'Frank Pig Says Hello' by Pat McCabe

This theatre performance, produced in association with An Grianan Theatre, Letterkenny, contributes to two strands of research: theatre and mental health and Irish Physical Theatre in the 1990s.

IQ motif selectivity in human IQGAP1: binding of myosin essential light chain and S100B.

IQGAPs are cytoskeletal scaffolding proteins which link signalling pathways to the reorganisation of actin and microtubules. Human IQGAP1 has four IQ motifs each of which binds to calmodulin. The same region has been implicated in binding to two calmodulin-like proteins, the myosin essential light chain Mlc1sa and the calcium and zinc ion binding protein S100B. Using synthetic peptides corresponding to the four IQ motifs of human IQGAP1, we showed by native gel electrophoresis that only the first IQ motif interacts with Mlc1sa. This IQ motif, and also the fourth, interacts with the budding yeast myosin essential light chain Mlc1p. The first and second IQ motifs interact with S100B in the presence of calcium ions. This clearly establishes that S100B can interact with its targets through IQ motifs in addition to interacting via previously reported sequences. These results are discussed in terms of the function of IQGAP1 and IQ motif recognition.

Plasma diagnostics of active-region evolution and implications for coronal heating

A detailed study is presented of the decaying solar-active region NOAA 10103 observed with the Coronal Diagnostic Spectrometer (CDS), the Michelson Doppler Imager (MDI) and the Extreme-ultraviolet Imaging Telescope (EIT) onboard the Solar and Heliospheric Observatory (SOHO). Electron-density maps formed using Si x (356.03 angstrom/347.41 angstrom) show that the density varies from similar to 10(10) cm(-3) in the active-region core to similar to 7 x 108 cm-3 at the region boundaries. Over the 5 d of observations, the average electron density fell by similar to 30 per cent. Temperature maps formed using Fe XVI (335.41 angstrom)/Fe XIV (334.18 angstrom) show electron temperatures of similar to 2.34 x 10(6) K in the active-region core and similar to 2.10 x 10(6) K at the region boundaries. Similarly to the electron density, there was a small decrease in the average electron temperature over the 5-d period. The radiative, conductive and mass-flow losses were calculated and used to determine the resultant heating rate (P-H). Radiative losses were found to dominate the active-region cooling process. As the region decayed, the heating rate decreased by almost a factor of 5 between the first and last day of observations. The heating rate was then compared to the total unsigned magnetic flux (Phi(tot) = integral dA vertical bar B-z vertical bar), yielding a power law of the form P-H similar to Phi(0.81 +/- 0.32)(tot) This result suggests that waves rather than nanoflares may be the dominant heating mechanism in this active region.

Composites of poly(ε-caprolactone) and Mo6S3I6 Nanowires

Composites of poly(e-caprolactone) (PCL) and molybdenum sulfur iodine (MoSI) nanowires were prepared using twin-screw extrusion. Extensive microscopic examination of the composites revealed the nanowires were well dispersed in the PCL matrix, although bundles of Mo6S3I6 ropes were evident at higher loadings. Secondary electron imaging (SEI) showed the nanowires had formed an extensive network throughout the PCL matrix, resulting in increased electrical conductivity of PCL, by eight orders of magnitude, and an electrical percolation threshold of 6.5T10S3vol%. Thermal analysis (DSC), WAXD, and hot stage polarized optical microscopy (HSPOM) experiments revealed Mo6S3I6 addition altered PCL crystallization kinetics, nucleation density, and crystalline content. A greater number of smaller spherulites were formed via heterogeneous nucleation. The onset of thermal decomposition (TGA) of PCL decreased by 70-C, a consequence of the thermal degradation of Mo6S3I6 to MoO3, which in turn accelerates the formation of volatile gases during the first stage of PCL decomposition.

Identification of GSK625433: A novel clinical candidate for the treatment of hepatitis C.

Hepatitis C is an infection of the liver caused by a pos. single-stranded RNA virus (HCV) which affects 170 million people worldwide. It is responsible for 40-60% of all liver disease and is the major cause of liver transplants in the United States. The HCV NS5B gene encodes the viral RNA-dependent RNA polymerase which is essential for HCV replication. We have previously reported the identification of acylpyrrolidines as potent inhibitors of NS5B; however their activity is attenuated against genotype 1a. The design of improved broader-spectrum compds., capable of effective inhibition of both genotypes 1b and 1a is desirable. An understanding of the binding site and genotype sequence differences was utilized to design compds. with greatly enhanced genotype 1a and 1b potency. Our studies led to the identification of GSK625433, a potent, homochiral inhibitor of these HCV genotypes in both enzyme and sub-genomic replicon cell-based assays. GSK625433 has a good pharmacokinetic profile in pre-clin. animal species, enabling progression to clin. evaluation.