Inherited or acquired photoreceptor degenerations, one of the leading causes of irreversible blindness in the world, are a group of retinal disorders that initially affect rods and cones, situated in ...the outer retina. For many years it was assumed that these diseases did not spread to the inner retina. However, it is now known that photoreceptor loss leads to an unavoidable chain of events that cause neurovascular changes in the retina including migration of retinal pigment epithelium cells, formation of "subretinal vascular complexes", vessel displacement, retinal ganglion cell (RGC) axonal strangulation by retinal vessels, axonal transport alteration and, ultimately, RGC death. These events are common to all photoreceptor degenerations regardless of the initial trigger and thus threaten the outcome of photoreceptor substitution as a therapeutic approach, because with a degenerating inner retina, the photoreceptor signal will not reach the brain. In conclusion, therapies should be applied early in the course of photoreceptor degeneration, before the remodeling process reaches the inner retina.
Quantum dots (QDs) are semiconductor nanoparticles with unique optical and electronic properties, whose interest as potential nano-theranostic platforms for imaging and sensing is increasing. The ...design and use of QDs requires the understanding of cell-nanoparticle interactions at a microscopic and nanoscale level. Model systems such as supported lipid bilayers (SLBs) are useful, less complex platforms mimicking physico-chemical properties of cell membranes. In this work, we investigated the effect of topographical homogeneity of SLBs bearing different surface charge in the adsorption of hydrophilic QDs. Using quartz-crystal microbalance, a label-free surface sensitive technique, we show significant differences in the interactions of QDs onto homogeneous and inhomogeneous SLBs formed following different strategies. Within short time scales, QDs adsorb onto topographically homogeneous, defect-free SLBs is driven by electrostatic interactions, leading to no layer disruption. After prolonged QD exposure, the nanomechanical stability of the SLB decreases suggesting nanoparticle insertion. In the case of inhomogeneous, defect containing layers, QDs target preferentially membrane defects, driven by a subtle interplay of electrostatic and entropic effects, inducing local vesicle rupture and QD insertion at membrane edges.
Display omitted
•Electrostatic interactions drive QDs adsorption onto defect-free supported lipid bilayers.•QDs exposure time leads to a decrease of the membrane nanomechanical stability.•QDs adsorption is stronger on defect containing membranes than on defect-free.•QDs target preferentially membrane defects.
The adequate formulation of topical vehicles to treat skin diseases is particularly complex. A desirable formulation should enhance the accumulation of the active drugs in the target tissue (the ...skin), while avoiding the penetration enhancement to be so large that the drugs reach the systemic circulation in toxic amounts. We have evaluated the transcutaneous penetration of three drugs chosen for their widely variable physicochemical properties: Amphotericin B, Imiquimod and Indole. We incorporated the drugs in fluid or ultra-flexible liposomes. Ultra-flexible liposomes produced enhancement of drug penetration into/through human skin in all cases in comparison with fluid liposomes without detergent, regardless of drug molecular weight. At the same time, our results indicate that liposomes can impede the transcutaneous penetration of molecules, in particular small ones.
We probe the merging channel of massive galaxies over the z = 0.3–1.3 redshift window by studying close pairs in a sample of 238 galaxies with stellar mass ≳1011 M⊙, from the SHARDS (Survey for ...High-z Absorption Red and Dead Sources) survey. SHARDS provides medium-band photometry equivalent to low-resolution optical spectra (R ∼ 50), allowing us to obtain extremely accurate photometric redshifts (median |Δz|/(1 + z) ∼ 0.55 per cent) and to improve the constraints on the age distribution of the stellar populations. Our data set is volume limited, probing merger progenitors with mass ratios 1:100 (μ ≡ M
sat/M
cen = 0.01) out to z = 1.3. A strong correlation is found between the age difference of host and companion galaxy and stellar mass ratio, from negligible age differences in major mergers to age differences ∼4 Gyr for 1:100 minor mergers. However, this correlation is simply a reflection of the mass–age trend in the general population. The dominant contributor to the growth of massive galaxies corresponds to mass ratios μ ≳ 0.3, followed by a decrease in the fractional mass growth rate linearly proportional to log μ, at least down to μ ∼ 0.01, suggesting a decreasing role of mergers involving low-mass companions, especially if dynamical friction time-scales are taken into account. A simple model results in an upper limit for the average mass growth rate of massive galaxies of (ΔM/M)/Δt ∼ 0.08 ± 0.02 Gyr−1, over the z ≲ 1 range, with an ∼70 per cent fractional contribution from (major) mergers with μ ≳ 0.3. The majority of the stellar mass contributed by mergers does not introduce significantly younger populations, in agreement with the small radial age gradients observed in present-day early-type galaxies.
The availability of high density panels of molecular markers has prompted the adoption of genomic selection (GS) methods in animal and plant breeding. In GS, parametric, semi-parametric and ...non-parametric regressions models are used for predicting quantitative traits. This article shows how to use neural networks with radial basis functions (RBFs) for prediction with dense molecular markers. We illustrate the use of the linear Bayesian LASSO regression model and of two non-linear regression models, reproducing kernel Hilbert spaces (RKHS) regression and radial basis function neural networks (RBFNN) on simulated data and real maize lines genotyped with 55,000 markers and evaluated for several trait–environment combinations. The empirical results of this study indicated that the three models showed similar overall prediction accuracy, with a slight and consistent superiority of RKHS and RBFNN over the additive Bayesian LASSO model. Results from the simulated data indicate that RKHS and RBFNN models captured epistatic effects; however, adding non-signal (redundant) predictors (interaction between markers) can adversely affect the predictive accuracy of the non-linear regression models.
The article here presented aims to contribute to renewable energies development at regional level, proposing a methodology for the establishment of strategies needed to reach, in the long term, an ...energy system more sustainable and mainly based upon autochthonous resources.
Current energy planning models are investigated, analysing its convenience to design a sustainable energy system, and a new methodology, that combines three different approaches, is proposed. Such new “hybrid” methodology resumes advantages of territorial strategic planning methods, based upon SWOT analysis, along with characteristics extracted both from Multicriteria decision analysis techniques and expert opinion “Delphi” methods.
Nowadays, decisions concerning energy system cannot be consider under one specific criterion. Different implications, energetic, environmental or socioeconomic, derived from changes on energy development make it unavoidable to use tools and techniques that could take into account such multiplicity. It has been also intended to take advantage of the know-how acquired along the territorial strategic planning process carried out in the region to analyse, from year 1997 to 2000. This approach has allowed to integrate, under a unique methodology, tools from energy planning with those one used, and successfully tested, for the elaboration of the strategic plan for Jaén Province.
The proposed methodology has been applied to Jaén Province in order to design a renewable energy plan for the region, setting strategic action lines and fixing strategic goals to be met on year 2010 by the provincial energy system. The objective regarding electricity production from renewable resources, on year 2010, is fixed above 1630GWh, which represents a 43% of the total foreseeable electricity consumption. Overall contribution of renewable sources in provincial energy system is finally set to 28.3%, in terms of final energy.
In the last 15 years, new types of display technologies have increasingly replaced cathode ray tube (CRT) screens, which has led to an increase in landfill of old discarded CRT televisions, which ...present a great environmental challenge throughout the world due to their high lead content. In addition, environmental awareness has led to greater use of recycled aggregates to reduce the exploitation of existing reserves. This document aims to study the feasibility of incorporating CRT glass waste with recycled aggregate (RA) in combinations for use in civil engineering, more specifically in road bases and sub-bases. For the mechanical and environmental assessment of all of the samples and materials, the following procedures have been performed: the compliance batch test of UNE-EN 12457-4:2004 for RA, CRT, and mixtures; the Percolation Test according CEN/TS 14405 for the mixtures, CRT, and RA; Modified Proctor and load capacity (the California Bearing Ratio, or CBR) in all mixtures without cement addition, and finally, compressive strength of the material treated with cement at different ages of curing. The analysis of the mechanical and environmental properties through different techniques of lixiviation was positive, showing the ability to use CRT for certain dosage percentages mixed with recycled aggregates.
Electroconvulsive therapy (ECT) is widely applied to treat severe depression resistant to standard treatment. Results from previous studies comparing the cost-effectiveness of this technique with ...treatment alternatives such as repetitive transcranial magnetic stimulation (rTMS) are conflicting.
We conducted a cost-effectiveness analysis comparing ECT alone, rTMS alone and rTMS followed by ECT when rTMS fails under the perspective of the Spanish National Health Service. The analysis is based on a Markov model which simulates the costs and health outcomes of individuals treated under these alternatives over a 12-month period. Data to populate this model were extracted and synthesized from a series of randomized controlled trials and other studies that have compared these techniques on the patient group of interest. We measure effectiveness using quality-adjusted life years (QALYs) and characterize the uncertainty using probabilistic sensitivity analyses.
ECT alone was found to be less costly and more effective than rTMS alone, while the strategy of providing rTMS followed by ECT when rTMS fails is the most expensive and effective option. The incremental cost per QALY gained of this latter strategy was found to be above the reference willingness-to-pay threshold used in these types of studies in Spain and other countries. The probability that ECT alone is the most cost-effective alternative was estimated to be around 70%.
ECT is likely to be the most cost-effective option in the treatment of resistant severe depression for a willingness to pay of €30,000 per QALY.
•Influence of Laser Tracker noise on the uncertainty of machine tool when a volumetric verification is carried out.•Estimation of a map of uncertainty by point on a machine tool ...workspace.•Calculation of Maximum Permissible Error for distances measuring.
Verification of workpieces is typically performed in the post-process with coordinate measuring machines, thereby increasing the manufacturing cycle time. However, machine tools presently can perform contact measuring operations by using a probe. Moreover, there is a growing need for in-process inspection of workpieces. Therefore, using the machine tool itself for the verification whilst the workpiece remains clamped to the machine can lead to an improvement in manufacturing efficiency, cost reduction, higher energy saving and better equipment productivity. However, the use of touch probes as a measurement tool in manufacturing requires some preparatory works. Firstly, the accuracy of the machine tool should be improved to reduce the influence of its geometric errors. Secondly, the uncertainties in calibration and measuring procedure should be determined to obtain the measurement uncertainty. This study presents a new tool that can analyse the effect of different verification parameters in calibration uncertainty based on Monte Carlo method. On the basis of the actual tests performed on a milling machine and its geometric errors, the effect of laser tracker measurement noise in calibration uncertainty is investigated.
A high-strength Mg-6Zn-1Y-1Ca (wt%) alloy has been processed by a powder metallurgy route. Rapidly solidified powders with a particle size below 100µm were used as a way for preventing formation of ...ternary MgZnCa compounds during subsequent extrusion at 250°C. The microstructure of the extruded alloy consists of an ultrafine-grain magnesium matrix, with an average grain size of 444nm, embedding a high volume fraction of fine I-phase particles aligned along the extrusion direction. The alloy combines an excellent ductility (14% of elongation to failure) with a high strength (ultimate strength of 469MPa and yield stress of 461MPa) at room temperature, mainly due to grain size refinement (around 70% of the yield stress). The strength is kept high up to 150°C (yield stress of 279MPa). Above this temperature, the mechanical strength falls to very low values but the ability to deform plastically is considerably enhanced, exhibiting superplastic behaviour from 200 to 350°C, with a maximum elongation of 477% at 350°C.
PDF
