Pluronic F68 block polymer, a very potent suppressor of carcinogenesis in the colon of rats and mice

Polyethylene-glycol (PEG) is a strong inhibitor of colon cancer in rats, and the most potent suppressor of aberrant crypt foci. 9 PEG-like block copolymers were tested in rodents, after an azoxymethane injection. Dietary pluronic F68 led to a 98.6% reduction in the number of aberrant crypt foci in a first rat study (P< 0.0001). Next 3 studies confirmed this pluronic efficacy in rats and mice. This non-toxic laxative seems roughly 5 times more potent than PEG for chemoprevention. © 2001 Cancer Research Campaign http://www.bjcancer.co

Exponential Random Graph Modeling for Complex Brain Networks

Exponential random graph models (ERGMs), also known as p* models, have been utilized extensively in the social science literature to study complex networks and how their global structure depends on underlying structural components. However, the literature on their use in biological networks (especially brain networks) has remained sparse. Descriptive models based on a specific feature of the graph (clustering coefficient, degree distribution, etc.) have dominated connectivity research in neuroscience. Corresponding generative models have been developed to reproduce one of these features. However, the complexity inherent in whole-brain network data necessitates the development and use of tools that allow the systematic exploration of several features simultaneously and how they interact to form the global network architecture. ERGMs provide a statistically principled approach to the assessment of how a set of interacting local brain network features gives rise to the global structure. We illustrate the utility of ERGMs for modeling, analyzing, and simulating complex whole-brain networks with network data from normal subjects. We also provide a foundation for the selection of important local features through the implementation and assessment of three selection approaches: a traditional p-value based backward selection approach, an information criterion approach (AIC), and a graphical goodness of fit (GOF) approach. The graphical GOF approach serves as the best method given the scientific interest in being able to capture and reproduce the structure of fitted brain networks

Obesity-induced insulin resistance in human skeletal muscle is characterised by defective activation of p42/p44 MAP kinase

Insulin resistance (IR), an impaired cellular, tissue and whole body response to insulin, is a major pathophysiological defect of type 2 diabetes mellitus. Although IR is closely associated with obesity, the identity of the molecular defect(s) underlying obesity-induced IR in skeletal muscle remains controversial; reduced post-receptor signalling of the insulin receptor substrate 1 (IRS1) adaptor protein and downstream effectors such as protein kinase B (PKB) have previously been implicated. We examined expression and/or activation of a number of components of the insulin-signalling cascade in skeletal muscle of 22 healthy young men (with body mass index (BMI) range, 20–37 kg/m2). Whole body insulin sensitivity (M value) and body composition was determined by the hyperinsulinaemic (40 mU. min−1.m−2.), euglycaemic clamp and by dual energy X-ray absorptiometry (DEXA) respectively. Skeletal muscle (vastus lateralis) biopsies were taken before and after one hour of hyperinsulinaemia and the muscle insulin signalling proteins examined by western blot and immunoprecipitation assay. There was a strong inverse relationship between M-value and BMI. The most striking abnormality was significantly reduced insulin-induced activation of p42/44 MAP kinase, measured by specific assay, in the volunteers with poor insulin sensitivity. However, there was no relationship between individuals' BMI or M-value and protein expression/phosphorylation of IRS1, PKB, or p42/44 MAP kinase protein, under basal or hyperinsulinaemic conditions. In the few individuals with poor insulin sensitivity but preserved p42/44 MAP kinase activation, other signalling defects were evident. These findings implicate defective p42/44 MAP kinase signalling as a potential contributor to obesity-related IR in a non-diabetic population, although clearly multiple signalling defects underlie obesity associated IR

All-sky search for time-integrated neutrino emission from astrophysical sources with 7 years of IceCube data

Since the recent detection of an astrophysical flux of high energy neutrinos, the question of its origin has not yet fully been answered. Much of what is known about this flux comes from a small event sample of high neutrino purity, good energy resolution, but large angular uncertainties. In searches for point-like sources, on the other hand, the best performance is given by using large statistics and good angular reconstructions. Track-like muon events produced in neutrino interactions satisfy these requirements. We present here the results of searches for point-like sources with neutrinos using data acquired by the IceCube detector over seven years from 2008--2015. The discovery potential of the analysis in the northern sky is now significantly below $E_\nu^2d\phi/dE_\nu=10^{-12}\:\mathrm{TeV\,cm^{-2}\,s^{-1}}$, on average $38\%$ lower than the sensitivity of the previously published analysis of four years exposure. No significant clustering of neutrinos above background expectation was observed, and implications for prominent neutrino source candidates are discussed.Comment: 19 pages, 17 figures, 3 tables; ; submitted to The Astrophysical Journa

Measurement of the multi-TeV neutrino cross section with IceCube using Earth absorption

Neutrinos interact only very weakly, so they are extremely penetrating. However, the theoretical neutrino-nucleon interaction cross section rises with energy such that, at energies above 40 TeV, neutrinos are expected to be absorbed as they pass through the Earth. Experimentally, the cross section has been measured only at the relatively low energies (below 400 GeV) available at neutrino beams from accelerators \cite{Agashe:2014kda, Formaggio:2013kya}. Here we report the first measurement of neutrino absorption in the Earth, using a sample of 10,784 energetic upward-going neutrino-induced muons observed with the IceCube Neutrino Observatory. The flux of high-energy neutrinos transiting long paths through the Earth is attenuated compared to a reference sample that follows shorter trajectories through the Earth. Using a fit to the two-dimensional distribution of muon energy and zenith angle, we determine the cross section for neutrino energies between 6.3 TeV and 980 TeV, more than an order of magnitude higher in energy than previous measurements. The measured cross section is $1.30^{+0.21}_{-0.19}$ (stat.) $^{+0.39}_{-0.43}$ (syst.) times the prediction of the Standard Model \cite{CooperSarkar:2011pa}, consistent with the expectation for charged and neutral current interactions. We do not observe a dramatic increase in the cross section, expected in some speculative models, including those invoking new compact dimensions \cite{AlvarezMuniz:2002ga} or the production of leptoquarks \cite{Romero:2009vu}.Comment: Preprint version of Nature paper 10.1038/nature2445

Search for astrophysical sources of neutrinos using cascade events in IceCube

The IceCube neutrino observatory has established the existence of a flux of high-energy astrophysical neutrinos inconsistent with the expectation from atmospheric backgrounds at a significance greater than $5\sigma$. This flux has been observed in analyses of both track events from muon neutrino interactions and cascade events from interactions of all neutrino flavors. Searches for astrophysical neutrino sources have focused on track events due to the significantly better angular resolution of track reconstructions. To date, no such sources have been confirmed. Here we present the first search for astrophysical neutrino sources using cascades interacting in IceCube with deposited energies as small as 1 TeV. No significant clustering was observed in a selection of 263 cascades collected from May 2010 to May 2012. We show that compared to the classic approach using tracks, this statistically-independent search offers improved sensitivity to sources in the southern sky, especially if the emission is spatially extended or follows a soft energy spectrum. This enhancement is due to the low background from atmospheric neutrinos forming cascade events and the additional veto of atmospheric neutrinos at declinations $\lesssim-30^\circ$.Comment: 14 pages, 9 figures, 1 tabl

Observation and Characterization of a Cosmic Muon Neutrino Flux from the Northern Hemisphere using six years of IceCube data

The IceCube Collaboration has previously discovered a high-energy astrophysical neutrino flux using neutrino events with interaction vertices contained within the instrumented volume of the IceCube detector. We present a complementary measurement using charged current muon neutrino events where the interaction vertex can be outside this volume. As a consequence of the large muon range the effective area is significantly larger but the field of view is restricted to the Northern Hemisphere. IceCube data from 2009 through 2015 have been analyzed using a likelihood approach based on the reconstructed muon energy and zenith angle. At the highest neutrino energies between 191 TeV and 8.3 PeV a significant astrophysical contribution is observed, excluding a purely atmospheric origin of these events at $5.6\,\sigma$ significance. The data are well described by an isotropic, unbroken power law flux with a normalization at 100 TeV neutrino energy of $\left(0.90^{+0.30}_{-0.27}\right)\times10^{-18}\,\mathrm{GeV^{-1}\,cm^{-2}\,s^{-1}\,sr^{-1}}$ and a hard spectral index of $\gamma=2.13\pm0.13$. The observed spectrum is harder in comparison to previous IceCube analyses with lower energy thresholds which may indicate a break in the astrophysical neutrino spectrum of unknown origin. The highest energy event observed has a reconstructed muon energy of $(4.5\pm1.2)\,\mathrm{PeV}$ which implies a probability of less than 0.005% for this event to be of atmospheric origin. Analyzing the arrival directions of all events with reconstructed muon energies above 200 TeV no correlation with known $\gamma$-ray sources was found. Using the high statistics of atmospheric neutrinos we report the currently best constraints on a prompt atmospheric muon neutrino flux originating from charmed meson decays which is below $1.06$ in units of the flux normalization of the model in Enberg et al. (2008).Comment: 20 pages, 21 figure