A yeast synthetic network for in-vivo assessment of reverse engineering and modelling.

Systems biology approaches are extensively used to model and reverse engineer gene regulatory networks from experimental data. Conversely, synthetic biology allows ‘‘de novo’’ construction of a regulatory network to seed new functions in the cell. At present, the usefulness and predictive ability of modeling and reverse engineering cannot be assessed and compared rigorously. We built in the yeast Saccharomyces cerevisiae a synthetic network, IRMA, for in vivo ‘‘benchmarking’’ of reverse-engineering and modeling approaches. The network is composed of five genes regulating each other through a variety of regulatory interactions; it is negligibly affected by endogenous genes, and it is responsive to small molecules. We measured time series and steady-state expression data after multiple perturbations. These data were used to assess state-of-the-art modeling and reverse-engi- neering techniques. A semiquantitative model was able to capture and predict the behavior of the network. Reverse engineering based on differential equations and Bayesian networks correctly inferred regulatory interactions from the experimental data

Spectrally resolved observations of atmospheric emitted radiance in the H2O rotation band

This paper presents the project Earth Cooling by Water Vapor Radiation, an observational programme, which aims at developing a database of spectrally resolved far infrared observations, in atmospheric dry conditions, in order to validate radiative transfer models and test the quality of water vapor continuum and line parameters. The project provides the very first set of far-infrared spectral downwelling radiance measurements, in dry atmospheric conditions, which are complemented with Raman Lidar-derived temperature and water vapor profiles

Constraints on planet X/Nemesis from Solar System's inner dynamics

We put full 3D constraints on a putative planet X by using the dynamics of the inner planets of the solar system. In particular, we compute the mimium distance of X as a function of its heliocentric latitude and longitude for different values of its mass.Comment: LaTex, MNRAS macros. 12 pages, 4 figures, 3 tables. To appear in Monthly Notices of the Royal Astronomical Society (MNRAS). Some typos fixe

First study on the peptidergic innervation of the brain superior sagittal sinus in humans.

The superior sagittal sinus (SSS) of the mammalian brain is a pain-sensitive intracranial vessel thought to play a role in the pathogenesis of migraine headaches. Here, we aimed to investigate the presence and the potential co-localization of some neurotransmitters in the human SSS. Immunohistochemical and double-labeling immunofluorescence analyses were applied to paraformaldehyde-fixed, paraffin-embedded, coronal sections of the SSS. Protein extraction and Western blotting technique were performed on the same material to confirm the morphological data. Our results showed nerve fibers clustered mainly in large bundles tracking parallel to the longitudinal axis of the sinus, close in proximity to the vascular endothelium. Smaller fascicles of fibers encircled the vascular lumen in a spiral fashion, extending through the subendothelial connective tissue. Isolated nerve fibers were observed around the openings of bridging veins in the sinus or around small vessels extending into the perisinusal dura. The neurotransmitters calcitonin gene related peptide (CGRP), substance P (SP), neuronal nitric oxide synthase (nNOS), vasoactive intestinal polypeptide (VIP), tyrosine hydroxylase (TH), and neuropeptide Y (NPY) were found in parietal nerve structures, distributed all along the length of the SSS. Overall, CGRP- and TH-containing nerve fibers were the most abundant. Neurotransmitters co-localized in the same fibers in the following pairs: CGRP/SP, CGRP/NOS, CGRP/VIP, and TH/NPY. Western blotting analysis confirmed the presence of such neurosubstances in the SSS wall. Overall our data provide the first evidence of the presence and co-localization of critical neurotransmitters in the SSS of the human brain, thus contributing to a better understanding of the sinus functional role

Towards developmental modelling of tree root systems

Knowledge of belowground structures and processes is essential for understanding and predicting ecosystem functioning, and consequently in the development of adaptive strategies to safeguard production from trees and woody plants into the future. In the past, research has mainly been concentrated on growth models for the prediction of agronomic or forest production. Newly emerging scientific challenges, e.g. climate change and sustainable development, call for new integrated predictive methods where root systems development will become a key element for understanding global biological systems. The types of input data available from the various branches of woody root research, including biomass allocation, architecture, biomechanics, water and nutrient supply, are discussed with a view to the possibility of incorporating them into a more generic developmental model. We discuss here the main focus of root system modelling to date, including a description of simple allometric biomass models, and biomechanical stress models, and then build in complexity through static growth models towards architecture models. The next progressive and logical step in developing an inclusive developmental model that integrates these modelling approaches is discussed.Knowledge of belowground structures and processes is essential for understanding and predicting ecosystem functioning, and consequently in the development of adaptive strategies to safeguard production from trees and woody plants into the future. In the past, research has mainly been concentrated on growth models for the prediction of agronomic or forest production. Newly emerging scientific challenges, e.g. climate change and sustainable development, call for new integrated predictive methods where root systems development will become a key element for understanding global biological systems. The types of input data available from the various branches of woody root research, including biomass allocation, architecture, biomechanics, water and nutrient supply, are discussed with a view to the possibility of incorporating them into a more generic developmental model. We discuss here the main focus of root system modelling to date, including a description of simple allometric biomass models, and biomechanical stress models, and then build in complexity through static growth models towards architecture models. The next progressive and logical step in developing an inclusive developmental model that integrates these modelling approaches is discussed.Knowledge of belowground structures and processes is essential for understanding and predicting ecosystem functioning, and consequently in the development of adaptive strategies to safeguard production from trees and woody plants into the future. In the past, research has mainly been concentrated on growth models for the prediction of agronomic or forest production. Newly emerging scientific challenges, e.g. climate change and sustainable development, call for new integrated predictive methods where root systems development will become a key element for understanding global biological systems. The types of input data available from the various branches of woody root research, including biomass allocation, architecture, biomechanics, water and nutrient supply, are discussed with a view to the possibility of incorporating them into a more generic developmental model. We discuss here the main focus of root system modelling to date, including a description of simple allometric biomass models, and biomechanical stress models, and then build in complexity through static growth models towards architecture models. The next progressive and logical step in developing an inclusive developmental model that integrates these modelling approaches is discussed.Peer reviewe

LETSGO: A spacecraft-based mission to accurately measure the solar angular momentum with frame-dragging

LETSGO (LEnse-Thirring Sun-Geo Orbiter) is a proposed space-based mission involving the use of a spacecraft moving along a highly eccentric heliocentric orbit perpendicular to the ecliptic. It aims to accurately measure some important physical properties of the Sun and to test some post-Newtonian features of its gravitational field by continuously monitoring the Earth-probe range. Preliminary sensitivity analyses show that, by assuming a cm-level accuracy in ranging to the spacecraft, it would be possible to detect, in principle, the Lense-Thirring effect on it at a 10^-3-10^-4 level over a timescale of 2 yr, while the larger Schwarzschild component of the solar gravitational field may be sensed with a relative accuracy of about 10^-8-10^-9 during the same temporal interval. The competing range perturbation due to the non-sphericity of the Sun would be a source of systematic error, but it turns out that all the three dynamical features of motion examined affect the Earth-probe range in different ways, allowing for a separation in data analyses. The high eccentricity would help in reducing the impact of the non-gravitational perturbations whose impact would certainly be severe when LETSGO would approach the Sun at just a few solar radii. Further studies should be devoted to investigate both the consequences of the non-conservative forces and the actual measurability of the effects of interest by means of extensive numerical data simulations, parameter estimations and covariance analyses. Also an alternative, fly-by configuration is worth of consideration.Comment: LaTex2e, double column, 19 pages, 3 figures, 3 tables, 97 references. Accepted for publication in Acta Astronautica. Proof corrections inserte

Residual vein thrombosis for assessing duration of anticoagulation after unprovoked deep vein thrombosis of the lower limbs: the extended DACUS study.

Abstract The safest duration of anticoagulation after idiopathic deep vein thrombosis (DVT) is unknown. We conducted a prospective study to assess the optimal duration of vitamin K antagonist (VKA) therapy considering the risk of recurrence of thrombosis according to residual vein thrombosis (RVT). Patients with a first unprovoked DVT were evaluated for the presence of RVT after 3 months of VKA administration; those without RVT suspended VKA, while those with RVT continued oral anticoagulation for up to 2 years. Recurrent thrombosis and/or bleeding events were recorded during treatment (RVT group) and 1 year after VKA withdrawal (both groups). Among 409 patients evaluated for unprovoked DVT, 33.2% (136 of 409 patients) did not have RVT and VKA was stopped. The remaining 273 (66.8%) patients with RVT received anticoagulants for an additional 21 months; during this period of treatment, recurrent venous thromboembolism and major bleeding occurred in 4.7% and 1.1% of patients, respectively. After VKA suspension, the rates of recurrent thrombotic events were 1.4% and 10.4% in the no-RVT and RVT groups, respectively (relative risk = 7.4; 95% confidence interval = 4.9-9.9). These results indicate that in patients without RVT, a short period of treatment with a VKA is sufficient; in those with persistent RVT, treatment extended to 2 years substantially reduces, but does not eliminate, the risk of recurrent thrombosis

Does oral sodium bicarbonate therapy improve function and quality of life in older patients with chronic kidney disease and low-grade acidosis (the BiCARB trial)? Study protocol for a randomized controlled trial

Date of acceptance: 01/07/2015 © 2015 Witham et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Acknowledgements UK NIHR HTA grant 10/71/01. We acknowledge the financial support of NHS Research Scotland in conducting this trial.Peer reviewedPublisher PD

TOpic: rare and special cases, the real "Strange cases"

Introduction: The bladder hernia represents approximately 1-3% of all inguinal hernias, where patients aged more than 50 years have a higher incidence (10%). Many factors contribute to the development of a bladder hernia, including the presence of a urinary outlet obstruction causing chronic bladder distention, the loss of bladder tone, pericystitis, the perivesical bladder fat protrusion and the obesity