Diurnal regulation of RNA polymerase III transcription is under the control of both the feeding-fasting response and the circadian clock.

RNA polymerase III (Pol III) synthesizes short noncoding RNAs, many of which are essential for translation. Accordingly, Pol III activity is tightly regulated with cell growth and proliferation by factors such as MYC, RB1, TRP53, and MAF1. MAF1 is a repressor of Pol III transcription whose activity is controlled by phosphorylation; in particular, it is inactivated through phosphorylation by the TORC1 kinase complex, a sensor of nutrient availability. Pol III regulation is thus sensitive to environmental cues, yet a diurnal profile of Pol III transcription activity is so far lacking. Here, we first use gene expression arrays to measure mRNA accumulation during the diurnal cycle in the livers of (1) wild-type mice, (2) arrhythmic javax.xml.bind.JAXBElement@59c2c50e knockout mice, (3) mice fed at regular intervals during both night and day, and (4) mice lacking the javax.xml.bind.JAXBElement@160cb27a gene, and so provide a comprehensive view of the changes in cyclic mRNA accumulation occurring in these different systems. We then show that Pol III occupancy of its target genes rises before the onset of the night, stays high during the night, when mice normally ingest food and when translation is known to be increased, and decreases in daytime. Whereas higher Pol III occupancy during the night reflects a MAF1-dependent response to feeding, the rise of Pol III occupancy before the onset of the night reflects a circadian clock-dependent response. Thus, Pol III transcription during the diurnal cycle is regulated both in response to nutrients and by the circadian clock, which allows anticipatory Pol III transcription

Extended-spectrum TEM- and SHV- Type beta-lactamase-producing Klebsiella pneumoniae strains causing Outbreaks in Intensive Care Units in Italy.

The aim of the present study was to investigate the production of extended-spectrum beta-lactamases (ESbetaLs) and the epidemiological correlations in a total of 107 Klebsiella pneumoniae strains resistant to third- and fourth-generation cephalosporins. The strains were collected from patients in four intensive care units (3 neonatal and 1 general) in three hospitals in Italy between March 1996 and July 1997. All strains were found to produce ESbetaLs. Phenotypic (antibiotyping and ESbetaL patterns) and genotypic (plasmid profile and pulsed-field gel electrophoresis) analyses showed that a single strain had been responsible for each outbreak in each of the four intensive care units. Isoelectric focusing, activity on substrates and gene sequencing showed that the strains produced SHV-5, SHV-2a, SHV-12 and TEM-52 beta-lactamases. This is not only the first time that ESbetaL-producing Klebsiella pneumoniae strains have been reported as causing epidemics in Italian hospitals, it is also, to the best of our knowledge, the first time that an outbreak caused by a TEM-52 ESbetaL-producing Klebsiella pneumoniae strain has been reported. The data presented here illustrate the complexity of determining the epidemiological pattern of ESbetaL producers in large hospitals that do not have an ESbetaL-monitoring program

3D modelling of drug-coated balloons for the treatment of calcified superficial femoral arteries

Background/Objectives Drug-coated balloon therapy for diseased superficial femoral arteries remains controversial. Despite its clinical relevance, only a few computational studies based on simplistic two-dimensional models have been proposed to investigate this endovascular therapy to date. This work addresses the aforementioned limitation by analyzing the drug transport and kinetics occurring during drug-coated balloon deployment in a three-dimensional geometry. Methods An idealized three-dimensional model of a superficial femoral artery presenting with a calcific plaque and treated with a drug-coated balloon was created to perform transient mass transport simulations. To account for the transport of drug (i.e. paclitaxel) released by the device, a diffusion-reaction equation was implemented by describing the drug bound to specific intracellular receptors through a non-linear, reversible reaction. The following features concerning procedural aspects, pathologies and modelling assumptions were investigated: (i) balloon application time (60–180 seconds); (ii) vessel wall composition (healthy vs. calcified wall); (iii) sequential balloon application; and (iv) drug wash-out by the blood stream vs. coating retention, modeled as exponential decay. Results The balloon inflation time impacted both the free and specifically-bound drug concentrations in the vessel wall. The vessel wall composition highly affected the drug concentrations. In particular, the specifically-bound drug concentration was four orders of magnitude lower in the calcific compared with healthy vessel wall portions, primarily as a result of reduced drug diffusion. The sequential application of two drug-coated balloons led to modest differences (~15%) in drug concentration immediately after inflation, which became negligible within 10 minutes. The retention of the balloon coating increased the drug concentration in the vessel wall fourfold. Conclusions The overall findings suggest that paclitaxel kinetics may be affected not only by the geometrical and compositional features of the vessel treated with the drug-coated balloon, but also by balloon design characteristics and procedural aspects that should be carefully considered

Application of the penalty coupling method for the analysis of blood vessels

Due to the significant health and economic impact of blood vessel diseases on modern society, its analysis is becoming of increasing importance for the medical sciences. The complexity of the vascular system, its dynamics and material characteristics all make it an ideal candidate for analysis through fluid structure interaction (FSI) simulations. FSI is a relatively new approach in numerical analysis and enables the multi-physical analysis of problems, yielding a higher accuracy of results than could be possible when using a single physics code to analyse the same category of problems. This paper introduces the concepts behind the Arbitrary Lagrangian Eulerian (ALE) formulation using the penalty coupling method. It moves on to present a validation case and compares it to available simulation results from the literature using a different FSI method. Results were found to correspond well to the comparison case as well as basic theory

Fattori di emissione dalla combustione di legna e pellet in piccoli apparecchi domestici

The aim of this study was to report emission factors of pollutants (i.e., carbon monoxide, nitrogen oxides, non-methane hydrocarbons, particulate matter, polycyclic aromatic hydrocarbons, dioxins) from biomass burning residential heating appliances. The influence of several factors such as biomass type, appliance and combustion cycle was investigated. Four manually fed (6-11 kW) firewood burning and two automatic wood pellets (8.8-25 kW) appliances were tested under real-world operating conditions in order to determine the actual environmental performance of the appliance. The experimental EFs were also compared with the values proposed by the European emission inventory guidebook used in the local inventory in order to evaluate their representativeness of real world emissions. The composite macropollutant EFs for manually fed appliances are: for CO 5858 g GJ-1, for NOx 122 g GJ-1, NMHC 542 g GJ-1, PM 254 g GJ-1, whereas emissions are much lower for automatic pellets appliances: CO 219 g GJ-1, for NOx 66 g GJ-1, NMHC 5 g GJ-1, PM 85 g GJ-1. The open fireplace appears to have very high emission factors, however traditional and advanced stoves show the highest overall CO EFs. Especially for the advanced stove real-world emissions are far worse than those measured under cycles used for type testing of residential solid fuel appliances. No great difference is observed for different firewood types in batch working appliances, diversely the quality of the pellets is observed to influence directly the emission performance of the automatic appliances. Benzo(b)fluoranthene is the PAH with the highest contribution (110 mg GJ-1 for manual appliances and 2 mg GJ-1 for automatic devices) followed by benzo(a)pyrene (77 mg GJ-1 for manual appliances and 0,8 mg GJ-1 for automatic devices)

On the uncertainty of phenological responses to climate change, and implications for a terrestrial biosphere model

Phenology, the timing of recurring life cycle events, controls numerous land surface feedbacks to the climate system through the regulation of exchanges of carbon, water and energy between the biosphere and atmosphere. <br><br> Terrestrial biosphere models, however, are known to have systematic errors in the simulation of spring phenology, which potentially could propagate to uncertainty in modeled responses to future climate change. Here, we used the Harvard Forest phenology record to investigate and characterize sources of uncertainty in predicting phenology, and the subsequent impacts on model forecasts of carbon and water cycling. Using a model-data fusion approach, we combined information from 20 yr of phenological observations of 11 North American woody species, with 12 leaf bud-burst models that varied in complexity. <br><br> Akaike's Information Criterion indicated support for spring warming models with photoperiod limitations and, to a lesser extent, models that included chilling requirements. <br><br> We assessed three different sources of uncertainty in phenological forecasts: parameter uncertainty, model uncertainty, and driver uncertainty. The latter was characterized running the models to 2099 using 2 different IPCC climate scenarios (A1fi vs. B1, i.e. high CO<sub>2</sub> emissions vs. low CO<sub>2</sub> emissions scenario). Parameter uncertainty was the smallest (average 95% Confidence Interval – CI: 2.4 days century<sup>−1</sup> for scenario B1 and 4.5 days century<sup>−1</sup> for A1fi), whereas driver uncertainty was the largest (up to 8.4 days century<sup>−1</sup> in the simulated trends). The uncertainty related to model structure is also large and the predicted bud-burst trends as well as the shape of the smoothed projections varied among models (±7.7 days century<sup>−1</sup> for A1fi, ±3.6 days century<sup>−1</sup> for B1). The forecast sensitivity of bud-burst to temperature (i.e. days bud-burst advanced per degree of warming) varied between 2.2 days °C<sup>−1</sup> and 5.2 days °C<sup>−1</sup> depending on model structure. <br><br> We quantified the impact of uncertainties in bud-burst forecasts on simulated photosynthetic CO<sub>2</sub> uptake and evapotranspiration (ET) using a process-based terrestrial biosphere model. Uncertainty in phenology model structure led to uncertainty in the description of forest seasonality, which accumulated to uncertainty in annual model estimates of gross primary productivity (GPP) and ET of 9.6% and 2.9%, respectively. A sensitivity analysis shows that a variation of ±10 days in bud-burst dates led to a variation of ±5.0% for annual GPP and about ±2.0% for ET. <br><br> For phenology models, differences among future climate scenarios (i.e. driver) represent the largest source of uncertainty, followed by uncertainties related to model structure, and finally, related to model parameterization. The uncertainties we have quantified will affect the description of the seasonality of ecosystem processes and in particular the simulation of carbon uptake by forest ecosystems, with a larger impact of uncertainties related to phenology model structure, followed by uncertainties related to phenological model parameterization

Biodegradable magnesium coronary stents: Material, design and fabrication

Biodegradable cardiovascular stents in magnesium (Mg) alloys constitute a promising option for a less intrusive treatment, due to their high compatibility with the body tissue and intrinsic dissolution in body fluids. The design and fabrication aspects of this medical device require an integrated approach considering different aspects such as mechanical properties, corrosion behaviour and biocompatibility. This work gathers and summarises a multidisciplinary work carried out by three different research teams for the design and fabrication of Mg stents. In particular, the paper discusses the design of the novel stent mesh, the deformability study of the Mg alloys for tubular raw material and laser microcutting for the realisation of the stent mesh. Although, the results are not fully validated as the device has not been fully tested, they show the feasibility of the used approaches, as the first prototype stents in Mg alloy were produced successfully. © 2013 Copyright Taylor and Francis Group, LLC