A Dynamical Study of the Black Hole X-ray Binary Nova Muscae 1991

We present a dynamical study of the Galactic black hole binary system Nova Muscae 1991 (GS/GRS 1124-683). We utilize 72 high resolution Magellan Echellette (MagE) spectra and 72 strictly simultaneous V-band photometric observations; the simultaneity is a unique and crucial feature of this dynamical study. The data were taken on two consecutive nights and cover the full 10.4-hour orbital cycle. The radial velocities of the secondary star are determined by cross-correlating the object spectra with the best-match template spectrum obtained using the same instrument configuration. Based on our independent analysis of five orders of the echellette spectrum, the semi-amplitude of the radial velocity of the secondary is measured to be K_2 = 406.8+/-2.7 km/s, which is consistent with previous work, while the uncertainty is reduced by a factor of 3. The corresponding mass function is f(M) = 3.02+/-0.06 M_\odot. We have also obtained an accurate measurement of the rotational broadening of the stellar absorption lines (v sin i = 85.0+/-2.6 km/s) and hence the mass ratio of the system q = 0.079+/-0.007. Finally, we have measured the spectrum of the non-stellar component of emission that veils the spectrum of the secondary. In a future paper, we will use our veiling-corrected spectrum of the secondary and accurate values of K_2 and q to model multi-color light curves and determine the systemic inclination and the mass of the black hole.Comment: ApJ accepted version; minor revision; added a subsection about systematic uncertaintie

Tomography of X-ray Nova Muscae 1991: Evidence for ongoing mass transfer and stream-disc overflow

We present a spectroscopic analysis of the black hole binary Nova Muscae 1991 in quiescence using data obtained in 2009 with MagE on the Magellan Clay telescope and in 2010 with IMACS on the Magellan Baade telescope at the Las Campanas Observatory. Emission from the disc is observed in H alpha, H beta and Ca II (8662 A). A prominent hotspot is observed in the Doppler maps of all three emission lines. The existence of this spot establishes ongoing mass transfer from the donor star in 2009-2010 and, given its absence in the 1993-1995 observations, demonstrates the presence of a variable hotspot in the system. We find the radial distance to the hotspot from the black hole to be consistent with the circularization radius. Our tomograms are suggestive of stream-disc overflow in the system. We also detect possible Ca II (8662 A) absorption from the donor star.Comment: 10 pages, 11 figures, 1 table. Accepted for publication in MNRA

IR Contamination in Galactic X-Ray Novae

The most widely used means of measuring the mass of black holes in Galactic binaries - specifically the X-ray novae - involves both radial velocity measurements of the secondary star, and photometric measurements of its ellipsoidal variability. The latter is important in constraining the inclination and mass ratio, and requires as direct a measure of the flux of the secondary as possible. Up to now, such measurements have been preferentially carried out in the NIR (1 -- 2.5$\mu m$), where the flux from the cooler secondary is expected to dominate over that from the accretion disc. However, here we present evidence of a significant non-stellar contribution to the NIR flux in many of those quiescent X-ray novae that are thought to contain a black hole primary. We discuss origins of this excess and the effect of such contamination on Galactic black hole mass measurements.Comment: 9 pages, 4 figures, 2 tables, accepted for publication in MNRA

3D human liver tissue from pluripotent stem cells displays stable phenotype in vitro and supports compromised liver function in vivo.

Liver disease is an escalating global health issue. While liver transplantation is an effective mode of therapy, patient mortality has increased due to the shortage of donor organs. Developing renewable sources of human liver tissue is therefore attractive. Pluripotent stem cell-derived liver tissue represents a potential alternative to cadaver derived hepatocytes and whole organ transplant. At present, two-dimensional differentiation procedures deliver tissue lacking certain functions and long-term stability. Efforts to overcome these limiting factors have led to the building of three-dimensional (3D) cellular aggregates. Although enabling for the field, their widespread application is limited due to their reliance on variable biological components. Our studies focused on the development of 3D liver tissue under defined conditions. In vitro generated 3D tissues exhibited stable phenotype for over 1 year in culture, providing an attractive resource for long-term in vitro studies. Moreover, 3D derived tissue provided critical liver support in two animal models, including immunocompetent recipients. Therefore, we believe that our study provides stable human tissue to better model liver biology 'in the dish', and in the future may permit the support of compromised liver function in humans

Human biliary epithelial cells from discarded donor livers rescue bile duct structure and function in a mouse model of biliary disease

Biliary diseases can cause inflammation, fibrosis, bile duct destruction, and eventually liver failure. There are no curative treatments for biliary disease except for liver transplantation. New therapies are urgently required. We have therefore purified human biliary epithelial cells (hBECs) from human livers that were not used for liver transplantation. hBECs were tested as a cell therapy in a mouse model of biliary disease in which the conditional deletion of Mdm2 in cholangiocytes causes senescence, biliary strictures, and fibrosis. hBECs are expandable and phenotypically stable and help restore biliary structure and function, highlighting their regenerative capacity and a potential alternative to liver transplantation for biliary disease

Assessment of Long Term Neurodevelopmental Outcome Following Trials of Medicinal Products in Newborn Infants

Importance: There is significant uncertainty over the assessment of long-term neurodevelopmental outcome (LTO) in neonatal clinical trials. Objective: To identify key issues in the assessment of LTO. Design: To examine optimal approaches to evaluate LTO for therapeutic trials in newborns. Sponsors and investigators will develop the study (including LTO) with other key stakeholders. Method: Multidisciplinary working group report. Conclusions and Relevance: 1. The potential of the investigational product to cause widespread effects drives the need to assess outcome in multiple organs. 2. The nature of the intervention a. Does the investigational product have an impact on the brain? b. Are there potential effects of the investigational product on LTO? c. Should safety be assessed? 3. All decisions need to be specific to the product being studied using published data and only considering expert opinion when prior evidence does not exist. 4. The balance of benefits, costs, and burdens of assessments to the researcher and families need to be considered. 5. Families and parent advocates should be involved in design and execution of the study. All key stakeholders may use the framework to determine the need, nature, and duration of LTO assessments in regulatory trials involving newborn infants