Constraining Torus Models for AGNs Using X-Ray Observations

In Unification Models, Active Galactic Nuclei (AGN) are believed to be surrounded by an axisymmetric structure of dust and gas, which greatly influences their observed properties according to the direction from which they are observed. The main aim of this work is to constrain the properties of this obscuring material using X-Ray observations. The distribution of column densities observed by Chandra in the Chandra Deep Field South is used to determine geometrical constraints for already proposed torus models. It is found that the best torus model is given by a classical `donut shape' with an exponential angular dependency of the density profile. The opening angle is strongly constrained by the observed column densities. Other proposed torus models are clearly rejected by the X-Ray observations.Comment: 10 pages, 4 figures, submitted to A&

The Covid-19 explosion in the state of Amapá: how is the most preserved region in the Brazilian Amazon currently fighting the SARS-COV 2 pandemic?

The state of Amap\ue1 is located in the extreme north of Brazil, within the Amazon rainforest and is crossed by the Equator. It has a hot and humid climate with rains that last 8 months a year and 4 months of unrelenting sun that melts rubber from car seals, fries eggs on the floor and even cooks a whole egg tub, in case you forget in a car exposed to the sun . It was believed that with this potent solar incidence, the Sars-COV 2 virus would not have so much impact in this region, a terrible mistake! Today Amap\ue1 has the highest incidence of Covid-19 in the whole of Brazil, with a maid of 600 cases per hundred thousand inhabitants and in the Amazon it is the 3rd in deaths and loses in this item only to the state of Amazonas and Par\ue1

PathwayMapper: A collaborative visual web editor for cancer pathways and genomic data

Motivation: While existing network visualization tools enable the exploration of cancer genomics data, most biologists prefer simplified, curated pathway diagrams, such as those featured in many manuscripts from The Cancer Genome Atlas (TCGA). These pathway diagrams typically summarize how a pathway is altered in individual cancer types, including alteration frequencies for each gene. Results: To address this need, we developed the web-based tool PathwayMapper, which runs in most common web browsers. It can be used for viewing pre-curated cancer pathways, or as a graphical editor for creating new pathways, with the ability to overlay genomic alteration data from cBioPortal. In addition, a collaborative mode is available that allows scientists to co-operate interactively on constructing pathways, with support for concurrent modifications and built-in conflict resolution. © 2017 The Author. Published by Oxford University Press. All rights reserved

Terrestrial Implications of Cosmological Gamma-Ray Burst Models

The observation by the BATSE instrument on the Compton Gamma Ray Observatory that gamma-ray bursts (GRBs) are distributed isotropically around the Earth but nonuniformly in distance has led to the widespread conclusion that GRBs are most likely to be at cosmological distances, making them the most luminous sources known in the Universe. If bursts arise from events that occur in normal galaxies, such as neutron star binary inspirals, then they will also occur in our Galaxy about every hundred thousand to million years. The gamma-ray flux at the Earth due to a Galactic GRB would far exceed that from even the largest solar flares. The absorption of this radiation in the atmosphere would substantially increase the stratospheric nitric oxide concentration through photodissociation of N$_2$, greatly reducing the ozone concentration for several years through NO$_x$ catalysis, with important biospheric effects due to increased solar ultraviolet flux. A nearby GRB may also leave traces in anomalous radionuclide abundances.Comment: uuencoded, gzip-ed postscript; 6 pages; submitted to ApJ Letter

Deletion of the GABAA α2-subunit does not alter self dministration of cocaine or reinstatement of cocaine seeking

Rationale GABAA receptors containing α2-subunits are highly represented in brain areas that are involved in motivation and reward, and have been associated with addiction to several drugs, including cocaine. We have shown previously that a deletion of the α2-subunit results in an absence of sensitisation to cocaine. Objective We investigated the reinforcing properties of cocaine in GABAA α2-subunit knockout (KO) mice using an intravenous self-administration procedure. Methods α2-subunit wildtype (WT), heterozygous (HT) and KO mice were trained to lever press for a 30 % condensed milk solution. After implantation with a jugular catheter, mice were trained to lever press for cocaine (0.5 mg/kg/infusion) during ten daily sessions. Responding was extinguished and the mice tested for cue- and cocaine-primed reinstatement. Separate groups of mice were trained to respond for decreasing doses of cocaine (0.25, 0.125, 0.06 and 0.03 mg/kg). Results No differences were found in acquisition of lever pressing for milk. All genotypes acquired self-administration of cocaine and did not differ in rates of self-administration, dose dependency or reinstatement. However, whilst WT and HT mice showed a dose-dependent increase in lever pressing during the cue presentation, KO mice did not. Conclusions Despite a reported absence of sensitisation, motivation to obtain cocaine remains unchanged in KO and HT mice. Reinstatement of cocaine seeking by cocaine and cocaine-paired cues is also unaffected. We postulate that whilst not directly involved in reward perception, the α2-subunit may be involved in modulating the “energising” aspect of cocaine’s effects on reward-seeking

Efficiency of primary saliva secretion: an analysis of parameter dependence in dynamic single-cell and acinus models, with application to aquaporin knockout studies

Secretion from the salivary glands is driven by osmosis following the establishment of osmotic gradients between the lumen, the cell and the interstitium by active ion transport. We consider a dynamic model of osmotically driven primary saliva secretion and use singular perturbation approaches and scaling assumptions to reduce the model. Our analysis shows that isosmotic secretion is the most efficient secretion regime and that this holds for single isolated cells and for multiple cells assembled into an acinus. For typical parameter variations, we rule out any significant synergistic effect on total water secretion of an acinar arrangement of cells about a single shared lumen. Conditions for the attainment of isosmotic secretion are considered, and we derive an expression for how the concentration gradient between the interstitium and the lumen scales with water- and chloride-transport parameters. Aquaporin knockout studies are interpreted in the context of our analysis and further investigated using simulations of transport efficiency with different membrane water permeabilities. We conclude that recent claims that aquaporin knockout studies can be interpreted as evidence against a simple osmotic mechanism are not supported by our work. Many of the results that we obtain are independent of specific transporter details, and our analysis can be easily extended to apply to models that use other proposed ionic mechanisms of saliva secretion

Emerging landscape of oncogenic signatures across human cancers.

Cancer therapy is challenged by the diversity of molecular implementations of oncogenic processes and by the resulting variation in therapeutic responses. Projects such as The Cancer Genome Atlas (TCGA) provide molecular tumor maps in unprecedented detail. The interpretation of these maps remains a major challenge. Here we distilled thousands of genetic and epigenetic features altered in cancers to ∼500 selected functional events (SFEs). Using this simplified description, we derived a hierarchical classification of 3,299 TCGA tumors from 12 cancer types. The top classes are dominated by either mutations (M class) or copy number changes (C class). This distinction is clearest at the extremes of genomic instability, indicating the presence of different oncogenic processes. The full hierarchy shows functional event patterns characteristic of multiple cross-tissue groups of tumors, termed oncogenic signature classes. Targetable functional events in a tumor class are suggestive of class-specific combination therapy. These results may assist in the definition of clinical trials to match actionable oncogenic signatures with personalized therapies