Bladder contractility is modulated by Kv7 channels in pig detrusor.

PubMed

Svalø, Julie; Bille, Michala; Parameswaran Theepakaran, Neeraja; Sheykhzade, Majid; Nordling, Jørgen; Bouchelouche, Pierre

2013-09-05

Kv7 channels are involved in smooth muscle relaxation, and accordingly we believe that they constitute potential targets for the treatment of overactive bladder syndrome. We have therefore used myography to examine the function of Kv7 channels in detrusor, i.e. pig bladder, with a view to determining the effects of the following potassium channel activators: ML213 (Kv7.2/Kv7.4 channels) and retigabine (Kv7.2-7.5 channels). Retigabine produced a concentration-dependent relaxation of carbachol- and electric field-induced contractions. The potency was similar in magnitude to that of ML213-induced relaxation, suggesting that Kv7.2 and/or Kv7.4 channels constitute the subtypes that are relevant to bladder contractility. The effects of retigabine and ML213 were attenuated by pre-incubation with 10µM XE991 (Kv7.1-7.5 channel blocker) (P<0.05), which in turn confirmed Kv7 channel selectivity. Subtype-selective effects were further investigated by incubating the detrusor with 10µM chromanol 293B (Kv7.1 channel blocker). Regardless of the experimental protocol, this did not cause a further increase in the evoked contraction. In contrast, the addition of XE991 potentiated the KCl-induced contractions, but not those induced by carbachol or electric field, indicating the presence of a phosphatidyl-inositol-4,5-biphosphate-dependent mechanism amongst the Kv7 channels in detrusor. qRT-PCR studies of the mRNA transcript level of Kv7.3-7.5 channels displayed a higher level of Kv7.4 transcript in detrusor compared to that present in brain cortex and heart tissues. Thus, we have shown that Kv7.4 channels are expressed and functionally active in pig detrusor, and that the use of selective Kv7.4 channel modulators in the treatment of detrusor overactivity seems promising. © 2013 Elsevier B.V. All rights reserved.

Development of a Position Decoding ASIC for SPECT using Silicon Photomultiplier

NASA Astrophysics Data System (ADS)

Cho, M.; Kim, H.; Lim, K. T.; Cho, G.

2016-01-01

Single Photon Emission Computed Tomography(SPECT) is a widely used diagnosis modality for detecting metabolic diseases. In general, SPECT system is consisted of a sensor, a pre-amplifier, position decoding circuits(PDC) and a data acquisition(DAQ) system. Due to such complexity, it is quite costly to assemble SPECT system by putting discrete components together. Moreover, using discrete components would make the system rather bulky. In this work, we designed a channel module ASIC for SPECT system. This system was composed of a transimpedance amplifier(TIA), comparators and digital logics. In this particular module, a TIA was selected as a preamplifier because the decay time and the rise time are shorter than that of other preamplifier topologies. In the proposed module, the amplified pulse from the TIA was split into two separate signals and each signal was then fed into two comparators with different reference levels, e.g., a low and high level. Then an XOR gate combined the comparator outputs and the output of XOR gate was sent to the suceeding digital logic. Furthermore, the output of each component in the module is composed of a signal packet. The packet includes the information on the energy, the time and the position of the incident photon. The energy and position information of a detected radiation can be derived from the output of the D-flipflop(DFF) in the module via time-over-threshold(TOT). The timing information was measured using a delayed rising edge from the low-level referenced comparator. There are several advantages in developing the channel module ASIC. First of all, the ASIC has only digital outputs and thus a correction circuit for analog signal distortion can be neglected. In addition, it is possible to cut down the system production cost because the volume of the system can be reduced due to the compactness of ASIC. The benefits of channel module is not only limited to SPECT but also beneficial to many other radiation detecting systems.

Inhalational anaesthetics and n-alcohols share a site of action in the neuronal Shaw2 Kv channel

PubMed Central

Bhattacharji, Aditya; Klett, Nathan; Go, Ramon Christopher V; Covarrubias, Manuel

2010-01-01

Background and purpose: Neuronal ion channels are key targets of general anaesthetics and alcohol, and binding of these drugs to pre-existing and relatively specific sites is thought to alter channel gating. However, the underlying molecular mechanisms of this action are still poorly understood. Here, we investigated the neuronal Shaw2 voltage-gated K+ (Kv) channel to ask whether the inhalational anaesthetic halothane and n-alcohols share a binding site near the activation gate of the channel. Experimental approach: Focusing on activation gate mutations that affect channel modulation by n-alcohols, we investigated n-alcohol-sensitive and n-alcohol-resistant Kv channels heterologously expressed in Xenopus oocytes to probe the functional modulation by externally applied halothane using two-electrode voltage clamping and a gas-tight perfusion system. Key results: Shaw2 Kv channels are reversibly inhibited by halothane in a dose-dependent and saturable manner (K0.5= 400 µM; nH= 1.2). Also, discrete mutations in the channel's S4S5 linker are sufficient to reduce or confer inhibition by halothane (Shaw2-T330L and Kv3.4-G371I/T378A respectively). Furthermore, a point mutation in the S6 segment of Shaw2 (P410A) converted the halothane-induced inhibition into halothane-induced potentiation. Lastly, the inhibition resulting from the co-application of n-butanol and halothane is consistent with the presence of overlapping binding sites for these drugs and weak binding cooperativity. Conclusions and implications: These observations strongly support a molecular model of a general anaesthetic binding site in the Shaw2 Kv channel. This site may involve the amphiphilic interface between the S4S5 linker and the S6 segment, which plays a pivotal role in Kv channel activation. PMID:20136839

Development of multichannel MEG system at IGCAR

NASA Astrophysics Data System (ADS)

Mariyappa, N.; Parasakthi, C.; Gireesan, K.; Sengottuvel, S.; Patel, Rajesh; Janawadkar, M. P.; Radhakrishnan, T. S.; Sundar, C. S.

2013-02-01

We describe some of the challenging aspects in the indigenous development of the whole head multichannel magnetoencephalography (MEG) system at IGCAR, Kalpakkam. These are: i) fabrication and testing of a helmet shaped sensor array holder of a polymeric material experimentally tested to be compatible with liquid helium temperatures, ii) the design and fabrication of the PCB adapter modules, keeping in mind the inter-track cross talk considerations between the electrical leads used to provide connections from SQUID at liquid helium temperature (4.2K) to the electronics at room temperature (300K) and iii) use of high resistance manganin wires for the 86 channels (86×8 leads) essential to reduce the total heat leak which, however, inevitably causes an attenuation of the SQUID output signal due to voltage drop in the leads. We have presently populated 22 of the 86 channels, which include 6 reference channels to reject the common mode noise. The whole head MEG system to cover all the lobes of the brain will be progressively assembled when other three PCB adapter modules, presently under fabrication, become available. The MEG system will be used for a variety of basic and clinical studies including localization of epileptic foci during pre-surgical mapping in collaboration with neurologists.

Activation of KV7 channels stimulates vasodilatation of human placental chorionic plate arteries.

PubMed

Mills, T A; Greenwood, S L; Devlin, G; Shweikh, Y; Robinson, M; Cowley, E; Hayward, C E; Cottrell, E C; Tropea, T; Brereton, M F; Dalby-Brown, W; Wareing, M

2015-06-01

Potassium (K(+)) channels are key regulators of vascular smooth muscle cell (VSMC) excitability. In systemic small arteries, Kv7 channel expression/activity has been noted and a role in vascular tone regulation demonstrated. We aimed to demonstrate functional Kv7 channels in human fetoplacental small arteries. Human placental chorionic plate arteries (CPAs) were obtained at term. CPA responses to Kv7 channel modulators was determined by wire myography. Presence of Kv7 channel mRNA (encoded by KCNQ1-5) and protein expression were assessed by RT-PCR and immunohistochemistry/immunofluorescence, respectively. Kv7 channel blockade with linopirdine increased CPA basal tone and AVP-induced contraction. Pre-contracted CPAs (AVP; 80 mM K(+) depolarization solution) exhibited significant relaxation to flupirtine, retigabine, the acrylamide (S)-1, and (S) BMS-204352, differential activators of Kv7.1 - Kv7.5 channels. All CPAs assessed expressed KCNQ1 and KCNQ3-5 mRNA; KCNQ2 was expressed only in a subset of CPAs. Kv7 protein expression was confirmed in intact CPAs and isolated VSMCs. Kv7 channels are present and active in fetoplacental vessels, contributing to vascular tone regulation in normal pregnancy. Targeting these channels may represent a therapeutic intervention in pregnancies complicated by increased vascular resistance. Copyright © 2015 Elsevier Ltd. All rights reserved.

Symmetric 40-Gb/s TWDM-PON with 51-dB loss budget by using a single SOA as preamplifier, booster and format converter in ONU.

PubMed

Li, Zhengxuan; Yi, Lilin; Hu, Weisheng

2014-10-06

In this paper, we propose to use a semiconductor optical amplifier (SOA) in the optical network unit (ONU) to improve the loss budget in time and wavelength division multiplexed-passive optical network (TWDM-PON) systems. The SOA boosts the upstream signal to increase the output power of the electro-absorption modulated laser (EML) and simultaneously pre-amplifies the downstream signal for sensitivity improvement. The penalty caused by cross gain modulation (XGM) effect is negligible due to the low extinction ratio (ER) of upstream signal and the large wavelength difference between upstream and downstream links. In order to achieve a higher output power, the SOA is driven into its saturation region, where the self-phase modulation (SPM) effect converts the intensity into phase information and realizes on-off-keying (OOK) to phase-shifted-keying (PSK) format conversion. In this way, the pattern effect is eliminated, which releases the requirement of gain-clamping on SOA. To further improve the loss budget of upstream link, an Erbium doped fiber amplifier (EDFA) is used in the optical line terminal (OLT) to pre-amplify the received signal. For the downstream direction, directly modulated laser (DML) is used as the laser source. Taking advantage of its carrier-less characteristic, directly modulated signal shows high tolerance to fiber nonlinearity, which could support a downstream launch power as high as + 16 dBm per channel. In addition, the signal is pre-amplified by the SOA in ONU before being detected, so the sensitivity limitation for downstream link is also removed. As a result, a truly passive symmetric 40-Gb/s TWDM-PON was demonstrated, achieving a link loss budget of 51 dB.

Ent-7α-acetoxytrachyloban-18-oic acid and ent-7α-hydroxytrachyloban-18-oic acid from Xylopia langsdorfiana A. St-Hil. & Tul. modulate K(+) and Ca(2+) channels to reduce cytosolic calcium concentration on guinea pig ileum.

PubMed

Santos, Rosimeire F; Martins, Italo R R; Travassos, Rafael A; Tavares, Josean F; Silva, Marcelo S; Paredes-Gamero, Edgar J; Ferreira, Alice T; Nouailhetas, Viviane L A; Aboulafia, Jeannine; Rigoni, Vera L S; da Silva, Bagnólia A

2012-03-05

In this study we investigated the mechanism underlying the spasmolytic action of ent-7α-acetoxytrachyloban-18-oic acid (trachylobane-360) and ent-7α-hydroxytrachyloban-18-oic acid (trachylobane-318), diterpenes obtained from Xylopia langsdorfiana, on guinea pig ileum. Both compounds inhibited histamine-induced cumulative contractions (slope=3.5±0.9 and 4.4±0.7) that suggests a noncompetitive antagonism to histaminergic receptors. CaCl(2)-induced contractions were nonparallelly and concentration-dependently reduced by both diterpenes, indicating blockade of calcium influx through voltage-dependent calcium channels (Ca(v)). The Ca(v) participation was confirmed since both trachylobanes equipotently relaxed ileum pre-contracted with S-(-)-Bay K8644 (EC(50)=3.5±0.7×10-(5) and 1.1±0.2×10-(5)M) and KCl (EC(50)=5.5±0.3×10-(5) and 1.4±0.2×10-(5)M). K(+) channels participation was confirmed since diterpene-induced relaxation curves were significantly shifted to right in the presence of 5mM tetraethylammonium (TEA(+)) (EC(50)=0.5±0.04×10-(4) and 2.0±0.5×10-(5)M). ATP-sensitive K(+) channel (K(ATP)), voltage activated K(+) channels (K(V)), small conductance calcium-activated K(+) channels (SK(Ca)) or big conductance calcium-activated K(+) channels (BK(Ca)) did not seem to participate of trachylobane-360 spasmolytic action. However trachylobane-318 modulated positively K(ATP), K(V) and SK(Ca) (EC(50)=1.1±0.3×10-(5), 0.7±0.2×10-(5) and 0.7±0.2×10-(5)M), but not BK(Ca). A fluorescence analysis technique confirmed the decrease of cytosolic calcium concentration ([Ca(2+)](c)) induced by both trachylobanes in ileal myocytes. In conclusion, trachylobane-360 and trachylobane-318 induced spasmolytic activity by K(+) channel positive modulation and Ca(2+) channel blockade, which results in [Ca(2+)](c) reduction at cellular level leading to smooth muscle relaxation. Copyright © 2011. Published by Elsevier B.V.

Multiple C-terminal tail Ca2+/CaMs regulate CaV1.2 function but do not mediate channel dimerization

PubMed Central

Kim, Eun Young; Rumpf, Christine H; Van Petegem, Filip; Arant, Ryan J; Findeisen, Felix; Cooley, Elizabeth S; Isacoff, Ehud Y; Minor, Daniel L

2010-01-01

Interactions between voltage-gated calcium channels (CaVs) and calmodulin (CaM) modulate CaV function. In this study, we report the structure of a Ca2+/CaM CaV1.2 C-terminal tail complex that contains two PreIQ helices bridged by two Ca2+/CaMs and two Ca2+/CaM–IQ domain complexes. Sedimentation equilibrium experiments establish that the complex has a 2:1 Ca2+/CaM:C-terminal tail stoichiometry and does not form higher order assemblies. Moreover, subunit-counting experiments demonstrate that in live cell membranes CaV1.2s are monomers. Thus, contrary to previous proposals, the crystallographic dimer lacks physiological relevance. Isothermal titration calorimetry and biochemical experiments show that the two Ca2+/CaMs in the complex have different properties. Ca2+/CaM bound to the PreIQ C-region is labile, whereas Ca2+/CaM bound to the IQ domain is not. Furthermore, neither of lobes of apo-CaM interacts strongly with the PreIQ domain. Electrophysiological studies indicate that the PreIQ C-region has a role in calcium-dependent facilitation. Together, the data show that two Ca2+/CaMs can bind the CaV1.2 tail simultaneously and indicate a functional role for Ca2+/CaM at the C-region site. PMID:20953164

Multiple C-terminal tail Ca(2+)/CaMs regulate Ca(V)1.2 function but do not mediate channel dimerization.

PubMed

Kim, Eun Young; Rumpf, Christine H; Van Petegem, Filip; Arant, Ryan J; Findeisen, Felix; Cooley, Elizabeth S; Isacoff, Ehud Y; Minor, Daniel L

2010-12-01

Interactions between voltage-gated calcium channels (Ca(V)s) and calmodulin (CaM) modulate Ca(V) function. In this study, we report the structure of a Ca(2+)/CaM Ca(V)1.2 C-terminal tail complex that contains two PreIQ helices bridged by two Ca(2+)/CaMs and two Ca(2+)/CaM-IQ domain complexes. Sedimentation equilibrium experiments establish that the complex has a 2:1 Ca(2+)/CaM:C-terminal tail stoichiometry and does not form higher order assemblies. Moreover, subunit-counting experiments demonstrate that in live cell membranes Ca(V)1.2s are monomers. Thus, contrary to previous proposals, the crystallographic dimer lacks physiological relevance. Isothermal titration calorimetry and biochemical experiments show that the two Ca(2+)/CaMs in the complex have different properties. Ca(2+)/CaM bound to the PreIQ C-region is labile, whereas Ca(2+)/CaM bound to the IQ domain is not. Furthermore, neither of lobes of apo-CaM interacts strongly with the PreIQ domain. Electrophysiological studies indicate that the PreIQ C-region has a role in calcium-dependent facilitation. Together, the data show that two Ca(2+)/CaMs can bind the Ca(V)1.2 tail simultaneously and indicate a functional role for Ca(2+)/CaM at the C-region site.

Monitoring devices and systems for monitoring frequency hopping wireless communications, and related methods

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

Derr, Kurt W.; Richardson, John G.

Monitoring devices and systems comprise a plurality of data channel modules coupled to processing circuitry. Each data channel module of the plurality of data channel modules is configured to capture wireless communications for a selected frequency channel. The processing circuitry is configured to receive captured wireless communications from the plurality of data channel modules and to organize received wireless communications according to at least one parameter. Related methods of monitoring wireless communications are also disclosed.

CNG-Modulin: a novel Ca-dependent modulator of ligand sensitivity in cone photoreceptor cGMP-gated ion channels

PubMed Central

Rebrik, Tatiana I.; Botchkina, Inna; Arshavsky, Vadim Y.; Craft, Cheryl M.; Korenbrot, Juan I.

2012-01-01

The transduction current in several different types of sensory neurons arises from the activity of cyclic nucleotide gated ion channels (CNG channels). The channels in these sensory neurons vary in structure and function, yet each one demonstrates calcium-dependent modulation of ligand sensitivity mediated by the interaction of the channel with a soluble modulator protein. In cone photoreceptors, the molecular identity of the modulator protein was previously unknown. We report the discovery and characterization of CNG-modulin, a novel 301 amino acid protein that interacts with the N-terminus of the β-subunit of the cGMP-gated channel, and modulates the cGMP sensitivity of the channels in cone photoreceptors of striped bass (Morone saxitilis). Immunohistochemistry and single cell PCR demonstrate that CNG-modulin is expressed in cone, but not rod photoreceptors. Adding purified recombinant CNG-modulin to cone membrane patches containing the native CNG channels shifts the midpoint of cGMP-dependence from ~91 μM in the absence of Ca2+ to ~332 μM in the presence of 20 μM Ca2+. At a fixed cGMP concentration, the midpoint of the Ca2+ dependence is ~857 nM Ca2+. These restored physiological features are statistically indistinguishable from the effects of the endogenous modulator. CNG-modulin binds Ca2+ with a concentration dependence that matches the calcium dependence of channel modulation. We conclude that CNG-modulin is the authentic Ca2+-dependent modulator of cone CNG channel ligand sensitivity. CNG-modulin is expressed in other tissues, such as brain, olfactory epithelium and the inner ear and may modulate the function of ion channels in those tissues as well. PMID:22378887

An experimental setup to characterize MR switched gradient-induced potentials.

PubMed

Fokapu, Odette; El-Tatar, Aziz

2013-06-01

We have developed an experimental setup as an in vitro research tool for studying the contamination of electrophysiological signals (EPS) by MRI environment; particularly, when due to the switched gradient-induced potentials. The system is composed of: 1) a MRI compatible module for the transmission of the EPS into the MRI tunnel, 2) a gelatin-based tissue-mimicking phantom, placed inside the tunnel, in which EPS is injected, 3) a detection module composed of a five input channel MRI compatible transmitter placed inside the tunnel, allowing an on-site pre-amplification of the bio-potentials and their transmission, via an optical fiber cable, to a four filtered output per channel receiver (350 Hz, 160 Hz, 80 Hz, and 40 Hz, for a total of 20 channels) placed in the control room, and 4) a signal processing algorithm used to analyze the generated induced potentials. A set of tests were performed to validate the electronic performances of the setup. We also present in this work an interesting application of the setup, i.e., the acquisition and analysis of the induced potentials with respect of the slice orientation for a given MRI sequence. Significant modifications of the time and frequency characteristics were observed with respect to axial, coronal or sagittal orientations.

Aberrant Splicing Induced by Dysregulated Rbfox2 Produces Enhanced Function of CaV1.2 Calcium Channel and Vascular Myogenic Tone in Hypertension.

PubMed

Zhou, Yingying; Fan, Jia; Zhu, Huayuan; Ji, Li; Fan, Wenyong; Kapoor, Isha; Wang, Yue; Wang, Yuan; Zhu, Guoqing; Wang, Juejin

2017-12-01

Calcium influx from activated voltage-gated calcium channel Ca V 1.2 in vascular smooth muscle cells is indispensable for maintaining myogenic tone and blood pressure. The function of Ca V 1.2 channel can be optimized by alternative splicing, one of post-transcriptional modification mechanisms. The splicing factor Rbfox2 is known to regulate the Ca V 1.2 pre-mRNA alternative splicing events during neuronal development. However, Rbfox2's roles in modulating the key function of vascular Ca V 1.2 channel and in the pathogenesis of hypertension remain elusive. Here, we report that the proportion of Ca V 1.2 channels with alternative exon 9* is increased by 10.3%, whereas that with alternative exon 33 is decreased by 10.5% in hypertensive arteries. Surprisingly, the expression level of Rbfox2 is increased ≈3-folds, presumably because of the upregulation of a dominant-negative isoform of Rbfox2. In vascular smooth muscle cells, we find that knockdown of Rbfox2 dynamically increases alternative exon 9*, whereas decreases exon 33 inclusion of Ca V 1.2 channels. By patch-clamp studies, we show that diminished Rbfox2-induced alternative splicing shifts the steady-state activation and inactivation curves of vascular Ca V 1.2 calcium channel to hyperpolarization, which makes the window current potential to more negative. Moreover, siRNA-mediated knockdown of Rbfox2 increases the pressure-induced vascular myogenic tone of rat mesenteric artery. Taken together, our data indicate that Rbfox2 modulates the functions of vascular Ca V 1.2 calcium channel by dynamically regulating the expressions of alternative exons 9* and 33, which in turn affects the vascular myogenic tone. Therefore, our work suggests a key role for Rbfox2 in hypertension, which provides a rational basis for designing antihypertensive therapies. © 2017 American Heart Association, Inc.

CNG-modulin: a novel Ca-dependent modulator of ligand sensitivity in cone photoreceptor cGMP-gated ion channels.

PubMed

Rebrik, Tatiana I; Botchkina, Inna; Arshavsky, Vadim Y; Craft, Cheryl M; Korenbrot, Juan I

2012-02-29

The transduction current in several different types of sensory neurons arises from the activity of cyclic nucleotide-gated (CNG) ion channels. The channels in these sensory neurons vary in structure and function, yet each one demonstrates calcium-dependent modulation of ligand sensitivity mediated by the interaction of the channel with a soluble modulator protein. In cone photoreceptors, the molecular identity of the modulator protein was previously unknown. We report the discovery and characterization of CNG-modulin, a novel 301 aa protein that interacts with the N terminus of the β subunit of the cGMP-gated channel and modulates the cGMP sensitivity of the channels in cone photoreceptors of striped bass (Morone saxatilis). Immunohistochemistry and single-cell PCR demonstrate that CNG-modulin is expressed in cone but not rod photoreceptors. Adding purified recombinant CNG-modulin to cone membrane patches containing the native CNG channels shifts the midpoint of cGMP dependence from ∼91 μM in the absence of Ca(2+) to ∼332 μM in the presence of 20 μM Ca(2+). At a fixed cGMP concentration, the midpoint of the Ca(2+) dependence is ∼857 nM Ca(2+). These restored physiological features are statistically indistinguishable from the effects of the endogenous modulator. CNG-modulin binds Ca(2+) with a concentration dependence that matches the calcium dependence of channel modulation. We conclude that CNG-modulin is the authentic Ca(2+)-dependent modulator of cone CNG channel ligand sensitivity. CNG-modulin is expressed in other tissues, such as brain, olfactory epithelium, and the inner ear, and may modulate the function of ion channels in those tissues as well.

Novel Roles for Kv7 Channels in Shaping Histamine-Induced Contractions and Bradykinin-Dependent Relaxations in Pig Coronary Arteries

PubMed Central

Chen, Xingjuan; Li, Wennan; Hiett, S. Christopher; Obukhov, Alexander G.

2016-01-01

Voltage-gated Kv7 channels are inhibited by agonists of Gq-protein-coupled receptors, such as histamine. Recent works have provided evidence that inhibition of vascular Kv7 channels may trigger vessel contractions. In this study, we investigated how Kv7 activity modulates the histamine-induced contractions in “healthy” and metabolic syndrome (MetS) pig right coronary arteries (CAs). We performed isometric tension and immunohistochemical studies with domestic, lean Ossabaw, and MetS Ossabaw pig CAs. We found that neither the Kv7.2/Kv7.4/Kv7.5 activator ML213 nor the general Kv7 inhibitor XE991 altered the tension of CA rings under preload, indicating that vascular Kv7 channels are likely inactive in the preloaded rings. Conversely, ML213 potently dilated histamine-pre-contracted CAs, suggesting that Kv7 channels are activated during histamine applications and yet partially inhibited by histamine. Immunohistochemistry analysis revealed strong Kv7.4 immunostaining in the medial and intimal layers of the CA wall, whereas Kv7.5 immunostaining intensity was strong in the intimal but weak in the medial layers. The medial Kv7 immunostaining was significantly weaker in MetS Ossabaw CAs as compared to lean Ossabaw or domestic CAs. Consistently, histamine-pre-contracted MetS Ossabaw CAs exhibited attenuated ML213-dependent dilations. In domestic pig CAs, where medial Kv7 immunostaining intensity was stronger, histamine-induced contractions spontaneously decayed to ~31% of the peak amplitude within 4 minutes. Oppositely, in Ossabaw CAs, where Kv7 immunostaining intensity was weaker, the histamine-induced contractions were more sustained. XE991 pretreatment significantly slowed the decay rate of histamine-induced contractions in domestic CAs, supporting the hypothesis that increased Kv7 activity correlates with a faster rate of histamine-induced contraction decay. Alternatively, XE991 significantly decreased the amplitude of bradykinin-dependent dilations in pre-contracted CAs. We propose that in CAs, a decreased expression or a loss of function of Kv7 channels may lead to sustained histamine-induced contractions and reduced endothelium-dependent relaxation, both risk factors for coronary spasm. PMID:26844882

All-optical UWB generation and modulation using SOA-XPM effect and DWDM-based multi-channel frequency discrimination.

PubMed

Wang, Fei; Dong, Jianji; Xu, Enming; Zhang, Xinliang

2010-11-22

An all-optical UWB pulses generation and modulation scheme using cross phase modulation (XPM) effect of semiconductor optical amplifier (SOA) and DWDM-based multi-channel frequency discrimination is proposed and demonstrated, which has potential application in multiuser UWB-Over-Fiber communication systems. When a Gaussian pulse light and a wavelength-tunable CW probe light are together injected into the SOA, the probe light out from the SOA will have a temporal chirp due to SOA-XPM effect. When the chirped probe light is tuned to the slopes of single DWDM channel transmittance curve, the optical phase modulation to intensity modulation conversion is achieved at DWDM that serves as a multi-channel frequency discriminator, the inverted polarity Gaussian monocycle and doublet pulse is detected by a photodetector, respectively. If the probe lights are simultaneously aimed to different slopes of several DWDM channels, multi-channel or binary-phase-coded UWB signal generation can be acquired. Using proposed scheme, pulse amplitude modulation (PAM), pulse polarity modulation (PPM) and pulse shape modulation (PSM) to UWB pulses also can be conveniently realized.

A Compact Low-Power Driver Array for VCSELs in 65-nm CMOS Technology

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

Zeng, Zhiyao; Sun, Kexu; Wang, Guanhua

This article presents a compact low-power 4 x 10 Gb/s quad-driver module for Vertical-Cavity Surface-Emitting Laser (VCSEL) arrays in a 65 nm CMOS technology. The side-by-side drivers can be directly wire bonded to the VCSEL diode array, supporting up to 4 channels. To increase the bandwidth of the driver, an internal feed-forward path is added for pole-zero cancellation, without increasing the power consumption. An edge-configurable pre-emphasis technique is proposed to achieve high bandwidth and minimize the asymmetry of the fall and rise times of the driver output current. Measurement results demonstrate a RMS jitter of 0.68 ps for 10 Gb/smore » operation. Tests demonstrate negligible crosstalk between channels. Under irradiation, the modulation amplitude degrades less than 5% up to 300 Mrad ionizing dose. Finally, the area of the quaddriver array is 500 μm by 1000 μm and the total power consumption for the entire driver array chip is 130 mW for the typical current setting.« less

A Compact Low-Power Driver Array for VCSELs in 65-nm CMOS Technology

DOE PAGES

Zeng, Zhiyao; Sun, Kexu; Wang, Guanhua; ...

2017-05-08

This article presents a compact low-power 4 x 10 Gb/s quad-driver module for Vertical-Cavity Surface-Emitting Laser (VCSEL) arrays in a 65 nm CMOS technology. The side-by-side drivers can be directly wire bonded to the VCSEL diode array, supporting up to 4 channels. To increase the bandwidth of the driver, an internal feed-forward path is added for pole-zero cancellation, without increasing the power consumption. An edge-configurable pre-emphasis technique is proposed to achieve high bandwidth and minimize the asymmetry of the fall and rise times of the driver output current. Measurement results demonstrate a RMS jitter of 0.68 ps for 10 Gb/smore » operation. Tests demonstrate negligible crosstalk between channels. Under irradiation, the modulation amplitude degrades less than 5% up to 300 Mrad ionizing dose. Finally, the area of the quaddriver array is 500 μm by 1000 μm and the total power consumption for the entire driver array chip is 130 mW for the typical current setting.« less

Analysis of synchronous digital-modulation schemes for satellite communication

NASA Technical Reports Server (NTRS)

Takhar, G. S.; Gupta, S. C.

1975-01-01

The multipath communication channel for space communications is modeled as a multiplicative channel. This paper discusses the effects of multiplicative channel processes on the symbol error rate for quadrature modulation (QM) digital modulation schemes. An expression for the upper bound on the probability of error is derived and numerically evaluated. The results are compared with those obtained for additive channels.

In-Depth Study of the Interaction, Sensitivity, and Gating Modulation by PUFAs on K+ Channels; Interaction and New Targets

PubMed Central

Moreno, Cristina; de la Cruz, Alicia; Valenzuela, Carmen

2016-01-01

Voltage gated potassium channels (KV) are membrane proteins that allow selective flow of K+ ions in a voltage-dependent manner. These channels play an important role in several excitable cells as neurons, cardiomyocytes, and vascular smooth muscle. Over the last 20 years, it has been shown that omega-3 polyunsaturated fatty acids (PUFAs) enhance or decrease the activity of several cardiac KV channels. PUFAs-dependent modulation of potassium ion channels has been reported to be cardioprotective. However, the precise cellular mechanism underlying the cardiovascular benefits remained unclear in part because new PUFAs targets and signaling pathways continue being discovered. In this review, we will focus on recent data available concerning the following aspects of the KV channel modulation by PUFAs: (i) the exact residues involved in PUFAs-KV channels interaction; (ii) the structural PUFAs determinants important for their effects on KV channels; (iii) the mechanism of the gating modulation of KV channels and, finally, (iv) the PUFAs modulation of a few new targets present in smooth muscle cells (SMC), KCa1.1, K2P, and KATP channels, involved in vascular relaxation. PMID:27933000

Modulation frequency discrimination with single and multiple channels in cochlear implant users

PubMed Central

Galvin, John J.; Oba, Sandy; Başkent, Deniz; Fu, Qian-Jie

2015-01-01

Temporal envelope cues convey important speech information for cochlear implant (CI) users. Many studies have explored CI users’ single-channel temporal envelope processing. However, in clinical CI speech processors, temporal envelope information is processed by multiple channels. Previous studies have shown that amplitude modulation frequency discrimination (AMFD) thresholds are better when temporal envelopes are delivered to multiple rather than single channels. In clinical fitting, current levels on single channels must often be reduced to accommodate multi-channel loudness summation. As such, it is unclear whether the multi-channel advantage in AMFD observed in previous studies was due to coherent envelope information distributed across the cochlea or to greater loudness associated with multi-channel stimulation. In this study, single- and multi-channel AMFD thresholds were measured in CI users. Multi-channel component electrodes were either widely or narrowly spaced to vary the degree of overlap between neural populations. The reference amplitude modulation (AM) frequency was 100 Hz, and coherent modulation was applied to all channels. In Experiment 1, single- and multi-channel AMFD thresholds were measured at similar loudness. In this case, current levels on component channels were higher for single- than for multi-channel AM stimuli, and the modulation depth was approximately 100% of the perceptual dynamic range (i.e., between threshold and maximum acceptable loudness). Results showed no significant difference in AMFD thresholds between similarly loud single- and multi-channel modulated stimuli. In Experiment 2, single- and multi-channel AMFD thresholds were compared at substantially different loudness. In this case, current levels on component channels were the same for single-and multi-channel stimuli (“summation-adjusted” current levels) and the same range of modulation (in dB) was applied to the component channels for both single- and multi-channel testing. With the summation-adjusted current levels, loudness was lower with single than with multiple channels and the AM depth resulted in substantial stimulation below single-channel audibility, thereby reducing the perceptual range of AM. Results showed that AMFD thresholds were significantly better with multiple channels than with any of the single component channels. There was no significant effect of the distribution of electrodes on multi-channel AMFD thresholds. The results suggest that increased loudness due to multi-channel summation may contribute to the multi-channel advantage in AMFD, and that that overall loudness may matter more than the distribution of envelope information in the cochlea. PMID:25746914

Cross-Layer Design for Video Transmission over Wireless Rician Slow-Fading Channels Using an Adaptive Multiresolution Modulation and Coding Scheme

NASA Astrophysics Data System (ADS)

Pei, Yong; Modestino, James W.

2007-12-01

We describe a multilayered video transport scheme for wireless channels capable of adapting to channel conditions in order to maximize end-to-end quality of service (QoS). This scheme combines a scalable H.263+ video source coder with unequal error protection (UEP) across layers. The UEP is achieved by employing different channel codes together with a multiresolution modulation approach to transport the different priority layers. Adaptivity to channel conditions is provided through a joint source-channel coding (JSCC) approach which attempts to jointly optimize the source and channel coding rates together with the modulation parameters to obtain the maximum achievable end-to-end QoS for the prevailing channel conditions. In this work, we model the wireless links as slow-fading Rician channel where the channel conditions can be described in terms of the channel signal-to-noise ratio (SNR) and the ratio of specular-to-diffuse energy[InlineEquation not available: see fulltext.]. The multiresolution modulation/coding scheme consists of binary rate-compatible punctured convolutional (RCPC) codes used together with nonuniform phase-shift keyed (PSK) signaling constellations. Results indicate that this adaptive JSCC scheme employing scalable video encoding together with a multiresolution modulation/coding approach leads to significant improvements in delivered video quality for specified channel conditions. In particular, the approach results in considerably improved graceful degradation properties for decreasing channel SNR.

47 CFR 73.128 - AM stereophonic broadcasting.

Code of Federal Regulations, 2012 CFR

2012-10-01

... channel reversed. (iii) Left and Right Channel only, under all conditions of modulation for the... (NRSC-1). (2) The left and right channel audio signals shall conform to frequency response limitations...)=audio signal left channel, R(t)=audio signal right channel, m=modulation factor, and mpeak(L(t)+R(t))=1...

Research on channel characteristics of differential multi pulse position modulation without background noise

NASA Astrophysics Data System (ADS)

Gao, Zhuo; Zhan, Weida; Sun, Quan; Hao, Ziqiang

2018-04-01

Differential multi-pulse position modulation (DMPPM) is a new type of modulation technology. There is a fast transmission rate, high bandwidth utilization, high modulation rate characteristics. The study of DMPPM modulation has important scientific value and practical significance. Channel capacity is one of the important indexes to measure the communication capability of communication system, and studying the channel capacity of DMPPM without background noise is the key to analyze the characteristics of DMPPM. The DMPPM theoretical model is established. The symbol structure of DMPPM with guard time slot is analyzed, and the channel capacity expression of DMPPM is deduced. Simulation analysis by MATLAB. The curves of unit channel capacity and capacity efficiency at different pulse and photon counting rates are analyzed. The results show that DMPPM is more advantageous than multi-pulse position modulation (MPPM), and is more suitable for future wireless optical communication system.

FPGA-based Trigger System for the Fermilab SeaQuest Experimentz

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

Shiu, Shiuan-Hal; Wu, Jinyuan; McClellan, Randall Evan

The SeaQuest experiment (Fermilab E906) detects pairs of energetic μ + and μ -produced in 120 GeV/c proton–nucleon interactions in a high rate environment. The trigger system we used consists of several arrays of scintillator hodoscopes and a set of field-programmable gate array (FPGA) based VMEbus modules. Signals from up to 96 channels of hodoscope are digitized by each FPGA with a 1-ns resolution using the time-to-digital convertor (TDC) firmware. The delay of the TDC output can be adjusted channel-by-channel in 1-ns step and then re-aligned with the beam RF clock. The hit pattern on the hodoscope planes is thenmore » examined against pre-determined trigger matrices to identify candidate muon tracks. Finally, information on the candidate tracks is sent to the 2nd-level FPGA-based track correlator to find candidate di-muon events. The design and implementation of the FPGA-based trigger system for SeaQuest experiment are presented.« less

FPGA-based trigger system for the Fermilab SeaQuest experimentz

NASA Astrophysics Data System (ADS)

Shiu, Shiuan-Hal; Wu, Jinyuan; McClellan, Randall Evan; Chang, Ting-Hua; Chang, Wen-Chen; Chen, Yen-Chu; Gilman, Ron; Nakano, Kenichi; Peng, Jen-Chieh; Wang, Su-Yin

2015-12-01

The SeaQuest experiment (Fermilab E906) detects pairs of energetic μ+ and μ- produced in 120 GeV/c proton-nucleon interactions in a high rate environment. The trigger system consists of several arrays of scintillator hodoscopes and a set of field-programmable gate array (FPGA) based VMEbus modules. Signals from up to 96 channels of hodoscope are digitized by each FPGA with a 1-ns resolution using the time-to-digital convertor (TDC) firmware. The delay of the TDC output can be adjusted channel-by-channel in 1-ns step and then re-aligned with the beam RF clock. The hit pattern on the hodoscope planes is then examined against pre-determined trigger matrices to identify candidate muon tracks. Information on the candidate tracks is sent to the 2nd-level FPGA-based track correlator to find candidate di-muon events. The design and implementation of the FPGA-based trigger system for SeaQuest experiment are presented.

FPGA-based Trigger System for the Fermilab SeaQuest Experimentz

DOE PAGES

Shiu, Shiuan-Hal; Wu, Jinyuan; McClellan, Randall Evan; ...

2015-09-10

The SeaQuest experiment (Fermilab E906) detects pairs of energetic μ + and μ -produced in 120 GeV/c proton–nucleon interactions in a high rate environment. The trigger system we used consists of several arrays of scintillator hodoscopes and a set of field-programmable gate array (FPGA) based VMEbus modules. Signals from up to 96 channels of hodoscope are digitized by each FPGA with a 1-ns resolution using the time-to-digital convertor (TDC) firmware. The delay of the TDC output can be adjusted channel-by-channel in 1-ns step and then re-aligned with the beam RF clock. The hit pattern on the hodoscope planes is thenmore » examined against pre-determined trigger matrices to identify candidate muon tracks. Finally, information on the candidate tracks is sent to the 2nd-level FPGA-based track correlator to find candidate di-muon events. The design and implementation of the FPGA-based trigger system for SeaQuest experiment are presented.« less

Experimental demonstration of the transmission performance for LDPC-coded multiband OFDM ultra-wideband over fiber system

NASA Astrophysics Data System (ADS)

He, Jing; Wen, Xuejie; Chen, Ming; Chen, Lin; Su, Jinshu

2015-01-01

To improve the transmission performance of multiband orthogonal frequency division multiplexing (MB-OFDM) ultra-wideband (UWB) over optical fiber, a pre-coding scheme based on low-density parity-check (LDPC) is adopted and experimentally demonstrated in the intensity-modulation and direct-detection MB-OFDM UWB over fiber system. Meanwhile, a symbol synchronization and pilot-aided channel estimation scheme is implemented on the receiver of the MB-OFDM UWB over fiber system. The experimental results show that the LDPC pre-coding scheme can work effectively in the MB-OFDM UWB over fiber system. After 70 km standard single-mode fiber (SSMF) transmission, at the bit error rate of 1 × 10-3, the receiver sensitivities are improved about 4 dB when the LDPC code rate is 75%.

Real-time co-registered ultrasound and photoacoustic imaging system based on FPGA and DSP architecture

NASA Astrophysics Data System (ADS)

Alqasemi, Umar; Li, Hai; Aguirre, Andres; Zhu, Quing

2011-03-01

Co-registering ultrasound (US) and photoacoustic (PA) imaging is a logical extension to conventional ultrasound because both modalities provide complementary information of tumor morphology, tumor vasculature and hypoxia for cancer detection and characterization. In addition, both modalities are capable of providing real-time images for clinical applications. In this paper, a Field Programmable Gate Array (FPGA) and Digital Signal Processor (DSP) module-based real-time US/PA imaging system is presented. The system provides real-time US/PA data acquisition and image display for up to 5 fps* using the currently implemented DSP board. It can be upgraded to 15 fps, which is the maximum pulse repetition rate of the used laser, by implementing an advanced DSP module. Additionally, the photoacoustic RF data for each frame is saved for further off-line processing. The system frontend consists of eight 16-channel modules made of commercial and customized circuits. Each 16-channel module consists of two commercial 8-channel receiving circuitry boards and one FPGA board from Analog Devices. Each receiving board contains an IC† that combines. 8-channel low-noise amplifiers, variable-gain amplifiers, anti-aliasing filters, and ADC's‡ in a single chip with sampling frequency of 40MHz. The FPGA board captures the LVDSξ Double Data Rate (DDR) digital output of the receiving board and performs data conditioning and subbeamforming. A customized 16-channel transmission circuitry is connected to the two receiving boards for US pulseecho (PE) mode data acquisition. A DSP module uses External Memory Interface (EMIF) to interface with the eight 16-channel modules through a customized adaptor board. The DSP transfers either sub-beamformed data (US pulse-echo mode or PAI imaging mode) or raw data from FPGA boards to its DDR-2 memory through the EMIF link, then it performs additional processing, after that, it transfer the data to the PC** for further image processing. The PC code performs image processing including demodulation, beam envelope detection and scan conversion. Additionally, the PC code pre-calculates the delay coefficients used for transmission focusing and receiving dynamic focusing for different types of transducers to speed up the imaging process. To further speed up the imaging process, a multi-threads technique is implemented in order to allow formation of previous image frame data and acquisition of the next one simultaneously. The system is also capable of doing semi-real-time automated SO2 imaging at 10 seconds per frame by changing the wavelength knob of the laser automatically using a stepper motor controlled by the system. Initial in vivo experiments were performed on animal tumors to map out its vasculature and hypoxia level, which were superimposed on co-registered US images. The real-time system allows capturing co-registered US/PA images free of motion artifacts and also provides dynamitic information when contrast agents are used.

Carvacrol modulates voltage-gated sodium channels kinetics in dorsal root ganglia.

PubMed

Joca, Humberto Cavalcante; Vieira, Daiana Cardoso Oliveira; Vasconcelos, Aliny Perreira; Araújo, Demetrius Antônio Machado; Cruz, Jader Santos

2015-06-05

Recent studies have shown that many of plant-derived compounds interact with specific ion channels and thereby modulate many sensing mechanisms, such as nociception. The monoterpenoid carvacrol (5-isopropyl-2-methylphenol) has an anti-nociceptive effect related to a reduction in neuronal excitability and voltage-gated Na(+) channels (NaV) inhibition in peripheral neurons. However, the detailed mechanisms of carvacrol-induced inhibition of neuronal NaV remain elusive. This study explores the interaction between carvacrol and NaV in isolated dorsal root ganglia neurons. Carvacrol reduced the total voltage-gated Na(+) current and tetrodotoxin-resistant (TTX-R) Na(+) current component in a concentration-dependent manner. Carvacrol accelerates current inactivation and induced a negative-shift in voltage-dependence of steady-state fast inactivation in total and TTX-R Na(+) current. Furthermore, carvacrol slowed the recovery from inactivation. Carvacrol provoked a leftward shift in both the voltage-dependence of steady-state inactivation and activation of the TTX-R Na(+) current component. In addition, carvacrol-induced inhibition of TTX-R Na(+) current was enhanced by an increase in stimulation frequency and when neurons were pre-conditioned with long depolarization pulse (5s at -50 mV). Taken all results together, we herein demonstrated that carvacrol affects NaV gating properties. The present findings would help to explain the mechanisms underlying the analgesic activity of carvacrol. Copyright © 2015 Elsevier B.V. All rights reserved.

Calibrated Link Budget of a Silicon Photonics WDM Transceiver with SOA and Semiconductor Mode-Locked Laser.

PubMed

Moscoso-Mártir, Alvaro; Müller, Juliana; Islamova, Elmira; Merget, Florian; Witzens, Jeremy

2017-09-20

Based on the single channel characterization of a Silicon Photonics (SiP) transceiver with Semiconductor Optical Amplifier (SOA) and semiconductor Mode-Locked Laser (MLL), we evaluate the optical power budget of a corresponding Wavelength Division Multiplexed (WDM) link in which penalties associated to multi-channel operation and the management of polarization diversity are introduced. In particular, channel cross-talk as well as Cross Gain Modulation (XGM) and Four Wave Mixing (FWM) inside the SOA are taken into account. Based on these link budget models, the technology is expected to support up to 12 multiplexed channels without channel pre-emphasis or equalization. Forward Error Correction (FEC) does not appear to be required at 14 Gbps if the SOA is maintained at 25 °C and MLL-to-SiP as well as SiP-to-SOA interface losses can be maintained below 3 dB. In semi-cooled operation with an SOA temperature below 55 °C, multi-channel operation is expected to be compatible with standard 802.3bj Reed-Solomon FEC at 14 Gbps provided interface losses are maintained below 4.5 dB. With these interface losses and some improvements to the Transmitter (Tx) and Receiver (Rx) electronics, 25 Gbps multi-channel operation is expected to be compatible with 7% overhead hard decision FEC.

Direct and remote modulation of L-channels in chromaffin cells: distinct actions on alpha1C and alpha1D subunits?

PubMed

Baldelli, Pietro; Hernández-Guijo, Jesus Miguel; Carabelli, Valentina; Novara, Monica; Cesetti, Tiziana; Andrés-Mateos, Eva; Montiel, Carmen; Carbone, Emilio

2004-02-01

Understanding precisely the functioning of voltage-gated Ca2+ channels and their modulation by signaling molecules will help clarifying the Ca(2+)-dependent mechanisms controlling exocytosis in chromaffin cells. In recent years, we have learned more about the various pathways through which Ca2+ channels can be up- or down-modulated by hormones and neurotransmitters and how these changes may condition chromaffin cell activity and catecolamine release. Recently, the attention has been focused on the modulation of L-channels (CaV 1), which represent the major Ca2+ current component in rat and human chromaffin cells. L-channels are effectively inhibited by the released content of secretory granules or by applying mixtures of exogenous ATP, opioids, and adrenaline through the activation of receptor-coupled G proteins. This unusual inhibition persists in a wide range of potentials and results from a direct (membrane-delimited) interaction of G protein subunits with the L-channels co-localized in membrane microareas. Inhibition of L-channels can be reversed when the cAMP/PKA pathway is activated by membrane permeable cAMP analog or when cells are exposed to isoprenaline (remote action), suggesting the existence of parallel and opposite effects on L-channel gating by distinctly activated membrane autoreceptors. Here, the authors review the molecular components underlying these two opposing signaling pathways and present new evidence supporting the presence of two L-channel types in rat chromaffin cells (alpha1C and alpha1D), which open new interesting issues concerning Ca(2+)-channel modulation. In light of recent findings on the regulation of exocytosis by Ca(2+)-channel modulation, the authors explore the possible role of L-channels in the autocontrol of catecholamine release.

Continuous-variable quantum key distribution with a leakage from state preparation

NASA Astrophysics Data System (ADS)

Derkach, Ivan; Usenko, Vladyslav C.; Filip, Radim

2017-12-01

We address side-channel leakage in a trusted preparation station of continuous-variable quantum key distribution with coherent and squeezed states. We consider two different scenarios: multimode Gaussian modulation, directly accessible to an eavesdropper, or side-channel loss of the signal states prior to the modulation stage. We show the negative impact of excessive modulation on both the coherent- and squeezed-state protocols. The impact is more pronounced for squeezed-state protocols and may require optimization of squeezing in the case of noisy quantum channels. Further, we demonstrate that the coherent-state protocol is immune to side-channel signal state leakage prior to modulation, while the squeezed-state protocol is vulnerable to such attacks, becoming more sensitive to the noise in the channel. In the general case of noisy quantum channels the signal squeezing can be optimized to provide best performance of the protocol in the presence of side-channel leakage prior to modulation. Our results demonstrate that leakage from the trusted source in continuous-variable quantum key distribution should not be underestimated and squeezing optimization is needed to overcome coherent state protocols.

Evaluation of a novel triple-channel radiochromic film analysis procedure using EBT2.

PubMed

van Hoof, Stefan J; Granton, Patrick V; Landry, Guillaume; Podesta, Mark; Verhaegen, Frank

2012-07-07

A novel approach to read out radiochromic film was introduced recently by the manufacturer of GafChromic film. In this study, the performance of this triple-channel film dosimetry method was compared against the conventional single-red-channel film dosimetry procedure, with and without inclusion of a pre-irradiation (pre-IR) film scan, using EBT2 film and kilo- and megavoltage photon beams up to 10 Gy. When considering regions of interest averaged doses, the triple-channel method and both single-channel methods produced equivalent results. Absolute dose discrepancies between the triple-channel method, both single-channel methods and the treatment planning system calculated dose values, were no larger than 5 cGy for dose levels up to 2.2 Gy. Signal to noise in triple-channel dose images was found to be similar to signal to noise in single-channel dose images. The accuracy of resulting dose images from the triple- and single-channel methods with inclusion of pre-IR film scan was found to be similar. Results of a comparison of EBT2 data from a kilovoltage depth dose experiment to corresponding Monte Carlo depth dose data produced dose discrepancies of 9.5 ± 12 cGy and 7.6 ± 6 cGy for the single-channel method with inclusion of a pre-IR film scan and the triple-channel method, respectively. EBT2 showed to be energy sensitive at low kilovoltage energies with response differences of 11.9% and 15.6% in the red channel at 2 Gy between 50-225 kVp and 80-225 kVp photon spectra, respectively. We observed that the triple-channel method resulted in non-uniformity corrections of ±1% and consistency values of 0-3 cGy for the batches and dose levels studied. Results of this study indicate that the triple-channel radiochromic film read-out method performs at least as well as the single-channel method with inclusion of a pre-IR film scan, reduces film non-uniformity and saves time with elimination of a pre-IR film scan.

Optimum Adaptive Modulation and Channel Coding Scheme for Frequency Domain Channel-Dependent Scheduling in OFDM Based Evolved UTRA Downlink

NASA Astrophysics Data System (ADS)

Miki, Nobuhiko; Kishiyama, Yoshihisa; Higuchi, Kenichi; Sawahashi, Mamoru; Nakagawa, Masao

In the Evolved UTRA (UMTS Terrestrial Radio Access) downlink, Orthogonal Frequency Division Multiplexing (OFDM) based radio access was adopted because of its inherent immunity to multipath interference and flexible accommodation of different spectrum arrangements. This paper presents the optimum adaptive modulation and channel coding (AMC) scheme when resource blocks (RBs) is simultaneously assigned to the same user when frequency and time domain channel-dependent scheduling is assumed in the downlink OFDMA radio access with single-antenna transmission. We start by presenting selection methods for the modulation and coding scheme (MCS) employing mutual information both for RB-common and RB-dependent modulation schemes. Simulation results show that, irrespective of the application of power adaptation to RB-dependent modulation, the improvement in the achievable throughput of the RB-dependent modulation scheme compared to that for the RB-common modulation scheme is slight, i.e., 4 to 5%. In addition, the number of required control signaling bits in the RB-dependent modulation scheme becomes greater than that for the RB-common modulation scheme. Therefore, we conclude that the RB-common modulation and channel coding rate scheme is preferred, when multiple RBs of the same coded stream are assigned to one user in the case of single-antenna transmission.

Bisphenol A stimulates human prostate cancer cell migration via remodelling of calcium signalling.

PubMed

Derouiche, Sandra; Warnier, Marine; Mariot, Pascal; Gosset, Pierre; Mauroy, Brigitte; Bonnal, Jean-Louis; Slomianny, Christian; Delcourt, Philippe; Prevarskaya, Natalia; Roudbaraki, Morad

2013-12-01

Bisphenol A (BPA), the principal constituent of reusable water bottles, metal cans, and plastic food containers, has been shown to be involved in human prostate cancer (PCa) cell proliferation. The aim of the present study was to explore the effect of BPA on PCa cell migration and the pathways involved in these processes. Using the transwell technique, we clearly show for the first time that the pre-treatment of the cells with BPA (1-10 nM) induces human PCa cell migration. Using a calcium imaging technique, we show that BPA pre-treatment induces an amplification of Store-Operated Calcium Entry (SOCE) in LNCaP cells. RT-PCR and Western blot experiments allowed the identification of the ion channel proteins which are up-regulated by BPA pre-treatments. These include the Orai1 protein, which is known as an important SOCE actor in various cell systems, including human PCa cells. Using a siRNA strategy, we observed that BPA-induced amplification of SOCE was Orai1-dependent. Interestingly, the BPA-induced PCa cell migration was suppressed when the calcium entry was impaired by the use of SOCE inhibitors (SKF96365, BTP2), or when the extracellular calcium was chelated. Taken together, the results presented here show that BPA induces PCa cells migration via a modulation of the ion channel protein expression involved in calcium entry and in cancer cell migration. The present data provide novel insights into the molecular mechanisms involved in the effects of an environmental factor on cancer cells and suggest both the necessity of preventive measures and the possibility of targeting ion channels in the treatment of PCa cell metastasis.

Ion Permeation and Mechanotransduction Mechanisms of Mechanosensitive Piezo Channels.

PubMed

Zhao, Qiancheng; Wu, Kun; Geng, Jie; Chi, Shaopeng; Wang, Yanfeng; Zhi, Peng; Zhang, Mingmin; Xiao, Bailong

2016-03-16

Piezo proteins have been proposed as the long-sought-after mechanosensitive cation channels in mammals that play critical roles in various mechanotransduction processes. However, the molecular bases that underlie their ion permeation and mechanotransduction have remained functionally undefined. Here we report our finding of the miniature pore-forming module of Piezo1 that resembles the pore architecture of other trimeric channels and encodes the essential pore properties. We further identified specific residues within the pore module that determine unitary conductance, pore blockage and ion selectivity for divalent and monovalent cations and anions. The non-pore-containing region of Piezo1 confers mechanosensitivity to mechano-insensitive trimeric acid-sensing ion channels, demonstrating that Piezo1 channels possess intrinsic mechanotransduction modules separate from their pore modules. In conclusion, this is the first report on the bona fide pore module and mechanotransduction components of Piezo channels, which define their ion-conducting properties and gating by mechanical stimuli, respectively. Copyright © 2016 Elsevier Inc. All rights reserved.

Modulation of the olfactory CNG channel by Ptdlns(3,4,5)P3.

PubMed

Zhainazarov, A B; Spehr, M; Wetzel, C H; Hatt, H; Ache, B W

2004-09-01

Recent data suggest that the 3-phosphoinositides can modulate cyclic nucleotide signaling in rat olfactory receptor neurons (ORNs). Given the ability of diverse lipids to modulate ion channels, we asked whether phosphatidylinositol 3,4,5-trisphosphate (PIP3) can regulate the olfactory cyclic nucleotide-gated (CNG) channel as a possible mechanism for this modulation. We show that applying PIP3 to the intracellular side of inside-out patches from rat ORNs inhibits activation of the olfactory CNG channel by cAMP. The effect of PIP3 is immediate and partially reversible, and reflects an increase in the EC50 of cAMP, not a reduction in the single-channel current amplitude. The effect of PIP3 is significantly stronger than that of PIP2; other phospholipids tested have no appreciable effect on channel activity. PIP3 similarly inhibits the recombinant heteromeric (A2/A4) and homomeric (A2) olfactory CNG channel expressed in HEK293 cells, suggesting that PIP3 acts directly on the channel. These findings indicate that 3-phosphoinositides can be functionally important regulators of CNG channels.

A Fully Integrated Wireless Compressed Sensing Neural Signal Acquisition System for Chronic Recording and Brain Machine Interface.

PubMed

Liu, Xilin; Zhang, Milin; Xiong, Tao; Richardson, Andrew G; Lucas, Timothy H; Chin, Peter S; Etienne-Cummings, Ralph; Tran, Trac D; Van der Spiegel, Jan

2016-07-18

Reliable, multi-channel neural recording is critical to the neuroscience research and clinical treatment. However, most hardware development of fully integrated, multi-channel wireless neural recorders to-date, is still in the proof-of-concept stage. To be ready for practical use, the trade-offs between performance, power consumption, device size, robustness, and compatibility need to be carefully taken into account. This paper presents an optimized wireless compressed sensing neural signal recording system. The system takes advantages of both custom integrated circuits and universal compatible wireless solutions. The proposed system includes an implantable wireless system-on-chip (SoC) and an external wireless relay. The SoC integrates 16-channel low-noise neural amplifiers, programmable filters and gain stages, a SAR ADC, a real-time compressed sensing module, and a near field wireless power and data transmission link. The external relay integrates a 32 bit low-power microcontroller with Bluetooth 4.0 wireless module, a programming interface, and an inductive charging unit. The SoC achieves high signal recording quality with minimized power consumption, while reducing the risk of infection from through-skin connectors. The external relay maximizes the compatibility and programmability. The proposed compressed sensing module is highly configurable, featuring a SNDR of 9.78 dB with a compression ratio of 8×. The SoC has been fabricated in a 180 nm standard CMOS technology, occupying 2.1 mm × 0.6 mm silicon area. A pre-implantable system has been assembled to demonstrate the proposed paradigm. The developed system has been successfully used for long-term wireless neural recording in freely behaving rhesus monkey.

Role of Dynamics in the Autoinhibition and Activation of the Hyperpolarization-activated Cyclic Nucleotide-modulated (HCN) Ion Channels*♦

PubMed Central

VanSchouwen, Bryan; Akimoto, Madoka; Sayadi, Maryam; Fogolari, Federico; Melacini, Giuseppe

2015-01-01

The hyperpolarization-activated cyclic nucleotide-modulated (HCN) ion channels control rhythmicity in neurons and cardiomyocytes. Cyclic AMP allosterically modulates HCN through the cAMP-dependent formation of a tetrameric gating ring spanning the intracellular region (IR) of HCN, to which cAMP binds. Although the apo versus holo conformational changes of the cAMP-binding domain (CBD) have been previously mapped, only limited information is currently available on the HCN IR dynamics, which have been hypothesized to play a critical role in the cAMP-dependent gating of HCN. Here, using molecular dynamics simulations validated and complemented by experimental NMR and CD data, we comparatively analyze HCN IR dynamics in the four states of the thermodynamic cycle arising from the coupling between cAMP binding and tetramerization equilibria. This extensive set of molecular dynamics trajectories captures the active-to-inactive transition that had remained elusive for other CBDs, and it provides unprecedented insight on the role of IR dynamics in HCN autoinhibition and its release by cAMP. Specifically, the IR tetramerization domain becomes more flexible in the monomeric states, removing steric clashes that the apo-CDB structure would otherwise impose. Furthermore, the simulations reveal that the active/inactive structural transition for the apo-monomeric CBD occurs through a manifold of pathways that are more divergent than previously anticipated. Upon cAMP binding, these pathways become disallowed, pre-confining the CBD conformational ensemble to a tetramer-compatible state. This conformational confinement primes the IR for tetramerization and thus provides a model of how cAMP controls HCN channel gating. PMID:25944904

TRPV4 antagonist GSK2193874 does not modulate cough response to osmotic stimuli.

PubMed

Buday, Tomas; Kovacikova, Lea; Ruzinak, Robert; Plevkova, Jana

2017-02-01

Osmolarity changes of airway superficial fluid are associated with cough and are used in research. TRPV4 is calcium channel initially described as osmosensor. In the airways, it can play role in increasing cough reflex sensitivity. The aim of our study was to test whether cough to osmotic stimuli is mediated via TRPV4 channel. Cough response was measured in 12 male guinea pigs by inhalation of saline, distilled water, hypertonic solution and citric acid for 10min in whole-body plethysmograph. Data were obtained in naïve animals and after pre-treatment with selective TRPV4 antagonist GSK2193874 in doses 300μg/kg (GSK300) and 900μg/kg (GSK900). Cough response to all tested aerosols was significantly higher than to saline. Pre-treatment with GSK300 did not influence response to osmotic stimuli - only reduced cough to citric acid. GSK900 reduced cough response to hypotonic stimuli and citric acid. TRPV4 mediated activation of airway afferents does not seem to be the exclusive mechanism responsible for cough to osmotic stimuli. Copyright © 2016 Elsevier B.V. All rights reserved.

Note: optical receiver system for 152-channel magnetoencephalography.

PubMed

Kim, Jin-Mok; Kwon, Hyukchan; Yu, Kwon-kyu; Lee, Yong-Ho; Kim, Kiwoong

2014-11-01

An optical receiver system composing 13 serial data restore/synchronizer modules and a single module combiner converted optical 32-bit serial data into 32-bit synchronous parallel data for a computer to acquire 152-channel magnetoencephalography (MEG) signals. A serial data restore/synchronizer module identified 32-bit channel-voltage bits from 48-bit streaming serial data, and then consecutively reproduced 13 times of 32-bit serial data, acting in a synchronous clock. After selecting a single among 13 reproduced data in each module, a module combiner converted it into 32-bit parallel data, which were carried to 32-port digital input board in a computer. When the receiver system together with optical transmitters were applied to 152-channel superconducting quantum interference device sensors, this MEG system maintained a field noise level of 3 fT/√Hz @ 100 Hz at a sample rate of 1 kSample/s per channel.

Optical transmission modules for multi-channel superconducting quantum interference device readouts.

PubMed

Kim, Jin-Mok; Kwon, Hyukchan; Yu, Kwon-kyu; Lee, Yong-Ho; Kim, Kiwoong

2013-12-01

We developed an optical transmission module consisting of 16-channel analog-to-digital converter (ADC), digital-noise filter, and one-line serial transmitter, which transferred Superconducting Quantum Interference Device (SQUID) readout data to a computer by a single optical cable. A 16-channel ADC sent out SQUID readouts data with 32-bit serial data of 8-bit channel and 24-bit voltage data at a sample rate of 1.5 kSample/s. A digital-noise filter suppressed digital noises generated by digital clocks to obtain SQUID modulation as large as possible. One-line serial transmitter reformed 32-bit serial data to the modulated data that contained data and clock, and sent them through a single optical cable. When the optical transmission modules were applied to 152-channel SQUID magnetoencephalography system, this system maintained a field noise level of 3 fT/√Hz @ 100 Hz.

P/Q-type calcium channel modulators

PubMed Central

Nimmrich, V; Gross, G

2012-01-01

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

Bidirectional optical subassembly-shaped 20-Gbit/s compact single-mode four-channel wavelength-division multiplexing optical modules for optical multimedia interfaces

NASA Astrophysics Data System (ADS)

Lim, Kwon-Seob; Yu, Hong-Yeon; Park, Hyoung-Jun; Kang, Hyun Seo; Jang, Jae-Hyung

2016-06-01

Low-cost single-mode four-channel optical transmitter and receiver modules using the wavelength-division multiplexing (WDM) method have been developed for long-reach fiber optic applications. The single-mode four-channel WDM optical transmitter and receiver modules consist of two dual-wavelength optical transmitter and receiver submodules, respectively. The integration of two channels in a glass-sealed transistor outline-can package is an effective way to reduce cost and size and to extend the number of channels. The clear eye diagrams with more than about 6 dB of the extinction ratio and the minimum receiver sensitivity of lower than -16 dBm at a bit error rate of 10-12 have been obtained for the transmitter and receiver modules, respectively, at 5 Gbps/channel. The 4K ultrahigh definition contents have been transmitted over a 1-km-long single-mode fiber using a pair of proposed four-channel transmitter optical subassembly and receiver optical subassembly.

Pre-Processed Recursive Lattice Reduction for Complexity Reduction in Spatially and Temporally Correlated MIMO Channels

NASA Astrophysics Data System (ADS)

An, Chan-Ho; Yang, Janghoon; Jang, Seunghun; Kim, Dong Ku

In this letter, a pre-processed lattice reduction (PLR) scheme is developed for the lattice reduction aided (LRA) detection of multiple input multiple-output (MIMO) systems in spatially correlated channel. The PLR computes the LLL-reduced matrix of the equivalent matrix, which is the product of the present channel matrix and unimodular transformation matrix for LR of spatial correlation matrix, rather than the present channel matrix itself. In conjunction with PLR followed by recursive lattice reduction (RLR) scheme [7], pre-processed RLR (PRLR) is shown to efficiently carry out the LR of the channel matrix, especially for the burst packet message in spatially and temporally correlated channel while matching the performance of conventional LRA detection.

Structural basis for modulation and agonist specificity of HCN pacemaker channels.

PubMed

Zagotta, William N; Olivier, Nelson B; Black, Kevin D; Young, Edgar C; Olson, Rich; Gouaux, Eric

2003-09-11

The family of hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channels are crucial for a range of electrical signalling, including cardiac and neuronal pacemaker activity, setting resting membrane electrical properties and dendritic integration. These nonselective cation channels, underlying the I(f), I(h) and I(q) currents of heart and nerve cells, are activated by membrane hyperpolarization and modulated by the binding of cyclic nucleotides such as cAMP and cGMP. The cAMP-mediated enhancement of channel activity is largely responsible for the increase in heart rate caused by beta-adrenergic agonists. Here we have investigated the mechanism underlying this modulation by studying a carboxy-terminal fragment of HCN2 containing the cyclic nucleotide-binding domain (CNBD) and the C-linker region that connects the CNBD to the pore. X-ray crystallographic structures of this C-terminal fragment bound to cAMP or cGMP, together with equilibrium sedimentation analysis, identify a tetramerization domain and the mechanism for cyclic nucleotide specificity, and suggest a model for ligand-dependent channel modulation. On the basis of amino acid sequence similarity to HCN channels, the cyclic nucleotide-gated, and eag- and KAT1-related families of channels are probably related to HCN channels in structure and mechanism.

Ion channel blockers for the treatment of neuropathic pain.

PubMed

Colombo, Elena; Francisconi, Simona; Faravelli, Laura; Izzo, Emanuela; Pevarello, Paolo

2010-05-01

Neuropathic pain, a severe chronic pain condition characterized by a complex pathophysiology, is a largely unmet medical need. Ion channels, which underlie cell excitability, are heavily implicated in the biological mechanisms that generate and sustain neuropathic pain. This review highlights the biological evidence supporting the involvement of voltage-, proton- and ligand-gated ion channels in the neuropathic pain setting. Ion channel modulators at different research or development stages are reviewed and referenced. Ion channel modulation is one of the main avenues to achieve novel, improved neuropathic pain treatments. Voltage-gated sodium and calcium channel and glutamate receptor modulators are likely to produce new, improved agents in the future. Rationally targeting subtypes of known ion channels, tackling recently discovered ion channel targets or combining drugs with different mechanism of action will be primary sources of new drugs in the longer term.

All-optical regenerator of multi-channel signals.

PubMed

Li, Lu; Patki, Pallavi G; Kwon, Young B; Stelmakh, Veronika; Campbell, Brandon D; Annamalai, Muthiah; Lakoba, Taras I; Vasilyev, Michael

2017-10-12

One of the main reasons why nonlinear-optical signal processing (regeneration, logic, etc.) has not yet become a practical alternative to electronic processing is that the all-optical elements with nonlinear input-output relationship have remained inherently single-channel devices (just like their electronic counterparts) and, hence, cannot fully utilise the parallel processing potential of optical fibres and amplifiers. The nonlinear input-output transfer function requires strong optical nonlinearity, e.g. self-phase modulation, which, for fundamental reasons, is always accompanied by cross-phase modulation and four-wave mixing. In processing multiple wavelength-division-multiplexing channels, large cross-phase modulation and four-wave mixing crosstalks among the channels destroy signal quality. Here we describe a solution to this problem: an optical signal processor employing a group-delay-managed nonlinear medium where strong self-phase modulation is achieved without such nonlinear crosstalk. We demonstrate, for the first time to our knowledge, simultaneous all-optical regeneration of up to 16 wavelength-division-multiplexing channels by one device. This multi-channel concept can be extended to other nonlinear-optical processing schemes.Nonlinear optical processing devices are not yet fully practical as they are single channel. Here the authors demonstrate all-optical regeneration of up to 16 channels by one device, employing a group-delay-managed nonlinear medium where strong self-phase modulation is achieved without nonlinear inter-channel crosstalk.

Non-binary LDPC-coded modulation for high-speed optical metro networks with backpropagation

NASA Astrophysics Data System (ADS)

Arabaci, Murat; Djordjevic, Ivan B.; Saunders, Ross; Marcoccia, Roberto M.

2010-01-01

To simultaneously mitigate the linear and nonlinear channel impairments in high-speed optical communications, we propose the use of non-binary low-density-parity-check-coded modulation in combination with a coarse backpropagation method. By employing backpropagation, we reduce the memory in the channel and in return obtain significant reductions in the complexity of the channel equalizer which is exponentially proportional to the channel memory. We then compensate for the remaining channel distortions using forward error correction based on non-binary LDPC codes. We propose non-binary-LDPC-coded modulation scheme because, compared to bit-interleaved binary-LDPC-coded modulation scheme employing turbo equalization, the proposed scheme lowers the computational complexity and latency of the overall system while providing impressively larger coding gains.

Effects of geometric modulation and surface potential heterogeneity on electrokinetic flow and solute transport in a microchannel

NASA Astrophysics Data System (ADS)

Bera, Subrata; Bhattacharyya, S.

2017-12-01

A numerical investigation is performed on the electroosmotic flow (EOF) in a surface-modulated microchannel to induce enhanced solute mixing. The channel wall is modulated by placing surface-mounted obstacles of trigonometric shape along which the surface potential is considered to be different from the surface potential of the homogeneous part of the wall. The characteristics of the electrokinetic flow are governed by the Laplace equation for the distribution of external electric potential; the Poisson equation for the distribution of induced electric potential; the Nernst-Planck equations for the distribution of ions; and the Navier-Stokes equations for fluid flow simultaneously. These nonlinear coupled set of governing equations are solved numerically by a control volume method over the staggered system. The influence of the geometric modulation of the surface, surface potential heterogeneity and the bulk ionic concentration on the EOF is analyzed. Vortical flow develops near a surface modulation, and it becomes stronger when the surface potential of the modulated region is in opposite sign to the surface potential of the homogeneous part of the channel walls. Vortical flow also depends on the Debye length when the Debye length is in the order of the channel height. Pressure drop along the channel length is higher for a ribbed wall channel compared to the grooved wall case. The pressure drop decreases with the increase in the amplitude for a grooved channel, but increases for a ribbed channel. The mixing index is quantified through the standard deviation of the solute distribution. Our results show that mixing index is higher for the ribbed channel compared to the grooved channel with heterogeneous surface potential. The increase in potential heterogeneity in the modulated region also increases the mixing index in both grooved and ribbed channels. However, the mixing performance, which is the ratio of the mixing index to pressure drop, reduces with the rise in the surface potential heterogeneity.

Effects of geometric modulation and surface potential heterogeneity on electrokinetic flow and solute transport in a microchannel

NASA Astrophysics Data System (ADS)

Bera, Subrata; Bhattacharyya, S.

2018-04-01

A numerical investigation is performed on the electroosmotic flow (EOF) in a surface-modulated microchannel to induce enhanced solute mixing. The channel wall is modulated by placing surface-mounted obstacles of trigonometric shape along which the surface potential is considered to be different from the surface potential of the homogeneous part of the wall. The characteristics of the electrokinetic flow are governed by the Laplace equation for the distribution of external electric potential; the Poisson equation for the distribution of induced electric potential; the Nernst-Planck equations for the distribution of ions; and the Navier-Stokes equations for fluid flow simultaneously. These nonlinear coupled set of governing equations are solved numerically by a control volume method over the staggered system. The influence of the geometric modulation of the surface, surface potential heterogeneity and the bulk ionic concentration on the EOF is analyzed. Vortical flow develops near a surface modulation, and it becomes stronger when the surface potential of the modulated region is in opposite sign to the surface potential of the homogeneous part of the channel walls. Vortical flow also depends on the Debye length when the Debye length is in the order of the channel height. Pressure drop along the channel length is higher for a ribbed wall channel compared to the grooved wall case. The pressure drop decreases with the increase in the amplitude for a grooved channel, but increases for a ribbed channel. The mixing index is quantified through the standard deviation of the solute distribution. Our results show that mixing index is higher for the ribbed channel compared to the grooved channel with heterogeneous surface potential. The increase in potential heterogeneity in the modulated region also increases the mixing index in both grooved and ribbed channels. However, the mixing performance, which is the ratio of the mixing index to pressure drop, reduces with the rise in the surface potential heterogeneity.

Reconfigurable WDM-PON empowered by a low-cost 8-channel directly modulated laser module

NASA Astrophysics Data System (ADS)

Zhang, Yi-ming; Liu, Yu; Zhang, Zhi-ke; Zhao, Ze-ping; Tian, Ye; Zhu, Ning-hua

2017-11-01

A 10 Gbit/s 16-km-long reconfigurable wavelength-division-multiplexing passive optical network (WDM-PON) is presented empowered by a low-cost multi-channel directly modulated laser (DML) module. Compared with the case using discrete devices in conventional scheme, the proposed DML module provides a cost-effective solution with reduced complexity. The clear eye diagram and the bit error rate ( BER) of less than 2×10-7 with a sensitivity of -7 dBm are obtained. Due to the special packaging design, the crosstalk between channels under condition of simultaneous operation can be negligible.

Blind Equalization and Fading Channel Signal Recovery of OFDM Modulation

DTIC Science & Technology

2011-03-01

Square LTI Linear Time Invariant MIMO Multiple-Input Multiple-Output OFDM Orthogonal Frequency-Division Multiplexing QPSK Quadrature Phase-Shift...AND FADING CHANNEL SIGNAL RECOVERY OF OFDM MODULATION by Anthony G. Stranges March 2011 Thesis Co-Advisors: Roberto Cristi Frank Kragh...Master’s Thesis 4. TITLE AND SUBTITLE Blind Equalization and Fading Channel Signal Recovery of OFDM Modulation 6. AUTHOR(S) Anthony G. Stranges

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

PubMed Central

Svalø, Julie; Sheykhzade, Majid; Nordling, Jørgen; Matras, Christina; Bouchelouche, Pierre

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 expression of KCNQ1, KCNQ3-KCNQ5 and KCNE1-5 in the human urinary bladder from patients with normal bladder function (n = 7) and in patients with bladder outflow obstruction (n = 3). Interestingly, a 3.4-fold up-regulation of KCNQ1 was observed in the latter. The Kv7 channel subtype selective modulators, ML277 (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. Furthermore, we investigated if there is interplay between Kv7 channels and β-adrenoceptors. Using cumulative additions of isoprenaline (β-adrenoceptor agonist) and forskolin (adenylyl cyclase activator) in combination with the Kv7 channel activator and blocker, retigabine and XE991, we did not find interplay 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. PMID:25692982

Functional and molecular evidence for Kv7 channel subtypes in human detrusor from patients with and without bladder outflow obstruction.

PubMed

Svalø, Julie; Sheykhzade, Majid; Nordling, Jørgen; Matras, Christina; Bouchelouche, Pierre

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 expression of KCNQ1, KCNQ3-KCNQ5 and KCNE1-5 in the human urinary bladder from patients with normal bladder function (n = 7) and in patients with bladder outflow obstruction (n = 3). Interestingly, a 3.4-fold up-regulation of KCNQ1 was observed in the latter. The Kv7 channel subtype selective modulators, ML277 (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. Furthermore, we investigated if there is interplay between Kv7 channels and β-adrenoceptors. Using cumulative additions of isoprenaline (β-adrenoceptor agonist) and forskolin (adenylyl cyclase activator) in combination with the Kv7 channel activator and blocker, retigabine and XE991, we did not find interplay 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.

Alternative splicing modulates Kv channel clustering through a molecular ball and chain mechanism

NASA Astrophysics Data System (ADS)

Zandany, Nitzan; Marciano, Shir; Magidovich, Elhanan; Frimerman, Teddy; Yehezkel, Rinat; Shem-Ad, Tzilhav; Lewin, Limor; Abdu, Uri; Orr, Irit; Yifrach, Ofer

2015-03-01

Ion channel clustering at the post-synaptic density serves a fundamental role in action potential generation and transmission. Here, we show that interaction between the Shaker Kv channel and the PSD-95 scaffold protein underlying channel clustering is modulated by the length of the intrinsically disordered C terminal channel tail. We further show that this tail functions as an entropic clock that times PSD-95 binding. We thus propose a ‘ball and chain’ mechanism to explain Kv channel binding to scaffold proteins, analogous to the mechanism describing channel fast inactivation. The physiological relevance of this mechanism is demonstrated in that alternative splicing of the Shaker channel gene to produce variants of distinct tail lengths resulted in differential channel cell surface expression levels and clustering metrics that correlate with differences in affinity of the variants for PSD-95. We suggest that modulating channel clustering by specific spatial-temporal spliced variant targeting serves a fundamental role in nervous system development and tuning.

TASK Channels on Basal Forebrain Cholinergic Neurons Modulate Electrocortical Signatures of Arousal by Histamine

PubMed Central

Vu, Michael T.; Du, Guizhi; Bayliss, Douglas A.

2015-01-01

Basal forebrain cholinergic neurons are the main source of cortical acetylcholine, and their activation by histamine elicits cortical arousal. TWIK-like acid-sensitive K+ (TASK) channels modulate neuronal excitability and are expressed on basal forebrain cholinergic neurons, but the role of TASK channels in the histamine-basal forebrain cholinergic arousal circuit is unknown. We first expressed TASK channel subunits and histamine Type 1 receptors in HEK cells. Application of histamine in vitro inhibited the acid-sensitive K+ current, indicating a functionally coupled signaling mechanism. We then studied the role of TASK channels in modulating electrocortical activity in vivo using freely behaving wild-type (n = 12) and ChAT-Cre:TASKf/f mice (n = 12), the latter lacking TASK-1/3 channels on cholinergic neurons. TASK channel deletion on cholinergic neurons significantly altered endogenous electroencephalogram oscillations in multiple frequency bands. We then identified the effect of TASK channel deletion during microperfusion of histamine into the basal forebrain. In non-rapid eye movement sleep, TASK channel deletion on cholinergic neurons significantly attenuated the histamine-induced increase in 30–50 Hz activity, consistent with TASK channels contributing to histamine action on basal forebrain cholinergic neurons. In contrast, during active wakefulness, histamine significantly increased 30–50 Hz activity in ChAT-Cre:TASKf/f mice but not wild-type mice, showing that the histamine response depended upon the prevailing cortical arousal state. In summary, we identify TASK channel modulation in response to histamine receptor activation in vitro, as well as a role of TASK channels on cholinergic neurons in modulating endogenous oscillations in the electroencephalogram and the electrocortical response to histamine at the basal forebrain in vivo. SIGNIFICANCE STATEMENT Attentive states and cognitive function are associated with the generation of γ EEG activity. Basal forebrain cholinergic neurons are important modulators of cortical arousal and γ activity, and in this study we investigated the mechanism by which these neurons are activated by the wake-active neurotransmitter histamine. We found that histamine inhibited a class of K+ leak channels called TASK channels and that deletion of TASK channels selectively on cholinergic neurons modulated baseline EEG activity as well as histamine-induced changes in γ activity. By identifying a discrete brain circuit where TASK channels can influence γ activity, these results represent new knowledge that enhances our understanding of how subcortical arousal systems may contribute to the generation of attentive states. PMID:26446210

Mechanisms of action of ligands of potential-dependent sodium channels.

PubMed

Tikhonov, D B

2008-06-01

Potential-dependent sodium channels play a leading role in generating action potentials in excitable cells. Sodium channels are the site of action of a variety of modulator ligands. Despite numerous studies, the mechanisms of action of many modulators remain incompletely understood. The main reason that many important questions cannot be resolved is that there is a lack of precise data on the structures of the channels themselves. Structurally, potential-dependent sodium channels are members of the P-loop channel superfamily, which also include potassium and calcium channels and glutamate receptor channels. Crystallization of a series of potassium channels showed that it was possible to analyze the structures of different members of the superfamily using the "homologous modeling" method. The present study addresses model investigations of the actions of ligands of sodium channels, including tetrodotoxin and batrachotoxin, as well as local anesthetics. Comparison of experimental data on sodium channel ligands with x-ray analysis data allowed us to reach a new level of understanding of the mechanisms of channel modulation and to propose a series of experimentally verifiable hypotheses.

Chloride channels as drug targets

PubMed Central

Verkman, Alan S.; Galietta, Luis J. V.

2013-01-01

Chloride channels represent a relatively under-explored target class for drug discovery as elucidation of their identity and physiological roles has lagged behind that of many other drug targets. Chloride channels are involved in a wide range of biological functions, including epithelial fluid secretion, cell-volume regulation, neuroexcitation, smooth-muscle contraction and acidification of intracellular organelles. Mutations in several chloride channels cause human diseases, including cystic fibrosis, macular degeneration, myotonia, kidney stones, renal salt wasting and hyperekplexia. Chloride-channel modulators have potential applications in the treatment of some of these disorders, as well as in secretory diarrhoeas, polycystic kidney disease, osteoporosis and hypertension. Modulators of GABAA (γ-aminobutyric acid A) receptor chloride channels are in clinical use and several small-molecule chloride-channel modulators are in preclinical development and clinical trials. Here, we discuss the broad opportunities that remain in chloride-channel-based drug discovery. PMID:19153558

Neuromodulation, development and synaptic plasticity.

PubMed

Foehring, R C; Lorenzon, N M

1999-03-01

We discuss parallels in the mechanisms underlying use-dependent synaptic plasticity during development and long-term potentiation (LTP) and long-term depression (LTD) in neocortical synapses. Neuromodulators, such as norepinephrine, serotonin, and acetylcholine have also been implicated in regulating both developmental plasticity and LTP/LTD. There are many potential levels of interaction between neuromodulators and plasticity. Ion channels are substrates for modulation in many cell types. We discuss examples of modulation of voltage-gated Ca2+ channels and Ca(2+)-dependent K+ channels and the consequences for neocortical pyramidal cell firing behaviour. At the time when developmental plasticity is most evident in rat cortex, the substrate for modulation is changing as the densities and relative proportions of various ion channels types are altered during ontogeny. We discuss examples of changes in K+ and Ca2+ channels and the consequence for modulation of neuronal activity.

Modulation/demodulation techniques for satellite communications. Part 2: Advanced techniques. The linear channel

NASA Technical Reports Server (NTRS)

Omura, J. K.; Simon, M. K.

1982-01-01

A theory is presented for deducing and predicting the performance of transmitter/receivers for bandwidth efficient modulations suitable for use on the linear satellite channel. The underlying principle used is the development of receiver structures based on the maximum-likelihood decision rule. The application of the performance prediction tools, e.g., channel cutoff rate and bit error probability transfer function bounds to these modulation/demodulation techniques.

DC biased low-frequency insulating constriction dielectrophoresis for protein biomolecules concentration.

PubMed

Zhang, Peng; Liu, Yuxin

2017-09-01

Sample enrichment or molecules concentration is considered an essential step in sample processing of miniaturized devices aimed at biosensing and bioanalysis. Among all the means involved to achieve this aim, dielectrophoresis (DEP) is increasingly employed in molecules manipulation and concentration because it is non-destructive and high efficiency. This paper presents a methodology to achieve protein concentration utilizing the combination effects of electrokinetics and low frequency insulating dielectrophoresis (iDEP) generated within a microfluidic device, in which a submicron constricted channel was fabricated using DNA molecular combing and replica molding. This fabrication technique avoids using e-beam lithography or other complicated nanochannel fabrication methods, and provides an easy and low cost approach with the flexibility of controlling channel dimensions to create highly constricted channels embedded in a microfluidic device. With theoretical analysis and experiments, we demonstrated that fluorescein isothiocyanate conjugated bovine serum albumin (FITC-BSA) protein molecules can be significantly concentrated to form an arc-shaped band near the constricted channel under the effects of a negative dielectrophoretic force and DC electrokinetic forces within a short period of time. It was also observed that the amplitudes of the applied DC and AC electric fields, the AC frequencies as well as the suspending medium conductivities had strong effects on the concentration responses of the FITC-BSA molecules, including the concentrated area and position, intensities of the focused molecules, and concentration speed. Our method provides a simple and flexible approach for quickly concentrating protein molecules by controlling the applied electric field parameters. The iDEP device reported in this paper can be used as a stand-alone sensor or worked as a pre-concentration module integrated with biosensors for protein biomarker detection. Furthermore, low frequency dielectrophoresis provides practical uses for integrating the concentration module with a portable biosensing system.

Mechanisms underlying the relaxant effect of Galetin 3,6- dimethyl ether, from Piptadenia stipulacea (Benth.) Ducke, on guinea-pig trachea.

PubMed

Macêdo, Cibério Landim; Vasconcelos, Luiz Henrique César; Correia, Ana Carolina de Carvalho; Martins, Italo Rossi Roseno; Lira, Daysianne Pereira de; Santos, Bárbara Viviana de Oliveira; Silva, Bagnólia Araújo da

2014-01-01

Galetin 3,6-dimethyl ether (FGAL), a flavonoid from the aerial parts of Piptadenia stipulacea (Benth.) Ducke, was found to exert a relaxant effect on carbachol (CCh)-pre-contracted guinea-pig trachea. Based on cumulative concentration-response curves to CCh, FGAL antagonized muscarinic receptors pseudo-irreversibly and noncompetitively, since it inhibited and shifted these curves towards higher concentrations in a nonparallel manner. In addition, FGAL was more potent in relaxing contractions induced by 18 mM as compared to 60 mM KCl (pD2 = 5:50 ±0:36 and 4.80 ±0.07, respectively), indicating the participation of K+ channels. In the presence of 10 mM tetraethylammonium (TEA+) chloride, a nonselective K+ channel blocker, the relaxant potency of FGAL was reduced (from pD2 = 5:12 ±0:07 to 4.87 ±0.02). Among several selective blockers of K+ channel subtypes, only apamin, an SKCa (small-conductance Ca2+-activated K+ channels) blocker, attenuated the relaxant potency of FGAL (pD2 = 4:85±0:06), suggesting SKCa activation. FGAL was equipotent in relaxing trachea contracted by 60 mM KCl (pD2 =4:80 ±0:07) or 10-6 M CCh (pD2 = 5:02 ±0:07), suggesting CaV (voltage-gated calcium channel), but not ROCs (receptor-operated calcium channels) participation. Furthermore, aminophylline-induced relaxation (pD2 = 4:12 ±0:06) was potentiated around 4-fold (pD2 = 4:80 ±0:44) in the presence of FGAL. Moreover, forskolininduced relaxation (pD2 = 6:51 ±0:06) was potentiated around 2.5-fold (pD2 = 6:90 ±0:05) by FGAL. Conversely, sodium nitroprusside-induced relaxation was unaffected, indicating that the AC/cAMP/PKA pathway, but not the NO pathway, may be modulated by the flavonoid. These results suggest that, in guinea-pig trachea, FGAL induces relaxation by pseudo-irreversible noncompetitive antagonism on muscarinic receptors, modulation of K+ and Ca2+ channels, as well as activation of the AC/cAMP/PKA pathway.

Antagonist action of progesterone at σ-receptors in the modulation of voltage-gated sodium channels

PubMed Central

Johannessen, Molly; Fontanilla, Dominique; Mavlyutov, Timur; Ruoho, Arnold E.

2011-01-01

σ-Receptors are integral membrane proteins that have been implicated in a number of biological functions, many of which involve the modulation of ion channels. A wide range of synthetic ligands activate σ-receptors, but endogenous σ-receptor ligands have proven elusive. One endogenous ligand, dimethyltryptamine (DMT), has been shown to act as a σ-receptor agonist. Progesterone and other steroids bind σ-receptors, but the functional consequences of these interactions are unclear. Here we investigated progesterone binding to σ1- and σ2-receptors and evaluated its effect on σ-receptor-mediated modulation of voltage-gated Na+ channels. Progesterone binds both σ-receptor subtypes in liver membranes with comparable affinities and blocks photolabeling of both subtypes in human embryonic kidney 293 cells that stably express the human cardiac Na+ channel Nav1.5. Patch-clamp recording in this cell line tested Na+ current modulation by the σ-receptor ligands ditolylguanidine, PB28, (+)SKF10047, and DMT. Progesterone inhibited the action of these ligands to varying degrees, and some of these actions were reduced by σ1-receptor knockdown with small interfering RNA. Progesterone inhibition of channel modulation by drugs was consistent with stronger antagonism of σ2-receptors. By contrast, progesterone inhibition of channel modulation by DMT was consistent with stronger antagonism of σ1-receptors. Progesterone binding to σ-receptors blocks σ-receptor-mediated modulation of a voltage-gated ion channel, and this novel membrane action of progesterone may be relevant to changes in brain and cardiovascular function during endocrine transitions. PMID:21084640

Antagonist action of progesterone at σ-receptors in the modulation of voltage-gated sodium channels.

PubMed

Johannessen, Molly; Fontanilla, Dominique; Mavlyutov, Timur; Ruoho, Arnold E; Jackson, Meyer B

2011-02-01

σ-Receptors are integral membrane proteins that have been implicated in a number of biological functions, many of which involve the modulation of ion channels. A wide range of synthetic ligands activate σ-receptors, but endogenous σ-receptor ligands have proven elusive. One endogenous ligand, dimethyltryptamine (DMT), has been shown to act as a σ-receptor agonist. Progesterone and other steroids bind σ-receptors, but the functional consequences of these interactions are unclear. Here we investigated progesterone binding to σ(1)- and σ(2)-receptors and evaluated its effect on σ-receptor-mediated modulation of voltage-gated Na(+) channels. Progesterone binds both σ-receptor subtypes in liver membranes with comparable affinities and blocks photolabeling of both subtypes in human embryonic kidney 293 cells that stably express the human cardiac Na(+) channel Na(v)1.5. Patch-clamp recording in this cell line tested Na(+) current modulation by the σ-receptor ligands ditolylguanidine, PB28, (+)SKF10047, and DMT. Progesterone inhibited the action of these ligands to varying degrees, and some of these actions were reduced by σ(1)-receptor knockdown with small interfering RNA. Progesterone inhibition of channel modulation by drugs was consistent with stronger antagonism of σ(2)-receptors. By contrast, progesterone inhibition of channel modulation by DMT was consistent with stronger antagonism of σ(1)-receptors. Progesterone binding to σ-receptors blocks σ-receptor-mediated modulation of a voltage-gated ion channel, and this novel membrane action of progesterone may be relevant to changes in brain and cardiovascular function during endocrine transitions.

Implications and mechanism of action of gabapentin in neuropathic pain.

PubMed

Kukkar, Ankesh; Bali, Anjana; Singh, Nirmal; Jaggi, Amteshwar Singh

2013-03-01

Gabapentin is an anti-epileptic agent but now it is also recommended as first line agent in neuropathic pain, particularly in diabetic neuropathy and post herpetic neuralgia. α2δ-1, an auxillary subunit of voltage gated calcium channels, has been documented as its main target and its specific binding to this subunit is described to produce different actions responsible for pain attenuation. The binding to α2δ-1 subunits inhibits nerve injury-induced trafficking of α1 pore forming units of calcium channels (particularly N-type) from cytoplasm to plasma membrane (membrane trafficking) of pre-synaptic terminals of dorsal root ganglion (DRG) neurons and dorsal horn neurons. Furthermore, the axoplasmic transport of α2δ-1 subunits from DRG to dorsal horns neurons in the form of anterograde trafficking is also inhibited in response to gabapentin administration. Gabapentin has also been shown to induce modulate other targets including transient receptor potential channels, NMDA receptors, protein kinase C and inflammatory cytokines. It may also act on supra-spinal region to stimulate noradrenaline mediated descending inhibition, which contributes to its anti-hypersensitivity action in neuropathic pain.

Separate channels for the analysis of the shape and the movement of moving visual stimulus.

PubMed

Tolhurst, D J

1973-06-01

1. The effects of temporal modulation on the properties of spatial frequency channels have been investigated using adaptation.2. Adapting to drifting sinusoidal gratings caused threshold elevation that was both spatial frequency and direction specific. Little systematic difference was found between the band widths of the elevation curves for drifting and stationary gratings.3. It was confirmed that adaptation fails to reveal channels at low spatial frequencies when stationary gratings are used. However, channels were revealed at frequencies at least as low as 0.66 c/deg when the test gratings were made to move. These channels are adapted only a little by stationary gratings, confirming their dependence on movement.4. The existence of movement-sensitive channels at low spatial frequencies explains the well known observation that temporal modulation greatly increases the sensitivity of the visual system to low spatial frequencies.5. Temporal modulation was effective at revealing these channels only when the flicker or movement of the test patterns was apparent to the observer; only at low spatial frequencies did patterns, modulated at low rates, actually appear to be temporarily modulated at threshold. At higher spatial frequencies, they were indistinguishable from stationary patterns until the contrast was some way above the detection threshold.6. It is suggested, therefore, that the movement-sensitive channels are responsible for signalling the occurrence of movement; the channels at higher spatial frequencies give no information about temporal changes. These two systems of channels are compared to the Y- and X-cells respectively of the cat.

Physiology and Evolution of Voltage-Gated Calcium Channels in Early Diverging Animal Phyla: Cnidaria, Placozoa, Porifera and Ctenophora

PubMed Central

Senatore, Adriano; Raiss, Hamad; Le, Phuong

2016-01-01

Voltage-gated calcium (Cav) channels serve dual roles in the cell, where they can both depolarize the membrane potential for electrical excitability, and activate transient cytoplasmic Ca2+ signals. In animals, Cav channels play crucial roles including driving muscle contraction (excitation-contraction coupling), gene expression (excitation-transcription coupling), pre-synaptic and neuroendocrine exocytosis (excitation-secretion coupling), regulation of flagellar/ciliary beating, and regulation of cellular excitability, either directly or through modulation of other Ca2+-sensitive ion channels. In recent years, genome sequencing has provided significant insights into the molecular evolution of Cav channels. Furthermore, expanded gene datasets have permitted improved inference of the species phylogeny at the base of Metazoa, providing clearer insights into the evolution of complex animal traits which involve Cav channels, including the nervous system. For the various types of metazoan Cav channels, key properties that determine their cellular contribution include: Ion selectivity, pore gating, and, importantly, cytoplasmic protein-protein interactions that direct sub-cellular localization and functional complexing. It is unclear when these defining features, many of which are essential for nervous system function, evolved. In this review, we highlight some experimental observations that implicate Cav channels in the physiology and behavior of the most early-diverging animals from the phyla Cnidaria, Placozoa, Porifera, and Ctenophora. Given our limited understanding of the molecular biology of Cav channels in these basal animal lineages, we infer insights from better-studied vertebrate and invertebrate animals. We also highlight some apparently conserved cellular functions of Cav channels, which might have emerged very early on during metazoan evolution, or perhaps predated it. PMID:27867359

Modulation of low-voltage-activated T-type Ca²⁺ channels.

PubMed

Zhang, Yuan; Jiang, Xinghong; Snutch, Terrance P; Tao, Jin

2013-07-01

Low-voltage-activated T-type Ca²⁺ channels contribute to a wide variety of physiological functions, most predominantly in the nervous, cardiovascular and endocrine systems. Studies have documented the roles of T-type channels in sleep, neuropathic pain, absence epilepsy, cell proliferation and cardiovascular function. Importantly, novel aspects of the modulation of T-type channels have been identified over the last few years, providing new insights into their physiological and pathophysiological roles. Although there is substantial literature regarding modulation of native T-type channels, the underlying molecular mechanisms have only recently begun to be addressed. This review focuses on recent evidence that the Ca(v)3 subunits of T-type channels, Ca(v)3.1, Ca(v)3.2 and Ca(v)3.3, are differentially modulated by a multitude of endogenous ligands including anandamide, monocyte chemoattractant protein-1, endostatin, and redox and oxidizing agents. The review also provides an overview of recent knowledge gained concerning downstream pathways involving G-protein-coupled receptors. This article is part of a Special Issue entitled: Calcium channels. Copyright © 2012 Elsevier B.V. All rights reserved.

A Comparative Study of Co-Channel Interference Suppression Techniques

NASA Technical Reports Server (NTRS)

Hamkins, Jon; Satorius, Ed; Paparisto, Gent; Polydoros, Andreas

1997-01-01

We describe three methods of combatting co-channel interference (CCI): a cross-coupled phase-locked loop (CCPLL); a phase-tracking circuit (PTC), and joint Viterbi estimation based on the maximum likelihood principle. In the case of co-channel FM-modulated voice signals, the CCPLL and PTC methods typically outperform the maximum likelihood estimators when the modulation parameters are dissimilar. However, as the modulation parameters become identical, joint Viterbi estimation provides for a more robust estimate of the co-channel signals and does not suffer as much from "signal switching" which especially plagues the CCPLL approach. Good performance for the PTC requires both dissimilar modulation parameters and a priori knowledge of the co-channel signal amplitudes. The CCPLL and joint Viterbi estimators, on the other hand, incorporate accurate amplitude estimates. In addition, application of the joint Viterbi algorithm to demodulating co-channel digital (BPSK) signals in a multipath environment is also discussed. It is shown in this case that if the interference is sufficiently small, a single trellis model is most effective in demodulating the co-channel signals.

A Simulation Testbed for Adaptive Modulation and Coding in Airborne Telemetry

DTIC Science & Technology

2014-05-29

its modulation waveforms and LDPC for the FEC codes . It also uses several sets of published telemetry channel sounding data as its channel models...waveforms and LDPC for the FEC codes . It also uses several sets of published telemetry channel sounding data as its channel models. Within the context...check ( LDPC ) codes with tunable code rates, and both static and dynamic telemetry channel models are included. In an effort to maximize the

80-Channel Multiplexer-Demultiplexer Module for DWDM Communications using Hybrid AWG -- Interleaver Technology

NASA Astrophysics Data System (ADS)

Rablau, Corneliu; Bredthauer, Lance

2007-10-01

Aside from the more traditional data, voice and e-mail communications, new bandwidth intensive applications in the larger consumer markets, such as music, digital pictures and movies, have led to an explosive increase in the demand for transmission capacity for optical communications networks. This has resulted in a widespread deployment of Dense Wavelength Division Multiplexing (DWDM) as a means of increasing the communications capacity by multiplexing and transmitting signals of different wavelengths (establishing multiple communication channels) through a single strand of fiber. We report on the design, assembly and characterization of a 50-GHz, 80-channel Mux-Demux module for DWDM systems. The module has been assembled from two commercially available 100 GHz, 40-channel Array Waveguide Grating (AWG) modules and a 50-GHz to 100-GHz interleaver. Relevant performance parameters such as insertion loss, channel uniformity, next-channel isolation (crosstalk) and integrated cross-talk are presented and discussed in contrast with the performance of other competing technologies such as Thin-Film-Filter-based Mux-Demux devices.

Distinct pH regulation of slow and rapid anion channels at the plasma membrane of Arabidopsis thaliana hypocotyl cells.

PubMed

Colcombet, Jean; Lelièvre, Françoise; Thomine, Sébastien; Barbier-Brygoo, Hélène; Frachisse, Jean-Marie

2005-07-01

Variations in both intracellular and extracellular pH are known to be involved in a wealth of physiological responses. Using the patch-clamp technique on Arabidopsis hypocotyl cells, it is shown that rapid-type and slow-type anion channels at the plasma membrane are both regulated by pH via distinct mechanisms. Modifications of pH modulate the voltage-dependent gating of the rapid channel. While intracellular alkalinization facilitates channel activation by shifting the voltage gate towards negative potentials, extracellular alkalinization shifts the activation threshold to more positive potentials, away from physiological resting membrane potentials. By contrast, pH modulates slow anion channel activity in a voltage-independent manner. Intracellular acidification and extracellular alkalinization increase slow anion channel currents. The possible role of these distinct modulations in physiological processes involving anion efflux and modulation of extracellular and/or intracellular pH, such as elicitor and ABA signalling, are discussed.

A BK (Slo1) channel journey from molecule to physiology

PubMed Central

Contreras, Gustavo F; Castillo, Karen; Enrique, Nicolás; Carrasquel-Ursulaez, Willy; Castillo, Juan Pablo; Milesi, Verónica; Neely, Alan; Alvarez, Osvaldo; Ferreira, Gonzalo; González, Carlos; Latorre, Ramón

2013-01-01

Calcium and voltage-activated potassium (BK) channels are key actors in cell physiology, both in neuronal and non-neuronal cells and tissues. Through negative feedback between intracellular Ca2+ and membrane voltage, BK channels provide a damping mechanism for excitatory signals. Molecular modulation of these channels by alternative splicing, auxiliary subunits and post-translational modifications showed that these channels are subjected to many mechanisms that add diversity to the BK channel α subunit gene. This complexity of interactions modulates BK channel gating, modifying the energetic barrier of voltage sensor domain activation and channel opening. Regions for voltage as well as Ca2+ sensitivity have been identified, and the crystal structure generated by the 2 RCK domains contained in the C-terminal of the channel has been described. The linkage of these channels to many intracellular metabolites and pathways, as well as their modulation by extracellular natural agents, has been found to be relevant in many physiological processes. This review includes the hallmarks of BK channel biophysics and its physiological impact on specific cells and tissues, highlighting its relationship with auxiliary subunit expression. PMID:24025517

Synchronous acquisition of multi-channel signals by single-channel ADC based on square wave modulation

NASA Astrophysics Data System (ADS)

Yi, Xiaoqing; Hao, Liling; Jiang, Fangfang; Xu, Lisheng; Song, Shaoxiu; Li, Gang; Lin, Ling

2017-08-01

Synchronous acquisition of multi-channel biopotential signals, such as electrocardiograph (ECG) and electroencephalograph, has vital significance in health care and clinical diagnosis. In this paper, we proposed a new method which is using single channel ADC to acquire multi-channel biopotential signals modulated by square waves synchronously. In this method, a specific modulate and demodulate method has been investigated without complex signal processing schemes. For each channel, the sampling rate would not decline with the increase of the number of signal channels. More specifically, the signal-to-noise ratio of each channel is n times of the time-division method or an improvement of 3.01 ×log2n dB, where n represents the number of the signal channels. A numerical simulation shows the feasibility and validity of this method. Besides, a newly developed 8-lead ECG based on the new method has been introduced. These experiments illustrate that the method is practicable and thus is potential for low-cost medical monitors.

A rigorous analysis of digital pre-emphasis and DAC resolution for interleaved DAC Nyquist-WDM signal generation in high-speed coherent optical transmission systems

NASA Astrophysics Data System (ADS)

Weng, Yi; Wang, Junyi; He, Xuan; Pan, Zhongqi

2018-02-01

The Nyquist spectral shaping techniques facilitate a promising solution to enhance spectral efficiency (SE) and further reduce the cost-per-bit in high-speed wavelength-division multiplexing (WDM) transmission systems. Hypothetically, any Nyquist WDM signals with arbitrary shapes can be generated by the use of the digital signal processing (DSP) based electrical filters (E-filter). Nonetheless, in actual 100G/ 200G coherent systems, the performance as well as DSP complexity are increasingly restricted by cost and power consumption. Henceforward it is indispensable to optimize DSP to accomplish the preferred performance at the least complexity. In this paper, we systematically investigated the minimum requirements and challenges of Nyquist WDM signal generation, particularly for higher-order modulation formats, including 16 quadrature amplitude modulation (QAM) or 64QAM. A variety of interrelated parameters, such as channel spacing and roll-off factor, have been evaluated to optimize the requirements of the digital-to-analog converter (DAC) resolution and transmitter E-filter bandwidth. The impact of spectral pre-emphasis has been predominantly enhanced via the proposed interleaved DAC architecture by at least 4%, and hence reducing the required optical signal to noise ratio (OSNR) at a bit error rate (BER) of 10-3 by over 0.45 dB at a channel spacing of 1.05 symbol rate and an optimized roll-off factor of 0.1. Furthermore, the requirements of sampling rate for different types of super-Gaussian E-filters are discussed for 64QAM Nyquist WDM transmission systems. Finally, the impact of the non-50% duty cycle error between sub-DACs upon the quality of the generated signals for the interleaved DAC structure has been analyzed.

Non-synaptic ion channels in insects--basic properties of currents and their modulation in neurons and skeletal muscles.

PubMed

Wicher, D; Walther, C; Wicher, C

2001-08-01

Insects are favoured objects for studying information processing in restricted neuronal networks, e.g. motor pattern generation or sensory perception. The analysis of the underlying processes requires knowledge of the electrical properties of the cells involved. These properties are determined by the expression pattern of ionic channels and by the regulation of their function, e.g. by neuromodulators. We here review the presently available knowledge on insect non-synaptic ion channels and ionic currents in neurons and skeletal muscles. The first part of this article covers genetic and structural informations, the localization of channels, their electrophysiological and pharmacological properties, and known effects of second messengers and modulators such as neuropeptides or biogenic amines. In a second part we describe in detail modulation of ionic currents in three particularly well investigated preparations, i.e. Drosophila photoreceptor, cockroach DUM (dorsal unpaired median) neuron and locust jumping muscle. Ion channel structures are almost exclusively known for the fruitfly Drosophila, and most of the information on their function has also been obtained in this animal, mainly based on mutational analysis and investigation of heterologously expressed channels. Now the entire genome of Drosophila has been sequenced, it seems almost completely known which types of channel genes--and how many of them--exist in this animal. There is much knowledge of the various types of channels formed by 6-transmembrane--spanning segments (6TM channels) including those where four 6TM domains are joined within one large protein (e.g. classical Na+ channel). In comparison, two TM channels and 4TM (or tandem) channels so far have hardly been explored. There are, however, various well characterized ionic conductances, e.g. for Ca2+, Cl- or K+, in other insect preparations for which the channels are not yet known. In some of the larger insects, i.e. bee, cockroach, locust and moth, rather detailed information has been established on the role of ionic currents in certain physiological or behavioural contexts. On the whole, however, knowledge of non-synaptic ion channels in such insects is still fragmentary. Modulation of ion currents usually involves activation of more or less elaborate signal transduction cascades. The three detailed examples for modulation presented in the second part indicate, amongst other things, that one type of modulator usually leads to concerted changes of several ion currents and that the effects of different modulators in one type of cell may overlap. Modulators participate in the adaptive changes of the various cells responsible for different physiological or behavioural states. Further study of their effects on the single cell level should help to understand how small sets of cells cooperate in order to produce the appropriate output.

Removal of eye blink artifacts in wireless EEG sensor networks using reduced-bandwidth canonical correlation analysis.

PubMed

Somers, Ben; Bertrand, Alexander

2016-12-01

Chronic, 24/7 EEG monitoring requires the use of highly miniaturized EEG modules, which only measure a few EEG channels over a small area. For improved spatial coverage, a wireless EEG sensor network (WESN) can be deployed, consisting of multiple EEG modules, which interact through short-distance wireless communication. In this paper, we aim to remove eye blink artifacts in each EEG channel of a WESN by optimally exploiting the correlation between EEG signals from different modules, under stringent communication bandwidth constraints. We apply a distributed canonical correlation analysis (CCA-)based algorithm, in which each module only transmits an optimal linear combination of its local EEG channels to the other modules. The method is validated on both synthetic and real EEG data sets, with emulated wireless transmissions. While strongly reducing the amount of data that is shared between nodes, we demonstrate that the algorithm achieves the same eye blink artifact removal performance as the equivalent centralized CCA algorithm, which is at least as good as other state-of-the-art multi-channel algorithms that require a transmission of all channels. Due to their potential for extreme miniaturization, WESNs are viewed as an enabling technology for chronic EEG monitoring. However, multi-channel analysis is hampered in WESNs due to the high energy cost for wireless communication. This paper shows that multi-channel eye blink artifact removal is possible with a significantly reduced wireless communication between EEG modules.

Architecture and Implementation of OpenPET Firmware and Embedded Software

PubMed Central

Abu-Nimeh, Faisal T.; Ito, Jennifer; Moses, William W.; Peng, Qiyu; Choong, Woon-Seng

2016-01-01

OpenPET is an open source, modular, extendible, and high-performance platform suitable for multi-channel data acquisition and analysis. Due to the flexibility of the hardware, firmware, and software architectures, the platform is capable of interfacing with a wide variety of detector modules not only in medical imaging but also in homeland security applications. Analog signals from radiation detectors share similar characteristics – a pulse whose area is proportional to the deposited energy and whose leading edge is used to extract a timing signal. As a result, a generic design method of the platform is adopted for the hardware, firmware, and software architectures and implementations. The analog front-end is hosted on a module called a Detector Board, where each board can filter, combine, timestamp, and process multiple channels independently. The processed data is formatted and sent through a backplane bus to a module called Support Board, where 1 Support Board can host up to eight Detector Board modules. The data in the Support Board, coming from 8 Detector Board modules, can be aggregated or correlated (if needed) depending on the algorithm implemented or runtime mode selected. It is then sent out to a computer workstation for further processing. The number of channels (detector modules), to be processed, mandates the overall OpenPET System Configuration, which is designed to handle up to 1,024 channels using 16-channel Detector Boards in the Standard System Configuration and 16,384 channels using 32-channel Detector Boards in the Large System Configuration. PMID:27110034

Removal of eye blink artifacts in wireless EEG sensor networks using reduced-bandwidth canonical correlation analysis

NASA Astrophysics Data System (ADS)

Somers, Ben; Bertrand, Alexander

2016-12-01

Objective. Chronic, 24/7 EEG monitoring requires the use of highly miniaturized EEG modules, which only measure a few EEG channels over a small area. For improved spatial coverage, a wireless EEG sensor network (WESN) can be deployed, consisting of multiple EEG modules, which interact through short-distance wireless communication. In this paper, we aim to remove eye blink artifacts in each EEG channel of a WESN by optimally exploiting the correlation between EEG signals from different modules, under stringent communication bandwidth constraints. Approach. We apply a distributed canonical correlation analysis (CCA-)based algorithm, in which each module only transmits an optimal linear combination of its local EEG channels to the other modules. The method is validated on both synthetic and real EEG data sets, with emulated wireless transmissions. Main results. While strongly reducing the amount of data that is shared between nodes, we demonstrate that the algorithm achieves the same eye blink artifact removal performance as the equivalent centralized CCA algorithm, which is at least as good as other state-of-the-art multi-channel algorithms that require a transmission of all channels. Significance. Due to their potential for extreme miniaturization, WESNs are viewed as an enabling technology for chronic EEG monitoring. However, multi-channel analysis is hampered in WESNs due to the high energy cost for wireless communication. This paper shows that multi-channel eye blink artifact removal is possible with a significantly reduced wireless communication between EEG modules.

The modulation of brain functional connectivity with manual acupuncture in healthy subjects: An electroencephalograph case study

NASA Astrophysics Data System (ADS)

Yi, Guo-Sheng; Wang, Jiang; Han, Chun-Xiao; Deng, Bin; Wei, Xi-Le; Li, Nuo

2013-02-01

Manual acupuncture is widely used for pain relief and stress control. Previous studies on acupuncture have shown its modulatory effects on the functional connectivity associated with one or a few preselected brain regions. To investigate how manual acupuncture modulates the organization of functional networks at a whole-brain level, we acupuncture at ST36 of a right leg to obtain electroencephalograph (EEG) signals. By coherence estimation, we determine the synchronizations between all pairwise combinations of EEG channels in three acupuncture states. The resulting synchronization matrices are converted into functional networks by applying a threshold, and the clustering coefficients and path lengths are computed as a function of threshold. The results show that acupuncture can increase functional connections and synchronizations between different brain areas. For a wide range of thresholds, the clustering coefficient during acupuncture and post-acupuncture period is higher than that during the pre-acupuncture control period, whereas the characteristic path length is shorter. We provide further support for the presence of “small-world" network characteristics in functional networks by using acupuncture. These preliminary results highlight the beneficial modulations of functional connectivity by manual acupuncture, which could contribute to the understanding of the effects of acupuncture on the entire brain, as well as the neurophysiological mechanisms underlying acupuncture. Moreover, the proposed method may be a useful approach to the further investigation of the complexity of patterns of interrelations between EEG channels.

Calmodulin permanently associates with rat olfactory CNG channels under native conditions.

PubMed

Bradley, Jonathan; Bönigk, Wolfgang; Yau, King-Wai; Frings, Stephan

2004-07-01

An important mechanism by which vertebrate olfactory sensory neurons rapidly adapt to odorants is feedback modulation of the Ca(2+)-permeable cyclic nucleotide-gated (CNG) transduction channels. Extensive heterologous studies of homomeric CNGA2 channels have led to a molecular model of channel modulation based on the binding of calcium-calmodulin to a site on the cytoplasmic amino terminus of CNGA2. Native rat olfactory CNG channels, however, are heteromeric complexes of three homologous but distinct subunits. Notably, in heteromeric channels, we found no role for CNGA2 in feedback modulation. Instead, an IQ-type calmodulin-binding site on CNGB1b and a similar but previously unidentified site on CNGA4 are necessary and sufficient. These sites seem to confer binding of Ca(2+)-free calmodulin (apocalmodulin), which is then poised to trigger inhibition of native channels in the presence of Ca(2+).

Impact of Dispersion Slope on SPM Degradation in WDM Systems With High Channel Count

NASA Astrophysics Data System (ADS)

Luí; S, Ruben S.; Cartaxo, Adolfo V. T.

2005-11-01

Dispersion management design in wavelength division multiplexing (WDM) intensity modulation-direct detection (IM-DD) systems is often difficult due to the complex relation between the dispersion-management parameters (inline and total residual dispersion) and nonlinear impairments, such as cross-phase modulation (XPM). In this paper, we investigate the dependence of the XPM degradation on the dispersion-management parameters of a two-channel system. Afterwards, the XPM degradation on systems with high channel count (161 channels) is analytically evaluated, and the observed behaviors are explained using the results obtained with a two-channel system. In the absence of dispersion-slope compensation (DSC), significant differences in the XPM degradation of different channels in the same system are shown. Such differences result mainly from the strong dependence of the phase-modulation-to-intensity-modulation conversion of the XPM on the dispersion-management parameters of each channel. Due to this dependence, numerical results show that, unlike systems without dispersion compensation (DC), the XPM degradation may increase steadily with the channel count, and the worst-case channel may not be the center channel of the transmitted band. DSC allows a remarkable equalization of the XPM degradation along the transmitted band, facilitating dispersion-management planning. However, variations of the dispersion parameter and excessive residual dispersion that is not compensated may still induce a tilt of the XPM degradation along the transmitted band.

Modulation of voltage- and Ca2+-dependent gating of CaV1.3 L-type calcium channels by alternative splicing of a C-terminal regulatory domain.

PubMed

Singh, Anamika; Gebhart, Mathias; Fritsch, Reinhard; Sinnegger-Brauns, Martina J; Poggiani, Chiara; Hoda, Jean-Charles; Engel, Jutta; Romanin, Christoph; Striessnig, Jörg; Koschak, Alexandra

2008-07-25

Low voltage activation of Ca(V)1.3 L-type Ca(2+) channels controls excitability in sensory cells and central neurons as well as sinoatrial node pacemaking. Ca(V)1.3-mediated pacemaking determines neuronal vulnerability of dopaminergic striatal neurons affected in Parkinson disease. We have previously found that in Ca(V)1.4 L-type Ca(2+) channels, activation, voltage, and calcium-dependent inactivation are controlled by an intrinsic distal C-terminal modulator. Because alternative splicing in the Ca(V)1.3 alpha1 subunit C terminus gives rise to a long (Ca(V)1.3(42)) and a short form (Ca(V)1.3(42A)), we investigated if a C-terminal modulatory mechanism also controls Ca(V)1.3 gating. The biophysical properties of both splice variants were compared after heterologous expression together with beta3 and alpha2delta1 subunits in HEK-293 cells. Activation of calcium current through Ca(V)1.3(42A) channels was more pronounced at negative voltages, and inactivation was faster because of enhanced calcium-dependent inactivation. By investigating several Ca(V)1.3 channel truncations, we restricted the modulator activity to the last 116 amino acids of the C terminus. The resulting Ca(V)1.3(DeltaC116) channels showed gating properties similar to Ca(V)1.3(42A) that were reverted by co-expression of the corresponding C-terminal peptide C(116). Fluorescence resonance energy transfer experiments confirmed an intramolecular protein interaction in the C terminus of Ca(V)1.3 channels that also modulates calmodulin binding. These experiments revealed a novel mechanism of channel modulation enabling cells to tightly control Ca(V)1.3 channel activity by alternative splicing. The absence of the C-terminal modulator in short splice forms facilitates Ca(V)1.3 channel activation at lower voltages expected to favor Ca(V)1.3 activity at threshold voltages as required for modulation of neuronal firing behavior and sinoatrial node pacemaking.

On the power spectral density of quadrature modulated signals. [satellite communication

NASA Technical Reports Server (NTRS)

Yan, T. Y.

1981-01-01

The conventional (no-offset) quadriphase modulation technique suffers from the fact that hardlimiting will restore the frequency sidelobes removed by proper filtering. Thus, offset keyed quadriphase modulation techniques are often proposed for satellite communication with bandpass hardlimiting. A unified theory is developed which is capable of describing the power spectral density before and after the hardlimiting process. Using the in-phase and the quadrature phase channel with arbitrary pulse shaping, analytical results are established for generalized quadriphase modulation. In particular MSK, OPSK or the recently introduced overlapped raised cosine keying all fall into this general category. It is shown that for a linear communication channel, the power spectral density of the modulated signal remains unchanged regardless of the offset delay. Furthermore, if the in phase and the quadrature phase channel have identical pulse shapes without offset, the spectrum after bandpass hardlimiting will be identical to that of the conventional QPSK modulation. Numerical examples are given for various modulation techniques. A case of different pulse shapes in the in phase and the quadrature phase channel is also considered.

Multiple channel data acquisition system

DOEpatents

Crawley, H. Bert; Rosenberg, Eli I.; Meyer, W. Thomas; Gorbics, Mark S.; Thomas, William D.; McKay, Roy L.; Homer, Jr., John F.

1990-05-22

A multiple channel data acquisition system for the transfer of large amounts of data from a multiplicity of data channels has a plurality of modules which operate in parallel to convert analog signals to digital data and transfer that data to a communications host via a FASTBUS. Each module has a plurality of submodules which include a front end buffer (FEB) connected to input circuitry having an analog to digital converter with cache memory for each of a plurality of channels. The submodules are interfaced with the FASTBUS via a FASTBUS coupler which controls a module bus and a module memory. The system is triggered to effect rapid parallel data samplings which are stored to the cache memories. The cache memories are uploaded to the FEBs during which zero suppression occurs. The data in the FEBs is reformatted and compressed by a local processor during transfer to the module memory. The FASTBUS coupler is used by the communications host to upload the compressed and formatted data from the module memory. The local processor executes programs which are downloaded to the module memory through the FASTBUS coupler.

Multiple channel data acquisition system

DOEpatents

Crawley, H.B.; Rosenberg, E.I.; Meyer, W.T.; Gorbics, M.S.; Thomas, W.D.; McKay, R.L.; Homer, J.F. Jr.

1990-05-22

A multiple channel data acquisition system for the transfer of large amounts of data from a multiplicity of data channels has a plurality of modules which operate in parallel to convert analog signals to digital data and transfer that data to a communications host via a FASTBUS. Each module has a plurality of submodules which include a front end buffer (FEB) connected to input circuitry having an analog to digital converter with cache memory for each of a plurality of channels. The submodules are interfaced with the FASTBUS via a FASTBUS coupler which controls a module bus and a module memory. The system is triggered to effect rapid parallel data samplings which are stored to the cache memories. The cache memories are uploaded to the FEBs during which zero suppression occurs. The data in the FEBs is reformatted and compressed by a local processor during transfer to the module memory. The FASTBUS coupler is used by the communications host to upload the compressed and formatted data from the module memory. The local processor executes programs which are downloaded to the module memory through the FASTBUS coupler. 25 figs.

Solid-state membrane module

DOEpatents

Hinklin, Thomas Ray; Lewinsohn, Charles Arthur

2015-06-30

A module for separating oxygen from an oxygen-containing gaseous mixture comprising planar solid-state membrane units, each membrane unit comprising planar dense mixed conducting oxides layers, planar channel-free porous support layers, and one or more planar intermediate support layers comprising at least one channeled porous support layer. The porosity of the planar channeled porous support layers is less than the porosity of the planar channel-free porous support layers.

Adaptive channel estimation for soft decision decoding over non-Gaussian optical channel

NASA Astrophysics Data System (ADS)

Xiang, Jing-song; Miao, Tao-tao; Huang, Sheng; Liu, Huan-lin

2016-10-01

An adaptive priori likelihood ratio (LLR) estimation method is proposed over non-Gaussian channel in the intensity modulation/direct detection (IM/DD) optical communication systems. Using the nonparametric histogram and the weighted least square linear fitting in the tail regions, the LLR is estimated and used for the soft decision decoding of the low-density parity-check (LDPC) codes. This method can adapt well to the three main kinds of intensity modulation/direct detection (IM/DD) optical channel, i.e., the chi-square channel, the Webb-Gaussian channel and the additive white Gaussian noise (AWGN) channel. The performance penalty of channel estimation is neglected.

An AWG-based 10 Gbit/s colorless WDM-PON system using a chirp-managed directly modulated laser

NASA Astrophysics Data System (ADS)

Latif, Abdul; Yu, Chong-xiu; Xin, Xiang-jun; Husain, Aftab; Hussain, Ashiq; Munir, Abid; Khan, Yousaf

2012-09-01

We propose an arrayed waveguide grating (AWG)-based 10 Gbit/s per channel full duplex wavelength division multiplexing passive optical network (WDM-PON). A chirp managed directly modulated laser with return-to-zero (RZ) differential phase shift keying (DPSK) modulation technique is utilized for downlink (DL) direction, and then the downlink signal is re-modulated for the uplink (UL) direction using intensity modulation technique with the data rate of 10 Gbit/s per channel. A successful WDM-PON transmission operation with the data rate of 10 Gbit/s per channel over a distance of 25 km without any optical amplification or dispersion compensation is demonstrated with low power penalty.

Bidirectional particle transport and size selective sorting of Brownian particles in a flashing spatially periodic energy landscape.

PubMed

Martinez-Pedrero, Fernando; Massana-Cid, Helena; Ziegler, Till; Johansen, Tom H; Straube, Arthur V; Tierno, Pietro

2016-09-29

We demonstrate a size sensitive experimental scheme which enables bidirectional transport and fractionation of paramagnetic colloids in a fluid medium. It is shown that two types of magnetic colloidal particles with different sizes can be simultaneously transported in opposite directions, when deposited above a stripe-patterned ferrite garnet film subjected to a square-wave magnetic modulation. Due to their different sizes, the particles are located at distinct elevations above the surface, and they experience two different energy landscapes, generated by the modulated magnetic substrate. By combining theoretical arguments and numerical simulations, we reveal such energy landscapes, which fully explain the bidirectional transport mechanism. The proposed technique does not require pre-imposed channel geometries such as in conventional microfluidics or lab-on-a-chip systems, and permits remote control over the particle motion, speed and trajectory, by using relatively low intense magnetic fields.

THG113.31, a specific PGF2alpha receptor antagonist, induces human myometrial relaxation and BKCa channel activation

PubMed Central

Doheny, Helen C; O'Reilly, Michael J; Sexton, Donal J; Morrison, John J

2007-01-01

Background PGF2alpha exerts a significant contractile effect on myometrium and is central to human labour. THG113.31, a specific non-competitive PGF2alpha receptor (FP) antagonist, exerts an inhibitory effect on myometrial contractility. The BKCa channel is ubiquitously encountered in human uterine tissue and plays a significant role in modulating myometrial cell membrane potential and excitability. The objective of this study was to investigate potential BKCa channel involvement in the response of human myometrium to THG113.31. Methods Single and whole-cell electrophysiological BKCa channel recordings from freshly dispersed myocytes, were investigated in the presence and absence of THG113.31. Functional studies investigated the effects of THG113.31 on isolated spontaneous myometrial contractions, in the presence and absence of the BKCa channel blocker, iberiotoxin. Results Single channel recordings identified the BKCa channel as a target of THG113.31. THG113.31 significantly increased the open state probability of these channels [control 0.023+/-0.006; 10 microM THG113.31 0.087+/-0.012 (P = 0.009); and 50 microM THG113.31 0.1356+/-0.018 (P = 0.001)]. In addition, THG113.31 increased whole-cell BKCa currents over a range of membrane potentials, and this effect was reversed by 100 nanoM IbTX. Isometric tension studies demonstrated that THG113.31 exerted a significant concentration-dependent relaxant effect on human myometrial tissue and pre-incubation of strips with IbTX abolished this effect on spontaneously occurring contractions. Conclusion These data suggests that activation of the BKCa channel may contribute, at least partially, to the uterorelaxant effect of THG113.31. PMID:17367527

Computational Model of the Insect Pheromone Transduction Cascade

PubMed Central

Gu, Yuqiao; Lucas, Philippe; Rospars, Jean-Pierre

2009-01-01

A biophysical model of receptor potential generation in the male moth olfactory receptor neuron is presented. It takes into account all pre-effector processes—the translocation of pheromone molecules from air to sensillum lymph, their deactivation and interaction with the receptors, and the G-protein and effector enzyme activation—and focuses on the main post-effector processes. These processes involve the production and degradation of second messengers (IP3 and DAG), the opening and closing of a series of ionic channels (IP3-gated Ca2+ channel, DAG-gated cationic channel, Ca2+-gated Cl− channel, and Ca2+- and voltage-gated K+ channel), and Ca2+ extrusion mechanisms. The whole network is regulated by modulators (protein kinase C and Ca2+-calmodulin) that exert feedback inhibition on the effector and channels. The evolution in time of these linked chemical species and currents and the resulting membrane potentials in response to single pulse stimulation of various intensities were simulated. The unknown parameter values were fitted by comparison to the amplitude and temporal characteristics (rising and falling times) of the experimentally measured receptor potential at various pheromone doses. The model obtained captures the main features of the dose–response curves: the wide dynamic range of six decades with the same amplitudes as the experimental data, the short rising time, and the long falling time. It also reproduces the second messenger kinetics. It suggests that the two main types of depolarizing ionic channels play different roles at low and high pheromone concentrations; the DAG-gated cationic channel plays the major role for depolarization at low concentrations, and the Ca2+-gated Cl− channel plays the major role for depolarization at middle and high concentrations. Several testable predictions are proposed, and future developments are discussed. PMID:19300479

Robust Stimulation of W1282X-CFTR Channel Activity by a Combination of Allosteric Modulators

PubMed Central

Wang, Wei; Hong, Jeong S.; Rab, Andras; Sorscher, Eric J.; Kirk, Kevin L.

2016-01-01

W1282X is a common nonsense mutation among cystic fibrosis patients that results in the production of a truncated Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel. Here we show that the channel activity of the W1282X-CFTR polypeptide is exceptionally low in excised membrane patches at normally saturating doses of ATP and PKA (single channel open probability (PO) < 0.01). However, W1282X-CFTR channels were stimulated by two CFTR modulators, the FDA-approved VX-770 and the dietary compound curcumin. Each of these compounds is an allosteric modulator of CFTR gating that promotes channel activity in the absence of the native ligand, ATP. Although W1282X-CFTR channels were stimulated by VX-770 in the absence of ATP their activities remained dependent on PKA phosphorylation. Thus, activated W1282X-CFTR channels should remain under physiologic control by cyclic nucleotide signaling pathways in vivo. VX-770 and curcumin exerted additive effects on W1282X-CFTR channel gating (opening/closing) in excised patches such that the Po of the truncated channel approached unity (> 0.9) when treated with both modulators. VX-770 and curcumin also additively stimulated W1282X-CFTR mediated currents in polarized FRT epithelial monolayers. In this setting, however, the stimulated W1282X-CFTR currents were smaller than those mediated by wild type CFTR (3–5%) due presumably to lower expression levels or cell surface targeting of the truncated protein. Combining allosteric modulators of different mechanistic classes is worth considering as a treatment option for W1282X CF patients perhaps when coupled with maneuvers to increase expression of the truncated protein. PMID:27007499

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

PubMed Central

Harteneck, Christian; Gollasch, Maik

2011-01-01

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

Smart radio: spectrum access for first responders

NASA Astrophysics Data System (ADS)

Silvius, Mark D.; Ge, Feng; Young, Alex; MacKenzie, Allen B.; Bostian, Charles W.

2008-04-01

This paper details the Wireless at Virginia Tech Center for Wireless Telecommunications' (CWT) design and implementation of its Smart Radio (SR) communication platform. The CWT SR can identify available spectrum within a pre-defined band, rendezvous with an intended receiver, and transmit voice and data using a selected quality of service (QoS). This system builds upon previous cognitive technologies developed by CWT for the public safety community, with the goal of providing a prototype mobile communications package for military and public safety First Responders. A master control (MC) enables spectrum awareness by characterizing the radio environment with a power spectrum sensor and an innovative signal detection and classification module. The MC also enables spectrum and signal memory by storing sensor results in a knowledge database. By utilizing a family radio service (FRS) waveform database, the CWT SR can create a new communication link on any designated FRS channel frequency using FM, BPSK, QPSK, or 8PSK modulations. With FM, it supports analog voice communications with legacy hand-held FRS radios. With digital modulations, it supports IP data services, including a CWT developed CVSD-based VoIP protocol. The CWT SR coordinates spectrum sharing between analog primary users and digital secondary users by applying a simple but effective channel-change protocol. It also demonstrates a novel rendezvous protocol to facilitate the detection and initialization of communications links with neighboring SR nodes through the transmission of frequency-hopped rendezvous beacons. By leveraging the GNU Radio toolkit, writing key modules entirely in Python, and utilizing the USRP hardware front-end, the CWT SR provides a dynamic spectrum test bed for future smart and cognitive radio research.

Clock and trigger synchronization between several chassis of digital data acquisition modules

NASA Astrophysics Data System (ADS)

Hennig, W.; Tan, H.; Walby, M.; Grudberg, P.; Fallu-Labruyere, A.; Warburton, W. K.; Vaman, C.; Starosta, K.; Miller, D.

2007-08-01

In applications with segmented high purity Ge detectors or other detector arrays with tens or hundreds of channels, the high development cost and limited flexibility of application specific integrated circuits outweigh their benefits of low power and small size. The readout electronics typically consist of multi-channel data acquisition modules in a common chassis for power, clock and trigger distribution, and data readout. As arrays become larger and reach several hundred channels, the readout electronics have to be divided over several chassis, but still must maintain precise synchronization of clocks and trigger signals across all channels. This division becomes necessary not only because of limits given by the instrumentation standards on module size and chassis slot numbers, but also because data readout times increase when more modules share the same data bus and because power requirements approach the limits of readily available power supplies. In this paper, we present a method for distributing clocks and triggers between 4 PXI chassis containing DGF Pixie-16 modules with up to 226 acquisition channels per chassis. The data acquisition system is intended to instrument the over 600 channels of the SeGA detector array at the National Superconducting Cyclotron Laboratory. Our solution is designed to achieve synchronous acquisition of detector waveforms from all channels with a jitter of less than 1 ns, and can be extended to a larger number of chassis if desired.

The design and research of anti-color-noise chaos M-ary communication system

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

Fu, Yongqing, E-mail: fuyongqing@hrbeu.edu.cn; Li, Xingyuan; Li, Yanan

Previously a novel chaos M-ary digital communication method based on spatiotemporal chaos Hamilton oscillator has been proposed. Without chaos synchronization circumstance, it has performance improvement in bandwidth efficiency, transmission efficiency and anti-white-noise performance compared with traditional communication method. In this paper, the channel noise influence on chaotic modulation signals and the construction problem of anti-color-noise chaotic M-ary communication system are studied. The formula of zone partition demodulator’s boundary in additive white Gaussian noise is derived, besides, the problem about how to determine the boundary of zone partition demodulator in additive color noise is deeply studied; Then an approach on constructingmore » anti-color-noise chaos M-ary communication system is proposed, in which a pre-distortion filter is added after the chaos baseband modulator in the transmitter and whitening filter is added before zone partition demodulator in the receiver. Finally, the chaos M-ary communication system based on Hamilton oscillator is constructed and simulated in different channel noise. The result shows that the proposed method in this paper can improve the anti-color-noise performance of the whole communication system compared with the former system, and it has better anti-fading and resisting disturbance performance than Quadrature Phase Shift Keying system.« less

H-II launch vehicle telemetry system realizing intelligent control of pre-processed data from remote terminal

NASA Astrophysics Data System (ADS)

Tanioka, Noritaka; Yoshida, Yasunori; Obi, Shinzo; Chiba, Ryoichi; Nakai, Kazumoto

The development of a PCM telemetry system for the Japanese H-II launch vehicle is discussed. PCM data streams acquire and process data from remote terminals which can be located at any place near the data source. The data are synchronized by a clock and are individually controlled by a central PCM data processing unit. The system allows the launch vehicle to acquire data from many different areas of the rocket, with a total of 879 channels. The data are multiplexed and processed into one PCM data stream and are down-linked on a phase-modulated RF carrier.

Pharmacology of the human red cell voltage-dependent cation channel; Part I. Activation by clotrimazole and analogues.

PubMed

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

2004-01-01

The activation and pharmacological modulation of the nonselective voltage-dependent cation (NSVDC) channel from human erythrocytes were studied. Basic channel activation was achieved by suspending red cells in a low Cl(-) Ringer (2 mM), where a positive membrane potential (V(m) = E(Cl)) immediately developed. Voltage- and time-dependent activation of the NSVDC channel occurred, reaching a cation conductance (g+) of 1.5-2.0 microS cm(-2). In the presence of the classical Gárdos channel blocker clotrimazole (0-50 microM), activation occurred faster, and g+ saturated dose-dependently (EC50 = 14 microM) at a value of about 4 microS cm(-2). The clotrimazole analogues TRAM-34, econazole, and miconazole also stimulated the channel, whereas the chemically more distant Gárdos channel inhibitors nitrendipine and cetiedil had no effects. Although the potency for modulation of the NSVDC channel is much lower than the IC50 value for Gárdos channel inhibition, clotrimazole (and its analogues) constitutes the first chemical class of positive modulators of the NSVDC channel. This may be an important pharmacological "fingerprint" in the identification of the cloned equivalent of the erythrocyte channel.

Schlieren, Phase-Contrast, and Spectroscopy Diagnostics for the LBNL HIF Plasma Channel Experiment

NASA Astrophysics Data System (ADS)

Ponce, D. M.; Niemann, C.; Fessenden, T. J.; Leemans, W.; Vandersloot, K.; Dahlbacka, G.; Yu, S. S.; Sharp, W. M.; Tauschwitz, A.

1999-11-01

The LBNL Plasma Channel experiment has demonstrated stable 42-cm Z-pinch discharge plasma channels with peak currents in excess of 50 kA for a 7 torr nitrogen, 30 kV discharge. These channels offer the possibility of transporting heavy-ion beams for inertial fusion. We postulate that the stability of these channels resides in the existance of a neutral-gas density depresion created by a pre-pulse discharge before the main capacitor bank discharge is created. Here, we present the results and experimental diagnostics setup used for the study of the pre-pulse and main bank channels. Observation of both the plasma and neutral gas dynamics is achieved. Schlieren, Zernike's phase-contrast, and spectroscopic techniques are used. Preliminary Schlieren results show a gas shockwave moving radially at a rate of ≈ 10^6 mm/sec as a result of the fast and localized deposited energy during the evolution of the pre-pulse channel. This data will be used to validate simulation codes (BUCKY and CYCLOPS).

Stuttering adults' lack of pre-speech auditory modulation normalizes when speaking with delayed auditory feedback.

PubMed

Daliri, Ayoub; Max, Ludo

2018-02-01

Auditory modulation during speech movement planning is limited in adults who stutter (AWS), but the functional relevance of the phenomenon itself remains unknown. We investigated for AWS and adults who do not stutter (AWNS) (a) a potential relationship between pre-speech auditory modulation and auditory feedback contributions to speech motor learning and (b) the effect on pre-speech auditory modulation of real-time versus delayed auditory feedback. Experiment I used a sensorimotor adaptation paradigm to estimate auditory-motor speech learning. Using acoustic speech recordings, we quantified subjects' formant frequency adjustments across trials when continually exposed to formant-shifted auditory feedback. In Experiment II, we used electroencephalography to determine the same subjects' extent of pre-speech auditory modulation (reductions in auditory evoked potential N1 amplitude) when probe tones were delivered prior to speaking versus not speaking. To manipulate subjects' ability to monitor real-time feedback, we included speaking conditions with non-altered auditory feedback (NAF) and delayed auditory feedback (DAF). Experiment I showed that auditory-motor learning was limited for AWS versus AWNS, and the extent of learning was negatively correlated with stuttering frequency. Experiment II yielded several key findings: (a) our prior finding of limited pre-speech auditory modulation in AWS was replicated; (b) DAF caused a decrease in auditory modulation for most AWNS but an increase for most AWS; and (c) for AWS, the amount of auditory modulation when speaking with DAF was positively correlated with stuttering frequency. Lastly, AWNS showed no correlation between pre-speech auditory modulation (Experiment II) and extent of auditory-motor learning (Experiment I) whereas AWS showed a negative correlation between these measures. Thus, findings suggest that AWS show deficits in both pre-speech auditory modulation and auditory-motor learning; however, limited pre-speech modulation is not directly related to limited auditory-motor adaptation; and in AWS, DAF paradoxically tends to normalize their otherwise limited pre-speech auditory modulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Architecture and Implementation of OpenPET Firmware and Embedded Software

DOE PAGES

Abu-Nimeh, Faisal T.; Ito, Jennifer; Moses, William W.; ...

2016-01-11

OpenPET is an open source, modular, extendible, and high-performance platform suitable for multi-channel data acquisition and analysis. Due to the versatility of the hardware, firmware, and software architectures, the platform is capable of interfacing with a wide variety of detector modules not only in medical imaging but also in homeland security applications. Analog signals from radiation detectors share similar characteristics-a pulse whose area is proportional to the deposited energy and whose leading edge is used to extract a timing signal. As a result, a generic design method of the platform is adopted for the hardware, firmware, and software architectures andmore » implementations. The analog front-end is hosted on a module called a Detector Board, where each board can filter, combine, timestamp, and process multiple channels independently. The processed data is formatted and sent through a backplane bus to a module called Support Board, where 1 Support Board can host up to eight Detector Board modules. The data in the Support Board, coming from 8 Detector Board modules, can be aggregated or correlated (if needed) depending on the algorithm implemented or runtime mode selected. It is then sent out to a computer workstation for further processing. The number of channels (detector modules), to be processed, mandates the overall OpenPET System Configuration, which is designed to handle up to 1,024 channels using 16-channel Detector Boards in the Standard System Configuration and 16,384 channels using 32-channel Detector Boards in the Large System Configuration.« less

Improvement of SPM nonlinear limit by chirped duobinary PolSK transmission

NASA Astrophysics Data System (ADS)

Yang, Lixiu; Fan, Jiayu; Wang, Lutang; Huang, Zhaoming

2005-02-01

In today's terrestrial long-haul optical fiber communication systems, high channel powers are required to obtain a large transmission distance with reasonable optical amplifier spacing. In such systems, however, the presence of nonlinear effects such as the self-phase modulation (SPM) and the fiber dispersion as well as their combined effects, called SPM-induced nonlinear limitation or SPM limit, will seriously degrade the system performances in respect of the effective transmission distance and ultimately become a limiting factor in high-speed, long-haul optical fiber transmission.In this paper, a new transmission format: chirped duobinary PolSK transmission, has been proposed to generate a pre-chirped duobianry signal with fixed polarity (either positive or negative), which is modulated by a PolSK modulator. This format is based on a transmitter setup consisting of a duobinary PolSK Modulation transmitter followed by an additional phase modulator. The chirped duobinary PolSK transmission reduces the signal degradation and spectral broadening in the nonlinear regime significantly. Thus it shifts this SPM nonlinear limit to enable more relaxed dispersion compensation at high optical power compared to the conventional duobinary schemes.The simulation results show chirped duobinary PolSK transmission enlarges the dispersion limited transmission distance, increases the dispersion tolerance and overcome the SPM nonlinear limit.

Development of a three-dimensional core dynamics analysis program for commercial boiling water reactors

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

Bessho, Yasunori; Yokomizo, Osamu; Yoshimoto, Yuichiro

1997-03-01

Development and qualification results are described for a three-dimensional, time-domain core dynamics analysis program for commercial boiling water reactors (BWRs). The program allows analysis of the reactor core with a detailed mesh division, which eliminates calculational ambiguity in the nuclear-thermal-hydraulic stability analysis caused by reactor core regional division. During development, emphasis was placed on high calculational speed and large memory size as attained by the latest supercomputer technology. The program consists of six major modules, namely a core neutronics module, a fuel heat conduction/transfer module, a fuel channel thermal-hydraulic module, an upper plenum/separator module, a feedwater/recirculation flow module, and amore » control system module. Its core neutronics module is based on the modified one-group neutron kinetics equation with the prompt jump approximation and with six delayed neutron precursor groups. The module is used to analyze one fuel bundle of the reactor core with one mesh (region). The fuel heat conduction/transfer module solves the one-dimensional heat conduction equation in the radial direction with ten nodes in the fuel pin. The fuel channel thermal-hydraulic module is based on separated three-equation, two-phase flow equations with the drift flux correlation, and it analyzes one fuel bundle of the reactor core with one channel to evaluate flow redistribution between channels precisely. Thermal margin is evaluated by using the GEXL correlation, for example, in the module.« less

A hybrid voice/data modulation for the VHF aeronautical channels

NASA Technical Reports Server (NTRS)

Akos, Dennis M.

1993-01-01

A method of improving the spectral efficiency of the existing Very High Frequency (VHF) Amplitude Modulation (AM) voice communication channels is proposed. The technique is to phase modulate the existing voice amplitude modulated carrier with digital data. This allows the transmission of digital information over an existing AM voice channel with no change to the existing AM signal format. There is no modification to the existing AM receiver to demodulate the voice signal and an additional receiver module can be added for processing of the digital data. The existing VHF AM transmitter requires only a slight modification for the addition of the digital data signal. The past work in the area is summarized and presented together with an improved system design and the proposed implementation.

New Strategies to Develop Novel Pain Therapies: Addressing Thermoreceptors from Different Points of View

PubMed Central

Fernández-Carvajal, Asia; Fernández-Ballester, Gregorio; Devesa, Isabel; González-Ros, José Manuel; Ferrer-Montiel, Antonio

2011-01-01

One approach to develop successful pain therapies is the modulation of dysfunctional ion channels that contribute to the detection of thermal, mechanical and chemical painful stimuli. These ion channels, known as thermoTRPs, promote the sensitization and activation of primary sensory neurons known as nociceptors. Pharmacological blockade and genetic deletion of thermoTRP have validated these channels as therapeutic targets for pain intervention. Several thermoTRP modulators have progressed towards clinical development, although most failed because of the appearance of unpredicted side effects. Thus, there is yet a need to develop novel channel modulators with improved therapeutic index. Here, we review the current state-of-the art and illustrate new pharmacological paradigms based on TRPV1 that include: (i) the identification of activity-dependent modulators of this thermoTRP channel; (ii) the design of allosteric modulators that interfere with protein-protein interaction involved in the functional coupling of stimulus sensing and gate opening; and (iii) the development of compounds that abrogate the inflammation-mediated increase of receptor expression in the neuronal surface. These new sites of action represent novel strategies to modulate pathologically active TRPV1, while minimizing an effect on the TRPV1 subpopulation involved in physiological and protective roles, thus increasing their potential therapeutic use. PMID:24288041

Breadboarding activities of the TROPOMI-SWIR module

NASA Astrophysics Data System (ADS)

Hoogeveen, Ruud W. M.; Jongma, Rienk T.; Tol, Paul J. J.; Gloudemans, Annemieke; Aben, Ilse; de Vries, Johan; Visser, Huib; Boslooper, Erik; Dobber, Marcel; Levelt, Pieternel F.

2007-10-01

The TROPOMI instrument concept is part of the TRAQ mission proposal to ESA in response to the Call for Ideas in 2005. TRAQ (TRopospheric composition and Air Quality) has been accepted for a further pre-phase A study for the next Earth Explorer core Mission. A very similar instrument has been proposed for the CAMEO platform to the US National Research Council decadal study, which has also been accepted for further study. TROPOMI is a nadir-viewing grating-based imaging spectrometer using the Dutch OMI and SCIAMACHY heritage. It includes an UV-VIS-NIR module that consists of three UV-VIS channels continuously covering the 270-490 nm range to determine O 3, NO II, HCHO, SO II, aerosols and a NIR-channel covering 710-775 nm for cloud detection and information on the aerosol height distribution using the oxygen A band. TROPOMI also includes a SWIR module covering 2305-2385 nm that mainly focuses on determination of CO and CH 4 total columns. All species are measured with sensitivity down to the Earth's surface, thus addressing issues of anthropogenic emissions and their impact on air quality and climate. In the TRAQ mission, unique diurnal time sampling with up to 5 daytime observations over midlatitude regions (Europe, North-America, China) is foreseen by using a non-sun-synchronous, medium-inclination drifting orbit and a 2600 km wide observational swath. Several more general aspects related to the TROPOMI instrument are discussed in a separate paper in this conference. This paper focuses on the development of the SWIR module. A breadboard model (BBM) has been designed and constructed which is as much as possible functionally flight representative. Critical technologies to be demonstrated with the BBM are the SWIR HgCdTe-based 2D focal plane array, the on-board SWIR calibration LED, and in particular, the SRON/TNO developed silicon-based immersed grating that allows a hugely reduced instrument volume. In the presentation the results of a performance analysis of the TROPOMI-SWIR channel will be discussed, as well as results of the detector characterization program on a representative off-the-shelf FPA, and details of the photolithographic production of the immersed grating.

Herbal Compounds and Toxins Modulating TRP Channels

PubMed Central

Vriens, Joris; Nilius, Bernd; Vennekens, Rudi

2008-01-01

Although the benefits are sometimes obvious, traditional or herbal medicine is regarded with skepticism, because the mechanism through which plant compounds exert their powers are largely elusive. Recent studies have shown however that many of these plant compounds interact with specific ion channels and thereby modulate the sensing mechanism of the human body. Especially members of the Transient Receptor Potential (TRP) channels have drawn large attention lately as the receptors for plant-derived compounds such as capsaicin and menthol. TRP channels constitute a large and diverse family of channel proteins that can serve as versatile sensors that allow individual cells and entire organisms to detect changes in their environment. For this family, a striking number of empirical views have turned into mechanism-based actions of natural compounds. In this review we will give an overview of herbal compounds and toxins, which modulate TRP channels. PMID:19305789

Progress in the structural understanding of voltage-gated calcium channel (CaV) function and modulation.

PubMed

Minor, Daniel L; Findeisen, Felix

2010-01-01

Voltage-gated calcium channels (CaVs) are large, transmembrane multiprotein complexes that couple membrane depolarization to cellular calcium entry. These channels are central to cardiac action potential propagation, neurotransmitter and hormone release, muscle contraction, and calcium-dependent gene transcription. Over the past six years, the advent of high-resolution structural studies of CaV components from different isoforms and CaV modulators has begun to reveal the architecture that underlies the exceptionally rich feedback modulation that controls CaV action. These descriptions of CaV molecular anatomy have provided new, structure-based insights into the mechanisms by which particular channel elements affect voltage-dependent inactivation (VDI), calcium‑dependent inactivation (CDI), and calcium‑dependent facilitation (CDF). The initial successes have been achieved through structural studies of soluble channel domains and modulator proteins and have proven most powerful when paired with biochemical and functional studies that validate ideas inspired by the structures. Here, we review the progress in this growing area and highlight some key open challenges for future efforts.

Capsaicin in Metabolic Syndrome

PubMed Central

Bliss, Edward

2018-01-01

Capsaicin, the major active constituent of chilli, is an agonist on transient receptor potential vanilloid channel 1 (TRPV1). TRPV1 is present on many metabolically active tissues, making it a potentially relevant target for metabolic interventions. Insulin resistance and obesity, being the major components of metabolic syndrome, increase the risk for the development of cardiovascular disease, type 2 diabetes, and non-alcoholic fatty liver disease. In vitro and pre-clinical studies have established the effectiveness of low-dose dietary capsaicin in attenuating metabolic disorders. These responses of capsaicin are mediated through activation of TRPV1, which can then modulate processes such as browning of adipocytes, and activation of metabolic modulators including AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor α (PPARα), uncoupling protein 1 (UCP1), and glucagon-like peptide 1 (GLP-1). Modulation of these pathways by capsaicin can increase fat oxidation, improve insulin sensitivity, decrease body fat, and improve heart and liver function. Identifying suitable ways of administering capsaicin at an effective dose would warrant its clinical use through the activation of TRPV1. This review highlights the mechanistic options to improve metabolic syndrome with capsaicin. PMID:29772784

Capsaicin in Metabolic Syndrome.

PubMed

Panchal, Sunil K; Bliss, Edward; Brown, Lindsay

2018-05-17

Capsaicin, the major active constituent of chilli, is an agonist on transient receptor potential vanilloid channel 1 (TRPV1). TRPV1 is present on many metabolically active tissues, making it a potentially relevant target for metabolic interventions. Insulin resistance and obesity, being the major components of metabolic syndrome, increase the risk for the development of cardiovascular disease, type 2 diabetes, and non-alcoholic fatty liver disease. In vitro and pre-clinical studies have established the effectiveness of low-dose dietary capsaicin in attenuating metabolic disorders. These responses of capsaicin are mediated through activation of TRPV1, which can then modulate processes such as browning of adipocytes, and activation of metabolic modulators including AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor α (PPARα), uncoupling protein 1 (UCP1), and glucagon-like peptide 1 (GLP-1). Modulation of these pathways by capsaicin can increase fat oxidation, improve insulin sensitivity, decrease body fat, and improve heart and liver function. Identifying suitable ways of administering capsaicin at an effective dose would warrant its clinical use through the activation of TRPV1. This review highlights the mechanistic options to improve metabolic syndrome with capsaicin.

Earth Observing System/Advanced Microwave Sounding Unit-A (EOS/AMSU-A): Reliability prediction report for module A1 (channels 3 through 15) and module A2 (channels 1 and 2)

NASA Technical Reports Server (NTRS)

Geimer, W.

1995-01-01

This report documents the final reliability prediction performed on the Earth Observing System/Advanced Microwave Sounding Unit-A (EOS/AMSU-A). The A1 Module contains Channels 3 through 15, and is referred to herein as 'EOS/AMSU-A1'. The A2 Module contains Channels 1 and 2, and is referred herein as 'EOS/AMSU-A2'. The 'specified' figures were obtained from Aerojet Reports 8897-1 and 9116-1. The predicted reliability figure for the EOS/AMSU-A1 meets the specified value and provides a Mean Time Between Failures (MTBF) of 74,390 hours. The predicted reliability figure for the EOS/AMSU-A2 meets the specified value and provides a MTBF of 193,110 hours.

Enhancement of electrical transport modulation in epitaxial VO2 nanowire field-effect transistor

NASA Astrophysics Data System (ADS)

Tanaka, Hidekazu; Chikanari, Masashi; Kanki, Teruo

Strongly correlated system vanadium dioxide VO2 has attracted widespread concerns from researchers as an exciting electronic material, due to the many intriguing features, especially metal-insulator transition (MIT) in vicinity of room temperature. In this work, we report a diverse geometry for high sensitivity in the transport modulation. By taking advantage of nanometer scale channel, instead of thin film channels, we demonstrated the enhancement of resistance modulation by applying gate voltage. Also we designed the insulating gate, consisting of high-k material Ta2O5/organic polymer parylene-C hybrid insulator. Such as this hybrid gate dielectric would effectively reduce interface deterioration of active channel oxide and provide sufficient carrier density. Moreover, benefited from the nanometer scale channel, the VO2 nanowire-based transistor could deliver a resistance modulation ratio over 8.5%, which are about 10 folds higher than that of the film case. Furthermore, this result is explained that in spite of the stronger field distribution in the edge parts of VO2 nanowire channel yielded little carrier density, the generated mobility modulation would biquadratic increase according to Brinkman-Rice picture as new finding.

Molecular mechanisms of subtype-specific inhibition of neuronal T-type calcium channels by ascorbate.

PubMed

Nelson, Michael T; Joksovic, Pavle M; Su, Peihan; Kang, Ho-Won; Van Deusen, Amy; Baumgart, Joel P; David, Laurence S; Snutch, Terrance P; Barrett, Paula Q; Lee, Jung-Ha; Zorumski, Charles F; Perez-Reyes, Edward; Todorovic, Slobodan M

2007-11-14

T-type Ca2+ channels (T-channels) are involved in the control of neuronal excitability and their gating can be modulated by a variety of redox agents. Ascorbate is an endogenous redox agent that can function as both an anti- and pro-oxidant. Here, we show that ascorbate selectively inhibits native Ca(v)3.2 T-channels in peripheral and central neurons, as well as recombinant Ca(v)3.2 channels heterologously expressed in human embryonic kidney 293 cells, by initiating the metal-catalyzed oxidation of a specific, metal-binding histidine residue in domain 1 of the channel. Our biophysical experiments indicate that ascorbate reduces the availability of Ca(v)3.2 channels over a wide range of membrane potentials, and inhibits Ca(v)3.2-dependent low-threshold-Ca2+ spikes as well as burst-firing in reticular thalamic neurons at physiologically relevant concentrations. This study represents the first mechanistic demonstration of ion channel modulation by ascorbate, and suggests that ascorbate may function as an endogenous modulator of neuronal excitability.

CSI feedback-based CS for underwater acoustic adaptive modulation OFDM system with channel prediction

NASA Astrophysics Data System (ADS)

Kuai, Xiao-yan; Sun, Hai-xin; Qi, Jie; Cheng, En; Xu, Xiao-ka; Guo, Yu-hui; Chen, You-gan

2014-06-01

In this paper, we investigate the performance of adaptive modulation (AM) orthogonal frequency division multiplexing (OFDM) system in underwater acoustic (UWA) communications. The aim is to solve the problem of large feedback overhead for channel state information (CSI) in every subcarrier. A novel CSI feedback scheme is proposed based on the theory of compressed sensing (CS). We propose a feedback from the receiver that only feedback the sparse channel parameters. Additionally, prediction of the channel state is proposed every several symbols to realize the AM in practice. We describe a linear channel prediction algorithm which is used in adaptive transmission. This system has been tested in the real underwater acoustic channel. The linear channel prediction makes the AM transmission techniques more feasible for acoustic channel communications. The simulation and experiment show that significant improvements can be obtained both in bit error rate (BER) and throughput in the AM scheme compared with the fixed Quadrature Phase Shift Keying (QPSK) modulation scheme. Moreover, the performance with standard CS outperforms the Discrete Cosine Transform (DCT) method.

Selective dopamine receptor 4 activation mediates the hippocampal neuronal calcium response via IP3 and ryanodine receptors.

PubMed

Wang, Ya-Li; Wang, Jian-Gang; Guo, Fang-Li; Gao, Xia-Huan; Zhao, Dan-Dan; Zhang, Lin; Wang, Jian-Zhi; Lu, Cheng-Biao

2017-09-01

Intracellular calcium is a key factor in most cellular processes, including cell growth, differentiation, proliferation and neurotransmitter release. Dopamine (DA) mediates synaptic transmission by regulating the intracellular calcium content. It is not clear, however, which specific subunit of the DA receptor contributes to DA modulation of intracellular calcium content changes. Through the traditional technique of Fura-2 calcium imaging, this study demonstrated that the DA can induce transient calcium in cultured hippocampal neurons and that this response can be mimicked by a selective dopamine receptor 4 (DR4) agonist PD168077 (PD). PD-induced calcium transience can be blocked by a calcium chelator, such as BAPTA-AM, or by pre-treatment of neurons with thapsigargin, a IP 3 receptor antagonist, or a micromolar concentration of ryanodine, a ryanodine receptor (RyR) antagonist. However PD-induced calcium transience cannot be blocked by pre-treatment of neurons with a free-calcium medium or a cocktail of NMDA receptor, L-type calcium channel and alpha7 nicotinic acetylcholine receptor blockers. These results indicate that the calcium response induced by DR4 activation is mainly through activation of IP 3 receptor in internal stores, which is likely to contribute to the DA modulation of synaptic transmission and cognitive function. Copyright © 2017. Published by Elsevier B.V.

Transient Receptor Potential Channels TRPM4 and TRPC3 Critically Contribute to Respiratory Motor Pattern Formation but not Rhythmogenesis in Rodent Brainstem Circuits

PubMed Central

Tariq, Mohammad F.; Phillips, Ryan S.; Mosher, Bryan; Thompson, Ryan; Zhang, Ruli

2018-01-01

Abstract Transient receptor potential channel, TRPM4, the putative molecular substrate for Ca2+-activated nonselective cation current (ICAN), is hypothesized to generate bursting activity of pre-Bötzinger complex (pre-BötC) inspiratory neurons and critically contribute to respiratory rhythmogenesis. Another TRP channel, TRPC3, which mediates Na+/Ca2+ fluxes, may be involved in regulating Ca2+-related signaling, including affecting TRPM4/ICAN in respiratory pre-BötC neurons. However, TRPM4 and TRPC3 expression in pre-BötC inspiratory neurons and functional roles of these channels remain to be determined. By single-cell multiplex RT-PCR, we show mRNA expression for these channels in pre-BötC inspiratory neurons in rhythmically active medullary in vitro slices from neonatal rats and mice. Functional contributions were analyzed with pharmacological inhibitors of TRPM4 or TRPC3 in vitro as well as in mature rodent arterially perfused in situ brainstem–spinal cord preparations. Perturbations of respiratory circuit activity were also compared with those by a blocker of ICAN. Pharmacologically attenuating endogenous activation of TRPM4, TRPC3, or ICAN in vitro similarly reduced the amplitude of inspiratory motoneuronal activity without significant perturbations of inspiratory frequency or variability of the rhythm. Amplitude perturbations were correlated with reduced inspiratory glutamatergic pre-BötC neuronal activity, monitored by multicellular dynamic calcium imaging in vitro. In more intact circuits in situ, the reduction of pre-BötC and motoneuronal inspiratory activity amplitude was accompanied by reduced post-inspiratory motoneuronal activity, without disruption of rhythm generation. We conclude that endogenously activated TRPM4, which likely mediates ICAN, and TRPC3 channels in pre-BötC inspiratory neurons play fundamental roles in respiratory pattern formation but are not critically involved in respiratory rhythm generation. PMID:29435486

Mechanisms of Gain Control by Voltage-Gated Channels in Intrinsically-Firing Neurons

PubMed Central

Patel, Ameera X.; Burdakov, Denis

2015-01-01

Gain modulation is a key feature of neural information processing, but underlying mechanisms remain unclear. In single neurons, gain can be measured as the slope of the current-frequency (input-output) relationship over any given range of inputs. While much work has focused on the control of basal firing rates and spike rate adaptation, gain control has been relatively unstudied. Of the limited studies on gain control, some have examined the roles of synaptic noise and passive somatic currents, but the roles of voltage-gated channels present ubiquitously in neurons have been less explored. Here, we systematically examined the relationship between gain and voltage-gated ion channels in a conductance-based, tonically-active, model neuron. Changes in expression (conductance density) of voltage-gated channels increased (Ca2+ channel), reduced (K+ channels), or produced little effect (h-type channel) on gain. We found that the gain-controlling ability of channels increased exponentially with the steepness of their activation within the dynamic voltage window (voltage range associated with firing). For depolarization-activated channels, this produced a greater channel current per action potential at higher firing rates. This allowed these channels to modulate gain by contributing to firing preferentially at states of higher excitation. A finer analysis of the current-voltage relationship during tonic firing identified narrow voltage windows at which the gain-modulating channels exerted their effects. As a proof of concept, we show that h-type channels can be tuned to modulate gain by changing the steepness of their activation within the dynamic voltage window. These results show how the impact of an ion channel on gain can be predicted from the relationship between channel kinetics and the membrane potential during firing. This is potentially relevant to understanding input-output scaling in a wide class of neurons found throughout the brain and other nervous systems. PMID:25816008

Salt Plug Formation Caused by Decreased River Discharge in a Multi-channel Estuary

PubMed Central

Shaha, Dinesh Chandra; Cho, Yang-Ki

2016-01-01

Freshwater input to estuaries may be greatly altered by the river barrages required to meet human needs for drinking water and irrigation and prevent salt water intrusion. Prior studies have examined the salt plugs associated with evaporation and salt outwelling from tidal salt flats in single-channel estuaries. In this work, we discovered a new type of salt plug formation in the multi-channel Pasur River Estuary (PRE) caused by decreasing river discharges resulting from an upstream barrage. The formation of a salt plug in response to changes in river discharge was investigated using a conductivity-temperature-depth (CTD) recorder during spring and neap tides in the dry and wet seasons in 2014. An exportation of saline water from the Shibsa River Estuary (SRE) to the PRE through the Chunkhuri Channel occurred during the dry season, and a salt plug was created and persisted from December to June near Chalna in the PRE. A discharge-induced, relatively high water level in the PRE during the wet season exerted hydrostatic pressure towards the SRE from the PRE and thereby prevented the intrusion of salt water from the SRE to the PRE. PMID:27255892

A three channel telemetry system

NASA Technical Reports Server (NTRS)

Lesho, Jeffery C.; Eaton, Harry A. C.

1993-01-01

A three channel telemetry system intended for biomedical applications is described. The transmitter is implemented in a single chip using a 2 micron BiCMOS processes. The operation of the system and the test results from the latest chip are discussed. One channel is always dedicated to temperature measurement while the other two channels are generic. The generic channels carry information from transducers that are interfaced to the system through on-chip general purpose operational amplifiers. The generic channels have different bandwidths: one from dc to 250 Hz and the other from dc to 1300 Hz. Each generic channel modulates a current controlled oscillator to produce a frequency modulated signal. The two frequency modulated signals are summed and used to amplitude modulate the temperature signal which acts as a carrier. A near-field inductive link telemeters the combined signals over a short distance. The chip operates on a supply voltage anywhere from 2.5 to 3.6 Volts and draws less than 1 mA when transmitting a signal. The chip can be incorporated into ingestible, implantable and other configurations. The device can free the patient from tethered data collection systems and reduces the possibility of infection from subcutaneous leads. Data telemetry can increase patient comfort leading to a greater acceptance of monitoring.

PKA modulation of Kv4.2-encoded A-type potassium channels requires formation of a supramolecular complex.

PubMed

Schrader, Laura A; Anderson, Anne E; Mayne, Amber; Pfaffinger, Paul J; Sweatt, John David

2002-12-01

A-type channels, encoded by the pore-forming alpha-subunits of the Kv4.x family, are particularly important in regulating membrane excitability in the CNS and the heart. Given the key role of modulation of A currents by kinases, we sought to investigate the protein structure-function relationships underlying the regulation of these currents by PKA. We have previously shown the existence of two PKA phosphorylation sites in the Kv4.2 sequence; therefore, we focused this study on the Kv4.2 primary subunit. In the present studies we made the surprising finding that PKA phosphorylation of the Kv4.2 alpha-subunit is necessary but not sufficient for channel modulation; channel modulation by PKA required the presence of an ancillary subunit, the K+ channel interacting protein (KChIP3). Therefore, these findings indicate a surprising complexity to kinase regulation of A currents, in that an interaction of two separate molecular events, alpha-subunit phosphorylation and the association of an ancillary subunit (KChIP3), are necessary for phosphorylation-dependent regulation of Kv4.2-encoded A channels by PKA. Overall, our studies indicate that PKA must of necessity act on a supramolecular complex of pore-forming alpha-subunits plus ancillary subunits to alter channel properties.

Comparison of Steroid Modulation of Spontaneous Inhibitory Postsynaptic Currents in Cultured Hippocampal Neurons and Steady-State Single-Channel Currents from Heterologously Expressed α1β2γ2L GABAA Receptors

PubMed Central

Chakrabarti, Sampurna; Qian, Mingxing; Krishnan, Kathiresan; Covey, Douglas F.; Mennerick, Steven

2016-01-01

Neuroactive steroids are efficacious modulators of γ-aminobutyric acid type A receptor (GABAA) receptor function. The effects of steroids on the GABAA receptor are typically determined by comparing steady-state single-channel open probability or macroscopic peak responses elicited by GABA in the absence and presence of a steroid. Due to differences in activation conditions (exposure duration, concentration of agonist), it is not obvious whether modulation measured using typical experimental protocols can be used to accurately predict the effect of a modulator on native receptors under physiologic conditions. In the present study, we examined the effects of 14 neuroactive steroids and analogs on the properties of spontaneous inhibitory postsynaptic currents (sIPSCs) in cultured rat hippocampal neurons. The goal was to determine whether the magnitude of modulation of the decay time course of sIPSCs correlates with the extent of modulation and kinetic properties of potentiation as determined in previous single-channel studies. The steroids were selected to cover a wide range of efficacy on heterologously expressed rat α1β2γ2L GABAA receptors, ranging from essentially inert to highly efficacious (strong potentiators of single-channel and macroscopic peak responses). The data indicate a strong correlation between prolongation of the decay time course of sIPSCs and potentiation of single-channel open probability. Furthermore, changes in intracluster closed time distributions were the single best predictor of prolongation of sIPSCs. We infer that the information obtained in steady-state single-channel recordings can be used to forecast modulation of synaptic currents. PMID:26769414

Lipid modulation of thermal transient receptor potential channels.

PubMed

Hernández-García, Enrique; Rosenbaum, Tamara

2014-01-01

There is a subgroup of transient receptor potential (TRP) ion channels that are responsive to temperature (thermo-TRP channels). These are important to a variety of sensory and physiological phenomena such as pain and taste perception. All thermo-TRP channels known to date are subject to modulation by lipidic molecules of many kinds, from the ubiquitous cholesterol to more specialized molecules such as prostaglandins. Although the mechanisms and sites of binding of lipids on thermo-TRPs are largely unknown, the explosion on research of lipids and ion channels has revealed previously unsuspected roles for them. Diacyl glycerol is a lipid produced by phospholipase C (PLC) and it was discovered to modulate TRP channels in the eye of the fly, and many mammal TRP channels have been found to interact with lipids. While most of the lipids acting on thermo-TRP channels have been found to activate them, there are a few capable of inhibition. Phosphatidylinositol 4,5-bisphosphate is even capable of both inhibition and activation on a couple of thermo-TRPs, depending on the cellular context. More data is required to assess the mechanism through which lipids affect thermo-TRP channel activity and the physiological importance of this interaction.

A low-cost, portable, micro-controlled device for multi-channel LED visual stimulation.

PubMed

Pinto, Marcos Antonio da Silva; de Souza, John Kennedy Schettino; Baron, Jerome; Tierra-Criollo, Carlos Julio

2011-04-15

Light emitting diodes (LEDs) are extensively used as light sources to investigate visual and visually related function and dysfunction. Here, we describe the design of a compact, low-cost, stand-alone LED-based system that enables the configuration, storage and presentation of elaborate visual stimulation paradigms. The core functionality of this system is provided by a microcontroller whose ultra-low power consumption makes it well suited for long lasting battery applications. The effective use of hardware resources is managed by multi-layered architecture software that provides an intuitive and user-friendly interface. In the configuration mode, different stimulation sequences can be created and memorized for ten channels, independently. LED-driving current output can be set either as continuous or pulse modulated, up to 500 Hz, by duty cycle adjustments. In run mode, multiple-channel stimulus sequences are automatically applied according to the pre-programmed protocol. Steady state visual evoked potentials were successfully recorded in five subjects with no visible electromagnetic interferences from the stimulator, demonstrating the efficacy of combining our prototyped equipment with electrophysiological techniques. Finally, we discuss a number of possible improvements for future development of our project. Copyright © 2011 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2013-01-01

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

Seeking structural specificity: direct modulation of pentameric ligand-gated ion channels by alcohols and general anesthetics.

PubMed

Howard, Rebecca J; Trudell, James R; Harris, R Adron

2014-01-01

Alcohols and other anesthetic agents dramatically alter neurologic function in a wide range of organisms, yet their molecular sites of action remain poorly characterized. Pentameric ligand-gated ion channels, long implicated in important direct effects of alcohol and anesthetic binding, have recently been illuminated in renewed detail thanks to the determination of atomic-resolution structures of several family members from lower organisms. These structures provide valuable models for understanding and developing anesthetic agents and for allosteric modulation in general. This review surveys progress in this field from function to structure and back again, outlining early evidence for relevant modulation of pentameric ligand-gated ion channels and the development of early structural models for ion channel function and modulation. We highlight insights and challenges provided by recent crystal structures and resulting simulations, as well as opportunities for translation of these newly detailed models back to behavior and therapy.

Seeking Structural Specificity: Direct Modulation of Pentameric Ligand-Gated Ion Channels by Alcohols and General Anesthetics

PubMed Central

Trudell, James R.; Harris, R. Adron

2014-01-01

Alcohols and other anesthetic agents dramatically alter neurologic function in a wide range of organisms, yet their molecular sites of action remain poorly characterized. Pentameric ligand-gated ion channels, long implicated in important direct effects of alcohol and anesthetic binding, have recently been illuminated in renewed detail thanks to the determination of atomic-resolution structures of several family members from lower organisms. These structures provide valuable models for understanding and developing anesthetic agents and for allosteric modulation in general. This review surveys progress in this field from function to structure and back again, outlining early evidence for relevant modulation of pentameric ligand-gated ion channels and the development of early structural models for ion channel function and modulation. We highlight insights and challenges provided by recent crystal structures and resulting simulations, as well as opportunities for translation of these newly detailed models back to behavior and therapy. PMID:24515646

Survival Skills. Pre-Apprenticeship Phase 2 Training. Instructors Guide

ERIC Educational Resources Information Center

Lane Community Coll., Eugene, OR.

This instructor's guide contains the 43 Survival Skills modules developed for Pre-Apprenticeship Phase 2 Training. Introductory materials include a description of components of the pre-apprenticeship project, recommendations for module implementation, and synopses of the modules that were developed to prompt social skills development. Each module…

Adaptive Pre-FFT Equalizer with High-Precision Channel Estimator for ISI Channels

NASA Astrophysics Data System (ADS)

Yoshida, Makoto

We present an attractive approach for OFDM transmission using an adaptive pre-FFT equalizer, which can select ICI reduction mode according to channel condition, and a degenerated-inverse-matrix-based channel estimator (DIME), which uses a cyclic sinc-function matrix uniquely determined by transmitted subcarriers. In addition to simulation results, the proposed system with an adaptive pre-FFT equalizer and DIME has been laboratory tested by using a software defined radio (SDR)-based test bed. The simulation and experimental results demonstrated that the system at a rate of more than 100Mbps can provide a bit error rate of less than 10-3 for a fast multi-path fading channel that has a moving velocity of more than 200km/h with a delay spread of 1.9µs (a maximum delay path of 7.3µs) in the 5-GHz band.

Ultra high speed optical transmission using subcarrier-multiplexed four-dimensional LDPC-coded modulation.

PubMed

Batshon, Hussam G; Djordjevic, Ivan; Schmidt, Ted

2010-09-13

We propose a subcarrier-multiplexed four-dimensional LDPC bit-interleaved coded modulation scheme that is capable of achieving beyond 480 Gb/s single-channel transmission rate over optical channels. Subcarrier-multiplexed four-dimensional LDPC coded modulation scheme outperforms the corresponding dual polarization schemes by up to 4.6 dB in OSNR at BER 10(-8).

Gray scale operation of a multichannel optical convolver using the Semetex magnetooptic spatial light modulator

NASA Technical Reports Server (NTRS)

Davis, Jeffrey A.; Day, Timothy; Lilly, Roger A.; Taber, Donald B.; Liu, Hua-Kuang

1988-01-01

A new multichannel optical correlator/convolver architecture which uses an acoustooptic light modulator for the input channel and a Semetex magnetooptic spatial light modulator (MOSLM) for the set of parallel reference channels is presented. Details of the anamorphic optical system are discussed. Experimental results illustrate the use of the system as a convolver for performing digital multiplication by analog convolution (DMAC). A limited gray scale capability for data stored by the MOSLM is demonstrated by implementing this DMAC algorithm with trinary logic. Use of the MOSLM allows the number of parallel channels for the convolver to be increased significantly compared with previously reported techniques while retaining the capability for updating both channels at high speeds.

Gray Scale Operation Of A Multichannel Optical Convolver Using The Semetex Magnetooptic Spatial Light Modulator

NASA Astrophysics Data System (ADS)

Davis, Jeffrey A.; Day, Timothy; Lilly, Roger A.; Taber, Donald B.; Liu, Hua-Kuang; Davis, J. A.; Day, T.; Lilly, R. A.; Taber, D. B.; Liu, H.-K.

1988-02-01

We present a new multichannel optical correlator/convolver architecture which uses an acoustooptic light modulator (AOLM) for the input channel and a Semetex magnetooptic spatial light modulator (MOSLM) for the set of parallel reference channels. Details of the anamorphic optical system are discussed. Experimental results illustrate use of the system as a convolver for performing digital multiplication by analog convolution (DMAC). A limited gray scale capability for data stored by the MOSLM is demonstrated by implementing this DMAC algorithm with trinary logic. Use of the MOSLM allows the number of parallel channels for the convolver to be increased significantly compared with previously reported techniques while retaining the capability for updating both channels at high speeds.

Gray scale operation of a multichannel optical convolver using the Semetex magnetooptic spatial light modulator

NASA Astrophysics Data System (ADS)

Davis, Jeffrey A.; Day, Timothy; Lilly, Roger A.; Taber, Donald B.; Liu, Hua-Kuang

A new multichannel optical correlator/convolver architecture which uses an acoustooptic light modulator for the input channel and a Semetex magnetooptic spatial light modulator (MOSLM) for the set of parallel reference channels is presented. Details of the anamorphic optical system are discussed. Experimental results illustrate the use of the system as a convolver for performing digital multiplication by analog convolution (DMAC). A limited gray scale capability for data stored by the MOSLM is demonstrated by implementing this DMAC algorithm with trinary logic. Use of the MOSLM allows the number of parallel channels for the convolver to be increased significantly compared with previously reported techniques while retaining the capability for updating both channels at high speeds.

Progress in the structural understanding of voltage-gated calcium channel (CaV) function and modulation

PubMed Central

Findeisen, Felix

2010-01-01

Voltage-gated calcium channels (CaVs) are large, transmembrane multiprotein complexes that couple membrane depolarization to cellular calcium entry. These channels are central to cardiac action potential propagation, neurotransmitter and hormone release, muscle contraction and calcium-dependent gene transcription. Over the past six years, the advent of high-resolution structural studies of CaV components from different isoforms and CaV modulators has begun to reveal the architecture that underlies the exceptionally rich feedback modulation that controls CaV action. These descriptions of CaV molecular anatomy have provided new, structure-based insights into the mechanisms by which particular channel elements affect voltage-dependent inactivation (VDI), calcium-dependent inactivation (CDI) and calcium-dependent facilitation (CDF). The initial successes have been achieved through structural studies of soluble channel domains and modulator proteins and have proven most powerful when paired with biochemical and functional studies that validate ideas inspired by the structures. Here, we review the progress in this growing area and highlight some key open challenges for future efforts. PMID:21139419

Ion Channel Modulators in Cystic Fibrosis.

PubMed

Gentzsch, Martina; Mall, Marcus A

2018-05-08

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and remains one of the most common life-shortening genetic diseases affecting the lung and other organs. CFTR functions as a cAMP-dependent anion channel that transports chloride and bicarbonate across epithelial surfaces and disruption of these ion transport processes plays a central role in the pathogenesis of CF. These findings provided the rationale for pharmacological modulation of ion transport, either by targeting mutant CFTR or alternative ion channels that can compensate for CFTR dysfunction, as a promising therapeutic approach. High throughput screening has supported the development of CFTR modulator compounds. CFTR correctors are designed to improve defective protein processing, trafficking and cell surface expression, whereas potentiators increase the activity of mutant CFTR at the cell surface. The approval of the first potentiator ivacaftor for the treatment of patients with specific CFTR mutations and, more recently the corrector lumacaftor in combination with ivacaftor for patients homozygous for the common F508del mutation, were major breakthroughs on the path to causal therapies for all patients with CF. In this review, we focus on recent developments and remaining challenges of CFTR-directed therapies, as well as modulators of other ion channels such as alternative chloride channels and the epithelial sodium channel (ENaC) as additional targets in CF lung disease. Further, we discuss how patient-derived precision medicine models may aid the translation of emerging next generation ion channel modulators from the laboratory to the clinic and tailor their use for optimal therapeutic benefits in individual patients with CF. Copyright © 2018. Published by Elsevier Inc.

Characterization of Ether-à-go-go Channels Present in Photoreceptors Reveals Similarity to IKx, a K+ Current in Rod Inner Segments

PubMed Central

Frings, Stephan; Brüll, Nicole; Dzeja, Claudia; Angele, Albert; Hagen, Volker; Kaupp, U. Benjamin; Baumann, Arnd

1998-01-01

In this study, we describe two splice variants of an ether-à-go-go (EAG) K+ channel cloned from bovine retina: bEAG1 and bEAG2. The bEAG2 polypeptide contains an additional insertion of 27 amino acids in the extracellular linker between transmembrane segments S3 and S4. The heterologously expressed splice variants differ in their activation kinetics and are differently modulated by extracellular Mg2+. Cooperativity of modulation by Mg2+ suggests that each subunit of the putative tetrameric channel binds a Mg2+ ion. The channels are neither permeable to Ca2+ ions nor modulated by cyclic nucleotides. In situ hybridization localizes channel transcripts to photoreceptors and retinal ganglion cells. Comparison of EAG currents with IKx, a noninactivating K+ current in the inner segment of rod photoreceptors, reveals an intriguing similarity, suggesting that EAG polypeptides are involved in the formation of Kx channels. PMID:9524140

Kv4 Potassium Channels Modulate Hippocampal EPSP-Spike Potentiation and Spatial Memory in Rats

ERIC Educational Resources Information Center

Truchet, Bruno; Manrique, Christine; Sreng, Leam; Chaillan, Franck A.; Roman, Francois S.; Mourre, Christiane

2012-01-01

Kv4 channels regulate the backpropagation of action potentials (b-AP) and have been implicated in the modulation of long-term potentiation (LTP). Here we showed that blockade of Kv4 channels by the scorpion toxin AmmTX3 impaired reference memory in a radial maze task. In vivo, AmmTX3 intracerebroventricular (i.c.v.) infusion increased and…

Gigascale Silicon Photonic Transmitters Integrating HBT-based Carrier-injection Electroabsorption Modulator Structures

NASA Astrophysics Data System (ADS)

Fu, Enjin

Demand for more bandwidth is rapidly increasing, which is driven by data intensive applications such as high-definition (HD) video streaming, cloud storage, and terascale computing applications. Next-generation high-performance computing systems require power efficient chip-to-chip and intra-chip interconnect yielding densities on the order of 1Tbps/cm2. The performance requirements of such system are the driving force behind the development of silicon integrated optical interconnect, providing a cost-effective solution for fully integrated optical interconnect systems on a single substrate. Compared to conventional electrical interconnect, optical interconnects have several advantages, including frequency independent insertion loss resulting in ultra wide bandwidth and link latency reduction. For high-speed optical transmitter modules, the optical modulator is a key component of the optical I/O channel. This thesis presents a silicon integrated optical transmitter module design based on a novel silicon HBT-based carrier injection electroabsorption modulator (EAM), which has the merits of wide optical bandwidth, high speed, low power, low drive voltage, small footprint, and high modulation efficiency. The structure, mechanism, and fabrication of the modulator structure will be discussed which is followed by the electrical modeling of the post-processed modulator device. The design and realization of a 10Gbps monolithic optical transmitter module integrating the driver circuit architecture and the HBT-based EAM device in a 130nm BiCMOS process is discussed. For high power efficiency, a 6Gbps ultra-low power driver IC implemented in a 130nm BiCMOS process is presented. The driver IC incorporates an integrated 27-1 pseudo-random bit sequence (PRBS) generator for reliable high-speed testing, and a driver circuit featuring digitally-tuned pre-emphasis signal strength. With outstanding drive capability, the driver module can be applied to a wide range of carrier injection modulators and light-emitting diodes (LED) with drive voltage requirements below 1.5V. Measurement results show an optical link based on a 70MHz red LED work well at 300Mbps by using the pre-emphasis driver module. A traveling wave electrode (TWE) modulator structure is presented, including a novel design methodology to address process limitations imposed by a commercial silicon fabrication technology. Results from 3D full wave EM simulation demonstrate the application of the design methodology to achieve specifications, including phase velocity matching, insertion loss, and impedance matching. Results show the HBT-based TWE-EAM system has the bandwidth higher than 60GHz.

RAWINPROC: Computer program for decommutating, interpreting, and interpolating Rawinsonde meteorological balloon sounding data

NASA Technical Reports Server (NTRS)

Staffanson, F. L.

1981-01-01

The FORTRAN computer program RAWINPROC accepts output from NASA Wallops computer program METPASS1; and produces input for NASA computer program 3.0.0700 (ECC-PRD). The three parts together form a software system for the completely automatic reduction of standard RAWINSONDE sounding data. RAWINPROC pre-edits the 0.1-second data, including time-of-day, azimuth, elevation, and sonde-modulated tone frequency, condenses the data according to successive dwells of the tone frequency, decommutates the condensed data into the proper channels (temperature, relative humidity, high and low references), determines the running baroswitch contact number and computes the associated pressure altitudes, and interpolates the data appropriate for input to ACC-PRD.

A design of a valid signal selecting and position decoding ASIC for PET using silicon photomultipliers

NASA Astrophysics Data System (ADS)

Cho, M.; Lim, K.-t.; Kim, H.; Yeom, J.-y.; Kim, J.; Lee, C.; Choi, H.; Cho, G.

2017-01-01

In most cases, a PET system has numerous electrical components and channel circuits and thus it would rather be a bulky product. Also, most existing systems receive analog signals from detectors which make them vulnerable to signal distortions. For these reasons, channel reduction techniques are important. In this work, an ASIC for PET module is being proposed. An ASIC chip for 16 PET detector channels, VSSPDC, has been designed and simulated. The main function of the chip is 16-to-1 channel reduction, i.e., finding the position of only the valid signals, signal timing, and magnitudes in all 16 channels at every recorded event. The ASIC comprises four of 4-channel modules and a 2nd 4-to-1 router. A single channel module comprises a transimpedance amplifier for the silicon photomultipliers, dual comparators with high and low level references, and a logic circuitry. While the high level reference was used to test the validity of the signal, the low level reference was used for the timing. The 1-channel module of the ASIC produced an energy pulse by time-over-threshold method and it also produced a time pulse with a fixed delayed time. Since the ASIC chip outputs only a few digital pulses and does not require an external clock, it has an advantage over noise properties. The cadence simulation showed the good performance of the chip as designed.

A protein interaction mechanism for suppressing the mechanosensitive Piezo channels.

PubMed

Zhang, Tingxin; Chi, Shaopeng; Jiang, Fan; Zhao, Qiancheng; Xiao, Bailong

2017-11-27

Piezo proteins are bona fide mammalian mechanotransduction channels for various cell types including endothelial cells. The mouse Piezo1 of 2547 residues forms a three-bladed, propeller-like homo-trimer comprising a central pore-module and three propeller-structures that might serve as mechanotransduction-modules. However, the mechanogating and regulation of Piezo channels remain unclear. Here we identify the sarcoplasmic /endoplasmic-reticulum Ca 2+ ATPase (SERCA), including the widely expressed SERCA2, as Piezo interacting proteins. SERCA2 strategically suppresses Piezo1 via acting on a 14-residue-constituted intracellular linker connecting the pore-module and mechanotransduction-module. Mutating the linker impairs mechanogating and SERCA2-mediated modulation of Piezo1. Furthermore, the synthetic linker-peptide disrupts the modulatory effects of SERCA2, demonstrating the key role of the linker in mechanogating and regulation. Importantly, the SERCA2-mediated regulation affects Piezo1-dependent migration of endothelial cells. Collectively, we identify SERCA-mediated regulation of Piezos and the functional significance of the linker, providing important insights into the mechanogating and regulation mechanisms of Piezo channels.

Spin-Current-Controlled Modulation of the Magnon Spin Conductance in a Three-Terminal Magnon Transistor

NASA Astrophysics Data System (ADS)

Cornelissen, L. J.; Liu, J.; van Wees, B. J.; Duine, R. A.

2018-03-01

Efficient manipulation of magnon spin transport is crucial for developing magnon-based spintronic devices. In this Letter, we provide proof of principle of a method for modulating the diffusive transport of thermal magnons in an yttrium iron garnet channel between injector and detector contacts. The magnon spin conductance of the channel is altered by increasing or decreasing the magnon chemical potential via spin Hall injection of magnons by a third modulator electrode. We obtain a modulation efficiency of 1.6 %/mA at T =250 K . Finite element modeling shows that this could be increased to well above 10 %/mA by reducing the thickness of the channel, providing interesting prospects for the development of thermal-magnon-based logic circuits.

Dopamine negatively modulates the NCA ion channels in C. elegans

PubMed Central

Topalidou, Irini; Pereira, Laura

2017-01-01

The NALCN/NCA ion channel is a cation channel related to voltage-gated sodium and calcium channels. NALCN has been reported to be a sodium leak channel with a conserved role in establishing neuronal resting membrane potential, but its precise cellular role and regulation are unclear. The Caenorhabditis elegans orthologs of NALCN, NCA-1 and NCA-2, act in premotor interneurons to regulate motor circuit activity that sustains locomotion. Recently we found that NCA-1 and NCA-2 are activated by a signal transduction pathway acting downstream of the heterotrimeric G protein Gq and the small GTPase Rho. Through a forward genetic screen, here we identify the GPCR kinase GRK-2 as a new player affecting signaling through the Gq-Rho-NCA pathway. Using structure-function analysis, we find that the GPCR phosphorylation and membrane association domains of GRK-2 are required for its function. Genetic epistasis experiments suggest that GRK-2 acts on the D2-like dopamine receptor DOP-3 to inhibit Go signaling and positively modulate NCA-1 and NCA-2 activity. Through cell-specific rescuing experiments, we find that GRK-2 and DOP-3 act in premotor interneurons to modulate NCA channel function. Finally, we demonstrate that dopamine, through DOP-3, negatively regulates NCA activity. Thus, this study identifies a pathway by which dopamine modulates the activity of the NCA channels. PMID:28968387

Dopamine negatively modulates the NCA ion channels in C. elegans.

PubMed

Topalidou, Irini; Cooper, Kirsten; Pereira, Laura; Ailion, Michael

2017-10-01

The NALCN/NCA ion channel is a cation channel related to voltage-gated sodium and calcium channels. NALCN has been reported to be a sodium leak channel with a conserved role in establishing neuronal resting membrane potential, but its precise cellular role and regulation are unclear. The Caenorhabditis elegans orthologs of NALCN, NCA-1 and NCA-2, act in premotor interneurons to regulate motor circuit activity that sustains locomotion. Recently we found that NCA-1 and NCA-2 are activated by a signal transduction pathway acting downstream of the heterotrimeric G protein Gq and the small GTPase Rho. Through a forward genetic screen, here we identify the GPCR kinase GRK-2 as a new player affecting signaling through the Gq-Rho-NCA pathway. Using structure-function analysis, we find that the GPCR phosphorylation and membrane association domains of GRK-2 are required for its function. Genetic epistasis experiments suggest that GRK-2 acts on the D2-like dopamine receptor DOP-3 to inhibit Go signaling and positively modulate NCA-1 and NCA-2 activity. Through cell-specific rescuing experiments, we find that GRK-2 and DOP-3 act in premotor interneurons to modulate NCA channel function. Finally, we demonstrate that dopamine, through DOP-3, negatively regulates NCA activity. Thus, this study identifies a pathway by which dopamine modulates the activity of the NCA channels.

Equalization enhanced phase noise in Nyquist-spaced superchannel transmission systems using multi-channel digital back-propagation

PubMed Central

Xu, Tianhua; Liga, Gabriele; Lavery, Domaniç; Thomsen, Benn C.; Savory, Seb J.; Killey, Robert I.; Bayvel, Polina

2015-01-01

Superchannel transmission spaced at the symbol rate, known as Nyquist spacing, has been demonstrated for effectively maximizing the optical communication channel capacity and spectral efficiency. However, the achievable capacity and reach of transmission systems using advanced modulation formats are affected by fibre nonlinearities and equalization enhanced phase noise (EEPN). Fibre nonlinearities can be effectively compensated using digital back-propagation (DBP). However EEPN which arises from the interaction between laser phase noise and dispersion cannot be efficiently mitigated, and can significantly degrade the performance of transmission systems. Here we report the first investigation of the origin and the impact of EEPN in Nyquist-spaced superchannel system, employing electronic dispersion compensation (EDC) and multi-channel DBP (MC-DBP). Analysis was carried out in a Nyquist-spaced 9-channel 32-Gbaud DP-64QAM transmission system. Results confirm that EEPN significantly degrades the performance of all sub-channels of the superchannel system and that the distortions are more severe for the outer sub-channels, both using EDC and MC-DBP. It is also found that the origin of EEPN depends on the relative position between the carrier phase recovery module and the EDC (or MC-DBP) module. Considering EEPN, diverse coding techniques and modulation formats have to be applied for optimizing different sub-channels in superchannel systems. PMID:26365422

Towards a “Sample-In, Answer-Out” Point-of-Care Platform for Nucleic Acid Extraction and Amplification: Using an HPV E6/E7 mRNA Model System

PubMed Central

Gulliksen, Anja; Keegan, Helen; Martin, Cara; O'Leary, John; Solli, Lars A.; Falang, Inger Marie; Grønn, Petter; Karlgård, Aina; Mielnik, Michal M.; Johansen, Ib-Rune; Tofteberg, Terje R.; Baier, Tobias; Gransee, Rainer; Drese, Klaus; Hansen-Hagge, Thomas; Riegger, Lutz; Koltay, Peter; Zengerle, Roland; Karlsen, Frank; Ausen, Dag; Furuberg, Liv

2012-01-01

The paper presents the development of a “proof-of-principle” hands-free and self-contained diagnostic platform for detection of human papillomavirus (HPV) E6/E7 mRNA in clinical specimens. The automated platform performs chip-based sample preconcentration, nucleic acid extraction, amplification, and real-time fluorescent detection with minimal user interfacing. It consists of two modular prototypes, one for sample preparation and one for amplification and detection; however, a common interface is available to facilitate later integration into one single module. Nucleic acid extracts (n = 28) from cervical cytology specimens extracted on the sample preparation chip were tested using the PreTect HPV-Proofer and achieved an overall detection rate for HPV across all dilutions of 50%–85.7%. A subset of 6 clinical samples extracted on the sample preparation chip module was chosen for complete validation on the NASBA chip module. For 4 of the samples, a 100% amplification for HPV 16 or 33 was obtained at the 1 : 10 dilution for microfluidic channels that filled correctly. The modules of a “sample-in, answer-out” diagnostic platform have been demonstrated from clinical sample input through sample preparation, amplification and final detection. PMID:22235204

Numerical investigation of the thermal and electrical performances for combined solar photovoltaic/thermal (PV/T) modules based on internally extruded fin flow channel

NASA Astrophysics Data System (ADS)

Deng, Y. C.; Li, Q. P.; Wang, G. J.

2017-11-01

A solar photovoltaic/thermal (PV/T) module based on internally extruded fin flow channel was investigated numerically in this paper. First of all, the structures of the thin plate heat exchanger and the PV/T module were presented. Then, a numerical model of the PV/T module considering solar irradiation, fluid flow and heat transfer was developed to analyze the performance of the module. Finally, the steady electrical and thermal efficiencies of the PV/T module at different inlet water temperatures and mass flow rates were achieved. These numerical results supply theory basis for practical application of the PV/T module.

THz photonic wireless links with 16-QAM modulation in the 375-450 GHz band.

PubMed

Jia, Shi; Yu, Xianbin; Hu, Hao; Yu, Jinlong; Guan, Pengyu; Da Ros, Francesco; Galili, Michael; Morioka, Toshio; Oxenløwe, Leif K

2016-10-17

We propose and experimentally demonstrate THz photonic wireless communication systems with 16-QAM modulation in the 375-450 GHz band. The overall throughput reaches as high as 80 Gbit/s by exploiting four THz channels with 5 Gbaud 16-QAM baseband modulation per channel. We create a coherent optical frequency comb (OFC) for photonic generation of multiple THz carriers based on photo-mixing in a uni-travelling carrier photodiode (UTC-PD). The OFC configuration also allows us to generate reconfigurable THz carriers with low phase noise. The multiple-channel THz radiation is received by using a Schottky mixer based electrical receiver after 0.5 m free-space wireless propagation. 2-channel (40 Gbit/s) and 4-channel (80 Gbit/s) THz photonic wireless links with 16-QAM modulation are reported in this paper, and the bit error rate (BER) performance for all channels in both cases is below the hard decision forward error correction (HD-FEC) threshold of 3.8e-3 with 7% overhead. In addition, we also successfully demonstrate hybrid photonic wireless transmission of 40 Gbit/s 16-QAM signal at carrier frequencies of 400 GHz and 425 GHz over 30 km standard single mode fiber (SSMF) between the optical baseband signal transmitter and the THz wireless transmitter with negligible induced power penalty.

Envelope Interactions in Multi-Channel Amplitude Modulation Frequency Discrimination by Cochlear Implant Users.

PubMed

Galvin, John J; Oba, Sandra I; Başkent, Deniz; Chatterjee, Monita; Fu, Qian-Jie

2015-01-01

Previous cochlear implant (CI) studies have shown that single-channel amplitude modulation frequency discrimination (AMFD) can be improved when coherent modulation is delivered to additional channels. It is unclear whether the multi-channel advantage is due to increased loudness, multiple envelope representations, or to component channels with better temporal processing. Measuring envelope interference may shed light on how modulated channels can be combined. In this study, multi-channel AMFD was measured in CI subjects using a 3-alternative forced-choice, non-adaptive procedure ("which interval is different?"). For the reference stimulus, the reference AM (100 Hz) was delivered to all 3 channels. For the probe stimulus, the target AM (101, 102, 104, 108, 116, 132, 164, 228, or 256 Hz) was delivered to 1 of 3 channels, and the reference AM (100 Hz) delivered to the other 2 channels. The spacing between electrodes was varied to be wide or narrow to test different degrees of channel interaction. Results showed that CI subjects were highly sensitive to interactions between the reference and target envelopes. However, performance was non-monotonic as a function of target AM frequency. For the wide spacing, there was significantly less envelope interaction when the target AM was delivered to the basal channel. For the narrow spacing, there was no effect of target AM channel. The present data were also compared to a related previous study in which the target AM was delivered to a single channel or to all 3 channels. AMFD was much better with multiple than with single channels whether the target AM was delivered to 1 of 3 or to all 3 channels. For very small differences between the reference and target AM frequencies (2-4 Hz), there was often greater sensitivity when the target AM was delivered to 1 of 3 channels versus all 3 channels, especially for narrowly spaced electrodes. Besides the increased loudness, the present results also suggest that multiple envelope representations may contribute to the multi-channel advantage observed in previous AMFD studies. The different patterns of results for the wide and narrow spacing suggest a peripheral contribution to multi-channel temporal processing. Because the effect of target AM frequency was non-monotonic in this study, adaptive procedures may not be suitable to measure AMFD thresholds with interfering envelopes. Envelope interactions among multiple channels may be quite complex, depending on the envelope information presented to each channel and the relative independence of the stimulated channels.

Envelope Interactions in Multi-Channel Amplitude Modulation Frequency Discrimination by Cochlear Implant Users

PubMed Central

2015-01-01

Rationale Previous cochlear implant (CI) studies have shown that single-channel amplitude modulation frequency discrimination (AMFD) can be improved when coherent modulation is delivered to additional channels. It is unclear whether the multi-channel advantage is due to increased loudness, multiple envelope representations, or to component channels with better temporal processing. Measuring envelope interference may shed light on how modulated channels can be combined. Methods In this study, multi-channel AMFD was measured in CI subjects using a 3-alternative forced-choice, non-adaptive procedure (“which interval is different?”). For the reference stimulus, the reference AM (100 Hz) was delivered to all 3 channels. For the probe stimulus, the target AM (101, 102, 104, 108, 116, 132, 164, 228, or 256 Hz) was delivered to 1 of 3 channels, and the reference AM (100 Hz) delivered to the other 2 channels. The spacing between electrodes was varied to be wide or narrow to test different degrees of channel interaction. Results Results showed that CI subjects were highly sensitive to interactions between the reference and target envelopes. However, performance was non-monotonic as a function of target AM frequency. For the wide spacing, there was significantly less envelope interaction when the target AM was delivered to the basal channel. For the narrow spacing, there was no effect of target AM channel. The present data were also compared to a related previous study in which the target AM was delivered to a single channel or to all 3 channels. AMFD was much better with multiple than with single channels whether the target AM was delivered to 1 of 3 or to all 3 channels. For very small differences between the reference and target AM frequencies (2–4 Hz), there was often greater sensitivity when the target AM was delivered to 1 of 3 channels versus all 3 channels, especially for narrowly spaced electrodes. Conclusions Besides the increased loudness, the present results also suggest that multiple envelope representations may contribute to the multi-channel advantage observed in previous AMFD studies. The different patterns of results for the wide and narrow spacing suggest a peripheral contribution to multi-channel temporal processing. Because the effect of target AM frequency was non-monotonic in this study, adaptive procedures may not be suitable to measure AMFD thresholds with interfering envelopes. Envelope interactions among multiple channels may be quite complex, depending on the envelope information presented to each channel and the relative independence of the stimulated channels. PMID:26431043

Web-based multi-channel analyzer

DOEpatents

Gritzo, Russ E.

2003-12-23

The present invention provides an improved multi-channel analyzer designed to conveniently gather, process, and distribute spectrographic pulse data. The multi-channel analyzer may operate on a computer system having memory, a processor, and the capability to connect to a network and to receive digitized spectrographic pulses. The multi-channel analyzer may have a software module integrated with a general-purpose operating system that may receive digitized spectrographic pulses for at least 10,000 pulses per second. The multi-channel analyzer may further have a user-level software module that may receive user-specified controls dictating the operation of the multi-channel analyzer, making the multi-channel analyzer customizable by the end-user. The user-level software may further categorize and conveniently distribute spectrographic pulse data employing non-proprietary, standard communication protocols and formats.

Plumbing. Pre-Apprenticeship Phase 2 Training. Student Training Modules.

ERIC Educational Resources Information Center

Brath, Ed

These 26 Student Training Modules on plumbing comprise one of nine sets of self-paced learning modules developed for Pre-Apprenticeship Phase 2 Training. (A companion instructor's guide is available separately as CE 031 577.) The modules are designed to impart trade knowledge and skills to the student. Each module contains some or all of the…

Plastering. Pre-Apprenticeship Phase 2 Training. Student Training Modules.

ERIC Educational Resources Information Center

Hamblen, Ron

These 20 Student Training Modules on plastering comprise one of nine sets of self-paced learning modules developed for Pre-Apprenticeship Phase 2 Training. (A companion instructor's guide is available separately as CE 031 569.) The modules are designed to impart trade knowledge and skills to the student. Each module contains some or all of the…

Drywall. Pre-Apprenticeship Phase 2 Training. Student Training Modules.

ERIC Educational Resources Information Center

Moore, Doug

These 18 Student Training Modules on drywall comprise one of nine sets of self-paced learning modules developed for Pre-Apprenticeship Phase 2 Training. (A companion instructor's guide is available separately as CE 031 573.) The modules are designed to impart trade knowledge and skills to the student. Each module contains some or all of the…

Floor Covering. Pre-Apprenticeship Phase 2 Training. Student Training Modules.

ERIC Educational Resources Information Center

Hamblen, Ron

These 21 Student Training Modules on floor covering comprise one of nine sets of self-paced learning modules developed for Pre-Apprenticeship Phase 2 Training. (A companion instructor's guide is available separately as CE 031 565.) The modules are designed to impart trade knowledge and skills to the student. Each module contains some or all of the…

Tilesetting. Pre-Apprenticeship Phase 2 Training. Student Training Modules.

ERIC Educational Resources Information Center

Ausland, Greg

These 24 Student Training Modules on tilesetting comprise one of nine sets of self-paced learning modules developed for Pre-Apprenticeship Phase 2 Training. (A companion instructor's guide is available separately as CE 031 563.) The modules are designed to impart trade knowledge and skills to the student. Each module contains some or all of the…

Bricklaying. Pre-Apprenticeship Phase 2 Training. Student Training Modules.

ERIC Educational Resources Information Center

Cholewinski, Scott

These 23 Student Training Modules on bricklaying comprise one of nine sets of self-paced learning modules developed for Pre-Apprenticeship Phase 2 Training. (A companion instructor's guide is available separately as CE 031 567.) The modules are designed to impart trade knowledge and skills to the student. Each module contains some or all of the…

Parts Counter. Pre-Apprenticeship Phase 2 Training. Student Training Modules.

ERIC Educational Resources Information Center

Snyder, James A.

These 23 Student Training Modules on parts counter comprise one of nine sets of self-paced learning modules developed for Pre-Apprenticeship Phase 2 Training. (A companion instructor's guide is available separately as CE 031 571.) The modules are designed to impart trade knowledge and skills to the student. Each module contains some or all of the…

Cement Finishing. Pre-Apprenticeship Phase 2 Training. Student Training Modules.

ERIC Educational Resources Information Center

Nama, Joe

These 20 Student Training Modules on cement finishing comprise one of nine sets of self-paced learning modules developed for Pre-Apprenticeship Phase 2 Training. (A companion instructor's guide is available separately as CE 031 575.) The modules are designed to impart trade knowledge and skills to the student. Each module contains some or all of…

Painting. Pre-Apprenticeship Phase 2 Training. Student Training Modules.

ERIC Educational Resources Information Center

Kracht, Shannon

These 21 Student Training Modules on painting comprise one of nine sets of self-paced learning modules developed for Pre-Apprenticeship Phase 2 Training. (A companion instructor's guide is available separately as CE 031 561.) The modules are designed to impart trade knowledge and skills to the student. Each module contains some or all of the…

Development of a front-end analog circuit for multi-channel SiPM readout and performance verification for various PET detector designs

NASA Astrophysics Data System (ADS)

Ko, Guen Bae; Yoon, Hyun Suk; Kwon, Sun Il; Lee, Chan Mi; Ito, Mikiko; Hong, Seong Jong; Lee, Dong Soo; Lee, Jae Sung

2013-03-01

Silicon photomultipliers (SiPMs) are outstanding photosensors for the development of compact imaging devices and hybrid imaging systems such as positron emission tomography (PET)/ magnetic resonance (MR) scanners because of their small size and MR compatibility. The wide use of this sensor for various types of scintillation detector modules is being accelerated by recent developments in tileable multichannel SiPM arrays. In this work, we present the development of a front-end readout module for multi-channel SiPMs. This readout module is easily extendable to yield a wider detection area by the use of a resistive charge division network (RCN). We applied this readout module to various PET detectors designed for use in small animal PET/MR, optical fiber PET/MR, and double layer depth of interaction (DOI) PET. The basic characteristics of these detector modules were also investigated. The results demonstrate that the PET block detectors developed using the readout module and tileable multi-channel SiPMs had reasonable performance.

Numerical study of mixed convection heat transfer enhancement in a channel with active flow modulation

NASA Astrophysics Data System (ADS)

Billah, Md. Mamun; Khan, Md Imran; Rahman, Mohammed Mizanur; Alam, Muntasir; Saha, Sumon; Hasan, Mohammad Nasim

2017-06-01

A numerical study of steady two dimensional mixed convention heat transfer phenomena in a rectangular channel with active flow modulation is carried out in this investigation. The flow in the channel is modulated via a rotating cylinder placed at the center of the channel. In this study the top wall of the channel is subjected to an isothermal low temperature while a discrete isoflux heater is positioned on the lower wall. The fluid flow under investigation is assumed to have a Prandtl number of 0.71 while the Reynolds No. and the Grashof No. are varied in wide range for four different situations such as: i) plain channel with no cylinder, ii) channel with stationary cylinder, iii) channel with clockwise rotating cylinder and iv) channel with counter clockwise rotating cylinder. The results obtained in this study are presented in terms of the distribution of streamlines, isotherms in the channel while the heat transfer process from the heat source is evaluated in terms of the local Nusselt number, average Nusselt number. The outcomes of this study also indicate that the results are strongly dependent on the type of configuration and direction of rotation of the cylinder and that the average Nusselt number value rises with an increase in Reynolds and Grashof numbers but the correlation between these parameters at higher values of Reynolds and Grashof numbers becomes weak.

LDQ10: a compact ultra low-power radiation-hard 4 × 10 Gb/s driver array

DOE PAGES

Zeng, Z.; Zhang, T.; Wang, G.; ...

2017-02-28

Here, a High-speed and low-power VCSEL driver is an important component of the Versatile Link for the high-luminosity LHC (HL-LHC) experiments. A compact low-power radiation-hard 4 × 10 Gb/s VCSEL driver array (LDQ10) has been developed in 65 nm CMOS technology. Each channel in LDQ10 can provide a modulation current up to 8 mA and bias current up to 12 mA. Edge pre-emphasis is employed to compensate for the bandwidth limitations due to parasitic and the turn-on delay of VCSEL devices. LDQ10 occupies a chip area of 1900 μm × 1700 μm and consumes 130 mW power for typical currentmore » settings. The modulation amplitude degrades less than 5% after 300 Mrad total ionizing dose. LDQ10 can be directly wire-bonded to the VCSEL array and it is a suitable candidate for the Versatile Link.« less

FIBER AND INTEGRATED OPTICS. OTHER TOPICS IN QUANTUM ELECTRONICS: Investigation of an electrooptic multichannel-waveguide modulator as a controlled transparency

NASA Astrophysics Data System (ADS)

Bykovskiĭ, Yu A.; Zheregi, V. G.; Kulchin, Yurii N.; Poryadin, Yu D.; Smirnov, V. L.; Fomichev, N. N.

1990-05-01

An investigation was made of a multichannel LiNbO3 waveguide modulator of light in space and time, suitable for processing of analog and digital signals. This modulator had 26 channels and the half-wave control voltage was 4.5 V. A theoretical analysis and an experimental study were made of the functional performance of this modulator depending on the channel interconnections and on the nature of the signals applied to the modulator. The feasibility of processing analog and digital signals was studied.

Pre and postprandial changes in orexigenic and anorexigenic factors in channel catfish Ictalurus punctatus

USDA-ARS?s Scientific Manuscript database

We examined pre- and postprandial changes in the expression of plasma ghrelin (GHRL) and mRNAs encoding GRLN, cocaine and amphetamine regulated transcript (CART), neuropeptide Y (NPY), and cholecystokinin (CCK) in channel catfish. Fish were either offered feed (Fed) or fasted (Unfed). Feeding incr...

Exogenous γ-aminobutyric acid (GABA) affects pollen tube growth via modulating putative Ca2+-permeable membrane channels and is coupled to negative regulation on glutamate decarboxylase

PubMed Central

Yu, Guang-Hui; Zou, Jie; Feng, Jing; Peng, Xiong-Bo; Wu, Ju-You; Wu, Ying-Liang; Palanivelu, Ravishankar; Sun, Meng-Xiang

2014-01-01

γ-Aminobutyric acid (GABA) is implicated in pollen tube growth, but the molecular and cellular mechanisms that it mediates are largely unknown. Here, it is shown that exogenous GABA modulates putative Ca2+-permeable channels on the plasma membranes of tobacco pollen grains and pollen tubes. Whole-cell voltage-clamp experiments and non-invasive micromeasurement technology (NMT) revealed that the influx of Ca2+ increases in pollen tubes in response to exogenous GABA. It is also demonstrated that glutamate decarboxylase (GAD), the rate-limiting enzyme of GABA biosynthesis, is involved in feedback controls of Ca2+-permeable channels to fluctuate intracellular GABA levels and thus modulate pollen tube growth. The findings suggest that GAD activity linked with Ca2+-permeable channels relays an extracellular GABA signal and integrates multiple signal pathways to modulate tobacco pollen tube growth. Thus, the data explain how GABA mediates the communication between the style and the growing pollen tubes. PMID:24799560

Linear modulator

NASA Technical Reports Server (NTRS)

1972-01-01

A study of frequency division multiplexing (FDM) systems was made for the purpose of determining the system performance that can be obtained with available state of the art components. System performance was evaluated on the basis of past experience, system analysis, and component evaluation. The system study was specifically directed to the area of FDM systems using subcarrier channel frequencies from 4 kHz to 200 kHz and channel information bandwidths of dc to 1, 2, 4, 8, and 16 kHz. The evaluation also assumes that the demodulation will be from a tape recorder which produces frequency modulation of + or - 1% on the signal due to the tape recorder wow and flutter. For the modulation system it is assumed that the pilot and carrier channel frequencies are stable to within + or - .005% and that the FM on the channel carriers is negligible. The modulator system was evaluated for the temperature range of -20 degree to +85 degree while the demodulator system was evaluated for operation at room temperature.

LDPC-coded MIMO optical communication over the atmospheric turbulence channel using Q-ary pulse-position modulation.

PubMed

Djordjevic, Ivan B

2007-08-06

We describe a coded power-efficient transmission scheme based on repetition MIMO principle suitable for communication over the atmospheric turbulence channel, and determine its channel capacity. The proposed scheme employs the Q-ary pulse-position modulation. We further study how to approach the channel capacity limits using low-density parity-check (LDPC) codes. Component LDPC codes are designed using the concept of pairwise-balanced designs. Contrary to the several recent publications, bit-error rates and channel capacities are reported assuming non-ideal photodetection. The atmospheric turbulence channel is modeled using the Gamma-Gamma distribution function due to Al-Habash et al. Excellent bit-error rate performance improvement, over uncoded case, is found.

CB1 cannabinoid receptor-mediated anandamide signalling reduces the defensive behaviour evoked through GABAA receptor blockade in the dorsomedial division of the ventromedial hypothalamus.

PubMed

Dos Anjos-Garcia, Tayllon; Ullah, Farhad; Falconi-Sobrinho, Luiz Luciano; Coimbra, Norberto Cysne

2017-02-01

The effects of cannabinoids in brain areas expressing cannabinoid receptors, such as hypothalamic nuclei, are not yet well known. Several studies have demonstrated the role of hypothalamic nuclei in the organisation of behavioural responses induced through innate fear and panic attacks. Panic-prone states are experimentally induced in laboratory animals through a reduction in the GABAergic activity. The aim of the present study was to examine panic-like elaborated defensive behaviour evoked by GABA A receptor blockade with bicuculline (BIC) in the dorsomedial division of the ventromedial hypothalamus (VMHdm). We also aimed to characterise the involvement of endocannabinoids and the CB 1 cannabinoid receptor in the modulation of elaborated defence behavioural responses organised with the VMHdm. The guide-cannula was stereotaxicaly implanted in VMHdm and the animals were treated with anandamide (AEA) at different doses, and the effective dose was used after the pre-treatment with the CB 1 receptor antagonist AM251, followed by GABA A receptor blockade in VMHdm. The results showed that the intra-hypothalamic administration of AEA at an intermediate dose (5 pmol) attenuated defence responses induced through the intra-VMHdm microinjection of bicuculline (40 ng). This effect, however, was inhibited when applied central microinjection of the CB 1 receptor antagonist AM251 in the VMHdm. Moreover, AM251 potentiates de non-oriented escape induced by bicuculline, effect blocked by pre-treatment with the TRPV 1 channel antagonist 6-I-CPS. These results indicate that AEA modulates the pro-aversive effects of intra-VMHdm-bicuculline treatment, recruiting CB 1 cannabinoid receptors and the TRPV1 channel is involved in the AM251-related potentiation of bicuculline effects on non-oriented escape behaviour. Copyright © 2016 Elsevier Ltd. All rights reserved.

Noncoherent Physical-Layer Network Coding with FSK Modulation: Relay Receiver Design Issues

DTIC Science & Technology

2011-03-01

222 IEEE TRANSACTIONS ON COMMUNICATIONS, VOL. 59, NO. 9, SEPTEMBER 2011 2595 Noncoherent Physical-Layer Network Coding with FSK Modulation: Relay... noncoherent reception, channel estima- tion. I. INTRODUCTION IN the two-way relay channel (TWRC), a pair of sourceterminals exchange information...2011 4. TITLE AND SUBTITLE Noncoherent Physical-Layer Network Coding with FSK Modulation:Relay Receiver Design Issues 5a. CONTRACT NUMBER 5b

Spin-Current-Controlled Modulation of the Magnon Spin Conductance in a Three-Terminal Magnon Transistor.

PubMed

Cornelissen, L J; Liu, J; van Wees, B J; Duine, R A

2018-03-02

Efficient manipulation of magnon spin transport is crucial for developing magnon-based spintronic devices. In this Letter, we provide proof of principle of a method for modulating the diffusive transport of thermal magnons in an yttrium iron garnet channel between injector and detector contacts. The magnon spin conductance of the channel is altered by increasing or decreasing the magnon chemical potential via spin Hall injection of magnons by a third modulator electrode. We obtain a modulation efficiency of 1.6%/mA at T=250  K. Finite element modeling shows that this could be increased to well above 10%/mA by reducing the thickness of the channel, providing interesting prospects for the development of thermal-magnon-based logic circuits.

A study on the co- and adjacent channel protection requirements for mobile satellite ACSSB modulation

NASA Technical Reports Server (NTRS)

Sydor, John T.

1988-01-01

Samples of speech modulated by narrowband frequency modulation (NBFM) (cellular) and amplitude companded single sideband (ACSSB) radios were subjected to simulated co- and adjacent channel interference environments typical of proposed frequency division multiple access (FDMA) mobile satellite systems. These samples were then listened to by a group of evaluators whose subjective responses to the samples were used to produce a series of graphs showing the relationship between subjective acceptability, carrier to noise density (C/No), carrier to interference ratio (C/I), and frequency offset. The results show that in a mobile satellite environment, ACSSB deteriorates more slowly than NBFM. The co- and adjacent channel protection ratios for both modulation techniques were roughly the same, even though the mechanism for signal deterioration is different.

The Sensorless Pore Module of Voltage-gated K+ Channel Family 7 Embodies the Target Site for the Anticonvulsant Retigabine.

PubMed

Syeda, Ruhma; Santos, Jose S; Montal, Mauricio

2016-02-05

KCNQ (voltage-gated K(+) channel family 7 (Kv7)) channels control cellular excitability and underlie the K(+) current sensitive to muscarinic receptor signaling (the M current) in sympathetic neurons. Here we show that the novel anti-epileptic drug retigabine (RTG) modulates channel function of pore-only modules (PMs) of the human Kv7.2 and Kv7.3 homomeric channels and of Kv7.2/3 heteromeric channels by prolonging the residence time in the open state. In addition, the Kv7 channel PMs are shown to recapitulate the single-channel permeation and pharmacological specificity characteristics of the corresponding full-length proteins in their native cellular context. A mutation (W265L) in the reconstituted Kv7.3 PM renders the channel insensitive to RTG and favors the conductive conformation of the PM, in agreement to what is observed when the Kv7.3 mutant is heterologously expressed. On the basis of the new findings and homology models of the closed and open conformations of the Kv7.3 PM, we propose a structural mechanism for the gating of the Kv7.3 PM and for the site of action of RTG as a Kv7.2/Kv7.3 K(+) current activator. The results validate the modular design of human Kv channels and highlight the PM as a high-fidelity target for drug screening of Kv channels. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

The Sensorless Pore Module of Voltage-gated K+ Channel Family 7 Embodies the Target Site for the Anticonvulsant Retigabine*

PubMed Central

Syeda, Ruhma; Santos, Jose S.; Montal, Mauricio

2016-01-01

KCNQ (voltage-gated K+ channel family 7 (Kv7)) channels control cellular excitability and underlie the K+ current sensitive to muscarinic receptor signaling (the M current) in sympathetic neurons. Here we show that the novel anti-epileptic drug retigabine (RTG) modulates channel function of pore-only modules (PMs) of the human Kv7.2 and Kv7.3 homomeric channels and of Kv7.2/3 heteromeric channels by prolonging the residence time in the open state. In addition, the Kv7 channel PMs are shown to recapitulate the single-channel permeation and pharmacological specificity characteristics of the corresponding full-length proteins in their native cellular context. A mutation (W265L) in the reconstituted Kv7.3 PM renders the channel insensitive to RTG and favors the conductive conformation of the PM, in agreement to what is observed when the Kv7.3 mutant is heterologously expressed. On the basis of the new findings and homology models of the closed and open conformations of the Kv7.3 PM, we propose a structural mechanism for the gating of the Kv7.3 PM and for the site of action of RTG as a Kv7.2/Kv7.3 K+ current activator. The results validate the modular design of human Kv channels and highlight the PM as a high-fidelity target for drug screening of Kv channels. PMID:26627826

Crystal Structure of a Fibroblast Growth Factor Homologous Factor (FHF) Defines a Conserved Surface on FHFs for Binding and Modulation of Voltage-gated Sodium Channels

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

Goetz, R.; Dover, K; Laezza, F

2009-01-01

Voltage-gated sodium channels (Nav) produce sodium currents that underlie the initiation and propagation of action potentials in nerve and muscle cells. Fibroblast growth factor homologous factors (FHFs) bind to the intracellular C-terminal region of the Nav alpha subunit to modulate fast inactivation of the channel. In this study we solved the crystal structure of a 149-residue-long fragment of human FHF2A which unveils the structural features of the homology core domain of all 10 human FHF isoforms. Through analysis of crystal packing contacts and site-directed mutagenesis experiments we identified a conserved surface on the FHF core domain that mediates channel bindingmore » in vitro and in vivo. Mutations at this channel binding surface impaired the ability of FHFs to co-localize with Navs at the axon initial segment of hippocampal neurons. The mutations also disabled FHF modulation of voltage-dependent fast inactivation of sodium channels in neuronal cells. Based on our data, we propose that FHFs constitute auxiliary subunits for Navs.« less

Microfluidics platform for single-shot dose-response analysis of chloride channel-modulating compounds.

PubMed

Jin, Byung-Ju; Ko, Eun-A; Namkung, Wan; Verkman, A S

2013-10-07

We previously developed cell-based kinetics assays of chloride channel modulators utilizing genetically encoded yellow fluorescent proteins. Fluorescence platereader-based high-throughput screens yielded small-molecule activators and inhibitors of the cAMP-activated chloride channel CFTR and calcium-activated chloride channels, including TMEM16A. Here, we report a microfluidics platform for single-shot determination of concentration-activity relations in which a 1.5 × 1.5 mm square area of adherent cultured cells is exposed for 5-10 min to a pseudo-logarithmic gradient of test compound generated by iterative, two-component channel mixing. Cell fluorescence is imaged following perfusion with an iodide-containing solution to give iodide influx rate at each location in the image field, thus quantifying modulator effects over a wide range of concentrations in a single measurement. IC50 determined for CFTR and TMEM16A activators and inhibitors by single-shot microfluidics were in agreement with conventional plate reader measurements. The microfluidics approach developed here may accelerate the discovery and characterization of chloride channel-targeted drugs.

Coherently coupled high-power fiber arrays

NASA Astrophysics Data System (ADS)

Anderegg, Jesse; Brosnan, Stephen; Cheung, Eric; Epp, Paul; Hammons, Dennis; Komine, Hiroshi; Weber, Mark; Wickham, Michael

2006-02-01

A four-element fiber array has demonstrated 470 watts of coherently phased, linearly polarized light energy in a single far-field spot. Each element consists of a single-mode fiber-amplifier chain. Phase control of each element is achieved with a Lithium-Niobate phase modulator. A master laser provides a linearly polarized, narrow linewidth signal that is split into five channels. Four channels are individually amplified using polarization maintaining fiber power amplifiers. The fifth channel is used as a reference arm. It is frequency shifted and then combined interferometrically with a portion of each channel's signal. Detectors sense the heterodyne modulation signal, and an electronics circuit measures the relative phase for each channel. Compensating adjustments are then made to each channel's phase modulator. This effort represents the results of a multi-year effort to achieve high power from a single element fiber amplifier and to understand the important issues involved in coherently combining many individual elements to obtain sufficient optical power for directed energy weapons. Northrop Grumman Corporation and the High Energy Laser Joint Technology Office jointly sponsored this work.

The Evolution of Riparian Landscape Elements Following Upstream Regulation and Depletion on the Rio Grande

NASA Astrophysics Data System (ADS)

Everitt, B. L.

2006-12-01

In 1915 closure of Elephant Butte Dam in central New Mexico profoundly altered the hydrologic regime of the Rio Grande for 560 km downstream, and set in motion a cascade of interwoven geomorphic, biological, and cultural responses. Geomorphic response included shrinking of the width and depth of the channel, and an increase in sinuosity. Cultural responses included artificial channel modification on 320 km of the river within the boundaries of the original irrigation project, beginning in 1933. The pre-dam river and its flood plain consisted of a mosaic of geomorphic elements that formed a functional riverine landscape, and founded a diverse habitat for the plants, animals, and people that lived there. A preliminary comparison of the modern river with pre-dam topographic mapping permits identification of individual landscape elements, including overflow land (flood plain) both cultivated and uncultivated, with oxbows and back-swamps. The pre-dam channel included a low water thread and un-vegetated flood bars. From pre-dam description and photographs we can assume the usual complement of pools and riffles, point bars and undercut banks. Until dredged in the 1970s, the unmodified reach retained the entire suite of landscape elements, although in somewhat different proportions from the pre-dam river, and remained a functional riparian system. Channel sinuosity increased from 1.45 in 1910 to 1.7 in 1970, thus riverbank habitat increased by 1.17%. In 1970 undercut banks still provided protection for fish, and point bars generated by lateral migration still provided seed beds for pioneer species. The smaller shallower channel raised groundwater beneath the flood plain and retarded flood waves, creating a generally more mesic environment, although the river occasionally dries up, as it did prior to 1915. In contrast, an impoverished suite of landscape elements characterizes the channelized reach. Lateral stability precludes point bars and undercut banks. Bounding levees separate the channel from its former flood plain. All areas are impacted by heavy machinery during periodic channel maintenance. I conclude that the environmental degradation caused by artificial channel modification has far outweighed any generated by upstream hydrologic control.

Distance constraints on activation of TRPV4 channels by AKAP150-bound PKCα in arterial myocytes

PubMed Central

Moreno, Claudia M.; O’Dwyer, Samantha; Woods, Sean

2017-01-01

TRPV4 (transient receptor potential vanilloid 4) channels are Ca2+-permeable channels that play a key role in regulating vascular tone. In arterial myocytes, opening of TRPV4 channels creates local increases in Ca2+ influx, detectable optically as “TRPV4 sparklets.” TRPV4 sparklet activity can be enhanced by the action of the vasoconstrictor angiotensin II (AngII). This modulation depends on the activation of subcellular signaling domains that comprise protein kinase C α (PKCα) bound to the anchoring protein AKAP150. Here, we used super-resolution nanoscopy, patch-clamp electrophysiology, Ca2+ imaging, and mathematical modeling approaches to test the hypothesis that AKAP150-dependent modulation of TRPV4 channels is critically dependent on the distance between these two proteins in the sarcolemma of arterial myocytes. Our data show that the distance between AKAP150 and TRPV4 channel clusters varies with sex and arterial bed. Consistent with our hypothesis, we further find that basal and AngII-induced TRPV4 channel activity decays exponentially as the distance between TRPV4 and AKAP150 increases. Our data suggest a maximum radius of action of ∼200 nm for local modulation of TRPV4 channels by AKAP150-associated PKCα. PMID:28507079

Connexin-Dependent Neuroglial Networking as a New Therapeutic Target.

PubMed

Charvériat, Mathieu; Naus, Christian C; Leybaert, Luc; Sáez, Juan C; Giaume, Christian

2017-01-01

Astrocytes and neurons dynamically interact during physiological processes, and it is now widely accepted that they are both organized in plastic and tightly regulated networks. Astrocytes are connected through connexin-based gap junction channels, with brain region specificities, and those networks modulate neuronal activities, such as those involved in sleep-wake cycle, cognitive, or sensory functions. Additionally, astrocyte domains have been involved in neurogenesis and neuronal differentiation during development; they participate in the "tripartite synapse" with both pre-synaptic and post-synaptic neurons by tuning down or up neuronal activities through the control of neuronal synaptic strength. Connexin-based hemichannels are also involved in those regulations of neuronal activities, however, this feature will not be considered in the present review. Furthermore, neuronal processes, transmitting electrical signals to chemical synapses, stringently control astroglial connexin expression, and channel functions. Long-range energy trafficking toward neurons through connexin-coupled astrocytes and plasticity of those networks are hence largely dependent on neuronal activity. Such reciprocal interactions between neurons and astrocyte networks involve neurotransmitters, cytokines, endogenous lipids, and peptides released by neurons but also other brain cell types, including microglial and endothelial cells. Over the past 10 years, knowledge about neuroglial interactions has widened and now includes effects of CNS-targeting drugs such as antidepressants, antipsychotics, psychostimulants, or sedatives drugs as potential modulators of connexin function and thus astrocyte networking activity. In physiological situations, neuroglial networking is consequently resulting from a two-way interaction between astrocyte gap junction-mediated networks and those made by neurons. As both cell types are modulated by CNS drugs we postulate that neuroglial networking may emerge as new therapeutic targets in neurological and psychiatric disorders.

Do TRPC channels support working memory? Comparing modulations of TRPC channels and working memory through G-protein coupled receptors and neuromodulators.

PubMed

Reboreda, Antonio; Theissen, Frederik M; Valero-Aracama, Maria J; Arboit, Alberto; Corbu, Mihaela A; Yoshida, Motoharu

2018-03-01

Working memory is a crucial ability we use in daily life. However, the cellular mechanisms supporting working memory still remain largely unclear. A key component of working memory is persistent neural firing which is believed to serve short-term (hundreds of milliseconds up to tens of seconds) maintenance of necessary information. In this review, we will focus on the role of transient receptor potential canonical (TRPC) channels as a mechanism underlying persistent firing. Many years of in vitro work have been suggesting a crucial role of TRPC channels in working memory and temporal association tasks. If TRPC channels are indeed a central mechanism for working memory, manipulations which impair or facilitate working memory should have a similar effect on TRPC channel modulation. However, modulations of working memory and TRPC channels were never systematically compared, and it remains unanswered whether TRPC channels indeed contribute to working memory in vivo or not. In this article, we review the effects of G-protein coupled receptors (GPCR) and neuromodulators, including acetylcholine, noradrenalin, serotonin and dopamine, on working memory and TRPC channels. Based on comparisons, we argue that GPCR and downstream signaling pathways that activate TRPC, generally support working memory, while those that suppress TRPC channels impair it. However, depending on the channel types, areas, and systems tested, this is not the case in all studies. Further work to clarify involvement of specific TRPC channels in working memory tasks and how they are affected by neuromodulators is still necessary in the future. Copyright © 2018 Elsevier B.V. All rights reserved.

KCNQ channels determine serotonergic modulation of ventral surface chemoreceptors and respiratory drive

PubMed Central

Hawryluk, Joanna M.; Moreira, Thiago S.; Takakura, Ana C.; Wenker, Ian C.; Tzingounis, Anastasios V.; Mulkey, Daniel K.

2012-01-01

Chemosensitive neurons in the retrotrapezoid nucleus (RTN) regulate breathing in response to CO2/H+ changes. Their activity is also sensitive to neuromodulatory inputs from multiple respiratory centers, and thus they serve as a key nexus of respiratory control. However, molecular mechanisms that control their activity and susceptibility to neuromodulation are unknown. Here, we show in vitro and in vivo that KCNQ channels are critical determinants of RTN neural activity. In particular, we find that pharmacological block of KCNQ channels (XE991, 10 μM) increased basal activity and CO2-responsivness of RTN neurons in rat brain slices; whereas KCNQ channel activation (retigabine 2–40 μM) silenced these neurons. Interestingly, we also find that KCNQ and apamin sensitive SK channels act synergistically to regulate firing rate of RTN chemoreceptors; simultaneous blockade of both channels led to a increase in CO2-responsivness. Furthermore, we also show that KCNQ channels but not SK channels are downstream effectors of serotonin modulation of RTN activity in vitro. In contrast, inhibition of KCNQ channel did not prevent modulation of RTN activity by Substance P or TRH; previously identified neuromodulators of RTN chemoreception. Importantly, we also show that KCNQ channels are critical for RTN activity in vivo. Inhibition of KCNQ channels lowered the CO2 threshold for phrenic nerve discharge in anesthetized rats and decreased the ventilatory response to serotonin in awake and anesthetized animals. Given that serotonergic dysfunction may contribute to respiratory failure, our findings suggest KCNQ channels as a new therapeutic avenue for respiratory complications associated with multiple neurological disorders. PMID:23175845

Welding Materials. Pre-Apprenticeship Phase 1 Training.

ERIC Educational Resources Information Center

Lane Community Coll., Eugene, OR.

This student training module on welding materials is one of three modules (see CE 032 889-890) on welding developed for Pre-Apprenticeship Phase 1 Training. (A companion instructor's guide is available separately as CE 032 888.) The modules are designed to introduce trade knowledge and skills to the student. This module contains a cover sheet…

Miniature biotelemeter gives multichannel wideband biomedical data

NASA Technical Reports Server (NTRS)

Carraway, J. B.

1972-01-01

A miniature biotelemeter was developed for sensing and transmitting multiple channels of biomedical data over a radio link. The design of this miniature, 10-channel, wideband (5 kHz/channel), pulse amplitude modulation/ frequency modulation biotelemeter takes advantage of modern device technology (e.g., integrated circuit operational amplifiers, complementary symmetry/metal oxide semiconductor logic, and solid state switches) and hybrid packaging techniques. The telemeter is being used to monitor 10 channels of neuron firings from specific regions of the brain in rats implanted with chronic electrodes. Design, fabrication, and testing of an engineering model biotelemeter are described.

FAST TRACK COMMUNICATION: Stable propagation of a modulated positron beam in a bent crystal channel

NASA Astrophysics Data System (ADS)

Kostyuk, A.; Korol, A. V.; Solov'yov, A. V.; Greiner, W.

2010-08-01

The propagation of a modulated positron beam in a planar crystal channel is investigated. It is demonstrated that the beam preserves its modulation at sufficiently large penetration depths, which opens the prospect of using a crystalline undulator as a coherent source of hard x-rays. This finding is a crucial milestone in developing a new type of laser radiating in the hard x-ray and gamma-ray range.

Connexin channels and phospholipids: association and modulation

PubMed Central

Locke, Darren; Harris, Andrew L

2009-01-01

Background For membrane proteins, lipids provide a structural framework and means to modulate function. Paired connexin hemichannels form the intercellular channels that compose gap junction plaques while unpaired hemichannels have regulated functions in non-junctional plasma membrane. The importance of interactions between connexin channels and phospholipids is poorly understood. Results Endogenous phospholipids most tightly associated with purified connexin26 or connexin32 hemichannels or with junctional plaques in cell membranes, those likely to have structural and/or modulatory effects, were identified by tandem electrospray ionization-mass spectrometry using class-specific interpretative methods. Phospholipids were characterized by headgroup class, charge, glycerol-alkyl chain linkage and by acyl chain length and saturation. The results indicate that specific endogenous phospholipids are uniquely associated with either connexin26 or connexin32 channels, and some phospholipids are associated with both. Functional effects of the major phospholipid classes on connexin channel activity were assessed by molecular permeability of hemichannels reconstituted into liposomes. Changes to phospholipid composition(s) of the liposome membrane altered the activity of connexin channels in a manner reflecting changes to the surface charge/potential of the membrane and, secondarily, to cholesterol content. Together, the data show that connexin26 and connexin32 channels have a preference for tight association with unique anionic phospholipids, and that these, independent of headgroup, have a positive effect on the activity of both connexin26 and connexin32 channels. Additionally, the data suggest that the likely in vivo phospholipid modulators of connexin channel structure-function that are connexin isoform-specific are found in the cytoplasmic leaflet. A modulatory role for phospholipids that promote negative curvature is also inferred. Conclusion This study is the first to identify (endogenous) phospholipids that tightly associate with connexin channels. The finding that specific phospholipids are associated with different connexin isoforms suggests connexin-specific regulatory and/or structural interactions with lipid membranes. The results are interpreted in light of connexin channel function and cell biology, as informed by current knowledge of lipid-protein interactions and membrane biophysics. The intimate involvement of distinct phospholipids with different connexins contributes to channel structure and/or function, as well as plaque integrity, and to modulation of connexin channels by lipophilic agents. PMID:19686581

Hybrid acousto-optic and digital equalization for microwave digital radio channels

NASA Astrophysics Data System (ADS)

Anderson, C. S.; Vanderlugt, A.

1990-11-01

Digital radio transmission systems use complex modulation schemes that require powerful signal-processing techniques to correct channel distortions and to minimize BERs. This paper proposes combining the computation power of acoustooptic processing and the accuracy of digital processing to produce a hybrid channel equalizer that exceeds the performance of digital equalization alone. Analysis shows that a hybrid equalizer for 256-level quadrature amplitude modulation (QAM) performs better than a digital equalizer for 64-level QAM.

Zinc as Allosteric Ion Channel Modulator: Ionotropic Receptors as Metalloproteins.

PubMed

Peralta, Francisco Andrés; Huidobro-Toro, Juan Pablo

2016-07-02

Zinc is an essential metal to life. This transition metal is a structural component of many proteins and is actively involved in the catalytic activity of cell enzymes. In either case, these zinc-containing proteins are metalloproteins. However, the amino acid residues that serve as ligands for metal coordination are not necessarily the same in structural proteins compared to enzymes. While crystals of structural proteins that bind zinc reveal a higher preference for cysteine sulfhydryls rather than histidine imidazole rings, catalytic enzymes reveal the opposite, i.e., a greater preference for the histidines over cysteines for catalysis, plus the influence of carboxylic acids. Based on this paradigm, we reviewed the putative ligands of zinc in ionotropic receptors, where zinc has been described as an allosteric modulator of channel receptors. Although these receptors do not strictly qualify as metalloproteins since they do not normally bind zinc in structural domains, they do transitorily bind zinc at allosteric sites, modifying transiently the receptor channel's ion permeability. The present contribution summarizes current information showing that zinc allosteric modulation of receptor channels occurs by the preferential metal coordination to imidazole rings as well as to the sulfhydryl groups of cysteine in addition to the carboxyl group of acid residues, as with enzymes and catalysis. It is remarkable that most channels, either voltage-sensitive or transmitter-gated receptor channels, are susceptible to zinc modulation either as positive or negative regulators.

A hybrid modulation for the dissemination of weather data to aircraft

NASA Technical Reports Server (NTRS)

Akos, Dennis M.

1991-01-01

Ohio University is continuing to conduct research to improve its system for weather data dissemination to aircraft. The current experimental system transmit compressed weather radar reflectivity patterns from a ground based station to aircraft. Although an effective system, the limited frequency spectrum does not provide a channel for transmission. This introduces the idea of a hybrid modulation. The hybrid technique encodes weather data using phase modulation (PM) onto an existing aeronautical channel which employs amplitude modulation (AM) for voice signal transmission. Ideally, the two modulations are independent of one another. The planned implementation and basis of the system are the reviewed.

Regulation of Transient Receptor Potential channels by the phospholipase C pathway

PubMed Central

Rohacs, Tibor

2013-01-01

Transient Receptor Potential (TRP) channels were discovered while analyzing visual mutants in drosophila. The protein encoded by the transient receptor potential (trp) gene is a Ca2+ permeable cation channel activated downstream of the phospholipase C (PLC) pathway. While searching for homologues in other organisms, a surprisingly large number of mammalian TRP channels were cloned. The regulation of TRP channels is quite diverse, but many of them are either activated downstream of the PLC pathway, or modulated by it. This review will summarize the current knowledge on regulation of TRP channels by the PLC pathway, with special focus on TRPC-s, which can be considered as effectors of the PLC pathway, and the heat and capsaicin sensitive TRPV1, which is modulated by the PLC pathway in a complex manner. PMID:23916247

Voltage-gated K+ channel modulators as neuroprotective agents.

PubMed

Leung, Yuk-Man

2010-05-22

A manifestation in neurodegeneration is apoptosis of neurons. Neurons undergoing apoptosis may lose a substantial amount of cytosolic K+ through a number of pathways including K+ efflux via voltage-gated K+ (Kv) channels. The consequent drop in cytosolic [K+] relieves inhibition of an array of pro-apoptotic enzymes such as caspases and nucleases. Blocking Kv channels has been known to prevent neuronal apoptosis by preventing K+ efflux. Some neural diseases such as epilepsy are caused by neuronal hyperexcitability, which eventually may lead to neuronal apoptosis. Reduction in activities of A-type Kv channels and Kv7 subfamily members is amongst the etiological causes of neuronal hyperexcitation; enhancing the opening of these channels may offer opportunities of remedy. This review discusses the potential uses of Kv channel modulators as neuroprotective drugs.

A 10 Gb/s laser driver in 130 nm CMOS technology for high energy physics applications

DOE PAGES

Zhang, T.; Tavernier, F.; Moreira, P.; ...

2015-02-19

The GigaBit Laser Driver (GBLD) is a key on-detector component of the GigaBit Transceiver (GBT) system at the transmitter side. We have developed a 10 Gb/s GBLD (GBLD10) in a 130 nm CMOS technology, as part of the design efforts towards the upgrade of the electrical components of the LHC experiments. The GBLD10 is based on the distributed-amplifier (DA) architecture and achieves data rates up to 10 Gb/s. It is capable of driving VCSELs with modulation currents up to 12 mA. Furthermore, a pre-emphasis function has been included in the proposed laser driver in order to compensate for the capacitivemore » load and channel losses.« less

Clofilium inhibits Slick and Slack potassium channels.

PubMed

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.

Genetic alteration of the metal/redox modulation of Cav3.2 T-type calcium channel reveals its role in neuronal excitability.

PubMed

Voisin, Tiphaine; Bourinet, Emmanuel; Lory, Philippe

2016-07-01

In this study, we describe a new knock-in (KI) mouse model that allows the study of the H191-dependent regulation of T-type Cav3.2 channels. Sensitivity to zinc, nickel and ascorbate of native Cav3.2 channels is significantly impeded in the dorsal root ganglion (DRG) neurons of this KI mouse. Importantly, we describe that this H191-dependent regulation has discrete but significant effects on the excitability properties of D-hair (down-hair) cells, a sub-population of DRG neurons in which Cav3.2 currents prominently regulate excitability. Overall, this study reveals that the native H191-dependent regulation of Cav3.2 channels plays a role in the excitability of Cav3.2-expressing neurons. This animal model will be valuable in addressing the potential in vivo roles of the trace metal and redox modulation of Cav3.2 T-type channels in a wide range of physiological and pathological conditions. Cav3.2 channels are T-type voltage-gated calcium channels that play important roles in controlling neuronal excitability, particularly in dorsal root ganglion (DRG) neurons where they are involved in touch and pain signalling. Cav3.2 channels are modulated by low concentrations of metal ions (nickel, zinc) and redox agents, which involves the histidine 191 (H191) in the channel's extracellular IS3-IS4 loop. It is hypothesized that this metal/redox modulation would contribute to the tuning of the excitability properties of DRG neurons. However, the precise role of this H191-dependent modulation of Cav3.2 channel remains unresolved. Towards this goal, we have generated a knock-in (KI) mouse carrying the mutation H191Q in the Cav3.2 protein. Electrophysiological studies were performed on a subpopulation of DRG neurons, the D-hair cells, which express large Cav3.2 currents. We describe an impaired sensitivity to zinc, nickel and ascorbate of the T-type current in D-hair neurons from KI mice. Analysis of the action potential and low-threshold calcium spike (LTCS) properties revealed that, contrary to that observed in WT D-hair neurons, a low concentration of zinc and nickel is unable to modulate (1) the rheobase threshold current, (2) the afterdepolarization amplitude, (3) the threshold potential necessary to trigger an LTCS or (4) the LTCS amplitude in D-hair neurons from KI mice. Together, our data demonstrate that this H191-dependent metal/redox regulation of Cav3.2 channels can tune neuronal excitability. This study validates the use of this Cav3.2-H191Q mouse model for further investigations of the physiological roles thought to rely on this Cav3.2 modulation. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

CTF Preprocessor User's Manual

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

Avramova, Maria; Salko, Robert K.

2016-05-26

This document describes how a user should go about using the CTF pre- processor tool to create an input deck for modeling rod-bundle geometry in CTF. The tool was designed to generate input decks in a quick and less error-prone manner for CTF. The pre-processor is a completely independent utility, written in Fortran, that takes a reduced amount of input from the user. The information that the user must supply is basic information on bundle geometry, such as rod pitch, clad thickness, and axial location of spacer grids--the pre-processor takes this basic information and determines channel placement and connection informationmore » to be written to the input deck, which is the most time-consuming and error-prone segment of creating a deck. Creation of the model is also more intuitive, as the user can specify assembly and water-tube placement using visual maps instead of having to place them by determining channel/channel and rod/channel connections. As an example of the benefit of the pre-processor, a quarter-core model that contains 500,000 scalar-mesh cells was read into CTF from an input deck containing 200,000 lines of data. This 200,000 line input deck was produced automatically from a set of pre-processor decks that contained only 300 lines of data.« less

76 FR 33656 - Television Broadcasting Services; Nashville, TN

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-09

.... SUMMARY: The Commission grants a petition for rulemaking filed by NewsChannel 5 Network, LLC (``News... Nashville. According to NewsChannel 5, after WTVF(TV) transitioned from its pre-transition digital channel...

Two-channel recording of auditory-evoked potentials to detect age-related deficits in temporal processing.

PubMed

Parthasarathy, Aravindakshan; Bartlett, Edward

2012-07-01

Auditory brainstem responses (ABRs), and envelope and frequency following responses (EFRs and FFRs) are widely used to study aberrant auditory processing in conditions such as aging. We have previously reported age-related deficits in auditory processing for rapid amplitude modulation (AM) frequencies using EFRs recorded from a single channel. However, sensitive testing of EFRs along a wide range of modulation frequencies is required to gain a more complete understanding of the auditory processing deficits. In this study, ABRs and EFRs were recorded simultaneously from two electrode configurations in young and old Fischer-344 rats, a common auditory aging model. Analysis shows that the two channels respond most sensitively to complementary AM frequencies. Channel 1, recorded from Fz to mastoid, responds better to faster AM frequencies in the 100-700 Hz range of frequencies, while Channel 2, recorded from the inter-aural line to the mastoid, responds better to slower AM frequencies in the 16-100 Hz range. Simultaneous recording of Channels 1 and 2 using AM stimuli with varying sound levels and modulation depths show that age-related deficits in temporal processing are not present at slower AM frequencies but only at more rapid ones, which would not have been apparent recording from either channel alone. Comparison of EFRs between un-anesthetized and isoflurane-anesthetized recordings in young animals, as well as comparison with previously published ABR waveforms, suggests that the generators of Channel 1 may emphasize more caudal brainstem structures while those of Channel 2 may emphasize more rostral auditory nuclei including the inferior colliculus and the forebrain, with the boundary of separation potentially along the cochlear nucleus/superior olivary complex. Simultaneous two-channel recording of EFRs help to give a more complete understanding of the properties of auditory temporal processing over a wide range of modulation frequencies which is useful in understanding neural representations of sound stimuli in normal, developmental or pathological conditions. Copyright © 2012 Elsevier B.V. All rights reserved.

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

PubMed

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

2006-12-01

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

A 1.3-μm four-channel directly modulated laser array fabricated by SAG-Upper-SCH technology

NASA Astrophysics Data System (ADS)

Guo, Fei; Lu, Dan; Zhang, Ruikang; Liu, Songtao; Sun, Mengdie; Kan, Qiang; Ji, Chen

2017-01-01

A monolithically integrated four-channel directly modulated laser (DML) array working at the 1.3-μm band is demonstrated. The laser was manufactured by using the techniques of selective area growth (SAG) of the upper separate confinement heterostructure (Upper-SCH) and modified butt-joint method. The fabricated device showed stable single mode operation with the side mode suppression ratio (SMSR) >35 dB, and high wavelength accuracy with the deviations from the linear fitted values <±0.03 nm for all channels. Furthermore, small signal modulation bandwidth >7 GHz was obtained, which may be suitable for 40 GbE applications in the 1.3-μm band.

Cooling techniques for turbojet pre-heater channels

NASA Astrophysics Data System (ADS)

Desaulty, M.; Troullot, P.; Coutor, S.

1985-09-01

Increases in the performance of turbojets with pre-heating are dependent upon technological research in the area of protection of the wall in pre-heater channels. The procedures used to cool the thermal protection jackets have undergone important improvements which have optimized performance, reduced weight and improved cooling efficiency. This report presents a comparison of the thermal protection jackets for several SNECMA engines, as well as the principal stages of development for the jacket from the design stages through static engines tests.

Retinovascular physiology and pathophysiology: new experimental approach/new insights

PubMed Central

Puro, Donald G.

2012-01-01

An important challenge in visual neuroscience is understand the physiology and pathophysiology of the intra-retinal vasculature, whose function is required for ophthalmoception by humans and most other mammals. In the quest to learn more about this highly specialized portion of the circulatory system, a newly developed method for isolating vast microvascular complexes from the rodent retina has opened the way for using techniques such as patch-clamping, fluorescence imaging and time-lapse photography to elucidate the functional organization of a capillary network and its pre-capillary arteriole. For example, the ability to obtain dual perforated-patch recordings from well-defined sites within an isolated microvascular complex permitted the first characterization of the electrotonic architecture of a capillary/arteriole unit. This analysis revealed that this operational unit is not simply a homogenous synctium, but has a complex functional organization that is dynamically modulated by extracellular signals such as angiotensin II. Another recent discovery is that a capillary and its pre-capillary arteriole have distinct physiological differences; capillaries have an abundance of ATP-sensitive potassium (KATP) channels and a dearth of voltage-dependent calcium channels (VDCCs) while the converse is true for arterioles. In addition, voltage transmission between abluminal cells and the endothelium is more efficient in the capillaries. Thus, the capillary network is well-equipped to generate and transmit voltages, and the pre-capillary arteriole is well-adapted to transduce a capillary-generated voltage into a change in abluminal cell calcium and thereby, a vasomotor response. Use of microvessels isolated from the diabetic retina has led to new insights concerning retinal vascular pathophysiology. For example, soon after the onset of diabetes, the efficacy of voltage transmission through the endothelium is diminished; arteriolar VDCCs is inhibited, and there is increased vulnerability to purinergic vasotoxicity, which is a newly identified pathobiological mechanism. Other recent studies reveal that KATP channels not only have an essential physiological role in generating vasomotor responses, but their activation substantially boosts the lethality of hypoxia. Thus, the pathophysiology of the retinal microvasculature is closely linked with its physiology. PMID:22333041

Substitutions in the domain III voltage-sensing module enhance the sensitivity of an insect sodium channel to a scorpion beta-toxin.

PubMed

Song, Weizhong; Du, Yuzhe; Liu, Zhiqi; Luo, Ningguang; Turkov, Michael; Gordon, Dalia; Gurevitz, Michael; Goldin, Alan L; Dong, Ke

2011-05-06

Scorpion β-toxins bind to the extracellular regions of the voltage-sensing module of domain II and to the pore module of domain III in voltage-gated sodium channels and enhance channel activation by trapping and stabilizing the voltage sensor of domain II in its activated state. We investigated the interaction of a highly potent insect-selective scorpion depressant β-toxin, Lqh-dprIT(3), from Leiurus quinquestriatus hebraeus with insect sodium channels from Blattella germanica (BgNa(v)). Like other scorpion β-toxins, Lqh-dprIT(3) shifts the voltage dependence of activation of BgNa(v) channels expressed in Xenopus oocytes to more negative membrane potentials but only after strong depolarizing prepulses. Notably, among 10 BgNa(v) splice variants tested for their sensitivity to the toxin, only BgNa(v)1-1 was hypersensitive due to an L1285P substitution in IIIS1 resulting from a U-to-C RNA-editing event. Furthermore, charge reversal of a negatively charged residue (E1290K) at the extracellular end of IIIS1 and the two innermost positively charged residues (R4E and R5E) in IIIS4 also increased the channel sensitivity to Lqh-dprIT(3). Besides enhancement of toxin sensitivity, the R4E substitution caused an additional 20-mV negative shift in the voltage dependence of activation of toxin-modified channels, inducing a unique toxin-modified state. Our findings provide the first direct evidence for the involvement of the domain III voltage-sensing module in the action of scorpion β-toxins. This hypersensitivity most likely reflects an increase in IIS4 trapping via allosteric mechanisms, suggesting coupling between the voltage sensors in neighboring domains during channel activation.

Welding Tools. Pre-Apprenticeship Phase 1 Training.

ERIC Educational Resources Information Center

Lane Community Coll., Eugene, OR.

This student training module on welding tools is one of three modules (see CE 032 889-891) on welding developed for Pre-Apprenticeship Phase 1 Training. (A companion instructor's guide is available separately as CE 032 888.) The modules are designed to introduce trade knowledge and skills to the student. This module contains a cover sheet listing…

Occupational Safety. Hand Tools. Pre-Apprenticeship Phase 1 Training.

ERIC Educational Resources Information Center

Lane Community Coll., Eugene, OR.

This self-paced student training module on safety when using hand tools is one of a number of modules developed for Pre-apprenticeship Phase 1 Training. Purpose of the module is to teach students the correct safety techniques for operating common hand- and arm-powered tools, including selection, maintenance, technique, and uses. The module may…

Neuroprotective role of ATP-sensitive potassium channels in cerebral ischemia

PubMed Central

Sun, Hong-shuo; Feng, Zhong-ping

2013-01-01

ATP-sensitive potassium (KATP) channels are weak, inward rectifiers that couple metabolic status to cell membrane electrical activity, thus modulating many cellular functions. An increase in the ADP/ATP ratio opens KATP channels, leading to membrane hyperpolarization. KATP channels are ubiquitously expressed in neurons located in different regions of the brain, including the hippocampus and cortex. Brief hypoxia triggers membrane hyperpolarization in these central neurons. In vivo animal studies confirmed that knocking out the Kir6.2 subunit of the KATP channels increases ischemic infarction, and overexpression of the Kir6.2 subunit reduces neuronal injury from ischemic insults. These findings provide the basis for a practical strategy whereby activation of endogenous KATP channels reduces cellular damage resulting from cerebral ischemic stroke. KATP channel modulators may prove to be clinically useful as part of a combination therapy for stroke management in the future. PMID:23123646

Modulation of Kv7 channels and excitability in the brain.

PubMed

Greene, Derek L; Hoshi, Naoto

2017-02-01

Neuronal Kv7 channels underlie a voltage-gated non-inactivating potassium current known as the M-current. Due to its particular characteristics, Kv7 channels show pronounced control over the excitability of neurons. We will discuss various factors that have been shown to drastically alter the activity of this channel such as protein and phospholipid interactions, phosphorylation, calcium, and numerous neurotransmitters. Kv7 channels locate to key areas for the control of action potential initiation and propagation. Moreover, we will explore the dynamic surface expression of the channel modulated by neurotransmitters and neural activity. We will also focus on known principle functions of neural Kv7 channels: control of resting membrane potential and spiking threshold, setting the firing frequency, afterhyperpolarization after burst firing, theta resonance, and transient hyperexcitability from neurotransmitter-induced suppression of the M-current. Finally, we will discuss the contribution of altered Kv7 activity to pathologies such as epilepsy and cognitive deficits.

Modulation of Kv7 channels and excitability in the brain

PubMed Central

Greene, Derek L; Hoshi, Naoto

2016-01-01

Neuronal Kv7 channels underlie a voltage-gated non-inactivating potassium current known as the M-current. Due to its particular characteristics, Kv7 channels show pronounced control over the excitability of neurons. We will discuss various factors that have been shown to drastically alter the activity of this channel such as protein and phospholipid interactions, phosphorylation, calcium, and numerous neurotransmitters. Kv7 channels locate to key areas for the control of action potential initiation and propagation. Moreover, we will explore the dynamic surface expression of the channel modulated by neurotransmitters and neural activity. We will also focus on known principle functions of neural Kv7 channels: control of resting membrane potential and spiking threshold, setting the firing frequency, afterhyperpolarization after burst firing, theta resonance, and transient hyperexcitability from neurotransmitter-induced suppression of the M-current. Finally, we will discuss the contribution of altered Kv7 activity to pathologies such as epilepsy and cognitive deficits. PMID:27645822

Molecular physiology and modulation of somatodendritic A-type potassium channels.

PubMed

Jerng, Henry H; Pfaffinger, Paul J; Covarrubias, Manuel

2004-12-01

The somatodendritic subthreshold A-type K+ current (ISA) in nerve cells is a critical component of the ensemble of voltage-gated ionic currents that determine somatodendritic signal integration. The underlying K+ channel belongs to the Shal subfamily of voltage-gated K+ channels. Most Shal channels across the animal kingdom share a high degree of structural conservation, operate in the subthreshold range of membrane potentials, and exhibit relatively fast inactivation and recovery from inactivation. Mammalian Shal K+ channels (Kv4) undergo preferential closed-state inactivation with features that are generally inconsistent with the classical mechanisms of inactivation typical of Shaker K+ channels. Here, we review (1) the physiological and genetic properties of ISA, 2 the molecular mechanisms of Kv4 inactivation and its remodeling by a family of soluble calcium-binding proteins (KChIPs) and a membrane-bound dipeptidase-like protein (DPPX), and (3) the modulation of Kv4 channels by protein phosphorylation.

Fluid front morphologies in gap-modulated Hele-Shaw cells

NASA Astrophysics Data System (ADS)

Díaz-Piola, Lautaro; Planet, Ramon; Campàs, Otger; Casademunt, Jaume; Ortín, Jordi

2017-09-01

We consider the displacement of an inviscid fluid (air) by a viscous fluid (oil) in a narrow channel with gap-thickness modulations. The interfacial dynamics of this problem is strongly nonlocal and exhibits competing effects from capillarity and permeability. We derive analytical predictions of steady-state front morphologies, which are exact at linear level in the case of a persistent modulation in the direction of front advancement. The theoretical predictions are in good agreement with experimental measurements of steady-state front morphologies obtained in a Hele-Shaw cell with modulations of the channel depth, consisting on three parallel tracks of reduced depth, for small gap modulations. The relative average distance between theoretical and experimental fronts in the region around the central track is smaller than about 4 % , provided that the height of the tracks is less than 13 % of the total channel depth and the local distortion of the front height h is small enough (|∇ h |<0.8 ) for the linear approximation to hold.

Capacity of the Generalized Pulse-Position Modulation Channel

NASA Technical Reports Server (NTRS)

Hamkins, J.; Klimesh, M.; McElience, R.; Moision, B.

2005-01-01

We show the capacity of a generalized pulse-position modulation (PPM) channel, where the input vectors may be any set that allows a transitive group of coordinate permutations, is achieved by a uniform input distribution. We derive a simple expression in terms of the Kullback Leibler distance for the binary case, and the asymptote in the PPM order. We prove a sub-additivity result for the PPM channel and use it to show PPM capacity is monotonic in the order.

Phasing of two amplifier channels for the coherent combining of laser beams with a total power of 60 W

NASA Astrophysics Data System (ADS)

Trikshev, A. I.; Pyrkov, Yu. N.; Tsvetkov, V. B.

2017-12-01

We have demonstrated stable operation of a system for maintaining a constant phase difference between two laser channels with a total output power of 60 W. The system is based on a two-channel fibre amplifier with phase modulators based on piezoceramic spools. At a main piezo element modulation frequency of 11 kHz, the phasing time after thermal and mechanical influences on the active medium is 100 ms.

High-quality recording of bioelectric events. Part 2. Low-noise, low-power multichannel amplifier design.

PubMed

Metting van Rijn, A C; Peper, A; Grimbergen, C A

1991-07-01

A multichannel instrumentation amplifier, developed to be used in a miniature universal eight-channel amplifier module, is described. After discussing the specific properties of a bioelectric recording, the difficulties of meeting the demanded specifications with a design based on operational amplifiers are reviewed. Because it proved impossible to achieve the demanded combination of low noise and low power consumption using commercially available operational amplifiers, an amplifier equipped with an input stage with discrete transistors was developed. A new design concept was used to expand the design to a multichannel version with an equivalent input noise voltage of 0.35 microV RMS in a bandwidth of 0.1-100 Hz and a power consumption of 0.6 mW per channel. The results of this study are applied to miniature, universal, eight-channel amplifier modules, manufactured with thick-film production techniques. The modules can be coupled to satisfy the demand for a multiple of eight channels. The low power consumption enables the modules to be used in all kinds of portable and telemetry measurement systems and simplifies the power supply in stationary measurement systems.

Turbo Trellis Coded Modulation With Iterative Decoding for Mobile Satellite Communications

NASA Technical Reports Server (NTRS)

Divsalar, D.; Pollara, F.

1997-01-01

In this paper, analytical bounds on the performance of parallel concatenation of two codes, known as turbo codes, and serial concatenation of two codes over fading channels are obtained. Based on this analysis, design criteria for the selection of component trellis codes for MPSK modulation, and a suitable bit-by-bit iterative decoding structure are proposed. Examples are given for throughput of 2 bits/sec/Hz with 8PSK modulation. The parallel concatenation example uses two rate 4/5 8-state convolutional codes with two interleavers. The convolutional codes' outputs are then mapped to two 8PSK modulations. The serial concatenated code example uses an 8-state outer code with rate 4/5 and a 4-state inner trellis code with 5 inputs and 2 x 8PSK outputs per trellis branch. Based on the above mentioned design criteria for fading channels, a method to obtain he structure of the trellis code with maximum diversity is proposed. Simulation results are given for AWGN and an independent Rayleigh fading channel with perfect Channel State Information (CSI).

Yield enhancement of 3D flash devices through broadband brightfield inspection of the channel hole process module

NASA Astrophysics Data System (ADS)

Lee, Jung-Youl; Seo, Il-Seok; Ma, Seong-Min; Kim, Hyeon-Soo; Kim, Jin-Woong; Kim, DoOh; Cross, Andrew

2013-03-01

The migration to a 3D implementation for NAND flash devices is seen as the leading contender to replace traditional planar NAND architectures. However the strategy of replacing shrinking design rules with greater aspect ratios is not without its own set of challenges. The yield-limiting defect challenges for the planar NAND front end were primarily bridges, protrusions and residues at the bottom of the gates, while the primary challenges for front end 3D NAND is buried particles, voids and bridges in the top, middle and bottom of high aspect ratio structures. Of particular interest are the yield challenges in the channel hole process module and developing an understanding of the contribution of litho and etch defectivity for this challenging new integration scheme. The key defectivity and process challenges in this module are missing, misshapen channel holes or under-etched channel holes as well as reducing noise sources related to other none yield limiting defect types and noise related to the process integration scheme. These challenges are expected to amplify as the memory density increases. In this study we show that a broadband brightfield approach to defect monitoring can be uniquely effective for the channel hole module. This approach is correlated to end-of-line (EOL) Wafer Bin Map for verification of capability.

Mechanisms of CO2/H+ chemoreception by respiratory rhythm generator neurons in the medulla from newborn rats in vitro.

PubMed

Kawai, Akira; Onimaru, Hiroshi; Homma, Ikuo

2006-04-15

We investigated mechanisms of CO(2)/H(+) chemoreception in the respiratory centre of the medulla by measuring membrane potentials of pre-inspiratory neurons, which are putative respiratory rhythm generators, in the brainstem-spinal cord preparation of the neonatal rat. Neuronal response was tested by changing superfusate CO(2) concentration from 2% to 8% at constant HCO(3)(-) concentration (26 mm) or by changing pH from 7.8 to 7.2 by reducing HCO(3)(-) concentration at constant CO(2) (5%). Both respiratory and metabolic acidosis lead to depolarization of neurons with increased excitatory synaptic input and increased burst rate. Respiratory acidosis potentiated the amplitude of the neuronal drive potential. In the presence of tetrodotoxin (TTX), membrane depolarization persisted during respiratory and metabolic acidosis. However, the depolarization was smaller than that before application of TTX, which suggests that some neurons are intrinsically, and others synaptically, chemosensitive to CO(2)/H(+). Application of Ba(2+) blocked membrane depolarization by respiratory acidosis, whereas significant depolarization in response to metabolic acidosis still remained after application of Cd(2+) and Ba(2+). We concluded that the intrinsic responses to CO(2)/H(+)changes were mediated by potassium channels during respiratory acidosis, and that some other mechanisms operate during metabolic acidosis. In low-Ca(2+), high-Mg(2+) solution, an increased CO(2) concentration induced a membrane depolarization with a simultaneous increase of the burst rate. Pre-inspiratory neurons could adapt their baseline membrane potential to external CO(2)/H(+) changes by integration of these mechanisms to modulate their burst rates. Thus, pre-inspiratory neurons might play an important role in modulation of respiratory rhythm by central chemoreception in the brainstem-spinal cord preparation.

Mechanisms of CO2/H+ chemoreception by respiratory rhythm generator neurons in the medulla from newborn rats in vitro

PubMed Central

Kawai, Akira; Onimaru, Hiroshi; Homma, Ikuo

2006-01-01

We investigated mechanisms of CO2/H+ chemoreception in the respiratory centre of the medulla by measuring membrane potentials of pre-inspiratory neurons, which are putative respiratory rhythm generators, in the brainstem–spinal cord preparation of the neonatal rat. Neuronal response was tested by changing superfusate CO2 concentration from 2% to 8% at constant HCO3− concentration (26 mm) or by changing pH from 7.8 to 7.2 by reducing HCO3− concentration at constant CO2 (5%). Both respiratory and metabolic acidosis lead to depolarization of neurons with increased excitatory synaptic input and increased burst rate. Respiratory acidosis potentiated the amplitude of the neuronal drive potential. In the presence of tetrodotoxin (TTX), membrane depolarization persisted during respiratory and metabolic acidosis. However, the depolarization was smaller than that before application of TTX, which suggests that some neurons are intrinsically, and others synaptically, chemosensitive to CO2/H+. Application of Ba2+ blocked membrane depolarization by respiratory acidosis, whereas significant depolarization in response to metabolic acidosis still remained after application of Cd2+ and Ba2+. We concluded that the intrinsic responses to CO2/H+changes were mediated by potassium channels during respiratory acidosis, and that some other mechanisms operate during metabolic acidosis. In low-Ca2+, high-Mg2+ solution, an increased CO2 concentration induced a membrane depolarization with a simultaneous increase of the burst rate. Pre-inspiratory neurons could adapt their baseline membrane potential to external CO2/H+ changes by integration of these mechanisms to modulate their burst rates. Thus, pre-inspiratory neurons might play an important role in modulation of respiratory rhythm by central chemoreception in the brainstem–spinal cord preparation. PMID:16469786

Validating Laser-Induced Birefringence Theory with Plasma Interferometry

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

Chen, Cecilia; Cornell Univ., Ithaca, NY

2015-09-02

Intense laser beams crossing paths in plasma is theorized to induce birefringence in the medium, resulting from density and refractive index modulations that affect the polarization of incoming light. The goal of the associated experiment, conducted on Janus at Lawrence Livermore’s Jupiter Laser Facility, was to create a tunable laser-plasma waveplate to verify the relationship between dephasing angle and beam intensity, plasma density, plasma temperature, and interaction length. Interferometry analysis of the plasma channel was performed to obtain a density map and to constrain temperature measured from Thomson scattering. Various analysis techniques, including Fast Fourier transform (FFT) and two variationsmore » of fringe-counting, were tried because interferograms captured in this experiment contained unusual features such as fringe discontinuity at channel edges, saddle points, and islands. The chosen method is flexible, semi-automated, and uses a fringe tracking algorithm on a reduced image of pre-traced synthetic fringes. Ultimately, a maximum dephasing angle of 49.6° was achieved using a 1200 μm interaction length, and the experimental results appear to agree with predictions.« less

Nonreciprocal mechanisms in up- and downregulation of spinal motoneuron excitability by modulators of KCNQ/Kv7 channels.

PubMed

Lombardo, Joseph; Harrington, Melissa A

2016-11-01

KCNQ/K v 7 channels form a slow noninactivating K + current, also known as the M current. They activate in the subthreshold range of membrane potentials and regulate different aspects of excitability in neurons of the central nervous system. In spinal motoneurons (MNs), KCNQ/K v 7 channels have been identified in the somata, axonal initial segment, and nodes of Ranvier, where they generate a slow, noninactivating, K + current sensitive to both muscarinic receptor-mediated inhibition and KCNQ/K v 7 channel blockers. In this study, we thoroughly reevaluated the function of up- and downregulation of KCNQ/K v 7 channels in mouse immature spinal MNs. Using electrophysiological techniques together with specific pharmacological modulators of the activity of KCNQ/K v 7 channels, we show that enhancement of the activity of these channels decreases the excitability of spinal MNs in mouse neonates. This action on MNs results from a combination of hyperpolarization of the resting membrane potential, a decrease in the input resistance, and depolarization of the voltage threshold. On the other hand, the effect of inhibition of KCNQ/K v 7 channels suggested that these channels play a limited role in regulating basal excitability. Computer simulations confirmed that pharmacological enhancement of KCNQ/K v 7 channel activity decreases excitability and also suggested that the effects of inhibition of KCNQ/K v 7 channels on the excitability of spinal MNs do not depend on a direct effect in these neurons but likely on spinal cord synaptic partners. These results indicate that KCNQ/K v 7 channels have a fundamental role in the modulation of the excitability of spinal MNs acting both in these neurons and in their local presynaptic partners. Copyright © 2016 the American Physiological Society.

Nonreciprocal mechanisms in up- and downregulation of spinal motoneuron excitability by modulators of KCNQ/Kv7 channels

PubMed Central

Lombardo, Joseph

2016-01-01

KCNQ/Kv7 channels form a slow noninactivating K+ current, also known as the M current. They activate in the subthreshold range of membrane potentials and regulate different aspects of excitability in neurons of the central nervous system. In spinal motoneurons (MNs), KCNQ/Kv7 channels have been identified in the somata, axonal initial segment, and nodes of Ranvier, where they generate a slow, noninactivating, K+ current sensitive to both muscarinic receptor-mediated inhibition and KCNQ/Kv7 channel blockers. In this study, we thoroughly reevaluated the function of up- and downregulation of KCNQ/Kv7 channels in mouse immature spinal MNs. Using electrophysiological techniques together with specific pharmacological modulators of the activity of KCNQ/Kv7 channels, we show that enhancement of the activity of these channels decreases the excitability of spinal MNs in mouse neonates. This action on MNs results from a combination of hyperpolarization of the resting membrane potential, a decrease in the input resistance, and depolarization of the voltage threshold. On the other hand, the effect of inhibition of KCNQ/Kv7 channels suggested that these channels play a limited role in regulating basal excitability. Computer simulations confirmed that pharmacological enhancement of KCNQ/Kv7 channel activity decreases excitability and also suggested that the effects of inhibition of KCNQ/Kv7 channels on the excitability of spinal MNs do not depend on a direct effect in these neurons but likely on spinal cord synaptic partners. These results indicate that KCNQ/Kv7 channels have a fundamental role in the modulation of the excitability of spinal MNs acting both in these neurons and in their local presynaptic partners. PMID:27512022

Deoxycholic acid inhibits smooth muscle contraction via protein kinase C-dependent modulation of L-type Ca2+ channels in rat proximal colon.

PubMed

Hu, Liu-Dan; Yu, Bao-Ping; Yang, Bin

2012-10-01

The aim of this study was to investigate the effects of deoxycholic acid (DCA) on the contractions of rat proximal colonic smooth muscle (PCSM) in vitro. The contractile response of rat PCSM strips was tested using a polyphysio-graph. The whole cell patch-clamp technique was also used in rat colonic smooth muscle cells (SMCs) isolated by an enzymatic procedure to record the L-type calcium current (I(Ca-L)) prior to and following the application of various concentrations of DCA. The application of DCA (10(-6)-10(-4) M) decreased the amplitude of spontaneous contractions of the PCSM strips in a dose-dependent manner. The administration of DCA (10(-5) M) caused the relaxation of isolated smooth muscle strips pre-contracted by acetylcholine (Ach) or KCl (by 12.2±1.5 and 16.3±6.9%, respectively). The concentration-response curve of CaCl2 was shifted to the right. Pre-treatment of the strips with the protein kinase C (PKC) inhibitor chelerythrine (1 µM) significantly attenuated the effects of DCA on the strips pre-contracted by Ach. DCA reduced the peak I(Ca-L) by 6.02±0.87% at 10(-6) M, 15.02±1.73% at 10(-5) M and 47.14±3.79% at 10(-4) M. DCA shifted the current-voltage (I-V) curve of ICa-L upward, but the contour of the I-V curve was unchanged, and the peak current-induced voltage remained at 0 mV. Pre-treatment with chelerythrine (1 µM) blocked the actions of DCA on the I(Ca-L). Taken together, the actions of DCA on I(Ca-L) in rat colonic SMCs contributed to a negative inotropic effect. These actions appear to be mediated through protein kinase C. Furthermore, this study suggests another possible mechanism for the DCA-related modulation of gastrointestinal motility.

Readout electronics for CBM-TOF super module quality evaluation based on 10 Gbps ethernet

NASA Astrophysics Data System (ADS)

Jiang, D.; Cao, P.; Huang, X.; Zheng, J.; Wang, Q.; Li, B.; Li, J.; Liu, S.; An, Q.

2017-07-01

The Compressed Baryonic Matter-Time of Flight (CBM-TOF) wall uses high performance of Multi-gap Resistive Plate Chambers (MRPC) assembled in super modules to identify charged particles with high channel density and high measurement precision at high event rate. Electronics meet the challenge for reading data out from a super module at high speed of about 6 Gbps in real time. In this paper, the readout electronics for CBM-TOF super module quality evaluation is proposed based on 10 Gigabit Ethernet. The digitized TOF data from one super module will be concentrated at the front-end electronics residing on the side of the super module and transmitted to an extreme speed readout module (XSRM) housed in the backend crate through the PCI Express (PCIe) protocol via optic channels. Eventually, the XSRM transmits data to the data acquisition (DAQ) system through four 10 Gbps Ethernet ports in real time. This readout structure has advantages of high performance and expansibility. Furthermore, it is easy to operate. Test results on the prototype show that the overall data readout performance for each XSRM can reach up to 28.8 Gbps, which means XSRM can meet the requirement of reading data out from 4 super modules with 1280 channels in real time.

Frequency bandwidth limitation of external pulse electric fields in cylindrical micro-channel electrophoresis with analyte velocity modulation.

PubMed

Wang, Shau-Chun; Chen, Hsiao-Ping; Lee, Chia-Yu; Yeo, Leslie Y

2005-04-15

In capillary electrophoresis, effective optical signal quality improvement is obtained when high frequency (>100 Hz) external pulse fields modulate analyte velocities with synchronous lock-in detection. However, the pulse frequency is constrained under a critical value corresponding to the time required for the bulk viscous flow, which arises due to viscous momentum diffusion from the electro-osmotic slip in the Debye layer, to reach steady-state. By solving the momentum diffusion equation for transient bulk flow in the micro-channel, we show that this set-in time to steady-state and hence, the upper limit for the pulse frequency is dependent on the characteristic diffusion length scale and therefore the channel geometry; for cylindrical capillaries, the set-in time is approximately one half of that for rectangular slot channels. From our estimation of the set-in time and hence the upper frequency modulation limit, we propose that the half width of planar channels does not exceed 100 microm and that the radii of cylindrical channels be limited to 140 microm such that there is a finite working bandwidth range above 100 Hz and below the upper limit in order for flicker noise to be effectively suppressed.

PIP₂ modulation of Slick and Slack K⁺ channels.

PubMed

de los Angeles Tejada, Maria; Jensen, Lars Jørn; Klaerke, Dan A

2012-07-27

Slick and Slack are members of the Slo family of high-conductance potassium channels. These channels are activated by Na(+) and Cl(-) and are highly expressed in the CNS, where they are believed to contribute to the resting membrane potential of neurons and the control of excitability. Herein, we provide evidence that Slick and Slack channels are regulated by the phosphoinositide PIP(2). Two stereoisomers of PIP(2) were able to exogenously activate Slick and Slack channels expressed in Xenopus oocytes, and in addition, it is shown that Slick and Slack channels are modulated by endogenous PIP(2). The activating effect of PIP(2) appears to occur by direct interaction with lysine 306 in Slick and lysine 339 in Slack, located at the proximal C-termini of both channels. Overall, our data suggest that PIP(2) is an important regulator of Slick and Slack channels, yet it is not involved in the recently described cell volume sensitivity of Slick channels, since mutated PIP(2)-insensitive Slick channels retained their sensitivity to cell volume. Copyright © 2012 Elsevier Inc. All rights reserved.

Defining regions of interest using cross-frequency coupling in extratemporal lobe epilepsy patients

NASA Astrophysics Data System (ADS)

Guirgis, Mirna; Chinvarun, Yotin; del Campo, Martin; Carlen, Peter L.; Bardakjian, Berj L.

2015-04-01

Objective. Clinicians identify seizure onset zones (SOZs) for resection in an attempt to localize the epileptogenic zone (EZ), which is the cortical tissue that is indispensible for seizure generation. An automated system is proposed to objectively localize this EZ by identifying regions of interest (ROIs). Methods. Intracranial electroencephalogram recordings were obtained from seven patients presenting with extratemporal lobe epilepsy and the interaction between neuronal rhythms in the form of phase-amplitude coupling was investigated. Modulation of the amplitude of high frequency oscillations (HFOs) by the phase of low frequency oscillations was measured by computing the modulation index (MI). Delta- (0.5-4 Hz) and theta- (4-8 Hz) modulation of HFOs (30-450 Hz) were examined across the channels of a 64-electrode subdural grid. Surrogate analysis was performed and false discovery rates were computed to determine the significance of the modulation observed. Mean MI values were subjected to eigenvalue decomposition (EVD) and channels defining the ROIs were selected based on the components of the eigenvector corresponding to the largest eigenvalue. ROIs were compared to the SOZs identified by two independent neurologists. Global coherence values were also computed. Main results. MI was found to capture the seizure in time for six of seven patients and identified ROIs in all seven. Patients were found to have a poorer post-surgical outcome when the number of EVD-selected channels that were not resected increased. Moreover, in patients who experienced a seizure-free outcome (i.e., Engel Class I) all EVD-selected channels were found to be within the resected tissue or immediately adjacent to it. In these Engel Class I patients, delta-modulated HFOs were found to identify more of the channels in the resected tissue compared to theta-modulated HFOs. However, for the Engel Class IV patient, the delta-modulated HFOs did not identify any of the channels in the resected tissue suggesting that the resected tissue was not appropriate, which was also suggested by the Engel Class IV outcome. A sensitivity of 75.4% and a false positive rate of 15.6% were achieved using delta-modulated HFOs in an Engel Class I patient. Significance. LFO-modulated HFOs can be used to identify ROIs in extratemporal lobe patients. Moreover, delta-modulated HFOs may provide more accurate localization of the EZ. These ROIs may result in better surgical outcomes when used to compliment the SOZs identified by clinicians for resection.

Modulation of Potassium Channels Inhibits Bunyavirus Infection.

PubMed

Hover, Samantha; King, Barnabas; Hall, Bradley; Loundras, Eleni-Anna; Taqi, Hussah; Daly, Janet; Dallas, Mark; Peers, Chris; Schnettler, Esther; McKimmie, Clive; Kohl, Alain; Barr, John N; Mankouri, Jamel

2016-02-12

Bunyaviruses are considered to be emerging pathogens facilitated by the segmented nature of their genome that allows reassortment between different species to generate novel viruses with altered pathogenicity. Bunyaviruses are transmitted via a diverse range of arthropod vectors, as well as rodents, and have established a global disease range with massive importance in healthcare, animal welfare, and economics. There are no vaccines or anti-viral therapies available to treat human bunyavirus infections and so development of new anti-viral strategies is urgently required. Bunyamwera virus (BUNV; genus Orthobunyavirus) is the model bunyavirus, sharing aspects of its molecular and cellular biology with all Bunyaviridae family members. Here, we show for the first time that BUNV activates and requires cellular potassium (K(+)) channels to infect cells. Time of addition assays using K(+) channel modulating agents demonstrated that K(+) channel function is critical to events shortly after virus entry but prior to viral RNA synthesis/replication. A similar K(+) channel dependence was identified for other bunyaviruses namely Schmallenberg virus (Orthobunyavirus) as well as the more distantly related Hazara virus (Nairovirus). Using a rational pharmacological screening regimen, two-pore domain K(+) channels (K2P) were identified as the K(+) channel family mediating BUNV K(+) channel dependence. As several K2P channel modulators are currently in clinical use, our work suggests they may represent a new and safe drug class for the treatment of potentially lethal bunyavirus disease. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Graphene Oxide: A Perfect Material for Spatial Light Modulation Based on Plasma Channels

PubMed Central

Tan, Chao; Wu, Xinghua; Wang, Qinkai; Tang, Pinghua; Shi, Xiaohui; Zhan, Shiping; Xi, Zaifang; Fu, Xiquan

2017-01-01

The graphene oxide (GO) is successfully prepared from a purified natural graphite through a pressurized oxidation method. We experimentally demonstrate that GO as an optical media can be used for spatial light modulation based on plasma channels induced by femtosecond pulses. The modulated beam exhibits good propagation properties in free space. It is easy to realize the spatial modulation on the probe beam at a high concentration of GO dispersion solutions, high power and smaller pulse width of the pump beam. We also find that the spatial modulation on the probe beam can be conveniently adjusted through the power and pulse width of pump lasers, dispersion solution concentration. PMID:28772712

Flipping interferometry and its application for quantitative phase microscopy in a micro-channel.

PubMed

Roitshtain, Darina; Turko, Nir A; Javidi, Bahram; Shaked, Natan T

2016-05-15

We present a portable, off-axis interferometric module for quantitative phase microscopy of live cells, positioned at the exit port of a coherently illuminated inverted microscope. The module creates on the digital camera an interference pattern between the image of the sample and its flipped version. The proposed simplified module is based on a retro-reflector modification in an external Michelson interferometer. The module does not contain any lenses, pinholes, or gratings and its alignment is straightforward. Still, it allows full control of the off-axis angle and does not suffer from ghost images. As experimentally demonstrated, the module is useful for quantitative phase microscopy of live cells rapidly flowing in a micro-channel.

Dynamic modulation of spike timing-dependent calcium influx during corticostriatal upstates

PubMed Central

Evans, R. C.; Maniar, Y. M.

2013-01-01

The striatum of the basal ganglia demonstrates distinctive upstate and downstate membrane potential oscillations during slow-wave sleep and under anesthetic. The upstates generate calcium transients in the dendrites, and the amplitude of these calcium transients depends strongly on the timing of the action potential (AP) within the upstate. Calcium is essential for synaptic plasticity in the striatum, and these large calcium transients during the upstates may control which synapses undergo plastic changes. To investigate the mechanisms that underlie the relationship between calcium and AP timing, we have developed a realistic biophysical model of a medium spiny neuron (MSN). We have implemented sophisticated calcium dynamics including calcium diffusion, buffering, and pump extrusion, which accurately replicate published data. Using this model, we found that either the slow inactivation of dendritic sodium channels (NaSI) or the calcium inactivation of voltage-gated calcium channels (CDI) can cause high calcium corresponding to early APs and lower calcium corresponding to later APs. We found that only CDI can account for the experimental observation that sensitivity to AP timing is dependent on NMDA receptors. Additional simulations demonstrated a mechanism by which MSNs can dynamically modulate their sensitivity to AP timing and show that sensitivity to specifically timed pre- and postsynaptic pairings (as in spike timing-dependent plasticity protocols) is altered by the timing of the pairing within the upstate. These findings have implications for synaptic plasticity in vivo during sleep when the upstate-downstate pattern is prominent in the striatum. PMID:23843436

Identification of a unique Ca2+-binding site in rat acid-sensing ion channel 3.

PubMed

Zuo, Zhicheng; Smith, Rachel N; Chen, Zhenglan; Agharkar, Amruta S; Snell, Heather D; Huang, Renqi; Liu, Jin; Gonzales, Eric B

2018-05-25

Acid-sensing ion channels (ASICs) evolved to sense changes in extracellular acidity with the divalent cation calcium (Ca 2+ ) as an allosteric modulator and channel blocker. The channel-blocking activity is most apparent in ASIC3, as removing Ca 2+ results in channel opening, with the site's location remaining unresolved. Here we show that a ring of rat ASIC3 (rASIC3) glutamates (Glu435), located above the channel gate, modulates proton sensitivity and contributes to the formation of the elusive Ca 2+ block site. Mutation of this residue to glycine, the equivalent residue in chicken ASIC1, diminished the rASIC3 Ca 2+ block effect. Atomistic molecular dynamic simulations corroborate the involvement of this acidic residue in forming a high-affinity Ca 2+ site atop the channel pore. Furthermore, the reported observations provide clarity for past controversies regarding ASIC channel gating. Our findings enhance understanding of ASIC gating mechanisms and provide structural and energetic insights into this unique calcium-binding site.

Adenosine triphosphate bioluminescence for bacteriological surveillance and reprocessing strategies for minimizing risk of infection transmission by duodenoscopes

PubMed Central

Sethi, Saurabh; Huang, Robert J.; Barakat, Monique T.; Banaei, Niaz; Friedland, Shai; Banerjee, Subhas

2017-01-01

Background/Aims Recent outbreaks of duodenoscope-transmitted infections underscore the importance of adequate endoscope reprocessing. Adenosine triphosphate (ATP) bioluminescence testing allows rapid evaluation of endoscopes for bacteriological/biological residue. In this prospective study we evaluate the utility of ATP in bacteriological surveillance, and the effects of endoscopy staff education and dual cycles of cleaning and high-level disinfection (HLD) on endoscope reprocessing. Methods ATP bioluminescence was measured after pre-cleaning, manual cleaning and HLD on rinsates from suction-biopsy channels of all endoscopes and elevator channels of duodenoscopes/linear echoendoscopes after use. ATP bioluminescence was re-measured in duodenoscopes (1) after re-education and competency testing of endoscopy staff, and subsequently (2) after 2 cycles of pre-cleaning and manual cleaning and single cycle of HLD, or (3) after 2 cycles of pre-cleaning, manual cleaning and HLD. Results The ideal ATP bioluminescence benchmark of <200 relative light units (RLUs) after manual cleaning was achieved from suction-biopsy channel rinsates of all endoscopes, but 9 of 10 duodenoscope elevator channel rinsates failed to meet this benchmark. Re-education reduced RLUs in duodenoscope elevator channel rinsates after pre-cleaning (23218.0 vs 1340.5 RLUs, p<0.01) and HLD (177.0 vs 12.0 RLUs, p<0.01). After 2 cycles of manual cleaning/HLD, duodenoscope elevator channel RLUs achieved levels similar to sterile water, with corresponding negative cultures. Conclusions ATP testing offers a rapid, inexpensive alternative for detection of endoscope microbial residue. Re-education of endoscopy staff and 2 cycles of cleaning and HLD decrease elevator channel RLUs to levels similar to sterile water and may therefore minimize the risk of transmission of infections by duodenoscopes. PMID:27818222

The geomorphic effectiveness of a large flood on the Rio Grande in the Big Bend region: insights on geomorphic controls and post-flood geomorphic response

USGS Publications Warehouse

Dean, David J.; Schmidt, John C.

2013-01-01

Since the 1940s, the Rio Grande in the Big Bend region has undergone long periods of channel narrowing, which have been occasionally interrupted by rare, large floods that widen the channel (termed a channel reset). The most recent channel reset occurred in 2008 following a 17-year period of extremely low stream flow and rapid channel narrowing. Flooding was caused by precipitation associated with the remnants of tropical depression Lowell in the Rio Conchos watershed, the largest tributary to the Rio Grande. Floodwaters approached 1500 m3/s (between a 13 and 15 year recurrence interval) and breached levees, inundated communities, and flooded the alluvial valley of the Rio Grande; the wetted width exceeding 2.5 km in some locations. The 2008 flood had the 7th largest magnitude of record, however, conveyed the largest volume of water than any other flood. Because of the narrow pre-flood channel conditions, record flood stages occurred. We used pre- and post-flood aerial photographs, channel and floodplain surveys, and 1-dimensional hydraulic models to quantify the magnitude of channel change, investigate the controls of flood-induced geomorphic changes, and measure the post-flood response of the widened channel. These analyses show that geomorphic changes included channel widening, meander migration, avulsions, extensive bar formation, and vertical floodplain accretion. Reach-averaged channel widening between 26 and 52% occurred, but in some localities exceeded 500%. The degree and style of channel response was related, but not limited to, three factors: 1) bed-load supply and transport, 2) pre-flood channel plan form, and 3) rapid declines in specific stream power downstream of constrictions and areas of high channel bed slope. The post-flood channel response has consisted of channel contraction through the aggradation of the channel bed and the formation of fine-grained benches inset within the widened channel margins. The most significant post-flood geomorphic changes have occurred at and downstream from ephemeral tributaries that contribute large volumes of sediment.

G-protein mediated gating of inward-rectifier K+ channels.

PubMed

Mark, M D; Herlitze, S

2000-10-01

G-protein regulated inward-rectifier potassium channels (GIRK) are part of a superfamily of inward-rectifier K+ channels which includes seven family members. To date four GIRK subunits, designated GIRK1-4 (also designated Kir3.1-4), have been identified in mammals, and GIRK5 has been found in Xenopus oocytes. GIRK channels exist in vivo both as homotetramers and heterotetramers. In contrast to the other mammalian GIRK family members, GIRK1 can not form functional channels by itself and has to assemble with GIRK2, 3 or 4. As the name implies, GIRK channels are modulated by G-proteins; they are also modulated by phosphatidylinositol 4,5-bisphosphate, intracellular sodium, ethanol and mechanical stretch. Recently a family of GTPase activating proteins known as regulators of G-protein signaling were shown to be the missing link for the fast deactivation kinetics of GIRK channels in native cells, which contrast with the slow kinetics observed in heterologously expressed channels. GIRK1, 2 and 3 are highly abundant in brain, while GIRK4 has limited distribution. Here, GIRK1/2 seems to be the predominant heterotetramer. In general, neuronal GIRK channels are involved in the regulation of the excitability of neurons and may contribute to the resting potential. Interestingly, only the GIRK1 and 4 subunits are distributed in the atrial and sinoatrial node cells of the heart and are involved in the regulation of cardiac rate. Our main objective of this review is to assess the current understanding of the G-protein modulation of GIRK channels and their physiological importance in mammals.

Equalization and detection for digital communication over nonlinear bandlimited satellite communication channels. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Gutierrez, Alberto, Jr.

1995-01-01

This dissertation evaluates receiver-based methods for mitigating the effects due to nonlinear bandlimited signal distortion present in high data rate satellite channels. The effects of the nonlinear bandlimited distortion is illustrated for digitally modulated signals. A lucid development of the low-pass Volterra discrete time model for a nonlinear communication channel is presented. In addition, finite-state machine models are explicitly developed for a nonlinear bandlimited satellite channel. A nonlinear fixed equalizer based on Volterra series has previously been studied for compensation of noiseless signal distortion due to a nonlinear satellite channel. This dissertation studies adaptive Volterra equalizers on a downlink-limited nonlinear bandlimited satellite channel. We employ as figure of merits performance in the mean-square error and probability of error senses. In addition, a receiver consisting of a fractionally-spaced equalizer (FSE) followed by a Volterra equalizer (FSE-Volterra) is found to give improvement beyond that gained by the Volterra equalizer. Significant probability of error performance improvement is found for multilevel modulation schemes. Also, it is found that probability of error improvement is more significant for modulation schemes, constant amplitude and multilevel, which require higher signal to noise ratios (i.e., higher modulation orders) for reliable operation. The maximum likelihood sequence detection (MLSD) receiver for a nonlinear satellite channel, a bank of matched filters followed by a Viterbi detector, serves as a probability of error lower bound for the Volterra and FSE-Volterra equalizers. However, this receiver has not been evaluated for a specific satellite channel. In this work, an MLSD receiver is evaluated for a specific downlink-limited satellite channel. Because of the bank of matched filters, the MLSD receiver may be high in complexity. Consequently, the probability of error performance of a more practical suboptimal MLSD receiver, requiring only a single receive filter, is evaluated.

5nsec Dead time multichannel scaling system for Mössbauer spectrometer

NASA Astrophysics Data System (ADS)

Verrastro, C.; Trombetta, G.; Pita, A.; Saragovi, C.; Duhalde, S.

1991-11-01

A PC programmable and fast multichannel scaling module has been designed to use a commercial Mössbauer spectrometer. This module is based on a 10 single chip 8 bits microcomputer (MC6805) and on a 35 fast ALU, which allows a high performance and low cost system. The module can operate in a stand-alone mode. Data analysis are performed in real time display, on XT/AT IBM PC or compatibles. The channels are ranged between 256 and 4096, the maximum number of counts is 232-1 per channel, the dwell time is 3 μsec and the dead time between channels is 5 nsec. A friendly software display the real time spectrum and offers menues with different options at each state.

From Modules to a Generator: An Integrated Heat Exchanger Concept for Car Applications of a Thermoelectric Generator

NASA Astrophysics Data System (ADS)

Bosch, Henry

2016-03-01

A heat exchanger concept for a thermoelectric generator with integrated planar modules for passenger car applications is introduced. The module housings, made of deep drawn stainless steel sheet metal, are brazed onto the exhaust gas channel to achieve an optimal heat transfer on the hot side of the modules. The cooling side consists of winding fluid channels, which are mounted directly onto the cold side of the modules. Only a thin foil separates the cooling media from the modules for an almost direct heat contact on the cooling side. Thermoelectric generators with up to 20 modules made of PbTe and Bi2Te3, respectively, are manufactured and tested on a hot gas generator to investigate electrical power output and performance of the thermoelectric generator. The proof of concept of the light weight heat exchanger design made of sheet metal with integrated modules is positively accomplished.

HCN Channels Modulators: The Need for Selectivity

PubMed Central

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

2016-01-01

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

Menthol Suppresses Nicotinic Acetylcholine Receptor Functioning in Sensory Neurons via Allosteric Modulation

PubMed Central

Wilhelm, M.; Swandulla, D.

2012-01-01

In this study, we have investigated how the function of native and recombinant nicotinic acetylcholine receptors (nAChRs) is modulated by the monoterpenoid alcohol from peppermint (−) menthol. In trigeminal neurons (TG), we found that nicotine (75 μM)-activated whole-cell currents through nAChRs were reversibly reduced by menthol in a concentration-dependent manner with an IC50 of 111 μM. To analyze the mechanism underlying menthol's action in more detail, we used single channel and whole-cell recordings from recombinant human α4β2 nAChR expressed in HEK tsA201 cells. Here, we found a shortening of channel open time and a prolongation of channel closed time, and an increase in single channel amplitude leading in summary to a reduction in single channel current. Furthermore, menthol did not affect nicotine's EC50 value for currents through recombinant human α4β2 nAChRs but caused a significant reduction in nicotine's efficacy. Taken together, these findings indicate that menthol is a negative allosteric modulator of nAChRs. PMID:22281529

Health Instruction Packages: Pregnancy and Childbirth.

ERIC Educational Resources Information Center

Ostrander, Betty; And Others

Text, illustrations, and reinforcement exercises are utilized in these nine learning modules to instruct nurses and expectant mothers in topics related to pre-natal care, labor, and post-partum readjustment. The first module, "Pre-Natal Evaluation" by Betty Ostrander, teaches the nurse to diagnose toxemia of pregnancy. The second module,…

Pre-Treatment. Training Module 2.102.2.77.

ERIC Educational Resources Information Center

Kirkwood Community Coll., Cedar Rapids, IA.

This document is an instructional module package designed in the objective format for use by an instructor familiar with pre-treatment unit operation. Included are objectives, instructor guide, student handouts and transparency masters. The module considers design, operation, maintenance, and safety of common methods of grit removal, screening,…

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

PubMed Central

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

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

PubMed

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.

Kv7 channels critically determine coronary artery reactivity: left-right differences and down-regulation by hyperglycaemia.

PubMed

Morales-Cano, Daniel; Moreno, Laura; Barreira, Bianca; Pandolfi, Rachele; Chamorro, Virginia; Jimenez, Rosario; Villamor, Eduardo; Duarte, Juan; Perez-Vizcaino, Francisco; Cogolludo, Angel

2015-04-01

Voltage-gated potassium channels encoded by KCNQ genes (Kv7 channels) are emerging as important regulators of vascular tone. In this study, we analysed the contribution of Kv7 channels to the vasodilation induced by hypoxia and the cyclic AMP pathway in the coronary circulation. We also assessed their regional distribution and possible impairment by diabetes. We examined the effects of Kv7 channel modulators on K+ currents and vascular reactivity in rat left and right coronary arteries (LCAs and RCAs, respectively). Currents from LCA were more sensitive to Kv7 channel inhibitors (XE991, linopirdine) and activators (flupirtine, retigabine) than those from RCA. Accordingly, LCAs were more sensitive than RCAs to the relaxation induced by Kv7 channel enhancers. Likewise, relaxation induced by the adenylyl cyclase activator forskolin and hypoxia, which were mediated through Kv7 channel activation, were greater in LCA than in RCA. KCNQ1 and KCNQ5 expression was markedly higher in LCA than in RCA. After incubation with high glucose (HG, 30 mmol/L), myocytes from LCA, but not from RCA, were more depolarized and showed reduced Kv7 currents. In HG-incubated LCA, the effects of Kv7 channel modulators and forskolin were diminished, and the expression of KCNQ1 and KCNQ5 was reduced. Finally, vascular responses induced by Kv7 channel modulators were impaired in LCA, but not in RCA, from type 1 diabetic rats. Our results reveal that the high expression and function of Kv7 channels in the LCA and their down-regulation by diabetes critically determine the sensitivity to key regulators of coronary tone. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Analyze the Role of a Teacher. Module. A Pre-Student Teaching Field Experience for Pre-Service Teachers.

ERIC Educational Resources Information Center

Browning, Ruth A.

This module is designed to aid preservice teachers in their first student teaching experience. The module is composed of five learning experiences which enable participants to assess their feelings toward teaching by focusing on three module components: (1) getting to know the students; (2) analyzing the role and activities of a teacher; and (3)…

High density, multi-range analog output Versa Module Europa board for control system applications

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

Singh, Kundan, E-mail: kundan@iuac.res.in; Das, Ajit Lal

2014-01-15

A new VMEDAC64, 12-bit 64 channel digital-to-analog converter, a Versa Module Europa (VME) module, features 64 analog voltage outputs with user selectable multiple ranges, has been developed for control system applications at Inter University Accelerator Centre. The FPGA (Field Programmable Gate Array) is the module's core, i.e., it implements the DAC control logic and complexity of VMEbus slave interface logic. The VMEbus slave interface and DAC control logic are completely designed and implemented on a single FPGA chip to achieve high density of 64 channels in a single width VME module and will reduce the module count in the controlmore » system applications, and hence will reduce the power consumption and cost of overall system. One of our early design goals was to develop the VME interface such that it can be easily integrated with the peripheral devices and satisfy the timing specifications of VME standard. The modular design of this module reduces the amount of time required to develop other custom modules for control system. The VME slave interface is written as a single component inside FPGA which will be used as a basic building block for any VMEbus interface project. The module offers multiple output voltage ranges depending upon the requirement. The output voltage range can be reduced or expanded by writing range selection bits in the control register. The module has programmable refresh rate and by default hold capacitors in the sample and hold circuit for each channel are charged periodically every 7.040 ms (i.e., update frequency 284 Hz). Each channel has software controlled output switch which disconnects analog output from the field. The modularity in the firmware design on FPGA makes the debugging very easy. On-board DC/DC converters are incorporated for isolated power supply for the analog section of the board.« less

A multi-module microfluidic platform for continuous pre-concentration of water-soluble ions and separation of oil droplets from oil-in-water (O/W) emulsions using a DC-biased AC electrokinetic technique.

PubMed

Das, Dhiman; Phan, Dinh-Tuan; Zhao, Yugang; Kang, Yuejun; Chan, Vincent; Yang, Chun

2017-03-01

A novel continuous flow microfluidic platform specifically designed for environmental monitoring of O/W emulsions during an aftermath of oil spills is reported herein. Ionized polycyclic aromatic hydrocarbons which are toxic are readily released from crude oil to the surrounding water phase through the smaller oil droplets with enhanced surface area. Hence, a multi-module microfluidic device is fabricated to form ion enrichment zones in the water phase of O/W emulsions for the ease of detection and to separate micron-sized oil droplets from the O/W emulsions. Fluorescein ions in the water phase are used to simulate the presence of these toxic ions in the O/W emulsion. A DC-biased AC electric field is employed in both modules. In the first module, a nanoporous Nafion membrane is used for activating the concentration polarization effect on the fluorescein ions, resulting in the formation of stable ion enrichment zones in the water phase of the emulsion. A 35.6% amplification of the fluorescent signal is achieved in the ion enrichment zone; corresponding to 100% enrichment of the fluorescent dye concentration. In this module, the main inlet is split into two channels by using a Y-junction so that there are two outlets for the oil droplets. The second module located downstream of the first module consists of two oil droplet entrapment zones at two outlets. By switching on the appropriate electrodes, either one of the two oil droplet entrapment zones can be activated and the droplets can be blocked in the corresponding outlet. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

MHD Electrode and wall constructions

DOEpatents

Way, Stewart; Lempert, Joseph

1984-01-01

Electrode and wall constructions for the walls of a channel transmitting the hot plasma in a magnetohydrodynamic generator. The electrodes and walls are made of a plurality of similar modules which are spaced from one another along the channel. The electrodes can be metallic or ceramic, and each module includes one or more electrodes which are exposed to the plasma and a metallic cooling bar which is spaced from the plasma and which has passages through which a cooling fluid flows to remove heat transmitted from the electrode to the cooling bar. Each electrode module is spaced from and electrically insulated from each adjacent module while interconnected by the cooling fluid which serially flows among selected modules. A wall module includes an electrically insulating ceramic body exposed to the plasma and affixed, preferably by mechanical clips or by brazing, to a metallic cooling bar spaced from the plasma and having cooling fluid passages. Each wall module is, similar to the electrode modules, electrically insulated from the adjacent modules and serially interconnected to other modules by the cooling fluid.

Resonance Properties of Class I and Class II Neurons Differentially Modulated by Channel Noise

NASA Astrophysics Data System (ADS)

Wang, Lei

2018-01-01

Resonance properties of two different neuron types (Class I and Class II) induced by channel noise are investigated in this study. It is found that for Class I neuron, spiking activity is enhanced when certain noise intensity is presented, especially under weak current stimuli -- a typical phenomenon of stochastic resonance (SR); while for Class II neuron, in addition to perform the SR, certain noise intensity would inhibit neuronal activity under some current stimuli -- a typical phenomenon of inverse stochastic resonance (ISR). Moreover, we show that only sodium channel noise or potassium channel noise variation can achieve the similar phenomena. Consequently, the model results suggest that channel noise may exert differential roles in modulating the resonance properties of Class I and Class II neurons.

Ergodic channel capacity of spatial correlated multiple-input multiple-output free space optical links using multipulse pulse-position modulation

NASA Astrophysics Data System (ADS)

Wang, Huiqin; Wang, Xue; Cao, Minghua

2017-02-01

The spatial correlation extensively exists in the multiple-input multiple-output (MIMO) free space optical (FSO) communication systems due to the channel fading and the antenna space limitation. Wilkinson's method was utilized to investigate the impact of spatial correlation on the MIMO FSO communication system employing multipulse pulse-position modulation. Simulation results show that the existence of spatial correlation reduces the ergodic channel capacity, and the reception diversity is more competent to resist this kind of performance degradation.

An Active Heater Control Concept to Meet IXO Type Mirror Module Thermal-Structural Distortion Requirement

NASA Technical Reports Server (NTRS)

Choi, Michael

2013-01-01

Flight mirror assemblies (FMAs) of large telescopes, such as the International X-ray Observatory (IXO), have very stringent thermal-structural distortion requirements. The spatial temperature gradient requirement within a FMA could be as small as 0.05 C. Con ventionally, heaters and thermistors are attached to the stray light baffle (SLB), and centralized heater controllers (i.e., heater controller boards located in a large electronics box) are used. Due to the large number of heater harnesses, accommodating and routing them is extremely difficult. The total harness length/mass is very large. This innovation uses a thermally conductive pre-collimator to accommodate heaters and a distributed heater controller approach. It minimizes the harness length and mass, and reduces the problem of routing and accommodating them. Heaters and thermistors are attached to a short (4.67 cm) aluminum portion of the pre-collimator, which is thermally coupled to the SLB. Heaters, which have a very small heater power density, and thermistors are attached to the exterior of all the mirror module walls. The major portion (23.4 cm) of the pre-collimator for the middle and outer modules is made of thin, non-conductive material. It minimizes the view factors from the FMA and heated portion of the precollimator to space. It also minimizes heat conduction from one end of the FMA to the other. Small and multi-channel heater controllers, which have adjustable set points and internal redundancy, are used. They are mounted to the mechanical support structure members adjacent to each module. The IXO FMA, which is 3.3 m in diameter, is an example of a large telescope. If the heater controller boards are centralized, routing and accommodating heater harnesses is extremely difficult. This innovation has the following advantages. It minimizes the length/mass of the heater harness between the heater controllers and heater circuits. It reduces the problem of routing and accommodating the harness on the FMA. It reduces the risk of X-ray attenuation caused by the heater harness. Its adjustable set point capability eliminates the need for survival heater circuits. The operating mode heater circuits can also be used as survival heater circuits. In the non-operating mode, a lower set point is used.

Yetter-Drinfeld modules for Hom-bialgebras

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

Makhlouf, Abdenacer, E-mail: Abdenacer.Makhlouf@uha.fr; Panaite, Florin, E-mail: Florin.Panaite@imar.ro

The aim of this paper is to define and study Yetter-Drinfeld modules over Hom-bialgebras, a generalized version of bialgebras obtained by modifying the algebra and coalgebra structures by a homomorphism. Yetter-Drinfeld modules over a Hom-bialgebra with bijective structure map provide solutions of the Hom-Yang-Baxter equation. The category H/HYD of Yetter-Drinfeld modules with bijective structure maps over a Hom-bialgebra H with bijective structure map can be organized, in two different ways, as a quasi-braided pre-tensor category. If H is quasitriangular (respectively, coquasitriangular) the first (respectively, second) quasi-braided pre-tensor category H/HYD contains, as a quasi-braided pre-tensor subcategory, the category of modules (respectively,more » comodules) with bijective structure maps over H.« less

Voltage gated sodium channels as drug discovery targets

PubMed Central

Bagal, Sharan K; Marron, Brian E; Owen, Robert M; Storer, R Ian; Swain, Nigel A

2015-01-01

Voltage-gated sodium (NaV) channels are a family of transmembrane ion channel proteins. They function by forming a gated, water-filled pore to help establish and control cell membrane potential via control of the flow of ions between the intracellular and the extracellular environments. Blockade of NaVs has been successfully accomplished in the clinic to enable control of pathological firing patterns that occur in a diverse range of conditions such as chronic pain, epilepsy, and cardiac arrhythmias. First generation sodium channel modulator drugs, despite low inherent subtype selectivity, preferentially act on over-excited cells which reduces undesirable side effects in the clinic. However, the limited therapeutic indices observed with the first generation demanded a new generation of sodium channel inhibitors. The structure, function and the state of the art in sodium channel modulator drug discovery are discussed in this chapter. PMID:26646477

Voltage gating of mechanosensitive PIEZO channels.

PubMed

Moroni, Mirko; Servin-Vences, M Rocio; Fleischer, Raluca; Sánchez-Carranza, Oscar; Lewin, Gary R

2018-03-15

Mechanosensitive PIEZO ion channels are evolutionarily conserved proteins whose presence is critical for normal physiology in multicellular organisms. Here we show that, in addition to mechanical stimuli, PIEZO channels are also powerfully modulated by voltage and can even switch to a purely voltage-gated mode. Mutations that cause human diseases, such as xerocytosis, profoundly shift voltage sensitivity of PIEZO1 channels toward the resting membrane potential and strongly promote voltage gating. Voltage modulation may be explained by the presence of an inactivation gate in the pore, the opening of which is promoted by outward permeation. Older invertebrate (fly) and vertebrate (fish) PIEZO proteins are also voltage sensitive, but voltage gating is a much more prominent feature of these older channels. We propose that the voltage sensitivity of PIEZO channels is a deep property co-opted to add a regulatory mechanism for PIEZO activation in widely different cellular contexts.

Generalized channeled polarimetry.

PubMed

Alenin, Andrey S; Tyo, J Scott

2014-05-01

Channeled polarimeters measure polarization by modulating the measured intensity in order to create polarization-dependent channels that can be demodulated to reveal the desired polarization information. A number of channeled systems have been described in the past, but their proposed designs often unintentionally sacrifice optimality for ease of algebraic reconstruction. To obtain more optimal systems, a generalized treatment of channeled polarimeters is required. This paper describes methods that enable handling of multi-domain modulations and reconstruction of polarization information using linear algebra. We make practical choices regarding use of either Fourier or direct channels to make these methods more immediately useful. Employing the introduced concepts to optimize existing systems often results in superficial system changes, like changing the order, orientation, thickness, or spacing of polarization elements. For the two examples we consider, we were able to reduce noise in the reconstruction to 34.1% and 57.9% of the original design values.

Thin membrane sensor with biochemical switch

NASA Technical Reports Server (NTRS)

Worley, III, Jennings F. (Inventor); Case, George D. (Inventor)

1994-01-01

A modular biosensor system for chemical or biological agent detection utilizes electrochemical measurement of an ion current across a gate membrane triggered by the reaction of the target agent with a recognition protein conjugated to a channel blocker. The sensor system includes a bioresponse simulator or biochemical switch module which contains the recognition protein-channel blocker conjugate, and in which the detection reactions occur, and a transducer module which contains a gate membrane and a measuring electrode, and in which the presence of agent is sensed electrically. In the poised state, ion channels in the gate membrane are blocked by the recognition protein-channel blocker conjugate. Detection reactions remove the recognition protein-channel blocker conjugate from the ion channels, thus eliciting an ion current surge in the gate membrane which subsequently triggers an output alarm. Sufficiently large currents are generated that simple direct current electronics are adequate for the measurements. The biosensor has applications for environmental, medical, and industrial use.

Electron cryo-microscopy structure of the canonical TRPC4 ion channel

PubMed Central

Vinayagam, Deivanayagabarathy; Mager, Thomas; Apelbaum, Amir; Bothe, Arne; Merino, Felipe; Hofnagel, Oliver; Gatsogiannis, Christos

2018-01-01

Canonical transient receptor channels (TRPC) are non-selective cation channels. They are involved in receptor-operated Ca2+ signaling and have been proposed to act as store-operated channels (SOC). Their malfunction is related to cardiomyopathies and their modulation by small molecules has been shown to be effective against renal cancer cells. The molecular mechanism underlying the complex activation and regulation is poorly understood. Here, we report the electron cryo-microscopy structure of zebrafish TRPC4 in its unliganded (apo), closed state at an overall resolution of 3.6 Å. The structure reveals the molecular architecture of the cation conducting pore, including the selectivity filter and lower gate. The cytoplasmic domain contains two key hubs that have been shown to interact with modulating proteins. Structural comparisons with other TRP channels give novel insights into the general architecture and domain organization of this superfamily of channels and help to understand their function and pharmacology. PMID:29717981

On the suitability of fibre optical parametric amplifiers for use in all-optical agile photonic networks

NASA Astrophysics Data System (ADS)

Gryspolakis, Nikolaos

The objective of this thesis is to investigate the suitability of fibre optical parametric amplifiers (FOPAs) for use in multi-channel, dynamic networks. First, we investigate their quasi-static behaviour in such an environment. We study the behaviour of a FOPA under realistic conditions and we examine the impact on the gain spectrum of channel addition for several different operating conditions and regimes. In particular, we examine the impact of surviving channel(s) position, input power and channel spacing. We see how these parameters affect the gain tilt as well as its dynamic characteristics, namely the generation of under or over-shoots at the transition point, possible dependence of rise and fall times on any of the aforementioned parameters and how the gain excursions depend on those parameters. For these studies we assume continuous wave operation for all signals. We observe that the gain spectrum changes are a function of the position and the spacing of the channels. We also find that the gain excursion can reach several dBs (up to 5 dB) in the case of channel add/drop and are heavily dependent on the position of the surviving channels. The channels located in the middle of the transmission band are more prone to channel add/drop-induced gain changes. Moreover, we investigate for the first time the FOPA dynamic behaviour in a packet switching scenario. This part of the study assumes that all but one channels normally vary in a packet-switched fashion. The remaining channel (probe channel) is expected to undergo gain variations due to the perturbation of the system experienced by the other channels. Furthermore, we consider several different scenarios for which the channels spacing, per channel input power (PCIP), variance of the power fluctuation and position of the probe channel will change. We find that when the FOPA operates near saturation the target gain is not achieved more than 50% of the time while the peak-to-peak gain excursions can exceed 1 dB. Next, we introduce modulated channels to the amplifier in order to compare their effect on the Bit Error Rate (BER) performance. We consider the impact on FOPAs when employing different modulation formats, such as RZ, NRZ and RZ-DPSK. Carefully selected modulation formats can improve BER performance and reduce the effects of cross-phase modulation, four wave mixing (FWM) products generation or dispersion (non-linear and linear inter-channel interference). Especially for the case of FOPAs, because of the ultra-fast interaction times of the FWM phenomenon, cross gain modulation can be a great deterrent for using FOPAs. We use RZ-DPSK in order to suppress the WDM signal crosstalk. Only by using RZ-DPSK, we obtain an improved receiver sensitivity of 5 dB when operating at 40 Gb/s. Finally, we investigate ways to mitigate such effects as the ones described above (gain excursions, gain tilt, etc.). We demonstrate that by using a ring configuration with optical feedback for the first time in FOPAs, we can achieve all-optical gain clamping (AOGC), mitigating gain excursions and attaining gain, independent of channel input power for a large range of PCIP. For example, with the use of AOGC, we reduce the add/drop-induced gain excursions from 4 dB to 0.6 dB. Also, by the combined use of AOGC and RZ-DPSK, we mitigate most of the aforementioned hindrances described above.

NMDA receptor modulators: an updated patent review (2013-2014).

PubMed

Strong, Katie L; Jing, Yao; Prosser, Anthony R; Traynelis, Stephen F; Liotta, Dennis C

2014-12-01

The NMDA receptor mediates a slow component of excitatory synaptic transmission, and NMDA receptor dysfunction has been implicated in numerous neurological disorders. Thus, interest in developing modulators that are capable of regulating the channel continues to be strong. Recent research has led to the discovery of a number of compounds that hold therapeutic and clinical value. Deeper insight into the NMDA intersubunit interactions and structural motifs gleaned from the recently solved crystal structures of the NMDA receptor should facilitate a deeper understanding of how these compounds modulate the receptor. This article discusses the known pharmacology of NMDA receptors. A discussion of the patent literature since 2012 is also included, with an emphasis on those that claimed new chemical entities as regulators of the NMDA receptor. The number of patents involving novel NMDA receptor modulators suggests a renewed interest in the NMDA receptor as a therapeutic target. Subunit-selective modulators continue to show promise, and the development of new subunit-selective NMDA receptor modulators appears poised for continued growth. Although a modest number of channel blocker patents were published, successful clinical outcomes involving ketamine have led to a resurgent interest in low-affinity channel blockers as therapeutics.

Large current modulation and tunneling magnetoresistance change by a side-gate electric field in a GaMnAs-based vertical spin metal-oxide-semiconductor field-effect transistor.

PubMed

Kanaki, Toshiki; Yamasaki, Hiroki; Koyama, Tomohiro; Chiba, Daichi; Ohya, Shinobu; Tanaka, Masaaki

2018-05-08

A vertical spin metal-oxide-semiconductor field-effect transistor (spin MOSFET) is a promising low-power device for the post scaling era. Here, using a ferromagnetic-semiconductor GaMnAs-based vertical spin MOSFET with a GaAs channel layer, we demonstrate a large drain-source current I DS modulation by a gate-source voltage V GS with a modulation ratio up to 130%, which is the largest value that has ever been reported for vertical spin field-effect transistors thus far. We find that the electric field effect on indirect tunneling via defect states in the GaAs channel layer is responsible for the large I DS modulation. This device shows a tunneling magnetoresistance (TMR) ratio up to ~7%, which is larger than that of the planar-type spin MOSFETs, indicating that I DS can be controlled by the magnetization configuration. Furthermore, we find that the TMR ratio can be modulated by V GS . This result mainly originates from the electric field modulation of the magnetic anisotropy of the GaMnAs ferromagnetic electrodes as well as the potential modulation of the nonmagnetic semiconductor GaAs channel layer. Our findings provide important progress towards high-performance vertical spin MOSFETs.

A new scalable modular data acquisition system for SPECT (PET)

NASA Astrophysics Data System (ADS)

Stenstrom, P.; Rillbert, A.; Bergquist, M.; Habte, F.; Bohm, C.; Larsson, S. A.

1998-06-01

Describes a modular decentralized data acquisition system that continuously samples shaped PMT pulses from a SPECT detector. The pulse waveform data are used by signal processors to accurately reconstruct amplitude and time for each scintillation event. Data acquisition for a PMT channel is triggered in two alternative ways, either when its own signal exceeds a selected digital threshold, or when it receives a trigger pulse from one of its neighboring PMTs. The triggered region is restricted to seven, thirteen or nineteen neighboring PMT channels. Each acquisition module supports three PMT channels and connects to all other modules and a reconstruction computer via Firewire to cover the 72 channels in the Stockholm University/Karolinska Hospital cylindrical SPECT camera.

Learning as Students to become Better Teachers: Pre-Service Teachers' IWB Learning Experience

ERIC Educational Resources Information Center

Divaharan, Shanti; Koh, Joyce Hwee Ling

2010-01-01

The study presented in this paper involved 124 Singaporean pre-service teachers who were attending a core information and communications technology (ICT) module, which is a component of their teacher education program. During this module, the pre-service teachers were introduced to the interactive whiteboard (IWB) through an instructional approach…

An allosteric Sec61 inhibitor traps nascent transmembrane helices at the lateral gate

PubMed Central

MacKinnon, Andrew L; Paavilainen, Ville O; Sharma, Ajay; Hegde, Ramanujan S; Taunton, Jack

2014-01-01

Membrane protein biogenesis requires the coordinated movement of hydrophobic transmembrane domains (TMD) from the cytosolic vestibule of the Sec61 channel into the lipid bilayer. Molecular insight into TMD integration has been hampered by the difficulty of characterizing intermediates during this intrinsically dynamic process. In this study, we show that cotransin, a substrate-selective Sec61 inhibitor, traps nascent TMDs in the cytosolic vestibule, permitting detailed interrogation of an early pre-integration intermediate. Site-specific crosslinking revealed the pre-integrated TMD docked to Sec61 near the cytosolic tip of the lateral gate. Escape from cotransin-arrest depends not only on cotransin concentration, but also on the biophysical properties of the TMD. Genetic selection of cotransin-resistant cancer cells uncovered multiple mutations clustered near the lumenal plug of Sec61α, thus revealing cotransin’s likely site of action. Our results suggest that TMD/lateral gate interactions facilitate TMD transfer into the membrane, a process that is allosterically modulated by cotransin binding to the plug. DOI: http://dx.doi.org/10.7554/eLife.01483.001 PMID:24497544

Compliant, low profile, independently releasing, non-protruding and genderless docking system for robotic modules

NASA Technical Reports Server (NTRS)

Khoshnevis, Behrokh (Inventor)

2010-01-01

An apparatus for coupling with a mating coupling module to facilitate the joining of two disjoined structures without requiring precise alignment between the disjoined structures during the coupling of them may include a rotating drive mechanism, a hollow cylindrical body operatively connected to the rotating drive mechanism, wherein the hollow cylindrical body has at least one internal spiral channel, and at least one connector claw positioned within the hollow cylindrical body and guided by the internal spiral channel, wherein the at least one connector claw is configured to extend outwardly from the coupling module to engage the mating coupling module when brought in close proximity but not necessarily in precise alignment with the mating coupling module.

12.5 Gb/s multi-channel broadcasting transmission for free-space optical communication based on the optical frequency comb module.

PubMed

Tan, Jun; Zhao, Zeping; Wang, Yuehui; Zhang, Zhike; Liu, Jianguo; Zhu, Ninghua

2018-01-22

A wide-spectrum, ultra-stable optical frequency comb (OFC) module with 100 GHz frequency intervals based on a quantum dot mode locked (QDML) laser is fabricated by our lab, and a scheme with 12.5 Gb/s multi-channel broadcasting transmission for free-space optical (FSO) communication is proposed based on the OFC module. The output power of the OFC is very stable, with the specially designed circuit and the flatness of the frequency comb over the span of 6 nm, which can be limited to 1.5 dB. Four channel wavelengths are chosen to demonstrate one-to-many channels for FSO communication, like optical wireless broadcast. The outdoor experiment is established to test the bit error rate (BER) and eye diagrams with 12.5 Gb/s on-off keying (OOK). The indoor experiment is used to test the highest traffic rate, which is up to 21 Gb/s for one-hop FSO communication. To the best of our knowledge, this scheme is the first to propose the realization of one-to-many broadcasting transmission for FSO communication based on the OFC module. The advantages of integration, miniaturization, channelization, low power consumption, and unlimited bandwidth of one-to-many broadcasting communication scheme, shows promising results on constructing the future space-air-ground-ocean (SAGO) FSO communication networks.

Zinc as Allosteric Ion Channel Modulator: Ionotropic Receptors as Metalloproteins

PubMed Central

Peralta, Francisco Andrés; Huidobro-Toro, Juan Pablo

2016-01-01

Zinc is an essential metal to life. This transition metal is a structural component of many proteins and is actively involved in the catalytic activity of cell enzymes. In either case, these zinc-containing proteins are metalloproteins. However, the amino acid residues that serve as ligands for metal coordination are not necessarily the same in structural proteins compared to enzymes. While crystals of structural proteins that bind zinc reveal a higher preference for cysteine sulfhydryls rather than histidine imidazole rings, catalytic enzymes reveal the opposite, i.e., a greater preference for the histidines over cysteines for catalysis, plus the influence of carboxylic acids. Based on this paradigm, we reviewed the putative ligands of zinc in ionotropic receptors, where zinc has been described as an allosteric modulator of channel receptors. Although these receptors do not strictly qualify as metalloproteins since they do not normally bind zinc in structural domains, they do transitorily bind zinc at allosteric sites, modifying transiently the receptor channel’s ion permeability. The present contribution summarizes current information showing that zinc allosteric modulation of receptor channels occurs by the preferential metal coordination to imidazole rings as well as to the sulfhydryl groups of cysteine in addition to the carboxyl group of acid residues, as with enzymes and catalysis. It is remarkable that most channels, either voltage-sensitive or transmitter-gated receptor channels, are susceptible to zinc modulation either as positive or negative regulators. PMID:27384555

Parts Counter. Pre-Apprenticeship Phase 1 Training. Instructor's Guide.

ERIC Educational Resources Information Center

Lane Community Coll., Eugene, OR.

This instructor's guide is designed to accompany self-paced student training modules on the Parts Counter Trade. Introductory materials include an introduction to pre-apprenticeship training, and a course outline. Teaching outlines are then provided for the 11 modules that comprise this course. For each module some or all of this material may be…

Computational Methods of Studying the Binding of Toxins From Venomous Animals to Biological Ion Channels: Theory and Applications

PubMed Central

Chen, Rong; Chung, Shin-Ho

2013-01-01

The discovery of new drugs that selectively block or modulate ion channels has great potential to provide new treatments for a host of conditions. One promising avenue revolves around modifying or mimicking certain naturally occurring ion channel modulator toxins. This strategy appears to offer the prospect of designing drugs that are both potent and specific. The use of computational modeling is crucial to this endeavor, as it has the potential to provide lower cost alternatives for exploring the effects of new compounds on ion channels. In addition, computational modeling can provide structural information and theoretical understanding that is not easily derivable from experimental results. In this review, we look at the theory and computational methods that are applicable to the study of ion channel modulators. The first section provides an introduction to various theoretical concepts, including force-fields and the statistical mechanics of binding. We then look at various computational techniques available to the researcher, including molecular dynamics, Brownian dynamics, and molecular docking systems. The latter section of the review explores applications of these techniques, concentrating on pore blocker and gating modifier toxins of potassium and sodium channels. After first discussing the structural features of these channels, and their modes of block, we provide an in-depth review of past computational work that has been carried out. Finally, we discuss prospects for future developments in the field. PMID:23589832

Suppressing effect of C a2 + blips on puff amplitudes by inhibiting channels to prevent recovery

NASA Astrophysics Data System (ADS)

Chen, Yuan; Qi, Hong; Li, Xiang; Cai, Meichun; Chen, Xingqiang; Liu, Wen; Shuai, Jianwei

2016-08-01

As local signals, calcium puffs arise from the concerted opening of a few nearby inositol 1,4,5-trisphospate receptor channels to release C a2 + ions from the endoplasmic reticulum. Although C a2 + puffs have been well studied, little is known about the modulation of cytosolic basal C a2 + concentration ([Ca2 +] Basal) on puff dynamics. In this paper we consider a puff model to study how the statistical properties of puffs are modulated by [Ca2 +] Basal. The puff frequency and lifetime trivially increase with the increasing [Ca2 +] Basal, but an unexpected result is that the puff amplitude and the maximum open-channel number of the puff show decreasing relationship with the increasing [Ca2 +] Basal. The underlying dynamics is related not only to the increasing puff frequency which gives a shorter recovery time, but also to the increasing frequency of blips with only one channel open. We indicate that C a2 + blips cause the channels to be inhibited and prevent their recovery during interpuff intervals, resulting in the suppressing effect on puff amplitudes. With increasing [Ca2 +] Basal, more blips occur to cause more channels to be inhibited, leaving fewer channels available for puff events. This study shows that the blips may play relevant functions in global C a2 + waves through modulating puff dynamics.

Fuel injection nozzle and method of manufacturing the same

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

Monaghan, James Christopher; Johnson, Thomas Edward; Ostebee, Heath Michael

A fuel injection head for use in a fuel injection nozzle comprises a monolithic body portion comprising an upstream face, an opposite downstream face, and a peripheral wall extending therebetween. A plurality of pre-mix tubes are integrally formed with and extend axially through the body portion. Each of the pre-mix tubes comprises an inlet adjacent the upstream face, an outlet adjacent the downstream face, and a channel extending between the inlet and the outlet. Each pre-mix tube also includes at least one fuel injector that at least partially extends outward from an exterior surface of the pre-mix tube, wherein themore » fuel injector is integrally formed with the pre-mix tube and is configured to facilitate fuel flow between the body portion and the channel.« less

Power module assemblies with staggered coolant channels

DOEpatents

Herron, Nicholas Hayden; Mann, Brooks S; Korich, Mark D

2013-07-16

A manifold is provided for supporting a power module assembly with a plurality of power modules. The manifold includes a first manifold section. The first face of the first manifold section is configured to receive the first power module, and the second face of the first manifold section defines a first cavity with a first baseplate thermally coupled to the first power module. The first face of the second manifold section is configured to receive the second power module, and the second face of the second manifold section defines a second cavity with a second baseplate thermally coupled to the second power module. The second face of the first manifold section and the second face of the second manifold section are coupled together such that the first cavity and the second cavity form a coolant channel. The first cavity is at least partially staggered with respect to second cavity.

Radar channel balancing with commutation

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

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.

Effect of scene illumination conditions on digital enhancement techniques of multispectral scanner LANDSAT images

NASA Technical Reports Server (NTRS)

Parada, N. D. J.; Novo, E. M. L. M.

1983-01-01

Two sets of MSS/LANDSAT data with solar elevation ranging from 22 deg to 41 deg were used at the Image-100 System to implement the Eliason et alii technique for extracting the topographic modulation component. An unsupervised cluster analysis was used to obtain an average brightness image for each channel. Analysis of the enhanced imaged shows that the technique for extracting topographic modulation component is more appropriated to MSS data obtained under high sun elevation ngles. Low sun elevation increases the variance of each cluster so that the average brightness doesn't represent its albedo proprties. The topographic modulation component applied to low sun elevation angle damages rather than enhance topographic information. Better results were produced for channels 4 and 5 than for channels 6 and 7.

An extensive investigation of work function modulated trapezoidal recessed channel MOSFET

NASA Astrophysics Data System (ADS)

Lenka, Annada Shankar; Mishra, Sikha; Mishra, Satyaranjan; Bhanja, Urmila; Mishra, Guru Prasad

2017-11-01

The concept of silicon on insulator (SOI) and grooved gate help to lessen the short channel effects (SCEs). Again the work function modulation along the metal gate gives a better drain current due to the uniform electric field along the channel. So all these concepts are combined and used in the proposed MOSFET structure for more improved performance. In this work, trapezoidal recessed channel silicon on insulator (TRC-SOI) MOSFET and work function modulated trapezoidal recessed channel silicon on insulator (WFM-TRC-SOI) MOSFET are compared with DC and RF parameters and later linearity of both the devices is tested. An analytical model is formulated by using a 2-D Poisson's equation and develops a compact equation for threshold voltage using minimum surface potential. In this work we analyze the effect of negative junction depth and the corner angle on various device parameters such as minimum surface potential, sub-threshold slope (SS), drain induced barrier lowering (DIBL) and threshold voltage. The analysis interprets that the switching performance of WFM-TRC-SOI MOSFET surpasses TRC-SOI MOSFET in terms of high Ion/Ioff ratio and also the proposed structure can minimize the short channel effects (SCEs) in RF application. The validity of proposed model has been verified with simulation result performed on Sentaurus TCAD device simulator.

Multidimensional Trellis Coded Phase Modulation Using a Multilevel Concatenation Approach. Part 2; Codes for AWGN and Fading Channels

NASA Technical Reports Server (NTRS)

Rajpal, Sandeep; Rhee, DoJun; Lin, Shu

1997-01-01

In this paper, we will use the construction technique proposed in to construct multidimensional trellis coded modulation (TCM) codes for both the additive white Gaussian noise (AWGN) and the fading channels. Analytical performance bounds and simulation results show that these codes perform very well and achieve significant coding gains over uncoded reference modulation systems. In addition, the proposed technique can be used to construct codes which have a performance/decoding complexity advantage over the codes listed in literature.

Frequency-specific attentional modulation in human primary auditory cortex and midbrain.

PubMed

Riecke, Lars; Peters, Judith C; Valente, Giancarlo; Poser, Benedikt A; Kemper, Valentin G; Formisano, Elia; Sorger, Bettina

2018-07-01

Paying selective attention to an audio frequency selectively enhances activity within primary auditory cortex (PAC) at the tonotopic site (frequency channel) representing that frequency. Animal PAC neurons achieve this 'frequency-specific attentional spotlight' by adapting their frequency tuning, yet comparable evidence in humans is scarce. Moreover, whether the spotlight operates in human midbrain is unknown. To address these issues, we studied the spectral tuning of frequency channels in human PAC and inferior colliculus (IC), using 7-T functional magnetic resonance imaging (FMRI) and frequency mapping, while participants focused on different frequency-specific sounds. We found that shifts in frequency-specific attention alter the response gain, but not tuning profile, of PAC frequency channels. The gain modulation was strongest in low-frequency channels and varied near-monotonically across the tonotopic axis, giving rise to the attentional spotlight. We observed less prominent, non-tonotopic spatial patterns of attentional modulation in IC. These results indicate that the frequency-specific attentional spotlight in human PAC as measured with FMRI arises primarily from tonotopic gain modulation, rather than adapted frequency tuning. Moreover, frequency-specific attentional modulation of afferent sound processing in human IC seems to be considerably weaker, suggesting that the spotlight diminishes toward this lower-order processing stage. Our study sheds light on how the human auditory pathway adapts to the different demands of selective hearing. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Iron overload causes endolysosomal deficits modulated by NAADP-regulated 2-pore channels and RAB7A

PubMed Central

Fernández, Belén; Fdez, Elena; Gómez-Suaga, Patricia; Gil, Fernando; Molina-Villalba, Isabel; Ferrer, Isidro; Patel, Sandip; Churchill, Grant C.; Hilfiker, Sabine

2016-01-01

ABSTRACT Various neurodegenerative disorders are associated with increased brain iron content. Iron is known to cause oxidative stress, which concomitantly promotes cell death. Whereas endolysosomes are known to serve as intracellular iron storage organelles, the consequences of increased iron on endolysosomal functioning, and effects on cell viability upon modulation of endolysosomal iron release remain largely unknown. Here, we show that increasing intracellular iron causes endolysosomal alterations associated with impaired autophagic clearance of intracellular protein aggregates, increased cytosolic oxidative stress and increased cell death. These effects are subject to regulation by NAADP, a potent second messenger reported to target endolysosomal TPCNs (2-pore channels). Consistent with endolysosomal iron storage, cytosolic iron levels are modulated by NAADP, and increased cytosolic iron is detected when overexpressing active, but not inactive TPCNs, indicating that these channels can modulate endolysosomal iron release. Cell death triggered by altered intralysosomal iron handling is abrogated in the presence of an NAADP antagonist or when inhibiting RAB7A activity. Taken together, our results suggest that increased endolysosomal iron causes cell death associated with increased cytosolic oxidative stress as well as autophagic impairments, and these effects are subject to modulation by endolysosomal ion channel activity in a RAB7A-dependent manner. These data highlight alternative therapeutic strategies for neurodegenerative disorders associated with increased intracellular iron load. PMID:27383256

SK3/TRPC1/Orai1 complex regulates SOCE-dependent colon cancer cell migration: a novel opportunity to modulate anti-EGFR mAb action by the alkyl-lipid Ohmline

PubMed Central

Guéguinou, Maxime; Harnois, Thomas; Crottes, David; Uguen, Arnaud; Deliot, Nadine; Gambade, Audrey; Chantôme, Aurélie; Haelters, Jean Pierre; Jaffrès, Paul Alain; Jourdan, Marie Lise; Weber, Günther; Soriani, Olivier; Bougnoux, Philippe; Mignen, Olivier; Bourmeyster, Nicolas; Constantin, Bruno; Lecomte, Thierry

2016-01-01

Background Barely 10-20% of patients with metastatic colorectal cancer (mCRC) receive a clinical benefit from the use of anti-EGFR monoclonal antibodies (mAbs). We hypothesized that this could depends on their efficiency to reduce Store Operated Calcium Entry (SOCE) that are known to enhance cancer cells. Results In the present study, we demonstrate that SOCE promotes migration of colon cancer cell following the formation of a lipid raft ion channel complex composed of TRPC1/Orai1 and SK3 channels. Formation of this complex is stimulated by the phosphorylation of the reticular protein STIM1 by EGF and activation of the Akt pathway. Our data show that, in a positive feedback loop SOCE activates both Akt pathway and SK3 channel activity which lead to SOCE amplification. This amplification occurs through the activation of Rac1/Calpain mediated by Akt. We also show that Anti-EGFR mAbs can modulate SOCE and cancer cell migration through the Akt pathway. Interestingly, the alkyl-lipid Ohmline, which we previously showed to be an inhibitor of SK3 channel, can dissociated the lipid raft ion channel complex through decreased phosphorylation of Akt and modulation of mAbs action. Conclusions This study demonstrates that the inhibition of the SOCE-dependent colon cancer cell migration trough SK3/TRPC1/Orai1 channel complex by the alkyl-lipid Ohmline may be a novel strategy to modulate Anti-EGFR mAb action in mCRC. PMID:27102434

Performance improvement of PEFC modules with cell containing low amount of platinum

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

Miyake, Y.; Kadowaki, M.; Hamada, A.

1996-12-31

Cell components of the PEFC module were studied to improve the module performance. The cell performance in a high air utilization region was improved by selecting an air channel design of the separator in which high air flow speed was obtained. Optimization of Teflon{reg_sign} amount on the cathode backing carbon paper also contributed the cell performance. Modifications of the gas channel design and the backing carbon paper were carried out in a 200 cm{sup 2} x 20-cell module and 36-cell module. Dependence of air utilization on module performance was remarkably improved and power density of more than 0.3 W/cm{sup 2}more » was achieved in spite of the platinum amount in the cells was decreased to 1.1 Mg/cm{sup 2}.« less

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

NASA Technical Reports Server (NTRS)

Lin, Shu; Rhee, Dojun

1996-01-01

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

1060-nm VCSEL-based parallel-optical modules for optical interconnects

NASA Astrophysics Data System (ADS)

Nishimura, N.; Nagashima, K.; Kise, T.; Rizky, A. F.; Uemura, T.; Nekado, Y.; Ishikawa, Y.; Nasu, H.

2015-03-01

The capability of mounting a parallel-optical module onto a PCB through solder-reflow process contributes to reduce the number of piece parts, simplify its assembly process, and minimize a foot print for both AOC and on-board applications. We introduce solder-reflow-capable parallel-optical modules employing 1060-nm InGaAs/GaAs VCSEL which leads to the advantages of realizing wider modulation bandwidth, longer transmission distance, and higher reliability. We demonstrate 4-channel parallel optical link performance operated at a bit stream of 28 Gb/s 231-1 PRBS for each channel and transmitted through a 50-μm-core MMF beyond 500 m. We also introduce a new mounting technology of paralleloptical module to realize maintaining good coupling and robust electrical connection during solder-reflow process between an optical module and a polymer-waveguide-embedded PCB.

The Sodium-Activated Potassium Channel Slack Is Required for Optimal Cognitive Flexibility in Mice

ERIC Educational Resources Information Center

Bausch, Anne E.; Dieter, Rebekka; Nann, Yvette; Hausmann, Mario; Meyerdierks, Nora; Kaczmarek, Leonard K.; Ruth, Peter; Lukowski, Robert

2015-01-01

"Kcnt1" encoded sodium-activated potassium channels (Slack channels) are highly expressed throughout the brain where they modulate the firing patterns and general excitability of many types of neurons. Increasing evidence suggests that Slack channels may be important for higher brain functions such as cognition and normal intellectual…

G-protein-coupled inward rectifier potassium channels involved in corticostriatal presynaptic modulation.

PubMed

Meneses, David; Mateos, Verónica; Islas, Gustavo; Barral, Jaime

2015-09-01

Presynaptic modulation has been associated mainly with calcium channels but recent data suggests that inward rectifier potassium channels (K(IR)) also play a role. In this work we set to characterize the role of presynaptic K(IR) channels in corticostriatal synaptic transmission. We elicited synaptic potentials in striatum by stimulating cortical areas and then determined the synaptic responses of corticostriatal synapsis by using paired pulse ratio (PPR) in the presence and absence of several potassium channel blockers. Unspecific potassium channels blockers Ba(2+) and Cs(+) reduced the PPR, suggesting that these channels are presynaptically located. Further pharmacological characterization showed that application of tertiapin-Q, a specific K(IR)3 channel family blocker, also induced a reduction of PPR, suggesting that K(IR)3 channels are present at corticostriatal terminals. In contrast, exposure to Lq2, a specific K(IR)1.1 inward rectifier potassium channel, did not induce any change in PPR suggesting the absence of these channels in the presynaptic corticostriatal terminals. Our results indicate that K(IR)3 channels are functionally expressed at the corticostriatal synapses, since blockage of these channels result in PPR decrease. Our results also help to explain how synaptic activity may become sensitive to extracellular signals mediated by G-protein coupled receptors. A vast repertoire of receptors may influence neurotransmitter release in an indirect manner through regulation of K(IR)3 channels. © 2015 Wiley Periodicals, Inc.

Study of information transfer optimization for communication satellites

NASA Technical Reports Server (NTRS)

Odenwalder, J. P.; Viterbi, A. J.; Jacobs, I. M.; Heller, J. A.

1973-01-01

The results are presented of a study of source coding, modulation/channel coding, and systems techniques for application to teleconferencing over high data rate digital communication satellite links. Simultaneous transmission of video, voice, data, and/or graphics is possible in various teleconferencing modes and one-way, two-way, and broadcast modes are considered. A satellite channel model including filters, limiter, a TWT, detectors, and an optimized equalizer is treated in detail. A complete analysis is presented for one set of system assumptions which exclude nonlinear gain and phase distortion in the TWT. Modulation, demodulation, and channel coding are considered, based on an additive white Gaussian noise channel model which is an idealization of an equalized channel. Source coding with emphasis on video data compression is reviewed, and the experimental facility utilized to test promising techniques is fully described.

Teacher Preparation for Movement Education: Increasing Pre-Service Teachers' Competence for Working with Young Children

ERIC Educational Resources Information Center

Sevimli-Celik, Serap; Johnson, James E.

2016-01-01

This study explores pre-service teachers' perceptions of movement education, the benefits they perceive from participating in a 12-week movement education module in a course on play, and the module's effects on their confidence and competence in regard to incorporating movement into a curriculum. Findings suggest that the pre-service teachers…

An Interdisciplinary Approach to Designing Online Learning: Fostering Pre-Service Mathematics Teachers' Capabilities in Mathematical Modelling

ERIC Educational Resources Information Center

Geiger, Vince; Mulligan, Joanne; Date-Huxtable, Liz; Ahlip, Rehez; Jones, D. Heath; May, E. Julian; Rylands, Leanne; Wright, Ian

2018-01-01

In this article we describe and evaluate processes utilized to develop an online learning module on mathematical modelling for pre-service teachers. The module development process involved a range of professionals working within the STEM disciplines including mathematics and science educators, mathematicians, scientists, in-service and pre-service…

Occupational Safety. Hygiene Safety. Pre-Apprenticeship Phase 1 Training.

ERIC Educational Resources Information Center

Lane Community Coll., Eugene, OR.

This self-paced student training module on hygiene safety is one of a number of modules developed for Pre-apprenticeship Phase 1 Training. Purpose of the module is to familiarize students with the different types of airborne contaminants--including noise--which may be health hazards and with the proper hygienic measures for dealing with them. The…

Environmental Education: Module for Pre-Service Training of Teachers and Supervisors for Primary Schools. Environmental Educational Series 5.

ERIC Educational Resources Information Center

United Nations Educational, Scientific and Cultural Organization, Paris (France). Div. of Science, Technical and Vocational Education.

A series of experimental modules for teachers has been developed under the direction of the International Environmental Education Programme (IEEP) of UNESCO. This particular module focuses on the pre-service training of elementary school teachers and supervisors in environmental education. Section 1, Content for Environmental Education, traces the…

Vibration Sensitivity of a Wide-Temperature Electronically Scanned Pressure Measurement (ESP) Module

NASA Technical Reports Server (NTRS)

Zuckerwar, Allan J.; Garza, Frederico R.

2001-01-01

A vibration sensitivity test was conducted on a Wide-Temperature ESP module. The test object was Module "M4," a 16-channel, 4 psi unit scheduled for installation in the Arc Sector of NTF. The module was installed on a vibration exciter and loaded to positive then negative full-scale pressures (+/-2.5 psid). Test variables were the following: Vibration frequencies: 20, 55, 75 Hz. Vibration level: 1 g. Vibration axes: X, Y, Z. The pressure response was measured on each channel, first without and then with the vibration turned on, and the difference analyzed by means of the statistical t-test. The results show that the vibration sensitivity does not exceed 0.01% Full Scale Output per g (with the exception of one channel on one axis) to a 95 percent confidence level. This specification, limited by the resolution of the pressure source, lies well below the total uncertainty specification of 0.1 percent Full Scale Output.

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

PubMed

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

2017-01-01

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

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

PubMed Central

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

2017-01-01

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

Frequency Hopping, Multiple Frequency-Shift Keying, Coding, and Optimal Partial-Band Jamming.

DTIC Science & Technology

1982-08-01

receivers appropriate for these two strategies. Each receiver is noncoherent (a coherent receiver is generally impractical) and implements hard...Advances in Coding and Modulation for Noncoherent Channels Affected by Fading, Partial Band, and Multiple- . Access Interference, in A. J. Viterbi...Modulation for Noncoherent Channels Affected by Fading, Partial Band, and Multiple-Access interference, in A. J. Viterbi, ed., Advances in Coumunication

Relative Time-scale for Channeling Events Within Chaotic Terrains, Margaritifer Sinus, Mars

NASA Technical Reports Server (NTRS)

Janke, D.

1985-01-01

A relative time scale for ordering channel and chaos forming events was constructed for areas within the Margaritifer Sinus region of Mars. Transection and superposition relationships of channels, chaotic terrain, and the surfaces surrounding them were used to create the relative time scale; crater density studies were not used. Channels and chaos in contact with one another were treated as systems. These systems were in turn treated both separately (in order to understand internal relationships) and as members of the suite of Martian erosional forms (in order to produce a combined, master time scale). Channeling events associated with chaotic terrain development occurred over an extended geomorphic period. The channels can be divided into three convenient groups: those that pre-date intercrater plains development post-plains, pre-chasma systems; and those associated with the development of the Vallis Marineris chasmata. No correlations with cyclic climatic changes, major geologic events in other regions on Mars, or triggering phenomena (for example, specific impact events) were found.

Sexy DEG/ENaC channels involved in gustatory detection of fruit fly pheromones.

PubMed

Pikielny, Claudio W

2012-11-06

Hydrocarbon pheromones on the cuticle of Drosophila melanogaster modulate the complex courtship behavior of males. Recently, three members of the degenerin/epithelial Na+ channel (DEG/ENaC) family of sodium channel subunits, Ppk25, Ppk23, and Ppk29 (also known as Nope), have been shown to function in gustatory perception of courtship-modulating contact pheromones. All three proteins are required for the activation of male courtship by female pheromones. Specific interactions between two of them have been demonstrated in cultured cells, suggesting that, in a subset of cells where they are coexpressed, these three subunits function within a common heterotrimeric DEG/ENaC channel. Such a DEG/ENaC channel may be gated by pheromones, either directly or indirectly, or alternatively may control the excitability of pheromone-sensing cells. In addition, these studies identify taste neurons that respond specifically to courtship-modulating pheromones and mediate their effects on male behavior. Two types of pheromone-sensing taste neurons, F and M cells, have been defined on the basis of their specific response to either female or male pheromones. These reports set the stage for the dissection of the molecular and cellular mechanisms that mediate gustatory detection of contact pheromones.

47 CFR 101.811 - Modulation requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... signaling on frequencies below 500 MHz is not authorized. (b) When amplitude modulation is used, the... frequency modulation is used for single channel radiotelephony on frequencies below 500 MHz, the deviation... 47 Telecommunication 5 2010-10-01 2010-10-01 false Modulation requirements. 101.811 Section 101...

Characteristics of III-nitride based laser diode employed for short range underwater wireless optical communications

NASA Astrophysics Data System (ADS)

Xue, Bin; Liu, Zhe; Yang, Jie; Feng, Liangsen; Zhang, Ning; Wang, Junxi; Li, Jinmin

2018-03-01

An off-the-shelf green laser diode (LD) was measured to investigate its temperature dependent characteristics. Performance of the device was severely restricted by rising temperature in terms of increasing threshold current and decreasing modulation bandwidth. The observation reveals that dynamic characteristics of the LD is sensitive to temperature. Influence of light attenuation on the modulation bandwidth of the green LD was also studied. The impact of light attenuation on the modulation bandwidth of the LD in short and low turbid water channel was not obvious while slight difference in modulation bandwidth under same injection level was observed between water channel and free space even at short range.

Multiple frequency optical mixer and demultiplexer and apparatus for remote sensing

NASA Technical Reports Server (NTRS)

Chen, Jeffrey R. (Inventor)

2010-01-01

A pulsed laser system includes a modulator module configured to provide pulsed electrical signals and a plurality of solid-state seed sources coupled to the modulator module and configured to operate, responsive to the pulsed electrical signals, in a pulse mode. Each of the plurality of solid-state seed sources is tuned to a different frequency channel separated from any adjacent frequency channel by a frequency offset. The pulsed laser system also includes a combiner that combines outputs from each of the solid state seed sources into a single optical path and an optical doubler and demultiplexer coupled to the single optical path and providing each doubled seed frequency on a separate output path.

Device for modular input high-speed multi-channel digitizing of electrical data

DOEpatents

VanDeusen, Alan L.; Crist, Charles E.

1995-09-26

A multi-channel high-speed digitizer module converts a plurality of analog signals to digital signals (digitizing) and stores the signals in a memory device. The analog input channels are digitized simultaneously at high speed with a relatively large number of on-board memory data points per channel. The module provides an automated calibration based upon a single voltage reference source. Low signal noise at such a high density and sample rate is accomplished by ensuring the A/D converters are clocked at the same point in the noise cycle each time so that synchronous noise sampling occurs. This sampling process, in conjunction with an automated calibration, yields signal noise levels well below the noise level present on the analog reference voltages.

Expression and effects of modulation of the K2P potassium channels TREK-1 (KCNK2) and TREK-2 (KCNK10) in the normal human ovary and epithelial ovarian cancer.

PubMed

Innamaa, A; Jackson, L; Asher, V; van Schalkwyk, G; Warren, A; Keightley, A; Hay, D; Bali, A; Sowter, H; Khan, R

2013-11-01

Aberrant expression of potassium (K(+)) channels contributes to cancer cell proliferation and apoptosis, and K(+) channel blockers can inhibit cell proliferation. TREK-1 and -2 belong to the two-pore domain (K2P) superfamily. We report TREK-1 and -2 expression in ovarian cancer and normal ovaries, and the effects of TREK-1 modulators on cell proliferation and apoptosis. The cellular localisation of TREK-1 and -2 was investigated by immunofluorescence in SKOV-3 and OVCAR-3 cell lines and in cultured ovarian surface epithelium and cancer. Channel expression in normal ovaries and cancer was quantified by western blotting. Immunohistochemical analysis demonstrated the association between channel expression and disease prognosis, stage, and grade. TREK-1 modulation of cell proliferation in the cell lines was investigated with the MTS-assay and the effect on apoptosis determined using flow cytometry. Expression was identified in both cell lines, ovarian cancer (n = 22) and normal ovaries (n = 6). IHC demonstrated positive staining for TREK-1 and -2 in 95.7 % of tumours (n = 69) and 100 % of normal ovaries (n = 9). A reduction in cell proliferation (P < 0.05) was demonstrated at 96 h in SKOV-3 and OVCAR-3 cells incubated TREK-1 modulating agents. Curcumin caused a significant reduction in early apoptosis in SKOV-3 (P < 0.001) and OVCAR-3 (P < 0.0001) cells and a significant increase in late apoptosis in SKOV-3 (P < 0.01) and OVCAR-3 cells (P < 0.0001). TREK-1 and -2 are expressed in normal ovaries and ovarian cancer. TREK-1 modulators have a significant effect on cell proliferation and apoptosis. We propose investigation of the therapeutic potential of TREK-1 blockers is warranted.

Nitroxyl inhibits overt pain-like behavior in mice: role of cGMP/PKG/ATP-sensitive potassium channel signaling pathway

PubMed Central

Staurengo-Ferrari, Larissa; Zarpelon, Ana C.; Longhi-Balbinot, Daniela T.; Marchesi, Mario; Cunha, Thiago M.; Alves-Filho, José C.; Cunha, Fernando Q.; Ferreira, Sergio H.; Casagrande, Rubia; Miranda, Katrina M.; Verri, Waldiceu A.

2014-01-01

Background Several lines of evidence have indicated that nitric oxide (NO) plays complex and diverse roles in modulation of pain/analgesia. However, the roles of charged and uncharged congeners of NO are less well understood. In the present study, the antinociceptive effect of the nitroxyl (HNO) donor, Angeli’s salt (Na2N2O3; AS) was investigated in models of overt pain-like behavior. Moreover, whether the antinociceptive effect of nitroxyl was dependent on the activation of cGMP (cyclic guanosine monophosphate)/PKG (protein kinase G)/ATP-sensitive potassium channels was addressed. Methods The antinociceptive effect of AS was evaluated on phenyl-p-benzoquinone (PBQ)- and acetic acid-induced writhings and via the formalin test. In addition, pharmacological treatments targeting guanylate cyclase (ODQ), PKG (KT5923) and ATP-sensitive potassium channel (glybenclamide) were used. Results PBQ and acetic acid induced significant writhing responses over 20 min. The nociceptive response in these models were significantly reduced in a dose-dependent manner by subcutaneous pre-treatment with AS. Furthermore, AS also inhibited both phases of the formalin test. Subsequently, the inhibitory effect of AS in writhing and flinching responses were prevented by ODQ, KT5823 and glybenclamide, although these inhibitors alone did not alter the writhing score. Furthermore, pretreatment with L-cysteine, an HNO scavenger, confirmed that the antinociceptive effect of AS depends on HNO. Conclusion The present study demonstrates the efficacy of a nitroxyl donor and its analgesic mechanisms in overt pain-like behavior by activating the cGMP/PKG/ATP-sensitive potassium channel (K+) signaling pathway. PMID:24948073

Increases in reactive oxygen species enhance vascular endothelial cell migration through a mechanism dependent on the transient receptor potential melastatin 4 ion channel.

PubMed

Sarmiento, Daniela; Montorfano, Ignacio; Cerda, Oscar; Cáceres, Mónica; Becerra, Alvaro; Cabello-Verrugio, Claudio; Elorza, Alvaro A; Riedel, Claudia; Tapia, Pablo; Velásquez, Luis A; Varela, Diego; Simon, Felipe

2015-03-01

A hallmark of severe inflammation is reactive oxygen species (ROS) overproduction induced by increased inflammatory mediators secretion. During systemic inflammation, inflammation mediators circulating in the bloodstream interact with endothelial cells (ECs) raising intracellular oxidative stress at the endothelial monolayer. Oxidative stress mediates several pathological functions, including an exacerbated EC migration. Because cell migration critically depends on calcium channel-mediated Ca(2+) influx, the molecular identification of the calcium channel involved in oxidative stress-modulated EC migration has been the subject of intense investigation. The transient receptor potential melastatin 4 (TRPM4) protein is a ROS-modulated non-selective cationic channel that performs several cell functions, including regulating intracellular Ca(2+) overload and Ca(2+) oscillation. This channel is expressed in multiple tissues, including ECs, and contributes to the migration of certain immune cells. However, whether the TRPM4 ion channel participates in oxidative stress-mediated EC migration is not known. Herein, we investigate whether oxidative stress initiates or enhances EC migration and study the role played by the ROS-modulated TRPM4 ion channel in oxidative stress-mediated EC migration. We demonstrate that oxidative stress enhances, but does not initiate, EC migration in a dose-dependent manner. Notably, we demonstrate that the TRPM4 ion channel is critical in promoting H2O2-enhanced EC migration. These results show that TRPM4 is a novel pharmacological target for the possible treatment of severe inflammation and other oxidative stress-mediated inflammatory diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

Enhanced pre-synaptic glutamate release in deep-dorsal horn contributes to calcium channel alpha-2-delta-1 protein-mediated spinal sensitization and behavioral hypersensitivity

PubMed Central

Nguyen, David; Deng, Ping; Matthews, Elizabeth A; Kim, Doo-Sik; Feng, Guoping; Dickenson, Anthony H; Xu, Zao C; Luo, Z David

2009-01-01

Nerve injury-induced expression of the spinal calcium channel alpha-2-delta-1 subunit (Cavα2δ1) has been shown to mediate behavioral hypersensitivity through a yet identified mechanism. We examined if this neuroplasticity modulates behavioral hypersensitivity by regulating spinal glutamatergic neurotransmission in injury-free transgenic mice overexpressing the Cavα2δ1 proteins in neuronal tissues. The transgenic mice exhibited hypersensitivity to mechanical stimulation (allodynia) similar to the spinal nerve ligation injury model. Intrathecally delivered antagonists for N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptors, but not for the metabotropic glutamate receptors, caused a dose-dependent allodynia reversal in the transgenic mice without changing the behavioral sensitivity in wild-type mice. This suggests that elevated spinal Cavα2δ1 mediates allodynia through a pathway involving activation of selective glutamate receptors. To determine if this is mediated by enhanced spinal neuronal excitability or pre-synaptic glutamate release in deep-dorsal horn, we examined wide-dynamic-range (WDR) neuron excitability with extracellular recording and glutamate-mediated excitatory postsynaptic currents with whole-cell patch recording in deep-dorsal horn of the Cavα2δ1 transgenic mice. Our data indicated that overexpression of Cavα2δ1 in neuronal tissues led to increased frequency, but not amplitude, of miniature excitatory post synaptic currents mediated mainly by AMPA/kainate receptors at physiological membrane potentials, and also by NMDA receptors upon depolarization, without changing the excitability of WDR neurons to high intensity stimulation. Together, these findings support a mechanism of Cavα2δ1-mediated spinal sensitization in which elevated Cavα2δ1 causes increased pre-synaptic glutamate release that leads to reduced excitation thresholds of post-synaptic dorsal horn neurons to innocuous stimuli. This spinal sensitization mechanism may mediate at least partially the neuropathic pain states derived from increased pre-synaptic Cavα2δ1 expression. PMID:19216737

DPSK-3ASK transmission optimization by adapting modulation levels

NASA Astrophysics Data System (ADS)

Eiselt, Michael H.; Teipen, Brian T.

2008-11-01

For metro and regional 100-Gbps transmission, a transparent channel reach of 500-600 km is required and a 100-GHz channel grid is typically used. For these applications, a cost effective modulation format is introduced which can make use of electronic components designed for the already established 40-Gbps market, bypassing the requirements for novel electronic developments and therefore reducing the component cost. With this DPSK-3ASK modulation format, five information bits are transmitted in two consecutive symbols, leading to a symbol rate of 45 Gbaud, including overhead for framing and FEC. To minimize hardware requirements and to create a cost-effective solution, a single Mach-Zehnder modulator can be used to create the optical DPSK-3ASK signal after combining the phase and amplitude modulation signals into a 6-level modulator drive voltage. In this paper, it is demonstrated by numerical simulations that these voltage levels can be modified to adapt to varying signal distortions and thereby yield improved transmission performance. It is shown that by dynamically modifying the modulation levels based on the channel performance, dynamic signal impairments such as the non-linear effects from varying power levels, changes in chromatic dispersion, or varying PMD levels can be mitigated. Error-free performance (with FEC) can be obtained with 24 dB OSNR and 7ps DGD for a 112-Gbps (45-Gbaud) optical signal.

Appropriate Work Habits and Attitudes. Pre-Apprenticeship Phase 1 Training.

ERIC Educational Resources Information Center

Lane Community Coll., Eugene, OR.

This self-paced student training module on work attitudes and habits is one of a number of modules developed for Pre-apprenticeship Phase 1 Training. Purpose of the module is to make students aware of the importance of developing appropriate work habits and attitudes and to teach them how best to prove these to fellow workers, supervisors, and…

A Self Rating Scale as a Pre and Post Assessment Tool for Use with Instructional Modules.

ERIC Educational Resources Information Center

Gotts, Sandra Harris

This article describes a self rating pre- and post-assessment instrument that has been developed at the Central Michigan University (CMU). Nine instructional modules have been developed and are being used in science methods courses at CMU. Each module focuses on an identified area of competency for elementary science teachers and contains a…

Using Participatory Action Research to Develop a Course Module on Education for Sustainable Development in Pre-Service Chemistry Teacher Education

ERIC Educational Resources Information Center

Burmeister, Mareike; Eilks, Ingo

2013-01-01

This paper describes the development of a course module on sustainability issues and Education for Sustainable Development in German pre-service chemistry teacher education. The module was inspired by empirical research findings about the knowledge base of student teachers. It was created and cyclically refined using Participatory Action Research.…

Physiological modulators of Kv3.1 channels adjust firing patterns of auditory brain stem neurons.

PubMed

Brown, Maile R; El-Hassar, Lynda; Zhang, Yalan; Alvaro, Giuseppe; Large, Charles H; Kaczmarek, Leonard K

2016-07-01

Many rapidly firing neurons, including those in the medial nucleus of the trapezoid body (MNTB) in the auditory brain stem, express "high threshold" voltage-gated Kv3.1 potassium channels that activate only at positive potentials and are required for stimuli to generate rapid trains of actions potentials. We now describe the actions of two imidazolidinedione derivatives, AUT1 and AUT2, which modulate Kv3.1 channels. Using Chinese hamster ovary cells stably expressing rat Kv3.1 channels, we found that lower concentrations of these compounds shift the voltage of activation of Kv3.1 currents toward negative potentials, increasing currents evoked by depolarization from typical neuronal resting potentials. Single-channel recordings also showed that AUT1 shifted the open probability of Kv3.1 to more negative potentials. Higher concentrations of AUT2 also shifted inactivation to negative potentials. The effects of lower and higher concentrations could be mimicked in numerical simulations by increasing rates of activation and inactivation respectively, with no change in intrinsic voltage dependence. In brain slice recordings of mouse MNTB neurons, both AUT1 and AUT2 modulated firing rate at high rates of stimulation, a result predicted by numerical simulations. Our results suggest that pharmaceutical modulation of Kv3.1 currents represents a novel avenue for manipulation of neuronal excitability and has the potential for therapeutic benefit in the treatment of hearing disorders. Copyright © 2016 the American Physiological Society.

Physiological modulators of Kv3.1 channels adjust firing patterns of auditory brain stem neurons

PubMed Central

Brown, Maile R.; El-Hassar, Lynda; Zhang, Yalan; Alvaro, Giuseppe; Large, Charles H.

2016-01-01

Many rapidly firing neurons, including those in the medial nucleus of the trapezoid body (MNTB) in the auditory brain stem, express “high threshold” voltage-gated Kv3.1 potassium channels that activate only at positive potentials and are required for stimuli to generate rapid trains of actions potentials. We now describe the actions of two imidazolidinedione derivatives, AUT1 and AUT2, which modulate Kv3.1 channels. Using Chinese hamster ovary cells stably expressing rat Kv3.1 channels, we found that lower concentrations of these compounds shift the voltage of activation of Kv3.1 currents toward negative potentials, increasing currents evoked by depolarization from typical neuronal resting potentials. Single-channel recordings also showed that AUT1 shifted the open probability of Kv3.1 to more negative potentials. Higher concentrations of AUT2 also shifted inactivation to negative potentials. The effects of lower and higher concentrations could be mimicked in numerical simulations by increasing rates of activation and inactivation respectively, with no change in intrinsic voltage dependence. In brain slice recordings of mouse MNTB neurons, both AUT1 and AUT2 modulated firing rate at high rates of stimulation, a result predicted by numerical simulations. Our results suggest that pharmaceutical modulation of Kv3.1 currents represents a novel avenue for manipulation of neuronal excitability and has the potential for therapeutic benefit in the treatment of hearing disorders. PMID:27052580

Trace metals in the brain: allosteric modulators of ligand-gated receptor channels, the case of ATP-gated P2X receptors.

PubMed

Huidobro-Toro, J Pablo; Lorca, Ramón A; Coddou, Claudio

2008-03-01

Zinc and copper are indispensable trace metals for life with a recognized role as catalysts in enzyme actions. We now review evidence supporting the role of trace metals as novel allosteric modulators of ionotropic receptors: a new and fundamental physiological role for zinc and copper in neuronal and brain excitability. The review is focussed on ionotropic receptor channels including nucleotide receptors, in particular the P2X receptor family. Since zinc and copper are stored within synaptic vesicles in selected brain regions, and released to the synaptic cleft upon electrical nerve ending depolarization, it is plausible that zinc and copper reach concentrations in the synapse that profoundly affect ligand-gated ionic channels, including the ATP-gated currents of P2X receptors. The identification of key P2X receptor amino acids that act as ligands for trace metal coordination, carves the structural determinants underlying the allosteric nature of the trace metal modulation. The recognition that the identified key residues such as histidines, aspartic and glutamic acids or cysteines in the extracellular domain are different for each P2X receptor subtype and may be different for each metal, highlights the notion that each P2X receptor subtype evolved independent strategies for metal coordination, which form upon the proper three-dimensional folding of the receptor channels. The understanding of the molecular mechanism of allosteric modulation of ligand-operated ionic channels by trace metals is a new contribution to metallo-neurobiology.

Gating current studies reveal both intra- and extracellular cation modulation of K+ channel deactivation

PubMed Central

Wang, Zhuren; Zhang, Xue; Fedida, David

1999-01-01

The presence of permeant ions can modulate the rate of gating charge return in wild-type human heart K+ (hKv1.5) channels. Here we employ gating current measurements in a non-conducting mutant, W472F, of the hKv1.5 channel to investigate how different cations can modulate charge return and whether the actions can be specifically localized at the internal as well as the external mouth of the channel pore. Intracellular cations were effective at accelerating charge return in the sequence Cs+ > Rb+ > K+ > Na+ > NMG+. Extracellular cations accelerated charge return with the selectivity sequence Cs+ > Rb+ > Na+ = NMG+. Intracellular and extracellular cation actions were of relatively low affinity. The Kd for preventing slowing of the time constant of the off-gating current decay (τoff) was 20.2 mM for intracellular Cs+ (Csi+) and 358 mM for extracellular Cs+ (Cso+). Both intracellular and extracellular cations can regulate the rate of charge return during deactivation of hKv1.5, but intracellular cations are more effective. We suggest that ion crystal radius is an important determinant of this action, with larger ions preventing slowing more effectively. Important parallels exist with cation-dependent modulation of slow inactivation of ionic currents in this channel. However, further experiments are required to understand the exact relationship between acceleration of charge return and the slowing of inactivation of ionic currents by cations. PMID:10050001

Self-balanced modulation and magnetic rebalancing method for parallel multilevel inverters

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

Li, Hui; Shi, Yanjun

A self-balanced modulation method and a closed-loop magnetic flux rebalancing control method for parallel multilevel inverters. The combination of the two methods provides for balancing of the magnetic flux of the inter-cell transformers (ICTs) of the parallel multilevel inverters without deteriorating the quality of the output voltage. In various embodiments a parallel multi-level inverter modulator is provide including a multi-channel comparator to generate a multiplexed digitized ideal waveform for a parallel multi-level inverter and a finite state machine (FSM) module coupled to the parallel multi-channel comparator, the FSM module to receive the multiplexed digitized ideal waveform and to generate amore » pulse width modulated gate-drive signal for each switching device of the parallel multi-level inverter. The system and method provides for optimization of the output voltage spectrum without influence the magnetic balancing.« less

Blind equalization and automatic modulation classification based on subspace for subcarrier MPSK optical communications

NASA Astrophysics Data System (ADS)

Chen, Dan; Guo, Lin-yuan; Wang, Chen-hao; Ke, Xi-zheng

2017-07-01

Equalization can compensate channel distortion caused by channel multipath effects, and effectively improve convergent of modulation constellation diagram in optical wireless system. In this paper, the subspace blind equalization algorithm is used to preprocess M-ary phase shift keying (MPSK) subcarrier modulation signal in receiver. Mountain clustering is adopted to get the clustering centers of MPSK modulation constellation diagram, and the modulation order is automatically identified through the k-nearest neighbor (KNN) classifier. The experiment has been done under four different weather conditions. Experimental results show that the convergent of constellation diagram is improved effectively after using the subspace blind equalization algorithm, which means that the accuracy of modulation recognition is increased. The correct recognition rate of 16PSK can be up to 85% in any kind of weather condition which is mentioned in paper. Meanwhile, the correct recognition rate is the highest in cloudy and the lowest in heavy rain condition.

X-ray structure of the mammalian GIRK2-βγ G-protein complex

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

Whorton, Matthew R.; MacKinnon, Roderick

2013-07-30

G-protein-gated inward rectifier K + (GIRK) channels allow neurotransmitters, through G-protein-coupled receptor stimulation, to control cellular electrical excitability. In cardiac and neuronal cells this control regulates heart rate and neural circuit activity, respectively. Here we present the 3.5Å resolution crystal structure of the mammalian GIRK2 channel in complex with βγ G-protein subunits, the central signalling complex that links G-protein-coupled receptor stimulation to K + channel activity. Short-range atomic and long-range electrostatic interactions stabilize four βγ G-protein subunits at the interfaces between four K + channel subunits, inducing a pre-open state of the channel. The pre-open state exhibits a conformation thatmore » is intermediate between the closed conformation and the open conformation of the constitutively active mutant. The resultant structural picture is compatible with ‘membrane delimited’ activation of GIRK channels by G proteins and the characteristic burst kinetics of channel gating. The structures also permit a conceptual understanding of how the signalling lipid phosphatidylinositol-4,5-bisphosphate (PIP 2) and intracellular Na + ions participate in multi-ligand regulation of GIRK channels.« less

Cloud screening Coastal Zone Color Scanner images using channel 5

NASA Technical Reports Server (NTRS)

Eckstein, B. A.; Simpson, J. J.

1991-01-01

Clouds are removed from Coastal Zone Color Scanner (CZCS) data using channel 5. Instrumentation problems require pre-processing of channel 5 before an intelligent cloud-screening algorithm can be used. For example, at intervals of about 16 lines, the sensor records anomalously low radiances. Moreover, the calibration equation yields negative radiances when the sensor records zero counts, and pixels corrupted by electronic overshoot must also be excluded. The remaining pixels may then be used in conjunction with the procedure of Simpson and Humphrey to determine the CZCS cloud mask. These results plus in situ observations of phytoplankton pigment concentration show that pre-processing and proper cloud-screening of CZCS data are necessary for accurate satellite-derived pigment concentrations. This is especially true in the coastal margins, where pigment content is high and image distortion associated with electronic overshoot is also present. The pre-processing algorithm is critical to obtaining accurate global estimates of pigment from spacecraft data.

Cryogenic refrigeration apparatus

DOEpatents

Crunkleton, James A.

1992-01-01

A technique for producing a cold environment in a refrigerant system in which input fluid from a compressor at a first temperature is introduced into an input channel of the system and is pre-cooled to a second temperature for supply to one of at least two stages of the system, and to a third temperature for supply to another stage thereof. The temperatures at such stages are reduced to fourth and fifth temperatures below the second and third temperatures, respectively. Fluid at the fourth temperature from the one stage is returned through the input channel to the compressor and fluid at the fifth temperature from the other stage is returned to the compressor through an output channel so that pre-cooling of the input fluid to the one stage occurs by regenerative cooling and counterflow cooling and pre-cooling of the input fluid to the other stage occurs primarily by counterflow cooling.

Cryogenic refrigeration apparatus

DOEpatents

Crunkleton, J.A.

1992-03-31

A technique for producing a cold environment in a refrigerant system in which input fluid from a compressor at a first temperature is introduced into an input channel of the system and is pre-cooled to a second temperature for supply to one of at least two stages of the system, and to a third temperature for supply to another stage thereof. The temperatures at such stages are reduced to fourth and fifth temperatures below the second and third temperatures, respectively. Fluid at the fourth temperature from the one stage is returned through the input channel to the compressor and fluid at the fifth temperature from the other stage is returned to the compressor through an output channel so that pre-cooling of the input fluid to the one stage occurs by regenerative cooling and counterflow cooling and pre-cooling of the input fluid to the other stage occurs primarily by counterflow cooling. 6 figs.

Zero-forcing pre-coding for MIMO WiMAX transceivers: Performance analysis and implementation issues

NASA Astrophysics Data System (ADS)

Cattoni, A. F.; Le Moullec, Y.; Sacchi, C.

Next generation wireless communication networks are expected to achieve ever increasing data rates. Multi-User Multiple-Input-Multiple-Output (MU-MIMO) is a key technique to obtain the expected performance, because such a technique combines the high capacity achievable using MIMO channel with the benefits of space division multiple access. In MU-MIMO systems, the base stations transmit signals to two or more users over the same channel, for this reason every user can experience inter-user interference. This paper provides a capacity analysis of an online, interference-based pre-coding algorithm able to mitigate the multi-user interference of the MU-MIMO systems in the context of a realistic WiMAX application scenario. Simulation results show that pre-coding can significantly increase the channel capacity. Furthermore, the paper presents several feasibility considerations for implementation of the analyzed technique in a possible FPGA-based software defined radio.

Performance of coded MFSK in a Rician fading channel. [Multiple Frequency Shift Keyed modulation

NASA Technical Reports Server (NTRS)

Modestino, J. W.; Mui, S. Y.

1975-01-01

The performance of convolutional codes in conjunction with noncoherent multiple frequency shift-keyed (MFSK) modulation and Viterbi maximum likelihood decoding on a Rician fading channel is examined in detail. While the primary motivation underlying this work has been concerned with system performance on the planetary entry channel, it is expected that the results are of considerably wider interest. Particular attention is given to modeling the channel in terms of a few meaningful parameters which can be correlated closely with the results of theoretical propagation studies. Fairly general upper bounds on bit error probability performance in the presence of fading are derived and compared with simulation results using both unquantized and quantized receiver outputs. The effects of receiver quantization and channel memory are investigated and it is concluded that the coded noncoherent MFSK system offers an attractive alternative to coherent BPSK in providing reliable low data rate communications in fading channels typical of planetary entry missions.

Voltage-dependent gating of KCNH potassium channels lacking a covalent link between voltage-sensing and pore domains

PubMed Central

Lörinczi, Éva; Gómez-Posada, Juan Camilo; de la Peña, Pilar; Tomczak, Adam P.; Fernández-Trillo, Jorge; Leipscher, Ulrike; Stühmer, Walter; Barros, Francisco; Pardo, Luis A.

2015-01-01

Voltage-gated channels open paths for ion permeation upon changes in membrane potential, but how voltage changes are coupled to gating is not entirely understood. Two modules can be recognized in voltage-gated potassium channels, one responsible for voltage sensing (transmembrane segments S1 to S4), the other for permeation (S5 and S6). It is generally assumed that the conversion of a conformational change in the voltage sensor into channel gating occurs through the intracellular S4–S5 linker that provides physical continuity between the two regions. Using the pathophysiologically relevant KCNH family, we show that truncated proteins interrupted at, or lacking the S4–S5 linker produce voltage-gated channels in a heterologous model that recapitulate both the voltage-sensing and permeation properties of the complete protein. These observations indicate that voltage sensing by the S4 segment is transduced to the channel gate in the absence of physical continuity between the modules. PMID:25818916

Voltage-dependent gating of KCNH potassium channels lacking a covalent link between voltage-sensing and pore domains.

PubMed

Lörinczi, Éva; Gómez-Posada, Juan Camilo; de la Peña, Pilar; Tomczak, Adam P; Fernández-Trillo, Jorge; Leipscher, Ulrike; Stühmer, Walter; Barros, Francisco; Pardo, Luis A

2015-03-30

Voltage-gated channels open paths for ion permeation upon changes in membrane potential, but how voltage changes are coupled to gating is not entirely understood. Two modules can be recognized in voltage-gated potassium channels, one responsible for voltage sensing (transmembrane segments S1 to S4), the other for permeation (S5 and S6). It is generally assumed that the conversion of a conformational change in the voltage sensor into channel gating occurs through the intracellular S4-S5 linker that provides physical continuity between the two regions. Using the pathophysiologically relevant KCNH family, we show that truncated proteins interrupted at, or lacking the S4-S5 linker produce voltage-gated channels in a heterologous model that recapitulate both the voltage-sensing and permeation properties of the complete protein. These observations indicate that voltage sensing by the S4 segment is transduced to the channel gate in the absence of physical continuity between the modules.

Voltage-dependent gating of KCNH potassium channels lacking a covalent link between voltage-sensing and pore domains

NASA Astrophysics Data System (ADS)

Lörinczi, Éva; Gómez-Posada, Juan Camilo; de La Peña, Pilar; Tomczak, Adam P.; Fernández-Trillo, Jorge; Leipscher, Ulrike; Stühmer, Walter; Barros, Francisco; Pardo, Luis A.

2015-03-01

Voltage-gated channels open paths for ion permeation upon changes in membrane potential, but how voltage changes are coupled to gating is not entirely understood. Two modules can be recognized in voltage-gated potassium channels, one responsible for voltage sensing (transmembrane segments S1 to S4), the other for permeation (S5 and S6). It is generally assumed that the conversion of a conformational change in the voltage sensor into channel gating occurs through the intracellular S4-S5 linker that provides physical continuity between the two regions. Using the pathophysiologically relevant KCNH family, we show that truncated proteins interrupted at, or lacking the S4-S5 linker produce voltage-gated channels in a heterologous model that recapitulate both the voltage-sensing and permeation properties of the complete protein. These observations indicate that voltage sensing by the S4 segment is transduced to the channel gate in the absence of physical continuity between the modules.

The Muon Portal Double Tracker for the Inspection of Travelling Containers

NASA Astrophysics Data System (ADS)

Pugliatti, C.; Antonuccio, V.; Bandieramonte, M.; Becciani, U.; Belluomo, F.; Blancato, A.; Bonanno, G.; Costa, A.; Fallica, P. G.; Garozzo, S.; Grillo, A.; Indelicato, V.; La Rocca, P.; Leonora, E.; Longhitano, F.; Longo, S.; Lo Presti, D.; Marano, D.; Massimino, P.; Petta, C.; Pistagna, C.; Puglisi, M.; Randazzo, N.; Riggi, F.; Riggi, S.; Romeo, G.; Russo, G. V.; Santagati, G.; Timpanaro, M. C.; Valvo, G.; Vitello, F.; Zaia, A.

2015-12-01

The Muon Portal Project has as its goal the design and construction of a real-size working detector prototype in scale 1:1, to inspect the content of travelling containers by means of the secondary cosmic-ray muon radiation and to recognize high-Z hidden materials (i.e. U, Pu). The tomographic image is obtained by reconstructing the input and output trajectories of each muon when it crosses the container and, consequently, the scattering angle, making use of two trackers placed above and below the container. The scan is performed without adding any external radiation, in a reasonable time (few minutes) and with a good spatial and angular resolution. The detector consists of 8 planes each segmented in 6 identical modules. Each module is made of scintillating strips with two WaveLength Shifting fibers (WLS) inside, coupled to Silicon photomultipliers. The customized read-out electronics employs programmable boards. Thanks to a smart read-out system, the number of output channels is reduced by a factor 10. The signals from the front-end modules are sent to the read-out boards, in order to convert analog signals to digital ones, by comparison with a threshold. The data are pre-analyzed and stored into a data acquisition PC. After an intense measurement and simulation campaign to carefully characterize the detector components, the first detection modules ( 1 ×3 m2) have been already built. In this paper the detector architecture, particularly focusing on the used electronics and the main preliminary results will be presented.

Performance Evaluation and Nonlinear Mitigation through DQPSK Modulation in 32 × 40 Gbps Long-Haul DWDM Systems

NASA Astrophysics Data System (ADS)

Sharan, Lucky; Agrawal, Vaibhav M.; Chaubey, V. K.

2017-08-01

Higher spectral efficiency and greater data rate per channel are the most cost-effective strategies to meet the exponential demand of data traffic in the optical core network. Multilevel modulation formats being spectrally efficient enhance the transmission capacity by coding information in the amplitude, phase, polarization or a combination of all. This paper presents the design architecture of a 32-channel dense wavelength division multiplexed (DWDM) system, where each channel operates with multi-level phase modulation formats at 40 Gbps. The proposed design has been simulated for 50 GHz channel spacing to numerically compute the performance of both differential phase-shift keying (DPSK) and differential quadrature phase-shift keying (DQPSK) modulation formats in such high-speed DWDM system. The transmission link is analyzed with perfect dispersion compensation and also with under-compensation scheme. The link performance in terms of quality factor (Q) for varying input powers with different dispersion compensation schemes has been evaluated. The simulation study shows significant nonlinear mitigation for both DPSK- and DQPSK-based DWDM systems up to 1,000 km and beyond. It is concluded that at higher power levels DQPSK format having a narrower spectrum shows better tolerance to dispersion and nonlinearities than DPSK format.

The development of an Alzheimer's disease channel for the Michigan Interactive Health Kiosk Project.

PubMed

Connell, Cathleen M; Shaw, Benjamin A; Holmes, Sara B; Hudson, Margaret L; Derry, Holly A; Strecher, Victor J

2003-01-01

The overall objective of this article is to describe the development and implementation of an Alzheimer's disease (AD) module for the Michigan Interactive Health Kiosk Project. This project provides access to health information via 100 kiosks located in public places throughout the state (e.g., churches, senior centers, schools, shopping malls, grocery stores, hospitals) using interactive multimedia software. Because the kiosk screen was designed to resemble a television set, program modules are referred to as "channels." The AD channel is designed to increase knowledge and awareness of the disease among the general public. After an overview of the overall project, the steps involved in developing the AD channel and strategies designed to monitor its use are described, including touch-screen usage data and an on-line user survey. Finally, marketing and promotion of the channel and the implications of this initiative for disseminating information about AD are discussed.

Transmission of 2.5 Gbit/s Spectrum-sliced WDM System for 50 km Single-mode Fiber

NASA Astrophysics Data System (ADS)

Ahmed, Nasim; Aljunid, Sayed Alwee; Ahmad, R. Badlisha; Fadil, Hilal Adnan; Rashid, Mohd Abdur

2011-06-01

The transmission of a spectrum-sliced WDM channel at 2.5 Gbit/s for 50 km of single mode fiber using an system channel spacing only 0.4 nm is reported. We have investigated the system performance using NRZ modulation format. The proposed system is compared with conventional system. The system performance is characterized as the bit-error-rate (BER) received against the system bit rates. Simulation results show that the NRZ modulation format performs well for 2.5 Gbit/s system bit rates. Using this narrow channel spectrum-sliced technique, the total number of multiplexed channels can be increased greatly in WDM system. Therefore, 0.4 nm channel spacing spectrum-sliced WDM system is highly recommended for the long distance optical access networks, like the Metro Area Network (MAN), Fiber-to-the-Building (FTTB) and Fiber-to-the-Home (FTTH).

Allosteric mechanism of water channel gating by Ca2+–calmodulin

PubMed Central

Reichow, Steve L.; Clemens, Daniel M.; Freites, J. Alfredo; Németh-Cahalan, Karin L.; Heyden, Matthias; Tobias, Douglas J.; Hall, James E.; Gonen, Tamir

2013-01-01

Calmodulin (CaM) is a universal regulatory protein that communicates the presence of calcium to its molecular targets and correspondingly modulates their function. This key signaling protein is important for controlling the activity of hundreds of membrane channels and transporters. However, our understanding of the structural mechanisms driving CaM regulation of full-length membrane proteins has remained elusive. In this study, we determined the pseudo-atomic structure of full-length mammalian aquaporin-0 (AQP0, Bos Taurus) in complex with CaM using electron microscopy to understand how this signaling protein modulates water channel function. Molecular dynamics and functional mutation studies reveal how CaM binding inhibits AQP0 water permeability by allosterically closing the cytoplasmic gate of AQP0. Our mechanistic model provides new insight, only possible in the context of the fully assembled channel, into how CaM regulates multimeric channels by facilitating cooperativity between adjacent subunits. PMID:23893133

[Modulation of Kv4 channels by KChIPs clamping].

PubMed

Cui, Yuan-Yuan; Wang, Ke-Wei

2009-01-01

The rapidly inactivating (A-type) potassium channels regulate membrane excitability that defines the fundamental mechanism of neuronal functions such as pain signaling. Cytosolic Kv channel-interacting proteins KChIPs co-assemble with Kv4 (Shal) alpha subunits to form a native complex. The specific binding of auxiliary KChIPs to the Kv4 N-terminus results in modulation of gating properties, surface expression and subunit assembly of Kv4 channels. Based on recent structural efforts, here we attempt to emphasize the interaction between KChIPs and Kv4 channel complex in which a single KChIP1 molecule laterally clamps two neighboring Kv4.3 N-termini in a 4:4 manner. Greater insights into molecular mechanism between KChIPs and Kv4 interaction may provide therapeutic potentials by structure-based design of chemical compounds aimed at disrupting the protein-protein interaction for treatment of membrane excitability-related disorders.

Human EAG channels are directly modulated by PIP2 as revealed by electrophysiological and optical interference investigations

PubMed Central

Han, Bo; He, Kunyan; Cai, Chunlin; Tang, Yin; Yang, Linli; Heinemann, Stefan H.; Hoshi, Toshinori; Hou, Shangwei

2016-01-01

Voltage-gated ether à go-go (EAG) K+ channels are expressed in various types of cancer cells and also in the central nervous system. Aberrant overactivation of human EAG1 (hEAG1) channels is associated with cancer and neuronal disorders such as Zimmermann-Laband and Temple-Baraitser syndromes. Although hEAG1 channels are recognized as potential therapeutic targets, regulation of their functional properties is only poorly understood. Here, we show that the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) is a potent inhibitory gating modifier of hEAG1 channels. PIP2 inhibits the channel activity by directly binding to a short N-terminal segment of the channel important for Ca2+/calmodulin (CaM) binding as evidenced by bio-layer interferometry measurements. Conversely, depletion of endogenous PIP2 either by serotonin-induced phospholipase C (PLC) activation or by a rapamycin-induced translocation system enhances the channel activity at physiological membrane potentials, suggesting that PIP2 exerts a tonic inhibitory influence. Our study, combining electrophysiological and direct binding assays, demonstrates that hEAG1 channels are subject to potent inhibitory modulation by multiple phospholipids and suggests that manipulations of the PIP2 signaling pathway may represent a strategy to treat hEAG1 channel-associated diseases. PMID:27005320

Implementation Strategies for a Universal Acquisition and Tracking Channel Applied to Real GNSS Signals.

PubMed

Fortin, Marc-Antoine; Landry, René

2016-05-02

This paper presents a universal GNSS receiver channel capable of tracking any civil GNSS signal. This fundamentally differs from dedicated channels, each customized for a given signal. A mobile device could integrate fewer universal channels to harvest all available signals. This would allow securing signal availability, while minimizing power consumption and chip size, thus maximizing battery lifetime. In fact, the universal channel allows sequential acquisition and tracking of any chipping rate, carrier frequency, FDMA channel, modulation, or constellation, and is totally configurable (any integration time, any discriminator, etc.). It can switch from one signal to another in 1.07 ms, making it possible for the receiver to rapidly adapt to its sensed environment. All this would consume 3.5 mW/channel in an ASIC implementation, i.e., with a slight overhead compared to the original GPS L1 C/A dedicated channel from which it was derived. After extensive surveys on GNSS signals and tracking channels, this paper details the implementation strategies that led to the proposed universal channel architecture. Validation is achieved using GNSS signals issued from different constellations, frequency bands, modulations and spreading code schemes. A discussion on acquisition approaches and conclusive remarks follow, which open up a new signal selection challenge, rather than satellite selection.

Implementation Strategies for a Universal Acquisition and Tracking Channel Applied to Real GNSS Signals

PubMed Central

Fortin, Marc-Antoine; Landry, René

2016-01-01

This paper presents a universal GNSS receiver channel capable of tracking any civil GNSS signal. This fundamentally differs from dedicated channels, each customized for a given signal. A mobile device could integrate fewer universal channels to harvest all available signals. This would allow securing signal availability, while minimizing power consumption and chip size, thus maximizing battery lifetime. In fact, the universal channel allows sequential acquisition and tracking of any chipping rate, carrier frequency, FDMA channel, modulation, or constellation, and is totally configurable (any integration time, any discriminator, etc.). It can switch from one signal to another in 1.07 ms, making it possible for the receiver to rapidly adapt to its sensed environment. All this would consume 3.5 mW/channel in an ASIC implementation, i.e., with a slight overhead compared to the original GPS L1 C/A dedicated channel from which it was derived. After extensive surveys on GNSS signals and tracking channels, this paper details the implementation strategies that led to the proposed universal channel architecture. Validation is achieved using GNSS signals issued from different constellations, frequency bands, modulations and spreading code schemes. A discussion on acquisition approaches and conclusive remarks follow, which open up a new signal selection challenge, rather than satellite selection. PMID:27144569

Non-FG mediated transport of the large pre-ribosomal subunit through the nuclear pore complex by the mRNA export factor Gle2

PubMed Central

Occhipinti, Laura; Chang, Yiming; Altvater, Martin; Menet, Anna M.; Kemmler, Stefan; Panse, Vikram G.

2013-01-01

Multiple export receptors passage bound pre-ribosomes through nuclear pore complexes (NPCs) by transiently interacting with the Phe-Gly (FG) meshwork of their transport channels. Here, we reveal how the non-FG interacting yeast mRNA export factor Gly-Leu-FG lethal 2 (Gle2) functions in the export of the large pre-ribosomal subunit (pre-60S). Structure-guided studies uncovered conserved platforms used by Gle2 to export pre-60S: an uncharacterized basic patch required to bind pre-60S, and a second surface that makes non-FG contacts with the nucleoporin Nup116. A basic patch mutant of Gle2 is able to function in mRNA export, but not pre-60S export. Thus, Gle2 provides a distinct interaction platform to transport pre-60S to the cytoplasm. Notably, Gle2’s interaction platforms become crucial for pre-60S export when FG-interacting receptors are either not recruited to pre-60S or are impaired. We propose that large complex cargos rely on non-FG as well as FG-interactions for their efficient translocation through the nuclear pore complex channel. PMID:23907389

Changes in habitat availability for outmigrating juvenile salmon (Oncorhychus spp.) following estuary restoration

USGS Publications Warehouse

Ellings, Christopher S.; Davis, Melanie; Grossman, Eric E.; Hodgson, Sayre; Turner, Kelley L.; Woo PR, Isa; Nakai, Glynnis; Takekawa, Jean E.; Takekawa, John Y.

2016-01-01

The restoration of the Nisqually River Delta (Washington, U.S.A.) represents one of the largest efforts toward reestablishing the ecosystem function and resilience of modified habitat in the Puget Sound, particularly for anadromous salmonid species. The opportunity for outmigrating salmon to access and benefit from the expansion of available tidal habitat can be quantified by several physical attributes, which are related to the ecological and physiological responses of juvenile salmon. We monitored a variety of physical parameters to measure changes in opportunity potential from historic, pre-restoration, and post-restoration habitat conditions at several sites across the delta. These parameters included channel morphology, water quality, tidal elevation, and landscape connectivity. We conducted fish catch surveys across the delta to determine if salmon was utilizing restored estuary habitat. Overall major channel area increased 42% and major channel length increased 131% from pre- to post-restoration conditions. Furthermore, the results of our tidal inundation model indicated that major channels were accessible up to 75% of the time, as opposed to 30% pre-restoration. Outmigrating salmon utilized this newly accessible habitat as quickly as 1 year post-restoration. The presence of salmon in restored tidal channels confirmed rapid post-restoration increases in opportunity potential on the delta despite habitat quality differences between restored and reference sites.

Pre-treatment with vinpocetine protects against retinal ischemia.

PubMed

Nivison-Smith, Lisa; Khoo, Pauline; Acosta, Monica L; Kalloniatis, Michael

2017-01-01

Vinpocetine has been shown to have beneficial effects for tissues of the central nervous system subjected to ischemia and other related metabolic insults. We recently showed vinpocetine promotes glucose availability, prevents unregulated cation channel permeability and regulates glial reactivity when present during retinal ischemia. Less is known however about the ability of vinpocetine to protect against future ischemic insults. This study explores the effect of vinpocetine when used as a pre-treatment in an ex vivo model for retinal ischemia using cation channel permeability of agmatine (AGB) combined with immunohistochemistry as a measure for cell functionality. We found that vinpocetine pre-treatment reduced cation channel permeability and apoptotic marker immunoreactivity in the GCL and increased parvalbumin immunoreactivity of inner retinal neurons in the inner nuclear layer following ischemic insult. Vinpocetine pre-treatment also reduced Müller cell reactivity following ischemic insults of up to 120 min compared to untreated controls. Many of vinpocetine's effects however were transient in nature suggesting the drug can protect retinal neurons against future ischemic damage but may have limited long-term applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Calculation of the electron wave function in a graded-channel double-heterojunction modulation-doped field-effect transistor

NASA Technical Reports Server (NTRS)

Mui, D. S. L.; Patil, M. B.; Morkoc, H.

1989-01-01

Three double-heterojunction modulation-doped field-effect transistor structures with different channel composition are investigated theoretically. All of these transistors have an In(x)Ga(1-x)As channel sandwiched between two doped Al(0.3)Ga(0.7)As barriers with undoped spacer layers. In one of the structures, x varies from 0 from either heterojunction to 0.15 at the center of the channel quadratically; in the other two, constant values of x of 0 and 0.15 are used. The Poisson and Schroedinger equations are solved self-consistently for the electron wave function in all three cases. The results showed that the two-dimensional electron gas (2DEG) concentration in the channel of the quadratically graded structure is higher than the x = 0 one and slightly lower than the x = 0.15 one, and the mean distance of the 2DEG is closer to the center of the channel for this transistor than the other two. These two effects have important implications on the electron mobility in the channel.

The First Extracellular Linker Is Important for Several Aspects of the Gating Mechanism of Human TRPA1 Channel

PubMed Central

Marsakova, Lenka; Barvik, Ivan; Zima, Vlastimil; Zimova, Lucie; Vlachova, Viktorie

2017-01-01

Transient receptor potential ankyrin 1 (TRPA1) is an excitatory ion channel involved in pain, inflammation and itching. This channel gates in response to many irritant and proalgesic agents, and can be modulated by calcium and depolarizing voltage. While the closed-state structure of TRPA1 has been recently resolved, also having its open state is essential for understanding how this channel works. Here we use molecular dynamics simulations combined with electrophysiological measurements and systematic mutagenesis to predict and explore the conformational changes coupled to the expansion of the presumptive channel's lower gate. We show that, upon opening, the upper part of the sensor module approaches the pore domain of an adjacent subunit and the conformational dynamics of the first extracellular flexible loop may govern the voltage-dependence of multimodal gating, thereby serving to stabilize the open state of the channel. These results are generally important in understanding the structure and function of TRPA1 and offer new insights into the gating mechanism of TRPA1 and related channels. PMID:28197074

Retro-modulators and fast beam steering for free-space optical communications

NASA Astrophysics Data System (ADS)

Chan, Trevor Keith

Free-space optical (FSO) communications is a means of secure, high bandwidth communication through the use of a modulated laser beam in free-space as the information medium. The chaotic nature of the atmosphere and the motion of the communication nodes make laser alignment a crucial concern. The employment of retro-reflecting modulators makes the bidirectional quality of a communication link into a one sided alignment problem. While there are existing retro-reflecting modulators, their trade-offs create a lack of abilities (such as aperture size, angular range, high modulation speeds, economic viability) which do not fulfill the requirements for certain applications. Also, the beam must be directed towards the intended receiver. Form mobile or scintillated communication links, beam direction must be adaptable in real time. Once again, this area suffers from trade-offs where beamsteering speed is often limited. Research used to mitigate the trade-offs and adapt the devices into viable options for a wider range of applications is explored in this dissertation. Two forms of retro-modulators were explored; a MEMS deformable mirror retro-modulator and a solid silicon retro-modulator that modulated the light by frustrated total internal reflection (FTIR). The MEMS version offered a high speed, scalable, wavelength/angle insensitive retro-modulator which can be massed produced at low cost, while the solid retro-modulator offered a large field of view with low cost as well. Both modulator's design, simulated performances, fabrication and experimental characterization are described in this dissertation. An ultra-fast beamscanner was also designed using 2-dimensional dispersion. By using wavelength switching for directional control, a beamscanner was developed that could switch light faster than pre-existing beamscanners while the beams characteristics (most importantly its aperture) could be freely adjusted by the independent optics. This beamscanner was preceded by our work on a large channel wavelength demultiplexer which combined two orthogonally oriented wavelength demultiplexers. This created a 2-dimensional array of spots in free-space. The light was directed be a collimating lens into a specific direction based on its wavelength. The performance of this beamscanner was simulated by modeling the dispersive properties of the components.

Rrp5p, Noc1p and Noc2p form a protein module which is part of early large ribosomal subunit precursors in S. cerevisiae

PubMed Central

Hierlmeier, Thomas; Merl, Juliane; Sauert, Martina; Perez-Fernandez, Jorge; Schultz, Patrick; Bruckmann, Astrid; Hamperl, Stephan; Ohmayer, Uli; Rachel, Reinhard; Jacob, Anja; Hergert, Kristin; Deutzmann, Rainer; Griesenbeck, Joachim; Hurt, Ed; Milkereit, Philipp; Baßler, Jochen; Tschochner, Herbert

2013-01-01

Eukaryotic ribosome biogenesis requires more than 150 auxiliary proteins, which transiently interact with pre-ribosomal particles. Previous studies suggest that several of these biogenesis factors function together as modules. Using a heterologous expression system, we show that the large ribosomal subunit (LSU) biogenesis factor Noc1p of Saccharomyces cerevisiae can simultaneously interact with the LSU biogenesis factor Noc2p and Rrp5p, a factor required for biogenesis of the large and the small ribosomal subunit. Proteome analysis of RNA polymerase-I-associated chromatin and chromatin immunopurification experiments indicated that all members of this protein module and a specific set of LSU biogenesis factors are co-transcriptionally recruited to nascent ribosomal RNA (rRNA) precursors in yeast cells. Further ex vivo analyses showed that all module members predominantly interact with early pre-LSU particles after the initial pre-rRNA processing events have occurred. In yeast strains depleted of Noc1p, Noc2p or Rrp5p, levels of the major LSU pre-rRNAs decreased and the respective other module members were associated with accumulating aberrant rRNA fragments. Therefore, we conclude that the module exhibits several binding interfaces with pre-ribosomes. Taken together, our results suggest a co- and post-transcriptional role of the yeast Rrp5p–Noc1p–Noc2p module in the structural organization of early LSU precursors protecting them from non-productive RNase activity. PMID:23209026

A 16-channel cassette tape recorder system for clinical EEGs.

PubMed

Barlow, J S

1975-02-01

A 16-channel EEG tape recorder system having a frequency response of DC-100 Hz for each channel is described. The system utilized standard commercially available highfidelity audio tape decks in conjunction with specially designed circuits for time-division multiplexing a balanced amplitude modulation

Carrier recovery techniques on satellite mobile channels

NASA Technical Reports Server (NTRS)

Vucetic, B.; Du, J.

1990-01-01

An analytical method and a stored channel model were used to evaluate error performance of uncoded quadrature phase shift keying (QPSK) and M-ary phase shift keying (MPSK) trellis coded modulation (TCM) over shadowed satellite mobile channels in the presence of phase jitter for various carrier recovery techniques.

Essential oil from Xylopia frutescens Aubl. reduces cytosolic calcium levels on guinea pig ileum: mechanism underlying its spasmolytic potential.

PubMed

Souza, Iara Leão Luna de; Correia, Ana Carolina de Carvalho; Araujo, Layanne Cabral da Cunha; Vasconcelos, Luiz Henrique César; Silva, Maria da Conceição Correia; Costa, Vicente Carlos de Oliveira; Tavares, Josean Fechine; Paredes-Gamero, Edgar Julian; Cavalcante, Fabiana de Andrade; Silva, Bagnólia Araújo da

2015-09-16

Xylopia frutescens Aubl. (embira, semente-de-embira or embira-vermelha), is used in folk medicine as antidiarrheal. The essential oil from its leaves (XF-EO) has been found to cause smooth muscle relaxation. Thus, the aim of this study was to investigate the spasmolytic action by which XF-EO acts on guinea pig ileum. The components of the XF-EO were identified by gas chromatography-mass spectrometry. Segments of guinea pig ileum were suspended in organ bath containing modified Krebs solution at 37 °C, bubbled with carbogen mixture under a resting tension of 1 g. Isotonic contractions were registered using kymographs and isometric contractions using force transducer coupled to an amplifier and computer. Fluorescence measurements were obtained with a microplate reader using Fluo-4. Forty-three constituents were identified in XF-EO, mostly mono- and sesquiterpenes. XF-EO has been found to cause relaxation on guinea pig ileum. The essential oil inhibited in a concentration-dependent manner both CCh- and histamine-induced phasic contractions, being more potent on histamine-induced contractions as well as antagonized histamine-induced cumulative contractions in a non-competitive antagonism profile. XF-EO relaxed in a concentration-dependent manner the ileum pre-contracted with KCl and histamine. Since the potency was smaller in organ pre-contracted with KCl, it was hypothesized that XF-OE would be acting as a K(+) channel positive modulator. In the presence of CsCl (non-selective K(+) channel blocker), the relaxant potency of XF-OE was not altered, indicating a non-participation of these channels. Moreover, XF-EO inhibited CaCl2-induced cumulative contractions in a depolarizing medium nominally without Ca(2+) and relaxed the ileum pre-contracted with S-(-)-Bay K8644 in a concentration-dependent manner, thus, was confirmed the inhibition of Ca(2+) influx through Cav1 by XF-EO. In cellular experiments, the viability of longitudinal layer myocytes from guinea pig ileum was not altered in the presence of XF-OE and the Fluo-4-associated fluorescence intensity in these intestinal myocytes stimulated by histamine was reduced by the essential oil, indicating a [Ca(2+)]c reduction. Spasmolytic action mechanism of XF-EO on guinea pig ileum can involve histaminergic receptor antagonism and Ca(2+) influx blockade, which results in [Ca(2+)]c reduction leading to smooth muscle relaxation.

CaV1.3 L-type Ca2+ channels modulate depression-like behaviour in mice independent of deaf phenotype.

PubMed

Busquet, Perrine; Nguyen, Ngoc Khoi; Schmid, Eduard; Tanimoto, Naoyuki; Seeliger, Mathias W; Ben-Yosef, Tamar; Mizuno, Fengxia; Akopian, Abram; Striessnig, Jörg; Singewald, Nicolas

2010-05-01

Mounting evidence suggests that voltage-gated L-type Ca2+ channels can modulate affective behaviour. We therefore explored the role of CaV1.3 L-type Ca2+ channels in depression- and anxiety-like behaviours using CaV1.3-deficient mice (CaV1.3-/-). We showed that CaV1.3-/- mice displayed less immobility in the forced swim test as well as in the tail suspension test, indicating an antidepressant-like phenotype. Locomotor activity in the home cage or a novel open-field test was not influenced. In the elevated plus maze (EPM), CaV1.3-/- mice entered the open arms more frequently and spent more time there indicating an anxiolytic-like phenotype which was, however, not supported in the stress-induced hyperthermia test. By performing parallel experiments in Claudin 14 knockout mice (Cldn14-/-), which like CaV1.3-/- mice are congenitally deaf, an influence of deafness on the antidepressant-like phenotype could be ruled out. On the other hand, a similar EPM behaviour indicative of an anxiolytic phenotype was also found in the Cldn14-/- animals. Using electroretinography and visual behavioural tasks we demonstrated that at least in mice, CaV1.3 channels do not significantly contribute to visual function. However, marked morphological changes were revealed in synaptic ribbons in the outer plexiform layer of CaV1.3-/- retinas by immunohistochemistry suggesting a possible role of this channel type in structural plasticity at the ribbon synapse. Taken together, our findings indicate that CaV1.3 L-type Ca2+ channels modulate depression-like behaviour but are not essential for visual function. The findings raise the possibility that selective modulation of CaV1.3 channels could be a promising new therapeutic concept for the treatment of mood disorders.

Post-translational regulation of P2X receptor channels: modulation by phospholipids

PubMed Central

Bernier, Louis-Philippe; Ase, Ariel R.; Séguéla, Philippe

2013-01-01

P2X receptor channels mediate fast excitatory signaling by ATP and play major roles in sensory transduction, neuro-immune communication and inflammatory response. P2X receptors constitute a gene family of calcium-permeable ATP-gated cation channels therefore the regulation of P2X signaling is critical for both membrane potential and intracellular calcium homeostasis. Phosphoinositides (PIPn) are anionic signaling phospholipids that act as functional regulators of many types of ion channels. Direct PIPn binding was demonstrated for several ligand- or voltage-gated ion channels, however no generic motif emerged to accurately predict lipid-protein binding sites. This review presents what is currently known about the modulation of the different P2X subtypes by phospholipids and about critical determinants underlying their sensitivity to PIPn levels in the plasma membrane. All functional mammalian P2X subtypes tested, with the notable exception of P2X5, have been shown to be positively modulated by PIPn, i.e., homomeric P2X1, P2X2, P2X3, P2X4, and P2X7, as well as heteromeric P2X1/5 and P2X2/3 receptors. Based on various results reported on the aforementioned subtypes including mutagenesis of the prototypical PIPn-sensitive P2X4 and PIPn-insensitive P2X5 receptor subtypes, an increasing amount of functional, biochemical and structural evidence converges on the modulatory role of a short polybasic domain located in the proximal C-terminus of P2X subunits. This linear motif, semi-conserved in the P2X family, seems necessary and sufficient for encoding direct modulation of ATP-gated channels by PIPn. Furthermore, the physiological impact of the regulation of ionotropic purinergic responses by phospholipids on pain pathways was recently revealed in the context of native crosstalks between phospholipase C (PLC)-linked metabotropic receptors and P2X receptor channels in dorsal root ganglion sensory neurons and microglia. PMID:24324400

Photocontrol of Voltage-Gated Ion Channel Activity by Azobenzene Trimethylammonium Bromide in Neonatal Rat Cardiomyocytes

PubMed Central

Frolova, Sheyda R.; Gaiko, Olga; Tsvelaya, Valeriya A.; Pimenov, Oleg Y.; Agladze, Konstantin I.

2016-01-01

The ability of azobenzene trimethylammonium bromide (azoTAB) to sensitize cardiac tissue excitability to light was recently reported. The dark, thermally relaxed trans- isomer of azoTAB suppressed spontaneous activity and excitation propagation speed, whereas the cis- isomer had no detectable effect on the electrical properties of cardiomyocyte monolayers. As the membrane potential of cardiac cells is mainly controlled by activity of voltage-gated ion channels, this study examined whether the sensitization effect of azoTAB was exerted primarily via the modulation of voltage-gated ion channel activity. The effects of trans- and cis- isomers of azoTAB on voltage-dependent sodium (INav), calcium (ICav), and potassium (IKv) currents in isolated neonatal rat cardiomyocytes were investigated using the whole-cell patch-clamp technique. The experiments showed that azoTAB modulated ion currents, causing suppression of sodium (Na+) and calcium (Ca2+) currents and potentiation of net potassium (K+) currents. This finding confirms that azoTAB-effect on cardiac tissue excitability do indeed result from modulation of voltage-gated ion channels responsible for action potential. PMID:27015602

Secure polarization-independent subcarrier quantum key distribution in optical fiber channel using BB84 protocol with a strong reference.

PubMed

Gleim, A V; Egorov, V I; Nazarov, Yu V; Smirnov, S V; Chistyakov, V V; Bannik, O I; Anisimov, A A; Kynev, S M; Ivanova, A E; Collins, R J; Kozlov, S A; Buller, G S

2016-02-08

A quantum key distribution system based on the subcarrier wave modulation method has been demonstrated which employs the BB84 protocol with a strong reference to generate secure bits at a rate of 16.5 kbit/s with an error of 0.5% over an optical channel of 10 dB loss, and 18 bits/s with an error of 0.75% over 25 dB of channel loss. To the best of our knowledge, these results represent the highest channel loss reported for secure quantum key distribution using the subcarrier wave approach. A passive unidirectional scheme has been used to compensate for the polarization dependence of the phase modulators in the receiver module, which resulted in a high visibility of 98.8%. The system is thus fully insensitive to polarization fluctuations and robust to environmental changes, making the approach promising for use in optical telecommunication networks. Further improvements in secure key rate and transmission distance can be achieved by implementing the decoy states protocol or by optimizing the mean photon number used in line with experimental parameters.

Device for modular input high-speed multi-channel digitizing of electrical data

DOEpatents

VanDeusen, A.L.; Crist, C.E.

1995-09-26

A multi-channel high-speed digitizer module converts a plurality of analog signals to digital signals (digitizing) and stores the signals in a memory device. The analog input channels are digitized simultaneously at high speed with a relatively large number of on-board memory data points per channel. The module provides an automated calibration based upon a single voltage reference source. Low signal noise at such a high density and sample rate is accomplished by ensuring the A/D converters are clocked at the same point in the noise cycle each time so that synchronous noise sampling occurs. This sampling process, in conjunction with an automated calibration, yields signal noise levels well below the noise level present on the analog reference voltages. 1 fig.

Acidic pH modulation of Na+ channels in trigeminal mesencephalic nucleus neurons.

PubMed

Kang, In-Sik; Cho, Jin-Hwa; Choi, In-Sun; Kim, Do-Yeon; Jang, Il-Sung

2016-12-07

Cell bodies of trigeminal mesencephalic nucleus (Vmes) neurons are located within the central nervous system, and therefore, peripheral as well as central acidosis can modulate the excitability of Vmes neurons. Here, we report the effect of acidic pH on voltage-gated Na channels in acutely isolated rat Vmes neurons using a conventional whole-cell patch clamp technique. Acidic pH (pH 6.0) slightly but significantly shifted both the activation and steady-state fast inactivation relationships toward depolarized potentials. However, acidic pH (pH 6.0) had a minor effect on the inactivation kinetics of voltage-gated Na channels. Less sensitivity of voltage-gated Na channels to acidic pH may allow Vmes neurons to transduce the precise proprioceptive information even under acidic pH conditions.

The Role of MicroRNAs in the Regulation of K+ Channels in Epithelial Tissue

PubMed Central

Pilmore, Elliot; Hamilton, Kirk L.

2015-01-01

Our understanding of the modulation of proteins has shifted in direction with the discovery of microRNAs (miRs) over twenty years ago. MiRs are now in the “limelight” as these non-coding pieces of RNA (generally ~22 nucleotides long) result in altered translation and function of proteins. Indeed, miRs are now reported to be potential biomarkers of disease. Epithelial K+ channels play many roles in electrolyte and fluid homeostasis of the human body and have been suggested to be therapeutic targets of disease. Interestingly, the role of miRs in modulating K+ channels of epithelial tissues is only emerging now. This minireview focuses on recent novel findings into the role of miRs in the regulation of K+ channels of epithelia. PMID:26648872

Calcium Domains around Single and Clustered IP3 Receptors and Their Modulation by Buffers

PubMed Central

Rüdiger, S.; Nagaiah, Ch.; Warnecke, G.; Shuai, J.W.

2010-01-01

Abstract We study Ca2+ release through single and clustered IP3 receptor channels on the ER membrane under presence of buffer proteins. Our computational scheme couples reaction-diffusion equations and a Markovian channel model and allows our investigating the effects of buffer proteins on local calcium concentrations and channel gating. We find transient and stationary elevations of calcium concentrations around active channels and show how they determine release amplitude. Transient calcium domains occur after closing of isolated channels and constitute an important part of the channel's feedback. They cause repeated openings (bursts) and mediate increased release due to Ca2+ buffering by immobile proteins. Stationary domains occur during prolonged activity of clustered channels, where the spatial proximity of IP3Rs produces a distinct [Ca2+] scale (0.5–10 μM), which is smaller than channel pore concentrations (>100 μM) but larger than transient levels. While immobile buffer affects transient levels only, mobile buffers in general reduce both transient and stationary domains, giving rise to Ca2+ evacuation and biphasic modulation of release amplitude. Our findings explain recent experiments in oocytes and provide a general framework for the understanding of calcium signals. PMID:20655827

Adaptive Precoded MIMO for LTE Wireless Communication

NASA Astrophysics Data System (ADS)

Nabilla, A. F.; Tiong, T. C.

2015-04-01

Long-Term Evolution (LTE) and Long Term Evolution-Advanced (ATE-A) have provided a major step forward in mobile communication capability. The objectives to be achieved are high peak data rates in high spectrum bandwidth and high spectral efficiencies. Technically, pre-coding means that multiple data streams are emitted from the transmit antenna with independent and appropriate weightings such that the link throughput is maximized at the receiver output thus increasing or equalizing the received signal to interference and noise (SINR) across the multiple receiver terminals. However, it is not reliable enough to fully utilize the information transfer rate to fit the condition of channel according to the bandwidth size. Thus, adaptive pre-coding is proposed. It applies pre-coding matrix indicator (PMI) channel state making it possible to change the pre-coding codebook accordingly thus improving the data rate higher than fixed pre-coding.

Using LiDAR to Estimate Surface Erosion Volumes within the Post-storm 2012 Bagley Fire

NASA Astrophysics Data System (ADS)

Mikulovsky, R. P.; De La Fuente, J. A.; Mondry, Z. J.

2014-12-01

The total post-storm 2012 Bagley fire sediment budget of the Squaw Creek watershed in the Shasta-Trinity National Forest was estimated using many methods. A portion of the budget was quantitatively estimated using LiDAR. Simple workflows were designed to estimate the eroded volume's of debris slides, fill failures, gullies, altered channels and streams. LiDAR was also used to estimate depositional volumes. Thorough manual mapping of large erosional features using the ArcGIS 10.1 Geographic Information System was required as these mapped features determined the eroded volume boundaries in 3D space. The 3D pre-erosional surface for each mapped feature was interpolated based on the boundary elevations. A surface difference calculation was run using the estimated pre-erosional surfaces and LiDAR surfaces to determine volume of sediment potentially delivered into the stream system. In addition, cross sections of altered channels and streams were taken using stratified random selection based on channel gradient and stream order respectively. The original pre-storm surfaces of channel features were estimated using the cross sections and erosion depth criteria. Open source software Inkscape was used to estimate cross sectional areas for randomly selected channel features and then averaged for each channel gradient and stream order classes. The average areas were then multiplied by the length of each class to estimate total eroded altered channel and stream volume. Finally, reservoir and in-channel depositional volumes were estimated by mapping channel forms and generating specific reservoir elevation zones associated with depositional events. The in-channel areas and zones within the reservoir were multiplied by estimated and field observed sediment thicknesses to attain a best guess sediment volume. In channel estimates included re-occupying stream channel cross sections established before the fire. Once volumes were calculated, other erosion processes of the Bagley sedimentation study, such as surface soil erosion were combined to estimate the total fire and storm sediment budget for the Squaw Creek watershed. The LiDAR-based measurement workflows can be easily applied to other sediment budget studies using one high resolution LiDAR dataset.

24-channel dual microcontroller-based voltage controller for ion optics remote control

NASA Astrophysics Data System (ADS)

Bengtsson, L.

2018-05-01

The design of a 24-channel voltage control instrument for Wenzel Elektronik N1130 NIM modules is described. This instrument is remote controlled from a LabVIEW GUI on a host Windows computer and is intended for ion optics control in electron affinity measurements on negative ions at the CERN-ISOLDE facility. Each channel has a resolution of 12 bits and has a normally distributed noise with a standard deviation of <1 mV. The instrument is designed as a standard 2-unit NIM module where the electronic hardware consists of a printed circuit board with two asynchronously operating microcontrollers.

Quaternary pulse position modulation electronics for free-space laser communications

NASA Technical Reports Server (NTRS)

Budinger, J. M.; Kerslake, S. D.; Nagy, L. A.; Shalkhauser, M. J.; Soni, N. J.; Cauley, M. A.; Mohamed, J. H.; Stover, J. B.; Romanofsky, R. R.; Lizanich, P. J.

1991-01-01

The development of a high data-rate communications electronic subsystem for future application in free-space, direct-detection laser communications is described. The dual channel subsystem uses quaternary pulse position modulation (GPPM) and operates at a throughput of 650 megabits per second. Transmitting functions described include source data multiplexing, channel data multiplexing, and QPPM symbol encoding. Implementation of a prototype version in discrete gallium arsenide logic, radiofrequency components, and microstrip circuitry is presented.

Electrical Transport and Channel Length Modulation in Semiconducting Carbon Nanotube Field-Effect Transistors

DTIC Science & Technology

2013-11-25

a ballistic one-dimensional conductor is / = £>(£) ■ VgiE)[fR(E) - fdEME , (1) where Vg(E) is the group velocity, D(E) is the density of states... AEROSPACE REPORT NO. ATR-2013-01138 Electrical Transport and Channel Length Modulation in Semiconducting Carbon Nanotube Field-Effect Transistors...SCIENCES LABORATORIES The Aerospace Corporation functions as an "architect-engineer" for national security programs, specializing in advanced military

Quaternary pulse position modulation electronics for free-space laser communications

NASA Technical Reports Server (NTRS)

Budinger, J. M.; Kerslake, S. D.; Nagy, L. A.; Shalkhauser, M. J.; Soni, N. J.; Cauley, M. A.; Mohamed, J. H.; Stover, J. B.; Romanofsky, R. R.; Lizanich, P. J.

1991-01-01

The development of a high data-rate communications electronic subsystem for future application in free-space, direct-detection laser communications is described. The dual channel subsystem uses quaternary pulse position modulation (QPPM) and operates at a throughput of 650 megabits per second. Transmitting functions described include source data multiplexing, channel data multiplexing, and QPPM symbol encoding. Implementation of a prototype version in discrete gallium arsenide logic, radiofrequency components, and microstrip circuitry is presented.

Modulation of RBC volume distributions by oxidants (phenazine methosulfate and tert-butyl hydroperoxide): role of Gardos channel activation.

PubMed

Lisovskaya, Irina L; Shcherbachenko, Irina M; Volkova, Rimma I; Tikhonov, Vladimir P

2008-06-01

A study was made comparing the effects of two oxidants--phenazine methosulfate (50-1500 microM)+10 mM ascorbate and t-butyl hydroperoxide (1-3 mM)--on the volume-related parameters of normal human red blood cells. Incubation with either oxidative system for 20-30 min resulted in red blood cell density and osmotic resistance distribution shifts. Treatment with the phenazine methosulfate+ascorbate system in the presence of Ca(2+) led to cell shrinking, with the maximum effect being more than 20%. In contrast, under the same conditions, t-BHP caused cell swelling by up to 15%. Modification of the suspending medium (Ca(2+) removing, clotrimazole addition, or enrichment with K(+)) modulated the redistribution effects, suggesting that they were mediated to some extent by Gardos channel activation. These findings are important for understanding how oxidants modulate RBC cation channels.

Modulation of neuronal sodium channels by the sea anemone peptide BDS-I

PubMed Central

Liu, Pin; Jo, Sooyeon

2012-01-01

Blood-depressing substance I (BDS-I), a 43 amino-acid peptide from sea anemone venom, is used as a specific inhibitor of Kv3-family potassium channels. We found that BDS-I acts with even higher potency to modulate specific types of voltage-dependent sodium channels. In rat dorsal root ganglion (DRG) neurons, 3 μM BDS-I strongly enhanced tetrodotoxin (TTX)-sensitive sodium current but weakly inhibited TTX-resistant sodium current. In rat superior cervical ganglion (SCG) neurons, which express only TTX-sensitive sodium current, BDS-I enhanced current elicited by small depolarizations and slowed decay of currents at all voltages (EC50 ∼ 300 nM). BDS-I acted with exceptionally high potency and efficacy on cloned human Nav1.7 channels, slowing inactivation by 6-fold, with an EC50 of approximately 3 nM. BDS-I also slowed inactivation of sodium currents in N1E-115 neuroblastoma cells (mainly from Nav1.3 channels), with an EC50 ∼ 600 nM. In hippocampal CA3 pyramidal neurons (mouse) and cerebellar Purkinje neurons (mouse and rat), BDS-I had only small effects on current decay (slowing inactivation by 20–50%), suggesting relatively weak sensitivity of Nav1.1 and Nav1.6 channels. The biggest effect of BDS-I in central neurons was to enhance resurgent current in Purkinje neurons, an effect reflected in enhancement of sodium current during the repolarization phase of Purkinje neuron action potentials. Overall, these results show that BDS-I acts to modulate sodium channel gating in a manner similar to previously known neurotoxin receptor site 3 anemone toxins but with different isoform sensitivity. Most notably, BDS-I acts with very high potency on human Nav1.7 channels. PMID:22442564

Redox-Dependent Modulation of T-Type Ca(2+) Channels in Sensory Neurons Contributes to Acute Anti-Nociceptive Effect of Substance P.

PubMed

Huang, Dongyang; Huang, Sha; Gao, Haixia; Liu, Yani; Qi, Jinlong; Chen, Pingping; Wang, Caixue; Scragg, Jason L; Vakurov, Alexander; Peers, Chris; Du, Xiaona; Zhang, Hailin; Gamper, Nikita

2016-08-10

Neuropeptide substance P (SP) is produced and released by a subset of peripheral sensory neurons that respond to tissue damage (nociceptors). SP exerts excitatory effects in the central nervous system, but peripheral SP actions are still poorly understood; therefore, here, we aimed at investigating these peripheral mechanisms. SP acutely inhibited T-type voltage-gated Ca(2+) channels in nociceptors. The effect was mediated by neurokinin 1 (NK1) receptor-induced stimulation of intracellular release of reactive oxygen species (ROS), as it can be prevented or reversed by the reducing agent dithiothreitol and mimicked by exogenous or endogenous ROS. This redox-mediated T-type Ca(2+) channel inhibition operated through the modulation of CaV3.2 channel sensitivity to ambient zinc, as it can be prevented or reversed by zinc chelation and mimicked by exogenous zinc. Elimination of the zinc-binding site in CaV3.2 rendered the channel insensitive to SP-mediated inhibition. Importantly, peripherally applied SP significantly reduced bradykinin-induced nociception in rats in vivo; knock-down of CaV3.2 significantly reduced this anti-nociceptive effect. This atypical signaling cascade shared the initial steps with the SP-mediated augmentation of M-type K(+) channels described earlier. Our study established a mechanism underlying the peripheral anti-nociceptive effect of SP whereby this neuropeptide produces ROS-dependent inhibition of pro-algesic T-type Ca(2+) current and concurrent enhancement of anti-algesic M-type K(+) current. These findings will lead to a better understanding of mechanisms of endogenous analgesia. SP modulates T-type channel activity in nociceptors by a redox-dependent tuning of channel sensitivity to zinc; this novel modulatory pathway contributes to the peripheral anti-nociceptive effect of SP. Antioxid. Redox Signal. 25, 233-251.

A Nested Phosphorus and Proton Coil Array for Brain Magnetic Resonance Imaging and Spectroscopy

PubMed Central

Brown, Ryan; Lakshmanan, Karthik; Madelin, Guillaume; Parasoglou, Prodromos

2015-01-01

A dual-nuclei radiofrequency coil array was constructed for phosphorus and proton magnetic resonance imaging and spectroscopy of the human brain at 7 Tesla. An eight-channel transceive degenerate birdcage phosphorus module was implemented to provide whole-brain coverage and significant sensitivity improvement over a standard dual-tuned loop coil. A nested eight-channel proton module provided adequate sensitivity for anatomical localization without substantially sacrificing performance on the phosphorus module. The developed array enabled phosphorus spectroscopy, a saturation transfer technique to calculate the global creatine kinase forward reaction rate, and single-metabolite whole-brain imaging with 1.4 cm nominal isotropic resolution in 15 min (2.3 cm actual resolution), while additionally enabling 1 mm isotropic proton imaging. This study demonstrates that a multi-channel array can be utilized for phosphorus and proton applications with improved coverage and/or sensitivity over traditional single-channel coils. The efficient multi-channel coil array, time-efficient pulse sequences, and the enhanced signal strength available at ultra-high fields can be combined to allow volumetric assessment of the brain and could provide new insights into the underlying energy metabolism impairment in several neurodegenerative conditions, such as Alzheimer’s and Parkinson’s diseases, as well as mental disorders such as schizophrenia. PMID:26375209

Cysteine-3635 is responsible for skeletal muscle ryanodine receptor modulation by NO

PubMed Central

Sun, Junhui; Xin, Chunlin; Eu, Jerry P.; Stamler, Jonathan S.; Meissner, Gerhard

2001-01-01

We have shown previously that at physiologically relevant oxygen tension (pO2 ≈ 10 mmHg), NO S-nitrosylates 1 of ≈50 free cysteines per ryanodine receptor 1 (RyR1) subunit and transduces a calcium-sensitizing effect on the channel by means of calmodulin (CaM). It has been suggested that cysteine-3635 is part of a CaM-binding domain, and its reactivity is attenuated by CaM [Porter Moore, C., Zhang, J. Z., Hamilton, S. L. (1999) J. Biol. Chem. 274, 36831–36834]. Therefore, we tested the hypothesis that the effect of NO was mediated by C3635. The full-length RyR1 single-site C3635A mutant was generated and expressed in HEK293 cells. The mutation resulted in the loss of CaM-dependent NO modulation of channel activity and reduced S-nitrosylation by NO to background levels but did not affect NO-independent channel modulation by CaM or the redox sensitivity of the channel to O2 and glutathione. Our results reveal that different cysteines within the channel have been adapted to serve in nitrosative and oxidative responses, and that S-nitrosylation of the cysteine-containing CaM-binding domain underlies the mechanism of CaM-dependent regulation of RyR1 by NO. PMID:11562475

A nested phosphorus and proton coil array for brain magnetic resonance imaging and spectroscopy.

PubMed

Brown, Ryan; Lakshmanan, Karthik; Madelin, Guillaume; Parasoglou, Prodromos

2016-01-01

A dual-nuclei radiofrequency coil array was constructed for phosphorus and proton magnetic resonance imaging and spectroscopy of the human brain at 7T. An eight-channel transceive degenerate birdcage phosphorus module was implemented to provide whole-brain coverage and significant sensitivity improvement over a standard dual-tuned loop coil. A nested eight-channel proton module provided adequate sensitivity for anatomical localization without substantially sacrificing performance on the phosphorus module. The developed array enabled phosphorus spectroscopy, a saturation transfer technique to calculate the global creatine kinase forward reaction rate, and single-metabolite whole-brain imaging with 1.4cm nominal isotropic resolution in 15min (2.3cm actual resolution), while additionally enabling 1mm isotropic proton imaging. This study demonstrates that a multi-channel array can be utilized for phosphorus and proton applications with improved coverage and/or sensitivity over traditional single-channel coils. The efficient multi-channel coil array, time-efficient pulse sequences, and the enhanced signal strength available at ultra-high fields can be combined to allow volumetric assessment of the brain and could provide new insights into the underlying energy metabolism impairment in several neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, as well as mental disorders such as schizophrenia. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed

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

2012-09-01

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

Proposed scheme for parallel 10Gb/s VSR system and its verilog HDL realization

NASA Astrophysics Data System (ADS)

Zhou, Yi; Chen, Hongda; Zuo, Chao; Jia, Jiuchun; Shen, Rongxuan; Chen, Xiongbin

2005-02-01

This paper proposes a novel and innovative scheme for 10Gb/s parallel Very Short Reach (VSR) optical communication system. The optimized scheme properly manages the SDH/SONET redundant bytes and adjusts the position of error detecting bytes and error correction bytes. Compared with the OIF-VSR4-01.0 proposal, the scheme has a coding process module. The SDH/SONET frames in transmission direction are disposed as follows: (1) The Framer-Serdes Interface (FSI) gets 16×622.08Mb/s STM-64 frame. (2) The STM-64 frame is byte-wise stripped across 12 channels, all channels are data channels. During this process, the parity bytes and CRC bytes are generated in the similar way as OIF-VSR4-01.0 and stored in the code process module. (3) The code process module will regularly convey the additional parity bytes and CRC bytes to all 12 data channels. (4) After the 8B/10B coding, the 12 channels is transmitted to the parallel VCSEL array. The receive process approximately in reverse order of transmission process. By applying this scheme to 10Gb/s VSR system, the frame size in VSR system is reduced from 15552×12 bytes to 14040×12 bytes, the system redundancy is reduced obviously.

Modulation of Ionic Channels and Insulin Secretion by Drugs and Hormones in Pancreatic Beta Cells.

PubMed

Velasco, Myrian; Díaz-García, Carlos Manlio; Larqué, Carlos; Hiriart, Marcia

2016-09-01

Pancreatic beta cells, unique cells that secrete insulin in response to an increase in glucose levels, play a significant role in glucose homeostasis. Glucose-stimulated insulin secretion (GSIS) in pancreatic beta cells has been extensively explored. In this mechanism, glucose enters the cells and subsequently the metabolic cycle. During this process, the ATP/ADP ratio increases, leading to ATP-sensitive potassium (KATP) channel closure, which initiates depolarization that is also dependent on the activity of TRP nonselective ion channels. Depolarization leads to the opening of voltage-gated Na(+) channels (Nav) and subsequently voltage-dependent Ca(2+) channels (Cav). The increase in intracellular Ca(2+) triggers the exocytosis of insulin-containing vesicles. Thus, electrical activity of pancreatic beta cells plays a central role in GSIS. Moreover, many growth factors, incretins, neurotransmitters, and hormones can modulate GSIS, and the channels that participate in GSIS are highly regulated. In this review, we focus on the principal ionic channels (KATP, Nav, and Cav channels) involved in GSIS and how classic and new proteins, hormones, and drugs regulate it. Moreover, we also discuss advances on how metabolic disorders such as metabolic syndrome and diabetes mellitus change channel activity leading to changes in insulin secretion. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

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

Lentine, Anthony L.; Cox, Jonathan Albert

Methods and systems for stabilizing a resonant modulator include receiving pre-modulation and post-modulation portions of a carrier signal, determining the average power from these portions, comparing an average input power to the average output power, and operating a heater coupled to the modulator based on the comparison. One system includes a pair of input structures, one or more processing elements, a comparator, and a control element. The input structures are configured to extract pre-modulation and post-modulation portions of a carrier signal. The processing elements are configured to determine average powers from the extracted portions. The comparator is configured to comparemore » the average input power and the average output power. The control element operates a heater coupled to the modulator based on the comparison.« less

Modulation for terrestrial broadcasting of digital HDTV

NASA Technical Reports Server (NTRS)

Kohn, Elliott S.

1991-01-01

The digital modulation methods used by the DigiCipher, DSC-HDTV, ADTV, and ATVA-P digital high-definition television (HDTV) systems are discussed. Three of the systems use a quadrature amplitude modulation method, and the fourth uses a vestigial sideband modulation method. The channel equalization and spectrum sharing of the digital HDTV systems is discussed.

Resistance modulation in VO2 nanowires induced by an electric field via air-gap gates

NASA Astrophysics Data System (ADS)

Kanki, Teruo; Chikanari, Masashi; Wei, Tingting; Tanaka, Hidekazu; The Institute of Scientific; Industrial Research Team

Vanadium dioxide (VO2) shows huge resistance change with metal-insulator transition (MIT) at around room temperature. Controlling of the MIT by applying an electric field is a topical ongoing research toward the realization of Mott transistor. In this study, we have successfully switched channel resistance of VO2 nano-wire channels by a pure electrostatic field effect using a side-gate-type field-effect transistor (SG-FET) viaair gap and found that single crystalline VO2 nanowires and the channels with narrower width enhance transport modulation rate. The rate of change in resistance ((R0-R)/R, where R0 and R is the resistance of VO2 channel with off state and on state gate voltage (VG) , respectively) was 0.42 % at VG = 30 V in in-plane poly-crystalline VO2 channels on Al2O3(0001) substrates, while the rate in single crystalline channels on TiO2 (001) substrates was 3.84 %, which was 9 times higher than that using the poly-crystalline channels. With reducing wire width from 3000 nm to 400 nm of VO2 on TiO2 (001) substrate, furthermore, resistance modulation ratio enhanced from 0.67 % to 3.84 %. This change can not be explained by a simple free-electron model. In this presentation, we will compare the electronic properties between in-plane polycrystalline VO2 on Al2O3 (0001) and single crystalline VO2 on TiO2 (001) substrates, and show experimental data in detail..

Cytosolic Nucleotides Block and Regulate the Arabidopsis Vacuolar Anion Channel AtALMT9*

PubMed Central

Zhang, Jingbo; Martinoia, Enrico; De Angeli, Alexis

2014-01-01

The aluminum-activated malate transporters (ALMTs) form a membrane protein family exhibiting different physiological roles in plants, varying from conferring tolerance to environmental Al3+ to the regulation of stomatal movement. The regulation of the anion channels of the ALMT family is largely unknown. Identifying intracellular modulators of the activity of anion channels is fundamental to understanding their physiological functions. In this study we investigated the role of cytosolic nucleotides in regulating the activity of the vacuolar anion channel AtALMT9. We found that cytosolic nucleotides modulate the transport activity of AtALMT9. This modulation was based on a direct block of the pore of the channel at negative membrane potentials (open channel block) by the nucleotide and not by a phosphorylation mechanism. The block by nucleotides of AtALMT9-mediated currents was voltage dependent. The blocking efficiency of intracellular nucleotides increased with the number of phosphate groups and ATP was the most effective cellular blocker. Interestingly, the ATP block induced a marked modification of the current-voltage characteristic of AtALMT9. In addition, increased concentrations of vacuolar anions were able to shift the ATP block threshold to a more negative membrane potential. The block of AtALMT9-mediated anion currents by ATP at negative membrane potentials acts as a gate of the channel and vacuolar anion tune this gating mechanism. Our results suggest that anion transport across the vacuolar membrane in plant cells is controlled by cytosolic nucleotides and the energetic status of the cell. PMID:25028514

Cytosolic nucleotides block and regulate the Arabidopsis vacuolar anion channel AtALMT9.

PubMed

Zhang, Jingbo; Martinoia, Enrico; De Angeli, Alexis

2014-09-12

The aluminum-activated malate transporters (ALMTs) form a membrane protein family exhibiting different physiological roles in plants, varying from conferring tolerance to environmental Al(3+) to the regulation of stomatal movement. The regulation of the anion channels of the ALMT family is largely unknown. Identifying intracellular modulators of the activity of anion channels is fundamental to understanding their physiological functions. In this study we investigated the role of cytosolic nucleotides in regulating the activity of the vacuolar anion channel AtALMT9. We found that cytosolic nucleotides modulate the transport activity of AtALMT9. This modulation was based on a direct block of the pore of the channel at negative membrane potentials (open channel block) by the nucleotide and not by a phosphorylation mechanism. The block by nucleotides of AtALMT9-mediated currents was voltage dependent. The blocking efficiency of intracellular nucleotides increased with the number of phosphate groups and ATP was the most effective cellular blocker. Interestingly, the ATP block induced a marked modification of the current-voltage characteristic of AtALMT9. In addition, increased concentrations of vacuolar anions were able to shift the ATP block threshold to a more negative membrane potential. The block of AtALMT9-mediated anion currents by ATP at negative membrane potentials acts as a gate of the channel and vacuolar anion tune this gating mechanism. Our results suggest that anion transport across the vacuolar membrane in plant cells is controlled by cytosolic nucleotides and the energetic status of the cell. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Gating modifier toxins isolated from spider venom: modulation of voltage-gated sodium channels and the role of lipid membranes.

PubMed

Agwa, Akello J; Peigneur, Steve; Chow, Chun Yuen; Lawrence, Nicole; Craik, David J; Tytgat, Jan; King, Glenn F; Henriques, Sonia Troeira; Schroeder, Christina I

2018-04-27

Gating modifier toxins (GMTs) are venom-derived peptides isolated from spiders and other venomous creatures that modulate activity of disease-relevant voltage-gated ion channels and are therefore being pursued as therapeutic leads. The amphipathic surface profile of GMTs has prompted the proposal that some GMTs simultaneously bind to the cell membrane and voltage-gated ion channels in a trimolecular complex. Here we examined whether there is a relationship among spider GMT amphipathicity, membrane binding and potency or selectivity for voltage-gated sodium (NaV) channels. We used NMR spectroscopy and in silico calculations to examine the structures and physicochemical properties of a panel of nine GMTs and deployed surface plasmon resonance to measure GMT affinity for lipids putatively found in proximity to NaV channels. Electrophysiology was used to quantify GMT activity on NaV1.7, an ion channel linked to chronic pain. Selectivity of the peptides was further examined against a panel of NaV channel subtypes. We show that GMTs adsorb to the outer leaflet of anionic lipid bilayers through electrostatic interactions. We did not observe a direct correlation between GMT amphipathicity and affinity for lipid bilayers. Furthermore, GMT-lipid bilayer interactions did not correlate with potency or selectivity for NaVs. We therefore propose that increased membrane binding is unlikely to improve subtype selectivity and that the conserved amphipathic GMT surface profile is an adaptation that facilitates simultaneous modulation of multiple NaVs. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Neuromodulatory changes in short-term synaptic dynamics may be mediated by two distinct mechanisms of presynaptic calcium entry.

PubMed

Oh, Myongkeun; Zhao, Shunbing; Matveev, Victor; Nadim, Farzan

2012-12-01

Although synaptic output is known to be modulated by changes in presynaptic calcium channels, additional pathways for calcium entry into the presynaptic terminal, such as non-selective channels, could contribute to modulation of short term synaptic dynamics. We address this issue using computational modeling. The neuropeptide proctolin modulates the inhibitory synapse from the lateral pyloric (LP) to the pyloric dilator (PD) neuron, two slow-wave bursting neurons in the pyloric network of the crab Cancer borealis. Proctolin enhances the strength of this synapse and also changes its dynamics. Whereas in control saline the synapse shows depression independent of the amplitude of the presynaptic LP signal, in proctolin, with high-amplitude presynaptic LP stimulation the synapse remains depressing while low-amplitude stimulation causes facilitation. We use simple calcium-dependent release models to explore two alternative mechanisms underlying these modulatory effects. In the first model, proctolin directly targets calcium channels by changing their activation kinetics which results in gradual accumulation of calcium with low-amplitude presynaptic stimulation, leading to facilitation. The second model uses the fact that proctolin is known to activate a non-specific cation current I ( MI ). In this model, we assume that the MI channels have some permeability to calcium, modeled to be a result of slow conformation change after binding calcium. This generates a gradual increase in calcium influx into the presynaptic terminals through the modulatory channel similar to that described in the first model. Each of these models can explain the modulation of the synapse by proctolin but with different consequences for network activity.

Effects of Small Molecule Calcium-Activated Chloride Channel Inhibitors on Structure and Function of Accessory Cholera Enterotoxin (Ace) of Vibrio cholerae

PubMed Central

Chatterjee, Tanaya; Sheikh, Irshad Ali; Chakravarty, Devlina; Chakrabarti, Pinak; Sarkar, Paramita; Saha, Tultul; Chakrabarti, Manoj K.; Hoque, Kazi Mirajul

2015-01-01

Cholera pathogenesis occurs due to synergistic pro-secretory effects of several toxins, such as cholera toxin (CTX) and Accessory cholera enterotoxin (Ace) secreted by Vibrio cholerae strains. Ace activates chloride channels stimulating chloride/bicarbonate transport that augments fluid secretion resulting in diarrhea. These channels have been targeted for drug development. However, lesser attention has been paid to the interaction of chloride channel modulators with bacterial toxins. Here we report the modulation of the structure/function of recombinant Ace by small molecule calcium-activated chloride channel (CaCC) inhibitors, namely CaCCinh-A01, digallic acid (DGA) and tannic acid. Biophysical studies indicate that the unfolding (induced by urea) free energy increases upon binding CaCCinh-A01 and DGA, compared to native Ace, whereas binding of tannic acid destabilizes the protein. Far-UV CD experiments revealed that the α-helical content of Ace-CaCCinh-A01 and Ace-DGA complexes increased relative to Ace. In contrast, binding to tannic acid had the opposite effect, indicating the loss of protein secondary structure. The modulation of Ace structure induced by CaCC inhibitors was also analyzed using docking and molecular dynamics (MD) simulation. Functional studies, performed using mouse ileal loops and Ussing chamber experiments, corroborate biophysical data, all pointing to the fact that tannic acid destabilizes Ace, inhibiting its function, whereas DGA stabilizes the toxin with enhanced fluid accumulation in mouse ileal loop. The efficacy of tannic acid in mouse model suggests that the targeted modulation of Ace structure may be of therapeutic benefit for gastrointestinal disorders. PMID:26540279

Identification of a pre-active conformation of a pentameric channel receptor

PubMed Central

Menny, Anaïs; Lefebvre, Solène N; Schmidpeter, Philipp AM; Drège, Emmanuelle; Fourati, Zaineb; Delarue, Marc; Edelstein, Stuart J; Nimigean, Crina M; Joseph, Delphine; Corringer, Pierre-Jean

2017-01-01

Pentameric ligand-gated ion channels (pLGICs) mediate fast chemical signaling through global allosteric transitions. Despite the existence of several high-resolution structures of pLGICs, their dynamical properties remain elusive. Using the proton-gated channel GLIC, we engineered multiple fluorescent reporters, each incorporating a bimane and a tryptophan/tyrosine, whose close distance causes fluorescence quenching. We show that proton application causes a global compaction of the extracellular subunit interface, coupled to an outward motion of the M2-M3 loop near the channel gate. These movements are highly similar in lipid vesicles and detergent micelles. These reorganizations are essentially completed within 2 ms and occur without channel opening at low proton concentration, indicating that they report a pre-active intermediate state in the transition pathway toward activation. This provides a template to investigate the gating of eukaryotic neurotransmitter receptors, for which intermediate states also participate in activation. DOI: http://dx.doi.org/10.7554/eLife.23955.001 PMID:28294942

Protein conformational modulation by photons: a mechanism for laser treatment effects.

PubMed

Liebert, Ann D; Bicknell, Brian T; Adams, Roger D

2014-03-01

Responsiveness to low-level laser treatment (LLTT) at a wavelength of 450-910 nm has established it as an effective treatment of medical, veterinary and dental chronic pain, chronic inflammation conditions (arthritis and macular degeneration), wound repair, and lymphoedema, yet the mechanisms underlying the effectiveness of LLLT remain unclear. However, there is now sufficient evidence from recent research to propose an integrated model of LLLT action. The hypothesis presented in this paper is that external applications of photons (through laser at an appropriate dose) modulates the nervous system through an integrated mechanism. This stimulated mechanism involves protein-to-protein interaction, where two or more proteins bind together to facilitate molecular processes, including modification of proteins by members of SUMO (small ubiquitin-related modifier proteins) and also protein phosphorylation and tyrosination. SUMO has been shown to have a role in multiple nuclear and perinuclear targets, including ion channels, and in the maintenance of telomeres and the post-translational modification of genes. The consequence of laser application in treatment, therefore, can be seen as influencing the transmission of neural information via an integrated and rapid modulation of ion channels, achieved through both direct action on photo-acceptors (such as cytochrome c-oxidase) and through indirect modulation via enzymes, including tyrosine hydroxylase (TH), tyrosine kinases and tyrosine kinase receptors. This exogenous action then facilitates an existing photonic biomodulation mechanism within the body, and initiates ion channel modulation both in the periphery and the central nervous system (CNS). Evidence indicates that the ion channel modulation functions predominately through the potassium channels, including two pore leak channels (K2P), which act as signal integrators from the periphery to the cortex. Photonic action also transforms SUMOylation processes at the cell membrane, nucleus and telomeres via signalling processes from the mitochondria (which is the main target of laser absorption) to these targets. Under the hypothesis, these observed biological effects would play a part in the bystander effect, the abscopal effect, and other systemic effects observed with the application of low level laser (LLLT). The implications of the hypothesis are important in that they point to mechanisms that can account for the effectiveness of laser in the treatment and prevention of inflammatory diseases, chronic pain and neurodegenerative disorders. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Conopeptide Vt3.1 preferentially inhibits BK potassium channels containing β4 subunits via electrostatic interactions.

PubMed

Li, Min; Chang, Shan; Yang, Longjin; Shi, Jingyi; McFarland, Kelli; Yang, Xiao; Moller, Alyssa; Wang, Chunguang; Zou, Xiaoqin; Chi, Chengwu; Cui, Jianmin

2014-02-21

BK channel β subunits (β1-β4) modulate the function of channels formed by slo1 subunits to produce tissue-specific phenotypes. The molecular mechanism of how the homologous β subunits differentially alter BK channel functions and the role of different BK channel functions in various physiologic processes remain unclear. By studying channels expressed in Xenopus laevis oocytes, we show a novel disulfide-cross-linked dimer conopeptide, Vt3.1 that preferentially inhibits BK channels containing the β4 subunit, which is most abundantly expressed in brain and important for neuronal functions. Vt3.1 inhibits the currents by a maximum of 71%, shifts the G-V relation by 45 mV approximately half-saturation concentrations, and alters both open and closed time of single channel activities, indicating that the toxin alters voltage dependence of the channel. Vt3.1 contains basic residues and inhibits voltage-dependent activation by electrostatic interactions with acidic residues in the extracellular loops of the slo1 and β4 subunits. These results suggest a large interaction surface between the slo1 subunit of BK channels and the β4 subunit, providing structural insight into the molecular interactions between slo1 and β4 subunits. The results also suggest that Vt3.1 is an excellent tool for studying β subunit modulation of BK channels and for understanding the physiological roles of BK channels in neurophysiology.

Direct cooled power electronics substrate

DOEpatents

Wiles, Randy H [Powell, TN; Wereszczak, Andrew A [Oak Ridge, TN; Ayers, Curtis W [Kingston, TN; Lowe, Kirk T [Knoxville, TN

2010-09-14

The disclosure describes directly cooling a three-dimensional, direct metallization (DM) layer in a power electronics device. To enable sufficient cooling, coolant flow channels are formed within the ceramic substrate. The direct metallization layer (typically copper) may be bonded to the ceramic substrate, and semiconductor chips (such as IGBT and diodes) may be soldered or sintered onto the direct metallization layer to form a power electronics module. Multiple modules may be attached to cooling headers that provide in-flow and out-flow of coolant through the channels in the ceramic substrate. The modules and cooling header assembly are preferably sized to fit inside the core of a toroidal shaped capacitor.

A 16-ch module for thermal neutron detection using ZnS:6LiF scintillator with embedded WLS fibers coupled to SiPMs and its dedicated readout electronics

NASA Astrophysics Data System (ADS)

Mosset, J.-B.; Stoykov, A.; Greuter, U.; Gromov, A.; Hildebrandt, M.; Panzner, T.; Schlumpf, N.

2017-02-01

A scalable 16-ch thermal neutron detection system has been developed in the framework of the upgrade of a neutron diffractometer. The detector is based on a ZnS:6LiF scintillator with embedded WLS fibers which are read out with SiPMs. In this paper, we present the 16-ch module, the dedicated readout electronics, a direct comparison between the performance of the diffractometer obtained with the current 3He detector and with the 16-ch detection module, and the channel-to-channel uniformity.

Multiple Trellis Coded Modulation (MTCM): An MSAT-X report

NASA Technical Reports Server (NTRS)

Divsalar, D.; Simon, M. K.

1986-01-01

Conventional trellis coding outputs one channel symbol per trellis branch. The notion of multiple trellis coding is introduced wherein more than one channel symbol per trellis branch is transmitted. It is shown that the combination of multiple trellis coding with M-ary modulation yields a performance gain with symmetric signal set comparable to that previously achieved only with signal constellation asymmetry. The advantage of multiple trellis coding over the conventional trellis coded asymmetric modulation technique is that the potential for code catastrophe associated with the latter has been eliminated with no additional cost in complexity (as measured by the number of states in the trellis diagram).

Simultaneous polarization-insensitive phase-space trans-multiplexing and wavelength multicasting via cross-phase modulation in a photonic crystal fiber at 10 GBd

NASA Astrophysics Data System (ADS)

Cannon, Brice M.

This thesis investigates the all-optical combination of amplitude and phase modulated signals into one unified multi-level phase modulated signal, utilizing the Kerr nonlinearity of cross-phase modulation (XPM). Predominantly, the first experimental demonstration of simultaneous polarization-insensitive phase-transmultiplexing and multicasting (PI-PTMM) will be discussed. The PI-PTMM operation combines the data of a single 10-Gbaud carrier-suppressed return-to-zero (CSRZ) on-off keyed (OOK) pump signal and 4x10-Gbaud return-to-zero (RZ) binary phase-shift keyed (BPSK) probe signals to generate 4x10-GBd RZ-quadrature phase-shift keyed (QPSK) signals utilizing a highly nonlinear, birefringent photonic crystal fiber (PCF). Since XPM is a highly polarization dependent nonlinearity, a polarization sensitivity reduction technique was used to alleviate the fluctuations due to the remotely generated signals' unpredictable states of polarization (SOP). The measured amplified spontaneous emission (ASE) limited receiver sensitivity optical signal-to-noise ratio (OSNR) penalty of the PI-PTMM signal relative to the field-programmable gate array (FPGA) pre-coded RZ-DQPSK baseline at a forward-error correction (FEC) limit of 10-3 BER was ≈ 0.3 dB. In addition, the OSNR of the remotely generated CSRZ-OOK signal could be degraded to ≈ 29 dB/0.1nm, before the bit error rate (BER) performance of the PI-PTMM operation began to exponentially degrade. A 138-km dispersion-managed recirculating loop system with a 100-GHz, 13-channel mixed-format dense-wavelength-division multiplexed (DWDM) transmitter was constructed to investigate the effect of metro/long-haul transmission impairments. The PI-PTMM DQPSK and the FPGA pre-coded RZ-DQPSK baseline signals were transmitted 1,900 km and 2,400 km in the nonlinearity-limited transmission regime before reaching the 10-3 BER FEC limit. The relative reduction in transmission distance for the PI-PTMM signal was due to the additional transmitter impairments in the PCF that interact negatively with the transmission fiber.

Dopaminergic Modulation of Excitatory Transmission in the Anterior Cingulate Cortex of Adult Mice

PubMed Central

Darvish-Ghane, Soroush; Yamanaka, Manabu

2016-01-01

Dopamine (DA) possesses potent neuromodulatory properties in the central nervous system. In the anterior cingulate cortex, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPAR) are key ion channels in mediating nerve injury induced long-term potentiation (LTP) and chronic pain phenotype. In the present study, we reported the effects of DA on glutamate mediated excitatory post-synaptic currents (EPSCs) in pyramidal neurons of layer II/III of the ACC in adult mice. Bath application of DA (50 μM) caused a significant, rapid and reversible inhibition of evoked EPSCs (eEPSC). This inhibitory effect is dose-related and was absent in lower concentration of DA (5 μM). Furthermore, selective postsynaptic application of GDP-β-S (1.6 mM) in the internal solution completely abolished the inhibitory effects of DA (50 μM). We also investigated modulation of spontaneous EPSCs (sEPSCs) and TTX sensitive, miniature EPSCs (mEPSCs) by DA. Our results indicated mixed effects of potentiation and inhibition of frequency and amplitude for sEPSCs and mEPSCs. Furthermore, high doses of SCH23390 (100 μM) and sulpiride (100 μM) revealed that, inhibition of eEPSCs is mediated by postsynaptic D2-receptors (D2R). Our finding posits a pre- and postsynaptic mode of pyramidal neuron EPSC modulation in mice ACC by DA. PMID:27317578

A miniature 48-channel pressure sensor module capable of in situ calibration

NASA Technical Reports Server (NTRS)

Gross, C.; Juanarena, D. B.

1977-01-01

A new high data rate pressure sensor module with in situ calibration capability has been developed by the Langley Research Center to help reduce energy consumption in wind-tunnel facilities without loss of measurement accuracy. The sensor module allows for nearly a two order of magnitude increase in data rates over conventional electromechanically scanned pressure sampling techniques. This module consists of 16 solid state pressure sensor chips and signal multiplexing electronics integrally mounted to a four position pressure selector switch. One of the four positions of the pressure selector switch allows the in situ calibration of the 16 pressure sensors; the three other positions allow 48 channels (three sets of 16) pressure inputs to be measured by sensors. The small size of the sensor module will allow mounting within many wind-tunnel models, thus eliminating long tube lengths and their corresponding slow pressure response.

Assessing the potential for change in the middle Yangtze River channel following impoundment of the Three Gorges Dam

NASA Astrophysics Data System (ADS)

Yuan, Wenhao; Yin, Daowei; Finlayson, Brian; Chen, Zhongyuan

2012-04-01

The geomorphic impacts of dams on downstream river channels are complex, not readily predictable for specific cases, but widely reported in the literature. For the Three Gorges Dam on the Yangtze (Changjiang) River in China, no studies of the impact of the changed flow and sediment conditions below the dam on the behaviour of the channel were included in the pre-dam feasibility report. We have assembled a database of flow and sediment data for the middle Yangtze River from Yichang to Hankou and used this to analyse changes following the closure of the dam. While total flow is little affected, the operating strategy for the dam that provides for storage of part of the summer high flows to maintain hydroelectric power generation in winter (the low flow season) is reflected in changes to the seasonal distribution of flow below the dam. We calculated potential sediment carrying capacity and compared it with measured sediment concentrations for both pre- and post-dam conditions. While channel sedimentation is indicated along the middle Yangtze for pre-dam conditions, scour is indicated for post-dam conditions, highest at Yichang immediately below the dam and decreasing downstream.

Proof-of-principle test of coherent-state continuous variable quantum key distribution through turbulent atmosphere (Conference Presentation)

NASA Astrophysics Data System (ADS)

Derkach, Ivan D.; Peuntinger, Christian; Ruppert, László; Heim, Bettina; Gunthner, Kevin; Usenko, Vladyslav C.; Elser, Dominique; Marquardt, Christoph; Filip, Radim; Leuchs, Gerd

2016-10-01

Continuous-variable quantum key distribution is a practical application of quantum information theory that is aimed at generation of secret cryptographic key between two remote trusted parties and that uses multi-photon quantum states as carriers of key bits. Remote parties share the secret key via a quantum channel, that presumably is under control of of an eavesdropper, and which properties must be taken into account in the security analysis. Well-studied fiber-optical quantum channels commonly possess stable transmittance and low noise levels, while free-space channels represent a simpler, less demanding and more flexible alternative, but suffer from atmospheric effects such as turbulence that in particular causes a non-uniform transmittance distribution referred to as fading. Nonetheless free-space channels, providing an unobstructed line-of-sight, are more apt for short, mid-range and potentially long-range (using satellites) communication and will play an important role in the future development and implementation of QKD networks. It was previously theoretically shown that coherent-state CV QKD should be in principle possible to implement over a free-space fading channel, but strong transmittance fluctuations result in the significant modulation-dependent channel excess noise. In this regime the post-selection of highly transmitting sub-channels may be needed, which can even restore the security of the protocol in the strongly turbulent channels. We now report the first proof-of-principle experimental test of coherent state CV QKD protocol using different levels Gaussian modulation over a mid-range (1.6-kilometer long) free-space atmospheric quantum channel. The transmittance of the link was characterized using intensity measurements for the reference but channel estimation using the modulated coherent states was also studied. We consider security against Gaussian collective attacks, that were shown to be optimal against CV QKD protocols . We assumed a general entangling cloner collective attack (modeled using data obtained from the state measurement results on both trusted sides of the protocol), that allows to purify the noise added in the quantum channel . Our security analysis of coherent-state protocol also took into account the effect of imperfect channel estimation, limited post-processing efficiency and finite data ensemble size on the performance of the protocol. In this regime we observe the positive key rate even without the need of applying post-selection. We show the positive improvement of the key rate with increase of the modulation variance, still remaining low enough to tolerate the transmittance fluctuations. The obtained results show that coherent-state CV QKD protocol that uses real free-space atmospheric channel can withstand negative influence of transmittance fluctuations, limited post-processing efficiency, imperfect channel estimation and other finite-size effects, and be successfully implemented. Our result paves the way to the full-scale implementation of the CV QKD in real free-space channels at mid-range distances.

SPM and XPM crosstalk in WDM systems with DRA: Channel spacing and attenuation effects

NASA Astrophysics Data System (ADS)

Morsy, Emadeldeen; Fayed, Heba A.; Abd El Aziz, Ahmed; Aly, Moustafa H.

2018-06-01

This paper presents a theoretical analysis of a closed formula for nonlinear crosstalk due to self-phase modulation (SPM) and cross phase modulation (XPM) in wavelength division multiplexing (WDM) systems. The influence of channel spacing and attenuation on the system behavior is modeled and investigated. The system under consideration is a standard single-mode fiber (SSMF) with a single-span distributed Raman amplifier (DRA) and is operating at 100 Gbps.

High-volume production of single and compound emulsions in a microfluidic parallelization arrangement coupled with coaxial annular world-to-chip interfaces.

PubMed

Nisisako, Takasi; Ando, Takuya; Hatsuzawa, Takeshi

2012-09-21

This study describes a microfluidic platform with coaxial annular world-to-chip interfaces for high-throughput production of single and compound emulsion droplets, having controlled sizes and internal compositions. The production module consists of two distinct elements: a planar square chip on which many copies of a microfluidic droplet generator (MFDG) are arranged circularly, and a cubic supporting module with coaxial annular channels for supplying fluids evenly to the inlets of the mounted chip, assembled from blocks with cylinders and holes. Three-dimensional flow was simulated to evaluate the distribution of flow velocity in the coaxial multiple annular channels. By coupling a 1.5 cm × 1.5 cm microfluidic chip with parallelized 144 MFDGs and a supporting module with two annular channels, for example, we could produce simple oil-in-water (O/W) emulsion droplets having a mean diameter of 90.7 μm and a coefficient of variation (CV) of 2.2% at a throughput of 180.0 mL h(-1). Furthermore, we successfully demonstrated high-throughput production of Janus droplets, double emulsions and triple emulsions, by coupling 1.5 cm × 1.5 cm - 4.5 cm × 4.5 cm microfluidic chips with parallelized 32-128 MFDGs of various geometries and supporting modules with 3-4 annular channels.

Renal intercalated cells and blood pressure regulation.

PubMed

Wall, Susan M

2017-12-01

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

Macro-channel cooled high power fiber coupled diode lasers exceeding 1.2kW of output power

NASA Astrophysics Data System (ADS)

Koenning, Tobias; Alegria, Kim; Wang, Zuolan; Segref, Armin; Stapleton, Dean; Faßbender, Wilhelm; Flament, Marco; Rotter, Karsten; Noeske, Axel; Biesenbach, Jens

2011-03-01

We report on a new series of fiber coupled diode laser modules exceeding 1.2kW of single wavelength optical power from a 400um / 0.2NA fiber. The units are constructed from passively cooled laser bars as opposed to other comparably powered, commercially available modules that use micro-channel heat-sinks. Micro-channel heat sinks require cooling water to meet demanding specifications and are therefore prone to failures due to contamination and increase the overall cost to operate and maintain the laser. Dilas' new series of high power fiber coupled diode lasers are designed to eliminate micro channel coolers and their associated failure mechanisms. Low-smile soldering processes were developed to maximize the brightness available from each diode laser bar. The diode laser brightness is optimally conserved using Dilas' recently developed propriety laser bar stacking geometry and optics. A total of 24 bars are coupled into a single fiber core using a polarization multiplexing scheme. The modular design permits further power scaling through wavelength multiplexing. Other customer critical features such as industrial grade fibers, pilot beams, fiber interlocks and power monitoring are standard features on these modules. The optical design and the beam parameter calculations will be presented to explain the inherit design trade offs. Results for single and dual wavelengths modules will be presented.

A Novel Adaptive Modulation Based on Nondata-Aided Error Vector Magnitude in Non-Line-Of-Sight Condition of Wireless Sensor Network.

PubMed

Yang, Fan; Zeng, Xiaoping; Mao, Haiwei; Jian, Xin; Tan, Xiaoheng; Du, Derong

2018-01-15

The high demand for multimedia applications in environmental monitoring, invasion detection, and disaster aid has led to the rise of wireless sensor network (WSN). With the increase of reliability and diversity of information streams, the higher requirements on throughput and quality of service (QoS) have been put forward in data transmission between two sensor nodes. However, lower spectral efficiency becomes a bottleneck in non-line-of-sight (NLOS) transmission of WSN. This paper proposes a novel nondata-aided error vector magnitude based adaptive modulation (NDA-EVM-AM) to solve the problem. NDA-EVM is considered as a new metric to evaluate the quality of NLOS link for adaptive modulation in WSN. By modeling the NLOS scenario as the η - μ fading channel, a closed-form expression for the NDA-EVM of multilevel quadrature amplitude modulation (MQAM) signals over the η - μ fading channel is derived, and the relationship between SER and NDA-EVM is also formulated. Based on these results, NDA-EVM state machine is designed for adaptation strategy. The algorithmic complexity of NDA-EVM-AM is analyzed and the outage capacity of NDA-EVM-AM in an NLOS scenario is also given. The performances of NDA-EVM-AM are compared by simulation, and the results show that NDA-EVM-AM is an effective technique to be used in the NLOS scenarios of WSN. This technique can accurately reflect the channel variations and efficiently adjust modulation order to better match the channel conditions, hence, obtaining better performance in average spectral efficiency.

Capacity of the generalized PPM channel

NASA Technical Reports Server (NTRS)

Hamkins, Jon; Klimesh, Matt; McEliece, Bob; Moision, Bruce

2004-01-01

We show the capacity of a generalized pulse-position-modulation (PPM) channel, where the input vectors may be any set that allows a transitive group of coordinate permutations, is achieved by a uniform input distribution.

Modulation of K(Ca)3.1 channels by eicosanoids, omega-3 fatty acids, and molecular determinants.

PubMed

Kacik, Michael; Oliván-Viguera, Aida; Köhler, Ralf

2014-01-01

Cytochrome P450- and ω-hydrolase products (epoxyeicosatrienoic acids (EETs), hydroxyeicosatetraeonic acid (20-HETE)), natural omega-3 fatty acids (ω3), and pentacyclic triterpenes have been proposed to contribute to a wide range of vaso-protective and anti-fibrotic/anti-cancer signaling pathways including the modulation of membrane ion channels. Here we studied the modulation of intermediate-conductance Ca(2+)/calmodulin-regulated K(+) channels (K(Ca)3.1) by EETs, 20-HETE, ω3, and pentacyclic triterpenes and the structural requirements of these fatty acids to exert channel blockade. We studied modulation of cloned human hK(Ca)3.1 and the mutant hK(Ca)3.1(V275A) in HEK-293 cells, of rK(Ca)3.1 in aortic endothelial cells, and of mK(Ca)3.1 in 3T3-fibroblasts by inside-out and whole-cell patch-clamp experiments, respectively. In inside-out patches, Ca(2+)-activated hK(Ca)3.1 were inhibited by the ω3, DHA and α-LA, and the ω6, AA, in the lower µmolar range and with similar potencies. 5,6-EET, 8,9-EET, 5,6-DiHETE, and saturated arachidic acid, had no appreciable effects. In contrast, 14,15-EET, its stable derivative, 14,15-EEZE, and 20-HETE produced channel inhibition. 11,12-EET displayed less inhibitory activity. The K(Ca)3.1(V275A) mutant channel was insensitive to any of the blocking EETs. Non-blocking 5,6-EET antagonized the inhibition caused by AA and augmented cloned hK(Ca)3.1 and rK(Ca)3.1 whole-cell currents. Pentacyclic triterpenes did not modulate K(Ca)3.1 currents. Inhibition of K(Ca)3.1 by EETs (14,15-EET), 20-HETE, and ω3 critically depended on the presence of electron double bonds and hydrophobicity within the 10 carbons preceding the carboxyl-head of the molecules. From the physiological perspective, metabolism of AA to non-blocking 5,6,- and 8,9-EET may cause AA-de-blockade and contribute to cellular signal transduction processes influenced by these fatty acids.

Negative gating modulation by (R)-N-(benzimidazol-2-yl)-1,2,3,4-tetrahydro-1-naphthylamine (NS8593) depends on residues in the inner pore vestibule: pharmacological evidence of deep-pore gating of K(Ca)2 channels.

PubMed

Jenkins, David Paul; Strøbæk, Dorte; Hougaard, Charlotte; Jensen, Marianne L; Hummel, Rene; Sørensen, Ulrik S; Christophersen, Palle; Wulff, Heike

2011-06-01

Acting as a negative gating modulator, (R)-N-(benzimidazol-2-yl)-1,2,3,4-tetrahydro-1-naphthylamine (NS8593) shifts the apparent Ca(2+)-dependence of the small-conductance Ca(2+)-activated K(+) channels K(Ca)2.1-2.3 to higher Ca(2+) concentrations. Similar to the positive K(Ca) channel-gating modulators 1-ethyl-2-benzimidazolinone (1-EBIO) and cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methylpyrimidin-4-yl]-amine (CyPPA), the binding site for NS8593 has been assumed to be located in the C-terminal region, in which these channels interact with their Ca(2+) sensor calmodulin. However, by using a progressive chimeric approach, we were able to localize the site-of-action of NS8593 to the K(Ca)2 pore. For example, when we transferred the C terminus from the NS8593-insensitive intermediate-conductance K(Ca)3.1 channel to K(Ca)2.3, the chimeric channel remained as sensitive to NS8593 as wild-type K(Ca)2.3. In contrast, when we transferred the K(Ca)2.3 pore to K(Ca)3.1, the channel became sensitive to NS8593. Using site-directed mutagenesis, we subsequently identified two specific residues in the inner vestibule of K(Ca)2.3 (Ser507 and Ala532) that determined the effect of NS8593. Mutation of these residues to the corresponding residues in K(Ca)3.1 (Thr250 and Val275) made K(Ca)2.3 insensitive to NS8593, whereas introduction of serine and alanine into K(Ca)3.1 was sufficient to render this channel highly sensitive to NS8593. It is noteworthy that the same two residue positions have been found previously to mediate sensitivity of K(Ca)3.1 to clotrimazole and 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34). The location of Ser507 in the pore-loop near the selectivity filter and Ala532 in an adjacent position in S6 are within the region predicted to contain the K(Ca)2 channel gate. Hence, we propose that NS8593-mediated gating modulation occurs via interaction with gating structures at a position deep within the inner pore vestibule.

Coding and Modulation for LMDS and Analysis of the LMDS Channel

PubMed Central

Håkegård, Jan Erik

2000-01-01

Local Multipoint Distribution Service (LMDS) has the potential to become a viable alternative to coaxial cable, fiber and other wired and wireless technologies providing “last mile” communication services. A major obstacle, however, is the high equipment cost. While for example cable modems supporting two-way services are available for $200 to $300, LMDS modem providing similar services will cost over $1000. The major cost driver of LMDS equipment is the radio frequency (RF) unit, as Ka-band technology still is quite expensive. The modem design must minimize the overall architecture cost, and low-cost modems requiring an expensive architecture should not be used. The channel characteristics of LMDS systems are very different from those of fiber, coaxial cable, and lower frequency wireless links, major channel impairments being non-linear high power amplifier (HPA), high phase noise and high co-channel interference. Modems should therefore be developed specifically for LMDS systems. This report deals with the choice of coding and modulation schemes, the LMDS channel, and how the channel impairments should be overcome by digital signal processing algorithms. PMID:27551634

Kv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization

PubMed Central

Vivekananda, Umesh; Novak, Pavel; Bello, Oscar D.; Korchev, Yuri E.; Krishnakumar, Shyam S.; Volynski, Kirill E.; Kullmann, Dimitri M.

2017-01-01

Although action potentials propagate along axons in an all-or-none manner, subthreshold membrane potential fluctuations at the soma affect neurotransmitter release from synaptic boutons. An important mechanism underlying analog–digital modulation is depolarization-mediated inactivation of presynaptic Kv1-family potassium channels, leading to action potential broadening and increased calcium influx. Previous studies have relied heavily on recordings from blebs formed after axon transection, which may exaggerate the passive propagation of somatic depolarization. We recorded instead from small boutons supplied by intact axons identified with scanning ion conductance microscopy in primary hippocampal cultures and asked how distinct potassium channels interact in determining the basal spike width and its modulation by subthreshold somatic depolarization. Pharmacological or genetic deletion of Kv1.1 broadened presynaptic spikes without preventing further prolongation by brief depolarizing somatic prepulses. A heterozygous mouse model of episodic ataxia type 1 harboring a dominant Kv1.1 mutation had a similar broadening effect on basal spike shape as deletion of Kv1.1; however, spike modulation by somatic prepulses was abolished. These results argue that the Kv1.1 subunit is not necessary for subthreshold modulation of spike width. However, a disease-associated mutant subunit prevents the interplay of analog and digital transmission, possibly by disrupting the normal stoichiometry of presynaptic potassium channels. PMID:28193892

Carbon monoxide is a rapid modulator of recombinant and native P2X(2) ligand-gated ion channels.

PubMed

Wilkinson, W J; Gadeberg, H C; Harrison, A W J; Allen, N D; Riccardi, D; Kemp, P J

2009-10-01

Carbon monoxide (CO) is a potent modulator of a wide variety of physiological processes, including sensory signal transduction. Many afferent sensory pathways are dependent upon purinergic neurotransmission, but direct modulation of the P2X purinoceptors by this important, endogenously produced gas has never been investigated. Whole-cell patch-clamp experiments were used to measure ATP-elicited currents in human embryonic kidney 293 cells heterologously expressing P2X(2), P2X(3), P2X(2/3) and P2X(4) receptors and in rat pheochromocytoma (PC12) cells known to express native P2X(2) receptors. Modulation was investigated using solutions containing CO gas and the CO donor molecule, tricarbonyldichlororuthenium (II) dimer (CORM-2). CO was a potent and selective modulator of native P2X(2) receptors, and these effects were mimicked by a CO donor (CORM-2). Neither pre-incubation with 8-bromoguanosine-3',5'-cyclomonophosphate nor 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (a potent blocker of soluble guanylyl cyclase) affected the ability of the CO donor to enhance the ATP-evoked P2X(2) currents. The CO donor caused a small, but significant inhibition of currents evoked by P2X(2/3) and P2X(4) receptors, but was without effect on P2X(3) receptors. These data provided an explanation for how CO might regulate sensory neuronal traffic in physiological reflexes such as systemic oxygen sensing but also showed that CO could be used as a selective pharmacological tool to assess the involvement of homomeric P2X(2) receptors in physiological systems.

Components of cross-frequency modulation in health and disease.

PubMed

Allen, Elena A; Liu, Jingyu; Kiehl, Kent A; Gelernter, Joel; Pearlson, Godfrey D; Perrone-Bizzozero, Nora I; Calhoun, Vince D

2011-01-01

The cognitive deficits associated with schizophrenia are commonly believed to arise from the abnormal temporal integration of information, however a quantitative approach to assess network coordination is lacking. Here, we propose to use cross-frequency modulation (cfM), the dependence of local high-frequency activity on the phase of widespread low-frequency oscillations, as an indicator of network coordination and functional integration. In an exploratory analysis based on pre-existing data, we measured cfM from multi-channel EEG recordings acquired while schizophrenia patients (n = 47) and healthy controls (n = 130) performed an auditory oddball task. Novel application of independent component analysis (ICA) to modulation data delineated components with specific spatial and spectral profiles, the weights of which showed covariation with diagnosis. Global cfM was significantly greater in healthy controls (F(1,175) = 9.25, P < 0.005), while modulation at fronto-temporal electrodes was greater in patients (F(1,175) = 17.5, P < 0.0001). We further found that the weights of schizophrenia-relevant components were associated with genetic polymorphisms at previously identified risk loci. Global cfM decreased with copies of 957C allele in the gene for the dopamine D2 receptor (r = -0.20, P < 0.01) across all subjects. Additionally, greater "aberrant" fronto-temporal modulation in schizophrenia patients was correlated with several polymorphisms in the gene for the α2-subunit of the GABA(A) receptor (GABRA2) as well as the total number of risk alleles in GABRA2 (r = 0.45, P < 0.01). Overall, our results indicate great promise for this approach in establishing patterns of cfM in health and disease and elucidating the roles of oscillatory interactions in functional connectivity.

Land Mobile Satellite Service (LMSS) channel simulator: An end-to-end hardware simulation and study of the LMSS communications links

NASA Technical Reports Server (NTRS)

Salmasi, A. B. (Editor); Springett, J. C.; Sumida, J. T.; Richter, P. H.

1984-01-01

The design and implementation of the Land Mobile Satellite Service (LMSS) channel simulator as a facility for an end to end hardware simulation of the LMSS communications links, primarily with the mobile terminal is described. A number of studies are reported which show the applications of the channel simulator as a facility for validation and assessment of the LMSS design requirements and capabilities by performing quantitative measurements and qualitative audio evaluations for various link design parameters and channel impairments under simulated LMSS operating conditions. As a first application, the LMSS channel simulator was used in the evaluation of a system based on the voice processing and modulation (e.g., NBFM with 30 kHz of channel spacing and a 2 kHz rms frequency deviation for average talkers) selected for the Bell System's Advanced Mobile Phone Service (AMPS). The various details of the hardware design, qualitative audio evaluation techniques, signal to channel impairment measurement techniques, the justifications for criteria of different parameter selection in regards to the voice processing and modulation methods, and the results of a number of parametric studies are further described.

Local anesthetic and antiepileptic drug access and binding to a bacterial voltage-gated sodium channel

PubMed Central

Boiteux, Céline; Vorobyov, Igor; French, Robert J.; French, Christopher; Yarov-Yarovoy, Vladimir; Allen, Toby W.

2014-01-01

Voltage-gated sodium (Nav) channels are important targets in the treatment of a range of pathologies. Bacterial channels, for which crystal structures have been solved, exhibit modulation by local anesthetic and anti-epileptic agents, allowing molecular-level investigations into sodium channel-drug interactions. These structures reveal no basis for the “hinged lid”-based fast inactivation, seen in eukaryotic Nav channels. Thus, they enable examination of potential mechanisms of use- or state-dependent drug action based on activation gating, or slower pore-based inactivation processes. Multimicrosecond simulations of NavAb reveal high-affinity binding of benzocaine to F203 that is a surrogate for FS6, conserved in helix S6 of Domain IV of mammalian sodium channels, as well as low-affinity sites suggested to stabilize different states of the channel. Phenytoin exhibits a different binding distribution owing to preferential interactions at the membrane and water–protein interfaces. Two drug-access pathways into the pore are observed: via lateral fenestrations connecting to the membrane lipid phase, as well as via an aqueous pathway through the intracellular activation gate, despite being closed. These observations provide insight into drug modulation that will guide further developments of Nav inhibitors. PMID:25136136

Sterol Regulation of Voltage-Gated K+ Channels.

PubMed

Balajthy, Andras; Hajdu, Peter; Panyi, Gyorgy; Varga, Zoltan

2017-01-01

Cholesterol is an essential lipid building block of the cellular plasma membrane. In addition to its structural role, it regulates the fluidity and raft structure of the membrane and influences the course of numerous membrane-linked signaling pathways and the function of transmembrane proteins, including ion channels. This is supported by a vast body of scientific data, which demonstrates the modulation of ion channels with a great variety of ion selectivity, gating, and tissue distribution by changes in membrane cholesterol. Here, we review what is currently known about the modulation of voltage-gated K + (Kv) channels by changes in membrane cholesterol content, considering raft association of the channels, the roles of cholesterol recognition sites, and those of adaptor proteins in cholesterol-Kv channel interactions. We specifically focus on Kv1.3, the dominant K + channel of human T cells. Effects of cholesterol depletion and enrichment and 7-dehydrocholesterol enrichment on Kv1.3 gating are discussed in the context of the immunological synapse and the comparison of the in vitro effects of sterol modifications on Kv1.3 function with ex vivo effects on cells from hypercholesterolemic and Smith-Lemli-Opitz patients. © 2017 Elsevier Inc. All rights reserved.

Subcarrier multiplexing with dispersion reduction and direct detection

DOEpatents

Sargis, Paul D.; Haigh, Ronald E.; McCammon, Kent G.

1997-01-01

An SCM system for simultaneously reducing the concomitant problems of receiver complexity and dispersion penalty and without requiring the use of an expensive, high-bandwidth optical detector. The system provides both a dispersion reduction and a direct detection to the receiver, with microwave mixers and lithium niobate external modulators that produce sidebands that are only separated by a few gigahertz from a principal laser optical carrier. Digital data streams are independently impressed upon these sidebands for transmission over an ordinary single-mode fiber. Independent high-speed data streams are upconverted to microwave frequencies. These subcarriers are then combined with a microwave power combiner and amplified with a microwave amplifier. A solid-state 1550-nm laser carrier is modulated by the microwave subcarriers. An erbium-doped fiber amplifier (EDFA) is used just prior to long-distance transmission over ordinary single-mode fiber. The transmitted optical signal may then traverse multiple EDFAs to compensate for long-haul optical fiber losses prior to detection. At a receiving end, the optical signal is split into multiple paths. The subcarrier channels are optically pre-selected using a narrowband optical filter, such as a fiber Fabry-Perot (FFP) filter. An optical detector converts the selected optical signal into a baseband electrical data stream.

An efficient system for reliably transmitting image and video data over low bit rate noisy channels

NASA Technical Reports Server (NTRS)

Costello, Daniel J., Jr.; Huang, Y. F.; Stevenson, Robert L.

1994-01-01

This research project is intended to develop an efficient system for reliably transmitting image and video data over low bit rate noisy channels. The basic ideas behind the proposed approach are the following: employ statistical-based image modeling to facilitate pre- and post-processing and error detection, use spare redundancy that the source compression did not remove to add robustness, and implement coded modulation to improve bandwidth efficiency and noise rejection. Over the last six months, progress has been made on various aspects of the project. Through our studies of the integrated system, a list-based iterative Trellis decoder has been developed. The decoder accepts feedback from a post-processor which can detect channel errors in the reconstructed image. The error detection is based on the Huber Markov random field image model for the compressed image. The compression scheme used here is that of JPEG (Joint Photographic Experts Group). Experiments were performed and the results are quite encouraging. The principal ideas here are extendable to other compression techniques. In addition, research was also performed on unequal error protection channel coding, subband vector quantization as a means of source coding, and post processing for reducing coding artifacts. Our studies on unequal error protection (UEP) coding for image transmission focused on examining the properties of the UEP capabilities of convolutional codes. The investigation of subband vector quantization employed a wavelet transform with special emphasis on exploiting interband redundancy. The outcome of this investigation included the development of three algorithms for subband vector quantization. The reduction of transform coding artifacts was studied with the aid of a non-Gaussian Markov random field model. This results in improved image decompression. These studies are summarized and the technical papers included in the appendices.

Hyaluronan modulates TRPV1 channel opening, reducing peripheral nociceptor activity and pain

PubMed Central

Caires, Rebeca; Luis, Enoch; Taberner, Francisco J.; Fernandez-Ballester, Gregorio; Ferrer-Montiel, Antonio; Balazs, Endre A.; Gomis, Ana; Belmonte, Carlos; de la Peña, Elvira

2015-01-01

Hyaluronan (HA) is present in the extracellular matrix of all body tissues, including synovial fluid in joints, in which it behaves as a filter that buffers transmission of mechanical forces to nociceptor nerve endings thereby reducing pain. Using recombinant systems, mouse-cultured dorsal root ganglia (DRG) neurons and in vivo experiments, we found that HA also modulates polymodal transient receptor potential vanilloid subtype 1 (TRPV1) channels. HA diminishes heat, pH and capsaicin (CAP) responses, thus reducing the opening probability of the channel by stabilizing its closed state. Accordingly, in DRG neurons, HA decreases TRPV1-mediated impulse firing and channel sensitization by bradykinin. Moreover, subcutaneous HA injection in mice reduces heat and capsaicin nocifensive responses, whereas the intra-articular injection of HA in rats decreases capsaicin joint nociceptor fibres discharge. Collectively, these results indicate that extracellular HA reduces the excitability of the ubiquitous TRPV1 channel, thereby lowering impulse activity in the peripheral nociceptor endings underlying pain. PMID:26311398

Waveguide module comprising a first plate with a waveguide channel and a second plate with a raised portion in which a sealing layer is forced into the waveguide channel by the raised portion

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

Strassner, II, Bernd H.; Liedtke, Richard; McDonald, Jacob Jeremiah

The various technologies presented herein relate to utilizing a sealing layer of malleable material to seal gaps, etc., at a joint between edges of a waveguide channel formed in a first plate and a surface of a clamping plate. A compression pad is included in the surface of the clamping plate and is dimensioned such that the upper surface of the pad is less than the area of the waveguide channel opening on the first plate. The sealing layer is placed between the waveguide plate and the clamping plate, and during assembly of the waveguide module, the compression pad deformsmore » a portion of the sealing layer such that it ingresses into the waveguide channel opening. Deformation of the sealing layer results in the gaps, etc., to be filled, improving the operational integrity of the joint.« less

Impaired redox environment modulates cardiogenic and ion-channel gene expression in cardiac-resident and non-resident mesenchymal stem cells.

PubMed

Subramani, Baskar; Subbannagounder, Sellamuthu; Ramanathanpullai, Chithra; Palanivel, Sekar; Ramasamy, Rajesh

2017-03-01

Redox homeostasis plays a crucial role in the regulation of self-renewal and differentiation of stem cells. However, the behavioral actions of mesenchymal stem cells in redox imbalance state remain elusive. In the present study, the effect of redox imbalance that was induced by either hydrogen peroxide (H 2 O 2 ) or ascorbic acid on human cardiac-resident (hC-MSCs) and non-resident (umbilical cord) mesenchymal stem cells (hUC-MSCs) was evaluated. Both cells were sensitive and responsive when exposed to either H 2 O 2 or ascorbic acid at a concentration of 400 µmol/L. Ascorbic acid pre-treated cells remarkably ameliorated the reactive oxygen species level when treated with H 2 O 2 . The endogenous antioxidative enzyme gene (Sod1, Sod2, TRXR1 and Gpx1) expressions were escalated in both MSCs in response to reactive oxygen species elevation. In contrast, ascorbic acid pre-treated hUC-MSCs attenuated considerable anti-oxidative gene (TRXR1 and Gpx1) expressions, but not the hC-MSCs. Similarly, the cardiogenic gene (Nkx 2.5, Gata4, Mlc2a and β-MHC) and ion-channel gene ( I KDR , I KCa , I to and I Na.TTX ) expressions were significantly increased in both MSCs on the oxidative state. On the contrary, reduced environment could not alter the ion-channel gene expression and negatively regulated the cardiogenic gene expressions except for troponin-1 in both cells. In conclusion, redox imbalance potently alters the cardiac-resident and non-resident MSCs stemness, cardiogenic, and ion-channel gene expressions. In comparison with cardiac-resident MSC, non-resident umbilical cord-MSC has great potential to tolerate the redox imbalance and positively respond to cardiac regeneration. Impact statement Human mesenchymal stem cells (h-MSCs) are highly promising candidates for tissue repair in cardiovascular diseases. However, the retention of cells in the infarcted area has been a major challenge due to its poor viability and/or low survival rate after transplantation. The regenerative potential of mesenchymal stem cells (MSCs) repudiate and enter into premature senescence via oxidative stress. Thus, various strategies have been attempted to improve the MSC survival in 'toxic' conditions. Similarly, we investigated the response of cardiac resident MSC (hC-MSCs) and non-resident MSCs against the oxidative stress induced by H 2 O 2 . Supplementation of ascorbic acid (AA) into MSCs culture profoundly rescued the stem cells from oxidative stress induced by H 2 O 2 . Our data showed that the pre-treatment of AA is able to inhibit the cell death and thus preserving the viability and differentiation potential of MSCs.

Using King Vision video laryngoscope with a channeled blade prolongs time for tracheal intubation in different training levels, compared to non-channeled blade.

PubMed

Kriege, Marc; Alflen, Christian; Noppens, Ruediger R

2017-01-01

It is generally accepted that using a video laryngoscope is associated with an improved visualization of the glottis. However, correctly placing the endotracheal tube might be challenging. Channeled video laryngoscopic blades have an endotracheal tube already pre-loaded, allowing to advance the tube once the glottis is visualized. We hypothesized that use of a channel blade with pre-loaded endotracheal tube results in a faster intubation, compared to a curved Macintosh blade video laryngoscope. After ethical approval and informed consent, patients were randomized to receive endotracheal Intubation with either the King Vision® video laryngoscope with curved blade (control) or channeled blade (channeled). Success rate, evaluation of the glottis view (percentage of glottic opening (POGO), Cormack&Lehane (C&L)) and intubating time were evaluated. Over a two-month period, a total of 46 patients (control n = 23; channeled n = 23) were examined. The first attempt success rates were comparable between groups (control 100% (23/23) vs. channeled 96% (22/23); p = 0.31). Overall intubation time was significantly shorter with control (median 40 sec; IQR [24-58]), compared to channeled (59 sec [40-74]; p = 0.03). There were no differences in glottis visualization between groups. Compared with the King Vision channeled blade, time for tracheal intubation was shorter with the control group using a non-channeled blade. First attempt success and visualization of the glottis were comparable. These data do not support the hypothesis that a channeled blade is superior to a curved video laryngoscopic blade without tube guidance. ClinicalTrials.gov NCT02344030.

Engineering Design Modules as Physics Teaching Tools

ERIC Educational Resources Information Center

Oliver, Douglas L.; Kane, Jackie

2011-01-01

Pre-engineering is increasingly being taught as a high school subject. This development presents challenges as well as opportunities for the physics education community. If pre-engineering is taught as a separate class, it may divert resources and students from traditional physics classes. However, design modules can be used as physics teaching…

Tilesetting. Pre-Apprenticeship Phase 2 Training. Instructor's Guide.

ERIC Educational Resources Information Center

Ausland, Greg

This instructor's guide accompanies the self-paced student training modules on tilesetting, available separately as CE 031 564. Introductory materials include a description of the components of the pre-apprenticeship project, discussion of teacher's role in students' completion of the modules, and scope and contents of Phase 2 training. Each of…

Dynamics of neuromodulatory feedback determines frequency modulation in a reduced respiratory network: a computational study.

PubMed

Toporikova, Natalia; Butera, Robert J

2013-02-01

Neuromodulators, such as amines and neuropeptides, alter the activity of neurons and neuronal networks. In this work, we investigate how neuromodulators, which activate G(q)-protein second messenger systems, can modulate the bursting frequency of neurons in a critical portion of the respiratory neural network, the pre-Bötzinger complex (preBötC). These neurons are a vital part of the ponto-medullary neuronal network, which generates a stable respiratory rhythm whose frequency is regulated by neuromodulator release from the nearby Raphe nucleus. Using a simulated 50-cell network of excitatory preBötC neurons with a heterogeneous distribution of persistent sodium conductance and Ca(2+), we determined conditions for frequency modulation in such a network by simulating interaction between Raphe and preBötC nuclei. We found that the positive feedback between the Raphe excitability and preBötC activity induces frequency modulation in the preBötC neurons. In addition, the frequency of the respiratory rhythm can be regulated via phasic release of excitatory neuromodulators from the Raphe nucleus. We predict that the application of a G(q) antagonist will eliminate this frequency modulation by the Raphe and keep the network frequency constant and low. In contrast, application of a G(q) agonist will result in a high frequency for all levels of Raphe stimulation. Our modeling results also suggest that high [K(+)] requirement in respiratory brain slice experiments may serve as a compensatory mechanism for low neuromodulatory tone. Copyright © 2012 Elsevier B.V. All rights reserved.

Pre-electroconvulsive shock administration of calcium channel blockers reduces retrograde amnesia induced by ECS.

PubMed

Sushma, M; Sudha, S; Guido, S

2004-11-01

Effect of pre-electroconvulsive shock (ECS) administration of calcium channel blockers (CCBs) like verapamil, diltiazem, nifedipine, nimodipine, flunarizine and cinnarizine on retrograde amnesia induced by ECS was examined using passive avoidance paradigm in rats. The groups (Gr 1-7) of adult, male Wistar rats received true ECS with CCBs (5mg/kg; i.p) or vehicle (10 ml/kg; ip) and other groups (Gr 8-14) received sham ECS with CCBs (5mg/kg; i.p) or vehicle (10 ml/kg; i.p). The anti-amnestic activity of CCBs were evaluated using the passive avoidance paradigm in rats. Results showed that, the baseline latencies for all the groups did not differ significantly. Rats receiving true ECS produced significantly lower latencies. There was increase in the post ECS step through latencies of the rats administered CCBs before ECS. Therefore, pre-ECS administration of calcium channel blockers might reduce retrograde amnesia produced by ECS without altering seizure duration.

Polymerase chain reaction system using magnetic beads for analyzing a sample that includes nucleic acid

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

Nasarabadi, Shanavaz

2011-01-11

A polymerase chain reaction system for analyzing a sample containing nucleic acid includes providing magnetic beads; providing a flow channel having a polymerase chain reaction chamber, a pre polymerase chain reaction magnet position adjacent the polymerase chain reaction chamber, and a post pre polymerase magnet position adjacent the polymerase chain reaction chamber. The nucleic acid is bound to the magnetic beads. The magnetic beads with the nucleic acid flow to the pre polymerase chain reaction magnet position in the flow channel. The magnetic beads and the nucleic acid are washed with ethanol. The nucleic acid in the polymerase chain reactionmore » chamber is amplified. The magnetic beads and the nucleic acid are separated into a waste stream containing the magnetic beads and a post polymerase chain reaction mix containing the nucleic acid. The reaction mix containing the nucleic acid flows to an analysis unit in the channel for analysis.« less

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

PubMed Central

Tykocki, Nathan R.; Boerman, Erika M.; Jackson, William F.

2017-01-01

Vascular tone of resistance arteries and arterioles determines peripheral vascular resistance, contributing to the regulation of blood pressure and blood flow to, and within the body’s tissues and organs. Ion channels in the plasma membrane and endoplasmic reticulum of vascular smooth muscle cells (SMCs) in these blood vessels importantly contribute to the regulation of intracellular Ca2+ concentration, the primary determinant of SMC contractile activity and vascular tone. Ion channels provide the main source of activator Ca2+ that determines vascular tone, and strongly contribute to setting and regulating membrane potential, which, in turn, regulates the open-state-probability of voltage gated Ca2+ channels (VGCCs), the primary source of Ca2+ in resistance artery and arteriolar SMCs. Ion channel function is also modulated by vasoconstrictors and vasodilators, contributing to all aspects of the regulation of vascular tone. This review will focus on the physiology of VGCCs, voltage-gated K+ (KV) channels, large-conductance Ca2+-activated K+ (BKCa) channels, strong-inward-rectifier K+ (KIR) channels, ATP-sensitive K+ (KATP) channels, ryanodine receptors (RyRs), inositol 1,4,5-trisphosphate receptors (IP3Rs), and a variety of transient receptor potential (TRP) channels that contribute to pressure-induced myogenic tone in resistance arteries and arterioles, the modulation of the function of these ion channels by vasoconstrictors and vasodilators, their role in the functional regulation of tissue blood flow and their dysfunction in diseases such as hypertension, obesity, and diabetes. PMID:28333380

Natural products modulating the hERG channel: heartaches and hope.

PubMed

Kratz, Jadel M; Grienke, Ulrike; Scheel, Olaf; Mann, Stefan A; Rollinger, Judith M

2017-08-02

Covering: 1996-December 2016The human Ether-à-go-go Related Gene (hERG) channel is a voltage-gated potassium channel playing an essential role in the normal electrical activity in the heart. It is involved in the repolarization and termination of action potentials in excitable cardiac cells. Mutations in the hERG gene and hERG channel blockage by small molecules are associated with increased risk of fatal arrhythmias. Several drugs have been withdrawn from the market due to hERG channel-related cardiotoxicity. Moreover, as a result of its notorious ligand promiscuity, this ion channel has emerged as an important antitarget in early drug discovery and development. Surprisingly, the hERG channel blocking profile of natural compounds present in frequently consumed botanicals (i.e. dietary supplements, spices, and herbal medicinal products) is not routinely assessed. This comprehensive review will address these issues and provide a critical compilation of hERG channel data for isolated natural products and extracts over the past two decades (1996-2016). In addition, the review will provide (i) a solid basis for the molecular understanding of the physiological functions of the hERG channel, (ii) the translational potential of in vitro/in vivo results to cardiotoxicity in humans, (iii) approaches for the identification of hERG channel blockers from natural sources, (iv) future perspectives for cardiac safety guidelines and their applications within phytopharmaceuticals and dietary supplements, and (v) novel applications of hERG channel modulation (e.g. as a drug target).

STIM1 converts TRPC1 from a receptor-operated to a store-operated channel: moving TRPC1 in and out of lipid rafts.

PubMed

Alicia, Sampieri; Angélica, Zepeda; Carlos, Saldaña; Alfonso, Salgado; Vaca, Luis

2008-11-01

While the role of members from the TRPC family of channels as receptor-operated channels (ROC) is well established and supported by numerous studies, the role of this family of channels as store-operated channels (SOC) has been the focus of a heated controversy over the last few years. In the present study, we have explored the modulation of STIM1 on human TRPC1 channel. We show that the association of STIM1 to TRPC1 favors the insertion of TRPC1 into lipid rafts, where TRPC1 functions as a SOC. In the absence of STIM1, TRPC1 associates to other members from the TRPC family of channels to form ROCs. A novel TIRFM-FRET method illustrates the relevance of the dynamic association between STIM1 and TRPC1 for the activation of SOC and the lipid raft localization of the STIM1-TRPC1 complex. This study provides new evidence about the dual activity of TRPC1 (forming ROC or SOC) and the partners needed to determine TRPC1 functional fate. It highlights also the role of plasma membrane microdomains and ER-PM junctions in modulating TRPC1 channel function and its association to STIM1.

Calcium channel currents in bovine adrenal chromaffin cells and their modulation by anaesthetic agents.

PubMed Central

Charlesworth, P; Pocock, G; Richards, C D

1994-01-01

1. The calcium channel currents of bovine adrenal chromaffin cells were characterized using a variety of voltage pulse protocols and selective channel blockers before examination of their modulation by anaesthetic agents. 2. All the anaesthetics studied (halothane, methoxyflurane, etomidate and methohexitone) inhibited the calcium channel currents in a concentration-dependent manner and increased the rate of current decay. 3. The anaesthetics did not shift the current-voltage relation nor did they change the voltage for half-maximal channel activation derived from analysis of the voltage dependence of the tail currents. None of the anaesthetics appeared to alter the time constant of tail current decay. 4. To complement earlier studies of the inhibitory actions of anaesthetics on K(+)-evoked catecholamine secretion and the associated Ca2+ uptake, the IC50 values for etomidate and methohexitone were determined using a biochemical assay. The IC50 values for anaesthetic inhibition of calcium channel currents corresponded closely with those for inhibition of K(+)-evoked calcium uptake and catecholamine secretion. 5. The inhibitory effect of the volatile anaesthetics and etomidate is best explained by dual action: a reduction in the probability of channel opening coupled with an increase in the rate of channel inactivation. Methohexitone appeared to inhibit the currents by a use-dependent slow block. PMID:7707224

Anaesthetic modulation of nicotinic ion channel kinetics in bovine chromaffin cells.

PubMed Central

Charlesworth, P; Richards, C D

1995-01-01

1. We have investigated the action of the anaesthetics methoxyflurane, methohexitone and etomidate on the nicotinic acetylcholine receptor channel of bovine adrenal chromaffin cells using the whole cell patch clamp technique. 2. Spectral analysis of macroscopic currents evoked by 25 microM carbachol revealed that each of the agents tested reduced the lifetime of the channel open state in a dose-dependent manner. The whole cell current was inhibited in a concentration-dependent fashion by each agent. 3. Channel gating parameters were calculated from single channel studies and the results used to test models explaining the modulation of nicotinic acetylcholine receptor channels by anaesthetics. 4. Each of the agents studied reduced the mean channel open time in a concentration-dependent manner. Anaesthetic concentrations reducing mean open time by 50% were: 370 microM methoxyflurane, 30 microM methohexitone or 23 microM etomidate. 5. Methohexitone and etomidate produced an increase in the number of brief closures within bursts, while no such increase was observed with methoxyflurane. Despite these inter-burst gaps, mean burst length was reduced by each of the agents tested. 6. It is concluded that a simple sequential blocking model fails to account for the action of these anaesthetics. An extended model, in which blocked channels can close, may be applicable. PMID:7773553

Piezoelectric coupling in a field-effect transistor with a nanohybrid channel of ZnO nanorods grown vertically on graphene.

PubMed

Quang Dang, Vinh; Kim, Do-Il; Thai Duy, Le; Kim, Bo-Yeong; Hwang, Byeong-Ung; Jang, Mi; Shin, Kyung-Sik; Kim, Sang-Woo; Lee, Nae-Eung

2014-12-21

Piezoelectric coupling phenomena in a graphene field-effect transistor (GFET) with a nano-hybrid channel of chemical-vapor-deposited Gr (CVD Gr) and vertically aligned ZnO nanorods (NRs) under mechanical pressurization were investigated. Transfer characteristics of the hybrid channel GFET clearly indicated that the piezoelectric effect of ZnO NRs under static or dynamic pressure modulated the channel conductivity (σ) and caused a positive shift of 0.25% per kPa in the Dirac point. However, the GFET without ZnO NRs showed no change in either σ or the Dirac point. Analysis of the Dirac point shifts indicated transfer of electrons from the CVD Gr to ZnO NRs due to modulation of their interfacial barrier height under pressure. High responsiveness of the hybrid channel device with fast response and recovery times was evident in the time-dependent behavior at a small gate bias. In addition, the hybrid channel FET could be gated by mechanical pressurization only. Therefore, a piezoelectric-coupled hybrid channel GFET can be used as a pressure-sensing device with low power consumption and a fast response time. Hybridization of piezoelectric 1D nanomaterials with a 2D semiconducting channel in FETs enables a new design for future nanodevices.

TRPV1 channels in cardiovascular system: A double edged sword?

PubMed

Randhawa, Puneet Kaur; Jaggi, Amteshwar Singh

2017-02-01

Apart from modulating nociception, there is vital role of TRPV 1 channels in modulating atherosclerosis, congestive heart failure, systemic hypertension, pulmonary hypertension, hemorrhagic shock and vascular remodeling. TRPV 1 channel activation has shielding effect against the development of atherosclerosis and systemic hypertension. TRPV 1 channel activation alleviates the formation of atherosclerotic lesions via increasing the expression of cholesterol efflux regulatory protein, UCP 2 and enhancing autophagy. Furthermore, activation of these channels enhances Na + excretion and NO release to reduce the blood pressure. TRPV 1 channel activation in the cardiac sensory neurons and subsequent CGRP release reduces ischemia-reperfusion injury. Activation of these channels during conditioning enhances CGRP and SP release from the sensory nerve fibers innervating the heart to induce cardioprotection. However, activation of these channels may elicit detrimental effects in pulmonary hypertension, hemorrhage and vascular remodeling. Activation of TRPV 1 channels enhances smooth muscle cell proliferation to promote pulmonary hypertension. Moreover, TRPV 1 channel inhibition reduces massive catecholamine release, improves survival during hemorrhage. Activation of these channels enhances vascular remodeling via enhancing NO release. Furthermore, dual role of TRPV 1 channels has been reported in the perpetuation of congestive heart failure. On one hand, TRPV 1 channel activation increases the expression of UCP2, PPAR- δ and mitochondrial sirtuin 3 to decrease oxidative stress and reduce heart injury. On the other hand, activation of these channels may enhance the expression of hypertrophic fibrotic proteins viz. GATA4, MMP to promote cardiac fibrosis. The present review discusses the dual role of activation of TRPV 1 channels in diseases associated with cardiovascular system. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Hippocampal effective synchronization values are not pre-seizure indicator without considering the state of the onset channels

PubMed Central

Shayegh, Farzaneh; Sadri, Saeed; Amirfattahi, Rassoul; Ansari-Asl, Karim; Bellanger, Jean-Jacques; Senhadji, Lotfi

2014-01-01

In this paper, a model-based approach is presented to quantify the effective synchrony between hippocampal areas from depth-EEG signals. This approach is based on the parameter identification procedure of a realistic Multi-Source/Multi-Channel (MSMC) hippocampal model that simulates the function of different areas of hippocampus. In the model it is supposed that the observed signals recorded using intracranial electrodes are generated by some hidden neuronal sources, according to some parameters. An algorithm is proposed to extract the intrinsic (solely relative to one hippocampal area) and extrinsic (coupling coefficients between two areas) model parameters, simultaneously, by a Maximum Likelihood (ML) method. Coupling coefficients are considered as the measure of effective synchronization. This work can be considered as an application of Dynamic Causal Modeling (DCM) that enables us to understand effective synchronization changes during transition from inter-ictal to pre -ictal state. The algorithm is first validated by using some synthetic datasets. Then by extracting the coupling coefficients of real depth-EEG signals by the proposed approach, it is observed that the coupling values show no significant difference between ictal, pre-ictal and inter-ictal states, i.e., either the increase or decrease of coupling coefficients has been observed in all states. However, taking the value of intrinsic parameters into account, pre-seizure state can be distinguished from inter-ictal state. It is claimed that seizures start to appear when there are seizure-related physiological parameters on the onset channel, and its coupling coefficient toward other channels increases simultaneously. As a result of considering both intrinsic and extrinsic parameters as the feature vector, inter-ictal, pre-ictal and ictal activities are discriminated from each other with an accuracy of 91.33% accuracy. PMID:25061815

A TDM link with channel coding and digital voice.

NASA Technical Reports Server (NTRS)

Jones, M. W.; Tu, K.; Harton, P. L.

1972-01-01

The features of a TDM (time-division multiplexed) link model are described. A PCM telemetry sequence was coded for error correction and multiplexed with a digitized voice channel. An all-digital implementation of a variable-slope delta modulation algorithm was used to digitize the voice channel. The results of extensive testing are reported. The measured coding gain and the system performance over a Gaussian channel are compared with theoretical predictions and computer simulations. Word intelligibility scores are reported as a measure of voice channel performance.

Numerical analysis of field-modulated electroosmotic flows in microchannels with arbitrary numbers and configurations of discrete electrodes.

PubMed

Chao, Kan; Chen, Bo; Wu, Jiankang

2010-12-01

The formation of an electric double layer and electroosmosis are important theoretic foundations associated with microfluidic systems. Field-modulated electroosmotic flows in microchannels can be obtained by applying modulating electric fields in a direction perpendicular to a channel wall. This paper presents a systematic numerical analysis of modulated electroosmotic flows in a microchannel with discrete electrodes on the basis of the Poisson equation of electric fields in a liquid-solid coupled domain, the Navier-Stokes equation of liquid flow, and the Nernst-Planck equation of ion transport. These equations are nonlinearly coupled and are simultaneously solved numerically for the electroosmotic flow velocity, electric potential, and ion concentrations in the microchannel. A number of numerical examples of modulated electroosmotic flows in microchannels with discrete electrodes are presented, including single electrodes, symmetric/asymmetric double electrodes, and triple electrodes. Numerical results indicate that chaotic circulation flows, micro-vortices, and effective fluid mixing can be realized in microchannels by applying modulating electric fields with various electrode configurations. The interaction of a modulating field with an applied field along the channel is also discussed.

Fiber-based polarization-sensitive Mueller matrix optical coherence tomography with continuous source polarization modulation.

PubMed

Jiao, Shuliang; Todorović, Milos; Stoica, George; Wang, Lihong V

2005-09-10

We report on a new configuration of fiber-based polarization-sensitive Mueller matrix optical coherence tomography that permits the acquisition of the round-trip Jones matrix of a biological sample using only one light source and a single depth scan. In this new configuration, a polarization modulator is used in the source arm to continuously modulate the incident polarization state for both the reference and the sample arms. The Jones matrix of the sample can be calculated from the two frequency terms in the two detection channels. The first term is modulated by the carrier frequency, which is determined by the longitudinal scanning mechanism, whereas the other term is modulated by the beat frequency between the carrier frequency and the second harmonic of the modulation frequency of the polarization modulator. One important feature of this system is that, for the first time to our knowledge, the Jones matrix of the sample can be calculated with a single detection channel and a single measurement when diattenuation is negligible. The system was successfully tested by imaging both standard polarization elements and biological samples.

Small Molecule Modulators of Pre-mRNA Splicing in Cancer Therapy.

PubMed

Salton, Maayan; Misteli, Tom

2016-01-01

Pre-mRNA splicing is a fundamental process in mammalian gene expression and alternative RNA splicing plays a considerable role in generating protein diversity. RNA splicing events are also key to the pathology of numerous diseases, particularly cancers. Some tumors are molecularly addicted to specific RNA splicing isoforms making interference with pre-mRNA processing a viable therapeutic strategy. Several RNA splicing modulators have recently been characterized, some showing promise in preclinical studies. While the targets of most splicing modulators are constitutive RNA processing components, possibly leading to undesirable side effects, selectivity for individual splicing events has been observed. Given the high prevalence of splicing defects in cancer, small molecule modulators of RNA processing represent a potentially promising novel therapeutic strategy in cancer treatment. Here, we review their reported effects, mechanisms, and limitations. Published by Elsevier Ltd.

Real-time experimental demonstrations of software reconfigurable optical OFDM transceivers utilizing DSP-based digital orthogonal filters for SDN PONs.

PubMed

Duan, X; Giddings, R P; Bolea, M; Ling, Y; Cao, B; Mansoor, S; Tang, J M

2014-08-11

Real-time optical OFDM (OOFDM) transceivers with on-line software-controllable channel reconfigurability and transmission performance adaptability are experimentally demonstrated, for the first time, utilizing Hilbert-pair-based 32-tap digital orthogonal filters implemented in FPGAs. By making use of an 8-bit DAC/ADC operating at 2GS/s, an oversampling factor of 2 and an EML intensity modulator, the demonstrated RF conversion-free transceiver supports end-to-end real-time simultaneous adaptive transmissions, within a 1GHz signal spectrum region, of a 2.03Gb/s in-phase OOFDM channel and a 1.41Gb/s quadrature-phase OOFDM channel over a 25km SSMF IMDD system. In addition, detailed experimental explorations are also undertaken of key physical mechanisms limiting the maximum achievable transmission performance, impacts of transceiver's channel multiplexing/demultiplexing operations on the system BER performance, and the feasibility of utilizing adaptive modulation to combat impairments associated with low-complexity digital filter designs. Furthermore, experimental results indicate that the transceiver incorporating a fixed digital orthogonal filter DSP architecture can be made transparent to various signal modulation formats up to 64-QAM.

Application of DFT Filter Banks and Cosine Modulated Filter Banks in Filtering

NASA Technical Reports Server (NTRS)

Lin, Yuan-Pei; Vaidyanathan, P. P.

1994-01-01

None given. This is a proposal for a paper to be presented at APCCAS '94 in Taipei, Taiwan. (From outline): This work is organized as follows: Sec. II is devoted to the construction of the new 2m channel under-decimated DFT filter bank. Implementation and complexity of this DFT filter bank are discussed therein. IN a similar manner, the new 2m channel cosine modulated filter bank is discussed in Sec. III. Design examples are given in Sec. IV.

Mechanisms involved in the gastroprotective activity of esculin on acute gastric lesions in mice.

PubMed

Rios, Emiliano Ricardo Vasconcelos; Rocha, Nayrton Flávio Moura; Venâncio, Edith Teles; Moura, Brinell Arcanjo; Feitosa, Mariana Lima; Cerqueira, Gilberto Santos; Soares, Pedro Marcos Gomes; Woods, David John; de Sousa, Francisca Cléa Florenço; Leal, Luzia Kalyne Almeida Moreira; Fonteles, Marta Maria de França

2010-10-06

This work describes the gastroprotective actions of esculin (6,7-dihydroxycoumarin-6-o-glucoside) against indomethacin- or ethanol-induced lesions and verifies the role of nitric oxide, ATP-dependent K(+) channels, prostaglandins, transient receptor potential vanilloid 1 and antioxidant effects in the gastroprotective mechanism of esculin in the ethanol-induced gastric lesion model. The intragastric administration of esculin at doses of 12.5, 25 and 50 mg/kg was able to protect the gastric mucosa against ethanol (0.2 mL/animal p.o.), and esculin at doses of 25 and 50 mg/kg protected against indomethacin-induced lesions (20mg/kg p.o.). Administration of l-NAME (10mg/kg i.p.), glibenclamide (10mg/kg i.p.) or indomethacin (10mg/kg p.o.), but not capsazepine (5mg/kg p.o.), was able to reduce the gastroprotection promoted by esculin (25mg/kg) on the ethanol-induced lesions. Measurements of nitrite, a NO metabolite, were increased in the group that was pretreated with esculin. In terms of antioxidant activity as a gastroprotective mechanism of esculin, the results show that pre-treatment with esculin decreased the amount of GSH, increased SOD activity, did not interfere with the CAT activity and decreased both the MPO activity and the MDA amount. In conclusion, pre-treatment with esculin confers significant gastroprotective and antioxidant activity and leads to a reduction in gastric injury; the mechanisms underlying these effects include stimulation of endogenous prostaglandins, nitric oxide synthesis, opening of K(ATP) channels and reduction of free radicals or modulation of antioxidant enzyme systems. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Implementing online quantitative support modules in an intermediate-level course

NASA Astrophysics Data System (ADS)

Daly, J.

2011-12-01

While instructors typically anticipate that students in introductory geology courses enter a class with a wide range of quantitative ability, we often overlook the fact that this may also be true in upper-level courses. Some students are drawn to the subject and experience success in early courses with an emphasis on descriptive geology, then experience frustration and disappointment in mid- and upper-level courses that are more quantitative. To bolster student confidence in quantitative skills and enhance their performance in an upper-level course, I implemented several modules from The Math You Need (TMYN) online resource with a 200-level geomorphology class. Student facility with basic quantitative skills (rearranging equations, manipulating units, and graphing) was assessed with an online pre- and post-test. During the semester, modules were assigned to complement existing course activities (for example, the module on manipulating units was assigned prior to a lab on measurement of channel area and water velocity, then calculation of discharge). The implementation was designed to be a concise review of relevant skills for students with higher confidence in their quantitative abilities, and to provide a self-paced opportunity for students with less quantitative facility to build skills. This course already includes a strong emphasis on quantitative data collection, analysis, and presentation; in the past, student performance in the course has been strongly influenced by their individual quantitative ability. I anticipate that giving students the opportunity to improve mastery of fundamental quantitative skills will improve their performance on higher-stakes assignments and exams, and will enhance their sense of accomplishment in the course.

KCNQ1 channel modulation by KCNE proteins via the voltage-sensing domain.

PubMed

Nakajo, Koichi; Kubo, Yoshihiro

2015-06-15

The gating of the KCNQ1 potassium channel is drastically regulated by auxiliary subunit KCNE proteins. KCNE1, for example, slows the activation kinetics of KCNQ1 by two orders of magnitude. Like other voltage-gated ion channels, the opening of KCNQ1 is regulated by the voltage-sensing domain (VSD; S1-S4 segments). Although it has been known that KCNE proteins interact with KCNQ1 via the pore domain, some recent reports suggest that the VSD movement may be altered by KCNE. The altered VSD movement of KCNQ1 by KCNE proteins has been examined by site-directed mutagenesis, the scanning cysteine accessibility method (SCAM), voltage clamp fluorometry (VCF) and gating charge measurements. These accumulated data support the idea that KCNE proteins interact with the VSDs of KCNQ1 and modulate the gating of the KCNQ1 channel. In this review, we will summarize recent findings and current views of the KCNQ1 modulation by KCNE via the VSD. In this context, we discuss our recent findings that KCNE1 may alter physical interactions between the S4 segment (VSD) and the S5 segment (pore domain) of KCNQ1. Based on these findings from ourselves and others, we propose a hypothetical mechanism for how KCNE1 binding alters the VSD movement and the gating of the channel. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Effects of ginger and its pungent constituents on transient receptor potential channels.

PubMed

Kim, Young-Soo; Hong, Chan Sik; Lee, Sang Weon; Nam, Joo Hyun; Kim, Byung Joo

2016-12-01

Ginger extract is used as an analeptic in herbal medicine and has been reported to exert antioxidant effects. Transient receptor potential (TRP) canonical 5 (TRPC5), TRP cation channel, subfamily M, member 7 (TRPM7; melastatin 7), and TRP cation channel, subfamily A, member 1 (TRPA1; ankyrin 1) are non-selective cation channels that are modulated by reactive oxygen/nitrogen species (ROS/RNS) and subsequently control various cellular processes. The aim of this study was to evaluate whether ginger and its pungent constituents modulate these channels and exert antioxidant effects. It was found that TRPC5 and TRPA1 currents were modulated by ginger extract and by its pungent constituents, [6]-gingerol, zingerone and [6]-shogaol. In particular, [6]-shogaol markedly and dose-dependently inhibited TRPC5 currents with an IC50 of value of ~18.3 µM. Furthermore, the strong dose-dependent activation of TRPA1 currents by [6]-shogaol was abolished by A‑967079 (a selective TRPA1 inhibitor). However, ginger extract and its pungent constituents had no effect on TRPM7 currents. These results suggest the antioxidant effects of ginger extract and its pungent constituents are mediated through TRPC5 and TRPA1, and that [6]-shogaol is predominantly responsible for the regulation of TRPC5 and TRPA1 currents by ginger extract.

An improved adaptive interpolation clock recovery loop based on phase splitting algorithm for coherent optical communication system

NASA Astrophysics Data System (ADS)

Liu, Xuan; Liu, Bo; Zhang, Li-jia; Xin, Xiang-jun; Zhang, Qi; Wang, Yong-jun; Tian, Qing-hua; Tian, Feng; Mao, Ya-ya

2018-01-01

Traditional clock recovery scheme achieves timing adjustment by digital interpolation, thus recovering the sampling sequence. Based on this, an improved clock recovery architecture joint channel equalization for coherent optical communication system is presented in this paper. The loop is different from the traditional clock recovery. In order to reduce the interpolation error caused by the distortion in the frequency domain of the interpolator and to suppress the spectral mirroring generated by the sampling rate change, the proposed algorithm joint equalization, improves the original interpolator in the loop, along with adaptive filtering, and makes error compensation for the original signals according to the balanced pre-filtering signals. Then the signals are adaptive interpolated through the feedback loop. Furthermore, the phase splitting timing recovery algorithm is adopted in this paper. The time error is calculated according to the improved algorithm when there is no transition between the adjacent symbols, making calculated timing error more accurate. Meanwhile, Carrier coarse synchronization module is placed before the beginning of timing recovery to eliminate the larger frequency offset interference, which effectively adjust the sampling clock phase. In this paper, the simulation results show that the timing error is greatly reduced after the loop is changed. Based on the phase splitting algorithm, the BER and MSE are better than those in the unvaried architecture. In the fiber channel, using MQAM modulation format, after 100 km-transmission of single-mode fiber, especially when ROF(roll-off factor) values tends to 0, the algorithm shows a better clock performance under different ROFs. When SNR values are less than 8, the BER could achieve 10-2 to 10-1 magnitude. Furthermore, the proposed timing recovery is more suitable for the situation with low SNR values.

Activation of MEK/ERK signaling contributes to the PACAP-induced increase in guinea pig cardiac neuron excitability

PubMed Central

Tompkins, John D.; Clason, Todd A.; Hardwick, Jean C.; Girard, Beatrice M.; Merriam, Laura A.; May, Victor

2016-01-01

Pituitary adenylate cyclase (PAC)-activating polypeptide (PACAP) peptides (Adcyap1) signaling at the selective PAC1 receptor (Adcyap1r1) participate in multiple homeostatic and stress-related responses, yet the cellular mechanisms underlying PACAP actions remain to be completely elucidated. PACAP/PAC1 receptor signaling increases excitability of neurons within the guinea pig cardiac ganglia, and as these neurons are readily accessible, this neuronal system is particularly amenable to study of PACAP modulation of ionic conductances. The present study investigated how PACAP activation of MEK/ERK signaling contributed to the peptide-induced increase in cardiac neuron excitability. Treatment with the MEK inhibitor PD 98059 blocked PACAP-stimulated phosphorylated ERK and, in parallel, suppressed the increase in cardiac neuron excitability. However, PD 98059 did not blunt the ability of PACAP to enhance two inward ionic currents, one flowing through hyperpolarization-activated nonselective cationic channels (Ih) and another flowing through low-voltage-activated calcium channels (IT), which support the peptide-induced increase in excitability. Thus a PACAP- and MEK/ERK-sensitive, voltage-dependent conductance(s), in addition to Ih and IT, modulates neuronal excitability. Despite prior work implicating PACAP downregulation of the KV4.2 potassium channel in modulation of excitability in other cells, treatment with the KV4.2 current blocker 4-aminopyridine did not replicate the PACAP-induced increase in excitability in cardiac neurons. However, cardiac neurons express the ERK target, the NaV1.7 sodium channel, and treatment with the selective NaV1.7 channel inhibitor PF-04856264 decreased the PACAP modulation of excitability. From these results, PACAP/PAC1 activation of MEK/ERK signaling may phosphorylate the NaV1.7 channel, enhancing sodium currents near the threshold, an action contributing to repetitive firing of the cardiac neurons exposed to PACAP. PMID:27488668

Diabetes attenuates urothelial modulation of detrusor contractility and spontaneous activity.

PubMed

Wang, Yi; Tar, Moses T; Fu, Shibo; Melman, Arnold; Davies, Kelvin P

2014-10-01

To investigate the effect of diabetes on urothelial modulation of bladder contractility. Bladder strips (urothelium intact or denuded) were prepared from 8-week-old streptozotocin-induced diabetic (n = 19) and non-diabetic control rats (n = 10). The effect of modulators of MaxiK (iberiotoxin and tetraethylammonium) and Kv7 (XE991 and retigabine) potassium channel activity were investigated for their effects on both carbachol-induced force generation and spontaneous contractile activity. In bladder strips from non-diabetic animals, the presence of the urothelium resulted in marked sensitivity to carbachol-induced force generation by modulators of MaxiK and Kv7 channel activity, whereas in the diabetic animal urothelial sensitivity to these agents was significantly diminished. Urothelial-intact bladder strips from non-diabetic animals were more sensitive to modulators of Kv7 activity in reducing the amplitude of spontaneous phasic contractions than urothelial-denuded bladder strips, whereas in diabetic animals the presence or absence of the urothelium did not alter the sensitivity to modulators of Kv7 activity. Spontaneous activity in the presence of tetraethylammonium was not affected by the urothelium in bladder strips from either diabetic or non-diabetic animals. The presence of the urothelium in bladders from non-diabetic animals modulates the activity of potassium blockers to affect bladder contractility, whereas in the diabetic bladder this effect is attenuated. These findings could help to explain the lack of success of pharmaceutical treatments targeting potassium channels to treat bladder pathology in patients with diseases imparing urothelial function. © 2014 The Japanese Urological Association.

Adaptive software-defined coded modulation for ultra-high-speed optical transport

NASA Astrophysics Data System (ADS)

Djordjevic, Ivan B.; Zhang, Yequn

2013-10-01

In optically-routed networks, different wavelength channels carrying the traffic to different destinations can have quite different optical signal-to-noise ratios (OSNRs) and signal is differently impacted by various channel impairments. Regardless of the data destination, an optical transport system (OTS) must provide the target bit-error rate (BER) performance. To provide target BER regardless of the data destination we adjust the forward error correction (FEC) strength. Depending on the information obtained from the monitoring channels, we select the appropriate code rate matching to the OSNR range that current channel OSNR falls into. To avoid frame synchronization issues, we keep the codeword length fixed independent of the FEC code being employed. The common denominator is the employment of quasi-cyclic (QC-) LDPC codes in FEC. For high-speed implementation, low-complexity LDPC decoding algorithms are needed, and some of them will be described in this invited paper. Instead of conventional QAM based modulation schemes, we employ the signal constellations obtained by optimum signal constellation design (OSCD) algorithm. To improve the spectral efficiency, we perform the simultaneous rate adaptation and signal constellation size selection so that the product of number of bits per symbol × code rate is closest to the channel capacity. Further, we describe the advantages of using 4D signaling instead of polarization-division multiplexed (PDM) QAM, by using the 4D MAP detection, combined with LDPC coding, in a turbo equalization fashion. Finally, to solve the problems related to the limited bandwidth of information infrastructure, high energy consumption, and heterogeneity of optical networks, we describe an adaptive energy-efficient hybrid coded-modulation scheme, which in addition to amplitude, phase, and polarization state employs the spatial modes as additional basis functions for multidimensional coded-modulation.

A software platform for continuum modeling of ion channels based on unstructured mesh

NASA Astrophysics Data System (ADS)

Tu, B.; Bai, S. Y.; Chen, M. X.; Xie, Y.; Zhang, L. B.; Lu, B. Z.

2014-01-01

Most traditional continuum molecular modeling adopted finite difference or finite volume methods which were based on a structured mesh (grid). Unstructured meshes were only occasionally used, but an increased number of applications emerge in molecular simulations. To facilitate the continuum modeling of biomolecular systems based on unstructured meshes, we are developing a software platform with tools which are particularly beneficial to those approaches. This work describes the software system specifically for the simulation of a typical, complex molecular procedure: ion transport through a three-dimensional channel system that consists of a protein and a membrane. The platform contains three parts: a meshing tool chain for ion channel systems, a parallel finite element solver for the Poisson-Nernst-Planck equations describing the electrodiffusion process of ion transport, and a visualization program for continuum molecular modeling. The meshing tool chain in the platform, which consists of a set of mesh generation tools, is able to generate high-quality surface and volume meshes for ion channel systems. The parallel finite element solver in our platform is based on the parallel adaptive finite element package PHG which wass developed by one of the authors [1]. As a featured component of the platform, a new visualization program, VCMM, has specifically been developed for continuum molecular modeling with an emphasis on providing useful facilities for unstructured mesh-based methods and for their output analysis and visualization. VCMM provides a graphic user interface and consists of three modules: a molecular module, a meshing module and a numerical module. A demonstration of the platform is provided with a study of two real proteins, the connexin 26 and hemolysin ion channels.

The Kinetics and the Permeation Properties of Piezo Channels.

PubMed

Gnanasambandam, R; Gottlieb, P A; Sachs, F

2017-01-01

Piezo channels are eukaryotic, cation-selective mechanosensitive channels (MSCs), which show rapid activation and voltage-dependent inactivation. The kinetics of these channels are largely consistent across multiple cell types and different stimulation paradigms with some minor variability. No accessory subunits that associate with Piezo channels have been reported. They are homotrimers and each ∼300kD monomer has an N-terminal propeller blade-like mechanosensing module, which can confer mechanosensing capabilities on ASIC-1 (the trimeric non-MSC, acid-sensing ion channel-1) and a C-terminal pore module, which influences conductance, selectivity, and channel inactivation. Repeated stimulation can cause domain fracture and diffusion of these channels leading to synchronous loss of inactivation. The reconstituted channels spontaneously open only in asymmetric bilayers but lack inactivation. Mutations that cause hereditary xerocytosis alter PIEZO1 kinetics. The kinetics of the wild-type PIEZO1 and alterations thereof in mutants (M2225R, R2456K, and DhPIEZO1) are summarized in the form of a quantitative model and hosted online. The pore is permeable to alkali ions although Li + permeates poorly. Divalent cations, notably Ca 2+ , traverse the channel and inhibit the flux of monovalents. The large monovalent organic cations such as tetramethyl ammonium and tetraethyl ammonium can traverse the channel, but slowly, suggesting a pore diameter of ∼8Å, and the estimated in-plane area change upon opening is around 6-20nm 2 . Ruthenium red can enter the channel only from the extracellular side and seems to bind in a pocket close to residue 2496. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2010-01-01

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

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

PubMed

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

2010-04-15

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

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

PubMed

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.

Efficacy of metomidate and tricaine methanesulfonate to modulate the short-term cortisol stress response in channel catfish Ictalurus punctatus

USDA-ARS?s Scientific Manuscript database

The ability of the anesthetics metomidate and tricaine methanesulfonate to mitigate the cortisol stress response of channel catfish Ictalurus punctatus was evaluated during a 10 min confinement stress. Channel catfish (11.9 ± 0.5 g; mean ± SE) were transferred from holding tanks to confinement buck...

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

PubMed Central

2016-01-01

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

An adaptive threshold detector and channel parameter estimator for deep space optical communications

NASA Technical Reports Server (NTRS)

Arabshahi, P.; Mukai, R.; Yan, T. -Y.

2001-01-01

This paper presents a method for optimal adaptive setting of ulse-position-modulation pulse detection thresholds, which minimizes the total probability of error for the dynamically fading optical fee space channel.

Modulation of Respiratory Frequency by Peptidergic Input to Rhythmogenic Neurons in the PreBötzinger Complex

PubMed Central

Gray, Paul A.; Rekling, Jens C.; Bocchiaro, Christopher M.; Feldman, Jack L.

2010-01-01

Neurokinin-1 receptor (NK1R) and μ-opioid receptor (μOR) agonists affected respiratory rhythm when injected directly into the preBötzinger Complex (preBötC), the hypothesized site for respiratory rhythmogenesis in mammals. These effects were mediated by actions on preBötC rhythmogenic neurons. The distribution of NK1R+ neurons anatomically defined the preBötC. Type 1 neurons in the preBötC, which have rhythmogenic properties, expressed both NK1Rs and μORs, whereas type 2 neurons expressed only NK1Rs. These findings suggest that the preBötC is a definable anatomic structure with unique physiological function and that a subpopulation of neurons expressing both NK1Rs and μORs generate respiratory rhythm and modulate respiratory frequency. PMID:10567264

Ciguatoxins: Cyclic Polyether Modulators of Voltage-gated Iion Channel Function

PubMed Central

Nicholson, Graham M.; Lewis, Richard J.

2006-01-01

Ciguatoxins are cyclic polyether toxins, derived from marine dinoflagellates, which are responsible for the symptoms of ciguatera poisoning. Ingestion of tropical and subtropical fin fish contaminated by ciguatoxins results in an illness characterised by neurological, cardiovascular and gastrointestinal disorders. The pharmacology of ciguatoxins is characterised by their ability to cause persistent activation of voltage-gated sodium channels, to increase neuronal excitability and neurotransmitter release, to impair synaptic vesicle recycling, and to cause cell swelling. It is these effects, in combination with an action to block voltage-gated potassium channels at high doses, which are believed to underlie the complex of symptoms associated with ciguatera. This review examines the sources, structures and pharmacology of ciguatoxins. In particular, attention is placed on their cellular modes of actions to modulate voltage-gated ion channels and other Na+-dependent mechanisms in numerous cell types and to current approaches for detection and treatment of ciguatera.

Structural and Functional Similarities of Calcium Homeostasis Modulator 1 (CALHM1) Ion Channel with Connexins, Pannexins, and Innexins*

PubMed Central

Siebert, Adam P.; Ma, Zhongming; Grevet, Jeremy D.; Demuro, Angelo; Parker, Ian; Foskett, J. Kevin

2013-01-01

CALHM1 (calcium homeostasis modulator 1) forms a plasma membrane ion channel that mediates neuronal excitability in response to changes in extracellular Ca2+ concentration. Six human CALHM homologs exist with no homology to other proteins, although CALHM1 is conserved across >20 species. Here we demonstrate that CALHM1 shares functional and quaternary and secondary structural similarities with connexins and evolutionarily distinct innexins and their vertebrate pannexin homologs. A CALHM1 channel is a hexamer, comprised of six monomers, each of which possesses four transmembrane domains, cytoplasmic amino and carboxyl termini, an amino-terminal helix, and conserved extracellular cysteines. The estimated pore diameter of the CALHM1 channel is ∼14 Å, enabling permeation of large charged molecules. Thus, CALHMs, connexins, and pannexins and innexins are structurally related protein families with shared and distinct functional properties. PMID:23300080

Allosteric Modulation of Ca2+ flux in Ligand-gated Cation Channel (P2X4) by Actions on Lateral Portals*

PubMed Central

Samways, Damien S. K.; Khakh, Baljit S.; Egan, Terrance M.

2012-01-01

Human P2X receptors are a family of seven ATP-gated ion channels that transport Na+, K+, and Ca2+ across cell surface membranes. The P2X4 receptor is unique among family members in its sensitivity to the macrocyclic lactone, ivermectin, which allosterically modulates both ion conduction and channel gating. In this paper we show that removing the fixed negative charge of a single acidic amino acid (Glu51) in the lateral entrance to the transmembrane pore markedly attenuates the effect of ivermectin on Ca2+ current and channel gating. Ca2+ entry through P2X4 receptors is known to trigger downstream signaling pathways in microglia. Our experiments show that the lateral portals could present a novel target for drugs in the treatment of microglia-associated disease including neuropathic pain. PMID:22219189

Continuous variable quantum key distribution with modulated entangled states.

PubMed

Madsen, Lars S; Usenko, Vladyslav C; Lassen, Mikael; Filip, Radim; Andersen, Ulrik L

2012-01-01

Quantum key distribution enables two remote parties to grow a shared key, which they can use for unconditionally secure communication over a certain distance. The maximal distance depends on the loss and the excess noise of the connecting quantum channel. Several quantum key distribution schemes based on coherent states and continuous variable measurements are resilient to high loss in the channel, but are strongly affected by small amounts of channel excess noise. Here we propose and experimentally address a continuous variable quantum key distribution protocol that uses modulated fragile entangled states of light to greatly enhance the robustness to channel noise. We experimentally demonstrate that the resulting quantum key distribution protocol can tolerate more noise than the benchmark set by the ideal continuous variable coherent state protocol. Our scheme represents a very promising avenue for extending the distance for which secure communication is possible.

Drug Management of Visceral Pain: Concepts from Basic Research

PubMed Central

Davis, Mellar P.

2012-01-01

Visceral pain is experienced by 40% of the population, and 28% of cancer patients suffer from pain arising from intra- abdominal metastasis or from treatment. Neuroanatomy of visceral nociception and neurotransmitters, receptors, and ion channels that modulate visceral pain are qualitatively or quantitatively different from those that modulate somatic and neuropathic pain. Visceral pain should be recognized as distinct pain phenotype. TRPV1, Na 1.8, and ASIC3 ion channels and peripheral kappa opioid receptors are important mediators of visceral pain. Mu agonists, gabapentinoids, and GABAB agonists reduce pain by binding to central receptors and channels. Combinations of analgesics and adjuvants in animal models have supra-additive antinociception and should be considered in clinical trials. This paper will discuss the neuroanatomy, receptors, ion channels, and neurotransmitters important to visceral pain and provide a basic science rationale for analgesic trials and management. PMID:22619712

Redox modulation of A-type K+ currents in pain-sensing dorsal root ganglion neurons.

PubMed

Hsieh, Chi-Pan

2008-06-06

Redox modulation of fast inactivation has been described in certain cloned A-type voltage-gated K(+) (Kv) channels in expressing systems, but the effects remain to be demonstrated in native neurons. In this study, we examined the effects of cysteine-specific redox agents on the A-type K(+) currents in acutely dissociated small diameter dorsal root ganglion (DRG) neurons from rats. The fast inactivation of most A-type currents was markedly removed or slowed by the oxidizing agents 2,2'-dithio-bis(5-nitropyridine) (DTBNP) and chloramine-T. Dithiothreitol, a reducing agent for the disulfide bond, restored the inactivation. These results demonstrated that native A-type K(+) channels, probably Kv1.4, could switch the roles between inactivating and non-inactivating K(+) channels via redox regulation in pain-sensing DRG neurons. The A-type channels may play a role in adjusting pain sensitivity in response to peripheral redox conditions.

Drywall. Pre-Apprenticeship Phase 2 Training. Instructor's Guide.

ERIC Educational Resources Information Center

Moore, Doug

This instructor's guide accompanies the self-paced student training modules on drywall available separately as CE 031 574. Introductory materials include a description of the components of the pre-apprenticeship project, discussion of teacher's role in students' completion of the modules, and scope and contents of Phase 2 training. Each of the 18…

Bricklaying. Pre-Apprenticeship Phase 2 Training. Instructor's Guide.

ERIC Educational Resources Information Center

Cholewinski, Scott

This instructor's guide accompanies the self-paced student training modules on bricklaying available separately as CE 031 568. Introductory materials include a description of the components of the pre-apprenticeship project, discussion of teacher's role in students' completion of the modules, and scope and contents of Phase 2 training. Each of the…

Parts Counter. Pre-Apprenticeship Phase 2 Training. Instructor's Guide.

ERIC Educational Resources Information Center

Snyder, James A.

This instructor's guide accompanies the self-paced student training modules on parts counter, available separately as CE 031 572. Introductory materials include a description of the components of the pre-apprenticeship project, discussion of teacher's role in students' completion of the modules, and scope and contents of Phase 2 training. Each of…

Cement Finishing. Pre-Apprenticeship Phase 2 Training. Instructor's Guide.

ERIC Educational Resources Information Center

Nama, Joe

This instructor's guide accompanies the self-paced student training modules on cement finishing, available separately as CE 031 576. Introductory materials include a description of the components of the pre-apprenticeship project, discussion of teacher's role in students' completion of the modules, and scope and contents of Phase 2 training. Each…

32-channel single photon counting module for ultrasensitive detection of DNA sequences

NASA Astrophysics Data System (ADS)

Gudkov, Georgiy; Dhulla, Vinit; Borodin, Anatoly; Gavrilov, Dmitri; Stepukhovich, Andrey; Tsupryk, Andrey; Gorbovitski, Boris; Gorfinkel, Vera

2006-10-01

We continue our work on the design and implementation of multi-channel single photon detection systems for highly sensitive detection of ultra-weak fluorescence signals, for high-performance, multi-lane DNA sequencing instruments. A fiberized, 32-channel single photon detection (SPD) module based on single photon avalanche diode (SPAD), model C30902S-DTC, from Perkin Elmer Optoelectronics (PKI) has been designed and implemented. Unavailability of high performance, large area SPAD arrays and our desire to design high performance photon counting systems drives us to use individual diodes. Slight modifications in our quenching circuit has doubled the linear range of our system from 1MHz to 2MHz, which is the upper limit for these devices and the maximum saturation count rate has increased to 14 MHz. The detector module comprises of a single board computer PC-104 that enables data visualization, recording, processing, and transfer. Very low dark count (300-1000 counts/s), robust, efficient, simple data collection and processing, ease of connectivity to any other application demanding similar requirements and similar performance results to the best commercially available single photon counting module (SPCM from PKI) are some of the features of this system.

On the performance evaluation of LQAM-MPPM techniques over exponentiated Weibull fading free-space optical channels

NASA Astrophysics Data System (ADS)

Khallaf, Haitham S.; Elfiqi, Abdulaziz E.; Shalaby, Hossam M. H.; Sampei, Seiichi; Obayya, Salah S. A.

2018-06-01

We investigate the performance of hybrid L-ary quadrature-amplitude modulation-multi-pulse pulse-position modulation (LQAM-MPPM) techniques over exponentiated Weibull (EW) fading free-space optical (FSO) channel, considering both weather and pointing-error effects. Upper bound and approximate-tight upper bound expressions for the bit-error rate (BER) of LQAM-MPPM techniques over EW FSO channels are obtained, taking into account the effects of fog, beam divergence, and pointing-error. Setup block diagram for both the transmitter and receiver of the LQAM-MPPM/FSO system are introduced and illustrated. The BER expressions are evaluated numerically and the results reveal that LQAM-MPPM technique outperforms ordinary LQAM and MPPM schemes under different fading levels and weather conditions. Furthermore, the effect of modulation-index is investigated and it turned out that a modulation-index greater than 0.4 is required in order to optimize the system performance. Finally, the effect of pointing-error introduces a great power penalty on the LQAM-MPPM system performance. Specifically, at a BER of 10-9, pointing-error introduces power penalties of about 45 and 28 dB for receiver aperture sizes of DR = 50 and 200 mm, respectively.

Strong G-Protein-Mediated Inhibition of Sodium Channels.

PubMed

Mattheisen, Glynis B; Tsintsadze, Timur; Smith, Stephen M

2018-05-29

Voltage-gated sodium channels (VGSCs) are strategically positioned to mediate neuronal plasticity because of their influence on action potential waveform. VGSC function may be strongly inhibited by local anesthetic and antiepileptic drugs and modestly modulated via second messenger pathways. Here, we report that the allosteric modulators of the calcium-sensing receptor (CaSR) cinacalcet, calindol, calhex, and NPS 2143 completely inhibit VGSC current in the vast majority of cultured mouse neocortical neurons. This form of VGSC current block persisted in CaSR-deficient neurons, indicating a CaSR-independent mechanism. Cinacalcet-mediated blockade of VGSCs was prevented by the guanosine diphosphate (GDP) analog GDPβs, indicating that G-proteins mediated this effect. Cinacalcet inhibited VGSCs by increasing channel inactivation, and block was reversed by prolonged hyperpolarization. Strong cinacalcet inhibition of VGSC currents was also present in acutely isolated mouse cortical neurons. These data identify a dynamic signaling pathway by which G-proteins regulate VGSC current to indirectly modulate central neuronal excitability. Published by Elsevier Inc.

A 32-channel photon counting module with embedded auto/cross-correlators for real-time parallel fluorescence correlation spectroscopy

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

Gong, S.; Labanca, I.; Rech, I.

2014-10-15

Fluorescence correlation spectroscopy (FCS) is a well-established technique to study binding interactions or the diffusion of fluorescently labeled biomolecules in vitro and in vivo. Fast FCS experiments require parallel data acquisition and analysis which can be achieved by exploiting a multi-channel Single Photon Avalanche Diode (SPAD) array and a corresponding multi-input correlator. This paper reports a 32-channel FPGA based correlator able to perform 32 auto/cross-correlations simultaneously over a lag-time ranging from 10 ns up to 150 ms. The correlator is included in a 32 × 1 SPAD array module, providing a compact and flexible instrument for high throughput FCS experiments.more » However, some inherent features of SPAD arrays, namely afterpulsing and optical crosstalk effects, may introduce distortions in the measurement of auto- and cross-correlation functions. We investigated these limitations to assess their impact on the module and evaluate possible workarounds.« less

Data acquisition and control system with a programmable logic controller (PLC) for a pulsed chemical oxygen-iodine laser

NASA Astrophysics Data System (ADS)

Yu, Haijun; Li, Guofu; Duo, Liping; Jin, Yuqi; Wang, Jian; Sang, Fengting; Kang, Yuanfu; Li, Liucheng; Wang, Yuanhu; Tang, Shukai; Yu, Hongliang

2015-02-01

A user-friendly data acquisition and control system (DACS) for a pulsed chemical oxygen -iodine laser (PCOIL) has been developed. It is implemented by an industrial control computer，a PLC, and a distributed input/output (I/O) module, as well as the valve and transmitter. The system is capable of handling 200 analogue/digital channels for performing various operations such as on-line acquisition, display, safety measures and control of various valves. These operations are controlled either by control switches configured on a PC while not running or by a pre-determined sequence or timings during the run. The system is capable of real-time acquisition and on-line estimation of important diagnostic parameters for optimization of a PCOIL. The DACS system has been programmed using software programmable logic controller (PLC). Using this DACS, more than 200 runs were given performed successfully.

Effects of channel tap spacing on delay-lock tracking

NASA Astrophysics Data System (ADS)

Dana, Roger A.; Milner, Brian R.; Bogusch, Robert L.

1995-12-01

High fidelity simulations of communication links operating through frequency selective fading channels require both accurate channel models and faithful reproduction of the received signal. In modern radio receivers, processing beyond the analog-to-digital converter (A/D) is done digitally, so a high fidelity simulation is actually an emulation of this digital signal processing. The 'simulation' occurs in constructing the output of the A/D. One approach to constructing the A/D output is to convolve the channel impulse response function with the combined impulse response of the transmitted modulation and the A/D. For both link simulations and hardware channel simulators, the channel impulse response function is then generated with a finite number of samples per chip, and the convolution is implemented in a tapped delay line. In this paper we discuss the effects of the channel model tap spacing on the performance of delay locked loops (DLLs) in both direct sequence and frequency hopped spread spectrum systems. A frequency selective fading channel is considered, and the channel impulse response function is constructed with an integer number of taps per modulation symbol or chip. The tracking loop time delay is computed theoretically for this tapped delay line channel model and is compared to the results of high fidelity simulations of actual DLLs. A surprising result is obtained. The performance of the DLL depends strongly on the number of taps per chip. As this number increases the DLL delay approaches the theoretical limit.

Modulation of Diabetes-Induced Oxidative Stress, Apoptosis, and Ca2+ Entry Through TRPM2 and TRPV1 Channels in Dorsal Root Ganglion and Hippocampus of Diabetic Rats by Melatonin and Selenium.

PubMed

Kahya, Mehmet Cemal; Nazıroğlu, Mustafa; Övey, İshak Suat

2017-04-01

Neuropathic pain and hippocampal injury can arise from the overload of diabetes-induced calcium ion (Ca 2+ ) entry and oxidative stress. The transient receptor potential (TRP) melastatin 2 (TRPM2) and TRP vanilloid type 1 (TRPV1) are expressed in sensory neurons and hippocampus. Moreover, activations of TRPM2 and TRPV1 during oxidative stress have been linked to neuronal death. Melatonin (MEL) and selenium (Se) have been considered potent antioxidants that detoxify a variety of reactive oxygen species (ROS) in neurological diseases. In order to better characterize the actions of MEL and Se in diabetes-induced peripheral pain and hippocampal injury through modulation of TRPM2 and TRPV1, we tested the effects of MEL and Se on apoptosis and oxidative stress in the hippocampal and dorsal root ganglion (DRG) neurons of streptozotocin (STZ)-induced diabetic rats. Fifty-eight rats were divided into six groups. The first group was used as control. The second group was used as the diabetic group. The third and fourth groups received Se and MEL, respectively. Intraperitoneal Se and MEL were given to diabetic rats in the fifth and sixth groups. On the 14th day, hippocampal and DRG neuron samples were freshly taken from all animals. The neurons were stimulated with a TRPV1 channel agonist (capsaicin) and a TRPM2 channel agonist (cumene hydroperoxide). We observed a modulator role of MEL and Se on intracellular free Ca 2+ concentrations, current densities of TRPM2 and TRPV1 channels, apoptosis, caspase 3, caspase 9, mitochondrial depolarization, reduced glutathione, glutathione peroxidase, lipid peroxidation, and intracellular ROS production values in the neurons. In addition, procaspase 3 and 9 activities in western blot analyses of the brain cortex were also decreased by MEL and Se treatments. In conclusion, in our diabetes experimental model, TRPM2 and TRPV1 channels are involved in the Ca 2+ entry-induced neuronal death and modulation of this channel activity by MEL and Se treatment may account for their neuroprotective activity against apoptosis and Ca 2+ entry. Graphical Abstract Possible molecular pathways of involvement of melatonin and selenium in diabetes-induced apoptosis, oxidative stress, and calcium accumulation through TRPM2 and TRPV1 channels in the hippocampus and DRG neurons of rats. The TRPM2 channel is activated by ADP-ribose and oxidative stress although it is inhibited by ACA. The TRPV1 channel is activated by oxidative stress and capsaicin and it is blocked by capsazepine (CPZ). Diabetes can result in augmented ROS release in hippocampal and DRG neurons through polyol reactions, leading to Ca 2+ uptake through TRPM2 and TRPV1 channels. Mitochondria were reported to accumulate Ca 2+ provided intracellular Ca 2+ rises, thereby leading to the depolarization of mitochondrial membranes and release of apoptosis-inducing factors such as caspase 3 and caspase 9. Melatonin and selenium reduce TRPM2 and TRPV1 channel activation through the modulation of polyol oxidative reactions and selenium-dependent glutathione peroxidase (GSH-Px) antioxidant pathways.

Blind ICA detection based on second-order cone programming for MC-CDMA systems

NASA Astrophysics Data System (ADS)

Jen, Chih-Wei; Jou, Shyh-Jye

2014-12-01

The multicarrier code division multiple access (MC-CDMA) technique has received considerable interest for its potential application to future wireless communication systems due to its high data rate. A common problem regarding the blind multiuser detectors used in MC-CDMA systems is that they are extremely sensitive to the complex channel environment. Besides, the perturbation of colored noise may negatively affect the performance of the system. In this paper, a new coherent detection method will be proposed, which utilizes the modified fast independent component analysis (FastICA) algorithm, based on approximate negentropy maximization that is subject to the second-order cone programming (SOCP) constraint. The aim of the proposed coherent detection is to provide robustness against small-to-medium channel estimation mismatch (CEM) that may arise from channel frequency response estimation error in the MC-CDMA system, which is modulated by downlink binary phase-shift keying (BPSK) under colored noise. Noncoherent demodulation schemes are preferable to coherent demodulation schemes, as the latter are difficult to implement over time-varying fading channels. Differential phase-shift keying (DPSK) is therefore the natural choice for an alternative modulation scheme. Furthermore, the new blind differential SOCP-based ICA (SOCP-ICA) detection without channel estimation and compensation will be proposed to combat Doppler spread caused by time-varying fading channels in the DPSK-modulated MC-CDMA system under colored noise. In this paper, numerical simulations are used to illustrate the robustness of the proposed blind coherent SOCP-ICA detector against small-to-medium CEM and to emphasize the advantage of the blind differential SOCP-ICA detector in overcoming Doppler spread.

cAMP-dependent kinase does not modulate the Slack sodium-activated potassium channel.

PubMed

Nuwer, Megan O; Picchione, Kelly E; Bhattacharjee, Arin

2009-09-01

The Slack gene encodes a Na(+)-activated K(+) channel and is expressed in many different types of neurons. Like the prokaryotic Ca(2+)-gated K(+) channel MthK, Slack contains two 'regulator of K(+) conductance' (RCK) domains within its carboxy terminal, domains likely involved in Na(+) binding and channel gating. It also contains multiple consensus protein kinase C (PKC) and protein kinase A (PKA) phosphorylation sites and although regulated by protein kinase C (PKC) phosphorylation, modulation by PKA has not been determined. To test if PKA directly regulates Slack, nystatin-perforated patch whole-cell currents were recorded from a human embryonic kidney (HEK-293) cell line stably expressing Slack. Bath application of forskolin, an adenylate cyclase activator, caused a rapid and complete inhibition of Slack currents however, the inactive homolog of forskolin, 1,9-dideoxyforskolin caused a similar effect. In contrast, bath application of 8-bromo-cAMP did not affect the amplitude nor the activation kinetics of Slack currents. In excised inside-out patch recordings, direct application of the PKA catalytic subunit to patches did not affect the open probability of Slack channels nor was open probability affected by direct application of protein phosphatase 2B. Preincubation of cells with the protein kinase A inhibitor KT5720 also did not change current density. Finally, mutating the consensus phosphorylation site located between RCK domain 1 and domain 2 from serine to glutamate did not affect current activation kinetics. We conclude that unlike PKC, phosphorylation by PKA does not acutely modulate the function and gating activation kinetics of Slack channels.

Development and evaluation of an internet-based blended-learning module in biomedicine for university applicants--Education as a challenge for the future.

PubMed

Klümper, Christian; Neunzehn, Jörg; Wegmann, Ute; Kruppke, Benjamin; Joos, Ulrich; Wiesmann, Hans Peter

2016-03-25

Biomedical science, especially biomaterials, is an expanding field in medicine. Universities are being challenged to gain the best students for a later academic career. Pre-university assessment of pupils has become crucial to reach this aim. Blended learning is an emerging paradigm for science education even though it has not yet been rigorously assessed, especially in the pupil/undergraduate situation. The aim of the study was to develop and preliminarily test a blended-learning system in biomedicine for university applicants. An internet-based blended-learning module in material science was developed in close collaboration between a university (Biomaterials Department, Dresden TU), a German Gymnasium and an internationally oriented medical college (IMC®, Münster). Forty pre-university students were taught by this learning module composed of school education and internet-based knowledge transfer and involved in the evaluation of the utility of this learning tool. Finally, the students took first-year university examinations in order to evaluate the success of this kind of education. The internet-based blended-learning module as a combination of e-learning tutorials and live online lectures which was applied in phase 3 of this study was developed on the basis of the findings of both pre-university studies. The results of the learning behavior regarding the number of invokes and the dwell time of the individual pages of the pre-university learning material, the results of the online evaluation and the results of the pre-phase examination were successively used to optimize the next phase. At the end of the pre-university learning, seven of eight participants were able to pass the first-year university examination followed by nationally accepted credit award. Internet-based blended-learning module proved to be suitable to prepare students for biomedical university education while also giving them the possibility to assess their qualifications for studying biomedicine and subsequent scientific careers. Moreover, the module can help universities to find the best students.

Renal intercalated cells and blood pressure regulation

PubMed Central

Wall, Susan M.

2017-01-01

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

Solar thermoelectric cooling using closed loop heat exchangers with macro channels

NASA Astrophysics Data System (ADS)

Atta, Raghied M.

2017-07-01

In this paper we describe the design, analysis and experimental study of an advanced coolant air conditioning system which cools or warms airflow using thermoelectric (TE) devices powered by solar cells. Both faces of the TE devices are directly connected to closed-loop highly efficient channels plates with macro scale channels and liquid-to-air heat exchangers. The hot side of the system consists of a pump that moves a coolant through the hot face of the TE modules, a radiator that drives heat away into the air, and a fan that transfer the heat over the radiator by forced convection. The cold side of the system consists also of a pump that moves coolant through the cold face of the TE modules, a radiator that drives cold away into the air, and a fan that blows cold air off the radiator. The system was integrated with solar panels, tested and its thermal performance was assessed. The experimental results verify the possibility of heating or cooling air using TE modules with a relatively high coefficient of performance (COP). The system was able to cool a closed space of 30 m3 by 14 °C below ambient within 90 min. The maximum COP of the whole system was 0.72 when the TE modules were running at 11.2 Å and 12 V. This improvement in the system COP over the air cooled heat sink is due to the improvement of the system heat exchange by means of channels plates.

MODULAR CORE UNITS FOR A NEUTRONIC REACTOR

DOEpatents

Gage, J.F. Jr.; Sherer, D.B.

1964-04-01

A modular core unit for use in a nuclear reactor is described. Many identical core modules can be placed next to each other to make up a complete core. Such a module includes a cylinder of moderator material surrounding a fuel- containing re-entrant coolant channel. The re-entrant channel provides for the circulation of coolant such as liquid sodium from one end of the core unit, through the fuel region, and back out through the same end as it entered. Thermal insulation surrounds the moderator exterior wall inducing heat to travel inwardly to the coolant channel. Spaces between units may be used to accommodate control rods and support structure, which may be cooled by a secondary gas coolant, independently of the main coolant. (AEC)

The K+ channel KZM2 is involved in stomatal movement by modulating inward K+ currents in maize guard cells.

PubMed

Gao, Yong-Qiang; Wu, Wei-Hua; Wang, Yi

2017-11-01

Stomata are the major gates in plant leaf that allow water and gas exchange, which is essential for plant transpiration and photosynthesis. Stomatal movement is mainly controlled by the ion channels and transporters in guard cells. In Arabidopsis, the inward Shaker K + channels, such as KAT1 and KAT2, are responsible for stomatal opening. However, the characterization of inward K + channels in maize guard cells is limited. In the present study, we identified two KAT1-like Shaker K + channels, KZM2 and KZM3, which were highly expressed in maize guard cells. Subcellular analysis indicated that KZM2 and KZM3 can localize at the plasma membrane. Electrophysiological characterization in HEK293 cells revealed that both KZM2 and KZM3 were inward K + (K in ) channels, but showing distinct channel kinetics. When expressed in Xenopus oocytes, only KZM3, but not KZM2, can mediate inward K + currents. However, KZM2 can interact with KZM3 forming heteromeric K in channel. In oocytes, KZM2 inhibited KZM3 channel conductance and negatively shifted the voltage dependence of KZM3. The activation of KZM2-KZM3 heteromeric channel became slower than the KZM3 channel. Patch-clamping results showed that the inward K + currents of maize guard cells were significantly increased in the KZM2 RNAi lines. In addition, the RNAi lines exhibited faster stomatal opening after light exposure. In conclusion, the presented results demonstrate that KZM2 functions as a negative regulator to modulate the K in channels in maize guard cells. KZM2 and KZM3 may form heteromeric K in channel and control stomatal opening in maize. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Pre-processing liquid chromatography/high-resolution mass spectrometry data: extracting pure mass spectra by deconvolution from the invariance of isotopic distribution.

PubMed

Krishnan, Shaji; Verheij, Elwin E R; Bas, Richard C; Hendriks, Margriet W B; Hankemeier, Thomas; Thissen, Uwe; Coulier, Leon

2013-05-15

Mass spectra obtained by deconvolution of liquid chromatography/high-resolution mass spectrometry (LC/HRMS) data can be impaired by non-informative mass-over-charge (m/z) channels. This impairment of mass spectra can have significant negative influence on further post-processing, like quantification and identification. A metric derived from the knowledge of errors in isotopic distribution patterns, and quality of the signal within a pre-defined mass chromatogram block, has been developed to pre-select all informative m/z channels. This procedure results in the clean-up of deconvoluted mass spectra by maintaining the intensity counts from m/z channels that originate from a specific compound/molecular ion, for example, molecular ion, adducts, (13) C-isotopes, multiply charged ions and removing all m/z channels that are not related to the specific peak. The methodology has been successfully demonstrated for two sets of high-resolution LC/MS data. The approach described is therefore thought to be a useful tool in the automatic processing of LC/HRMS data. It clearly shows the advantages compared to other approaches like peak picking and de-isotoping in the sense that all information is retained while non-informative data is removed automatically. Copyright © 2013 John Wiley & Sons, Ltd.

Endothelial SK(Ca) and IK(Ca) channels regulate brain parenchymal arteriolar diameter and cortical cerebral blood flow.

PubMed

Hannah, Rachael M; Dunn, Kathryn M; Bonev, Adrian D; Nelson, Mark T

2011-05-01

Calcium-sensitive potassium (K(Ca)) channels have been shown to modulate the diameter of cerebral pial arteries; however, little is known regarding their roles in controlling cerebral parenchymal arterioles (PAs). We explored the function and cellular distribution of small-conductance (SK(Ca)) and intermediate-conductance (IK(Ca)) K(Ca) channels and large-conductance K(Ca) (BK(Ca)) channels in endothelial cells (ECs) and smooth muscle cells (SMCs) of PAs. Both SK(Ca) and IK(Ca) channels conducted the outward current in isolated PA ECs (current densities, ~20 pA/pF and ~28 pA/pF at +40 mV, respectively), but these currents were not detected in PA SMCs. In contrast, BK(Ca) currents were prominent in PA SMCs (~154 pA/pF), but were undetectable in PA ECs. Pressurized PAs constricted to inhibition of SK(Ca) (~16%) and IK(Ca) (~16%) channels, but were only modestly affected by inhibition of BK(Ca) channels (~5%). Blockade of SK(Ca) and IK(Ca) channels decreased resting cortical cerebral blood flow (CBF) by ~15%. NS309 (6,7-dichloro-1H-indole-2,3-dione3-oxime), a SK(Ca)/IK(Ca) channel opener, hyperpolarized PA SMCs by ~27 mV, maximally dilated pressurized PAs, and increased CBF by ~40%. In conclusion, these data show that SK(Ca) and IK(Ca) channels in ECs profoundly modulate PA tone and CBF, whereas BK(Ca) channels in SMCs only modestly influence PA diameter.

Functional Properties of a Newly Identified C-terminal Splice Variant of Cav1.3 L-type Ca2+ Channels*

PubMed Central

Bock, Gabriella; Gebhart, Mathias; Scharinger, Anja; Jangsangthong, Wanchana; Busquet, Perrine; Poggiani, Chiara; Sartori, Simone; Mangoni, Matteo E.; Sinnegger-Brauns, Martina J.; Herzig, Stefan; Striessnig, Jörg; Koschak, Alexandra

2011-01-01

An intramolecular interaction between a distal (DCRD) and a proximal regulatory domain (PCRD) within the C terminus of long Cav1.3 L-type Ca2+ channels (Cav1.3L) is a major determinant of their voltage- and Ca2+-dependent gating kinetics. Removal of these regulatory domains by alternative splicing generates Cav1.342A channels that activate at a more negative voltage range and exhibit more pronounced Ca2+-dependent inactivation. Here we describe the discovery of a novel short splice variant (Cav1.343S) that is expressed at high levels in the brain but not in the heart. It lacks the DCRD but, in contrast to Cav1.342A, still contains PCRD. When expressed together with α2δ1 and β3 subunits in tsA-201 cells, Cav1.343S also activated at more negative voltages like Cav1.342A but Ca2+-dependent inactivation was less pronounced. Single channel recordings revealed much higher channel open probabilities for both short splice variants as compared with Cav1.3L. The presence of the proximal C terminus in Cav1.343S channels preserved their modulation by distal C terminus-containing Cav1.3- and Cav1.2-derived C-terminal peptides. Removal of the C-terminal modulation by alternative splicing also induced a faster decay of Ca2+ influx during electrical activities mimicking trains of neuronal action potentials. Our findings extend the spectrum of functionally diverse Cav1.3 L-type channels produced by tissue-specific alternative splicing. This diversity may help to fine tune Ca2+ channel signaling and, in the case of short variants lacking a functional C-terminal modulation, prevent excessive Ca2+ accumulation during burst firing in neurons. This may be especially important in neurons that are affected by Ca2+-induced neurodegenerative processes. PMID:21998310

A complicated complex: Ion channels, voltage sensing, cell membranes and peptide inhibitors.

PubMed

Zhang, Alan H; Sharma, Gagan; Undheim, Eivind A B; Jia, Xinying; Mobli, Mehdi

2018-04-21

Voltage-gated ion channels (VGICs) are specialised ion channels that have a voltage dependent mode of action, where ion conduction, or gating, is controlled by a voltage-sensing mechanism. VGICs are critical for electrical signalling and are therefore important pharmacological targets. Among these, voltage-gated sodium channels (Na V s) have attracted particular attention as potential analgesic targets. Na V s, however, comprise several structurally similar subtypes with unique localisations and distinct functions, ranging from amplification of action potentials in nociception (e.g. Na V 1.7) to controlling electrical signalling in cardiac function (Na V 1.5). Understanding the structural basis of Na V function is therefore of great significance, both to our knowledge of electrical signalling and in development of subtype and state selective drugs. An important tool in this pursuit has been the use of peptides from animal venoms as selective Na V modulators. In this review, we look at peptides, particularly from spider venoms, that inhibit Na V s by binding to the voltage sensing domain (VSD) of this channel, known as gating modifier toxins (GMT). In the first part of the review, we look at the structural determinants of voltage sensing in VGICs, the gating cycle and the conformational changes that accompany VSD movement. Next, the modulation of the analgesic target Na V 1.7 by GMTs is reviewed to develop bioinformatic tools that, based on sequence information alone, can identify toxins that are likely to inhibit this channel. The same approach is also used to define VSD sequences, other than that from Na V 1.7, which are likely to be sensitive to this class of toxins. The final section of the review focuses on the important role of the cellular membrane in channel modulation and also how the lipid composition affects measurements of peptide-channel interactions both in binding kinetics measurements in solution and in cell-based functional assays. Copyright © 2018 Elsevier B.V. All rights reserved.

Modulation of Kv7 potassium channels by a novel opener pyrazolo[1,5-a]pyrimidin-7(4H)-one compound QO-58

PubMed Central

Zhang, F; Mi, Y; Qi, JL; Li, JW; Si, M; Guan, BC; Du, XN; An, HL; Zhang, HL

2013-01-01

Background and Purpose Modulation of Kv7/M channel function represents a relatively new strategy to treat neuronal excitability disorders such as epilepsy and neuropathic pain. We designed and synthesized a novel series of pyrazolo[1,5-a] pyrimidin-7(4H)-one compounds, which activate Kv7 channels. Here, we characterized the effects of the lead compound, QO-58, on Kv7 channels and investigated its mechanism of action. Experimental Approach A perforated whole-cell patch technique was used to record Kv7 currents expressed in mammalian cell lines and M-type currents from rat dorsal root ganglion neurons. The effects of QO-58 in a rat model of neuropathic pain, chronic constriction injury (CCI) of the sciatic nerve, were also examined. Key Results QO-58 increased the current amplitudes, shifted the voltage-dependent activation curve in a more negative direction and slowed the deactivation of Kv7.2/Kv7.3 currents. QO-58 activated Kv7.1, Kv7.2, Kv7.4 and Kv7.3/Kv7.5 channels with a more selective effect on Kv7.2 and Kv7.4, but little effect on Kv7.3. The mechanism of QO-58's activation of Kv7 channels was clearly distinct from that used by retigabine. A chain of amino acids, Val224Val225Tyr226, in Kv7.2 was important for QO-58 activation of this channel. QO-58 enhanced native neuronal M currents, resulting in depression of evoked action potentials. QO-58 also elevated the pain threshold of neuropathic pain in the sciatic nerve CCI model. Conclusions and Implications The results indicate that QO-58 is a potent modulator of Kv7 channels with a mechanism of action different from those of known Kv7 openers. Hence, QO-58 shows potential as a treatment for diseases associated with neuronal hyperexcitability. PMID:23013484

Different KChIPs compete for heteromultimeric assembly with pore-forming Kv4 subunits.

PubMed

Zhou, Jingheng; Tang, Yiquan; Zheng, Qin; Li, Meng; Yuan, Tianyi; Chen, Liangyi; Huang, Zhuo; Wang, KeWei

2015-06-02

Auxiliary Kv channel-interacting proteins 1-4 (KChIPs1-4) coassemble with pore-forming Kv4 α-subunits to form channel complexes underlying somatodendritic subthreshold A-type current that regulates neuronal excitability. It has been hypothesized that different KChIPs can competitively bind to Kv4 α-subunit to form variable channel complexes that can exhibit distinct biophysical properties for modulation of neural function. In this study, we use single-molecule subunit counting by total internal reflection fluorescence microscopy in combinations with electrophysiology and biochemistry to investigate whether different isoforms of auxiliary KChIPs, KChIP4a, and KChIP4bl, can compete for binding of Kv4.3 to coassemble heteromultimeric channel complexes for modulation of channel function. To count the number of photobleaching steps solely from cell membrane, we take advantage of a membrane tethered k-ras-CAAX peptide that anchors cytosolic KChIP4 proteins to the surface for reduction of background noise. Single-molecule subunit counting reveals that the number of KChIP4 isoforms in Kv4.3-KChIP4 complexes can vary depending on the KChIP4 expression level. Increasing the amount of KChIP4bl gradually reduces bleaching steps of KChIP4a isoform proteins, and vice versa. Further analysis of channel gating kinetics from different Kv4-KChIP4 subunit compositions confirms that both KChIP4a and KChIP4bl can modulate the channel complex function upon coassembly. Taken together, our findings show that auxiliary KChIPs can heteroassemble with Kv4 in a competitive manner to form heteromultimeric Kv4-KChIP4 channel complexes that are biophysically distinct and regulated under physiological or pathological conditions. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Advancing Underwater Acoustic Communication for Autonomous Distributed Networks via Sparse Channel Sensing, Coding, and Navigation Support

DTIC Science & Technology

2014-09-30

underwater acoustic communication technologies for autonomous distributed underwater networks , through innovative signal processing, coding, and...4. TITLE AND SUBTITLE Advancing Underwater Acoustic Communication for Autonomous Distributed Networks via Sparse Channel Sensing, Coding, and...coding: 3) OFDM modulated dynamic coded cooperation in underwater acoustic channels; 3 Localization, Networking , and Testbed: 4) On-demand

Identification of ion-channel modulators that protect against aminoglycoside-induced hair cell death

PubMed Central

Kenyon, Emma J.; Kirkwood, Nerissa K.; Kitcher, Siân R.; O’Reilly, Molly; Cantillon, Daire M.; Goodyear, Richard J.; Secker, Abigail; Baxendale, Sarah; Bull, James C.; Waddell, Simon J.; Whitfield, Tanya T.; Ward, Simon E.; Kros, Corné J.; Richardson, Guy P.

2017-01-01

Aminoglycoside antibiotics are used to treat life-threatening bacterial infections but can cause deafness due to hair cell death in the inner ear. Compounds have been described that protect zebrafish lateral line hair cells from aminoglycosides, but few are effective in the cochlea. As the aminoglycosides interact with several ion channels, including the mechanoelectrical transducer (MET) channels by which they can enter hair cells, we screened 160 ion-channel modulators, seeking compounds that protect cochlear outer hair cells (OHCs) from aminoglycoside-induced death in vitro. Using zebrafish, 72 compounds were identified that either reduced loading of the MET-channel blocker FM 1-43FX, decreased Texas red–conjugated neomycin labeling, or reduced neomycin-induced hair cell death. After testing these 72 compounds, and 6 structurally similar compounds that failed in zebrafish, 13 were found that protected against gentamicin-induced death of OHCs in mouse cochlear cultures, 6 of which are permeant blockers of the hair cell MET channel. None of these compounds abrogated aminoglycoside antibacterial efficacy. By selecting those without adverse effects at high concentrations, 5 emerged as leads for developing pharmaceutical otoprotectants to alleviate an increasing clinical problem. PMID:29263311

Interpreting anomalously low voltage noise in two-channel measurement systems.

PubMed

Ivanov, Eugene N; Walls, Fred L

2002-01-01

In this work we 1) analyze and give a theoretical explanation for the anomalously low cross-spectral density of voltage fluctuations that is observed when two thermal noise sources with matched intensities are coupled to the inputs of two-channel phase modulation (PM) or amplitude modulation (AM) noise measurement systems (NMS), 2) empirically evaluate spectral resolutions of different types of measurement systems, and 3) discuss noise measurement techniques involving cross-correlation signal processing. Our work shows that the statistical uncertainty, which sets the ultimate spectral resolution in the thermal noise limited regime, is approximately the same for both systems. However, in practical terms, the non-stationary nature of the noise, the temporal separation of calibration and measurement, and the difficulty of reproducing the calibrations for two measurements make it extremely difficult to resolve noise that is more than 10 dB below the noise floor in a single channel NMS. In a two-channel NMS, however, the calibrations of the two channels are carried out simultaneously, and one can take full advantage of a large number of averages and make reproducible noise measurements with resolution 10 dB below the noise floor of a single channel NMS.

Identification of ion-channel modulators that protect against aminoglycoside-induced hair cell death.

PubMed

Kenyon, Emma J; Kirkwood, Nerissa K; Kitcher, Siân R; O'Reilly, Molly; Derudas, Marco; Cantillon, Daire M; Goodyear, Richard J; Secker, Abigail; Baxendale, Sarah; Bull, James C; Waddell, Simon J; Whitfield, Tanya T; Ward, Simon E; Kros, Corné J; Richardson, Guy P

2017-12-21

Aminoglycoside antibiotics are used to treat life-threatening bacterial infections but can cause deafness due to hair cell death in the inner ear. Compounds have been described that protect zebrafish lateral line hair cells from aminoglycosides, but few are effective in the cochlea. As the aminoglycosides interact with several ion channels, including the mechanoelectrical transducer (MET) channels by which they can enter hair cells, we screened 160 ion-channel modulators, seeking compounds that protect cochlear outer hair cells (OHCs) from aminoglycoside-induced death in vitro. Using zebrafish, 72 compounds were identified that either reduced loading of the MET-channel blocker FM 1-43FX, decreased Texas red-conjugated neomycin labeling, or reduced neomycin-induced hair cell death. After testing these 72 compounds, and 6 structurally similar compounds that failed in zebrafish, 13 were found that protected against gentamicin-induced death of OHCs in mouse cochlear cultures, 6 of which are permeant blockers of the hair cell MET channel. None of these compounds abrogated aminoglycoside antibacterial efficacy. By selecting those without adverse effects at high concentrations, 5 emerged as leads for developing pharmaceutical otoprotectants to alleviate an increasing clinical problem.

Extending prematuration with cAMP modulators enhances the cumulus contribution to oocyte antioxidant defence and oocyte quality via gap junctions.

PubMed

Li, H J; Sutton-McDowall, M L; Wang, X; Sugimura, S; Thompson, J G; Gilchrist, R B

2016-04-01

Can bovine oocyte antioxidant defence and oocyte quality be improved by extending the duration of pre-in vitro maturation (IVM) with cyclic adenosine mono-phosphate (cAMP) modulators? Lengthening the duration of cAMP-modulated pre-IVM elevates intra-oocyte reduced glutathione (GSH) content and reduces hydrogen peroxide (H2O2) via increased cumulus cell-oocyte gap-junctional communication (GJC), associated with an improvement in subsequent embryo development and quality. Oocytes are susceptible to oxidative stress and the oocyte's most important antioxidant glutathione is supplied, at least in part, by cumulus cells. A temporary inhibition of spontaneous meiotic resumption in oocytes can be achieved by preventing a fall in cAMP, and cyclic AMP-modulated pre-IVM maintains cumulus-oocyte GJC and improves subsequent embryo development. This study consisted of a series of 10 experiments using bovine oocytes in vitro, each with multiple replicates. A range of pre-IVM durations were examined as the key study treatments which were compared with a control. The study was designed to examine if one of the oocyte's major antioxidant defences can be enhanced by pre-IVM with cAMP modulators, and to examine the contribution of cumulus-oocyte GJC on these processes. Immature bovine cumulus-oocyte complexes were treated in vitro without (control) or with the cAMP modulators; 100 µM forskolin (FSK) and 500 µM 3-isobutyl-1-methyxanthine (IBMX), for 0, 2, 4 or 6 h (pre-IVM phase) prior to IVM. Oocyte developmental competence was assessed by embryo development and quality post-IVM/IVF. Cumulus-oocyte GJC, intra-oocyte GSH and H2O2 were quantified at various time points during pre-IVM and IVM, in the presence and the absence of functional inhibitors: carbenoxolone (CBX) to block GJC and buthionine sulfoximide (BSO) to inhibit glutathione synthesis. Pre-IVM with FSK + IBMX increased subsequent blastocyst formation rate and quality compared with standard IVM (P < 0.05), regardless of pre-IVM duration. The final blastocyst yields (proportion of blastocysts/immature oocyte) were 26.3% for the control, compared with 39.2, 35.2 and 34.2%, for the 2, 4 and 6 h pre-IVM FSK + IBMX treatments, respectively. In contrast to standard IVM (control), pre-IVM with cAMP modulators maintained open gap junctions between cumulus cells and oocytes for the duration (6 h) of pre-IVM examined, and persisted for a further 8 h in the IVM phase. Cyclic AMP-modulated pre-IVM increased intra-oocyte GSH levels at the completion of both pre-IVM and IVM, in a pre-IVM duration-dependent manner (P < 0.05), which was ablated when GJC was blocked using CBX (P < 0.05). By 4 h of pre-IVM treatment with cAMP modulators, oocyte H2O2 levels were reduced compared the control (P < 0.05), although this beneficial effect was lost when oocytes were co-treated with BSO. Inhibiting glutathione synthesis with BSO during pre-IVM ablated any positive benefits of cAMP-mediated pre-IVM on oocyte developmental competence (P < 0.01). It is unclear if the improvement in oocyte antioxidant defence and developmental competence reported here is due to direct transfer of total and/or reduced glutathione from cumulus cells to the oocyte via gap junctions, or whether a GSH synthesis signal and/or amino acid substrates are supplied to the oocyte via gap junctions. Embryo transfer experiments are required to determine if the cAMP-mediated improvement in blastocyst rates leads to improved live birth rates. IVM offers significant benefits to infertile and cancer patients and has the potential to significantly alter ART practice, if IVM efficiency in embryo production could be improved closer to that of conventional IVF (using ovarian hyperstimulation). Pre-IVM with cAMP modulators is a simple and reliable means to improve IVM outcomes. This work was supported by grants and fellowships from the National Health and Medical Research Council of Australia (1007551, 627007, 1008137, 1023210) and by scholarships from the Chinese Scholarship Council (CSC) awarded to H.J.L. and the Japanese Society for the Promotion of Science Postdoctoral Fellowship for Research Abroad awarded to S.S. The Fluoview FV10i confocal microscope was purchased as part of the Sensing Technologies for Advanced Reproductive Research (STARR) facility, funded by the South Australian Premier's Science and Research Fund. We acknowledge partial support from the Australian Research Council Centre of Excellence for Nanoscale BioPhotonics (CE140100003). We declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Microwave Imaging Radar Reflectometer System Utilizing Digital Beam Forming

NASA Astrophysics Data System (ADS)

Hu, Fengqi; Li, Meijiao; Domier, Calvin W.; Liu, Xiaoguang; Luhmann, Neville C., Jr.

2016-10-01

Microwave Imaging Reflectometry is a radar-like technique developed to measure the electron density fluctuations in fusion plasmas. Phased Antenna Arrays can serve as electronically controlled ``lenses'' that can generate the required wavefronts by phase shifting and amplitude scaling, which is being realized in the digital domain with higher flexibility and faster processing speed. In the transmitter, the resolution of the phase control is 1.4 degrees and the amplitude control is 0.5 dB/ step. A V-band double-sided, printed bow tie antenna which exhibits 49% bandwidth (46 - 76 GHz) is employed. The antenna is fed by a microstrip transmission line for easy impedance matching. The simple structure and the small antenna are suitable for low cost fabrication, easy circuit integration, and phased antenna array multi-frequency applications. In the receiver part, a sub-array of 32 channels with 200 mil spacing is used to collect the scattered reflected signal from one unit spot on the plasma cutoff surface. Pre-amplification is used to control the noise level of the system and wire bondable components are used to accommodate the small spacing between each channel. After down converting, base band signals are digitized and processed in an FPGA module. U.S. Department of Energy Grant No. DE-FG02-99ER54531.

Advances in Front-end Enabling Technologies for Thermal Infrared ` THz Torch' Wireless Communications

NASA Astrophysics Data System (ADS)

Hu, Fangjing; Lucyszyn, Stepan

2016-09-01

The thermal (emitted) infrared frequency bands (typically 20-40 and 60-100 THz) are best known for remote sensing applications that include temperature measurement (e.g. non-contacting thermometers and thermography), night vision and surveillance (e.g. ubiquitous motion sensing and target acquisition). This unregulated part of the electromagnetic spectrum also offers commercial opportunities for the development of short-range secure communications. The ` THz Torch' concept, which fundamentally exploits engineered blackbody radiation by partitioning thermally generated spectral radiance into pre-defined frequency channels, was recently demonstrated by the authors. The thermal radiation within each channel can be independently pulse-modulated, transmitted and detected, to create a robust form of short-range secure communications within the thermal infrared. In this paper, recent progress in the front-end enabling technologies associated with the THz Torch concept is reported. Fundamental limitations of this technology are discussed; possible engineering solutions for further improving the performance of such thermal-based wireless links are proposed and verified either experimentally or through numerical simulations. By exploring a raft of enabling technologies, significant enhancements to both data rate and transmission range can be expected. With good engineering solutions, the THz Torch concept can exploit nineteenth century physics with twentieth century multiplexing schemes for low-cost twenty-first century ubiquitous applications in security and defence.

A 4-channel coil array interconnection by analog direct modulation optical link for 1.5-T MRI.

PubMed

Yuan, Jing; Wei, Juan; Shen, Gary X

2008-10-01

Optical glass fiber shows great advantages over coaxial cables in terms of electromagnetic interference, thus, it should be considered a potential alternative for magnetic resonance imaging (MRI) receive coil interconnection, especially for a large number coil array at high field. In this paper, we propose a 4-channel analog direct modulation optical link for a 1.5-T MRI coil array interconnection. First, a general direct modulated optical link is compared to an external modulated optical link. And then the link performances of the proposed direct modulated optical link, including power gain, frequency response, and dynamic range, are analyzed and measured. Phantom and in vivo head images obtained using this optical link are demonstrated for comparison with those obtained by cable connections. The signal-to-noise (SNR) analysis shows that the optical link achieves 6%-8% SNR a improvement over coaxial cables by elimination of electrical interference between cables during MR signal transmission.

On the Study of a Quadrature DCSK Modulation Scheme for Cognitive Radio

NASA Astrophysics Data System (ADS)

Quyen, Nguyen Xuan

The past decade has witnessed a boom of wireless communications which necessitate an increasing improvement of data rate, error-rate performance, bandwidth efficiency, and information security. In this work, we propose a quadrature (IQ) differential chaos-shift keying (DCSK) modulation scheme for the application in cognitive radio (CR), named CR-IQ-DCSK, which offers the above improvement. Chaotic signal is generated in frequency domain and then converted into time domain via an inverse Fourier transform. The real and imaginary components of the frequency-based chaotic signal are simultaneously used in in-phase and quadrature branches of an IQ modulator, where each branch conveys two bits by means of a DCSK-based modulation. Schemes and operating principle of the modulator and demodulator are proposed and described. Analytical BER performance for the proposed schemes over a typical multipath Rayleigh fading channel is derived and verified by numerical simulations. Results show that the proposed scheme outperforms DCSK, CDSK and performs better with the increment of the number of channel paths.

The Natural Plant Product Rottlerin Activates Kv7.1/KCNE1 Channels.

PubMed

Matschke, Veronika; Piccini, Ilaria; Schubert, Janina; Wrobel, Eva; Lang, Florian; Matschke, Johann; Amedonu, Elsie; Meuth, Sven G; Strünker, Timo; Strutz-Seebohm, Nathalie; Greber, Boris; Scherkenbeck, Jürgen; Seebohm, Guiscard

2016-01-01

Acquired as well as inherited channelopathies are disorders that are caused by altered ion channel function. A family of channels whose malfunction is associated with different channelopathies is the Kv7 K+ channel family; and restoration of normal Kv7 channel function by small molecule modulators is a promising approach for treatment of these often fatal diseases. Here, we show the modulation of Kv7 channels by the natural compound Rottlerin heterologously expressed in Xenopus laevis oocytes and on iPSC cardiomyocytes overexpressing Kv7.1 channels. We show that currents carried by Kv7.1 (EC50 = 1.48 μM), Kv7.1/KCNE1 (EC50 = 4.9 μM), and Kv7.4 (EC50 = 0.148 μM) are strongly enhanced by the compound, whereas Kv7.2, Kv7.2/Kv7.3, and Kv7.5 are not sensitive to Rottlerin. Studies on Kv7.1/KCNE1 mutants and in silico modelling indicate that Rottlerin binds to the R-L3-activator site. Rottlerin mediated activation of Kv7.1/KCNE1 channels might be a promising approach in long QT syndrome. As a proof of concept, we show that Rottlerin shortens cardiac repolarisation in iPSC-derived cardiomyocytes expressing Kv7.1. Rottlerin or an optimized derivative holds a potential as QT interval correcting drug. © 2016 The Author(s) Published by S. Karger AG, Basel.

Closed-state inactivation involving an internal gate in Kv4.1 channels modulates pore blockade by intracellular quaternary ammonium ions

PubMed Central

Fineberg, Jeffrey D.; Szanto, Tibor G.; Panyi, Gyorgy; Covarrubias, Manuel

2016-01-01

Voltage-gated K+ (Kv) channel activation depends on interactions between voltage sensors and an intracellular activation gate that controls access to a central pore cavity. Here, we hypothesize that this gate is additionally responsible for closed-state inactivation (CSI) in Kv4.x channels. These Kv channels undergo CSI by a mechanism that is still poorly understood. To test the hypothesis, we deduced the state of the Kv4.1 channel intracellular gate by exploiting the trap-door paradigm of pore blockade by internally applied quaternary ammonium (QA) ions exhibiting slow blocking kinetics and high-affinity for a blocking site. We found that inactivation gating seemingly traps benzyl-tributylammonium (bTBuA) when it enters the central pore cavity in the open state. However, bTBuA fails to block inactivated Kv4.1 channels, suggesting gated access involving an internal gate. In contrast, bTBuA blockade of a Shaker Kv channel that undergoes open-state P/C-type inactivation exhibits fast onset and recovery inconsistent with bTBuA trapping. Furthermore, the inactivated Shaker Kv channel is readily blocked by bTBuA. We conclude that Kv4.1 closed-state inactivation modulates pore blockade by QA ions in a manner that depends on the state of the internal activation gate. PMID:27502553