103 research outputs found

    Molecular Gas in the z=1.2 Ultraluminous Merger GOODS J123634.53+621241.3

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    We report the detection of CO(2-1) emission from the z=1.2 ultraluminous infrared galaxy (ULIRG) GOODS J123634.53+621241.3 (also known as the sub-millimeter galaxy GN26). These observations represent the first discovery of high-redshift CO emission using the new Combined Array for Research in Millimeter-Wave Astronomy (CARMA). Of all high-redshift (z>1) galaxies within the GOODS-North field, this source has the largest far-infrared (FIR) flux observed in the Spitzer 70um and 160um bands. The CO redshift confirms the optical identification of the source, and the bright CO(2-1) line suggests the presence of a large molecular gas reservoir of about 7x10^10 M(sun). The infrared-to-CO luminosity ratio of L(IR)/L'(CO) = 80+/-30 L(sun) (K Km/s pc^2)^-1 is slightly smaller than the average ratio found in local ULIRGs and high-redshift sub-millimeter galaxies. The short star-formation time scale of about 70 Myr is consistent with a starburst associated with the merger event and is much shorter than the time scales for spiral galaxies and estimates made for high-redshift galaxies selected on the basis of their B-z and z-K colors.Comment: Accepted for publication in ApJ Letter

    Clinical evaluation of magnetic resonance imaging in coronary heart disease: The CE-MARC study

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    <p>Abstract</p> <p>Background</p> <p>Several investigations are currently available to establish the diagnosis of coronary heart disease (CHD). Of these, cardiovascular magnetic resonance (CMR) offers the greatest information from a single test, allowing the assessment of myocardial function, perfusion, viability and coronary artery anatomy. However, data from large scale studies that prospectively evaluate the diagnostic accuracy of multi-parametric CMR for the detection of CHD in unselected populations are lacking, and there are few data on the performance of CMR compared with current diagnostic tests, its prognostic value and cost-effectiveness.</p> <p>Methods/design</p> <p>This is a prospective diagnostic accuracy cohort study of 750 patients referred to a cardiologist with suspected CHD. Exercise tolerance testing (ETT) will be preformed if patients are physically able. Recruited patients will then undergo CMR and single photon emission tomography (SPECT) followed in all patients by invasive X-ray coronary angiography. The order of the CMR and SPECT tests will be randomised. The CMR study will comprise rest and adenosine stress perfusion, cine imaging, late gadolinium enhancement and whole-heart MR coronary angiography. SPECT will use a gated stress/rest protocol. The primary objective of the study is to determine the diagnostic accuracy of CMR in detecting significant coronary stenosis, as defined by X-ray coronary angiography. Secondary objectives include an assessment of the prognostic value of CMR imaging, a comparison of its diagnostic accuracy against SPECT and ETT, and an assessment of cost-effectiveness.</p> <p>Discussion</p> <p>The CE-MARC study is a prospective, diagnostic accuracy cohort study of 750 patients assessing the performance of a multi-parametric CMR study in detecting CHD using invasive X-ray coronary angiography as the reference standard and comparing it with ETT and SPECT.</p> <p>Trial Registration</p> <p>Current Controlled Trials ISRCTN77246133</p

    In vivo modeling of patient genetic heterogeneity identifies new ways to target cholangiocarcinoma.

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    L. Boulter was funded by The Wellcome Trust (207793/Z/17/Z), AMMF (2016/108, 2017/115), and Cancer Research UK (C52499/A27948). L. Boulter is also supported by an MRC university grant to the MRC Human Genetics Unit

    Senolytic treatment preserves biliary regenerative capacity lost through cellular senescence during cold storage

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    Liver transplantation is the only curative option for patients with end-stage liver disease. Despite improvements in surgical techniques, nonanastomotic strictures (characterized by the progressive loss of biliary tract architecture) continue to occur after liver transplantation, negatively affecting liver function and frequently leading to graft loss and retransplantation. To study the biological effects of organ preservation before liver transplantation, we generated murine models that recapitulate liver procurement and static cold storage. In these models, we explored the response of cholangiocytes and hepatocytes to cold storage, focusing on responses that affect liver regeneration, including DNA damage, apoptosis, and cellular senescence. We show that biliary senescence was induced during organ retrieval and exacerbated during static cold storage, resulting in impaired biliary regeneration. We identified decoy receptor 2 (DCR2)–dependent responses in cholangiocytes and hepatocytes, which differentially affected the outcome of those populations during cold storage. Moreover, CRISPR-mediated DCR2 knockdown in vitro increased cholangiocyte proliferation and decreased cellular senescence but had the opposite effect in hepatocytes. Using the p21KO model to inhibit senescence onset, we showed that biliary tract architecture was better preserved during cold storage. Similar results were achieved by administering senolytic ABT737 to mice before procurement. Last, we perfused senolytics into discarded human donor livers and showed that biliary architecture and regenerative capacities were better preserved. Our results indicate that cholangiocytes are susceptible to senescence and identify the use of senolytics and the combination of senotherapies and machine-perfusion preservation to prevent this phenotype and reduce the incidence of biliary injury after transplantation.This work was supported by the UK Medical Research MRC (MR/K017047/1) (to S.J.F.), the Computational and Chemical Biology of Stem Cell Niche (MR/L012766/1) (to S.J.F.), the UK Regenerative Medicine Platform (MR/K026666/1) (to S.J.F.), and the Wellcome Trust Institutional Translational Partnership Award (WT iTPA) (to S.F.-G.). J.M.B. was supported by the Spanish Carlos III Health Institute (ISCIII) (PI15/01132, PI18/01075, and Miguel Servet Program CON14/00129 and CPII19/00008) cofinanced by “Fondo Europeo de Desarrollo Regional” (FEDER); “Instituto de Salud Carlos III” (CIBERehd), Spain; “Euskadi RIS3” (2019222054 and 2020333010); and the Department of Industry of the Basque Country (Elkartek: KK-2020/00008). This research was funded in whole or in part by The Wellcome Trust (grant number 209710/Z/17/Z), a cOAlition S organization

    Multi-wavelength lens construction of a Planck and Herschel-detected star-bursting galaxy

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    We present a source-plane reconstruction of a Herschel and Planck-detected gravitationally lensed dusty star-forming galaxy (DSFG) at z = 1.68 using Hubble, Submillimeter Array (SMA), and Keck observations. The background submillimeter galaxy (SMG) is strongly lensed by a foreground galaxy cluster at z = 0.997 and appears as an arc with a length of ∼15″ in the optical images. The continuum dust emission, as seen by SMA, is limited to a single knot within this arc. We present a lens model with source-plane reconstructions at several wavelengths to show the difference in magnification between the stars and dust, and highlight the importance of multi-wavelength lens models for studies involving lensed DSFGs. We estimate the physical properties of the galaxy by fitting the flux densities to model spectral energy distributions leading to a magnification-corrected starformation rate (SFR) of 390 ± 60 M yr−1 and a stellar mass of 1.1 ± 0.4 10 x 11 M. These values are consistent with high-redshift massive galaxies that have formed most of their stars already. The estimated gas-to-baryon fraction, molecular gas surface density, and SFR surface density have values of 0.43 ± 0.13, 350 ± 200 M pc−2, and ~ 12 7 M yr−1 kpc−2, respectively. The ratio of SFR surface density to molecular gas surface density puts this among the most star-forming systems, similar to other measured SMGs and local ULIRGs

    Sequences, Annotation and Single Nucleotide Polymorphism of the Major Histocompatibility Complex in the Domestic Cat

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    Two sequences of major histocompatibility complex (MHC) regions in the domestic cat, 2.976 and 0.362 Mbps, which were separated by an ancient chromosome break (55–80 MYA) and followed by a chromosomal inversion were annotated in detail. Gene annotation of this MHC was completed and identified 183 possible coding regions, 147 human homologues, possible functional genes and 36 pseudo/unidentified genes) by GENSCAN and BLASTN, BLASTP RepeatMasker programs. The first region spans 2.976 Mbp sequence, which encodes six classical class II antigens (three DRA and three DRB antigens) lacking the functional DP, DQ regions, nine antigen processing molecules (DOA/DOB, DMA/DMB, TAPASIN, and LMP2/LMP7,TAP1/TAP2), 52 class III genes, nineteen class I genes/gene fragments (FLAI-A to FLAI-S). Three class I genes (FLAI-H, I-K, I-E) may encode functional classical class I antigens based on deduced amino acid sequence and promoter structure. The second region spans 0.362 Mbp sequence encoding no class I genes and 18 cross-species conserved genes, excluding class I, II and their functionally related/associated genes, namely framework genes, including three olfactory receptor genes. One previously identified feline endogenous retrovirus, a baboon retrovirus derived sequence (ECE1) and two new endogenous retrovirus sequences, similar to brown bat endogenous retrovirus (FERVmlu1, FERVmlu2) were found within a 140 Kbp interval in the middle of class I region. MHC SNPs were examined based on comparisons of this BAC sequence and MHC homozygous 1.9× WGS sequences and found that 11,654 SNPs in 2.84 Mbp (0.00411 SNP per bp), which is 2.4 times higher rate than average heterozygous region in the WGS (0.0017 SNP per bp genome), and slightly higher than the SNP rate observed in human MHC (0.00337 SNP per bp)

    Molecular Imaging of Pulmonary Tuberculosis in an Ex-Vivo Mouse Model Using Spectral Photon-Counting Computed Tomography and Micro-CT

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    Assessment of disease burden and drug efficacy is achieved preclinically using high resolution micro computed tomography (CT). However, micro-CT is not applicable to clinical human imaging due to operating at high dose. In addition, the technology differences between micro-CT and standard clinical CT prevent direct translation of preclinical applications. The current proof-of-concept study presents spectral photon-counting CT as a clinically translatable, molecular imaging tool by assessing contrast uptake in an ex-vivo mouse model of pulmonary tuberculosis (TB). Iodine, a common contrast used in clinical CT imaging, was introduced into a murine model of TB. The excised mouse lungs were imaged using a standard micro-CT subsystem (SuperArgus) and the contrast enhanced TB lesions quantified. The same lungs were imaged using a spectral photoncounting CT system (MARS small-bore scanner). Iodine and soft tissues (water and lipid) were materially separated, and iodine uptake quantified. The volume of the TB infection quantified by spectral CT and micro-CT was found to be 2.96 mm(3) and 2.83 mm(3), respectively. This proof-of-concept study showed that spectral photon-counting CT could be used as a predictive preclinical imaging tool for the purpose of facilitating drug discovery and development. Also, as this imaging modality is available for human trials, all applications are translatable to human imaging. In conclusion, spectral photon-counting CT could accelerate a deeper understanding of infectious lung diseases using targeted pharmaceuticals and intrinsic markers, and ultimately improve the efficacy of therapies by measuring drug delivery and response to treatment in animal models and later in humans
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