The Hot and Energetic Universe: Astrophysics of feedback in local AGN

Understanding the astrophysics of feedback in active galactic nuclei (AGN) is key to understanding the growth and co-evolution of supermassive black holes and galaxies. AGN-driven winds/outflows are potentially the most effective way of transporting energy and momentum from the nuclear scales to the host galaxy, quenching star formation by sweeping away the gas reservoir. Key questions in this field are: 1) how do accretion disks around black holes launch winds/outflows, and how much energy do these carry? 2) How are the energy and metals accelerated in winds/outflows transferred and deposited into the circumgalactic medium? X-ray observations are a unique way to address these questions because they probe the phase of the outflows which carries most of the kinetic energy. We show how a high throughput, high spectral resolution instrument like the X-ray Integral Field Unit (X-IFU) on Athena+ will allow us to address these questions by determining the physical parameters (ionization state, density, temperature, abundances, velocities, geometry, etc.) of the outflows on a dynamical time-scale, in a broad sample of nearby bright AGN. The X-IFU will also allow direct spectral imaging of the impact of these winds on the host galaxy for local AGN, forming a template for understanding AGN at higher redshifts where wind shocks cannot be resolved.Comment: Supporting paper for the science theme "The Hot and Energetic Universe" to be implemented by the Athena+ X-ray observatory (http://www.the-athena-x-ray-observatory.eu). 10 pages, 6 figure

Características físico-químicas y estabilidad oxidativa de aceites de diferentes ecotipos de ricino peruano

The aim of this research was to assess the physico-chemical properties and shelf-life of oils press-extracted at two temperatures (60 °C and 80 °C) from five Peruvian castor bean ecotypes. A wide variation for all traits was observed. Low acidity index, low peroxide index and absence of p-anisidine were recorded. The total tocopherol contents ranged from 798 to 1040 mg/kg. A higher antioxidant capacity was detected in methanolic extracts than in hexane extract. From the Rancimat performed at 150-170 °C, the predicted shelf-life at 25 °C ranged from 0.15 to 8.93 years; the higher extraction temperature led to a longer shelf-life, probably because of enzyme inactivation.El objetivo de esta investigación fue estudiar las propiedades fisicoquímicas y la vida útil de aceite de ricino extraido a presión a dos temperaturas (60 y 80 °C) de cinco ecotipos peruanos. Se notó una amplia variación para todas las características. Se observaron bajos índice de acidez, bajo índice de peróxido y ausencia de p-anisidina. El contenido total de tocoferoles osciló entre 798 y 1040 mg/kg. Se detectó una mayor capacidad antioxidante en los extractos en metanol que en los extractos en hexano. A partir del Rancimat realizado a 150-170 °C, la vida útil prevista a 25 °C osciló entre 0.15 y 8.93 años; la mayor temperatura de extracción condujo a una vida útil más larga, probablemente debido a inactivación de las enzimas. &nbsp

Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca's large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells

Observation of an Excited Bc+ State

Using pp collision data corresponding to an integrated luminosity of 8.5 fb-1 recorded by the LHCb experiment at center-of-mass energies of s=7, 8, and 13 TeV, the observation of an excited Bc+ state in the Bc+π+π- invariant-mass spectrum is reported. The observed peak has a mass of 6841.2±0.6(stat)±0.1(syst)±0.8(Bc+) MeV/c2, where the last uncertainty is due to the limited knowledge of the Bc+ mass. It is consistent with expectations of the Bc∗(2S31)+ state reconstructed without the low-energy photon from the Bc∗(1S31)+→Bc+γ decay following Bc∗(2S31)+→Bc∗(1S31)+π+π-. A second state is seen with a global (local) statistical significance of 2.2σ (3.2σ) and a mass of 6872.1±1.3(stat)±0.1(syst)±0.8(Bc+) MeV/c2, and is consistent with the Bc(2S10)+ state. These mass measurements are the most precise to date

Aberrant iPSC-derived human astrocytes in Alzheimer's disease

The pathological potential of human astroglia in Alzheimer's disease (AD) was analysed in vitro using induced pluripotent stem cell (iPSC) technology. Here, we report development of a human iPSC-derived astrocyte model created from healthy individuals and patients with either early-onset familial AD (FAD) or the late-onset sporadic form of AD (SAD). Our chemically-defined and highly efficient model provides >95% homogeneous populations of human astrocytes within 30 days of differentiation from cortical neural progenitor cells (NPCs). All astrocytes expressed functional markers including; glial fibrillary acidic protein (GFAP), excitatory amino acid transporter 1 (EAAT1), S100B and glutamine synthetase (GS) comparable to that of adult astrocytes in vivo. However, induced astrocytes derived from both SAD and FAD patients exhibit a pronounced pathological phenotype, with a significantly less complex morphological appearance, overall atrophic profiles, and abnormal localisation of key functional astroglial markers. Furthermore, NPCs derived from identical patients did not show any differences, therefore, validating that remodelled astroglia are not as a result of defective neuronal intermediates. This work not only presents a novel model to study the mechanisms of human astrocytes in vitro, but also provides an ideal platform for further interrogation of early astroglial cell-autonomous events in AD and the possibility of identification of novel therapeutic targets for the treatment of AD

Selected Schizosaccharomyces pombe Strains Have Characteristics That Are Beneficial for Winemaking

At present, wine is generally produced using Saccharomyces yeast followed by Oenococus bacteria to complete malolactic fermentation. This method has some unsolved problems, such as the management of highly acidic musts and the production of potentially toxic products including biogenic amines and ethyl carbamate. Here we explore the potential of the fission yeast Schizosaccharomyces pombe to solve these problems. We characterise an extensive worldwide collection of S. pombe strains according to classic biochemical parameters of oenological interest. We identify three genetically different S. pombe strains that appear suitable for winemaking. These strains compare favourably to standard Saccharomyces cerevisiae winemaking strains, in that they perform effective malic acid deacidification and significantly reduce levels of biogenic amines and ethyl carbamate precursors without the need for any secondary bacterial malolactic fermentation. These findings indicate that the use of certain S. pombe strains could be advantageous for winemaking in regions where malic acid is problematic, and these strains also show superior performance with respect to food safety