On the Capacity of Non-Uniform Phase MIMO Nakagami-m Fading Channels

This letter investigates the ergodic capacity of MIMO Nakagami-m fading channels with both uniformly and non-uniformly distributed phases. We first obtain a tight capacity upper bound for the channel and then derive exact expressions for the low signal-to-noise ratio (SNR) capacity metrics, based on which we examine the impact of fading parameter m on the capacity.

Altered stress stimulation of inward rectifier potassium channels in Andersen-Tawil syndrome

Inward rectifier potassium channels of the Kir2 subfamily are important determinants of the electrical activity of brain and muscle cells. Genetic mutations in Kir2.1 associate with Andersen-Tawil syndrome (ATS), a familial disorder leading to stress-triggered periodic paralysis and ventricular arrhythmia. To identify the molecular mechanisms of this stress trigger, we analyze Kir channel function and localization electrophysiologically and by time-resolved confocal microscopy. Furthermore, we employ a mathematical model of muscular membrane potential. We identify a novel corticoid signaling pathway that, when activated by glucocorticoids, leads to enrichment of Kir2 channels in the plasma membranes of mammalian cell lines and isolated cardiac and skeletal muscle cells. We further demonstrate that activation of this pathway can either partly restore (40% of cases) or further impair (20% of cases) the function of mutant ATS channels, depending on the particular Kir2.1 mutation. This means that glucocorticoid treatment might either alleviate or deteriorate symptoms of ATS depending on the patient's individual Kir2.1 genotype. Thus, our findings provide a possible explanation for the contradictory effects of glucocorticoid treatment on symptoms in patients with ATS and may open new pathways for the design of personalized medicines in ATS therapy. © FASEB.

Identification of ML204, a novel potent antagonist that selectively modulates native TRPC4/C5 ion channels.

Transient receptor potential canonical (TRPC) channels are Ca(2+)-permeable nonselective cation channels implicated in diverse physiological functions, including smooth muscle contractility and synaptic transmission. However, lack of potent selective pharmacological inhibitors for TRPC channels has limited delineation of the roles of these channels in physiological systems. Here we report the identification and characterization of ML204 as a novel, potent, and selective TRPC4 channel inhibitor. A high throughput fluorescent screen of 305,000 compounds of the Molecular Libraries Small Molecule Repository was performed for inhibitors that blocked intracellular Ca(2+) rise in response to stimulation of mouse TRPC4ß by µ-opioid receptors. ML204 inhibited TRPC4ß-mediated intracellular Ca(2+) rise with an IC(50) value of 0.96 µm and exhibited 19-fold selectivity against muscarinic receptor-coupled TRPC6 channel activation. In whole-cell patch clamp recordings, ML204 blocked TRPC4ß currents activated through either µ-opioid receptor stimulation or intracellular dialysis of guanosine 5'-3-O-(thio)triphosphate (GTP?S), suggesting a direct interaction of ML204 with TRPC4 channels rather than any interference with the signal transduction pathways. Selectivity studies showed no appreciable block by 10-20 µm ML204 of TRPV1, TRPV3, TRPA1, and TRPM8, as well as KCNQ2 and native voltage-gated sodium, potassium, and calcium channels in mouse dorsal root ganglion neurons. In isolated guinea pig ileal myocytes, ML204 blocked muscarinic cation currents activated by bath application of carbachol or intracellular infusion of GTP?S, demonstrating its effectiveness on native TRPC4 currents. Therefore, ML204 represents an excellent novel tool for investigation of TRPC4 channel function and may facilitate the development of therapeutics targeted to TRPC4.

Hydrodynamic cavitation in micro channels with channel sizes of 100 and 750 micrometers

Decreasing the constriction size and residence time in hydrodynamic cavitation is predicted to give increased hot spot temperatures at bubble collapse and increased radical formation rate. Cavitation in a 100 x 100 mu m(2) rectangular micro channel and in a circular 750 mu m diameter milli channel has been investigated with computational fluid dynamics software and with imaging and radical production experiments. No radical production has been measured in the micro channel. This is probably because there is no spherically symmetrical collapse of the gas pockets in the channel which yield high hot spot temperatures. The potassium iodide oxidation yield in the presence of chlorohydrocarbons in the milli channel of up to 60 nM min(-1) is comparable to values reported on hydrodynamic cavitation in literature, but lower than values for ultrasonic cavitation. These small constrictions can create high apparent cavitation collapse frequencies.

Hydrodynamics and mixer-induced bubble formation in micro bubble columns with single and multiple-channels

A hydrodynamic characterization of an industrially used gas-liquid contacting microchannel. device is discussed, viz. the micro bubble column of IMM. Furthermore, similar characterization of a gas-liquid flow microchip of TU/e, with two tailored mixer designs, is used to solve fundamental issues on hydrodynamics, and therefore, to achieve further design and operating optimization of that chip and the IMM device. Flow pattern maps are presented in a dimensionless fashion for further predictions on new fluidic systems for optimum single-channel multiphase operation. Bubble formation was investigated in the two types of mixers and pinch-off and hydrodynamic decay mechanisms are observed. The impact of these mechanisms on bubble size, bubble size distributions, and on the corresponding flow patterns, i.e., the type of mixer design, can be decisive for the flow pattern map and thus, may be used to alter flow pattern maps. The bubble sizes and their distribution were improved for the tailored designs, i.e., smaller and more regular bubbles were generated. Finally, the impact of multi-channel distribution for gas and liquid flow is demonstrated. Intermediate flow patterns such as slug-annular flow, also found for single-phase operation, and the simultaneous coexistence of flow regimes are presented, with the latter providing evidence of flow maldistribution.

Feedback via Ca²⁺-activated ion channels modulates endothelin 1 signaling in retinal arteriolar smooth muscle

PURPOSE: To investigate the role of feedback by Ca²?-sensitive plasma-membrane ion channels in endothelin 1 (Et1) signaling in vitro and in vivo. Methods. Et1 responses were imaged from Fluo-4-loaded smooth muscle in isolated segments of rat retinal arteriole using two-dimensional (2-D) confocal laser microscopy. Vasoconstrictor responses to intravitreal injections of Et1 were recorded in the absence and presence of appropriate ion channel blockers using fluorescein angiograms imaged using a confocal scanning laser ophthalmoscope. Results. Et1 (10 nM) increased both basal [Ca²?](i) and the amplitude and frequency of Ca²?-waves in retinal arterioles. The Ca²?-activated Cl?-channel blockers DIDS and 9-anthracene carboxylic acid (9AC) blocked Et1-induced increases in wave frequency, and 9AC also inhibited the increase in amplitude. Iberiotoxin, an inhibitor of large conductance (BK) Ca²?-activated K?-channels, increased wave amplitude in the presence of Et1 but had no effect on frequency. None of these drugs affected basal [Ca²?](i). The voltage-operated Ca²?-channel inhibitor nimodipine inhibited wave frequency and amplitude and also lowered basal [Ca²?](i) in the presence of Et1. Intravitreal injection of Et1 caused retinal arteriolar vasoconstriction. This was inhibited by DIDS but not by iberiotoxin or penitrem A, another BK-channel inhibitor. Conclusions. Et1 evokes increases in the frequency of arteriolar Ca²?-waves in vitro, resulting in vasoconstriction in vivo. These responses, initiated by release of stored Ca²?, also require positive feedback via Ca²?-activated Cl?-channels and L-type Ca²?-channels.

Relativistic laser interactions with preformed plasma channels and gamma-ray measurements

The propagation of a 1-ps laser pulse at intensities exceeding 10(19) Wcm(-2) in a low-density plasma channel was experimentally tested. The channel was produced by a lower intensity preceding pulse of the same duration. Plasma electrons were accelerated during the propagation of the main pulse, and high energy gamma -ray detectors were used to detect their bremsstrahlung emission. The gamma -ray yield was studied for different channel conditions, by varying the delay between the channel forming pulse and the high intensity pulse. These results are correlated with the interferograms of the propagation region into the plasma.

Observations of collimated ionization channels in aluminum-coated glass targets irradiated by ultraintense laser pulses

Filamentary ionization tracks have been observed via optical probing inside Al-coated glass targets after the interaction of a picosecond 20-TW laser pulse at intensities above 10(19) W/cm(2). The tracks, up to 700 mu m in length and between 10 and 20 mu m in width, originate from the focal spot region of the laser beam. Simulations performed with 3D particle-in-cell and 2D Fokker-Planck hybrid codes indicate that the observations are consistent with ionization induced in the glass target by magnetized, collimated beams of high-energy electrons produced during the laser interaction.