Multimode LD-pumped all-fiber Raman laser with excellent quality of 2nd-order Stokes output beam at 1019†nm.

A multimode all-fiber Raman laser enabling cascaded generation of high-quality 1019-nm output beam at direct pumping by highly-multimode (M2>30) 940-nm laser diodes has been demonstrated. The laser is made of a 100/140 graded-index fiber with special in-fiber Bragg gratings which secure sequential generation of the 1st (976 nm) and 2nd (1019 nm) Stokes orders. Comparing different 1019-nm cavity structures shows that the half-open cavity with one FBG and distributed feedback via random Rayleigh backscattering provides excellent quality (M2∼1.3) with higher slope efficiency of pump-to-2nd Stokes conversion than in the conventional 2-FBG cavity. The maximum achieved slope efficiency amounts to about 40% at output powers of up to 12 W limited by the 3rd Stokes generation.

All-fiber holmium distributed feedback laser at 2.07 µm.

In this Letter, we present the results on fabrication and investigation of a holmium (Ho) distributed fiber laser based on a π-phase-shifted FBG inscribed in a heavily Ho-doped fiber by IR femtosecond laser pulses. Single-polarization and single-transverse mode operation regimes were observed with a linewidth of the order of 10 kHz and output power up to 53 mW at 2.07 µm. Lasing regimes are compared for room and cryogenic (77 K) temperatures of the laser cavity. To the best of our knowledge, this is the first realization of such type of fiber laser based on holmium active medium.

Random Raman fiber laser based on a twin-core fiber with FBGs inscribed by femtosecond radiation.

Narrowband Raman lasing in a polarization-maintaining two-core fiber (TCF) is demonstrated. Femtosecond point-by-point inscription of fiber Bragg gratings (FBGs) in individual cores produces a half-open cavity with random distributed feedback. The laser linewidth in the cavity with a single FBG inscribed in one core of the TCF reduced by ∼2 times with respect to the cavity with a fiber loop mirror. It is shown that the inscription of two FBGs in different cores leads to the formation of a Michelson-type interferometer, leading to the modulation of generation spectra near threshold. This technique offers new possibilities for spectral filtering or multi-wavelength generation.

Nearly single-mode Raman lasing at 954 nm in a graded-index fiber directly pumped by a multimode laser diode.

High beam quality and narrow spectrum have been obtained in a Raman fiber laser based on a 1.1 km long graded-index fiber directly pumped by a multimode 915 nm laser diode. The generation of a near-diffraction-limited beam at 954 nm with M2≤1.27 and Δλ=0.42 nm at an output power above 10 W is enabled by a cavity mirror made of a special fiber Bragg grating inscribed by a femtosecond technique in the central part of the graded-index fiber core.

Femtosecond point-by-point inscription of Bragg gratings by drawing a coated fiber through ferrule.

A ferrule-based method of direct fs FBG inscription through protective plastic coating is demonstrated. Fluctuations of fiber core position relative to the writing fs beam are compensated by the developed auto-alignment system. As a result, high-quality FBGs with length from 0.1 to 50 mm are fabricated in polyimide-coated fibers, whose spectra are well described by the theory. The fabricated FBGs have great potential in sensor applications at high temperature and harsh environments both point-action and distributed ones.

Quantitative characterization of energy absorption in femtosecond laser micro-modification of fused silica.

We present the results of experimental and theoretical study of an energy absorption of femtosecond laser pulse in fused silica. Fundamental and second harmonics of ytterbium laser were used in experiment while general case was considered theoretically and numerically. More efficient absorption at the second harmonics is confirmed both experimentally and numerically. Quantitative characterization of the theoretical model is performed by fitting key parameters of the absorption process such as cross-section of multi-photon absorption and effective electronic collision and recombination times.

Analysis of whole-cell currents by patch clamp of guinea-pig myenteric neurones in intact ganglia.

Whole-cell patch-clamp recordings taken from guinea-pig duodenal myenteric neurones within intact ganglia were used to determine the properties of S and AH neurones. Major currents that determine the states of AH neurones were identified and quantified. S neurones had resting potentials of -47 +/- 6 mV and input resistances (R(in)) of 713 +/- 49 MOmega at voltages ranging from -90 to -40 mV. At more negative levels, activation of a time-independent, caesium-sensitive, inward-rectifier current (I(Kir)) decreased R(in) to 103 +/- 10 MOmega. AH neurones had resting potentials of -57 +/- 4 mV and R(in) was 502 +/- 27 MOmega. R(in) fell to 194 +/- 16 MOmega upon hyperpolarization. This decrease was attributable mainly to the activation of a cationic h current, I(h), and to I(Kir). Resting potential and R(in) exhibited a low sensitivity to changes in [K(+)](o) in both AH and S neurones. This indicates that both cells have a low background K(+) permeability. The cationic current, I(h), contributed about 20 % to the resting conductance of AH neurones. It had a half-activation voltage of -72 +/- 2 mV, and a voltage sensitivity of 8.2 +/- 0.7 mV per e-fold change. I(h) has relatively fast, voltage-dependent kinetics, with on and off time constants in the range of 50-350 ms. AH neurones had a previously undescribed, low threshold, slowly inactivating, sodium-dependent current that was poorly sensitive to TTX. In AH neurones, the post-action-potential slow hyperpolarizing current, I(AHP), displayed large variation from cell to cell. I(AHP) appeared to be highly Ca(2+) sensitive, since its activation with either membrane depolarization or caffeine (1 mM) was not prevented by perfusing the cell with 10 mM BAPTA. We determined the identity of the Ca(2+) channels linked to I(AHP). Action potentials of AH neurones that were elongated by TEA (10 mM) were similarly shortened and I(AHP) was suppressed with each of the three omega-conotoxins GVIA, MVIIA and MVIIC (0.3-0.5 microM), but not with omega-agatoxin IVA (0.2 microM). There was no additivity between the effects of the three conotoxins, which indicates the presence of N- but not of P/Q-type Ca(2+) channels. A residual Ca(2+) current, resistant to all toxins, but blocked by 0.5 mM Cd(2+), could not generate I(AHP). This patch-clamp study, performed on intact ganglia, demonstrates that the AH neurones of the guinea-pig duodenum are under the control of four major currents, I(AHP), I(h), an N-type Ca(2+) current and a slowly inactivating Na(+) current.

Characterization of receptor-mediated signal transduction by Escherichia coli type IIa heat-labile enterotoxin in the polarized human intestinal cell line T84.

Escherichia coli type IIa heat-labile enterotoxin (LTIIa) binds in vitro with highest affinity to ganglioside GD1b. It also binds in vitro with lower affinity to several other oligosialogangliosides and to ganglioside GM1, the functional receptor for cholera toxin (CT). In the present study, we characterized receptor-mediated signal transduction by LTIIa in the cultured T84 cell model of human intestinal epithelium. Wild-type LTIIa bound tightly to the apical surface of polarized T84 cell monolayers and elicited a Cl(-) secretory response. LTIIa activity, unlike CT activity, was not blocked by the B subunit of CT. Furthermore, an LTIIa variant with a T14I substitution in its B subunit, which binds in vitro to ganglioside GM1 but not to ganglioside GD1b, was unable to bind to intact T84 cells and did not elicit a Cl(-) secretory response. These findings show that ganglioside GM1 on T84 cells is not a functional receptor for LTIIa. The LTIIa receptor on T84 cells was inactivated by treatment with neuraminidase. Furthermore, LTIIa binding was blocked by tetanus toxin C fragment, which binds to gangliosides GD1b and GT1b. These findings support the hypothesis that ganglioside GD1b, or possibly a glycoconjugate with a GD1b-like oligosaccharide, is the functional receptor for LTIIa on T84 cells. The LTIIa-receptor complexes from T84 cells were associated with detergent-insoluble membrane microdomains (lipid rafts), extending the correlation between toxin binding to lipid rafts and toxin function that was previously established for CT. However, the extent of association with lipid rafts and the magnitude of the Cl(-) secretory response in T84 cells were less for LTIIa than for CT. These properties of LTIIa and the previous finding that enterotoxin LTIIb binds to T84 cells but does not associate with lipid rafts or elicit a Cl(-) secretory response may explain the low pathogenicity for humans of type II enterotoxin-producing isolates of E. coli.

Floating cholera toxin into epithelial cells: functional association with caveolae-like detergent-insoluble membrane microdomains.

In polarized cells, signal transduction by cholera toxin (CT) requires apical endocytosis and retrograde transport into Golgi cisternae and likely endoplasmic reticulum (ER) (Lencer et al., J. Cell Biol. 131, 951-962 (1995)). We have recently found that the toxin's apical membrane receptor ganglioside GM1 acts specifically in this signal transduction pathway, likely by coupling CT with caveolae or caveolae-related membrane domains (lipid rafts) (Wolf et al., J. Cell Biol. 141, 917-927 (1998)). Work in progress shows that 1) cholesterol depletion uncouples the CT-GM1 receptor complex from signal transduction, a characteristic of lipid rafts; 2) the GM1 acyl chains rather than the carbohydrate head groups appear to account for the structural basis of ganglioside specificity in toxin trafficking; and 3) intestinal epithelial cells obtained from normal adult humans exhibit lipid rafts which differentiate between CT-GM1 and LTIIb-GD1a complexes and which contain caveolin 1.

Ganglioside structure dictates signal transduction by cholera toxin and association with caveolae-like membrane domains in polarized epithelia.

In polarized cells, signal transduction by cholera toxin (CT) requires apical endocytosis and retrograde transport into Golgi cisternae and perhaps ER (Lencer, W.I., C. Constable, S. Moe, M. Jobling, H.M. Webb, S. Ruston, J.L. Madara, T. Hirst, and R. Holmes. 1995. J. Cell Biol. 131:951-962). In this study, we tested whether CT's apical membrane receptor ganglioside GM1 acts specifically in toxin action. To do so, we used CT and the related Escherichia coli heat-labile type II enterotoxin LTIIb. CT and LTIIb distinguish between gangliosides GM1 and GD1a at the cell surface by virtue of their dissimilar receptor-binding B subunits. The enzymatically active A subunits, however, are homologous. While both toxins bound specifically to human intestinal T84 cells (Kd approximately 5 nM), only CT elicited a cAMP-dependent Cl- secretory response. LTIIb, however, was more potent than CT in eliciting a cAMP-dependent response from mouse Y1 adrenal cells (toxic dose 10 vs. 300 pg/well). In T84 cells, CT fractionated with caveolae-like detergent-insoluble membranes, but LTIIb did not. To investigate further the relationship between the specificity of ganglioside binding and partitioning into detergent-insoluble membranes and signal transduction, CT and LTIIb chimeric toxins were prepared. Analysis of these chimeric toxins confirmed that toxin-induced signal transduction depended critically on the specificity of ganglioside structure. The mechanism(s) by which ganglioside GM1 functions in signal transduction likely depends on coupling CT with caveolae or caveolae-related membrane domains.

On a unified theory of cancer etiology and treatment based on the superconduction double-dipole model.

The human biological cell is a complex nonlinear system that behaves electrically as a double dipole. The nonlinear property of the cytoplasmic membrane permits is to divide; but it is the double-dipole property that motivates division and growth. Increasing the double-dipole moment increases speed of division. If the time required for division due to forces developed by the double-dipole becomes much less than the time needed for the chromatin material of the nucleus to properly develop and mature, defective genes will be formed, producing mutated daughter cells. Thus any stimulus that for prolonged periods increases the double-dipole moment can be responsible for producing mutated cells. One such stimulus is a "supercurrent" from an organic superconducting source. This supercurrent applied to tissue increases the cellular dipole moment, hence can produce an uncontrolled proliferation of biological cells giving rise to a tumor. In contrast, an injury current produces a controlled proliferation of embryonic cells in the traumatized area of the system. The latter proliferation is regulated by the negative feedback action of the host, which does not occur in the case of the supercurrent produced by an organic superconductor. Knowledge of the kind of organic superconductor involved, its transition temperature, and the critical magnetic field could make feasible a therapy aimed at terminating the offending supercurrent in the host.

Diamagnetic levitation in the fractionally superconducting bile cholates.

Diamagnetic levitation similar to that seen in metallic superconductors has been observed in organic compounds; namely, the bile cholates. Levitation phenomena, with forces exceeding 400 lbs/in, occurred in repeated experiments at transition temperatures extablished by susceptibility and resistivity measurements. With crystalline phase change ruled out by X-ray diffraction studies, the observed levitation must be regarded as due to superconductive effects occurring in small domains randomly dispersed throughout the insulating bulk of the investigated cholates. The transition temperatures observed in some of these compounds were higher than those seen in the metals.

Experimental evidence for high-temperature organic fractional superconduction in cholates.

Experimental data are presented indicating that six organic compounds (homologous cholates) possess properties associated with high-temperature superconductivity. From magnetic and electrical measurements it is deduced that behavior resembling superconductivity occurs below characteristic transition temperatures in small domains included in the insulating bulk of the sample material, which is therefore designated a fractional o Type III superconductor. The six cholates exhibit this superconductivity below transition temperatures ranging from approximately 7.5 degrees K for sodium dioxycholate to 277 degrees K for sodium cholanate. It has been further established that the diamagnetic shifts with temperature cannot be attributed to ferrielectric, ferroelectric, or capacitive effects. Below the transition temperatures the cholates behave like perfect diamagnets, susceptible to forceful repulsion by a moderate magnetic field. Observed in a sensitive susceptometer, magnetic flux trapped in the material gave rise to a 3% remnant magnetic moment. Studied in particular detail were sodium cholate, sodium deoxycholate, and lithocholic acid, which showed transition temperatures of 30 degrees K, 60 degrees K, and 130 degrees K respectively. The hydrophobic property of the closed four-ring structure (R-group) common to the cholates, along with the hydrophilic property of the carboxylate group (S-group), are responsible for domain formation. Because of those properties, clustering of the S-groups occurs when traces of water are introduced into the material. When followed by slow desiccation, the clusters form the micelles constituting the superconducting domains.