Measurement of the 2S_{1/2}-8D_{5/2} Transition in Hydrogen.

We present a measurement of the hydrogen 2S_{1/2}-8D_{5/2} transition performed with a cryogenic atomic beam. The measured resonance frequency is ν=770649561570.9(2.0) kHz, which corresponds to a relative uncertainty of 2.6×10^{-12}. Combining our result with the most recent measurement of the 1S-2S transition, we find a proton radius of r_{p}=0.8584(51) fm and a Rydberg constant of R_{∞}=10973731.568332(52) m^{-1}. This result has a combined 3.1σ disagreement with the Committee on Data for Science and Technology (CODATA) 2018 recommended value.

Cryogenic atomic hydrogen beam apparatus with velocity characterization.

Precision spectroscopy of hydrogen often relies on effusive thermal atomic beams, and the uncertainty in the velocity distribution of these beams can introduce systematic errors and complicate lineshape models. Here, we present an apparatus capable of high signal-to-noise studies of these velocity distributions at cryogenic temperatures for both ground state (1S) and metastable (2S) hydrogen using a simple time-of-flight technique. We also investigate how the cryogenic nozzle geometry affects these results.

Highly coherent, watt-level deep-UV radiation via a frequency-quadrupled Yb-fiber laser system.

We demonstrate a 1.4 W continuous-wave (CW) laser at 243.1 nm. The radiation is generated through frequency quadrupling the output of a ytterbium-doped fiber amplifier system. which produces >10 W of CW power at 972.5 nm. We demonstrate absolute frequency control by locking the laser to an optical frequency comb and exciting the 1S-2S transition in atomic hydrogen. This frequency-stabilized, high-power deep-UV laser is of significant interest for precision spectroscopy of simple and exotic atoms, two-photon laser cooling of hydrogen, and Raman spectroscopy.

Cavity-enhanced deep ultraviolet laser for two-photon cooling of atomic hydrogen.

We demonstrate a 650 mW 243 nm continuous-wave laser coupled to a linear optical enhancement cavity. The enhancement cavity can maintain >30 W of intracavity power for 1 h of continuous operation without degradation. This system has sufficient power for a demonstration of two-photon laser cooling of hydrogen and may be useful for experiments on other simple two-body atomic systems.

Reduced phase noise in an erbium frequency comb via intensity noise suppression.

We present a coherent erbium fiber frequency comb that achieves low phase noise operation through the active suppression of amplitude fluctuations within the laser oscillator. The amplitude noise servo has a bandwidth of 550 kHz and is achieved by current actuation of the laser pump diode. This servo reduces the integrated phase noise of the carrier envelope offset frequency of the comb, fceo, due to the strong coupling of amplitude and phase noise in the laser oscillator. Additionally, we use a composite error signal that utilizes information from both the amplitude noise and the fceo error signal to actuate the pump diode current, which further increases the coherence of the comb. With this locking scheme, the integrated phase noise on fceo is measured to be 270 mrad from 10 Hz to 1.5 MHz, indicating 93% of the optical carrier power is in the coherent signal. A simultaneous phase lock to a narrow-linewidth continuous-wave laser is achieved by actuating on the cavity length, and shows an integrated phase noise of 44 mrad.

Effect of estradiol on the induction of porphyria by hexachlorobenzene in the rat.

Hexachlorobenzene (HCB) is porphyrinogenic in adult female but not in male rats. This study aimed to assess the role of 17beta-estradiol in the induction of porphyria by HCB in both sexes by adding or removing the hormone. Groups of intact females, ovariectomized females (Ova), castrated males (Cas), and Cas receiving 17beta-estradiol (4 mg/kg, i.m., once a week beginning 2 weeks prior to HCB) were given five consecutive daily doses of HCB (100 mg/kg in corn oil, p.o.). Porphyria was assessed by urinary uroporphyrin excretion measured at days 16, 31, 38, 45, 52, 59, and 87. The percentage of porphyric rats in intact females increased from day 31 (58%) to day 87 (75%), whereas none of the Ova or Cas rats responded. However, administration of estradiol (days 120-169) and another sequence of HCB doses (days 134-138) to the same Ova rats caused porphyria (50% at day 186). Cas rats given estradiol also developed porphyria (43 and 86% on days 31 and 87, respectively). HCB-treated Ova rats given two doses of estradiol at either days 1 and 8 or days 22 and 29 developed a porphyria of similar magnitude (day 52). The role of estradiol cannot be explained by a reduction of pentachlorothiophenol formation, a putative detoxication pathway. Overall, results show that both sexes have the ability to respond to HCB when 17beta-estradiol is present and suggest that the sexual dimorphism in HCB-induced porphyria in the rat is related to the hormonal status.

Enantioselective determination of oxprenolol and its metabolites in human urine by cyclodextrin-modified capillary zone electrophoresis.

A stereospecific capillary electrophoresis assay for oxprenolol enantiomers and their basic metabolites in human urine has been developed using hydroxypropyl-beta-CD as a chiral selector in the mobile phase. The bioassay method has been validated and the detection limit from spiked urine samples is 0.2 micrograms/ml. The calibration curves are linear from 0.4 to 16 micrograms/ml. Extraction recovery ranged from 84.7 to 96.4% for all the compounds studied. The influence of various parameters on the chiral separation of oxprenolol and its basic metabolites have been investigated. Urinary excretion profiles of oxprenolol enantiomers and those of two metabolites have also been studied, following a single oral dose of racemic oxprenolol.

Determination of the enantiomers of metoprolol and its major acidic metabolite in human urine by high-performance liquid chromatography with fluorescence detection.

Enantiomers of metoprolol and its acidic metabolite H 117/04 were determined in human urine by high-performance liquid chromatography (HPLC) with fluorometric detection after chiral derivatization. The carboxyl functional group of the major metabolite was blocked by esterification after solid-phase extraction, which helped to quantitate this compound from interfering substances. The assay method was validated. The recovery of (-)- and (+)-metoprolol from urine was 86.3-90.5%; and the recovery of the (-)- and (+)-acidic metabolite H 117/04 from urine was 74.4-83.9% at different concentrations.

Determination of the enantiomers of bunolol in human urine by high-performance liquid chromatography on a chiral AGP stationary phase and identification of their metabolites by gas chromatography-mass spectrometry.

A high-performance liquid chromatographic method using a chiral AGP column was developed to screen and determine the enantiomers of bunolol in human urine. The recovery of (+)- and (-)-bunolol from urine was 91.79-95.23% at different concentrations. The coefficients of variation (C.V.) were less than 2.1 and 2.3% for intra- and inter-assays, respectively. Urinary metabolites were detected using GC-MS after derivatization with N-methyl(trimethylsilyl)trifluroacetamide. The influences of pH and modifier on a chiral AGP column were studied.

The metabolism of piperidine-type phenothiazine antipsychotic agents. II. Sulforidazine in dog and human.

1. The metabolism of sulforidazine was studied in female dogs and adult male humans after oral administration of 37.5 mg and 25.0 mg, respectively. 2. Metabolites in organic extracts of dog urine were separated by h.p.l.c. and individually collected prior to mass spectrometric analysis, while organic extracts of human urine were directly subjected to plasmaspray h.p.l.c.-mass spectrometric determination. In the case of phenolic metabolites, the urinary extracts from both species were derivatized with a silylating reagent (with or without prior enzymic hydrolysis) and subsequently analysed by h.p.l.c.-mass spectrometry. The structures of metabolites with the exception of phenols were confirmed by comparison of their mass spectra and chromatographic behaviours with those of authentic standards. 3. The compounds identified in urine of both species were sulforidazine, two diastereomers of sulforidazine ring sulphoxide, the lactam of sulforidazine ring sulphoxide and a phenolic derivative of sulforidazine, whereas sulforidazine N-oxide and the lactam of sulforidazine were identified only in human urine. Moreover the phenolic metabolite was present in human urine in both unconjugated and conjugated forms, whereas dog urine had only the conjugated form. 4. Sulforidazine and some of its major metabolites were quantified by an h.p.l.c. method. The mean urinary excretions (0-48 h) of sulforidazine were similar in human (n = 3) and dog (n = 3) (5.9 +/- 0.7% and 7.2 +/- 1.9%), as were the excretions of sulforidazine ring sulphoxide (13.2 +/- 4.6% and 13.3 +/- 4.4%), while the lactam of sulforidazine ring sulphoxide was a major metabolite only in human (7.5 +/- 2.8% and < 0.1%). The lactam of sulforidazine was a minor metabolite in human. 5. The metabolites observed in human urine were similar to those previously reported in rat, except that sulforidazine N-oxide was found only in human, whereas the two diastereomers of N-desmethylsulforidazine ring sulphoxide were observed only in rat. These data suggest that rat may be a more suitable animal than dog for further study of the metabolism of the piperidine ring of sulforidazine.

Determination and identification of amiloride in human urine by high-performance liquid chromatography and gas chromatography-mass spectrometry.

A simple and sensitive high-performance liquid chromatographic method was developed to screen and determine amiloride (I) in human urine. The detection limit of the method is 0.12 micrograms/ml and the recovery of amiloride from urine was 80.4-85.5% at different concentrations. The coefficients of variation were less than 2.8 and 4.4% for intra- and inter-assays, respectively. Total urinary excretion of I in 24 h after oral administration of 5 mg or 15 mg of I ranged from 22.0 to 33.3% of the total dose for three different subjects. I could be detected in urine up to at least 44 h after a 5-mg dose and 72 h after a 15-mg dose. A gas chromatographic-mass spectrometric (GC-MS) confirmatory method was established based on the methanolysis of I to methyl 3,5-diamino-6-chloropyrazine-carboxylate (II). The di-N-trimethylsilyl derivative of II showed very good GC-MS properties and provided reliable structure information for confirmation analysis of I. This is the first time that a reliable GC-MS method has been reported for the detection of urinary I.

Comprehensive screening procedure for diuretics in urine by high-performance liquid chromatography.

A rapid and reliable screening procedure using high-performance liquid chromatography for the detection of 23 diuretics (belonging to five different pharmacological groups) in urine has been developed. Two aliquots of 2-ml urine samples were extracted separately under acidic and basic conditions. The acidic and basic extracts were pooled, evaporated to dryness and reconstituted in methanol. The methanolic extract was injected onto a Hewlett-Packard Hypersil ODS C18 (5 microns) column (column I) and a Hewlett-Packard LiChrosorb RP-18 (5 microns) column (column II; an alternative column). The same gradient mobile phase was used for both columns. A diode array ultraviolet detector was set to monitor the signal to the integrator (Chem Station) at 230 and 275 nm. Recovery studies of the 23 diuretics were performed under acidic and basic conditions. The overall lower limits for detection on column I using both extraction procedures ranged from 0.5 to 1.5 micrograms/ml of urine (average 1.0 micrograms/ml). Amiloride, ethacrynic acid and probenecid could not be detected below 5 micrograms/ml of urine. No interference from the biological matrix was apparent. Amiloride could be detected in urine 4 h after oral administration of 15 mg of amiloride to a healthy volunteer, when the sample was extracted under alkaline conditions. The suitability of the screening method for the analysis of urine samples was tested by studying the variation with time of chlorthalidone, furosemide, probenecid, acetazolamide, quinethazone, spironolactone, bendroflumethiazide, bumetanide, triameterene and hydrochlorothiazide concentrations in the urine of normal human volunteers after minimum single or multiple (probenecid) doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification and quantitation of N-nitrosamines in human postmortem organs.

A gas-liquid chromatographic method for quantitative determination of six volatile N-nitrosamines in human postmortem organs (brain, liver, kidneys, and pancreas) is described. This method, which is highly sensitive and selective, makes use of two different detectors, i.e., the electron capture detector (ECD) and the thermal energy analyzer (TEA). The mean absolute percentage recoveries of N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosodipropylamine (NDPA), N-nitrosodibutylamine (NDBA), N-nitrosodipropylamine (NDPA, N-nitrosodibutylamine (NDBA), N-nitrosopiperidine (NPIP), and N-nitrosopyrrolidine (NPY) were 54.7, 80.0, 79.6, 72.5, 75.5, and 79.6, respectively. N-Nitrosamines in the organ extracts were converted to their corresponding N-nitramine analogs by pertrifluoroacetic acid oxidation. These derivatives were purified by adsorption chromatography on basic alumina and then analyzed by ECD. N-Nitrosamines were analyzed without derivatization in the organ extracts with the TEA detector. The described method did not cause artifactual formation of N-nitrosomethyl-N-butylamine (NMBA) when methyl-N-butylamine was used as an internal marker of nitrosation. NDMA was found in all the organs examined, whereas NDPA was only detected in the liver of one in four subjects. NDMA was found in all brain samples, indicating that it crosses the blood-brain barrier.

Comparative bioavailability of two oral formulations of flurazepam in human subjects.

The systemic availability of an investigational oral formulation of flurazepam was compared to that of a commercially available product whose therapeutic efficacy has been well established by usage. The experiment was designed to dissociate formula on factors from all other sources of variation including differences between subjects, sexes, sequences of administration, experimental periods, as well as sex by sequence, sex by period, and sex by formulation interactions. Systemic availability was assessed by conventional pharmacokinetic techniques. Pharmacokinetic interpretation and statistical analysis of plasma concentrations of flurazepam and its major blood metabolites namely N-1-hydroxyethylfurazepam and N-1-desalkylflurazepam as a function of time and of systemic availability indicators revealed a nearly identical biopharmaceutical behaviour for the two preparations. A significant difference could be seen in the plasma levels of N-1-desalkylflurazepam between male and female subjects. The results collectively indicate a very similar biopharmaceutical performance of the two oral formulations of flurazepam.

Gas--liquid chromatographic determination of flurazepam and its major metabolites in plasma with electron-capture detection.

A sensitive and selective gas--liquid chromatographic method, using the electron-capture detector for the quantitative determination of flurazepam and its major blood metabolites is described. After extraction and back-extraction steps, flurazepam (I) is well separated from its main metabolites, N-1-hydroxyethylflurazepam (metabolite II) and N-1-desalkylflurazepam (metabolite III). Metabolite II is quantitated after forming its stable tert.-butyl-dimethylsilyl derivative by reaction with tert.-butyldimethylchlorosilane--imidazole reagent. The procedure permits the rapid and selective routine determination of flurazepam and its metabolites (II and III) in plasma with a detection limit of 3 ng/ml for flurazepam (I), 1 ng/ml for metabolite II and 0.6 ng/ml for metabolite III. The procedure is linear over the range of concentrations encountered after administration of a single oral therapeutic dose. No interference from the biological matrix is apparent. The suitability of the method for the analysis of biological samples was tested by studying the variation with time of flurazepam and its metabolites' plasma concentrations in normal human volunteers after a single, therapeutic 30-mg oral dose of flurazepam.

Genetic study on the effects of the repair-deficient mutant females mei-9a, mei-41D5, mus101D1, mus104D1 and mus302D1 of Drosophila on spontaneous and X-ray-induced chromosome loss in the paternal genome.

The repair-deficient mutants mei-9a, mei-41D5, mus101D1, mus104D1 and mus302D1 in Drosophila melanogaster were investigated regarding their effects on spontaneous and X-ray-induced chromosome loss in postmeiotic cells. Each mutant was incorporated singly into XC2, and the ring-X male provided with BSYy+. From matings of males carrying mus101D1, mus302D1 or mei-41D5, mutants identifying a caffeine-sensitive (CAS) postreplication-repair pathway, with corresponding mutant females, and non-mutant males to non-mutant females, overall frequencies of spontaneous partial loss and spontaneous complete loss were significantly increased in each mutant cross except for spontaneous complete loss with mus302 where an increase was noted only in brood 2. Similar findings were noted when males carrying the excision-repair mutant mei-9a were mated with mei-9a females. Males carrying the mutant mus104D1, identifying a caffeine-insensitive (CIS) postreplication-repair pathway, tested with mus104D1 females, produced results that were not significantly different from non-mutant controls. When males were given 3000 rad X-irradiation, frequencies of induced partial loss were significantly higher with mus101D1, mus302D1, mei-41D5 and mei91, and not significantly higher with mus101D1, mus302D1, mei41D5 and mei-9a, and not significantly different from controls with mus104D1. It was suggested that the functional CAS postreplication-repair pathway primarily promotes repair of breaks while an alternative pathway(s) not defined by mus104 promotes misrepair. Therefore, the significant increases in both spontaneous and induced partial loss with the excision-repair-deficient mutant mei-9a suggests the possibility that (a) the excision-repair-pathway may not function in misrepair and (b) the undefined misrepair pathway may be dominant pathway for postreplication repair in Drosophila since mei-9a females presumably have functional postreplication repair and misrepair capacity. The suggestion that the CAS postreplication-repair pathway and the excision-repair pathway function primarily in repair, and an undefined pathway in misrepair is in line with the finding that with mus104D1, no significant increase was found in spontaneous complete loss, but with mus101D1, mus302D1, mei-41D5 and mei-9a significant increases were observed. Results on induced complete loss, with the exception of those with mei-41D5, show a poor correlation with other classes of loss of each of the mutants. Possible explanations for this discrepancy are discussed.

A genetic study of the effects of the repair-deficient mei-9a mutation in Drosophila on spontaneous and X-ray-induced paternal sex chromosome loss.

The repair-deficient mutant, mei-9a in Drosophila melanogaster was investigated regarding its effect on spontaneous and X-ray-induced chromosome loss in male postmeiotic cells. From matings of males carrying a mei-9a or an ordinary ring-X and a doubly marked Y chromosome (BSYy+) with mei-9a or ordinary females, the spontaneous frequencies of complete loss, partial loss, and inferred ring-X loss (based on shifts in sex ratio female:male) were significantly higher with mei-9a than with non-mei-9a. When males were given 3000 rad X-irradiation, frequencies of induced partial loss, inferred ring-X loss and the reduction in the number of progeny per female were significantly greater with mei-9a than with non-mei-9a. The results provide evidence that the mei-9a is a potentiator of both spontaneous and X-ray-induced chromosome lesions in sperm of the Drosophila male. Evidence is presented which implicates the presence of mei-9a in the P1 female and not the male as (at least) largely responsible for the characteristic mei-9a effects.