From car to bike. Marketing and dialogue as a driver of change

The Paris Climate Agreement has sent a key message to the international community regarding the need to increase efforts to move towards a low-carbon economy and help slow climate change, while underpinning global long-term economic growth and sustainable development. COP 21 recognizes the social, economic and environmental value of voluntary mitigation actions and their co-benefits for adaptation, health and sustainable development. In this framework, the PTP Cycle project, running from 2013 to 2016 and funded by the European Commission through the Intelligent Energy Europe program, introduces a non-market approach through voluntary participation in the adoption of sustainable transport modes such as cycling, based on marketing to potential customers through Personalized Travel Plans. The medium-sized city of Burgos (Spain) and the cities of Ljubljana, Riga, Antwerp and London (boroughs of Haringey and Greenwich) developed a new policy instrument (Personalized Travel Plans) in order to increase bike patronage. Beyond potential savings of CO2, the results show that PTP as a form of Active Mobility Consultancy is a suitable instrument to influence modal shift to public transport, walking and cycling, and to address the challenges of climate change, while fostering sustainable transportation by changing mobility behaviour. These results, matching with the state-of-the-art of studies and pilot applications in other countries, allows deriving differentiated results for medium-size and large urban areas

Unitarity of the Leptonic Mixing Matrix

We determine the elements of the leptonic mixing matrix, without assuming unitarity, combining data from neutrino oscillation experiments and weak decays. To that end, we first develop a formalism for studying neutrino oscillations in vacuum and matter when the leptonic mixing matrix is not unitary. To be conservative, only three light neutrino species are considered, whose propagation is generically affected by non-unitary effects. Precision improvements within future facilities are discussed as well.Comment: Standard Model radiative corrections to the invisible Z width included. Some numerical results modified at the percent level. Updated with latest bounds on the rare tau decay. Physical conculsions unchange

Developing a Macroscopic Mechanistic Model for Low Molecular Weight Diffusion through Polymers in the Rubbery State

Raman microspectroscopy was used to determine the Fickian diffusivity of two families of low molecular weight molecules through amorphous polystyrene in the rubbery state. Different effects of the temperature on diffusivity for each of the families suggested that molecular mobility is controlled by both the volume and flexibility of the diffusing substance when the movement of polymer chains can generate stress induced deformation of molecules. The diffusing molecules were represented as Newtonian spring-bead systems, which allowed us to quantify their flexibility, in function of the vibration frequency of their bonds by reconstructing their theoretical spectra. Results showed that the use of molecular descriptors that take into account flexibility rather than the most stable conformation of the diffusing molecules may improve the description of the diffusion behavior caused by variations in shape and size of the free volumes of the polymeric matrix in the rubbery state

A Comprehensive Analysis of 5G Heterogeneous Cellular Systems operating over κ\kappa-μ\mu Shadowed Fading Channels

Emerging cellular technologies such as those proposed for use in 5G communications will accommodate a wide range of usage scenarios with diverse link requirements. This will include the necessity to operate over a versatile set of wireless channels ranging from indoor to outdoor, from line-of-sight (LOS) to non-LOS, and from circularly symmetric scattering to environments which promote the clustering of scattered multipath waves. Unfortunately, many of the conventional fading models adopted in the literature to develop network models lack the flexibility to account for such disparate signal propagation mechanisms. To bridge the gap between theory and practical channels, we consider $\kappa$-$\mu$ shadowed fading, which contains as special cases, the majority of the linear fading models proposed in the open literature, including Rayleigh, Rician, Nakagami-m, Nakagami-q, One-sided Gaussian, $\kappa$-$\mu$, $\eta$-$\mu$, and Rician shadowed to name but a few. In particular, we apply an orthogonal expansion to represent the $\kappa$-$\mu$ shadowed fading distribution as a simplified series expression. Then using the series expressions with stochastic geometry, we propose an analytic framework to evaluate the average of an arbitrary function of the SINR over $\kappa$-$\mu$ shadowed fading channels. Using the proposed method, we evaluate the spectral efficiency, moments of the SINR, bit error probability and outage probability of a $K$-tier HetNet with $K$ classes of BSs, differing in terms of the transmit power, BS density, shadowing characteristics and small-scale fading. Building upon these results, we provide important new insights into the network performance of these emerging wireless applications while considering a diverse range of fading conditions and link qualities

Insulin gene polymorphisms in type I diabetes, Addison's disease and the polyglandular autoimmune syndrome type II

Background: Polymorphisms within the insulin gene can influence insulin expression in the pancreas and especially in the thymus, where self-antigens are processed, shaping the T cell repertoire into selftolerance, a process that protects from ß-cell autoimmunity. Methods: We investigated the role of the -2221Msp(C/T) and -23HphI(A/T) polymorphisms within the insulin gene in patients with a monoglandular autoimmune endocrine disease [patients with isolated type 1 diabetes (T1D, n = 317), Addison´s disease (AD, n = 107) or Hashimoto´s thyroiditis (HT, n = 61)], those with a polyglandular autoimmune syndrome type II (combination of T1D and/or AD with HT or GD, n = 62) as well as in healthy controls (HC, n = 275). Results: T1D patients carried significantly more often the homozygous genotype "CC" -2221Msp(C/T) and "AA" -23HphI(A/T) polymorphisms than the HC (78.5% vs. 66.2%, p = 0.0027 and 75.4% vs. 52.4%, p = 3.7 × 10-8, respectively). The distribution of insulin gene polymorphisms did not show significant differences between patients with AD, HT, or APS-II and HC. Conclusion: We demonstrate that the allele "C" of the -2221Msp(C/T) and "A" -23HphI(A/T) insulin gene polymorphisms confer susceptibility to T1D but not to isolated AD, HT or as a part of the APS-II

Effect of Build Parameters and Build Geometries on Residual Microstructures and Mechanical Properties of Ti-6Al-4V Components Built by Electron Beam Melting (EBM)

In this study, involving additive manufacturing (AM) using electron beam melting (EBM), we have examined build defects which result from beam tripping, porosities (including unmelted or unsintered zones) due to excursions from optimal build parameters (especially variations in melt scan beam current and scan speed), and gas bubbles trapped in atomized Ti-6Al-4V starting powder as well as recycled powder, and retained in the build. At optimized build conditions we have also examined microstructure-mechanical property (hardness, tensile strength, and elongation) variations for multiple rake building and multiple melt scans using optical metallography and scanning and transmission electron microscopy (SEM and TEM). These build variances cause cooling rate variances which promote α-phase growth and variations in dislocation density, as well as α-to-α' (martensite) phase changes, all of which produce some degree of mechanical property variations. These features (especially α-to-α' phase changes) are notable on comparing solid builds in comparison with a variety of mesh arrays where strut dimension and build-element complexities alter the cooling rates in a significant way. We illustrate these microstructure variations with corresponding variations in microindentation hardness measurements made directly on fine mesh (strut) structures. Finally, we have examined Ti-6Al-4V powder chemistries and solid build chemistries which for single-pass melt scans at optimized build conditions are shown to be relatively constant up to 40 cycles of powder reuse with the exception of Al content which was reduced by 10 to 15% in solid builds at optimized conditions. However, Al loss in solid builds approached 25% for multiple (2 and 3) melt scans, while no changes in Ar gas-bubble density were observed with changes in α-phase (grain) width which increased from 3 µm for a single melt scan to 4.5 and 6 µm for 2 and 3 melt scans, respectively. Corresponding Rockwell C-scale (HRC) hardness varied from 37, 36, and 35, respectively; with ultimate tensile strengths exceeding 1.2 GPa at elongations of 12% or higher for this melt scan sequence.Mechanical Engineerin

Defects of splicing in antithrombin deficiency

Background: There is increasing evidence supporting the relevance of aberrant splicing in multiple disorders. In antithrombin deficiency only 22 intronic mutations affecting splicing sites (7% of SERPINC1 mutations) are considered as splicing mutations. Methods: SERPINC1 was analyzed by Sanger sequencing and MLPA in 141 unrelated cases with antithrombin deficiency. Plasma antithrombin was studied by functional and western blot assays, purified by FPLC and characterized by proteomic analysis. In silico predictions on splicing was done with the Human Splicing Finder software. Results: We detected 89 different SERPINC1 defects, 13 with potential effect on splicing. Ten cases presented 9 mutations disturbing splicing sites, 5 new. Three gross or small gene defects also disturbed a correct splicing. Interestingly, the first duplication of a single exon ever described (c.1154-13_1218+115dup), caused mild deficiency (75%). A deeper intronic mutation (c.1154-14G>A), identified in three unrelated patients with traces of disulphide dimers of antithrombin in plasma, created a cryptic splicing site that might generate a variant with 4 additional in frame residues according to in silico predictions. This aberrant splicing was confirmed by proteomic analysis of the dimer purified from plasma. Conclusions: A high proportion of cases with antithrombin deficiency (up to 13%) may be explained by an aberrant splicing. Up to 15% of mutations in SERPINC1: splicing site variations, gross gene defects and deep intronic mutations, may affect a correct splicing with three potential consequences type I, type II, and even moderate antithrombin deficiency

PI3Kα inhibition reduces obesity in mice

Partial inhibition of PI3K is one of the best-validated and evolutionary conserved manipulations to extend longevity. The best known health beneficial effects of reduced PI3K are related to metabolism and include increased energy expenditure, reduced nutrient storage, and protection from obesity. We have previously shown that a dual chemical inhibitor of the alpha and delta PI3K isoforms (CNIO-PI3Ki) reduces obesity in mice and monkeys, without evident toxic effects after long-term treatment. Here, we dissect the role of the alpha and delta PI3K isoforms by making use of selective inhibitors against PI3Kα (BYL-719 also known as alpelisib) or PI3Kδ (GS-9820 also known as acalisib). Treatment of mice with the above mentioned inhibitors indicated that BYL-719 increases energy expenditure in normal mice and efficiently reduces body weight in obese (ob/ob) mice, whereas these effects were not observed with GS-9820. Of note, the dose of BYL-719 required to reduce obesity was 10x higher than the equivalent dose of CNIO-PI3Ki, which could suggest that simultaneous inhibition of PI3K alpha and delta is more beneficial than single inhibition of the alpha isoform. In summary, we conclude that inhibition of PI3Kα is sufficient to increase energy expenditure and reduce obesity, and suggest that concomitant PI3Kα inhibition could play an auxiliary role