900 resultados para Dementia With Lewy Bodies


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Transverse galloping is a type of aeroelastic instability characterised by large amplitude, low frequency oscillation of a structure in the direction normal to the mean wind direction. It normally appears in bodies with small stiffness and structural damping, provided the incident flow velocity is high enough. In the simplest approach transverse galloping can be considered as a one-degree-of-freedom oscillator subjected to aerodynamic forces, which in turn can be described by using a quasi-steady description. In this frame it has been demonstrated that hysteresis phenomena in transverse galloping is related to the existence of inflection points in the curve giving the dependence with the angle of attack of the aerodynamic coefficient normal to the incident flow. Aiming at experimentally checking such a relationship between these inflection points and hysteresis, wind tunnel experiments have been conducted. Experiments have been restricted to isosceles triangular cross-section bodies, whose galloping behaviour is well documented. Experimental results show that, according to theoretical predictions, hysteresis takes place at the angles of attack where there are inflection points in the lift coefficient curve, provided that the body is prone to gallop at these angles of attack.

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It is still an open question whether subjective memory complaints (SMC) can actually be considered to be clinically relevant predictors for the development of an objective memory impairment and even dementia. There is growing evidence that suggests that SMC are associated with an increased risk of dementia and with the presence of biological correlates of early Alzheimer's disease. In this paper, in order to shed some light on this issue, we try to discern whether subjects with SMC showed a different profile of functional connectivity compared with subjects with mild cognitive impairment (MCI) and healthy elderly subjects. In the present study, we compare the degree of synchronization of brain signals recorded with magnetoencephalography between three groups of subjects (56 in total): 19 with MCI, 12 with SMC and 25 healthy controls during a memory task. Synchronization likelihood, an index based on the theory of nonlinear dynamical systems, was used to measure functional connectivity. Briefly, results show that subjects with SMC have a very similar pattern of connectivity to control group, but on average, they present a lower synchronization value. These results could indicate that SMC are representing an initial stage with a hypo-synchronization (in comparison with the control group) where the brain system is still not compensating for the failing memory networks, but behaving as controls when compared with the MCI subjects.

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In the mid-long-term after a nuclear accident, the contamination of drinking water sources, fish and other aquatic foodstuffs, irrigation supplies and people?s exposure during recreational activities may create considerable public concern, even though dose assessment may in certain situations indicate lesser importance than for other sources, as clearly experienced in the aftermath of past accidents. In such circumstances there are a number of available countermeasure options, ranging from specific chemical treatment of lakes to bans on fish ingestion or on the use of water for crop irrigation. The potential actions can be broadly grouped into four main categories, chemical, biological, physical and social. In some cases a combination of actions may be the optimal strategy and a decision support system (DSS) like MOIRA-PLUS can be of great help to optimise a decision. A further option is of course not to take any remedial actions, although this may also have significant socio-economic repercussions which should be adequately evaluated. MOIRA-PLUS is designed to allow for a reliable assessment of the long-term evolution of the radiological situation and of feasible alternative rehabilitation strategies, including an objective evaluation of their social, economic and ecological impacts in a rational and comprehensive manner. MOIRA-PLUS also features a decision analysis methodology, making use of multi-attribute analysis, which can take into account the preferences and needs of different types of stakeholders. The main functions and elements of the system are described summarily. Also the conclusions from end-user?s experiences with the system are discussed, including exercises involving the organizations responsible for emergency management and the affected services, as well as different local and regional stakeholders. MOIRAPLUS has proven to be a mature system, user friendly and relatively easy to set up. It can help to better decisionmaking by enabling a realistic evaluation of the complete impacts of possible recovery strategies. Also, the interaction with stakeholders has allowed identifying improvements of the system that have been recently implemented.

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The asymptotic structure of the far-wake behind a charged body in a rarefied plasma flow is investigated under the assumption of small ion-to-electron temperature ratio and of flow speed hypersonic with respect to the ions but not with respect to the electrons. It is found that waves are excited even if the flow is subacoustic (flow velocity less than the ion-acoustic speed). For both superacoustic and subacoustic velocities a steep wave front develops separating the weakly perturbed, quasineutral plasma ahead, from the region behind where ion waves appear. Near the axis a trailing front develops;the region between this and the axis is quasineutral for superacoustic speeds. The decay laws in all of these regions, the self-similar structure of the fronts and the general character of the waves are determined.The damping of the waves and special flow detail for bodies large and small compared with the Debye length are discussed. A nonlinear analysis of the leading wave front in superacoustic flow is carried out. A hyperacoustic equivalence principle is presented.

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A sensitivity analysis has been performed to assess the influence of the inertial properties of railway vehicles on their dynamic behaviour. To do this, 216 dynamic simulations were performed modifying, one at a time, the masses, moments of inertia and heights of the centre of gravity of the carbody, the bogie and the wheelset. Three values were assigned to each parameter, corresponding to the percentiles 10, 50 and 90 of a data set stored in a database of railway vehicles. After processing the results of these simulations, the analyzed parameters were sorted by increasing influence. It was also found which of these parameters could be estimated with a lesser degree of accuracy for future simulations without appreciably affecting the simulation results. In general terms, it was concluded that the most sensitive inertial properties are the mass and the vertical moment of inertia, and the least sensitive ones the longitudinal and lateral moments of inertia.

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Transverse galloping is a type of aeroelastic instability characterized by oscillations perpendicular to wind direction, large amplitude and low frequency, which appears in some elastic two-dimensional bluff bodies when they are subjected to an incident flow, provided that the flow velocity exceeds a threshold critical value. Understanding the galloping phenomenon of different cross-sectional geometries is important in a number of engineering applications: for energy harvesting applications the interest relies on strongly unstable configurations but in other cases the purpose is to avoid this type of aeroelastic phenomenon. In this paper the aim is to analyze the transverse galloping behavior of rhombic bodies to understand, on the one hand, the dependence of the instability with a geometrical parameter such as the relative thickness and, on the other hand, why this cross-section shape, that is generally unstable, shows a small range of relative thickness values where it is stable. Particularly, the non-galloping rhombus-shaped prism?s behavior is revised through wind tunnel experiments. The bodies are allowed to freely move perpendicularly to the incoming flow and the amplitude of movement and pressure distributions on the surfaces is measured.

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Esta tesis doctoral se ha centrado en el estudio de las cargas aerodinámicas no estacionario en romos cuerpos o no aerodinámicos (bluff bodies). Con este objetivo se han identificado y analizado los siguientes puntos: -Caracterización del flujo medido con diferentes tipos de tubos de Pitot y anemómetro de hilo caliente en condiciones de flujo no estacionario inestable generado por un túnel aerodinamico de ráfagas. -Diseño e integración de los montajes experimentales requeridos para medir las cargas de viento internas y externas que actúan sobre los cuerpos romos en condiciones de flujo de viento con ráfagas. -Implementación de modelos matemáticos semi-empíricos basados en flujo potencial y las teorías fenomenológicas pertinentes para simular los resultados experimentales. -En diversan condiciones de flujo con ráfagas, la identificación y el análisis de la influencia de los parámetros obtenida a partir de los modelos teóricos desarrollados. -Se proponen estimaciones empíricas para averiguar los valores adecuados de los parámetros que influyente, mediante el ajuste de los resultados experimentales y los predichos teóricamente. Los montajes experimentales se has reakizado en un tunel aerodinamico de circuito abierto, provisto de baja velocidad, cámara de ensayes cerrada, un nuevo concepto de mecanismo generador de ráfaga sinusoidal, diseñado y construido en el Instituto de Microgravedad "Ignacio Da Riva" de la Universidad Politécnica de Madrid, (IDR / UPM). La principal característica de este túnel aerodynamico es la capacidad de generar un flujo con un perfil de velocidad uniforme y una fluctuación sinusoidal en el tiempo. Se han realizado pruebas experimentales para estudiar el efecto de los flujos no estacionarios en cuerpos romos situados en el suelo. Se han propuesto dos modelos teóricos para diterminar las cargas de presión externas e internas respectivamente. Con el fin de satisfacer la necesidad de la crea ráfagas de viento sinusoidales para comprobar las predicciones de los modelos teóricos, se han obtenido velocidades de hasta 30 m/s y frecuencias ráfaga de hasta 10 Hz. La sección de la cámara de ensayos es de 0,39 m x 0,54 m, dimensiónes adecuadas para llevar a cabo experimentos con modelos de ensayos. Se muestra que en la gama de parámetros explorados los resultados experimentales están en buen acuerdo con las predicciones de los modelos teóricos. Se han realizado pruebas experimentales para estudiar los efectos del flujo no estacionario, las cuales pueden ayudar a aclarar el fenómeno de las cargas de presión externa sobre los cuerpos romos sometidos a ráfagas de viento: y tambien para determinan las cargas de presión interna, que dependen del tamaño de los orificios de ventilación de la construcción. Por último, se ha analizado la contribución de los términos provenientes del flujo no estacionario, y se han caracterizado o los saltos de presión debido a la pérdida no estacionario de presión a través de los orificios de ventilación. ABSTRACT This Doctoral dissertation has been focused to study the unsteady aerodynamic loads on bluff bodies. To this aim the following points have been identified and analyzed: -Characterization of the flow measured with different types of Pitot tubes and hot wire anemometer at unsteady flow conditions generated by a gust wind tunnel. -Design and integrating of the experimental setups required to measure the internal and external wind loads acting on bluff bodies at gusty wind flow conditions. -Implementation of semi-empirical mathematical models based on potential flow and relevant phenomenological theories to simulate the experimental results.-At various gusty flow conditions, extracting and analyzing the influence of parameters obtained from the developed theoretical models. -Empirical estimations are proposed to find out suitable values of the influencing parameters, by fitting the experimental and theoretically predicted results. The experimental setups are performed in an open circuit, closed test section, low speed wind tunnel, with a new sinusoidal gust generator mechanism concept, designed and built at the Instituto de Microgravedad “Ignacio Da Riva” of the Universidad Politécnica de Madrid, (IDR/UPM). The main characteristic of this wind tunnel is the ability to generate a flow with a uniform velocity profile and a sinusoidal time fluctuation of the speed. Experimental tests have been devoted to study the effect of unsteady flows on bluff bodies lying on the ground. Two theoretical models have been proposed to measure the external and internal pressure loads respectively. In order to meet the need of creating sinusoidal wind gusts to check the theoretical model predictions, the gust wind tunnel maximum flow speed and, gust frequency in the test section have been limited to 30 m/s and 10 Hz, respectively have been obtained. The test section is 0.39 m × 0.54 m, which is suitable to perform experiments with testing models. It is shown that, in the range of parameters explored, the experimental results are in good agreement with the theoretical model predictions. Experimental tests have been performed to study the unsteady flow effects, which can help in clarifying the phenomenon of the external pressure loads on bluff bodies under gusty winds: and also to study internal pressure loads, which depend on the size of the venting holes of the building. Finally, the contribution of the unsteady flow terms in the theoretical model has been analyzed, and the pressure jumps due to the unsteady pressure losses through the venting holes have been characterized.

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In acute promyelocytic leukemia (APL), the typical t(15;17) and the rare t(11;17) translocations express, respectively, the PML/RARα and PLZF/RARα fusion proteins (where RARα is retinoic acid receptor α). Herein, we demonstrate that the PLZF and PML proteins interact with each other and colocalize onto nuclear bodies (NBs). Furthermore, induction of PML expression by interferons leads to a recruitment of PLZF onto NBs without increase in the levels of the PLZF protein. PML/RARα and PLZF/RARα localize to the same microspeckled nuclear domains that appear to be common targets for the two fusion proteins in APL. Although PLZF/RARα does not affect the localization of PML, PML/RARα delocalizes the endogenous PLZF protein in t(15;17)-positive NB4 cells, pointing to a hierarchy in the nuclear targeting of these proteins. Thus, our results unify the molecular pathogenesis of APL with at least two different RARα gene translocations and stress the importance of alterations of PLZF and RARα nuclear localizations in this disease.

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In human beings of both sexes, dehydroepiandrosterone sulfate (DHEAS) circulating in blood is mostly an adrenally secreted steroid whose serum concentration (in the micromolar range and 30–50% higher in men than in women) decreases with age, toward ≈20–10% of its value in young adults during the 8th and 9th decades. The mechanism of action of DHEA and DHEAS is poorly known and may include partial transformation into sex steroids, increase of bioavailable insulin-like growth factor I, and effects on neurotransmitter receptors. Whether there is a cause-to-effect relationship between the decreasing levels of DHEAS with age and physiological and pathological manifestations of aging is still undecided, but this is of obvious theoretical and practical interest in view of the easy restoration by DHEA administration. Here we report on 622 subjects over 65 years of age, studied for the 4 years since DHEAS baseline values had been obtained, in the frame of the PAQUID program, analyzing the functional, psychological, and mental status of a community-based population in the south-west of France. We confirm the continuing decrease of DHEAS serum concentration with age, more in men than in women, even if men retain higher levels. Significantly lower values of baseline DHEAS were recorded in women in cases of functional limitation (Instrumental Activities of Daily Living), confinement, dyspnea, depressive symptomatology, poor subjective perception of health and life satisfaction, and usage of various medications. In men, there was a trend for the same correlations, even though not statistically significant in most categories. No differences in DHEAS levels were found in cases of incident dementia in the following 4 years. In men (but not in women), lower DHEAS was significantly associated with increased short-term mortality at 2 and 4 years after baseline measurement. These results, statistically established by taking into account corrections for age, sex, and health indicators, suggest the need for further careful trials of the administration of replacement doses of DHEA in aging humans. Indeed, the first noted results of such “treatment” are consistent with correlations observed here between functional and psychological status and endogenous steroid serum concentrations.

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The stem-loop binding protein (SLBP1) binds the 3′ stem-loop of histone pre-mRNA and is required for efficient processing of histone transcripts in the nucleus. We examined the localization of SLBP1 in the germinal vesicle of Xenopus laevis oocytes. In spread preparations of germinal vesicle contents, an anti-SLBP1 antibody stained coiled bodies and specific chromosomal loci, including terminal granules, axial granules, and some loops. After injection of myc-tagged SLBP1 transcripts into the oocyte cytoplasm, newly translated myc-SLBP1 protein was detectable in coiled bodies within 4 h and in terminal and axial granules by 8 h. To identify the region(s) of SLBP1 necessary for subnuclear localization, we subcloned various parts of the SLBP1 cDNA and injected transcripts of these into the cytoplasm of oocytes. We determined that 113 amino acids at the carboxy terminus of SLBP1 are sufficient for coiled body localization and that disruption of a previously defined RNA-binding domain did not alter this localization. Coiled bodies also contain the U7 small nuclear ribonucleoprotein particle (snRNP), which participates in cleavage of the 3′ end of histone pre-mRNA. The colocalization of SLBP1 and the U7 snRNP in the coiled body suggests coordinated control of their functions, perhaps through a larger histone-processing particle. Some coiled bodies are attached to the lampbrush chromosomes at the histone gene loci, consistent with the view that coiled bodies in the oocyte recruit histone-processing factors to the sites of histone pre-mRNA transcription. The non-histone chromosomal sites at which SLBP1 is found include the genes coding for 5 S rRNA, U1 snRNA, and U2 snRNA, suggesting a wider role for SLBP1 in the biosynthesis of small non-spliced RNAs.

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We have cloned from rat brain the cDNA encoding an 89,828-Da kinesin-related polypeptide KIF3C that is enriched in brain, retina, and lung. Immunocytochemistry of hippocampal neurons in culture shows that KIF3C is localized to cell bodies, dendrites, and, in lesser amounts, to axons. In subcellular fractionation experiments, KIF3C cofractionates with a distinct population of membrane vesicles. Native KIF3C binds to microtubules in a kinesin-like, nucleotide-dependent manner. KIF3C is most similar to mouse KIF3B and KIF3A, two closely related kinesins that are normally present as a heteromer. In sucrose density gradients, KIF3C sediments at two distinct densities, suggesting that it may be part of two different multimolecular complexes. Immunoprecipitation experiments show that KIF3C is in part associated with KIF3A, but not with KIF3B. Unlike KIF3B, a significant portion of KIF3C is not associated with KIF3A. Consistent with these biochemical properties, the distribution of KIF3C in the CNS has both similarities and differences compared with KIF3A and KIF3B. These results suggest that KIF3C is a vesicle-associated motor that functions both independently and in association with KIF3A.

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Antisense oligonucleotides are powerful tools for the in vivo regulation of gene expression. We have characterized the intracellular distribution of fluorescently tagged phosphorothioate oligodeoxynucleotides (PS-ONs) at high resolution under conditions in which PS-ONs have the potential to display antisense activity. Under these conditions PS-ONs predominantly localized to the cell nucleus where they accumulated in 20–30 bright spherical foci designated phosphorothioate bodies (PS bodies), which were set against a diffuse nucleoplasmic population excluding nucleoli. PS bodies are nuclear structures that formed in cells after PS-ON delivery by transfection agents or microinjection but were observed irrespectively of antisense activity or sequence. Ultrastructurally, PS bodies corresponded to electron-dense structures of 150–300 nm diameter and resembled nuclear bodies that were found with lower frequency in cells lacking PS-ONs. The environment of a living cell was required for the de novo formation of PS bodies, which occurred within minutes after the introduction of PS-ONs. PS bodies were stable entities that underwent noticeable reorganization only during mitosis. Upon exit from mitosis, PS bodies were assembled de novo from diffuse PS-ON pools in the daughter nuclei. In situ fractionation demonstrated an association of PS-ONs with the nuclear matrix. Taken together, our data provide evidence for the formation of a nuclear body in cells after introduction of phosphorothioate oligodeoxynucleotides.