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1.
Opt Lett ; 44(21): 5222-5225, 2019 Nov 01.
Article in English | MEDLINE | ID: mdl-31674973

ABSTRACT

We present a power-scalable laser source with 30 fs pulse duration, 530 W average power at 500 kHz repetition rate, and beam quality M2<1.2. The compact and efficient setup consists of ytterbium-based Innoslab amplifiers and subsequent nonlinear pulse compression with an argon-filled Herriott cell.

2.
Opt Express ; 26(12): 14928-14935, 2018 Jun 11.
Article in English | MEDLINE | ID: mdl-30114797

ABSTRACT

We present, to the best of our knowledge, design and performance data of the first diode-pumped Alexandrite ring laser in Q-switched single-longitudinal mode (SLM) operation. The laser resonator contains two Alexandrite crystals, which are pumped longitudinally by means of two laser diode-bar modules emitting at 636 nm. Single-longitudinal mode operation is achieved by seeding the laser with a diode laser operating in SLM and actively stabilizing the cavity, yielding a linewidth of < 10 MHz at the potassium resonance line at 770 nm. The pulse energy is 1 mJ at a repetition rate of 150 Hz and 0.65 mJ at 320 Hz. The beam quality of M2 < 1.2 in both directions remains unchanged for the different repetition rates. After characterization in the laboratory, the laser was implemented in a novel mobile lidar system and first atmospheric measurements were conducted successfully.

3.
Opt Express ; 26(13): 16074-16085, 2018 Jun 25.
Article in English | MEDLINE | ID: mdl-30119444

ABSTRACT

We developed a high repetition rate optical parametric chirped-pulse amplification (OPCPA) laser system based on fiber-laser-seeded Innoslab to generate few-cycle pulses around 2 µm with passively stable carrier-envelope phase (CEP) by difference frequency generation (DFG). Incorporating a piezo mirror before the DFG stage permits rapid CEP control. The OPCPA system is seeded by a stable supercontinuum generated in bulk material with the picosecond Innoslab pulses. Few-cycle pulses with durations of 17 fs and energies of over 100 µJ were produced in a single OPCPA stage. Three different nonlinear crystals: BBO, BiBO, and LNB were tested in the final parametric amplifier, and their average power related limitations are addressed.

4.
Opt Express ; 21(10): 12302-8, 2013 May 20.
Article in English | MEDLINE | ID: mdl-23736448

ABSTRACT

Gain-switching of a CW fiber laser is a simple and cost-effective approach to generate pulses using an all-fiber system. We report on the construction of a narrow bandwidth (below 0.1 nm) gain-switched fiber laser and optimize the pulse energy and pulse duration under this constraint. The extracted pulse energy is 20 µJ in a duration of 135 ns at 7 kHz. The bandwidth increases for a higher pump pulse energy and repetition rate, and this sets the limit of the output pulse energy. A single power amplifier is added to raise the peak power to the kW-level and the pulse energy to 230 µJ while keeping the bandwidth below 0.1 nm. This allows frequency doubling in a periodically poled lithium tantalate crystal with a reasonable conversion efficiency.


Subject(s)
Amplifiers, Electronic , Fiber Optic Technology/instrumentation , Lasers , Equipment Design , Equipment Failure Analysis
5.
Opt Express ; 20(16): 18362-9, 2012 Jul 30.
Article in English | MEDLINE | ID: mdl-23038387

ABSTRACT

We present a laser plasma based x-ray microscope for the water window employing a high-average power laser system for plasma generation. At 90 W laser power a brightness of 7.4 x 10(11) photons/(s x sr x µm(2)) was measured for the nitrogen Lyα line emission at 2.478 nm. Using a multilayer condenser mirror with 0.3 % reflectivity 10(6) photons/(µm(2) x s) were obtained in the object plane. Microscopy performed at a laser power of 60 W resolves 40 nm lines with an exposure time of 60 s. The exposure time can be further reduced to 20 s by the use of new multilayer condenser optics and operating the laser at its full power of 130 W.

6.
Opt Lett ; 35(24): 4169-71, 2010 Dec 15.
Article in English | MEDLINE | ID: mdl-21165126

ABSTRACT

We demonstrate a compact diode-pumped Yb:KGW femtosecond oscillator-Yb:YAG Innoslab amplifier master oscillator power amplifier (MOPA) with nearly transform-limited 636 fs pulses at 620 W average output power, 20 MHz repetition rate, and beam quality of M(x)(2) = 1.43 and M(y)(2) = 1.35. By cascading two amplifiers, we attain an average output power of 1.1 kW, a peak power of 80 MW, and a 615 fs pulse width in a single linearly polarized beam. The power-scalable MOPA is operated at room temperature, and no chirped-pulse amplification technique is used.

7.
Toxicol Lett ; 199(3): 364-71, 2010 Dec 15.
Article in English | MEDLINE | ID: mdl-20933064

ABSTRACT

Polyurethanes (PU) are polymers made with diisocyanates such as MDI (4,4'-methylene diphenyl diisocyanate) and TDI (2,4-toluene diisocyanate and 2,6-toluene diisocyanate). Investigations have been undertaken with MDI and TDI to assess dermal uptake and resulting systemic exposure. Absorption, distribution and excretion of MDI was studied in rats using a single dermal administration of (14)C-MDI dissolved in acetone at nominal 165 mg/kg body weight and 15 mg/kg bw (4.0 and 0.4 mg/cm(2)) and intradermal injection of (14)C-MDI dissolved in corn oil at nominal 1.4 mg/kg bw. Dermal absorption of (14)C-MDI (at both doses) was low; at or below 1% of the applied dose. Considerable amounts of the applied radioactivity were found at the application site which could not be washed off. By intradermal administration of (14)C-MDI approximately 66% of applied radioactivity remained at the application site with approximately 26% recovered in excreta, cage wash, tissues and carcass. The absorption, distribution and excretion of 2,4-TDI was studied in rats following a single dermal administration of radiolabelled (14)C-2,4-TDI at nominal 350 mg/kg body weight (12 mg/cm(2)). Dermal absorption of (14)C-2,4-TDI was at or below 1% of the applied dose. Considerable amounts of the applied radioactivity were found at the application site which could not be washed off. In summary the results show that dermal uptake of MDI and TDI is very low. Due to the chemical reactivity of isocyanates it can be expected that small amounts which might be absorbed will react with tissue constituents directly at the exposed skin area, or will be converted to adducts with biomacromolecules or to biologically inactive oligoureas. Overall it is concluded that, following dermal exposure to MDI and TDI, systemic exposures and resulting toxicity, other than the known sensitization, can be expected to be very low. In addition studies were performed with dermal application of unlabelled 2,4 and 2,6 TDI to check the availability and fate of this chemical on rat skin surface and to assess possible tissue damage. These experiments showed that unchanged test material can be detected on rat skin for up to 8h if not washed off. Dermal treatment with 2,4 or 2,6 TDI was associated with irritation with increased severity over a 48 h period after washing with a decontaminant solution.


Subject(s)
Isocyanates/pharmacokinetics , Skin/metabolism , Toluene 2,4-Diisocyanate/pharmacokinetics , Animals , Carbon Radioisotopes , Male , Rats , Rats, Wistar , Skin/drug effects , Skin/pathology , Toluene 2,4-Diisocyanate/toxicity
8.
Opt Express ; 17(15): 12230-45, 2009 Jul 20.
Article in English | MEDLINE | ID: mdl-19654625

ABSTRACT

The Innoslab design, already established for neodymium doped laser crystals, was applied to ytterbium doped laser materials. Recent progresses in brightness of high power diode lasers facilitate efficient pumping of quasi-three-level laser materials. Innoslab amplifiers are compared to competing thin-disk and fiber fs-amplifiers. A compact diode-pumped Yb:YAG Innoslab fs-oscillator-amplifier system, scalable to the kilowatt range, was realized. Numerical simulations result in conditions for high efficiency and beam quality. Nearly transform and diffraction limited 680 fs pulses at 400 W average output power and 76 MHz repetition rate without using CPA technology have been achieved at room temperature so far.

9.
Toxicol Lett ; 138(1-2): 75-102, 2003 Feb 18.
Article in English | MEDLINE | ID: mdl-12559694

ABSTRACT

Styrene (ST) occurs ubiquitously in the environment and it is an important industrial chemical. After its uptake by the exposed mammalian organism, ST is oxidized to styrene-7,8-oxide (SO) by cytochrome P450 dependent monooxygenases. This reactive intermediate is further metabolized by epoxide hydrolase (EH) and glutathione S-transferase (GST). In long-term animal studies, ST induced lung tumors in mice but not in rats. Considering the lung to be the relevant target organ for ST induced carcinogenicity in mice, we extended a previously developed physiological toxicokinetic model in order to simulate the lung burden with ST and SO in the ST exposed mouse, rat and human. The new model describes oral and pulmonary uptake of ST, its distribution into various tissues, its exhalation and its metabolism to SO in lung and liver. It also simulates the distribution of the produced SO into the tissues and its EH and GST mediated metabolism in liver and in lung. In both organs the ST induced GSH consumption is described together with the formation of adducts to hemoglobin and to DNA of lymphocytes in ST exposed mice, rats and humans. The model includes compartments for arterial, venous and pulmonary blood, liver, muscle, fat, richly perfused tissues and lung. The latter organ is represented by two compartments, namely by the conducting and the alveolar zone. The physiological description of the pulmonary compartments relies on measured alveolar retentions, literature values of surface area of capillary endothelium, of the thickness of the tissue 'air-to-plasma', of the partition coefficient lung:blood and of metabolic parameters of ST and SO measured in pulmonary cell fractions of rodents and humans. Simulations of average pulmonary GSH levels in ST exposed rodents agree with measured data. The model predicts a significant GSH depletion (40%) in the conducting zone of mice exposed for 6 h to a ST concentration of only 20 ppm. In the conducting zone of rats, exposure to 200 ppm ST results in a loss of GSH of about 15% only. In humans, a pulmonary GSH reduction does not occur. The highest average pulmonary SO concentrations are predicted for mice, somewhat lower values for rats and by far the lowest ones for humans. Following steady state exposure to 20 ppm ST, the average SO concentration in mouse lungs is expected to be only three times higher than in rats. This difference diminishes to a factor of less than two at 70 ppm. In humans exposed to 20 ppm ST for 8 h, the average pulmonary SO burden of 0.016 micromol/kg is predicted to be about 17 and 50 times smaller than the corresponding values for rat and mouse. In agreement with reported values, pulmonary DNA adduct levels in rodents exposed to 160 ppm ST were simulated to be similar in rats and mice. In summary, there was no dramatic difference in the calculated average pulmonary SO burden between both animal species. However, pulmonary GSH loss was by far more expressed in ST exposed mice than rats. Since the model was validated on all available ST/SO data in mice, rats and humans, we consider it to be useful for estimating the risk resulting from exposure to ST.


Subject(s)
Carcinogens/pharmacokinetics , Carcinogens/toxicity , Epoxy Compounds/pharmacokinetics , Epoxy Compounds/toxicity , Lung/drug effects , Models, Biological , Styrene/pharmacokinetics , Styrene/toxicity , Administration, Inhalation , Animals , Carcinogens/administration & dosage , DNA Adducts/analysis , Epoxy Compounds/administration & dosage , Hemoglobins/metabolism , Humans , Lung/metabolism , Mice , Rats , Species Specificity , Styrene/administration & dosage
10.
Chemistry ; 7(16): 3482-93, 2001 Aug 17.
Article in English | MEDLINE | ID: mdl-11560318

ABSTRACT

Three [2]catenanes and three [3]catenanes incorporating one or two pi-electron-rich macrocyclic polyethers and one pi-electron-deficient polycationic cyclophane have been synthesized in yields ranging from 4 to 38%. The pi-electron-rich macrocyclic components possess either two 1,4-dioxybenzene or two 1.5-dioxynaphthalene recognition sites. The pi-electron-deficient cyclophane components incorporate two bipyridinium and either one or two dialkylammonium recognition sites. The template-directed syntheses of these catenanes rely on i) pi...pi stacking interactions between the dioxyarene and bipyridinium recognition sites, ii) C-H...O hydrogen bonds between some of the bipyridinium hydrogen atoms and some of the polyether oxygen atoms, and iii) C-H...pi interactions between some of the dioxyarene hydrogen atoms and the aromatic spacers separating the bipyridinium units. The six catenanes were characterized by mass spectrometry and by both 1H and 13C NMR spectroscopy. The absorption spectra and the electrochemical properties of the catenanes have been investigated and compared with those exhibited by the component macrocycles and by related known catenanes. Broad and weak absorption bands in the visible region, originating from charge-transfer (CT) interactions between electron-donor and electron-acceptor units, have been observed. Such charge-transfer interactions are responsible for the quenching of the potentially fluorescent excited states of the aromatic units of the macrocyclic polyether components. The redox behavior of these novel compounds has been investigated and correlations among the observed redox potentials are illustrated and discussed. The catenanes undergo co-conformational switching upon one-electron reduction of the two bipyridinium units. One of them--in its reduced form--can be also switched by acid/base inputs and exhibits AND logic behavior. The co-conformational rearrangements induced by the redox and acid/base stimulations lend themselves to exploitation in the development of molecular-level machines and logic gates.

11.
Arch Toxicol ; 75(3): 159-75, 2001 May.
Article in English | MEDLINE | ID: mdl-11409538

ABSTRACT

Two independent bioassays are available which have examined the potential carcinogenicity of monomeric and polymeric methylene diphenyl diisocyanate (MDI) following long-term inhalation exposure in rats. These studies are not directly comparable, however, due to differences in design and conduct of the in-life phase, and differences in nomenclature used for some of the histopathological findings. This paper presents a definitive overview ofthe pulmonary toxicity of MDI developed following a thorough review of both investigations. As part of this process, the test materials and the designs of the studies were compared, and an in-depth review of lung lesions was conducted by an independent reviewing pathologist. This included the re-examination of the original lung slides, supported by an analysis of the exposure regimens, the results of which were used to develop an accurate profile of the doses received by the animals in the two studies. Histopathological findings were then combined with this information to give an overall dose-response curve for both studies as a whole. The range of total inhalation exposures to MDI was calculated as 559, 1972, 2881, 6001, 17,575 and 17,728 mgh/m3. Major pulmonary effects included increased lung weights together with bronchiolo-alveolar adenomas and hyperplasia, and interstitial fibrosis which occurred consistently in both studies, indicating a very similar qualitative response of the lungs to polymeric and monomeric MDI. The quantitative response of the lung was clearly dose-related in each study, and when the studies were considered as a whole a reasonable overall dose-response relationship was apparent for major lung lesions. Lung tumours (in low incidences) only occurred at the highest dose level in both studies (17,575 and 17,728 mgh/m3). For inflammatory and other non-neoplastic pulmonary changes, the lowest dose examined (559 mgh/m3) was regarded as a no-observed-adverse-effect-level for both polymeric and monomeric MDI. It was concluded that the results of the two studies could be combined to serve as a basis for human risk assessment of MDI.


Subject(s)
Adenoma/chemically induced , Carcinogens/toxicity , Isocyanates/toxicity , Lung Neoplasms/chemically induced , Pulmonary Fibrosis/chemically induced , Adenoma/pathology , Administration, Inhalation , Aerosols , Animals , Body Weight/drug effects , Carcinogens/administration & dosage , Chronic Disease , Dose-Response Relationship, Drug , Female , Hyperplasia/chemically induced , Hyperplasia/pathology , Inhalation Exposure , Isocyanates/administration & dosage , Longevity/drug effects , Lung Neoplasms/pathology , Male , Organ Size/drug effects , Pulmonary Fibrosis/pathology , Rats , Rats, Wistar
12.
Mutat Res ; 413(1): 83-94, 1998 Feb 23.
Article in English | MEDLINE | ID: mdl-9602861

ABSTRACT

The dose-response relationships for DNA fragmentation (assessed by pulsed-field gel electrophoresis, PFGE) and for viability (evaluated by measuring the reduction of MTT dye which can be accomplished by viable cells only) were investigated in order to discriminate between genotoxicity and cytotoxicity in the pathogenesis of DNA double-strand breaks (DSB). Cultured human lung epithelial cells (A549) were treated with the DNA-intrastrand crosslinker cisplatin, the DNA-interstrand crosslinker melphalan and the topoisomerase II inhibitor etoposide. The cytotoxic mode of DSB induction was investigated by using the mitochondrial respiratory chain toxin potassium cyanide (KCN) and the detergent Triton X-100. gamma-Irradiation induced a linear dose response for DSB which were efficiently repaired and did not cause reduction in cell survival over a period of 72 h. With etoposide and melphalan a significant increase in DSB was seen 8 h after treatment initiation with concentrations that did not affect cell survival, implicating genotoxicity as the causal event. In contrast, induction of DSB by KCN and Triton X-100, and also by cisplatin, was seen only after cell viability was reduced to less than about 60%, indicating that DSB were the consequence of extragenomic damage. This mechanistic distinction of the two classes was supported by DNA fragment length analysis. In line with a genotoxic mechanism and absence of additional cytotoxic effects, the DNA fragments generated by gamma-irradiation as well as by etoposide and melphalan displayed a distribution between 1 and 4 Mbp with a peak around 2 Mbp. In contrast, DNA fragments induced by Triton X-100 and KCN peaked below 0.5 Mbp, implicating activation of DNA-degrading enzymes. This type of investigation is suggested for the study of chemicals for potential DNA interstrand crosslinking, an important promutagenic type of DNA damage. To avoid false positive results in genetic toxicity testing it is suggested that all assays include a dose-response relationship for both genotoxicity and viability.


Subject(s)
Antineoplastic Agents/toxicity , DNA Damage , Mutagens/toxicity , Cell Line , Cisplatin/toxicity , DNA Fragmentation , Electrophoresis, Gel, Pulsed-Field , Etoposide/toxicity , Gamma Rays , Humans , Melphalan/toxicity , Octoxynol/toxicity , Potassium Cyanide/toxicity
13.
Toxicol Ind Health ; 11(1): 13-32, 1995.
Article in English | MEDLINE | ID: mdl-7652749

ABSTRACT

Although respiratory sensitization and pulmonary irritation have been the subject of particular studies with toluene diisocyanate (TDI), in recent years the potential carcinogenicity of TDI has been a reason for concern and speculation. This has arisen from the expectation that following exposure to TDI the chemical would hydrolyze at aqueous tissue surfaces to give rise to toluene diamine (TDA), a mutagen and rodent carcinogen. The chemistry of TDI suggests that the reaction with biological NH2 groups such as those on proteins, and polymerization to oligoureas, will compete with the hydrolysis reaction. This has been shown with results of in vitro studies where conjugation to protein occurs without detectable formation of TDA when protein solutions in saline are exposed to TDI vapor. Lower pH levels leading to high protonation of biological NH2 groups facilitate hydrolysis of TDI to TDA and subsequent formation of polyureas. These observations are consistent with comparative toxicokinetic studies in rats, which demonstrate significant levels of TDA following oral dosing with TDI--due to the acidic environment in the stomach--but not after inhalation. These results provide an explanation for the tumors observed in rodents after oral dosing of TDI in corn oil, but not after inhalation. Inhalation is the relevant route of human exposure for TDI and the toxicokinetics of TDI exposure at occupational exposure limits have been studied. These data provide a means by which quantitative estimates of the risk of carcinogenicity possibly resulting from the intermediate formation of TDA during TDI exposure can be obtained. Several calculations have been made, all of which lead to the conclusion that TDI exposure by inhalation at the recommended occupational limits will not give rise to significant carcinogenic risk.


Subject(s)
Toluene 2,4-Diisocyanate/pharmacokinetics , Toluene 2,4-Diisocyanate/toxicity , Administration, Inhalation , Administration, Oral , Animals , Carcinogenicity Tests , Humans , Mutagenicity Tests , Neoplasms/epidemiology , Occupational Exposure , Phenylenediamines/toxicity , Reproduction/drug effects , Risk Assessment , Toluene 2,4-Diisocyanate/chemistry
14.
Arzneimittelforschung ; 32(1): 1-6, 1982.
Article in German | MEDLINE | ID: mdl-7199335

ABSTRACT

A high-pressure liquid chromatographic method with internal analogue standardization is described for the determination of 2'-(2-hydroxy-3-propylamino-propoxy)-3-phenylpropiophenone hydrochloride (propafenone, Rytmonorm) in plasma. The requirement of selectivity is met: there is no interference of plasma components and propafenone metabolites found in plasma extracts. When using a 2-ml sample the lower limit of detection is approximately 1 ng/ml, the lower limit of determination about 5 ng/ml. In the concentration range up to 250 ng/ml a mean weighted relative error of about 3% has to be expected.


Subject(s)
Propiophenones/blood , Biotransformation , Chromatography, High Pressure Liquid/methods , Humans , Propafenone
15.
Arzneimittelforschung ; 31(9a): 1566-74, 1981.
Article in English | MEDLINE | ID: mdl-7197971

ABSTRACT

The possible sites of action of 4-amino-6-methoxy-1-phenyl-pyridazinium methyl sulfate (ameziniummetilsulfate, LU 1631, Regulton), in the following briefly called amezinium, were investigated in biochemical experiments. 1. In vivo in mice, amezinium inhibits the uptake of 3H-noradrenaline into heart and adrenals (among other tissues). The Ki for this inhibition determined in vitro with rat atria is 1.3 x 10(-7) mol/l. As is shown with synaptosomes amezinium exhibits a predilection for the noradrenaline transport, the uptake of dopamine and serotonin being also inhibited, but less so. 2. Amezinium itself is taken up into synaptosomes. This transport follows Michaelis-Menten kinetics, showing the same dependence on Na+ and K+ as uptake 1 of noradrenaline, and is also inhibited by desipramine and cocaine. 3. Storage of 3H-amezinium in rat atria in vivo is almost completely inhibited by pretreatment with 6-hydroxy-dopamine and by approx. 50% inhibited by pretreatment with reserpine. This indicates that amezinium is at least partly stored in the neuronal granules. 4. Amezinium inhibits MAO-A in rat heart homogenate with a Ki of 3 x 10(-6) mol/l and MAO-B in liver homogenate with a Ki of 3 x 10(-4) mol/l; the inhibition is reversible. 5. Even high doses of amezinium do not deplete catecholamines in the heart or adrenals of the rat. The role of the various sites of action is discussed and the effect of amezinium interpreted as the result of noradrenaline release with simultaneous inhibition of intraneuronal and extraneuronal MAO-A and of uptake 1.


Subject(s)
Monoamine Oxidase Inhibitors , Neurons/metabolism , Pyridazines/pharmacology , Animals , Brain/metabolism , Dopamine/metabolism , Drug Interactions , In Vitro Techniques , Male , Neurons/drug effects , Norepinephrine/metabolism , Rats , Rats, Inbred Strains , Serotonin/metabolism , Synaptosomes/metabolism
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