968 research outputs found

    APPLICATION OF QUALITATIVE REASONING IN ENGINEERING

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    Qualitative reasoning is an alternative problem-solving technique useful for the conceptual design of structures. Qualitative reasoning represents the relationships between parameters in a model, and a search computation assigns values represented by intervals and relevant points in the behavior. The traditional difference between analysis and design or input and output parameters in a procedural computation is not existent in qualitative reasoning, since all the parameters in a model are equally represented. Qualitative reasoning derives values for parameters even with incomplete and imprecise knowledge about the model. This work presents a qualitative structural analysis framework, suitable for the evaluation of conceptual designs as well as for tutoring systems. The framework has been implemented in a computer program called Agrippa using the computer language Prolog. Based on a representation of fundamental principles of equilibrium, compatibility, and force-deformation and an incomplete knowledge of geometry and topology, Agrippa derives the signs and relative magnitude of forces and displacements for three-dimensional models of structures

    Pooling financial resources for universal health coverage: options for reform.

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    Universal health coverage (UHC) means that all people can access health services of good quality without experiencing financial hardship. Three health financing functions - revenue raising, pooling of funds and purchasing health services - are vital for UHC. This article focuses on pooling: the accumulation and management of prepaid financial resources. Pooling creates opportunities for redistribution of resources to support equitable access to needed services and greater financial protection even if additional revenues for UHC cannot be raised. However, in many countries pooling arrangements are very fragmented, which create barriers to redistribution. The purpose of this article is to provide an overview of pooling reform options to support countries who are exploring ways to enhance redistribution of funds. We outline four broad types of pooling reforms and discuss their potential and challenges in addressing fragmentation of health financing: (i) shifting to compulsory or automatic coverage for everybody; (ii) merging different pools to increase the number of pool members and the diversity of pool members' health needs and risks; (iii) cross-subsidization of pools that have members with lower revenues and higher health risks; and (iv) harmonization across pools, such as benefits, payment methods and rates. Countries can combine several reform elements. Whether the potential for redistribution is actually realized through a pooling reform also depends on the alignment of the pooling structure with revenue raising and purchasing arrangements. Finally, the scope for reform is constrained by institutional and political feasibility, and the political economy around pooling reforms needs to be anticipated and managed

    Solitary-wave Vortices in Quadratic Nonlinear Media

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    We find families of vortex solitary waves in bulk quadratic nonlinear media under conditions for second-harmonic generation. We show that the vortex solitary waves are azimuthally unstable and that they decay into sets of stable spatial solitons. We calculate the growth rates of the azimuthal perturbations and show how those affect the pattern of output light. © 1998 Optical Society of AmericaThis work has been partially supported by the Spanish Government under grant PB95-0768.Peer Reviewe

    Reglas de similitud para modos TE en guias opticas no lineales

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    We have shown that the stationary propcrties of TE guided waves in a slab optical waveguidewith a nonlinear Kerr-likc bounding medium can be described in a compact way bymeans of the usual normalized effective modal index (b) and a set of only four independent normalized parameters: the well-known normalized thickness (V) and asymmetry measure (a) of the waveguide, the generalized aspect ratio between film and substrate refractive indices and a new guided power measure. Allowed and forbidden regions in the{b, V,a}-space in order that a guided solution exists have been recognized and classified. As a further application or the normalized parameters, we focus on the cutoff properties of the TEo guided wave.Peer ReviewedPostprint (published version

    Investigating the Role of Mitochondrial Haplogroups in Genetic Predisposition to Meningococcal Disease

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    BACKGROUND AND AIMS: Meningococcal disease remains one of the most important infectious causes of death in industrialized countries. The highly diverse clinical presentation and prognosis of Neisseria meningitidis infections are the result of complex host genetics and environmental interactions. We investigated whether mitochondrial genetic background contributes to meningococcal disease (MD) susceptibility. METHODOLOGY/PRINCIPAL FINDINGS: Prospective controlled study was performed through a national research network on MD that includes 41 Spanish hospitals. Cases were 307 paediatric patients with confirmed MD, representing the largest series of MD patients analysed to date. Two independent sets of ethnicity-matched control samples (CG1 [N = 917]), and CG2 [N = 616]) were used for comparison. Cases and controls underwent mtDNA haplotyping of a selected set of 25 mtDNA SNPs (mtSNPs), some of them defining major European branches of the mtDNA phylogeny. In addition, 34 ancestry informative markers (AIMs) were genotyped in cases and CG2 in order to monitor potential hidden population stratification. Samples of known African, Native American and European ancestry (N = 711) were used as classification sets for the determination of ancestral membership of our MD patients. A total of 39 individuals were eliminated from the main statistical analyses (including fourteen gypsies) on the basis of either non-Spanish self-reported ancestry or the results of AIMs indicating a European membership lower than 95%. Association analysis of the remaining 268 cases against CG1 suggested an overrepresentation of the synonym mtSNP G11719A variant (Pearson's chi-square test; adjusted P-value = 0.0188; OR [95% CI] = 1.63 [1.22-2.18]). When cases were compared with CG2, the positive association could not be replicated. No positive association has been observed between haplogroup (hg) status of cases and CG1/CG2 and hg status of cases and several clinical variants. CONCLUSIONS: We did not find evidence of association between mtSNPs and mtDNA hgs with MD after carefully monitoring the confounding effect of population sub-structure. MtDNA variability is particularly stratified in human populations owing to its low effective population size in comparison with autosomal markers and therefore, special care should be taken in the interpretation of seeming signals of positive associations in mtDNA case-control association studies

    Robustness of Quadratic Solitons with Periodic Gain

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    We address the robustness of quadratic solitons with periodic non-conservative perturbations. We find the evolution equations for guiding-center solitons under conditions for second-harmonic generation in the presence of periodic multi-band loss and gain. Under proper conditions, a robust guiding-center soliton formation is revealed.Comment: 5 pages, 5 figures, submitted to Optics Communicatio

    A-to-I editing on tRNAs: Biochemical, biological and evolutionary implications

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    AbstractInosine on transfer RNAs (tRNAs) are post-transcriptionally formed by a deamination mechanism of adenosines at positions 34, 37 and 57 of certain tRNAs. Despite its ubiquitous nature, the biological role of inosine in tRNAs remains poorly understood. Recent developments in the study of nucleotide modifications are beginning to indicate that the dynamics of such modifications are used in the control of specific genetic programs. Likewise, the essentiality of inosine-modified tRNAs in genome evolution and animal biology is becoming apparent. Here we review our current understanding on the role of inosine in tRNAs, the enzymes that catalyze the modification and the evolutionary link between such enzymes and other deaminases

    Describing ion transport and water splitting in an electrodialysis stack with bipolar membranes by a 2-D model: Experimental validation

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    Electrodialysis with bipolar membranes (EDBM) has drawn attention motivated by their application in gener- ating reagents from salts. Due to the water splitting (WS) occurring at the junction of the bipolar membranes (BPMs), where the anion and cation layers are in strict contact, H+ and OH- are released from the BPM producing acid and alkali on the respective compartment. Considering this application, the interest of this work is to provide further understanding of the mechanisms of WS and transport of species in EDBM. This work develops and utilizes, for the first time, an experimentally validated two-dimensional (2-D) computational model, in which the Navier-Stokes and Nernst-Planck equations are coupled with the description of WS given by the Second Wien effect. In addition, a 1-D geometry is also proposed to perform a comparison between electroneutrality and Poisson charge conservation. The model is computationally solved using COMSOL Multiphysics. According to simulations, electroneutrality is valid for 2-D geometries. Moreover, the semipermeable characteristics of the membranes are assessed by means of evidencing a polarization effect resulting in a double-electric layer. The model proposed predicts a significant proton leakage, and facilitates the study of WS within the BPMs.Peer ReviewedPostprint (published version

    Human alpha-synuclein overexpression in mouse serotonin neurons triggers a depressive-like phenotype. Rescue by oligonucleotide therapy

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    Anxiety and depression affect 35–50% of patients with Parkinson’s disease (PD), often precede the onset of motor symptoms, and have a negative impact on their quality of life. Dysfunction of the serotonergic (5-HT) system, which regulates mood and emotional pathways, occurs during the premotor phase of PD and contributes to a variety of non-motor symptoms. Furthermore, α-synuclein (α-Syn) aggregates were identified in raphe nuclei in the early stages of the disease. However, there are very few animal models of PD-related neuropsychiatric disorders. Here, we develop a new mouse model of α-synucleinopathy in the 5-HT system that mimics prominent histopathological and neuropsychiatric features of human PD. We showed that adeno-associated virus (AAV5)-induced overexpression of wild-type human α-Syn (h-α-Syn) in raphe 5-HT neurons triggers progressive accumulation, phosphorylation, and aggregation of h-α-Syn protein in the 5-HT system. Specifically, AAV5-injected mice displayed axonal impairment in the output brain regions of raphe neurons, and deficits in brain-derived neurotrophic factor (BDNF) expression and 5-HT neurotransmission, resulting in a depressive-like phenotype. Intracerebroventricular treatment with an indatraline-conjugated antisense oligonucleotide (IND-ASO) for four weeks induced an effective and safe reduction of h-α-Syn synthesis in 5-HT neurons and its accumulation in the forebrain, alleviating early deficits of 5-HT function and improving the behavioural phenotype. Altogether, our findings show that α-synucleinopathy in 5-HT neurons negatively affects brain circuits that control mood and emotions, resembling the expression of neuropsychiatric symptoms occurring at the onset of PD. Early preservation of 5-HT function by reducing α-Syn synthesis/accumulation may alleviate PD-related depressive symptoms
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