Streamlining or watering down? Assessing the 'smartness' of policy and standards for the promotion of low and zero carbon homes in England 2010-15

The knowledge and enforcement problems faced by governments in defining traditional ‘command and control’ regulation are well known. Significant legal scholarship offers alternative models of ‘smart,’ ‘responsive’ environmental regulation, emphasising the need for policy instrument mixes, including the vital role of voluntary, industry-led sustainability standards. Yet, as is being increasingly recognised, these contributions leave open the need for detailed, qualitative evaluation of instrument mixes as a complement to primarily quantitative cost-benefit analyses that predominate in regulatory impact assessments by governments. Addressing this need, this paper evaluates policy and standards for low and zero carbon homes in England during the Coalition government (2010-2015) when the ecological modernisation discourse of the previous New Labour government became subsumed by a deregulation agenda. Our study, incorporating 70 stakeholder interviews, suggests that, in supplier-driven markets such as housing in England, a ‘smart’ mix of mandatory and voluntary standards requires a strong, central role for government in setting national, mandatory standards and supporting their delivery. There is an important potential supplementary role for voluntary tools and local authority discretion, though our study highlights problems that can arise when such different instruments promote diverging roadmaps towards a policy goal

Julian of Norwich and her children today: Editions, translations and versions of her revelations

The viability of such concepts as "authorial intention," "the original text," "critical edition" and, above all, "scholarly editorial objectivity" is not what it was, and a study of the textual progeny of the revelations of Julian of Norwich--editions, versions, translations and selections--does little to rehabilitate them. Rather it tends to support the view that a history of reading is indeed a history of misreading or, more positively, that texts can have an organic life of their own that allows them to reproduce and evolve quite independently of their author. Julian's texts have had a more robustly continuous life than those of any other Middle English mystic. Their history--in manuscript and print, in editions more or less approximating Middle English and in translations more or less approaching Modern English--is virtually unbroken since the fifteenth century. But on this perilous journey, many and strange are the clutches into which she and her textual progeny have fallen

A proof-of-concept Bitter-like HTS electromagnet fabricated from a silver-infiltrated (RE)BCO ceramic bulk

A novel concept for a compact high-field magnet coil is introduced. This is based on stacking slit annular discs cut from bulk rare-earth barium cuprate ((RE)BCO) ceramic in a Bitter-like architecture. Finite-element modelling shows that a small 20 turn stack (with a total coil volume of <20 cm3) is capable of generating a central bore magnetic field of >2 T at 77 K and >20 T at 30 K. Unlike resistive Bitter magnets, the high-temperature superconducting (HTS) Bitter stack exhibits significant non-linear field behaviour during current ramping, caused by current filling proceeding from the inner radius outwards in each HTS layer. Practical proof-of-concept for this architecture was then demonstrated through fabricating an uninsulated four-turn prototype coil stack and operating this at 77 K. A maximum central field of 0.382 T was measured at 1.2 kA, with an accompanying 6.1 W of internal heat dissipation within the coil. Strong magnetic hysteresis behaviour was observed within the prototype coil, with ≈30% of the maximum central field still remaining trapped 45 min after the current had been removed. The coil was thermally stable during a 15 min hold at 1 kA, and survived thermal cycling to room temperature without noticeable deterioration in performance. A final test-to-destruction of the coil showed that the limiting weak point in the stack was growth-sector boundaries present in the original (RE)BCO bulk

Evaluation of machine-learning methods for ligand-based virtual screening

Machine-learning methods can be used for virtual screening by analysing the structural characteristics of molecules of known (in)activity, and we here discuss the use of kernel discrimination and naive Bayesian classifier (NBC) methods for this purpose. We report a kernel method that allows the processing of molecules represented by binary, integer and real-valued descriptors, and show that it is little different in screening performance from a previously described kernel that had been developed specifically for the analysis of binary fingerprint representations of molecular structure. We then evaluate the performance of an NBC when the training-set contains only a very few active molecules. In such cases, a simpler approach based on group fusion would appear to provide superior screening performance, especially when structurally heterogeneous datasets are to be processed

Phylogenetic and Biogeographic Analysis of Sphaerexochine Trilobites

BACKGROUND: Sphaerexochinae is a speciose and widely distributed group of cheirurid trilobites. Their temporal range extends from the earliest Ordovician through the Silurian, and they survived the end Ordovician mass extinction event (the second largest mass extinction in Earth history). Prior to this study, the individual evolutionary relationships within the group had yet to be determined utilizing rigorous phylogenetic methods. Understanding these evolutionary relationships is important for producing a stable classification of the group, and will be useful in elucidating the effects the end Ordovician mass extinction had on the evolutionary and biogeographic history of the group. METHODOLOGY/PRINCIPAL FINDINGS: Cladistic parsimony analysis of cheirurid trilobites assigned to the subfamily Sphaerexochinae was conducted to evaluate phylogenetic patterns and produce a hypothesis of relationship for the group. This study utilized the program TNT, and the analysis included thirty-one taxa and thirty-nine characters. The results of this analysis were then used in a Lieberman-modified Brooks Parsimony Analysis to analyze biogeographic patterns during the Ordovician-Silurian. CONCLUSIONS/SIGNIFICANCE: The genus Sphaerexochus was found to be monophyletic, consisting of two smaller clades (one composed entirely of Ordovician species and another composed of Silurian and Ordovician species). By contrast, the genus Kawina was found to be paraphyletic. It is a basal grade that also contains taxa formerly assigned to Cydonocephalus. Phylogenetic patterns suggest Sphaerexochinae is a relatively distinctive trilobite clade because it appears to have been largely unaffected by the end Ordovician mass extinction. Finally, the biogeographic analysis yields two major conclusions about Sphaerexochus biogeography: Bohemia and Avalonia were close enough during the Silurian to exchange taxa; and during the Ordovician there was dispersal between Eastern Laurentia and the Yangtze block (South China) and between Eastern Laurentia and Avalonia

Physiochemical property space distribution among human metabolites, drugs and toxins

<p>Abstract</p> <p>Background</p> <p>The current approach to screen for drug-like molecules is to sieve for molecules with biochemical properties suitable for desirable pharmacokinetics and reduced toxicity, using predominantly biophysical properties of chemical compounds, based on empirical rules such as Lipinski's "rule of five" (Ro5). For over a decade, Ro5 has been applied to combinatorial compounds, drugs and ligands, in the search for suitable lead compounds. Unfortunately, till date, a clear distinction between drugs and non-drugs has not been achieved. The current trend is to seek out drugs which show metabolite-likeness. In identifying similar physicochemical characteristics, compounds have usually been clustered based on some characteristic, to reduce the search space presented by large molecular datasets. This paper examines the similarity of current drug molecules with human metabolites and toxins, using a range of computed molecular descriptors as well as the effect of comparison to clustered data compared to searches against complete datasets.</p> <p>Results</p> <p>We have carried out statistical and substructure functional group analyses of three datasets, namely human metabolites, drugs and toxin molecules. The distributions of various molecular descriptors were investigated. Our analyses show that, although the three groups are distinct, present-day drugs are closer to toxin molecules than to metabolites. Furthermore, these distributions are quite similar for both clustered data as well as complete or unclustered datasets.</p> <p>Conclusion</p> <p>The property space occupied by metabolites is dissimilar to that of drugs or toxin molecules, with current drugs showing greater similarity to toxins than to metabolites. Additionally, empirical rules like Ro5 can be refined to identify drugs or drug-like molecules that are clearly distinct from toxic compounds and more metabolite-like. The inclusion of human metabolites in this study provides a deeper insight into metabolite/drug/toxin-like properties and will also prove to be valuable in the prediction or optimization of small molecules as ligands for therapeutic applications.</p

Facile access to a heterocyclic, sp3-rich chemical scaffold via a tandem condensation/intramolecular nitrone–alkene [3+2] cycloaddition strategy

A heterocyclic, sp3-rich chemical scaffold was synthesised in just 6 steps via a highly regio- and diastereo-selective tandem nitrone formation/intramolecular nitrone–alkene [3+2] cycloaddition reaction. A library of 543 lead-like compounds based on the scaffold core has been produced