Femtosecond graphene mode-locked Fe:ZnSe laser at 4.4 µm.

We report, for the first time, to the best of our knowledge, a femtosecond mode-locked Fe:ZnSe laser. Passive mode locking is implemented using graphene as a saturable absorber. The laser operates at 4.4 µm with a repetition frequency of 100 MHz and 415 mW output power pumped by a fiber 7 W Er:ZBLAN laser. The pulse duration of about 732 fs is retrieved from the first-order autocorrelation function. Additionally, we observe pulsed nanosecond oscillation under continuous-wave pumping and strong amplitude modulation caused by Kerr self-focusing. This Letter fills the gap in operating regimes of Fe:ZnSe lasers and paves the way for the development of powerful ultrafast high-repetition-rate mid-IR sources for the most advanced fields of science.

Fluoride-fiber-based side-pump coupler for high-power fiber lasers at 2.8 µm.

A side-pump coupler made of fluoride fibers was fabricated and tested. The tested device had a coupling efficiency of 83% and was driven with an incident pump power of up to 83.5 W, demonstrating high-power operation. Stable laser output of 15 W at a wavelength of around 2.8 µm was achieved over 1 h when using an erbium-doped double-clad fiber as the active medium. To the best of our knowledge, this is the first time a fluoride-glass-fiber-based side-pump coupler has been developed. A test with two devices demonstrated further power scalability.

Compact, highly efficient, 2.1-W continuous-wave mid-infrared Fe:ZnSe coherent source, pumped by an Er:ZBLAN fiber laser.

In this Letter, we report a compact and robust coherent source, operating in mid-infrared (IR) and based on the Fe:ZnSe chalcogenide gain medium, optically pumped by an Er:ZBLAN fiber laser. The output power of 2.1 W with a 59% slope efficiency with respect to the absorbed pump power at liquid nitrogen cooling is achieved. We show that strong re-absorption at a high pump power and iron ion doping concentrations leads to a continuous tuning of central wavelength from 4012 to 4198 nm. The robustness of a high-power Er:ZBLAN fiber laser combined with prominent spectroscopic properties of Fe:ZnSe media pave the way for the development of a reliable tunable continuous-wave mid-IR sources for scientific and industrial purposes.

Super-strong magnetic field-dominated ion beam dynamics in focusing plasma devices.

High energy density physics is the field of physics dedicated to the study of matter and plasmas in extreme conditions of temperature, densities and pressures. It encompasses multiple disciplines such as material science, planetary science, laboratory and astrophysical plasma science. For the latter, high energy density states can be accompanied by extreme radiation environments and super-strong magnetic fields. The creation of high energy density states in the laboratory consists in concentrating/depositing large amounts of energy in a reduced mass, typically solid material sample or dense plasma, over a time shorter than the typical timescales of heat conduction and hydrodynamic expansion. Laser-generated, high current-density ion beams constitute an important tool for the creation of high energy density states in the laboratory. Focusing plasma devices, such as cone-targets are necessary in order to focus and direct these intense beams towards the heating sample or dense plasma, while protecting the proton generation foil from the harsh environments typical of an integrated high-power laser experiment. A full understanding of the ion beam dynamics in focusing devices is therefore necessary in order to properly design and interpret the numerous experiments in the field. In this work, we report a detailed investigation of large-scale, kilojoule-class laser-generated ion beam dynamics in focusing devices and we demonstrate that high-brilliance ion beams compress magnetic fields to amplitudes exceeding tens of kilo-Tesla, which in turn play a dominant role in the focusing process, resulting either in a worsening or enhancement of focusing capabilities depending on the target geometry.

Non-thermal ablation of expanded polytetrafluoroethylene with an intense femtosecond-pulse laser.

Ablation of expanded polytetrafluoroethylene without disruption of the fine porous structure is demonstrated using an intense femtosecond-pulse laser. As a result of laser-matter interactions near ablation threshold fluence, high-energy ions are emitted, which cannot be produced by thermal dissociation of the molecules. The ion energy is produced by Coulomb explosion of the elements of (-CF(2)-CF(2)-)(n) and the energy spectra of the ions show contributions from the Coulomb explosions of the ions rather than those of thermal expansion to generate high-energy ions. The dependence of ion energy on the laser fluence of a 180-fs pulse, compared with that of a 400-ps pulse, also suggests that the high-energy ions are accelerated by Coulomb explosion.

Enhancing laser beam performance by interfering intense laser beamlets.

Increasing the laser energy absorption into energetic particle beams represents a longstanding quest in intense laser-plasma physics. During the interaction with matter, part of the laser energy is converted into relativistic electron beams, which are the origin of secondary sources of energetic ions, γ-rays and neutrons. Here we experimentally demonstrate that using multiple coherent laser beamlets spatially and temporally overlapped, thus producing an interference pattern in the laser focus, significantly improves the laser energy conversion efficiency into hot electrons, compared to one beam with the same energy and nominal intensity as the four beamlets combined. Two-dimensional particle-in-cell simulations support the experimental results, suggesting that beamlet interference pattern induces a periodical shaping of the critical density, ultimately playing a key-role in enhancing the laser-to-electron energy conversion efficiency. This method is rather insensitive to laser pulse contrast and duration, making this approach robust and suitable to many existing facilities.

Multi-millijoule, diode-pumped, cryogenically-cooled Yb:KY(WO(4))(2) chirped-pulse regenerative amplifier.

A diode-pumped, cryogenically-cooled Yb:KYW regenerative amplifier utilizing chirped-pulse amplification and regenerative pulse shaping has been developed. An amplified pulse with an energy of 5.5 mJ and a broad bandwidth of 3.4 nm is achieved.

Boosting laser-ion acceleration with multi-picosecond pulses.

Using one of the world most powerful laser facility, we demonstrate for the first time that high-contrast multi-picosecond pulses are advantageous for proton acceleration. By extending the pulse duration from 1.5 to 6 ps with fixed laser intensity of 1018 W cm-2, the maximum proton energy is improved more than twice (from 13 to 33 MeV). At the same time, laser-energy conversion efficiency into the MeV protons is enhanced with an order of magnitude, achieving 5% for protons above 6 MeV with the 6 ps pulse duration. The proton energies observed are discussed using a plasma expansion model newly developed that takes the electron temperature evolution beyond the ponderomotive energy in the over picoseconds interaction into account. The present results are quite encouraging for realizing ion-driven fast ignition and novel ion beamlines.

Exogenous quinones inhibit photosynthetic electron transfer in Chloroflexus aurantiacus by specific quenching of the excited bacteriochlorophyll c antenna.

In the photosynthetic green filamentous bacterium Chloroflexus aurantiacus, excitation energy is transferred from a large bacteriochlorophyll (BChl) c antenna via smaller BChl a antennas to the reaction center. The effects of substituted 1,4-naphthoquinones on BChl c and BChl a fluorescence and on flash-induced cytochrome c oxidation were studied in whole cells under aerobic conditions. BChl c fluorescence in a cell suspension with 5.4 microM BChl c was quenched to 50% by addition of 0.6 microM shikonin ((R)-2-(1-hydroxy-4-methyl-3-pentenyl)-5,8-dihydroxy-1, 4-naphthoquinone), 0.9 microM 5-hydroxy-1,4-naphthoquinone, or 4 microM 2-acetyl-3-methyl-1,4-naphthoquinone. Between 25 and 100 times higher quinone concentrations were needed to quench BChl a fluorescence to a similar extent. These quinones also efficiently inhibited flash-induced cytochrome c oxidation when BChl c was excited, but not when BChl a was excited. The quenching of BChl c fluorescence induced by these quinones correlated with the inhibition of flash-induced cytochrome c oxidation. We concluded that the quinones inhibited electron transfer in the reaction center by specifically quenching the excitation energy in the BChl c antenna. Our results provide a model system for studying the redox-dependent antenna quenching in green sulfur bacteria because the antennas in these bacteria inherently exhibit a sensitivity to O(2) similar to the quinone-supplemented cells of Cfx. aurantiacus.

Anti-idiotypic monoclonal antibody recognizes a consensus recognition site for phosphatidylserine in phosphatidylserine-specific monoclonal antibody and protein kinase C.

In order to elucidate the molecular mechanisms responsible for the specific lipid-protein interactions, we have undertaken structural and idiotypic analyses of a monoclonal antibody, PS4A7, which binds specifically to phosphatidylserine (PS). Here we showed that one of the anti-idiotypic monoclonal antibodies raised against PS4A7 cross-reacted extensively with protein kinase C (PKC) and inhibited the activation of the enzymatic activity. The binding of the anti-idiotypic antibody to PKC was inhibited specifically by PS, but not by other phospholipids including 1,2-diacyl-sn-glycero-3-phospho-D-serine or 1,2-diacyl-sn-glycero-3-phospho-L-homoserine. In contrast, the binding of the anti-idiotypic mAb to the enzyme was significantly enhanced in the presence of either diacylglycerol or sphingosine. These findings indicate that the PS-specific monoclonal antibody and PKC share a consensus structure which is responsible for the specific interaction with PS and both diacylglycerol and sphingosine may induce a similar conformational change which exposes the PS-specific binding site of the enzyme.

Specific cross-reaction of IgG anti-phospholipid antibody with platelet glycoprotein IIIa.

To study the pathological functions of anti-phospholipid (anti-PL) antibodies, we have analyzed their effect on platelet function. We identified an IgG anti-PL mAb, designated PSG3, which cross-reacted specifically with glycoprotein (GP) IIIa in human platelets and inhibited platelet aggregation. PSG3 bound also to certain polyanionic substances, such as double-stranded DNA, heparan sulfate, dextran sulfate and acetylated-LDL, but not to other polyanionic substances. The binding of PSG3 to GPIIIa was completely inhibited by heparan sulfate and dextran sulfate, indicating that PSG3 recognizes a particular array of negative charges expressed on both GPIIIa and the specified polyanionic substances. Since neither neuraminidase- nor endoglycopeptidase F-treatment of GPIIIa had any significant effect on the binding of PSG3, this array must be located within the amino acid sequence of GPIIIa but not in the carbohydrate moiety. Reduction of the disulfide bonds in GPIIIa greatly reduced its reactivity, suggesting that the negative charges in the epitope are arranged in a particular conformation. PSG3 inhibited platelet aggregation induced by either ADP or collagen, it also inhibited fibrinogen binding to activated platelets in a dose-dependent fashion. PSG3, however, did not inhibit the binding of GRGDSP peptide to activated platelets. These results suggest that the PSG3 epitope on GPIIIa contains a particular array of negative charges, and possibly affects the fibrinogen binding to GPIIb/IIIa complex necessary for platelet aggregation.

Effective induction of anti-phospholipid and anticoagulant antibodies in normal mouse.

Anti-phosphatidylserine (anti-PS) antibodies of the IgG isotype in the serum of BALB/c mouse were effectively induced by the intrasplenic immunization of phosphatidylserine (PS), while only a slight increase of the titer was observed when the antigen was injected intravenously. The serum antibodies cross-reacted extensively with other acidic phospholipids, but not with phosphatidylcholine (PC). A remarkable frequency of anti-PS mAbs of the IgG isotype was also observed even when mAbs were produced 10 days after the intrasplenic injection of the antigen. Reactivities of the fifteen mAbs, which had been established from BALB/c mice by the intrasplenic immunization with PS, were further analyzed. Among the fifteen mAbs examined, thirteen cross-reacted with ssDNA and two bound to dsDNA. Seven mAbs had lupus anticoagulant activity and four bound to cultured human umbilical vein endothelial cells (HUVECs). No significant correlation was found among phospholipid specificities, anti-DNA, anticoagulant, and HUVEC binding activities. One mAb of the IgG2b subclass, named PSG3, which had been produced 10 days after the immunization, was shown to have a strong lupus anticoagulant, dsDNA binding, and HUVEC binding activities.

Quenching of bacteriochlorophyll fluorescence in chlorosomes from Chloroflexus aurantiacus by exogenous quinones.

The quenching of bacteriochlorophyll (BChl) c fluorescence in chlorosomes isolated from Chloroflexus aurantiacus was examined by the addition of various benzoquinones, naphthoquinones (NQ), and anthraquinones (AQ). Many quinones showed strong quenching in the micromolar or submicromolar range. The number of quinone molecules bound to the chlorosomes was estimated to be as small as one quinone molecule per 50 BChl c molecules. Quinones which exhibit a high quenching effect have sufficient hydrophobicity and one or more hydroxyl groups in the alpha positions of NQ and AQ. Chlorobiumquinone has been suggested to be essential for the endogenous quenching of chlorosome fluorescence in Chlorobium tepidum under oxic conditions. We suggest that the quenching effect of chlorobiumquinone in chlorosomes from Chl. tepidum is related to the 1'-oxo group neighboring the dicarbonyl group.

[Clinical efficacy of arbekacin in patients with methicillin-resistant Staphylococcus aureus infections. Research Group of MRSA Forum].

We investigated the clinical efficacy of arbekacin (ABK) in patients with methicillin-resistant Staphylococcus aureus (MRSA) infections, and also studied coagulase types, beta-lactamase producing activity and drug sensitivity of MRSA isolated from various clinical specimens. A total of 23 patients with MRSA infections (13 cases of pneumonia, 1 case of sepsis, 1 case of pneumonia and sepsis and 8 cases of the others) who were hospitalized from April 1992 to September 1993 were enrolled in this study. They were 14 males and 9 females, and the mean age was 66.9 years (range, 18-91 years). All patients had underlying diseases (mainly malignant tumors and cerebrovascular diseases). ABK was given intravenously at doses ranging from 75 to 100 mg twice daily. The clinical efficacy rate was 90%; 8 cases showed excellent responses, 10 cases good, 1 case fair, 1 case poor and 3 cases were unevaluable. The eradication rate of MRSA was 81.8%; 16 cases were judged as eradicated, 3 cases decreased, 2 cases replaced, 1 case unchanged and in 1 case the bacteriological response was unknown. Side effects were not observed, but S-GPT was elevated in 1 case. Coagulase types of MRSA (123 strains) isolated at the institutes involved in the study were type II (56 strains), type IV (12 strains), type VII (13 strains) and other types (2 strains), but coagulase types of 40 strains could not be determined. Eighty-four strains (68.3%) produced beta-lactamases. MICs of ABK were 0.5 microgram/ml against 43 strains and 1 microgram/ml against 37 strains, and all of the MICs were under 4 micrograms/ml. In summary, ABK showed high antimicrobial activity against MRSA and clinical usefulness in the infections investigated.

[Effect of ethacrynic acid on contractility and Ca flux of guinea pig taenia coli smooth muscle (author's transl)].

The effects of ethacrynic acid (ETCA) which has been known as an -SH groups inhibitor on the contractility and the Ca flux of guinea pig taenia coli were investigated. The results obtained were as follow: 1) Contractures induced by 10(-4) M ACh, or the tonic component of 150 mM K-contractures were markedly suppressed by previous treatment with a low concentration (2 X 10(-4) M) of ETCA for 40 min. Conversely with the same treatment, the phasic component of this K-contracture was only slightly suppressed. The inhibitory effects of ETCA in both cases were reversed by the repetitive washing out of ETCA from taenia coli with normal tris-buffered solution. 2) ETCA, at concentrations higher than 10(-3) M, more markedly inhibited the ACh-, and the K-contractures. In this case these inhibitions were irreversible. 3) Cysteine in an equimolar concentration of ETCA prevented the inhibitory effects of ETCA on both contractures. 4) ETCA (10(-4) M) inhibited the ACh-contracture in Ca2+-free isotonic KCl solution to approximately the same degree as that in normal solution. 5) Inhibition of ACh-contracture by ETCA in Na+-free isotonic LiCl solution was less than that in normal solution. 6) ETCA (2 X 10(-4), or 10(-3) M) markedly stimulated 45Ca efflux from taenia coli in 20 mM Ca-EGTA tris-buffered solution. 7) 45Ca efflux acceleration by ETCA in Na+-free (replaced by Li+) 20 mM Ca-EGTA tris-buffered solution was less than that in 20 mM Ca-EGTA tris-buffered solution. These results may be explained by assuming that the inhibitory effect of ETCA on ACh-contracture can be attributed to the depletion of stored intracellular Ca and the acceleration of Ca efflux as a result of ETCA treatment.

The effects of a novel histamine-3 receptor inverse agonist on essential tremor in comparison to stable levels of alcohol.

Essential tremor (ET) is a common movement disorder. Animal studies show that histaminergic modulation may affect the pathological processes involved in the generation of ET. Histamine-3 receptor inverse agonists (H3RIA) have demonstrated attenuating effects on ET in the harmaline rat model. In this double-blind, three-way cross-over, single-dose, double-dummy study the effects of 25 mg of a novel H3RIA (MK-0249) and a stable alcohol level (0.6 g L(-1)) were compared with placebo, in 18 patients with ET. Tremor was evaluated using laboratory tremorography, portable tremorography and a clinical rating scale. The Leeds Sleep Evaluation Questionnaire (LSEQ) and a choice reaction time (CRT) test were performed to evaluate potential effects on sleep and attention, respectively. A steady state of alcohol significantly diminished tremor as assessed by laboratory tremorography, portable tremorography and clinical ratings compared with placebo. A high single MK-0249 dose was not effective in reducing tremor, but caused significant effects on the LSEQ and the CRT test. These results suggest that treatment with a single dose of MK-0249 does not improve tremor in alcohol-responsive patients with ET, whereas stable levels of alcohol as a positive control reproduced the commonly reported tremor-diminishing effects of alcohol.

Mechanism of the anti-obesity effects induced by a novel melanin-concentrating hormone 1-receptor antagonist in mice.

BACKGROUND AND PURPOSE: Melanin-concentrating hormone (MCH) is an orexigenic neuropeptide expressed in the lateral hypothalamus that is involved in feeding and body weight regulation. Intracerebroventricular infusion of a peptidic MCH1 receptor antagonist ameliorated obesity in murine models. Recently, small molecule MCH1 receptor antagonists have been developed and characterized for the treatment of obesity. However, little is known of the mechanism of the anti-obesity effects of MCH1 receptor antagonists. EXPERIMENTAL APPROACH: To examine the mechanisms of action of the anti-obesity effect of MCH1 receptor antagonists more precisely, we conducted a pair-feeding study in mice with diet-induced obesity (DIO), chronically treated with an orally active and highly selective MCH1 receptor antagonist and examined changes in mRNA expression levels in liver, brown and white adipose tissues. We also assessed the acute effects of the MCH1 receptor antagonist in energy expenditure under thermoneutral conditions. KEY RESULTS: Treatment with the MCH1 receptor antagonist at 30 mg.kg(-1) for 1 month moderately suppressed feeding and significantly reduced body weight by 24%. In contrast, pair-feeding resulted in a smaller weight reduction of 10%. Treatment with the MCH1 receptor antagonist resulted in a higher body temperature compared with the pair-fed group. TaqMan and calorimetry data suggested that the MCH1 receptor antagonist also stimulated thermogenesis. CONCLUSIONS AND IMPLICATIONS: Our results indicate that an MCH1 receptor antagonist caused anti-obesity effects im mice by acting on both energy intake and energy expenditure.

High-energy, diode-pumped, picosecond Yb:YAG chirped-pulse regenerative amplifier for pumping optical parametric chirped-pulse amplification.

A diode-pumped, cryogenic-cooled Yb:YAG regenerative amplifier utilizing gain-narrowing has been developed. A 1.2-ns chirped-seed pulse was simultaneously amplified and compressed in the regenerative amplifier, which generated a 35-ps pulse with ~8-mJ of energy without a pulse compressor. Second-harmonics of the amplified pulse was used to pump picosecond two-color optical parametric amplification.