894 resultados para PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA


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A low-cost vibration monitoring system has been developed and installed on an urban steel- plated stress-ribbon footbridge. The system continuously measures: the acceleration (using 18 triaxial MEMS accelerometers distributed along the structure), the ambient temperature and the wind velocity and direction. Automated output-only modal parameter estimation based on the Stochastic Subspace Identification (SSI) is carried out in order to extract the modal parameters, i.e., the natural frequencies, damping ratios and modal shapes. Thus, this paper analyzes the time evolution of the modal parameters over a whole-year data monitoring. Firstly, for similar environmental/operational factors, the uncertainties associated to the time window size used are studied and quantified. Secondly, a methodology to track the vibration modes has been established since several of them with closely-spaced natural frequencies are identified. Thirdly, the modal parameters have been correlated against external factors. It has been shown that this stress-ribbon structure is highly sensitive to temperature variation (frequency changes of more than 20%) with strongly seasonal and daily trends

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This brief communication concerns the unsteady aerodynamic external pressure loads acting on a semi-circular bluff body lying on a floor under wind gusts and describes the theoretical model, experimental setup, and experimental results obtained. The experimental setup is based on an open circuit, closed test section, low speed wind tunnel, which includes a sinusoidal gust generating mechanism, designed and built at the Instituto de Microgravedad “Ignacio Da Riva” of the Universidad Politécnica de Madrid (IDR/UPM). Based on the potential flow theory, a theoretical model has been proposed to analyse the problem, and experimental tests have been performed to study the unsteady aerodynamic loads on a semi-circular bluff body. By fitting the theoretical model predictions with the experimental results, influencing parameters of the unsteady aerodynamic loads are ascertained. The values of these parameters can help in clarifying the phenomenon of the external pressure loads on semi-circular bluff body under various gust frequencies. The theoretical model proposed allows the pressure variation to be split into two contributions, a quasi-steady term and an unsteady term with a simple physical meaning

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Es sabido que tras abandonar la carrera de arquitectura Chillida marcha a Paris a comenzar su carrera como escultor. De vuelta al País Vasco el hierro es el material en el que encuentra un camino propio. Toda la obra de su primera década está muy alejada en el aspecto formal de la arquitectura. Sin embargo, las líneas de fuerza que los hierros configuran muestran un interés espacial que queda manifiesto en una obra de 1953 denominada Consejo al espacio I. A partir de aquí su obra gira en torno al vacío. Las formas cambiarán con los materiales pero no el propósito. En sus dibujos, las manos expresan, más allá de su condición figurativa, la búsqueda del espacio cóncavo que los dedos encierran. El espacio que encuentra en la palma de la mano es equivalente al que construye con dedos gigantes de madera u hormigón. Chillida observa sus obras con una mirada cuya idea de escala se distancia del concepto de dimensión. Adquieren así una posibilidad de crecer que facilita imaginar sus espacios como arquitectura. Tras el hierro, el trabajo en madera y alabastro aproxima -en el aspecto formal- la obra de Chillida a la arquitectura. Los títulos de numerosas obras hacen referencia a ella o a conceptos con ella relacionados. Elogio de la arquitectura, Homenaje a la arquitectura, Arquitectura heterodoxa, Modulación del espacio, construcción heterodoxa, Alrededor del vacío, Mesa del arquitecto o Casa de luz, son algunos de ellos. La introducción del vacío en el alabastro da comienzo a un proceso tendente a que el espacio interior tenga una importancia inversamente proporcional a su presencia en la forma exterior. Un proceso de progresivo hermetismo donde pequeños espacios interiores son expresados mediante grandes masas envolventes. El espacio interior es el principal motivo por el que vemos la obra de Eduardo Chillida como arquitectura. La condición de interior, apreciable igualmente en sus grandes obras en el espacio público, hace que estas no constituyan únicamente hitos visuales sino espacios de protección con los que cuerpo interactúa estableciendo una nueva relación con el paisaje, el horizonte o el cosmos. La búsqueda de un interior vacío tiene como consecuencia la evolución hacia la desaparición de la forma exterior. Tal evolución comienza con el diálogo entre el bolo natural de alabastro y el vacío tallado de Homenaje a Goethe, y, como muestra de la inter-escalabilidad de la obra de Chillida, concluye con la introducción de un vacío oculto en la montaña sagrada de Tindaya. El gran vacío de Tindaya nos hace mirar la obra de pequeño formato a través de su filtro de aumento. Nos permite entender que el límite entre arquitectura y escultura es difuso en la obra del escultor vasco. Que la arquitectura puede estar en el origen de su escultura. Que su escultura puede ser el germen de muchas arquitecturas. ABSTRACT It is well known that after leaving his architectural studies Chillida went to Paris in order to begin his career as a sculptor. Back again to the Basque Country, iron is the material in which he finds his own way. In terms of form, his work from the very first ten years is far away from architecture. However, the strength lines set by the iron show a spatial will that is clearly evident in a 1953 piece called Advice to space I. From there on, his work focuses on void. Different materials will set different forms but the purpose will remain the same. In his drawings, hands are expressing, beyond its figurative condition, the search of the concave space that fingers are enclosing. The space founded in the palm of the hand is equivalent to the one built with giant wood or concrete fingers. Chillida faces his work with a look where the idea of scale takes distance to the concept of dimension. His works gets then a possibility to grow that allow us to imagine his spaces as architecture. Following iron, wood and alabaster pieces, in the formal aspect, approaches Chillida´s work to architecture. The titles of many sculptures are referred to it or to the concept related to it. In praise of architecture, Homage to architecture, Heterodox architecture, Modulation of space, Heterodox construction, Around the void, Architect’s table, or House of light, are some of them. The introduction of void in alabaster begins a process leading to the interior space has a presence inversely proportional to its importance in the external form. A process of progressive secrecy where small interior spaces are expressed through large enveloping masses. The interior space is the main reason why we see the work of Eduardo Chillida as architecture. The condition of inner space, equally noticeable in his great works in public space, makes this not only constitute visual landmarks, but protection spaces that body interacts with establishing a new relationship with the landscape, the horizon or the cosmos. The search of an inner void leads to an evolution towards the disappearance of the external form. The evolution begins in the dialogue between the natural bolus of alabaster and the carved void of Homage to Goethe, and as a sign of inter-scalability of the work of Chillida, it concludes with the introduction of a hidden void in the sacred mountain of Tindaya. The great void of Tindaya makes us look at a small format work trough the filter of his increase filter. It allows us to understand that the boundary between architecture and sculpture is diffuse in the work of the Basque sculptor. That architecture can be at the origin of his sculpture. That his sculpture may be the seed of many architectures.

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The polymerase (PB2) and nucleocapsid (NP) genes encoded by the genome of influenza virus are essential for replication of the virus. When synthetic genes that express RNAs for external guide sequences targeted to the mRNAs of the PB2 and NP genes are stably incorporated into mouse cells in tissue culture, infection of these cells with influenza virus is nonproductive. Endogenous RNase P cleaves the targeted influenza virus mRNAs when they are in a complex with the external guide sequences. Targeting two different mRNAs simultaneously inhibits viral particle production more efficiently than does targeting only one mRNA.

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An essential component of regulated steroidogenesis is the translocation of cholesterol from the cytoplasm to the inner mitochondrial membrane where the cholesterol side-chain cleavage enzyme carries out the first committed step in steroidogenesis. Recent studies showed that a 30-kDa mitochondrial phosphoprotein, designated steroidogenic acute regulatory protein (StAR), is essential for this translocation. To allow us to explore the roles of StAR in a system amenable to experimental manipulation and to develop an animal model for the human disorder lipoid congenital adrenal hyperplasia (lipoid CAH), we used targeted gene disruption to produce StAR knockout mice. These StAR knockout mice were indistinguishable initially from wild-type littermates, except that males and females had female external genitalia. After birth, they failed to grow normally and died from adrenocortical insufficiency. Hormone assays confirmed severe defects in adrenal steroids—with loss of negative feedback regulation at hypothalamic–pituitary levels—whereas hormones constituting the gonadal axis did not differ significantly from levels in wild-type littermates. Histologically, the adrenal cortex of StAR knockout mice contained florid lipid deposits, with lesser deposits in the steroidogenic compartment of the testis and none in the ovary. The sex-specific differences in gonadal involvement support a two-stage model of the pathogenesis of StAR deficiency, with trophic hormone stimulation inducing progressive accumulation of lipids within the steroidogenic cells and ultimately causing their death. These StAR knockout mice provide a useful model system in which to determine the mechanisms of StAR’s essential roles in adrenocortical and gonadal steroidogenesis.

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Divalent cations are thought essential for motile function of leukocytes in general, and for the function of critical adhesion molecules in particular. In the current study, under direct microscopic observation with concomitant time-lapse video recording, we examined the effects of 10 mM EDTA on locomotion of human blood polymorphonuclear leukocytes (PMN). In very thin slide preparations, EDTA did not impair either random locomotion or chemotaxis; motile behavior appeared to benefit from the close approximation of slide and coverslip (“chimneying”). In preparations twice as thick, PMN in EDTA first exhibited active deformability with little or no displacement, then rounded up and became motionless. However, on creation of a chemotactic gradient, the same cells were able to orient and make their way to the target, often, however, losing momentarily their purchase on the substrate. In either of these preparations without EDTA, specific antibodies to β2 integrins did not prevent random locomotion or chemotaxis, even when we added antibodies to β1 and αvβ3 integrins and to integrin-associated protein, and none of these antibodies added anything to the effects of EDTA. In the more turbulent environment of even more media, effects of anti-β2 integrins became evident: PMN still could locomote but adhered to substrate largely by their uropods and by uropod-associated filaments. We relate these findings to the reported independence from integrins of PMN in certain experimental and disease states. Moreover, we suggest that PMN locomotion in close quarters is not only integrin-independent, but independent of external divalent cations as well.

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A cross-sectional survey was made in 56 exceptionally healthy males, ranging in age from 20 to 84 years. Measurements were made of selected steroidal components and peptidic hormones in blood serum, and cognitive and physical tests were performed. Of those blood serum variables that gave highly significant negative correlations with age (r > −0.6), bioavailable testosterone (BT), dehydroepiandrosterone sulfate (DHEAS), and the ratio of insulin-like growth factor 1 (IGF-1) to growth hormone (GH) showed a stepwise pattern of age-related changes most closely resembling those of the age steps themselves. Of these, BT correlated best with significantly age-correlated cognitive and physical measures. Because DHEAS correlated well with BT and considerably less well than BT with the cognitive and physical measures, it seems likely that BT and/or substances to which BT gives rise in tissues play a more direct role in whatever processes are rate-limiting in the functions measured and that DHEAS relates more indirectly to these functions. The high correlation of IGF-1/GH with age, its relatively low correlation with BT, and the patterns of correlations of IGF-1/GH and BT with significantly age-correlated cognitive and physical measures suggest that the GH–IGF-1 axis and BT play independent roles in affecting these functions. Serial determinations made after oral ingestion of pregnenolone and data from the literature suggest there is interdependence of steroid metabolic systems with those operational in control of interrelations in the GH–IGF-1 axis. Longitudinal concurrent measurements of serum levels of BT, DHEAS, and IGF-1/GH together with detailed studies of their correlations with age-correlated functional measures may be useful in detecting early age-related dysregulations and may be helpful in devising ameliorative approaches.

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The correlation between telomerase activity and human tumors has led to the hypothesis that tumor growth requires reactivation of telomerase and that telomerase inhibitors represent a class of chemotherapeutic agents. Herein, we examine the effects of inhibition of telomerase inside human cells. Peptide nucleic acid and 2′-O-MeRNA oligomers inhibit telomerase, leading to progressive telomere shortening and causing immortal human breast epithelial cells to undergo apoptosis with increasing frequency until no cells remain. Telomere shortening is reversible: if inhibitor addition is terminated, telomeres regain their initial lengths. Our results validate telomerase as a target for the discovery of anticancer drugs and supply general insights into the properties that successful agents will require regardless of chemical type. Chemically similar oligonucleotides are in clinical trials and have well characterized pharmacokinetics, making the inhibitors we describe practical lead compounds for testing for an antitelomerase chemotherapeutic strategy.

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The Ca2+ channel α1A-subunit is a voltage-gated, pore-forming membrane protein positioned at the intersection of two important lines of research: one exploring the diversity of Ca2+ channels and their physiological roles, and the other pursuing mechanisms of ataxia, dystonia, epilepsy, and migraine. α1A-Subunits are thought to support both P- and Q-type Ca2+ channel currents, but the most direct test, a null mutant, has not been described, nor is it known which changes in neurotransmission might arise from elimination of the predominant Ca2+ delivery system at excitatory nerve terminals. We generated α1A-deficient mice (α1A−/−) and found that they developed a rapidly progressive neurological deficit with specific characteristics of ataxia and dystonia before dying ≈3–4 weeks after birth. P-type currents in Purkinje neurons and P- and Q-type currents in cerebellar granule cells were eliminated completely whereas other Ca2+ channel types, including those involved in triggering transmitter release, also underwent concomitant changes in density. Synaptic transmission in α1A−/− hippocampal slices persisted despite the lack of P/Q-type channels but showed enhanced reliance on N-type and R-type Ca2+ entry. The α1A−/− mice provide a starting point for unraveling neuropathological mechanisms of human diseases generated by mutations in α1A.

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To investigate the nature of plasticity in the adult visual system, perceptual learning was measured in a peripheral orientation discrimination task with systematically varying amounts of external (environmental) noise. The signal contrasts required to achieve threshold were reduced by a factor or two or more after training at all levels of external noise. The strong quantitative regularities revealed by this novel paradigm ruled out changes in multiplicative internal noise, changes in transducer nonlinearites, and simple attentional tradeoffs. Instead, the regularities specify the mechanisms of perceptual learning at the behavioral level as a combination of external noise exclusion and stimulus enhancement via additive internal noise reduction. The findings also constrain the neural architecture of perceptual learning. Plasticity in the weights between basic visual channels and decision is sufficient to account for perceptual learning without requiring the retuning of visual mechanisms.

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Accelerating hippocampal sprouting by making unilateral progressive lesions of the entorhinal cortex spared the spatial memory of rats tested for retention of a learned alternation task. Subsequent transection of the sprouted crossed temporodentate pathway (CTD), as well as a simultaneous CTD transection and progressive entorhinal lesion, produced a persistent deficit on the memory task. These results suggest that CTD sprouting, which is homologous to the original perforant path input to the dentate gyrus of the hippocampus, is behaviorally significant and can ameliorate at least some of the memory deficits associated with hippocampal deafferentation.

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We previously have described a mouse model for polycystic kidney disease (PKD) caused by either of two mutations, kat or kat2J, that map to the same locus on chromosome 8. The homozygous mutant animals have a latent onset, slowly progressing form of PKD with renal pathology similar to the human autosomal-dominant PKD. In addition, the mutant animals show pleiotropic effects that include facial dysmorphism, dwarfing, male sterility, anemia, and cystic choroid plexus. We previously fine-mapped the kat2J mutation to a genetic distance of 0.28 ± 0.12 centimorgan between D8Mit128 and D8Mit129. To identify the underlying molecular defect in this locus, we constructed an integrated genetic and physical map of the critical region surrounding the kat2J mutation. Cloning and expression analysis of the transcribed sequences from this region identified Nek1, a NIMA (never in mitosis A)-related kinase as a candidate gene. Further analysis of the Nek1 gene from both kat/kat and kat2J/kat2J mutant animals identified a partial internal deletion and a single-base insertion as the molecular basis for these mutations. The complex pleiotropic phenotypes seen in the homozygous mutant animals suggest that the NEK1 protein participates in different signaling pathways to regulate diverse cellular processes. Our findings identify a previously unsuspected role for Nek1 in the kidney and open a new avenue for studying cystogenesis and identifying possible modes of therapy.

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A comparison was made of the competence for neoplastic transformation in three different sublines of NIH 3T3 cells and multiple clonal derivatives of each. Over 90% of the neoplastic foci produced by an uncloned transformed (t-SA′) subline on a confluent background of nontransformed cells were of the dense, multilayered type, but about half of the t-SA′ clones produced only light foci in assays without background. This asymmetry apparently arose from the failure of the light focus formers to register on a background of nontransformed cells. Comparison was made of the capacity for confluence-mediated transformation between uncloned parental cultures and their clonal derivatives by using two nontransformed sublines, one of which was highly sensitive and the other relatively refractory to confluence-mediated transformation. Transformation was more frequent in the clones than in the uncloned parental cultures for both sublines. This was dramatically so in the refractory subline, where the uncloned culture showed no overt sign of transformation in serially repeated assays but increasing numbers of its clones exhibited progressive transformation. The reason for the greater susceptibility of the pure clones is apparently the suppression of transformation among the diverse membership that makes up the uncloned parental culture. Progressive selection toward increasing degrees of transformation in confluent cultures plays a major role in the development of dense focus formers, but direct induction by the constraint of confluence may contribute by heritably damaging cells. In view of our finding of increased susceptibility to transformation in clonal versus uncloned populations, expansion of some clones at the expense of others during the aging process would contribute to the marked increase of cancer with age.

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We report the study of the dynamics of the unbinding process under a force load f of adsorbed proteins (fibrinogen) on a solid surface (hydrophilic silica) by means of atomic force microscopy spectroscopy. By varying the loading rate rf, defined by f = rf t, t being the time, we find that, as for specific interactions, the mean rupture force increases with rf. This unbinding process is analyzed in the framework of the widely used Bell model. The typical dissociation rate at zero force entering in the model lies between 0.02 and 0.6 s−1. Each measured rupture is characterized by a force f0, which appears to be quantized in integer multiples of 180–200 pN.