A Microfabricated Platform for Generating Physiologically-Relevant Hepatocyte Zonation

In vitro liver models have been important tools for more than 40 years for academic research and preclinical toxicity screening by the pharmaceutical industry. Hepatocytes, the highly metabolic parenchymal cells of the liver, are efficient at different metabolic chemistries depending on their relative spatial location along the sinusoid from the portal triad to the central vein. Although replicating hepatocyte metabolic zonation is vitally important for physiologically-relevant in vitro liver tissue and organ models, it is most often completely overlooked. Here, we demonstrate the creation of spatially-controlled zonation across multiple hepatocyte metabolism levels through the application of precise concentration gradients of exogenous hormone (insulin and glucagon) and chemical (3-methylcholanthrene) induction agents in a microfluidic device. Observed gradients in glycogen storage via periodic acid-Schiff staining, urea production via carbamoyl phosphatase synthetase I staining, and cell viability after exposure to allyl alcohol and acetaminophen demonstrated the in vitro creation of hepatocyte carbohydrate, nitrogen, alcohol degradation, and drug conjugation metabolic zonation. This type of advanced control system will be crucial for studies evaluating drug metabolism and toxicology using in vitro constructs

Exploratory Chandra Observations of the Three Highest Redshift Quasars Known

We report on exploratory Chandra observations of the three highest redshift quasars known (z = 5.82, 5.99, and 6.28), all found in the Sloan Digital Sky Survey. These data, combined with a previous XMM-Newton observation of a z = 5.74 quasar, form a complete set of color-selected, z > 5.7 quasars. X-ray emission is detected from all of the quasars at levels that indicate that the X-ray to optical flux ratios of z ~ 6 optically selected quasars are similar to those of lower redshift quasars. The observations demonstrate that it will be feasible to obtain quality X-ray spectra of z ~ 6 quasars with current and future X-ray missions.Comment: 15 pages, ApJL, in press; small revisions to address referee Comment

ARITHMETIC USING WORD-WISE HOMOMORPHIC ENCRYPTION

Homomorphic encryption has progressed rapidly in both efficiency and versatility since its emergence in 2009. Meanwhile, a multitude of pressing privacy needs --- ranging from cloud computing to healthcare management to the handling of shared databases such as those containing genomics data --- call for immediate solutions that apply fully homomorpic encryption (FHE) and somewhat homomorphic encryption (SHE) technologies. Further progress towards these ends requires new ideas for the efficient implementation of algebraic operations on word-based (as opposed to bit-wise) encrypted data. Whereas handling data encrypted at the bit level leads to % leaves us with prohibitively slow algorithms for the arithmetic operations that are essential for cloud computing, the word-based approach hits its bottleneck when operations such as integer comparison are needed. In this work, we tackle this challenging problem, proposing solutions to problems --- including comparison and division --- in word-based encryption via a leveled FHE scheme. We present concrete performance figures for all proposed primitives

NTRU Modular Lattice Signature Scheme on CUDA GPUs

In this work we show how to use Graphics Processing Units (GPUs) with Compute Unified Device Architecture (CUDA) to accelerate a lattice based signature scheme, namely, the NTRU modular lattice signature (NTRU-MLS) scheme. Lattice based schemes require operations on large vectors that are perfect candidates for GPU implementations. In addition, similar to most lattice based signature schemes, NTRU-MLS provides transcript security with a rejection sampling technique. With a GPU implementation, we are able to generate many candidates simultaneously, and hence mitigate the performance slowdown from rejection sampling. Our implementation results show that for the original NTRU-MLS parameter sets, we obtain a 2x improvement in the signing speed; for the revised parameter sets, where acceptance rate of rejection sampling is down to around 1%, our implementation can be as much as 47x faster than a CPU implementation

Microvessel stenosis, enlarged perivascular spaces, and fibrinogen deposition are associated with ischemic periventricular white matter hyperintensities

Periventricular white matter hyperintensities (pvWMH) are neuroimaging abnormalities surrounding the lateral ventricles that are apparent on magnetic resonance imaging (MRI). They are associated with age, neurodegenerative disease, and cerebrovascular risk factors. While pvWMH ultimately represent a loss of white matter structural integrity, the pathological causes are heterogeneous in nature, and currently, cannot be distinguished using neuroimaging alone. pvWMH could occur because of a combination of small vessel disease (SVD), ependymal loss, blood–brain barrier dysfunction, and microgliosis. In this study we aimed to characterize microvascular stenosis, fibrinogen extravasation, and microgliosis within pvWMH with and without imaging evidence of periventricular infarction. Using postmortem neuroimaging of human brains (n = 20), we identified pvWMH with and without periventricular infarcts (PVI). We performed histological analysis of microvessel stenosis, perivascular spaces, microgliosis, and immunohistochemistry against fibrinogen as a measure of serum protein extravasation. Herein, we report distinctions between pvWMH with and without periventricular infarcts based on associations with microvessel stenosis, enlarged perivascular spaces, and fibrinogen IHC. Microvessel stenosis was significantly associated with PVI and with cellular deposition of fibrinogen in the white matter. The presence of fibrinogen was associated with PVI and increased number of microglia. These findings suggest that neuroimaging-based detection of infarction within pvWMH may help distinguish more severe lesions, associated with underlying microvascular disease and BBB dysfunction, from milder pvWMH that are a highly frequent finding on MRI

The First High Redshift Quasar from Pan-STARRS

We present the discovery of the first high redshift (z > 5.7) quasar from the Panoramic Survey Telescope and Rapid Response System 1 (Pan-STARRS1 or PS1). This quasar was initially detected as an i dropoutout in PS1, confirmed photometrically with the SAO Widefield InfraRed Camera (SWIRC) at Arizona's Multiple Mirror Telescope (MMT) and the Gamma-Ray Burst Optical/Near-Infrared Detector (GROND) at the MPG 2.2 m telescope in La Silla. The quasar was verified spectroscopically with the the MMT Spectrograph, Red Channel and the Cassegrain Twin Spectrograph (TWIN) at the Calar Alto 3.5 m telescope. It has a redshift of 5.73, an AB z magnitude of 19.4, a luminosity of 3.8 x 10^47 erg/s and a black hole mass of 6.9 x 10^9 solar masses. It is a Broad Absorption Line quasar with a prominent Ly-beta peak and a very blue continuum spectrum. This quasar is the first result from the PS1 high redshift quasar search that is projected to discover more than a hundred i dropout quasars, and could potentially find more than 10 z dropout (z > 6.8) quasars.Comment: 8 pages, 7 figure

Ernst Freund as Precursor of the Rational Study of Corporate Law

Gindis, David, Ernst Freund as Precursor of the Rational Study of Corporate Law (October 27, 2017). Journal of Institutional Economics, Forthcoming. Available at SSRN: https://ssrn.com/abstract=2905547, doi: https://dx.doi.org/10.2139/ssrn.2905547The rise of large business corporations in the late 19th century compelled many American observers to admit that the nature of the corporation had yet to be understood. Published in this context, Ernst Freund's little-known The Legal Nature of Corporations (1897) was an original attempt to come to terms with a new legal and economic reality. But it can also be described, to paraphrase Oliver Wendell Holmes, as the earliest example of the rational study of corporate law. The paper shows that Freund had the intuitions of an institutional economist, and engaged in what today would be called comparative institutional analysis. Remarkably, his argument that the corporate form secures property against insider defection and against outsiders anticipated recent work on entity shielding and capital lock-in, and can be read as an early contribution to what today would be called the theory of the firm.Peer reviewe