MicroRNA antagonism of the picornaviral life cycle: alternative mechanisms of interference.

In addition to modulating the function and stability of cellular mRNAs, microRNAs can profoundly affect the life cycles of viruses bearing sequence complementary targets, a finding recently exploited to ameliorate toxicities of vaccines and oncolytic viruses. To elucidate the mechanisms underlying microRNA-mediated antiviral activity, we modified the 3' untranslated region (3'UTR) of Coxsackievirus A21 to incorporate targets with varying degrees of homology to endogenous microRNAs. We show that microRNAs can interrupt the picornavirus life-cycle at multiple levels, including catalytic degradation of the viral RNA genome, suppression of cap-independent mRNA translation, and interference with genome encapsidation. In addition, we have examined the extent to which endogenous microRNAs can suppress viral replication in vivo and how viruses can overcome this inhibition by microRNA saturation in mouse cancer models.

Evaluating Alternative Nutrient Sources in Subsistence-Level Aquaponic Systems

Many food production methods are both economically and environmentally unsustainable. Our project investigated aquaponics, an alternative method of agriculture that could address these issues. Aquaponics combines fish and plant crop production in a symbiotic, closed-loop system. We aimed to reduce the initial and operating costs of current aquaponic systems by utilizing alternative feeds. These improvements may allow for sustainable implementation of the system in rural or developing regions. We conducted a multi-phase process to determine the most affordable and effective feed alternatives for use in an aquaponic system. At the end of two preliminary phases, soybean meal was identified as the most effective potential feed supplement. In our final phase, we constructed and tested six full-scale aquaponic systems of our own design. Data showed that soybean meal can be used to reduce operating costs and reliance on fishmeal. However, a more targeted investigation is needed to identify the optimal formulation of alternative feed blends.

The FUELGEN alternative: an evolutionary approach. The architecture

This paper introduces a few architectural concepts from FUELGEN, that generates a "cloud" of reload patterns, like the generator in the FUELCON expert system, but unlike that generator, is based on a genetic algorithm. There are indications FUELGEN may outperform FUELCON and other tools as reported in the literature, in well-researched case studies, but careful comparisons have to be carried out. This paper complements the information in two other recent papers on FUELGEN. Moreover, a sequel project is outlined.

Exploring genetic alternative concepts for FUELGEN

This paper describes new crossover operators and mutation strategies for the FUELGEN system, a genetic algorithm which designs fuel loading patterns for nuclear power reactors. The new components are applications of new ideas from recent research in genetic algorithms. They are designed to improve the performance of FUELGEN by using information in the problem as yet not made explicit in the genetic algorithm's representation. The paper introduces new developments in genetic algorithm design and explains how they motivate the proposed new components.

A small screen alternative to stone and bronze: The Great War series and British television

This article examines the first major British television series about the First World War, The Great War (BBC, 1964), in terms of its cultural, historical and aesthetic significance. As a central component of the BBC`s 50th anniversary commemorative programme to mark the outbreak of war, the series was a major media event -a small-screen memorial cast in sounds and images instead of stone and bronze. This article looks at how the British television audience responded to this form of on-screen commemoration. Material for this article was derived from the series' extensive production records housed in the BBC Written Archives Centre at Caversham, Berkshire. This was supplemented by, among other sources, material from interviews and correspondence with several surviving members of the production team. This allows a broader understanding of the motivations of those involved in the production of a groundbreaking historical series, while acknowledging the wide-ranging nature of its audience. [From the Publisher]

Drug calculations part 2: alternative strategies to the formula

Drug calculations are an essential skill for nurses. The clinical skill of performing a drug calculation has come under recent scrutiny,resulting in the development of essential skills clusters inwhich pre-registration nurses must be competent before qualifying (Nursing and Midwifery Council 2007). The focuson drug calculation skills places renewed emphasis on how these skills are taught in higher education institutions and how they are learned by students theoretically and in clinical practice.

XoxF encoding an alternative methanol dehydrogenase is widespread in coastal marine environments

The xoxF gene, encoding a pyrroloquinoline quinone-dependent methanol dehydrogenase, is found in all known proteobacterial methylotrophs. In several newly discovered methylotrophs, XoxF is the active methanol dehydrogenase, catalysing the oxidation of methanol to formaldehyde. Apart from that, its potential role in methylotrophy and carbon cycling is unknown. So far, the diversity of xoxF in the environment has received little attention. We designed PCR primer sets targeting clades of the xoxF gene, and used 454 pyrosequencing of PCR amplicons obtained from DNA of four coastal marine environments for a unique assessment of the diversity of xoxF in these habitats. Phylogenetic analysis of the data obtained revealed a high diversity of xoxF genes from two of the investigated clades, and substantial differences in sequence composition between environments. Sequences were classified as being related to a wide range of both methylotrophs and non-methylotrophs from Alpha-, Beta- and Gammaproteobacteria. The most prominent sequences detected were related to the family Rhodobacteraceae, the genus Methylotenera and the OM43 clade of Methylophilales, and are thus related to organisms that employ XoxF for methanol oxidation. Furthermore, our analyses revealed a high degree of so far undescribed sequences, suggesting a high number of unknown species in these habitats.

Evolution of alternative biosynthetic pathways for vitamin C following plastid acquisition in photosynthetic eukaryotes.

Ascorbic acid (vitamin C) is an enzyme co-factor in eukaryotes that also plays a critical role in protecting photosynthetic eukaryotes against damaging reactive oxygen species derived from the chloroplast. Many animal lineages, including primates, have become ascorbate auxotrophs due to the loss of the terminal enzyme in their biosynthetic pathway, L-gulonolactone oxidase (GULO). The alternative pathways found in land plants and Euglena use a different terminal enzyme, L-galactonolactone dehydrogenase (GLDH). The evolutionary processes leading to these differing pathways and their contribution to the cellular roles of ascorbate remain unclear. Here we present molecular and biochemical evidence demonstrating that GULO was functionally replaced with GLDH in photosynthetic eukaryote lineages following plastid acquisition. GULO has therefore been lost repeatedly throughout eukaryote evolution. The formation of the alternative biosynthetic pathways in photosynthetic eukaryotes uncoupled ascorbate synthesis from hydrogen peroxide production and likely contributed to the rise of ascorbate as a major photoprotective antioxidant.

Could benzalkonium chloride be a suitable alternative to mercuric chloride for preservation of seawater samples?

Instrumental equipment unsuitable or unavailable for fieldwork as well as lack of ship space can necessitate the preservation of seawater samples prior to analysis in a shore-based laboratory. Mercuric chloride (HgCl2/ is routinely used for such preservation, but its handling and subsequent disposal incur environmental risks and significant expense. There is therefore a strong motivation to find less hazardous alternatives. Benzalkonium chloride (BAC) has been used previously as microbial inhibitor for freshwater samples. Here, we assess the use of BAC for marine samples prior to the measurement of oxygen-to-argon (O2 = Ar) ratios, as used for the determination of biological net community production. BAC at a concentration of 50 mg dm-3 inhibited microbial activity for at least 3 days in samples tested with chlorophyll a (Chl a) concentrations up to 1 mgm-3. BAC concentrations of 100 and 200 mg dm

Contingent screening for down syndrome is an efficient alternative to non-disclosure sequential screening

Objective To present a first and second trimester Down syndrome screening strategy, whereby second-trimester marker determination is contingent on the first-trimester results. Unlike non-disclosure sequential screening (the Integrated test), which requires all women to have markers in both trimesters, this allows a large proportion of the women to complete screening in the first trimester. Methods Two first-trimester risk cut-offs defined three types of results: positive and referred for early diagnosis; negative with screening complete; and intermediate, needing second-trimester markers. Multivariate Gaussian modelling with Monte Carlo simulation was used to estimate the false-positive rate for a fixed 85% detection rate. The false-positive rate was evaluated for various early detection rates and early test completion rates. Model parameters were taken from the SURUSS trial. Results Completion of screening in the first trimester for 75% of women resulted in a 30% early detection rate and a 55% second trimester detected rate (net 85%) with a false-positive rate only 0.1% above that achievable by the Integrated test. The screen-positive rate was 0.1% in the first trimester and 4.7% for those continuing to be tested in the second trimester. If the early detection rate were to be increased to 45% or the early completion rate were to be increased to 80%, there would be a further 0.1% increase in the false-positive rate. Conclusion Contingent screening can achieve results comparable with the Integrated test but with earlier completion of screening for most women. Both strategies need to be evaluated in large-scale prospective studies particularly in relation to psychological impact and practicability.

Monitoring electrical resistance of concretes containing alternative cementitious materials to assess their resistance to chloride penetration

This is an invited contribution in a special issue of the Journal of Cement and Concrete Composites