995 resultados para Burnet, Gilbert, 1643-1715.
Resumo:
1. We compared the changes in binding energy generated by two mutations that shift in divergent directions the constitutive activity of the human beta(2) adrenergic receptor (beta(2)AR). 2. A constitutively activating mutant (CAM) and the double alanine replacement (AA mutant) of catechol-binding serines (S204A, S207A) in helix 5 were stably expressed in CHO cell lines, and used to measure the binding affinities of more than 40 adrenergic ligands. Moreover, the efficacy of the same group of compounds was determined as intrinsic activity for maximal adenylyl cyclase stimulation in wild-type beta(2)AR. 3. Although the two mutations had opposite effects on ligand affinity, the extents of change were in both cases largely correlated with the degree of ligand efficacy. This was particularly evident if the extra loss of binding energy due to hydrogen bond deletion in the AA mutant was taken into account. Thus the data demonstrate that there is an overall linkage between the configuration of the binding pocket and the intrinsic equilibrium between active and inactive receptor forms. 4. We also found that AA mutation-induced affinity changes for catecholamine congeners gradually lacking ethanolamine substituents were linearly correlated to the loss of affinity that such modifications of the ligand cause for wild-type receptor. This indicates that the strength of bonds between catechol ring and helix 5 is critically dependent on the rest of interactions of the beta-ethanolamine tail with other residues of the beta(2)-AR binding pocket.
Resumo:
Whether maximal surgical resection of glioblastoma improves patient survival has been controversial, as it is difficult to perform an unbiased assessment of extent of resection (EOR) independent of other patient-specific prognostic factors. Recently, glioblastoma has been sub-classified into 4 distinct molecular risk groups (RGs), which have been validated as prognostic biomarkers in the randomized clinical trial of temozolomide dosing in glioblastoma: the Radiation Therapy Oncology Group 0525 (RTOG-0525) trial. We sought to perform exploratory analyses examining gross total resection (GTR) versus sub-total resection (STR) within these RGs in RTOG-0525 patients. Across all randomized patients, n ¼ 354 had STR and n ¼ 450 had GTR as determined by neurosurgeon operative report. GTR was not significantly associated with survival across the overall study group. A total of 725 patients had sufficient tissue for determination of molecular RG. There were no significant differences in percentage of GTR between each of the 4 RGs (P ¼ 0.64). In exploratory subgroup analyses, GTR was associated with improved survival only for patients with tumors from RG4. Hazard ratios (95% confidence intervals) were 0.52 (0.08-2.07) for RG1 (n ¼ 28, 68% GTR), 1.74 (0.75-4.05) for RG2 (n ¼ 39, 56% GTR), 1.09 (0.84-1.42) for RG3 (n ¼ 284, 56% GTR), and 1.26 (1.01-1.56) for RG4 (n ¼ 374, 55% GTR). In univariate analysis within RG4, GTR was associated with a median survival of 14.6 months vs 12.7 months for STR (P ¼ 0.0352. In a Cox model adjusting for age, KPS, and neurologic function (NF), surgery remained an independent factor within RG4: GTR (P ¼ 0.0331), age (P ¼ 0.0014), KPS (P ¼ .3289), and NF (P ¼ 0.3804). There are important cautions in the interpretation of these data, including lack of MRI confirmation of EOR, and inclusion of a range of STR (from biopsy to near-total resection). However, these exploratory results raise the possibility that upfront characterization of tumor molecular profile may allow for personalized therapeutic strategies to improve outcomes for patients with glioblastoma.
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Échelle(s) : [1:4 100 000 environ], Mille Pas Geometriques, ou Mille d'Italie 180 [= 8 cm]
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Échelle(s) : [1:4 100 000 environ], Mille Pas Geometriques, ou Mille d'Italie 180 [= 8 cm]
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Échelle(s) : [1:2 581 000 environ] A Scale of English Miles 100 [= 7,2 cm]
Resumo:
The aim of this randomised controlled trial was to see if the addition of 4 mg/ml DNA-C priming given by the intramuscular route at weeks 0 and 4 to NYVAC-C at weeks 20 and 24, safely increased the proportion of participants with HIV-specific T-cell responses measured by the interferon (IFN)-gamma ELISpot assay at weeks 26 and/or 28 compared to NYVAC-C alone. Although 2 individuals discontinued after the first DNA-C due to adverse events (1 vaso-vagal; 1 transient, asymptomatic elevation in alanine transaminase), the vaccines were well tolerated. Three others failed to complete the regimen (1 changed her mind; 2 lost to follow-up). Of the 35 that completed the regimen 90% (18/20) in the DNA-C group had ELISpot responses compared to 33% (5/15) that received NYVAC-C alone (p=0.001). Responses were to envelope in the majority (21/23). Of the 9 individuals with responses to envelope and other peptides, 8 were in the DNA-C group. These promising results suggest that DNA-C was an effective priming agent, that merits further investigation.
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Échelle(s) : [1:895 000 environ], Miglia Italiane 30 [= 6,1 cm]
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Échelle(s) : [1:1 460 500 environ], Scala di Miglia Italiane 60 [= 7,6 cm]
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El presente trabajo se inscribe en el ámbito de la traducción especializada jurídico-económica inglés-español. El documento objeto de estudio es una Directiva del Parlamento Europeo y de la Comisión, por ende, pertenece al ordenamiento jurídico comunitario. El tema que trataremos es el régimen para el comercio de derechos de emisión de gases de efecto invernadero.
Resumo:
Aquest treball acadèmic pretén demostrar que la traducció jurídica i la traducció assistida són dues disciplines plenament compatibles, així com establir la utilitat d'apropar aquests dos àmbits. Per tal d'acomplir aquest objectiu, es creen projectes de traducció, bases de dades terminològiques i memòries de traducció de textos jurídics mercantils (contractes d'agència) i civils (certificats de defunció) tot utilitzant el sistema de traducció assistida per ordinador (TAO) Foreign Desk/Frog. Les conclusions del treball es van extreure amb el bolcatge en altres projectes de les memòries generades, així com la reutilització en altres projectes de les BDTs creades.
Resumo:
Aquest treball s’emmarca dins del dret de successions dels Estats Units. Pretén simular una situació real de traducció al català d’un formulari d‘un testament en anglès i recull els principals problemes que planteja la traducció jurídica d’aquests documents per contribuir a facilitar la tasca dels futurs professionals d‘aquest àmbit d‘especialitat.
Resumo:
"Traducció jurídicoeconòmica d'una fragment del Tractat pel qual s'estableix una Constitució per a Europa, amb el propòsit d'establir una sèrie de directrius sòlides per a la traducció al català en el context de la Unió Europea, tot seguint les indicacions dels organismes catalans competents."
Resumo:
Este trabajo consta de tres partes diferentes pero profundamente relacionadas. A partir de la propuesta de traducción de un texto científico se establece una metodología para la traducción de textos especializados. Se describen los problemas que surgen al enfrentarse a esta actividad y se propone una clasificación. Finalmente, se recogen los problemas terminológicos y fraseológicos del texto trabajado en un glosario.
Resumo:
Aquest treball constitueix un estudi reflexiu i pràctic de les diferències dialectials entre el català oriental i el valencià en la producció i traducció de textos normatius. Pretén, a més, ser un punt de partida per a la creació d'uns criteris estàndard de redacció en valencià d'aquest tipus de textos