The Chicken Yolk Sac IgY Receptor, a Mammalian Mannose Receptor Family Member, Transcytoses IgY across Polarized Epithelial Cells

In mammals the transfer of passive immunity from mother to young is mediated by the MHC-related receptor FcRn, which transports maternal IgG across epithelial cell barriers. In birds, maternal IgY in egg yolk is transferred across the yolk sac to passively immunize chicks during gestation and early independent life. The chicken yolk sac IgY receptor (FcRY) is the ortholog of the mammalian phospholipase A2 receptor, a mannose receptor family member, rather than an FcRn or MHC homolog. FcRn and FcRY both exhibit ligand binding at the acidic pH of endosomes and ligand release at the slightly basic pH of blood. Here we show that FcRY expressed in polarized mammalian epithelial cells functioned in endocytosis, bidirectional transcytosis, and recycling of chicken FcY/IgY. Confocal immunofluorescence studies demonstrated that IgY binding and endocytosis occurred at acidic but not basic pH, mimicking pH-dependent uptake of IgG by FcRn. Colocalization studies showed FcRY-mediated internalization via clathrin-coated pits and transport involving early and recycling endosomes. Disruption of microtubules partially inhibited apical-to-basolateral and basolateral-to-apical transcytosis, but not recycling, suggesting the use of different trafficking machinery. Our results represent the first cell biological evidence of functional equivalence between FcRY and FcRn and provide an intriguing example of how evolution can give rise to systems in which similar biological requirements in different species are satisfied utilizing distinct protein folds

The Spatial Distribution of the Galactic First Stars I: High-Resolution N-body Approach

We study the spatial distribution of Galactic metal-free stars by combining an extremely high-resolution (7.8 X 10^5 solar masses per particle) Cold Dark Matter N-body simulation of the Milky-Way with a semi-analytic model of metal enrichment. This approach allows us to resolve halos with virial temperatures down to the 10^4K atomic cooling limit, and it is sufficiently flexible to make a number of robust conclusions, despite the extremely uncertain properties of the first stars. Galactic metal-free stars are formed over a large redshift range, which peaks at z~10, but continues down to z~5, contributing stars at wide range of Galactocentric radii. Stars containing only metals generated by primordial stars are similarly widespread. Neither changing the efficiency of metal dispersal by two orders of magnitude, nor drastically changing the approximations in our semi-analytical model can affect these result. Thus, if they have sufficiently long lifetimes, a significant number of stars formed in initially primordial star clusters should be found in the nearby Galactic halo regardless of the specifics of metal-free star formation. Observations of metal abundances in Galactic halo stars should be taken as directly constraining the properties of primordial stars, and the lack of metal-free halo stars today should be taken as strongly suggesting a 0.8 solar mass lower limit on the primordial initial mass function.Comment: 17 Pages, ApJ, in Press. Higher resolution version available here: http://www.ociw.edu/~dkawata/for/evan/draft/final/ms.pd

The Universe Was Reionized Twice

We show the universe was reionized twice, first at z~15-16 and second at z~6. Such an outcome appears inevitable, when normalizing to two well determined observational measurements, namely, the epoch of the final cosmological reionization at z~6 and the density fluctuations at z~6, which in turn are tight ly constrained by Lyman alpha forest observations at z~3. These two observations most importantly fix the product of star formation efficiency and ionizing photon escape fraction from galaxies at high redshift. To the extent that the relative star formation efficiencies in gaseous minihalos with H2 cooling and large halos with atomic cooling at high redshift are still unknown, the primary source for the first reionization could be Pop III stars either in minihalos or in large halos. We show that gas in minihalos can be cooled efficiently by H2 molecules and star formation can continue to take place largely unimpeded throughout the first reionization period, thanks to two new mechanisms for generating a high X-ray background during the Pop III era, put forth here. Moreover, an important process for producing a large number of H2 molecules in relic HII regions of Pop III galaxies, first pointed out by Ricotti, Gnedin, & Shull, is quantified here. It is shown that the Lyman-Werner background may never build up during the Pop III era. The long cosmological reionization and reheating history is complex. We discuss a wide range of implications and possible tests for this new reionization picture. In particular, Thomson scattering optical depth is increased to 0.10 +- 0.03, compared to 0.027 for the case of only one rapid reionization at z=6. Upcoming Microwave Anisotropy Probe observation of the polarization of the cosmic microwave background should be able to distinguish between these two scenarios.Comment: submitted to ApJ, 69 pages, substantial revision made and conclusions strengthene

Trieste: Efficiently Exploring The Depths of Black-box Functions with TensorFlow

We present Trieste, an open-source Python package for Bayesian optimization and active learning benefiting from the scalability and efficiency of TensorFlow. Our library enables the plug-and-play of popular TensorFlow-based models within sequential decision-making loops, e.g. Gaussian processes from GPflow or GPflux, or neural networks from Keras. This modular mindset is central to the package and extends to our acquisition functions and the internal dynamics of the decision-making loop, both of which can be tailored and extended by researchers or engineers when tackling custom use cases. Trieste is a research-friendly and production-ready toolkit backed by a comprehensive test suite, extensive documentation, and available at https://github.com/secondmind-labs/trieste

Modes of Foreign Entry under Asymmetric Information about Potential Technology Spillovers

This paper studies the effect of technology spillovers on the entry decision of a multinational enterprise into a foreign market. Two alternative entry modes for a foreign direct investment are considered: Greenfield investment versus acquisition. We find that with quantity competition a spillover makes acquisitions less attractive, while with price competition acquisitions become more attractive. Asymmetric information about potential spillovers always reduces the number of acquisitions independently of whether the host country or the entrant has private information. Interestingly, we find that asymmetric information always hurts the entrant, while it sometimes is in favor of the host country

Oscillatory Shear Flow-Induced Alignment of Lamellar Melts of Hydrogen-Bonded Comb Copolymer Supramolecules

In this work we present the orientational behavior of comb copolymer-like supramolecules P4VP(PDP)1.0, obtained by hydrogen bonding between poly(4-vinylpyridine) and pentadecylphenol, during large-amplitude oscillatory shear flow experiments over a broad range of frequencies (0.001-10 Hz). The alignment diagram, presenting the macroscopic alignment in T/TODT vs ω/ωc, contains three regions of parallel alignment separated by a region of perpendicular alignment. For our material, the order-disorder temperature TODT = 67 °C and ωc, the frequency above which the distortion of the chain conformation dominates the materials’ viscoelasticity, is around 0.1 Hz at 61 °C. For the first time flipping from a pure transverse alignment via biaxial transverse/perpendicular alignment to a perpendicular alignment as a function of the strain amplitude was found.

Possible changes to arable crop yields by 2050

By 2050, the world population is likely to be 9.1 billion, the CO2 concentration 550 ppm, the ozone concentration 60 ppb and the climate warmer by ca 2°C. In these conditions, what contribution can increased crop yield make to feeding the world

FcRn-mediated antibody transport across epithelial cells revealed by electron tomography

The neonatal Fc receptor (FcRn) transports maternal IgG across epithelial barriers, thereby providing the fetus or newborn with humoral immunity before its immune system is fully functional. In newborn rats, FcRn transfers IgG from milk to blood by apical-to-basolateral transcytosis across intestinal epithelial cells. The pH difference between the apical (pH 6.0–6.5) and basolateral (pH 7.4) sides of intestinal epithelial cells facilitates the efficient unidirectional transport of IgG, because FcRn binds IgG at pH 6.0–6.5 but not at pH 7 or more. As milk passes through the neonatal intestine, maternal IgG is removed by FcRn-expressing cells in the proximal small intestine (duodenum and jejunum); remaining proteins are absorbed and degraded by FcRn-negative cells in the distal small intestine (ileum). Here we use electron tomography to make jejunal transcytosis visible directly in space and time, developing new labelling and detection methods to map individual nanogold-labelled Fc within transport vesicles and simultaneously to characterize these vesicles by immunolabelling. Combining electron tomography with a nonperturbing endocytic label allowed us to conclusively identify receptor-bound ligands, resolve interconnecting vesicles, determine whether a vesicle was microtubule-associated, and accurately trace FcRn-mediated transport of IgG. Our results present a complex picture in which Fc moves through networks of entangled tubular and irregular vesicles, only some of which are microtubule-associated, as it migrates to the basolateral surface. New features of transcytosis are elucidated, including transport involving multivesicular body inner vesicles/tubules and exocytosis through clathrin-coated pits. Markers for early, late and recycling endosomes each labelled vesicles in different and overlapping morphological classes, revealing spatial complexity in endo-lysosomal trafficking

Rethinking Radical Democracy

Over the course of three decades, vocabularies of radical democracy have pressed their stamp on democratic thought. Trading on the intuition that there is more to democracy than elections, they have generated critical insights into the important role that practices of pluralisation and critique play in bettering institutional politics. As a result, few would today deny the radical democratic contribution to democratic thought. What many might question, however, is its continuing traction. The paper probes this question, focusing on the nuanced place of democracy in contemporary radical work. It grapples with the difficulties that this poses for radical democrats and it suggests that a way of overcoming these difficulties – that threaten to undermine the coherence of radical democracy – is to rethink and reconstruct the distinctiveness of its vocabulary. The paper attempts such a reconstruction. It develops the idea of the promissory rule of the many and it discusses the ways it rejuvenates broader democratic thought