Circadian Entrainment Triggers Maturation of Human In Vitro Islets

Stem-cell-derived tissues could transform disease research and therapy, yet most methods generate functionally immature products. We investigate how human pluripotent stem cells (hPSCs) differentiate into pancreatic islets in vitro by profiling DNA methylation, chromatin accessibility, and histone modification changes. We find that enhancer potential is reset upon lineage commitment and show how pervasive epigenetic priming steers endocrine cell fates. Modeling islet differentiation and maturation regulatory circuits reveals genes critical for generating endocrine cells and identifies circadian control as limiting for in vitro islet function. Entrainment to circadian feeding/fasting cycles triggers islet metabolic maturation by inducing cyclic synthesis of energy metabolism and insulin secretion effectors, including antiphasic insulin and glucagon pulses. Following entrainment, hPSC-derived islets gain persistent chromatin changes and rhythmic insulin responses with a raised glucose threshold, a hallmark of functional maturity, and function within days of transplantation. Thus, hPSC-derived tissues are amenable to functional improvement by circadian modulation

Second bound state of PsH

The existence of a second bound state of PsH that is electronically stable and also stable against positron annihilation by the normal 2gamma and 3gamma processes is demonstrated by explicit calculation. The state can be found in the 2,4So symmetries with the two electrons in a spin triplet state. The binding energy against dissociation into the H(2p) + Ps(2p) channel was 6.06x10-4 Hartree. The dominant decay mode of the states will be radiative decay into a configuration that autoionizes or undergoes positron annihilation. The NaPs system of the same symmetry is also electronically stable with a binding energy of 1.553x10-3 Hartree with respect to the Na(3p) + Ps(2p) channel.Comment: 4 pages, 2 figures, RevTex styl

The Revealing Dust: Mid-Infrared Activity in Hickson Compact Group Galaxy Nuclei

We present a sample of 46 galaxy nuclei from 12 nearby (z<4500 km/s) Hickson Compact Groups (HCGs) with a complete suite of 1-24 micron 2MASS+Spitzer nuclear photometry. For all objects in the sample, blue emission from stellar photospheres dominates in the near-IR through the 3.6 micron IRAC band. Twenty-five of 46 (54%) galaxy nuclei show red, mid-IR continua characteristic of hot dust powered by ongoing star formation and/or accretion onto a central black hole. We introduce alpha_{IRAC}, the spectral index of a power-law fit to the 4.5-8.0 micron IRAC data, and demonstrate that it cleanly separates the mid-IR active and non-active HCG nuclei. This parameter is more powerful for identifying low to moderate-luminosity mid-IR activity than other measures which include data at rest-frame lambda<3.6 micron that may be dominated by stellar photospheric emission. While the HCG galaxies clearly have a bimodal distribution in this parameter space, a comparison sample from the Spitzer Nearby Galaxy Survey (SINGS) matched in J-band total galaxy luminosity is continuously distributed. A second diagnostic, the fraction of 24 micron emission in excess of that expected from quiescent galaxies, f_{24D}, reveals an additional 3 nuclei to be active at 24 micron. Comparing these two mid-IR diagnostics of nuclear activity to optical spectroscopic identifications from the literature reveals some discrepancies, and we discuss the challenges of distinguishing the source of ionizing radiation in these and other lower luminosity systems. We find a significant correlation between the fraction of mid-IR active galaxies and the total HI mass in a group, and investigate possible interpretations of these results in light of galaxy evolution in the highly interactive system of a compact group environment.Comment: 20 pages, 17 figures (1 color), uses emulateapj. Accepted for publication by Ap

When the Window Cracks: Transparency and the Fractured Self in Depersonalisation

There has recently been a resurgence of philosophical and scientific interest in the foundations of self-consciousness, with particular focus on its altered, anomalous forms. This paper looks at the altered forms of self-awareness in Depersonalization Disorder (DPD), a condition in which people feel detached from their self, their body and the world (Derealisation). Building upon the phenomenological distinction between reflective and pre-reflective self-consciousness, we argue that DPD may alter the transparency of basic embodied forms of pre-reflective self-consciousness, as well as the capacity to flexibly modulate and switch between the reflective and pre-reflective facets of self-awareness. Empirical evidence will be invoked in support of the idea that impaired processing of bodily signals is characteristic of the condition. We provide first-hand subjective reports describing the experience of self-detachment or fracture between an observing and an observed self. This split is compared with similar self-detachment phenomena reported in certain Buddhist-derived meditative practices. We suggest that these alterations and changes may reveal the underlying and tacit transparency that characterises the embodied and basic pre-reflective forms of self-consciousness, in the same way that a crack in a transparent glass may indicate the presence of an unnoticed window

Performance of three-photon PET imaging: Monte Carlo simulations

We have recently introduced the idea of making use of three-photon positron annihilations in positron emission tomography. In this paper the basic characteristics of the three-gamma imaging in PET are studied by means of Monte Carlo simulations and analytical computations. Two typical configurations of human and small animal scanners are considered. Three-photon imaging requires high energy resolution detectors. Parameters currently attainable by CdZnTe semiconductor detectors, the technology of choice for the future development of radiation imaging, are assumed. Spatial resolution is calculated as a function of detector energy resolution and size, position in the field of view, scanner size, and the energies of the three gamma annihilation photons. Possible ways to improve the spatial resolution obtained for nominal parameters: 1.5 cm and 3.2 mm FWHM for human and small animal scanners, respectively, are indicated. Counting rates of true and random three-photon events for typical human and small animal scanning configurations are assessed. A simple formula for minimum size of lesions detectable in the three-gamma based images is derived. Depending on the contrast and total number of registered counts, lesions of a few mm size for human and sub mm for small animal scanners can be detected

Defining the complementarities between antibodies and haptens to refine our understanding and aid the prediction of a successful binding interaction

Acknowledgments The authors would like to thank the Scottish Universities Life Sciences Alliance (SULSA) for their support.Peer reviewedPublisher PD