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Stroke is the second leading cause of death. However, effective pharmocologic treatment options are still extremely limited and applicable to only a small fraction of patents. The translational failure in finding an effective neuroprotectant for ischemic strokes has generated an active discussion in this field. One focus has been on validating systems for testing neuroprotectants. This review discusses some fundamental issues in experimental stroke that are worthy of further exploration. We begin with a general review of the current status of experimental stroke research and then move on to a discussion of the determining factors and processes that control and differentiate the fate of ischemic ischemic cells and tissue. We propose several strategies of neuroprotection for ischemic strokes with an emphasis on manipulating cellular energy state.




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Bartholdi's early models were all similar in concept: a female figure in neoclassical style representing liberty, wearing a stola and pella (gown and cloak, common in depictions of Roman goddesses) and holding a torch aloft. According to popular accounts, the face was modeled after that of Charlotte Beysser Bartholdi, the sculptor's mother,[31] but Regis Huber, the curator of the Bartholdi Museum is on record as saying that this, as well as other similar speculations, have no basis in fact.[32] He designed the figure with a strong, uncomplicated silhouette, which would be set off well by its dramatic harbor placement and allow passengers on vessels entering New York Bay to experience a changing perspective on the statue as they proceeded toward Manhattan. He gave it bold classical contours and applied simplified modeling, reflecting the huge scale of the project and its solemn purpose.[25] Bartholdi wrote of his technique:


The car was divided into two superimposed compartments, each holding 25 passengers, with the lift operator occupying an exterior platform on the first level. Motive power was provided by an inclined hydraulic ram 12.67 m (41 ft 7 in) long and 96.5 cm (38.0 in) in diameter in the tower leg with a stroke of 10.83 m (35 ft 6 in): this moved a carriage carrying six sheaves. Five fixed sheaves were mounted higher up the leg, producing an arrangement similar to a block and tackle but acting in reverse, multiplying the stroke of the piston rather than the force generated. The hydraulic pressure in the driving cylinder was produced by a large open reservoir on the second level. After being exhausted from the cylinder, the water was pumped back up to the reservoir by two pumps in the machinery room at the base of the south leg. This reservoir also provided power to the lifts to the first level.[citation needed]


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In two studies published in Nature (Hussein et al. and Tonge et al.), Nagy and colleagues used a secondary reprogramming system, in which the starting differentiated cells are mouse iPS cell-derived fibroblasts containing doxycycline-inducible OSKM. This system produces enough reprogrammed cells to enable detailed molecular analyses to be carried out. Previous secondary reprogramming studies provided evidence that reprogramming occurs in multiple steps via transitions through defined transcriptional and chromatin states. To characterize these steps, the authors generated multiple omic profiles at specific time points. Such profiles included the transcriptome (for both long and short transcripts), the global and cell-surface proteome, and the epigenome. The latter tracked different chromatin marks, specifically activating histone H3 lysine 4 trimethylation (H3K4me3), repressive H3K27me3 and H3K36me3, which is indicative of transcriptional elongation. 041b061a72


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