Towards artificial ribonucleases: the sequence-specific cleavage of RNA in a duplex

Lanthanide complexes covalently attached to oligonucleotides have been shown to cleave RNA in a sequence-specific manner. Efficient cleavage, however, is at present limited to single-stranded RNA regions, as RNA in a duplex is considerably more resistant to strand scission. To overcome this limitation, we have designed and synthesised artificial nucleases comprising lanthanide complexes covalently linked to oligodeoxyribonucleotides which cleave a partially complementary RNA at a bulged site, in the duplex region. Strand scission occurs at or near the bulge. Cleavage of the RNA target by the metal complex can be addressed via the major or the minor groove. In an example of a competitive situation, where the cleavage moiety has access to both a bulge and a single-strand region, transesterification at the bulge is favoured. Such artificial ribonucleases may find application as antisense agents and as tools in molecular biology. In addition, the results may have importance for the design of artificial ribonucleases which are able to act with catalytic turnover.     

Cytogenetic abnormalities and clonal evolution in an adult hepatoblastoma

Hepatoblastomas usually occur in children < 3 years of age, and only occasional adult cases have been described. To date, 20 cytogenetically abnormal childhood hepatoblastomas have been reported. Karyotypic investigations have shown that most hepatoblastomas are diploid or hyperdiploid, often displaying trisomies for chromosomes 2 and 20. We have cytogenetically investigated an adult hepatoblastoma for which no previous karyotypic data exist. A hypertriploid stemline with multiple numerical and structural chromosomal aberrations, including +2 and +20, was found. In addition, the tumor displayed extensive clonal evolution with 11 subclones. Although the tumor thus displayed some chromosomal abnormalities commonly observed in childhood tumors, providing further support for the importance of these abnormalities in the development of hepatoblastoma, the level of genomic complexity seen in the present case has never been described in childhood hepatoblastomas and may suggest a different etiology or pathogenesis.     

Elastic-viscoplastic differential equations on a manifold modelling of in-plane stretching of sheet metal

The computational method for large deformation plasticity called differential equations on a manifold (DEM) has previously been shown to be effective for axisymmetric and plane strain sheet metal forming problems. The method has now been formulated for in-plane stretching problems, incorporated into a computer code, and applied to several problems. The code's performance is robust and accurate, as evidenced by a comparison with other published results. Incorporation of an automatic mesh generator significantly reduces data preparation time.     

Practice nurses' self-reported opportunistic smoking cessation advice in three contexts.

Little is known of the current smoking cessation activities of practice nurses and their attitudes toward giving smoking cessation advice. This study aimed to (a) compare practice nurses' reports of giving smoking cessation advice as part of cervical screening with their reports of giving such advice in cardiovascular disease screening and diabetes care, (b) compare their beliefs about providing such advice in these three contexts, and (c) determine the strongest predictors of their reports of giving smoking cessation advice. A survey was completed by 152 practice nurses in the United Kingdom. The frequency with which they reported giving smoking cessation advice and their beliefs about giving such advice in three contexts are reported. Nurses reported being more likely to give smoking cessation advice and had more positive beliefs about giving it in the more traditional contexts of cardiovascular screening and diabetes care compared with cervical screening. Beliefs about the appropriateness and practicality of giving such advice in the latter context were the strongest predictors of nurses' reports of doing so. This study provides guidance on the potential barriers that need to be overcome to increase the frequency with which nurses give smoking cessation advice in the context of cervical screening.     

Phlebotomus papatasi sand fly salivary gland lysate down-regulates a Th1, but up-regulates a Th2, response in mice infected with Leishmania major

A vertebrate host becomes infected with Leishmania major when the sand fly vector injects parasites into skin along with saliva. Previous studies showed that salivary gland lysate of the New World sand fly Lutzomyia longipalpis markedly enhanced L. major infection in CBA mice. However, L. major is an Old World parasite transmitted in nature by the Old World sand fly Phlebotomus papatasi. Here we examine the ability of P. papatasi salivary gland lysate to enhance infection (lesion size and parasite burden) by L. major. In addition, we examine the effects of salivary gland lysate on the immune response to L. major by monitoring the levels of cytokine mRNA from the lymph nodes draining cutaneous lesions. We found that P. papatasi salivary gland lysate dramatically exacerbated lesion development in disease-resistant CBA mice. This exacerbation of disease correlated with inhibition of the production of Thl cytokines and associated factors (IFN-gamma, IL-12, and inducible nitric oxide synthase), but with enhancement of the Th2 cytokine IL-4, whereas no changes in the levels of IL-10 and TGF-beta were noted. Importantly, salivary gland lysate directly up-regulated expression of IL-4 mRNA in mice in the absence of infection with L. major.     

Web evolution and Web Science

This paper examines the evolution of the World Wide Web as a network of networks and discusses the emergence of Web Science as an interdisciplinary area that can provide us with insights on how the Web developed, and how it has affected and is affected by society. Through its different stages of evolution, the Web has gradually changed from a technological network of documents to a network where documents, data, people and organisations are interlinked in various and often unexpected ways. It has developed from a technological artefact separate from people to an integral part of human activity that is having an increasingly significant impact on the world. This paper outlines the lessons from this retrospective examination of the evolution of the Web, presents the main outcomes of Web Science activities and discusses directions along which future developments could be anticipated.     

Texture and hydrodynamics of a thin slab of superfluid3He-A in a torsional oscillator. II. Experiment

Experiments on a torsional oscillator containing a slab of liquid³He of thickness 105 µm and diameter 8.38 mm are described. Normal phase experiments confirm the theory of the oscillator dynamics but an apparent descrase in the measured value of T ² at lowT casts doubt on the existing slip theory. Measurements for the uniform texture for the A phase give values of _s and ₄₄. The _s measurements suggest that the A-phase energy gap is enhanced by a factor 1.24 over the BCS value. Distortion of the uniform texture by a magnetic field perpendicular to the slab occurs at a threshold field slightly smaller than predicted. Measurements for fields at different angles to the slab enable accurate values to be deduced for the superfluid density anisotropy and two other viscosity coefficients. The remaining two viscosity coefficients are only poorly determined. Flow alignment of the orbital texture was achieved by increasing the oscillator amplitude. A different texture obtained on some occasions after warming from the B phase was investigated but is not understood.