451 research outputs found

    Viabilità minore motore di sviluppo

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    Nel mondo, molte strade extraurbane (viabilità minore o locale) si caratterizzano per il ridotto transito giornaliero dei veicoli, transito che assume un valore variabile in relazione ai diversi contesti. Però è soltanto questa rete secondaria che assicura i collegamenti indispensabili per la popolazione insediata lontano dai grandi centri urbani, popolazione che, pur potendo provvedere al proprio sostentamento, attingendo alle sole risorse presenti di fatto dipende, per tutte le funzioni di ordine superiore (commercio, educazione, sanità, servizi) da questa rete stradale. Strade quindi che sono indispensabili per chi risiede lontano dai centri urbani. Ma le risorse assegnate per la manutenzione sono molto scarse. Quando si tratta di pianificare e di investire sulla rete locale, si fa ricorso ai modelli tradizionali di investimento (ivi inclusa l’analisi costi-benefici e la stima dei costi sociali connessi), modelli utilizzati per le reti di traffico di una certa rilevanza ma del tutto inappropriati se applicati a contesti locali

    A high order compact scheme for hypersonic aerothermodynamics

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    A novel high order compact scheme for solving the compressible Navier-Stokes equations has been developed. The scheme is an extension of a method originally proposed for solving the Euler equations, and combines several techniques for the solution of compressible flowfields, such as upwinding, limiting and flux vector splitting, with the excellent properties of high order compact schemes. Extending the method to the Navier-Stokes equations is achieved via a Kinetic Flux Vector Splitting technique, which represents an unusual and attractive way to include viscous effects. This approach offers a more accurate and less computationally expensive technique than discretizations based on more conventional operator splitting. The Euler solver has been validated against several inviscid test cases, and results for several viscous test cases are also presented. The results confirm that the method is stable, accurate and has excellent shock-capturing capabilities for both viscous and inviscid flows

    Contribution of polymorphic variation of inositol hexakisphosphate kinase 3 (IP6K3) gene promoter to the susceptibility to late onset Alzheimer's disease

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    Maintenance of electric potential and synaptic transmission are energetically demanding tasks that neuronal metabolism must continually satisfy. Inability to fulfil these energy requirements leads to the development of neurodegenerative disorders, including Alzheimer's disease. A prominent feature of Alzheimer's disease is in fact neuronal glucose hypometabolism. Thus understanding the fine control of energetic metabolism might help to understand neurodegenerative disorders. Recent research has indicated that a novel class of signalling molecules, the inositol pyrophosphates, act as energy sensors. They are able to alter the balance between mitochondrial oxidative phosphorylation and glycolytic flux, ultimately affecting the cellular level of ATP. The neuronal inositol pyrophosphate synthesis relies on the activity of the neuron enriched inositol hexakisphosphate kinase 3 (IP6K3) enzyme. To verify an involvement of inositol pyrophosphate signalling in neurodegenerative disorders, we performed tagging single nucleotide polymorphism (SNP) analysis of the IP6K3 gene in patients with familial and sporadic late onset Alzheimer's disease (LOAD). Two SNPs in the 5'-flanking promoter region of the IP6K3 gene were found to be associated with sporadic LOAD. Characterizing the functionality of the two polymorphisms by luciferase assay revealed that one of them (rs28607030) affects IP6K3 promoter activity, with the G allele showing an increased activity. As the same allele has a beneficial effect on disease risk, this may be related to upregulation of IP6K3 expression, with a consequent increase in inositol pyrophosphate synthesis. In conclusion, we provide the first evidence for a contribution of genetic variability in the IP6K3 gene to LOAD pathogenesis

    Comparison of Reconstruction Algorithms for Brain Stroke Microwave Imaging

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    The aim of this paper is to describe and compare the performances of three image reconstruction algorithms that can be used for brain stroke microwave imaging. The algorithms belong to the class of non-linear iterative algorithms and are capable of providing a quantitative map of the imaged scenario. The first algorithm is the Contrast Source Inversion (CSI) method, which uses the Finite Element Method (FEM) to discretize the domain of interest. The second one is the Subspace-Based Optimization Method (SOM) that has some properties in common with the CSI method, and it also uses FEM to discretize the domain. The last one is the Distorted Born Iterative Method with the inverse solver Two-step Iterative Shrinkage/Thresholding (DBIM-TwIST), which exploits the forward Finite Difference Time Domain (FDTD) solver. The reconstruction examples are created with 3-D synthetic data modelling realistic brain tissues with the presence of a blood region, representing the stroke area in the brain, whereas the inversion step is carried out using a 2-D model

    Cancellation of vorticity in steady-state non-isentropic flows of complex fluids

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    In steady-state non-isentropic flows of perfect fluids there is always thermodynamic generation of vorticity when the difference between the product of the temperature with the gradient of the entropy and the gradient of total enthalpy is different from zero. We note that this property does not hold in general for complex fluids for which the prominent influence of the material substructure on the gross motion may cancel the thermodynamic vorticity. We indicate the explicit condition for this cancellation (topological transition from vortex sheet to shear flow) for general complex fluids described by coarse-grained order parameters and extended forms of Ginzburg-Landau energies. As a prominent sample case we treat first Korteweg's fluid, used commonly as a model of capillary motion or phase transitions characterized by diffused interfaces. Then we discuss general complex fluids. We show also that, when the entropy and the total enthalpy are constant throughout the flow, vorticity may be generated by the inhomogeneous character of the distribution of material substructures, and indicate the explicit condition for such a generation. We discuss also some aspects of unsteady motion and show that in two-dimensional flows of incompressible perfect complex fluids the vorticity is in general not conserved, due to a mechanism of transfer of energy between different levels.Comment: 12 page

    IP6K3 and IPMK variations in LOAD and longevity: evidence for a multifaceted signaling network at the crossroad between neurodegeneration and survival

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    Several studies reported that genetic variants predisposing to neurodegeneration were at higher frequencies in centenarians than in younger controls, suggesting they might favor also longevity. IP6K3 and IPMK regulate many crucial biological functions by mediating synthesis of inositol poly- and pyrophosphates and by acting non-enzymatically via protein–protein interactions. Our previous studies suggested they affect Late Onset Alzheimer Disease (LOAD) and longevity, respectively. Here, in the same sample groups, we investigated whether variants of IP6K3 also affect longevity, and variants of IPMK also influence LOAD susceptibility. We found that: i) a SNP of IP6K3 previously associated with increased risk of LOAD increased the chance to become long-lived, ii) SNPs of IPMK, previously associated with decreased longevity, were protective factors for LOAD, as previously observed for UCP4. SNP-SNP interaction analysis, including our previous data, highlighted phenotype-specific interactions between sets of alleles. Moreover, linkage disequilibrium and eQTL data associated to analyzed variants suggested mitochondria as crossroad of interconnected pathways crucial for susceptibility to neurodegeneration and/or longevity. Overall, data support the view that in these traits interactions may be more important than single polymorphisms. This phenomenon may contribute to the non-additive heritability of neurodegeneration and longevity and be part of the missing heritability of these traits

    Bitter taste receptor polymorphisms and human aging.

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    Several studies have shown that genetic factors account for 25% of the variation in human life span. On the basis of published molecular, genetic and epidemiological data, we hypothesized that genetic polymorphisms of taste receptors, which modulate food preferences but are also expressed in a number of organs and regulate food absorption processing and metabolism, could modulate the aging process. Using a tagging approach, we investigated the possible associations between longevity and the common genetic variation at the three bitter taste receptor gene clusters on chromosomes 5, 7 and 12 in a population of 941 individuals ranging in age from 20 to 106 years from the South of Italy. We found that one polymorphism, rs978739, situated 212 bp upstream of the TAS2R16 gene, shows a statistically significant association (p = 0.001) with longevity. In particular, the frequency of A/A homozygotes increases gradually from 35% in subjects aged 20 to 70 up to 55% in centenarians. These data provide suggestive evidence on the possible correlation between human longevity and taste genetics

    Erythropoietin (EPO) haplotype associated with all-cause mortality in a cohort of Italian patients with Type-2 Diabetes

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    Type-2 Diabetes (T2D), diabetic complications, and their clinical risk factors harbor a substantial genetic component but the genetic factors contributing to overall diabetes mortality remain unknown. Here, we examined the association between genetic variants at 21 T2D-susceptibility loci and all-cause mortality in an elderly cohort of 542 Italian diabetic patients who were followed for an average of 12.08 years. Univariate Cox regression analyses detected age, waist-to-hip ratio (WHR), glycosylated haemoglobin (HbA1c), diabetes duration, retinopathy, nephropathy, chronic kidney disease (CKD), and anaemia as predictors of all-cause mortality. When Cox proportional hazards multivariate models adjusted for these factors were run, three erythropoietin (EPO) genetic variants in linkage disequilibrium (LD) with each other (rs1617640-T/G, rs507392-T/C and rs551238-A/C) were significantly (False Discovery Rate < 0.1) associated with mortality. Haplotype multivariate analysis revealed that patients carrying the G-C-C haplotype have an increased probability of survival, while an opposite effect was observed among subjects carrying the T-T-A haplotype. Our findings provide evidence that the EPO gene is an independent predictor of mortality in patients with T2D. Thus, understanding the mechanisms by which the genetic variability of EPO affects the mortality of T2D patients may provide potential targets for therapeutic interventions to improve the survival of these patients
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