S; Back, J J; Badalov, A; Baesso, C; Baker, S; Balagura, V; Baldini, W; Baranov, A; Barlow, R J; Barschel, C; Barsuk, S; Barter, W; Baryshnikov, F; Batozskaya, V; Battista, V; Bay, A; Beaucourt, L; Beddow, J; Bedeschi, F; Bediaga, I; Beiter, A; Bel, L J; Beliy, N; Bellee, V; Belloli, N; Belous, K; Belyaev, I; Ben-Haim, E; Bencivenni, G; Benson, S; Beranek, S; Berezhnoy, A; Bernet, R; Berninghoff, D; Bertholet, E; Bertolin, A; Betancourt, C; Betti, F; Bettler, M-O; van Beuzekom, M; Bezshyiko, Ia; Bifani, S; Billoir, P; Birnkraut, A; Bitadze, A; Bizzeti, A; Bjoern, M B; Blake, T; Blanc, F; Blouw, J; Blusk, S; Bocci, V; Boettcher, T; Bondar, A; Bondar, N; Bonivento, W; Bordyuzhin, I; Borgheresi, A; Borghi, S; Borisyak, M; Borsato, M; Borysova, M; Bossu, F; Boubdir, M; Bowcock, T J V; Bowen, E; Bozzi, C; Braun, S; Britton, T; Brodzicka, J; Brundu, D; Buchanan, E; Burr, C; Bursche, A; Buytaert, J; Byczynski, W; Cadeddu, S; Cai, H; Calabrese, R; Calladine, R; Calvi, M; Calvo Gomez, M; Camboni, A; Campana, P; Campora Perez, D H; Capriotti, L; Carbone, A; Carboni, G; Cardinale, R; Cardini, A; Carniti, P; Carson, L; Carvalho Akiba, K; Casse, G; Cassina, L; Castillo Garcia, L; Cattaneo, M; Cavallero, G; Cenci, R; Chamont, D; Charles, M; Charpentier, Ph; Chatzikonstantinidis, G; Chefdeville, M; Chen, S; Cheung, S F; Chitic, S-G; Chobanova, V; Chrzaszcz, M; Chubykin, A; Ciambrone, P; Cid Vidal, X; Ciezarek, G; Clarke, P E L; Clemencic, M; Cliff, H V; Closier, J; Cogan, J; Cogneras, E; Cogoni, V; Cojocariu, L; Collins, P; Colombo, T; Comerma-Montells, A; Contu, A; Cook, A; Coombs, G; Coquereau, S; Corti, G; Corvo, M; Costa Sobral, C M; Couturier, B; Cowan, G A; Craik, D C; Crocombe, A; Cruz Torres, M; Currie, R; D'Ambrosio, C; Da Cunha Marinho, F; Dall'Occo, E; Dalseno, J; Davis, A; De Aguiar Francisco, O; De Capua, S; De Cian, M; De Miranda, J M; De Paula, L; De Serio, M; De Simone, P; Dean, C T; Decamp, D; Del Buono, L; Dembinski, H-P; Demmer, M; Dendek, A; Derkach, D; Deschamps, O; Dettori, F; Dey, B; Di Canto, A; Di Nezza, P; Dijkstra, H; Dordei, F; Dorigo, M; Dosil Suárez, A; Douglas, L; Dovbnya, A; Dreimanis, K; Dufour, L; Dujany, G; Durante, P; Dzhelyadin, R; Dziewiecki, M; Dziurda, A; Dzyuba, A; Easo, S; Ebert, M; Egede, U; Egorychev, V; Eidelman, S; Eisenhardt, S; Eitschberger, U; Ekelhof, R; Eklund, L; Ely, S; Esen, S; Evans, H M; Evans, T; Falabella, A; Farley, N; Farry, S; Fay, R; Fazzini, D; Federici, L; Ferguson, D; Fernandez, G; Fernandez Declara, P; Fernandez Prieto, A; Ferrari, F; Ferreira Rodrigues, F; Ferro-Luzzi, M; Filippov, S; Fini, R A; Fiore, M; Fiorini, M; Firlej, M; Fitzpatrick, C; Fiutowski, T; Fleuret, F; Fohl, K; Fontana, M; Fontanelli, F; Forshaw, D C; Forty, R; Franco Lima, V; Frank, M; Frei, C; Fu, J; Funk, W; Furfaro, E; Färber, C; Gabriel, E; Gallas Torreira, A; Galli, D; Gallorini, S; Gambetta, S; Gandelman, M; Gandini, P; Gao, Y; Garcia Martin, L M; García Pardiñas, J; Garra Tico, J; Garrido, L; Garsed, P J; Gascon, D; Gaspar, C; Gavardi, L; Gazzoni, G; Gerick, D; Gersabeck, E; Gersabeck, M; Gershon, T; Ghez, Ph; Gianì, S; Gibson, V; Girard, O G; Giubega, L; Gizdov, K; Gligorov, V V; Golubkov, D; Golutvin, A; Gomes, A; Gorelov, I V; Gotti, C; Govorkova, E; Grabowski, J P; Graciani Diaz, R; Granado Cardoso, L A; Graugés, E; Graverini, E; Graziani, G; Grecu, A; Greim, R; Griffith, P; Grillo, L; Gruber, L; Gruberg Cazon, B R; Grünberg, O; Gushchin, E; Guz, Yu; Gys, T; Göbel, C; Hadavizadeh, T; Hadjivasiliou, C; Haefeli, G; Haen, C; Haines, S C; Hamilton, B; Han, X; Hancock, T; Hansmann-Menzemer, S; Harnew, N; Harnew, S T; Harrison, J; Hasse, C; Hatch, M; He, J; Hecker, M; Heinicke, K; Heister, A; Hennessy, K; Henrard, P; Henry, L; van Herwijnen, E; Heß, M; Hicheur, A; Hill, D; Hombach, C; Hopchev, P H; Huard, Z-C; Hulsbergen, W; Humair, T; Hushchyn, M; Hutchcroft, D; Ibis, P; Idzik, M; Ilten, P; Jacobsson, R; Jalocha, J; Jans, E; Jawahery, A; Jiang, F; John, M; Johnson, D; Jones, C R; Joram, C; Jost, B; Jurik, N; Kandybei, S; Karacson, M; Kariuki, J M; Karodia, S; Kazeev, N; Kecke, M; Kelsey, M; Kenzie, M; Ketel, T; Khairullin, E; Khanji, B; Khurewathanakul, C; Kirn, T; Klaver, S; Klimaszewski, K; Klimkovich, T; Koliiev, S; Kolpin, M; Komarov, I; Kopecna, R; Koppenburg, P; Kosmyntseva, A; Kotriakhova, S; Kozeiha, M; Kreps, M; Krokovny, P; Kruse, F; Krzemien, W; Kucewicz, W; Kucharczyk, M; Kudryavtsev, V; Kuonen, A K; Kurek, K; Kvaratskheliya, T; Lacarrere, D; Lafferty, G; Lai, A; Lanfranchi, G; Langenbruch, C; Latham, T; Lazzeroni, C; Le Gac, R; van Leerdam, J; Leflat, A; Lefrançois, J; Lefèvre, R; Lemaitre, F; Lemos Cid, E; Leroy, O; Lesiak, T; Leverington, B; Li, P-R; Li, T; Li, Y; Li, Z; Likhomanenko, T; Lindner, R; Lionetto, F; Lisovskyi, V; Liu, X; Loh, D; Loi, A; Longstaff, I; Lopes, J H; Lucchesi, D; Lucio Martinez, M; Luo, H; Lupato, A; Luppi, E; Lupton, O; Lusiani, A; Lyu, X; Machefert, F; Maciuc, F; Macko, V; Mackowiak, P; Maddock, B; Maddrell-Mander, S; Maev, O; Maguire, K; Maisuzenko, D; Majewski, M W; Malde, S; Malinin, A; Maltsev, T; Manca, G; Mancinelli, G; Manning, P; Marangotto, D; Maratas, J; Marchand, J F; Marconi, U; Marin Benito, C; Marinangeli, M; Marino, P; Marks, J; Martellotti, G; Martin, M; Martinelli, M; Martinez Santos, D; Martinez Vidal, F; Martins Tostes, D; Massacrier, L M; Massafferri, A; Matev, R; Mathad, A; Mathe, Z; Matteuzzi, C; Mauri, A; Maurice, E; Maurin, B; Mazurov, A; McCann, M; McNab, A; McNulty, R; Mead, J V; Meadows, B; Meaux, C; Meier, F; Meinert, N; Melnychuk, D; Merk, M; Merli, A; Michielin, E; Milanes, D A; Millard, E; Minard, M-N; Minzoni, L; Mitzel, D S; Mogini, A; Molina Rodriguez, J; Mombacher, T; Monroy, I A; Monteil, S; Morandin, M; Morello, M J; Morgunova, O; Moron, J; Morris, A B; Mountain, R; Muheim, F; Mulder, M; Müller, D; Müller, J; Müller, K; Müller, V; Naik, P; Nakada, T; Nandakumar, R; Nandi, A; Nasteva, I; Needham, M; Neri, N; Neubert, S; Neufeld, N; Neuner, M; Nguyen, T D; Nguyen-Mau, C; Nieswand, S; Niet, R; Nikitin, N; Nikodem, T; Nogay, A; O'Hanlon, D P; Oblakowska-Mucha, A; Obraztsov, V; Ogilvy, S; Oldeman, R; Onderwater, C J G; Ossowska, A; Otalora Goicochea, J M; Owen, P; Oyanguren, A; Pais, P R; Palano, A; Palutan, M; Papanestis, A; Pappagallo, M; Pappalardo, L L; Pappenheimer, C; Parker, W; Parkes, C; Passaleva, G; Pastore, A; Patel, M; Patrignani, C; Pearce, A; Pellegrino, A; Penso, G; Pepe Altarelli, M; Perazzini, S; Perret, P; Pescatore, L; Petridis, K; Petrolini, A; Petrov, A; Petruzzo, M; Picatoste Olloqui, E; Pietrzyk, B; Pikies, M; Pinci, D; Pistone, A; Piucci, A; Placinta, V; Playfer, S; Plo Casasus, M; Polci, F; Poli Lener, M; Poluektov, A; Polyakov, I; Polycarpo, E; Pomery, G J; Ponce, S; Popov, A; Popov, D; Poslavskii, S; Potterat, C; Price, E; Prisciandaro, J; Prouve, C; Pugatch, V; Puig Navarro, A; Pullen, H; Punzi, G; Qian, W; Quagliani, R; Quintana, B; Rachwal, B; Rademacker, J H; Rama, M; Ramos Pernas, M; Rangel, M S; Raniuk, I; Ratnikov, F; Raven, G; Ravonel Salzgeber, M; Reboud, M; Redi, F; Reichert, S; Dos Reis, A C; Remon Alepuz, C; Renaudin, V; Ricciardi, S; Richards, S; Rihl, M; Rinnert, K; Rives Molina, V; Robbe, P; Robert, A; Rodrigues, A B; Rodrigues, E; Rodriguez Lopez, J A; Rodriguez Perez, P; Rogozhnikov, A; Roiser, S; Rollings, A; Romanovskiy, V; Romero Vidal, A; Ronayne, J W; Rotondo, M; Rudolph, M S; Ruf, T; Ruiz Valls, P; Ruiz Vidal, J; Saborido Silva, J J; Sadykhov, E; Sagidova, N; Saitta, B; Salustino Guimaraes, V; Sanchez Gonzalo, D; Sanchez Mayordomo, C; Sanmartin Sedes, B; Santacesaria, R; Santamarina Rios, C; Santimaria, M; Santovetti, E; Sarpis, G; Sarti, A; Satriano, C; Satta, A; Saunders, D M; Savrina, D; Schael, S; Schellenberg, M; Schiller, M; Schindler, H; Schlupp, M; Schmelling, M; Schmelzer, T; Schmidt, B; Schneider, O; Schopper, A; Schreiner, H F; Schubert, K; Schubiger, M; Schune, M-H; Schwemmer, R; Sciascia, B; Sciubba, A; Semennikov, A; Sergi, A; Serra, N; Serrano, J; Sestini, L; Seyfert, P; Shapkin, M; Shapoval, I; Shcheglov, Y; Shears, T; Shekhtman, L; Shevchenko, V; Siddi, B G; Silva Coutinho, R; Silva de Oliveira, L; Simi, G; Simone, S; Sirendi, M; Skidmore, N; Skwarnicki, T; Smith, E; Smith, I T; Smith, J; Smith, M; Soares Lavra, L; Sokoloff, M D; Soler, F J P; Souza De Paula, B; Spaan, B; Spradlin, P; Sridharan, S; Stagni, F; Stahl, M; Stahl, S; Stefko, P; Stefkova, S; Steinkamp, O; Stemmle, S; Stenyakin, O; Stepanova, M; Stevens, H; Stone, S; Storaci, B; Stracka, S; Stramaglia, M E; Straticiuc, M; Straumann, U; Sun, L; Sutcliffe, W; Swientek, K; Syropoulos, V; Szczekowski, M; Szumlak, T; Szymanski, M; T'Jampens, S; Tayduganov, A; Tekampe, T; Tellarini, G; Teubert, F; Thomas, E; van Tilburg, J; Tilley, M J; Tisserand, V; Tobin, M; Tolk, S; Tomassetti, L; Tonelli, D; Toriello, F; Tourinho Jadallah Aoude, R; Tournefier, E; Traill, M; Tran, M T; Tresch, M; Trisovic, A; Tsaregorodtsev, A; Tsopelas, P; Tully, A; Tuning, N; Ukleja, A; Usachov, A; Ustyuzhanin, A; Uwer, U; Vacca, C; Vagner, A; Vagnoni, V; Valassi, A; Valat, S; Valenti, G; Vazquez Gomez, R; Vazquez Regueiro, P; Vecchi, S; van Veghel, M; Velthuis, J J; Veltri, M; Veneziano, G; Venkateswaran, A; Verlage, T A; Vernet, M; Vesterinen, M; Viana Barbosa, J V; Viaud, B; Vieira, D; Vieites Diaz, M; Viemann, H; Vilasis-Cardona, X; Vitti, M; Volkov, V; Vollhardt, A; Voneki, B; Vorobyev, A; Vorobyev, V; Voß, C; de Vries, J A; Vázquez Sierra, C; Waldi, R; Wallace, C; Wallace, R; Walsh, J; Wang, J; Ward, D R; Wark, H M; Watson, N K; Websdale, D; Weiden, A; Whitehead, M; Wicht, J; Wilkinson, G; Wilkinson, M; Williams, M; Williams, M P; Williams, M; Williams, T; Wilson, F F; Wimberley, J; Winn, M A; Wishahi, J; Wislicki, W; Witek, M; Wormser, G; Wotton, S A; Wraight, K; Wyllie, K; Xie, Y; Xu, Z; Yang, Z; Yang, Z; Yao, Y; Yin, H; Yu, J; Yuan, X; Yushchenko, O; Zarebski, K A; Zavertyaev, M; Zhang, L; Zhang, Y; Zhelezov, A; Zheng, Y; Zhu, X; Zhukov, V; Zonneveld, J B; Zucchelli, S

2017-09-15

A highly significant structure is observed in the Λ_{c}^{+}K^{-}π^{+}π^{+} mass spectrum, where the Λ_{c}^{+} baryon is reconstructed in the decay mode pK^{-}π^{+}. The structure is consistent with originating from a weakly decaying particle, identified as the doubly charmed baryon Ξ_{cc}^{++}. The difference between the masses of the Ξ_{cc}^{++} and Λ_{c}^{+} states is measured to be 1334.94±0.72(stat.)±0.27(syst.)  MeV/c^{2}, and the Ξ_{cc}^{++} mass is then determined to be 3621.40±0.72(stat.)±0.27(syst.)±0.14(Λ_{c}^{+})  MeV/c^{2}, where the last uncertainty is due to the limited knowledge of the Λ_{c}^{+} mass. The state is observed in a sample of proton-proton collision data collected by the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.7  fb^{-1}, and confirmed in an additional sample of data collected at 8 TeV.

Observation of the Doubly Charmed Baryon Ξcc ++

NASA Astrophysics Data System (ADS)

Aaij, R.; Adeva, B.; Adinolfi, M.; Ajaltouni, Z.; Akar, S.; Albrecht, J.; Alessio, F.; Alexander, M.; Alfonso Albero, A.; Ali, S.; Alkhazov, G.; Alvarez Cartelle, P.; Alves, A. A.; Amato, S.; Amerio, S.; Amhis, Y.; An, L.; Anderlini, L.; Andreassi, G.; Andreotti, M.; Andrews, J. E.; Appleby, R. B.; Archilli, F.; d'Argent, P.; Arnau Romeu, J.; Artamonov, A.; Artuso, M.; Aslanides, E.; Auriemma, G.; Baalouch, M.; Babuschkin, I.; Bachmann, S.; Back, J. J.; Badalov, A.; Baesso, C.; Baker, S.; Balagura, V.; Baldini, W.; Baranov, A.; Barlow, R. J.; Barschel, C.; Barsuk, S.; Barter, W.; Baryshnikov, F.; Batozskaya, V.; Battista, V.; Bay, A.; Beaucourt, L.; Beddow, J.; Bedeschi, F.; Bediaga, I.; Beiter, A.; Bel, L. J.; Beliy, N.; Bellee, V.; Belloli, N.; Belous, K.; Belyaev, I.; Ben-Haim, E.; Bencivenni, G.; Benson, S.; Beranek, S.; Berezhnoy, A.; Bernet, R.; Berninghoff, D.; Bertholet, E.; Bertolin, A.; Betancourt, C.; Betti, F.; Bettler, M.-O.; van Beuzekom, M.; Bezshyiko, Ia.; Bifani, S.; Billoir, P.; Birnkraut, A.; Bitadze, A.; Bizzeti, A.; Bjoern, M. B.; Blake, T.; Blanc, F.; Blouw, J.; Blusk, S.; Bocci, V.; Boettcher, T.; Bondar, A.; Bondar, N.; Bonivento, W.; Bordyuzhin, I.; Borgheresi, A.; Borghi, S.; Borisyak, M.; Borsato, M.; Borysova, M.; Bossu, F.; Boubdir, M.; Bowcock, T. J. V.; Bowen, E.; Bozzi, C.; Braun, S.; Britton, T.; Brodzicka, J.; Brundu, D.; Buchanan, E.; Burr, C.; Bursche, A.; Buytaert, J.; Byczynski, W.; Cadeddu, S.; Cai, H.; Calabrese, R.; Calladine, R.; Calvi, M.; Calvo Gomez, M.; Camboni, A.; Campana, P.; Campora Perez, D. H.; Capriotti, L.; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carniti, P.; Carson, L.; Carvalho Akiba, K.; Casse, G.; Cassina, L.; Castillo Garcia, L.; Cattaneo, M.; Cavallero, G.; Cenci, R.; Chamont, D.; Charles, M.; Charpentier, Ph.; Chatzikonstantinidis, G.; Chefdeville, M.; Chen, S.; Cheung, S. F.; Chitic, S.-G.; Chobanova, V.; Chrzaszcz, M.; Chubykin, A.; Ciambrone, P.; Cid Vidal, X.; Ciezarek, G.; Clarke, P. E. L.; Clemencic, M.; Cliff, H. V.; Closier, J.; Cogan, J.; Cogneras, E.; Cogoni, V.; Cojocariu, L.; Collins, P.; Colombo, T.; Comerma-Montells, A.; Contu, A.; Cook, A.; Coombs, G.; Coquereau, S.; Corti, G.; Corvo, M.; Costa Sobral, C. M.; Couturier, B.; Cowan, G. A.; Craik, D. C.; Crocombe, A.; Cruz Torres, M.; Currie, R.; D'Ambrosio, C.; Da Cunha Marinho, F.; Dall'Occo, E.; Dalseno, J.; Davis, A.; De Aguiar Francisco, O.; De Capua, S.; De Cian, M.; De Miranda, J. M.; De Paula, L.; De Serio, M.; De Simone, P.; Dean, C. T.; Decamp, D.; Del Buono, L.; Dembinski, H.-P.; Demmer, M.; Dendek, A.; Derkach, D.; Deschamps, O.; Dettori, F.; Dey, B.; Di Canto, A.; Di Nezza, P.; Dijkstra, H.; Dordei, F.; Dorigo, M.; Dosil Suárez, A.; Douglas, L.; Dovbnya, A.; Dreimanis, K.; Dufour, L.; Dujany, G.; Durante, P.; Dzhelyadin, R.; Dziewiecki, M.; Dziurda, A.; Dzyuba, A.; Easo, S.; Ebert, M.; Egede, U.; Egorychev, V.; Eidelman, S.; Eisenhardt, S.; Eitschberger, U.; Ekelhof, R.; Eklund, L.; Ely, S.; Esen, S.; Evans, H. M.; Evans, T.; Falabella, A.; Farley, N.; Farry, S.; Fay, R.; Fazzini, D.; Federici, L.; Ferguson, D.; Fernandez, G.; Fernandez Declara, P.; Fernandez Prieto, A.; Ferrari, F.; Ferreira Rodrigues, F.; Ferro-Luzzi, M.; Filippov, S.; Fini, R. A.; Fiore, M.; Fiorini, M.; Firlej, M.; Fitzpatrick, C.; Fiutowski, T.; Fleuret, F.; Fohl, K.; Fontana, M.; Fontanelli, F.; Forshaw, D. C.; Forty, R.; Franco Lima, V.; Frank, M.; Frei, C.; Fu, J.; Funk, W.; Furfaro, E.; Färber, C.; Gabriel, E.; Gallas Torreira, A.; Galli, D.; Gallorini, S.; Gambetta, S.; Gandelman, M.; Gandini, P.; Gao, Y.; Garcia Martin, L. M.; García Pardiñas, J.; Garra Tico, J.; Garrido, L.; Garsed, P. J.; Gascon, D.; Gaspar, C.; Gavardi, L.; Gazzoni, G.; Gerick, D.; Gersabeck, E.; Gersabeck, M.; Gershon, T.; Ghez, Ph.; Gianı, S.; Gibson, V.; Girard, O. G.; Giubega, L.; Gizdov, K.; Gligorov, V. V.; Golubkov, D.; Golutvin, A.; Gomes, A.; Gorelov, I. V.; Gotti, C.; Govorkova, E.; Grabowski, J. P.; Graciani Diaz, R.; Granado Cardoso, L. A.; Graugés, E.; Graverini, E.; Graziani, G.; Grecu, A.; Greim, R.; Griffith, P.; Grillo, L.; Gruber, L.; Gruberg Cazon, B. R.; Grünberg, O.; Gushchin, E.; Guz, Yu.; Gys, T.; Göbel, C.; Hadavizadeh, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Haines, S. C.; Hamilton, B.; Han, X.; Hancock, T.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S. T.; Harrison, J.; Hasse, C.; Hatch, M.; He, J.; Hecker, M.; Heinicke, K.; Heister, A.; Hennessy, K.; Henrard, P.; Henry, L.; van Herwijnen, E.; Heß, M.; Hicheur, A.; Hill, D.; Hombach, C.; Hopchev, P. H.; Huard, Z.-C.; Hulsbergen, W.; Humair, T.; Hushchyn, M.; Hutchcroft, D.; Ibis, P.; Idzik, M.; Ilten, P.; Jacobsson, R.; Jalocha, J.; Jans, E.; Jawahery, A.; Jiang, F.; John, M.; Johnson, D.; Jones, C. R.; Joram, C.; Jost, B.; Jurik, N.; Kandybei, S.; Karacson, M.; Kariuki, J. M.; Karodia, S.; Kazeev, N.; Kecke, M.; Kelsey, M.; Kenzie, M.; Ketel, T.; Khairullin, E.; Khanji, B.; Khurewathanakul, C.; Kirn, T.; Klaver, S.; Klimaszewski, K.; Klimkovich, T.; Koliiev, S.; Kolpin, M.; Komarov, I.; Kopecna, R.; Koppenburg, P.; Kosmyntseva, A.; Kotriakhova, S.; Kozeiha, M.; Kreps, M.; Krokovny, P.; Kruse, F.; Krzemien, W.; Kucewicz, W.; Kucharczyk, M.; Kudryavtsev, V.; Kuonen, A. K.; Kurek, K.; Kvaratskheliya, T.; Lacarrere, D.; Lafferty, G.; Lai, A.; Lanfranchi, G.; Langenbruch, C.; Latham, T.; Lazzeroni, C.; Le Gac, R.; van Leerdam, J.; Leflat, A.; Lefrançois, J.; Lefèvre, R.; Lemaitre, F.; Lemos Cid, E.; Leroy, O.; Lesiak, T.; Leverington, B.; Li, P.-R.; Li, T.; Li, Y.; Li, Z.; Likhomanenko, T.; Lindner, R.; Lionetto, F.; Lisovskyi, V.; Liu, X.; Loh, D.; Loi, A.; Longstaff, I.; Lopes, J. H.; Lucchesi, D.; Lucio Martinez, M.; Luo, H.; Lupato, A.; Luppi, E.; Lupton, O.; Lusiani, A.; Lyu, X.; Machefert, F.; Maciuc, F.; Macko, V.; Mackowiak, P.; Maddock, B.; Maddrell-Mander, S.; Maev, O.; Maguire, K.; Maisuzenko, D.; Majewski, M. W.; Malde, S.; Malinin, A.; Maltsev, T.; Manca, G.; Mancinelli, G.; Manning, P.; Marangotto, D.; Maratas, J.; Marchand, J. F.; Marconi, U.; Marin Benito, C.; Marinangeli, M.; Marino, P.; Marks, J.; Martellotti, G.; Martin, M.; Martinelli, M.; Martinez Santos, D.; Martinez Vidal, F.; Martins Tostes, D.; Massacrier, L. M.; Massafferri, A.; Matev, R.; Mathad, A.; Mathe, Z.; Matteuzzi, C.; Mauri, A.; Maurice, E.; Maurin, B.; Mazurov, A.; McCann, M.; McNab, A.; McNulty, R.; Mead, J. V.; Meadows, B.; Meaux, C.; Meier, F.; Meinert, N.; Melnychuk, D.; Merk, M.; Merli, A.; Michielin, E.; Milanes, D. A.; Millard, E.; Minard, M.-N.; Minzoni, L.; Mitzel, D. S.; Mogini, A.; Molina Rodriguez, J.; Mombacher, T.; Monroy, I. A.; Monteil, S.; Morandin, M.; Morello, M. J.; Morgunova, O.; Moron, J.; Morris, A. B.; Mountain, R.; Muheim, F.; Mulder, M.; Müller, D.; Müller, J.; Müller, K.; Müller, V.; Naik, P.; Nakada, T.; Nandakumar, R.; Nandi, A.; Nasteva, I.; Needham, M.; Neri, N.; Neubert, S.; Neufeld, N.; Neuner, M.; Nguyen, T. D.; Nguyen-Mau, C.; Nieswand, S.; Niet, R.; Nikitin, N.; Nikodem, T.; Nogay, A.; O'Hanlon, D. P.; Oblakowska-Mucha, A.; Obraztsov, V.; Ogilvy, S.; Oldeman, R.; Onderwater, C. J. G.; Ossowska, A.; Otalora Goicochea, J. M.; Owen, P.; Oyanguren, A.; Pais, P. R.; Palano, A.; Palutan, M.; Papanestis, A.; Pappagallo, M.; Pappalardo, L. L.; Pappenheimer, C.; Parker, W.; Parkes, C.; Passaleva, G.; Pastore, A.; Patel, M.; Patrignani, C.; Pearce, A.; Pellegrino, A.; Penso, G.; Pepe Altarelli, M.; Perazzini, S.; Perret, P.; Pescatore, L.; Petridis, K.; Petrolini, A.; Petrov, A.; Petruzzo, M.; Picatoste Olloqui, E.; Pietrzyk, B.; Pikies, M.; Pinci, D.; Pistone, A.; Piucci, A.; Placinta, V.; Playfer, S.; Plo Casasus, M.; Polci, F.; Poli Lener, M.; Poluektov, A.; Polyakov, I.; Polycarpo, E.; Pomery, G. J.; Ponce, S.; Popov, A.; Popov, D.; Poslavskii, S.; Potterat, C.; Price, E.; Prisciandaro, J.; Prouve, C.; Pugatch, V.; Puig Navarro, A.; Pullen, H.; Punzi, G.; Qian, W.; Quagliani, R.; Quintana, B.; Rachwal, B.; Rademacker, J. H.; Rama, M.; Ramos Pernas, M.; Rangel, M. S.; Raniuk, I.; Ratnikov, F.; Raven, G.; Ravonel Salzgeber, M.; Reboud, M.; Redi, F.; Reichert, S.; dos Reis, A. C.; Remon Alepuz, C.; Renaudin, V.; Ricciardi, S.; Richards, S.; Rihl, M.; Rinnert, K.; Rives Molina, V.; Robbe, P.; Robert, A.; Rodrigues, A. B.; Rodrigues, E.; Rodriguez Lopez, J. A.; Rodriguez Perez, P.; Rogozhnikov, A.; Roiser, S.; Rollings, A.; Romanovskiy, V.; Romero Vidal, A.; Ronayne, J. W.; Rotondo, M.; Rudolph, M. S.; Ruf, T.; Ruiz Valls, P.; Ruiz Vidal, J.; Saborido Silva, J. J.; Sadykhov, E.; Sagidova, N.; Saitta, B.; Salustino Guimaraes, V.; Sanchez Gonzalo, D.; Sanchez Mayordomo, C.; Sanmartin Sedes, B.; Santacesaria, R.; Santamarina Rios, C.; Santimaria, M.; Santovetti, E.; Sarpis, G.; Sarti, A.; Satriano, C.; Satta, A.; Saunders, D. M.; Savrina, D.; Schael, S.; Schellenberg, M.; Schiller, M.; Schindler, H.; Schlupp, M.; Schmelling, M.; Schmelzer, T.; Schmidt, B.; Schneider, O.; Schopper, A.; Schreiner, H. F.; Schubert, K.; Schubiger, M.; Schune, M.-H.; Schwemmer, R.; Sciascia, B.; Sciubba, A.; Semennikov, A.; Sergi, A.; Serra, N.; Serrano, J.; Sestini, L.; Seyfert, P.; Shapkin, M.; Shapoval, I.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenko, V.; Siddi, B. G.; Silva Coutinho, R.; Silva de Oliveira, L.; Simi, G.; Simone, S.; Sirendi, M.; Skidmore, N.; Skwarnicki, T.; Smith, E.; Smith, I. T.; Smith, J.; Smith, M.; Soares Lavra, l.; Sokoloff, M. D.; Soler, F. J. P.; Souza De Paula, B.; Spaan, B.; Spradlin, P.; Sridharan, S.; Stagni, F.; Stahl, M.; Stahl, S.; Stefko, P.; Stefkova, S.; Steinkamp, O.; Stemmle, S.; Stenyakin, O.; Stepanova, M.; Stevens, H.; Stone, S.; Storaci, B.; Stracka, S.; Stramaglia, M. E.; Straticiuc, M.; Straumann, U.; Sun, L.; Sutcliffe, W.; Swientek, K.; Syropoulos, V.; Szczekowski, M.; Szumlak, T.; Szymanski, M.; T'Jampens, S.; Tayduganov, A.; Tekampe, T.; Tellarini, G.; Teubert, F.; Thomas, E.; van Tilburg, J.; Tilley, M. J.; Tisserand, V.; Tobin, M.; Tolk, S.; Tomassetti, L.; Tonelli, D.; Toriello, F.; Tourinho Jadallah Aoude, R.; Tournefier, E.; Traill, M.; Tran, M. T.; Tresch, M.; Trisovic, A.; Tsaregorodtsev, A.; Tsopelas, P.; Tully, A.; Tuning, N.; Ukleja, A.; Usachov, A.; Ustyuzhanin, A.; Uwer, U.; Vacca, C.; Vagner, A.; Vagnoni, V.; Valassi, A.; Valat, S.; Valenti, G.; Vazquez Gomez, R.; Vazquez Regueiro, P.; Vecchi, S.; van Veghel, M.; Velthuis, J. J.; Veltri, M.; Veneziano, G.; Venkateswaran, A.; Verlage, T. A.; Vernet, M.; Vesterinen, M.; Viana Barbosa, J. V.; Viaud, B.; Vieira, D.; Vieites Diaz, M.; Viemann, H.; Vilasis-Cardona, X.; Vitti, M.; Volkov, V.; Vollhardt, A.; Voneki, B.; Vorobyev, A.; Vorobyev, V.; Voß, C.; de Vries, J. A.; Vázquez Sierra, C.; Waldi, R.; Wallace, C.; Wallace, R.; Walsh, J.; Wang, J.; Ward, D. R.; Wark, H. M.; Watson, N. K.; Websdale, D.; Weiden, A.; Whitehead, M.; Wicht, J.; Wilkinson, G.; Wilkinson, M.; Williams, M.; Williams, M. P.; Williams, M.; Williams, T.; Wilson, F. F.; Wimberley, J.; Winn, M. A.; Wishahi, J.; Wislicki, W.; Witek, M.; Wormser, G.; Wotton, S. A.; Wraight, K.; Wyllie, K.; Xie, Y.; Xu, Z.; Yang, Z.; Yang, Z.; Yao, Y.; Yin, H.; Yu, J.; Yuan, X.; Yushchenko, O.; Zarebski, K. A.; Zavertyaev, M.; Zhang, L.; Zhang, Y.; Zhelezov, A.; Zheng, Y.; Zhu, X.; Zhukov, V.; Zonneveld, J. B.; Zucchelli, S.; LHCb Collaboration

2017-09-01

A highly significant structure is observed in the Λc+K-π+π+ mass spectrum, where the Λc+ baryon is reconstructed in the decay mode p K-π+. The structure is consistent with originating from a weakly decaying particle, identified as the doubly charmed baryon Ξcc ++. The difference between the masses of the Ξcc ++ and Λc+ states is measured to be 1334.94 ±0.72 (stat.) ±0.27 (syst. ) MeV /c2 , and the Ξcc ++ mass is then determined to be 3621.40 ±0.72 (stat.) ±0.27 (syst. ) ±0.14 (Λc+) MeV /c2 , where the last uncertainty is due to the limited knowledge of the Λc+ mass. The state is observed in a sample of proton-proton collision data collected by the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.7 fb-1, and confirmed in an additional sample of data collected at 8 TeV.

The Fisher-KPP problem with doubly nonlinear diffusion

NASA Astrophysics Data System (ADS)

Audrito, Alessandro; Vázquez, Juan Luis

2017-12-01

The famous Fisher-KPP reaction-diffusion model combines linear diffusion with the typical KPP reaction term, and appears in a number of relevant applications in biology and chemistry. It is remarkable as a mathematical model since it possesses a family of travelling waves that describe the asymptotic behaviour of a large class solutions 0 ≤ u (x , t) ≤ 1 of the problem posed in the real line. The existence of propagation waves with finite speed has been confirmed in some related models and disproved in others. We investigate here the corresponding theory when the linear diffusion is replaced by the "slow" doubly nonlinear diffusion and we find travelling waves that represent the wave propagation of more general solutions even when we extend the study to several space dimensions. A similar study is performed in the critical case that we call "pseudo-linear", i.e., when the operator is still nonlinear but has homogeneity one. With respect to the classical model and the "pseudo-linear" case, the "slow" travelling waves exhibit free boundaries.

Reconstructive techniques for creation of catheterizable channels: tunneled and nipple valve channels

PubMed Central

Levy, Mya E.

2016-01-01

Cutaneous catheterizable channels allow for continent bladder emptying when an alternate route is desired. The goals of channel creation in the neurogenic bladder population are successful urine elimination, renal preservation, continence and lastly cosmesis. In addition to a particular surgeon’s comfort and experience with a given procedure, individual patient factors such as medical comorbidities, anatomic factors, and occupational function should be central to the selection of a surgical approach. An ideal channel is one that is short, straight, and well supported by associated blood supply and surrounding adventitia, so as to minimize difficulty with catheterization. Two types of channel continence mechanisms are discussed at length in this review—the tunneled channel, and the nipple valve. The appendicovesicostomy (Mitrofanoff), and reconfigured ileum (Yang-Monti) are both tunneled channels. The ileocecal valve is a commonly used nipple valve and provides continence when reinforced. The continent catheterizable ileal cecocystoplasty (CCIC) is an example of this channel technique. This method couples a tapered ileal limb as a catheterizable channel, the ileocecal valve as the continence mechanism, and the cecum and ascending colon as a bladder augmentation. While this procedure has higher perioperative complications relative to a simple tunneled channel, it has increased channel length flexibility and is also coupled with a bladder augment, which is completely performed using one bowel segment. Continent channel creation in adults can improve quality of life and minimize morbidity associated with neurogenic bladder. However, the decision to proceed with creation of a catheterizable channel should be made only after careful consideration of the patient’s medical comorbidities, physical abilities social support, and surgeon experience. PMID:26904419

Massively parallel processor networks with optical express channels

DOEpatents

Deri, R.J.; Brooks, E.D. III; Haigh, R.E.; DeGroot, A.J.

1999-08-24

An optical method for separating and routing local and express channel data comprises interconnecting the nodes in a network with fiber optic cables. A single fiber optic cable carries both express channel traffic and local channel traffic, e.g., in a massively parallel processor (MPP) network. Express channel traffic is placed on, or filtered from, the fiber optic cable at a light frequency or a color different from that of the local channel traffic. The express channel traffic is thus placed on a light carrier that skips over the local intermediate nodes one-by-one by reflecting off of selective mirrors placed at each local node. The local-channel-traffic light carriers pass through the selective mirrors and are not reflected. A single fiber optic cable can thus be threaded throughout a three-dimensional matrix of nodes with the x,y,z directions of propagation encoded by the color of the respective light carriers for both local and express channel traffic. Thus frequency division multiple access is used to hierarchically separate the local and express channels to eliminate the bucket brigade latencies that would otherwise result if the express traffic had to hop between every local node to reach its ultimate destination. 3 figs.

Massively parallel processor networks with optical express channels

DOEpatents

Deri, Robert J.; Brooks, III, Eugene D.; Haigh, Ronald E.; DeGroot, Anthony J.

1999-01-01

An optical method for separating and routing local and express channel data comprises interconnecting the nodes in a network with fiber optic cables. A single fiber optic cable carries both express channel traffic and local channel traffic, e.g., in a massively parallel processor (MPP) network. Express channel traffic is placed on, or filtered from, the fiber optic cable at a light frequency or a color different from that of the local channel traffic. The express channel traffic is thus placed on a light carrier that skips over the local intermediate nodes one-by-one by reflecting off of selective mirrors placed at each local node. The local-channel-traffic light carriers pass through the selective mirrors and are not reflected. A single fiber optic cable can thus be threaded throughout a three-dimensional matrix of nodes with the x,y,z directions of propagation encoded by the color of the respective light carriers for both local and express channel traffic. Thus frequency division multiple access is used to hierarchically separate the local and express channels to eliminate the bucket brigade latencies that would otherwise result if the express traffic had to hop between every local node to reach its ultimate destination.

Analyzing the components of the free-energy landscape in a calcium selective ion channel by Widom's particle insertion method

NASA Astrophysics Data System (ADS)

Boda, Dezső; Giri, Janhavi; Henderson, Douglas; Eisenberg, Bob; Gillespie, Dirk

2011-02-01

The selectivity filter of the L-type calcium channel works as a Ca2 + binding site with a very large affinity for Ca2 + versus Na+. Ca2 + replaces half of the Na+ ions in the filter even when these ions are present in 1 μM and 30 mM concentrations in the bath, respectively. The energetics of this strong selectivity is analyzed in this paper. We use Widom's particle insertion method to compute the space-dependent profiles of excess chemical potential in our grand canonical Monte Carlo simulations. These profiles define the free-energy landscape for the various ions. Following Gillespie [Biophys. J. 94, 1169 (2008)], the difference of the excess chemical potentials for the two competing ions defines the advantage that one of the ions has over the other in the competition for space in the crowded selectivity filter. These advantages depend on ionic bath concentrations: the ion that is present in the bath in larger quantity (Na+) has the "number" advantage which is balanced by the free-energy advantage of the other ion (Ca2 +). The excess chemical potentials are decomposed into hard sphere exclusion and electrostatic components. The electrostatic terms correspond to interactions with the mean electric field produced by ions and induced charges as well to ionic correlations beyond the mean field description. Dielectrics are needed to produce micromolar Ca2 + versus Na+ selectivity in the L-type channel. We study the behavior of these terms with changes in bath concentrations of ions, charges, and diameters of ions, as well as geometrical parameters such as radius of the pore and the dielectric constant of the protein. Ion selectivity in calcium binding proteins probably has a similar mechanism.

Analyzing the components of the free-energy landscape in a calcium selective ion channel by Widom's particle insertion method.

PubMed

Boda, Dezso; Giri, Janhavi; Henderson, Douglas; Eisenberg, Bob; Gillespie, Dirk

2011-02-07

The selectivity filter of the L-type calcium channel works as a Ca(2+) binding site with a very large affinity for Ca(2+) versus Na(+). Ca(2+) replaces half of the Na(+) ions in the filter even when these ions are present in 1 μM and 30 mM concentrations in the bath, respectively. The energetics of this strong selectivity is analyzed in this paper. We use Widom's particle insertion method to compute the space-dependent profiles of excess chemical potential in our grand canonical Monte Carlo simulations. These profiles define the free-energy landscape for the various ions. Following Gillespie [Biophys. J. 94, 1169 (2008)], the difference of the excess chemical potentials for the two competing ions defines the advantage that one of the ions has over the other in the competition for space in the crowded selectivity filter. These advantages depend on ionic bath concentrations: the ion that is present in the bath in larger quantity (Na(+)) has the "number" advantage which is balanced by the free-energy advantage of the other ion (Ca(2+)). The excess chemical potentials are decomposed into hard sphere exclusion and electrostatic components. The electrostatic terms correspond to interactions with the mean electric field produced by ions and induced charges as well to ionic correlations beyond the mean field description. Dielectrics are needed to produce micromolar Ca(2+) versus Na(+) selectivity in the L-type channel. We study the behavior of these terms with changes in bath concentrations of ions, charges, and diameters of ions, as well as geometrical parameters such as radius of the pore and the dielectric constant of the protein. Ion selectivity in calcium binding proteins probably has a similar mechanism.

The hitchhiker’s guide to the voltage-gated sodium channel galaxy

PubMed Central

2016-01-01

Eukaryotic voltage-gated sodium (Nav) channels contribute to the rising phase of action potentials and served as an early muse for biophysicists laying the foundation for our current understanding of electrical signaling. Given their central role in electrical excitability, it is not surprising that (a) inherited mutations in genes encoding for Nav channels and their accessory subunits have been linked to excitability disorders in brain, muscle, and heart; and (b) Nav channels are targeted by various drugs and naturally occurring toxins. Although the overall architecture and behavior of these channels are likely to be similar to the more well-studied voltage-gated potassium channels, eukaryotic Nav channels lack structural and functional symmetry, a notable difference that has implications for gating and selectivity. Activation of voltage-sensing modules of the first three domains in Nav channels is sufficient to open the channel pore, whereas movement of the domain IV voltage sensor is correlated with inactivation. Also, structure–function studies of eukaryotic Nav channels show that a set of amino acids in the selectivity filter, referred to as DEKA locus, is essential for Na+ selectivity. Structures of prokaryotic Nav channels have also shed new light on mechanisms of drug block. These structures exhibit lateral fenestrations that are large enough to allow drugs or lipophilic molecules to gain access into the inner vestibule, suggesting that this might be the passage for drug entry into a closed channel. In this Review, we will synthesize our current understanding of Nav channel gating mechanisms, ion selectivity and permeation, and modulation by therapeutics and toxins in light of the new structures of the prokaryotic Nav channels that, for the time being, serve as structural models of their eukaryotic counterparts. PMID:26712848

TRPM4 non-selective cation channels influence action potentials in rabbit Purkinje fibres.

PubMed

Hof, Thomas; Sallé, Laurent; Coulbault, Laurent; Richer, Romain; Alexandre, Joachim; Rouet, René; Manrique, Alain; Guinamard, Romain

2016-01-15

The transient receptor potential melastatin 4 (TRPM4) inhibitor 9-phenanthrol reduces action potential duration in rabbit Purkinje fibres but not in ventricle. TRPM4-like single channel activity is observed in isolated rabbit Purkinje cells but not in ventricular cells. The TRPM4-like current develops during the notch and early repolarization phases of the action potential in Purkinje cells. Transient receptor potential melastatin 4 (TRPM4) Ca(2+)-activated non-selective cation channel activity has been recorded in cardiomyocytes and sinus node cells from mammals. In addition, TRPM4 gene mutations are associated with human diseases of cardiac conduction, suggesting that TRPM4 plays a role in this aspect of cardiac function. Here we evaluate the TRPM4 contribution to cardiac electrophysiology of Purkinje fibres. Ventricular strips with Purkinje fibres were isolated from rabbit hearts. Intracellular microelectrodes recorded Purkinje fibre activity and the TRPM4 inhibitor 9-phenanthrol was applied to unmask potential TRPM4 contributions to the action potential. 9-Phenanthrol reduced action potential duration measured at the point of 50 and 90% repolarization with an EC50 of 32.8 and 36.1×10(-6) mol l(-1), respectively, but did not modulate ventricular action potentials. Inside-out patch-clamp recordings were used to monitor TRPM4 activity in isolated Purkinje cells. TRPM4-like single channel activity (conductance = 23.8 pS; equal permeability for Na(+) and K(+); sensitivity to voltage, Ca(2+) and 9-phenanthrol) was observed in 43% of patches from Purkinje cells but not from ventricular cells (0/16). Action potential clamp experiments performed in the whole-cell configuration revealed a transient inward 9-phenanthrol-sensitive current (peak density = -0.65 ± 0.15 pA pF(-1); n = 5) during the plateau phases of the Purkinje fibre action potential. These results show that TRPM4 influences action potential characteristics in rabbit Purkinje fibres and thus could modulate

Pharmacological Modulation of Diacylglycerol-Sensitive TRPC3/6/7 Channels

PubMed Central

Harteneck, Christian; Gollasch, Maik

2011-01-01

Members of the classic type of transient receptor potential channels (TRPC) represent important molecules involved in hormonal signal transduction. TRPC3/6/7 channels are of particular interest as they are components of phospholipase C driven signalling pathways. Upon receptor-activation, G-protein-mediated stimulation of phospholipase C results in breakdown of phosphatidylinositides leading to increased intracellular diacylglycerol and inositol-trisphosphate levels. Diacylglycerol activates protein kinase C, but more interestingly diacylglycerol directly activates TRPC2/3/6/7 channels. Molecular cloning, expression and characterization of TRP channels enabled reassignment of traditional inhibitors of receptor-dependent calcium entry such as SKF-96365 and 2-APB as blockers of TRPC3/6/7 and several members of non-classic TRP channels. Furthermore, several enzyme inhibitors have also been identified as TRP channel blockers, such as ACA, a phospholipase A2 inhibitor, and W-7, a calmodulin antagonist. Finally, the naturally occurring secondary plant compound hyperforin has been identified as TRPC6-selective drug, providing an exciting proof of concept that it is possible to generate TRPC-selective channel modulators. The description of Pyr3 as the first TRPC3-selective inhibitor shows that not only nature but also man is able to generate TRP-selective modulators. The review sheds lights on the current knowledge and historical development of pharmacological modulators of TRPC3/6/7. Our analysis indicates that Pyr3 and hyperforin provide promising core structures for the development of new, selective and more potent modulators of TRPC3/6/7 activity. PMID:20932261

Biophysics of BK Channel Gating.

PubMed

Pantazis, A; Olcese, R

2016-01-01

BK channels are universal regulators of cell excitability, given their exceptional unitary conductance selective for K(+), joint activation mechanism by membrane depolarization and intracellular [Ca(2+)] elevation, and broad expression pattern. In this chapter, we discuss the structural basis and operational principles of their activation, or gating, by membrane potential and calcium. We also discuss how the two activation mechanisms interact to culminate in channel opening. As members of the voltage-gated potassium channel superfamily, BK channels are discussed in the context of archetypal family members, in terms of similarities that help us understand their function, but also seminal structural and biophysical differences that confer unique functional properties. © 2016 Elsevier Inc. All rights reserved.

Radiative rates for forbidden M1 and E2 transitions of astrophysical interest in doubly ionized iron-peak elements

NASA Astrophysics Data System (ADS)

Fivet, V.; Quinet, P.; Bautista, M. A.

2016-01-01

Aims: Accurate and reliable atomic data for lowly ionized Fe-peak species (Sc, Ti, V, Cr, Mn, Fe, Co, and Ni) are of paramount importance for analyzing the high-resolution astrophysical spectra currently available. The third spectra of several iron group elements have been observed in different galactic sources, such as Herbig-Haro objects in the Orion Nebula and stars like Eta Carinae. However, forbidden M1 and E2 transitions between low-lying metastable levels of doubly charged iron-peak ions have been investigated very little so far, and radiative rates for those lines remain sparse or nonexistent. We attempt to fill that gap and provide transition probabilities for the most important forbidden lines of all doubly ionized iron-peak elements. Methods: We carried out a systematic study of the electronic structure of doubly ionized Fe-peak species. The magnetic dipole (M1) and electric quadrupole (E2) transition probabilities were computed using the pseudo-relativistic Hartree-Fock (HFR) code of Cowan and the central Thomas-Fermi-Dirac-Amaldi potential approximation implemented in AUTOSTRUCTURE. This multiplatform approach allowed for consistency checks and intercomparison and has proven very useful in many previous works for estimating the uncertainties affecting the radiative data. Results: We present transition probabilities for the M1 and E2 forbidden lines depopulating the metastable even levels belonging to the 3dk and 3dk-14s configurations in Sc III (k = 1), Ti III (k = 2), V III (k = 3), Cr III (k = 4), Mn III (k = 5), Fe III (k = 6), Co III (k = 7), and Ni III (k = 8).

Investigation of the role of non-selective calcium channel blocker (flunarizine) on cerebral ischemic-reperfusion associated cognitive dysfunction in aged mice.

PubMed

Gulati, Puja; Muthuraman, Arunachalam; Kaur, Parneet

2015-04-01

The present study was designed to investigate the role of flunarizine (a non-selective calcium channel blocker) on cerebral ischemic-reperfusion associated cognitive dysfunction in aged mice. Bilateral carotid artery occlusion of 12min followed by reperfusion for 24h was given to induce cerebral injury in male Swiss mice. The assessment of learning & memory was performed by Morris water maze test; motor in-coordination was evaluated by rota rod, lateral push and inclined beam walking tests; cerebral infarct size was quantified by triphenyltetrazolium chloride staining. In addition, reduced glutathione (GSH), total calcium and acetylcholinesterase (AChE) activity were also estimated in aged brain tissue. Donepezil treated group served as a positive control in this study. Ischemia reperfusion (I/R) injury produced significant increase in cerebral infarct size. A significant loss of memory along with impairment of motor performance was also noted. Further, I/R injury also produced significant increase in levels of total calcium, AChE activity and decrease in GSH levels. Pretreatment of flunarizine significantly attenuated I/R induced infarct size, behavioral and biochemical changes. Hence, it may be concluded that, a non-selective calcium channel blocker can be useful in I/R associated cognitive dysfunction due to its anti-oxidant, anti-infarct and modulatory actions of neurotransmitters & calcium channels. Copyright © 2015 Elsevier Inc. All rights reserved.

Doubly resonant three-wave-mixing spectroscopy of a chiral coupled-chromophore system in solution: coherent two-dimensional optical activity spectroscopy.

PubMed

Cheon, Sangheon; Lee, Hochan; Choi, Jun-Ho; Cho, Minhaeng

2007-02-07

Theoretical descriptions of doubly resonant two-dimensional (2D) sum-frequency-generation (SFG) and difference-frequency-generation (DFG) spectroscopies of coupled-chromophore systems are presented. Despite that each electronic or vibrational chromophore is achiral, the interaction-induced chirality of a coupled multichromophore system in solution can be measured by using the doubly resonant 2D three-wave-mixing (3WM) spectroscopic method. An electronically coupled dimer, where each monomer is modeled as a simple two-level system, can have nonvanishing SFG (or DFG) properties, e.g., susceptibility in frequency domain or nonlinear response function in time domain, if the induced dipole vector of the dimer is not orthogonal to the vector product of the two monomer electronic transition dipole vectors. In order to demonstrate that these 2D 3WM spectroscopic methods can be used to determine the solution structure of a polypeptide, the authors carried out quantum chemistry calculations for an alanine dipeptide and obtained first- and second-order dipole derivatives associated with the amide I vibrational transitions of the dipeptide. It is shown that the numerically simulated 2D IR-IR SFG spectrum is highly sensitive to the dipeptide secondary structure and provides rich information on the one- and two-exciton states. It is believed that the theoretically proposed doubly resonant 2D 3WM spectroscopy, which can be considered to be an optical activity spectroscopy, will be of use in studying both structural and dynamical aspects of coupled multichromophore systems, such as proteins, nucleic acids, nanoparticle aggregates etc.

Theoretical and experimental evidence of non-symmetric doubly localized rogue waves

PubMed Central

He, Jingsong; Guo, Lijuan; Zhang, Yongshuai; Chabchoub, Amin

2014-01-01

We present determinant expressions for vector rogue wave (RW) solutions of the Manakov system, a two-component coupled nonlinear Schrödinger (NLS) equation. As a special case, we generate a family of exact and non-symmetric RW solutions of the NLS equation up to third order, localized in both space and time. The derived non-symmetric doubly localized second-order solution is generated experimentally in a water wave flume for deep-water conditions. Experimental results, confirming the characteristic non-symmetric pattern of the solution, are in very good agreement with theory as well as with numerical simulations, based on the modified NLS equation, known to model accurately the dynamics of weakly nonlinear wave packets in deep water. PMID:25383023

Microwave photon generation in a doubly tunable superconducting resonator

NASA Astrophysics Data System (ADS)

Svensson, I.-M.; Pierre, M.; Simoen, M.; Wustmann, W.; Krantz, P.; Bengtsson, A.; Johansson, G.; Bylander, J.; Shumeiko, V.; Delsing, P.

2018-03-01

We have created a doubly tunable resonator, with the intention to simulate relativistic motion of the resonator boundaries in real space. Our device is a superconducting coplanar-waveguide microwave resonator, with fundamental resonant frequency ω 1 /(2π) ~ 5 GHz. Both of its ends are terminated to ground via dc-SQUIDs, which serve as magnetic-flux-controlled inductances. Applying a flux to either SQUID allows the tuning of ω 1 /(2π) by approximately 700 MHz. Using two separate on-chip magnetic-flux lines, we modulate the SQUIDs with two tones of equal frequency, close to 2ω 1. We observe photon generation, at ω 1, above a certain pump amplitude threshold. By varying the relative phase of the two pumps we are able to control this threshold, in good agreement with a theoretical model. At the same time, some of our observations deviate from the theoretical predictions, which we attribute to parasitic couplings resulting in current driving of the SQUIDs.

Molecular Mechanism of Action and Selectivity of Sodium Channel Blocker Insecticides

PubMed Central

Silver, Kristopher; Dong, Ke; Zhorov, Boris S.

2017-01-01

Sodium channel blocker insecticides (SCBIs) are a relatively new class of insecticides that are represented by two commercially registered compounds, indoxacarb and metaflumizone. SCBIs, like pyrethroids and DDT, target voltage-gated sodium channels (VGSCs) to intoxicate insects. In contrast to pyrethroids, however, SCBIs inhibit VGSCs at a distinct receptor site that overlaps those of therapeutic inhibitors of sodium channels, such as local anesthetics, anticonvulsants and antiarrhythmics. This review will recount the development of the SCBI insecticide class from its roots as chitin synthesis inhibitors, discuss the symptoms of poisoning and evidence supporting inhibition of VGSCs as their mechanism of action, describe the current model for SCBI-induced inhibition of VGSCs, present a model for the receptor for SCBIs on VGSCs, and highlight differences between data collected from mammalian and insect experimental models. PMID:27993108

Affinity purification of the voltage-sensitive sodium channel from electroplax with resins selective for sialic acid

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

James, W.M.; Emerick, M.C.; Agnew, W.S.

1989-07-11

The voltage-sensitive sodium channel present in the eel (Electrophorus electricus) has an unusually high content of sialic acid, including {alpha}-(2{yields}8)-linked polysialic acid, not found in other electroplax membrane glycopeptides. Lectins from Limax flavus (LFA) and wheat germ (WGA) proved the most effective of 11 lectin resins tried. The most selective resin was prepared from IgM antibodies against Neisseria meningitidis {alpha}-(2{yields}8)-polysialic acid which were affinity purified and coupled to Sepharose 4B. The sodium channel was found to bind to WGA, LFA, and IgM resins and was readily eluted with the appropriate soluble carbohydrates. Experiments with LFA and IgM resins demonstrated bindingmore » and unbinding rates and displacement kinetics, which suggest highly specific binding at multiple sites on the sodium channel protein. In preparative-scale purification of protein previously fractionated by anion-exchange chromatography, without stabilizing TTX, high yields were reproducibly obtained. Further, when detergent extracts were prepared from electroplax membranes fractionated by low-speed sedimentation, a single step over the IgM resin provided a 70-fold purification, yielding specific activities of 3,200 pmol of ({sup 3}H)TTX-binding sites/mg of protein and a single polypeptide of {approximately}285,000 Da on SDS-acrylamide gels. No small peptides were observed after this 5-h isolation. The authors describe a cation-dependent stabilization with millimolar levels of monovalent and micromolar levels of divalent species.« less

Application of a multivariate normal distribution methodology to the dissociation of doubly ionized molecules: The DMDS (CH3 -SS-CH3 ) case.

PubMed

Varas, Lautaro R; Pontes, F C; Santos, A C F; Coutinho, L H; de Souza, G G B

2015-09-15

The ion-ion-coincidence mass spectroscopy technique brings useful information about the fragmentation dynamics of doubly and multiply charged ionic species. We advocate the use of a matrix-parameter methodology in order to represent and interpret the entire ion-ion spectra associated with the ionic dissociation of doubly charged molecules. This method makes it possible, among other things, to infer fragmentation processes and to extract information about overlapped ion-ion coincidences. This important piece of information is difficult to obtain from other previously described methodologies. A Wiley-McLaren time-of-flight mass spectrometer was used to discriminate the positively charged fragment ions resulting from the sample ionization by a pulsed 800 eV electron beam. We exemplify the application of this methodology by analyzing the fragmentation and ionic dissociation of the dimethyl disulfide (DMDS) molecule as induced by fast electrons. The doubly charged dissociation was analyzed using the Multivariate Normal Distribution. The ion-ion spectrum of the DMDS molecule was obtained at an incident electron energy of 800 eV and was matrix represented using the Multivariate Distribution theory. The proposed methodology allows us to distinguish information among [CH n SH n ] + /[CH 3 ] + (n = 1-3) fragment ions in the ion-ion coincidence spectra using ion-ion coincidence data. Using the momenta balance methodology for the inferred parameters, a secondary decay mechanism is proposed for the [CHS] + ion formation. As an additional check on the methodology, previously published data on the SiF 4 molecule was re-analyzed with the present methodology and the results were shown to be statistically equivalent. The use of a Multivariate Normal Distribution allows for the representation of the whole ion-ion mass spectrum of doubly or multiply ionized molecules as a combination of parameters and the extraction of information among overlapped data. We have successfully

First evidence of γ collectivity close to the doubly magic core Sn 132

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

Urban, W.; Sieja, K.; Rząca-Urban, T.

2016-03-01

The Te-138 and Xe-140 nuclei have been reinvestigated using prompt gamma-ray data from spontaneous fission of Cm-248, collected with the EUROGAM2 Ge array. gamma bands have been identified in both nuclei. The gamma band observed in Te-138, a nucleus with only six valence nucleons, indicates the presence of collectivity very close to the doubly magic Sn-132 core. Such band is even more pronounced in Xe-140, the N = 86 isotone of Te-138. The newly observed bands are interpreted within the shell model, which reproduce well the. collectivity at N = 86.

Tight junctions of the proximal tubule and their channel proteins.

PubMed

Fromm, Michael; Piontek, Jörg; Rosenthal, Rita; Günzel, Dorothee; Krug, Susanne M

2017-08-01

The renal proximal tubule achieves the majority of renal water and solute reabsorption with the help of paracellular channels which lead through the tight junction. The proteins forming such channels in the proximal tubule are claudin-2, claudin-10a, and possibly claudin-17. Claudin-2 forms paracellular channels selective for small cations like Na + and K + . Independently of each other, claudin-10a and claudin-17 form anion-selective channels. The claudins form the paracellular "pore pathway" and are integrated, together with purely sealing claudins and other tight junction proteins, in the belt of tight junction strands surrounding the tubular epithelial cells. In most species, the proximal tubular tight junction consists of only 1-2 (pars convoluta) to 3-5 (pars recta) horizontal strands. Even so, they seal the tubule very effectively against leak passage of nutrients and larger molecules. Remarkably, claudin-2 channels are also permeable to water so that 20-25% of proximal water absorption may occur paracellularly. Although the exact structure of the claudin-2 channel is still unknown, it is clear that Na + and water share the same pore. Already solved claudin crystal structures reveal a characteristic β-sheet, comprising β-strands from both extracellular loops, which is anchored to a left-handed four-transmembrane helix bundle. This allowed homology modeling of channel-forming claudins present in the proximal tubule. The surface of cation- and anion-selective claudins differ in electrostatic potentials in the area of the proposed ion channel, resulting in the opposite charge selectivity of these claudins. Presently, while models of the molecular structure of the claudin-based oligomeric channels have been proposed, its full understanding has only started.

Anion channels in the sea urchin sperm plasma membrane.

PubMed

Morales, E; de la Torre, L; Moy, G W; Vacquier, V D; Darszon, A

1993-10-01

Ionic fluxes in sea urchin sperm plasma membrane regulate cell motility and the acrosome reaction (AR). Although cationic channels mediate some of the ionic movements, little is known about anion channels in these cells. The fusion of sperm plasma membranes into lipid bilayers allowed identification of a 150 pS anion channel. This anion channel was enriched from detergent-solubilized sperm plasma membranes using a wheat germ agglutinin Sepharose column. Vesicles formed from this preparation were fused into black lipid membranes (BLM), yielding single channel anion-selective activity with the properties of those found in the sperm membranes. The following anion selectivity sequence was found: NO3- > CNS- > Br- > Cl-. This anion channel has a high open probability at the holding potentials tested, it is partially blocked by 4,4'-diisothiocyano-2,2'-stilbendisulfonic acid (DIDS), and it often displays substates. The sperm AR was also inhibited by DIDS.

Pair Production of the Doubly Charged Leptons Associated with a Gauge Boson γ or Z in e+e- and γγ Collisions at Future Linear Colliders

NASA Astrophysics Data System (ADS)

Zeng, Qing-Guo; Ji, Li; Yang, Shuo

2015-03-01

In this paper, we investigate the production of a pair of doubly charged leptons associated with a gauge boson V(γ or Z) at future linear colliders via e+e- and γγ collisions. The numerical results show that the possible signals of the doubly charged leptons may be detected via the processes e+e- → VX++X-- and γγ → VX++X-- at future ILC or CLIC experiments. Supported in part by the National Natural Science Foundation of China under Grants Nos. 11275088, 11205023, 11375248 and the Program for Liaoning Excellent Talents in University under Grant No. LJQ2014135

Ion channels in plants.

PubMed

Hedrich, Rainer

2012-10-01

Since the first recordings of single potassium channel activities in the plasma membrane of guard cells more than 25 years ago, patch-clamp studies discovered a variety of ion channels in all cell types and plant species under inspection. Their properties differed in a cell type- and cell membrane-dependent manner. Guard cells, for which the existence of plant potassium channels was initially documented, advanced to a versatile model system for studying plant ion channel structure, function, and physiology. Interestingly, one of the first identified potassium-channel genes encoding the Shaker-type channel KAT1 was shown to be highly expressed in guard cells. KAT1-type channels from Arabidopsis thaliana and its homologs from other species were found to encode the K(+)-selective inward rectifiers that had already been recorded in early patch-clamp studies with guard cells. Within the genome era, additional Arabidopsis Shaker-type channels appeared. All nine members of the Arabidopsis Shaker family are localized at the plasma membrane, where they either operate as inward rectifiers, outward rectifiers, weak voltage-dependent channels, or electrically silent, but modulatory subunits. The vacuole membrane, in contrast, harbors a set of two-pore K(+) channels. Just very recently, two plant anion channel families of the SLAC/SLAH and ALMT/QUAC type were identified. SLAC1/SLAH3 and QUAC1 are expressed in guard cells and mediate Slow- and Rapid-type anion currents, respectively, that are involved in volume and turgor regulation. Anion channels in guard cells and other plant cells are key targets within often complex signaling networks. Here, the present knowledge is reviewed for the plant ion channel biology. Special emphasis is drawn to the molecular mechanisms of channel regulation, in the context of model systems and in the light of evolution.

Spectral representation of the three-body Coulomb problem. I. Nonautoionizing doubly excited states of high angular momentum in helium

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

Eiglsperger, Johannes; Piraux, Bernard; Madronero, Javier

2010-04-15

We investigate high-lying doubly excited nonautoionizing states of helium with total angular momentum L=1,2,...,9 with the help of a configuration interaction approach. We provide highly precise nonrelativistic energies of these states and discuss the properties of the wave functions with respect to the particle exchange operator.

Theoretical and experimental quantification of doubly and singly differential cross sections for electron-induced ionization of isolated tetrahydrofuran molecules

DOE PAGES

Champion, Christophe; Quinto, Michele A.; Bug, Marion U.; ...

2014-07-29

Electron-induced ionization of the commonly used surrogate of the DNA sugar-phosphate backbone, namely, the tetrahydrofuran molecule, is here theoretically described within the 1 st Born approximation by means of quantum-mechanical approach. Comparisons between theory and recent experiments are reported in terms of doubly and singly differential cross sections.

Molecular Dynamics Simulation Reveals Specific Interaction Sites between Scorpion Toxins and Kv1.2 Channel: Implications for Design of Highly Selective Drugs

PubMed Central

Yuan, Shouli; Gao, Bin

2017-01-01

The Kv1.2 channel plays an important role in the maintenance of resting membrane potential and the regulation of the cellular excitability of neurons, whose silencing or mutations can elicit neuropathic pain or neurological diseases (e.g., epilepsy and ataxia). Scorpion venom contains a variety of peptide toxins targeting the pore region of this channel. Despite a large amount of structural and functional data currently available, their detailed interaction modes are poorly understood. In this work, we choose four Kv1.2-targeted scorpion toxins (Margatoxin, Agitoxin-2, OsK-1, and Mesomartoxin) to construct their complexes with Kv1.2 based on the experimental structure of ChTx-Kv1.2. Molecular dynamics simulation of these complexes lead to the identification of hydrophobic patches, hydrogen-bonds, and salt bridges as three essential forces mediating the interactions between this channel and the toxins, in which four Kv1.2-specific interacting amino acids (D353, Q358, V381, and T383) are identified for the first time. This discovery might help design highly selective Kv1.2-channel inhibitors by altering amino acids of these toxins binding to the four channel residues. Finally, our results provide new evidence in favor of an induced fit model between scorpion toxins and K+ channel interactions. PMID:29104247

Natural abundance deuterium and 18-oxygen effects on the precision of the doubly labeled water method

NASA Technical Reports Server (NTRS)

Horvitz, M. A.; Schoeller, D. A.

2001-01-01

The doubly labeled water method for measuring total energy expenditure is subject to error from natural variations in the background 2H and 18O in body water. There is disagreement as to whether the variations in background abundances of the two stable isotopes covary and what relative doses of 2H and 18O minimize the impact of variation on the precision of the method. We have performed two studies to investigate the amount and covariance of the background variations. These were a study of urine collected weekly from eight subjects who remained in the Madison, WI locale for 6 wk and frequent urine samples from 14 subjects during round-trip travel to a locale > or = 500 miles from Madison, WI. Background variation in excess of analytical error was detected in six of the eight nontravelers, and covariance was demonstrated in four subjects. Background variation was detected in all 14 travelers, and covariance was demonstrated in 11 subjects. The median slopes of the regression lines of delta2H vs. delta18O were 6 and 7, respectively. Modeling indicated that 2H and 18O doses yielding a 6:1 ratio of final enrichments should minimize this error introduced to the doubly labeled water method.

Natural abundance deuterium and 18-oxygen effects on the precision of the doubly labeled water method.

PubMed

Horvitz, M A; Schoeller, D A

2001-06-01

The doubly labeled water method for measuring total energy expenditure is subject to error from natural variations in the background 2H and 18O in body water. There is disagreement as to whether the variations in background abundances of the two stable isotopes covary and what relative doses of 2H and 18O minimize the impact of variation on the precision of the method. We have performed two studies to investigate the amount and covariance of the background variations. These were a study of urine collected weekly from eight subjects who remained in the Madison, WI locale for 6 wk and frequent urine samples from 14 subjects during round-trip travel to a locale > or = 500 miles from Madison, WI. Background variation in excess of analytical error was detected in six of the eight nontravelers, and covariance was demonstrated in four subjects. Background variation was detected in all 14 travelers, and covariance was demonstrated in 11 subjects. The median slopes of the regression lines of delta2H vs. delta18O were 6 and 7, respectively. Modeling indicated that 2H and 18O doses yielding a 6:1 ratio of final enrichments should minimize this error introduced to the doubly labeled water method.

Search for doubly charged Higgs bosons with lepton-flavor-violating decays involving tau leptons.

PubMed

Aaltonen, T; Adelman, J; Akimoto, T; Albrow, M G; Alvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Apresyan, A; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Aurisano, A; Azfar, F; Azzi-Bacchetta, P; Azzurri, P; Bacchetta, N; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Bartsch, V; Bauer, G; Beauchemin, P-H; Bedeschi, F; Bednar, P; Behari, S; Bellettini, G; Bellinger, J; Belloni, A; Benjamin, D; Beretvas, A; Beringer, J; Berry, T; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bolshov, A; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Bridgeman, A; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Byrum, K L; Cabrera, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Compostella, G; Convery, M E; Conway, J; Cooper, B; Copic, K; Cordelli, M; Cortiana, G; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Dagenhart, D; Datta, M; Davies, T; de Barbaro, P; De Cecco, S; Deisher, A; De Lentdecker, G; De Lorenzo, G; Dell'Orso, M; Demortier, L; Deng, J; Deninno, M; De Pedis, D; Derwent, P F; Di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Donati, S; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Ferrazza, C; Field, R; Flanagan, G; Forrest, R; Forrester, S; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garberson, F; Garcia, J E; Garfinkel, A F; Genser, K; Gerberich, H; Gerdes, D; Giagu, S; Giakoumopolou, V; Giannetti, P; Gibson, K; Gimmell, J L; Ginsburg, C M; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Grinstein, S; Grosso-Pilcher, C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Hamilton, A; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, D; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Hays, C; Heck, M; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hewamanage, S; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ivanov, A; Iyutin, B; James, E; Jayatilaka, B; Jeans, D; Jeon, E J; Jindariani, S; Johnson, W; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Kar, D; Karchin, P E; Kato, Y; Kephart, R; Kerzel, U; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Klute, M; Knuteson, B; Ko, B R; Koay, S A; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kraus, J; Kreps, M; Kroll, J; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhlmann, S E; Kuhr, T; Kulkarni, N P; Kusakabe, Y; Kwang, S; Laasanen, A T; Lai, S; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; LeCompte, T; Lee, J; Lee, J; Lee, Y J; Lee, S W; Lefèvre, R; Leonardo, N; Leone, S; Levy, S; Lewis, J D; Lin, C; Lin, C S; Linacre, J; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Lovas, L; Lu, R-S; Lucchesi, D; Lueck, J; Luci, C; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; MacQueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Malik, S; Manca, G; Manousakis, A; Margaroli, F; Marino, C; Marino, C P; Martin, A; Martin, M; Martin, V; Martínez, M; Martínez-Ballarín, R; Maruyama, T; Mastrandrea, P; Masubuchi, T; Mattson, M E; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Miao, T; Miladinovic, N; Miles, J; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyake, H; Moed, S; Moggi, N; Moon, C S; Moore, R; Morello, M; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Nagano, A; Naganoma, J; Nakamura, K; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nodulman, L; Norman, M; Norniella, O; Nurse, E; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Oldeman, R; Orava, R; Osterberg, K; Pagan Griso, S; Pagliarone, C; Palencia, E; Papadimitriou, V; Papaikonomou, A; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Piedra, J; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Portell, X; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Roy, P; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Safonov, A; Sakumoto, W K; Salamanna, G; Saltó, O; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, E E; Schmidt, M A; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyrla, A; Shalhout, S Z; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soderberg, M; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spinella, F; Spreitzer, T; Squillacioti, P; Stanitzki, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Sun, H; Suslov, I; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thompson, G A; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Tourneur, S; Trischuk, W; Tu, Y; Turini, N; Ukegawa, F; Uozumi, S; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Vellidis, C; Veszpremi, V; Vidal, M; Vidal, R; Vila, I; Vilar, R; Vine, T; Vogel, M; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner-Kuhr, J; Wagner, W; Wakisaka, T; Wallny, R; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Yagil, A; Yamamoto, K; Yamaoka, J; Yamashita, T; Yang, C; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zheng, Y; Zucchelli, S

2008-09-19

We search for pair production of doubly charged Higgs particles (H+/- +/-) followed by decays into electron-tau (etau) and muon-tau (mutau) pairs using data (350 pb(-1) collected from [over]pp collisions at sqrt[s]=1.96 TeV by the CDF II experiment. We search separately for cases where three or four final-state leptons are detected, and combine results for exclusive decays to left-handed etau (mutau) pairs. We set an H+/- +/- lower mass limit of 114(112) GeV/c(2) at the 95% confidence level.

Philosophy of voltage-gated proton channels

PubMed Central

DeCoursey, Thomas E.; Hosler, Jonathan

2014-01-01

In this review, voltage-gated proton channels are considered from a mainly teleological perspective. Why do proton channels exist? What good are they? Why did they go to such lengths to develop several unique hallmark properties such as extreme selectivity and ΔpH-dependent gating? Why is their current so minuscule? How do they manage to be so selective? What is the basis for our belief that they conduct H+ and not OH–? Why do they exist in many species as dimers when the monomeric form seems to work quite well? It is hoped that pondering these questions will provide an introduction to these channels and a way to logically organize their peculiar properties as well as to understand how they are able to carry out some of their better-established biological functions. PMID:24352668

Structural implications of weak Ca2+ block in Drosophila cyclic nucleotide–gated channels

PubMed Central

Lam, Yee Ling; Zeng, Weizhong; Derebe, Mehabaw Getahun

2015-01-01

Calcium permeability and the concomitant calcium block of monovalent ion current (“Ca2+ block”) are properties of cyclic nucleotide–gated (CNG) channel fundamental to visual and olfactory signal transduction. Although most CNG channels bear a conserved glutamate residue crucial for Ca2+ block, the degree of block displayed by different CNG channels varies greatly. For instance, the Drosophila melanogaster CNG channel shows only weak Ca2+ block despite the presence of this glutamate. We previously constructed a series of chimeric channels in which we replaced the selectivity filter of the bacterial nonselective cation channel NaK with a set of CNG channel filter sequences and determined that the resulting NaK2CNG chimeras displayed the ion selectivity and Ca2+ block properties of the parent CNG channels. Here, we used the same strategy to determine the structural basis of the weak Ca2+ block observed in the Drosophila CNG channel. The selectivity filter of the Drosophila CNG channel is similar to that of most other CNG channels except that it has a threonine at residue 318 instead of a proline. We constructed a NaK chimera, which we called NaK2CNG-Dm, which contained the Drosophila selectivity filter sequence. The high resolution structure of NaK2CNG-Dm revealed a filter structure different from those of NaK and all other previously investigated NaK2CNG chimeric channels. Consistent with this structural difference, functional studies of the NaK2CNG-Dm chimeric channel demonstrated a loss of Ca2+ block compared with other NaK2CNG chimeras. Moreover, mutating the corresponding threonine (T318) to proline in Drosophila CNG channels increased Ca2+ block by 16 times. These results imply that a simple replacement of a threonine for a proline in Drosophila CNG channels has likely given rise to a distinct selectivity filter conformation that results in weak Ca2+ block. PMID:26283200

Structural implications of weak Ca2+ block in Drosophila cyclic nucleotide-gated channels.

PubMed

Lam, Yee Ling; Zeng, Weizhong; Derebe, Mehabaw Getahun; Jiang, Youxing

2015-09-01

Calcium permeability and the concomitant calcium block of monovalent ion current ("Ca(2+) block") are properties of cyclic nucleotide-gated (CNG) channel fundamental to visual and olfactory signal transduction. Although most CNG channels bear a conserved glutamate residue crucial for Ca(2+) block, the degree of block displayed by different CNG channels varies greatly. For instance, the Drosophila melanogaster CNG channel shows only weak Ca(2+) block despite the presence of this glutamate. We previously constructed a series of chimeric channels in which we replaced the selectivity filter of the bacterial nonselective cation channel NaK with a set of CNG channel filter sequences and determined that the resulting NaK2CNG chimeras displayed the ion selectivity and Ca(2+) block properties of the parent CNG channels. Here, we used the same strategy to determine the structural basis of the weak Ca(2+) block observed in the Drosophila CNG channel. The selectivity filter of the Drosophila CNG channel is similar to that of most other CNG channels except that it has a threonine at residue 318 instead of a proline. We constructed a NaK chimera, which we called NaK2CNG-Dm, which contained the Drosophila selectivity filter sequence. The high resolution structure of NaK2CNG-Dm revealed a filter structure different from those of NaK and all other previously investigated NaK2CNG chimeric channels. Consistent with this structural difference, functional studies of the NaK2CNG-Dm chimeric channel demonstrated a loss of Ca(2+) block compared with other NaK2CNG chimeras. Moreover, mutating the corresponding threonine (T318) to proline in Drosophila CNG channels increased Ca(2+) block by 16 times. These results imply that a simple replacement of a threonine for a proline in Drosophila CNG channels has likely given rise to a distinct selectivity filter conformation that results in weak Ca(2+) block. © 2015 Lam et al.

Metal-insulator transition in a doubly orbitally degenerate model with correlated hopping

NASA Astrophysics Data System (ADS)

Didukh, L.; Skorenkyy, Yu.; Dovhopyaty, Yu.; Hankevych, V.

2000-03-01

In the present paper, we propose a doubly orbitally degenerate narrow-band model with correlated hopping. The peculiarity of the model is taking into account the matrix element of electron-electron interaction, which describes intersite hoppings of electrons. In particular, this leads to the concentration dependence of the effective hopping integral. The cases of the strong and weak Hund's coupling are considered. By means of a generalized mean-field approximation the single-particle Green function and quasiparticle energy spectrum are calculated. Metal-insulator transition is studied in the model at different integer values of the electron concentration. With the help of the obtained energy spectrum, we find energy gap width and criteria of metal-insulator transition.

TMEM16A Channels Contribute to the Myogenic Response in Cerebral Arteries

PubMed Central

Bulley, Simon; Neeb, Zachary P.; Burris, Sarah K.; Bannister, John P.; Thomas-Gatewood, Candice M.; Jangsangthong, Wanchana; Jaggar, Jonathan H.

2013-01-01

Rationale Pressure-induced arterial depolarization and constriction (the myogenic response), is a smooth muscle cell (myocyte)-specific mechanism that controls regional organ blood flow and systemic blood pressure. Several different non-selective cation channels contribute to pressure-induced depolarization, but signaling mechanisms involved are unclear. Similarly uncertain is the contribution of anion channels to the myogenic response and physiological functions and mechanisms of regulation of recently discovered transmembrane 16A (TMEM16A) chloride (Cl−) channels in arterial myocytes. Objective Investigate the hypothesis that myocyte TMEM16A channels control membrane potential and contractility and contribute to the myogenic response in cerebral arteries. Methods and Results Cell swelling induced by hyposmotic bath solution stimulated Cl− currents in arterial myocytes that were blocked by TMEM16A channel inhibitory antibodies, RNAi-mediated selective TMEM16A channel knockdown, removal of extracellular calcium (Ca2+), replacement of intracellular EGTA with BAPTA, a fast Ca2+ chelator, and Gd3+ and SKF-96365, non-selective cation channel blockers. In contrast, nimodipine, a voltage-dependent Ca2+ channel inhibitor, or thapsigargin, which depletes intracellular Ca2+ stores, did not alter swelling-activated TMEM16A currents. Pressure (−40 mmHg)-induced membrane stretch activated ion channels in arterial myocyte cell-attached patches that were inhibited by TMEM16A antibodies and were of similar amplitude to recombinant TMEM16A channels. TMEM16A knockdown reduced intravascular pressure-induced depolarization and vasoconstriction, but did not alter depolarization (60 mmol/L K+)-induced vasoconstriction. Conclusions Membrane stretch activates arterial myocyte TMEM16A channels, leading to membrane depolarization and vasoconstriction. Data also provide a mechanism by which a local Ca2+ signal generated by non-selective cation channels stimulates TMEM16A channels to

Evaluation of habitat quality for selected wildlife species associated with back channels.

USGS Publications Warehouse

Anderson, James T.; Zadnik, Andrew K.; Wood, Petra Bohall; Bledsoe, Kerry

2013-01-01

The islands and associated back channels on the Ohio River, USA, are believed to provide critical habitat features for several wildlife species. However, few studies have quantitatively evaluated habitat quality in these areas. Our main objective was to evaluate the habitat quality of back and main channel areas for several species using habitat suitability index (HSI) models. To test the effectiveness of these models, we attempted to relate HSI scores and the variables measured for each model with measures of relative abundance for the model species. The mean belted kingfisher (Ceryle alcyon) HSI was greater on the main than back channel. However, the model failed to predict kingfisher abundance. The mean reproduction component of the great blue heron (Ardea herodias) HSI, total common muskrat (Ondatra zibethicus) HSI, winter cover component of the snapping turtle (Chelydra serpentina) HSI, and brood-rearing component of the wood duck (Aix sponsa) HSI were all greater on the back than main channel, and were positively related with the relative abundance of each species. We found that island back channels provide characteristics not found elsewhere on the Ohio River and warrant conservation as important riparian wildlife habitat. The effectiveness of using HSI models to predict species abundance on the river was mixed. Modifications to several of the models are needed to improve their use on the Ohio River and, likely, other large rivers.

Identification and characterization of a selective allosteric antagonist of human P2X4 receptor channels.

PubMed

Ase, Ariel R; Honson, Nicolette S; Zaghdane, Helmi; Pfeifer, Tom A; Séguéla, Philippe

2015-04-01

P2X4 is an ATP-gated nonselective cation channel highly permeable to calcium. There is increasing evidence that this homomeric purinoceptor, which is expressed in several neuronal and immune cell types, is involved in chronic pain and inflammation. The current paucity of unambiguous pharmacological tools available to interrogate or modulate P2X4 function led us to pursue the search for selective antagonists. In the high-throughput screen of a compound library, we identified the phenylurea BX430 (1-(2,6-dibromo-4-isopropyl-phenyl)-3-(3-pyridyl)urea, molecular weight = 413), with antagonist properties on human P2X4-mediated calcium uptake. Patch-clamp electrophysiology confirmed direct inhibition of P2X4 currents by extracellular BX430, with submicromolar potency (IC50 = 0.54 µM). BX430 is highly selective, having virtually no functional impact on all other P2X subtypes, namely, P2X1-P2X3, P2X5, and P2X7, at 10-100 times its IC50. Unexpected species differences were noticed, as BX430 is a potent antagonist of zebrafish P2X4 but has no effect on rat and mouse P2X4 orthologs. The concentration-response curve for ATP on human P2X4 in the presence of BX430 shows an insurmountable blockade, indicating a noncompetitive allosteric mechanism of action. Using a fluorescent dye uptake assay, we observed that BX430 also effectively suppresses ATP-evoked and ivermectin-potentiated membrane permeabilization induced by P2X4 pore dilation. Finally, in single-cell calcium imaging, we validated its selective inhibitory effects on native P2X4 channels at the surface of human THP-1 cells that were differentiated into macrophages. In summary, this ligand provides a novel molecular probe to assess the specific role of P2X4 in inflammatory and neuropathic conditions, where ATP signaling has been shown to be dysfunctional. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Chemical Selectivity and Sensitivity of a 16-Channel Electronic Nose for Trace Vapour Detection

PubMed Central

Strle, Drago; Trifkovič, Mario; Van Miden, Marion; Kvasić, Ivan; Zupanič, Erik; Muševič, Igor

2017-01-01

Good chemical selectivity of sensors for detecting vapour traces of targeted molecules is vital to reliable detection systems for explosives and other harmful materials. We present the design, construction and measurements of the electronic response of a 16 channel electronic nose based on 16 differential microcapacitors, which were surface-functionalized by different silanes. The e-nose detects less than 1 molecule of TNT out of 10+12 N2 molecules in a carrier gas in 1 s. Differently silanized sensors give different responses to different molecules. Electronic responses are presented for TNT, RDX, DNT, H2S, HCN, FeS, NH3, propane, methanol, acetone, ethanol, methane, toluene and water. We consider the number density of these molecules and find that silane surfaces show extreme affinity for attracting molecules of TNT, DNT and RDX. The probability to bind these molecules and form a surface-adsorbate is typically 10+7 times larger than the probability to bind water molecules, for example. We present a matrix of responses of differently functionalized microcapacitors and we propose that chemical selectivity of multichannel e-nose could be enhanced by using artificial intelligence deep learning methods. PMID:29292764

Selective activation of heteromeric SK channels contributes to action potential repolarization in mouse atrial myocytes.

PubMed

Hancock, Jane M; Weatherall, Kate L; Choisy, Stéphanie C; James, Andrew F; Hancox, Jules C; Marrion, Neil V

2015-05-01

Activation of small conductance calcium-activated potassium (SK) channels is proposed to contribute to repolarization of the action potential in atrial myocytes. This role is controversial, as these cardiac SK channels appear to exhibit an uncharacteristic pharmacology. The objectives of this study were to resolve whether activation of SK channels contributes to atrial action potential repolarization and to determine the likely subunit composition of the channel. The effect of 2 SK channel inhibitors was assessed on outward current evoked in voltage clamp and on action potential duration in perforated patch and whole-cell current clamp recording from acutely isolated mouse atrial myocytes. The presence of SK channel subunits was assessed using immunocytochemistry. A significant component of outward current was reduced by the SK channel blockers apamin and UCL1684. Block by apamin displayed a sensitivity indicating that this current was carried by homomeric SK2 channels. Action potential duration was significantly prolonged by UCL1684, but not by apamin. This effect was accompanied by an increase in beat-to-beat variability and action potential triangulation. This pharmacology was matched by that of expressed heteromeric SK2-SK3 channels in HEK293 cells. Immunocytochemistry showed that atrial myocytes express both SK2 and SK3 channels with an overlapping expression pattern. Only proposed heteromeric SK2-SK3 channels are physiologically activated to contribute to action potential repolarization, which is indicated by the difference in pharmacology of evoked outward current and prolongation of atrial action potential duration. The effect of blocking this channel on the action potential suggests that SK channel inhibition during cardiac function has the potential to be proarrhythmic. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

The pore properties of human nociceptor channel TRPA1 evaluated in single channel recordings

PubMed Central

Bobkov, Y.V.; Corey, E.A.; Ache, B.W.

2011-01-01

TRPA channels detect stimuli of different sensory modalities, including a broad spectrum of chemosensory stimuli, noxious stimuli associated with tissue damage and inflammation, mechanical stimuli, and thermal stimuli. Despite a growing understanding of potential modulators, agonists, and antagonists for these channels, the exact mechanisms of channel regulation and activation remain mostly unknown or controversial and widely debated. Relatively little is also known about the basic biophysical parameters of both native and heterologously expressed TRPA channels. Here we use conventional single channel inside-out and outside-out patch recording from the human TRPA1 channel transiently expressed in human embryonic kidney 293T cells to characterize the selectivity of the channel for inorganic mono-/divalent and organic monovalent cations in the presence of Allylisothiocyanate (AITC). We show the relative permeability of the hTRPA1 channel to inorganic cations to be: Ca2+(5.1)>Ba2+(3.5)>Mg2+(2.8)>NH4+(1.5)>Li+(1.2)>Na+(1.0)≥K+(0.98)≥Rb+(0.98)>Cs+(0.95); and to organic cations: Na+(1.0)≥Dimethylamine(0.99)>Trimethylamine(0.7)>Tetramethylammonium(0.4)>N-methyl-d-glucamine(0.1). Activation of the hTRPA1 channels by AITC appears to recruit the channels to a conformational state with an increased permeability to large organic cations. The pore of the channels in this state can be characterized as dilated by approximately 1–2.5A. These findings provide important insight into the basic fundamental properties and function of TRPA1 channels in general and human TRPA1 channel in particular. PMID:21195050

NASTRAN implementation of an isoparametric doubly-curved quadrilateral shell element

NASA Technical Reports Server (NTRS)

Potvin, A. B.; Leick, R. D.

1978-01-01

A quadrilateral shell element, CQUAD4, was added to level 15.5 and subsequently to level 16.0 of NASTRAN. The element exhibited doubly curved surfaces and used biquadratic interpolation functions. Reduced integration techniques were used to improve the performance of the element in thin shell problems. The creation of several new bulk data items is discussed, along with a special module, GPNORM, to process SHLNORM bulk data cards. In addition to the theoretical basis for the element stiffness matrix, consistent mass and load matrices are presented. Several potential sources of degenerate behavior of the element were investigated. Guidelines for proper use of the element were suggested. Performance of the element on several widely published classical examples was demonstrated. The results showed a significant improvement over presently available NASTRAN shell elements for even the coarsest meshes. Potential applications to two classes of practical problems are discussed.

Generation of doubly charged vortex beam by concentrated loading of glass disks along their diameter.

PubMed

Skab, Ihor; Vasylkiv, Yuriy; Krupych, Oleh; Savaryn, Viktoriya; Vlokh, Rostyslav

2012-04-10

We show that a system of glass disks compressed along their diameters enables one to induce a doubly charged vortex beam in the emergent light when the incident light is circularly polarized. Using such a disk system, one can control the efficiency of conversion of the spin angular momentum to the orbital angular momentum by a loading force. The consideration presented here can be extended for the case of crystalline materials with high optical damage thresholds in order to induce high-power vortex beams.

N-Protonated Isomers and Coulombic Barriers to Dissociation of Doubly Protonated Ala8Arg

NASA Astrophysics Data System (ADS)

Haeffner, Fredrik; Irikura, Karl K.

2017-10-01

Collision-induced dissociation (or tandem mass spectrometry, MS/MS) of a protonated peptide results in a spectrum of fragment ions that is useful for inferring amino acid sequence. This is now commonplace and a foundation of proteomics. The underlying chemical and physical processes are believed to be those familiar from physical organic chemistry and chemical kinetics. However, first-principles predictions remain intractable because of the conflicting necessities for high accuracy (to achieve qualitatively correct kinetics) and computational speed (to compensate for the high cost of reliable calculations on such large molecules). To make progress, shortcuts are needed. Inspired by the popular mobile proton model, we have previously proposed a simplified theoretical model in which the gas-phase fragmentation pattern of protonated peptides reflects the relative stabilities of N-protonated isomers, thus avoiding the need for transition-state information. For singly protonated Ala n ( n = 3-11), the resulting predictions were in qualitative agreement with the results from low-energy MS/MS experiments. Here, the comparison is extended to a model tryptic peptide, doubly protonated Ala8Arg. This is of interest because doubly protonated tryptic peptides are the most important in proteomics. In comparison with experimental results, our model seriously overpredicts the degree of backbone fragmentation at N9. We offer an improved model that corrects this deficiency. The principal change is to include Coulombic barriers, which hinder the separation of the product cations from each other. Coulombic barriers may be equally important in MS/MS of all multiply charged peptide ions. [Figure not available: see fulltext.

Voltage-gated sodium channels as targets for pyrethroid insecticides.

PubMed

Field, Linda M; Emyr Davies, T G; O'Reilly, Andrias O; Williamson, Martin S; Wallace, B A

2017-10-01

The pyrethroid insecticides are a very successful group of compounds that have been used extensively for the control of arthropod pests of agricultural crops and vectors of animal and human disease. Unfortunately, this has led to the development of resistance to the compounds in many species. The mode of action of pyrethroids is known to be via interactions with the voltage-gated sodium channel. Understanding how binding to the channel is affected by amino acid substitutions that give rise to resistance has helped to elucidate the mode of action of the compounds and the molecular basis of their selectivity for insects vs mammals and between insects and other arthropods. Modelling of the channel/pyrethroid interactions, coupled with the ability to express mutant channels in oocytes and study function, has led to knowledge of both how the channels function and potentially how to design novel insecticides with greater species selectivity.

Routing channels in VLSI layout

NASA Astrophysics Data System (ADS)

Cai, Hong

A number of algorithms for the automatic routing of interconnections in Very Large Scale Integration (VLSI) building-block layouts are presented. Algorithms for the topological definition of channels, the global routing and the geometrical definition of channels are presented. In contrast to traditional approaches the definition and ordering of the channels is done after the global routing. This approach has the advantage that global routing information can be taken into account to select the optimal channel structure. A polynomial algorithm for the channel definition and ordering problem is presented. The existence of a conflict-free channel structure is guaranteed by enforcing a sliceable placement. Algorithms for finding the shortest connection path are described. A separate algorithm is developed for the power net routing, because the two power nets must be planarly routed with variable wire width. An integrated placement and routing system for generating building-block layout is briefly described. Some experimental results and design experiences in using the system are also presented. Very good results are obtained.

Human trypanolytic factor APOL1 forms pH-gated cation-selective channels in planar lipid bilayers: Relevance to trypanosome lysis

PubMed Central

Thomson, Russell; Finkelstein, Alan

2015-01-01

Apolipoprotein L-1 (APOL1), the trypanolytic factor of human serum, can lyse several African trypanosome species including Trypanosoma brucei brucei, but not the human-infective pathogens T. brucei rhodesiense and T. brucei gambiense, which are resistant to lysis by human serum. Lysis follows the uptake of APOL1 into acidic endosomes and is apparently caused by colloid-osmotic swelling due to an increased ion permeability of the plasma membrane. Here we demonstrate that nanogram quantities of full-length recombinant APOL1 induce ideally cation-selective macroscopic conductances in planar lipid bilayers. The conductances were highly sensitive to pH: their induction required acidic pH (pH 5.3), but their magnitude could be increased 3,000-fold upon alkalinization of the milieu (pKa = 7.1). We show that this phenomenon can be attributed to the association of APOL1 with the bilayer at acidic pH, followed by the opening of APOL1-induced cation-selective channels upon pH neutralization. Furthermore, the conductance increase at neutral pH (but not membrane association at acidic pH) was prevented by the interaction of APOL1 with the serum resistance-associated protein, which is produced by T. brucei rhodesiense and prevents trypanosome lysis by APOL1. These data are consistent with a model of lysis that involves endocytic recycling of APOL1 and the formation of cation-selective channels, at neutral pH, in the parasite plasma membrane. PMID:25730870

Mechanism of allosteric activation of TMEM16A/ANO1 channels by a commonly used chloride channel blocker

PubMed Central

Ta, Chau M; Adomaviciene, Aiste; Rorsman, Nils J G; Garnett, Hannah

2016-01-01

Background and Purpose Calcium‐activated chloride channels (CaCCs) play varied physiological roles and constitute potential therapeutic targets for conditions such as asthma and hypertension. TMEM16A encodes a CaCC. CaCC pharmacology is restricted to compounds with relatively low potency and poorly defined selectivity. Anthracene‐9‐carboxylic acid (A9C), an inhibitor of various chloride channel types, exhibits complex effects on native CaCCs and cloned TMEM16A channels providing both activation and inhibition. The mechanisms underlying these effects are not fully defined. Experimental Approach Patch‐clamp electrophysiology in conjunction with concentration jump experiments was employed to define the mode of interaction of A9C with TMEM16A channels. Key Results In the presence of high intracellular Ca2+, A9C inhibited TMEM16A currents in a voltage‐dependent manner by entering the channel from the outside. A9C activation, revealed in the presence of submaximal intracellular Ca2+ concentrations, was also voltage‐dependent. The electric distance of A9C inhibiting and activating binding site was ~0.6 in each case. Inhibition occurred according to an open‐channel block mechanism. Activation was due to a dramatic leftward shift in the steady‐state activation curve and slowed deactivation kinetics. Extracellular A9C competed with extracellular Cl−, suggesting that A9C binds deep in the channel's pore to exert both inhibiting and activating effects. Conclusions and Implications A9C is an open TMEM16A channel blocker and gating modifier. These effects require A9C to bind to a region within the pore that is accessible from the extracellular side of the membrane. These data will aid the future drug design of compounds that selectively activate or inhibit TMEM16A channels. PMID:26562072

Fault-tolerant communication channel structures

NASA Technical Reports Server (NTRS)

Tai, Ann T. (Inventor); Alkalai, Leon (Inventor); Chau, Savio N. (Inventor)

2006-01-01

Systems and techniques for implementing fault-tolerant communication channels and features in communication systems. Selected commercial-off-the-shelf devices can be integrated in such systems to reduce the cost.

An easy-to-use semiquantitative food record validated for energy intake by using doubly labelled water technique.

PubMed

Koebnick, C; Wagner, K; Thielecke, F; Dieter, G; Höhne, A; Franke, A; Garcia, A L; Meyer, H; Hoffmann, I; Leitzmann, P; Trippo, U; Zunft, H J F

2005-09-01

Estimating dietary intake is important for both epidemiological and clinical studies, but often lacks accuracy. To investigate the accuracy and validity of energy intake estimated by an easy-to-use semiquantitative food record (EI(SQFR)) compared to total energy expenditure (TEE) estimated by doubly labelled water technique (EE(DLW)). TEE was measured in 29 nonobese subjects using the doubly labelled water method over a period of 14 days. Within this period, subjects reported their food consumption by a newly developed semiquantitative food record for 4 consecutive days. Energy intake was calculated using the German Food Code and Nutrition Data Base BLS II.3. A good correlation was observed between EI(SQFR) and EE(DLW) (r = 0.685, P < 0.001). The mean difference between EI(SQFR) and EE(DLW) was -1.7+/-2.6 MJ/day (-14+/-21%, P = 0.002). An underestimation of EI(SQFR) <10% was observed in nine subjects (31%), of 10-20% in six subjects (21%), and of >20% in nine subjects (31%). In five subjects (17%), an overestimation of EI(SQFR) was observed. The easy-to-use semiquantitative food record provided good estimates of EI in free-living and nonobese adults without prior detailed verbal instructions. The presented food record has limitations regarding accuracy at the individual level.

Ion channel gene expression predicts survival in glioma patients

PubMed Central

Wang, Rong; Gurguis, Christopher I.; Gu, Wanjun; Ko, Eun A; Lim, Inja; Bang, Hyoweon; Zhou, Tong; Ko, Jae-Hong

2015-01-01

Ion channels are important regulators in cell proliferation, migration, and apoptosis. The malfunction and/or aberrant expression of ion channels may disrupt these important biological processes and influence cancer progression. In this study, we investigate the expression pattern of ion channel genes in glioma. We designate 18 ion channel genes that are differentially expressed in high-grade glioma as a prognostic molecular signature. This ion channel gene expression based signature predicts glioma outcome in three independent validation cohorts. Interestingly, 16 of these 18 genes were down-regulated in high-grade glioma. This signature is independent of traditional clinical, molecular, and histological factors. Resampling tests indicate that the prognostic power of the signature outperforms random gene sets selected from human genome in all the validation cohorts. More importantly, this signature performs better than the random gene signatures selected from glioma-associated genes in two out of three validation datasets. This study implicates ion channels in brain cancer, thus expanding on knowledge of their roles in other cancers. Individualized profiling of ion channel gene expression serves as a superior and independent prognostic tool for glioma patients. PMID:26235283

Inhibition of collagen synthesis by select calcium and sodium channel blockers can be mitigated by ascorbic acid and ascorbyl palmitate

PubMed Central

Ivanov, Vadim; Ivanova, Svetlana; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra; Rath, Matthias

2016-01-01

Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition to the side effects mentioned above by different channel blockers, these drugs can cause arterial wall damage, thereby contributing to vascular wall structure destabilization and promoting events facilitating rupture of plaques. Collagen synthesis is regulated by ascorbic acid, which is also essential for its optimum structure as a cofactor in lysine and proline hydroxylation, a precondition for optimum crosslinking of collagen and elastin. Therefore, the main objective in this study was to evaluate effects of various types of channel blockers on intracellular accumulation and cellular functions of ascorbate, specifically in relation to formation and extracellular deposition of major collagen types relevant for vascular function. Effects of select Na- and Ca- channel blockers on collagen synthesis and deposition were evaluated in cultured human dermal fibroblasts and aortic smooth muscle cells by immunoassay. All channel blockers tested demonstrated inhibitory effects on collagen type I deposition to the ECM by fibroblasts, each to a different degree. Ascorbic acid significantly increased collagen I ECM deposition. Nifedipine (50 µM), a representative of channel blockers tested, significantly reduced ascorbic acid and ascorbyl palmitate-dependent ECM deposition of collagen type l and collagen type lV by cultured aortic smooth muscle cells. In addition, nifedipine (50 µM) significantly reduced ascorbate-dependent collagen type l and type lV synthesis by cultured aortic smooth

Inhibition of collagen synthesis by select calcium and sodium channel blockers can be mitigated by ascorbic acid and ascorbyl palmitate.

PubMed

Ivanov, Vadim; Ivanova, Svetlana; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra; Rath, Matthias

2016-01-01

Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition to the side effects mentioned above by different channel blockers, these drugs can cause arterial wall damage, thereby contributing to vascular wall structure destabilization and promoting events facilitating rupture of plaques. Collagen synthesis is regulated by ascorbic acid, which is also essential for its optimum structure as a cofactor in lysine and proline hydroxylation, a precondition for optimum crosslinking of collagen and elastin. Therefore, the main objective in this study was to evaluate effects of various types of channel blockers on intracellular accumulation and cellular functions of ascorbate, specifically in relation to formation and extracellular deposition of major collagen types relevant for vascular function. Effects of select Na- and Ca- channel blockers on collagen synthesis and deposition were evaluated in cultured human dermal fibroblasts and aortic smooth muscle cells by immunoassay. All channel blockers tested demonstrated inhibitory effects on collagen type I deposition to the ECM by fibroblasts, each to a different degree. Ascorbic acid significantly increased collagen I ECM deposition. Nifedipine (50 µM), a representative of channel blockers tested, significantly reduced ascorbic acid and ascorbyl palmitate-dependent ECM deposition of collagen type l and collagen type lV by cultured aortic smooth muscle cells. In addition, nifedipine (50 µM) significantly reduced ascorbate-dependent collagen type l and type lV synthesis by cultured aortic smooth

Identifying cochlear implant channels with poor electrode-neuron interface: partial tripolar, single-channel thresholds and psychophysical tuning curves

PubMed Central

Bierer, Julie Arenberg; Faulkner, Kathleen F.

2010-01-01

Objectives The goal of this study was to evaluate the ability of a threshold measure, made with a restricted electrode configuration, to identify channels exhibiting relatively poor spatial selectivity. With a restricted electrode configuration, channel-to-channel variability in threshold may reflect variations in the interface between the electrodes and auditory neurons (i.e., nerve survival, electrode placement, tissue impedance). These variations in the electrode-neuron interface should also be reflected in psychophysical tuning curve measurements. Specifically, it is hypothesized that high single-channel thresholds obtained with the spatially focused partial tripolar electrode configuration are predictive of wide or tip-shifted psychophysical tuning curves. Design Data were collected from five cochlear implant listeners implanted with the HiRes 90k cochlear implant (Advanced Bionics). Single-channel thresholds and most comfortable listening levels were obtained for stimuli that varied in presumed electrical field size by using the partial tripolar configuration, for which a fraction of current (σ) from a center active electrode returns through two neighboring electrodes and the remainder through a distant indifferent electrode. Forward-masked psychophysical tuning curves were obtained for channels with the highest, lowest, and median tripolar (σ=1 or 0.9) thresholds. The probe channel and level were fixed and presented with either the monopolar (σ=0) or a more focused partial tripolar (σ ≥ 0.55) configuration. The masker channel and level were varied while the configuration was fixed to σ = 0.5. A standard, three-interval, two-alternative forced choice procedure was used for thresholds and masked levels. Results Single-channel threshold and variability in threshold across channels systematically increased as the compensating current, σ, increased and the presumed electrical field became more focused. Across subjects, channels with the highest single-channel

Identifying cochlear implant channels with poor electrode-neuron interface: partial tripolar, single-channel thresholds and psychophysical tuning curves.

PubMed

Bierer, Julie Arenberg; Faulkner, Kathleen F

2010-04-01

The goal of this study was to evaluate the ability of a threshold measure, made with a restricted electrode configuration, to identify channels exhibiting relatively poor spatial selectivity. With a restricted electrode configuration, channel-to-channel variability in threshold may reflect variations in the interface between the electrodes and auditory neurons (i.e., nerve survival, electrode placement, and tissue impedance). These variations in the electrode-neuron interface should also be reflected in psychophysical tuning curve (PTC) measurements. Specifically, it is hypothesized that high single-channel thresholds obtained with the spatially focused partial tripolar (pTP) electrode configuration are predictive of wide or tip-shifted PTCs. Data were collected from five cochlear implant listeners implanted with the HiRes90k cochlear implant (Advanced Bionics Corp., Sylmar, CA). Single-channel thresholds and most comfortable listening levels were obtained for stimuli that varied in presumed electrical field size by using the pTP configuration for which a fraction of current (sigma) from a center-active electrode returns through two neighboring electrodes and the remainder through a distant indifferent electrode. Forward-masked PTCs were obtained for channels with the highest, lowest, and median tripolar (sigma = 1 or 0.9) thresholds. The probe channel and level were fixed and presented with either the monopolar (sigma = 0) or a more focused pTP (sigma > or = 0.55) configuration. The masker channel and level were varied, whereas the configuration was fixed to sigma = 0.5. A standard, three-interval, two-alternative forced choice procedure was used for thresholds and masked levels. Single-channel threshold and variability in threshold across channels systematically increased as the compensating current, sigma, increased and the presumed electrical field became more focused. Across subjects, channels with the highest single-channel thresholds, when measured with a

Atrial fibrillation: Therapeutic potential of atrial K+ channel blockers.

PubMed

Ravens, Ursula; Odening, Katja E

2017-08-01

Despite the epidemiological scale of atrial fibrillation, current treatment strategies are of limited efficacy and safety. Ideally, novel drugs should specifically correct the pathophysiological mechanisms responsible for atrial fibrillation with no other cardiac or extracardiac actions. Atrial-selective drugs are directed toward cellular targets with sufficiently different characteristics in atria and ventricles to modify only atrial function. Several potassium (K + ) channels with either predominant expression in atria or distinct electrophysiological properties in atria and ventricles can serve as atrial-selective drug targets. These channels include the ultra-rapidly activating, delayed outward-rectifying Kv1.5 channel conducting I Kur , the acetylcholine-activated inward-rectifying Kir3.1/Kir3.4 channel conducting I K,ACh , the Ca 2+ -activated K + channels of small conductance (SK) conducting I SK , and the two pore domain K + (K2P) channels TWIK-1, TASK-1 and TASK-3 that are responsible for voltage-independent background currents I TWIK-1 , I TASK-1 , and I TASK-3 . Here, we briefly review the characteristics of these K + channels and their roles in atrial fibrillation. The antiarrhythmic potential of drugs targeting the described channels is discussed as well as their putative value in treatment of atrial fibrillation. Copyright © 2016 Elsevier Inc. All rights reserved.

Grafting voltage and pharmacological sensitivity in potassium channels.

PubMed

Lan, Xi; Fan, Chunyan; Ji, Wei; Tian, Fuyun; Xu, Tao; Gao, Zhaobing

2016-08-01

A classical voltage-gated ion channel consists of four voltage-sensing domains (VSDs). However, the roles of each VSD in the channels remain elusive. We developed a GVTDT (Graft VSD To Dimeric TASK3 channels that lack endogenous VSDs) strategy to produce voltage-gated channels with a reduced number of VSDs. TASK3 channels exhibit a high host tolerance to VSDs of various voltage-gated ion channels without interfering with the intrinsic properties of the TASK3 selectivity filter. The constructed channels, exemplified by the channels grafted with one or two VSDs from Kv7.1 channels, exhibit classical voltage sensitivity, including voltage-dependent opening and closing. Furthermore, the grafted Kv7.1 VSD transfers the potentiation activity of benzbromarone, an activator that acts on the VSDs of the donor channels, to the constructed channels. Our study indicates that one VSD is sufficient to voltage-dependently gate the pore and provides new insight into the roles of VSDs.

Plasma polar lipid profiles of channel catfish with different growth rates

USDA-ARS?s Scientific Manuscript database

Increased growth in channel catfish is an economically important trait and has been used as a criterion for the selection and development of brood fish. Selection of channel catfish toward increased growth usually results in the accumulation of large amounts of fats in their abdomen rather than incr...

Quantification of gap junction selectivity.

PubMed

Ek-Vitorín, Jose F; Burt, Janis M

2005-12-01

Gap junctions, which are essential for functional coordination and homeostasis within tissues, permit the direct intercellular exchange of small molecules. The abundance and diversity of this exchange depends on the number and selectivity of the comprising channels and on the transjunctional gradient for and chemical character of the permeant molecules. Limited knowledge of functionally significant permeants and poor detectability of those few that are known have made it difficult to define channel selectivity. Presented herein is a multifaceted approach to the quantification of gap junction selectivity that includes determination of the rate constant for intercellular diffusion of a fluorescent probe (k2-DYE) and junctional conductance (gj) for each junction studied, such that the selective permeability (k2-DYE/gj) for dyes with differing chemical characteristics or junctions with differing connexin (Cx) compositions (or treatment conditions) can be compared. In addition, selective permeability can be correlated using single-channel conductance when this parameter is also measured. Our measurement strategy is capable of detecting 1) rate constants and selective permeabilities that differ across three orders of magnitude and 2) acute changes in that rate constant. Using this strategy, we have shown that 1) the selective permeability of Cx43 junctions to a small cationic dye varied across two orders of magnitude, consistent with the hypothesis that the various channel configurations adopted by Cx43 display different selective permeabilities; and 2) the selective permeability of Cx37 vs. Cx43 junctions was consistently and significantly lower.

A subtraction scheme for computing QCD jet cross sections at NNLO: integrating the doubly unresolved subtraction terms

NASA Astrophysics Data System (ADS)

Somogyi, Gábor

2013-04-01

We finish the definition of a subtraction scheme for computing NNLO corrections to QCD jet cross sections. In particular, we perform the integration of the soft-type contributions to the doubly unresolved counterterms via the method of Mellin-Barnes representations. With these final ingredients in place, the definition of the scheme is complete and the computation of fully differential rates for electron-positron annihilation into two and three jets at NNLO accuracy becomes feasible.

Selective activation of the K(+)(ATP) channel is a mechanism by which sudden death is produced by low-energy chest-wall impact (Commotio cordis).

PubMed

Link, M S; Wang, P J; VanderBrink, B A; Avelar, E; Pandian, N G; Maron, B J; Estes, N A

1999-07-27

Sudden death due to relatively innocent chest-wall impact has been described in young individuals (commotio cordis). In our previously reported swine model of commotio cordis, ventricular fibrillation (with T-wave strikes) and ST-segment elevation (with QRS strikes) were produced by 30-mph baseball impacts to the precordium. Because activation of the K(+)(ATP) channel has been implicated in the pathogenesis of ST elevation and ventricular fibrillation in myocardial ischemia, we hypothesized that this channel could be responsible for the electrophysiologic findings in our experimental model and in victims of commotio cordis. In the initial experiment, 6 juvenile swine were given 0.5 mg/kg IV glibenclamide, a selective inhibitor of the K(+)(ATP) channel, and chest impact was given on the QRS. The results of these strikes were compared with animals in which no glibenclamide was given. In the second phase, 20 swine were randomized to receive glibenclamide or a control vehicle (in a double-blind fashion), with chest impact delivered just before the T-wave peak. With QRS impacts, the maximal ST elevation was significantly less in those animals given glibenclamide (0.16+/-0.10 mV) than in controls (0.35+/-0.20 mV; P=0.004). With T-wave impacts, the animals that received glibenclamide had significantly fewer occurrences of ventricular fibrillation (1 episode in 27 impacts; 4%) than controls (6 episodes in 18 impacts; 33%; P=0.01). In this experimental model of commotio cordis, blockade of the K(+)(ATP) channel reduced the incidence of ventricular fibrillation and the magnitude of ST-segment elevation. Therefore, selective K(+)(ATP) channel activation may be a pivotal mechanism in sudden death resulting from low-energy chest-wall trauma in young people during sporting activities.

Crystal structure of the epithelial calcium channel TRPV6.

PubMed

Saotome, Kei; Singh, Appu K; Yelshanskaya, Maria V; Sobolevsky, Alexander I

2016-06-23

Precise regulation of calcium homeostasis is essential for many physiological functions. The Ca(2+)-selective transient receptor potential (TRP) channels TRPV5 and TRPV6 play vital roles in calcium homeostasis as Ca(2+) uptake channels in epithelial tissues. Detailed structural bases for their assembly and Ca(2+) permeation remain obscure. Here we report the crystal structure of rat TRPV6 at 3.25 Å resolution. The overall architecture of TRPV6 reveals shared and unique features compared with other TRP channels. Intracellular domains engage in extensive interactions to form an intracellular 'skirt' involved in allosteric modulation. In the K(+) channel-like transmembrane domain, Ca(2+) selectivity is determined by direct coordination of Ca(2+) by a ring of aspartate side chains in the selectivity filter. On the basis of crystallographically identified cation-binding sites at the pore axis and extracellular vestibule, we propose a Ca(2+) permeation mechanism. Our results provide a structural foundation for understanding the regulation of epithelial Ca(2+) uptake and its role in pathophysiology.

Connexin Channel Permeability to Cytoplasmic Molecules

PubMed Central

Harris, Andrew L.

2007-01-01

Connexin channels are known to be permeable to a variety of cytoplasmic molecules. The first observation of second messenger junctional permeability, made ∼30 years ago, sparked broad interest in gap junction channels as mediators of intercellular molecular signaling. Since then, much has been learned about the diversity of connexin channels with regard to isoform diversity, tissue and developmental distribution, modes of channel regulation, assembly and expression, biochemical modification and permeability, all of which appear to be dynamically regulated. This information has expanded the potential roles of connexin channels in development, physiology and disease, and made their elucidation much more complex - 30 years ago such an orchestra of junctional dynamics was unanticipated. Only recently, however, have investigators been able to directly address, in this more complex framework, the key issue: What specific biological molecules, second messengers and others, are able to permeate the various types of connexin channels, and how well? An important related issue, given the ever-growing list of connexin-related pathologies, is how these permeabilities are altered by disease-causing connexin mutations. Together, many studies show that a variety of cytoplasmic molecules can permeate the different types of connexin channels. A few studies reveal differences in permeation by different molecules through a particular type of connexin channel, and differences in permeation by a particular molecule through different types of connexin channels. This article describes and evaluates the various methods used to obtain these data, presents an annotated compilation of the results, and discusses the findings in the context of what can be inferred about mechanism of selectivity and potential relevance to signaling. The data strongly suggest that highly specific interactions take place between connexin pores and specific biological molecular permeants, and that those

Ionic selectivity of native ATP-activated (P2X) receptor channels in dissociated neurones from rat parasympathetic ganglia

PubMed Central

Liu, Dong-Mei; Adams, David J

2001-01-01

The relative permeability of the native P2X receptor channel to monovalent and divalent inorganic and organic cations was determined from reversal potential measurements of ATP-evoked currents in parasympathetic neurones dissociated from rat submandibular ganglia using the dialysed whole-cell patch clamp technique. The P2X receptor-channel exhibited weak selectivity among the alkali metals with a selectivity sequence of Na+ > Li+ > Cs+ > Rb+ > K+, and permeability ratios relative to Cs+ (PX/PCs) ranging from 1.11 to 0.86. The selectivity for the divalent alkaline earth cations was also weak with the sequence Ca2+ > Sr2+ > Ba2+ > Mn2+ > Mg2+. ATP-evoked currents were strongly inhibited when the extracellular divalent cation concentration was increased. The calculated permeability ratios of different ammonium cations are higher than those of the alkali metal cations. The permeability sequence obtained for the saturated organic cations is inversely correlated with the size of the cation. The unsaturated organic cations have a higher permeability than that predicted by molecular size. Acidification to pH 6.2 increased the ATP-induced current amplitude twofold, whereas alkalization to 8.2 and 9.2 markedly reduced current amplitude. Cell dialysis with either anti-P2X2 and/or anti-P2X4 but not anti-P2X1 antibodies attenuated the ATP-evoked current amplitude. Taken together, these data are consistent with homomeric and/or heteromeric P2X2 and P2X4 receptor subtypes expressed in rat submandibular neurones. The permeability ratios for the series of monovalent organic cations, with the exception of unsaturated cations, were approximately related to the ionic size. The relative permeabilities of the monovalent inoganic and organic cations tested are similar to those reported previously for cloned rat P2X2 receptors expressed in mammalian cells. PMID:11454961

Fragmentation network of doubly charged methionine: Interpretation using graph theory

NASA Astrophysics Data System (ADS)

Ha, D. T.; Yamazaki, K.; Wang, Y.; Alcamí, M.; Maeda, S.; Kono, H.; Martín, F.; Kukk, E.

2016-09-01

The fragmentation of doubly charged gas-phase methionine (HO2CCH(NH2)CH2CH2SCH3) is systematically studied using the self-consistent charge density functional tight-binding molecular dynamics (MD) simulation method. We applied graph theory to analyze the large number of the calculated MD trajectories, which appears to be a highly effective and convenient means of extracting versatile information from the large data. The present theoretical results strongly concur with the earlier studied experimental ones. Essentially, the dication dissociates into acidic group CO2H and basic group C4NSH10. The former may carry a single or no charge and stays intact in most cases, whereas the latter may hold either a single or a double charge and tends to dissociate into smaller fragments. The decay of the basic group is observed to follow the Arrhenius law. The dissociation pathways to CO2H and C4NSH10 and subsequent fragmentations are also supported by ab initio calculations.

Fabrication and characterization of GaN nanowire doubly clamped resonators

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

Maliakkal, Carina B., E-mail: carina@tifr.res.in; Mathew, John P.; Hatui, Nirupam

2015-09-21

Gallium nitride (GaN) nanowires (NWs) have been intensely researched as building blocks for nanoscale electronic and photonic device applications; however, the mechanical properties of GaN nanostructures have not been explored in detail. The rigidity, thermal stability, and piezoelectric properties of GaN make it an interesting candidate for nano-electromechanical systems. We have fabricated doubly clamped GaN NW electromechanical resonators on sapphire using electron beam lithography and estimated the Young's modulus of GaN from resonance frequency measurements. For wires of triangular cross section with side ∼90 nm, we obtained values for the Young's modulus to be about 218 and 691 GPa, which are ofmore » the same order of magnitude as the values reported for bulk GaN. We also discuss the role of residual strain in the nanowire on the resonant frequency and the orientation dependence of the Young's modulus in wurtzite crystals.« less

Analysis and control of the vibration of doubly fed wind turbine

NASA Astrophysics Data System (ADS)

Yu, Manye; Lin, Ying

2017-01-01

The fault phenomena of the violent vibration of certain doubly-fed wind turbine were researched comprehensively, and the dynamic characteristics, load and fault conditions of the system were discussed. Firstly, the structural dynamics analysis of wind turbine is made, and the dynamics mold is built. Secondly, the vibration testing of wind turbine is done with the German test and analysis systems BBM. Thirdly, signal should be analyzed and dealt with. Based on the experiment, spectrum analysis of the motor dynamic balance can be made by using signal processing toolbox of MATLAB software, and the analysis conclusions show that the vibration of wind turbine is caused by dynamic imbalance. The results show that integrating mechanical system dynamics theory with advanced test technology can solve the vibration problem more successfully, which is important in vibration diagnosis of mechanical equipment.

The electrostatics of VDAC: implications for selectivity and gating.

PubMed

Choudhary, Om P; Ujwal, Rachna; Kowallis, William; Coalson, Rob; Abramson, Jeff; Grabe, Michael

2010-02-26

The voltage-dependent anion channel (VDAC) is the major pathway mediating the transfer of metabolites and ions across the mitochondrial outer membrane. Two hallmarks of the channel in the open state are high metabolite flux and anion selectivity, while the partially closed state blocks metabolites and is cation selective. Here we report the results from electrostatics calculations carried out on the recently determined high-resolution structure of murine VDAC1 (mVDAC1). Poisson-Boltzmann calculations show that the ion transfer free energy through the channel is favorable for anions, suggesting that mVDAC1 represents the open state. This claim is buttressed by Poisson-Nernst-Planck calculations that predict a high single-channel conductance indicative of the open state and an anion selectivity of 1.75--nearly a twofold selectivity for anions over cations. These calculations were repeated on mutant channels and gave selectivity changes in accord with experimental observations. We were then able to engineer an in silico mutant channel with three point mutations that converted mVDAC1 into a channel with a preference for cations. Finally, we investigated two proposals for how the channel gates between the open and the closed state. Both models involve the movement of the N-terminal helix, but neither motion produced the observed voltage sensitivity, nor did either model result in a cation-selective channel, which is observed experimentally. Thus, we were able to rule out certain models for channel gating, but the true motion has yet to be determined. Copyright (c) 2009. Elsevier Ltd. All rights reserved.

Adaptive Pre-FFT Equalizer with High-Precision Channel Estimator for ISI Channels

NASA Astrophysics Data System (ADS)

Yoshida, Makoto

We present an attractive approach for OFDM transmission using an adaptive pre-FFT equalizer, which can select ICI reduction mode according to channel condition, and a degenerated-inverse-matrix-based channel estimator (DIME), which uses a cyclic sinc-function matrix uniquely determined by transmitted subcarriers. In addition to simulation results, the proposed system with an adaptive pre-FFT equalizer and DIME has been laboratory tested by using a software defined radio (SDR)-based test bed. The simulation and experimental results demonstrated that the system at a rate of more than 100Mbps can provide a bit error rate of less than 10-3 for a fast multi-path fading channel that has a moving velocity of more than 200km/h with a delay spread of 1.9µs (a maximum delay path of 7.3µs) in the 5-GHz band.

Voltage-gated Proton Channels

PubMed Central

DeCoursey, Thomas E.

2014-01-01

Voltage-gated proton channels, HV1, have vaulted from the realm of the esoteric into the forefront of a central question facing ion channel biophysicists, namely the mechanism by which voltage-dependent gating occurs. This transformation is the result of several factors. Identification of the gene in 2006 revealed that proton channels are homologues of the voltage-sensing domain of most other voltage-gated ion channels. Unique, or at least eccentric, properties of proton channels include dimeric architecture with dual conduction pathways, perfect proton selectivity, a single-channel conductance ~103 smaller than most ion channels, voltage-dependent gating that is strongly modulated by the pH gradient, ΔpH, and potent inhibition by Zn2+ (in many species) but an absence of other potent inhibitors. The recent identification of HV1 in three unicellular marine plankton species has dramatically expanded the phylogenetic family tree. Interest in proton channels in their own right has increased as important physiological roles have been identified in many cells. Proton channels trigger the bioluminescent flash of dinoflagellates, facilitate calcification by coccolithophores, regulate pH-dependent processes in eggs and sperm during fertilization, secrete acid to control the pH of airway fluids, facilitate histamine secretion by basophils, and play a signaling role in facilitating B-cell receptor mediated responses in B lymphocytes. The most elaborate and best-established functions occur in phagocytes, where proton channels optimize the activity of NADPH oxidase, an important producer of reactive oxygen species. Proton efflux mediated by HV1 balances the charge translocated across the membrane by electrons through NADPH oxidase, minimizes changes in cytoplasmic and phagosomal pH, limits osmotic swelling of the phagosome, and provides substrate H+ for the production of H2O2 and HOCl, reactive oxygen species crucial to killing pathogens. PMID:23798303

Structural basis for the selective permeability of channels made of communicating junction proteins

PubMed Central

Ek-Vitorin, Jose F.; Burt, Janis M.

2012-01-01

The open state(s) of gap junction channels is evident from their permeation by small ions in response to an applied intercellular (transjunctional/transchannel) voltage gradient. That an open channel allows variable amounts of current to transit from cell-to-cell in the face of a constant intercellular voltage difference indicates channel open/closing can be complete or partial. The physiological significance of such open state options is, arguably, the main concern of junctional regulation. Because gap junctions are permeable to many substances, it is sensible to inquire whether and how each open state influences the intercellular diffusion of molecules as valuable as, but less readily detected than current-carrying ions. Presumably, structural changes perceived as shifts in channel conductivity would significantly alter the transjunctional diffusion of molecules whose limiting diameter approximates the pore’s limiting diameter. Moreover, changes in junctional permeability to some molecules might occur without evident changes in conductivity, either at macroscopic or single channel level. Open gap junction channels allow the exchange of cytoplasmic permeants between contacting cells by simple diffusion. The identity of such permeants, and the functional circumstances and consequences of their junctional exchange presently constitute the most urgent (and demanding) themes of the field. Here, we consider the necessity for regulating this exchange, the possible mechanism(s) and structural elements likely involved in such regulation, and how regulatory phenomena could be perceived as changes in chemical vs. electrical coupling; an overall reflection on our collective knowledge of junctional communication is then applied to suggest new avenues of research. PMID:22342665

The Earliest Ion Channels in Protocellular Membranes

NASA Technical Reports Server (NTRS)

Mijajlovic, Milan; Pohorille, Andrew; Wilson, Michael; Wei, Chenyu

2010-01-01

indicates that their structures are unique and stable. In addition, it is also believed that the trichotoxin channel displays some selectivity between potassium and chloride ions. This makes trichotoxin and antiamoebin ideal models of the earliest ion channels that could provide insight into the origins of ion conductance and selectivity. In the absence of crystal structure of the trichotoxin and antiamoebin channels, we propose their molecular models based on experimentally determined number of monomers forming the bundles. We use molecular dynamics simulations to validate the models in terms of their conductance and selectivity. On the basis of our simulations we show that the emergence of channels built of small, alpha-helical peptides was protobiologically plausible and did not require highly specific amino acid sequences, which is a convenient evolutionary trait. Despite their simple structure, such channels could possess properties that, at the first sight, appear to require markedly larger complexity. To this end, we will discuss how the amino acid sequence and structure of primitive channels give rise to the phenomena of ionic conductance and selectivity across the earliest cell walls, which were essential functions for the emergence and early evolution of protocells. Furthermore, we will argue that even though architectures of membrane proteins are not nearly as diverse as those of water-soluble proteins, they are sufficiently flexible to adapt readily to the functional demands arising during evolution.

The earliest ion channels in protocellular membranes

NASA Astrophysics Data System (ADS)

Mijajlovic, Milan; Pohorille, Andrew; Wilson, Michael; Wei, Chenyu

indicates that their structures are unique and stable. In addition, it is also believed that the trichotoxin channel displays some selectivity between potassium and chloride ions. This makes trichotoxin and antiamoebin ideal models of the earliest ion channels that could provide insight into the origins of ion conductance and selectivity. In the absence of crystal structure of the trichotoxin and antiamoebin channels, we propose their molecular models based on experimentally determined number of monomers forming the bundles. We use molecular dynamics simulations to validate the models in terms of their conductance and selectivity. On the basis of our simulations we show that the emergence of channels built of small, α-helical peptides was protobiologically plausible and did not require highly specific amino acid sequences, which is a convenient evolutionary trait. Despite their simple structure, such channels could possess properties that, at the first sight, appear to require markedly larger complexity. To this end, we will discuss how the amino acid sequence and structure of primitive channels give rise to the phenomena of ionic conductance and selectivity across the earliest cell walls, which were essential functions for the emergence and early evolution of protocells. Furthermore, we will argue that even though architectures of membrane proteins are not nearly as diverse as those of water-soluble proteins, they are sufficiently flexible to adapt readily to the functional demands arising during evolution.

Skyrmion-based multi-channel racetrack

NASA Astrophysics Data System (ADS)

Song, Chengkun; Jin, Chendong; Wang, Jinshuai; Xia, Haiyan; Wang, Jianbo; Liu, Qingfang

2017-11-01

Magnetic skyrmions are promising for the application of racetrack memories, logic gates, and other nano-devices, owing to their topologically protected stability, small size, and low driving current. In this work, we propose a skyrmion-based multi-channel racetrack memory where the skyrmion moves in the selected channel by applying voltage-controlled magnetic anisotropy gates. It is demonstrated numerically that a current-dependent skyrmion Hall effect can be restrained by the additional potential of the voltage-controlled region, and the skyrmion velocity and moving channel in the racetrack can be operated by tuning the voltage-controlled magnetic anisotropy, gate position, and current density. Our results offer a potential application of racetrack memory based on skyrmions.

Effect of a selective chloride channel activator, lubiprostone, on gastrointestinal transit, gastric sensory, and motor functions in healthy volunteers.

PubMed

Camilleri, Michael; Bharucha, Adil E; Ueno, Ryuji; Burton, Duane; Thomforde, George M; Baxter, Kari; McKinzie, Sanna; Zinsmeister, Alan R

2006-05-01

Chloride channels modulate gastrointestinal neuromuscular functions in vitro. Lubiprostone, a selective type 2 chloride channel (ClC-2) activator, induces intestinal secretion and has been shown to relieve constipation in clinical trials; however, the effects of lubiprostone on gastric function and whole gut transit in humans are unclear. Our aim was to compare the effects of the selective ClC-2 activator lubiprostone on maximum tolerated volume (MTV) of a meal, postprandial symptoms, gastric volumes, and gastrointestinal and colonic transit in humans. We performed a randomized, parallel-group, double-blind, placebo-controlled study evaluating the effects of lubiprostone (24 microg bid) in 30 healthy volunteers. Validated methods were used: scintigraphic gastrointestinal and colonic transit, SPECT to measure gastric volumes, and the nutrient drink ("satiation") test to measure MTV and postprandial symptoms. Lubiprostone accelerated small bowel and colonic transit, increased fasting gastric volume, and retarded gastric emptying. MTV values were reduced compared with placebo; however, the MTV was within the normal range for healthy adults in 13 of 14 participants, and there was no significant change compared with baseline measurements. Lubiprostone had no significant effect on postprandial gastric volume or aggregate symptoms but did decrease fullness 30 min after the fully satiating meal. Thus the ClC-2 activator lubiprostone accelerates small intestinal and colonic transit, which confers potential in the treatment of constipation.

Pyroptosis is driven by non-selective gasdermin-D pore and its morphology is different from MLKL channel-mediated necroptosis

PubMed Central

Chen, Xin; He, Wan-ting; Hu, Lichen; Li, Jingxian; Fang, Yuan; Wang, Xin; Xu, Xiaozheng; Wang, Zhuo; Huang, Kai; Han, Jiahuai

2016-01-01

Necroptosis and pyroptosis are two forms of programmed cell death with a common feature of plasma membrane rupture. Here we studied the morphology and mechanism of pyroptosis in comparison with necroptosis. Different from necroptosis, pyroptosis undergoes membrane blebbing and produces apoptotic body-like cell protrusions (termed pyroptotic bodies) prior to plasma membrane rupture. The rupture in necroptosis is explosion-like, whereas in pyroptosis it leads to flattening of cells. It is known that the execution of necroptosis is mediated by mixed lineage kinase domain-like (MLKL) oligomers in the plasma membrane, whereas gasdermin-D (GSDMD) mediates pyroptosis after its cleavage by caspase-1 or caspase-11. We show that N-terminal fragment of GSDMD (GSDMD-N) generated by caspase cleavage also forms oligomer and migrates to the plasma membrane to kill cells. Both MLKL and GSDMD-N are lipophilic and the N-terminal sequences of both proteins are important for their oligomerization and plasma membrane translocation. Unlike MLKL which forms channels on the plasma membrane that induces influx of selected ions which osmotically swell the cells to burst, GSDMD-N forms non-selective pores and does not rely on increased osmolarity to disrupt cells. Our study reveals the pore-forming activity of GSDMD and channel-forming activity of MLKL determine different ways of plasma membrane rupture in pyroptosis and necroptosis. PMID:27573174

Pyroptosis is driven by non-selective gasdermin-D pore and its morphology is different from MLKL channel-mediated necroptosis.

PubMed

Chen, Xin; He, Wan-Ting; Hu, Lichen; Li, Jingxian; Fang, Yuan; Wang, Xin; Xu, Xiaozheng; Wang, Zhuo; Huang, Kai; Han, Jiahuai

2016-09-01

Necroptosis and pyroptosis are two forms of programmed cell death with a common feature of plasma membrane rupture. Here we studied the morphology and mechanism of pyroptosis in comparison with necroptosis. Different from necroptosis, pyroptosis undergoes membrane blebbing and produces apoptotic body-like cell protrusions (termed pyroptotic bodies) prior to plasma membrane rupture. The rupture in necroptosis is explosion-like, whereas in pyroptosis it leads to flattening of cells. It is known that the execution of necroptosis is mediated by mixed lineage kinase domain-like (MLKL) oligomers in the plasma membrane, whereas gasdermin-D (GSDMD) mediates pyroptosis after its cleavage by caspase-1 or caspase-11. We show that N-terminal fragment of GSDMD (GSDMD-N) generated by caspase cleavage also forms oligomer and migrates to the plasma membrane to kill cells. Both MLKL and GSDMD-N are lipophilic and the N-terminal sequences of both proteins are important for their oligomerization and plasma membrane translocation. Unlike MLKL which forms channels on the plasma membrane that induces influx of selected ions which osmotically swell the cells to burst, GSDMD-N forms non-selective pores and does not rely on increased osmolarity to disrupt cells. Our study reveals the pore-forming activity of GSDMD and channel-forming activity of MLKL determine different ways of plasma membrane rupture in pyroptosis and necroptosis.

Power enhancement of burst-mode UV pulses using a doubly-resonant optical cavity

DOE PAGES

Rahkman, Abdurahim; Notcutt, Mark; Liu, Yun

2015-11-24

We report a doubly-resonant enhancement cavity (DREC) that can realize a simultaneous enhancement of two incoming laser beams at different wavelengths and different temporal structures. The double-resonance condition is theoretically analyzed and different DREC locking methods are experimentally investigated. Simultaneous locking of a Fabry-Perot cavity to both an infrared (IR, 1064 nm) and its frequency tripled ultraviolet (UV, 355 nm) pulses has been demonstrated by controlling the frequency difference between the two beams with a fiber optic frequency shifter. The DREC technique opens a new paradigm in the applications of optical cavities to power enhancement of burst-mode lasers with arbitrarymore » macropulse width and repetition rate.« less

Well-posedness for a class of doubly nonlinear stochastic PDEs of divergence type

NASA Astrophysics Data System (ADS)

Scarpa, Luca

2017-08-01

We prove well-posedness for doubly nonlinear parabolic stochastic partial differential equations of the form dXt - div γ (∇Xt) dt + β (Xt) dt ∋ B (t ,Xt) dWt, where γ and β are the two nonlinearities, assumed to be multivalued maximal monotone operators everywhere defined on Rd and R respectively, and W is a cylindrical Wiener process. Using variational techniques, suitable uniform estimates (both pathwise and in expectation) and some compactness results, well-posedness is proved under the classical Leray-Lions conditions on γ and with no restrictive smoothness or growth assumptions on β. The operator B is assumed to be Hilbert-Schmidt and to satisfy some classical Lipschitz conditions in the second variable.

Outage Performance Analysis of Relay Selection Schemes in Wireless Energy Harvesting Cooperative Networks over Non-Identical Rayleigh Fading Channels.

PubMed

Do, Nhu Tri; Bao, Vo Nguyen Quoc; An, Beongku

2016-02-26

In this paper, we study relay selection in decode-and-forward wireless energy harvesting cooperative networks. In contrast to conventional cooperative networks, the relays harvest energy from the source's radio-frequency radiation and then use that energy to forward the source information. Considering power splitting receiver architecture used at relays to harvest energy, we are concerned with the performance of two popular relay selection schemes, namely, partial relay selection (PRS) scheme and optimal relay selection (ORS) scheme. In particular, we analyze the system performance in terms of outage probability (OP) over independent and non-identical (i.n.i.d.) Rayleigh fading channels. We derive the closed-form approximations for the system outage probabilities of both schemes and validate the analysis by the Monte-Carlo simulation. The numerical results provide comprehensive performance comparison between the PRS and ORS schemes and reveal the effect of wireless energy harvesting on the outage performances of both schemes. Additionally, we also show the advantages and drawbacks of the wireless energy harvesting cooperative networks and compare to the conventional cooperative networks.

Substrate influence on the interlayer electron-phonon couplings in fullerene films probed with doubly-resonant SFG spectroscopy.

PubMed

Elsenbeck, Dennis; Das, Sushanta K; Velarde, Luis

2017-07-19

We present doubly-resonant sum frequency generation (DR-SFG) spectra of fullerene thin films on metallic and dielectric substrates as a way to investigate the interplay between nuclear and electronic coupling at buried interfaces. Modal and substrate selectivity in the electronic enhancement of the C 60 vibrational signatures is demonstrated for excitation wavelengths spanning the visible range. While the SFG response of the totally symmetric A g (2) mode of fullerene is distinctly coupled to the optically allowed electronic transition corresponding to the HOMO-LUMO+1 of C 60 (ca. 2.6 eV), the T 1u (4) vibrational mode appears to be coupled to a symmetry-forbidden HOMO-LUMO transition at lower energies (ca. 2.0 eV). For dielectric substrates, the DR-SFG intensity of the T 1u (4) mode shows lack of enhancement for upconversion wavelengths off-resonance with the optically-dark LUMO. However, the T 1u (4) mode shows a unique coupling to an intermediate state (∼2.4 eV) only for the fullerene films on the gold substrate. We attribute this coupling to unique interactions at the buried C 60 /gold interface. These results demonstrate the occurrence of clear electron-phonon couplings at the C 60 /substrate interfaces and shed light on the impact of these couplings on the optical response of electronically excited fullerene. This coupling may influence charge and energy transport in organic electronic devices mediated by vibrational motions. We also demonstrate a potential use of this added selectivity in chemical imaging.

Increase in cytosolic Ca2+ produced by hypoxia and other depolarizing stimuli activates a non-selective cation channel in chemoreceptor cells of rat carotid body

PubMed Central

Kang, Dawon; Wang, Jiaju; Hogan, James O; Vennekens, Rudi; Freichel, Marc; White, Carl; Kim, Donghee

2014-01-01

The current model of O2 sensing by carotid body chemoreceptor (glomus) cells is that hypoxia inhibits the outward K+ current and causes cell depolarization, Ca2+ influx via voltage-dependent Ca2+ channels and a rise in intracellular [Ca2+] ([Ca2+]i). Here we show that hypoxia (<5% O2), in addition to inhibiting the two-pore domain K+ channels TASK-1/3 (TASK), indirectly activates an ∼20 pS channel in isolated glomus cells. The 20 pS channel was permeable to K+, Na+ and Cs+ but not to Cl− or Ca2+. The 20 pS channel was not sensitive to voltage. Inhibition of TASK by external acid, depolarization of glomus cells with high external KCl (20 mm) or opening of the Ca2+ channel with FPL64176 activated the 20 pS channel when 1 mm Ca2+ was present in the external solution. Ca2+ (10 μm) applied to the cytosolic side of inside-out patches activated the 20 pS channel. The threshold [Ca2+]i for activation of the 20 pS channel in cell-attached patches was ∼200 nm. The reversal potential of the 20 pS channel was estimated to be −28 mV. Our results reveal a sequential mechanism in which hypoxia (<5% O2) first inhibits the K+ conductance and then activates a Na+-permeable, non-selective cation channel via depolarization-induced rise in [Ca2+]i. Our results suggest that inhibition of K+ efflux and stimulation of Na+ influx both contribute to the depolarization of glomus cells during moderate to severe hypoxia. PMID:24591572

Structural and functional characterization of a calcium-activated cation channel from Tsukamurella paurometabola

NASA Astrophysics Data System (ADS)

Dhakshnamoorthy, Balasundaresan; Rohaim, Ahmed; Rui, Huan; Blachowicz, Lydia; Roux, Benoît

2016-09-01

The selectivity filter is an essential functional element of K+ channels that is highly conserved both in terms of its primary sequence and its three-dimensional structure. Here, we investigate the properties of an ion channel from the Gram-positive bacterium Tsukamurella paurometabola with a selectivity filter formed by an uncommon proline-rich sequence. Electrophysiological recordings show that it is a non-selective cation channel and that its activity depends on Ca2+ concentration. In the crystal structure, the selectivity filter adopts a novel conformation with Ca2+ ions bound within the filter near the pore helix where they are coordinated by backbone oxygen atoms, a recurrent motif found in multiple proteins. The binding of Ca2+ ion in the selectivity filter controls the widening of the pore as shown in crystal structures and in molecular dynamics simulations. The structural, functional and computational data provide a characterization of this calcium-gated cationic channel.

Optimal electrode selection for multi-channel electroencephalogram based detection of auditory steady-state responses.

PubMed

Van Dun, Bram; Wouters, Jan; Moonen, Marc

2009-07-01

Auditory steady-state responses (ASSRs) are used for hearing threshold estimation at audiometric frequencies. Hearing impaired newborns, in particular, benefit from this technique as it allows for a more precise diagnosis than traditional techniques, and a hearing aid can be better fitted at an early age. However, measurement duration of current single-channel techniques is still too long for clinical widespread use. This paper evaluates the practical performance of a multi-channel electroencephalogram (EEG) processing strategy based on a detection theory approach. A minimum electrode set is determined for ASSRs with frequencies between 80 and 110 Hz using eight-channel EEG measurements of ten normal-hearing adults. This set provides a near-optimal hearing threshold estimate for all subjects and improves response detection significantly for EEG data with numerous artifacts. Multi-channel processing does not significantly improve response detection for EEG data with few artifacts. In this case, best response detection is obtained when noise-weighted averaging is applied on single-channel data. The same test setup (eight channels, ten normal-hearing subjects) is also used to determine a minimum electrode setup for 10-Hz ASSRs. This configuration allows to record near-optimal signal-to-noise ratios for 80% of subjects.

Structural basis for the selective permeability of channels made of communicating junction proteins.

PubMed

Ek-Vitorin, Jose F; Burt, Janis M

2013-01-01

The open state(s) of gap junction channels is evident from their permeation by small ions in response to an applied intercellular (transjunctional/transchannel) voltage gradient. That an open channel allows variable amounts of current to transit from cell-to-cell in the face of a constant intercellular voltage difference indicates channel open/closing can be complete or partial. The physiological significance of such open state options is, arguably, the main concern of junctional regulation. Because gap junctions are permeable to many substances, it is sensible to inquire whether and how each open state influences the intercellular diffusion of molecules as valuable as, but less readily detected than current-carrying ions. Presumably, structural changes perceived as shifts in channel conductivity would significantly alter the transjunctional diffusion of molecules whose limiting diameter approximates the pore's limiting diameter. Moreover, changes in junctional permeability to some molecules might occur without evident changes in conductivity, either at macroscopic or single channel level. Open gap junction channels allow the exchange of cytoplasmic permeants between contacting cells by simple diffusion. The identity of such permeants, and the functional circumstances and consequences of their junctional exchange presently constitute the most urgent (and demanding) themes of the field. Here, we consider the necessity for regulating this exchange, the possible mechanism(s) and structural elements likely involved in such regulation, and how regulatory phenomena could be perceived as changes in chemical vs. electrical coupling; an overall reflection on our collective knowledge of junctional communication is then applied to suggest new avenues of research. This article is part of a Special Issue entitled: The Communicating junctions, roles and dysfunctions. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of channel tap spacing on delay-lock tracking

NASA Astrophysics Data System (ADS)

Dana, Roger A.; Milner, Brian R.; Bogusch, Robert L.

1995-12-01

High fidelity simulations of communication links operating through frequency selective fading channels require both accurate channel models and faithful reproduction of the received signal. In modern radio receivers, processing beyond the analog-to-digital converter (A/D) is done digitally, so a high fidelity simulation is actually an emulation of this digital signal processing. The 'simulation' occurs in constructing the output of the A/D. One approach to constructing the A/D output is to convolve the channel impulse response function with the combined impulse response of the transmitted modulation and the A/D. For both link simulations and hardware channel simulators, the channel impulse response function is then generated with a finite number of samples per chip, and the convolution is implemented in a tapped delay line. In this paper we discuss the effects of the channel model tap spacing on the performance of delay locked loops (DLLs) in both direct sequence and frequency hopped spread spectrum systems. A frequency selective fading channel is considered, and the channel impulse response function is constructed with an integer number of taps per modulation symbol or chip. The tracking loop time delay is computed theoretically for this tapped delay line channel model and is compared to the results of high fidelity simulations of actual DLLs. A surprising result is obtained. The performance of the DLL depends strongly on the number of taps per chip. As this number increases the DLL delay approaches the theoretical limit.

Biomarker selection for determining bone biocompatibility of pure magnesium processed by equal channel angular pressing (ECAP) using immunohistochemistry

NASA Astrophysics Data System (ADS)

Handayani, Lisa; Sulistyani, Lilies Dwi; Supriadi, Sugeng; Priosoeryanto, Bambang Pontjo; Latief, Benny Syariefsyah

2018-02-01

Since grain refinement is proved to be favorable to improve mechanical properties and corrosion resistance, a new conceptual metal forming process, equal channel angular pressing (ECAP), has been carried out on magnesium, a very promising biodegradable material in the field of oral and maxillofacial surgery. The popularity of immunohisto-chemistry (IHC) has been rising following the discovery of biomarker. In the meantime, more antibodies being produced for research have been continuously rising and becoming more varied. This review provides a conceptual framework to understand the roles of IHC on determination of bone biocompatibility to ECAP magnesium by selecting biomarker and point needed to either select or make an antibody to the target. From the review, it has been concluded that the most suitable biomarkers for biocompatibility test of bone implanted with ECAP magnesium are collagen-1, osteocalcin, smooth muscle actin, and CD68.

Identification of an HV 1 voltage-gated proton channel in insects.

PubMed

Chaves, Gustavo; Derst, Christian; Franzen, Arne; Mashimo, Yuta; Machida, Ryuichiro; Musset, Boris

2016-04-01

The voltage-gated proton channel 1 (HV 1) is an important component of the cellular proton extrusion machinery and is essential for charge compensation during the respiratory burst of phagocytes. HV 1 has been identified in a wide range of eukaryotes throughout the animal kingdom, with the exception of insects. Therefore, it has been proposed that insects do not possess an HV 1 channel. In the present study, we report the existence of an HV 1-type proton channel in insects. We searched insect transcriptome shotgun assembly (TSA) sequence databases and found putative HV 1 orthologues in various polyneopteran insects. To confirm that these putative HV 1 orthologues were functional channels, we studied the HV 1 channel of Nicoletia phytophila (NpHV 1), an insect of the Zygentoma order, in more detail. NpHV 1 comprises 239 amino acids and is 33% identical to the human voltage-gated proton channel 1. Patch clamp measurements in a heterologous expression system showed proton selectivity, as well as pH- and voltage-dependent gating. Interestingly, NpHV 1 shows slightly enhanced pH-dependent gating compared to the human channel. Mutations in the first transmembrane segment at position 66 (Asp66), the presumed selectivity filter, lead to a loss of proton-selective conduction, confirming the importance of this aspartate residue in voltage-gated proton channels. Nucleotide sequence data have been deposited in the GenBank database under accession number KT780722. © 2016 Federation of European Biochemical Societies.

Photonic Crystal Fiber-Based Surface Plasmon Resonance Sensor with Selective Analyte Channels and Graphene-Silver Deposited Core

PubMed Central

Rifat, Ahmmed A.; Mahdiraji, G. Amouzad; Chow, Desmond M.; Shee, Yu Gang; Ahmed, Rajib; Adikan, Faisal Rafiq Mahamd

2015-01-01

We propose a surface plasmon resonance (SPR) sensor based on photonic crystal fiber (PCF) with selectively filled analyte channels. Silver is used as the plasmonic material to accurately detect the analytes and is coated with a thin graphene layer to prevent oxidation. The liquid-filled cores are placed near to the metallic channel for easy excitation of free electrons to produce surface plasmon waves (SPWs). Surface plasmons along the metal surface are excited with a leaky Gaussian-like core guided mode. Numerical investigations of the fiber’s properties and sensing performance are performed using the finite element method (FEM). The proposed sensor shows maximum amplitude sensitivity of 418 Refractive Index Units (RIU−1) with resolution as high as 2.4 × 10−5 RIU. Using the wavelength interrogation method, a maximum refractive index (RI) sensitivity of 3000 nm/RIU in the sensing range of 1.46–1.49 is achieved. The proposed sensor is suitable for detecting various high RI chemicals, biochemical and organic chemical analytes. Additionally, the effects of fiber structural parameters on the properties of plasmonic excitation are investigated and optimized for sensing performance as well as reducing the sensor’s footprint. PMID:25996510

One-Neutron Removal Measurement Reveals {sup 24}O as a New Doubly Magic Nucleus

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

Kanungo, R.; Perro, C.; Nociforo, C.

The first measurement of the momentum distribution for one-neutron removal from {sup 24}O at 920A MeV performed at GSI, Darmstadt is reported. The observed distribution has a width (FWHM) of 99{+-}4 MeV/c in the projectile rest frame and a one-neutron removal cross section of 63{+-}7 mb. The results are well explained with a nearly pure 2s{sub 1/2} neutron spectroscopic factor of 1.74{+-}0.19 within the eikonal model. This large s-wave probability shows a spherical shell closure thereby confirming earlier suggestions that {sup 24}O is a new doubly magic nucleus.

The Rotational Spectrum of Singly and Doubly 13C-SUBSTITUTED Dimethylether

NASA Astrophysics Data System (ADS)

Koerber, Monika; Endres, Christian P.; Lewen, Frank; Giesen, Thomas F.; Schlemmer, Stephan; Pohl, Roland; Klein, Axel

2010-06-01

Dimethylether (DME) is a nearly prolate asymmetric top with two internal rotors (methyl groups) which undergo periodic large amplitude motions and show a complicated torsional splitting of each rotational energy level. Due to its complex spectrum and its high abundance in hot cores such as Orion KL or Sagittarius B2 at temperatures exceeding 100 K, DME is very prominent in astronomical line surveys and contributes to spectral line confusion of such sources. The interpretation of astronomical observations therefore depends on the knowledge of accurate rest frequencies and reliable intensities. Precise predictions for the ground state of DME's main isotopologue are now available up to 2.1 THz In contrast, very little is known about 13C-substituted DME. Only a few data are available on singly 13C-substituted DME, 12CH_3O13CH_3. However, no data are available on doubly 13C-substituted DME, (13CH_3)_2O, yet. While in (13CH_3)_2O the two internal rotating methyl groups are equivalent and the splitting of rotational energy levels into four substates is comparable to the main isotopologue, singly 13C-substituted DME has two non-equivalent internal rotors resulting in torsional splitting of rotational energy levels into five substates. The purpose of our new laboratory measurements is to extend the knowledge on the astrophysically relevant species 12CH_3O13CH_3. To analyze the complicated spectrum resulting from a 13C-enriched sample of DME, containing all different 13C-substituted species as well as the main isotopologue, also precise data on doubly 13C-substituted DME are inevitable. We performed measurements in the frequency region 35-120 GHz using an all solid state spectrometer. Rotational as well as torsional parameters have been obtained for (13CH_3)_2O as well as 12CH_3O13CH_3 by fitting the assigned transitions to an effective rotational Hamiltonian introduced by Peter Groner. C. Comito et al., Astrophys. J. Suppl. Ser. 156, 127-167 (2005) C. P. Endres et al

Doubly stratified MHD tangent hyperbolic nanofluid flow due to permeable stretched cylinder

NASA Astrophysics Data System (ADS)

Nagendramma, V.; Leelarathnam, A.; Raju, C. S. K.; Shehzad, S. A.; Hussain, T.

2018-06-01

An investigation is exhibited to analyze the presence of heat source and sink in doubly stratified MHD incompressible tangent hyperbolic fluid due to stretching of cylinder embedded in porous space under nanoparticles. To develop the mathematical model of tangent hyperbolic nanofluid, movement of Brownian and thermophoretic are accounted. The established equations of continuity, momentum, thermal and solutal boundary layers are reassembled into sets of non-linear expressions. These assembled expressions are executed with the help of Runge-Kutta scheme with MATLAB. The impacts of sundry parameters are illustrated graphically and the engineering interest physical quantities like skin friction, Nusselt and Sherwood number are examined by computing numerical values. It is clear that the power-law index parameter and curvature parameter shows favorable effect on momentum boundary layer thickness whereas Weissennberg number reveals inimical influence.

Solution structure for Pandinus toxin K-alpha (PiTX-K alpha), a selective blocker of A-type potassium channels.

PubMed

Tenenholz, T C; Rogowski, R S; Collins, J H; Blaustein, M P; Weber, D J

1997-03-11

PiTX-K alpha, a 35-residue peptide recently isolated from the venom of Pandinus imperator, blocks the rapidly inactivating (A-type) K+ channel(s) in rat brain synaptosomes and the cloned Kv 1.2 potassium channel at very low toxin concentrations (6 nM and 32 pM, respectively) [Rogowski, R. S., Collins, J. H., O'Neil, T. J., Gustafson, T. A., Werkman, T. A., Rogawski, M. A., Tenenholz, T. C., Weber, D. J., & Blaustein, M. P. (1996) Mol. Pharmacol. 50, 1167-1177]. The three-dimensional structure of PiTX-K alpha was determined using NMR spectroscopy in order to understand its selectivity and affinity toward K+ channels. PiTX-K alpha was found to have an alpha-helix from residues 10 to 21 and two beta-strands (betaI, 26-28; betaII, 33-35) connected by a type II beta-turn to form a small antiparallel beta-sheet. Three disulfide bonds, which are conserved in all members of the charybdotoxin family (alpha-K toxins), anchor one face of the alpha-helix to the beta-sheet. The N-terminal portion of PiTX-K alpha has three fewer residues than other alpha-K toxins such as charybdotoxin. Rather than forming a third beta-strand as found for other alpha-K toxins, the N-terminal region of PiTX-K alpha adopts an extended conformation. This structural difference in PiTX-K alpha together with differences in sequence at Pro-10, Tyr-14, and Asn-25 (versus Ser-10, Trp-14, and Arg-25 in CTX) may explain why PiTX-K alpha does not block maxi-K+ channels. Differences in three-dimensional structure between PiTX-K alpha and charybdotoxin are also observed in both the tight turn and the loop that connects the first beta-strand to the alpha-helix. As a result, side chains of two residues (Tyr-23 and Arg-31) are in regions of PiTX-K alpha that probably interact with rapidly inactivating A-type K+ channels. The analogous residues in charybdotoxin are positioned differently on the toxin surface. Thus, the locations of Tyr-23 and Arg-31 side chains in PiTX-K alpha could explain why this toxin blocks A

CASEIN KINASE-MEDIATED PHOSPHORYLATION OF SERINE 839 IS NECESSARY FOR BASOLATERAL LOCALIZATION OF THE Ca2+-ACTIVATED NON-SELECTIVE CATION CHANNEL TRPM4

PubMed Central

Cerda, Oscar; Cáceres, Mónica; Park, Kang-Sik; Leiva-Salcedo, Elías; Romero, Aníbal; Varela, Diego

2014-01-01

TRPM4 is a Ca2+-activated non-selective cation channel expressed in a wide range of human tissues. TRPM4 participates in a variety of physiological processes such as T cell activation, myogenic vasoconstriction and allergic reactions. TRPM4 Ca2+ sensitivity is enhanced by calmodulin (CaM) and phosphathydilinositol 4, 5-biphosphate (PI(4,5)P2) binding, as well as, under certain conditions, PKC activation. However, information as to the mechanisms of modulation of this channel remain unknown, including direct identification of phosphorylation sites on TRPM4 and their role in channel features. Here, we use mass-spectrometric-based proteomic approaches (immunoprecipitation and tandem mass spectrometry), to unambiguously identify S839 as a phosphorylation site present on human TRPM4 expressed in a human cell line. Site-directed mutagenesis employing a serine to alanine mutation to eliminate phosphorylation, and a phospho-mimetic aspartate mutation, as well as biochemical and immunocytochemical experiments, revealed a role for S839 phosphorylation in the basolateral expression of TRPM4 channels in epithelial cells. Moreover, we demonstrated that casein kinase 1 (CK1) phosphorylates S839 and is responsible for the basolateral localization of TRPM4. PMID:25231975

Voltage Sensor Inactivation in Potassium Channels

PubMed Central

Bähring, Robert; Barghaan, Jan; Westermeier, Regina; Wollberg, Jessica

2012-01-01

In voltage-gated potassium (Kv) channels membrane depolarization causes movement of a voltage sensor domain. This conformational change of the protein is transmitted to the pore domain and eventually leads to pore opening. However, the voltage sensor domain may interact with two distinct gates in the pore domain: the activation gate (A-gate), involving the cytoplasmic S6 bundle crossing, and the pore gate (P-gate), located externally in the selectivity filter. How the voltage sensor moves and how tightly it interacts with these two gates on its way to adopt a relaxed conformation when the membrane is depolarized may critically determine the mode of Kv channel inactivation. In certain Kv channels, voltage sensor movement leads to a tight interaction with the P-gate, which may cause conformational changes that render the selectivity filter non-conductive (“P/C-type inactivation”). Other Kv channels may preferably undergo inactivation from pre-open closed-states during voltage sensor movement, because the voltage sensor temporarily uncouples from the A-gate. For this behavior, known as “preferential” closed-state inactivation, we introduce the term “A/C-type inactivation”. Mechanistically, P/C- and A/C-type inactivation represent two forms of “voltage sensor inactivation.” PMID:22654758

The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential

PubMed Central

Zamponi, Gerald W.; Striessnig, Joerg; Koschak, Alexandra

2015-01-01

Voltage-gated calcium channels are required for many key functions in the body. In this review, the different subtypes of voltage-gated calcium channels are described and their physiologic roles and pharmacology are outlined. We describe the current uses of drugs interacting with the different calcium channel subtypes and subunits, as well as specific areas in which there is strong potential for future drug development. Current therapeutic agents include drugs targeting L-type CaV1.2 calcium channels, particularly 1,4-dihydropyridines, which are widely used in the treatment of hypertension. T-type (CaV3) channels are a target of ethosuximide, widely used in absence epilepsy. The auxiliary subunit α2δ-1 is the therapeutic target of the gabapentinoid drugs, which are of value in certain epilepsies and chronic neuropathic pain. The limited use of intrathecal ziconotide, a peptide blocker of N-type (CaV2.2) calcium channels, as a treatment of intractable pain, gives an indication that these channels represent excellent drug targets for various pain conditions. We describe how selectivity for different subtypes of calcium channels (e.g., CaV1.2 and CaV1.3 L-type channels) may be achieved in the future by exploiting differences between channel isoforms in terms of sequence and biophysical properties, variation in splicing in different target tissues, and differences in the properties of the target tissues themselves in terms of membrane potential or firing frequency. Thus, use-dependent blockers of the different isoforms could selectively block calcium channels in particular pathologies, such as nociceptive neurons in pain states or in epileptic brain circuits. Of important future potential are selective CaV1.3 blockers for neuropsychiatric diseases, neuroprotection in Parkinson’s disease, and resistant hypertension. In addition, selective or nonselective T-type channel blockers are considered potential therapeutic targets in epilepsy, pain, obesity, sleep, and

The Kinetics and the Permeation Properties of Piezo Channels.

PubMed

Gnanasambandam, R; Gottlieb, P A; Sachs, F

2017-01-01

Piezo channels are eukaryotic, cation-selective mechanosensitive channels (MSCs), which show rapid activation and voltage-dependent inactivation. The kinetics of these channels are largely consistent across multiple cell types and different stimulation paradigms with some minor variability. No accessory subunits that associate with Piezo channels have been reported. They are homotrimers and each ∼300kD monomer has an N-terminal propeller blade-like mechanosensing module, which can confer mechanosensing capabilities on ASIC-1 (the trimeric non-MSC, acid-sensing ion channel-1) and a C-terminal pore module, which influences conductance, selectivity, and channel inactivation. Repeated stimulation can cause domain fracture and diffusion of these channels leading to synchronous loss of inactivation. The reconstituted channels spontaneously open only in asymmetric bilayers but lack inactivation. Mutations that cause hereditary xerocytosis alter PIEZO1 kinetics. The kinetics of the wild-type PIEZO1 and alterations thereof in mutants (M2225R, R2456K, and DhPIEZO1) are summarized in the form of a quantitative model and hosted online. The pore is permeable to alkali ions although Li + permeates poorly. Divalent cations, notably Ca 2+ , traverse the channel and inhibit the flux of monovalents. The large monovalent organic cations such as tetramethyl ammonium and tetraethyl ammonium can traverse the channel, but slowly, suggesting a pore diameter of ∼8Å, and the estimated in-plane area change upon opening is around 6-20nm 2 . Ruthenium red can enter the channel only from the extracellular side and seems to bind in a pocket close to residue 2496. Copyright © 2017 Elsevier Inc. All rights reserved.

Meroterpenoid Chrodrimanins Are Selective and Potent Blockers of Insect GABA-Gated Chloride Channels

PubMed Central

Ihara, Makoto; Ling, Yun; Yang, Xinling; Kai, Kenji; Hayashi, Hideo; Matsuda, Kazuhiko

2015-01-01

Meroterpenoid chrodrimanins, produced from Talaromyces sp. YO-2, are known to paralyze silkworm (Bombyx mori) larvae, but their target is unknown. We have investigated the actions of chrodrimanin B on ligand-gated ion channels of silkworm larval neurons using patch-clamp electrophysiology. Chrodrimanin B had no effect on membrane currents when tested alone at 1 μM. However, it completely blocked the γ-aminobutyric acid (GABA)-induced current and showed less pronounced actions on acetylcholine- and L-glutamate-induced currents, when delivered at 1 μM for 1 min prior to co-application with transmitter GABA. Thus, chrodrimanins were also tested on a wild-type isoform of the B. mori GABA receptor (GABAR) RDL using two-electrode voltage-clamp electrophysiology. Chrodrimanin B attenuated the peak current amplitude of the GABA response of RDL with an IC50 of 1.66 nM. The order of the GABAR-blocking potency of chrodrimanins B > D > A was in accordance with their reported insecticidal potency. Chrodrimanin B had no open channel blocking action when tested at 3 nM on the GABA response of RDL. Co-application with 3 nM chrodrimanin B shifted the GABA concentration response curve to a higher concentration and further increase of chrodrimanin B concentration to10 nM; it reduced maximum current amplitude of the GABA response, pointing to a high-affinity competitive action and a lower affinity non-competitive action. The A282S;T286V double mutation of RDL, which impairs the actions of fipronil, hardly affected the blocking action of chrodrimanin B, indicating a binding site of chrodrimanin B distinct from that of fipronil. Chrodrimanin B showed approximately 1,000-fold lower blocking action on human α1β2γ2 GABAR compared to RDL and thus is a selective blocker of insect GABARs. PMID:25902139

Evolutionary origins of mechanosensitive ion channels.

PubMed

Martinac, Boris; Kloda, Anna

2003-01-01

According to the recent revision, the universal phylogenetic tree is composed of three domains: Eukarya (eukaryotes), Bacteria (eubacteria) and Archaea (archaebacteria). Mechanosensitive (MS) ion channels have been documented in cells belonging to all three domains suggesting their very early appearance during evolution of life on Earth. The channels show great diversity in conductance, selectivity and voltage dependence, while sharing the property of being gated by mechanical stimuli exerted on cell membranes. In prokaryotes, MS channels were first documented in Bacteria followed by their discovery in Archaea. The finding of MS channels in archaeal cells helped to recognize and establish the evolutionary relationship between bacterial and archaeal MS channels and to show that this relationship extends to eukaryotic Fungi (Schizosaccharomyces pombe) and Plants (Arabidopsis thaliana). Similar to their bacterial and archaeal homologues, MS channels in eukaryotic cell-walled Fungi and Plants may serve in protecting the cellular plasma membrane from excessive dilation and rupture that may occur during osmotic stress. This review summarizes briefly some of the recent developments in the MS channel research field that may ultimately lead to elucidation of the biophysical and evolutionary principles underlying the mechanosensory transduction in living cells.