299 research outputs found

    Non-canonical functions of the RB protein in cancer

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    The canonical model of RB-mediated tumour suppression developed over the past 30 years is based on the regulation of E2F transcription factors to restrict cell cycle progression. Several additional functions have been proposed for RB, on the basis of which a non-canonical RB pathway can be described. Mechanistically, the non-canonical RB pathway promotes histone modification and regulates chromosome structure in a manner distinct from cell cycle regulation. These functions have implications for chemotherapy response and resistance to targeted anticancer agents. This Opinion offers a framework to guide future studies of RB in basic and clinical research

    HST Imaging Polarimetry of the Gravitational Lens FSC10214+4724

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    We present imaging polarimetry of the extremely luminous, redshift 2.3 IRAS source FSC10214+4724. The observations were obtained with HST's Faint Object Camera in the F437M filter, which is free of strong emission lines. The 0.7 arcsec long arc is unresolved to 0.04 arcsec FWHM in the transverse direction, and has an integrated polarization of 28 +/- 3 percent, in good agreement with ground-based observations. The polarization position angle varies along the arc by up to 35 deg. The overall position angle is 62 +/- 3 deg east of north. No counterimage is detected to B = 27.5 mag (3σ3\sigma), giving an observed arc to counterimage flux ratio greater than 250, considerably greater than the flux ratio of 100 measured previously in the I-band. This implies that the configuration of the object in the source plane at the B-band is different from that at I-band, and/or that the lensing galaxy is dusty.Comment: 17 pages, 3 figures. Accepted for publication in Astronomical Journal, February 199

    Mass fluxes and isofluxes of methane (CH4) at a New Hampshire fen measured by a continuous wave quantum cascade laser spectrometer

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    We have developed a mid‐infrared continuous‐wave quantum cascade laser direct‐absorption spectrometer (QCLS) capable of high frequency (≥1 Hz) measurements of 12CH4 and 13CH4 isotopologues of methane (CH4) with in situ 1‐s RMS image precision of 1.5 ‰ and Allan‐minimum precision of 0.2 ‰. We deployed this QCLS in a well‐studied New Hampshire fen to compare measurements of CH4 isoflux by eddy covariance (EC) to Keeling regressions of data from automated flux chamber sampling. Mean CH4 fluxes of 6.5 ± 0.7 mg CH4 m−2 hr−1 over two days of EC sampling in July, 2009 were indistinguishable from mean autochamber CH4 fluxes (6.6 ± 0.8 mgCH4 m−2 hr−1) over the same period. Mean image composition of emitted CH4 calculated using EC isoflux methods was −71 ± 8 ‰ (95% C.I.) while Keeling regressions of 332 chamber closing events over 8 days yielded a corresponding value of −64.5 ± 0.8 ‰. Ebullitive fluxes, representing ∼10% of total CH4 fluxes at this site, were on average 1.2 ‰ enriched in 13C compared to diffusive fluxes. CH4 isoflux time series have the potential to improve process‐based understanding of methanogenesis, fully characterize source isotopic distributions, and serve as additional constraints for both regional and global CH4 modeling analysis

    Cluster randomized adaptive implementation trial comparing a standard versus enhanced implementation intervention to improve uptake of an effective re-engagement program for patients with serious mental illness

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    Abstract Background Persons with serious mental illness (SMI) are disproportionately burdened by premature mortality. This disparity is exacerbated by poor continuity of care with the health system. The Veterans Health Administration (VA) developed Re-Engage, an effective population-based outreach program to identify veterans with SMI lost to care and to reconnect them with VA services. However, such programs often encounter barriers getting implemented into routine care. Adaptive designs are needed when the implementation intervention requires augmentation within sites that do not initially respond to an initial implementation intervention. This protocol describes the methods used in an adaptive implementation design study that aims to compare the effectiveness of a standard implementation strategy (Replicating Effective Programs, or REP) with REP enhanced with External Facilitation (enhanced REP) to promote the uptake of Re-Engage. Methods/Design This study employs a four-phase, two-arm, longitudinal, clustered randomized trial design. VA sites (n = 158) across the United States with a designated Re-Engage provider, at least one Veteran with SMI lost to care, and who received standard REP during a six-month run-in phase. Subsequently, 88 sites with inadequate uptake were stratified at the cluster level by geographic region (n = 4) and VA regional service network (n = 20) and randomized to REP (n = 49) vs. enhanced REP (n = 39) in phase two. The primary outcome was the percentage of veterans on each facility outreach list documented on an electronic web registry. The intervention was at the site and network level and consisted of standard REP versus REP enhanced by external phone facilitation consults. At 12 months, enhanced REP sites returned to standard REP and 36 sites with inadequate participation received enhanced REP for six months in phase three. Secondary implementation outcomes included the percentage of veterans contacted directly by site providers and the percentage re-engaged in VA health services. Discussion Adaptive implementation designs consisting of a sequence of decision rules that are tailored based on a site’s uptake of an effective program may produce more relevant, rapid, and generalizable results by more quickly validating or rejecting new implementation strategies, thus enhancing the efficiency and sustainability of implementation research and potentially leading to the rollout of more cost-efficient implementation strategies. Trial registration Current Controlled Trials ISRCTN21059161 .http://deepblue.lib.umich.edu/bitstream/2027.42/112609/1/13012_2013_Article_711.pd

    Kidney transplant graft outcomes in 379 257 recipients on 3 continents

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145422/1/ajt14694_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145422/2/ajt14694.pd

    The Type Ic Supernova 1994I in M51: Detection of Helium and Spectral Evolution

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    We present a series of spectra of SN 1994I in M51, starting 1 week prior to maximum brightness. The nebular phase began about 2 months after the explosion; together with the rapid decline of the optical light, this suggests that the ejected mass was small. Although lines of He I in the optical region are weak or absent, consistent with the Type Ic classification, we detect strong He I λ10830 absorption during the first month past maximum. Thus, if SN 1994I is a typical Type Ic supernova, the atmospheres of these objects cannot be completely devoid of helium. The emission-line widths are smaller than predicted by the model of Nomoto and coworkers, in which the iron core of a low-mass carbon-oxygen star collapses. They are, however, larger than in Type Ib supernovae
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