Ergodic secret message capacity of the wiretap channel with finite-rate feedback

KAUST Repository

Rezki, Zouheir; Khisti, Ashish J.; Alouini, Mohamed-Slim

2014-01-01

We study the secret message capacity of an ergodic block fading wiretap channel with partial channel state information at the transmitter and perfect channel state information at the receivers, under both a short term power constraint (STPC) and a long term power constraint (LTPC). We consider that in addition to the statistics of the main and the eavesdropper channel state information (CSI), the sender is provided by the legitimate receiver with a q-bit feedback, at the beginning of each coherence block, through an error-free public channel, with capacity q bits. We establish upper and lower bounds on the secrecy capacity. We show that the lower and the upper bounds coincide asymptotically as q → ∞. When applied to Rayleigh fading channels, we show that, a 4-bit feedback achieves about 90% of the secrecy capacity when perfect main CSI is available at the transmitter. Finally, asymptotic analysis at high and low Signal-to-Noise Ratio (SNR) is presented. It is found that the capacity is bounded at high-SNR, whereas at asymptotically low-SNR, the lower bounds and the upper bound scale linearly with SNR under STPC. Furthermore, subject to LTPC, the capacity at low-SNR is equal to the capacity of the main channel without secrecy constraint and with perfect CSI at both the transmitter and the receiver, under a mild condition on the fading statistics. We also show that a positive secrecy rate is achievable even when the feedback is at the end of each coherence block and q=1. © 2002-2012 IEEE.

On the ergodic secret message capacity of the wiretap channel with finite-rate feedback

KAUST Repository

Rezki, Zouheir

2012-07-01

We study the secret message capacity of an ergodic block fading wiretap channel with partial channel state information at the transmitter and perfect channel state information at the receivers. We consider that in addition to the statistics of the main and the eavesdropper channel state information (CSI), the sender is provided by the legitimate receiver with a q-bit feedback, at the beginning of each coherence block, through an error-free feedback channel, with capacity q bits. We establish upper and lower bounds on the secrecy capacity. We show that a positive secrecy rate is achievable even when the feedback is at the end of each coherence block and q = 1. We also show that the lower and the upper bounds coincide asymptotically as q → ∞. Finally, asymptotic analysis at high Signal-to-Noise Ratio (SNR) are presented where it is found that the capacity is bounded at high-SNR and present a simple suboptimal scalar quantizer that is capacity achieving, without the need of any numerical optimization, as q → ∞. When applied to Rayleigh fading channels, we show that, at high-SNR, a 4-bit feedback achieves 90% of the secrecy capacity when perfect main CSI is available at the transmitter. © 2012 IEEE.

On the ergodic secret message capacity of the wiretap channel with finite-rate feedback

KAUST Repository

Rezki, Zouheir; Khisti, Ashish J.; Alouini, Mohamed-Slim

2012-01-01

We study the secret message capacity of an ergodic block fading wiretap channel with partial channel state information at the transmitter and perfect channel state information at the receivers. We consider that in addition to the statistics of the main and the eavesdropper channel state information (CSI), the sender is provided by the legitimate receiver with a q-bit feedback, at the beginning of each coherence block, through an error-free feedback channel, with capacity q bits. We establish upper and lower bounds on the secrecy capacity. We show that a positive secrecy rate is achievable even when the feedback is at the end of each coherence block and q = 1. We also show that the lower and the upper bounds coincide asymptotically as q → ∞. Finally, asymptotic analysis at high Signal-to-Noise Ratio (SNR) are presented where it is found that the capacity is bounded at high-SNR and present a simple suboptimal scalar quantizer that is capacity achieving, without the need of any numerical optimization, as q → ∞. When applied to Rayleigh fading channels, we show that, at high-SNR, a 4-bit feedback achieves 90% of the secrecy capacity when perfect main CSI is available at the transmitter. © 2012 IEEE.

Secure Network Coding against Wiretapping and Byzantine Attacks

Directory of Open Access Journals (Sweden)

Qin Guo

2010-01-01

Full Text Available In wireless networks, an attacker can tune a receiver and tap the communication between two nodes. Whether or not some meaningful information is obtained by tapping a wireless connection depends on the transmission scheme. In this paper, we design some secure network coding by combining information-theoretic approaches with cryptographic approaches. It ensures that the wiretapper cannot get any meaningful information no matter how many channels are wiretapped. In addition, if each source packet is augmented with a hash symbol which is computed from a simple nonlinear polynomial function of the data symbols, then the probability of detecting the modification is very high.

Wiretapping End-to-End Encrypted VoIP Calls: Real-World Attacks on ZRTP

Directory of Open Access Journals (Sweden)

Schürmann Dominik

2017-07-01

Full Text Available Voice calls are still one of the most common use cases for smartphones. Often, sensitive personal information but also confidential business information is shared. End-to-end security is required to protect against wiretapping of voice calls. For such real-time communication, the ZRTP key-agreement protocol has been proposed. By verbally comparing a small number of on-screen characters or words, called Short Authentication Strings, the participants can be sure that no one is wiretapping the call. Since 2011, ZRTP is an IETF standard implemented in several VoIP clients.

Position-based coding and convex splitting for private communication over quantum channels

Science.gov (United States)

Wilde, Mark M.

2017-10-01

The classical-input quantum-output (cq) wiretap channel is a communication model involving a classical sender X, a legitimate quantum receiver B, and a quantum eavesdropper E. The goal of a private communication protocol that uses such a channel is for the sender X to transmit a message in such a way that the legitimate receiver B can decode it reliably, while the eavesdropper E learns essentially nothing about which message was transmitted. The ɛ -one-shot private capacity of a cq wiretap channel is equal to the maximum number of bits that can be transmitted over the channel, such that the privacy error is no larger than ɛ \\in (0,1). The present paper provides a lower bound on the ɛ -one-shot private classical capacity, by exploiting the recently developed techniques of Anshu, Devabathini, Jain, and Warsi, called position-based coding and convex splitting. The lower bound is equal to a difference of the hypothesis testing mutual information between X and B and the "alternate" smooth max-information between X and E. The one-shot lower bound then leads to a non-trivial lower bound on the second-order coding rate for private classical communication over a memoryless cq wiretap channel.

Authentication over Noisy Channels

OpenAIRE

Lai, Lifeng; Gamal, Hesham El; Poor, H. Vincent

2008-01-01

In this work, message authentication over noisy channels is studied. The model developed in this paper is the authentication theory counterpart of Wyner's wiretap channel model. Two types of opponent attacks, namely impersonation attacks and substitution attacks, are investigated for both single message and multiple message authentication scenarios. For each scenario, information theoretic lower and upper bounds on the opponent's success probability are derived. Remarkably, in both scenarios,...

On the Secrecy Capacity of MISO Visible Light Communication Channels

KAUST Repository

Arfaoui, Mohamed Amine; Rezki, Zouheir; Ghrayeb, Ali; Alouini, Mohamed-Slim

2017-01-01

We study the secrecy capacity of the multiple- input single-output (MISO) Gaussian wiretap visible light communication (VLC) channel. We study a typical VLC scenario with one transmitter, one legitimate receiver, and one eavesdropper. Specifically

On the secrecy capacity of the broadcast wiretap channel with imperfect channel state information

KAUST Repository

Hyadi, Amal

2014-12-01

In this paper, we consider secure broadcasting over fast fading channels. Assuming imperfect main channel state information (CSI) at the transmitter, we first provide an upper and a lower bounds on the ergodic secrecy capacity when a common message is broadcasted to multiple legitimate receivers in the presence of one eavesdropper. For this case, we show that the secrecy rate is limited by the legitimate receiver having, on average, the worst main channel link. Then, we present an expression for the achievable secrecy sum-rate when each legitimate receiver is interested in an independent message. The special cases of high SNR, perfect and no-main CSI are also analyzed. Numerical results are presented to illustrate the obtained results for the case of independent but not necessarily identically distributed Rayleigh fading channels.

On the ergodic secrecy capacity of the wiretap channel under imperfect main channel estimation

KAUST Repository

Rezki, Zouheir; Khisti, Ashish J.; Alouini, Mohamed-Slim

2011-01-01

imperfect main channel estimation at the transmitter. Inner and outer bounds on the ergodic secrecy capacity are derived for a class of independent identically distributed (i.i.d.) fading channels. The achievable rate is a simple on-off scheme using a

RFID Ownership Transfer with Positive Secrecy Capacity Channels

Directory of Open Access Journals (Sweden)

Jorge Munilla

2016-12-01

Full Text Available RFID ownership transfer protocols (OTPs transfer tag ownership rights. Recently, there has been considerable interest in such protocols; however, guaranteeing privacy for symmetric-key settings without trusted third parties (TTPs is a challenge still unresolved. In this paper, we address this issue and show that it can be solved by using channels with positive secrecy capacity. We implement these channels with noisy tags and provide practical values, thus proving that perfect secrecy is theoretically possible. We then define a communication model that captures spatiotemporal events and describe a first example of symmetric-key based OTP that: (i is formally secure in the proposed communication model and (ii achieves privacy with a noisy tag wiretap channel without TTPs.

Secure Degrees of Freedom Regions of Multiple Access and Interference Channels: The Polytope Structure

OpenAIRE

Xie, Jianwei; Ulukus, Sennur

2014-01-01

The sum secure degrees of freedom (s.d.o.f.) of two fundamental multi-user network structures, the K-user Gaussian multiple access (MAC) wiretap channel and the K-user interference channel (IC) with secrecy constraints, have been determined recently as K(K-1)/(K(K-1)+1) [1,2] and K(K-1)/(2K-1) [3,4], respectively. In this paper, we determine the entire s.d.o.f. regions of these two channel models. The converse for the MAC follows from a middle step in the converse of [1,2]. The converse for t...

On the diversity-multiplexing tradeoff of secret-key agreement over multiple-antenna channels

KAUST Repository

Zorgui, Marwen

2014-09-01

We consider secret-key agreement with public discussion over Rayleigh fading quasi-static channels. First, the secret-key diversity gain and the secret-key multiplexing gain are defined. Then, the secret-key diversity multiplexing tradeoff (DMT) is established. The eavesdropper is shown to \\'steal\\' only transmit antennas. We show that likewise the DMT without secrecy constraint, the secret-key DMT is the same either with or without full channel state information (CSI) at the transmitter (CSI-T). This insensitivity of secret-key DMT toward CSI-T highlights a fundamental difference between secret-key agreement and the wiretap channel whose secret DMT depends crucially on CSI-T. Several secret-key DMT-achieving schemes are presented in case of full CSI-T.

On the diversity-multiplexing tradeoff of secret-key agreement over multiple-antenna channels

KAUST Repository

Zorgui, Marwen; Rezki, Zouheir; Alomair, Basel; Alouini, Mohamed-Slim

2014-01-01

We consider secret-key agreement with public discussion over Rayleigh fading quasi-static channels. First, the secret-key diversity gain and the secret-key multiplexing gain are defined. Then, the secret-key diversity multiplexing tradeoff (DMT) is established. The eavesdropper is shown to 'steal' only transmit antennas. We show that likewise the DMT without secrecy constraint, the secret-key DMT is the same either with or without full channel state information (CSI) at the transmitter (CSI-T). This insensitivity of secret-key DMT toward CSI-T highlights a fundamental difference between secret-key agreement and the wiretap channel whose secret DMT depends crucially on CSI-T. Several secret-key DMT-achieving schemes are presented in case of full CSI-T.

On the secrecy capacity of the broadcast wiretap channel with limited CSI feedback

KAUST Repository

Hyadi, Amal

2016-10-27

In this paper, we investigate the problem of secure broadcasting over block-fading channels with limited channel knowledge at the transmitter. More particularly, we analyze the effect of having imperfect channel state information (CSI) via a finite rate feedback on the throughput of a broadcast channel where the transmission is intended for multiple legitimate receivers in the presence of an eavesdropper. First, we partially characterize the ergodic secrecy capacity of the system when the source broadcasts the same information to all the receivers, i.e., common message transmission. Then, we look at the independent messages case, where the transmitter broadcasts multiple independent messages to the legitimate receivers. For this case, we present lower and upper bounds on the ergodic secrecy sum-capacity. In both scenarios, we show that the proposed lower and upper bounds coincide asymptotically as the capacity of the feedback links becomes large, hence, fully characterizing the secrecy capacity in this case.

On the secrecy capacity of the broadcast wiretap channel with limited CSI feedback

KAUST Repository

Hyadi, Amal; Rezki, Zouheir; Alouini, Mohamed-Slim

2016-01-01

In this paper, we investigate the problem of secure broadcasting over block-fading channels with limited channel knowledge at the transmitter. More particularly, we analyze the effect of having imperfect channel state information (CSI) via a finite rate feedback on the throughput of a broadcast channel where the transmission is intended for multiple legitimate receivers in the presence of an eavesdropper. First, we partially characterize the ergodic secrecy capacity of the system when the source broadcasts the same information to all the receivers, i.e., common message transmission. Then, we look at the independent messages case, where the transmitter broadcasts multiple independent messages to the legitimate receivers. For this case, we present lower and upper bounds on the ergodic secrecy sum-capacity. In both scenarios, we show that the proposed lower and upper bounds coincide asymptotically as the capacity of the feedback links becomes large, hence, fully characterizing the secrecy capacity in this case.

Identification of the functional binding pocket for compounds targeting small-conductance Ca2+-activated potassium channels

Science.gov (United States)

Zhang, Miao; Pascal, John M.; Schumann, Marcel; Armen, Roger S.; Zhang, Ji-fang

2012-01-01

Small- and intermediate-conductance Ca2+-activated potassium channels, activated by Ca2+-bound calmodulin, play an important role in regulating membrane excitability. These channels are also linked to clinical abnormalities. A tremendous amount of effort has been devoted to developing small molecule compounds targeting these channels. However, these compounds often suffer from low potency and lack of selectivity, hindering their potentials for clinical use. A key contributing factor is the lack of knowledge of the binding site(s) for these compounds. Here we demonstrate by X-ray crystallography that the binding pocket for the compounds of the 1-EBIO class is located at the calmodulin-channel interface. We show that, based on structure data and molecular docking, mutations of the channel can effectively change the potency of these compounds. Our results provide insight into the molecular nature of the binding pocket and its contribution to the potency and selectivity of the compounds of the 1-EBIO class. PMID:22929778

THREE DIMENSIONAL CFD MODELLING OF FLOW STRUCTURE IN COMPOUND CHANNELS

Directory of Open Access Journals (Sweden)

Usman Ghani

2010-10-01

Full Text Available The computational modeling of three dimensional flows in a meandering compound channel has been performed in this research work. The flow calculations are performed by solving 3D steady state continuity and Reynolds averaged Navier-Stokes equations. The turbulence closure is approximated with standard - turbulence model. The model equations are solved numerically with a general purpose software package. A comprehensive validation of the simulated results against the experimental data and a demonstration that the software used in this study has matured enough for investigating practical engineering problems are the major contributions of this paper. The model was initially validated. This was achieved by computing streamwise point velocities at different depths of various sections and depth averaged velocities at three cross sections along the main channel and comparing these results with experimental data. After the validation of the model, predictions were made for different flow parameters including velocity contours at the surface, pressure distribution, turbulence intensity etc. The results gave an overall understanding of these flow variables in meandering channels. The simulation also established the good prediction capability of the standard - turbulence model for flows in compound channels.

Effects of flow depth and wall roughness on turbulence in compound channels

International Nuclear Information System (INIS)

Prinos, P.; Townsend, R.; Tavoularis, S.

1985-01-01

Current methods for estimating discharge in compound channels often lead to large errors. The error is largely due to momentum transfer mechanism (MTM) generated in the junction regions of the flow field (between adjacent deep and shallow zones). The MTM adversely affects system conveyance, particularly when the velocity differential between the deep and shallow zones is large. Improved prediction methods, therefore, will necessarily reflect the MTM's presence and its effect on the compound flow field. The mechanism's influence on system hydraulics is best examined by analysing the related turbulence characteristics in the junction zones of the compound section. Townsend reported increased turbulence levels in the junction region between a main channel and its shallower flood plain zone and Elsawy, McKee and McKeogh found that observed normal turbulent stresses in a similar region were of the same order of magnitude as the apparent shear stress on the junction's vertical interface plane. The objective of the present study is to measure turbulent stresses in the junction region of a symmetrical compound open channel and examine their dependence on relative depth and relative boundary roughness. Further details of this phase of the larger study are presented elsewhere. (author)

DETERMINATION OF CHLORINATED ORGANIC COMPOUNDS IN THE MAIN DRAINAGE CHANNEL OF KONYA

Directory of Open Access Journals (Sweden)

Mehmet Emin AYDIN

2000-03-01

Full Text Available The main drainage channel of Konya collects drainage waters from farmlands of Konya and discharges to the salt lake. Since there is not any city municipal sewarage system in Konya sewage of the city also discharged to the main drainage channel. Along the channel, farmers use the channels water for irrigation purposes. Therefore a through examination of wastewater and determination of chlorinated compounds were necessary. In this research, analyses were carried by gas chromatography (GC on water samples collected hourly, daily and monthly from the channel.

Identification of the functional binding pocket for compounds targeting small-conductance Ca²⁺-activated potassium channels.

Science.gov (United States)

Zhang, Miao; Pascal, John M; Schumann, Marcel; Armen, Roger S; Zhang, Ji-Fang

2012-01-01

Small- and intermediate-conductance Ca(2+)-activated potassium channels, activated by Ca(2+)-bound calmodulin, have an important role in regulating membrane excitability. These channels are also linked to clinical abnormalities. A tremendous amount of effort has been devoted to developing small molecule compounds targeting these channels. However, these compounds often suffer from low potency and lack of selectivity, hindering their potential for clinical use. A key contributing factor is the lack of knowledge of the binding site(s) for these compounds. Here we demonstrate by X-ray crystallography that the binding pocket for the compounds of the 1-ethyl-2-benzimidazolinone (1-EBIO) class is located at the calmodulin-channel interface. We show that, based on structure data and molecular docking, mutations of the channel can effectively change the potency of these compounds. Our results provide insight into the molecular nature of the binding pocket and its contribution to the potency and selectivity of the compounds of the 1-EBIO class.

A numerical study of the complex flow structure in a compound meandering channel

Science.gov (United States)

Moncho-Esteve, Ignacio J.; García-Villalba, Manuel; Muto, Yasu; Shiono, Koji; Palau-Salvador, Guillermo

2018-06-01

In this study, we report large eddy simulations of turbulent flow in a periodic compound meandering channel for three different depth conditions: one in-bank and two overbank conditions. The flow configuration corresponds to the experiments of Shiono and Muto (1998). The predicted mean streamwise velocities, mean secondary motions, velocity fluctuations, turbulent kinetic energy as well as mean flood flow angle to meandering channel are in good agreement with the experimental measurements. We have analyzed the flow structure as a function of the inundation level, with particular emphasis on the development of the secondary motions due to the interaction between the main channel and the floodplain flow. Bed shear stresses have been also estimated in the simulations. Floodplain flow has a significant impact on the flow structure leading to significantly different bed shear stress patterns within the main meandering channel. The implications of these results for natural compound meandering channels are also discussed.

Shear and shearless Lagrangian structures in compound channels

Science.gov (United States)

Enrile, F.; Besio, G.; Stocchino, A.

2018-03-01

Transport processes in a physical model of a natural stream with a composite cross-section (compound channel) are investigated by means of a Lagrangian analysis based on nonlinear dynamical system theory. Two-dimensional free surface Eulerian experimental velocity fields of a uniform flow in a compound channel form the basis for the identification of the so-called Lagrangian Coherent Structures. Lagrangian structures are recognized as the key features that govern particle trajectories. We seek for two particular class of Lagrangian structures: Shear and shearless structures. The former are generated whenever the shear dominates the flow whereas the latter behave as jet-cores. These two type of structures are detected as ridges and trenches of the Finite-Time Lyapunov Exponents fields, respectively. Besides, shearlines computed applying the geodesic theory of transport barriers mark Shear Lagrangian Coherent Structures. So far, the detection of these structures in real experimental flows has not been deeply investigated. Indeed, the present results obtained in a wide range of the controlling parameters clearly show a different behaviour depending on the shallowness of the flow. Shear and Shearless Lagrangian Structures detected from laboratory experiments clearly appear as the flow develops in shallow conditions. The presence of these Lagrangian Structures tends to fade in deep flow conditions.

Ion channeling study of defects in multicomponent semiconductor compounds

International Nuclear Information System (INIS)

Turos, A.; Nowicki, L.; Stonert, A.

2002-01-01

Compound semiconductor crystals are of great technological importance as basic materials for production of modern opto- and microelectronic devices. Ion implantation is one of the principal techniques for heterostructures processing. This paper reports the results of the study of defect formation and transformation in binary and ternary semiconductor compounds subjected to ion implantation with ions of different mass and energy. The principal analytical technique was He-ion channeling. The following materials were studied: GaN and InGaN epitaxial layers. First the semi empirical method of channeling spectra analysis for ion implanted multicomponent single crystal was developed. This method was later complemented by the more sophisticated method based on the Monte Carlo simulation of channeling spectra. Next, the damage buildup in different crystals and epitaxial layers as a function of the implantation dose was studied for N, Mg, Te, and Kr ions. The influence of the substrate temperature on the defect transformations was studied for GaN epitaxial layers implanted with Mg ions. Special attention was devoted to the study of growth conditions of InGaN/GaN/sapphire heterostructures, which are important component of the future blue laser diodes. In-atom segregation and tetragonal distortion of the epitaxial layer were observed and characterized. Next problem studied was the incorporation of hydrogen atoms in GaAs and GaN. Elastic recoil detection (ERDA) and nuclear reaction analysis (NRA) were applied for the purpose. (author)

CFTR chloride channel as a molecular target of anthraquinone compounds in herbal laxatives

Science.gov (United States)

Yang, Hong; Xu, Li-na; He, Cheng-yan; Liu, Xin; Fang, Rou-yu; Ma, Tong-hui

2011-01-01

Aim: To clarify whether CFTR is a molecular target of intestinal fluid secretion caused by the anthraquinone compounds from laxative herbal plants. Methods: A cell-based fluorescent assay to measure I− influx through CFTR chloride channel. A short-circuit current assay to measure transcellular Cl− current across single layer FRT cells and freshly isolated colon mucosa. A closed loop experiment to measure colon fluid secretion in vivo. Results: Anthraquinone compounds rhein, aloe-emodin and 1,8-dihydroxyanthraquinone (DHAN) stimulated I− influx through CFTR chloride channel in a dose-dependent manner in the presence of physiological concentration of cAMP. In the short-circuit current assay, the three compound enhanced Cl− currents in epithelia formed by CFTR-expressing FRT cells with EC50 values of 73±1.4, 56±1.7, and 50±0.5μmol/L, respectively, and Rhein also enhanced Cl− current in freshly isolated rat colonic mucosa with a similar potency. These effects were completely reversed by the CFTR selective blocker CFTRinh-172. In in vivo closed loop experiments, rhein 2 mmol/L stimulated colonic fluid accumulation that was largely blocked by CFTRinh-172. The anthraquinone compounds did not elevate cAMP level in cultured FRT cells and rat colonic mucosa, suggesting a direct effect on CFTR activity. Conclusion: Natural anthraquinone compounds in vegetable laxative drugs are CFTR potentiators that stimulated colonic chloride and fluid secretion. Thus CFTR chloride channel is a molecular target of vegetable laxative drugs. PMID:21602836

Flow discharge prediction in compound channels using linear genetic programming

Science.gov (United States)

Azamathulla, H. Md.; Zahiri, A.

2012-08-01

SummaryFlow discharge determination in rivers is one of the key elements in mathematical modelling in the design of river engineering projects. Because of the inundation of floodplains and sudden changes in river geometry, flow resistance equations are not applicable for compound channels. Therefore, many approaches have been developed for modification of flow discharge computations. Most of these methods have satisfactory results only in laboratory flumes. Due to the ability to model complex phenomena, the artificial intelligence methods have recently been employed for wide applications in various fields of water engineering. Linear genetic programming (LGP), a branch of artificial intelligence methods, is able to optimise the model structure and its components and to derive an explicit equation based on the variables of the phenomena. In this paper, a precise dimensionless equation has been derived for prediction of flood discharge using LGP. The proposed model was developed using published data compiled for stage-discharge data sets for 394 laboratories, and field of 30 compound channels. The results indicate that the LGP model has a better performance than the existing models.

Gradually varied flow in compound open channels; Flujo gradualmente variado en canales de seccion compuesta

Energy Technology Data Exchange (ETDEWEB)

Sotela Avila, Gilberto [Universidad Nacional Autonoma de Mexico (Mexico)

2001-03-01

The author shows that the computation of gradually-varied-flow profiles in prismatic compound channels involves the solution of the dynamic equation, but using the compound channel Froude number defined by Blalock and Sturm. The same equation is used for non-prismatic channels by dividing the channel into short reaches and carrying the computation step by step through an iterative process. [Spanish] El autor demuestra que los perfiles del flujo gradualmente variado en canales prismaticos de seccion compuesta se pueden determinar mediante la integracion de la llamada ecuacion dinamica, pero usando el numero de Froude definido por Blalock y Sturm para este tipo de canales. Cuando no son prismaticos, tambien se aplica la ecuacion de la energia por tramos y el calculo sigue un proceso iterativo una vez definidos los tirantes criticos multiples y la zona en que se desarrolla el perfil.

The Diversity-Multiplexing Tradeoff of Secret-Key Agreement over Multiple-Antenna Channels

KAUST Repository

Zorgui, Marwen; Rezki, Zouheir; Alomair, Basel; Alouini, Mohamed-Slim

2015-01-01

We study the problem of secret-key agreement between two legitimate parties, Alice and Bob, in presence an of eavesdropper Eve. There is a public channel with unlimited capacity that is available to the legitimate parties and is also observed by Eve. Our focus is on Rayleigh fading quasi-static channels. The legitimate receiver and the eavesdropper are assumed to have perfect channel knowledge of their channels. We study the system in the high-power regime. First, we define the secret-key diversity gain and the secret-key multiplexing gain. Second, we establish the secret-key diversity multiplexing tradeoff (DMT) under no channel state information (CSI) at the transmitter (CSI-T). The eavesdropper is shown to “steal” only transmit antennas. We show that, likewise the DMT without secrecy constraint, the secret-key DMT is the same either with or without full channel state information at the transmitter. This insensitivity of secret-key DMT toward CSI-T features a fundamental difference between secret-key agreement and the wiretap channel, in which secret DMT depends heavily on CSI-T. Finally, we present several secret-key DMT-achieving schemes in case of full CSI-T. We argue that secret DMT-achieving schemes are also key DMT-achieving. Moreover, we show formally that artificial noise (AN), likewise zero-forcing (ZF), is DMT-achieving. We also show that the public feedback channel improves the outage performance without having any effect on the DMT.

The Diversity-Multiplexing Tradeoff of Secret-Key Agreement over Multiple-Antenna Channels

KAUST Repository

Zorgui, Marwen

2015-10-26

We study the problem of secret-key agreement between two legitimate parties, Alice and Bob, in presence an of eavesdropper Eve. There is a public channel with unlimited capacity that is available to the legitimate parties and is also observed by Eve. Our focus is on Rayleigh fading quasi-static channels. The legitimate receiver and the eavesdropper are assumed to have perfect channel knowledge of their channels. We study the system in the high-power regime. First, we define the secret-key diversity gain and the secret-key multiplexing gain. Second, we establish the secret-key diversity multiplexing tradeoff (DMT) under no channel state information (CSI) at the transmitter (CSI-T). The eavesdropper is shown to “steal” only transmit antennas. We show that, likewise the DMT without secrecy constraint, the secret-key DMT is the same either with or without full channel state information at the transmitter. This insensitivity of secret-key DMT toward CSI-T features a fundamental difference between secret-key agreement and the wiretap channel, in which secret DMT depends heavily on CSI-T. Finally, we present several secret-key DMT-achieving schemes in case of full CSI-T. We argue that secret DMT-achieving schemes are also key DMT-achieving. Moreover, we show formally that artificial noise (AN), likewise zero-forcing (ZF), is DMT-achieving. We also show that the public feedback channel improves the outage performance without having any effect on the DMT.

On the finite-SNR diversity-multiplexing tradeoff of zero-forcing transmit scheme under secrecy constraint

KAUST Repository

Rezki, Zouheir

2011-06-01

In this paper, we address the finite Signal-to-Noise Ratio (SNR) Diversity-Multiplexing Tradeoff (DMT) of the Multiple Input Multiple Output (MIMO) wiretap channel, where a Zero-Forcing (ZF) transmit scheme, that intends to send the secret information in the orthogonal space of the eavesdropper channel, is used. First, we introduce the secret multiplexing gain at finite-SNR that generalizes the definition at high-SNR. Then, we provide upper and lower bounds on the outage probability under secrecy constraint, from which secret diversity gain estimates of ZF are derived. Through asymptotic analysis, we show that the upper bound underestimates the secret diversity gain, whereas the lower bound is tight at high-SNR, and thus its related diversity gain estimate is equal to the actual asymptotic secret diversity gain of the Multiple-Input Multiple-Output (MIMO) wiretap channel. © 2011 IEEE.

Secure diversity-multiplexing tradeoff of zero-forcing transmit scheme at finite-SNR

KAUST Repository

Rezki, Zouheir

2012-04-01

In this paper, we address the finite Signal-to-Noise Ratio (SNR) Diversity-Multiplexing Tradeoff (DMT) of the Multiple Input Multiple Output (MIMO) wiretap channel, where a Zero-Forcing (ZF) transmit scheme, that intends to send the secret information in the orthogonal space of the eavesdropper channel, is used. First, we introduce the secrecy multiplexing gain at finite-SNR that generalizes the definition at high-SNR. Then, we provide upper and lower bounds on the outage probability under secrecy constraint, from which secrecy diversity gain estimates of ZF are derived. Through asymptotic analysis, we show that the upper bound underestimates the secrecy diversity gain, whereas the lower bound is tight at high-SNR, and thus its related diversity gain estimate is equal to the actual asymptotic secrecy diversity gain of the MIMO wiretap channel. © 2012 IEEE.

Quantum photonic network and physical layer security.

Science.gov (United States)

Sasaki, Masahide; Endo, Hiroyuki; Fujiwara, Mikio; Kitamura, Mitsuo; Ito, Toshiyuki; Shimizu, Ryosuke; Toyoshima, Morio

2017-08-06

Quantum communication and quantum cryptography are expected to enhance the transmission rate and the security (confidentiality of data transmission), respectively. We study a new scheme which can potentially bridge an intermediate region covered by these two schemes, which is referred to as quantum photonic network. The basic framework is information theoretically secure communications in a free space optical (FSO) wiretap channel, in which an eavesdropper has physically limited access to the main channel between the legitimate sender and receiver. We first review a theoretical framework to quantify the optimal balance of the transmission efficiency and the security level under power constraint and at finite code length. We then present experimental results on channel characterization based on 10 MHz on-off keying transmission in a 7.8 km terrestrial FSO wiretap channel.This article is part of the themed issue 'Quantum technology for the 21st century'. © 2017 The Author(s).

Entrance channel dependent light-charged particle emission of the 156Er compound

International Nuclear Information System (INIS)

Liang, J.F.; Bierman, J.D.; Kelly, M.P.; Sonzogni, A.A.; Vandenbosch, R.; van Schagen, J.P.S.

1996-01-01

Light-charged particle decay from the 156 Er compound nucleus, populated by 12 C+ 144 Sm and 60 Ni+ 96 Zr at the same excitation energy, were measured in coincidence with the evaporation residues. The high energy slope of charged particle spectra for the 60 Ni-induced reaction is steeper than for the 12 C-induced reaction. Model calculations including particle evaporation during compound nucleus formation result in good agreement with the data. This suggests that the difference in the charged particle spectra between the two entrance channels is due to a longer formation time in the 60 Ni-induced reaction. 14 refs., 3 figs

LES Modeling with Experimental Validation of a Compound Channel having Converging Floodplain

Science.gov (United States)

Mohanta, Abinash; Patra, K. C.

2018-04-01

Computational fluid dynamics (CFD) is often used to predict flow structures in developing areas of a flow field for the determination of velocity field, pressure, shear stresses, effect of turbulence and others. A two phase three-dimensional CFD model along with the large eddy simulation (LES) model is used to solve the turbulence equation. This study aims to validate CFD simulations of free surface flow or open channel flow by using volume of fluid method by comparing the data observed in hydraulics laboratory of the National Institute of Technology, Rourkela. The finite volume method with a dynamic sub grid scale was carried out for a constant aspect ratio and convergence condition. The results show that the secondary flow and centrifugal force influence flow pattern and show good agreement with experimental data. Within this paper over-bank flows have been numerically simulated using LES in order to predict accurate open channel flow behavior. The LES results are shown to accurately predict the flow features, specifically the distribution of secondary circulations both for in-bank channels as well as over-bank channels at varying depth and width ratios in symmetrically converging flood plain compound sections.

General anesthetic octanol and related compounds activate wild-type and delF508 cystic fibrosis chloride channels

OpenAIRE

Marcet, Brice; Becq, Frédéric; Norez, Caroline; Delmas, Patrick; Verrier, Bernard

2004-01-01

Cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel is defective during cystic fibrosis (CF). Activators of the CFTR Cl− channel may be useful for therapy of CF. Here, we demonstrate that a range of general anesthetics like normal-alkanols (n-alkanols) and related compounds can stimulate the Cl− channel activity of wild-type CFTR and delF508-CFTR mutant.The effects of n-alkanols like octanol on CFTR activity were measured by iodide (125I) efflux and patch-clamp techniques o...

Extracts and compounds active on TRP ion channels from Waldheimia glabra, a ritual medicinal plant from Himalaya.

Science.gov (United States)

Giorgi, Annamaria; Bassoli, Angela; Borgonovo, Gigliola; Panseri, Sara; Manzo, Alessandra; Pentimalli, Daniela; Schiano Moriello, Aniello; De Petrocellis, Luciano

2017-08-15

Waldheimia glabra (Decne.) Regel is a wild plant from the Himalayan Mountains, commonly known as Smooth Ground Daisy. This plant is traditionally used by local populations in religious rituals (incense) or in traditional herbal medicine to treat skin diseases, headache, joint pain and fever. In literature few data are available on the investigation of this aromatic plant. The present work aims at deepening knowledge about the chemical composition of W. glabra extracts and incense, as well as its activity on TRP ion channels. Extracts and incense of W. glabra were analyzed by using HS-SPME GC/MS, GC/MS and NMR analysis. Tests on the activity of W. glabra extracts and isolated compounds (+)-ludartin 1 and B-ring-homo-tonghaosu 2 on TRP channels were also performed. Some extracts and pure compounds from W. glabra showed an interesting activity in terms of efficacy and potency on rat TRPA1, an ion channel involved in several sensory mechanisms, including pungency, environmental irritation and pain perception. Activity is discussed and compared with that of other known TRPA1 natural agonists with different chemical structures. All compounds showed only a negligible inhibition activity on rat TRPM8 ion channel. Our findings demonstrate that W. glabra is involved in the receptor activation mechanism and therefore represents a new natural product potentially useful in pharmaceutical and agrifood research. Copyright © 2017 Elsevier GmbH. All rights reserved.

Wireless Physical Layer Security with CSIT Uncertainty

KAUST Repository

Hyadi, Amal

2017-09-01

Recent years have been marked by an enormous growth of wireless communication networks and an extensive use of wireless applications. In return, this phenomenal expansion induced more concerns about the privacy and the security of the users. Physical layer security is one of the most promising solutions that were proposed to enhance the security of next generation wireless systems. The fundamental idea behind this technique is to exploit the randomness and the fluctuations of the wireless channel to achieve security without conditional assumptions on the computational capabilities of the eavesdropper. In fact, while these elements have traditionally been associated with signal deterioration, physical layer security uses them to ensure the confidentiality of the users. Nevertheless, these technical virtues rely heavily on perhaps idealistic channel state information assumptions. In that regard, the aim of this thesis is to look at the physical layer security paradigm from the channel uncertainty perspective. In particular, we discuss the ergodic secrecy capacity of different wiretap channels when the transmitter is hampered by the imperfect knowledge of the channel state information (CSI). We consider two prevalent causes of uncertainty for the CSI at transmitter (CSIT); either an error of estimation occurs at the transmitter and he can only base his coding and the transmission strategies on a noisy version of the CSI, or the CSI feedback link has a limited capacity and the legitimate receivers can only inform the transmitter about the quantized CSI. We investigate both the single-user multiple-input multiple-output (MIMO) wiretap channel and the multi-user broadcast wiretap channel. In the latter scenario, we distinguish between two situations: multiple messages transmission and common message transmission. We also discuss the broadcast channel with confidential messages (BCCM) where the transmitter has one common message to be transmitted to two users and one

Large Eddy Simulation of turbulent flows in compound channels with a finite element code

International Nuclear Information System (INIS)

Xavier, C.M.; Petry, A.P.; Moeller, S.V.

2011-01-01

This paper presents the numerical investigation of the developing flow in a compound channel formed by a rectangular main channel and a gap in one of the sidewalls. A three dimensional Large Eddy Simulation computational code with the classic Smagorinsky model is introduced, where the transient flow is modeled through the conservation equations of mass and momentum of a quasi-incompressible, isothermal continuous medium. Finite Element Method, Taylor-Galerkin scheme and linear hexahedrical elements are applied. Numerical results of velocity profile show the development of a shear layer in agreement with experimental results obtained with Pitot tube and hot wires. (author)

PERFORMANCE ANALYSIS OF COOPERATION SCHEMES IN EAVESDROPPER ASSISTED RELAY CHANNEL

Directory of Open Access Journals (Sweden)

Vaibhav Kumar Gupta

2014-06-01

Full Text Available The prominence of the wireless communication has been urging the monotonically increasing demand of security and privacy. In wireless systems, the notion of perfect secrecy of information with respect to illegitimate nodes can be ensured via physical layer security (PLS techniques. Unfortunately, they can be made less effective if source- eavesdropper wiretap channel is better than the main source-receiver channel. The various node cooperation schemes can be employed to combat this limitation where a relay node assists the communication to improve the performance significantly. In this paper, a four node wireless communication system consisting of a source, a destination, a relay and an eavesdropper as wire-tapper has been considered. The performance of the traditional cooperation schemes in terms of secrecy rate has been investigated with a different scenario where relay node helps the eavesdropper to deteriorate the secrecy rate. In addition, since legitimate receiver can overhear the transmission of relay, it favours the achievable secrecy rate. We formulate an analytical expression of conditional secrecy outage probability for the investigated system. From the obtained simulation results, it has been observed that secrecy rate is monotonically increases with path loss index. Furthermore, the proper selection of the system parameters leads to enhance the secrecy performance of the system even if relay pertains to degrade the performance. Amplify-and-forward, cooperation, decode-and-Forward, secrecy rate, relay.

On Secrecy Outage of Relay Selection in Underlay Cognitive Radio Networks over Nakagami-m Fading Channels

KAUST Repository

Lei, Hongjiang; Zhang, Huan; Ansari, Imran Shafique; Ren, Zhi; Pan, Gaofeng; Qaraqe, Khalid A.; Alouini, Mohamed-Slim

2017-01-01

In this paper, the secrecy outage performance of an underlay cognitive decode-and-forward relay network over independent but not necessarily identical distributed (i.n.i.d) Nakagami-m fading channels is investigated, in which the secondary user transmitter communicates with the secondary destination via relays, and an eavesdropper attempts to overhear the information. Based on whether the channel state information (CSI) of the wiretap links is available or not, we analyze the secrecy outage performance with optimal relay selection (ORS) and suboptimal relay selection (SRS) schemes, and multiple relays combining scheme (MRC) scheme is considered for comparison purpose. The exact and asymptotic closed-form expressions for the secrecy outage probability with three different relay selection schemes are derived and verified by Monte-Carlo simulations. The numerical results illustrate that ORS scheme always outperforms SRS and MRC schemes, and SRS scheme is better than MRC scheme in the lower fading parameters scenario. Furthermore, through asymptotic analysis, we find that these three different schemes achieve the same secrecy diversity order, which is determined by the number of the relays, and the fading parameters of the links among the relays and the destination.

On Secrecy Outage of Relay Selection in Underlay Cognitive Radio Networks over Nakagami-m Fading Channels

KAUST Repository

Lei, Hongjiang

2017-10-02

In this paper, the secrecy outage performance of an underlay cognitive decode-and-forward relay network over independent but not necessarily identical distributed (i.n.i.d) Nakagami-m fading channels is investigated, in which the secondary user transmitter communicates with the secondary destination via relays, and an eavesdropper attempts to overhear the information. Based on whether the channel state information (CSI) of the wiretap links is available or not, we analyze the secrecy outage performance with optimal relay selection (ORS) and suboptimal relay selection (SRS) schemes, and multiple relays combining scheme (MRC) scheme is considered for comparison purpose. The exact and asymptotic closed-form expressions for the secrecy outage probability with three different relay selection schemes are derived and verified by Monte-Carlo simulations. The numerical results illustrate that ORS scheme always outperforms SRS and MRC schemes, and SRS scheme is better than MRC scheme in the lower fading parameters scenario. Furthermore, through asymptotic analysis, we find that these three different schemes achieve the same secrecy diversity order, which is determined by the number of the relays, and the fading parameters of the links among the relays and the destination.

Study on a resource allocation scheme in multi-hop MIMO-OFDM systems over lognormal-rayleigh compound channels

Directory of Open Access Journals (Sweden)

LIU Jun

2015-10-01

Full Text Available For new generation wireless communication networks,this paper studies the optimization of the capacity and end-to-end throughput of the MIMO-OFDM based multi-hop relay systems.A water-filling power allocation method is proposed to improve the channel capacity and the throughput of the MIMO-OFDM system based multi-hop relay system in the Lognormal-Rayleigh shadowing compound channels.Simulations on the capacity and throughput show that the water-filling algorithm can improve the system throughput effectively in the MIMO-OFDM multi-hop relay system.

On the Secrecy Capacity of MISO Visible Light Communication Channels

KAUST Repository

Arfaoui, Mohamed Amine

2017-02-07

We study the secrecy capacity of the multiple- input single-output (MISO) Gaussian wiretap visible light communication (VLC) channel. We study a typical VLC scenario with one transmitter, one legitimate receiver, and one eavesdropper. Specifically, we compute the achievable secrecy rate for various input signaling distributions, including the truncated generalized normal (TGN) and uniform distributions. The transmitter is equipped with multiple light sources, while the legitimate and unauthorized receivers are each equipped with a single photodetector. We analyze the achievable secrecy rates via transmit beamforming and artificial noise. In addition, both zero-forcing beamforming and robust beamforming are considered. In the former case, the location of the eavesdropper is assumed to be known, whereas in the latter case, the location of the eavesdropper is unknown. Our numerical results show that the secrecy rate achieved by the TGN distribution is significantly improved as compared to those achieved by the truncated Gaussian and uniform distributions, for both zero-forcing beamforming and robust beamforming. We also derive an upper bound on the achievable secrecy capacity that we used to assess the closeness of the achievable secrecy rates to the derived bound.

Investigating the Lateral Mixing Coefficient in a Compound Channel with Emergent Vegetation over the Floodplain

Directory of Open Access Journals (Sweden)

Hossein hamidifar

2017-02-01

Full Text Available Introduction: Water quality control is very important for people, animals and plants. Predicting the spread of contaminants is important for managing and protecting rivers and streams to the balance of the ecosystem. Pollutants are introduced into waterways, though a variety of sources such as point and non-point sources. Under steady state conditions, where longitudinal mixing is not significant, studying the lateral mixing is essential in evaluating the influence of pollutants on water quality. Lateral or transverse mixing is the hydraulic process by which a plume of contaminant spreads laterally and dilutes. In water quality management, the transverse mixing is more significant than either vertical or longitudinal dispersion, especially, when dealing with the release of wastes from point sources. Hence, a wide range of field, laboratory and numerical modelling approaches, including laboratory and field measurements, and analytical and numerical investigations have been developed, to quantify the lateral mixing coefficient. However, most of the researchers have ignored the effects of vegetation on the lateral mixing process in their studies. Many studies have shown that the flow characteristics through vegetation are different from those in non-vegetated waterways. For example, laboratory studies have revealed that flow velocity and large-scale turbulence tend to be greatly decreased within a plant canopy, because the resistance to flow by the vegetation. Also, vegetation affects the transport of dissolved and particulate material, such as sediment, nutrients and pollutants. In this study, the effect of the floodplain vegetation on lateral mixing coefficient in compound channels is investigated experimentally. Also, a comparison is made between the results of the present study with those obtained by previous researchers. Materials and Methods: Experiments were carried out in a laboratory flume 18m long, 0.9m wide and 0.6m high with an

Involvement of transient receptor potential A1 channel in algesic and analgesic actions of the organic compound limonene.

Science.gov (United States)

Kaimoto, T; Hatakeyama, Y; Takahashi, K; Imagawa, T; Tominaga, M; Ohta, T

2016-08-01

TRPA1 is a Ca-permeable nonselective cation channel expressed in sensory neurons and acts as a nocisensor. Recent reports show that some monoterpenes, a group of naturally occurring organic compounds, modulate TRP channel activity. Here, we report that limonene, being contained in citrus fruits and mushrooms, shows a unique bimodal action on TRPA1 channel. We examine the effects of limonene on sensory neurons from wild-type, TRPV1- and TRPA1-gene-deficient mice and on heterologously expressed channels in vitro. Molecular determinants were identified with using mutated channels. Cellular excitability is monitored with ratiometric Ca imaging. Nociceptive and analgesic actions of limonene are also examined in vivo. In wild-type mouse sensory neurons, limonene increased the intracellular Ca(2+) concentration ([Ca(2+) ]i ), which was inhibited by selective inhibitors of TRPA1 but not TRPV1. Limonene-responsive neurons highly corresponded to TRPA1 agonist-sensitive ones. Limonene failed to stimulate sensory neurons from the TRPA1 (-/-) mouse. Heterologously expressed mouse TRPA1 was activated by limonene. Intraplantar injection of limonene elicited acute pain, which was significantly less in TRPA1 (-/-) mice. Systemic administration of limonene reduced nociceptive behaviours evoked by H2 O2 . In both heterologously and endogenously expressed TRPA1, a low concentration of limonene significantly inhibited H2 O2 -induced TRPA1 activation. TRPA1 activation by limonene was abolished in H2 O2 -insensitive cysteine-mutated channels. Topically applied limonene stimulates TRPA1, resulting in elicitation of acute pain, but its systemic application inhibits nociception induced by oxidative stress. Because limonene is a safe compound, it may be utilized for pain control due to its inhibition of TRPA1 channels. What does this study add: Limonene, a monoterpene in essential oils of various plants, has been known for its antitumor and anti-inflammatory properties. However, molecular

Fission via compound states and JπK A. Bohr's channels: what we can learn from recent studies with slow neutrons

Directory of Open Access Journals (Sweden)

Furman W.I.

2012-02-01

Full Text Available Last data on angular correlations of fission fragments from slow (s-wave neutron induced binary fission of spin-aligned nuclei 235U are discussed in the context of JπK A. Bohrs channels. Special attention is paid to K = 0 channel. Reasons for its suppression are specified for compound nucleus states of negative parity. A brief overview of recent data on T-odd angular correlations in ternary and binary (with emission of a third particle, a neutron or γ-quantum fission induced by slow polarized neutrons is presented. On the basis of the developed theoretical approach it is shown that a valuable information on JπK fission channels at scission point can be inferred from these T-odd angular correlations.

Computation of gradually varied flow in compound open channel ...

Indian Academy of Sciences (India)

The flow of water in an open channel can be treated as steady, gradually varied flow for ... channel between two nodes is treated as a single reach to calculate the loss ... dition at control points and (iii) critical depth is also required to verify the ...

Clofilium inhibits Slick and Slack potassium channels.

Science.gov (United States)

de Los Angeles Tejada, Maria; Stolpe, Kathleen; Meinild, Anne-Kristine; Klaerke, Dan A

2012-01-01

Slick and Slack high-conductance potassium channels have been recently discovered, and are found in the central nervous system and in the heart. Both channels are activated by Na(+) and Cl(-), and Slick channels are also inhibited by adenosine triphospate (ATP). An important role of setting the resting membrane potential and controlling the basal excitability of neurons has been suggested for these channels. In addition, no specific blockers for these channels are known up to the present. With the purpose of studying the pharmacological characteristics of Slick and Slack channels, the effects of exposure to the antiarrhythmic compound clofilium were evaluated. Clofilium was able to modulate the activity of Slick and Slack channels effectively, with a stronger effect on Slack than Slick channels. In order to evaluate the pharmacological behavior of Slick and Slack channels further, 38 commonly used potassium channel blockers were tested. Screening of these compounds did not reveal any modulators of Slick and Slack channels, except for clofilium. The present study provides a first approach towards elucidating the pharmacological characteristics of Slick and Slack channels and could be the basis for future studies aimed at developing potent and specific blockers and activators for these channels.

Ion channeling study of defects in compound crystals using Monte Carlo simulations

Science.gov (United States)

Turos, A.; Jozwik, P.; Nowicki, L.; Sathish, N.

2014-08-01

Ion channeling is a well-established technique for determination of structural properties of crystalline materials. Defect depth profiles have been usually determined basing on the two-beam model developed by Bøgh (1968) [1]. As long as the main research interest was focused on single element crystals it was considered as sufficiently accurate. New challenge emerged with growing technological importance of compound single crystals and epitaxial heterostructures. Overlap of partial spectra due to different sublattices and formation of complicated defect structures makes the two beam method hardly applicable. The solution is provided by Monte Carlo computer simulations. Our paper reviews principal aspects of this approach and the recent developments in the McChasy simulation code. The latter made it possible to distinguish between randomly displaced atoms (RDA) and extended defects (dislocations, loops, etc.). Hence, complex defect structures can be characterized by the relative content of these two components. The next refinement of the code consists of detailed parameterization of dislocations and dislocation loops. Defect profiles for variety of compound crystals (GaN, ZnO, SrTiO3) have been measured and evaluated using the McChasy code. Damage accumulation curves for RDA and extended defects revealed non monotonous defect buildup with some characteristic steps. Transition to each stage is governed by the different driving force. As shown by the complementary high resolution XRD measurements lattice strain plays here the crucial role and can be correlated with the concentration of extended defects.

Private channels in plant-pollinator mutualisms

Science.gov (United States)

Chen, Chun; Hossaert-McKey, Martine

2010-01-01

Volatile compounds often mediate plant-pollinator interactions, and may promote specialization in plant-pollinator relationships, notably through private channels of unusual compounds. Nevertheless, the existence of private channels, i.e., the potential for exclusive communication via unique signals and receptors, is still debated in the literature. Interactions between figs and their pollinating wasps offer opportunities for exploring this concept. Several experiments have demonstrated that chemical mediation is crucial in ensuring the encounter between figs and their species-specific pollinators. Indeed, chemical messages emitted by figs are notably species- and developmental stage-specific, making them reliable cues for the pollinator. In most cases, the species-specificity of wasp attraction is unlikely to result from the presence of a single specific compound. Nevertheless, a recent paper on the role of scents in the interaction between Ficus semicordata and its pollinating wasp Ceratosolen gravelyi showed that a single compound, 4-methylanisole, is the main signal compound in the floral scent, and is sufficient by itself to attract the obligate pollinator. Mainly focusing on these results, we propose here that a floral scent can act as a private channel, attracting only the highly specific pollinator. PMID:20484975

State-dependent compound inhibition of Nav1.2 sodium channels using the FLIPR Vm dye: on-target and off-target effects of diverse pharmacological agents.

Science.gov (United States)

Benjamin, Elfrida R; Pruthi, Farhana; Olanrewaju, Shakira; Ilyin, Victor I; Crumley, Gregg; Kutlina, Elena; Valenzano, Kenneth J; Woodward, Richard M

2006-02-01

Voltage-gated sodium channels (NaChs) are relevant targets for pain, epilepsy, and a variety of neurological and cardiac disorders. Traditionally, it has been difficult to develop structure-activity relationships for NaCh inhibitors due to rapid channel kinetics and state-dependent compound interactions. Membrane potential (Vm) dyes in conjunction with a high-throughput fluorescence imaging plate reader (FLIPR) offer a satisfactory 1st-tier solution. Thus, the authors have developed a FLIPR Vm assay of rat Nav1.2 NaCh. Channels were opened by addition of veratridine, and Vm dye responses were measured. The IC50 values from various structural classes of compounds were compared to the resting state binding constant (Kr)and inactivated state binding constant (Ki)obtained using patch-clamp electrophysiology (EP). The FLIPR values correlated with Ki but not Kr. FLIPRIC50 values fell within 0.1-to 1.5-fold of EP Ki values, indicating that the assay generally reports use-dependent inhibition rather than resting state block. The Library of Pharmacologically Active Compounds (LOPAC, Sigma) was screened. Confirmed hits arose from diverse classes such as dopamine receptor antagonists, serotonin transport inhibitors, and kinase inhibitors. These data suggest that NaCh inhibition is inherent in a diverse set of biologically active molecules and may warrant counterscreening NaChs to avoid unwanted secondary pharmacology.

Channelling phenomenon in the gamma irradiated Benzo-quinone and other compounds observed under the scanning electron microscope

International Nuclear Information System (INIS)

Suleiman, Y.M.

1984-01-01

Scanning Electron Microscope (S.E.M.), has been used to examine the gamma irradiated pure crystals of Benzo-quinone and other compounds in the polycrystaline form. After gamma irradiation, shallow lines (channels) were observed on the crystal's surfaces when the crystal layers arrangements are parallel to the photons beam direction. Holes were also observed when those layers of the crystals are in the nonparallel case. The phenomenon has been studied and analysed in connected with the H-atom bonds disruption, and H-atoms migration through the crystal's layers. (author)

Mechanism of HERG potassium channel inhibition by tetra-n-octylammonium bromide and benzethonium chloride

International Nuclear Information System (INIS)

Long, Yan; Lin, Zuoxian; Xia, Menghang; Zheng, Wei; Li, Zhiyuan

2013-01-01

Tetra-n-octylammonium bromide and benzethonium chloride are synthetic quaternary ammonium salts that are widely used in hospitals and industries for the disinfection and surface treatment and as the preservative agent. Recently, the activities of HERG channel inhibition by these compounds have been found to have potential risks to induce the long QT syndrome and cardiac arrhythmia, although the mechanism of action is still elusive. This study was conducted to investigate the mechanism of HERG channel inhibition by these compounds by using whole-cell patch clamp experiments in a CHO cell line stably expressing HERG channels. Tetra-n-octylammonium bromide and benzethonium chloride exhibited concentration-dependent inhibitions of HERG channel currents with IC 50 values of 4 nM and 17 nM, respectively, which were also voltage-dependent and use-dependent. Both compounds shifted the channel activation I–V curves in a hyperpolarized direction for 10–15 mV and accelerated channel activation and inactivation processes by 2-fold. In addition, tetra-n-octylammonium bromide shifted the inactivation I–V curve in a hyperpolarized direction for 24.4 mV and slowed the rate of channel deactivation by 2-fold, whereas benzethonium chloride did not. The results indicate that tetra-n-octylammonium bromide and benzethonium chloride are open-channel blockers that inhibit HERG channels in the voltage-dependent, use-dependent and state-dependent manners. - Highlights: ► Tetra-n-octylammonium and benzethonium are potent HERG channel inhibitors. ► Channel activation and inactivation processes are accelerated by the two compounds. ► Both compounds are the open-channel blockers to HERG channels. ► HERG channel inhibition by both compounds is use-, voltage- and state dependent. ► The in vivo risk of QT prolongation needs to be studied for the two compounds

Mechanism of HERG potassium channel inhibition by tetra-n-octylammonium bromide and benzethonium chloride

Energy Technology Data Exchange (ETDEWEB)

Long, Yan; Lin, Zuoxian [Key Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530 (China); Xia, Menghang; Zheng, Wei [National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892 (United States); Li, Zhiyuan, E-mail: li_zhiyuan@gibh.ac.cn [Key Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530 (China)

2013-03-01

Tetra-n-octylammonium bromide and benzethonium chloride are synthetic quaternary ammonium salts that are widely used in hospitals and industries for the disinfection and surface treatment and as the preservative agent. Recently, the activities of HERG channel inhibition by these compounds have been found to have potential risks to induce the long QT syndrome and cardiac arrhythmia, although the mechanism of action is still elusive. This study was conducted to investigate the mechanism of HERG channel inhibition by these compounds by using whole-cell patch clamp experiments in a CHO cell line stably expressing HERG channels. Tetra-n-octylammonium bromide and benzethonium chloride exhibited concentration-dependent inhibitions of HERG channel currents with IC{sub 50} values of 4 nM and 17 nM, respectively, which were also voltage-dependent and use-dependent. Both compounds shifted the channel activation I–V curves in a hyperpolarized direction for 10–15 mV and accelerated channel activation and inactivation processes by 2-fold. In addition, tetra-n-octylammonium bromide shifted the inactivation I–V curve in a hyperpolarized direction for 24.4 mV and slowed the rate of channel deactivation by 2-fold, whereas benzethonium chloride did not. The results indicate that tetra-n-octylammonium bromide and benzethonium chloride are open-channel blockers that inhibit HERG channels in the voltage-dependent, use-dependent and state-dependent manners. - Highlights: ► Tetra-n-octylammonium and benzethonium are potent HERG channel inhibitors. ► Channel activation and inactivation processes are accelerated by the two compounds. ► Both compounds are the open-channel blockers to HERG channels. ► HERG channel inhibition by both compounds is use-, voltage- and state dependent. ► The in vivo risk of QT prolongation needs to be studied for the two compounds.

Voltage-gated sodium channels as targets for pyrethroid insecticides.

Science.gov (United States)

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.

On the secrecy capacity of the broadcast wiretap channel with imperfect channel state information

KAUST Repository

Hyadi, Amal; Rezki, Zouheir; Khisti, Ashish J.; Alouini, Mohamed-Slim

2014-01-01

for the achievable secrecy sum-rate when each legitimate receiver is interested in an independent message. The special cases of high SNR, perfect and no-main CSI are also analyzed. Numerical results are presented to illustrate the obtained results for the case

Simulation study of ballistic spin-MOSFET devices with ferromagnetic channels based on some Heusler and oxide compounds

Science.gov (United States)

Graziosi, Patrizio; Neophytou, Neophytos

2018-02-01

Newly emerged materials from the family of Heuslers and complex oxides exhibit finite bandgaps and ferromagnetic behavior with Curie temperatures much higher than even room temperature. In this work, using the semiclassical top-of-the-barrier FET model, we explore the operation of a spin-MOSFET that utilizes such ferromagnetic semiconductors as channel materials, in addition to ferromagnetic source/drain contacts. Such a device could retain the spin polarization of injected electrons in the channel, the loss of which limits the operation of traditional spin transistors with non-ferromagnetic channels. We examine the operation of four material systems that are currently considered some of the most prominent known ferromagnetic semiconductors: three Heusler-type alloys (Mn2CoAl, CrVZrAl, and CoVZrAl) and one from the oxide family (NiFe2O4). We describe their band structures by using data from DFT (Density Functional Theory) calculations. We investigate under which conditions high spin polarization and significant ION/IOFF ratio, two essential requirements for the spin-MOSFET operation, are both achieved. We show that these particular Heusler channels, in their bulk form, do not have adequate bandgap to provide high ION/IOFF ratios and have small magnetoconductance compared to state-of-the-art devices. However, with confinement into ultra-narrow sizes down to a few nanometers, and by engineering their spin dependent contact resistances, they could prove promising channel materials for the realization of spin-MOSFET transistor devices that offer combined logic and memory functionalities. Although the main compounds of interest in this paper are Mn2CoAl, CrVZrAl, CoVZrAl, and NiFe2O4 alone, we expect that the insight we provide is relevant to other classes of such materials as well.

The effect of background absorption on the compound cross-section in resonance scattering

International Nuclear Information System (INIS)

Frenkel, A.

1976-01-01

The effect of channel-channel correlations in the compound cross-section is studied in a model of a resonance above a compound background characterized by equal absorption in all open channels. A general rule which cannot be derived from unitarity alone is proved for the fluctuating cross-section. It provides new understanding of level-level correlations in scattering through compound nucleus states. (author)

Chloride channels as tools for developing selective insecticides.

Science.gov (United States)

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

General anesthetic octanol and related compounds activate wild-type and delF508 cystic fibrosis chloride channels.

Science.gov (United States)

Marcet, Brice; Becq, Frédéric; Norez, Caroline; Delmas, Patrick; Verrier, Bernard

2004-03-01

1. Cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel is defective during cystic fibrosis (CF). Activators of the CFTR Cl(-) channel may be useful for therapy of CF. Here, we demonstrate that a range of general anesthetics like normal-alkanols (n-alkanols) and related compounds can stimulate the Cl(-) channel activity of wild-type CFTR and delF508-CFTR mutant. 2. The effects of n-alkanols like octanol on CFTR activity were measured by iodide ((125)I) efflux and patch-clamp techniques on three distinct cellular models: (1). CFTR-expressing Chinese hamster ovary cells, (2). human airway Calu-3 epithelial cells and (3). human airway JME/CF15 epithelial cells which express the delF508-CFTR mutant. 3. Our data show for the first time that n-alkanols activate both wild-type CFTR and delF508-CFTR mutant. Octanol stimulated (125)I efflux in a dose-dependent manner in CFTR-expressing cells (wild-type and delF508) but not in cell lines lacking CFTR. (125)I efflux and Cl(-) currents induced by octanol were blocked by glibenclamide but insensitive to 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, as expected for a CFTR Cl(-) current. 4. CFTR activation by octanol was neither due to cell-to-cell uncoupling properties of octanol nor to an intracellular cAMP increase. CFTR activation by octanol requires phosphorylation by protein kinase-A (PKA) since it was prevented by H-89, a PKA inhibitor. 5. n-Alkanols chain length was an important determinant for channel activation, with rank order of potencies: 1-heptanoloctanoloctanol<1-decanol. Our findings may be of valuable interest for developing novel therapeutic strategies for CF.

Plant Natural compounds with antibacterial activity towards common pathogens of pond-cultured channel catfish (Ictalurus punctatus).

Science.gov (United States)

Schrader, Kevin K

2010-07-01

The bacteria Edwardsiella ictaluri and Flavobacterium columnare cause enteric septicemia and columnaris disease, respectively, in channel catfish (Ictalurus punctatus). Natural therapeutants may provide an alternative to current management approaches used by producers. In this study, a rapid bioassay identified plant compounds as potential therapeutants. Chelerythrine chloride and ellagic acid were the most toxic toward E. ictaluri, with 24-h IC50 of 7.3 mg/L and 15.1 mg/L, respectively, and MIC of 2.1 mg/L and 6.5 mg/L, respectively. Chelerythrine chloride, ellagic acid, β-glycyrrhetinic acid, sorgoleone, and wogonin were the most toxic towards two genomovars of F. columnare, and wogonin had the strongest antibacterial activity (MIC = 0.3 mg/L).

On the dynamics of compound bedforms in high-energy tidal channels: field observations in the German Bight and the Danish Wadden Sea

Science.gov (United States)

Ernstsen, Verner B.; Winter, Christian; Becker, Marius; Bartholdy, Jesper

2010-05-01

Tidal inlets are a common feature along much of the world's coastlines. They interrupt the alongshore continuity of shoreline processes, and by being exposed to both wave and current forcing, tidal inlets belong to the morphologically most dynamic and complex coastal systems on Earth. The tidal channels in these inlets are characterized by high flow velocities and, accordingly, the channel beds are typically sandy and covered with bedforms. The bedform fields in nature are often complex systems with larger primary-bedforms superimposed by smaller secondary-bedforms (cf. Bartholdy et al., 2002). There is a considerable amount of detailed field investigations on the dynamics of primary-bedforms at various temporal scales, ranging from short- to long-term tide-related cycles to flood hydrographs to seasonality. However, Julien et al. (2002) stated that a composite analysis of primary- and secondary-bedforms is recommended for future studies on resistance to flow. Such knowledge on the behaviour of compound bedforms is still deficient. In this study, we combine the findings on the dynamics of primary- and secondary-bedform height from detailed field investigations carried out in two high-energy tidal channels during 2007 and 2008: the Knudedyb tidal inlet channel in the Danish Wadden Sea and the Innenjade tidal channel in the Jade Bay, German Bight (both survey areas being ebb-dominated). We provide process-based explanations of the bedform behaviour and present a conceptual model of compound bedform dynamics. The conducted field investigations comprised repetitive, simultaneous measurements of high-resolution swath bathymetry (using a multibeam echosounder system) and flow velocity (using an acoustic Doppler current profiler) in combination with detailed spatial mapping of bed material characteristics (from grab sampling of bed material). For an objective and discrete analysis of primary- and secondary-bedforms a modified version of the bedform tracking tool

Electrophysiological characterisation of KCNQ channel modulators

DEFF Research Database (Denmark)

Schrøder, R.L

Potassium (K+) ion channels are ubiquitously expressed in mammalian cells, and each channel serves a precise physiological role due to its specific biophysical characteristics and expression pattern. A few K+ channels are targets for certain drugs, and in this thesis it is suggested that the KCNQ K......+ channels may be targets for neuroprotective, anti-epileptic and anti-nociceptive compounds. The importance of these channels is underscored by the fact that four out of five KCNQ channel subtypes are involved in severe human diseases. However, the pharmacology of the KCNQ channels is yet poorly understood...... as these channels were identified only recently. Therefore, there is a need for understanding the biophysical behavior and pharmacology of these ion channels. KCNQ channels belong to the group of voltage-activated K+ channels. The subfamily consists of KCNQ1-5, which is primarily expressed in the CNS, heart, ear...

Compounded natural convection enhancement in a vertical parallel-plate channel

Energy Technology Data Exchange (ETDEWEB)

Andreozzi, Assunta [Dipartimento di Energetica, Termofluidodinamica Applicata e Condizionamenti Ambientali, Universita degli Studi di Napoli Federico II, Piazzale Tecchio 80, 80125 Napoli (Italy); Campo, Antonio [Department of Mechanical Engineering, The University of Vermont, 33 Colchester Ave., Burlington, VT 05405 (United States); Manca, Oronzio [Dipartimento di Ingegneria Aerospaziale e Meccanica, Seconda Universita degli Studi di Napoli, via Roma 29, Aversa (CE) 81031 (Italy)

2008-06-15

This paper addresses the natural convection behavior of air when heated in single vertical, parallel-plate channels. To enhance the heat transfer two passive schemes are combined: (1) an equidistant short plate is inserted at the inlet and (2) two parallel, colinear insulated plates are appended at the exit. The channel plates are symmetrically heated with a uniform heat flux. The computational procedure is made by solving the full elliptic Navier-Stokes and energy equations with the finite-volume methodology in an I-type computational domain that is much larger than the physical domain. Within the framework of a ''proof-of-concept'' the controlling Grashof number based on the heated plate height ranges between 10{sup 3} and 10{sup 6}. The numerical velocity, pressure and temperature fields are post-processed to compute the quantities of engineering interest such as the induced mass flow rate, the pressure at the channel mid-plane and the temperature along the plates. In addition, the Nusselt number and the average Nusselt number, both based on the heated plate height, are presented in graphical form. At the end, optimal channel configurations expressed in terms of the highest average Nusselt number are obtained for the pair of pre-assigned Grashof numbers. (author)

Molecular Docking Analysis of Ginger Active Compound on Transient Receptor Potential Cation Channel Subfamily V Member 1 (TRPV1

Directory of Open Access Journals (Sweden)

Fifteen Aprila Fajrin

2018-02-01

Full Text Available Ginger had been reported to ameliorate painful diabetic neuropathy (PDN in an animal model. Gingerol and shogaol were active compounds of ginger that potentially act on transient receptor potential cation channel subfamily V member 1 (TRPV1, a key receptor in PDN. This study aims to predict the binding of gingerol and shogaol to TRPV1 using an in silico model. The ligands of the docking study were 3 chemical compounds of each gingerol and shogaol, i.e. 6-shogaol, 8-shogaol, 10-shogaol, 6-gingerol, 8 gingerol and 10-gingerol. Capsaicin, a TRPV1 agonist, was used as a native ligand. The TRPV1 structure was taken from Protein Data Bank (ID 3J9J. The docking analysis was performed using Autodock Vina. The result showed that among the ginger active compounds, 6-shogaol had the strongest binding energy (-7.10 kcal/mol to TRPV1. The 6-shogaol lacked the potential hydrogen bond to Ile265 of TRPV1 protein, which capsacin had. However, it's binding energy towards TRPV1 was not significantly different compared to capsaicin. Therefore, 6-shogaol had potential to be developed as a treatment for PDN.

Quantum communication under channel uncertainty

International Nuclear Information System (INIS)

Noetzel, Janis Christian Gregor

2012-01-01

This work contains results concerning transmission of entanglement and subspaces as well as generation of entanglement in the limit of arbitrary many uses of compound- and arbitrarily varying quantum channels (CQC, AVQC). In both cases, the channel is described by a set of memoryless channels. Only forward communication between one sender and one receiver is allowed. A code is said to be ''good'' only, if it is ''good'' for every channel out of the set. Both settings describe a scenario, in which sender and receiver have only limited channel knowledge. For different amounts of information about the channel available to sender or receiver, coding theorems are proven for the CQC. For the AVQC, both deterministic and randomised coding schemes are considered. Coding theorems are proven, as well as a quantum analogue of the Ahlswede-dichotomy. The connection to zero-error capacities of stationary memoryless quantum channels is investigated. The notion of symmetrisability is defined and used for both classes of channels.

Smart multi-channel two-dimensional micro-gas chromatography for rapid workplace hazardous volatile organic compounds measurement.

Science.gov (United States)

Liu, Jing; Seo, Jung Hwan; Li, Yubo; Chen, Di; Kurabayashi, Katsuo; Fan, Xudong

2013-03-07

We developed a novel smart multi-channel two-dimensional (2-D) micro-gas chromatography (μGC) architecture that shows promise to significantly improve 2-D μGC performance. In the smart μGC design, a non-destructive on-column gas detector and a flow routing system are installed between the first dimensional separation column and multiple second dimensional separation columns. The effluent from the first dimensional column is monitored in real-time and decision is then made to route the effluent to one of the second dimensional columns for further separation. As compared to the conventional 2-D μGC, the greatest benefit of the smart multi-channel 2-D μGC architecture is the enhanced separation capability of the second dimensional column and hence the overall 2-D GC performance. All the second dimensional columns are independent of each other, and their coating, length, flow rate and temperature can be customized for best separation results. In particular, there is no more constraint on the upper limit of the second dimensional column length and separation time in our architecture. Such flexibility is critical when long second dimensional separation is needed for optimal gas analysis. In addition, the smart μGC is advantageous in terms of elimination of the power intensive thermal modulator, higher peak amplitude enhancement, simplified 2-D chromatogram re-construction and potential scalability to higher dimensional separation. In this paper, we first constructed a complete smart 1 × 2 channel 2-D μGC system, along with an algorithm for automated control/operation of the system. We then characterized and optimized this μGC system, and finally employed it in two important applications that highlight its uniqueness and advantages, i.e., analysis of 31 workplace hazardous volatile organic compounds, and rapid detection and identification of target gas analytes from interference background.

Quantum communication under channel uncertainty

Energy Technology Data Exchange (ETDEWEB)

Noetzel, Janis Christian Gregor

2012-09-06

This work contains results concerning transmission of entanglement and subspaces as well as generation of entanglement in the limit of arbitrary many uses of compound- and arbitrarily varying quantum channels (CQC, AVQC). In both cases, the channel is described by a set of memoryless channels. Only forward communication between one sender and one receiver is allowed. A code is said to be ''good'' only, if it is ''good'' for every channel out of the set. Both settings describe a scenario, in which sender and receiver have only limited channel knowledge. For different amounts of information about the channel available to sender or receiver, coding theorems are proven for the CQC. For the AVQC, both deterministic and randomised coding schemes are considered. Coding theorems are proven, as well as a quantum analogue of the Ahlswede-dichotomy. The connection to zero-error capacities of stationary memoryless quantum channels is investigated. The notion of symmetrisability is defined and used for both classes of channels.

KCNQ4 channel activation by BMS-204352 and retigabine

DEFF Research Database (Denmark)

Schrøder, Rikke Louise K.; Jespersen, Thomas; Christophersen, P

2001-01-01

Activation of potassium channels generally reduces cellular excitability, making potassium channel openers potential drug candidates for the treatment of diseases related to hyperexcitabilty such as epilepsy, neuropathic pain, and neurodegeneration. Two compounds, BMS-204352 and retigabine, prese...

HCN Channels Modulators: The Need for Selectivity

Science.gov (United States)

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

KATP Channels in the Cardiovascular System.

Science.gov (United States)

Foster, Monique N; Coetzee, William A

2016-01-01

KATP channels are integral to the functions of many cells and tissues. The use of electrophysiological methods has allowed for a detailed characterization of KATP channels in terms of their biophysical properties, nucleotide sensitivities, and modification by pharmacological compounds. However, even though they were first described almost 25 years ago (Noma 1983, Trube and Hescheler 1984), the physiological and pathophysiological roles of these channels, and their regulation by complex biological systems, are only now emerging for many tissues. Even in tissues where their roles have been best defined, there are still many unanswered questions. This review aims to summarize the properties, molecular composition, and pharmacology of KATP channels in various cardiovascular components (atria, specialized conduction system, ventricles, smooth muscle, endothelium, and mitochondria). We will summarize the lessons learned from available genetic mouse models and address the known roles of KATP channels in cardiovascular pathologies and how genetic variation in KATP channel genes contribute to human disease. Copyright © 2016 the American Physiological Society.

New Trends in Cancer Therapy: Targeting Ion Channels and Transporters

Directory of Open Access Journals (Sweden)

Annarosa Arcangeli

2010-04-01

Full Text Available The expression and activity of different channel types mark and regulate specific stages of cancer establishment and progression. Blocking channel activity impairs the growth of some tumors, both in vitro and in vivo, which opens a new field for pharmaceutical research. However, ion channel blockers may produce serious side effects, such as cardiac arrhythmias. For instance, Kv11.1 (hERG1 channels are aberrantly expressed in several human cancers, in which they control different aspects of the neoplastic cell behaviour. hERG1 blockers tend to inhibit cancer growth. However they also retard the cardiac repolarization, thus lengthening the electrocardiographic QT interval, which can lead to life-threatening ventricular arrhythmias. Several possibilities exist to produce less harmful compounds, such as developing specific drugs that bind hERG1 channels in the open state or disassemble the ion channel/integrin complex which appears to be crucial in certain stages of neoplastic progression. The potential approaches to improve the efficacy and safety of ion channel targeting in oncology include: (1 targeting specific conformational channel states; (2 finding ever more specific inhibitors, including peptide toxins, for channel subtypes mainly expressed in well-identified tumors; (3 using specific ligands to convey traceable or cytotoxic compounds; (4 developing channel blocking antibodies; (5 designing new molecular tools to decrease channel expression in selected cancer types. Similar concepts apply to ion transporters such as the Na+/K+ pump and the Na+/H+ exchanger. Pharmacological targeting of these transporters is also currently being considered in anti-neoplastic therapy.

Potential Antifreeze Compounds in Present-Day Martian Seepage Groundwater

Directory of Open Access Journals (Sweden)

Jiin-Shuh Jean

2008-01-01

Full Text Available Is the recently found seepage groundwater on Mars pure H2O, or mixed with salts and other antifreeze compounds? Given the surface conditions of Mars, it is unlikely that pure water could either exist in its liquid state or have shaped Mars¡¦ fluid erosional landforms (gullies, channels, and valley networks. More likely is that Mars¡¦ seepage groundwater contains antifreeze and salt compounds that resist freezing and suppress evaporation. This model better accounts for Mars¡¦ enigmatic surface erosion. This paper suggests 17 antifreeze compounds potentially present in Martian seepage groundwater. Given their liquid state and physical properties, triethylene glycol, diethylene glycol, ethylene glycol, and 1,3-propylene glycol are advanced as the most likely candidate compounds. This paper also explores how a mixing of glycol or glycerol with salts in the Martian seepage groundwater may have lowered water¡¦s freezing point and raised its boiling point, with consequences that created fluid gully and channel erosion. Ethylene glycol and related hydrocarbon compounds have been identified in Martian and other interstellar meteorites. We suggest that these compounds and their proportions to water be included for detection in future explorations.

Single-shot secure quantum network coding on butterfly network with free public communication

Science.gov (United States)

Owari, Masaki; Kato, Go; Hayashi, Masahito

2018-01-01

Quantum network coding on the butterfly network has been studied as a typical example of quantum multiple cast network. We propose a secure quantum network code for the butterfly network with free public classical communication in the multiple unicast setting under restricted eavesdropper’s power. This protocol certainly transmits quantum states when there is no attack. We also show the secrecy with shared randomness as additional resource when the eavesdropper wiretaps one of the channels in the butterfly network and also derives the information sending through public classical communication. Our protocol does not require verification process, which ensures single-shot security.

Modulation of ERG channels by XE991

DEFF Research Database (Denmark)

Elmedyb, Pernille; Calloe, Kirstine; Schmitt, Nicole

2007-01-01

In neuronal tissue, KCNQ2-5 channels conduct the physiologically important M-current. In some neurones, the M-current may in addition be conducted partly by ERG potassium channels, which have widely overlapping expression with the KCNQ channel subunits. XE991 and linopiridine are known to be stan......In neuronal tissue, KCNQ2-5 channels conduct the physiologically important M-current. In some neurones, the M-current may in addition be conducted partly by ERG potassium channels, which have widely overlapping expression with the KCNQ channel subunits. XE991 and linopiridine are known...... to be standard KCNQ potassium channel blockers. These compounds have been used in many different tissues as specific pharmacological tools to discern native currents conducted by KCNQ channels from other potassium currents. In this article, we demonstrate that ERG1-2 channels are also reversibly inhibited by XE......991 in the micromolar range (EC(50) 107 microM for ERG1). The effect has been characterized in Xenopus laevis oocytes expressing ERG1-2 and in the mammalian HEK293 cell line stably expressing ERG1 channels. The IC(50) values for block of KCNQ channels by XE991 range 1-65 microM. In conclusion, great...

Flood routing in an ephemeral channel with compound cross-section

Indian Academy of Sciences (India)

M Balamurugan

protecting downstream cities and few more water man- agement activities ... face and pseudo 2-D sub-surface model are compared with those obtained ... each sub-section is treated as single channel, where Bm is ..... to the hini value as long as it is small. The inflow .... Comprehensive experimental data, either laboratory or.

KCNMA1 encoded cardiac BK channels afford protection against ischemia-reperfusion injury

DEFF Research Database (Denmark)

Soltysinska, Ewa; Bentzen, Bo Hjorth; Barthmes, Maria

2014-01-01

Mitochondrial potassium channels have been implicated in myocardial protection mediated through pre-/postconditioning. Compounds that open the Ca2+- and voltage-activated potassium channel of big-conductance (BK) have a pre-conditioning-like effect on survival of cardiomyocytes after ischemia/rep...

Fluctuations of nuclear cross sections in the region of strong overlapping resonances and at large number of open channels

International Nuclear Information System (INIS)

Kun, S.Yu.

1985-01-01

On the basis of the symmetrized Simonius representation of the S matrix statistical properties of its fluctuating component in the presence of direct reactions are investigated. The case is considered where the resonance levels are strongly overlapping and there is a lot of open channels, assuming that compound-nucleus cross sections which couple different channels are equal. It is shown that using the averaged unitarity condition on the real energy axis one can eliminate both resonance-resonance and channel-channel correlations from partial r transition amplitudes. As a result, we derive the basic points of the Epicson fluctuation theory of nuclear cross sections, independently of the relation between the resonance overlapping and the number of open channels, and the validity of the Hauser-Feshbach model is established. If the number of open channels is large, the time of uniform population of compound-nucleus configurations, for an open excited nuclear system, is much smaller than the Poincare time. The life time of compound nucleus is discussed

Conduction mechanism of nitronyl-nitroxide molecular magnetic compounds

Science.gov (United States)

Dotti, N.; Heintze, E.; Slota, M.; Hübner, R.; Wang, F.; Nuss, J.; Dressel, M.; Bogani, L.

2016-04-01

We investigate the conduction mechanisms of nitronyl-nitroxide (NIT) molecular radicals, as useful for the creation of nanoscopic molecular spintronic devices, finding that it does not correspond to standard Mott behavior, as previously postulated. We provide a complete investigation using transport measurements, low-energy, sub-THz spectroscopy and introducing differently substituted phenyl appendages. We show that a nontrivial surface-charge-limited regime is present in addition to the standard low-voltage Ohmic conductance. Scaling analysis allows one to determine all the main transport parameters for the compounds and highlights the presence of charge-trapping effects. Comparison among the different compounds shows the relevance of intermolecular stacking between the aromatic ring of the phenyl appendix and the NIT motif in the creation of useful electron transport channels. The importance of intermolecular pathways is further highlighted by electronic structure calculations, which clarify the nature of the electronic channels and their effect on the Mott character of the compounds.

Leptin Suppresses Mouse Taste Cell Responses to Sweet Compounds.

Science.gov (United States)

Yoshida, Ryusuke; Noguchi, Kenshi; Shigemura, Noriatsu; Jyotaki, Masafumi; Takahashi, Ichiro; Margolskee, Robert F; Ninomiya, Yuzo

2015-11-01

Leptin is known to selectively suppress neural and behavioral responses to sweet-tasting compounds. However, the molecular basis for the effect of leptin on sweet taste is not known. Here, we report that leptin suppresses sweet taste via leptin receptors (Ob-Rb) and KATP channels expressed selectively in sweet-sensitive taste cells. Ob-Rb was more often expressed in taste cells that expressed T1R3 (a sweet receptor component) than in those that expressed glutamate-aspartate transporter (a marker for Type I taste cells) or GAD67 (a marker for Type III taste cells). Systemically administered leptin suppressed taste cell responses to sweet but not to bitter or sour compounds. This effect was blocked by a leptin antagonist and was absent in leptin receptor-deficient db/db mice and mice with diet-induced obesity. Blocking the KATP channel subunit sulfonylurea receptor 1, which was frequently coexpressed with Ob-Rb in T1R3-expressing taste cells, eliminated the effect of leptin on sweet taste. In contrast, activating the KATP channel with diazoxide mimicked the sweet-suppressing effect of leptin. These results indicate that leptin acts via Ob-Rb and KATP channels that are present in T1R3-expressing taste cells to selectively suppress their responses to sweet compounds. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

On Secure NOMA Systems with Transmit Antenna Selection Schemes

KAUST Repository

Lei, Hongjiang; Zhang, Jianming; Park, Kihong; Xu, Peng; Ansari, Imran Shafique; Pan, Gaofeng; Alomair, Basel; Alouini, Mohamed-Slim

2017-01-01

This paper investigates the secrecy performance of a two-user downlink non-orthogonal multiple access systems. Both single-input and single-output and multiple-input and singleoutput systems with different transmit antenna selection (TAS) strategies are considered. Depending on whether the base station has the global channel state information of both the main and wiretap channels, the exact closed-form expressions for the secrecy outage probability (SOP) with suboptimal antenna selection and optimal antenna selection schemes are obtained and compared with the traditional space-time transmission scheme. To obtain further insights, the asymptotic analysis of the SOP in high average channel power gains regime is presented and it is found that the secrecy diversity order for all the TAS schemes with fixed power allocation is zero. Furthermore, an effective power allocation scheme is proposed to obtain the nonzero diversity order with all the TAS schemes. Monte-Carlo simulations are performed to verify the proposed analytical results.

On Secure NOMA Systems with Transmit Antenna Selection Schemes

KAUST Repository

Lei, Hongjiang

2017-08-09

This paper investigates the secrecy performance of a two-user downlink non-orthogonal multiple access systems. Both single-input and single-output and multiple-input and singleoutput systems with different transmit antenna selection (TAS) strategies are considered. Depending on whether the base station has the global channel state information of both the main and wiretap channels, the exact closed-form expressions for the secrecy outage probability (SOP) with suboptimal antenna selection and optimal antenna selection schemes are obtained and compared with the traditional space-time transmission scheme. To obtain further insights, the asymptotic analysis of the SOP in high average channel power gains regime is presented and it is found that the secrecy diversity order for all the TAS schemes with fixed power allocation is zero. Furthermore, an effective power allocation scheme is proposed to obtain the nonzero diversity order with all the TAS schemes. Monte-Carlo simulations are performed to verify the proposed analytical results.

Spatial channel interactions in cochlear implants

Science.gov (United States)

Tang, Qing; Benítez, Raul; Zeng, Fan-Gang

2011-08-01

The modern multi-channel cochlear implant is widely considered to be the most successful neural prosthesis owing to its ability to restore partial hearing to post-lingually deafened adults and to allow essentially normal language development in pre-lingually deafened children. However, the implant performance varies greatly in individuals and is still limited in background noise, tonal language understanding, and music perception. One main cause for the individual variability and the limited performance in cochlear implants is spatial channel interaction from the stimulating electrodes to the auditory nerve and brain. Here we systematically examined spatial channel interactions at the physical, physiological, and perceptual levels in the same five modern cochlear implant subjects. The physical interaction was examined using an electric field imaging technique, which measured the voltage distribution as a function of the electrode position in the cochlea in response to the stimulation of a single electrode. The physiological interaction was examined by recording electrically evoked compound action potentials as a function of the electrode position in response to the stimulation of the same single electrode position. The perceptual interactions were characterized by changes in detection threshold as well as loudness summation in response to in-phase or out-of-phase dual-electrode stimulation. To minimize potentially confounding effects of temporal factors on spatial channel interactions, stimulus rates were limited to 100 Hz or less in all measurements. Several quantitative channel interaction indexes were developed to define and compare the width, slope and symmetry of the spatial excitation patterns derived from these physical, physiological and perceptual measures. The electric field imaging data revealed a broad but uniformly asymmetrical intracochlear electric field pattern, with the apical side producing a wider half-width and shallower slope than the basal

Reservoir architecture patterns of sandy gravel braided distributary channel

Directory of Open Access Journals (Sweden)

Senlin Yin

2016-06-01

Full Text Available The purpose of this study was to discuss shape, scale and superimposed types of sandy gravel bodies in sandy-gravel braided distributary channel. Lithofacies analysis, hierarchy bounding surface analysis and subsurface dense well pattern combining with outcrops method were used to examine reservoir architecture patterns of sandy gravel braided distributary channel based on cores, well logging, and outcrops data, and the reservoir architecture patterns of sandy gravel braided distributary channels in different grades have been established. The study shows: (1 The main reservoir architecture elements for sandy gravel braided channel delta are distributary channel and overbank sand, while reservoir flow barrier elements are interchannel and lacustrine mudstone. (2 The compound sand bodies in the sandy gravel braided delta distributary channel take on three shapes: sheet-like distributary channel sand body, interweave strip distributary channel sand body, single strip distributary channel sand body. (3 Identification marks of single distributary channel include: elevation of sand body top, lateral overlaying, “thick-thin-thick” feature of sand bodies, interchannel mudstone and overbank sand between distributary channels and the differences in well log curve shape of sand bodies. (4 Nine lithofacies types were distinguished in distributary channel unit interior, different channel units have different lithofacies association sequence.

Channel Responses and Hydromodification in Southern California

Science.gov (United States)

Hawley, R. J.; Dust, D. W.; Bledsoe, B. P.

2007-12-01

Hydromodification (changes in watershed hydrologic characteristics, and the resulting hydraulics and channel forms due to urbanization) is ubiquitous in Southern California. In this region, the effects of hydromodification are driven and compounded by the arid/semiarid climate, high relief, erodible soils, high urbanization rates, and relatively low frequency of retention/detention. We conducted a preliminary survey of over 50 stream reaches along a gradient from least disturbed to fully urbanized. All stages of the Channel Evolution Model (CEM) of Schumm et al. (1984) were observed, from stable to degrading, widening, aggrading, and quasi-equilibrium channels. Several sites have CEM stages II through V in close proximity due to headcutting, hardpoints, and infrastructure. We also observed channels in undeveloped watersheds impacted by downstream urbanization via headcutting. A range of intervention measures was observed, with the frequent evolutionary endpoint as a concrete engineered flood control channel. We also observed multiple channel evolution sequences that deviate from the CEM for single-thread, incising channels. An alternative channel response, particularly on smaller urbanized streams is a stabilized, vegetation encroached low-flow channel with regular baseflow supplied by residential irrigation runoff. The limited cases of unimpacted streams that remain tend to be high gradient, high energy systems that are naturally proximate to the transition between braided and meandering form for a given sediment size.

Substituted 4-phenyl-2-aminoimidazoles and 4-phenyl-4,5-dihydro-2-aminoimidazoles as voltage-gated sodium channel modulators.

Science.gov (United States)

Zidar, Nace; Jakopin, Žiga; Madge, David J; Chan, Fiona; Tytgat, Jan; Peigneur, Steve; Dolenc, Marija Sollner; Tomašić, Tihomir; Ilaš, Janez; Mašič, Lucija Peterlin; Kikelj, Danijel

2014-03-03

Voltage-gated sodium channels play an integral part in neurotransmission and their dysfunction is frequently a cause of various neurological disorders. On the basis of the structure of marine alkaloid clathrodin, twenty eight new analogs were designed, synthesized and tested for their ability to block human NaV1.3, NaV1.4 and NaV1.7 channels, as well as for their selectivity against human cardiac isoform NaV1.5, using automated patch clamp electrophysiological assay. Several compounds exhibited promising activities on different NaV channel isoforms in the medium micromolar range and some of the compounds showed also moderate isoform selectivities. The most promising results were obtained for the NaV1.3 channel, for which four compounds were found to possess IC₅₀ values lower than 15 μM. All of the active compounds bind to the open-inactivated states of the channels and therefore act as state-dependent modulators. The obtained results validate the approach of using natural products driven chemistry for drug discovery starting points and represent a good foundation for future design of selective NaV modulators. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Engineering of metabolic pathways by artificial enzyme channels

Directory of Open Access Journals (Sweden)

Marlene ePröschel

2015-10-01

Full Text Available Application of industrial enzymes for production of valuable chemical compounds has greatly benefited from recent developments in Systems and Synthetic Biology. Both, in vivo and in vitro systems have been established, allowing conversion of simple into complex compounds. Metabolic engineering in living cells needs to be balanced which is achieved by controlling gene expression levels, translation, scaffolding, compartmentation and flux control. In vitro applications are often hampered by limited protein stability/half-life and insufficient rates of substrate conversion. To improve stability and catalytic activity, proteins are post-translationally modified and arranged in artificial metabolic channels. Within the review article we will first discuss the supramolecular organization of enzymes in living systems and secondly summarize current and future approaches to design artificial metabolic channels by additive manufacturing for the efficient production of desired products.

Rhynchophylline from Uncaria rhynchophylla functionally turns delayed rectifiers into A-Type K+ channels.

Science.gov (United States)

Chou, Chun-Hsiao; Gong, Chi-Li; Chao, Chia-Chia; Lin, Chia-Huei; Kwan, Chiu-Yin; Hsieh, Ching-Liang; Leung, Yuk-Man

2009-05-22

Rhynchophylline (1), a neuroprotective agent isolated from the traditional Chinese medicinal herb Uncaria rhynchophylla, was shown to affect voltage-gated K(+) (Kv) channel slow inactivation in mouse neuroblastoma N2A cells. Extracellular 1 (30 microM) accelerated the slow decay of Kv currents and shifted the steady-state inactivation curve to the left. Intracellular dialysis of 1 did not accelerate the slow current decay, suggesting that this compound acts extracellularly. In addition, the percent blockage of Kv currents by this substance was independent of the degree of depolarization and the intracellular K(+) concentration. Therefore, 1 did not appear to directly block the outer channel pore, with the results obtained suggesting that it drastically accelerated Kv channel slow inactivation. Interestingly, 1 also shifted the activation curve to the left. This alkaloid also strongly accelerated slow inactivation and caused a left shift of the activation curve of Kv1.2 channels heterologously expressed in HEK293 cells. Thus, this compound functionally turned delayed rectifiers into A-type K(+) channels.

MODELING OF TECHNICAL CHANNELS OF INFORMATION LEAKAGE AT DISTRIBUTED CONTROL OBJECTS

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Aleksander Vladimirovich Karpov

2018-05-01

Full Text Available The significant increase in requirements for distributed control objects’ functioning can’t be realized only at the expense of the widening and strengthening of security control measures. The first step in ensuring the information security at such objects is the analysis of the conditions of their functioning and modeling of technical channels of information leakage. The development of models of such channels is essentially the only method of complete study of their opportunities and it is pointed toward receiving quantitative assessments of the safe operation of compound objects. The evaluation data are necessary to make a decision on the degree of the information security from a leak according to the current criterion. The existing models are developed for the standard concentrated objects and allow to evaluate the level of information security from a leak on each of channels separately, what involves the significant increase in the required protective resource and time of assessment of information security on an object in general. The article deals with a logical-and-probabilistic method of a security assessment of structurally-compound objects. The model of a security leak on the distributed control objects is cited as an example. It is recommended to use a software package of an automated structurally-logistical modeling of compound systems, which allows to evaluate risk of information leakage in the loudspeaker. A possibility of information leakage by technical channels is evaluated and such differential characteristics of the safe operation of the distributed control objects as positive and negative contributions of the initiating events and conditions, which cause a leak are calculated. Purpose. The aim is a quantitative assessment of data risk, which is necessary for justifying the rational composition of organizational and technical protection measures, as well as a variant of the structure of the information security system from a

Mathematical expression of discharge capacity of compound open ...

Indian Academy of Sciences (India)

value of 0.162 has the best performance, among the various analytical methods tested. ...... Iran, who introduced us to the advanced concept of compound open channel ... management in practice: Better water management for development ...

Automated Electrophysiology Makes the Pace for Cardiac Ion Channel Safety Screening

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Clemens eMoeller

2011-11-01

Full Text Available The field of automated patch-clamp electrophysiology has emerged from the tension between the pharmaceutical industry’s need for high-throughput compound screening versus its need to be conservative due to regulatory requirements. On the one hand, hERG channel screening was increasingly requested for new chemical entities, as the correlation between blockade of the ion channel coded by hERG and Torsades de Pointes cardiac arrhythmia gained increasing attention. On the other hand, manual patch-clamping, typically quoted as the gold-standard for understanding ion channel function and modulation, was far too slow (and, consequently, too expensive for keeping pace with the numbers of compounds submitted for hERG channel investigations from pharmaceutical R&D departments. In consequence it became more common for some pharmaceutical companies to outsource safety pharmacological investigations, with a focus on hERG channel interactions. This outsourcing has allowed those pharmaceutical companies to build up operational flexibility and greater independence from internal resources, and allowed them to obtain access to the latest technological developments that emerged in automated patch-clamp electrophysiology – much of which arose in specialized biotech companies. Assays for nearly all major cardiac ion channels are now available by automated patch-clamping using heterologous expression systems, and recently, automated action potential recordings from stem-cell derived cardiomyocytes have been demonstrated. Today, most of the large pharmaceutical companies have acquired automated electrophysiology robots and have established various automated cardiac ion channel safety screening assays on these, in addition to outsourcing parts of their needs for safety screening.

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

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Sigrid Marie Blom

Full Text Available 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.

Pharmacological consequences of the coexpression of BK channel α and auxiliary β subunits

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Yolima P. Torres

2014-10-01

Full Text Available Coded by a single gene (Slo1, KCM and activated by depolarizing potentials and by a rise in intracellular Ca2+ concentration, the large conductance voltage- and Ca+2-activated K+ channel (BK is unique among the superfamily of K+ channels. BK channels are tetramers characterized by a pore-forming α subunit containing seven transmembrane segments (instead of the six found in voltage-dependent K+ channels and a large C terminus composed of two regulators of K+ conductance domains (RCK domains, where the Ca2+-binding sites reside. BK channels can be associated with accessory β subunits and, although different BK modulatory mechanisms have been described, greater interest has recently been placed on the role that the β subunits may play in the modulation of BK channel gating due to its physiological importance. Four β subunits have currently been identified (i.e., β1, β2, β3 & β4 and despite the fact that they all share the same topology, it has been shown that every β subunit has a specific tissue distribution and that they modify channel kinetics as well as their pharmacological properties and the apparent Ca+2 sensitivity of the α subunit in different ways. Additionally, different studies have shown that natural, endogenous and synthetic compounds can modulate BK channels through β subunits. Considering the importance of these channels in different pathological conditions, such as hypertension and neurological disorders, this review focuses on the mechanisms by which these compounds modulate the biophysical properties of BK channels through the regulation of β subunits, as well as their potential therapeutic uses for diseases such as those mentioned above.

Pharmacological consequences of the coexpression of BK channel α and auxiliary β subunits.

Science.gov (United States)

Torres, Yolima P; Granados, Sara T; Latorre, Ramón

2014-01-01

Coded by a single gene (Slo1, KCM) and activated by depolarizing potentials and by a rise in intracellular Ca(2+) concentration, the large conductance voltage- and Ca(2+)-activated K(+) channel (BK) is unique among the superfamily of K(+) channels. BK channels are tetramers characterized by a pore-forming α subunit containing seven transmembrane segments (instead of the six found in voltage-dependent K(+) channels) and a large C terminus composed of two regulators of K(+) conductance domains (RCK domains), where the Ca(2+)-binding sites reside. BK channels can be associated with accessory β subunits and, although different BK modulatory mechanisms have been described, greater interest has recently been placed on the role that the β subunits may play in the modulation of BK channel gating due to its physiological importance. Four β subunits have currently been identified (i.e., β1, β2, β3, and β4) and despite the fact that they all share the same topology, it has been shown that every β subunit has a specific tissue distribution and that they modify channel kinetics as well as their pharmacological properties and the apparent Ca(2+) sensitivity of the α subunit in different ways. Additionally, different studies have shown that natural, endogenous, and synthetic compounds can modulate BK channels through β subunits. Considering the importance of these channels in different pathological conditions, such as hypertension and neurological disorders, this review focuses on the mechanisms by which these compounds modulate the biophysical properties of BK channels through the regulation of β subunits, as well as their potential therapeutic uses for diseases such as those mentioned above.

Pharmacological consequences of the coexpression of BK channel α and auxiliary β subunits

Science.gov (United States)

Torres, Yolima P.; Granados, Sara T.; Latorre, Ramón

2014-01-01

Coded by a single gene (Slo1, KCM) and activated by depolarizing potentials and by a rise in intracellular Ca2+ concentration, the large conductance voltage- and Ca2+-activated K+ channel (BK) is unique among the superfamily of K+ channels. BK channels are tetramers characterized by a pore-forming α subunit containing seven transmembrane segments (instead of the six found in voltage-dependent K+ channels) and a large C terminus composed of two regulators of K+ conductance domains (RCK domains), where the Ca2+-binding sites reside. BK channels can be associated with accessory β subunits and, although different BK modulatory mechanisms have been described, greater interest has recently been placed on the role that the β subunits may play in the modulation of BK channel gating due to its physiological importance. Four β subunits have currently been identified (i.e., β1, β2, β3, and β4) and despite the fact that they all share the same topology, it has been shown that every β subunit has a specific tissue distribution and that they modify channel kinetics as well as their pharmacological properties and the apparent Ca2+ sensitivity of the α subunit in different ways. Additionally, different studies have shown that natural, endogenous, and synthetic compounds can modulate BK channels through β subunits. Considering the importance of these channels in different pathological conditions, such as hypertension and neurological disorders, this review focuses on the mechanisms by which these compounds modulate the biophysical properties of BK channels through the regulation of β subunits, as well as their potential therapeutic uses for diseases such as those mentioned above. PMID:25346693

N-(2-methoxyphenyl) benzenesulfonamide, a novel regulator of neuronal G protein-gated inward rectifier K+ channels.

Science.gov (United States)

Walsh, Kenneth B; Gay, Elaine A; Blough, Bruce E; Geurkink, David W

2017-11-15

G protein-gated inward rectifier K + (GIRK) channels are members of the super-family of proteins known as inward rectifier K + (Kir) channels and are expressed throughout the peripheral and central nervous systems. Neuronal GIRK channels are the downstream targets of a number of neuromodulators including opioids, somatostatin, dopamine and cannabinoids. Previous studies have demonstrated that the ATP-sensitive K + channel, another member of the Kir channel family, is regulated by sulfonamide drugs. Therefore, to determine if sulfonamides also modulate GIRK channels, we screened a library of arylsulfonamide compounds using a GIRK channel fluorescent assay that utilized pituitary AtT20 cells expressing GIRK channels along with the somatostatin type-2 and -5 receptors. Enhancement of the GIRK channel fluorescent signal by one compound, N-(2-methoxyphenyl) benzenesulfonamide (MPBS), was dependent on the activation of the channel by somatostatin. In whole-cell patch clamp experiments, application of MPBS both shifted the somatostatin concentration-response curve (EC 50 = 3.5nM [control] vs.1.0nM [MPBS]) for GIRK channel activation and increased the maximum GIRK current measured with 100nM somatostatin. However, GIRK channel activation was not observed when MPBS was applied to the cells in the absence of somatostatin. While the MPBS structural analog 4-fluoro-N-(2-methoxyphenyl) benzenesulfonamide also augmented the somatostatin-induced GIRK fluorescent signal, no increase in the signal was observed with the sulfonamides tolbutamide, sulfapyridine and celecoxib. In conclusion, MPBS represents a novel prototypic GPCR-dependent regulator of neuronal GIRK channels. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects on the sodium channel of some new cardiotonic drugs: the 4-, 5-, and 6-pyridyl-2(1H)-quinolone derivatives

International Nuclear Information System (INIS)

Grima, M.; Beguin, M.F.; Millanvoye-Van Brussel, E.M.; Decker, N.; Schwartz, J.

1988-01-01

To study the action of some new cardiotonic drugs, the 4-, 5-, and 6-pyridyl-2(1H)-quinolone series, on the fast Na+ channel, we compared the effects of eight compounds of this series and milrinone on 22 Na uptake in rat brain synaptosomes and in rat heart muscle cells in culture. The action of tetrodotoxin, a specific Na+ channel blocker, on the positive inotropic effect of these compounds on guinea pig atria was also examined. The new positive inotropic agents enhance 22 Na uptake in synaptosomes in a dose-dependent manner. The activities, expressed as percentage of the maximum activity of protoveratrine B, a classic Na+ channel agonist, reached 70% for milrinone, 60% for compound 7, 57% for compound 6, and less than 50% for the other drugs. For compound 8, but not for milrinone, it was possible to observe a stimulatory effect of the 22 Na uptake on heart muscle cells in culture. Tetrodotoxin (1 and 100 microM) inhibited the stimulatory effects of the inotropic drugs on both preparations. The positive inotropic activities of protoveratrine B, milrinone, and compounds 5 and 8, in guinea pig atria, were inhibited by tetrodotoxin. The affinity and the activity of the other compounds were unchanged in the presence of tetrodotoxin. Our results showed that the stimulation of Na+ influx through the fast Na+ channel might represent a part of the mechanism of action of the inotropic effect of some new cardiotonic drugs

Effects on the sodium channel of some new cardiotonic drugs: the 4-, 5-, and 6-pyridyl-2(1H)-quinolone derivatives

Energy Technology Data Exchange (ETDEWEB)

Grima, M.; Beguin, M.F.; Millanvoye-Van Brussel, E.M.; Decker, N.; Schwartz, J.

1988-09-01

To study the action of some new cardiotonic drugs, the 4-, 5-, and 6-pyridyl-2(1H)-quinolone series, on the fast Na+ channel, we compared the effects of eight compounds of this series and milrinone on /sup 22/Na uptake in rat brain synaptosomes and in rat heart muscle cells in culture. The action of tetrodotoxin, a specific Na+ channel blocker, on the positive inotropic effect of these compounds on guinea pig atria was also examined. The new positive inotropic agents enhance /sup 22/Na uptake in synaptosomes in a dose-dependent manner. The activities, expressed as percentage of the maximum activity of protoveratrine B, a classic Na+ channel agonist, reached 70% for milrinone, 60% for compound 7, 57% for compound 6, and less than 50% for the other drugs. For compound 8, but not for milrinone, it was possible to observe a stimulatory effect of the /sup 22/Na uptake on heart muscle cells in culture. Tetrodotoxin (1 and 100 microM) inhibited the stimulatory effects of the inotropic drugs on both preparations. The positive inotropic activities of protoveratrine B, milrinone, and compounds 5 and 8, in guinea pig atria, were inhibited by tetrodotoxin. The affinity and the activity of the other compounds were unchanged in the presence of tetrodotoxin. Our results showed that the stimulation of Na+ influx through the fast Na+ channel might represent a part of the mechanism of action of the inotropic effect of some new cardiotonic drugs.

Reaction channels of 6,7Li+28Si at near-barrier energies

International Nuclear Information System (INIS)

Pakou, A; Rusek, K; Nicolis, N G; Alamanos, N; Doukelis, G; Gillibert, A; Kalyva, G; Kokkoris, M; Lagoyannis, A; Musumarra, A; Papachristodoulou, C; Perdikakis, G; Pierroutsakou, D; Pollacco, E C; Spyrou, A; Zarkadas, Ch

2005-01-01

The production of α-particles in the reactions 6,7 Li+ 28 Si was studied as a means to disentangle the various reaction channels at near-barrier energies. The competition between compound and direct reactions was determined by using the shape of angular distributions and statistical model calculations. DWBA calculations were also performed to probe the various direct channels. It was found that, approaching barrier, transfer channels are the most dominant for both reactions. For 7 Li+ 28 Si d-transfer is one of the contributing channels without excluding t-transfer, while for 6 Li+ 28 Si, n-transfer and p-transfer have substantial contribution but without excluding d-transfer

Search for entrance channel effects in fusion reactions via neutron evaporation

International Nuclear Information System (INIS)

Ajay Kumar; Kaur, J.; Kumar, A.; Singh, G.; Govil, I.M.; Rakesh Kumar; Datta, S.K.; Chatterjee, M.B.; Yogi, B.K.

2001-01-01

It is generally expected that the compound nuclei formed at the given excitation energies and the angular momenta follow a statistical decay pattern independent of a particular reaction that led to fusion. In order to search the entrance channel effects in the decay of compound nucleus, the reaction 16 O + 64 Zn at oxygen beam energy of 91 MeV and 95 MeV are investigated

Improving Wireless Physical Layer Security via Exploiting Co-Channel Interference

Science.gov (United States)

Li, Lingxiang; Petropulu, Athina P.; Chen, Zhi; Fang, Jun

2016-12-01

This paper considers a scenario in which a source-destination pair needs to establish a confidential connection against an external eavesdropper, aided by the interference generated by another source-destination pair that exchanges public messages. The goal is to compute the maximum achievable secrecy degrees of freedom (S.D.o.F) region of a MIMO two-user wiretap network. First, a cooperative secrecy transmission scheme is proposed, whose feasible set is shown to achieve all S.D.o.F. pairs on the S.D.o.F. region boundary. In this way, the determination of the S.D.o.F. region is reduced to a problem of maximizing the S.D.o.F. pair over the proposed transmission scheme. The maximum achievable S.D.o.F. region boundary points are obtained in closed form, and the construction of the precoding matrices achieving the maximum S.D.o.F. region boundary is provided. The obtained analytical expressions clearly show the relation between the maximum achievable S.D.o.F. region and the number of antennas at each terminal.

Clostridium botulinum C2 toxin. Identification of the binding site for chloroquine and related compounds and influence of the binding site on properties of the C2II channel.

Science.gov (United States)

Neumeyer, Tobias; Schiffler, Bettina; Maier, Elke; Lang, Alexander E; Aktories, Klaus; Benz, Roland

2008-02-15

Clostridium botulinum C2 toxin belongs to the family of binary AB type toxins that are structurally organized into distinct enzyme (A, C2I) and binding (B, C2II) components. The proteolytically activated 60-kDa C2II binding component is essential for C2I transport into target cells. It oligomerizes into heptamers and forms channels in lipid bilayer membranes. The C2II channel is cation-selective and can be blocked by chloroquine and related compounds. Residues 303-330 of C2II contain a conserved pattern of alternating hydrophobic and hydrophilic residues, which has been implicated in the formation of two amphipathic beta-strands involved in membrane insertion and channel formation. In the present study, C2II mutants created by substitution of different negatively charged amino acids by alanine-scanning mutagenesis were analyzed in artificial lipid bilayer membranes. The results suggested that most of the C2II mutants formed SDS-resistant oligomers (heptamers) similar to wild type. The mutated negatively charged amino acids did not influence channel properties with the exception of Glu(399) and Asp(426), which are probably localized in the vestibule near the channel entrance. These mutants show a dramatic decrease in their affinity for binding of chloroquine and its analogues. Similarly, F428A, which represents the Phi-clamp in anthrax protective antigen, was mutated in C2II in several other amino acids. The C2II mutants F428A, F428D, F428Y, and F428W not only showed altered chloroquine binding but also had drastically changed single channel properties. The results suggest that amino acids Glu(399), Asp(426), and Phe(428) have a major impact on the function of C2II as a binding protein for C2I delivery into target cells.

Two-Channel Kondo Physics due to As Vacancies in the Layered Compound ZrAs1.58Se0.39

Science.gov (United States)

Kirchner, Stefan; Cichorek, T.; Bochenek, L.; Schmidt, M.; Niewa, R.; Czuluccki, A.; Auffermann, G.; Steglich, F.; Kniep, R.

We address the origin of the magnetic-field independent - | A | T 1 / 2 term observed in the low-temperature resistivity of several As-based metallic systems of the PbFCl structure type. For the layered compound ZrAs1.58Se0.39, we show that vacancies in the square nets of As give rise to the low-temperature transport anomaly over a wide temperature regime of almost two decades in temperature. This low-temperature behavior is in line with the non-magnetic version of the two-channel Kondo effect, whose origin we ascribe to a dynamic Jahn-Teller effect operating at the vacancy-carrying As layer with a C4 symmetry. The pair-breaking nature of the dynamical defects in the square nets of As explains the low superconducting transition temperature Tc 0 . 14 K of ZrAs1.58Se0.39, as compared to the free-of-vacancies homologue ZrP1.54S0.46 (Tc 3 . 7 K). Our findings should be relevant to a wide class of metals with disordered pnictogen layers.

Paraffin molecule mobility in channel clathrates of urea on spectroscopic NMR relaxation data

CERN Document Server

Kriger, Y G; Chekhova, G N

2001-01-01

The temperature dependences of the protons spin-lattice relaxation time (T sub I) in the channel clathrates of urea with paraffins are measured. The data on the T sub I are interpreted within the frames of the model of the paraffins molecules and their fragments orientation in the clathrate channels. The dynamics peculiarities are connected with the disproportion effects of these compounds

Activation of ERG2 potassium channels by the diphenylurea NS1643

DEFF Research Database (Denmark)

Elmedyb, Pernille; Olesen, Søren-Peter; Grunnet, Morten

2007-01-01

Three members of the ERG potassium channel family have been described (ERG1-3 or Kv 11.1-3). ERG1 is by far the best characterized subtype and it constitutes the molecular component of the cardiac I(Kr) current. All three channel subtypes are expressed in neurons but their function remains unclear....... The lack of functional information is at least partly due to the lack of specific pharmacological tools. The compound NS1643 has earlier been reported as an ERG1 channel activator. We found that NS1643 also activates the ERG2 channel; however, the molecular mechanism of the activation differs between...... the ERG1 and ERG2 channels. This is surprising since ERG1 and ERG2 channels have very similar biophysical and structural characteristics. For ERG2, NS1643 causes a left-ward shift of the activation curve, a faster time-constant of activation and a slower time-constant of inactivation as well...

Targeting channels and transporters in protozoan parasite infections

Science.gov (United States)

Meier, Anna; Erler, Holger; Beitz, Eric

2018-03-01

Infectious diseases caused by pathogenic protozoa are among the most significant causes of death in humans. Therapeutic options are scarce and massively challenged by the emergence of resistant parasite strains. Many of the current anti-parasite drugs target soluble enzymes, generate unspecific oxidative stress, or act by an unresolved mechanism within the parasite. In recent years, collections of drug-like compounds derived from large-scale phenotypic screenings, such as the malaria or pathogen box, have been made available to researchers free of charge boosting the identification of novel promising targets. Remarkably, several of the compound hits have been found to inhibit membrane proteins at the periphery of the parasites, i.e. channels and transporters for ions and metabolites. In this review, we will focus on the progress made on targeting channels and transporters at different levels and the potential for use against infections with apicomplexan parasites mainly Plasmodium spp. (malaria) and Toxoplasma gondii (toxoplasmosis), with kinetoplastids Trypanosoma brucei (sleeping sickness), Trypanosoma cruzi (Chagas disease) and Leishmania ssp. (leishmaniasis), and the amoeba Entamoeba histolytica (amoebiasis).

Inhibition of connexin43 gap junction channels by the endocrine disruptor ioxynil

International Nuclear Information System (INIS)

Leithe, Edward; Kjenseth, Ane; Bruun, Jarle; Sirnes, Solveig; Rivedal, Edgar

2010-01-01

Gap junctions are intercellular plasma membrane domains containing channels that mediate transport of ions, metabolites and small signaling molecules between adjacent cells. Gap junctions play important roles in a variety of cellular processes, including regulation of cell growth and differentiation, maintenance of tissue homeostasis and embryogenesis. The constituents of gap junction channels are a family of trans-membrane proteins called connexins, of which the best-studied is connexin43. Connexin43 functions as a tumor suppressor protein in various tissue types and is frequently dysregulated in human cancers. The pesticide ioxynil has previously been shown to act as an endocrine disrupting chemical and has multiple effects on the thyroid axis. Furthermore, both ioxynil and its derivative ioxynil octanoate have been reported to induce tumors in animal bioassays. However, the molecular mechanisms underlying the possible tumorigenic effects of these compounds are unknown. In the present study we show that ioxynil and ioxynil octanoate are strong inhibitors of connexin43 gap junction channels. Both compounds induced rapid loss of connexin43 gap junctions at the plasma membrane and increased connexin43 degradation. Ioxynil octanoate, but not ioxynil, was found to be a strong activator of ERK1/2. The compounds also had different effects on the phosphorylation status of connexin43. Taken together, the data show that ioxynil and ioxynil octanoate are potent inhibitors of intercellular communication via gap junctions.

Modulation of T-type Ca2+ channels by Lavender and Rosemary extracts.

Directory of Open Access Journals (Sweden)

Chaymae El Alaoui

Full Text Available Medicinal plants represent a significant reservoir of unexplored substances for early-stage drug discovery. Of interest, two flowering Mediterranean plants have been used for thousands of years for their beneficial effects on nervous disorders, including anxiety and mood. However, the therapeutic potential of these plants regarding their ability to target ion channels and neuronal excitability remains largely unknown. Towards this goal, we have investigated the ability of Lavender and Rosemary to modulate T-type calcium channels (TTCCs. TTCCs play important roles in neuronal excitability, neuroprotection, sensory processes and sleep. These channels are also involved in epilepsy and pain. Using the whole-cell patch-clamp technique, we have characterized how Lavender and Rosemary extracts, as well as their major active compounds Linalool and Rosmarinic acid, modulate the electrophysiological properties of recombinant TTCCs (CaV3.2 expressed in HEK-293T cells. Both the methanolic and essential oil extracts as well as the active compounds of these plants inhibit Cav3.2 current in a concentration-dependent manner. In addition, these products also induce a negative shift of the steady-state inactivation of CaV3.2 current with no change in the activation properties. Taken together, our findings reveal that TTCCs are a molecular target of the Lavender and Rosemary compounds, suggesting that inhibition of TTCCs could contribute to the anxiolytic and the neuroprotective effects of these plants.

Fusion-Fission like studies from medium heavy to light compound systems

International Nuclear Information System (INIS)

Heusch, B.

1991-01-01

It has been shown that for systems as light as A CN = 47 up to systems just above the Businaro Gallone point in the mass region of 100 to 110 the probability for a system to deexcite by the fission channel, is not negligible. As predicted, the asymmetrical separation becomes dominant when the A CN mass is decreasing but the symmetrical mode remains measurable. The ambiguities in the measured outgoing fragment distributions arise from the competition with IMF emissions as well as dynamical fission processes which depend strongly on the studied system. Fully relaxed DIC has also be used to interpret the results. I tried to show that precise checks on the behavior of two neighbouring systems as well as search for entrance channel effect and/or energy dependence bring evidence enough that the deexcitation of the compound nucleus can account for the symmetric and asymmetric fission channels as well as IMF emissions. This is strongly supported by different recent calculations all done in this frame. These all conclusions indicate also that the RLDM fails in the data interpretation. The strength of the fission channel depends strongly on the possibilities a system has to deexcite. For very light systems especially the number of open channels available determines directly the flux repartition between direct or compound processes and therefore very large differences in the general behaviour of two neighbouring systems can be observed. 15 figs

Effects of transgenic sterilization constructs and their repressor compounds on hatch, developmental rate and early survival of electroporated channel catfish embryos and fry.

Science.gov (United States)

Su, Baofeng; Shang, Mei; Li, Chao; Perera, Dayan A; Pinkert, Carl A; Irwin, Michael H; Peatman, Eric; Grewe, Peter; Patil, Jawahar G; Dunham, Rex A

2015-04-01

Channel catfish (Ictalurus punctatus) embryos were electroporated with sterilization constructs targeting primordial germ cell proteins or with buffer. Some embryos then were treated with repressor compounds, cadmium chloride, copper sulfate, sodium chloride or doxycycline, to prevent expression of the transgene constructs. Promoters included channel catfish nanos and vasa, salmon transferrin (TF), modified yeast Saccharomyces cerevisiae copper transport protein (MCTR) and zebrafish racemase (RM). Knock-down systems were the Tet-off (nanos and vasa constructs), MCTR, RM and TF systems. Knock-down genes included shRNAi targeting 5' nanos (N1), 3' nanos (N2) or dead end (DND), or double-stranded nanos RNA (dsRNA) for overexpression of nanos mRNA. These constructs previously were demonstrated to knock down nanos, vasa and dead end, with the repressors having variable success. Exogenous DNA affected percentage hatch (% hatch), as all 14 constructs, except for the TF dsRNA, TF N1 (T), RM DND (C), vasa DND (C), vasa N1 (C) and vasa N2 (C), had lower % hatch than the control electroporated with buffer. The MCTR and RM DND (T) constructs resulted in delayed hatch, and the vasa and nanos constructs had minimal effects on time of hatch (P nanos constructs, doxycycline greatly delayed hatch (P < 0.05). Adverse effects of the transgenes and repressors continued for several treatments for the first 6 days after hatch, but only in a few treatments during the next 10 days. Repressors and gene expression impacted the yield of putative transgenic channel catfish fry, and need to be considered and accounted for in the hatchery phase of producing transgenically sterilized catfish fry and their fertile counterparts. This fry output should be considered to ensure that sufficient numbers of transgenic fish are produced for future applications and for defining repressor systems that are the most successful.

The reaction of astatine with aromatic diazonium compounds

International Nuclear Information System (INIS)

Visser, G.W.M.; Diemer, E.L.

1982-01-01

Astatine reacts prefrentially with that type of aromatic diazonium salt that decomposes via a radical reaction channel (homolytic breakage of the C-N bond). The dediazonation with p-aminobenzoic acid and p-toluidine as model compounds was investigated through estatin produced in the 209 Bi(α,2n) 211 At reaction. (author)

Effects of Compound K-Distributed Sea Clutter on Angle Measurement of Wideband Monopulse Radar

Directory of Open Access Journals (Sweden)

Hong Zhu

2017-01-01

Full Text Available The effects of compound K-distributed sea clutter on angle measurement of wideband monopulse radar are investigated in this paper. We apply the conditional probability density function (pdf of monopulse ratio (MR error to analyze these effects. Based on the angle measurement procedure of the wideband monopulse radar, this conditional pdf is first deduced in detail for the case of compound K-distributed sea clutter plus noise. Herein, the spatial correlation of the texture components for each channel clutter and the correlation of the texture components between the sum and difference channel clutters are considered, and two extreme situations for each of them are tackled. Referring to the measured sea clutter data, angle measurement performances in various K-distributed sea clutter plus noise circumstances are simulated, and the effects of compound K-distributed sea clutter on angle measurement are discussed.

A structural view of ligand-dependent activation in thermoTRP channels

Directory of Open Access Journals (Sweden)

Ximena eSteinberg

2014-05-01

Full Text Available Transient Receptor Potential (TRP proteins are a large family of ion channels, grouped intoseven sub-families. Although great advances have been made regarding the activation andmodulation of TRP channel activity, detailed molecular mechanisms governing TRPchannel gating are still needed. Sensitive to electric, chemical, mechanical, and thermalcues, TRP channels are tightly associated with the detection and integration of sensoryinput, emerging as a model to study the polymodal activation of ion channel proteins.Among TRP channels, the temperature-activated kind constitute a subgroup by itself,formed by Vanilloid receptors 1-4, Melastatin receptors 2, 4, 5 and 8, TRPC5, and TRPA1.Some of the so-called thermoTRP channels participate in the detection of noxious stimulimaking them an interesting pharmacological target for the treatment of pain. However, thepoor specificity of the compounds available in the market represents an important obstacleto overcome. Understanding the molecular mechanics underlying ligand-dependentmodulation of TRP channels may help with the rational design of novel syntheticanalgesics. The present review focuses on the structural basis of ligand-dependentactivation of TRPV1 and TRPM8 channels. Special attention is drawn to the dissection ofligand-binding sites within TRPV1, PIP 2 -dependent modulation of TRP channels, and thestructure of natural and synthetic ligands.

The antiparasitic isoxazoline A1443 is a potent blocker of insect ligand-gated chloride channels.

Science.gov (United States)

Ozoe, Yoshihisa; Asahi, Miho; Ozoe, Fumiyo; Nakahira, Kunimitsu; Mita, Takeshi

2010-01-01

A structurally unique isoxazoline class compound, A1443, exhibits antiparasitic activity against cat fleas and dog ticks comparable to that of the commercial ectoparasiticide fipronil. This isoxazoline compound inhibits specific binding of the gamma-aminobutyric acid (GABA) receptor channel blocker [(3)H]4'-ethynyl-4-n-propylbicycloorthobenzoate (EBOB) to housefly-head membranes, with an IC(50) value of 455pM. In contrast, the IC(50) value in rat-brain membranes is>10muM. To study the mode of action of this isoxazoline, we utilized MdGBCl and MdGluCl cDNAs, which encode the subunits of housefly GABA- and glutamate-gated chloride channels, respectively. Two-electrode voltage clamp electrophysiology was used to confirm that A1443 blocks GABA- and glutamate-induced chloride currents in Xenopus oocytes expressing MdGBCl or MdGluCl channels, with IC(50) values of 5.32 and 79.9 nM, respectively. Blockade by A1443 was observed in A2'S-MdGBCl and S2'A-MdGluCl mutant channels at levels similar to those of the respective wild-types, and houseflies expressing A2'S-MdGBCl channels were as susceptible to A1443 as standard houseflies. These findings indicate that A1443 is a novel and specific blocker of insect ligand-gated chloride channels. Copyright 2009 Elsevier Inc. All rights reserved.

Channel Power in Multi-Channel Environments

NARCIS (Netherlands)

M.G. Dekimpe (Marnik); B. Skiera (Bernd)

2004-01-01

textabstractIn the literature, little attention has been paid to instances where companies add an Internet channel to their direct channel portfolio. However, actively managing multiple sales channels requires knowing the customers’ channel preferences and the resulting channel power. Two key

Voltage-Gated Potassium Channels Kv1.3--Potentially New Molecular Target in Cancer Diagnostics and Therapy.

Science.gov (United States)

Teisseyre, Andrzej; Gąsiorowska, Justyna; Michalak, Krystyna

2015-01-01

Voltage-gated potassium channels, Kv1.3, which were discovered in 1984, are integral membrane proteins which are activated ("open") upon change of the cell membrane potential, enabling a passive flux of potassium ions across the cell membrane. The channels are expressed in many different tissues, both normal and cancer. Since 2005 it has been known that the channels are expressed not only in the plasma membrane, but also in the inner mitochondrial membrane. The activity of Kv1.3 channels plays an important role, among others, in setting the cell resting membrane potential, cell proliferation, apoptosis and volume regulation. For some years, these channels have been considered a potentially new molecular target in both the diagnostics and therapy of some cancer diseases. This review article focuses on: 1) changes of expression of the channels in cancer disorders with special regard to correlations between the channels' expression and stage of the disease, 2) influence of inhibitors of Kv1.3 channels on proliferation and apoptosis of cancer cells, 3) possible future applications of Kv1.3 channels' inhibitors in therapy of some cancer diseases. In the last section, the results of studies performed in our Laboratory of Bioelectricity on the influence of selected biologically active plant-derived compounds from the groups of flavonoids and stilbenes and their natural and synthetic derivatives on the activity of Kv1.3 channels in normal and cancer cells are reviewed. A possible application of some compounds from these groups to support therapy of cancer diseases, such as breast, colon and lymph node cancer, and melanoma or chronic lymphocytic leukemia (B-CLL), is announced.

Performance evaluation of spatial compounding in the presence of aberration and adaptive imaging

Science.gov (United States)

Dahl, Jeremy J.; Guenther, Drake; Trahey, Gregg E.

2003-05-01

Spatial compounding has been used for years to reduce speckle in ultrasonic images and to resolve anatomical features hidden behind the grainy appearance of speckle. Adaptive imaging restores image contrast and resolution by compensating for beamforming errors caused by tissue-induced phase errors. Spatial compounding represents a form of incoherent imaging, whereas adaptive imaging attempts to maintain a coherent, diffraction-limited aperture in the presence of aberration. Using a Siemens Antares scanner, we acquired single channel RF data on a commercially available 1-D probe. Individual channel RF data was acquired on a cyst phantom in the presence of a near field electronic phase screen. Simulated data was also acquired for both a 1-D and a custom built 8x96, 1.75-D probe (Tetrad Corp.). The data was compounded using a receive spatial compounding algorithm; a widely used algorithm because it takes advantage of parallel beamforming to avoid reductions in frame rate. Phase correction was also performed by using a least mean squares algorithm to estimate the arrival time errors. We present simulation and experimental data comparing the performance of spatial compounding to phase correction in contrast and resolution tasks. We evaluate spatial compounding and phase correction, and combinations of the two methods, under varying aperture sizes, aperture overlaps, and aberrator strength to examine the optimum configuration and conditions in which spatial compounding will provide a similar or better result than adaptive imaging. We find that, in general, phase correction is hindered at high aberration strengths and spatial frequencies, whereas spatial compounding is helped by these aberrators.

Odd-Z Transactinide Compound Nucleus Reactions Including the Discovery of 260Bh

International Nuclear Information System (INIS)

Nelson, Sarah L; Nelson, Sarah L

2008-01-01

Several reactions producing odd-Z transactinide compound nuclei were studied with the 88-Inch Cyclotron and the Berkeley Gas-Filled Separator at the Lawrence Berkeley National Laboratory. The goal was to produce the same compound nucleus at or near the same excitation energy with similar values of angular momentum via different nuclear reactions. In doing so, it can be determined if there is a preference in entrance channel, because under these experimental conditions the survival portion of Swiatecki, Siwek-Wilcznska, and Wilczynski's 'Fusion By Diffusion' model is nearly identical for the two reactions. Additionally, because the same compound nucleus is produced, the exit channel is the same. Four compound nuclei were examined in this study: 258Db, 262Bh, 266Mt, and 272Rg. These nuclei were produced by using very similar heavy-ion induced-fusion reactions which differ only by one proton in the projectile or target nucleus (e.g.: 50Ti + 209Bi vs. 51V + 208Pb). Peak 1n exit channel cross sections were determined for each reaction in each pair, and three of the four pairs; cross sections were identical within statistical uncertainties. This indicates there is not an obvious preference of entrance channel in these paired reactions. Charge equilibration immediately prior to fusion leading to a decreased fusion barrier is the likely cause of this phenomenon. In addition to this systematic study, the lightest isotope of element 107, bohrium, was discovered in the 209Bi(52Cr,n) reaction. 260Bh was found to decay by emission of a 10.16 MeV alpha particle with a half-life of 35 ms. The cross section is 59 pb at an excitation energy of 15.0 MeV. The effect of the N = 152 shell is also seen in this isotope's alpha particle energy, the first evidence of such an effect in Bh. All reactions studied are also compared to model predictions by Swiatecki, Siwek-Wilcznska, and Wilczynski's 'Fusion By Diffusion' theory

PERTURBATION OF VOLTAGE-SENSITIVE Ca2+ CHANNEL FUNCTION BY VOLATILE ORGANIC SOLVENTS.

Science.gov (United States)

The mechanisms underlying the acute neurophysiological and behavioral effects of volatile organic compounds (VOCs) remain to be elucidated. However, the function of neuronal ion channels is perturbed by VOCs. The present study examined effects of toluene (TOL), trichloroethylene ...

Real-time ambient air monitoring adjacent to the Houston ship channel for volatile organic compounds associated with the refinery operations using the trace atmospheric gas analyzer (TAGA)

International Nuclear Information System (INIS)

Mickunas, D.B.

2009-01-01

An Urban Air Toxic Monitoring Program was developed by the United States Environmental Protection Agency (US EPA) to help evaluate the potential toxic air pollution in urban areas. The Trace Atmospheric Gas Analyzer (TAGA) was used to monitor the ambient air for target compounds associated with industrial, motor vehicle, and natural emissions sources in areas adjacent to the Houston Ship Channel in Texas. In this study, the TAGA used triple quadrupole technology to perform qualitative and quantitative analyses for benzene, toluene, xylenes, styrene, 1,3-butadiene, methyl tert-butyl ether, and 1,2,3-trichloropropane. The concentrations for the various ion pairs of the target compounds were updated approximately every 2 seconds. The information was incorporated into the geographic information system (GIS) along with the global positioning system (GPS) information for the TAGA location, aerial views of the monitoring area, and meteorological data for the associated region. The information is used to isolate the emission sources and help reduce air pollution. The GPS output helps determine a path-averaged concentration along various routes. Combined with meteorological data, this information can be used in risk assessment to calculate downwind impacts associated with the target compounds under other meteorological conditions and to determine health impacts. It was concluded that the TAGA can provide rapid, accurate and reliable analytical information for monitoring ambient air. 2 refs., 1 tab., 9 figs

Real-time ambient air monitoring adjacent to the Houston ship channel for volatile organic compounds associated with the refinery operations using the trace atmospheric gas analyzer (TAGA)

Energy Technology Data Exchange (ETDEWEB)

Mickunas, D.B. [United States Environmental Protection Agency, Research Triangle Park, NC (United States). Environmental Response Team; Wood, J.; Weeks, W. [Lockheed Martin Response Engineering and Analytical Contract, Edison, NJ (Canada)

2009-07-01

An Urban Air Toxic Monitoring Program was developed by the United States Environmental Protection Agency (US EPA) to help evaluate the potential toxic air pollution in urban areas. The Trace Atmospheric Gas Analyzer (TAGA) was used to monitor the ambient air for target compounds associated with industrial, motor vehicle, and natural emissions sources in areas adjacent to the Houston Ship Channel in Texas. In this study, the TAGA used triple quadrupole technology to perform qualitative and quantitative analyses for benzene, toluene, xylenes, styrene, 1,3-butadiene, methyl tert-butyl ether, and 1,2,3-trichloropropane. The concentrations for the various ion pairs of the target compounds were updated approximately every 2 seconds. The information was incorporated into the geographic information system (GIS) along with the global positioning system (GPS) information for the TAGA location, aerial views of the monitoring area, and meteorological data for the associated region. The information is used to isolate the emission sources and help reduce air pollution. The GPS output helps determine a path-averaged concentration along various routes. Combined with meteorological data, this information can be used in risk assessment to calculate downwind impacts associated with the target compounds under other meteorological conditions and to determine health impacts. It was concluded that the TAGA can provide rapid, accurate and reliable analytical information for monitoring ambient air. 2 refs., 1 tab., 9 figs.

Stage-discharge relationship in tidal channels

Science.gov (United States)

Kearney, W. S.; Mariotti, G.; Deegan, L.; Fagherazzi, S.

2016-12-01

Long-term records of the flow of water through tidal channels are essential to constrain the budgets of sediments and biogeochemical compounds in salt marshes. Statistical models which relate discharge to water level allow the estimation of such records from more easily obtained records of water stage in the channel. While there is clearly structure in the stage-discharge relationship, nonlinearity and nonstationarity of the relationship complicates the construction of statistical stage-discharge models with adequate performance for discharge estimation and uncertainty quantification. Here we compare four different types of stage-discharge models, each of which is designed to capture different characteristics of the stage-discharge relationship. We estimate and validate each of these models on a two-month long time series of stage and discharge obtained with an Acoustic Doppler Current Profiler in a salt marsh channel. We find that the best performance is obtained by models which account for the nonlinear and time-varying nature of the stage-discharge relationship. Good performance can also be obtained from a simplified version of these models which approximates the fully nonlinear and time-varying models with a piecewise linear formulation.

Mini-review: Molecular mechanisms of antifouling compounds

KAUST Repository

Qian, Pei-Yuan

2013-04-01

Various antifouling (AF) coatings have been developed to protect submerged surfaces by deterring the settlement of the colonizing stages of fouling organisms. A review of the literature shows that effective AF compounds with specific targets are ones often considered non-toxic. Such compounds act variously on ion channels, quorum sensing systems, neurotransmitters, production/release of adhesive, and specific enzymes that regulate energy production or primary metabolism. In contrast, AF compounds with general targets may or may not act through toxic mechanisms. These compounds affect a variety of biological activities including algal photosynthesis, energy production, stress responses, genotoxic damage, immunosuppressed protein expression, oxidation, neurotransmission, surface chemistry, the formation of biofilms, and adhesive production/release. Among all the targets, adhesive production/release is the most common, possibly due to a more extensive research effort in this area. Overall, the specific molecular targets and the molecular mechanisms of most AF compounds have not been identified. Thus, the information available is insufficient to draw firm conclusions about the types of molecular targets to be used as sensitive biomarkers for future design and screening of compounds with AF potential. In this review, the relevant advantages and disadvantages of the molecular tools available for studying the molecular targets of AF compounds are highlighted briefly and the molecular mechanisms of the AF compounds, which are largely a source of speculation in the literature, are discussed. © 2013 Copyright Taylor and Francis Group, LLC.

Equation of state for neutron matter in the Quark Compound Bag model

Science.gov (United States)

Krivoruchenko, M. I.

2017-11-01

The equation of state for neutron matter is derived in the framework of the Quark Compound Bag model, in which the nucleon-nucleon interaction is generated by the s-channel exchange of six-quark Jaffe-Low primitives.

Superspace group descriptions of the symmetries of incommensurate urea inclusion compounds

NARCIS (Netherlands)

vanSmaalen, S; Harris, KDM

1996-01-01

Urea inclusion compounds are a class of incommensurate composite crystals. The urea molecules form a three-dimensionally connected network, with approximate space group symmetry P6(1)22. This network contains tunnels (channels), which accommodate guest molecules. The periodicities of the urea

A novel dihydropyridine with 3-aryl meta-hydroxyl substitution blocks L-type calcium channels in rat cardiomyocytes

International Nuclear Information System (INIS)

Galvis-Pareja, David; Zapata-Torres, Gerald; Hidalgo, Jorge; Ayala, Pedro

2014-01-01

Rationale: Dihydropyridines are widely used for the treatment of several cardiac diseases due to their blocking activity on L-type Ca 2+ channels and their renowned antioxidant properties. Methods: We synthesized six novel dihydropyridine molecules and performed docking studies on the binding site of the L-type Ca 2+ channel. We used biochemical techniques on isolated adult rat cardiomyocytes to assess the efficacy of these molecules on their Ca 2+ channel-blocking activity and antioxidant properties. The Ca 2+ channel-blocking activity was evaluated by confocal microscopy on fluo-3AM loaded cardiomyocytes, as well as using patch clamp experiments. Antioxidant properties were evaluated by flow cytometry using the ROS sensitive dye 1,2,3 DHR. Results: Our docking studies show that a novel compound with 3-OH substitution inserts into the active binding site of the L-type Ca 2+ channel previously described for nitrendipine. In biochemical assays, the novel meta-OH group in the aryl in C4 showed a high blocking effect on L-type Ca 2+ channel as opposed to para-substituted compounds. In the tests we performed, none of the molecules showed antioxidant properties. Conclusions: Only substitutions in C2, C3 and C5 of the aryl ring render dihydropyridine compounds with the capacity of blocking LTCC. Based on our docking studies, we postulate that the antioxidant activity requires a larger group than the meta-OH substitution in C2, C3 or C5 of the dihydropyridine ring. - Highlights: • Dihydropyridine (DHP) molecules are widely used in cardiovascular disease. • DHPs block Ca 2+ entry through LTCC—some DHPs have antioxidant activity as well. • We synthesized 6 new DHPs and tested their Ca 2+ blocking and antioxidant activities. • 3-Aryl meta-hydroxyl substitution strongly increases their Ca 2+ blocking activity. • 3-Aryl meta-hydroxyl substitution did not affect the antioxidant properties

Essential Oils and Their Constituents Targeting the GABAergic System and Sodium Channels as Treatment of Neurological Diseases

Directory of Open Access Journals (Sweden)

Ze-Jun Wang

2018-05-01

Full Text Available Essential oils and the constituents in them exhibit different pharmacological activities, such as antinociceptive, anxiolytic-like, and anticonvulsant effects. They are widely applied as a complementary therapy for people with anxiety, insomnia, convulsion, pain, and cognitive deficit symptoms through inhalation, oral administration, and aromatherapy. Recent studies show that essential oils are emerging as a promising source for modulation of the GABAergic system and sodium ion channels. This review summarizes the recent findings regarding the pharmacological properties of essential oils and compounds from the oils and the mechanisms underlying their effects. Specifically, the review focuses on the essential oils and their constituents targeting the GABAergic system and sodium channels, and their antinociceptive, anxiolytic, and anticonvulsant properties. Some constituents target transient receptor potential (TRP channels to exert analgesic effects. Some components could interact with multiple therapeutic target proteins, for example, inhibit the function of sodium channels and, at the same time, activate GABAA receptors. The review concentrates on perspective compounds that could be better candidates for new drug development in the control of pain and anxiety syndromes.

A two-channel detection method for autofluorescence correction and efficient on-bead screening of one-bead one-compound combinatorial libraries using the COPAS fluorescence activated bead sorting system

International Nuclear Information System (INIS)

Hintersteiner, Martin; Auer, Manfred

2013-01-01

One-bead one-compound combinatorial library beads exhibit varying levels of autofluorescence after solid phase combinatorial synthesis. Very often this causes significant problems for automated on-bead screening using TentaGel beads and fluorescently labeled target proteins. Herein, we present a method to overcome this limitation when fluorescence activated bead sorting is used as the screening method. We have equipped the COPAS bead sorting instrument with a high-speed profiling unit and developed a spectral autofluorescence correction method. The correction method is based on a simple algebraic operation using the fluorescence data from two detection channels and is applied on-the-fly in order to reliably identify hit beads by COPAS bead sorting. Our method provides a practical tool for the fast and efficient isolation of hit beads from one-bead one-compound library screens using either fluorescently labeled target proteins or biotinylated target proteins. This method makes hit bead identification easier and more reliable. It reduces false positives and eliminates the need for time-consuming pre-sorting of library beads in order to remove autofluorescent beads. (technical note)

Radiation damage calculations for compound materials

International Nuclear Information System (INIS)

Greenwood, L.R.

1990-01-01

This paper reports on the SPECOMP computer code, developed to calculate neutron-induced displacement damage cross sections for compound materials such as alloys, insulators, and ceramic tritium breeders for fusion reactors. These new calculations rely on recoil atom energy distributions previously computed with the DISCS computer code, the results of which are stored in SPECTER computer code master libraries. All reaction channels were considered in the DISCS calculations and the neutron cross sections were taken from ENDF/B-V. Compound damage calculations with SPECOMP thus do not need to perform any recoil atom calculations and consequently need no access to ENDF or other neutron data bases. The calculations proceed by determining secondary displacements for each combination of recoil atom and matrix atom using the Lindhard partition of the recoil energy to establish the damage energy

Design, synthesis, and biological testing of thiosalicylamides as a novel class of calcium channel blockers.

Science.gov (United States)

Mehanna, Ahmed S; Kim, Jin Yung

2005-07-01

The current research aimed to investigate the importance of the heterocyclic ring system in the structure of the cardiovascular drug diltiazem for its calcium channel blocking activity. The manuscript describes the design, synthesis, and biological testing of a total of 10 S-(p-methoxybenzyl), N-substituted thiosalicylamides as a series of non-cyclic compounds derived from diltiazem's structure. The new compounds maintained all diltiazem pharmacophores except the thiazepine ring system. In vitro evaluation of the new series for calcium channel blocking effects revealed moderate activities with IC50 values in the range of 4.8-56.0 microM. The data suggest that the ring system is not essential for activity; however, its absence leads to a considerable drop of activity relative to that of diltiazem (IC50=0.3 microM). Compounds of the current series showed optimum activity when the aliphatic alkyl chain on the salicylamide nitrogen is part of a piperidine or piperazine ring system substituted at the terminal nitrogen with a benzyl group.

Structure-activity relationships for the action of 11 pyrethroid insecticides on rat Nav1.8 sodium channels expressed in Xenopus oocytes

International Nuclear Information System (INIS)

Choi, J.-S.; Soderlund, David M.

2006-01-01

Pyrethroid insecticides bind to voltage-sensitive sodium channels and modify their gating kinetics, thereby disrupting nerve function. This paper describes the action of 11 structurally diverse commercial pyrethroid insecticides on the rat Na v 1.8 sodium channel isoform, the principal carrier of the tetrodotoxin-resistant, pyrethroid-sensitive sodium current of sensory neurons, expressed in Xenopus laevis oocytes. All 11 compounds produced characteristic sodium tail currents following a depolarizing pulse that ranged from rapidly-decaying monoexponential currents (allethrin, cismethrin and permethrin) to persistent biexponential currents (cyfluthrin, cyhalothrin, cypermethrin and deltamethrin). Tail currents for the remaining compounds (bifenthrin, fenpropathrin, fenvalerate and tefluthrin) were monoexponential and decayed with kinetics intermediate between these extremes. Reconstruction of currents carried solely by the pyrethroid-modified subpopulation of channels revealed two types of pyrethroid-modified currents. The first type, found with cismethrin, allethrin, permethrin and tefluthrin, activated relatively rapidly and inactivated partially during a 40-ms depolarization. The second type, found with cypermethrin, cyfluthrin, cyhalothrin, deltamethrin, fenpropathrin and fenvalerate, activated more slowly and did not detectably inactivate during a 40-ms depolarization. Only bifenthrin did not produce modified currents that fit clearly into either of these categories. In all cases, the rate of activation of modified channels was strongly correlated with the rate of tail current decay following repolarization. Modification of Na v 1.8 sodium channels by cyfluthrin, cyhalothrin, cypermethrin and deltamethrin was enhanced 2.3- to 3.4-fold by repetitive stimulation; this effect appeared to result from the accumulation of persistently open channels rather than preferential binding to open channel states. Fenpropathrin was the most effective compound against Na v 1

Evolutionary conservation and changes in insect TRP channels.

Science.gov (United States)

Matsuura, Hironori; Sokabe, Takaaki; Kohno, Keigo; Tominaga, Makoto; Kadowaki, Tatsuhiko

2009-09-10

TRP (Transient Receptor Potential) channels respond to diverse stimuli and thus function as the primary integrators of varied sensory information. They are also activated by various compounds and secondary messengers to mediate cell-cell interactions as well as to detect changes in the local environment. Their physiological roles have been primarily characterized only in mice and fruit flies, and evolutionary studies are limited. To understand the evolution of insect TRP channels and the mechanisms of integrating sensory inputs in insects, we have identified and compared TRP channel genes in Drosophila melanogaster, Bombyx mori, Tribolium castaneum, Apis mellifera, Nasonia vitripennis, and Pediculus humanus genomes as part of genome sequencing efforts. All the insects examined have 2 TRPV, 1 TRPN, 1 TRPM, 3 TRPC, and 1 TRPML subfamily members, demonstrating that these channels have the ancient origins in insects. The common pattern also suggests that the mechanisms for detecting mechanical and visual stimuli and maintaining lysosomal functions may be evolutionarily well conserved in insects. However, a TRPP channel, the most ancient TRP channel, is missing in B. mori, A. mellifera, and N. vitripennis. Although P. humanus and D. melanogaster contain 4 TRPA subfamily members, the other insects have 5 TRPA subfamily members. T. castaneum, A. mellifera, and N. vitripennis contain TRPA5 channels, which have been specifically retained or gained in Coleoptera and Hymenoptera. Furthermore, TRPA1, which functions for thermotaxis in Drosophila, is missing in A. mellifera and N. vitripennis; however, they have other Hymenoptera-specific TRPA channels (AmHsTRPA and NvHsTRPA). NvHsTRPA expressed in HEK293 cells is activated by temperature increase, demonstrating that HsTRPAs function as novel thermal sensors in Hymenoptera. The total number of insect TRP family members is 13-14, approximately half that of mammalian TRP family members. As shown for mammalian TRP channels, this

Evolutionary conservation and changes in insect TRP channels

Directory of Open Access Journals (Sweden)

Tominaga Makoto

2009-09-01

Full Text Available Abstract Background TRP (Transient Receptor Potential channels respond to diverse stimuli and thus function as the primary integrators of varied sensory information. They are also activated by various compounds and secondary messengers to mediate cell-cell interactions as well as to detect changes in the local environment. Their physiological roles have been primarily characterized only in mice and fruit flies, and evolutionary studies are limited. To understand the evolution of insect TRP channels and the mechanisms of integrating sensory inputs in insects, we have identified and compared TRP channel genes in Drosophila melanogaster, Bombyx mori, Tribolium castaneum, Apis mellifera, Nasonia vitripennis, and Pediculus humanus genomes as part of genome sequencing efforts. Results All the insects examined have 2 TRPV, 1 TRPN, 1 TRPM, 3 TRPC, and 1 TRPML subfamily members, demonstrating that these channels have the ancient origins in insects. The common pattern also suggests that the mechanisms for detecting mechanical and visual stimuli and maintaining lysosomal functions may be evolutionarily well conserved in insects. However, a TRPP channel, the most ancient TRP channel, is missing in B. mori, A. mellifera, and N. vitripennis. Although P. humanus and D. melanogaster contain 4 TRPA subfamily members, the other insects have 5 TRPA subfamily members. T. castaneum, A. mellifera, and N. vitripennis contain TRPA5 channels, which have been specifically retained or gained in Coleoptera and Hymenoptera. Furthermore, TRPA1, which functions for thermotaxis in Drosophila, is missing in A. mellifera and N. vitripennis; however, they have other Hymenoptera-specific TRPA channels (AmHsTRPA and NvHsTRPA. NvHsTRPA expressed in HEK293 cells is activated by temperature increase, demonstrating that HsTRPAs function as novel thermal sensors in Hymenoptera. Conclusion The total number of insect TRP family members is 13-14, approximately half that of mammalian TRP

Activity of Palythoa caribaeorum Venom on Voltage-Gated Ion Channels in Mammalian Superior Cervical Ganglion Neurons.

Science.gov (United States)

Lazcano-Pérez, Fernando; Castro, Héctor; Arenas, Isabel; García, David E; González-Muñoz, Ricardo; Arreguín-Espinosa, Roberto

2016-05-05

The Zoanthids are an order of cnidarians whose venoms and toxins have been poorly studied. Palythoa caribaeorum is a zoanthid commonly found around the Mexican coastline. In this study, we tested the activity of P. caribaeorum venom on voltage-gated sodium channel (NaV1.7), voltage-gated calcium channel (CaV2.2), the A-type transient outward (IA) and delayed rectifier (IDR) currents of KV channels of the superior cervical ganglion (SCG) neurons of the rat. These results showed that the venom reversibly delays the inactivation process of voltage-gated sodium channels and inhibits voltage-gated calcium and potassium channels in this mammalian model. The compounds responsible for these effects seem to be low molecular weight peptides. Together, these results provide evidence for the potential use of zoanthids as a novel source of cnidarian toxins active on voltage-gated ion channels.

Entrance channel systematics of pre-scission neutron multiplicities

International Nuclear Information System (INIS)

Shareef, M.; Prasad, E.; Chatterjee, A.

2016-01-01

Statistical model analysis has been performed for the available neutron multiplicity (ν_p_r_e) data in the literature. Larger ν_p_r_e values for more symmetric reactions have been observed in comparison with asymmetric reactions forming the same compound nucleus, in most cases. A reverse trend has also been noticed in a few cases. A systematic entrance channel dependence of fission timescale is brought out in this work. Fission timescales calculated using the experimental ν_p_r_e values fall into two distinct groups according to the entrance channel mass asymmetry of the reaction with respect to the Businaro-Gallone critical mass asymmetry. The difference in the delay between these two groups ranges between 20 and 100 zs, which is larger than that reported in some cases. (orig.)

Evolutionary conservation and changes in insect TRP channels

OpenAIRE

Tominaga Makoto; Kohno Keigo; Sokabe Takaaki; Matsuura Hironori; Kadowaki Tatsuhiko

2009-01-01

Abstract Background TRP (Transient Receptor Potential) channels respond to diverse stimuli and thus function as the primary integrators of varied sensory information. They are also activated by various compounds and secondary messengers to mediate cell-cell interactions as well as to detect changes in the local environment. Their physiological roles have been primarily characterized only in mice and fruit flies, and evolutionary studies are limited. To understand the evolution of insect TRP c...

Biological evaluation of [18F]-nifedipine as a novel PET tracer for L-type calcium channel imaging

International Nuclear Information System (INIS)

Sadeghpour, H.; Jalilian, A.R.; Akhlaghi, M.; Mirzaii, M.; Saddadi, F.; Shafiee, A.; Miri, R.

2008-01-01

Due to interesting role of dihydropyridines in cardiovascular diseases and drug resistance studies and lack of a fluorine-18 labeled imaging agent for L-type calcium channel studies, this study was designed. [ 18 F] Dimethyl 2 - (fluoromethyl) - 6 - methyl - 4 - (2 - nitrophenyl) - 1,4 - dihydropyridine - 3,5 - dicarboxylate 2 was prepared in no-carrier-added (n.c.a.) form from a starting brominated compound in one step at 80 o C in Kryptofix2.2.2/[ 18 F]. Compound 2 was administered to normal rats via their tail veins for preliminary biodistribution studies and the ID/g % of the labeled compound was determined up to 3 h post injections. Coincidence images were obtained in rats 5 to 120 min. Radiofluorination on bromo precursor gave a fluorinated compound in 95 % radiochemical purity and a 8% yield shown by RTLC and HPLC. Biodistribution studies showed that the tracer is accumulated in the heart in the first few minutes, followed by metabolism resulting in very soluble 18 F-containing metabolites eliminated through the urinary tract. In coincidence images, the target organ was shown to be the heart. Lung had high accumulation possibly due to the presence of Ca 2+ channels and/or hydrolyzing enzymes showing a significant myocardial uptake at 120 min. The data demonstrates a significant agreement with the reported L-type calcium channels throughout the animal body. To our knowledge, this is the first example of 18 F-DHPs in the literature. (authors)

Charged and Neutral Particles Channeling Phenomena Channeling 2008

Science.gov (United States)

Dabagov, Sultan B.; Palumbo, Luigi

2010-04-01

regime by a buried oxide layer / V. Guidi, A. Mazzolari and V. V. Tikhomirov -- A positron source using channeling in crystals for linear colliders / X. Artru ... [et al.] -- Parametric channeling and collapse of charged particles beams in crystals / M. Vysotskyy and V. Vysotskii.The formation and usage of coherent correlated charged particles states in the physics of channeling in crystals / S. V. Adamenko, V. I. Vysotskii and M. V. Vysotskyy -- Surface channeling of magnetic-charged particles on multilayer surface / S. V. Adamenko and V. I. Vysotskii -- Coherent creation of anti-hydrogen atoms in a crystal by relativistic antiproton / Yu. P. Kunashenko -- Thermal equilibrium of light ions in heavy crystals / E. Tsyganov -- Photon emission of electrons in a crystalline undulator / H. Backe ... [et al.] -- Channeling radiation from relativistic electrons in a crystal target as complementary x-ray and gamma ray source at synchrotron light facilities / K. B. Korotchenko, Yu. L. Pivovarov and T. A. Tukhfatullin -- Diffracted channeling radiation and other compound radiation processes / H. Nitta -- Collective scattering on the atom planes under the condition of full transition / A. R. Mkrtchyan ... [et al.] -- The proposal of the experiment on the research of the diffracted channeling radiation / D. A. Baklanov ... [et al.] -- Positron channeling at the DaOne BTF Facility: the cup experiment / L. Quintieri ... [et al.] -- Radiation spectra of 200 MeV electrons in diamond and silicon crystals at axial and planar orientations / K. Fissum ... [et al.] -- Channeling experiments with electrons at the Mainz Microtron Mami / W. Lauth ... [et al.] -- Dechanneling of positrons by dislocations: effects of anharmonic interactions / J. George and A. P. Pathak -- Diffracted channeling radiation from axially channeled relativistic electrons / K. B. Korotchenko ... [et al.] -- Intensive quasi-monochromatic, directed x-ray radiation of planar channeled positron bunch / L. Gevorgian

Computer simulations of channel meandering and the formation of point bars: Linking channel dynamics to the preserved stratigraphy

Science.gov (United States)

Sun, T.; Covault, J. A.; Pyrcz, M.; Sullivan, M.

2012-12-01

Meandering rivers are probably one of the most recognizable geomorphic features on earth. As they meander across alluvial and delta plains, channels migrate laterally and develop point bars, splays, levees and other geomorphic and sedimentary features that compose substantial portions of the fill within many sedimentary basins. These basins can include hydrocarbon producing fields. Therefore, a good understanding of the processes of meandering channels and their associated deposits is critical for exploiting these reservoirs in the subsurface. In the past couple of decades, significant progress has been made in our understanding of the morphodynamics of channel meandering. Basic fluid dynamics and sediment transport (Ikeda and Parker, 1981; Howard, 1992) has shown that many characteristic features of meandering rivers, such as the meandering wavelength, growth rate and downstream migration rate, can be predicted quantitatively. As a result, a number of variations and improvement of the theory have emerged (e.g., Blondeaux and Seminara, 1985; Parker and Andrews, 1985, 1986; and Sun et al., 2001a, b).The main improvements include the recognition of so called "bar-bend" interactions, where the development of bars on the channel bed and their interactions with the channel bend is recognized as a primary cause for meandering channels to develop greater complexity than the classic goose-neck meander bend shapes, such as compound bend. Recently, Sun and others have shown that the spatial patterns of width variations in meandering channels can be explained by an extrinsic periodic flow variations coupled with the intrinsic bend instability dynamics. In contrast to the significant improvement of our understanding of channel meandering, little work has been done to link the geomorphic features of meandering channels to the geometry and heterogeneity of the deposits they form and ultimately preserves. A computer simulation model based on the work of Sun and others (1996, 2001

Channeling and coherent bremsstrahlung effects for relativistic positrons and electrons

International Nuclear Information System (INIS)

Walker, R.L.

1976-01-01

Channeling of positrons in single crystals of silicon was observed in transmission and scattering measurements for incident energies from 16 to 28 MeV. In addition, the spectral dependence upon crystal orientation of the forward coherent bremsstrahlung produced by beams of 28-MeV positrons and electrons incident upon a 5 μm thick single crystal of silicon was measured with a NaI photon spectrometer. Effects of channeling and perhaps of the nonvalidity of the first Born approximation were observed for beam directions near the [111] axis of the crystal, and coherent peaks near 0.5 MeV were observed for a compound interference direction, in agreement with first-order theoretical calculations. 32 fig

Activity of Palythoa caribaeorum Venom on Voltage-Gated Ion Channels in Mammalian Superior Cervical Ganglion Neurons

Directory of Open Access Journals (Sweden)

Fernando Lazcano-Pérez

2016-05-01

Full Text Available The Zoanthids are an order of cnidarians whose venoms and toxins have been poorly studied. Palythoa caribaeorum is a zoanthid commonly found around the Mexican coastline. In this study, we tested the activity of P. caribaeorum venom on voltage-gated sodium channel (NaV1.7, voltage-gated calcium channel (CaV2.2, the A-type transient outward (IA and delayed rectifier (IDR currents of KV channels of the superior cervical ganglion (SCG neurons of the rat. These results showed that the venom reversibly delays the inactivation process of voltage-gated sodium channels and inhibits voltage-gated calcium and potassium channels in this mammalian model. The compounds responsible for these effects seem to be low molecular weight peptides. Together, these results provide evidence for the potential use of zoanthids as a novel source of cnidarian toxins active on voltage-gated ion channels.

A novel dihydropyridine with 3-aryl meta-hydroxyl substitution blocks L-type calcium channels in rat cardiomyocytes

Energy Technology Data Exchange (ETDEWEB)

Galvis-Pareja, David [Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Químicas y Farmacéuticas and Facultad Medicina, Universidad de Chile, Santiago (Chile); Centro Estudios Moleculares de la Célula (CEMC), Facultad de Ciencias Químicas y Farmacéuticas and Facultad Medicina, Universidad de Chile, Santiago (Chile); Zapata-Torres, Gerald [Departamento de Química Inorgánica y Analítica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago (Chile); Hidalgo, Jorge [Centro Estudios Moleculares de la Célula (CEMC), Facultad de Ciencias Químicas y Farmacéuticas and Facultad Medicina, Universidad de Chile, Santiago (Chile); Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago (Chile); Ayala, Pedro [Centro Estudios Moleculares de la Célula (CEMC), Facultad de Ciencias Químicas y Farmacéuticas and Facultad Medicina, Universidad de Chile, Santiago (Chile); and others

2014-08-15

Rationale: Dihydropyridines are widely used for the treatment of several cardiac diseases due to their blocking activity on L-type Ca{sup 2+} channels and their renowned antioxidant properties. Methods: We synthesized six novel dihydropyridine molecules and performed docking studies on the binding site of the L-type Ca{sup 2+} channel. We used biochemical techniques on isolated adult rat cardiomyocytes to assess the efficacy of these molecules on their Ca{sup 2+} channel-blocking activity and antioxidant properties. The Ca{sup 2+} channel-blocking activity was evaluated by confocal microscopy on fluo-3AM loaded cardiomyocytes, as well as using patch clamp experiments. Antioxidant properties were evaluated by flow cytometry using the ROS sensitive dye 1,2,3 DHR. Results: Our docking studies show that a novel compound with 3-OH substitution inserts into the active binding site of the L-type Ca{sup 2+} channel previously described for nitrendipine. In biochemical assays, the novel meta-OH group in the aryl in C4 showed a high blocking effect on L-type Ca{sup 2+} channel as opposed to para-substituted compounds. In the tests we performed, none of the molecules showed antioxidant properties. Conclusions: Only substitutions in C2, C3 and C5 of the aryl ring render dihydropyridine compounds with the capacity of blocking LTCC. Based on our docking studies, we postulate that the antioxidant activity requires a larger group than the meta-OH substitution in C2, C3 or C5 of the dihydropyridine ring. - Highlights: • Dihydropyridine (DHP) molecules are widely used in cardiovascular disease. • DHPs block Ca{sup 2+} entry through LTCC—some DHPs have antioxidant activity as well. • We synthesized 6 new DHPs and tested their Ca{sup 2+} blocking and antioxidant activities. • 3-Aryl meta-hydroxyl substitution strongly increases their Ca{sup 2+} blocking activity. • 3-Aryl meta-hydroxyl substitution did not affect the antioxidant properties.

Fast fission phenomenon, deep inelastic reactions and compound nucleus formation described within a dynamical macroscopic model

International Nuclear Information System (INIS)

Gregoire, C.; Ngo, C.; Remaud, B.

1982-01-01

We present a dynamical model to describe dissipative heavy ion reactions. It treats explicitly the relative motion of the two ions, the mass asymmetry of the system and the projection of the isospin of each ion. The deformations, which are induced during the collision, are simulated with a time-dependent interaction potential. This is done by a time-dependent transition between a sudden interaction potential in the entrance channel and an adiabatic potential in the exit channel. The model allows us to compute the compound-nucleus cross section and multidifferential cross-sections for deep inelastic reactions. In addition, for some systems, and under certain conditions which are discussed in detail, a new dissipative heavy ion collision appears: fast-fission phenomenon which has intermediate properties between deep inelastic and compound nucleus reactions. The calculated properties concerning fast fission are compared with experimental results and reproduce some of those which could not be understood as belonging to deep inelastic or compound-nucleus reactions. (orig.)

Channelling and electromagnetic radiation of channelling particles

International Nuclear Information System (INIS)

Kalashnikov, N.

1983-01-01

A brief description is presented of the channelling of charged particles between atoms in the crystal lattice. The specificities are discussed of the transverse motion of channelling particles as are the origin and properties of quasi-characteristic radiation of channelling particles which accompany transfers from one band of permissible energies of the transverse motion of channelling particles to the other. (B.S.)

Activation of TRPM7 channels by small molecules under physiological conditions.

Science.gov (United States)

Hofmann, T; Schäfer, S; Linseisen, M; Sytik, L; Gudermann, T; Chubanov, V

2014-12-01

Transient receptor potential cation channel, subfamily M, member 7 (TRPM7) is a cation channel covalently linked to a protein kinase domain. TRPM7 is ubiquitously expressed and regulates key cellular processes such as Mg(2+) homeostasis, motility, and proliferation. TRPM7 is involved in anoxic neuronal death, cardiac fibrosis, and tumor growth. The goal of this work was to identify small molecule activators of the TRPM7 channel and investigate their mechanism of action. We used an aequorin bioluminescence-based assay to screen for activators of the TRPM7 channel. Valid candidates were further characterized using patch clamp electrophysiology. We identified 20 drug-like compounds with various structural backbones that can activate the TRPM7 channel. Among them, the δ opioid antagonist naltriben was studied in greater detail. Naltriben's action was selective among the TRP channels tested. Naltriben activates TRPM7 currents without prior depletion of intracellular Mg(2+) even under conditions of low PIP2. Moreover, naltriben interfered with the effect of the TRPM7 inhibitor NS8593. Finally, our experiments with TRPM7 variants carrying mutations in the pore, TRP, and kinase domains indicate that the site of TRPM7 activation by this small-molecule ligand is most likely located in or near the TRP domain. In conclusion, we identified the first organic small-molecule activators of TRPM7 channels, thus providing new experimental tools to study TRPM7 function in native cellular environments.

Slopes To Prevent Trapping of Bubbles in Microfluidic Channels

Science.gov (United States)

Greer, Harold E.; Lee, Michael C.; Smith, J. Anthony; Willis, Peter A.

2010-01-01

The idea of designing a microfluidic channel to slope upward along the direction of flow of the liquid in the channel has been conceived to help prevent trapping of gas bubbles in the channel. In the original application that gave rise to this idea, the microfluidic channels are parts of micro-capillary electrophoresis (microCE) devices undergoing development for use on Mars in detecting compounds indicative of life. It is necessary to prevent trapping of gas bubbles in these devices because uninterrupted liquid pathways are essential for sustaining the electrical conduction and flows that are essential for CE. The idea is also applicable to microfluidic devices that may be developed for similar terrestrial microCE biotechnological applications or other terrestrial applications in which trapping of bubbles in microfluidic channels cannot be tolerated. A typical microCE device in the original application includes, among other things, multiple layers of borosilicate float glass wafers. Microfluidic channels are formed in the wafers, typically by use of wet chemical etching. The figure presents a simplified cross section of part of such a device in which the CE channel is formed in the lowermost wafer (denoted the channel wafer) and, according to the present innovation, slopes upward into a via hole in another wafer (denoted the manifold wafer) lying immediately above the channel wafer. Another feature of the present innovation is that the via hole in the manifold wafer is made to taper to a wider opening at the top to further reduce the tendency to trap bubbles. At the time of reporting the information for this article, an effort to identify an optimum technique for forming the slope and the taper was in progress. Of the techniques considered thus far, the one considered to be most promising is precision milling by use of femtosecond laser pulses. Other similar techniques that may work equally well are precision milling using a focused ion beam, or a small diamond

Activation of human IK and SK Ca2+ -activated K+ channels by NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime)

DEFF Research Database (Denmark)

Strøbaek, Dorte; Teuber, Lene; Jørgensen, Tino D

2004-01-01

We have identified and characterized the compound NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) as a potent activator of human Ca2+ -activated K+ channels of SK and IK types, whereas it is devoid of effect on BK type channels. IK- and SK-channels have previously been reported to be activated...

Cyanated diazatetracene diimides with ultrahigh electron affinity for n-channel field effect transistors

KAUST Repository

Ye, Qun

2013-03-15

Several diazatetracene diimides with high electron affinity (up to 4.66 eV!) were prepared and well characterized. The LUMO energy level of these electron-deficient molecules was found to be closely related to their material stability. Compound 7 with ultrahigh electron affinity suffered from reduction and hydrolysis in the presence of silica gel or water. The stable compounds 3 and 6 showed n-channel FET behavior with an average electron mobility of 0.002 and 0.005 cm2 V-1 s-1, respectively, using a solution processing method. © 2013 American Chemical Society.

Acrolein-mediated conduction loss is partially restored by K+ channel blockers

Science.gov (United States)

Yan, Rui; Page, Jessica C.

2015-01-01

Acrolein-mediated myelin damage is thought to be a critical mechanism leading to conduction failure following neurotrauma and neurodegenerative diseases. The exposure and activation of juxtaparanodal voltage-gated K+ channels due to myelin damage leads to conduction block, and K+ channel blockers have long been studied as a means for restoring axonal conduction in spinal cord injury (SCI) and multiple sclerosis (MS). In this study, we have found that 100 μM K+ channel blockers 4-aminopyridine-3-methanol (4-AP-3-MeOH), and to a lesser degree 4-aminopyridine (4-AP), can significantly restore compound action potential (CAP) conduction in spinal cord tissue following acrolein-mediated myelin damage using a well-established ex vivo SCI model. In addition, 4-AP-3-MeOH can effectively restore CAP conduction in acrolein-damaged axons with a range of concentrations from 0.1 to 100 μM. We have also shown that while both compounds at 100 μM showed no preference of small- and large-caliber axons when restoring CAP conduction, 4-AP-3-MeOH, unlike 4-AP, is able to augment CAP amplitude while causing little change in axonal responsiveness measured in refractory periods and response to repetitive stimuli. In a prior study, we show that 4-AP-3-MeOH was able to functionally rescue mechanically injured axons. In this investigation, we conclude that 4-AP-3-MeOH is an effective K+ channel blocker in restoring axonal conduction following both primary (physical) and secondary (chemical) insults. These findings also suggest that 4-AP-3-MeOH is a viable alternative of 4-AP for treating myelin damage and improving function following central nervous system trauma and neurodegenerative diseases. PMID:26581866

Synthesis and biological evaluation of pyrrolidine derivatives as novel and potent sodium channel blockers for the treatment of ischemic stroke.

Science.gov (United States)

Seki, Maki; Tsuruta, Osamu; Tatsumi, Ryo; Soejima, Aki

2013-07-15

A novel series of pyrrolidine derivatives as Na(+) channel blockers was synthesized and evaluated for their inhibitory effects on neuronal Na(+) channels. Structure-activity relationship (SAR) studies of a pyrrolidine analogue 2 led to the discovery of 5e as a potent Na(+) channel blocker with a low inhibitory action against human ether-a-go-go-related gene (hERG) channels. Compound 5e showed remarkably neuroprotective activity in a rat transient middle cerebral artery occlusion (MCAO) model, suggesting that 5e would act as a neuroprotectant for ischemic stroke. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Super-Radiant Mechanism and the Widths of Compound Nuclear States

International Nuclear Information System (INIS)

Auerbach, N

2012-01-01

In the introduction I will present the theory of the super-radiant mechanism as applied to various phenomena. I will then discuss the statistics of resonance widths in a many-body Fermi system with open decay channels. Depending on the strength of the coupling to the continuum such systems show deviations from the standard Porter-Thomas distribution. The deviations result from the process of increasing interaction of the intrinsic states through the common decay channels. In the limit of very strong coupling this leads to super-radiance. The results I will present are important for the understanding of recent experimental data concerning the width distribution of compound neutron resonances in nuclei.

Advanced applications of ion channeling for the study of imperfections in crystals

Energy Technology Data Exchange (ETDEWEB)

Swanson, M L [North Carolina Univ., Chapel Hill, NC (United States)

1997-03-01

A review will be given of the applications of medium energy ion channeling for the studies of imperfections in the near-surface regions of crystals. The following topics will be discussed: (1.) epitaxial layers, including elemental depositions of a few monolayers, strained-layer superlattices, and compound layers; (2.) lattice defects, including ion damage in diamond, dislocation networks in Si, and anomalous lattice vibrations in high temperature superconductors; (3.) lattice sites of solute atoms, including substitutional sites in compounds (LiNbO{sub 3} and GaP), and interstitial sites produced by association with point defects. (author)

EFFECTS OF PYRETHROIDS ON VOLTAGE-SENSITIVE CALCIUM CHANNELS: A CRITICAL EVALUATION OF STRENGTHS, WEAKNESSES, DATA NEEDS, AND RELATIONSHIP TO ASSESSMENT OF CUMULATIVE NEUROTOXICITY.

Science.gov (United States)

A recently published review (Soderlund et al., 2002, Toxicology 171, 3-59.) of the mechanisms of acute neurotoxicity of pyrethroid compounds postulated that voltage-sensitive calcium channels (VSCC) may be a target of some pyrethroid compounds and that effects on VSCC may contrib...

An Effective Channel Allocation Scheme to Reduce Co-Channel and Adjacent Channel Interference for WMN Backhaul

International Nuclear Information System (INIS)

Abbasi, S.; Ismaili, I.A.; Khuhawar, F.Y.

2016-01-01

Two folded work presents channel allocation scheme sustaining channel orthogonality and channel spacing to reduce CCI (Co-Channel Interference) and ACI (Adjacent Channel Interference) for inter flow of an intra-flow link. Proposed scheme as a part of radio resource allocation is applied on infrastructure based backhaul of wireless mesh network using directional antennas. The proposed approach is applied separately on 2.4 and 5GHz bands. Interference of connectivity graph is modelled by strongly connected directed graph and greedy algorithms are used for channel allocation. We have used OPNET Modeller suite to simulate network models for this research. The proposed arrangement reduces the channel interference and increases system throughput. In this research, the influence of channel is computed in terms of network throughput and delay. (author)

Effect of the I(to) activator NS5806 on cloned K(V)4 channels depends on the accessory protein KChIP2

DEFF Research Database (Denmark)

Lundby, Alicia; Jespersen, Thomas; Schmitt, Nicole

2010-01-01

The compound NS5806 increases the transient outward current (I(to)) in canine ventricular cardiomyocytes and slows current decay. In human and canine ventricle, I(to) is thought to be mediated by K(V)4.3 and various ancillary proteins, yet, the exact subunit composition of I(to) channels is still...... debated. Here we characterize the effect of NS5806 on heterologously expressed putative I(to) channel subunits and other potassium channels....

Lattice location of impurities in semiconductors: a RBS/channeling and proton-induced x-ray emission study

Energy Technology Data Exchange (ETDEWEB)

Kringhoj, P. [Australian National Univ., Canberra, ACT (Australia). Research School of Physical Sciences

1993-12-31

Rutherford backscattering spectrometry (RBS)/channeling and proton-induced x-ray emission (PIXE) are two well established and characterised techniques. Over the last three decades RBS/channeling measurements has been performed to extract the substitutional fraction of impurities in both elemental and compound semiconductors. However, due to the limitation of RBS, only elements heavier than the host crystal can be examined (except for a few elements, where a nuclear reaction or a resonance can be used). In silicon this limitation is acceptable, due to the low mass of Si, but in the III-V compounds (e.g. InP), the technique is limited to a few elements of hardly no technological or fundamental interest. One can overcome this by combining RBS/channeling with PIXE, where PIXE is applied to detect elements with a mass lower than the host crystal. In the present work, the lattice location of Ge in InP has been studied and compared to the group-III impurity Ga, and the group-VI impurity Se which is known to be a donor. The (RBS)/channeling technique has been used to detect not only the substitutional fraction, but also the relative population of the two sublattices. The half-width is approximately equal to the characteristic angle, {psi}{sub 1}. The channeling data obtained indicate that all three dopants are located exclusively on substitutional sites and that Ga is occuping the In position, Se theP position and that Ge is distributed equally between both sublattices. 6 refs., 1 tab., 3 figs.

Lattice location of impurities in semiconductors: a RBS/channeling and proton-induced x-ray emission study

Energy Technology Data Exchange (ETDEWEB)

Kringhoj, P [Australian National Univ., Canberra, ACT (Australia). Research School of Physical Sciences

1994-12-31

Rutherford backscattering spectrometry (RBS)/channeling and proton-induced x-ray emission (PIXE) are two well established and characterised techniques. Over the last three decades RBS/channeling measurements has been performed to extract the substitutional fraction of impurities in both elemental and compound semiconductors. However, due to the limitation of RBS, only elements heavier than the host crystal can be examined (except for a few elements, where a nuclear reaction or a resonance can be used). In silicon this limitation is acceptable, due to the low mass of Si, but in the III-V compounds (e.g. InP), the technique is limited to a few elements of hardly no technological or fundamental interest. One can overcome this by combining RBS/channeling with PIXE, where PIXE is applied to detect elements with a mass lower than the host crystal. In the present work, the lattice location of Ge in InP has been studied and compared to the group-III impurity Ga, and the group-VI impurity Se which is known to be a donor. The (RBS)/channeling technique has been used to detect not only the substitutional fraction, but also the relative population of the two sublattices. The half-width is approximately equal to the characteristic angle, {psi}{sub 1}. The channeling data obtained indicate that all three dopants are located exclusively on substitutional sites and that Ga is occuping the In position, Se theP position and that Ge is distributed equally between both sublattices. 6 refs., 1 tab., 3 figs.

Improved Iterative Decoding of Network-Channel Codes for Multiple-Access Relay Channel.

Science.gov (United States)

Majumder, Saikat; Verma, Shrish

2015-01-01

Cooperative communication using relay nodes is one of the most effective means of exploiting space diversity for low cost nodes in wireless network. In cooperative communication, users, besides communicating their own information, also relay the information of other users. In this paper we investigate a scheme where cooperation is achieved using a common relay node which performs network coding to provide space diversity for two information nodes transmitting to a base station. We propose a scheme which uses Reed-Solomon error correcting code for encoding the information bit at the user nodes and convolutional code as network code, instead of XOR based network coding. Based on this encoder, we propose iterative soft decoding of joint network-channel code by treating it as a concatenated Reed-Solomon convolutional code. Simulation results show significant improvement in performance compared to existing scheme based on compound codes.

Pre-compound neutron evaporation in heavy ion fusion reactions

International Nuclear Information System (INIS)

Ajay Kumar; Singh, Hardev; Rajesh Kumar; Govil, I.M.; Golda, K.S.; Rakesh Kumar; Datta, S.K.; Yogi, B.K.; Viesti, G.

2007-01-01

In the present investigation, exclusive neutron spectra have been measured in coincidence with the observed γ-rays characteristic to the residual nuclei 53 Fe, 55 Fe and 56 Co. In this new experimental study, we have followed the strategy of forming the compound nucleus 58 Ni at the same excitation energy through two different entrance channels viz the mass symmetric reaction 31 P + 27 Al and the mass asymmetric reaction 12 C + 46 Ti

Bidirectional shifts of TRPM8 channel gating by temperature and chemical agents modulate the cold sensitivity of mammalian thermoreceptors.

Science.gov (United States)

Mälkiä, Annika; Madrid, Rodolfo; Meseguer, Victor; de la Peña, Elvira; Valero, María; Belmonte, Carlos; Viana, Félix

2007-05-15

TRPM8, a member of the melastatin subfamily of transient receptor potential (TRP) cation channels, is activated by voltage, low temperatures and cooling compounds. These properties and its restricted expression to small sensory neurons have made it the ion channel with the most advocated role in cold transduction. Recent work suggests that activation of TRPM8 by cold and menthol takes place through shifts in its voltage-activation curve, which cause the channel to open at physiological membrane potentials. By contrast, little is known about the actions of inhibitors on the function of TRPM8. We investigated the chemical and thermal modulation of TRPM8 in transfected HEK293 cells and in cold-sensitive primary sensory neurons. We show that cold-evoked TRPM8 responses are effectively suppressed by inhibitor compounds SKF96365, 4-(3-chloro-pyridin-2-yl)-piperazine-1-carboxylic acid (4-tert-butyl-phenyl)-amide (BCTC) and 1,10-phenanthroline. These antagonists exert their effect by shifting the voltage dependence of TRPM8 activation towards more positive potentials. An opposite shift towards more negative potentials is achieved by the agonist menthol. Functionally, the bidirectional shift in channel gating translates into a change in the apparent temperature threshold of TRPM8-expressing cells. Accordingly, in the presence of the antagonist compounds, the apparent response-threshold temperature of TRPM8 is displaced towards colder temperatures, whereas menthol sensitizes the response, shifting the threshold in the opposite direction. Co-application of agonists and antagonists produces predictable cancellation of these effects, suggesting the convergence on a common molecular process. The potential for half maximal activation of TRPM8 activation by cold was approximately 140 mV more negative in native channels compared to recombinant channels, with a much higher open probability at negative membrane potentials in the former. In functional terms, this difference translates

Small-conductance calcium-activated potassium (SK) channels contribute to action potential repolarization in human atria

DEFF Research Database (Denmark)

Skibsbye, Lasse; Poulet, Claire; Diness, Jonas Goldin

2014-01-01

(+) currents by ∼15% and prolonged action potential duration (APD), but no effect was observed in myocytes from AF patients. In trabeculae muscle strips from right atrial appendages of SR patients, both compounds increased APD and effective refractory period, and depolarized the resting membrane potential......, while only NS8593 induced these effects in tissue from AF patients. SK channel inhibition did not alter any electrophysiological parameter in human interventricular septum tissue. CONCLUSIONS: SK channels are present in human atria where they participate in repolarization. SK2 and SK3 were down...

Wall-slip of highly filled powder injection molding compounds: Effect of flow channel geometry and roughness

Science.gov (United States)

Hausnerova, Berenika; Sanetrnik, Daniel; Paravanova, Gordana

2014-05-01

The paper deals with the rheological behavior of highly filled compounds proceeded via powder injection molding (PIM) and applied in many sectors of industry (automotive, medicine, electronic or military). Online rheometer equipped with slit dies varying in surface roughness and dimensions was applied to investigate the wall-slip as a rheological phenomenon, which can be considered as a parameter indicating the separation of compound components (polymer binder and metallic powder) during high shear rates when injection molded.

Novel Compound-Forming Technology Using Bioprinting and Electrospinning for Patterning a 3D Scaffold Construct with Multiscale Channels

Directory of Open Access Journals (Sweden)

Yuanshao Sun

2016-12-01

Full Text Available One of the biggest challenges for tissue engineering is to efficiently provide oxygen and nutrients to cells on a three-dimensional (3D engineered scaffold structure. Thus, achieving sufficient vascularization of the structure is a critical problem in tissue engineering. This facilitates the need to develop novel methods to enhance vascularization. Use of patterned hydrogel structures with multiscale channels can be used to achieve the required vascularization. Patterned structures need to be biocompatible and biodegradable. In this study, gelatin was used as the main part of a hydrogel to prepare a biological structure with 3D multiscale channels using bioprinting combined with selection of suitable materials and electrostatic spinning. Human umbilical vein endothelial cells (HUVECs were then used to confirm efficacy of the structure, inferred from cell viability on different engineered construct designs. HUVECs were seeded on the surface of channels and cultured in vitro. HUVECs showed high viability and diffusion within the construct. This method can be used as a practical platform for the fabrication of engineered construct for vascularization.

The efficacy of mass-marking channel catfish fingerlings by immersion in oxytetracycline

Science.gov (United States)

Stewart, David R.

2011-01-01

Oxytetracycline (OTC) has been extensively used for marking a variety of fish species, but has never been successfully used to mark channel catfish Ictalurus punctatus. Channel catfish fingerlings (~ 25 mm TL) obtained from the Oklahoma Department of Wildlife Conservation at Byron Fish Hatchery were kept in Living Streams (791 to 1,018 L) equipped with recirculation units. Marking trials consisted of immersing channel catfish in one of three concentrations (250, 450, and 700 mg/L) OTC hydrochloride [HCl] for 6 hours. Samples of channel catfish were obtained from each group at 1-week and 4-week postimmersion. Lapilli otoliths and pectoral spines were removed to assess mark presence with an epi-fluorescent compound microscope. After one week, no marks were detected on pectoral spines for all treatments, mark detection on otoliths depended on concentration, but never exceeded 43% (700 mg/L). After four weeks, all otoliths and pectoral spines were determined marked for 700 mg/L OTC, 20% for fish immersed in 450 mg/L OTC, and 0% were marked after four weeks at the 250 mg/L OTC. Results show, channel catfish fingerlings can be successfully marked with immersion in OTC at 700 mg/L for at least 6 hours.

Citizens and service channels: channel choice and channel management implications

NARCIS (Netherlands)

Pieterson, Willem Jan

2010-01-01

The arrival of electronic channels in the 1990s has had a huge impact on governmental service delivery. The new channels have led to many new opportunities to improve public service delivery, not only in terms of citizen satisfaction, but also in cost reduction for governmental agencies. However,

Ladder-Shaped Ion Channel Ligands: Current State of Knowledge

Science.gov (United States)

Shmukler, Yuri B.; Nikishin, Denis A.

2017-01-01

Ciguatoxins (CTX) and brevetoxins (BTX) are polycyclic ethereal compounds biosynthesized by the worldwide distributed planktonic and epibenthic dinoflagellates of Gambierdiscus and Karenia genera, correspondingly. Ciguatera, evoked by CTXs, is a type of ichthyosarcotoxism, which involves a variety of gastrointestinal and neurological symptoms, while BTXs cause so-called neurotoxic shellfish poisoning. Both types of toxins are reviewed together because of similar mechanisms of their action. These are the only molecules known to activate voltage-sensitive Na+-channels in mammals through a specific interaction with site 5 of its α-subunit and may compete for it, which results in an increase in neuronal excitability, neurotransmitter release and impairment of synaptic vesicle recycling. Most marine ciguatoxins potentiate Nav channels, but a considerable number of them, such as gambierol and maitotoxin, have been shown to affect another ion channel. Although the extrinsic function of these toxins is probably associated with the function of a feeding deterrent, it was suggested that their intrinsic function is coupled with the regulation of photosynthesis via light-harvesting complex II and thioredoxin. Antagonistic effects of BTXs and brevenal may provide evidence of their participation as positive and negative regulators of this mechanism. PMID:28726749

Ladder-Shaped Ion Channel Ligands: Current State of Knowledge

Directory of Open Access Journals (Sweden)

Yuri B. Shmukler

2017-07-01

Full Text Available Ciguatoxins (CTX and brevetoxins (BTX are polycyclic ethereal compounds biosynthesized by the worldwide distributed planktonic and epibenthic dinoflagellates of Gambierdiscus and Karenia genera, correspondingly. Ciguatera, evoked by CTXs, is a type of ichthyosarcotoxism, which involves a variety of gastrointestinal and neurological symptoms, while BTXs cause so-called neurotoxic shellfish poisoning. Both types of toxins are reviewed together because of similar mechanisms of their action. These are the only molecules known to activate voltage-sensitive Na+-channels in mammals through a specific interaction with site 5 of its α-subunit and may compete for it, which results in an increase in neuronal excitability, neurotransmitter release and impairment of synaptic vesicle recycling. Most marine ciguatoxins potentiate Nav channels, but a considerable number of them, such as gambierol and maitotoxin, have been shown to affect another ion channel. Although the extrinsic function of these toxins is probably associated with the function of a feeding deterrent, it was suggested that their intrinsic function is coupled with the regulation of photosynthesis via light-harvesting complex II and thioredoxin. Antagonistic effects of BTXs and brevenal may provide evidence of their participation as positive and negative regulators of this mechanism.

Total and Compound Formation Cross Sections for Americium Nuclei: Recommendations for Coupled-Channels Calculations

Energy Technology Data Exchange (ETDEWEB)

Escher, J. E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2017-04-11

Calculations for total cross sections and compound-nucleus (CN) formation cross sections for americium isotopes are described, for use in the 2017 NA-22 evaluation effort. The code ECIS 2006 was used in conjunction with Frank Dietrich's wrapper `runtemplate'.

Single-channel kinetics of BK (Slo1 channels

Directory of Open Access Journals (Sweden)

Yanyan eGeng

2015-01-01

Full Text Available Single-channel kinetics has proven a powerful tool to reveal information about the gating mechanisms that control the opening and closing of ion channels. This introductory review focuses on the gating of large conductance Ca2+- and voltage-activated K+ (BK or Slo1 channels at the single-channel level. It starts with single-channel current records and progresses to presentation and analysis of single-channel data and the development of gating mechanisms in terms of discrete state Markov (DSM models. The DSM models are formulated in terms of the tetrameric modular structure of BK channels, consisting of a central transmembrane pore-gate domain (PGD attached to four surrounding transmembrane voltage sensing domains (VSD and a large intracellular cytosolic domain (CTD, also referred to as the gating ring. The modular structure and data analysis shows that the Ca2+ and voltage dependent gating considered separately can each be approximated by 10-state two-tiered models with 5 closed states on the upper tier and 5 open states on the lower tier. The modular structure and joint Ca2+ and voltage dependent gating are consistent with a 50 state two-tiered model with 25 closed states on the upper tier and 25 open states on the lower tier. Adding an additional tier of brief closed (flicker states to the 10-state or 50-state models improved the description of the gating. For fixed experimental conditions a channel would gate in only a subset of the potential number of states. The detected number of states and the correlations between adjacent interval durations are consistent with the tiered models. The examined models can account for the single-channel kinetics and the bursting behavior of gating. Ca2+ and voltage activate BK channels by predominantly increasing the effective opening rate of the channel with a smaller decrease in the effective closing rate. Ca2+ and depolarization thus activate by mainly destabilizing the closed states.

P-matrix in the quark compound bag model

International Nuclear Information System (INIS)

Kalashnikova, Yu.S.; Narodetskij, I.M.; Veselov, A.I.

1983-01-01

Meaning of the P-matrix analysis is discussed within the quark compound bag (QCB) model. The most general version of this model is considered including the arbitrary coupling between quark and hadronic channels and the arbitrary smearipg of the surface interection region. The behaviour of P-matrix poles as functions of matching radius r,L0 is discussed for r 0 > + . In conclusion are presented the parameters of an illustrative set of NN potentials that has been obtained from the P-matrix fit to experimental data

In-channel electrochemical detection in the middle of microchannel under high electric field.

Science.gov (United States)

Kang, Chung Mu; Joo, Segyeong; Bae, Je Hyun; Kim, Yang-Rae; Kim, Yongseong; Chung, Taek Dong

2012-01-17

We propose a new method for performing in-channel electrochemical detection under a high electric field using a polyelectrolytic gel salt bridge (PGSB) integrated in the middle of the electrophoretic separation channel. The finely tuned placement of a gold working electrode and the PGSB on an equipotential surface in the microchannel provided highly sensitive electrochemical detection without any deterioration in the separation efficiency or interference of the applied electric field. To assess the working principle, the open circuit potentials between gold working electrodes and the reference electrode at varying distances were measured in the microchannel under electrophoretic fields using an electrically isolated potentiostat. In addition, "in-channel" cyclic voltammetry confirmed the feasibility of electrochemical detection under various strengths of electric fields (∼400 V/cm). Effective separation on a microchip equipped with a PGSB under high electric fields was demonstrated for the electrochemical detection of biological compounds such as dopamine and catechol. The proposed "in-channel" electrochemical detection under a high electric field enables wider electrochemical detection applications in microchip electrophoresis.

75 FR 4527 - Sunshine Act Notice

Science.gov (United States)

2010-01-28

... on Civil Rights announced a business meeting to be held on Friday, January 15, 2010 at the Commission... on Covert Wiretapping in the War on Terror. Multi-Ethnic Placement Act Briefing Report. [[Page 4528...

Mechanisms underlying probucol-induced hERG-channel deficiency

Directory of Open Access Journals (Sweden)

Shi YQ

2015-07-01

Full Text Available Yuan-Qi Shi,1,* Cai-Chuan Yan,1,* Xiao Zhang,1 Meng Yan,1 Li-Rong Liu,1 Huai-Ze Geng,1 Lin Lv,1 Bao-Xin Li1,21Department of Pharmacology, Harbin Medical University, 2State-Province Key Laboratory of Biopharmaceutical Engineering, Harbin, Heilongjiang, People’s Republic of China*These authors contributed equally to this workAbstract: The hERG gene encodes the pore-forming α-subunit of the rapidly activating delayed rectifier potassium channel (IKr, which is important for cardiac repolarization. Reduction of IhERG due to genetic mutations or drug interferences causes long QT syndrome, leading to life-threatening cardiac arrhythmias (torsades de pointes or sudden death. Probucol is a cholesterol-lowering drug that could reduce hERG current by decreasing plasma membrane hERG protein expression and eventually cause long QT syndrome. Here, we investigated the mechanisms of probucol effects on IhERG and hERG-channel expression. Our data demonstrated that probucol reduces SGK1 expression, known as SGK isoform, in a concentration-dependent manner, resulting in downregulation of phosphorylated E3 ubiquitin ligase Nedd4-2 expression, but not the total level of Nedd4-2. As a result, the hERG protein reduces, due to the enhanced ubiquitination level. On the contrary, carbachol could enhance the phosphorylation level of Nedd4-2 as an alternative to SGK1, and thus rescue the ubiquitin-mediated degradation of hERG channels caused by probucol. These discoveries provide a novel mechanism of probucol-induced hERG-channel deficiency, and imply that carbachol or its analog may serve as potential therapeutic compounds for the handling of probucol cardiotoxicity.Keywords: long QT, hERG potassium channels, probucol, SGK1, Nedd4-2

[Synopsis about the hypothesis of "information channel" of channel-collateral system].

Science.gov (United States)

Chang, Xi-Lang

2008-10-01

The author of the present paper founded a theorem about the "incompleteness of single channel structure" (nerve, blood vessel, lymphatic, interspace, aperture, etc.) through quantitative and qualitative analysis about the economic information channel in the human body, which eliminates the probability of single channel structure in the information channel of channel (meridian)-collateral system. After comprehensive analysis on the current researches, the author puts forward a neodoxy, i.e., the body "information channel" structure of the channel-collateral system, mainly follows the distribution regularity of systemic statistics, and is not a single specific entity; various layers of the information channel in the main stems of the channel-collaterals are composed of optimized structure tissues. Hence, the structure of this information channel of channel-collateral system is an overall-optimized, sequential and compatible systemic structure. From this neodoxy, the author brings forward a working principle of channel-collaterals, which is supported theoretically by bio-auxology. The longitudinal distribution of the main stems of meridian-collaterals is considered to result from that in the process of the animal evolution, in the animals moving forward, the microscopic complicated movement of intracorporeal information and energy molecules is related to the forward macroscopic and non-uniform movement of organism in trans-measure. Its impulse and kinetic momentum forms a main vector in the longitudinal direction of the body (the direction of the main stem of channel-collaterals). In order to adapt to and utilize natural regularities, the main stems of the channel-collaterals gradually differentiate and evolve in the living organism, forming a whole system. The "hypothesis of biological origin of channel-collateral system" and "that of information channel of the channel-collaterals in the body" constitute a relatively complete theoretical system framework.

Inhibition of herpes simplex virus type 1 entry by chloride channel inhibitors tamoxifen and NPPB

Energy Technology Data Exchange (ETDEWEB)

Zheng, Kai [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); College of Life Science and Technology, Jinan University, Guangzhou (China); Chen, Maoyun [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); College of pharmacy, Jinan University, Guangzhou (China); Xiang, Yangfei; Ma, Kaiqi [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); Jin, Fujun [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); College of pharmacy, Jinan University, Guangzhou (China); Wang, Xiao [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006 (China); Wang, Xiaoyan; Wang, Shaoxiang [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China); Wang, Yifei, E-mail: twang-yf@163.com [Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou (China)

2014-04-18

Highlights: • We analyze the anti-HSV potential of chloride channel inhibitors. • Tamoxifen and NPPB show anti-HSV-1 and anti-ACV-resistant HSV-1 activities. • HSV-1 infection induces intracellular chloride concentration increasing. • Tamoxifen and NPPB inhibit HSV-1 early infection. • Tamoxifen and NPPB prevent the fusion process of HSV-1. - Abstract: Herpes simplex virus type 1 (HSV-1) infection is very common worldwide and can cause significant health problems from periodic skin and corneal lesions to encephalitis. Appearance of drug-resistant viruses in clinical therapy has made exploring novel antiviral agents emergent. Here we show that chloride channel inhibitors, including tamoxifen and 5-nitro-2-(3-phenyl-propylamino) benzoic acid (NPPB), exhibited extensive antiviral activities toward HSV-1 and ACV-resistant HSV viruses. HSV-1 infection induced chloride ion influx while treatment with inhibitors reduced the increase of intracellular chloride ion concentration. Pretreatment or treatment of inhibitors at different time points during HSV-1 infection all suppressed viral RNA synthesis, protein expression and virus production. More detailed studies demonstrated that tamoxifen and NPPB acted as potent inhibitors of HSV-1 early entry step by preventing viral binding, penetration and nuclear translocation. Specifically the compounds appeared to affect viral fusion process by inhibiting virus binding to lipid rafts and interrupting calcium homeostasis. Taken together, the observation that tamoxifen and NPPB can block viral entry suggests a stronger potential for these compounds as well as other ion channel inhibitors in antiviral therapy against HSV-1, especially the compound tamoxifen is an immediately actionable drug that can be reused for treatment of HSV-1 infections.

Inhibition of herpes simplex virus type 1 entry by chloride channel inhibitors tamoxifen and NPPB

International Nuclear Information System (INIS)

Zheng, Kai; Chen, Maoyun; Xiang, Yangfei; Ma, Kaiqi; Jin, Fujun; Wang, Xiao; Wang, Xiaoyan; Wang, Shaoxiang; Wang, Yifei

2014-01-01

Highlights: • We analyze the anti-HSV potential of chloride channel inhibitors. • Tamoxifen and NPPB show anti-HSV-1 and anti-ACV-resistant HSV-1 activities. • HSV-1 infection induces intracellular chloride concentration increasing. • Tamoxifen and NPPB inhibit HSV-1 early infection. • Tamoxifen and NPPB prevent the fusion process of HSV-1. - Abstract: Herpes simplex virus type 1 (HSV-1) infection is very common worldwide and can cause significant health problems from periodic skin and corneal lesions to encephalitis. Appearance of drug-resistant viruses in clinical therapy has made exploring novel antiviral agents emergent. Here we show that chloride channel inhibitors, including tamoxifen and 5-nitro-2-(3-phenyl-propylamino) benzoic acid (NPPB), exhibited extensive antiviral activities toward HSV-1 and ACV-resistant HSV viruses. HSV-1 infection induced chloride ion influx while treatment with inhibitors reduced the increase of intracellular chloride ion concentration. Pretreatment or treatment of inhibitors at different time points during HSV-1 infection all suppressed viral RNA synthesis, protein expression and virus production. More detailed studies demonstrated that tamoxifen and NPPB acted as potent inhibitors of HSV-1 early entry step by preventing viral binding, penetration and nuclear translocation. Specifically the compounds appeared to affect viral fusion process by inhibiting virus binding to lipid rafts and interrupting calcium homeostasis. Taken together, the observation that tamoxifen and NPPB can block viral entry suggests a stronger potential for these compounds as well as other ion channel inhibitors in antiviral therapy against HSV-1, especially the compound tamoxifen is an immediately actionable drug that can be reused for treatment of HSV-1 infections

Channel box

International Nuclear Information System (INIS)

Tanabe, Akira.

1993-01-01

In a channel box of a BWR type reactor, protruding pads are disposed in axial position on the lateral side of a channel box opposing to a control rod and facing the outer side portion of the control rod in a reactor core loaded state. In the initial loading stage of fuel assemblies, channel fasteners and spacer pads are abutted against each other in the upper portion between the channel boxes sandwiching the control rod therebetween. Further, in the lower portion, a gap as a channel for the movement of the control rod is ensured by the support of fuel support metals. If the channel box is bent toward the control rod along with reactor operation, the pads are abutted against each other to always ensure the gap through which the control rod can move easily. Further, when the pads are brought into contact with each other, the bending deformation of the channel box is corrected by urging to each other. Thus, the control rod can always be moved smoothly to attain reactor safety operation. (N.H.)

Synthesis and characterisation of NS13558: a new important tool for addressing KCa1.1 channel function ex vivo

DEFF Research Database (Denmark)

Bentzen, Bo Hjorth; Andersen, Rune Wederkinck; Olesen, Søren-Peter

2009-01-01

Pharmacological activation of the large-conductance Ca(2+)-activated K(+) channel (KCa1.1) in the cardiac inner mitochondrial membrane has been found to protect the heart against ischemia reperfusion injuries. However, there are concerns about the selectivity of the pharmacological tools used...... to modulate the channel. Here, we address this issue by synthesising a methylated analogue of the tool KCa1.1 channel activator NS11021. The compound (NS13558) is designed as a structurally closely related and biologically inactive analogue of NS11021. NS13558 did not elicit any significant opening of cloned...... human KCa1.1 channels, but maintained comparable biological activity towards other cardiac ion channels as compared to NS11021. In isolated perfused rat hearts subjected to ischemia-reperfusion, infarct size was reduced from 29% in control to 7% in NS11021 treated hearts. In comparison, the inactive...

Competition between neutron and charged particle emission from compound nuclei around A=160

CERN Document Server

Kossakowski, R; Barci, V; Genevey, J; Gizon, A; Gizon, J; Jastrzebski, J J; Preibisz, Z; Rymuza, P; Skulski, W

1981-01-01

Cross sections of reaction products from the interaction of 5-10 MeV /nucleon /sup 12/C, /sup 14/N and /sup 16/O ions with targets of mass around A=150 are investigated using gamma ray detection techniques. The competition between various reaction channels in which from 0 to 4 charges are removed from the compound nucleus is studied as a function of excitation energy of the compound nucleus (CN) and of the distance of the CN from the stability line. The experimental data are compared with the predictions of the evaporation model using the ALICE code. (1 refs).

Investigations of the isospin in the highly excited compound nuclei 52Cr and 58Co

International Nuclear Information System (INIS)

Roth, K.

1978-01-01

The influence of T states excited by p bombardment on the quantities in the correlation function is investigated by means of a fluctuation analysis of the excitation function in the p and α decay channels of the compound nuclei 52 Cr and 58 Co. (AH) [de

Neuroleptics as therapeutic compounds stabilizing neuromuscular transmission in amyotrophic lateral sclerosis.

Science.gov (United States)

Patten, Shunmoogum A; Aggad, Dina; Martinez, Jose; Tremblay, Elsa; Petrillo, Janet; Armstrong, Gary Ab; La Fontaine, Alexandre; Maios, Claudia; Liao, Meijiang; Ciura, Sorana; Wen, Xiao-Yan; Rafuse, Victor; Ichida, Justin; Zinman, Lorne; Julien, Jean-Pierre; Kabashi, Edor; Robitaille, Richard; Korngut, Lawrence; Parker, J Alexander; Drapeau, Pierre

2017-11-16

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, fatal disorder with no effective treatment. We used simple genetic models of ALS to screen phenotypically for potential therapeutic compounds. We screened libraries of compounds in C. elegans, validated hits in zebrafish, and tested the most potent molecule in mice and in a small clinical trial. We identified a class of neuroleptics that restored motility in C. elegans and in zebrafish, and the most potent was pimozide, which blocked T-type Ca2+ channels in these simple models and stabilized neuromuscular transmission in zebrafish and enhanced it in mice. Finally, a short randomized controlled trial of sporadic ALS subjects demonstrated stabilization of motility and evidence of target engagement at the neuromuscular junction. Simple genetic models are, thus, useful in identifying promising compounds for the treatment of ALS, such as neuroleptics, which may stabilize neuromuscular transmission and prolong survival in this disease.

Vulnerabilities of GSM and Wiretapping

Directory of Open Access Journals (Sweden)

A. V. Novitskiy

2012-09-01

Full Text Available The article presents the main methods used by hackers to listen to telephone conversations of subscribers and also offers ways to protect against them. The authors justify the necessity of developing a trusted operating system that implements a given security measures.

PELANGGARAN TERHADAP HAK KEKEBALAN DIPLOMATIK (STUDI KASUS PENYADAPAN KEDUTAAN BESAR REPUBLIK INDONESIA (KBRI DI YANGON MYANMAR BERDASARKAN KONVENSI WINA 1961

Directory of Open Access Journals (Sweden)

Dewa Gede Sudika Mangku

2010-07-01

Full Text Available The immunities and privileges owned by a diplomatic representative is based on providing greater opportunities to the diplomatic representatives in performing their duties perfectly. This is a form of protection to the diplomatic mission and its facilities-related facilities including the building of foreign diplomatic representative. Responsibility of the state of birth if the state committed acts contrary to law because of mistakes or negligence resulting in violations of international legal obligations. In case of violation of diplomatic immunities and privileges of the vice, then the recipient country can not be said to provide protection and comfort against the run function and diplomatic missions. Settlement of international disputes between Indonesia and Myanmar in diplomatic buildings wiretapping case can be achieved in various ways such as through a political settlement procedures, legal (juridical and within the framework of ASEAN cooperation. But use diplomatic channels or channels of negotiation that is based on good faith from both countries who are the best first step in dispute resolution. When the deal failed to be taken in diplomacy, it can be done in ways legal dispute resolution and bring it to the International Court of Justice.

Ion channeling

International Nuclear Information System (INIS)

Erramli, H.; Blondiaux, G.

1994-01-01

Channeling phenomenon was predicted, many years ago, by stark. The first channeling experiments were performed in 1963 by Davies and his coworkers. Parallely Robinson and Oen have investigated this process by simulating trajectories of ions in monocrystals. This technique has been combined with many methods like Rutherford Backscattering Spectrometry (R.B.S.), Particles Induced X-rays Emission (P.I.X.E) and online Nuclear Reaction (N.R.A.) to localize trace elements in the crystal or to determine crystalline quality. To use channeling for material characterization we need data about the stopping power of the incident particle in the channeled direction. The ratios of channeled to random stopping powers of silicon for irradiation in the direction have been investigated and compared to the available theoretical results. We describe few applications of ion channeling in the field of materials characterization. Special attention is given to ion channeling combined with Charged Particle Activation Analysis (C.P.A.A.) for studying the behaviour of oxygen atoms in Czochralski silicon lattices under the influence of internal gettering and in different gaseous atmospheres. Association between ion channeling and C.P.A.A was also utilised for studying the influence of the growing conditions on concentration and position of carbon atoms at trace levels in the MOVPE Ga sub (1-x) Al sub x lattice. 6 figs., 1 tab., 32 refs. (author)

Channel characteristics and coordination in three-echelon dual-channel supply chain

Science.gov (United States)

Saha, Subrata

2016-02-01

We explore the impact of channel structure on the manufacturer, the distributer, the retailer and the entire supply chain by considering three different channel structures in radiance of with and without coordination. These structures include a traditional retail channel and two manufacturer direct channels with and without consistent pricing. By comparing the performance of the manufacturer, the distributer and the retailer, and the entire supply chain in three different supply chain structures, it is established analytically that, under some conditions, a dual channel can outperform a single retail channel; as a consequence, a coordination mechanism is developed that not only coordinates the dual channel but also outperforms the non-cooperative single retail channel. All the analytical results are further analysed through numerical examples.

The antipsychotic drug loxapine is an opener of the sodium-activated potassium channel slack (Slo2.2).

Science.gov (United States)

Biton, B; Sethuramanujam, S; Picchione, Kelly E; Bhattacharjee, A; Khessibi, N; Chesney, F; Lanneau, C; Curet, O; Avenet, P

2012-03-01

Sodium-activated potassium (K(Na)) channels have been suggested to set the resting potential, to modulate slow after-hyperpolarizations, and to control bursting behavior or spike frequency adaptation (Trends Neurosci 28:422-428, 2005). One of the genes that encodes K(Na) channels is called Slack (Kcnt1, Slo2.2). Studies found that Slack channels were highly expressed in nociceptive dorsal root ganglion neurons and modulated their firing frequency (J Neurosci 30:14165-14172, 2010). Therefore, Slack channel openers are of significant interest as putative analgesic drugs. We screened the library of pharmacologically active compounds with recombinant human Slack channels expressed in Chinese hamster ovary cells, by using rubidium efflux measurements with atomic absorption spectrometry. Riluzole at 500 μM was used as a reference agonist. The antipsychotic drug loxapine and the anthelmintic drug niclosamide were both found to activate Slack channels, which was confirmed by using manual patch-clamp analyses (EC(50) = 4.4 μM and EC(50) = 2.9 μM, respectively). Psychotropic drugs structurally related to loxapine were also evaluated in patch-clamp experiments, but none was found to be as active as loxapine. Loxapine properties were confirmed at the single-channel level with recombinant rat Slack channels. In dorsal root ganglion neurons, loxapine was found to behave as an opener of native K(Na) channels and to increase the rheobase of action potential. This study identifies new K(Na) channel pharmacological tools, which will be useful for further Slack channel investigations.

Complex versus simple models: ion-channel cardiac toxicity prediction.

Science.gov (United States)

Mistry, Hitesh B

2018-01-01

There is growing interest in applying detailed mathematical models of the heart for ion-channel related cardiac toxicity prediction. However, a debate as to whether such complex models are required exists. Here an assessment in the predictive performance between two established large-scale biophysical cardiac models and a simple linear model B net was conducted. Three ion-channel data-sets were extracted from literature. Each compound was designated a cardiac risk category using two different classification schemes based on information within CredibleMeds. The predictive performance of each model within each data-set for each classification scheme was assessed via a leave-one-out cross validation. Overall the B net model performed equally as well as the leading cardiac models in two of the data-sets and outperformed both cardiac models on the latest. These results highlight the importance of benchmarking complex versus simple models but also encourage the development of simple models.

Complex versus simple models: ion-channel cardiac toxicity prediction

Directory of Open Access Journals (Sweden)

Hitesh B. Mistry

2018-02-01

Full Text Available There is growing interest in applying detailed mathematical models of the heart for ion-channel related cardiac toxicity prediction. However, a debate as to whether such complex models are required exists. Here an assessment in the predictive performance between two established large-scale biophysical cardiac models and a simple linear model Bnet was conducted. Three ion-channel data-sets were extracted from literature. Each compound was designated a cardiac risk category using two different classification schemes based on information within CredibleMeds. The predictive performance of each model within each data-set for each classification scheme was assessed via a leave-one-out cross validation. Overall the Bnet model performed equally as well as the leading cardiac models in two of the data-sets and outperformed both cardiac models on the latest. These results highlight the importance of benchmarking complex versus simple models but also encourage the development of simple models.

MONETARY TRANSMISSION CHANNELS IN ROMANIA – THE CREDIT CHANNEL

Directory of Open Access Journals (Sweden)

Magdalena RĂDULESCU

2009-12-01

Full Text Available The theoretical – intuitive analysis applied to the segment of monetary transmission evidences the fact that forming the traditional monetary impulses transmission channels are in a starting phase due to the long financial non – intermediary process which Romanian economy had known. In these conditions, the exchange rate channel, and also NBR currency purchases was, for a long time, an important way through which monetary authorities actions influenced macro economical behaviors. But starting with 2000, it is observed a credit channel reactivation and, especially, interest rate channel. Anyhow, the credit channel continues to be undermined by the existence of liquidity surplus within the system, by the phenomena of substitution of national currency credit with currency credits, and also moral hazardous displays. Albeit some of these phenomena also affect the interest rate channel, its role in sending monetary policy impulses is in a continuous progress. Apparently, it acts by way of nominal interest rates, their real level seeming less relevant. Once with remaking the two traditional channels, the companies and households balance is configured and consolidated, which shall potentate in the future the efficiency of the monetary policy. This paper analyses the credit channel in Romania, through an unrestricted VAR analysis.. It shows the responses of exchange rate, inflation rate, GDP, interest rate, imports and exports to a shock on non-governmental credit

ZnO-channel thin-film transistors: Channel mobility

International Nuclear Information System (INIS)

Hoffman, R.L.

2004-01-01

ZnO-channel thin-film transistor (TFT) test structures are fabricated using a bottom-gate structure on thermally oxidized Si; ZnO is deposited via RF sputtering from an oxide target, with an unheated substrate. Electrical characteristics are evaluated, with particular attention given to the extraction and interpretation of transistor channel mobility. ZnO-channel TFT mobility exhibits severe deviation from that assumed by ideal TFT models; mobility extraction methodology must accordingly be recast so as to provide useful insight into device operation. Two mobility metrics, μ avg and μ inc , are developed and proposed as relevant tools in the characterization of nonideal TFTs. These mobility metrics are employed to characterize the ZnO-channel TFTs reported herein; values for μ inc as high as 25 cm2/V s are measured, comprising a substantial increase in ZnO-channel TFT mobility as compared to previously reported performance for such devices

Disguising quantum channels by mixing and channel distance trade-off

International Nuclear Information System (INIS)

Fung, Chi-Hang Fred; Chau, H F

2014-01-01

We consider the reverse problem of the distinguishability of two quantum channels, which we call the disguising problem. Given two quantum channels, the goal here is to make the two channels identical by mixing with some other channels with minimal mixing probabilities. This quantifies how much one channel can disguise as the other. In addition, the possibility to trade-off between the two mixing probabilities allows one channel to be more preserved (less mixed) at the expense of the other. We derive lower- and upper-bounds of the trade-off curve and apply them to a few example channels. Optimal trade-off is obtained in one example. We relate the disguising problem and the distinguishability problem by showing that the former can lower and upper bound the diamond norm. We also show that the disguising problem gives an upper-bound on the key generation rate in quantum cryptography. (paper)

Comparative effects of sodium channel blockers in short term rat whole embryo culture

Energy Technology Data Exchange (ETDEWEB)

Nilsson, Mats F, E-mail: Mats.Nilsson@farmbio.uu.se [Department of Pharmaceutical Biosciences, Uppsala University (Sweden); Sköld, Anna-Carin; Ericson, Ann-Christin; Annas, Anita; Villar, Rodrigo Palma [AstraZeneca R and D Södertälje (Sweden); Cebers, Gvido [AstraZeneca R and D, iMed, 141 Portland Street, Cambridge, MA 02139 (United States); Hellmold, Heike; Gustafson, Anne-Lee [AstraZeneca R and D Södertälje (Sweden); Webster, William S [Department of Anatomy and Histology, University of Sydney (Australia)

2013-10-15

This study was undertaken to examine the effect on the rat embryonic heart of two experimental drugs (AZA and AZB) which are known to block the sodium channel Nav1.5, the hERG potassium channel and the L-type calcium channel. The sodium channel blockers bupivacaine, lidocaine, and the L-type calcium channel blocker nifedipine were used as reference substances. The experimental model was the gestational day (GD) 13 rat embryo cultured in vitro. In this model the embryonic heart activity can be directly observed, recorded and analyzed using computer assisted image analysis as it responds to the addition of test drugs. The effect on the heart was studied for a range of concentrations and for a duration up to 3 h. The results showed that AZA and AZB caused a concentration-dependent bradycardia of the embryonic heart and at high concentrations heart block. These effects were reversible on washout. In terms of potency to cause bradycardia the compounds were ranked AZB > bupivacaine > AZA > lidocaine > nifedipine. Comparison with results from previous studies with more specific ion channel blockers suggests that the primary effect of AZA and AZB was sodium channel blockage. The study shows that the short-term rat whole embryo culture (WEC) is a suitable system to detect substances hazardous to the embryonic heart. - Highlights: • Study of the effect of sodium channel blocking drugs on embryonic heart function • We used a modified method rat whole embryo culture with image analysis. • The drugs tested caused a concentration dependent bradycardia and heart block. • The effect of drugs acting on multiple ion channels is difficult to predict. • This method may be used to detect cardiotoxicity in prenatal development.

Comparative effects of sodium channel blockers in short term rat whole embryo culture

International Nuclear Information System (INIS)

Nilsson, Mats F; Sköld, Anna-Carin; Ericson, Ann-Christin; Annas, Anita; Villar, Rodrigo Palma; Cebers, Gvido; Hellmold, Heike; Gustafson, Anne-Lee; Webster, William S

2013-01-01

This study was undertaken to examine the effect on the rat embryonic heart of two experimental drugs (AZA and AZB) which are known to block the sodium channel Nav1.5, the hERG potassium channel and the L-type calcium channel. The sodium channel blockers bupivacaine, lidocaine, and the L-type calcium channel blocker nifedipine were used as reference substances. The experimental model was the gestational day (GD) 13 rat embryo cultured in vitro. In this model the embryonic heart activity can be directly observed, recorded and analyzed using computer assisted image analysis as it responds to the addition of test drugs. The effect on the heart was studied for a range of concentrations and for a duration up to 3 h. The results showed that AZA and AZB caused a concentration-dependent bradycardia of the embryonic heart and at high concentrations heart block. These effects were reversible on washout. In terms of potency to cause bradycardia the compounds were ranked AZB > bupivacaine > AZA > lidocaine > nifedipine. Comparison with results from previous studies with more specific ion channel blockers suggests that the primary effect of AZA and AZB was sodium channel blockage. The study shows that the short-term rat whole embryo culture (WEC) is a suitable system to detect substances hazardous to the embryonic heart. - Highlights: • Study of the effect of sodium channel blocking drugs on embryonic heart function • We used a modified method rat whole embryo culture with image analysis. • The drugs tested caused a concentration dependent bradycardia and heart block. • The effect of drugs acting on multiple ion channels is difficult to predict. • This method may be used to detect cardiotoxicity in prenatal development

Growth and Filling Regularities of Filamentary Channels in Non-Metallic Inorganic Coatings Under Anodic Oxidation of Valve Metals. Mathematical Modeling

Science.gov (United States)

Mamaev, A. I.; Mamaeva, V. A.; Kolenchin, N. F.; Chubenko, A. K.; Kovalskaya, Ya. B.; Dolgova, Yu. N.; Beletskaya, E. Yu.

2015-12-01

Theoretical models are developed for growth and filling processes in filamentary channels of nanostructured non-metallic coatings produced by anodizing and microplasma oxidation. Graphical concentration distributions are obtained for channel-reacting anions, cations, and sparingly soluble reaction products depending on the time of electric current transmission and the length of the filamentary channel. Graphical distributions of the front moving velocity for the sparingly soluble compound are presented. The resulting model representation increases the understanding of the anodic process nature and can be used for a description and prediction of porous anodic film growth and filling. It is shown that the character of the filamentary channel growth and filling causes a variety of processes determining the textured metal - nonmetallic inorganic coating phase boundary formation.

ATP Release Channels

Directory of Open Access Journals (Sweden)

Akiyuki Taruno

2018-03-01

Full Text Available Adenosine triphosphate (ATP has been well established as an important extracellular ligand of autocrine signaling, intercellular communication, and neurotransmission with numerous physiological and pathophysiological roles. In addition to the classical exocytosis, non-vesicular mechanisms of cellular ATP release have been demonstrated in many cell types. Although large and negatively charged ATP molecules cannot diffuse across the lipid bilayer of the plasma membrane, conductive ATP release from the cytosol into the extracellular space is possible through ATP-permeable channels. Such channels must possess two minimum qualifications for ATP permeation: anion permeability and a large ion-conducting pore. Currently, five groups of channels are acknowledged as ATP-release channels: connexin hemichannels, pannexin 1, calcium homeostasis modulator 1 (CALHM1, volume-regulated anion channels (VRACs, also known as volume-sensitive outwardly rectifying (VSOR anion channels, and maxi-anion channels (MACs. Recently, major breakthroughs have been made in the field by molecular identification of CALHM1 as the action potential-dependent ATP-release channel in taste bud cells, LRRC8s as components of VRACs, and SLCO2A1 as a core subunit of MACs. Here, the function and physiological roles of these five groups of ATP-release channels are summarized, along with a discussion on the future implications of understanding these channels.

Bupivacaine inhibits large conductance, voltage- and Ca2+- activated K+ channels in human umbilical artery smooth muscle cells

Science.gov (United States)

Martín, Pedro; Enrique, Nicolás; Palomo, Ana R. Roldán; Rebolledo, Alejandro; Milesi, Veronica

2012-01-01

Bupivacaine is a local anesthetic compound belonging to the amino amide group. Its anesthetic effect is commonly related to its inhibitory effect on voltage-gated sodium channels. However, several studies have shown that this drug can also inhibit voltage-operated K+ channels by a different blocking mechanism. This could explain the observed contractile effects of bupivacaine on blood vessels. Up to now, there were no previous reports in the literature about bupivacaine effects on large conductance voltage- and Ca2+-activated K+ channels (BKCa). Using the patch-clamp technique, it is shown that bupivacaine inhibits single-channel and whole-cell K+ currents carried by BKCa channels in smooth muscle cells isolated from human umbilical artery (HUA). At the single-channel level bupivacaine produced, in a concentration- and voltage-dependent manner (IC50 324 µM at +80 mV), a reduction of single-channel current amplitude and induced a flickery mode of the open channel state. Bupivacaine (300 µM) can also block whole-cell K+ currents (~45% blockage) in which, under our working conditions, BKCa is the main component. This study presents a new inhibitory effect of bupivacaine on an ion channel involved in different cell functions. Hence, the inhibitory effect of bupivacaine on BKCa channel activity could affect different physiological functions where these channels are involved. Since bupivacaine is commonly used during labor and delivery, its effects on umbilical arteries, where this channel is highly expressed, should be taken into account. PMID:22688134

Plaadid / Lauri Sommer

Index Scriptorium Estoniae

Sommer, Lauri, 1973-

2002-01-01

Uutest plaatidest Aswad "Cool Summer Raggae", Scarface "The Fix", Jose Padilla "El Sue̜o de Ibiza", Sparta "Wiretap Scars", Filter "Amalgamut", Simon & Garfunkel "Live From New York City 1967", "Party At The Palace", Bill Frisell "The Willies"

Channel sandstone and bar morphology of the Beaufort group uranium district near Beaufort West

International Nuclear Information System (INIS)

Stear, W.M.

1980-01-01

Sheet-like and lenticular sandstone bodies in the Lower Beaufort Group (Adelaide Subgroup) uranium district occur in megacyclic repetition as superimposed systems of ephemeral fluvial channels that display characteristics of complex lateral and vertical accretion. Channel sandstone bodies are defined on morphological grounds into two types. Sheet sandstone bodies are the commonest type and comprise the bulk of sandstone packages in arenaceous zones of megacycles. Composite sandstone sheets result from multilateral coalescence of individual sandstone bodies. Isolated lenticular sandstone units in argillaceous zones of megacycles comprise sheet and ribbon sandstone types. Multi-storeying is a prominent feature of most channel sandstone bodies and often results in local sandstone thickening. Bedforms relate to the formation of compound bars and record periods of dynamic accretion and erosion. Rarely preserved palaeosurfaces vividly illustrate the fluctuating hydrodynamic conditions that typified ephemeral fluvial sedimentation in a semi-arid environment during Lower Beaufort times

High spin spectroscopy near the N=Z line: Channel selection and excitation energy systematics

Energy Technology Data Exchange (ETDEWEB)

Svensson, C.E.; Cameron, J.A.; Flibotte, S. [McMaster Univ., Ontario (Canada)] [and others

1996-12-31

The total {gamma}-ray and charged-particle energies emitted in fusion-evaporation reactions leading to N=Z compound systems in the A = 50-70 mass region have been measured with the 8{pi} {gamma}-ray spectrometer and the miniball charged-particle detector array. A new method of channel selection has been developed which combines particle identification with these total energy measurements and greatly improves upon the selectivity possible with particle detection alone. In addition, the event by event measurement of total {gamma}-ray energies using the BGO ball of the 8{pi} spectrometer has allowed a determination of excitation energies following particle evaporation for a large number of channels in several different reactions. The new channel selection procedure and excitation energy systematics are illustrated with data from the reaction of {sup 24}Mg on {sup 40}Ca at E{sub lab} = 80MeV.

Channel sandstone and bar morphology of the Beaufort group uranium district near Beaufort West

Energy Technology Data Exchange (ETDEWEB)

Stear, W M

1980-01-01

Sheet-like and lenticular sandstone bodies in the Lower Beaufort Group (Adelaide Subgroup) uranium district occur in megacyclic repetition as superimposed systems of ephemeral fluvial channels that display characteristics of complex lateral and vertical accretion. Channel sandstone bodies are defined on morphological grounds into two types. Sheet sandstone bodies are the commonest type and comprise the bulk of sandstone packages in arenaceous zones of megacycles. Composite sandstone sheets result from multilateral coalescence of individual sandstone bodies. Isolated lenticular sandstone units in argillaceous zones of megacycles comprise sheet and ribbon sandstone types. Multi-storeying is a prominent feature of most channel sandstone bodies and often results in local sandstone thickening. Bedforms relate to the formation of compound bars and record periods of dynamic accretion and erosion. Rarely preserved palaeosurfaces vividly illustrate the fluctuating hydrodynamic conditions that typified ephemeral fluvial sedimentation in a semi-arid environment during Lower Beaufort times.

ASIC3 Channels Integrate Agmatine and Multiple Inflammatory Signals through the Nonproton Ligand Sensing Domain

Directory of Open Access Journals (Sweden)

Cao Hui

2010-12-01

Full Text Available Abstract Background Acid-sensing ion channels (ASICs have long been known to sense extracellular protons and contribute to sensory perception. Peripheral ASIC3 channels represent natural sensors of acidic and inflammatory pain. We recently reported the use of a synthetic compound, 2-guanidine-4-methylquinazoline (GMQ, to identify a novel nonproton sensing domain in the ASIC3 channel, and proposed that, based on its structural similarity with GMQ, the arginine metabolite agmatine (AGM may be an endogenous nonproton ligand for ASIC3 channels. Results Here, we present further evidence for the physiological correlation between AGM and ASIC3. Among arginine metabolites, only AGM and its analog arcaine (ARC activated ASIC3 channels at neutral pH in a sustained manner similar to GMQ. In addition to the homomeric ASIC3 channels, AGM also activated heteromeric ASIC3 plus ASIC1b channels, extending its potential physiological relevance. Importantly, the process of activation by AGM was highly sensitive to mild acidosis, hyperosmolarity, arachidonic acid (AA, lactic acid and reduced extracellular Ca2+. AGM-induced ASIC3 channel activation was not through the chelation of extracellular Ca2+ as occurs with increased lactate, but rather through a direct interaction with the newly identified nonproton ligand sensing domain. Finally, AGM cooperated with the multiple inflammatory signals to cause pain-related behaviors in an ASIC3-dependent manner. Conclusions Nonproton ligand sensing domain might represent a novel mechanism for activation or sensitization of ASIC3 channels underlying inflammatory pain-sensing under in vivo conditions.

Spark Channels

Energy Technology Data Exchange (ETDEWEB)

Haydon, S. C. [Department of Physics, University of New England, Armidale, NSW (Australia)

1968-04-15

A brief summary is given of the principal methods used for initiating spark channels and the various highly time-resolved techniques developed recently for studies with nanosecond resolution. The importance of the percentage overvoltage in determining the early history and subsequent development of the various phases of the growth of the spark channel is discussed. An account is then given of the recent photographic, oscillographic and spectroscopic investigations of spark channels initiated by co-axial cable discharges of spark gaps at low [{approx} 1%] overvoltages. The phenomena observed in the development of the immediate post-breakdown phase, the diffuse glow structure, the growth of the luminous filament and the final formation of the spark channel in hydrogen are described. A brief account is also given of the salient features emerging from corresponding studies of highly overvolted spark gaps in which the spark channel develops from single avalanche conditions. The essential differences between the two types of channel formation are summarized and possible explanations of the general features are indicated. (author)

Joint source/channel coding of scalable video over noisy channels

Energy Technology Data Exchange (ETDEWEB)

Cheung, G.; Zakhor, A. [Department of Electrical Engineering and Computer Sciences University of California Berkeley, California94720 (United States)

1997-01-01

We propose an optimal bit allocation strategy for a joint source/channel video codec over noisy channel when the channel state is assumed to be known. Our approach is to partition source and channel coding bits in such a way that the expected distortion is minimized. The particular source coding algorithm we use is rate scalable and is based on 3D subband coding with multi-rate quantization. We show that using this strategy, transmission of video over very noisy channels still renders acceptable visual quality, and outperforms schemes that use equal error protection only. The flexibility of the algorithm also permits the bit allocation to be selected optimally when the channel state is in the form of a probability distribution instead of a deterministic state. {copyright} {ital 1997 American Institute of Physics.}

Action of insecticidal N-alkylamides at site 2 of the voltage-sensitive sodium channel

International Nuclear Information System (INIS)

Ottea, J.A.; Payne, G.T.; Soderlund, D.M.

1990-01-01

Nine synthetic N-alkylamides were examined as inhibitors of the specific binding of [ 3 H]batrachotoxinin A 20α-benzoate ([ 3 H]BTX-B) to sodium channels and as activators of sodium uptake in mouse brain synaptoneurosomes. In the presence of scorpion (Leiurus quinquestriatus) venom, the six insecticidal analogues were active as both inhibitors of [ 3 H]BTX-B binding and stimulators of sodium uptake. These findings are consistent with an action of these compounds at the alkaloid activator recognition site (site 2) of the voltage-sensitive sodium channel. The three noninsecticidal N-alkylamides also inhibited [ 3 H]BTX-B binding but were ineffective as activators of sodium uptake. Concentration-response studies revealed that some of the insecticidal amides also enhanced sodium uptake through a second, high-affinity interaction that does not involve site 2, but this secondary effect does not appear to be correlated with insecticidal activity. The activities of N-alkylamides as sodium channel activators were influenced by the length of the alkenyl chain and the location of unsaturation within the molecule. These results further define the actions of N-alkylamides on sodium channels and illustrate the significance of the multiple binding domains of the sodium channel as target sites for insect control agents

Spatial distributions of and diurnal variations in low molecular weight carbonyl compounds in coastal seawater, and the controlling factors

Energy Technology Data Exchange (ETDEWEB)

Takeda, Kazuhiko, E-mail: takedaq@hiroshima-u.ac.jp [Graduate School of Biosphere Science, Hiroshima University, 1-7-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8521 (Japan); Katoh, Shinya; Mitsui, Yumi; Nakano, Shinichi [Graduate School of Biosphere Science, Hiroshima University, 1-7-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8521 (Japan); Nakatani, Nobutake [Graduate School of Biosphere Science, Hiroshima University, 1-7-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8521 (Japan); Department of Environmental and Symbiotic Sciences, Rakuno Gakuen University, 582 Bunkyodai-Midorimachi, Ebetsu, Hokkaido 069-8501 (Japan); Sakugawa, Hiroshi [Graduate School of Biosphere Science, Hiroshima University, 1-7-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8521 (Japan)

2014-09-15

We studied the spatial distributions of and the diurnal variations in four low molecular weight (LMW) carbonyl compounds, formaldehyde, acetaldehyde, propionaldehyde, and glyoxal, in coastal seawater. The samples were taken from the coastal areas of Hiroshima Bay, the Iyo Nada, and the Bungo Channel, western Japan. The formaldehyde, acetaldehyde, and glyoxal concentrations were higher in the northern part of Hiroshima Bay than at offshore sampling points in the Iyo Nada and the Bungo Channel. These three compounds were found at much higher concentrations in the surface water than in deeper water layers in Hiroshima Bay. It is noteworthy that propionaldehyde was not detected in any of the seawater samples, the concentrations present being lower than the detection limit (1 nanomole per liter (nM)) of the high performance liquid chromatography (HPLC) system we used. Photochemical and biological experiments were performed in the laboratory to help understand the characteristic distributions and fates of the LMW carbonyl compounds. The primary process controlling their fate in the coastal environment appears to be their biological consumption. The direct photo degradation of propionaldehyde, initiated by ultraviolet (UV) absorption, was observed, although formaldehyde and acetaldehyde were not degraded by UV irradiation. Our results suggest that the degradation of the LMW carbonyl compounds by photochemically formed hydroxyl radicals is relatively insignificant in the study area. Atmospheric deposition is a possible source of soluble carbonyl compounds in coastal surface seawater, but it may not influence the carbonyl concentrations in offshore waters. - Highlights: • Low molecular weight (LMW) carbonyl compounds in coastal seawater were determined. • Photochemical productions of LMW carbonyl compounds in seawater were observed. • LMW carbonyl compounds were largely consumed biologically. • Photochemical degradation was relatively insignificant in the study area.

Spatial distributions of and diurnal variations in low molecular weight carbonyl compounds in coastal seawater, and the controlling factors

International Nuclear Information System (INIS)

Takeda, Kazuhiko; Katoh, Shinya; Mitsui, Yumi; Nakano, Shinichi; Nakatani, Nobutake; Sakugawa, Hiroshi

2014-01-01

We studied the spatial distributions of and the diurnal variations in four low molecular weight (LMW) carbonyl compounds, formaldehyde, acetaldehyde, propionaldehyde, and glyoxal, in coastal seawater. The samples were taken from the coastal areas of Hiroshima Bay, the Iyo Nada, and the Bungo Channel, western Japan. The formaldehyde, acetaldehyde, and glyoxal concentrations were higher in the northern part of Hiroshima Bay than at offshore sampling points in the Iyo Nada and the Bungo Channel. These three compounds were found at much higher concentrations in the surface water than in deeper water layers in Hiroshima Bay. It is noteworthy that propionaldehyde was not detected in any of the seawater samples, the concentrations present being lower than the detection limit (1 nanomole per liter (nM)) of the high performance liquid chromatography (HPLC) system we used. Photochemical and biological experiments were performed in the laboratory to help understand the characteristic distributions and fates of the LMW carbonyl compounds. The primary process controlling their fate in the coastal environment appears to be their biological consumption. The direct photo degradation of propionaldehyde, initiated by ultraviolet (UV) absorption, was observed, although formaldehyde and acetaldehyde were not degraded by UV irradiation. Our results suggest that the degradation of the LMW carbonyl compounds by photochemically formed hydroxyl radicals is relatively insignificant in the study area. Atmospheric deposition is a possible source of soluble carbonyl compounds in coastal surface seawater, but it may not influence the carbonyl concentrations in offshore waters. - Highlights: • Low molecular weight (LMW) carbonyl compounds in coastal seawater were determined. • Photochemical productions of LMW carbonyl compounds in seawater were observed. • LMW carbonyl compounds were largely consumed biologically. • Photochemical degradation was relatively insignificant in the study area

Food-Derived Natural Compounds for Pain Relief in Neuropathic Pain.

Science.gov (United States)

Lim, Eun Yeong; Kim, Yun Tai

2016-01-01

Neuropathic pain, defined as pain caused by a lesion or disease of the somatosensory nervous system, is characterized by dysesthesia, hyperalgesia, and allodynia. The number of patients with this type of pain has increased rapidly in recent years. Yet, available neuropathic pain medicines have undesired side effects, such as tolerance and physical dependence, and do not fully alleviate the pain. The mechanisms of neuropathic pain are still not fully understood. Injury causes inflammation and immune responses and changed expression and activity of receptors and ion channels in peripheral nerve terminals. Additionally, neuroinflammation is a known factor in the development and maintenance of neuropathic pain. During neuropathic pain development, the C-C motif chemokine receptor 2 (CCR2) acts as an important signaling mediator. Traditional plant treatments have been used throughout the world for treating diseases. We and others have identified food-derived compounds that alleviate neuropathic pain. Here, we review the natural compounds for neuropathic pain relief, their mechanisms of action, and the potential benefits of natural compounds with antagonistic effects on GPCRs, especially those containing CCR2, for neuropathic pain treatment.

Harde-kernsupporters, gelegenheidsstructuren en georganiseerde criminaliteit

NARCIS (Netherlands)

Kleemans, E.R.; Collard, Bart J.

2017-01-01

This paper describes the results of twelve criminal investigations into criminal activities of hardcore supporters of a Dutch soccer club. The information from these criminal investigations consists of among other 74,246 transcribed, wiretapped telephone conversations and 643 pages with transcribed

Up-Regulatory Effects of Curcumin on Large Conductance Ca2+-Activated K+ Channels

Science.gov (United States)

Hei, Hongya; Li, Fangping; Wang, Yunman; Peng, Wen; Zhang, Xuemei

2015-01-01

Large conductance Ca2+-activated potassium channels (BK) are targets for research that explores therapeutic means to various diseases, owing to the roles of the channels in mediating multiple physiological processes in various cells and tissues. We investigated the pharmacological effects of curcumin, a compound isolated from the herb Curcuma longa, on BK channels. As recorded by whole-cell patch-clamp, curcumin increased BK (α) and BK (α+β1) currents in transfected HEK293 cells as well as the current density of BK in A7r5 smooth muscle cells in a dose-dependent manner. By incubating with curcumin for 24 hours, the current density of exogenous BK (α) in HEK293 cells and the endogenous BK in A7r5 cells were both enhanced notably, though the steady-state activation of the channels did not shift significantly, except for BK (α+β1). Curcumin up-regulated the BK protein expression without changing its mRNA level in A7r5 cells. The surface expression and the half-life of BK channels were also increased by curcumin in HEK293 cells. These effects of curcumin were abolished by MG-132, a proteasome inhibitor. Curcumin also increased ERK 1/2 phosphorylation, while inhibiting ERK by U0126 attenuated the curcumin-induced up-regulation of BK protein expression. We also observed that the curcumin-induced relaxation in the isolated rat aortic rings was significantly attenuated by paxilline, a BK channel specific blocker. These results show that curcumin enhances the activity of the BK channels by interacting with BK directly as well as enhancing BK protein expression through inhibiting proteasomal degradation and activating ERK signaling pathway. The findings suggest that curcumin is a potential BK channel activator and provide novel insight into its complicated pharmacological effects and the underlying mechanisms. PMID:26672753

Up-Regulatory Effects of Curcumin on Large Conductance Ca2+-Activated K+ Channels.

Directory of Open Access Journals (Sweden)

Qijing Chen

Full Text Available Large conductance Ca2+-activated potassium channels (BK are targets for research that explores therapeutic means to various diseases, owing to the roles of the channels in mediating multiple physiological processes in various cells and tissues. We investigated the pharmacological effects of curcumin, a compound isolated from the herb Curcuma longa, on BK channels. As recorded by whole-cell patch-clamp, curcumin increased BK (α and BK (α+β1 currents in transfected HEK293 cells as well as the current density of BK in A7r5 smooth muscle cells in a dose-dependent manner. By incubating with curcumin for 24 hours, the current density of exogenous BK (α in HEK293 cells and the endogenous BK in A7r5 cells were both enhanced notably, though the steady-state activation of the channels did not shift significantly, except for BK (α+β1. Curcumin up-regulated the BK protein expression without changing its mRNA level in A7r5 cells. The surface expression and the half-life of BK channels were also increased by curcumin in HEK293 cells. These effects of curcumin were abolished by MG-132, a proteasome inhibitor. Curcumin also increased ERK 1/2 phosphorylation, while inhibiting ERK by U0126 attenuated the curcumin-induced up-regulation of BK protein expression. We also observed that the curcumin-induced relaxation in the isolated rat aortic rings was significantly attenuated by paxilline, a BK channel specific blocker. These results show that curcumin enhances the activity of the BK channels by interacting with BK directly as well as enhancing BK protein expression through inhibiting proteasomal degradation and activating ERK signaling pathway. The findings suggest that curcumin is a potential BK channel activator and provide novel insight into its complicated pharmacological effects and the underlying mechanisms.

Quantum Channels With Memory

International Nuclear Information System (INIS)

Rybar, T.

2012-01-01

Quantum memory channels represent a very general, yet simple and comprehensible model for causal processes. As such they have attracted considerable research interest, mostly aimed on their transfer capabilities and structure properties. Most notably it was shown that memory channels can be implemented via physically naturally motivated collision models. We also define the concept of repeatable channels and show that only unital channels can be implemented repeat ably with pure memory channels. In the special case of qubit channels we also show that every unital qubit channel has a repeatable implementation. We also briefly explore the possibilities of stroboscopical simulation of channels and show that all random unitary channels can be stroboscopically simulated. Particularly in qubit case, all indivisible qubit channels are also random unitary, hence for qubit all indivisible channels can be stroboscopically simulated. Memory channels also naturally capture the framework of correlated experiments. We develop methods to gather and interpret data obtained in such setting and in detail examine the two qubit case. We also show that for control unitary interactions the measured data will never contradict a simple unitary evolution. Thus no memory effects can be spotted then. (author)

Mimicking multi-channel scattering with single-channel approaches

OpenAIRE

Grishkevich, Sergey; Schneider, Philipp-Immanuel; Vanne, Yulian V.; Saenz, Alejandro

2009-01-01

The collision of two atoms is an intrinsic multi-channel (MC) problem as becomes especially obvious in the presence of Feshbach resonances. Due to its complexity, however, single-channel (SC) approximations, which reproduce the long-range behavior of the open channel, are often applied in calculations. In this work the complete MC problem is solved numerically for the magnetic Feshbach resonances (MFRs) in collisions between generic ultracold 6Li and 87Rb atoms in the ground state and in the ...

Fine Channel Networks

Science.gov (United States)

1997-01-01

A color image of fine channel networks on Mars; north toward top. The scene shows heavily cratered highlands dissected by dendritic open channel networks that dissect steep slopes of impact crater walls. This image is a composite of Viking high-resolution images in black and white and low-resolution images in color. The image extends from latitude 9 degrees S. to 5 degrees S. and from longitude 312 degrees to 320 degrees; Mercator projection. The dendritic pattern of the fine channels and their location on steep slopes leads to the interpretation that these are runoff channels. The restriction of these types of channels to ancient highland rocks suggests that these channels are old and date from a time on Mars when conditions existed for precipitation to actively erode rocks. After the channels reach a low plain, they appear to end. Termination may have resulted from burial by younger deposits or perhaps the flows percolated into the surface materials and continued underground.

Mechanism of sodium channel block by local anesthetics, antiarrhythmics, and anticonvulsants.

Science.gov (United States)

Tikhonov, Denis B; Zhorov, Boris S

2017-04-03

Local anesthetics, antiarrhythmics, and anticonvulsants include both charged and electroneutral compounds that block voltage-gated sodium channels. Prior studies have revealed a common drug-binding region within the pore, but details about the binding sites and mechanism of block remain unclear. Here, we use the x-ray structure of a prokaryotic sodium channel, NavMs, to model a eukaryotic channel and dock representative ligands. These include lidocaine, QX-314, cocaine, quinidine, lamotrigine, carbamazepine (CMZ), phenytoin, lacosamide, sipatrigine, and bisphenol A. Preliminary calculations demonstrated that a sodium ion near the selectivity filter attracts electroneutral CMZ but repels cationic lidocaine. Therefore, we further docked electroneutral and cationic drugs with and without a sodium ion, respectively. In our models, all the drugs interact with a phenylalanine in helix IVS6. Electroneutral drugs trap a sodium ion in the proximity of the selectivity filter, and this same site attracts the charged group of cationic ligands. At this position, even small drugs can block the permeation pathway by an electrostatic or steric mechanism. Our study proposes a common pharmacophore for these diverse drugs. It includes a cationic moiety and an aromatic moiety, which are usually linked by four bonds. © 2017 Tikhonov and Zhorov.

Development and validation of a thallium flux-based functional assay for the sodium channel NaV1.7 and its utility for lead discovery and compound profiling.

Science.gov (United States)

Du, Yu; Days, Emily; Romaine, Ian; Abney, Kris K; Kaufmann, Kristian; Sulikowski, Gary; Stauffer, Shaun; Lindsley, Craig W; Weaver, C David

2015-06-17

Ion channels are critical for life, and they are targets of numerous drugs. The sequencing of the human genome has revealed the existence of hundreds of different ion channel subunits capable of forming thousands of ion channels. In the face of this diversity, we only have a few selective small-molecule tools to aid in our understanding of the role specific ion channels in physiology which may in turn help illuminate their therapeutic potential. Although the advent of automated electrophysiology has increased the rate at which we can screen for and characterize ion channel modulators, the technique's high per-measurement cost and moderate throughput compared to other high-throughput screening approaches limit its utility for large-scale high-throughput screening. Therefore, lower cost, more rapid techniques are needed. While ion channel types capable of fluxing calcium are well-served by low cost, very high-throughput fluorescence-based assays, other channel types such as sodium channels remain underserved by present functional assay techniques. In order to address this shortcoming, we have developed a thallium flux-based assay for sodium channels using the NaV1.7 channel as a model target. We show that the assay is able to rapidly and cost-effectively identify NaV1.7 inhibitors thus providing a new method useful for the discovery and profiling of sodium channel modulators.

Study of the angular momentum distribution of compound nuclei obtained from fusion reactions close to the Coulomb barrier

International Nuclear Information System (INIS)

Romain, P.

1990-03-01

The effect of the mass asymmetry of the input channel on the compound nuclei spin distribution. The 16 O + 144 Nd and 80 Se + 80 Se reactions produce the same 160 Er compound nucleus in the 38 to 68 MeV energy range. In certain cases, the incident energies required to form the compound nucleus, at the same excitation energies, are very close to the Coulomb barrier. In the experimental device, the 'Chateau de Cristal' multidetector and additional sensors are used. The angular momentum distribution of the different evaporation products are measured by gamma spectrometry techniques. The fusion cross sections are measured by the time-of-flight technique. Theoretical predictions and experimental results concerning the distribution of the compound nucleus angular momentum are compared [fr

Differential state-dependent modification of rat Na{sub v}1.6 sodium channels expressed in human embryonic kidney (HEK293) cells by the pyrethroid insecticides tefluthrin and deltamethrin

Energy Technology Data Exchange (ETDEWEB)

He, Bingjun [College of Life Sciences, Nankai University, Tianjin 300071 (China); Soderlund, David M., E-mail: dms6@cornell.edu [Department of Entomology, Cornell University, New York State Agricultural Experiment Station, Geneva, NY 14456 (United States)

2011-12-15

We expressed rat Na{sub v}1.6 sodium channels in combination with the rat {beta}1 and {beta}2 auxiliary subunits in human embryonic kidney (HEK293) cells and evaluated the effects of the pyrethroid insecticides tefluthrin and deltamethrin on expressed sodium currents using the whole-cell patch clamp technique. Both pyrethroids produced concentration-dependent, resting modification of Na{sub v}1.6 channels, prolonging the kinetics of channel inactivation and deactivation to produce persistent 'late' currents during depolarization and tail currents following repolarization. Both pyrethroids also produced concentration dependent hyperpolarizing shifts in the voltage dependence of channel activation and steady-state inactivation. Maximal shifts in activation, determined from the voltage dependence of the pyrethroid-induced late and tail currents, were {approx} 25 mV for tefluthrin and {approx} 20 mV for deltamethrin. The highest attainable concentrations of these compounds also caused shifts of {approx} 5-10 mV in the voltage dependence of steady-state inactivation. In addition to their effects on the voltage dependence of inactivation, both compounds caused concentration-dependent increases in the fraction of sodium current that was resistant to inactivation following strong depolarizing prepulses. We assessed the use-dependent effects of tefluthrin and deltamethrin on Na{sub v}1.6 channels by determining the effect of trains of 1 to 100 5-ms depolarizing prepulses at frequencies of 20 or 66.7 Hz on the extent of channel modification. Repetitive depolarization at either frequency increased modification by deltamethrin by {approx} 2.3-fold but had no effect on modification by tefluthrin. Tefluthrin and deltamethrin were equally potent as modifiers of Na{sub v}1.6 channels in HEK293 cells using the conditions producing maximal modification as the basis for comparison. These findings show that the actions of tefluthrin and deltamethrin of Na{sub v}1.6 channels

Radiosynthesis of dimethyl-2-[{sup 18}F]-(fluoromethyl)-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate for L-type calcium channel imaging

Energy Technology Data Exchange (ETDEWEB)

Sadeghpour, H. [Nuclear Medicine Research Group, Agricultural, Medical and Industrial Research School (AMIRS), Karaj (Iran); Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran Univ. of Medical Sciences, Tehran (Iran); Jalilian, A.R.; Akhlaghi, M.; Mirzaei, M. [Nuclear Medicine Research Group, Agricultural, Medical and Industrial Research School (AMIRS), Karaj (Iran); Shafiee, A. [Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran Univ. of Medical Sciences, Tehran (Iran); Miri, R. [Medicinal and Natural Products Chemistry Research Center, Shiraz Univ. of Medical Sciences, Shiraz (Iran)

2008-07-01

Dimethyl 2-(fluoromethyl)-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate 4a, a fluorinated nifedipine analog, has been shown to elicit significant calcium channel blocker activity using a guinea pig ileal longitudinal smooth muscle model. In order to perform biological studies for detection of L-type calcium channel distribution, we decided to prepare the [{sup 18}F]-labeled compound. The latter compound was prepared in no-carrier-added (n.c.a.) form from dimethyl 2-(bromomethyl)-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate 2 in one step at 80 C in Kryptofix[222]/K[{sup 18}F]F and acetonitrile as a solvent in 15 min. Column chromatography afforded the radiochemically pure compound in 20 min. Radiochemical purity of the {sup 18}F-nifedipine was determined by RTLC and HPLC (> 98%) and specific activity of 21-48 GBq/{mu}mol (EOB). (orig.)

Active Sites of Spinoxin, a Potassium Channel Scorpion Toxin, Elucidated by Systematic Alanine Scanning.

Science.gov (United States)

Peigneur, Steve; Yamaguchi, Yoko; Kawano, Chihiro; Nose, Takeru; Nirthanan, Selvanayagam; Gopalakrishnakone, Ponnampalam; Tytgat, Jan; Sato, Kazuki

2016-05-31

Peptide toxins from scorpion venoms constitute the largest group of toxins that target the voltage-gated potassium channel (Kv). Spinoxin (SPX) isolated from the venom of scorpion Heterometrus spinifer is a 34-residue peptide neurotoxin cross-linked by four disulfide bridges. SPX is a potent inhibitor of Kv1.3 potassium channels (IC50 = 63 nM), which are considered to be valid molecular targets in the diagnostics and therapy of various autoimmune disorders and cancers. Here we synthesized 25 analogues of SPX and analyzed the role of each amino acid in SPX using alanine scanning to study its structure-function relationships. All synthetic analogues showed similar disulfide bond pairings and secondary structures as native SPX. Alanine replacements at Lys(23), Asn(26), and Lys(30) resulted in loss of activity against Kv1.3 potassium channels, whereas replacements at Arg(7), Met(14), Lys(27), and Tyr(32) also largely reduced inhibitory activity. These results suggest that the side chains of these amino acids in SPX play an important role in its interaction with Kv1.3 channels. In particular, Lys(23) appears to be a key residue that underpins Kv1.3 channel inhibition. Of these seven amino acid residues, four are basic amino acids, suggesting that the positive electrostatic potential on the surface of SPX is likely required for high affinity interaction with Kv1.3 channels. This study provides insight into the structure-function relationships of SPX with implications for the rational design of new lead compounds targeting potassium channels with high potency.

3D Printed Microtransporters: Compound Micromachines for Spatiotemporally Controlled Delivery of Therapeutic Agents.

Science.gov (United States)

Huang, Tian-Yun; Sakar, Mahmut Selman; Mao, Angelo; Petruska, Andrew J; Qiu, Famin; Chen, Xue-Bo; Kennedy, Stephen; Mooney, David; Nelson, Bradley J

2015-11-01

Functional compound micromachines are fabricated by a design methodology using 3D direct laser writing and selective physical vapor deposition of magnetic materials. Microtransporters with a wirelessly controlled Archimedes screw pumping mechanism are engineered. Spatiotemporally controlled collection, transport, and delivery of micro particles, as well as magnetic nanohelices inside microfluidic channels are demonstrated. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Conotoxins Targeting Neuronal Voltage-Gated Sodium Channel Subtypes: Potential Analgesics?

Directory of Open Access Journals (Sweden)

Jeffrey R. McArthur

2012-11-01

Full Text Available Voltage-gated sodium channels (VGSC are the primary mediators of electrical signal amplification and propagation in excitable cells. VGSC subtypes are diverse, with different biophysical and pharmacological properties, and varied tissue distribution. Altered VGSC expression and/or increased VGSC activity in sensory neurons is characteristic of inflammatory and neuropathic pain states. Therefore, VGSC modulators could be used in prospective analgesic compounds. VGSCs have specific binding sites for four conotoxin families: μ-, μO-, δ- and ί-conotoxins. Various studies have identified that the binding site of these peptide toxins is restricted to well-defined areas or domains. To date, only the μ- and μO-family exhibit analgesic properties in animal pain models. This review will focus on conotoxins from the μ- and μO-families that act on neuronal VGSCs. Examples of how these conotoxins target various pharmacologically important neuronal ion channels, as well as potential problems with the development of drugs from conotoxins, will be discussed.

Volume Regulated Channels

DEFF Research Database (Denmark)

Klausen, Thomas Kjær

of volume perturbations evolution have developed system of channels and transporters to tightly control volume homeostasis. In the past decades evidence has been mounting, that the importance of these volume regulated channels and transporters are not restricted to the defense of cellular volume...... but are also essential for a number of physiological processes such as proliferation, controlled cell death, migration and endocrinology. The thesis have been focusing on two Channels, namely the swelling activated Cl- channel (ICl, swell) and the transient receptor potential Vanilloid (TRPV4) channel. I: Cl......- serves a multitude of functions in the mammalian cell, regulating the membrane potential (Em), cell volume, protein activity and the driving force for facilitated transporters giving Cl- and Cl- channels a major potential of regulating cellular function. These functions include control of the cell cycle...

Identification and preclinical testing of novel antiepileptic compounds.

Science.gov (United States)

Meldrum, B S

1997-01-01

Procedures for identifying novel antiepileptic drugs (AEDs) are changing and need to change more. Widespread reliance on two primary screens has led to the identification of novel compounds that resemble either phenytoin (suppressing high-frequency repetitive firing in cultured neurons and prolonging inactivation of voltage-dependent sodium channels identified by the maximal electroshock test) or benzodiazepines (potentiating the inhibitory effect of gamma-aminobutyric acid (GABA), identified by the threshold pentylenetetrazol test). Advances in molecular neurobiology have identified specific molecular targets (subunits of ion channels, neurotransmitter receptors, and transporters) and have made them available in a form permitting high-throughput screening. AEDs can be designed to interact with specific sites on the target molecules. Alternatively, the molecular screens can be used to identify active components in natural products, including folk remedies. Preclinical in vivo screens can be improved by using animals with genetic or acquired epilepsies that have similar modifications in the properties of the target molecules as do human epilepsy syndromes. Future work is likely to define molecular targets for AEDs that will block or reverse chronic epileptogenesis.

Use of calcium channel blockers in hypertension.

Science.gov (United States)

Conlin, P R; Williams, G H

1998-01-01

During the past 20 years the number of subclasses of calcium channel blockers has increased from one to four. Three classes have only a single clinically approved compound: verapamil, diltiazem, and mibefradil. The fourth class, dihydropyridines, contains numerous compounds. All agents are effective in lowering blood pressure in short-term studies, and side effects that trouble the patient are infrequent. Long-term studies in hypertensive patients are limited. Short-acting agents such as nifedipine have been associated with an increased cardiovascular risk in some, but not all studies. These agents also probably create a compliance problem for hypertensive patients because of the need for multiple daily doses and their unpleasant side effects, e.g., ankle edema, palpitations, and flushing. Therefore, they are not useful or indicated for the treatment of hypertensive patients. No data have suggested that long-acting dihydropyridines or nondihydropyridine calcium channel blockers share the same fate. Indeed, several lines of evidence suggest the opposite: they have a cardioprotective effect. However, definitive information will require the completion of several long-term trials, including ALLHAT, CONVINCE, HOT, INSIGHT and NORDIL. Finally, it is important to reflect on the lessons learned from the controversy associated with the potential risks of calcium channel blockers. First, disagreements are common when one uses case-controlled studies and are reflective of the poor precision of the methods used. What is statistically relevant in one study may not hold true for another and may have no clinical relevance, particularly if the relative risk is less than 2. Investigators need to temper their enthusiasm to reflect this reality. Second, at the cutting edge of science there is probably relatively little agreement about what is correct among equally competent scientists. All have bias in their positions and should both recognize and admit so to themselves and their

Functional and Molecular Evidence for Kv7 Channel Subtypes in Human Detrusor from Patients with and without Bladder Outflow Obstruction

DEFF Research Database (Denmark)

Svalø, Julie; Sheykhzade, Majid; Nordling, Jørgen

2015-01-01

The aim of the study was to investigate whether Kv7 channels and their ancillary β-subunits, KCNE, are functionally expressed in the human urinary bladder. Kv7 channels were examined at the molecular level and by functional studies using RT-qPCR and myography, respectively. We found mRNA expressi...... between Kv7 channels and β-adrenoceptors in the human urinary bladder. The performed gene expression analysis combined with the organ bath studies imply that compounds that activate Kv7 channels could be useful for treatment of overactive bladder syndrome.......The aim of the study was to investigate whether Kv7 channels and their ancillary β-subunits, KCNE, are functionally expressed in the human urinary bladder. Kv7 channels were examined at the molecular level and by functional studies using RT-qPCR and myography, respectively. We found mRNA expression...... (activator of Kv7.1 channels, 10 μM) and ML213 (activator of Kv7.2, Kv7.4, Kv7.4/7.5 and Kv7.5 channels, 10 μM), reduced the tone of 1 μM carbachol pre-constricted bladder strips. XE991 (blocker of Kv7.1-7.5 channels, 10 μM) had opposing effects as it increased contractions achieved with 20 mM KPSS...

Targeting aquaporin function: potent inhibition of aquaglyceroporin-3 by a gold-based compound.

Directory of Open Access Journals (Sweden)

Ana Paula Martins

Full Text Available Aquaporins (AQPs are membrane channels that conduct water and small solutes such as glycerol and are involved in many physiological functions. Aquaporin-based modulator drugs are predicted to be of broad potential utility in the treatment of several diseases. Until today few AQP inhibitors have been described as suitable candidates for clinical development. Here we report on the potent inhibition of AQP3 channels by gold(III complexes screened on human red blood cells (hRBC and AQP3-transfected PC12 cells by a stopped-flow method. Among the various metal compounds tested, Auphen is the most active on AQP3 (IC(50 = 0.8±0.08 µM in hRBC. Interestingly, the compound poorly affects the water permeability of AQP1. The mechanism of gold inhibition is related to the ability of Au(III to interact with sulphydryls groups of proteins such as the thiolates of cysteine residues. Additional DFT and modeling studies on possible gold compound/AQP adducts provide a tentative description of the system at a molecular level. The mapping of the periplasmic surface of an homology model of human AQP3 evidenced the thiol group of Cys40 as a likely candidate for binding to gold(III complexes. Moreover, the investigation of non-covalent binding of Au complexes by docking approaches revealed their preferential binding to AQP3 with respect to AQP1. The high selectivity and low concentration dependent inhibitory effect of Auphen (in the nanomolar range together with its high water solubility makes the compound a suitable drug lead for future in vivo studies. These results may present novel metal-based scaffolds for AQP drug development.

TRPA1 channels in Drosophila and honey bee ectoparasitic mites share heat sensitivity and temperature-related physiological functions

Directory of Open Access Journals (Sweden)

Guangda Peng

2016-10-01

Full Text Available The transient receptor potential cation channel, subfamily A, member 1 (TRPA1 is conserved between many arthropods, and in some has been shown to function as a chemosensor for noxious compounds. Activation of arthropod TRPA1 channels by temperature fluctuations has been tested in only a few insect species, and all of them were shown to be activated by heat. The recent identification of chemosensitive TRPA1 channels from two honey bee ectoparasitic mite species (VdTRPA1 and TmTRPA1 have provided an opportunity to study the temperature-dependent activation and the temperature-associated physiological functions of TRPA1 channels in non-insect arthropods. We found that both mite TRPA1 channels are heat sensitive and capable of rescuing the temperature-related behavioral defects of a Drosophila melanogaster trpA1 mutant. These results suggest that heat-sensitivity of TRPA1 could be conserved between many arthropods despite its amino acid sequence diversity. Nevertheless, the ankyrin repeats (ARs 6 and 7 are well-conserved between six heat-sensitive arthropod TRPA1 channels and have critical roles for the heat activation of VdTRPA1.

Data on Occurrence of Selected Trace Metals, Organochlorines, and Semivolatile Organic Compounds in Edible Fish Tissues From Lake Worth, Fort Worth, Texas 1999

National Research Council Canada - National Science Library

Moring, J. B

2002-01-01

... organic compounds to support a human health risk assessment. Left-side, skin-off fillet samples were collected from 10 individuals each of channel catfish, common carp, freshwater drum (gaspergou...

On Secure Underlay MIMO Cognitive Radio Networks with Energy Harvesting and Transmit Antenna Selection

KAUST Repository

Lei, Hongjiang

2017-03-20

In this paper, we consider an underlay multipleinput- multiple-output (MIMO) cognitive radio network (CRN) including a pair of primary nodes, a couple of secondary nodes, and an eavesdropper, where the secondary transmitter is powered by the renewable energy harvested from the primary transmitter in order to improve both energy efficiency and spectral efficiency. Based on whether the channel state information (CSI) of wiretap links are available or not, the secrecy outage performance of the optimal antenna selection (OAS) scheme and suboptimal antenna selection (SAS) scheme for underlay MIMO CRN with energy harvesting are investigated and compared with traditional space-time transmission scheme. The closed-form expressions for exact and asymptotic secrecy outage probability are derived. Monte-Carlo simulations are conducted to testify the accuracy of the analytical results. The analysis illustrates that OAS scheme outperforms SAS scheme. Furthermore, the asymptotic result shows that no matter which scheme is considered, the OAS and SAS schemes can achieve the same secrecy diversity order.

Hiding data selected topics : Rudolf Ahlswede’s lectures on information theory 3

CERN Document Server

Althöfer, Ingo; Deppe, Christian; Tamm, Ulrich

2016-01-01

Devoted to information security, this volume begins with a short course on cryptography, mainly based on lectures given by Rudolf Ahlswede at the University of Bielefeld in the mid 1990s. It was the second of his cycle of lectures on information theory which opened with an introductory course on basic coding theorems, as covered in Volume 1 of this series. In this third volume, Shannon’s historical work on secrecy systems is detailed, followed by an introduction to an information-theoretic model of wiretap channels, and such important concepts as homophonic coding and authentication. Once the theoretical arguments have been presented, comprehensive technical details of AES are given. Furthermore, a short introduction to the history of public-key cryptology, RSA and El Gamal cryptosystems is provided, followed by a look at the basic theory of elliptic curves, and algorithms for efficient addition in elliptic curves. Lastly, the important topic of “oblivious transfer” is discussed, which is strongly conne...

Wireless Information-Theoretic Security in an Outdoor Topology with Obstacles: Theoretical Analysis and Experimental Measurements

Directory of Open Access Journals (Sweden)

Dagiuklas Tasos

2011-01-01

Full Text Available This paper presents a Wireless Information-Theoretic Security (WITS scheme, which has been recently introduced as a robust physical layer-based security solution, especially for infrastructureless networks. An autonomic network of moving users was implemented via 802.11n nodes of an ad hoc network for an outdoor topology with obstacles. Obstructed-Line-of-Sight (OLOS and Non-Line-of-Sight (NLOS propagation scenarios were examined. Low-speed user movement was considered, so that Doppler spread could be discarded. A transmitter and a legitimate receiver exchanged information in the presence of a moving eavesdropper. Average Signal-to-Noise Ratio (SNR values were acquired for both the main and the wiretap channel, and the Probability of Nonzero Secrecy Capacity was calculated based on theoretical formula. Experimental results validate theoretical findings stressing the importance of user location and mobility schemes on the robustness of Wireless Information-Theoretic Security and call for further theoretical analysis.

Contribution of DIAMANT and EUROGAM detectors association to the study of heavy ion-induced fusion-evaporation reactions. Application to the de-excitation study of 90Ru compound nucleus formed in the 32S + 58Ni reaction at 120 MeV

International Nuclear Information System (INIS)

Bourgine, Frederic

1996-01-01

For the first time, the sensitivity of statistical evaporation model has been established in detail from 1 H and 4 He energy distributions analysis for different exit channels. The association of the light charged particle multidetector DIAMANT and the γ-spectrometer EUROGAM II shows that precise study of the compound nucleus high spin states deexcitation can be done for small particle channels. These channels are fed by the biggest angular momentum values of the compound nucleus. The analysis of pα channel in 32 S + 58 Ni at 120 MeV reaction exhibits that a particles have an energy distribution which leads to an entry region of the residual nucleus 85 Nb parallel to the yrast line. (author) [fr

Expression and activity of acid-sensing ion channels in the mouse anterior pituitary.

Directory of Open Access Journals (Sweden)

Jianyang Du

Full Text Available Acid sensing ion channels (ASICs are proton-gated cation channels that are expressed in the nervous system and play an important role in fear learning and memory. The function of ASICs in the pituitary, an endocrine gland that contributes to emotions, is unknown. We sought to investigate which ASIC subunits were present in the pituitary and found mRNA expression for all ASIC isoforms, including ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3 and ASIC4. We also observed acid-evoked ASIC-like currents in isolated anterior pituitary cells that were absent in mice lacking ASIC1a. The biophysical properties and the responses to PcTx1, amiloride, Ca2+ and Zn2+ suggested that ASIC currents were mediated predominantly by heteromultimeric channels that contained ASIC1a and ASIC2a or ASIC2b. ASIC currents were also sensitive to FMRFamide (Phe-Met-Arg-Phe amide, suggesting that FMRFamide-like compounds might endogenously regulate pituitary ASICs. To determine whether ASICs might regulate pituitary cell function, we applied low pH and found that it increased the intracellular Ca2+ concentration. These data suggest that ASIC channels are present and functionally active in anterior pituitary cells and may therefore influence their function.

A channel profile analyser

International Nuclear Information System (INIS)

Gobbur, S.G.

1983-01-01

It is well understood that due to the wide band noise present in a nuclear analog-to-digital converter, events at the boundaries of adjacent channels are shared. It is a difficult and laborious process to exactly find out the shape of the channels at the boundaries. A simple scheme has been developed for the direct display of channel shape of any type of ADC on a cathode ray oscilliscope display. This has been accomplished by sequentially incrementing the reference voltage of a precision pulse generator by a fraction of a channel and storing ADC data in alternative memory locations of a multichannel pulse height analyser. Alternative channels are needed due to the sharing at the boundaries of channels. In the flat region of the profile alternate memory locations are channels with zero counts and channels with the full scale counts. At the boundaries all memory locations will have counts. The shape of this is a direct display of the channel boundaries. (orig.)

Dual passivation of intrinsic defects at the compound semiconductor/oxide interface using an oxidant and a reductant.

Science.gov (United States)

Kent, Tyler; Chagarov, Evgeniy; Edmonds, Mary; Droopad, Ravi; Kummel, Andrew C

2015-05-26

Studies have shown that metal oxide semiconductor field-effect transistors fabricated utilizing compound semiconductors as the channel are limited in their electrical performance. This is attributed to imperfections at the semiconductor/oxide interface which cause electronic trap states, resulting in inefficient modulation of the Fermi level. The physical origin of these states is still debated mainly because of the difficulty in assigning a particular electronic state to a specific physical defect. To gain insight into the exact source of the electronic trap states, density functional theory was employed to model the intrinsic physical defects on the InGaAs (2 × 4) surface and to model the effective passivation of these defects by utilizing both an oxidant and a reductant to eliminate metallic bonds and dangling-bond-induced strain at the interface. Scanning tunneling microscopy and spectroscopy were employed to experimentally determine the physical and electronic defects and to verify the effectiveness of dual passivation with an oxidant and a reductant. While subsurface chemisorption of oxidants on compound semiconductor substrates can be detrimental, it has been shown theoretically and experimentally that oxidants are critical to removing metallic defects at oxide/compound semiconductor interfaces present in nanoscale channels, oxides, and other nanostructures.

The interaction between room and musical instruments studied by multi-channel auralization

DEFF Research Database (Denmark)

Rindel, Jens Holger; Otondo, Felipe

2005-01-01

in the anechoic recording. With this technique the variations in sound radiation from the musical instrument during the performance e.g. due to changes in level or movements can be reproduced with the influence of the surrounding room surfaces. Examples include a grand piano and a clarinet.......The directivity of musical instruments is very complicated and typically changes from one tone to the next. So, instead of measuring the average directivity, a multi-channel auralization method has been developed, which allows a highly accurate and realistic sounding auralization of musical...... instruments in rooms. Anechoic recordings have been made with 5 and 13 evenly distributed microphones around the musical instrument. The reproduction is made with a room acoustics simulation software using a compound source, which is in fact a number of highly directive sources, one for each of the channels...

Micromolar-Affinity Benzodiazepine Receptors Regulate Voltage-Sensitive Calcium Channels in Nerve Terminal Preparations

Science.gov (United States)

Taft, William C.; Delorenzo, Robert J.

1984-05-01

Benzodiazepines in micromolar concentrations significantly inhibit depolarization-sensitive Ca2+ uptake in intact nerve-terminal preparations. Benzodiazepine inhibition of Ca2+ uptake is concentration dependent and stereospecific. Micromolar-affinity benzodiazepine receptors have been identified and characterized in brain membrane and shown to be distinct from nanomolar-affinity benzodiazepine receptors. Evidence is presented that micromolar, and not nanomolar, benzodiazepine binding sites mediate benzodiazepine inhibition of Ca2+ uptake. Irreversible binding to micromolar benzodiazepine binding sites also irreversibly blocked depolarization-dependent Ca2+ uptake in synaptosomes, indicating that these compounds may represent a useful marker for identifying the molecular components of Ca2+ channels in brain. Characterization of benzodiazepine inhibition of Ca2+ uptake demonstrates that these drugs function as Ca2+ channel antagonists, because benzodiazepines effectively blocked voltage-sensitive Ca2+ uptake inhibited by Mn2+, Co2+, verapamil, nitrendipine, and nimodipine. These results indicate that micromolar benzodiazepine binding sites regulate voltage-sensitive Ca2+ channels in brain membrane and suggest that some of the neuronal stabilizing effects of micromolar benzodiazepine receptors may be mediated by the regulation of Ca2+ conductance.

Formation and properties of radicals in γ-irradiated molecular compounds of urea with dicarboxylic acids

International Nuclear Information System (INIS)

Kasparov, M.S.; Trofimov, V.I.

1978-01-01

Radiation chemical yields of paramagnetic centres and their nature have been studied as well as secondary reactions in channel inclusion compounds of urea with sebacic acid and in mixed crystals of urea with succinic acid. In inclusion compounds of urea with sebacic acid the yield exceeds additive at 77 K. In mixed crystals of urea with succinic acid the yield at 77 K is equal to additive. In mixed crystals at all temperatures quazistationary concentrations of radicals are lower than in pure succinic acid. In inclusion compounds quazistationary concentration of radicals are higher than in pure sebacic acid. It has been shown that in solid two-component systems, when the nature of the components is identical, the matrix structure exerts an essential influence on the radiolysis of the system

Ion channels in plants.

Science.gov (United States)

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.

Coarse architecture of the transient receptor potential vanilloid 1 (TRPV1) ion channel determined by fluorescence resonance energy transfer.

Science.gov (United States)

De-la-Rosa, Víctor; Rangel-Yescas, Gisela E; Ladrón-de-Guevara, Ernesto; Rosenbaum, Tamara; Islas, León D

2013-10-11

The transient receptor potential vanilloid 1 ion channel is responsible for the perception of high temperatures and low extracellular pH, and it is also involved in the response to some pungent compounds. Importantly, it is also associated with the perception of pain and noxious stimuli. Here, we attempt to discern the molecular organization and location of the N and C termini of the transient receptor potential vanilloid 1 ion channel by measuring FRET between genetically attached enhanced yellow and cyan fluorescent protein to the N or C terminus of the channel protein, expressed in transfected HEK 293 cells or Xenopus laevis oocytes. The static measurements of the domain organization were mapped into an available cryo-electron microscopy density of the channel with good agreement. These measurements also provide novel insights into the organization of terminal domains and their proximity to the plasma membrane.

Channel and Timeslot Co-Scheduling with Minimal Channel Switching for Data Aggregation in MWSNs

Directory of Open Access Journals (Sweden)

Sanggil Yeoum

2017-05-01

Full Text Available Collision-free transmission and efficient data transfer between nodes can be achieved through a set of channels in multichannel wireless sensor networks (MWSNs. While using multiple channels, we have to carefully consider channel interference, channel and time slot (resources optimization, channel switching delay, and energy consumption. Since sensor nodes operate on low battery power, the energy consumed in channel switching becomes an important challenge. In this paper, we propose channel and time slot scheduling for minimal channel switching in MWSNs, while achieving efficient and collision-free transmission between nodes. The proposed scheme constructs a duty-cycled tree while reducing the amount of channel switching. As a next step, collision-free time slots are assigned to every node based on the minimal data collection delay. The experimental results demonstrate that the validity of our scheme reduces the amount of channel switching by 17.5%, reduces energy consumption for channel switching by 28%, and reduces the schedule length by 46%, as compared to the existing schemes.

Surface channeling

International Nuclear Information System (INIS)

Sizmann, R.; Varelas, C.

1976-01-01

There is experimental evidence that swift light ions incident at small angles towards single crystalline surfaces can lose an appreciable fraction of their kinetic energy during reflection. It is shown that these projectiles penetrate into the bulk surface region of the crystal. They can travel as channeled particles along long paths through the solid (surface channeling). The angular distribution and the depth history of the re-emerged projectiles are investigated by computer simulations. A considerable fraction of the penetrating projectiles re-emerges from the crystal with constant transverse energy if the angle of incidence is smaller than the critical angle for axial channeling. Analytical formulae are derived based on a diffusion model for surface channeling. A comparison with experimental data exhibits the relevance of the analytical solutions. (Auth.)

Numerical simulation of sediment movement and deposition in a meandering channel

International Nuclear Information System (INIS)

Ghani, U.

2011-01-01

In this research work, predictions have been made for the transport and deposition of incoming sediments in an open channel. Attempt has been made to understand the behavior of sediments flowing in the channel. The geometry consisted of a meandering compound channel with a constant inflow of sediments. For this purpose, 3D version of CFD (Computational Fluid Dynamics) code FLUENT has been used as a research tool. The turbulence closure of Reynolds Averaged Navior-Stokes equation was performed with standard -turbulence model. The Lagrangian particle tracking technique available in the code has been used for modeling sediment movement and deposition. For this purpose, nine different ranges of the particle diameters were released at the inlet of the channel. Initially, the model was validated using point velocities in the downstream direction and discharge values at five cross sections along the meander wavelength. The channel used for simulation purposes had a rectangular section. Once the model validated, it was then used for simulation of sediments. The numerical modeling gave a detailed picture of sediment deposited and transported through the channel. As the model was used with - turbulence model and Lagrangian particle tracking technique and then validated, it showed that when this combination of particle tracking and turbulence closure option will be used, the prediction will be fairly good and trustworthy. A number of numerical experiments were conducted to get the impact of sediment inflow velocity and its diameter on deposition patterns. It showed that boundary shearing stresses and secondary flows had considerable impact on sediment deposition in a river bend. The current study revealed that CFD technique can be used for predicting sediment distribution patterns with reasonable confidence. Such prediction techniques are not only economical but also provide details of complex flow and sediment movement behavior which are difficult to get through

Three-dimensional flow structure and patterns of bed shear stress in an evolving compound meander bend

Science.gov (United States)

Engel, Frank; Rhoads, Bruce L.

2016-01-01

Compound meander bends with multiple lobes of maximum curvature are common in actively evolving lowland rivers. Interaction among spatial patterns of mean flow, turbulence, bed morphology, bank failures and channel migration in compound bends is poorly understood. In this paper, acoustic Doppler current profiler (ADCP) measurements of the three-dimensional (3D) flow velocities in a compound bend are examined to evaluate the influence of channel curvature and hydrologic variability on the structure of flow within the bend. Flow structure at various flow stages is related to changes in bed morphology over the study timeframe. Increases in local curvature within the upstream lobe of the bend reduce outer bank velocities at morphologically significant flows, creating a region that protects the bank from high momentum flow and high bed shear stresses. The dimensionless radius of curvature in the upstream lobe is one-third less than that of the downstream lobe, with average bank erosion rates less than half of the erosion rates for the downstream lobe. Higher bank erosion rates within the downstream lobe correspond to the shift in a core of high velocity and bed shear stresses toward the outer bank as flow moves through the two lobes. These erosion patterns provide a mechanism for continued migration of the downstream lobe in the near future. Bed material size distributions within the bend correspond to spatial patterns of bed shear stress magnitudes, indicating that bed material sorting within the bend is governed by bed shear stress. Results suggest that patterns of flow, sediment entrainment, and planform evolution in compound meander bends are more complex than in simple meander bends. Moreover, interactions among local influences on the flow, such as woody debris, local topographic steering, and locally high curvature, tend to cause compound bends to evolve toward increasing planform complexity over time rather than stable configurations.

Computer-aided mapping of stream channels beneath the Lawrence Livermore National Laboratory Super Fund Site

Energy Technology Data Exchange (ETDEWEB)

Sick, M. [Lawrence Livermore National Lab., CA (United States)

1994-12-01

The Lawrence Livermore National Laboratory (LLNL) site rests upon 300-400 feet of highly heterogeneous braided stream sediments which have been contaminated by a plume of Volatile Organic Compounds (VOCs). The stream channels are filled with highly permeable coarse grained materials that provide quick avenues for contaminant transport. The plume of VOCs has migrated off site in the TFA area, making it the area of greatest concern. I mapped the paleo-stream channels in the TFA area using SLICE an LLNL Auto-CADD routine. SLICE constructed 2D cross sections and sub-horizontal views of chemical, geophysical, and lithologic data sets. I interpreted these 2D views as a braided stream environment, delineating the edges of stream channels. The interpretations were extracted from Auto-CADD and placed into Earth Vision`s 3D modeling and viewing routines. Several 3D correlations have been generated, but no model has yet been chosen as a best fit.

An information-guided channel-hopping scheme for block-fading channels with estimation errors

KAUST Repository

Yang, Yuli

2010-12-01

Information-guided channel-hopping technique employing multiple transmit antennas was previously proposed for supporting high data rate transmission over fading channels. This scheme achieves higher data rates than some mature schemes, such as the well-known cyclic transmit antenna selection and space-time block coding, by exploiting the independence character of multiple channels, which effectively results in having an additional information transmitting channel. Moreover, maximum likelihood decoding may be performed by simply decoupling the signals conveyed by the different mapping methods. In this paper, we investigate the achievable spectral efficiency of this scheme in the case of having channel estimation errors, with optimum pilot overhead for minimum meansquare error channel estimation, when transmitting over blockfading channels. Our numerical results further substantiate the robustness of the presented scheme, even with imperfect channel state information. ©2010 IEEE.

Fusion-fission of heavy systems: influence of the entrance channel mass assymmetry

International Nuclear Information System (INIS)

Rivet, M.F.; Alami, R.; Borderie, B.; Fuchs, H.; Gardes, D.; Gauvin, H.

1988-02-01

The influence of the entrance channel on fission processes was studied by forming the same composite system by two different target-projectile combinations ( 40 Ar + 209 Bi and 56 Fe + 187 Re, respectively). Compound nucleus fission and quasi fission were observed and the analysis was performed in the framework of the extra-extra-push model, which provides a qualitative interpretation of the results; limits for the extra-extra-push threshold are given, but problems with quantitative predictions for the extra-push are noted

Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8.

Science.gov (United States)

De Petrocellis, Luciano; Vellani, Vittorio; Schiano-Moriello, Aniello; Marini, Pietro; Magherini, Pier Cosimo; Orlando, Pierangelo; Di Marzo, Vincenzo

2008-06-01

The plant cannabinoids (phytocannabinoids), cannabidiol (CBD), and Delta(9)-tetrahydrocannabinol (THC) were previously shown to activate transient receptor potential channels of both vanilloid type 1 (TRPV1) and ankyrin type 1 (TRPA1), respectively. Furthermore, the endocannabinoid anandamide is known to activate TRPV1 and was recently found to antagonize the menthol- and icilin-sensitive transient receptor potential channels of melastatin type 8 (TRPM8). In this study, we investigated the effects of six phytocannabinoids [i.e., CBD, THC, CBD acid, THC acid, cannabichromene (CBC), and cannabigerol (CBG)] on TRPA1- and TRPM8-mediated increase in intracellular Ca2+ in either HEK-293 cells overexpressing the two channels or rat dorsal root ganglia (DRG) sensory neurons. All of the compounds tested induced TRPA1-mediated Ca2+ elevation in HEK-293 cells with efficacy comparable with that of mustard oil isothiocyanates (MO), the most potent being CBC (EC(50) = 60 nM) and the least potent being CBG and CBD acid (EC(50) = 3.4-12.0 microM). CBC also activated MO-sensitive DRG neurons, although with lower potency (EC(50) = 34.3 microM). Furthermore, although none of the compounds tested activated TRPM8-mediated Ca2+ elevation in HEK-293 cells, they all, with the exception of CBC, antagonized this response when it was induced by either menthol or icilin. CBD, CBG, THC, and THC acid were equipotent (IC(50) = 70-160 nM), whereas CBD acid was the least potent compound (IC(50) = 0.9-1.6 microM). CBG inhibited Ca2+ elevation also in icilin-sensitive DRG neurons with potency (IC(50) = 4.5 microM) similar to that of anandamide (IC(50) = 10 microM). Our findings suggest that phytocannabinoids and cannabis extracts exert some of their pharmacological actions also by interacting with TRPA1 and TRPM8 channels, with potential implications for the treatment of pain and cancer.

Deciphering the mode of action of clinically relevant next generation c2 corrector compounds GLPG2737 and GLPG3221

NARCIS (Netherlands)

Peters, F.; Sahasrabudhe, P.; Gross-Wilde, H.; Kleizen, Bertrand; Conrath, K.; Braakman, I.

2017-01-01

The current therapeutic strategy to repair cystic fibrosis-causing defects in the chloride channel CFTR is to develop novel and better correctors (to improve folding) and potentiators (to improve function). Galapagos- AbbVie identified C2 correctors by high-throughput compound screening and Med Chem

Potassium channels in brain mitochondria.

Science.gov (United States)

Bednarczyk, Piotr

2009-01-01

Potassium channels are the most widely distributed class of ion channels. These channels are transmembrane proteins known to play important roles in both normal and pathophysiological functions in all cell types. Various potassium channels are recognised as potential therapeutic targets in the treatment of Parkinson's disease, Alzheimer's disease, brain/spinal cord ischaemia and sepsis. In addition to their importance as therapeutic targets, certain potassium channels are known for their beneficial roles in anaesthesia, cardioprotection and neuroprotection. Some types of potassium channels present in the plasma membrane of various cells have been found in the inner mitochondrial membrane as well. Potassium channels have been proposed to regulate mitochondrial membrane potential, respiration, matrix volume and Ca(+) ion homeostasis. It has been proposed that mitochondrial potassium channels mediate ischaemic preconditioning in various tissues. However, the specificity of a pharmacological agents and the mechanisms underlying their effects on ischaemic preconditioning remain controversial. The following potassium channels from various tissues have been identified in the inner mitochondrial membrane: ATP-regulated (mitoK(ATP)) channel, large conductance Ca(2+)-regulated (mitoBK(Ca)) channel, intermediate conductance Ca(2+)-regulated (mitoIK(Ca)) channel, voltage-gated (mitoKv1.3 type) channel, and twin-pore domain (mitoTASK-3) channel. It has been shown that increased potassium flux into brain mitochondria induced by either the mitoK(ATP) channel or mitoBK(Ca) channel affects the beneficial effects on neuronal cell survival under pathological conditions. Recently, differential distribution of mitoBK(Ca) channels has been observed in neuronal mitochondria. These findings may suggest a neuroprotective role for the mitoBK(Ca) channel in specific brain structures. This minireview summarises current data on brain mitochondrial potassium channels and the efforts to identify

Channel allocation and rate adaptation for relayed transmission over correlated fading channels

KAUST Repository

Hwang, Kyusung

2009-09-01

We consider, in this paper, channel allocation and rate adaptation scheme for relayed transmission over correlated fading channels via cross-layer design. Specifically, jointly considering the data link layer buffer occupancy and channel quality at both the source and relay nodes, we develop an optimal channel allocation and rate adaptation policy for a dual-hop relayed transmission. As such the overall transmit power for the relayed system is minimized while a target packet dropping rate (PDR) due to buffer over flows is guaranteed. In order to find such an optimal policy, the channel allocation and rate adaptation transmission framework is formulated as a constraint Markov decision process (CMDP). The PDR performance of the optimal policy is compared with that of two conventional suboptimal schemes, namely the channel quality based and the buffer occupancy based channel allocation schemes. Numerical results show that for a given power budget, the optimal scheme requires significantly less power than the conventional schemes in order to maintain a target PDR. ©2009 IEEE.

Evaluation and optimization of compound solubilization and delivery methods in a two-tiered ion channel lead optimization triage.

Science.gov (United States)

Hendricson, Adam W; Gallagher, Liz; Matchett, Michele; Ferrante, Meredith; Spence, Steve; Paiva, Tony; Shou, Wilson; Tertyshnikova, Svetlana; Krambis, Mike; Post-Munson, Deborah; Zhang, Litao; Knox, Ron

2012-04-01

Low-volume dispensing of neat dimethyl sulfoxide (DMSO) into plate-based assays conserves compound, assay reagents, and intermediate dilution plate cost and, as we demonstrate here, significantly improves structure-activity relationship resolution. Acoustic dispensing of DMSO solutions into standard volume 384W plates yielded inconsistent results in studies with 2 cell lines because of apparent effects on the integrity of the cell monolayer (increased intracellular Ca⁺⁺ levels as indicated by elevated basal dye fluorescence after acoustic transfer). PocketTip-mediated transfer was successful at increasing apparent potency on a more consistent basis. Notably, the correlation coefficient among fluorescence imaging plate reader (FLIPR):electrophysiology (EP) across a representative ~125 compound collection was increased ~5× via conversion to a PocketTip direct dispensation, indicating a triage assay more predictive of activity in the decisional patch-clamp assay. Very importantly, the EP-benchmarked false-negative rate as measured by compounds with FLIPR EC₅₀ more than the highest concentration tested fell from >11% to 5% assay-wide, and the relative FLIPR:EP rank-order fidelity increased from 55% to 78%. Elimination of the aqueous intermediate step provided additional benefits, including reduced assay cost, decreased cycle time, and reduced wet compound consumption rate. Direct DMSO dispensing has broad applicability to cell-based functional assays of multiple varieties, especially in cases where limit solubility in assay buffer is a recognized impediment to maximizing interassay connectivity.

Transient receptor potential channel ankyrin-1 is not a cold sensor for autonomic thermoregulation in rodents.

Science.gov (United States)

de Oliveira, Cristiane; Garami, Andras; Lehto, Sonya G; Pakai, Eszter; Tekus, Valeria; Pohoczky, Krisztina; Youngblood, Beth D; Wang, Weiya; Kort, Michael E; Kym, Philip R; Pinter, Erika; Gavva, Narender R; Romanovsky, Andrej A

2014-03-26

The rodent transient receptor potential ankyrin-1 (TRPA1) channel has been hypothesized to serve as a temperature sensor for thermoregulation in the cold. We tested this hypothesis by using deletion of the Trpa1 gene in mice and pharmacological blockade of the TRPA1 channel in rats. In both Trpa1(-/-) and Trpa1(+/+) mice, severe cold exposure (8°C) resulted in decreases of skin and deep body temperatures to ∼8°C and 13°C, respectively, both temperatures being below the reported 17°C threshold temperature for TRPA1 activation. Under these conditions, Trpa1(-/-) mice had the same dynamics of body temperature as Trpa1(+/+) mice and showed no weakness in the tail skin vasoconstriction response or thermogenic response to cold. In rats, the effects of pharmacological blockade were studied by using two chemically unrelated TRPA1 antagonists: the highly potent and selective compound A967079, which had been characterized earlier, and the relatively new compound 43 ((4R)-1,2,3,4-tetrahydro-4-[3-(3-methoxypropoxy)phenyl]-2-thioxo-5H-indeno[1,2-d]pyrimidin-5-one), which we further characterized in the present study and found to be highly potent (IC50 against cold of ∼8 nm) and selective. Intragastric administration of either antagonist at 30 mg/kg before severe (3°C) cold exposure did not affect the thermoregulatory responses (deep body and tail skin temperatures) of rats, even though plasma concentrations of both antagonists well exceeded their IC50 value at the end of the experiment. In the same experimental setup, blocking the melastatin-8 (TRPM8) channel with AMG2850 (30 mg/kg) attenuated cold-defense mechanisms and led to hypothermia. We conclude that TRPA1 channels do not drive autonomic thermoregulatory responses to cold in rodents.

Comparison of Channel Estimation Protocols for Coherent AF Relaying Networks in the Presence of Additive Noise and LO Phase Noise

Directory of Open Access Journals (Sweden)

Stefan Berger

2010-01-01

Full Text Available Channel estimation protocols for wireless two-hop networks with amplify-and-forward (AF relays are compared. We consider multiuser relaying networks, where the gain factors are chosen such that the signals from all relays add up coherently at the destinations. While the destinations require channel knowledge in order to decode, our focus lies on the channel estimates that are used to calculate the relay gains. Since knowledge of the compound two-hop channels is generally not sufficient to do this, the protocols considered here measure all single-hop coefficients in the network. We start from the observation that the direction in which the channels are measured determines (1 the number of channel uses required to estimate all coefficient and (2 the need for global carrier phase reference. Four protocols are identified that differ in the direction in which the first-hop and the second-hop channels are measured. We derive a sensible measure for the accuracy of the channel estimates in the presence of additive noise and phase noise and compare the protocols based on this measure. Finally, we provide a quantitative performance comparison for a simple single-user application example. It is important to note that the results can be used to compare the channel estimation protocols for any two-hop network configuration and gain allocation scheme.

Anti-Convulsant Activity of Boerhaavia diffusa: Plausible Role of Calcium Channel Antagonism

Directory of Open Access Journals (Sweden)

Mandeep Kaur

2011-01-01

Full Text Available “Ethnopharmacological” use of roots of Boerhaavia diffusa (B. diffusa in the treatment of epilepsy in Nigerian folk medicine and reports showing the presence of a calcium channel antagonistic compound “liriodendrin” in its roots, led us to undertake the present study. The study was designed to investigate the methanolic root extract of B. diffusa and its different fractions including liriodendrin-rich fraction for exploring the possible role of liriodendrin in its anti-convulsant activity. Air-dried roots of B. diffusa were extracted with methanol by cold maceration. The methanol soluble fraction of extract thus obtained was successively extracted to obtain liriodendrin-rich fraction and two side fractions, that is, chloroform fraction and phenolic compound fraction. Anti-convulsant activity of methanolic extract (1000, 1500 and 2000 mg kg-1, intraperitoneally (i.p. and its different fractions, that is, liriodendrin-rich fraction (10, 20 and 40 mg kg-1, i.p., chloroform fraction (20 mg kg-1, i.p. and phenolic compound fraction (1 mg kg-1, i.p. were studied in pentylenetetrazol (PTZ-induced seizures (75 mg kg-1, i.p.. The crude methanolic extract of B. diffusa and only its liriodendrin-rich fraction showed a dose-dependent protection against PTZ-induced convulsions. The liriodendrin-rich fraction also showed significant protection against seizures induced by BAY k-8644. These findings reiterated the anti-convulsant activity of methanolic extract of B. diffusa roots. Furthermore, it can be concluded that the observed anti-convulsant activity was due to its calcium channel antagonistic action as this activity was retained only in the liodendrin-rich fraction, which has additionally been confirmed by significant anti-convulsant activity of liriodendrin-rich fraction in BAY k-8644-induced seizures.

Laser-induced thermal coagulation enhances skin uptake of topically applied compounds

DEFF Research Database (Denmark)

Haak, C S; Hannibal, J; Paasch, U

2017-01-01

microchannels surrounded by CZ compared to channels with no CZ (CZ-20 and CZ-80>CZ-0).The thickness of CZ affected PEG distribution in skin. A thin CZ-20 favored significantly higher mean fluorescence intensities inside CZ areas compared to CZ-80 (PEG 350, 1,000, and 5,000; P ...BACKGROUND: Ablative fractional laser (AFL) generates microchannels in skin surrounded by a zone of thermally altered tissue, termed the coagulation zone (CZ). The thickness of CZ varies according to applied wavelength and laser settings. It is well-known that AFL channels facilitate uptake...... of topically applied compounds, but the importance of CZ is unknown. METHODS: Franz Cells were used to investigate skin uptake and permeation of fluorescent labeled polyethylene glycols (PEGs) with mean molecular weights (MW) of 350, 1,000, and 5,000 Da. Microchannels with CZ thicknesses ranging from 0 to 80...

Thermodynamic Simulation of Equilibrium Composition of Reaction Products at Dehydration of a Technological Channel in a Uranium-Graphite Reactor

Science.gov (United States)

Pavliuk, A. O.; Zagumennov, V. S.; Kotlyarevskiy, S. G.; Bespala, E. V.

2018-01-01

The problems of accumulation of nuclear fuel spills in the graphite stack in the course of operation of uranium-graphite nuclear reactors are considered. The results of thermodynamic analysis of the processes in the graphite stack at dehydration of a technological channel, fuel element shell unsealing and migration of fission products, and activation of stable nuclides in structural elements of the reactor and actinides inside the graphite moderator are given. The main chemical reactions and compounds that are produced in these modes in the reactor channel during its operation and that may be hazardous after its shutdown and decommissioning are presented. Thermodynamic simulation of the equilibrium composition is performed using the specialized code TERRA. The results of thermodynamic simulation of the equilibrium composition in different cases of technological channel dehydration in the course of the reactor operation show that, if the temperature inside the active core of the nuclear reactor increases to the melting temperature of the fuel element, oxides and carbides of nuclear fuel are produced. The mathematical model of the nonstationary heat transfer in a graphite stack of a uranium-graphite reactor in the case of the technological channel dehydration is presented. The results of calculated temperature evolution at the center of the fuel element, the replaceable graphite element, the air gap, and in the surface layer of the block graphite are given. The numerical results show that, in the case of dehydration of the technological channel in the uranium-graphite reactor with metallic uranium, the main reaction product is uranium dioxide UO2 in the condensed phase. Low probability of production of pyrophoric uranium compounds (UH3) in the graphite stack is proven, which allows one to disassemble the graphite stack without the risk of spontaneous graphite ignition in the course of decommissioning of the uranium-graphite nuclear reactor.

Investigation of spin-gapless semiconductivity and half-metallicity in Ti2MnAl-based compounds

International Nuclear Information System (INIS)

Lukashev, P.; Staten, B.; Hurley, N.; Kharel, P.; Gilbert, S.; Fuglsby, R.; Huh, Y.; Valloppilly, S.; Zhang, W.; Skomski, R.; Sellmyer, D. J.; Yang, K.

2016-01-01

The increasing interest in spin-based electronics has led to a vigorous search for new materials that can provide a high degree of spin polarization in electron transport. An ideal candidate would act as an insulator for one spin channel and a conductor or semiconductor for the opposite spin channel, corresponding to the respective cases of half-metallicity and spin-gapless semiconductivity. Our first-principle electronic-structure calculations indicate that the metallic Heusler compound Ti 2 MnAl becomes half-metallic and spin-gapless semiconducting if half of the Al atoms are replaced by Sn and In, respectively. These electronic structures are associated with structural transitions from the regular cubic Heusler structure to the inverted cubic Heusler structure.

Study of elastic scattering between heavy ions. Reaction channel influence

International Nuclear Information System (INIS)

Doubre, Hubert.

1978-01-01

The role of absorption on the behavior of heavy ion angular distributions and excitaton functions has been investigated on light and medium mass systems. Comparison between 20 Ne+ 12 C and 16 O+ 16 O systems which lead to the same compound nucleus, shows that it originates from the direct channels strongly coupled to the entrance channel. Structures in the excitation functions occur for almost all the light systems and it is shown that the damping observed for heavier systems such as 40 Ca+ 40 Ca, essentially results on the predominance of Coulomb effects which hide the nuclear structure effects. Thus no valuable information on the details of S-matrix can be extracted for such an heavy system. A coherent description of the elastic scattering, based on a splitting of the scattering amplitude into two components, the modulus of each component varying smoothly as a function of energy and angle. The interference between these sub-amplitudes give rise to interference effects in angular distributions and excitation functions. The study of the main reaction channels of the 40 Ca+ 40 Ca system - i.e. deep inelastic reactions and fusion - also shows that the closed-shell nature of the interacting nuclei does not play any role in these processes due to the excitation processes in the first stage of the reactions which destroy the specific structure of the nuclei [fr

Two novel 3-D bismuth oxalates with organic amines protruding in channels

International Nuclear Information System (INIS)

Yu Xiaohong; Zhang Hanhui; Cao Yanning; Hu Zhongjian; Chen Yiping; Wang Zhen

2006-01-01

Two novel 3-D oxalate-containing bismuth compounds of formula (C 3 N 2 H 5 ) 2 [Bi 2 (C 2 O 4 ) 4 (H 2 O) 2 ].2H 2 O 1 and [NH(C 2 H 5 ) 3 ][Bi 3 (C 2 O 4 ) 5 ] 2 were obtained by hydrothermal synthesis and characterized by single-crystal X-ray diffraction. Compound 1 crystallizes in the monoclinic P2/n space group with a=9.7541(13)A, b=17.7404(15)A, c=14.6321(6)A, β=97.280(3) o , Z=4, R 1 =0.0340 and wR 2 =0.0766 for unique 4734 reflections I>2σ(I). Compound 2 belongs to the orthorhombic Pbcn space group with a=14.803(4)A, b=19.783(7)A, c=8.202(2)A, Z=4, R 1 =0.0222 and wR 2 =0.0568 for unique 2472 reflections I>2σ(I). The Bi III centers have nine-fold coordination for 1 and eight-fold for 2 with the Bi atoms in distorted monocapped square antiprism and distorted dodecahedron, respectively. And oxalate ligands adopt different coordination modes: bidentate for 1, bidentate and tricoordinate for 2. Compounds 1 and 2 are both 3-D open-framework structures containing channels with guest molecules. These two compounds exhibit intense blue luminescence with the emission peaks at 419nm for 1 and 442nm for 2, respectively, in the solid state at room temperature. These compounds with novel structural frameworks could be useful in the field of photoactive materials

A linearization of quantum channels

Science.gov (United States)

Crowder, Tanner

2015-06-01

Because the quantum channels form a compact, convex set, we can express any quantum channel as a convex combination of extremal channels. We give a Euclidean representation for the channels whose inverses are also valid channels; these are a subset of the extreme points. They form a compact, connected Lie group, and we calculate its Lie algebra. Lastly, we calculate a maximal torus for the group and provide a constructive approach to decomposing any invertible channel into a product of elementary channels.

Channel Characteristics and Transmission Performance for Various Channel Configurations at 60 GHz

Directory of Open Access Journals (Sweden)

Yang Haibing

2007-01-01

Full Text Available Extensive measurements are conducted in room environments at 60 GHz to analyze the channel characteristics for various channel configurations. Channel parameters retrieved from measurements are presented and analyzed based on generic channel models. Particularly, a simple single-cluster model is applied for the parameter retrieval and performance evaluation. By this model, power delay profiles are simply described by a -factor, a root-mean-squared delay spread, and a shape parameter. The considered channels are configured with the combination of omnidirectional, fan-beam, and pencil-beam antennas at transmitter and receiver sides. Both line-of-sight (LOS and non-LOS (NLOS channels are considered. Further, to evaluate the transmission performance, we analyze the link budget in the considered environments, then design and simulate an OFDM system with a data rate of 2 Gbps to compare the bit-error-rate (BER performance by using the measured and modeled channels. Both coded and uncoded OFDM systems are simulated. It is observed that the BER performance agrees well for the measured and modeled channels. In addition, directive configurations can provide sufficient link margins and BER performance for high data rate communications. To increase the coverage and performance in the NLOS area, it is preferable to apply directive antennas.

Channel Characteristics and Transmission Performance for Various Channel Configurations at 60 GHz

Directory of Open Access Journals (Sweden)

Haibing Yang

2007-05-01

Full Text Available Extensive measurements are conducted in room environments at 60 GHz to analyze the channel characteristics for various channel configurations. Channel parameters retrieved from measurements are presented and analyzed based on generic channel models. Particularly, a simple single-cluster model is applied for the parameter retrieval and performance evaluation. By this model, power delay profiles are simply described by a K-factor, a root-mean-squared delay spread, and a shape parameter. The considered channels are configured with the combination of omnidirectional, fan-beam, and pencil-beam antennas at transmitter and receiver sides. Both line-of-sight (LOS and non-LOS (NLOS channels are considered. Further, to evaluate the transmission performance, we analyze the link budget in the considered environments, then design and simulate an OFDM system with a data rate of 2 Gbps to compare the bit-error-rate (BER performance by using the measured and modeled channels. Both coded and uncoded OFDM systems are simulated. It is observed that the BER performance agrees well for the measured and modeled channels. In addition, directive configurations can provide sufficient link margins and BER performance for high data rate communications. To increase the coverage and performance in the NLOS area, it is preferable to apply directive antennas.

A new candidate of calcium channel blocker in silico from Tectona grandis for treatment of gestational hypertension

Science.gov (United States)

Azizah, A.; Suselo, Y. H.; Muthmainah, M.; Indarto, D.

2018-05-01

Gestational Hypertension is one of the three main causes of maternal mortality in Indonesia. Nifedipine which blockes the Cav1.2 calcium channel has frequently been used to treat gestational hypertension. However the efficacy of nifedipine has not been established yet and the prevalence of gestational hypertension is still high (27.1 %). Indonesian herbal plants have potential to be developed as natural drugs. Molecular docking, a computational method, is very often used to depict interaction between molecules and target receptor This study was therefore to identify Indonesian herbal plants that could inhibit the calcium channel in silico. This was a bioinformatics study with molecular docking approach. Three-dimensional structure of human calcium channel Cav1.2 was determined by modelling with rabbit calcium channel (ID:5GJW) as template and using the SWISS MODEL software. Nifedipine was used as a standard ligand and obtained from ZINC database with the access code ZINC19594578. Active compounds of Indonesian herbal plants were registered in HerbalDB database and their molecular structure was obtained from PubChem. Binding affinity of human Cav1.2 model-ligand complexes were assesed using AutoDock Vina 1.1.2 software and visualization of molecular conformation used Chimera 1.10 and PyMol 1.3 softwares. The Lipinsky’s rules of five were used to determine active compounds which fullfilled drug criteria. The human Cav1-2 model had 72.35% sequence identity with rabbit Cav1.1. Nifedipine bound to the human Cav1.2 model with -2.1 kcal/mol binding affinity and had binding sites at Gln1060, Phe1129, Ser1132, and Ile1173 residues. A lower binding affinity was observed in 8 phytochemicals but only obtusifolin 2-glucoside (-2.2 kcal/mol) had similar binding sites as nifedipin did. In addition, obtusifolin 2-glucoside met the Lipinsky criteria and the molecule conformation was similar with nifedipine. From the HerbalDB database, obtusifolin 2-glucoside is found in Tectona

Volume of the space of qubit-qubit channels and state transformations under random quantum channels

OpenAIRE

Lovas, Attila; Andai, Attila

2017-01-01

The simplest building blocks for quantum computations are the qubit-qubit quantum channels. In this paper, we analyze the structure of these channels via their Choi representation. The restriction of a quantum channel to the space of classical states (i.e. probability distributions) is called the underlying classical channel. The structure of quantum channels over a fixed classical channel is studied, the volume of general and unital qubit channels with respect to the Lebesgue measure is comp...

Astringency is a trigeminal sensation that involves the activation of G protein-coupled signaling by phenolic compounds.

Science.gov (United States)

Schöbel, Nicole; Radtke, Debbie; Kyereme, Jessica; Wollmann, Nadine; Cichy, Annika; Obst, Katja; Kallweit, Kerstin; Kletke, Olaf; Minovi, Amir; Dazert, Stefan; Wetzel, Christian H; Vogt-Eisele, Angela; Gisselmann, Günter; Ley, Jakob P; Bartoshuk, Linda M; Spehr, Jennifer; Hofmann, Thomas; Hatt, Hanns

2014-07-01

Astringency is an everyday sensory experience best described as a dry mouthfeel typically elicited by phenol-rich alimentary products like tea and wine. The neural correlates and cellular mechanisms of astringency perception are still not well understood. We explored taste and astringency perception in human subjects to study the contribution of the taste as well as of the trigeminal sensory system to astringency perception. Subjects with either a lesion or lidocaine anesthesia of the Chorda tympani taste nerve showed no impairment of astringency perception. Only anesthesia of both the lingual taste and trigeminal innervation by inferior alveolar nerve block led to a loss of astringency perception. In an in vitro model of trigeminal ganglion neurons of mice, we studied the cellular mechanisms of astringency perception. Primary mouse trigeminal ganglion neurons showed robust responses to 8 out of 19 monomeric phenolic astringent compounds and 8 polymeric red wine polyphenols in Ca(2+) imaging experiments. The activating substances shared one or several galloyl moieties, whereas substances lacking the moiety did not or only weakly stimulate responses. The responses depended on Ca(2+) influx and voltage-gated Ca(2+) channels, but not on transient receptor potential channels. Responses to the phenolic compound epigallocatechin gallate as well as to a polymeric red wine polyphenol were inhibited by the Gαs inactivator suramin, the adenylate cyclase inhibitor SQ, and the cyclic nucleotide-gated channel inhibitor l-cis-diltiazem and displayed sensitivity to blockers of Ca(2+)-activated Cl(-) channels. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Performance Analysis of Iterative Channel Estimation and Multiuser Detection in Multipath DS-CDMA Channels

Science.gov (United States)

Li, Husheng; Betz, Sharon M.; Poor, H. Vincent

2007-05-01

This paper examines the performance of decision feedback based iterative channel estimation and multiuser detection in channel coded aperiodic DS-CDMA systems operating over multipath fading channels. First, explicit expressions describing the performance of channel estimation and parallel interference cancellation based multiuser detection are developed. These results are then combined to characterize the evolution of the performance of a system that iterates among channel estimation, multiuser detection and channel decoding. Sufficient conditions for convergence of this system to a unique fixed point are developed.

Channel electron multipliers

International Nuclear Information System (INIS)

Seidman, A.; Avrahami, Z.; Sheinfux, B.; Grinberg, J.

1976-01-01

A channel electron multiplier is described having a tubular wall coated with a secondary-electron emitting material and including an electric field for accelerating the electrons, the electric field comprising a plurality of low-resistive conductive rings each alternating with a high-resistive insulating ring. The thickness of the low-resistive rings is many times larger than that of the high-resistive rings, being in the order of tens of microns for the low-resistive rings and at least one order of magnitude lower for the high-resistive rings; and the diameter of the channel tubular walls is also many times larger than the thickness of the high-resistive rings. Both single-channel and multiple-channel electron multipliers are described. A very important advantage, particularly in making multiple-channel multipliers, is the simplicity of the procedure that may be used in constructing such multipliers. Other operational advantages are described

Acid-sensing ion channel (ASIC) structure and function: Insights from spider, snake and sea anemone venoms.

Science.gov (United States)

Cristofori-Armstrong, Ben; Rash, Lachlan D

2017-12-01

Acid-sensing ion channels (ASICs) are proton-activated cation channels that are expressed in a variety of neuronal and non-neuronal tissues. As proton-gated channels, they have been implicated in many pathophysiological conditions where pH is perturbed. Venom derived compounds represent the most potent and selective modulators of ASICs described to date, and thus have been invaluable as pharmacological tools to study ASIC structure, function, and biological roles. There are now ten ASIC modulators described from animal venoms, with those from snakes and spiders favouring ASIC1, while the sea anemones preferentially target ASIC3. Some modulators, such as the prototypical ASIC1 modulator PcTx1 have been studied in great detail, while some of the newer members of the club remain largely unstudied. Here we review the current state of knowledge on venom derived ASIC modulators, with a particular focus on their molecular interaction with ASICs, what they have taught us about channel structure, and what they might still reveal about ASIC function and pathophysiological roles. This article is part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools.' Copyright © 2017 Elsevier Ltd. All rights reserved.

The novel isoxazoline ectoparasiticide lotilaner (Credelio™: a non-competitive antagonist specific to invertebrates γ-aminobutyric acid-gated chloride channels (GABACls

Directory of Open Access Journals (Sweden)

Lucien Rufener

2017-11-01

Full Text Available Abstract Background The isoxazolines are a novel class of parasiticides that are potent inhibitors of γ-aminobutyric acid (GABA-gated chloride channels (GABACls and, to a lesser extent, of inhibitory glutamate-gated chloride channels (GluCls. Lotilaner (Credelio™, a novel representative of this chemical class, is currently evaluated for its excellent ectoparasiticide properties. Methods In this study, we investigated the molecular mode of action and pharmacology of lotilaner. We report the successful gene identification, cDNA cloning and functional expression in Xenopus oocytes of Drosohpila melanogaster (wild type and dieldrin/fipronil-resistant forms, Lepeophtheirus salmonis (an ectoparasite copepod crustacean of salmon, Rhipicephalus microplus and Canis lupus familiaris GABACls. Automated Xenopus oocyte two-electrode voltage clamp electrophysiology was used to assess GABACls functionality and to compare ion channel inhibition by lotilaner with that of established insecticides addressing GABACls as targets. Results In these assays, we demonstrated that lotilaner is a potent non-competitive antagonist of insects (fly GABACls. No cross-resistance with dieldrin or fipronil resistance mutations was detected, suggesting that lotilaner might bind to a site at least partly different from the one bound by known GABACl blockers. Using co-application experiments, we observed that lotilaner antagonism differs significantly from the classical open channel blocker fipronil. We finally confirmed for the first time that isoxazoline compounds are not only powerful antagonists of GABACls of acari (ticks but also of crustaceans (sea lice, while no activity on a dog GABAA receptor was observed up to a concentration of 10 μM. Conclusions Together, these results demonstrate that lotilaner is a non-competitive antagonist specific to invertebrate’s γ-aminobutyric acid-gated chloride channels (GABACls. They contribute to our understanding of the mode of

The novel isoxazoline ectoparasiticide lotilaner (Credelio™): a non-competitive antagonist specific to invertebrates γ-aminobutyric acid-gated chloride channels (GABACls).

Science.gov (United States)

Rufener, Lucien; Danelli, Vanessa; Bertrand, Daniel; Sager, Heinz

2017-11-01

The isoxazolines are a novel class of parasiticides that are potent inhibitors of γ-aminobutyric acid (GABA)-gated chloride channels (GABACls) and, to a lesser extent, of inhibitory glutamate-gated chloride channels (GluCls). Lotilaner (Credelio™), a novel representative of this chemical class, is currently evaluated for its excellent ectoparasiticide properties. In this study, we investigated the molecular mode of action and pharmacology of lotilaner. We report the successful gene identification, cDNA cloning and functional expression in Xenopus oocytes of Drosohpila melanogaster (wild type and dieldrin/fipronil-resistant forms), Lepeophtheirus salmonis (an ectoparasite copepod crustacean of salmon), Rhipicephalus microplus and Canis lupus familiaris GABACls. Automated Xenopus oocyte two-electrode voltage clamp electrophysiology was used to assess GABACls functionality and to compare ion channel inhibition by lotilaner with that of established insecticides addressing GABACls as targets. In these assays, we demonstrated that lotilaner is a potent non-competitive antagonist of insects (fly) GABACls. No cross-resistance with dieldrin or fipronil resistance mutations was detected, suggesting that lotilaner might bind to a site at least partly different from the one bound by known GABACl blockers. Using co-application experiments, we observed that lotilaner antagonism differs significantly from the classical open channel blocker fipronil. We finally confirmed for the first time that isoxazoline compounds are not only powerful antagonists of GABACls of acari (ticks) but also of crustaceans (sea lice), while no activity on a dog GABA A receptor was observed up to a concentration of 10 μM. Together, these results demonstrate that lotilaner is a non-competitive antagonist specific to invertebrate's γ-aminobutyric acid-gated chloride channels (GABACls). They contribute to our understanding of the mode of action of this new ectoparasiticide compound.

The acrylamide (S)-2 as a positive and negative modulator of Kv7 channels expressed in Xenopus laevis oocytes

DEFF Research Database (Denmark)

Blom, Sigrid Marie; Schmitt, Nicole; Jensen, Henrik Sindal

2009-01-01

Kv7.2-5, is now in clinical trial phase III for the treatment of partial onset seizures. One of the main obstacles in developing Kv7 channel active drugs has been to identify compounds that can discriminate between the neuronal subtypes, a feature that could help diminish side effects and increase...

Coherifying quantum channels

Science.gov (United States)

Korzekwa, Kamil; Czachórski, Stanisław; Puchała, Zbigniew; Życzkowski, Karol

2018-04-01

Is it always possible to explain random stochastic transitions between states of a finite-dimensional system as arising from the deterministic quantum evolution of the system? If not, then what is the minimal amount of randomness required by quantum theory to explain a given stochastic process? Here, we address this problem by studying possible coherifications of a quantum channel Φ, i.e., we look for channels {{{Φ }}}{ \\mathcal C } that induce the same classical transitions T, but are ‘more coherent’. To quantify the coherence of a channel Φ we measure the coherence of the corresponding Jamiołkowski state J Φ. We show that the classical transition matrix T can be coherified to reversible unitary dynamics if and only if T is unistochastic. Otherwise the Jamiołkowski state {J}{{Φ }}{ \\mathcal C } of the optimally coherified channel is mixed, and the dynamics must necessarily be irreversible. To assess the extent to which an optimal process {{{Φ }}}{ \\mathcal C } is indeterministic we find explicit bounds on the entropy and purity of {J}{{Φ }}{ \\mathcal C }, and relate the latter to the unitarity of {{{Φ }}}{ \\mathcal C }. We also find optimal coherifications for several classes of channels, including all one-qubit channels. Finally, we provide a non-optimal coherification procedure that works for an arbitrary channel Φ and reduces its rank (the minimal number of required Kraus operators) from {d}2 to d.

The Extended-Window Channel Estimator for Iterative Channel-and-Symbol Estimation

Directory of Open Access Journals (Sweden)

Barry John R

2005-01-01

Full Text Available The application of the expectation-maximization (EM algorithm to channel estimation results in a well-known iterative channel-and-symbol estimator (ICSE. The EM-ICSE iterates between a symbol estimator based on the forward-backward recursion (BCJR equalizer and a channel estimator, and may provide approximate maximum-likelihood blind or semiblind channel estimates. Nevertheless, the EM-ICSE has high complexity, and it is prone to misconvergence. In this paper, we propose the extended-window (EW estimator, a novel channel estimator for ICSE that can be used with any soft-output symbol estimator. Therefore, the symbol estimator may be chosen according to performance or complexity specifications. We show that the EW-ICSE, an ICSE that uses the EW estimator and the BCJR equalizer, is less complex and less susceptible to misconvergence than the EM-ICSE. Simulation results reveal that the EW-ICSE may converge faster than the EM-ICSE.

Microwave-assisted convenient syntheses of 2-indolizine derivatives from Morita-Baylis-Hillman adducts: new in silico potential ion channel modulators

International Nuclear Information System (INIS)

Cunha, Saraghina M.D.; Oliveira, Ramon G. de; Vasconcellos, Mario L.A.A.

2013-01-01

In this work, a microwave-assisted synthesis study by microwave irradiation to produce indolizine-2-carbonitrile and indolizine-2-carboxylate in good to high yields (70 and 81%, respectively) in one step from Morita-Baylis-Hillman adducts (MBHA) is presented. These compounds were subsequently transformed to high yields (94 to 100%, respectively) in three 2-indolizine derivatives. The five synthesized compounds were designed in silico aiming to present potential selective activities as ion channel modulators. These activities were suggested by the score values using Molinspiration Cheminformatics program. (author)

Microwave-assisted convenient syntheses of 2-indolizine derivatives from Morita-Baylis-Hillman adducts: new in silico potential ion channel modulators

Energy Technology Data Exchange (ETDEWEB)

Cunha, Saraghina M.D.; Oliveira, Ramon G. de; Vasconcellos, Mario L.A.A., E-mail: mlaav@quimica.ufpb.br [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Departamento de Quimica

2013-03-15

In this work, a microwave-assisted synthesis study by microwave irradiation to produce indolizine-2-carbonitrile and indolizine-2-carboxylate in good to high yields (70 and 81%, respectively) in one step from Morita-Baylis-Hillman adducts (MBHA) is presented. These compounds were subsequently transformed to high yields (94 to 100%, respectively) in three 2-indolizine derivatives. The five synthesized compounds were designed in silico aiming to present potential selective activities as ion channel modulators. These activities were suggested by the score values using Molinspiration Cheminformatics program. (author)

Channel identification machines.

Science.gov (United States)

Lazar, Aurel A; Slutskiy, Yevgeniy B

2012-01-01

We present a formal methodology for identifying a channel in a system consisting of a communication channel in cascade with an asynchronous sampler. The channel is modeled as a multidimensional filter, while models of asynchronous samplers are taken from neuroscience and communications and include integrate-and-fire neurons, asynchronous sigma/delta modulators and general oscillators in cascade with zero-crossing detectors. We devise channel identification algorithms that recover a projection of the filter(s) onto a space of input signals loss-free for both scalar and vector-valued test signals. The test signals are modeled as elements of a reproducing kernel Hilbert space (RKHS) with a Dirichlet kernel. Under appropriate limiting conditions on the bandwidth and the order of the test signal space, the filter projection converges to the impulse response of the filter. We show that our results hold for a wide class of RKHSs, including the space of finite-energy bandlimited signals. We also extend our channel identification results to noisy circuits.

Channel Identification Machines

Directory of Open Access Journals (Sweden)

Aurel A. Lazar

2012-01-01

Full Text Available We present a formal methodology for identifying a channel in a system consisting of a communication channel in cascade with an asynchronous sampler. The channel is modeled as a multidimensional filter, while models of asynchronous samplers are taken from neuroscience and communications and include integrate-and-fire neurons, asynchronous sigma/delta modulators and general oscillators in cascade with zero-crossing detectors. We devise channel identification algorithms that recover a projection of the filter(s onto a space of input signals loss-free for both scalar and vector-valued test signals. The test signals are modeled as elements of a reproducing kernel Hilbert space (RKHS with a Dirichlet kernel. Under appropriate limiting conditions on the bandwidth and the order of the test signal space, the filter projection converges to the impulse response of the filter. We show that our results hold for a wide class of RKHSs, including the space of finite-energy bandlimited signals. We also extend our channel identification results to noisy circuits.

CHANNEL ESTIMATION TECHNIQUE

DEFF Research Database (Denmark)

2015-01-01

A method includes determining a sequence of first coefficient estimates of a communication channel based on a sequence of pilots arranged according to a known pilot pattern and based on a receive signal, wherein the receive signal is based on the sequence of pilots transmitted over the communicat......A method includes determining a sequence of first coefficient estimates of a communication channel based on a sequence of pilots arranged according to a known pilot pattern and based on a receive signal, wherein the receive signal is based on the sequence of pilots transmitted over...... the communication channel. The method further includes determining a sequence of second coefficient estimates of the communication channel based on a decomposition of the first coefficient estimates in a dictionary matrix and a sparse vector of the second coefficient estimates, the dictionary matrix including...... filter characteristics of at least one known transceiver filter arranged in the communication channel....

Research on Cost Information Sharing and Channel Choice in a Dual-Channel Supply Chain

Directory of Open Access Journals (Sweden)

Huihui Liu

2016-01-01

Full Text Available Many studies examine information sharing in an uncertain demand environment in a supply chain. However there is little literature on cost information sharing in a dual-channel structure consisting of a retail channel and a direct sales channel. Assuming that the retail sale cost and direct sale cost are random variables with a general distribution, the paper investigates the retailer’s choice on cost information sharing in a Bertrand competition model. Based on the equilibrium outcome of information sharing, the manufacturer’s channel choice is discussed in detail. Our paper provides several interesting conclusions. In both single- and dual-channel structures, the retailer has little motivation to share its private cost information which is verified to be valuable for the manufacturer. When the cost correlation between the two channels increases, our analyses show that the manufacturer’s profit improves. However, when channel choice is involved, the value of information could play a different role. The paper finds that a dual-channel structure can benefit the manufacturer only when the cost correlation is sufficiently low. In addition, if the cost correlation is weak, the cost fluctuation will bring out the advantage of a dual-channel structure and adding a new direct channel will help in risk pooling.

Integrating Carbon Nanotubes into Microfluidic Chip for Separating Biochemical Compounds

DEFF Research Database (Denmark)

Chen, Miaoxiang Max; Mogensen, Klaus Bo; Bøggild, Peter

2012-01-01

We present a new type of device to separate biochemical compounds wherein carbon nanotubes (CNTs) are integrated as chromatographic stationary phase. The CNTs were directly grown on the bottom of microfluidic channels on Si/SiO2 substrates by chemical vapor deposition (CVD). Acetylene was used...... as carbon source and Ni was employed as catalyst. For electrokinetic separations, higher electrical field strength is usually required; therefore, the CNTs were constructed in pillar-array-form by patterning the catalyst layer. Electrical field strength of 2.0 kV/cm has been realized, which is more than one...

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

Directory of Open Access Journals (Sweden)

Darryl W Hondorp

Full Text Available 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

Voltage-Gated Calcium Channels

Science.gov (United States)

Zamponi, Gerald Werner

Voltage Gated Calcium Channels is the first comprehensive book in the calcium channel field, encompassing over thirty years of progress towards our understanding of calcium channel structure, function, regulation, physiology, pharmacology, and genetics. This book balances contributions from many of the leading authorities in the calcium channel field with fresh perspectives from risings stars in the area, taking into account the most recent literature and concepts. This is the only all-encompassing calcium channel book currently available, and is an essential resource for academic researchers at all levels in the areas neuroscience, biophysics, and cardiovascular sciences, as well as to researchers in the drug discovery area.

Prediction of Thorough QT study results using action potential simulations based on ion channel screens.

Science.gov (United States)

Mirams, Gary R; Davies, Mark R; Brough, Stephen J; Bridgland-Taylor, Matthew H; Cui, Yi; Gavaghan, David J; Abi-Gerges, Najah

2014-01-01

Detection of drug-induced pro-arrhythmic risk is a primary concern for pharmaceutical companies and regulators. Increased risk is linked to prolongation of the QT interval on the body surface ECG. Recent studies have shown that multiple ion channel interactions can be required to predict changes in ventricular repolarisation and therefore QT intervals. In this study we attempt to predict the result of the human clinical Thorough QT (TQT) study, using multiple ion channel screening which is available early in drug development. Ion current reduction was measured, in the presence of marketed drugs which have had a TQT study, for channels encoded by hERG, CaV1.2, NaV1.5, KCNQ1/MinK, and Kv4.3/KChIP2.2. The screen was performed on two platforms - IonWorks Quattro (all 5 channels, 34 compounds), and IonWorks Barracuda (hERG & CaV1.2, 26 compounds). Concentration-effect curves were fitted to the resulting data, and used to calculate a percentage reduction in each current at a given concentration. Action potential simulations were then performed using the ten Tusscher and Panfilov (2006), Grandi et al. (2010) and O'Hara et al. (2011) human ventricular action potential models, pacing at 1Hz and running to steady state, for a range of concentrations. We compared simulated action potential duration predictions with the QT prolongation observed in the TQT studies. At the estimated concentrations, simulations tended to underestimate any observed QT prolongation. When considering a wider range of concentrations, and conventional patch clamp rather than screening data for hERG, prolongation of ≥5ms was predicted with up to 79% sensitivity and 100% specificity. This study provides a proof-of-principle for the prediction of human TQT study results using data available early in drug development. We highlight a number of areas that need refinement to improve the method's predictive power, but the results suggest that such approaches will provide a useful tool in cardiac safety

Entrance-channel effects in the population of superdeformed bands

Energy Technology Data Exchange (ETDEWEB)

Smith, G.; Haas, B.; Alderson, A.; Ali, I.; Beausang, C.W.; Bentley, M.A.; Dagnall, P.; Fallon, P.; de France, G.; Forsyth, P.D.; Huttmeier, U.; Romain, P.; Santos, D.; Twin, P.J.; Vivien, J.P. (Oliver Lodge Laboratory, University of Liverpool, Liverpool L69 3BX (United Kingdom) Centre de Recherches Nucleaires, F-67037 Strasbourg CEDEX (France) Sciences and Engineering Research Council, Daresbury Laboratory, Warrington WA44AD (United Kingdom))

1992-01-13

In order to investigate whether entrance-channel effects influence the production of superdeformed nuclei, we have measured the yield of the yrast superdeformed band in {sup 152}Dy populated via nearly mass-symmetric ({sup 82}Se+{sup 74}Ge) and mass-asymmetric ({sup 48}Ca+{sup 108}Pd, {sup 36}S+{sup 120}Sn) fusion reactions leading to the same compound nucleus at similar excitation energies and angular momenta. Large differences in the relative intensity of the band compared with the total yield of the nucleus are observed in the various reactions. This effect indicates that the competition between fission and neutron evaporation is affected by the mode of formation of the fusing system.

n-Channel semiconductor materials design for organic complementary circuits.

Science.gov (United States)

Usta, Hakan; Facchetti, Antonio; Marks, Tobin J

2011-07-19

Organic semiconductors have unique properties compared to traditional inorganic materials such as amorphous or crystalline silicon. Some important advantages include their adaptability to low-temperature processing on flexible substrates, low cost, amenability to high-speed fabrication, and tunable electronic properties. These features are essential for a variety of next-generation electronic products, including low-power flexible displays, inexpensive radio frequency identification (RFID) tags, and printable sensors, among many other applications. Accordingly, the preparation of new materials based on π-conjugated organic molecules or polymers has been a central scientific and technological research focus over the past decade. Currently, p-channel (hole-transporting) materials are the leading class of organic semiconductors. In contrast, high-performance n-channel (electron-transporting) semiconductors are relatively rare, but they are of great significance for the development of plastic electronic devices such as organic field-effect transistors (OFETs). In this Account, we highlight the advances our team has made toward realizing moderately and highly electron-deficient n-channel oligomers and polymers based on oligothiophene, arylenediimide, and (bis)indenofluorene skeletons. We have synthesized and characterized a "library" of structurally related semiconductors, and we have investigated detailed structure-property relationships through optical, electrochemical, thermal, microstructural (both single-crystal and thin-film), and electrical measurements. Our results reveal highly informative correlations between structural parameters at various length scales and charge transport properties. We first discuss oligothiophenes functionalized with perfluoroalkyl and perfluoroarene substituents, which represent the initial examples of high-performance n-channel semiconductors developed in this project. The OFET characteristics of these compounds are presented with an

Synthesis and evaluation of calcium channel antagonist activity of new 1, 4-dihydropyridines containing phenylamineimidazolyl substitute in guinea-pig ileal smooth muscle

Directory of Open Access Journals (Sweden)

A Fassihi

2004-02-01

Full Text Available Background: 1,4-dihydropyridines are a class of drugs which are used in the treatment of some cardiovascular disorders. The prototype, Nifedipine, does not have optimal pharmacokinetic and pharmacodynamic properties. Several new derivatives of 1, 4-dihydropyridine have been produced and pharmacologically evaluated in order to find drugs with better pharmacological properties. Among them, those with a substituted heteroaromatic ring in the C4 position of the 1, 4-dihydropyridine ring, instead of the phenyl ring in Nifedipine, are most considered. In this study, eight novel derivatives of this class with “2-methylthio-1-(phenylaminoimidazole-5-yl” in the C4, C3 and C5 positions were prepared and evaluated as calcium channel antagonist agents. Methods: To prepare these compounds, Hantzsch method for the synthesis of 1, 4-dihydropyridine derivatives was deployed. An aldehyde was reacted with appropriate acetoacetate ester and ammonium acetate. This aldehyde was prepared in three steps. Cumulative doses were applied to determine the relaxing effect of the compounds on the longitudinal smooth muscle of male albino guinea pigs. Results: Chemical structures of the compounds were characterized by 1H nuclear magnetic resonance, infrared and mass spectroscopy. The IC50 of each compound was graphically determined from the concentration-response curves. Conclusions: Two compounds were more active than Nifedipine. Both had lipophilic ester groups with low steric hindrance that met the merits of a better receptor binding of 1, 4-dihydropyridines. These derivatives have high potential for further study. Keywords: 1, 4-dihydropyridine, Calcium channel antagonist, Phenylamineimidazolyl, Cardiovascular disorder

Discovery of talatisamine as a novel specific blocker for the delayed rectifier K+ channels in rat hippocampal neurons.

Science.gov (United States)

Song, M-K; Liu, H; Jiang, H-L; Yue, J-M; Hu, G-Y; Chen, H-Z

2008-08-13

Blocking specific K+ channels has been proposed as a promising strategy for the treatment of neurodegenerative diseases. Using a computational virtual screening approach and electrophysiological testing, we found four Aconitum alkaloids are potent blockers of the delayed rectifier K+ channel in rat hippocampal neurons. In the present study, we first tested the action of the four alkaloids on the voltage-gated K+, Na+ and Ca2+ currents in rat hippocampal neurons, and then identified that talatisamine is a specific blocker for the delayed rectifier K+ channel. External application of talatisamine reversibly inhibited the delayed rectifier K+ current (IK) with an IC50 value of 146.0+/-5.8 microM in a voltage-dependent manner, but exhibited very slight blocking effect on the voltage-gated Na+ and Ca2+ currents even at the high concentration of 1-3 mM. Moreover, talatisamine exerted a significant hyperpolarizing shift of the steady-state activation, but did not influence the steady state inactivation of IK and its recovery from inactivation, suggesting that talatisamine had no allosteric action on IK channel and was a pure blocker binding to the external pore entry of the channel. Our present study made the first discovery of potent and specific IK channel blocker from Aconitum alkaloids. It has been argued that suppressing K+ efflux by blocking IK channel may be favorable for Alzheimer's disease therapy. Talatisamine can therefore be considered as a leading compound worthy of further investigations.

Effect of beta-adrenoceptor blockers on human ether-a-go-go-related gene (HERG) potassium channels

DEFF Research Database (Denmark)

Dupuis, Delphine S; Klaerke, Dan A; Olesen, Søren-Peter

2005-01-01

Patients with congenital long QT syndrome may develop arrhythmias under conditions of increased sympathetic tone. We have addressed whether some of the beta-adrenoceptor blockers commonly used to prevent the development of these arrhythmias could per se block the cardiac HERG (Human Ether....... These data showed that HERG blockade by beta-adrenoceptor blockers occurred only at high micromolar concentrations, which are significantly above the recently established safe margin of 100 (Redfern et al., 2003).......-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride) blocked the HERG channel with similar affinity, whereas the beta1-receptor antagonists metoprolol and atenolol showed weak effects. Further, the four compounds blocked HERG channels expressed in a mammalian HEK293 cell line...

Analysis of radiometric signal in sedimentating suspension flow in open channel

Directory of Open Access Journals (Sweden)

Zych Marcin

2015-01-01

Full Text Available The article discusses issues related to the estimation of the sedimentating solid particles average flow velocity in an open channel using radiometric methods. Due to the composition of the compound, which formed water and diatomite, received data have a very weak signal to noise ratio. In the process analysis the known determining of the solid phase transportation time delay the classical cross-correlation function is the most reliable method. The use of advanced frequency analysis based on mutual spectral density function and wavelet transform of recorded signals allows a reduction of the noise contribution.

Evaluation channel performance in multichannel environments

NARCIS (Netherlands)

Gensler, S.; Dekimpe, M.; Skiera, B.

2007-01-01

Evaluating channel performance is crucial for actively managing multiple sales channels, and requires understanding the customers' channel preferences. Two key components of channel performance are (i) the existing customers' intrinsic loyalty to a particular channel and (ii) the channel's ability

Channel Choice: A Literature Review

DEFF Research Database (Denmark)

Østergaard Madsen, Christian; Kræmmergaard, Pernille

2015-01-01

The channel choice branch of e-government studies citizens’ and businesses’ choice of channels for interacting with government, and how government organizations can integrate channels and migrate users towards the most cost-efficient channels. In spite of the valuable contributions offered...

A dual-channel gas chromatography method for the quantitation of low and high concentrations of NF3 and CF4 to study membrane separation of the two compounds

OpenAIRE

Branken, D.J.; Le Roux, J.P.; Krieg, H.M.; Lachmann, G.

2013-01-01

A dual-channel gas chromatographic method is described in this paper that can be conveniently used for quantitation of NF3/CF4 mixtures with a thermal conductivity detector (TCD) on one channel for the quantitation of high-concentrations, and a pulsed discharge helium ionization detector (PDHID) on a second channel for the quantitation of low concentrations. It is shown that adequate separation is achieved on both channels with this dual single-column setup in which column switchi...

Reconfigurable virtual electrowetting channels.

Science.gov (United States)

Banerjee, Ananda; Kreit, Eric; Liu, Yuguang; Heikenfeld, Jason; Papautsky, Ian

2012-02-21

Lab-on-a-chip systems rely on several microfluidic paradigms. The first uses a fixed layout of continuous microfluidic channels. Such lab-on-a-chip systems are almost always application specific and far from a true "laboratory." The second involves electrowetting droplet movement (digital microfluidics), and allows two-dimensional computer control of fluidic transport and mixing. The merging of the two paradigms in the form of programmable electrowetting channels takes advantage of both the "continuous" functionality of rigid channels based on which a large number of applications have been developed to date and the "programmable" functionality of digital microfluidics that permits electrical control of on-chip functions. In this work, we demonstrate for the first time programmable formation of virtual microfluidic channels and their continuous operation with pressure driven flows using an electrowetting platform. Experimental, theoretical, and numerical analyses of virtual channel formation with biologically relevant electrolyte solutions and electrically-programmable reconfiguration are presented. We demonstrate that the "wall-less" virtual channels can be formed reliably and rapidly, with propagation rates of 3.5-3.8 mm s(-1). Pressure driven transport in these virtual channels at flow rates up to 100 μL min(-1) is achievable without distortion of the channel shape. We further demonstrate that these virtual channels can be switched on-demand between multiple inputs and outputs. Ultimately, we envision a platform that would provide rapid prototyping of microfluidic concepts and would be capable of a vast library of functions and benefitting applications from clinical diagnostics in resource-limited environments to rapid system prototyping to high throughput pharmaceutical applications.

KV7 potassium channels

DEFF Research Database (Denmark)

Stott, Jennifer B; Jepps, Thomas Andrew; Greenwood, Iain A

2014-01-01

Potassium channels are key regulators of smooth muscle tone, with increases in activity resulting in hyperpolarisation of the cell membrane, which acts to oppose vasoconstriction. Several potassium channels exist within smooth muscle, but the KV7 family of voltage-gated potassium channels have been...

Research variations the channel of gallbladder in relation to gender

Directory of Open Access Journals (Sweden)

Spasojević Goran

2014-01-01

Full Text Available Channel of the gallbladder (DC shows the different anatomical variations, the knowledge is important in the diagnosis and particularly abdominal surgery. The aim of this study was to investigate possible gender differences in the morphology of the gallbladder channel (DC. A total sample consists of 50 anatomical liver taken from autopsy cases of both sexes (32 men and 18 women. Samples of liver were fixed in 4% formalin for 4 weeks, and then studied microdissected under scrutiny. We were working length measurement channels of the gallbladder (DC and typing of junction of the cystic (DC with the common hepatic duct (DHC. We classify anatomical junction variations DC with DHC into three types: angular, parallel and spiral type, and then performed statistical analysis of the data with respect to gender. Results: The angular type compound we found approximately at 2/3 or 64% of the samples (men-60% of women-72%, the parallel type combination of a total of 22% of the sample (men-31% of women-6% and spiral type of 14% of the samples (males-9%, women 22%. Parallel and spiral type together make up about 1/3 of the cases. The average length of DC is 3.1 cm and the variation interval of 1.7 to 6.2 cm. We found that the difference circuit between DC and DHC the angular variable (parallel junction and spiral with respect to gender there but the difference was not statistically significant (p> 0.05.

Preservation of meandering river channels in uniformly aggrading channel belts

NARCIS (Netherlands)

Lageweg, W.I. van de; Schuurman, F.; Cohen, K.M.; Dijk, W.M. van; Shimizu, Y.; Kleinhans, M.G.

2016-01-01

Channel belt deposits from meandering river systems commonly display an internal architecture of stacked depositional features with scoured basal contacts due to channel and bedform migration across a range of scales. Recognition and correct interpretation of these bounding surfaces is essential to

Multi-channel service retailing: The effects of channel performance satisfaction on behavioral intentions.

NARCIS (Netherlands)

Birgelen, van M.; Jong, de A.; Ruyter, de J.C.

2006-01-01

Abstract The number of channels that retailers can use interchangeably to provide customer service has increased. We report on a study of clients of a large retail bank that investigates the channel performance satisfaction–behavioral intentions relationship when the traditional service channel

Minimizing Wide-Area Performance Disruptions in Inter-Domain Routing

Science.gov (United States)

2011-09-01

Servers As another example, we saw the average round-trip time double for an ISP in Malaysia . The RTT increase was caused by a traffic shift to different... censorship , conduct wiretapping, or offer poor performance. This is achieved by applying regular expressions to the AS-PATH to assign lower preference

The small molecule NS11021 is a potent and specific activator of Ca2+-activated big-conductance K+ channels

DEFF Research Database (Denmark)

Bentzen, Bo Hjorth; Nardi, Antonio; Calloe, Kirstine

2007-01-01

, a mitochondrial K(+) channel with KCa1.1-resembling properties has been found in the heart, where it may be involved in regulation of energy consumption. In the present study, the effect of a novel NeuroSearch compound, 1-(3,5-bis-trifluoromethyl-phenyl)-3-[4-bromo-2-(1H-tetrazol-5-yl)-phenyl]-thiourea (NS11021...

Channel Planform Dynamics Monitoring and Channel Stability Assessment in Two Sediment-Rich Rivers in Taiwan

Directory of Open Access Journals (Sweden)

Cheng-Wei Kuo

2017-01-01

Full Text Available Recurrent flood events induced by typhoons are powerful agents to modify channel morphology in Taiwan’s rivers. Frequent channel migrations reflect highly sensitive valley floors and increase the risk to infrastructure and residents along rivers. Therefore, monitoring channel planforms is essential for analyzing channel stability as well as improving river management. This study analyzed annual channel changes along two sediment-rich rivers, the Zhuoshui River and the Gaoping River, from 2008 to 2015 based on satellite images of FORMOSAT-2. Channel areas were digitized from mid-catchment to river mouth (~90 km. Channel stability for reaches was assessed through analyzing the changes of river indices including braid index, active channel width, and channel activity. In general, the valley width plays a key role in braided degree, active channel width, and channel activity. These indices increase as the valley width expands whereas the braid index decreases slightly close to the river mouth due to the change of river types. This downstream pattern in the Zhuoshui River was interrupted by hydraulic construction which resulted in limited changes downstream from the weir, due to the lack of water and sediment supply. A 200-year flood, Typhoon Morakot in 2009, induced significant changes in the two rivers. The highly active landscape in Taiwan results in very sensitive channels compared to other regions. An integrated Sensitivity Index was proposed for identifying unstable reaches, which could be a useful reference for river authorities when making priorities in river regulation strategy. This study shows that satellite image monitoring coupled with river indices analysis could be an effective tool to evaluate spatial and temporal changes in channel stability in highly dynamic river systems.

Distribution Channels Conflict and Management

OpenAIRE

Kiran, Dr Vasanth; Majumdar, Dr Mousumi; Kishore, Dr Krishna

2012-01-01

Relationships in distribution channels tend to be long-term oriented and members of the channel rely on each other to jointly realize their goals by serving buyers. Despite the channels focus on serving buyers, conflicts often arise between channel members because of each members self-interest. When conflicts arise, the perceptions of a channel member based on normative, rational/instrumental, or emotional reasoning will influence relational norms like trust and commitment that characterize t...

Complex Membrane Channel Blockade: A Unifying Hypothesis for the Prodromal and Acute Neuropsychiatric Sequelae Resulting from Exposure to the Antimalarial Drug Mefloquine

Directory of Open Access Journals (Sweden)

Jane C. Quinn

2015-01-01

Full Text Available The alkaloid toxin quinine and its derivative compounds have been used for many centuries as effective medications for the prevention and treatment of malaria. More recently, synthetic derivatives, such as the quinoline derivative mefloquine (bis(trifluoromethyl-(2-piperidyl-4-quinolinemethanol, have been widely used to combat disease caused by chloroquine-resistant strains of the malaria parasite, Plasmodium falciparum. However, the parent compound quinine, as well as its more recent counterparts, suffers from an incidence of adverse neuropsychiatric side effects ranging from mild mood disturbances and anxiety to hallucinations, seizures, and psychosis. This review considers how the pharmacology, cellular neurobiology, and membrane channel kinetics of mefloquine could lead to the significant and sometimes life-threatening neurotoxicity associated with mefloquine exposure. A key role for mefloquine blockade of ATP-sensitive potassium channels and connexins in the substantia nigra is considered as a unifying hypothesis for the pathogenesis of severe neuropsychiatric events after mefloquine exposure in humans.

Arylbenzazepines Are Potent Modulators for the Delayed Rectifier K+ Channel: A Potential Mechanism for Their Neuroprotective Effects

Science.gov (United States)

Chen, Xue-Qin; Zhang, Jing; Neumeyer, John L.; Jin, Guo-Zhang; Hu, Guo-Yuan; Zhang, Ao; Zhen, Xuechu

2009-01-01

(±) SKF83959, like many other arylbenzazepines, elicits powerful neuroprotection in vitro and in vivo. The neuroprotective action of the compound was found to partially depend on its D1-like dopamine receptor agonistic activity. The precise mechanism for the (±) SKF83959-mediated neuroprotection remains elusive. We report here that (±) SKF83959 is a potent blocker for delayed rectifier K+ channel. (±) SKF83959 inhibited the delayed rectifier K+ current (I K) dose-dependently in rat hippocampal neurons. The IC 50 value for inhibition of I K was 41.9±2.3 µM (Hill coefficient = 1.81±0.13, n = 6), whereas that for inhibition of I A was 307.9±38.5 µM (Hill coefficient = 1.37±0.08, n = 6). Thus, (±) SKF83959 is 7.3-fold more potent in suppressing I K than I A. Moreover, the inhibition of I K by (±) SKF83959 was voltage-dependent and not related to dopamine receptors. The rapidly onset of inhibition and recovery suggests that the inhibition resulted from a direct interaction of (±) SKF83959 with the K+ channel. The intracellular application of (±) SKF83959 had no effects of on I K, indicating that the compound most likely acts at the outer mouth of the pore of K+ channel. We also tested the enantiomers of (±) SKF83959, R-(+) SKF83959 (MCL-201), and S-(−) SKF83959 (MCL-202), as well as SKF38393; all these compounds inhibited I K. However, (±) SKF83959, at either 0.1 or 1 mM, exhibited the strongest inhibition on the currents among all tested drug. The present findings not only revealed a new potent blocker of I K , but also provided a novel mechanism for the neuroprotective action of arylbenzazepines such as (±) SKF83959. PMID:19503734

Role played by acid-sensitive ion channels in evoking the exercise pressor reflex.

Science.gov (United States)

Hayes, Shawn G; McCord, Jennifer L; Rainier, Jon; Liu, Zhuqing; Kaufman, Marc P

2008-10-01

The exercise pressor reflex arises from contracting skeletal muscle and is believed to play a role in evoking the cardiovascular responses to static exercise, effects that include increases in arterial pressure and heart rate. This reflex is believed to be evoked by the metabolic and mechanical stimulation of thin fiber muscle afferents. Lactic acid is known to be an important metabolic stimulus evoking the reflex. Until recently, the only antagonist for acid-sensitive ion channels (ASICs), the receptors to lactic acid, was amiloride, a substance that is also a potent antagonist for both epithelial sodium channels as well as voltage-gated sodium channels. Recently, a second compound, A-317567, has been shown to be an effective and selective antagonist to ASICs in vitro. Consequently, we measured the pressor responses to the static contraction of the triceps surae muscles in decerebrate cats before and after a popliteal arterial injection of A-317567 (10 mM solution; 0.5 ml). We found that this ASIC antagonist significantly attenuated by half (Pacid injection into the popliteal artery. In contrast, A-317567 had no effect on the pressor responses to tendon stretch, a pure mechanical stimulus, and to a popliteal arterial injection of capsaicin, which stimulated transient receptor potential vanilloid type 1 channels. We conclude that ASICs on thin fiber muscle afferents play a substantial role in evoking the metabolic component of the exercise pressor reflex.

Study of the interactions between uranium and organic compounds in the hydrothermal systems

International Nuclear Information System (INIS)

Salze, David

2008-01-01

Formers studies on the relations between organic matter and uranium have shown that these interactions go since the complexation and the transport of uranium in organics fluids until its reduction by the organic matter leading to the uranium-bearing mineral precipitation. An experimental study of these reactions to 200 deg. C and 500 bars between experimental compounds (pure organic compounds) such as the n-alkanes (n-pentane, n-hexane, n-heptane, n-octane, n-nonane, n-decane, n-dodecane, n-tetradecane and n-hexadecane), an n-alkene hydrocarbon (n-dec-1-ene), cycles (butyl-cyclohexane and cyclo-hexane) and the aromatic ones (butyl-benzene and naphthalene), and hexavalent uranium oxides was undertaken. These experiments allowed to show a progressive oxidation of n-alkanes starting from made up C6. The increasing size of the aliphatic chains and the increase in the time of setting in interaction are major factors of the increase in the environment oxidizing capacity in interaction with uranium on the organic compound. The determination of the oxidation step of uranium oxides after experiment made it possible to determine that in aqueous environment the aliphatic model compounds are reducers more powerful than the aromatic compounds. An organic matter from lake or marine origin generally has an aliphatic fraction larger than the organic matter of continental origin and thus will be more likely to reduce uranium. A natural example, the uranium deposits in the sandstones from Arlit, the tectono-lithologic type, was selected in order to apply the results obtained in the experimental part. They are located in fluviatile sandstones rich in organic matter of continental origin (type III) deposited in the paleo-channels. Former authors considered that only this organic matter of type III was responsible for the reduction of U (VI) in U (IV). Work which was undertaken in the present study shows that migrated oils of probable marine origin strongly contributed to the genesis

Inhibitory actions by ibandronate sodium, a nitrogen-containing bisphosphonate, on calcium-activated potassium channels in Madin–Darby canine kidney cells

Directory of Open Access Journals (Sweden)

Sheng-Nan Wu

2015-01-01

Full Text Available The nitrogen-containing bisphosphonates used for management of the patients with osteoporosis were reported to influence the function of renal tubular cells. However, how nitrogen-containing bisphosphates exert any effects on ion currents remains controversial. The effects of ibandronate (Iban, a nitrogen-containing bisphosphonate, on ionic channels, including two types of Ca2+-activated K+ (KCa channels, namely, large-conductance KCa (BKCa and intermediate-conductance KCa (IKCa channels, were investigated in Madin–Darby canine kidney (MDCK cells. In whole-cell current recordings, Iban suppressed the amplitude of voltage-gated K+ current elicited by long ramp pulse. Addition of Iban caused a reduction of BKCa channels accompanied by a right shift in the activation curve of BKCa channels, despite no change in single-channel conductance. Ca2+ sensitivity of these channels was modified in the presence of this compound; however, the magnitude of Iban-mediated decrease in BKCa-channel activity under membrane stretch with different negative pressure remained unchanged. Iban suppressed the probability of BKCa-channel openings linked primarily to a shortening in the slow component of mean open time in these channels. The dissociation constant needed for Iban-mediated suppression of mean open time in MDCK cells was 12.2 μM. Additionally, cell exposure to Iban suppressed the activity of IKCa channels, and DC-EBIO or 9-phenanthrol effectively reversed its suppression. Under current-clamp configuration, Iban depolarized the cells and DC-EBIO or PF573228 reversed its depolarizing effect. Taken together, the inhibitory action of Iban on KCa-channel activity may contribute to the underlying mechanism of pharmacological or toxicological actions of Iban and its structurally similar bisphosphonates on renal tubular cells occurring in vivo.

Pharmacological Targeting Of Neuronal Kv7.2/3 Channels: A Focus On Chemotypes And Receptor Sites.

Science.gov (United States)

Miceli, Francesco; Soldovieri, Maria Virginia; Ambrosino, Paolo; Manocchio, Laura; Medoro, Alessandro; Mosca, Ilaria; Taglialatela, Maurizio

2017-10-12

The Kv7 (KCNQ) subfamily of voltage-gated potassium channels consists of 5 members (Kv7.1-5) each showing a characteristic tissue distribution and physiological roles. Given their functional heterogeneity, Kv7 channels represent important pharmacological targets for development of new drugs for neuronal, cardiac and metabolic diseases. In the present manuscript, we focus on describing the pharmacological relevance and the potential therapeutic applications of drugs acting on neuronally-expressed Kv7.2/3 channels, placing particular emphasis on the different modulator chemotypes, and highlighting their pharmacodynamic and, whenever possible, pharmacokinetic peculiarities. The present work is based on an in-depth search of the currently available scientific literature, and on our own experience and knowledge in the field of neuronal Kv7 channel pharmacology. Space limitations impeded to describe the full pharmacological potential of Kv7 channels; thus, we have chosen to focus on neuronal channels composed of Kv7.2 and Kv7.3 subunits, and to mainly concentrate on their involvement in epilepsy. An astonishing heterogeneity in the molecular scaffolds exploitable to develop Kv7.2/3 modulators is evident, with important structural/functional peculiarities of distinct compound classes. In the present work we have attempted to show the current status and growing potential of the Kv7 pharmacology field. We anticipate a bright future for the field, and we express our hopes that the efforts herein reviewed will result in an improved treatment of hyperexcitability (or any other) diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Eight channel fast scalar

Energy Technology Data Exchange (ETDEWEB)

Waddoup, W D; Stubbs, R J [Durham Univ. (UK)

1977-11-01

An eight channel 64-bit scaler has been constructed with a static CMOS memory. Scaling frequencies are independently variable, at each channel, as are the number of bits/channel. The scaler, when used in conjunction with a multichannel charge to time converter results in a very flexible, gated multichannel ADC.

Automatic pickup of arrival time of channel wave based on multi-channel constraints

Science.gov (United States)

Wang, Bao-Li

2018-03-01

Accurately detecting the arrival time of a channel wave in a coal seam is very important for in-seam seismic data processing. The arrival time greatly affects the accuracy of the channel wave inversion and the computed tomography (CT) result. However, because the signal-to-noise ratio of in-seam seismic data is reduced by the long wavelength and strong frequency dispersion, accurately timing the arrival of channel waves is extremely difficult. For this purpose, we propose a method that automatically picks up the arrival time of channel waves based on multi-channel constraints. We first estimate the Jaccard similarity coefficient of two ray paths, then apply it as a weight coefficient for stacking the multichannel dispersion spectra. The reasonableness and effectiveness of the proposed method is verified in an actual data application. Most importantly, the method increases the degree of automation and the pickup precision of the channel-wave arrival time.

Functional modifications of acid-sensing ion channels by ligand-gated chloride channels.

Directory of Open Access Journals (Sweden)

Xuanmao Chen

Full Text Available Together, acid-sensing ion channels (ASICs and epithelial sodium channels (ENaC constitute the majority of voltage-independent sodium channels in mammals. ENaC is regulated by a chloride channel, the cystic fibrosis transmembrane conductance regulator (CFTR. Here we show that ASICs were reversibly inhibited by activation of GABA(A receptors in murine hippocampal neurons. This inhibition of ASICs required opening of the chloride channels but occurred with both outward and inward GABA(A receptor-mediated currents. Moreover, activation of the GABA(A receptors modified the pharmacological features and kinetic properties of the ASIC currents, including the time course of activation, desensitization and deactivation. Modification of ASICs by open GABA(A receptors was also observed in both nucleated patches and outside-out patches excised from hippocampal neurons. Interestingly, ASICs and GABA(A receptors interacted to regulate synaptic plasticity in CA1 hippocampal slices. The activation of glycine receptors, which are similar to GABA(A receptors, also modified ASICs in spinal neurons. We conclude that GABA(A receptors and glycine receptors modify ASICs in neurons through mechanisms that require the opening of chloride channels.

Coupling of SK channels, L-type Ca2+ channels, and ryanodine receptors in cardiomyocytes.

Science.gov (United States)

Zhang, Xiao-Dong; Coulibaly, Zana A; Chen, Wei Chun; Ledford, Hannah A; Lee, Jeong Han; Sirish, Padmini; Dai, Gu; Jian, Zhong; Chuang, Frank; Brust-Mascher, Ingrid; Yamoah, Ebenezer N; Chen-Izu, Ye; Izu, Leighton T; Chiamvimonvat, Nipavan

2018-03-16

Small-conductance Ca 2+ -activated K + (SK) channels regulate the excitability of cardiomyocytes by integrating intracellular Ca 2+ and membrane potentials on a beat-to-beat basis. The inextricable interplay between activation of SK channels and Ca 2+ dynamics suggests the pathology of one begets another. Yet, the exact mechanistic underpinning for the activation of cardiac SK channels remains unaddressed. Here, we investigated the intracellular Ca 2+ microdomains necessary for SK channel activation. SK currents coupled with Ca 2+ influx via L-type Ca 2+ channels (LTCCs) continued to be elicited after application of caffeine, ryanodine or thapsigargin to deplete SR Ca 2+ store, suggesting that LTCCs provide the immediate Ca 2+ microdomain for the activation of SK channels in cardiomyocytes. Super-resolution imaging of SK2, Ca v 1.2 Ca 2+ channel, and ryanodine receptor 2 (RyR2) was performed to quantify the nearest neighbor distances (NND) and localized the three molecules within hundreds of nanometers. The distribution of NND between SK2 and RyR2 as well as SK2 and Ca v 1.2 was bimodal, suggesting a spatial relationship between the channels. The activation mechanism revealed by our study paved the way for the understanding of the roles of SK channels on the feedback mechanism to regulate the activities of LTCCs and RyR2 to influence local and global Ca 2+ signaling.

Activation of TRPV1 channels inhibits mechanosensitive Piezo channel activity by depleting membrane phosphoinositides

Science.gov (United States)

Borbiro, Istvan; Badheka, Doreen; Rohacs, Tibor

2015-01-01

Capsaicin is an activator of the heat-sensitive TRPV1 (transient receptor potential vanilloid 1) ion channels and has been used as a local analgesic. We found that activation of TRPV1 channels with capsaicin either in dorsal root ganglion neurons or in a heterologous expression system inhibited the mechanosensitive Piezo1 and Piezo2 channels by depleting phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and its precursor PI(4)P from the plasma membrane through Ca2+-induced phospholipase Cδ (PLCδ) activation. Experiments with chemically inducible phosphoinositide phosphatases and receptor-induced activation of PLCβ indicated that inhibition of Piezo channels required depletion of both PI(4)P and PI(4,5)P2. The mechanically activated current amplitudes decreased substantially in the excised inside-out configuration, where the membrane patch containing Piezo1 channels is removed from the cell. PI(4,5)P2 and PI(4)P applied to these excised patches inhibited this decrease. Thus, we concluded that Piezo channel activity requires the presence of phosphoinositides, and the combined depletion of PI(4,5)P2 or PI(4)P reduces channel activity. In addition to revealing a role for distinct membrane lipids in mechanosensitive ion channel regulation, these data suggest that inhibition of Piezo2 channels may contribute to the analgesic effect of capsaicin. PMID:25670203

Odd-Z Transactinide Compound Nucleus Reactions Including the Discovery of 260Bh

Energy Technology Data Exchange (ETDEWEB)

Nelson, Sarah L. [Univ. of California, Berkeley, CA (United States)

2008-01-01

Several reactions producing odd-Z transactinide compound nuclei were studiedwith the 88-Inch Cyclotron and the Berkeley Gas-Filled Separator at the Lawrence Berkeley National Laboratory. The goal was to produce the same compound nucleus ator near the same excitation energy with similar values of angular momentum via differentnuclear reactions. In doing so, it can be determined if there is a preference in entrancechannel, because under these experimental conditions the survival portion of Swiatecki, Siwek-Wilcznska, and Wilczynski's"Fusion By Diffusion" model is nearly identical forthe two reactions. Additionally, because the same compound nucleus is produced, theexit channel is the same. Four compound nuclei were examined in this study: ²⁵⁸Db, ²⁶²Bh, ²⁶⁶Mt, and ²⁷²Rg. These nuclei were produced by using very similar heavy-ion induced-fusion reactions which differ only by one proton in the projectile or target nucleus (e.g.: ⁵⁰Ti + ²⁰⁹Bi vs. ⁵¹V + ²⁰⁸Pb). Peak 1n exit channel cross sections were determined for each reaction in each pair, and three of the four pairs' cross sections were identical within statistical uncertainties. This indicates there is not an obvious preference of entrancechannel in these paired reactions. Charge equilibration immediately prior to fusionleading to a decreased fusion barrier is the likely cause of this phenomenon. In addition to this systematic study, the lightest isotope of element 107, bohrium, was discovered in the ²⁰⁹Bi(⁵²Cr,n) reaction. ²⁶⁰Bh was found to decay by emission of a 10.16 MeV alpha particle with a half-life of 35$+19\\atop{-9}$ ms. The cross section is 59 pb at an excitation energy of 15.0 MeV. The effect of the N = 152 shell is also seen in this isotope's alpha particle energy, the first evidence of such an effect in Bh. All reactions studied are also compared to model predictions by Swiatecki

New Channels, New Possibilities

DEFF Research Database (Denmark)

Pieterson, Willem; Ebbers, Wolfgang; Østergaard Madsen, Christian

2017-01-01

In this contribution we discuss the characteristics of what we call the fourth generation of public sector service channels: social robots. Based on a review of relevant literature we discuss their characteristics and place into multi-channel models of service delivery. We argue that social robots......-channel models of service delivery. This is especially relevant given the current lack of evaluations of such models, the broad range of channels available, and their different stages of deployment at governments around the world. Nevertheless, social robots offer an potentially very relevant addition...

Ion channelling in diamond

International Nuclear Information System (INIS)

Derry, T.E.

1978-06-01

Diamond is one of the most extreme cases from a channelling point of view, having the smallest thermal vibration amplitude and the lowest atomic number of commonly-encountered crystals. These are the two parameters most important for determining channelling behaviour. It is of consiberable interest therefore to see how well the theories explaining and predicting the channeling properties of other substance, succeed with diamond. Natural diamond, although the best available form for these experiments, is rather variable in its physical properties. Part of the project was devoted to considering and solving the problem of obtaining reproducible results representative of the ideal crystal. Channelling studies were performed on several good crystals, using the Rutherford backscattering method. Critical angles for proton channelling were measured for incident energies from 0.6 to 4.5 MeV, in the three most open axes and three most open planes of the diamond structure, and for α-particle channelling at 0.7 and 1.0 MeV (He + ) in the same axes and planes. For 1.0 MeV protons, the crystal temperature was varied from 20 degrees Celsius to 700 degrees Celsius. The results are presented as curves of backscattered yield versus angle in the region of each axis or plane, and summarised in the form of tables and graphs. Generally the critical angles, axial minimum yields, and temperature dependence are well predicted by the accepted theories. The most valuable overall conclusion is that the mean thermal vibration amplitude of the atoms in a crytical determines the critical approach distance to the channel walls at which an ion can remain channelled, even when this distance is much smaller than the Thomas-Fermi screening distance of the atomic potential, as is the case in diamond. A brief study was made of the radiation damage caused by α-particle bombardment, via its effect on the channelling phenomenon. It was possible to hold damage down to negligible levels during the

Ion Channel Trafficking: Control of Ion Channel Density as a Target for Arrhythmias?

Directory of Open Access Journals (Sweden)

Elise Balse

2017-10-01

Full Text Available The shape of the cardiac action potential (AP is determined by the contributions of numerous ion channels. Any dysfunction in the proper function or expression of these ion channels can result in a change in effective refractory period (ERP and lead to arrhythmia. The processes underlying the correct targeting of ion channels to the plasma membrane are complex, and have not been fully characterized in cardiac myocytes. Emerging evidence highlights ion channel trafficking as a potential causative factor in certain acquired and inherited arrhythmias, and therapies which target trafficking as opposed to pore block are starting to receive attention. In this review we present the current evidence for the mechanisms which underlie precise control of cardiac ion channel trafficking and targeting.

Impact of Dendrimer Terminal Group Chemistry on Blockage of the Anthrax Toxin Channel: A Single Molecule Study.

Science.gov (United States)

Yamini, Goli; Kalu, Nnanya; Nestorovich, Ekaterina M

2016-11-15

Nearly all the cationic molecules tested so far have been shown to reversibly block K⁺ current through the cation-selective PA 63 channels of anthrax toxin in a wide nM-mM range of effective concentrations. A significant increase in channel-blocking activity of the cationic compounds was achieved when multiple copies of positively charged ligands were covalently linked to multivalent scaffolds, such as cyclodextrins and dendrimers. Even though multivalent binding can be strong when the individual bonds are relatively weak, for drug discovery purposes we often strive to design multivalent compounds with high individual functional group affinity toward the respective binding site on a multivalent target. Keeping this requirement in mind, here we perform a single-channel/single-molecule study to investigate kinetic parameters of anthrax toxin PA 63 channel blockage by second-generation (G2) poly(amido amine) (PAMAM) dendrimers functionalized with different surface ligands, including G2-NH₂, G2-OH, G2-succinamate, and G2-COONa. We found that the previously reported difference in IC 50 values of the G2-OH/PA 63 and G2-NH₂/PA 63 binding was determined by both on- and off-rates of the reversible dendrimer/channel binding reaction. In 1 M KCl, we observed a decrease of about three folds in k o n and a decrease of only about ten times in t r e s with G2-OH compared to G2-NH₂. At the same time for both blockers, k o n and t r e s increased dramatically with transmembrane voltage increase. PAMAM dendrimers functionalized with negatively charged succinamate, but not carboxyl surface groups, still had some residual activity in inhibiting the anthrax toxin channels. At 100 mV, the on-rate of the G2-succinamate binding was comparable with that of G2-OH but showed weaker voltage dependence when compared to G2-OH and G2-NH₂. The residence time of G2-succinamate in the channel exhibited opposite voltage dependence compared to G2-OH and G2-NH₂, increasing with the cis

Customer Responses to Channel Migration Strategies Toward the E-channel

NARCIS (Netherlands)

Trampe, Debra; Konus, Umut; Verhoef, Peter C.

2014-01-01

Many firms stimulate customers to use the E-channel for services, which provokes various consumer responses to such limits on their freedom of choice. In a study on bank customers, we examine the extent of customer reactance in response to various E-channel migration strategies, the potential of

Multi-rate control over AWGN channels via analog joint source-channel coding

KAUST Repository

Khina, Anatoly; Pettersson, Gustav M.; Kostina, Victoria; Hassibi, Babak

2017-01-01

We consider the problem of controlling an unstable plant over an additive white Gaussian noise (AWGN) channel with a transmit power constraint, where the signaling rate of communication is larger than the sampling rate (for generating observations and applying control inputs) of the underlying plant. Such a situation is quite common since sampling is done at a rate that captures the dynamics of the plant and which is often much lower than the rate that can be communicated. This setting offers the opportunity of improving the system performance by employing multiple channel uses to convey a single message (output plant observation or control input). Common ways of doing so are through either repeating the message, or by quantizing it to a number of bits and then transmitting a channel coded version of the bits whose length is commensurate with the number of channel uses per sampled message. We argue that such “separated source and channel coding” can be suboptimal and propose to perform joint source-channel coding. Since the block length is short we obviate the need to go to the digital domain altogether and instead consider analog joint source-channel coding. For the case where the communication signaling rate is twice the sampling rate, we employ the Archimedean bi-spiral-based Shannon-Kotel'nikov analog maps to show significant improvement in stability margins and linear-quadratic Gaussian (LQG) costs over simple schemes that employ repetition.

Multi-rate control over AWGN channels via analog joint source-channel coding

KAUST Repository

Khina, Anatoly

2017-01-05

We consider the problem of controlling an unstable plant over an additive white Gaussian noise (AWGN) channel with a transmit power constraint, where the signaling rate of communication is larger than the sampling rate (for generating observations and applying control inputs) of the underlying plant. Such a situation is quite common since sampling is done at a rate that captures the dynamics of the plant and which is often much lower than the rate that can be communicated. This setting offers the opportunity of improving the system performance by employing multiple channel uses to convey a single message (output plant observation or control input). Common ways of doing so are through either repeating the message, or by quantizing it to a number of bits and then transmitting a channel coded version of the bits whose length is commensurate with the number of channel uses per sampled message. We argue that such “separated source and channel coding” can be suboptimal and propose to perform joint source-channel coding. Since the block length is short we obviate the need to go to the digital domain altogether and instead consider analog joint source-channel coding. For the case where the communication signaling rate is twice the sampling rate, we employ the Archimedean bi-spiral-based Shannon-Kotel\\'nikov analog maps to show significant improvement in stability margins and linear-quadratic Gaussian (LQG) costs over simple schemes that employ repetition.

Channel sialic acids limit hERG channel activity during the ventricular action potential.

Science.gov (United States)

Norring, Sarah A; Ednie, Andrew R; Schwetz, Tara A; Du, Dongping; Yang, Hui; Bennett, Eric S

2013-02-01

Activity of human ether-a-go-go-related gene (hERG) 1 voltage-gated K(+) channels is responsible for portions of phase 2 and phase 3 repolarization of the human ventricular action potential. Here, we questioned whether and how physiologically and pathophysiologically relevant changes in surface N-glycosylation modified hERG channel function. Voltage-dependent hERG channel gating and activity were evaluated as expressed in a set of Chinese hamster ovary (CHO) cell lines under conditions of full glycosylation, no sialylation, no complex N-glycans, and following enzymatic deglycosylation of surface N-glycans. For each condition of reduced glycosylation, hERG channel steady-state activation and inactivation relationships were shifted linearly by significant depolarizing ∼9 and ∼18 mV, respectively. The hERG window current increased significantly by 50-150%, and the peak shifted by a depolarizing ∼10 mV. There was no significant change in maximum hERG current density. Deglycosylated channels were significantly more active (20-80%) than glycosylated controls during phases 2 and 3 of action potential clamp protocols. Simulations of hERG current and ventricular action potentials corroborated experimental data and predicted reduced sialylation leads to a 50-70-ms decrease in action potential duration. The data describe a novel mechanism by which hERG channel gating is modulated through physiologically and pathophysiologically relevant changes in N-glycosylation; reduced channel sialylation increases hERG channel activity during the action potential, thereby increasing the rate of action potential repolarization.

Course on Ionic Channels

CERN Document Server

1986-01-01

This book is based on a series of lectures for a course on ionic channels held in Santiago, Chile, on November 17-20, 1984. It is intended as a tutorial guide on the properties, function, modulation, and reconstitution of ionic channels, and it should be accessible to graduate students taking their first steps in this field. In the presentation there has been a deliberate emphasis on the spe­ cific methodologies used toward the understanding of the workings and function of channels. Thus, in the first section, we learn to "read" single­ channel records: how to interpret them in the theoretical frame of kinetic models, which information can be extracted from gating currents in re­ lation to the closing and opening processes, and how ion transport through an open channel can be explained in terms of fluctuating energy barriers. The importance of assessing unequivocally the origin and purity of mem­ brane preparations and the use of membrane vesicles and optical tech­ niques in the stUGY of ionic channels a...

XPM-induced degradation of multilevel phase modulated channel caused by neighboring NRZ modulated channels

DEFF Research Database (Denmark)

Jensen, Jesper Bevensee; Schiellerup, G.; Peucheret, Christophe

2008-01-01

The impact of XPM from NRZ modulated channels on an 8-level phase modulated channel in a WDM system was investigated. Requirements on launch power are found. 400 km transmission was achieved with negligible penalty.......The impact of XPM from NRZ modulated channels on an 8-level phase modulated channel in a WDM system was investigated. Requirements on launch power are found. 400 km transmission was achieved with negligible penalty....

Adrenaline-induced colonic K+ secretion is mediated by KCa1.1 (BK) channels

DEFF Research Database (Denmark)

Sørensen, Mads Vaarby; Sausbier, Matthias; Ruth, Peter

2010-01-01

. However, the secretory K(+) channel responsible for cAMP-induced K(+) secretion remains to be defined. In this study we used the Ussing chamber to identify adrenaline-induced electrogenic K(+) secretion. We found that the adrenaline-induced electrogenic ion secretion is a compound effect dominated...... variants in colonic enterocytes (STREX and ZERO). Importantly, the ZERO variant known to be activated by cAMP is differentially up-regulated in enterocytes from animals on a high K(+) diet. In summary, these results strongly suggest that the adrenaline-induced distal colonic K(+) secretion is mediated...

Substituted N-(biphenyl-4'-yl)methyl (R)-2-acetamido-3-methoxypropionamides: potent anticonvulsants that affect frequency (use) dependence and slow inactivation of sodium channels.

Science.gov (United States)

Lee, Hyosung; Park, Ki Duk; Torregrosa, Robert; Yang, Xiao-Fang; Dustrude, Erik T; Wang, Yuying; Wilson, Sarah M; Barbosa, Cindy; Xiao, Yucheng; Cummins, Theodore R; Khanna, Rajesh; Kohn, Harold

2014-07-24

We prepared 13 derivatives of N-(biphenyl-4'-yl)methyl (R)-2-acetamido-3-methoxypropionamide that differed in type and placement of a R-substituent in the terminal aryl unit. We demonstrated that the R-substituent impacted the compound's whole animal and cellular pharmacological activities. In rodents, select compounds exhibited excellent anticonvulsant activities and protective indices (PI=TD50/ED50) that compared favorably with clinical antiseizure drugs. Compounds with a polar, aprotic R-substituent potently promoted Na+ channel slow inactivation and displayed frequency (use) inhibition of Na+ currents at low micromolar concentrations. The possible advantage of affecting these two pathways to decrease neurological hyperexcitability is discussed.

Cardiac potassium channel subtypes

DEFF Research Database (Denmark)

Schmitt, Nicole; Grunnet, Morten; Olesen, Søren-Peter

2014-01-01

About 10 distinct potassium channels in the heart are involved in shaping the action potential. Some of the K(+) channels are primarily responsible for early repolarization, whereas others drive late repolarization and still others are open throughout the cardiac cycle. Three main K(+) channels...... drive the late repolarization of the ventricle with some redundancy, and in atria this repolarization reserve is supplemented by the fairly atrial-specific KV1.5, Kir3, KCa, and K2P channels. The role of the latter two subtypes in atria is currently being clarified, and several findings indicate...... that they could constitute targets for new pharmacological treatment of atrial fibrillation. The interplay between the different K(+) channel subtypes in both atria and ventricle is dynamic, and a significant up- and downregulation occurs in disease states such as atrial fibrillation or heart failure...

Channel Estimation in DCT-Based OFDM

Science.gov (United States)

Wang, Yulin; Zhang, Gengxin; Xie, Zhidong; Hu, Jing

2014-01-01

This paper derives the channel estimation of a discrete cosine transform- (DCT-) based orthogonal frequency-division multiplexing (OFDM) system over a frequency-selective multipath fading channel. Channel estimation has been proved to improve system throughput and performance by allowing for coherent demodulation. Pilot-aided methods are traditionally used to learn the channel response. Least square (LS) and mean square error estimators (MMSE) are investigated. We also study a compressed sensing (CS) based channel estimation, which takes the sparse property of wireless channel into account. Simulation results have shown that the CS based channel estimation is expected to have better performance than LS. However MMSE can achieve optimal performance because of prior knowledge of the channel statistic. PMID:24757439

A new simple model for composite fading channels: Second order statistics and channel capacity

KAUST Repository

Yilmaz, Ferkan; Alouini, Mohamed-Slim

2010-01-01

In this paper, we introduce the most general composite fading distribution to model the envelope and the power of the received signal in such fading channels as millimeter wave (60 GHz or above) fading channels and free-space optical channels, which

CANDU channel flow verification

International Nuclear Information System (INIS)

Mazalu, N.; Negut, Gh.

1997-01-01

The purpose of this evaluation was to obtain accurate information on each channel flow that enables us to assess precisely the level of reactor thermal power and, for reasons of safety, to establish which channel is boiling. In order to assess the channel flow parameters, computer simulations were done with the NUCIRC code and the results were checked by measurements. The complete channel flow measurements were made in the zero power cold condition. In hot conditions there were made flow measurements using the Shut Down System 1 (SDS 1) flow devices from 0.1 % F.P. up to 100 % F.P. The NUCIRC prediction for CANDU channel flows and the measurements by Ultrasonic Flow Meter at zero power cold conditions and SDS 1 flow channel measurements at different reactor power levels showed an acceptable agreement. The 100 % F.P. average errors for channel flow of R, shows that suitable NUCIRC flow assessment can be made. So, it can be done a fair prediction of the reactor power distribution. NUCIRC can predict accurately the onset of boiling and helps to warn at the possible power instabilities at high powers or it can detect the flow blockages. The thermal hydraulic analyst has in NUCIRC a suitable tool to do accurate predictions for the thermal hydraulic parameters for different steady state power levels which subsequently leads to an optimal CANDU reactor operation. (authors)

A dual-channel gas chromatography method for the quantitation of low and high concentrations of NF3 and CF4 to study membrane separation of the two compounds.

Science.gov (United States)

Branken, D J; le Roux, J P; Krieg, H M; Lachmann, G

2013-09-13

A dual-channel gas chromatographic method is described in this paper that can be conveniently used for quantitation of NF3/CF4 mixtures with a thermal conductivity detector (TCD) on one channel for the quantitation of high-concentrations, and a pulsed discharge helium ionization detector (PDHID) on a second channel for the quantitation of low concentrations. It is shown that adequate separation is achieved on both channels with this dual single-column setup in which column switching as used for NF3/CF4 analysis in industrial chromatographic methods are not required, thus yielding an effective analysis method for laboratory-scale investigations. In addition, the use of packed columns with purified divinylbenzene-styrene co-polymers as the sole stationary phase yields satisfactory resolution between NF3 and CF4 at isothermal conditions of 30°C, with elution times of less than 8min on the TCD channel and less than 4min on the PDHID channel. Consequently, this method allows for reliable, straight-forward quantitation of NF3/CF4 mixtures, which is necessary when studying the commercially important problem of NF3 and CF4 separation by different methods. Therefore, the applicability of the method to studying membrane separation of NF3 and CF4 is briefly discussed and illustrated, for which the dual-channel setup is especially beneficial. Copyright © 2013 Elsevier B.V. All rights reserved.

Channel Simulation in Quantum Metrology

Directory of Open Access Journals (Sweden)

Laurenza Riccardo

2018-04-01

Full Text Available In this review we discuss how channel simulation can be used to simplify the most general protocols of quantum parameter estimation, where unlimited entanglement and adaptive joint operations may be employed. Whenever the unknown parameter encoded in a quantum channel is completely transferred in an environmental program state simulating the channel, the optimal adaptive estimation cannot beat the standard quantum limit. In this setting, we elucidate the crucial role of quantum teleportation as a primitive operation which allows one to completely reduce adaptive protocols over suitable teleportation-covariant channels and derive matching upper and lower bounds for parameter estimation. For these channels,wemay express the quantum Cramér Rao bound directly in terms of their Choi matrices. Our review considers both discrete- and continuous-variable systems, also presenting some new results for bosonic Gaussian channels using an alternative sub-optimal simulation. It is an open problem to design simulations for quantum channels that achieve the Heisenberg limit.

Microchip electrophoresis with amperometric detection for a novel determination of phenolic compounds in olive oil.

Science.gov (United States)

Godoy-Caballero, María del Pilar; Acedo-Valenzuela, María Isabel; Galeano-Díaz, Teresa; Costa-García, Agustín; Fernández-Abedul, María Teresa

2012-11-07

The relevance of the development of microchip electrophoresis applications in the field of food analysis is considered in this work. A novel method to determine important phenolic compounds in extra virgin olive oil samples using a miniaturized chemical analysis system is presented in this paper. Three interesting phenolic compounds in olive oil and fruit (tyrosol, hydroxytyrosol and oleuropein glucoside) were studied by end-channel amperometric detection using a 100 μm gold wire as working electrode in glass microchip electrophoresis. The electrochemical behavior of these compounds was studied and the medium to carry out their detection was selected (0.1 M aqueous sulfuric acid). The best conditions for the separation were achieved in sodium tetraborate (10% methanol, pH 9.50) with different concentrations for the sample and the running buffer in order to allow the sample stacking phenomenon. The injection was carried out using 600 V for 3 s and the separation voltage was set at 1000 V. The quality of the method was evaluated through its analytical figures of merit and by its performance on real extra virgin olive oil samples. Determination of these compounds was carried out using the standard addition calibration method with good recoveries.

Isotopically modified compounds

International Nuclear Information System (INIS)

Kuruc, J.

2009-01-01

In this chapter the nomenclature of isotopically modified compounds in Slovak language is described. This chapter consists of following parts: (1) Isotopically substituted compounds; (2) Specifically isotopically labelled compounds; (3) Selectively isotopically labelled compounds; (4) Non-selectively isotopically labelled compounds; (5) Isotopically deficient compounds.

d-Tubocurarine and Berbamine: Alkaloids That Are Permeant Blockers of the Hair Cell's Mechano-Electrical Transducer Channel and Protect from Aminoglycoside Toxicity

Directory of Open Access Journals (Sweden)

Nerissa K. Kirkwood

2017-09-01

Full Text Available Aminoglycoside antibiotics are widely used for the treatment of life-threatening bacterial infections, but cause permanent hearing loss in a substantial proportion of treated patients. The sensory hair cells of the inner ear are damaged following entry of these antibiotics via the mechano-electrical transducer (MET channels located at the tips of the hair cell's stereocilia. d-Tubocurarine (dTC is a MET channel blocker that reduces the loading of gentamicin-Texas Red (GTTR into rat cochlear hair cells and protects them from gentamicin treatment. Berbamine is a structurally related alkaloid that reduces GTTR labeling of zebrafish lateral-line hair cells and protects them from aminoglycoside-induced cell death. Both compounds are thought to reduce aminoglycoside entry into hair cells through the MET channels. Here we show that dTC (≥6.25 μM or berbamine (≥1.55 μM protect zebrafish hair cells in vivo from neomycin (6.25 μM, 1 h. Protection of zebrafish hair cells against gentamicin (10 μM, 6 h was provided by ≥25 μM dTC or ≥12.5 μM berbamine. Hair cells in mouse cochlear cultures are protected from longer-term exposure to gentamicin (5 μM, 48 h by 20 μM berbamine or 25 μM dTC. Berbamine is, however, highly toxic to mouse cochlear hair cells at higher concentrations (≥30 μM whilst dTC is not. The absence of toxicity in the zebrafish assays prompts caution in extrapolating results from zebrafish neuromasts to mammalian cochlear hair cells. MET current recordings from mouse outer hair cells (OHCs show that both compounds are permeant open-channel blockers, rapidly and reversibly blocking the MET channel with half-blocking concentrations of 2.2 μM (dTC and 2.8 μM (berbamine in the presence of 1.3 mM Ca2+ at −104 mV. Berbamine, but not dTC, also blocks the hair cell's basolateral K+ current, IK,neo, and modeling studies indicate that berbamine permeates the MET channel more readily than dTC. These studies reveal key properties of

Effect of channel-protein interaction on translocation of a protein-like chain through a finite channel

International Nuclear Information System (INIS)

Sun Ting-Ting; Ma Hai-Zhu; Jiang Zhou-Ting

2012-01-01

We study the translocation of a protein-like chain through a finite cylindrical channel using the pruned-enriched Rosenbluth method (PERM) and the modified orientation-dependent monomer-monomer interaction (ODI) model. Attractive channels (in cp = −2.0, −1.0, −0.5), repulsive channels (in cp = 0.5, 1.0, 2.0), and a neutral channel (in cp = 0) are discussed. The results of the chain dimension and the energy show that Z 0 = 1.0 is an important case to distinguish the types of the channels. For the strong attractive channel, more contacts form during the process of translocation. It is also found that an external force is needed to drive the chain outside of the channel with the strong attraction. While for the neutral, the repulsive, and the weak attractive channels, the translocation is spontaneous. (interdisciplinary physics and related areas of science and technology)

Radar channel balancing with commutation

Energy Technology Data Exchange (ETDEWEB)

Doerry, Armin Walter

2014-02-01

When multiple channels are employed in a pulse-Doppler radar, achieving and maintaining balance between the channels is problematic. In some circumstances the channels may be commutated to achieve adequate balance. Commutation is the switching, trading, toggling, or multiplexing of the channels between signal paths. Commutation allows modulating the imbalance energy away from the balanced energy in Doppler, where it can be mitigated with filtering.

Cl- channels in apoptosis

DEFF Research Database (Denmark)

Wanitchakool, Podchanart; Ousingsawat, Jiraporn; Sirianant, Lalida

2016-01-01

A remarkable feature of apoptosis is the initial massive cell shrinkage, which requires opening of ion channels to allow release of K(+), Cl(-), and organic osmolytes to drive osmotic water movement and cell shrinkage. This article focuses on the role of the Cl(-) channels LRRC8, TMEM16/anoctamin......, and cystic fibrosis transmembrane conductance regulator (CFTR) in cellular apoptosis. LRRC8A-E has been identified as a volume-regulated anion channel expressed in many cell types. It was shown to be required for regulatory and apoptotic volume decrease (RVD, AVD) in cultured cell lines. Its presence also......(-) channels or as regulators of other apoptotic Cl(-) channels, such as LRRC8. CFTR has been known for its proapoptotic effects for some time, and this effect may be based on glutathione release from the cell and increase in cytosolic reactive oxygen species (ROS). Although we find that CFTR is activated...

Direct channel problems and phenomena

International Nuclear Information System (INIS)

Cutkosky, R.E.

1975-01-01

Direct channel problems and phenomena are considered covering the need for precision hadron spectroscopy, the data base for precision hadron spectroscopy, some relations between direct-channel and cross-channel effects, and spin rotation phenomena

Nuclear reactor coolant channels

International Nuclear Information System (INIS)

Macbeth, R.V.

1978-01-01

Reference is made to coolant channels for pressurised water and boiling water reactors and the arrangement described aims to improve heat transfer between the fuel rods and the coolant. Baffle means extending axially within the channel are provided and disposed relative to the fuel rods so as to restrict flow oscillations occurring within the coolant from being propagated transversely to the axis of the channel. (UK)

An FPGA-Based Adaptable 200 MHz Bandwidth Channel Sounder for Wireless Communication Channel Characterisation

Directory of Open Access Journals (Sweden)

David L. Ndzi

2011-01-01

Full Text Available This paper describes the development of a fast adaptable FPGA-based wideband channel sounder with signal bandwidths of up to 200 MHz and channel sampling rates up to 5.4 kHz. The application of FPGA allows the user to vary the number of real-time channel response averages, channel sampling interval, and duration of measurement. The waveform, bandwidth, and frequency resolution of the sounder can be adapted for any channel under investigation. The design approach and technology used has led to a reduction in size and weight by more than 60%. This makes the sounder ideal for mobile time-variant wireless communication channels studies. Averaging allows processing gains of up to 30 dB to be achieved for measurement in weak signal conditions. The technique applied also improves reliability, reduces power consumption, and has shifted sounder design complexity from hardware to software. Test results show that the sounder can detect very small-scale variations in channels.

Secrecy Outage of Max-Min TAS Scheme in MIMO-NOMA Systems

KAUST Repository

Lei, Hongjiang

2018-04-09

This paper considers a secure non-orthogonal multiple access system, where confidential messages are transmitted from a base station to multiple legitimate destinations and wiretapped by multiple illegitimate receivers. It is assumed that all the channels experience Nakagami-m fading model and all the nodes are equipped with multiple antennas, respectively. Both non-colluding and colluding eavesdroppers are respectively considered. Max-min (MM) transmit antenna selection (TAS) strategy is adopted to improve the secrecy performance of the target system, in which both users in user paring are considered simultaneously. In particular, closed-form expressions for the cumulative distribution function of the signal-to-interference-noise ratio at the legitimate user are derived firstly. Then we obtain the exact and asymptotic analytical results in a closed form for the secrecy outage probability of MM TAS scheme. Monte-Carlo simulation results are presented to corroborate the correctness of the analysis. The results show that the secrecy diversity order is zero and non-zero for fixed and dynamic power allocations, respectively.

Secrecy Outage of Max-Min TAS Scheme in MIMO-NOMA Systems

KAUST Repository

Lei, Hongjiang; Zhang, Jianming; Park, Kihong; Xu, Peng; Zhang, Zufan; Pan, Gaofeng; Alouini, Mohamed-Slim

2018-01-01

This paper considers a secure non-orthogonal multiple access system, where confidential messages are transmitted from a base station to multiple legitimate destinations and wiretapped by multiple illegitimate receivers. It is assumed that all the channels experience Nakagami-m fading model and all the nodes are equipped with multiple antennas, respectively. Both non-colluding and colluding eavesdroppers are respectively considered. Max-min (MM) transmit antenna selection (TAS) strategy is adopted to improve the secrecy performance of the target system, in which both users in user paring are considered simultaneously. In particular, closed-form expressions for the cumulative distribution function of the signal-to-interference-noise ratio at the legitimate user are derived firstly. Then we obtain the exact and asymptotic analytical results in a closed form for the secrecy outage probability of MM TAS scheme. Monte-Carlo simulation results are presented to corroborate the correctness of the analysis. The results show that the secrecy diversity order is zero and non-zero for fixed and dynamic power allocations, respectively.

Antibodies to the extracellular pore loop of TRPM8 act as antagonists of channel activation.

Directory of Open Access Journals (Sweden)

Silke Miller

Full Text Available The mammalian transient receptor potential melastatin channel 8 (TRPM8 is highly expressed in trigeminal and dorsal root ganglia. TRPM8 is activated by cold temperature or compounds that cause a cooling sensation, such as menthol or icilin. TRPM8 may play a role in cold hypersensitivity and hyperalgesia in various pain syndromes. Therefore, TRPM8 antagonists are pursued as therapeutics. In this study we explored the feasibility of blocking TRPM8 activation with antibodies. We report the functional characterization of a rabbit polyclonal antibody, ACC-049, directed against the third extracellular loop near the pore region of the human TRPM8 channel. ACC-049 acted as a full antagonist at recombinantly expressed human and rodent TRPM8 channels in cell based agonist-induced 45Ca2+ uptake assays. Further, several poly-and monoclonal antibodies that recognize the same region also blocked icilin activation of not only recombinantly expressed TRPM8, but also endogenous TRPM8 expressed in rat dorsal root ganglion neurons revealing the feasibility of generating monoclonal antibody antagonists. We conclude that antagonist antibodies are valuable tools to investigate TRPM8 function and may ultimately pave the way for development of therapeutic antibodies.

Blockade of TRPM7 channel activity and cell death by inhibitors of 5-lipoxygenase.

Directory of Open Access Journals (Sweden)

Hsiang-Chin Chen

2010-06-01

Full Text Available TRPM7 is a ubiquitous divalent-selective ion channel with its own kinase domain. Recent studies have shown that suppression of TRPM7 protein expression by RNA interference increases resistance to ischemia-induced neuronal cell death in vivo and in vitro, making the channel a potentially attractive pharmacological target for molecular intervention. Here, we report the identification of the 5-lipoxygenase inhibitors, NDGA, AA861, and MK886, as potent blockers of the TRPM7 channel. Using a cell-based assay, application of these compounds prevented cell rounding caused by overexpression of TRPM7 in HEK-293 cells, whereas inhibitors of 12-lipoxygenase and 15-lipoxygenase did not prevent the change in cell morphology. Application of the 5-lipoxygenase inhibitors blocked heterologously expressed TRPM7 whole-cell currents without affecting the protein's expression level or its cell surface concentration. All three inhibitors were also effective in blocking the native TRPM7 current in HEK-293 cells. However, two other 5-lipoxygenase specific inhibitors, 5,6-dehydro-arachidonic acid and zileuton, were ineffective in suppressing TRPM7 channel activity. Targeted knockdown of 5-lipoxygenase did not reduce TRPM7 whole-cell currents. In addition, application of 5-hydroperoxyeicosatetraenoic acid (5-HPETE, the product of 5-lipoxygenase, or 5-HPETE's downstream metabolites, leukotriene B4 and leukotriene D4, did not stimulate TRPM7 channel activity. These data suggested that NDGA, AA861, and MK886 reduced the TRPM7 channel activity independent of their effect on 5-lipoxygenase activity. Application of AA861 and NDGA reduced cell death for cells overexpressing TRPM7 cultured in low extracellular divalent cations. Moreover, treatment of HEK-293 cells with AA861 increased cell resistance to apoptotic stimuli to a level similar to that obtained for cells in which TRPM7 was knocked down by RNA interference. In conclusion, NDGA, AA861, and MK886 are potent blockers of

The KATP channel in migraine pathophysiology

DEFF Research Database (Denmark)

Al-Karagholi, Mohammad Al-Mahdi; Hansen, Jakob Møller; Severinsen, Johanne

2017-01-01

BACKGROUND: To review the distribution and function of KATP channels, describe the use of KATP channels openers in clinical trials and make the case that these channels may play a role in headache and migraine. DISCUSSION: KATP channels are widely present in the trigeminovascular system and play...... an important role in the regulation of tone in cerebral and meningeal arteries. Clinical trials using synthetic KATP channel openers report headache as a prevalent-side effect in non-migraine sufferers, indicating that KATP channel opening may cause headache, possibly due to vascular mechanisms. Whether KATP...... channel openers can provoke migraine in migraine sufferers is not known. CONCLUSION: We suggest that KATP channels may play an important role in migraine pathogenesis and could be a potential novel therapeutic anti-migraine target....

Six-channel adaptive fibre-optic interferometer

Energy Technology Data Exchange (ETDEWEB)

Romashko, R V; Bezruk, M N; Kamshilin, A A; Kulchin, Yurii N

2012-06-30

We have proposed and analysed a scheme for the multiplexing of orthogonal dynamic holograms in photorefractive crystals which ensures almost zero cross talk between the holographic channels upon phase demodulation. A six-channel adaptive fibre-optic interferometer was built, and the detection limit for small phase fluctuations in the channels of the interferometer was determined to be 2.1 Multiplication-Sign 10{sup -8} rad W{sup 1/2} Hz{sup -1/2}. The channel multiplexing capacity of the interferometer was estimated. The formation of 70 channels such that their optical fields completely overlap in the crystal reduces the relative detection limit in the working channel by just 10 %. We found conditions under which the maximum cross talk between the channels was within the intrinsic noise level in the channels (-47 dB).

On the description of the (HI, xn) reaction excitation functions for the case of weakly fissioning compound nuclei

International Nuclear Information System (INIS)

Kamanin, V.V.; Karamyan, S.A.

1980-01-01

A possibility to obtain parameters of nuclear temperature and critical angular momentum for the compound nucleus production on the base of the (HI, xn) reaction excitation function description are considered for the case of weakly fissioning nuclei. Experimental data on 152 Sm( 12 C, 2n) 162 Er, 148 Nd( 16 O, 3n) 161 Er, sup(150)Nd(sup(16)O, 3-5n)sup(163-161)Er, sup(148)Nd(sup(18)O, 4-5n)sup(162,161)Er, sup(118)Sn(sup(40)Ar, 5-6n)sup(153,152)Er and sup(74)Ge(sup(84)Kr, 5-6n)sup(153,152)Er reactions are discussed. The formulae, taking into accout the distribution of compound nuclei in angular momentum and competition between channels of the neutron and γ-ray emission, are given. The formulae are applied for the description of the excitation functions, characterized by a good accuracy of the particle energy measuring. A satisfactory accordance between the calculation and experiment is achieved. The conclusion on sensitivity of the nuclear temperature values to exact evaluation of competition between the neutron and γ-ray emission channels is drawn

G-Channel Restoration for RWB CFA with Double-Exposed W Channel.

Science.gov (United States)

Park, Chulhee; Song, Ki Sun; Kang, Moon Gi

2017-02-05

In this paper, we propose a green (G)-channel restoration for a red-white-blue (RWB) color filter array (CFA) image sensor using the dual sampling technique. By using white (W) pixels instead of G pixels, the RWB CFA provides high-sensitivity imaging and an improved signal-to-noise ratio compared to the Bayer CFA. However, owing to this high sensitivity, the W pixel values become rapidly over-saturated before the red-blue (RB) pixel values reach the appropriate levels. Because the missing G color information included in the W channel cannot be restored with a saturated W, multiple captures with dual sampling are necessary to solve this early W-pixel saturation problem. Each W pixel has a different exposure time when compared to those of the R and B pixels, because the W pixels are double-exposed. Therefore, a RWB-to-RGB color conversion method is required in order to restore the G color information, using a double-exposed W channel. The proposed G-channel restoration algorithm restores G color information from the W channel by considering the energy difference caused by the different exposure times. Using the proposed method, the RGB full-color image can be obtained while maintaining the high-sensitivity characteristic of the W pixels.

X-ray radiation channeling in micro-channel plates: Spectroscopy with a synchrotron radiation beam

International Nuclear Information System (INIS)

Mazuritskiy, M.I.; Dabagov, S.B.; Marcelli, A.; Dziedzic-Kocurek, K.; Lerer, A.M.

2015-01-01

We present here the angular distribution of the radiation propagated inside MultiChannel Plates with micro-channels of ∼3 μm diameter. The spectra collected at the exit of the channels present a complex distribution with contributions that can be assigned to the fluorescence radiation, originated from the excitation of the micro-channel walls. For radiation above the absorption edge, when the monochromatic energy in the region of the Si L-edge hits the micro-channel walls with a grazing angle θ ⩾ 5°, or at the O K-edge when θ ⩾ 2° a fluorescence radiation is detected. Additional information associated to the fine structures of the XANES spectra detected at the exit of MCPs are also presented and discussed

HIPPI and Fibre Channel

International Nuclear Information System (INIS)

Tolmie, D.E.

1992-01-01

The High-Performance Parallel Interface (HIPPI) and Fibre Channel are near-gigabit per second data communications interfaces being developed in ANSI standards Task Group X3T9.3. HIPPI is the current interface of choice in the high-end and supercomputer arena, and Fibre Channel is a follow-on effort. HIPPI came from a local area network background, and Fibre Channel came from a mainframe to peripheral interface background

Imaging subsurface geology and volatile organic compound plumes

International Nuclear Information System (INIS)

Qualheim, B.J.; Daley, P.F.; Johnson, V.; McPherrin, R.V.; Laguna, G.

1992-03-01

Lawrence Livermore National Laboratory (LLNL) (Fig. 1) is in the final stages of the Superfund decisionmaking process for site remediation and restoration. In the process of characterizing the subsurface of the LLNL site, we have developed unique methods of collecting, storing, retrieving, and imaging geologic and chemical data from more than 350 drill holes. The lateral and vertical continuity of subsurface paleostream channels were mapped for the entire LLNL site using geologic descriptions from core samples, cuttings, and interpretations from geophysical logs. A computer-aided design and drafting program, SLICE, written at LLNL, was used to create two-dimensional maps of subsurface sediments, and state-of-the-art software produced three-dimensional images of the volatile organic compound (VOC) plumes using data from water and core fluid analyses

TbNb6Sn6: the first ternary compound from the rare earth–niobium–tin system

Directory of Open Access Journals (Sweden)

Viktor Hlukhyy

2010-12-01

Full Text Available The title compound, terbium hexaniobium hexastannide, TbNb6Sn6, is the first ternary compound from the rare earth–niobium–tin system. It has the HfFe6Ge6 structure type, which can be analysed as an intergrowth of the Zr4Al3 and CaCu5 structures. All the atoms lie on special positions; their coordination geometries and site symmetries are: Tb (dodecahedron 6/mmm; Nb (distorted icosahedron 2mm; Sn (Frank–Caspar polyhedron, CN = 14–15 6mm and overline{6}m2; Sn (distorted icosahedron overline{6}m2. The structure contains a graphite-type Sn network, Kagome nets of Nb atoms, and Tb atoms alternating with Sn2 dumbbells in the channels.

Quantum channels with a finite memory

International Nuclear Information System (INIS)

Bowen, Garry; Mancini, Stefano

2004-01-01

In this paper we study quantum communication channels with correlated noise effects, i.e., quantum channels with memory. We derive a model for correlated noise channels that includes a channel memory state. We examine the case where the memory is finite, and derive bounds on the classical and quantum capacities. For the entanglement-assisted and unassisted classical capacities it is shown that these bounds are attainable for certain classes of channel. Also, we show that the structure of any finite-memory state is unimportant in the asymptotic limit, and specifically, for a perfect finite-memory channel where no information is lost to the environment, achieving the upper bound implies that the channel is asymptotically noiseless

Improvement of Metroliner Telephone Channel Capacity and Modeling of Telephone Channel Demands

Science.gov (United States)

1972-03-01

The channel capacity of the present Metroliner telephone system is analyzed and methods are proposed to increase that capacity without increasing the overall bandwidth. To determine the number of channels required, calculations have been carried out ...

Channel erosion in a rapidly urbanizing region of Tijuana, Mexico: Enlargement downstream of channel hardpoints

Science.gov (United States)

Taniguchi, Kristine; Biggs, Trent; Langendoen, Eddy; Castillo, Carlos; Gudiño, Napoleon; Yuan, Yongping; Liden, Douglas

2016-04-01

Urban-induced erosion in Tijuana, Mexico, has led to excessive sediment deposition in the Tijuana Estuary in the United States. Urban areas in developing countries, in contrast to developed countries, are characterized by much lower proportions of vegetation and impervious surfaces due to limited access to urban services such as road paving and landscaping, and larger proportions of exposed soils. In developing countries, traditional watershed scale variables such as impervious surfaces may not be good predictors of channel enlargement. In this research, we surveyed the stream channel network of an erodible tributary of the Tijuana River Watershed, Los Laureles Canyon, at 125 locations, including repeat surveys from 2008. Structure from Motion (SfM) and 3D photo-reconstruction techniques were used to create digital terrain models of stream reaches upstream and downstream of channel hardpoints. Channels are unstable downstream of hardpoints, with incision up to 2 meters and widening up to 12 meters. Coordinated channelization is essential to avoid piece-meal approaches that lead to channel degradation. Watershed impervious area is not a good predictor of channel erosion due to the overriding importance of hardpoints and likely to the high sediment supply from the unpaved roads which prevents channel erosion throughout the stream network.

Parallel inter channel interaction mechanisms

International Nuclear Information System (INIS)

Jovic, V.; Afgan, N.; Jovic, L.

1995-01-01

Parallel channels interactions are examined. For experimental researches of nonstationary regimes flow in three parallel vertical channels results of phenomenon analysis and mechanisms of parallel channel interaction for adiabatic condition of one-phase fluid and two-phase mixture flow are shown. (author)

Matching Dyadic Distributions to Channels

OpenAIRE

Böcherer, Georg; Mathar, Rudolf

2010-01-01

Many communication channels with discrete input have non-uniform capacity achieving probability mass functions (PMF). By parsing a stream of independent and equiprobable bits according to a full prefix-free code, a modu-lator can generate dyadic PMFs at the channel input. In this work, we show that for discrete memoryless channels and for memoryless discrete noiseless channels, searching for good dyadic input PMFs is equivalent to minimizing the Kullback-Leibler distance between a dyadic PMF ...

Multiplicative properties of quantum channels

Science.gov (United States)

Rahaman, Mizanur

2017-08-01

In this paper, we study the multiplicative behaviour of quantum channels, mathematically described by trace preserving, completely positive maps on matrix algebras. It turns out that the multiplicative domain of a unital quantum channel has a close connection to its spectral properties. A structure theorem (theorem 2.5), which reveals the automorphic property of an arbitrary unital quantum channel on a subalgebra, is presented. Various classes of quantum channels (irreducible, primitive, etc) are then analysed in terms of this stabilising subalgebra. The notion of the multiplicative index of a unital quantum channel is introduced, which measures the number of times a unital channel needs to be composed with itself for the multiplicative algebra to stabilise. We show that the maps that have trivial multiplicative domains are dense in completely bounded norm topology in the set of all unital completely positive maps. Some applications in quantum information theory are discussed.

Long Channel Carbon Nanotube as an Alternative to Nanoscale Silicon Channels in Scaled MOSFETs

Directory of Open Access Journals (Sweden)

Michael Loong Peng Tan

2013-01-01

Full Text Available Long channel carbon nanotube transistor (CNT can be used to overcome the high electric field effects in nanoscale length silicon channel. When maximum electric field is reduced, the gate of a field-effect transistor (FET is able to gain control of the channel at varying drain bias. The device performance of a zigzag CNTFET with the same unit area as a nanoscale silicon metal-oxide semiconductor field-effect transistor (MOSFET channel is assessed qualitatively. The drain characteristic of CNTFET and MOSFET device models as well as fabricated CNTFET device are explored over a wide range of drain and gate biases. The results obtained show that long channel nanotubes can significantly reduce the drain-induced barrier lowering (DIBL effects in silicon MOSFET while sustaining the same unit area at higher current density.

Local quantum channels preserving classical correlations

International Nuclear Information System (INIS)

Guo Zhihua; Cao Huaixin

2013-01-01

The aim of this paper is to discuss local quantum channels that preserve classical correlations. First, we give two equivalent characterizations of classical correlated states. Then we obtain the relationships among classical correlation-preserving local quantum channels, commutativity-preserving local quantum channels and commutativity-preserving quantum channels on each subsystem. Furthermore, for a two-qubit system, we show the general form of classical correlation-preserving local quantum channels. (paper)

USACE Navigation Channels 2012

Data.gov (United States)

California Natural Resource Agency — This dataset represents both San Francisco and Los Angeles District navigation channel lines. All San Francisco District channel lines were digitized from CAD files...

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

Energy Technology Data Exchange (ETDEWEB)

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.

Laser-induced thermal coagulation enhances skin uptake of topically applied compounds.

Science.gov (United States)

Haak, C S; Hannibal, J; Paasch, U; Anderson, R R; Haedersdal, M

2017-08-01

Ablative fractional laser (AFL) generates microchannels in skin surrounded by a zone of thermally altered tissue, termed the coagulation zone (CZ). The thickness of CZ varies according to applied wavelength and laser settings. It is well-known that AFL channels facilitate uptake of topically applied compounds, but the importance of CZ is unknown. Franz Cells were used to investigate skin uptake and permeation of fluorescent labeled polyethylene glycols (PEGs) with mean molecular weights (MW) of 350, 1,000, and 5,000 Da. Microchannels with CZ thicknesses ranging from 0 to 80 μm were generated from micro-needles (0 μm, CZ-0), and AFL (10,600 nm) applied to -80°C deep frozen skin (20 μm, CZ-20) and skin equilibrated to room temperature (80 μm, CZ-80). Channels penetrated into similar mid-dermal skin depths of 600-700 μm, and number of channels per skin area was similar. At 4 hours incubation, skin uptake of PEGs into CZ and dermis was evaluated by fluorescence microscopy at specific skin depths of 150, 400, and 1,000 μm and the transcutaneous permeation was quantified by fluorescence of receptor fluids. Overall, the highest uptake of PEGs was reached through microchannels surrounded by CZ compared to channels with no CZ (CZ-20 and CZ-80>CZ-0).The thickness of CZ affected PEG distribution in skin. A thin CZ-20 favored significantly higher mean fluorescence intensities inside CZ areas compared to CZ-80 (PEG 350, 1,000, and 5,000; P channels was significantly higher than through CZ-80 and CZ-0 at all skin depths (PEG 350, 1,000 and 5,000, 150-1,000 μm; P distribution, with highest PEG uptake achieved from microchannels surrounded by a thin CZ. Lasers Surg. Med. 49:582-591, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Sedimentary processes of the lower Monterey Fan channel and channel-mouth lobe

Science.gov (United States)

Klaucke, I.; Masson, D.G.; Kenyon, Neil H.; Gardner, J.V.

2004-01-01

The distribution of deposits, sediment transport pathways and processes on the lower Monterey Fan channel and channel-mouth lobe (CML) are studied through the integration of GLORIA and TOBI sidescan sonar data with 7-kHz subbottom profiler records and sediment cores for ground-truthing. The lower Monterey channel is characterised by an up to 30-m-deep channel with poorly developed levees and alternating muddy and silty muddy overbank deposits. The channel is discontinuous, disappearing where gradients are less than about 1:350. Ground-truthing of the large CML shows that the entire CML is characterised by widespread deposits of generally fine sand, with coarser sand at the base of turbidites. Sand is particularly concentrated in finger-like areas of low-backscatter intensity and is interpreted as the result of non-turbulent sediment-gravity flows depositing metres thick massive, fine sand. TOBI sidescan sonar data reveal recent erosional features in the form of scours, secondary channels, large flow slides, and trains of blocks at the distal end of the CML. Erosion is probably related to increasing gradient as the CML approaches Murray Fracture zone and to differential loading of sandy submarine fan deposits onto pelagic clays. Reworking of older flow slides by sediment transport processes on the lobe produces trains of blocks that are several metres in diameter and aligned parallel to the flow direction. ?? 2004 Elsevier B.V. All rights reserved.

Achievable Rates of Secure Transmission in Gaussian MISO Channel with Imperfect Main Channel Estimation

KAUST Repository

Zhou, Xinyu; Rezki, Zouheir; Alomair, Basel; Alouini, Mohamed-Slim

2016-01-01

A Gaussian multiple-input single-output (MISO) fading channel is considered. We assume that the transmitter, in addition to the statistics of all channel gains, is aware instantaneously of a noisy version of the channel to the legitimate receiver. On the other hand, the legitimate receiver is aware instantaneously of its channel to the transmitter, whereas the eavesdropper instantaneously knows all channel gains. We evaluate an achievable rate using a Gaussian input without indexing an auxiliary random variable. A sufficient condition for beamforming to be optimal is provided. When the number of transmit antennas is large, beamforming also turns out to be optimal. In this case, the maximum achievable rate can be expressed in a simple closed form and scales with the logarithm of the number of transmit antennas. Furthermore, in the case when a noisy estimate of the eavesdropper’s channel is also available at the transmitter, we introduce the SNR difference and the SNR ratio criterions and derive the related optimal transmission strategies and the corresponding achievable rates.

Achievable Rates of Secure Transmission in Gaussian MISO Channel with Imperfect Main Channel Estimation

KAUST Repository

Zhou, Xinyu

2016-03-15

A Gaussian multiple-input single-output (MISO) fading channel is considered. We assume that the transmitter, in addition to the statistics of all channel gains, is aware instantaneously of a noisy version of the channel to the legitimate receiver. On the other hand, the legitimate receiver is aware instantaneously of its channel to the transmitter, whereas the eavesdropper instantaneously knows all channel gains. We evaluate an achievable rate using a Gaussian input without indexing an auxiliary random variable. A sufficient condition for beamforming to be optimal is provided. When the number of transmit antennas is large, beamforming also turns out to be optimal. In this case, the maximum achievable rate can be expressed in a simple closed form and scales with the logarithm of the number of transmit antennas. Furthermore, in the case when a noisy estimate of the eavesdropper’s channel is also available at the transmitter, we introduce the SNR difference and the SNR ratio criterions and derive the related optimal transmission strategies and the corresponding achievable rates.

Sodium Channel Nav1.8 Underlies TTX-Resistant Axonal Action Potential Conduction in Somatosensory C-Fibers of Distal Cutaneous Nerves.

Science.gov (United States)

Klein, Amanda H; Vyshnevska, Alina; Hartke, Timothy V; De Col, Roberto; Mankowski, Joseph L; Turnquist, Brian; Bosmans, Frank; Reeh, Peter W; Schmelz, Martin; Carr, Richard W; Ringkamp, Matthias

2017-05-17

Voltage-gated sodium (Na V ) channels are responsible for the initiation and conduction of action potentials within primary afferents. The nine Na V channel isoforms recognized in mammals are often functionally divided into tetrodotoxin (TTX)-sensitive (TTX-s) channels (Na V 1.1-Na V 1.4, Na V 1.6-Na V 1.7) that are blocked by nanomolar concentrations and TTX-resistant (TTX-r) channels (Na V 1.8 and Na V 1.9) inhibited by millimolar concentrations, with Na V 1.5 having an intermediate toxin sensitivity. For small-diameter primary afferent neurons, it is unclear to what extent different Na V channel isoforms are distributed along the peripheral and central branches of their bifurcated axons. To determine the relative contribution of TTX-s and TTX-r channels to action potential conduction in different axonal compartments, we investigated the effects of TTX on C-fiber-mediated compound action potentials (C-CAPs) of proximal and distal peripheral nerve segments and dorsal roots from mice and pigtail monkeys ( Macaca nemestrina ). In the dorsal roots and proximal peripheral nerves of mice and nonhuman primates, TTX reduced the C-CAP amplitude to 16% of the baseline. In contrast, >30% of the C-CAP was resistant to TTX in distal peripheral branches of monkeys and WT and Na V 1.9 -/- mice. In nerves from Na V 1.8 -/- mice, TTX-r C-CAPs could not be detected. These data indicate that Na V 1.8 is the primary isoform underlying TTX-r conduction in distal axons of somatosensory C-fibers. Furthermore, there is a differential spatial distribution of Na V 1.8 within C-fiber axons, being functionally more prominent in the most distal axons and terminal regions. The enrichment of Na V 1.8 in distal axons may provide a useful target in the treatment of pain of peripheral origin. SIGNIFICANCE STATEMENT It is unclear whether individual sodium channel isoforms exert differential roles in action potential conduction along the axonal membrane of nociceptive, unmyelinated peripheral nerve

Taking It to the Streets: Assessing the FBI’s Approach to Combating Illicit Networks

Science.gov (United States)

2010-06-01

provides a review of many of these works and parses the differences between economists , political scientists, organizational theorists, sociologists...physical surveillance, electronic surveillance (wiretaps), undercover operations, and the use of pen registers. ETI can also utilize...surveillance, and undercover operations. By using one or both of the aforementioned investigations, investigators seek to gain evidence of the structure

Sensing with Ion Channels

CERN Document Server

Martinac, Boris

2008-01-01

All living cells are able to detect and translate environmental stimuli into biologically meaningful signals. Sensations of touch, hearing, sight, taste, smell or pain are essential to the survival of all living organisms. The importance of sensory input for the existence of life thus justifies the effort made to understand its molecular origins. Sensing with Ion Channels focuses on ion channels as key molecules enabling biological systems to sense and process the physical and chemical stimuli that act upon cells in their living environment. Its aim is to serve as a reference to ion channel specialists and as a source of new information to non specialists who want to learn about the structural and functional diversity of ion channels and their role in sensory physiology.

Microstructural information from channeling measurements

International Nuclear Information System (INIS)

Quere, Y.

1984-09-01

Channeling is sensitive to nearly all structural changes in solids. One briefly recalls how particles are dechanneled by lattice defects and describes the main applications of channeling to materials science: detection of radiation damage, location of impurity atoms, precipitations in alloys... Channeling being a phenomenon characteristic of perfect crystals, any type of lattice imperfection (phonons, crystal defects, precipitation etc.) is expected to produce dechanneling. Consequently channeling and its opposite, dechanneling, have both been used to study structure and structural changes of materials

Pharmacological modulation of SK3 channels

DEFF Research Database (Denmark)

Grunnet, M; Jespersen, Thomas; Angelo, K

2001-01-01

Small-conductance, calcium-activated K+ channels (SK channels) are voltage-insensitive channels that have been identified molecularly within the last few years. As SK channels play a fundamental role in most excitable cells and participate in afterhyperpolarization (AHP) and spike-frequency adapt...... at concentrations of 3 microM and above. Amitriptyline, a tricyclic antidepressive widely used clinically, inhibits SK3 channels with an IC50 of 39.1 +/- 10 microM (n=6)....

Optimising the Quality of Experience during Channel Zapping : The Impact of Advertisements during Channel Zapping

NARCIS (Netherlands)

Kooij, R.E.; Klos, V.B.; Godana, B.E.; Nicolai, F.P.; Ahmed, O.K.

2009-01-01

Nowadays various digital television services are available. However, the user of these services experiences longer delays than the traditional analog TV while switching from channel to channel. The digital TV operator usually displays a black screen with the channel number during zapping. However,

On the Capacity of the Dirty Paper Channel with Fast Fading and Discrete Channel States

OpenAIRE

Rini, Stefano; Shitz, Shlomo Shamai

2016-01-01

The "writing dirty paper" capacity result crucially dependents on the perfect channel knowledge at the transmitter as the presence of even a small uncertainty in the channel realization gravely hampers the ability of the transmitter to pre-code its transmission against the channel state. This is particularly disappointing as it implies that interference pre-coding in practical systems is effective only when the channel estimates at the users have very high precision, a condition which is gene...

Bisacenaphthopyrazinoquinoxaline derivatives: Synthesis, physical properties and applications as semiconductors for n-channel field effect transistors

KAUST Repository

Tong, Chenhua

2013-01-01

Several bisacenaphthopyrazinoquinoxaline (BAPQ) based derivatives 1-3 were synthesized by condensation between the acenaphthenequinones and 1,2,4,5-tetraaminobenzene tetrahydrochloride. Their optical, electrochemical and self-assembling properties are tuned by different substituents. Among them, compound 3 possesses a homogeneously distributed low-lying LUMO due to the peripheral substitution with four cyano groups. The corresponding n-channel field effect transistors showed a field effect electron mobility of 5 × 10-3 cm2 V-1 s-1. © 2013 The Royal Society of Chemistry.

Downlink Channel Estimation in Cellular Systems with Antenna Arrays at Base Stations Using Channel Probing with Feedback

Directory of Open Access Journals (Sweden)

Biguesh Mehrzad

2004-01-01

Full Text Available In mobile communication systems with multisensor antennas at base stations, downlink channel estimation plays a key role because accurate channel estimates are needed for transmit beamforming. One efficient approach to this problem is channel probing with feedback. In this method, the base station array transmits probing (training signals. The channel is then estimated from feedback reports provided by the users. This paper studies the performance of the channel probing method with feedback using a multisensor base station antenna array and single-sensor users. The least squares (LS, linear minimum mean square error (LMMSE, and a new scaled LS (SLS approaches to the channel estimation are studied. Optimal choice of probing signals is investigated for each of these techniques and their channel estimation performances are analyzed. In the case of multiple LS channel estimates, the best linear unbiased estimation (BLUE scheme for their linear combining is developed and studied.

TRP channels in kidney disease.

NARCIS (Netherlands)

Hsu, Y.J.; Hoenderop, J.G.J.; Bindels, R.J.M.

2007-01-01

Mammalian TRP channel proteins form six-transmembrane cation-permeable channels that may be grouped into six subfamilies on the basis of amino acid sequence homology (TRPC, TRPV, TRPM, TRPA, TRPP, and TRPML). Recent studies of TRP channels indicate that they are involved in numerous fundamental cell

Plasma channels for electron beam transport

International Nuclear Information System (INIS)

Schneider, R.F.; Smith, J.R.; Moffatt, M.E.; Nguyen, K.T.; Uhm, H.S.

1988-01-01

In recent years, there has been much interest in transport of intense relativistic electron beams using plasma channels. These channels are formed by either: ionization of an organic gas by UV photoionization or electron impact ionization of a low pressure gas utilizing a low energy (typically several hundred volts) electron gun. The second method is discussed here. As their electron gun, the authors used a 12 volt lightbulb filament which is biased to -400 volts with respect to the grounded 15 cm diameter drift tube. The electrons emitted from the filament are confined by an axial magnetic field of --100 Gauss to create a plasma channel which is less than 1 cm in radius. The channel density has been determined with Langmuir probes and the resulting line densities were found to be 10 11 to 10 12 per cm. When a multi-kiloamp electron beam is injected onto this channel, the beam space charge will eject the plasma electrons leaving the ions behind to charge neutralize the electron beam, hence allowing the beam to propagate. In this work, the authors performed experimental studies on the dynamics of the plasma channel. These include Langmuir probe measurements of a steady state (DC) channel, as well as time-resolved Langmuir probe studies of pulsed channels. In addition they performed experimental studies of beam propagation in these plasma channels. Specifically, they observed the behavior of current transport in these channels. Detailed results of beam transport and channel studies are presented

Novel Compound Heterozygous CLCNKB Gene Mutations (c.1755A>G/ c.848_850delTCT) Cause Classic Bartter Syndrome.

Science.gov (United States)

Wang, Chunli; Chen, Ying; Zheng, Bixia; Zhu, Mengshu; Fan, Jia; Wang, Juejin; Jia, Zhanjun; Huang, Songming; Zhang, Aihua

2018-02-14

Inactivated variants in CLCNKB gene encoding the basolateral chloride channel ClC-Kb cause classic Bartter syndrome characterized by hypokalemic metabolic alkalosis and hyperreninemic hyperaldosteronism. Here we identified two cBS siblings presenting hypokalemia in a Chinese family due to novel compound heterozygous CLCNKB mutations (c.848_850delTCT/c.1755A>G). Compound heterozygosity was confirmed by amplifying and sequencing the patient's genomic DNA. The synonymous mutation c.1755A>G (Thr585Thr) was located at +2bp from the 5' splice donor site in exon 15, further transcript analysis demonstrated that this single nucleotide mutation causes exclusion of exon 15 in the cDNA from the proband and his mother. Furthermore, we investigated the expression and protein trafficking change of c.848_850delTCT (TCT) and exon 15 deletion（E15）mutation in vitro. The E15 mutation markedly decreased the expression of ClC-Kb and resulted in a low-molecular-weight band (~55kD) trapping in the endoplasmic reticulum, while the TCT mutant only decreased the total and plasma membrane ClC-Kb protein expression but did not affect the subcellular localization. Finally, we studied the physiological functions of mutations by using whole-cell patch clamp and found that E15 or TCT mutation decreased the current of ClC-Kb/barttin channel. These results suggested that the compound defective mutations of CLCNKB gene are the molecular mechanism of the two cBS siblings.

Dystrophin is required for the normal function of the cardio-protective K(ATP channel in cardiomyocytes.

Directory of Open Access Journals (Sweden)

Laura Graciotti

Full Text Available Duchenne and Becker muscular dystrophy patients often develop a cardiomyopathy for which the pathogenesis is still unknown. We have employed the murine animal model of Duchenne muscular dystrophy (mdx, which develops a cardiomyopathy that includes some characteristics of the human disease, to study the molecular basis of this pathology. Here we show that the mdx mouse heart has defects consistent with alteration in compounds that regulate energy homeostasis including a marked decrease in creatine-phosphate (PC. In addition, the mdx heart is more susceptible to anoxia than controls. Since the cardio-protective ATP sensitive potassium channel (K(ATP complex and PC have been shown to interact we investigated whether deficits in PC levels correlate with other molecular events including K(ATP ion channel complex presence, its functionality and interaction with dystrophin. We found that this channel complex is present in the dystrophic cardiac cell membrane but its ability to sense a drop in the intracellular ATP concentration and consequently open is compromised by the absence of dystrophin. We further demonstrate that the creatine kinase muscle isoform (CKm is displaced from the plasma membrane of the mdx cardiac cells. Considering that CKm is a determinant of K(ATP channel complex function we hypothesize that dystrophin acts as a scaffolding protein organizing the K(ATP channel complex and the enzymes necessary for its correct functioning. Therefore, the lack of proper functioning of the cardio-protective K(ATP system in the mdx cardiomyocytes may be part of the mechanism contributing to development of cardiac disease in dystrophic patients.

The vacuolar channel VvALMT9 mediates malate and tartrate accumulation in berries of Vitis vinifera.

Science.gov (United States)

De Angeli, Alexis; Baetz, Ulrike; Francisco, Rita; Zhang, Jingbo; Chaves, Maria Manuela; Regalado, Ana

2013-08-01

Vitis vinifera L. represents an economically important fruit species. Grape and wine flavour is made from a complex set of compounds. The acidity of berries is a major parameter in determining grape berry quality for wine making and fruit consumption. Despite the importance of malic and tartaric acid (TA) storage and transport for grape berry acidity, no vacuolar transporter for malate or tartrate has been identified so far. Some members of the aluminium-activated malate transporter (ALMT) anion channel family from Arabidopsis thaliana have been shown to be involved in mediating malate fluxes across the tonoplast. Therefore, we hypothesised that a homologue of these channels could have a similar role in V. vinifera grape berries. We identified homologues of the Arabidopsis vacuolar anion channel AtALMT9 through a TBLASTX search on the V. vinifera genome database. We cloned the closest homologue of AtALMT9 from grape berry cDNA and designated it VvALMT9. The expression profile revealed that VvALMT9 is constitutively expressed in berry mesocarp tissue and that its transcription level increases during fruit maturation. Moreover, we found that VvALMT9 is targeted to the vacuolar membrane. Using patch-clamp analysis, we could show that, besides malate, VvALMT9 mediates tartrate currents which are higher than in its Arabidopsis homologue. In summary, in the present study we provide evidence that VvALMT9 is a vacuolar malate channel expressed in grape berries. Interestingly, in V. vinifera, a tartrate-producing plant, the permeability of the channel is apparently adjusted to TA.

Dimension measuring method for channel box

International Nuclear Information System (INIS)

Jo, Hiroto.

1995-01-01

The device of the present invention concerns detection of a channel box for spent fuel assemblies of a BWR type reactor, which measures a cross sectional shape and dimension of the channel box to check deformation amount such as expansion. That is, a customary fuel exchanger and a dimension measuring device are used. The lower end of the channel box is measured by a distance sensor of the dimension measuring device when it is aligned with a position of the distance sensor. The channel box is lowered at the same time while detecting axial position data of the fuel exchanger. The position of the channel box in an axial direction is detected based on axial position data of the fuel exchanger. The lower end of the channel box can accurately be recognized by the detection of both of them. Subsequent deformation measurement for the channel box at accurate axial positions is enabled. In addition, since the axial position data of the fuel exchanger per se are detected, an axial profile of the channel box can be measured even if a lifting speed of the channel box is varied on every region. (I.S.)

On the low SNR capacity of MIMO fading channels with imperfect channel state information

KAUST Repository

Benkhelifa, Fatma

2014-06-01

The capacity of multiple-input multiple-output (MIMO) Rayleigh fading channels with full knowledge of channel state information (CSI) at both the transmitter and the receiver (CSI-TR) has been shown recently to scale at low signal-to-noise ratio (SNR) essentially as SNR log(1/SNR), independently of the number of transmit and receive antennas. In this paper, we investigate the ergodic capacity of MIMO Rayleigh fading channel with estimated channel state information at the transmitter (CSI-T) and possibly imperfect channel state information at the receiver (CSI-R). Our framework can be seen as a generalization of previous works as it can capture the perfect CSI-TR as a special case when the estimation error variance goes to zero. In this paper, we mainly focus on the low SNR regime, and we show that the capacity scales as (1-α) SNR log(1/SNR), where α is the estimation error variance. This characterization shows the loss of performance due to error estimation over the perfect channel state information at both the transmitter and the receiver. As a by-product of our new analysis, we show that our framework can be also extended to characterize the capacity of MIMO Rician fading channels at low SNR with possibly imperfect CSI-T and CSI-R. © 1972-2012 IEEE.

On the low SNR capacity of MIMO fading channels with imperfect channel state information

KAUST Repository

Benkhelifa, Fatma

2014-05-01

The capacity of Multiple Input Multiple Output (MIMO) Rayleigh fading channels with full knowledge of channel state information (CSI) at both the transmitter and the receiver (CSI-TR) has been shown recently to scale at low Signal-to-Noise Ratio (SNR) essentially as SNR log(1=SNR), independently of the number of transmit and receive antennas. In this paper, we investigate the ergodic capacity of MIMO Rayleigh fading channel with estimated channel state information at the transmitter (CSI-T) and possibly imperfect channel state information at the receiver (CSI-R). Our framework can be seen as a generalization of previous works as it can capture the perfect CSI-TR as a special case when the estimation error variance goes to zero. In our work, we mainly focus on the low SNR regime and we show that the capacity scales as (1-α) SNR log(1=SNR), where α is the estimation error variance. This characterization shows the loss of performance due to error estimation over the perfect channel state information at both the transmitter and the receiver. As a by-product of our new analysis, we show that our framework can also be extended to characterize the capacity of MIMO Rician fading channels at low SNR with possibly imperfect CSI-T and CSI-R. © 2014 IFIP.

An Adaptive Channel Estimation Algorithm Using Time-Frequency Polynomial Model for OFDM with Fading Multipath Channels

Directory of Open Access Journals (Sweden)

Liu KJ Ray

2002-01-01

Full Text Available Orthogonal frequency division multiplexing (OFDM is an effective technique for the future 3G communications because of its great immunity to impulse noise and intersymbol interference. The channel estimation is a crucial aspect in the design of OFDM systems. In this work, we propose a channel estimation algorithm based on a time-frequency polynomial model of the fading multipath channels. The algorithm exploits the correlation of the channel responses in both time and frequency domains and hence reduce more noise than the methods using only time or frequency polynomial model. The estimator is also more robust compared to the existing methods based on Fourier transform. The simulation shows that it has more than improvement in terms of mean-squared estimation error under some practical channel conditions. The algorithm needs little prior knowledge about the delay and fading properties of the channel. The algorithm can be implemented recursively and can adjust itself to follow the variation of the channel statistics.

Demystifying Mechanosensitive Piezo Ion Channels.

Science.gov (United States)

Xu, X Z Shawn

2016-06-01

Mechanosensitive channels mediate touch, hearing, proprioception, and blood pressure regulation. Piezo proteins, including Piezo1 and Piezo2, represent a new class of mechanosensitive channels that have been reported to play key roles in most, if not all, of these modalities. The structural architecture and molecular mechanisms by which Piezos act as mechanosensitive channels, however, remain mysterious. Two new studies have now provided critical insights into the atomic structure and molecular basis of the ion permeation and mechano-gating properties of the Piezo1 channel.

Calcium channel blocker overdose

Science.gov (United States)

... this page: //medlineplus.gov/ency/article/002580.htm Calcium-channel blocker overdose To use the sharing features on this page, please enable JavaScript. Calcium-channel blockers are a type of medicine used ...

VKCDB: Voltage-gated potassium channel database

Directory of Open Access Journals (Sweden)

Gallin Warren J

2004-01-01

Full Text Available Abstract Background The family of voltage-gated potassium channels comprises a functionally diverse group of membrane proteins. They help maintain and regulate the potassium ion-based component of the membrane potential and are thus central to many critical physiological processes. VKCDB (Voltage-gated potassium [K] Channel DataBase is a database of structural and functional data on these channels. It is designed as a resource for research on the molecular basis of voltage-gated potassium channel function. Description Voltage-gated potassium channel sequences were identified by using BLASTP to search GENBANK and SWISSPROT. Annotations for all voltage-gated potassium channels were selectively parsed and integrated into VKCDB. Electrophysiological and pharmacological data for the channels were collected from published journal articles. Transmembrane domain predictions by TMHMM and PHD are included for each VKCDB entry. Multiple sequence alignments of conserved domains of channels of the four Kv families and the KCNQ family are also included. Currently VKCDB contains 346 channel entries. It can be browsed and searched using a set of functionally relevant categories. Protein sequences can also be searched using a local BLAST engine. Conclusions VKCDB is a resource for comparative studies of voltage-gated potassium channels. The methods used to construct VKCDB are general; they can be used to create specialized databases for other protein families. VKCDB is accessible at http://vkcdb.biology.ualberta.ca.

Morphology of channels and channel-sand bodies in the Glauconitic sandstone member (Upper Mannville), Little Bow area, Alberta

Energy Technology Data Exchange (ETDEWEB)

Hopkins, J.C.; Hermanson, S.W.; Lawton, D.C.

1982-12-01

Large channels in the Glauconitic sandstone member of southern Alberta have proved to be difficult exploration targets because of an irregular distribution of reservoir sands within the channels. In the Little Bow area, two channels are present in the lower part of the Glauconitic member and have cut into the underlying Calcareous member. The channels can be recognized where they truncate regional markers of the Calcareous member -- the Bantry shale and Ostracod limestone, and where channel-fill deposits exhibit uniform geophysical log characters, indicating sandstone- or mudstone-filled reaches. Sediments of the Glauconitic member adjacent to the channels comprise a series of splay sandstones and mudstones that prograded into interdistributary bays of the lower delta plain. The two channels associated with these deposits are interpreted as distributary channels. Sand bodies within the channels formed as lateral bars and are isolated by mudstones which mark the abandoned stream course. Geological exploration for these discontinuous channel sandstones is difficult, and high-resolutio seismic data integrated with sound geologic modelling are critical for successful prospect delineation.

A Mathematical Model of Membrane Gas Separation with Energy Transfer by Molecules of Gas Flowing in a Channel to Molecules Penetrating this Channel from the Adjacent Channel

Directory of Open Access Journals (Sweden)

Szwast Maciej

2015-06-01

Full Text Available The paper presents the mathematical modelling of selected isothermal separation processes of gaseous mixtures, taking place in plants using membranes, in particular nonporous polymer membranes. The modelling concerns membrane modules consisting of two channels - the feeding and the permeate channels. Different shapes of the channels cross-section were taken into account. Consideration was given to co-current and counter-current flows, for feeding and permeate streams, respectively, flowing together with the inert gas receiving permeate. In the proposed mathematical model it was considered that pressure of gas changes along the length of flow channels was the result of both - the drop of pressure connected with flow resistance, and energy transfer by molecules of gas flowing in a given channel to molecules which penetrate this channel from the adjacent channel. The literature on membrane technology takes into account only the drop of pressure connected with flow resistance. Consideration given to energy transfer by molecules of gas flowing in a given channel to molecules which penetrate this channel from the adjacent channel constitute the essential novelty in the current study. The paper also presents results of calculations obtained by means of a computer program which used equations of the derived model. Physicochemical data concerning separation of the CO2/CH4 mixture with He as the sweep gas and data concerning properties of the membrane made of PDMS were assumed for calculations.

Calcium channel blocker poisoning

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Miran Brvar

2005-04-01

Full Text Available Background: Calcium channel blockers act at L-type calcium channels in cardiac and vascular smooth muscles by preventing calcium influx into cells with resultant decrease in vascular tone and cardiac inotropy, chronotropy and dromotropy. Poisoning with calcium channel blockers results in reduced cardiac output, bradycardia, atrioventricular block, hypotension and shock. The findings of hypotension and bradycardia should suggest poisoning with calcium channel blockers.Conclusions: Treatment includes immediate gastric lavage and whole-bowel irrigation in case of ingestion of sustainedrelease products. All patients should receive an activated charcoal orally. Specific treatment includes calcium, glucagone and insulin, which proved especially useful in shocked patients. Supportive care including the use of catecholamines is not always effective. In the setting of failure of pharmacological therapy transvenous pacing, balloon pump and cardiopulmonary by-pass may be necessary.

Channel selection for automatic seizure detection

DEFF Research Database (Denmark)

Duun-Henriksen, Jonas; Kjaer, Troels Wesenberg; Madsen, Rasmus Elsborg

2012-01-01

Objective: To investigate the performance of epileptic seizure detection using only a few of the recorded EEG channels and the ability of software to select these channels compared with a neurophysiologist. Methods: Fifty-nine seizures and 1419 h of interictal EEG are used for training and testing...... of an automatic channel selection method. The characteristics of the seizures are extracted by the use of a wavelet analysis and classified by a support vector machine. The best channel selection method is based upon maximum variance during the seizure. Results: Using only three channels, a seizure detection...... sensitivity of 96% and a false detection rate of 0.14/h were obtained. This corresponds to the performance obtained when channels are selected through visual inspection by a clinical neurophysiologist, and constitutes a 4% improvement in sensitivity compared to seizure detection using channels recorded...

UMTS Common Channel Sensitivity Analysis

DEFF Research Database (Denmark)

Pratas, Nuno; Rodrigues, António; Santos, Frederico

2006-01-01

and as such it is necessary that both channels be available across the cell radius. This requirement makes the choice of the transmission parameters a fundamental one. This paper presents a sensitivity analysis regarding the transmission parameters of two UMTS common channels: RACH and FACH. Optimization of these channels...... is performed and values for the key transmission parameters in both common channels are obtained. On RACH these parameters are the message to preamble offset, the initial SIR target and the preamble power step while on FACH it is the transmission power offset....

Defect Distributions in Channeling Experiments

DEFF Research Database (Denmark)

Andersen, Hans Henrik; Sigmund, P.

1965-01-01

A simple collision model allows to calculate energy losses of perfectly channeled particles. The maximum energy loss is related in a simple way to the displacement energy of lattice atoms perpendicular to the channel. From that, one obtains rather definite predictions on the possibility...... of radiation damage by channeled particles. As an application, one gets a necessary criterion for the occurence of super tails in channeling experiments. The theory involves some assumptions on the behaviour of Born-Mayer potentials which are verified by comparison to experimental displacement energies....

Cholesterol influences voltage-gated calcium channels and BK-type potassium channels in auditory hair cells.

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Erin K Purcell

Full Text Available The influence of membrane cholesterol content on a variety of ion channel conductances in numerous cell models has been shown, but studies exploring its role in auditory hair cell physiology are scarce. Recent evidence shows that cholesterol depletion affects outer hair cell electromotility and the voltage-gated potassium currents underlying tall hair cell development, but the effects of cholesterol on the major ionic currents governing auditory hair cell excitability are unknown. We investigated the effects of a cholesterol-depleting agent (methyl beta cyclodextrin, MβCD on ion channels necessary for the early stages of sound processing. Large-conductance BK-type potassium channels underlie temporal processing and open in a voltage- and calcium-dependent manner. Voltage-gated calcium channels (VGCCs are responsible for calcium-dependent exocytosis and synaptic transmission to the auditory nerve. Our results demonstrate that cholesterol depletion reduced peak steady-state calcium-sensitive (BK-type potassium current by 50% in chick cochlear hair cells. In contrast, MβCD treatment increased peak inward calcium current (~30%, ruling out loss of calcium channel expression or function as a cause of reduced calcium-sensitive outward current. Changes in maximal conductance indicated a direct impact of cholesterol on channel number or unitary conductance. Immunoblotting following sucrose-gradient ultracentrifugation revealed BK expression in cholesterol-enriched microdomains. Both direct impacts of cholesterol on channel biophysics, as well as channel localization in the membrane, may contribute to the influence of cholesterol on hair cell physiology. Our results reveal a new role for cholesterol in the regulation of auditory calcium and calcium-activated potassium channels and add to the growing evidence that cholesterol is a key determinant in auditory physiology.

Discovery and characterization of a potent and selective inhibitor of Aedes aegypti inward rectifier potassium channels.

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Rene Raphemot

Full Text Available Vector-borne diseases such as dengue fever and malaria, which are transmitted by infected female mosquitoes, affect nearly half of the world's population. The emergence of insecticide-resistant mosquito populations is reducing the effectiveness of conventional insecticides and threatening current vector control strategies, which has created an urgent need to identify new molecular targets against which novel classes of insecticides can be developed. We previously demonstrated that small molecule inhibitors of mammalian Kir channels represent promising chemicals for new mosquitocide development. In this study, high-throughput screening of approximately 30,000 chemically diverse small-molecules was employed to discover potent and selective inhibitors of Aedes aegypti Kir1 (AeKir1 channels heterologously expressed in HEK293 cells. Of 283 confirmed screening 'hits', the small-molecule inhibitor VU625 was selected for lead optimization and in vivo studies based on its potency and selectivity toward AeKir1, and tractability for medicinal chemistry. In patch clamp electrophysiology experiments of HEK293 cells, VU625 inhibits AeKir1 with an IC50 value of 96.8 nM, making VU625 the most potent inhibitor of AeKir1 described to date. Furthermore, electrophysiology experiments in Xenopus oocytes revealed that VU625 is a weak inhibitor of AeKir2B. Surprisingly, injection of VU625 failed to elicit significant effects on mosquito behavior, urine excretion, or survival. However, when co-injected with probenecid, VU625 inhibited the excretory capacity of mosquitoes and was toxic, suggesting that the compound is a substrate of organic anion and/or ATP-binding cassette (ABC transporters. The dose-toxicity relationship of VU625 (when co-injected with probenecid is biphasic, which is consistent with the molecule inhibiting both AeKir1 and AeKir2B with different potencies. This study demonstrates proof-of-concept that potent and highly selective inhibitors of mosquito

Post-Translational Modifications of TRP Channels

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Olaf Voolstra

2014-04-01

Full Text Available Transient receptor potential (TRP channels constitute an ancient family of cation channels that have been found in many eukaryotic organisms from yeast to human. TRP channels exert a multitude of physiological functions ranging from Ca2+ homeostasis in the kidney to pain reception and vision. These channels are activated by a wide range of stimuli and undergo covalent post-translational modifications that affect and modulate their subcellular targeting, their biophysical properties, or channel gating. These modifications include N-linked glycosylation, protein phosphorylation, and covalent attachment of chemicals that reversibly bind to specific cysteine residues. The latter modification represents an unusual activation mechanism of ligand-gated ion channels that is in contrast to the lock-and-key paradigm of receptor activation by its agonists. In this review, we summarize the post-translational modifications identified on TRP channels and, when available, explain their physiological role.

Optical Communications Channel Combiner

Science.gov (United States)

Quirk, Kevin J.; Quirk, Kevin J.; Nguyen, Danh H.; Nguyen, Huy

2012-01-01

NASA has identified deep-space optical communications links as an integral part of a unified space communication network in order to provide data rates in excess of 100 Mb/s. The distances and limited power inherent in a deep-space optical downlink necessitate the use of photon-counting detectors and a power-efficient modulation such as pulse position modulation (PPM). For the output of each photodetector, whether from a separate telescope or a portion of the detection area, a communication receiver estimates a log-likelihood ratio for each PPM slot. To realize the full effective aperture of these receivers, their outputs must be combined prior to information decoding. A channel combiner was developed to synchronize the log-likelihood ratio (LLR) sequences of multiple receivers, and then combines these into a single LLR sequence for information decoding. The channel combiner synchronizes the LLR sequences of up to three receivers and then combines these into a single LLR sequence for output. The channel combiner has three channel inputs, each of which takes as input a sequence of four-bit LLRs for each PPM slot in a codeword via a XAUI 10 Gb/s quad optical fiber interface. The cross-correlation between the channels LLR time series are calculated and used to synchronize the sequences prior to combining. The output of the channel combiner is a sequence of four-bit LLRs for each PPM slot in a codeword via a XAUI 10 Gb/s quad optical fiber interface. The unit is controlled through a 1 Gb/s Ethernet UDP/IP interface. A deep-space optical communication link has not yet been demonstrated. This ground-station channel combiner was developed to demonstrate this capability and is unique in its ability to process such a signal.

Isospin influence on the decay modes of compound systems produced in the 78,86Kr + 40,48Ca at 10 AMeV

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Pirrone S.

2016-01-01

Full Text Available The study of the decay modes competition of the compound systems produced in the collisions 78Kr+40Ca and 86Kr+48Ca at 10AMeV is presented. In particular, the N/Z entrance channel influence on the decay paths of the compound systems, directly connected to the isospin influence, is investigated. The experiment was performed at the INFN Laboratori Nazionali del Sud (LNS in Catania by using the 4π multi-detector CHIMERA. Charge, mass, angular distributions and kinematical features of the reaction products were studied. The analysis shows some differences in the contribution arising from the various reaction mechanisms for the neutron poor and neutron rich systems. Comparison with theoretical statistical and dynamical models are presented for the two systems. Besides a study of the influence of the energy on the entrance channel is performed for the 78Kr+40Ca reaction, by comparing the results of this experiment to those obtained for the same system at 5.5 AMeV with the INDRA device at GANIL.

On the capacity of nakagami-m fading Channels with full channel state information at low SNR

KAUST Repository

Rezki, Zouheir

2012-06-01

The capacity of flat Rayleigh fading channels with full channel state information (CSI) at the transmitter and at the receiver at asymptotically low SNR has been recently shown to scale essentially as SNR log(1/SNR)}. In this paper, we investigate the Nakagami-m fading channel capacity with full CSI, and show that the capacity of this channel scales essentially as m/ Omega SNR log(1/SNR), where m is the Nakagami-m fading parameter and where Ω is the channel mean-square. We also show that one-bit CSI at the transmitter is enough to achieve this asymptotic capacity using an On-Off power control scheme. Our framework may be seen as a generalization of previous works as it captures the Rayleigh fading channel as a special case by taking m=1. © 2012 IEEE.

Identifying cochlear implant channels with poor electrode-neuron interface: partial tripolar, single-channel thresholds and psychophysical tuning curves.

Science.gov (United States)

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

Information transfer through quantum channels

International Nuclear Information System (INIS)

Kretschmann, D.

2007-01-01

This PhD thesis represents work done between Aug. 2003 and Dec. 2006 in Reinhard F. Werner's quantum information theory group at Technische Universitaet Braunschweig, and Artur Ekert's Centre for Quantum Computation at the University of Cambridge. My thesis falls into the field of abstract quantum information theory. This work investigates both fundamental properties of quantum channels and their asymptotic capacities for classical as well as quantum information transfer. Stinespring's theorem is the basic structure theorem for quantum channels. It implies that every quantum channel can be represented as a unitary evolution on an enlarged system. In Ch. 3 we present a continuity theorem for Stinespring's representation: two quantum channels are similar if and only if it is possible to find unitary implementations that are likewise similar, with dimension-independent norm bounds. The continuity theorem allows to derive a formulation of the information-disturbance tradeoff in terms of quantum channels, and a continuity estimate for the no-broadcasting principle. In Ch. 4 we then apply the continuity theorem to give a strengthened no-go proof for quantum bit commitment, an important cryptographic primitive. This result also provides a natural characterization of those protocols that fall outside the standard setting of unconditional security, and thus may allow secure bit commitment. We present a new such protocol whose security relies on decoherence in the receiver's lab. Ch. 5 reviews the capacities of quantum channels for the transfer of both classical and quantum information, and investigates several variations in the notion of channel capacity. Memory effects are then investigated in detail in Ch. 6. We advertise a model which is sufficiently general to encompass all causal automata: every quantum process in which the outputs up to any given time t do not depend on the inputs at times t'>t can be represented as a concatenated memory channel. We then explain how

Information transfer through quantum channels

Energy Technology Data Exchange (ETDEWEB)

Kretschmann, D.

2007-03-12

This PhD thesis represents work done between Aug. 2003 and Dec. 2006 in Reinhard F. Werner's quantum information theory group at Technische Universitaet Braunschweig, and Artur Ekert's Centre for Quantum Computation at the University of Cambridge. My thesis falls into the field of abstract quantum information theory. This work investigates both fundamental properties of quantum channels and their asymptotic capacities for classical as well as quantum information transfer. Stinespring's theorem is the basic structure theorem for quantum channels. It implies that every quantum channel can be represented as a unitary evolution on an enlarged system. In Ch. 3 we present a continuity theorem for Stinespring's representation: two quantum channels are similar if and only if it is possible to find unitary implementations that are likewise similar, with dimension-independent norm bounds. The continuity theorem allows to derive a formulation of the information-disturbance tradeoff in terms of quantum channels, and a continuity estimate for the no-broadcasting principle. In Ch. 4 we then apply the continuity theorem to give a strengthened no-go proof for quantum bit commitment, an important cryptographic primitive. This result also provides a natural characterization of those protocols that fall outside the standard setting of unconditional security, and thus may allow secure bit commitment. We present a new such protocol whose security relies on decoherence in the receiver's lab. Ch. 5 reviews the capacities of quantum channels for the transfer of both classical and quantum information, and investigates several variations in the notion of channel capacity. Memory effects are then investigated in detail in Ch. 6. We advertise a model which is sufficiently general to encompass all causal automata: every quantum process in which the outputs up to any given time t do not depend on the inputs at times t'>t can be represented as a concatenated memory

TRP channels: an overview

DEFF Research Database (Denmark)

Pedersen, Stine Falsig; Owsianik, Grzegorz; Nilius, Bernd

2005-01-01

The TRP ("transient receptor potential") family of ion channels now comprises more than 30 cation channels, most of which are permeable for Ca2+, and some also for Mg2+. On the basis of sequence homology, the TRP family can be divided in seven main subfamilies: the TRPC ('Canonical') family......, the TRPV ('Vanilloid') family, the TRPM ('Melastatin') family, the TRPP ('Polycystin') family, the TRPML ('Mucolipin') family, the TRPA ('Ankyrin') family, and the TRPN ('NOMPC') family. The cloning and characterization of members of this cation channel family has exploded during recent years, leading...... to a plethora of data on the roles of TRPs in a variety of tissues and species, including mammals, insects, and yeast. The present review summarizes the most pertinent recent evidence regarding the structural and functional properties of TRP channels, focusing on the regulation and physiology of mammalian TRPs....

On Channel Estimation for OFDM/TDM Using MMSE-FDE in a Fast Fading Channel

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Gacanin Haris

2009-01-01

Full Text Available Abstract MMSE-FDE can improve the transmission performance of OFDM combined with time division multiplexing (OFDM/TDM, but knowledge of the channel state information and the noise variance is required to compute the MMSE weight. In this paper, a performance evaluation of OFDM/TDM using MMSE-FDE with pilot-assisted channel estimation over a fast fading channel is presented. To improve the tracking ability against fast fading a robust pilot-assisted channel estimation is presented that uses time-domain filtering on a slot-by-slot basis and frequency-domain interpolation. We derive the mean square error (MSE of the channel estimator and then discuss a tradeoff between improving the tracking ability against fading and the noise reduction. The achievable bit error rate (BER performance is evaluated by computer simulation and compared with conventional OFDM. It is shown that the OFDM/TDM using MMSE-FDE achieves a lower BER and a better tracking ability against fast fading in comparison with conventional OFDM.

Sanskrit Compound Processor

Science.gov (United States)

Kumar, Anil; Mittal, Vipul; Kulkarni, Amba

Sanskrit is very rich in compound formation. Typically a compound does not code the relation between its components explicitly. To understand the meaning of a compound, it is necessary to identify its components, discover the relations between them and finally generate a paraphrase of the compound. In this paper, we discuss the automatic segmentation and type identification of a compound using simple statistics that results from the manually annotated data.

A Crash Course in Calcium Channels.

Science.gov (United States)

Zamponi, Gerald W

2017-12-20

Much progress has been made in understanding the molecular physiology and pharmacology of calcium channels. Recently, there have been tremendous advances in learning about calcium channel structure and function through crystallography and cryo-electron microscopy studies. Here, I will give an overview of our knowledge about calcium channels, and highlight two recent studies that give important insights into calcium channel structure.

Effects of dislocations on electron channeling

International Nuclear Information System (INIS)

George, Juby; Pathak, A P

2009-01-01

The phenomenon of electron channeling in a crystal affected by dislocations is considered. Earlier we had considered the quantum aspects of the positron channeling in a crystal bent by dislocations where the effects of longitudinal motion of the particle were also considered along with the transverse motion. In this paper, the effective potential for the electron case is found for the two regions of dislocation-affected channel. There is considerable shift in the potential minima due to dislocations. The frequency and the corresponding spectrum of the channeling radiation due to electrons channeling through the perfect channel and the two regions of dislocation-affected channels are calculated. The spectral distribution of radiation intensity changes with the parameters of dislocation. The continuity of wavefunctions and their derivatives is used at the three boundaries and the reflection and transmission coefficients are found using these boundary conditions in the same way as in the positron case.

Omni channel fashion shopping

NARCIS (Netherlands)

Kemperman, A.D.A.M.; van Delft, L.; Borgers, A.W.J.; Pantano, E.

2015-01-01

This chapter gives insight into consumers' online and offline fashion shopping behavior, consumers' omni-channel usage during the shopping process, and consumer fashion shopper segments. Based on a literature review, omni-channel shopping behavior during the shopping process was operationalized.

Flavonoid Regulation of HCN2 Channels*

Science.gov (United States)

Carlson, Anne E.; Rosenbaum, Joel C.; Brelidze, Tinatin I.; Klevit, Rachel E.; Zagotta, William N.

2013-01-01

The hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels are pacemaker channels whose currents contribute to rhythmic activity in the heart and brain. HCN channels open in response to hyperpolarizing voltages, and the binding of cAMP to their cyclic nucleotide-binding domain (CNBD) facilitates channel opening. Here, we report that, like cAMP, the flavonoid fisetin potentiates HCN2 channel gating. Fisetin sped HCN2 activation and shifted the conductance-voltage relationship to more depolarizing potentials with a half-maximal effective concentration (EC50) of 1.8 μm. When applied together, fisetin and cAMP regulated HCN2 gating in a nonadditive fashion. Fisetin did not potentiate HCN2 channels lacking their CNBD, and two independent fluorescence-based binding assays reported that fisetin bound to the purified CNBD. These data suggest that the CNBD mediates the fisetin potentiation of HCN2 channels. Moreover, binding assays suggest that fisetin and cAMP partially compete for binding to the CNBD. NMR experiments demonstrated that fisetin binds within the cAMP-binding pocket, interacting with some of the same residues as cAMP. Together, these data indicate that fisetin is a partial agonist for HCN2 channels. PMID:24085296

Transportation channels calculation method in MATLAB

International Nuclear Information System (INIS)

Averyanov, G.P.; Budkin, V.A.; Dmitrieva, V.V.; Osadchuk, I.O.; Bashmakov, Yu.A.

2014-01-01

Output devices and charged particles transport channels are necessary components of any modern particle accelerator. They differ both in sizes and in terms of focusing elements depending on particle accelerator type and its destination. A package of transport line designing codes for magnet optical channels in MATLAB environment is presented in this report. Charged particles dynamics in a focusing channel can be studied easily by means of the matrix technique. MATLAB usage is convenient because its information objects are matrixes. MATLAB allows the use the modular principle to build the software package. Program blocks are small in size and easy to use. They can be executed separately or commonly. A set of codes has a user-friendly interface. Transport channel construction consists of focusing lenses (doublets and triplets). The main of the magneto-optical channel parameters are total length and lens position and parameters of the output beam in the phase space (channel acceptance, beam emittance - beam transverse dimensions, particles divergence and image stigmaticity). Choice of the channel operation parameters is based on the conditions for satisfying mutually competing demands. And therefore the channel parameters calculation is carried out by using the search engine optimization techniques.

Qualification of a Multi-Channel Infrared Laser Absorption Spectrometer for Monitoring CO, HCl, HCN, HF, and CO2 Aboard Manned Spacecraft

Science.gov (United States)

Briggs, Ryan M.; Frez, Clifford; Forouhar, Siamak; May, Randy D.; Meyer, Marit E.; Kulis, Michael J.; Berger, Gordon M.

2015-01-01

Monitoring of specific combustion products can provide early-warning detection of accidental fires aboard manned spacecraft and also identify the source and severity of combustion events. Furthermore, quantitative in situ measurements are important for gauging levels of exposure to hazardous gases, particularly on long-duration missions where analysis of returned samples becomes impractical. Absorption spectroscopy using tunable laser sources in the 2 to 5 micrometer wavelength range enables accurate, unambiguous detection of CO, HCl, HCN, HF, and CO2, which are produced in varying amounts through the heating of electrical components and packaging materials commonly used aboard spacecraft. Here, we report on calibration and testing of a five-channel laser absorption spectrometer designed to accurately monitor ambient gas-phase concentrations of these five compounds, with low-level detection limits based on the Spacecraft Maximum Allowable Concentrations. The instrument employs a two-pass absorption cell with a total optical pathlength of 50 cm and a dedicated infrared semiconductor laser source for each target gas. We present results from testing the five-channel sensor in the presence of trace concentrations of the target compounds that were introduced using both gas sources and oxidative pyrolysis (non-flaming combustion) of solid material mixtures.

MARKETING CHANNELS

Directory of Open Access Journals (Sweden)

Ljiljana Stošić Mihajlović

2014-07-01

Full Text Available Marketing channel is a set of entities and institutions, completion of distribution and marketing activities, attend the efficient and effective networking of producers and consumers. Marketing channels include the total flows of goods, money and information taking place between the institutions in the system of marketing, establishing a connection between them. The functions of the exchange, the physical supply and service activities, inherent in the system of marketing and trade. They represent paths which products and services are moving after the production, which will ultimately end up buying and eating by the user.

Channel Bottom Morphology in the Deltaic Reach of the Song Hau (mekong) River Channel in Vietnam

Science.gov (United States)

Allison, M. A.; Weathers, H. D., III; Meselhe, E. A.

2016-02-01

Boat-based, channel bathymetry and bankline elevation studies were conducted in the tidal and estuarine Mekong River channel using multibeam bathymetry and LIDAR corrected for elevation by RTK satellite positioning. Two mapping campaigns, one at high discharge in October 2014 and one at low discharge in March 2015, were conducted in the lower 100 km reach of the Song Hau distributary channel to (1) examine bottom morphology and its relationship to sediment transport, and (2) to provide information to setup the grid for a multi-dimensional and reduced complexity models of channel hydrodynamics and sediment dynamics. Sand fields were identified in multibeam data by the presence of dunes that were as large as 2-4 m high and 40-80 m wavelength and by clean sands in bottom grabs. Extensive areas of sand at the head and toe of mid-channel islands displayed 10-25 m diameter circular pits that could be correlated with bucket dredge, sand mining activities observed at some of the sites. Large areas of the channel floor were relict (containing little or no modern sediment) in the high discharge campaign, identifiable by the presence of along channel erosional furrows and terraced outcrops along the channel floor and margins. Laterally extensive flat areas were also observed in the channel thalweg. Both these and the relict areas were sampled by bottom grab as stiff silty clays. Complex cross-channel combinations of these morphologies were observed in some transects, suggesting strong bottom steering of tidal and riverine currents. Relative to high discharge, transects above and below the salt penetration limit showed evidence of shallowing in the thalweg and adjacent sloping areas at low discharge in March 2015. This shallowing, combined with the reduced extent of sand fields and furrowed areas, and soft muds in grabs, suggests seasonal trapping of fine grained sediment is occurring by estuarine and tidal circulation.

Interior point decoding for linear vector channels

International Nuclear Information System (INIS)

Wadayama, T

2008-01-01

In this paper, a novel decoding algorithm for low-density parity-check (LDPC) codes based on convex optimization is presented. The decoding algorithm, called interior point decoding, is designed for linear vector channels. The linear vector channels include many practically important channels such as inter-symbol interference channels and partial response channels. It is shown that the maximum likelihood decoding (MLD) rule for a linear vector channel can be relaxed to a convex optimization problem, which is called a relaxed MLD problem

Interior point decoding for linear vector channels

Energy Technology Data Exchange (ETDEWEB)

Wadayama, T [Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya, Aichi, 466-8555 (Japan)], E-mail: wadayama@nitech.ac.jp

2008-01-15

In this paper, a novel decoding algorithm for low-density parity-check (LDPC) codes based on convex optimization is presented. The decoding algorithm, called interior point decoding, is designed for linear vector channels. The linear vector channels include many practically important channels such as inter-symbol interference channels and partial response channels. It is shown that the maximum likelihood decoding (MLD) rule for a linear vector channel can be relaxed to a convex optimization problem, which is called a relaxed MLD problem.

LDGM Codes for Channel Coding and Joint Source-Channel Coding of Correlated Sources

Directory of Open Access Journals (Sweden)

Javier Garcia-Frias

2005-05-01

Full Text Available We propose a coding scheme based on the use of systematic linear codes with low-density generator matrix (LDGM codes for channel coding and joint source-channel coding of multiterminal correlated binary sources. In both cases, the structures of the LDGM encoder and decoder are shown, and a concatenated scheme aimed at reducing the error floor is proposed. Several decoding possibilities are investigated, compared, and evaluated. For different types of noisy channels and correlation models, the resulting performance is very close to the theoretical limits.

Three-dimensional (3-D) video systems: bi-channel or single-channel optics?

Science.gov (United States)

van Bergen, P; Kunert, W; Buess, G F

1999-11-01

This paper presents the results of a comparison between two different three-dimensional (3-D) video systems, one with single-channel optics, the other with bi-channel optics. The latter integrates two lens systems, each transferring one half of the stereoscopic image; the former uses only one lens system, similar to a two-dimensional (2-D) endoscope, which transfers the complete stereoscopic picture. In our training centre for minimally invasive surgery, surgeons were involved in basic and advanced laparoscopic courses using both a 2-D system and the two 3-D video systems. They completed analog scale questionnaires in order to record a subjective impression of the relative convenience of operating in 2-D and 3-D vision, and to identify perceived deficiencies in the 3-D system. As an objective test, different experimental tasks were developed, in order to measure performance times and to count pre-defined errors made while using the two 3-D video systems and the 2-D system. Using the bi-channel optical system, the surgeon has a heightened spatial perception, and can work faster and more safely than with a single-channel system. However, single-channel optics allow the use of an angulated endoscope, and the free rotation of the optics relative to the camera, which is necessary for some operative applications.

Structure of conducting channel of lightning

International Nuclear Information System (INIS)

Alanakyan, Yu. R.

2013-01-01

The spatial distribution of the plasma density in a lightning channel is studied theoretically. It is shown that the electric-field double layer is formed at the channel boundary. In this case, the electron temperature changes abruptly and ions are accelerated by the electric field of the double layer. The ion momentum flux density is close to the surrounding gas pressure. Cleaning of the channel from heavy particles occurs in particle-exchange processes between the plasma channel and the surrounding air. Hydrogen ions are accumulated inside the expanding channel from the surrounding air, which is enriched by hydrogen-contained molecules. In this case, the plasma channel is unstable and splits to a chain of equidistant bunches of plasma. The hydrogen-enrich bunches burn diffusely after recombination exhibiting the bead lightning behavior

Multi-channel Kondo necklace

International Nuclear Information System (INIS)

Fazekas, P.; Kee Haeyoung.