Increased signaling entropy in cancer requires the scale-free property of protein interaction networks

One of the key characteristics of cancer cells is an increased phenotypic plasticity, driven by underlying genetic and epigenetic perturbations. However, at a systems-level it is unclear how these perturbations give rise to the observed increased plasticity. Elucidating such systems-level principles is key for an improved understanding of cancer. Recently, it has been shown that signaling entropy, an overall measure of signaling pathway promiscuity, and computable from integrating a sample's gene expression profile with a protein interaction network, correlates with phenotypic plasticity and is increased in cancer compared to normal tissue. Here we develop a computational framework for studying the effects of network perturbations on signaling entropy. We demonstrate that the increased signaling entropy of cancer is driven by two factors: (i) the scale-free (or near scale-free) topology of the interaction network, and (ii) a subtle positive correlation between differential gene expression and node connectivity. Indeed, we show that if protein interaction networks were random graphs, described by Poisson degree distributions, that cancer would generally not exhibit an increased signaling entropy. In summary, this work exposes a deep connection between cancer, signaling entropy and interaction network topology.Comment: 20 pages, 5 figures. In Press in Sci Rep 201

Postweaning growth and carcass traits in crossbred cattle from Hereford, Angus, Brangus, Beefmaster, Bonsmara, and Romosinuano maternal grandsires

The objective of this study was to characterize breeds representing diverse biological types for postweaning growth and carcass composition traits in terminal crossbred cattle. Postweaning growth and carcass traits were analyzed on 464 steers and 439 heifers obtained by mating F1 cows to Charolais and U.S. Meat Animal Research Center III (1/4 Hereford, 1/4 Angus, 1/4 Pinzgauer, and ¼ Red Poll) sires. The F1 cows were obtained from mating Angus and U.S. Meat Animal Research Center III dams to Hereford, Angus, Beefmaster, Brangus, Bonsmara, and Romosinuano sires. Traits evaluated were postweaning ADG, slaughter weight, HCW, dressing percentage, percentage of carcasses classified as USDA Choice, LM area, marbling score, USDA yield grade, fat thickness, retail product yield (percentage), and retail product weight. Maternal grandsire breed was significant (P \u3c 0.05) for all traits. Animals with Angus grandsires grew faster and had the heaviest carcasses, with the greatest percentage of carcasses classified as USDA Choice and the greatest marbling scores when compared with other grandsire breeds. Animals with Romosinuano and Bonsmara inheritance grew slower, had the lightest weights at slaughter, the lightest carcass weights, the least percentage of carcasses classified as USDA Choice, and the least amount of marbling and fat thickness. Animals with inheritance from these 2 breeds had a more desirable yield grade with the greatest retail product yield. Maternal granddam breed was significant (P \u3c 0.05) for marbling score, USDA yield grade, fat thickness, and retail product yield. Sex class was significant (P \u3c 0.05) for all traits except for retail product yield. Steers grew faster, were heavier, had heavier carcasses, and were leaner than heifers. Heifers had a greater dressing percentage, a greater percentage of carcasses classified as USDA Choice, a greater LM area, and a decreased yield grade when compared with steers. Sire and grandsire breed effects can be optimized by selection and use of appropriate crossbreeding systems

Cloud type comparisons of AIRS, CloudSat, and CALIPSO cloud height and amount

The precision of the two-layer cloud height fields derived from the Atmospheric Infrared Sounder (AIRS) is explored and quantified for a five-day set of observations. Coincident profiles of vertical cloud structure by CloudSat, a 94 GHz profiling radar, and the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO), are compared to AIRS for a wide range of cloud types. Bias and variability in cloud height differences are shown to have dependence on cloud type, height, and amount, as well as whether CloudSat or CALIPSO is used as the comparison standard. The CloudSat-AIRS biases and variability range from −4.3 to 0.5±1.2–3.6 km for all cloud types. Likewise, the CALIPSO-AIRS biases range from 0.6–3.0±1.2–3.6 km (−5.8 to −0.2±0.5–2.7 km) for clouds ≥7 km (<7 km). The upper layer of AIRS has the greatest sensitivity to Altocumulus, Altostratus, Cirrus, Cumulonimbus, and Nimbostratus, whereas the lower layer has the greatest sensitivity to Cumulus and Stratocumulus. Although the bias and variability generally decrease with increasing cloud amount, the ability of AIRS to constrain cloud occurrence, height, and amount is demonstrated across all cloud types for many geophysical conditions. In particular, skill is demonstrated for thin Cirrus, as well as some Cumulus and Stratocumulus, cloud types infrared sounders typically struggle to quantify. Furthermore, some improvements in the AIRS Version 5 operational retrieval algorithm are demonstrated. However, limitations in AIRS cloud retrievals are also revealed, including the existence of spurious Cirrus near the tropopause and low cloud layers within Cumulonimbus and Nimbostratus clouds. Likely causes of spurious clouds are identified and the potential for further improvement is discussed

Astrometric calibration and performance of the Dark Energy Camera

We characterize the ability of the Dark Energy Camera (DECam) to perform relative astrometry across its 500~Mpix, 3 deg^2 science field of view, and across 4 years of operation. This is done using internal comparisons of ~4x10^7 measurements of high-S/N stellar images obtained in repeat visits to fields of moderate stellar density, with the telescope dithered to move the sources around the array. An empirical astrometric model includes terms for: optical distortions; stray electric fields in the CCD detectors; chromatic terms in the instrumental and atmospheric optics; shifts in CCD relative positions of up to ~10 um when the DECam temperature cycles; and low-order distortions to each exposure from changes in atmospheric refraction and telescope alignment. Errors in this astrometric model are dominated by stochastic variations with typical amplitudes of 10-30 mas (in a 30 s exposure) and 5-10 arcmin coherence length, plausibly attributed to Kolmogorov-spectrum atmospheric turbulence. The size of these atmospheric distortions is not closely related to the seeing. Given an astrometric reference catalog at density ~0.7 arcmin^{-2}, e.g. from Gaia, the typical atmospheric distortions can be interpolated to 7 mas RMS accuracy (for 30 s exposures) with 1 arcmin coherence length for residual errors. Remaining detectable error contributors are 2-4 mas RMS from unmodelled stray electric fields in the devices, and another 2-4 mas RMS from focal plane shifts between camera thermal cycles. Thus the astrometric solution for a single DECam exposure is accurate to 3-6 mas (0.02 pixels, or 300 nm) on the focal plane, plus the stochastic atmospheric distortion.Comment: Submitted to PAS

Scaling of Saddle-Node Bifurcations: Degeneracies and Rapid Quantitative Changes

The scaling of the time delay near a "bottleneck" of a generic saddle-node bifurcation is well-known to be given by an inverse square-root law. We extend the analysis to several non-generic cases for smooth vector fields. We proceed to investigate $C^0$ vector fields. Our main result is a new phenomenon in two-parameter families having a saddle-node bifurcation upon changing the first parameter. We find distinct scalings for different values of the second parameter ranging from power laws with exponents in (0,1) to scalings given by O(1). We illustrate this rapid quantitative change of the scaling law by a an overdamped pendulum with varying length.Comment: preprint version - for final version see journal referenc

Awards, incentives and mutual benefit

Frey argues that if buyers and sellers of labour understand their relationship merely as exchange, workers’ intrinsic motivation can be impaired; this problem can be partially overcome by using awards as a supplementary reward mechanism. I argue that this proposal is self-defeating. In an economy that relies on the division of labour, it is an unavoidable fact that individuals are subject to the will of others; award-giving practices are merely camouflage. However, recognising this fact need not impair anyone’s sense of autonomy as a paid worker if participation in market exchanges is understood as expressing intentions for mutual benefit

Semliki Forest virus induced, immune mediated demyelination: the effect of irradiation

International audienceThe Dark Energy Camera has captured a large set of images as part of Science Verification (SV) for the Dark Energy Survey (DES). The SV footprint covers a large portion of the outer Large Magellanic Cloud (LMC), providing photometry 1.5 mag fainter than the main sequence turn-off of the oldest LMC stellar population. We derive geometrical and structural parameters for various stellar populations in the LMC disc. For the distribution of all LMC stars, we find an inclination of i = -38.14° ± 0.08° (near side in the north) and a position angle for the line of nodes of θ0 = 129.51° ± 0.17°. We find that stars younger than ∼4 Gyr are more centrally concentrated than older stars. Fitting a projected exponential disc shows that the scale radius of the old populations is R>4 Gyr = 1.41 ± 0.01 kpc, while the younger population has R = 0.72 ± 0.01 kpc. However, the spatial distribution of the younger population deviates significantly from the projected exponential disc model. The distribution of old stars suggests a large truncation radius of Rt = 13.5 ± 0.8 kpc. If this truncation is dominated by the tidal field of the Galaxy, we find that the LMC is {∼eq } 24^{+9}_{-6} times less massive than the encircled Galactic mass. By measuring the Red Clump peak magnitude and comparing with the best-fitting LMC disc model, we find that the LMC disc is warped and thicker in the outer regions north of the LMC centre. Our findings may either be interpreted as a warped and flared disc in the LMC outskirts, or as evidence of a spheroidal halo component