Twelve precisely! or, A night at Dover: an interlude, in one act. As performed at the Olympic Theatre, Strand, Monday, Jan 1, 1821.

Mode of access: Internet.

The strand magazine.

Mode of access: Internet.

The Strand magazine

Vol.13-#40# called also no. 73-#238#

Locating a strand of the Seattle Fault Zone in southeast Seattle, Washington through topographic analysis, borehole analysis and ground penetrating radar

Contributing to the evaluation of seismic hazards, a previously unmapped strand of the Seattle Fault Zone (SFZ), cutting across the southwest side of Lake Washington and southeast Seattle, is located and characterized on the basis of bathymetry, borehole logs, and ground penetrating radar (GPR). Previous geologic mapping and geophysical analysis of the Seattle area have generally mapped the locations of some strands of the SFZ, though a complete and accurate understanding of locations of all individual strands of the fault system is still incomplete. A bathymetric scarp-like feature and co-linear aeromagnetic anomaly lineament defined the extent of the study area. A 2-dimensional lithology cross-section was constructed using six boreholes, chosen from suitable boreholes in the study area. In addition, two GPR transects, oblique to the proposed fault trend, served to identify physical differences in subsurface materials. The proposed fault trace follows the previously mapped contact between the Oligocene Blakeley Formation and Quaternary deposits, and topographic changes in slope. GPR profiles in Seward Park and across the proposed fault location show the contact between the Blakeley Formation and unconsolidated glacial deposits, but it does not constrain an offset. However, north-dipping beds in the Blakely Formation are consistent with previous interpretations of P-wave seismic profiles on Mercer Island and Bellevue, Washington. The profiles show the mapped location of the aeromagnetic lineament in Lake Washington and the inferred location of the steeply-dipping, high-amplitude bedrock reflector, representing a fault strand. This north-dipping reflector is likely the same feature identified in my analysis. I characterize the strand as a splay fault, antithetic to the frontal fault of the SFZ. This new fault may pose a geologic hazard to the region.

Countering cooperative effects in protease inhibitors using constrained b-strand-mimicking templates in focused combinatorial libraries

A major problem in de novo design of enzyme inhibitors is the unpredictability of the induced fit, with the shape of both ligand and enzyme changing cooperatively and unpredictably in response to subtle structural changes within a ligand. We have investigated the possibility of dampening the induced fit by using a constrained template as a replacement for adjoining segments of a ligand. The template preorganizes the ligand structure, thereby organizing the local enzyme environment. To test this approach, we used templates consisting of constrained cyclic tripeptides, formed through side chain to main chain linkages, as structural mimics of the protease-bound extended beta-strand conformation of three adjoining amino acid residues at the N- or C-terminal sides of the scissile bond of substrates. The macrocyclic templates were derivatized to a range of 30 structurally diverse molecules via focused combinatorial variation of nonpeptidic appendages incorporating a hydroxyethylamine transition-state isostere. Most compounds in the library were potent inhibitors of the test protease (HIV-1 protease). Comparison of crystal structures for five protease-inhibitor complexes containing an N-terminal macrocycle and three protease-inhibitor complexes containing a C-terminal macrocycle establishes that the macrocycles fix their surrounding enzyme environment, thereby permitting independent variation of acyclic inhibitor components with only local disturbances to the protease. In this way, the location in the protease of various acyclic fragments on either side of the macrocyclic template can be accurately predicted. This type of templating strategy minimizes the problem of induced fit, reducing unpredictable cooperative effects in one inhibitor region caused by changes to adjacent enzyme-inhibitor interactions. This idea might be exploited in template-based approaches to inhibitors of other proteases, where a beta-strand mimetic is also required for recognition, and also other protein-binding ligands where different templates may be more appropriate.

Double-strand break repair gene polymorphisms and risk of breast or ovarian cancer

Deficiencies in DNA repair have been hypothesized to increase cancer risk and excess cancer incidence is a feature of inherited diseases caused by defects in DNA damage recognition and repair. We investigated, using a case-control design, whether the double-strand break repair gene polymorphisms RAD51 5' untranslated region -135 G > C, XRCC2 R188H G > A, and XRCC3 T241M C > T were associated with risk of breast or ovarian cancer in Australian women. Sample sets included 1,456 breast cancer cases and 793 age-matched controls ages under 60 years of age, 549 incident ovarian cancer cases, and 335 controls of similar age distribution. For the total sample and the subsample of Caucasian women, there were no significant differences in genotype distribution between breast cancer cases and controls or between ovarian cancer cases and combined control groups. The crude odds ratios (OR) and 95% confidence intervals (95% CI) associated with the RAD51 GC/CC genotype frequency was OR, 1.10; 95% CI, 0.80-1.41 for breast cancer and OR, 1.22; 95% CI, 0.92-1.62 for ovarian cancer. Similarly, there were no increased risks associated with the XRCC2 GA/AA genotype (OR, 0.98; 95% CI, 0.76-1.26 for breast cancer and OR, 0.93; 95% CI, 0.69-1.25 for ovarian cancer) or the XRCC3 CT/TT genotype (OR, 0.92; 95% Cl, 0.77-1.10 for breast cancer and OR, 0.87; 95% CI, 0.71-1.08 for ovarian cancer). Results were little changed after adjustment for age and other measured risk factors. Although there was little statistical power to detect modest increases in risk for the homozygote variant genotypes, particularly for the rare RAD51 and XRCC2 variants, the data suggest that none of these variants play a major role in the etiology of breast or ovarian cancer.

A strand of vermicelli:Dr Darwin's part in the creation of Frankenstein's monster

Although much has been written about Mary Shelley's Frankenstein, the part played by Erasmus Darwin (1731-1802) has been almost entirely neglected. This is odd as, apart from some ghost stories, Dr Darwin is the one influence mentioned in both the 1816 and 1831 prefaces to the book. The present contribution aims to redress that omission. It aims to show that Darwin's ideas about spontaneous generation, his anti-establishment ideas, and his literary genius played a significant role in forming the 'dark and shapeless substance' surging in Mary Shelley's mind during the summer of 1816 and from which her tale of Gothic horror emerged. It is, however, ultimately ironic that Frankenstein, which warns against a too enthusiastic use of scientific knowledge, should have been partly inspired by one of the most optimistically forward-looking of all late eighteenth-century thinkers. © 2007 Institute of Materials, Minerals and Mining.

Flexibility of short-strand RNA in aqueous solution as revealed by molecular dynamics simulation:are A′-RNA and A-RNA distinct conformational structures?

We use molecular dynamics simulations to compare the conformational structure and dynamics of a 21-base pair RNA sequence initially constructed according to the canonical A-RNA and A'-RNA forms in the presence of counterions and explicit water. Our study aims to add a dynamical perspective to the solid-state structural information that has been derived from X-ray data for these two characteristic forms of RNA. Analysis of the three main structural descriptors commonly used to differentiate between the two forms of RNA namely major groove width, inclination and the number of base pairs in a helical twist over a 30 ns simulation period reveals a flexible structure in aqueous solution with fluctuations in the values of these structural parameters encompassing the range between the two crystal forms and more. This provides evidence to suggest that the identification of distinct A-RNA and A'-RNA structures, while relevant in the crystalline form, may not be generally relevant in the context of RNA in the aqueous phase. The apparent structural flexibility observed in our simulations is likely to bear ramifications for the interactions of RNA with biological molecules (e.g. proteins) and non-biological molecules (e.g. non-viral gene delivery vectors). © CSIRO 2009.

Have the GIPSI settled down? Breaks and multivariate stochastic volatility models for, and not against, the European financial integration

We investigate the integration of the European peripheral financial markets with Germany, France, and the UK using a combination of tests for structural breaks and return correlations derived from several multivariate stochastic volatility models. Our findings suggest that financial integration intensified in anticipation of the Euro, further strengthened by the EMU inception, and amplified in response to the 2007/2008 financial crisis. Hence, no evidence is found of decoupling of the equity markets in more troubled European countries from the core. Interestingly, the UK, despite staying outside the EMU, is not worse integrated with the GIPSI than Germany or France. © 2013 Elsevier B.V.

Stock market efficiency before and after a financial liberalisation reform:do breaks in volatility dynamics matter?

This article focuses on the deviations from normality of stock returns before and after a financial liberalisation reform, and shows the extent to which inference based on statistical measures of stock market efficiency can be affected by not controlling for breaks. Drawing from recent advances in the econometrics of structural change, it compares the distribution of the returns of five East Asian emerging markets when breaks in the mean and variance are either (i) imposed using certain official liberalisation dates or (ii) detected non-parametrically using a data-driven procedure. The results suggest that measuring deviations from normality of stock returns with no provision for potentially existing breaks incorporates substantial bias. This is likely to severely affect any inference based on the corresponding descriptive or test statistics.