NMR imaging of the diffusion of water at 37 degrees C into poly(2-hydroxyethyl methacrylate) containing aspirin or vitamin B-12

The ingress of water into poly(2-hydroxyethyl methacrylate), PHEMA, loaded with either one of two model drugs, vitamin B-12 or aspirin, was studied at 37 degreesC using three-dimensional NMR imaging. PHEMA was loaded with 5 and 10 wt % of the drugs. From the imaging profiles, it was observed that incorporation of vitamin B-12 into PHEMA resulted in enhanced crack formation on sorption of water and the crack healing behind the diffusion front was slower than for PHEMA without added drug. This was accounted for by the anti-plasticization of PHEMA by vitamin B-12. Crack formation was inhibited in the P-HEMA-aspirin systems because of the plasticizing effect of the aspirin on the PHEMA matrix. All of the polymers were found to absorb water according to an underlying Fickian diffusion mechanism. For PHEMA loaded with 5 wt % of aspirin or vitamin B-12, the best values of the water diffusion coefficients were both found to be 1.3 +/- 0.1 x 10(-11) m(2) s(-1) at 37 degreesC, while the values for the polymer loaded with 10 wt % of the drugs were slightly higher, 1.5 +/- 0.1 x 10(-11) m(2) s(-1).

A METÁFORA DO CORPO NA I CARTA DE CLEMENTE DE ROMA AOS CORÍNTIOS (37.5-38.1): Uma análise dialógica

A I Carta de Clemente de Roma aos Coríntios faz parte de uma coleção de escritos cristãos antigos intitulados Pais Apostólicos. Esse texto é uma autêntica correspondência enviada da comunidade cristã de Roma para a comunidade cristã de Corinto, escrita pelo seu secretário Clemente. Esta pesquisa, em contraposição às desenvolvidas pela disciplina teológica chamada patrologia , analisa a carta a partir das teorias de Mikhail M. Bakhtin e seu círculo e da micro-história assumidamente relacionada com as teorias do mesmo autor delimitando o trecho 37.5-38.1, onde se encontra a metáfora do corpo.

The role of the 8-18 helix of CGRP 8-37 in mediating high affinity binding to CGRP receptors; coulombic and steric interactions

1. The role of individual residues in the 8-18 helix of CGRP 8-37 in promoting high-affinity binding to CGRP 1 receptors expressed on rat L6 and human SK-N-MC cells has been examined. The relative potencies of various derivatives were estimated from their ability to inhibit the human αCGRP-mediated increase in cyclic AMP production and the binding of [ 125I]-human αCGRP. 3. Arg 11 and Arg 18 were replaced by serines to give [Ser 11.18]CGRP 8-37. These bound with pKi values <6 to SK-N-MC cells and had apparent pA 2 values of 5.81 ± 0.04 and 5.31 ± 0.11 on SK-N-MC and L6 cells. CGRP 8-37 had a pKi of 8.22 on SK-N-MC cells and pK b values on the above cell lines of 8.95±0.04 and 8.76±0.04. 3. The arginines were replaced with glutamic acid residues. [Glu 11]CGRP 8-37 had a pK b of 7.14±0.14 on SK-N-MC cells (pKi=7.05±0.05) and 6.99±0.08 on L6 cells. [Glu 18]CGRP 8-37 had a pK b of 7.10±0.0.08 on SK-N-MC cells (pKi=6.91±0.23) and 7.12±0.09 on L6 cells. 4. Leu 12, Leu 15 and Leu 16 were replaced by benzoyl-phenylalanine (bpa) residues. On SK-N-MC cells, the apparent pA 2 values of [bpa 12]-, [bpa 15]- and [bpa 16]CGRP 8-37 were respectively 7.43±0.23, 8.34±0.11 and 5.66±0.16 (pKi values of 7.14±0.17, 7.66±0.21 and <6): on L6 cells they were 7.96±0.36, 8.28±0.21 and 6.09±0.04 (all n=3). 5. It is concluded that the Arg 11 and Arg 18 are involved in specific electrostatic interactions with other residues, either on the CGRP 1 receptors or elsewhere on CGRP 8-37. Leu 16 is in a conformationally restricted site when CGRP 8-37 binds to CGRP 1 receptors, unlike Leu 12 and Leu 15.

(Table 1) Alkenone concentration, UK'37 index and derived sea surface temperatures for ODP Site 167-1020

Uk'37 sea-surface temperature (SST) estimates obtained at ~2.5-k.y. resolution from Ocean Drilling Program Site 1020 show glacial-interglacial cyclicity with an amplitude of 7°-10°C over the last 780 k.y. This record shows a similar pattern of variability to another alkenone-based SST record obtained previously from the Santa Barbara Basin. Both records show that oxygen isotope Stage (OIS) 5.5 was warmer by ~3°C relative to the present and that glacial Uk'37 temperatures warm in advance of deglaciation, as inferred from benthic d18O records. The alkenone-based SST record at Site 1020 is longer than previously published work along the California margin. We show that warmer than present interglacial stages have occurred frequently during the last 800 k.y. Alkenone concentrations, a proxy for coccolithophorid productivity, indicate that sedimentary marine organic carbon content has also varied significantly over this interval, with higher contents during interglacial periods. A baseline shift to warmer SST and greater alkenone content occurs before OIS 13. We compare our results with those from previous multiproxy studies in this region and conclude that SST has increased by ~5°C since the last glacial period (21 ka). Our data show that maximum alkenone SSTs occur simultaneously with minimum ice volume at Site 1020, which is consistent with data from farther south along the margin. The presence of sea ice in the glacial northeast Pacific, the extent of which is inferred from locations of ice-rafted debris, provides further support for our notion of cold surface water within the northern California Current system, averaging 7°-8°C cooler during peak glacial conditions. The cooling of surface water during glacial stages most likely did not result from enhanced upwelling because alkenone concentrations and terrestrial redwood pollen assemblages are consistently lower during glacial periods.