Novel Venom Proteins Produced by Differential Domain-Expression Strategies in Beaded Lizards and Gila Monsters (genus Heloderma)

The origin and evolution of venom proteins in helodermatid lizards were investigated by multidisciplinary techniques. Our analyses elucidated novel toxin types resultant from three unique domain-expression processes: 1) The first full-length sequences of lethal toxin isoforms (helofensins) revealed this toxin type to be constructed by an ancestral monodomain, monoproduct gene (beta-defensin) that underwent three tandem domain duplications to encode a tetradomain, monoproduct with a possible novel protein fold; 2) an ancestral monodomain gene (encoding a natriuretic peptide) was medially extended to become a pentadomain, pentaproduct through the additional encoding of four tandemly repeated proline-rich peptides (helokinestatins), with the five discrete peptides liberated from each other by posttranslational proteolysis; and 3) an ancestral multidomain, multiproduct gene belonging to the vasoactive intestinal peptide (VIP)/glucagon family being mutated to encode for a monodomain, monoproduct (exendins) followed by duplication and diversification into two variant classes (exendins 1 and 2 and exendins 3 and 4). Bioactivity characterization of exendin and helokinestatin elucidated variable cardioactivity between isoforms within each class. These results highlight the importance of utilizing evolutionary-based search strategies for biodiscovery and the virtually unexplored potential of lizard venoms in drug design and discovery.

Revisioning assessment through a children’s rights approach: implications for policy, process and practice

The linkage between the impact of assessment and compliance with children’s rights is a connection, which although seemingly obvious, is nonetheless rarely made, particularly by governments, which, as signatories to the relevant human rights treaties, have the primary responsibility for ensuring that educational practice is compatible with international children’s rights standards. While some jurisdictions are explicit about an adherence to children’s rights frameworks in general policy documentation, such a commitment rarely features when the focus is on assessment and testing. Thus, in spite of significant public and academic attention given to the consequences of assessment for children and governments committed to working within children’s rights standards, the two are rarely considered together. This paper examines the implications for the policy, process and practice of assessment in light of international human rights standards. Three key children’s rights principles and standards are used as a critical lens to examine assessment policy and practice: (1) best interests; (2) non-discrimination; and (3) participation. The paper seeks new insights into the complexities of assessment practice from the critical perspective of children’s rights and argues that such standards not only provide a convenient benchmark for developing, implementing and evaluating assessment practices, but also acknowledge the significance of assessment in the delivery of children’s rights to, in and through education more generally.

‘Textes fossiles’: The Metatextual Geology of Verne's Voyage au centre de la Terre

Despite the compelling parallels between George Sand’s Laura; ou, le voyage dans le cristal and Jules Verne’s Voyage au centre de la Terre (both 1864), Sand’s place within the intertextual fabric of Verne’s novel has been occluded. By shifing the terms of the debate away from the vexed issues of borrowing, influence, or inspiration, and focusing on Verne’s sustained engagement with Sand’s work as a specifically geological fiction, this article sheds new light on the imbrication of the scientific and the fictional in Voyage au centre de la Terre, whereby geological and palaeontological references not only guarantee the text’s verisimilitude and underwrite its didactic objectives, but also fulfil an important metatextual function.

Anionic N,O-ligated Pd(II) complexes: highly active catalysts for alcohol oxidation.

There is a need to develop effective catalytic methods for alcohol oxidation. Pd(II) complexes have shown great promise as catalysts, however a comparatively small number of ligands have been reported so far. Herein we report the use of commercially available anionic N,O-ligands to produce highly active catalysts.

Developing outcomes for educational services: a children's rights-based approach

This article provides a rationale for and insight into an explicit children's rights-based approach to the identification of outcomes for proposed educational interventions. It presents a critical reflection on a research project which sought to integrate international children's rights standards into the design of services through a children's rights audit of potential outcomes and the meaningful engagement of children in the research and service design processes. While children are involved increasingly as co-researchers in qualitative studies, it is less common for this to occur in quantitative studies. This article offers some additional insight into children's participation in the interpretation of data from a large-scale baseline survey. The article concludes with an argument that international children's rights law provides not just a legal imperative but also a comprehensive framework with which to assert the case for increased recognition of children as salient stakeholders in all aspects of service design.

Direct versus delayed pathways in strong-field non-sequential double ionization

We report full-dimensionality quantum and classical calculations of double ionization (DI) of laser-driven helium at 390 nm. Good agreement is observed. We identify the relative importance of the two main non-sequential DI pathways, the direct|with an almost simultaneous ejection of both electrons|and the delayed. We find that the delayed pathway prevails at small intensities independently of total electron energy but at high intensities the direct pathway predominates up to a certain upper-limit in total energy which increases with intensity. An explanation for this increase with intensity is provided.

Non-aqueous silicone elastomer gels as a vaginal microbicide delivery system for the HIV-1 entry inhibitor maraviroc

Aqueous semi-solid polymeric gels, such as those based on hydroxyethylcellulose (HEC) and polyacrylic acid (e.g. Carbopol®), have a long history of use in vaginal drug delivery. However, despite their ubiquity, they often provide sub-optimal clinical performance, due to poor mucosal retention and limited solubility for poorly water-soluble actives. These issues are particularly pertinent for vaginal HIV microbicides, since many lead candidates are poorly water-soluble and where a major goal is the development of a coitally independent, once daily gel product. In this study, we report the use of a non-aqueous silicone elastomer gel for vaginal delivery of the HIV-1 entry inhibitor maraviroc. In vitro rheological, syringeability and retention studies demonstrated enhanced performance for silicone gels compared with a conventional aqueous HEC gel, while testing of the gels in the slug model confirmed a lack of mucosal irritancy. Pharmacokinetic studies following single dose vaginal administration of a maraviroc silicone gel in rhesus macaques showed higher and sustained MVC levels in vaginal fluid, vaginal tissue and plasma compared with a HEC gel containing the same maraviroc loading. The results demonstrate that non-aqueous silicone gels have potential as a formulation platform for coitally independent vaginal HIV microbicides.

Simple trapped-ion architecture for high-fidelity Toffoli gates

We discuss a simple architecture for a quantum TOFFOLI gate implemented using three trapped ions. The gate, which, in principle, can be implemented with a single laser-induced operation, is effective under rather general conditions and is strikingly robust (within any experimentally realistic range of values) against dephasing, heating, and random fluctuations of the Hamiltonian parameters. We provide a full characterization of the unitary and noise-affected gate using three-qubit quantum process tomography.

Distributing fully optomechanical quantum correlations

We present a scheme to prepare quantum correlated states of two mechanical systems based on the pouring of preavailable all-optical entanglement into the state of two micromirrors belonging to remote and noninteracting optomechanical cavities. We show that, under realistic experimental conditions, the protocol allows for the preparation of a genuine quantum state of a composite mesoscopic system whose nonclassical features extend beyond the occurrence of entanglement. We finally discuss a way to access such mechanical correlations.