The Impact Of Insider Trading On Market Liquidity In The NASDAQ Market

This study examines the relationship between insider trading and market liquidity (spread and depth) of NASDAQ-100 stocks. Tests on an intraday sample of sell trades show no evidence of cross-sectional association between the width of the spread and insider trading, but detect some widening of the spread after the fact. Overall, our results provide mixed evidence on the ability of NASDAQ dealers to unravel informed order flow and adjust spreads accordingly. Their short-term behavior suggests an inability to detect insider trading and widen spreads, but their behavior over time suggests that dealers may attempt to recover what they apparently lose at a given point and time

The Impact Of Insider Trading On Market Liquidity In The NASDAQ Market

This study examines the relationship between insider trading and market liquidity (spread and depth) of NASDAQ-100 stocks.  Tests on an intraday sample of sell trades show no evidence of cross-sectional association between the width of the spread and insider trading, but detect some widening of the spread after the fact.  Overall, our results provide mixed evidence on the ability of NASDAQ dealers to unravel informed order flow and adjust spreads accordingly.  Their short-term behavior suggests an inability to detect insider trading and widen spreads, but their behavior over time suggests that dealers may attempt to recover what they apparently lose at a given point and time

An electrostatic mechanism for Ca(2+)-mediated regulation of gap junction channels.

Gap junction channels mediate intercellular signalling that is crucial in tissue development, homeostasis and pathologic states such as cardiac arrhythmias, cancer and trauma. To explore the mechanism by which Ca(2+) blocks intercellular communication during tissue injury, we determined the X-ray crystal structures of the human Cx26 gap junction channel with and without bound Ca(2+). The two structures were nearly identical, ruling out both a large-scale structural change and a local steric constriction of the pore. Ca(2+) coordination sites reside at the interfaces between adjacent subunits, near the entrance to the extracellular gap, where local, side chain conformational rearrangements enable Ca(2+)chelation. Computational analysis revealed that Ca(2+)-binding generates a positive electrostatic barrier that substantially inhibits permeation of cations such as K(+) into the pore. Our results provide structural evidence for a unique mechanism of channel regulation: ionic conduction block via an electrostatic barrier rather than steric occlusion of the channel pore

Pea3 Transcription Factors and Wnt1-Induced Mouse Mammary Neoplasia

The role of the PEA3 subfamily of Ets transcription factors in breast neoplasia is controversial. Although overexpression of PEA3 (E1AF/ETV4), and of the related factors ERM (ETV5) and ER81 (ETV1), have been observed in human and mouse breast tumors, PEA3 factors have also been ascribed a tumor suppressor function. Here, we utilized the MMTV/Wnt1 mouse strain to further interrogate the role of PEA3 transcription factors in mammary tumorigenesis based on our previous observation that Pea3 is highly expressed in MMTV/Wnt1 mammary tumors. Pea3 expression in mouse mammary tissues was visualized using a Pea3NLSlacZ reporter strain. In normal mammary glands, Pea3 expression is predominantly confined to myoepithelial cells. Wnt1 transgene expression induced marked amplification of this cell compartment in nontumorous mammary glands, accompanied by an apparent increase in Pea3 expression. The pattern of Pea3 expression in MMTV/Wnt1 mammary glands recapitulated the cellular profile of activated β-catenin/TCF signaling, which was visualized using both β-catenin immunohistochemistry and the β-catenin/TCF-responsive reporter Axin2NLSlacZ. To test the requirement for PEA3 factors in Wnt1-induced tumorigenesis, we employed a mammary-targeted dominant negative PEA3 transgene, ΔNPEA3En. Expression of ΔNPEA3En delayed early-onset tumor formation in MMTV/Wnt1 virgin females (P = 0.03), suggesting a requirement for PEA3 factor function for Wnt1-driven tumor formation. Consistent with this observation, expression of the ΔNPEA3En transgene was profoundly reduced in mammary tumors compared to nontumorous mammary glands from bigenic MMTV/Wnt1, MMTV/ΔNPEA3En mice (P = 0.01). Our data provide the first description of Wnt1-mediated expansion of the Pea3-expressing myoepithelial compartment in nontumorous mammary glands. Consistent with this observation, mammary myoepithelium was selectively responsive to Wnt1. Together these data suggest the MMTV/Wnt1 strain as a potential model of basal breast cancer. Furthermore, this study provides evidence for a protumorigenic role of PEA3 factors in breast neoplasia, and supports targeting the PEA3 transcription factor family in breast cancer

The Atacama Cosmology Telescope: the stellar content of galaxy clusters selected using the Sunyaev-Zel'dovich effect

We present a first measurement of the stellar mass component of galaxy clusters selected via the Sunyaev-Zel'dovich (SZ) effect, using 3.6 um and 4.5 um photometry from the Spitzer Space Telescope. Our sample consists of 14 clusters detected by the Atacama Cosmology Telescope (ACT), which span the redshift range 0.27 < z < 1.07 (median z = 0.50), and have dynamical mass measurements, accurate to about 30 per cent, with median M500 = 6.9 x 10^{14} MSun. We measure the 3.6 um and 4.5 um galaxy luminosity functions, finding the characteristic magnitude (m*) and faint-end slope (alpha) to be similar to those for IR-selected cluster samples. We perform the first measurements of the scaling of SZ-observables (Y500 and y0) with both brightest cluster galaxy (BCG) stellar mass and total cluster stellar mass (M500star). We find a significant correlation between BCG stellar mass and Y500 (E(z)^{-2/3} DA^2 Y500 ~ M*^{1.2 +/- 0.6}), although we are not able to obtain a strong constraint on the slope of the relation due to the small sample size. Additionally, we obtain E(z)^{-2/3} DA^2 Y500 ~ M500star^{1.0 +/- 0.6} for the scaling with total stellar mass. The mass fraction in stars spans the range 0.006-0.034, with the second ranked cluster in terms of dynamical mass (ACT-CL J0237-4939) having an unusually low total stellar mass and the lowest stellar mass fraction. For the five clusters with gas mass measurements available in the literature, we see no evidence for a shortfall of baryons relative to the cosmic mean value.Comment: Accepted for publication in MNRAS; 12 pages, 10 figure

Metagenomic study of the viruses of African straw-coloured fruit bats: detection of a chiropteran poxvirus and isolation of a novel adenovirus

Viral emergence as a result of zoonotic transmission constitutes a continuous public health threat. Emerging viruses such as SARS coronavirus, hantaviruses and henipaviruses have wildlife reservoirs. Characterising the viruses of candidate reservoir species in geographical hot spots for viral emergence is a sensible approach to develop tools to predict, prevent, or contain emergence events. Here, we explore the viruses of Eidolon helvum, an Old World fruit bat species widely distributed in Africa that lives in close proximity to humans. We identified a great abundance and diversity of novel herpes and papillomaviruses, described the isolation of a novel adenovirus, and detected, for the first time, sequences of a chiropteran poxvirus closely related with Molluscum contagiosum. In sum, E. helvum display a wide variety of mammalian viruses, some of them genetically similar to known human pathogens, highlighting the possibility of zoonotic transmission

Combination vinorelbine and capecitabine for metastatic breast cancer using a non-body surface area dosing scheme

Purpose : This study sought to determine the maximum tolerated dose of flat-dosed vinorelbine in combination with capecitabine in patients with metastatic breast cancer. At the time of study initiation, it was anticipated that vinorelbine would be developed as an oral capsule. A flat dosing scheme of both drugs was used to facilitate development of the oral regimen, and because neither drug’s clearance is associated with body surface area (BSA), pharmacokinetic and pharmacogenetic endpoints were explored. Experimental Design : Capecitabine was administered orally at 3,000 mg/day on days 1–14. The starting dose of vinorelbine was 20 mg intravenously on days 1 and 8 of a 21-day cycle. The vinorelbine dose was escalated until dose limiting toxicity (DLT). Vinorelbine pharmacokinetics were measured after the first dose. Patients underwent genotype analysis for polymorphisms in the CYP3A5 gene, and the erythromycin breath test (ERMBT), a phenotypic test of CYP3A enzyme activity. Results : Twenty five eligible patients were enrolled. Hematologic DLT was seen at the 50 and 45 mg vinorelbine doses; thus the recommended dose is 40 mg on days 1 and 8. Response rate was 30%, and disease stabilization rate was 64% (all dose levels included). Vinorelbine clearance was not associated with ERMBT, BSA, or age. CYP3A5 genotype in this small sample did not have an obvious relationship to clearance or toxicity. Conclusions : A non-BSA based dosing scheme of capecitabine and vinorelbine is safe and efficacious. BSA did not affect vinorelbine clearance. We recommend future studies with capecitabine and/or vinorelbine to compare the safety and efficacy of flat dosed versus BSA-dosed treatment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46933/1/280_2005_Article_132.pd

L-Edge Spectroscopy of Dilute, Radiation-Sensitive Systems Using a Transition-Edge-Sensor Array

We present X-ray absorption spectroscopy and resonant inelastic X-ray scattering (RIXS) measurements on the iron L-edge of 0.5 mM aqueous ferricyanide. These measurements demonstrate the ability of high-throughput transition-edge-sensor (TES) spectrometers to access the rich soft X-ray (100-2000eV) spectroscopy regime for dilute and radiation-sensitive samples. Our low-concentration data are in agreement with high-concentration measurements recorded by conventional grating-based spectrometers. These results show that soft X-ray RIXS spectroscopy acquired by high-throughput TES spectrometers can be used to study the local electronic structure of dilute metal-centered complexes relevant to biology, chemistry and catalysis. In particular, TES spectrometers have a unique ability to characterize frozen solutions of radiation- and temperature-sensitive samples.Comment: 19 pages, 4 figure

Design and performance of the PALM-3000 3.5 kHz upgrade

PALM-3000 (P3K), the second-generation adaptive optics (AO) instrument for the 5.1 meter Hale telescope at Palomar Observatory, underwent a significant upgrade to its wavefront sensor (WFS) arm and real-time control (RTC) system in late 2019. Main features of this upgrade include an EMCCD WFS camera capable of 3.5 kHz framerates and advanced Digital Signal Processor (DSP) boards to replace the aging GPU based real-time control system. With this upgrade P3K is able to maintain a lock on natural guide stars fainter than mV=16. Here we present the design and on-sky re-commissioning results of the upgraded system

The influence of gravimetric moisture content on studded shoe–surface interactions in soccer

It is desirable for the studs of a soccer shoe to penetrate the sport surface and provide the player with sufficient traction when accelerating. Mechanical tests are often used to measure the traction of shoe–surface combinations. Mechanical testing offers a repeatable measure of shoe–surface traction, eliminating the inherent uncertainties that exist when human participant testing is employed, and are hence used to directly compare the performance of shoe–surface combinations. However, the influence specific surface characteristics has on traction is often overlooked. Examining the influence of surface characteristics on mechanical test results improves the understanding of the traction mechanisms at the shoe–surface interface. This allows footwear developers to make informed decisions on the design of studded outsoles. The aim of this paper is to understand the effect gravimetric moisture content has on the tribological mechanisms at play during stud–surface interaction. This study investigates the relationships between: the gravimetric moisture content of a natural sand-based soccer surface; surface stiffness measured via a bespoke impact test device; and surface traction measured via a bespoke mechanical test device. Regression analysis revealed that surface stiffness decreases linearly with increased gravimetric moisture content (p = 0.04). Traction was found to initially increase and then decrease with gravimetric moisture content. It was observed that: a surface of low moisture content provides low stud penetration and therefore reduced traction; a surface of high moisture content provides high stud penetration but also reduced traction due to a lubricating effect; and surfaces with moisture content in between the two extremes provide increased traction. In this study a standard commercially available stud was used and other studs may provide slightly different results. The results provide insight into the traction mechanisms at the stud–surface interface which are described in the paper. The variation between traction measurements shows the influence gravimetric moisture content will have on player performance. This highlights the requirement to understand surface conditions prior to making comparative shoe–surface traction studies and the importance of using a studded outsole that is appropriate to the surface condition during play