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Beaton, Benjamin P,Kwon, Deug-Nam,Choi, Yun-Jung,Kim, Jae-Hwan,Samuel, Melissa S,Benne, Joshua A,Wells, Kevin D,Lee, Kiho,Kim, Jin-Hoi,Prather, Randall S John WileySons, Ltd 2015 Xenotransplantation Vol.22 No.5
<P><B>Background</B></P><P>Recent advancements in gene editing techniques have increased in number and utility. These techniques are an attractive alternative to conventional gene targeting methods via homologous recombination due to the ease of use and the high efficiency of gene editing. We have previously produced cytidine monophosphate-N-acetylneuraminic acid hydroxylase (<I>CMAH</I>) knockout (KO) pigs in a Minnesota miniature pig genetic background. These pigs were generated using zinc-finger nucleases (ZFNs) in combination with donor DNA containing a total homology length of 1600 bp (800-bp homology on each arm). Our next aim was to introduce the targeted disruption of alpha-1,3-galactosyltransferase (<I>GGTA1</I>) in the <I>CMAH</I> KO genetic background and evaluate the effect of donor DNA homology length on meganuclease-mediated gene targeting.</P><P><B>Methods</B></P><P>Zinc-finger nucleases from a previous <I>CMAH</I> KO experiment were used as a proof of concept to identify a correlation between the length of donor DNA homology and targeting efficiency. Based on those results, experiments were designed to use transcription activator-like effector nucleases (TALENs) to generate bi-allelically modified <I>GGTA1</I> cells using donor DNAs carrying various lengths of homology. Donor DNA was designed to symmetrically flank the predicted cleavage sites in <I>CMAH</I> and <I>GGTA1</I> for both ZFN and TALEN cleavage sites, respectively. For both genes, the length of total homology ranged from 60 to 1799 bp. Sialyltransferase gene expression profiles were evaluated in <I>CMAH</I> and <I>GGTA1</I> double KO pig cells and were compared to wild-type and <I>CMAH</I> KO cells.</P><P><B>Results</B></P><P>Introduction of donor DNA with ZFNs demonstrated that small amounts of homology (60 bp) could facilitate homology-directed repair during ZFN-mediated targeting of <I>CMAH</I>; however, donor DNA with longer amounts of homology resulted in a higher frequency of homology-directed repair. For the <I>GGTA1</I> KO experiments that used TALENs and donor DNA, donor DNA alone did not result in detectable bi-allelic conversion of <I>GGTA1</I>. As the length of donor DNA increased, the bi-allelic disruption of <I>GGTA1</I> increased from 0.5% (TALENs alone, no donor DNA present) to a maximum of 3% (TALENs and donor DNA with total homology of 1799 bp). Inclusion of homologous donor DNA in TALEN-mediated gene targeting facilitated a higher incidence of bi-allelically modified cells. Using the generated cells, we were able to demonstrate the lack of <I>GGTA1</I> expression and the decrease in gene expression sialyltransferase-related genes.</P><P><B>Conclusions</B></P><P>The approach of using donor DNA in conjunction with a meganuclease can be used to increase the efficiency of gene targeting. The gene editing methods can be applied to other genes as well as other mammalian systems. Additionally, gene expression analysis further confirms that the <I>CMAH</I>/<I>GGTA1</I> double KO pigs can be a valuable source for the study of pig-to-human xenotransplantation.</P>
Beaton, Rachael L.,Freedman, Wendy L.,Madore, Barry F.,Bono, Giuseppe,Carlson, Erika K.,Clementini, Gisella,Durbin, Meredith J.,Garofalo, Alessia,Hatt, Dylan,Jang, In Sung,Kollmeier, Juna A.,Lee, Myun American Astronomical Society 2016 The Astrophysical journal Vol.832 No.2
<P>We present an overview of the Carnegie-Chicago Hubble Program, an ongoing program to obtain a 3% measurement of the Hubble constant (H-0) using alternative methods to the traditional Cepheid distance scale. We aim to establish a completely independent route to H-0 using RR Lyrae variables, the tip of the red giant branch (TRGB), and Type Ia supernovae (SNe Ia). This alternative distance ladder can be applied to galaxies of any Hubble type, of any inclination, and, using old stars in low-density environments, is robust to the degenerate effects of metallicity and interstellar extinction. Given the relatively small number of SNe. Ia host galaxies with independently measured distances, these properties provide a great systematic advantage in the measurement of H-0 via the distance ladder. Initially, the accuracy of our value of H-0 will be set by the five Galactic RR Lyrae calibrators with Hubble Space Telescope Fine-Guidance Sensor parallaxes. With Gaia, both the RR Lyrae zero-point and TRGB method will be independently calibrated, the former with at least an order of magnitude more calibrators and the latter directly through parallax measurement of tip red giants. As the first end-to-end 'distance ladder' completely independent of both Cepheid variables and the Large Magellanic Cloud, this path to H-0 will allow for the high-precision comparison at each rung of the traditional distance ladder that is necessary to understand tensions between this and other routes to H-0.</P>
Jessica Beaton,,Sharon Carey,Michael J Solomon,Ker-Kan Tan,Jane Young 대한대장항문학회 2014 Annals of Coloproctolgy Vol.30 No.2
Purpose: Malnutrition is associated with an increased risk of developing complications following gastrointestinal surgery, especially following radical surgeries such as pelvic exenteration. This study aims to determine if preoperative body mass index (BMI) is associated with 30-day morbidity, length of hospital stay and/or quality of life (QoL) in patients undergoing pelvic exenteration surgery for recurrent and locally-advanced rectal cancer prior to a prospective trial. Methods: A review of all patients who underwent pelvic exenteration surgery prior to 2008 was performed. Patients were included if they had a documented BMI as well as a QoL measurement (Functional Assessment Cancer Therapy - Colorectal questionnaire). Results: Thirty-one patients, with a mean age of 56 years, had preoperative height and weight data, as well as measures of postoperative QoL, and formed the study group. The numbers of patients with recurrent (n = 17) or locally-advanced rectal cancer (n = 14) were similar. The mean length of stay was 21 days while the mean BMI of the patients was 24.3 (± 5.9) kg/m2. The majority of the patients were either of normal weight (n = 15) or overweight/obese (n = 11). The average length of hospital stay was significantly longer in patients who were underweight compared to those who were of normal weight (F = 6.508, P = 0.006) and those who were overweight and obese (F = 6.508, P = 0.007). Conclusion: This study suggests that a lower body mass index preoperatively is associated with a longer length of hospital stay. BMI is not associated with long-term QoL in this patient group. However, further prospective research is required.
Hatt, Dylan,Beaton, Rachael L.,Freedman, Wendy L.,Madore, Barry F.,Jang, In-Sung,Hoyt, Taylor J.,Lee, Myung Gyoon,Monson, Andrew J.,Rich, Jeffrey A.,Scowcroft, Victoria,Seibert, Mark American Astronomical Society 2017 The Astrophysical Journal Vol.845 No.2
<P>IC 1613 is an isolated dwarf galaxy within the Local Group. Low foreground and internal extinction, low metallicity, and low crowding make it an invaluable testbed for the calibration of the local distance ladder. We present new, high-fidelity distance estimates to IC 1613 via its Tip of the Red Giant Branch (TRGB) and its RR Lyrae (RRL) variables as part of the Carnegie-Chicago Hubble Program, which seeks an alternate local route to H-0 using Population II stars. We have measured a TRGB magnitude I-ACS(TRGB) = 20.35 +/- 0.01(stat) +/- 0.01(sys) mag using wide-field observations obtained from the IMACS camera on the Magellan-Baade telescope. We have further constructed optical and near-infrared RRL light curves using archival BI-and new H-band observations from the ACS/WFC and WFC3/IR instruments on board the Hubble Space Telescope (HST). In advance of future Gaia data releases, we set provisional values for the TRGB luminosity via the Large Magellanic Cloud and Galactic RRL zero-points via HST parallaxes. We find corresponding true distance moduli mu(TRGB)(0) = 24.30 +/- 0.03(stat) +/- 0.05(sys) mag and mu(RRL)(0) 24.28 +/- 0.04(stat+sys) mag. We compare our results to a body of recent publications on IC 1613 and find no statistically significant difference between the distances derived from Population. I and II stars.</P>
Lee, Myung Gyoon,Jang, In Sung,Beaton, Rachael,Seibert, Mark,Bono, Giuseppe,Madore, Barry American Astronomical Society 2017 ASTROPHYSICAL JOURNAL LETTERS - Vol.835 No.2
<P>Ultra-faint dwarf galaxies (UFDs) are the faintest known galaxies, and due to their incredibly low surface brightness, it is difficult to find them beyond the Local Group. We report a serendipitous discovery of a UFD, Fornax UFD1, in the outskirts of NGC 1316, a giant galaxy in the Fornax cluster. The new galaxy is located at a projected radius of 55 kpc in the south-east of NGC 1316. This UFD is found as a small group of resolved stars in the Hubble Space Telescope images of a halo field of NGC 1316, obtained as part of the Carnegie-Chicago Hubble Program. Resolved stars in this galaxy are consistent with being mostly metal-poor red giant branch (RGB) stars. Applying the tip of the RGB method to the mean magnitude of the two brightest RGB stars, we estimate the distance to this galaxy, 19.0. +/-. 1.3 Mpc. Fornax UFD1 is probably a member of the Fornax cluster. The color-magnitude diagram of these stars is matched by a 12 Gyr isochrone with low metallicity ([Fe/H]approximate to-2.4). Total magnitude and effective radius of Fornax UFD1 are M-V approximate to -7.6 +/- 0.2 mag and r(eff) = 146 +/- 9 pc, which are similar to those of Virgo UFD1 that was discovered recently in the intracluster field of Virgo by Jang & Lee. Fornax UFD1 is the most distant known UFD that is confirmed by resolved stars. This indicates that UFDs are ubiquitous and that more UFDs remain to be discovered in the Fornax cluster.</P>
Jang, In Sung,Hatt, Dylan,Beaton, Rachael L.,Lee, Myung Gyoon,Freedman, Wendy L.,Madore, Barry F.,Hoyt, Taylor J.,Monson, Andrew J.,Rich, Jeffrey A.,Scowcroft, Victoria,Seibert, Mark American Astronomical Society 2018 The Astrophysical journal Vol.852 No.1
<P>The Carnegie-Chicago Hubble Program (CCHP) seeks to anchor the distance scale of Type la supernovae via the Tip of the Red Giant Branch (TRGB) method. Based on deep Hubble Space Telescope ACS/WFC imaging, we present an analysis of the TRGB for the metal-poor halo of NGC 1365, a giant spiral galaxy in the Fornax cluster that was host to the Type la supernova SN 2012fr. We have measured the extinction-corrected TRGB magnitude of NGC 1365 to be F814W = 27.34 +/- 0.03(stat) +/- 0.04(sys) mag. In advance of future direct calibration by Gala, we adopt a provisiona I-band TRGB luminosity set at the Large Magellanic Cloud and find a true distance modulus mu(0) = 31.29 +/- 0.04(stat) +/- 0.06(sys) mag or D = 18.1 +/- 0.3(stat) +/- 0.5(sys) Mpc. This measurement is in excellent agreement with recent Cepheid-based distances to NGC 1365 and reveals no significant difference in the distances derived from stars of Populations I and II for this galaxy. We revisit the error budget for the CCHP path to the Hubble constant based on the analysis presented here, i.e., that for one of the most distant Type la supernova hosts within our Program, and find that a 2.5% measurement is feasible with the current sample of galaxies and TRGB absolute calibration.</P>