996 resultados para 875.07[Eurípides]
Resumo:
本实用新型公开一种用于高真空密封连接的装置。本实用新型是在现有金属密封活套法兰的活套外环径向至少设有一个带内螺纹的通孔,在该通孔内配合有顶丝,在法兰肩环的外圆设有一内凹的环槽,在配合状态时所述顶丝的头部嵌入法兰肩环外圆上所设的内凹环槽内,使法兰肩环与活套外环间沿轴向的运动被约束。本实用新型的法兰肩环上的内凹环槽可以是V型截面,也可以是矩型或圆弧形截面。
Resumo:
2007
Resumo:
2007
Resumo:
2007
Resumo:
2007
Resumo:
Handwritten letter from Timothy Merritt to Rev. Epaphras "Kibbe[sic]" regarding religious developments in Boston as well as the death of Merritt's son. Dated 10/07/1803
Resumo:
Spank follows the journeys of two women as they reveal stories from private and public sources set apart by two centuries. It investigates notions of 'faction' and what is filtered out historically within a theme of female trauma and the body. [ABSTRACT BY THE AUTHOR]
Resumo:
Photodynamic therapy of deep or nodular skin tumours is currently limited by the poor tissue penetration of the porphyrin precursor 5-aminolevulinic acid (ALA). In this study, silicon microneedle arrays were used, for the first time, to enhance skin penetration of ALA in vitro and in vivo. Puncturing excised murine skin with 6x7 arrays of microneedles 270 mum in height, with a diameter of 240 mum at the base and an interspacing of 750 mum led to a significant increase in transdermal delivery of ALA released from a bioadhesive patch containing 19 mg ALA cm(-2). Microneedle puncture enhanced ALA delivery to the upper regions of excised porcine skin but, at mean depths of 1.875 mm, ALA concentrations were similar to control values, possibly reflecting binding of ALA by tissue components. However, and importantly, in vivo experiments using nude mice showed that microneedle puncture could reduce application time and ALA dose required to induce high levels of the photosensitiser protoporphyrin IX in skin. This clearly has implications for clinical practice, as shorter application times would mean improved patient and clinician convenience and also that more patients could be treated in the same session. As ALA is expensive and degrades rapidly via a second order reaction, reducing the required dose is also a notable advantage.
Resumo:
Performance at the Joinery, Dublin, at at Spatial Music Collective concert
Resumo:
BACKGROUND: The free fatty acid receptors (FFAs), including FFA1 (orphan name: GPR40), FFA2 (GPR43) and FFA3 (GPR41) are G protein-coupled receptors (GPCRs) involved in energy and metabolic homeostasis. Understanding the structural basis of ligand binding at FFAs is an essential step toward designing potent and selective small molecule modulators.
RESULTS: We analyse earlier homology models of FFAs in light of the newly published FFA1 crystal structure co-crystallized with TAK-875, an ago-allosteric ligand, focusing on the architecture of the extracellular binding cavity and agonist-receptor interactions. The previous low-resolution homology models of FFAs were helpful in highlighting the location of the ligand binding site and the key residues for ligand anchoring. However, homology models were not accurate in establishing the nature of all ligand-receptor contacts and the precise ligand-binding mode. From analysis of structural models and mutagenesis, it appears that the position of helices 3, 4 and 5 is crucial in ligand docking. The FFA1-based homology models of FFA2 and FFA3 were constructed and used to compare the FFA subtypes. From docking studies we propose an alternative binding mode for orthosteric agonists at FFA1 and FFA2, involving the interhelical space between helices 4 and 5. This binding mode can explain mutagenesis results for residues at positions 4.56 and 5.42. The novel FFAs structural models highlight higher aromaticity of the FFA2 binding cavity and higher hydrophilicity of the FFA3 binding cavity. The role of the residues at the second extracellular loop used in mutagenesis is reanalysed. The third positively-charged residue in the binding cavity of FFAs, located in helix 2, is identified and predicted to coordinate allosteric modulators.
CONCLUSIONS: The novel structural models of FFAs provide information on specific modes of ligand binding at FFA subtypes and new suggestions for mutagenesis and ligand modification, guiding the development of novel orthosteric and allosteric chemical probes to validate the importance of FFAs in metabolic and inflammatory conditions. Using our FFA homology modelling experience, a strategy to model a GPCR, which is phylogenetically distant from GPCRs with the available crystal structures, is discussed.
Resumo:
Identificar, analisar e interpretar as citações do texto de Eurípides na Medeia de Mário Cláudio como um expediente dramatúrgico eficaz de reconfiguração da personagem trágica é o objectivo central desta dissertação, que se divide em três partes fundamentais: I. Medeia em cena; II. As (re)citações de Eurípides na Medeia de Mário Cláudio; III. Medeia, uma actriz falhada. Na primeira parte, a autora contextualiza a peça de Mário Cláudio e retoma os principais tópicos da caracterização da figura de Medeia na tragédia homónima de Eurípides. Na segunda parte, identificam-se as citações da peça euripidiana na peça de Mário Cláudio e apresenta-se uma análise deste processo de criação dramatúrgica na peça de Mário Cláudio. Na terceira parte, pretendeu-se demonstrar como as (re)citações do texto euripidiano sustentam uma recriação mitificada da personagem de Medeia. Da dissertação fazem ainda parte uma introdução e considerações finais, a bibliografia, repartida por edições e comentários e por estudos críticos, e ainda um índice geral.
Resumo:
BACKGROUND: We conducted a randomized, phase II, multicenter study to evaluate the anti-epidermal growth factor receptor (EGFR) mAb panitumumab (P) in combination with chemoradiotherapy (CRT) with standard-dose capecitabine as neoadjuvant treatment for wild-type KRAS locally advanced rectal cancer (LARC). PATIENTS AND METHODS: Patients with wild-type KRAS, T3-4 and/or N+ LARC were randomly assigned to receive CRT with or without P (6 mg/kg). The primary end-point was pathological near-complete or complete tumor response (pNC/CR), defined as grade 3 (pNCR) or 4 (pCR) histological regression by Dworak classification (DC). RESULTS: Forty of 68 patients were randomly assigned to P + CRT and 28 to CRT. pNC/CR was achieved in 21 patients (53%) treated with P + CRT [95% confidence interval (CI) 36%-69%] versus 9 patients (32%) treated with CRT alone (95% CI: 16%-52%). pCR was achieved in 4 (10%) and 5 (18%) patients, and pNCR in 17 (43%) and 4 (14%) patients. In immunohistochemical analysis, most DC 3 cells were not apoptotic. The most common grade ≥3 toxic effects in the P + CRT/CRT arm were diarrhea (10%/6%) and anastomotic leakage (15%/4%). CONCLUSIONS: The addition of panitumumab to neoadjuvant CRT in patients with KRAS wild-type LARC resulted in a high pNC/CR rate, mostly grade 3 DC. The results of both treatment arms exceeded prespecified thresholds. The addition of panitumumab increased toxicity.