Liver Development, Regeneration, and Carcinogenesis

The identification of putative liver stem cells has brought closer the previously separate fields of liver development, regeneration, and carcinogenesis. Significant overlaps in the regulation of these processes are now being described. For example, studies in embryonic liver development have already provided the basis for directed differentiation of human embryonic stem cells and induced pluripotent stem cells into hepatocyte-like cells. As a result, the understanding of the cell biology of proliferation and differentiation in the liver has been improved. This knowledge can be used to improve the function of hepatocyte-like cells for drug testing, bioartificial livers, and transplantation. In parallel, the mechanisms regulating cancer cell biology are now clearer, providing fertile soil for novel therapeutic approaches. Recognition of the relationships between development, regeneration, and carcinogenesis, and the increasing evidence for the role of stem cells in all of these areas, has sparked fresh enthusiasm in understanding the underlying molecular mechanisms and has led to new targeted therapies for liver cirrhosis and primary liver cancers

Ketamine as the anaesthetic for electroconvulsive therapy:the KANECT randomised controlled trial

C.AS. reports grants from Vifor Pharma, outside the submitted work. I.C.R. (deceased) declared personal fees from AstraZeneca, Sanofi Aventis and Sunovion, and non-financial support from Lundbeck, between 2009 and 2014 and all outside the submitted work. Volume 212, Issue 5 May 2018 , p. 323 Ketamine as the anaesthetic for electroconvulsive therapy: the KANECT randomised controlled trial – CORRIGENDUM Gordon Fernie, James Currie, Jennifer S. Perrin, Caroline A. Stewart... https://doi.org/10.1192/bjp.2018.76 Published online: 06 April 2018 Summary: This notice describes a correction to the above mentioned paper.Peer reviewedPublisher PD

Modelling Hepatic Endoderm Development: Highly Efficient Differentiation of Human Embryonic Stem Cells to Functional Hepatic Endoderm Requires ActivinA and Wnt3a Signalling.

Human embryonic stem cells (hESCs) are a valuable source of pluripotential primary cells. However, their homogeneous cellular differentiation to specific cell types _in vitro_ has proven difficult thus far. Wnt signalling has been shown to play important roles in coordinating development and we demonstrate that Wnt3a is differentially expressed at critical stages of human liver development _in vivo_. The essential role of Wnt3a in hepatocyte differentiation from hESCs is paralleled by our _in vitro_ model, demonstrating the importance of a physiological approach to cellular differentiation. Our studies provide compelling evidence that Wnt3a signaling is important for coordinated hepato-cellular function _in vitro_ and _in vivo_. In addition, we demonstrate Wnt3a facilitates clonal plating of hESCs capable of hepatic endoderm differentiation. These studies represent an important step forward toward the use of hESC-derived hepatocytes in biomedical applications and has opened the door to high through-put metabolic analysis of human liver function

Application of a damped Locally Optimized Combination of Images method to the spectral characterization of faint companions using an Integral Field Spectrograph

High-contrast imaging instruments are now being equipped with integral field spectrographs (IFS) to facilitate the detection and characterization of faint substellar companions. Algorithms currently envisioned to handle IFS data, such as the Locally Optimized Combination of Images (LOCI) algorithm, rely upon aggressive point-spread-function (PSF) subtraction, which is ideal for initially identifying companions but results in significantly biased photometry and spectroscopy due to unwanted mixing with residual starlight. This spectro-photometric issue is further complicated by the fact that algorithmic color response is a function of the companion's spectrum, making it difficult to calibrate the effects of the reduction without using iterations involving a series of injected synthetic companions. In this paper, we introduce a new PSF calibration method, which we call "damped LOCI", that seeks to alleviate these concerns. By modifying the cost function that determines the weighting coefficients used to construct PSF reference images, and also forcing those coefficients to be positive, it is possible to extract companion spectra with a precision that is set by calibration of the instrument response and transmission of the atmosphere, and not by post-processing. We demonstrate the utility of this approach using on-sky data obtained with the Project 1640 IFS at Palomar. Damped-LOCI does not require any iterations on the underlying spectral type of the companion, nor does it rely upon priors involving the chromatic and statistical properties of speckles. It is a general technique that can readily be applied to other current and planned instruments that employ IFS's.Comment: Accepted to the Astrophysical Journal Supplement

Speckle Suppression with the Project 1640 Integral Field Spectrograph

Project 1640 is a high-contrast imaging instrument recently commissioned at Palomar observatory. A combination of a coronagraph with an integral field spectrograph (IFS), Project 1640 is designed to detect and characterize extrasolar planets, brown dwarfs, and circumstellar material orbiting nearby stars. In this paper, we present our data processing techniques for improving upon instrument raw sensitivity via the removal of quasi-static speckles. Our approach utilizes the chromatic image diversity provided by the IFS in combination with the locally-optimized combination of images (LOCI) algorithm to suppress the intensity of residual contaminating light in close angular proximity to target stars. We describe the Project 1640 speckle suppression pipeline (PSSP) and demonstrate the ability to detect companions with brightness comparable to and below that of initial speckle intensities using on-sky commissioning data. Our preliminary results indicate that suppression factors of at least one order of magnitude are consistently possible, reaching $5\sigma$ contrast levels of $2.1\times10^{-5}$ at 1\arcsec in the H-band in 20 minutes of on-source integration time when non-common-path errors are reasonably well-calibrated. These results suggest that near-infrared contrast levels of order $\approx10^{-7}$ at subarcsecond separations will soon be possible for Project 1640 and similarly designed instruments that receive a diffraction-limited beam corrected by adaptive optics (AO) systems employing deformable mirrors with high actuator-density.Comment: accepted to Ap

Macrophage phenotype is associated with disease severity in preterm infants with chronic lung disease.

The etiology of persistent lung inflammation in preterm infants with chronic lung disease of prematurity (CLD) is poorly characterized, hampering efforts to stratify prognosis and treatment. Airway macrophages are important innate immune cells with roles in both the induction and resolution of tissue inflammation