Dantrolene inhibition of sarcoplasmic reticulum Ca2+ release by direct and specific action at skeletal muscle ryanodine receptors

The skeletal muscle relaxant dantrolene inhibits the release of Ca2+ from the sarcoplasmic reticulum during excitation-contraction coupling and suppresses the uncontrolled Ca2+ release that underlies the skeletal muscle pharmacogenetic disorder malignant hyperthermia; however, the molecular mechanism by which dantrolene selectively affects skeletal muscle Ca2+ regulation remains to be defined. Here we provide evidence of a high-affinity, monophasic inhibition by dantrolene of ryanodine receptor Ca2+ channel function in isolated sarcoplasmic reticulum vesicles prepared from malignant hyperthermia-susceptible and normal pig skeletal muscle. In media simulating resting myoplasm, dantrolene increased the half-time for 45Ca2+ release from both malignant hyperthermia and normal vesicles approximately 3.5-fold and inhibited sarcoplasmic reticulum vesicle [3H]ryanodine binding (Ki approximately 150 nM for both malignant hyperthermia and normal). Inhibition of vesicle [3H]ryanodine binding by dantrolene was associated with a decrease in the extent of activation by both calmodulin and Ca2+. Dantrolene also inhibited [3H]ryanodine binding to purified skeletal muscle ryanodine receptor protein reconstituted into liposomes. In contrast, cardiac sarcoplasmic reticulum vesicle 45Ca2+ release and [3H]ryanodine binding were unaffected by dantrolene. Together, these results demonstrate selective effects of dantrolene on skeletal muscle ryanodine receptors that are consistent with the actions of dantrolene in vivo and suggest a mechanism of action in which dantrolene may act directly at the skeletal muscle ryanodine receptor complex to limit its activation by calmodulin and Ca2+. The potential implications of these results for understanding how dantrolene and malignant hyperthermia mutations may affect the voltage-dependent activation of Ca2+ release in intact skeletal muscle are discussed.     

A comparison of two correlation schemes

Processes involving the cross-correlation of two noisy data streams are frequently encountered in signal processing. The performances of two commonly used correlators, the simple and complex correlators, are examined. The conventional view is that the complex correlator is superior to the simple correlator by a factor of the square root of two in output signal-to-noise ratio (SNR). However, by modifying the simple correlator to utilize all the available information, its performance is improved. The development of the modified correlator is explained, and a computer simulation shows that this modified correlator is approximately equivalent to the complex correlator in noise performance     

Experimental investigation of variation of backscattered power level with numerical aperture in multimode optical fibres

Experiments have been performed to determine how the backscattered power level varies with numerical aperture. It is found that graded-index fibres are more sensitive to such variations than step-index fibres. By taking into account the dependence of the Rayleigh scattering coefficient on numerical aperture, the experimental results agree well with theory.     

Inexpensive in situ time-integrating seawater nutrient sampler

An in situ time-integrating seawater sampler in which air escaping from the sample bottle through a capillary regulates flow of seawater into the sampler is described for determination of average plant nutrient concentration during a 10–50 h period. The sampler collected water at a constant rate which was approximately equal to that predicted from the Hagen-Poiseuille equation. The sampler has advantages over those described previously: it is less susceptible to blockage from suspended particulates in seawater, less expensive, and the seawater collection rate should be less temperature-dependent.     

Characterization and simulation of proton exchanged integratedoptical modulators with various dielectric buffer layers

Fast and accurate numerical techniques are developed for calculating the optical depth of modulation of integrated optical devices with various dielectric buffer layers. The matrix effective refractive-index method is used in calculating the LiNbO₃ proton exchange single-channel optical mode parameters. An approximate technique for calculating electrode electric-field distributions as a function of various buffer layers is presented. Comparisons of computer simulations to experimental measurements performed on Mach-Zehnder modulators containing various buffer layers demonstrate that the numerical techniques are sufficiently accurate for computer-aided design use     

Characteristics of S-shaped waveguide structures by the annealedproton exchange process in LiNbO3

The loss of S-shaped waveguide bends in annealed proton-exchanged LiNbO₃ integrated optical devices is found to be dependent on the length of thermal annealing time. The minimum transition length required in order to have losses as low as 0.2 dB is 2.0 mm for a 0.1-mm lateral offset. Intersecting waveguides based on S-shaped structures have been characterized for passive crossovers. An angle greater than 6° is required to provide a crosstalk of less than -30 dB. At a particular angle, intersecting waveguides offer the possibility of making a 3-dB coupler if an insertion loss of 1.2 dB is not a big concern. Zero-gap couplers based on S-shaped structures have been characterized for applications as 3-dB couplers as well. This type of 3-dB coupler has a much lower insertion loss of roughly 0.4-0.5 dB. Both 3-dB intersecting waveguides and 3-dB zero-gap couplers are less sensitive to wavelength variations     

Theory of timing jitter in actively mode-locked lasers

An analysis of the pulse-to-pulse timing jitter in an actively mode-locked laser is presented. The model includes spontaneous emission noise, mode-locker driver phase noise, and cavity length detuning. Analytical expressions for the laser pulse train phase noise spectrum, the intensity power spectrum, and the RMS timing jitter are given. The timing fluctuations are characterized by a time constant proportional to the cavity round-trip time times the number of locked modes squared divided by the modulation depth. The contribution from the mode-locker driver phase noise will dominate unless high-stability RF sources are used. The residual timing jitter due to spontaneous emission noise is very sensitive to cavity detuning     

Backscattering signatures from optical fibers with differential mode attenuation

The effect of differential mode attenuation (DMA) on backscattering signatures of multimode graded-index fibers is investigated experimentally and theoretically. Differential mode attenuation curves are determined for various commercial fibers and subsequently used to predict the backscattering response of the fibers. Theory and experiment indicate that only small variations in the local backscatter attenuation coefficient appear between various mode-filtered excitations of a given fiber.     

Transition radiation caused by a chiral plate

A simple calculation is made of the electromagnetic field radiated due to a charged particle traversing a plate of chiral material. The transition radiation from this chiral plate is round to differ from the usual dielectrie transition radiation. Discussion is presented placing in evidence the characteristics of the radiation and comments are made concerning the possible applicability of the transition radiation mechanism.     

Wavelength dependence of irreversible photobleaching of dye-doped polymer waveguide materials

We report the irreversible bleaching characteristics of 4-(dicyanomethylene)-2-methyl-6-(p-dimethyl aminostyryl)-4H-pyran (DCM) doped into perfluorocyclobutene (PFCB) and a new material known as DH-6 doped into amorphous polycarbonate (APC) by a monochromatic bleaching source. The wavelength dependent rate constants for the irreversible bleaching process are found, and the experimental bleaching characteristics are compared to the theoretical bleaching characteristics determined from a kinetic model of the bleaching process.