Absolute-frequency measurements with a stabilized near-infrared optical frequency comb from a Cr:forsterite laser.

A frequency comb is generated with a chromium-doped forsterite femtosecond laser, spectrally broadened in a dispersion-shifted highly nonlinear fiber, and stabilized. The resultant evenly spaced comb of frequencies ranges from 1.1 to beyond 1.8 microm. The frequency comb was referenced simultaneously to the National Institute of Standards and Technology's optical frequency standard based on neutral calcium and to a hydrogen maser that is calibrated by a cesium atomic fountain clock. With this comb we measured two frequency references in the telecommunications band: one half of the frequency of the d/f crossover transition in 87Rb at 780 nm, and the methane v2 + 2v3 R(8) line at 1315 nm.

Apaf-1 deficiency and neural tube closure defects are found in fog mice.

The forebrain overgrowth mutation (fog) was originally described as a spontaneous autosomal recessive mutation mapping to mouse chromosome 10 that produces forebrain defects, facial defects, and spina bifida. Although the fog mutant has been characterized and available to investigators for several years, the underlying mutation causing the pathology has not been known. Because of its phenotypic resemblance to apoptotic protease activating factor-1 (Apaf-1) knockout mice, we have investigated the possibility that the fog mutation is in the Apaf-1 gene. Allelic complementation, Western blot analysis, and caspase activation assays indicate that fog mutant mice lack Apaf-1 activity. Northern blot and reverse transcription-PCR analysis show that Apaf-1 mRNA is aberrantly processed, resulting in greatly reduced expression levels of normal Apaf-1 mRNA. These findings are strongly suggestive of the fog mutation being a hypomorphic Apaf-1 defect and implicate neural progenitor cell death in the pathogenesis of spina bifida-a common human congenital malformation. Because a complete deficiency in Apaf-1 usually results in perinatal lethality and fog/fog mice more readily survive into adulthood, these mutants serve as a valuable model with which apoptotic cell death can be studied in vivo.

Interferometric measurement of refractive-index change in photosensitive glass.

We report on a technique for determining the change in the refractive index of photosensitive glass. We have demonstrated our interferometer-based technique on fiber preform and bulk glass samples, achieving an optical-path-difference (OPD) repeatability of 0.2 nm. For the bulk glass sample we measured an OPD of 15.2 ? 3.0 nm, corresponding to an index change of 2.1 ? 0.7 x 10(-5). Our technique was found to be insensitive to the effects of photodarkening and material compaction.

XIST RNA associates with specific regions of the inactive X chromatin.

Microscopy studies have shown that XIST RNA colocalizes with the inactive X chromosome (Xi). However, the molecular basis for this colocalization is unknown. Here we provide two lines of evidence from chromatin immunoprecipitation experiments that XIST RNA physically associates with the Xi chromatin. First, XIST RNA can be co-precipitated by antiserum against macroH2A, a histone H2A variant enriched in the Xi. Second, XIST RNA can be co-precipitated by antisera that recognize unacetylated, but not acetylated, isoforms of histones H3 and H4. The specificity of XIST RNA association with hypoacetylated chromatin, together with the previous finding that hypoacetylated histone H4 is enriched at promoters of X-inactivated genes, raises the possibility that XIST RNA may contribute to the hypoacetylation of specific regions of the Xi so as to alter the expression of X-linked genes.

Promoter-specific hypoacetylation of X-inactivated genes.

The histone H4 acetylation status of the active X (Xa) and inactive X (Xi) chromosomes was investigated at the level of individual genes. A moderate level of acetylation was observed along the lengths of genes on both the Xi and Xa, regardless of their X inactivation status. However, this moderate level of acetylation was modified specifically in promoter regions. Transcriptionally active genes showed elevated levels of acetylation at their promoters on both the Xi and Xa. In contrast, promoters of X-inactivated genes were markedly hypoacetylated, which coincided with the methylation of adjacent CG dinucleotides. This promoter-specific hypoacetylation may be a key component of an X inactivation machinery that operates at the level of individual genes.

Stability of short, single-mode erbium-doped fiber lasers.

We conducted a detailed study of the stability of short, erbium-doped fiber lasers fabricated with two UV-induced Bragg gratings written into the doped fiber. We find that the relative intensity noise of single-longitudinal-mode fiber grating lasers is approximately 3 orders of magnitude lower than that of a single-frequency 1.523-mum helium-neon laser. The frequency noise spectrum contains few resonances, none of which exceeds 0.6 kHz/Hz(1/2) rms; the integrated rms frequency noise from 50 Hz to 63 kHz is 36 kHz. We also demonstrate a simple method for monitoring the laser power and number of oscillating modes during laser fabrication.

Gender representation in illustrations, text, and topic areas in sexuality education curricula.

A content analysis instrument was developed to examine differences in gender representation in sexuality education curricula. Fourteen middle school and high school curricula, published between 1985 and 1995, were examined. Variables included illustrations, noun/pronoun usage, and specific topics within the two categories of biological function and mutual interest. The study examined differences in gender representation in illustrations, photographs, cartoons, drawings, and text. Omission of sexuality topics related to gender also was examined. Little difference occurred within the text of the curricula in noun and pronoun usage. Illustrations were few in number, but showed greater female representation. Greater male representation occurred in topics related to drug use, sexual exploitation, sexual desire, and homosexuality. Topics with greater female representation included body image, diseases of the reproductive organs, and hygiene.

Longitudinal study of astronaut health: mortality in the years 1959-1991.

We conducted a historical cohort study of mortality among 195 astronauts who were exposed to space and medical sources of radiation between 1959 and 1991. Cumulative occupational and medical radiation exposures were obtained from the astronaut radiation exposure history data base. Causes of death were obtained from obligatory death certificates and autopsy reports that were on file in the medical records. There was a total of 20 deaths that occurred during the 32-year follow-up period of which 16 were due to accidents. The all-cause standardized mortality ratio (SMR) was 181 (95% confidence interval 110, 279). There was 1 cancer death in the buccal cavity and pharyngeal ICD-9 rubric whose occurrence was significantly beyond expectation. Mortality for coronary disease was 53% lower than expected (2 deaths; SMR = 47; 95% confidence limits 5, 168). The crude death rate for 12 occupationally related accidents was 445 deaths per 100,000 person-years and was an order of magnitude greater than accidental death rates in the mining industries. The SMR of 1346 for fatal accidents was significantly beyond expectation (16 deaths; 95% confidence limits 769, 2168) and was similar to SMRs for accidents among aerial pesticide applicators. The 10-year cumulative risk of occupational fatalities based on the exponential, Weibull, Gompertz, and linear-exponential distributions was 10%. Mortality from motor vehicle accidents was slightly higher than expected, but was not significant (1 death; SMR = 165; 95% confidence limits 2,922). Radiation exposures from medical procedures accounted for a majority of cumulative dose when compared with space radiation exposures. Overall, it was found that astronauts are at a health disadvantage as a result of catastrophic accidents.

Frequency stabilization of a tunable erbium-doped fiber laser.

A single-frequency Er-doped fiber laser that is tunable from 1.52 to 1.58 ,microm has been constructed. The laser linewidth was determined to be less than 1.6 MHz FWHM by observing the spectrum of the beat between the fiber laser and a 1.523-microm He-Ne laser. The frequency of the fiber laser was locked to several absorption lines of acetylene near 1.53 microm. This research demonstrates the inherent stability of fiber lasers and their potential for use in a wavelength standard for optical communications.

Progress at NIST toward absolute frequency standards using stored ions.

Experiments directed toward the realization of frequency standards of high accuracy using stored ions are briefly summarized. In one experiment, an RF oscillator is locked to a nuclear spin-flip hyperfine transition (frequency approximately 3.03x10(8) Hz) in (9 )Be(+) ions that are stored in a Penning trap and sympathetically laser-cooled. Stability is better than 3x10(-12)tau(-(1/2)) and uncertainty in Doppler shifts is estimated to be less than 5x10(-15). In a second experiment, a stable laser is used to probe an electric quadrupole transition (frequency approximately 1.07x10(15) Hz) in a single laser-cooled (199)Hg(+) ion stored in a Paul trap. The measured Q value of this transition is approximately 10(13). Future possible experiments are discussed.

Laser-frequency stabilization using mode interference from a reflecting reference interferometer.

We present a new method for locking the frequency of a laser to a reference-interferometer cavity. For a nonmode-matched input beam, the light reflected off a cavity contains an interference between the wave fronts corresponding to the various cavity modes. A detector placed at the proper position on the interference pattern provides a signal proportional to the imaginary component of the reflected field. As a function of laser frequency, this signal is dispersion shaped and can be used as the error signal for electronic frequency stabilization.

Galactosyl transferase activity in rat bladder transitional cell carcinoma lines and in exfoliated cells in urine during carcinogenesis and reversible hyperplasia.

Cultured cells of rat bladder transitional cell carcinoma line AY-27, in suspension, were assayed for galactosyl transferase (GT) by measurement of the transfer of [3H]galactose from uridine diphosphate-[3H]galactose to desialylated ovine submaxillary mucin (OSM-NANA). The assay was optimized with respect to time and to protein, uridine diphosphate galactose, OSM-NANA and Triton X-100 concentrations. This assay was then applied weekly to suspensions of exfoliated bladder cells collected from urines of rats fed the bladder carcinogen N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide, and of control rats. Increases in activity over controls appeared 42 weeks after feeding the carcinogen, at a stage when bladder tumors were already microinvasive or deeply invasive, and activities at 52 weeks were about 10-fold greater than normal values. In contrast, a bladder cytotoxic agent inducing reversible hyperplasia was injected into rats, and exfoliated cells were collected from urines: these cells showed no greater GT activity than normal. Bladder tumor tissue from a transplanted tumor had the same high specific enzymatic GT activity as exfoliated cells from tumor-bearing rats.

Galactosyl transferase activity in human transitional cell carcinoma lines and in benign and neoplastic human bladder epithelium.

Cultured cells of human transitional cell carcinoma line MGH-U1, in suspension, were assayed for galactosyl transferase by measurement of the transfer of [3H]galactose from uridine diphosphate:[3H]galactose to desialylated ovine submaxillary mucin. The assay was optimized with respect to time and to protein, uridine disphosphate:galactose, desialyated ovine submaxillary mucin, and Triton X-100 concentrations. This assay was then applied to fresh specimens of benign, inflamed, and neoplastic bladder epithelium from 33 patients who under went cold-cup biopsies at cytoscopy. Transitional cell carcinoma specimens gave values in the range of 24.7 to 184.8 cpm [3H]galactose transferred per microgram protein per hr [72.0 +/- 44.7 (S.D.); n = 25]; normal and inflamed specimens ranged from 0.8 to 46.1 cpm/microgram protein per hr [8.3 +/- 8.4 (S.D.); n = 35]. By using a known method of cell rupture, cell ghosts, representing cell-surface membranes, were isolated both from the cultured cell line and from two biopsy specimens of transitional cell carcinoma. Although a complete enzymatic and electron microscopic analysis was not undertaken, the coincidence of an enzyme marker with the cell ghost fraction containing the elevated galactosyl transferase made it appear probable that this enzyme is located in the cell surface.