Delta-like and gtl2 are reciprocally expressed, differentially methylated linked imprinted genes on mouse chromosome 12

AbstractThe distal portion of mouse chromosome 12 is imprinted. To date, however, Gtl2 is the only imprinted gene identified on chromosome 12. Gtl2 encodes multiple alternatively spliced transcripts with no apparent open reading frame. Using conceptuses with maternal or paternal uniparental disomy for chromosome 12 (UPD12), we found that Gtl2 is expressed from the maternal allele and methylated at the 5′ end of the silent paternal allele. A reciprocally imprinted gene, Delta-like (Dlk), with homology to genes involved in the Notch signalling pathway was identified 80kb upstream of Gtl2. Dlk was expressed exclusively from the paternal allele in both the embryo and placenta, but the CpG-island promoter of Dlk was completely unmethylated on both parental alleles. Rather, a paternally methylated region was identified in the last exon of the active Dlk allele. The proximity, reciprocal imprinting and methylation in this domain are reminiscent of the co-ordinately regulated Igf2–H19 imprinted domain on mouse chromosome 7. Like H19 and Igf2, Gtl2 and Dlk were found to be co-expressed in the same tissues throughout development, though not after birth. These results have implications for the regulation, function and evolution of imprinted domains

Temperature perturbation model of the opto-galvanic effect in CO2-laser discharges

A detailed discharge model of the opto-galvanic effect in molecular laser gas mixtures is developed based on the temperature perturbation or discharge cooling mechanism of Smith and Brooks (1979). Excellent agreement between the model and experimental results in CO2 laser gas mixtures is obtained. The model should be applicable to other molecular systems where the OGE is being used for laser stabilisation and as a spectroscopic tool

Deep UV Luminosity Functions at the Infall Region of the Coma Cluster

We have used deep GALEX observations at the infall region of the Coma cluster to measure the faintest UV luminosity functions (LFs) presented for a rich galaxy cluster thus far. The Coma UV LFs are measured to M_UV = -10.5 in the GALEX FUV and NUV bands, or 3.5 mag fainter than previous studies, and reach the dwarf early-type galaxy population in Coma for the first time. The Schechter faint-end slopes (alpha = -1.39 in both GALEX bands) are shallower than reported in previous Coma UV LF studies owing to a flatter LF at faint magnitudes. A Gaussian-plus-Schechter model provides a slightly better parametrization of the UV LFs resulting in a faint-end slope of ~ -1.15 in both GALEX bands. The two-component model gives faint-end slopes shallower than -1 (a turnover) for the LFs constructed separately for passive and star forming galaxies. The UV LFs for star forming galaxies show a turnover at M_UV ~ -14 owing to a deficit of dwarf star forming galaxies in Coma with stellar masses below M*=10^8 Msun. A similar turnover is identified in recent UV LFs measured for the Virgo cluster suggesting this may be a common feature of local galaxy clusters, whereas the field UV LFs continue to rise at faint magnitudes. We did not identify an excess of passive galaxies as would be expected if the missing dwarf star forming galaxies were quenched inside the cluster. In fact, the LFs for both dwarf passive and star forming galaxies show the same turnover at faint magnitudes. We discuss the possible origin of the missing dwarf star forming galaxies in Coma and their expected properties based on comparisons to local field galaxies.Comment: accepted for publication in Ap

Halos of Spiral Galaxies. III. Metallicity Distributions

(Abriged) We report results of a campaign to image the stellar populations in the halos of highly inclined spiral galaxies, with the fields roughly 10 kpc (projected) from the nuclei. We use the F814W (I) and F606W (V) filters in the Wide Field Planetary Camera 2, on board the Hubble Space telescope. Extended halo populations are detected in all galaxies. The color-magnitude diagrams appear to be completely dominated by giant-branch stars, with no evidence for the presence of young stellar populations in any of the fields. We find that the metallicity distribution functions are dominated by metal-rich populations, with a tail extending toward the metal poor end. To first order, the overall shapes of the metallicity distribution functions are similar to what is predicted by simple, single-component model of chemical evolution with the effective yields increasing with galaxy luminosity. However, metallicity distributions significantly narrower than the simple model are observed for a few of the most luminous galaxies in the sample. It appears clear that more luminous spiral galaxies also have more metal-rich stellar halos. The increasingly significant departures from the closed-box model for the more luminous galaxies indicate that a parameter in addition to a single yield is required to describe chemical evolution. This parameter, which could be related to gas infall or outflow either in situ or in progenitor dwarf galaxies that later merge to form the stellar halo, tends to act to make the metallicity distributions narrower at high metallicity.Comment: 20 pages, 8 figures (ApJ, in press

Age Constraints for an M31 Globular Cluster from Main Sequence Photometry

We present a color-magnitude diagram (CMD) of the globular cluster SKHB-312 in the Andromeda galaxy (M31), obtained with the Advanced Camera for Surveys on the Hubble Space Telescope. The cluster was included in deep observations taken to measure the star formation history of the M31 halo. Overcoming a very crowded field, our photometry of SKHB-312 reaches V ~ 30.5 mag, more than 1 mag below the main sequence turnoff. These are the first observations to allow a direct age estimate from the turnoff in an old M31 cluster. We analyze its CMD and luminosity function using a finely-spaced grid of isochrones that have been calibrated using observations of Galactic clusters taken with the same camera and filters. The luminosity difference between the subgiant and horizontal branches is ~0.2 mag smaller in SKHB-312 than in the Galactic clusters 47 Tuc and NGC 5927, implying SKHB-312 is 2-3 Gyr younger. A quantitative comparison to isochrones yields an age of 10 +2.5/-1 Gyr

New treatments for advanced cancer: an approach to prioritization

The allocation of funding for new anticancer treatments within the UK has not kept pace with demand. Clinicians find themselves restricted in the use of licensed drugs which they feel are in the best interests of individual patients. Against this, health authorities have a duty to ensure that scarce resources are used equitably to meet the needs of the local population as a whole. Differential levels of funding for new treatments across the country have led to concerns about rationing by postcode. This paper outlines an approach to the prioritization of new treatment for advanced cancer developed jointly by clinicians and health authorities in South London. The approach involves evidence reviews and consensus meetings. Existing and new treatments are rated on a four-point ‘relative effectiveness scale’, which takes account of the impact of the treatment on quality of life and on survival. The strength of evidence supporting each effectiveness rating is also classified. Health Authorities have used these ratings to determine overall funding levels, while leaving decisions on individual patients to the relevant Trusts. © 2000 Cancer Research Campaig

A time-resolved fluorescence immunoassay for the measurement of testosterone in saliva: Monitoring of testosterone replacement therapy with testosterone buciclate

Monitoring of testosterone replacement therapy requires a reliable method for testosterone measurement. Determination of salivary testosterone, which reflects the hormone's biologically active plasma fraction, is a superior technique for this purpose. The aim of the present study was to establish a new sensitive time-resolved fluorescence immunoassay for the accurate measurement of testosterone levels in saliva and to validate it by monitoring testosterone replacement therapy in eight hypogonadal men. A clinical phase I- study with the new ester testosterone buciclate was performed to search for new testosterone preparations to produce constant serum levels in the therapy of male hypogonadism. After two control examinations eight male patients with primary hypogonadism were randomly assigned to two treatment groups (n = 2x4) and given single doses of either 200 mg (group I) or 600 mg (group II) testosterone buciclate intramuscularly. Saliva and blood samples were obtained 1, 2, 3, 5 and 7 days post injection and then weekly for three months. The time-resolved fluorescence immunoassay for salivary testosterone shows a detection limit of 16 pmol/l, an intra-assay CV of 8.9% (at a testosterone concentration of 302 pmol/l), an inter-assay CV of 8.7% (at a testosterone concentration of 305 pmol/l) and a good correlation with an established radioimmunsassay of r = 0.89. The sample volume required by this method is only 180 mu l for extraction and duplicate determination. The assay procedure requires no more than three hours. In group I (200 mg) testosterone did not increase to normal levels either in saliva or in serum. However, in group II, androgen levels increased significantly and were maintained in the normal range for up to 12 weeks with maximal salivary testosterone levels of 303 +/- 18 pmol/l (mean+/-SE) and maximal testosterone levels of 13.1 +/- 0.9 nmol/l (mean+/-SE) in serum in study week 6 and 7. The time-resolved fluorescence immunoassay for salivary testosterone provides a useful tool for monitoring androgen status in men and women and is well suited for the follow-up of testosterone replacement therapy on an outpatient basis. The long-acting ester testosterone buciclate is a promising agent for substitution therapy of male hypogonadism and in combination with testosterone monitoring in saliva offers an interesting new perspective for male contraception

“I was worried if I don’t have a broken leg they might not take it seriously”: Experiences of men accessing ambulance services for mental health and/or alcohol and other drug problems

Abstract Background A large proportion of ambulance callouts are for men with mental health and/or alcohol and other drug (AOD) problems, but little is known about their experiences of care. This study aimed to describe men's experiences of ambulance care for mental health and/or AOD problems, and factors that influence their care. Methods Interviews were undertaken with 30 men who used an ambulance service for mental health and/or AOD problems in Australia. Interviews were analysed using the Framework approach to thematic analysis. Results Three interconnected themes were abstracted from the data: (a) professionalism and compassion, (b) communication and (c) handover to emergency department staff. Positive experiences often involved paramedics communicating effectively and conveying compassion throughout the episode of care. Conversely, negative experiences often involved a perceived lack of professionalism, and poor communication, especially at handover to emergency department staff. Conclusion Increased training and organizational measures may be needed to enhance paramedics' communication when providing care to men with mental health and/or AOD problems