Triosephosphate isomerase: a highly evolved biocatalyst

Triosephosphate isomerase (TIM) is a perfectly evolved enzyme which very fast interconverts dihydroxyacetone phosphate and d-glyceraldehyde-3-phosphate. Its catalytic site is at the dimer interface, but the four catalytic residues, Asn11, Lys13, His95 and Glu167, are from the same subunit. Glu167 is the catalytic base. An important feature of the TIM active site is the concerted closure of loop-6 and loop-7 on ligand binding, shielding the catalytic site from bulk solvent. The buried active site stabilises the enediolate intermediate. The catalytic residue Glu167 is at the beginning of loop-6. On closure of loop-6, the Glu167 carboxylate moiety moves approximately 2 Å to the substrate. The dynamic properties of the Glu167 side chain in the enzyme substrate complex are a key feature of the proton shuttling mechanism. Two proton shuttling mechanisms, the classical and the criss-cross mechanism, are responsible for the interconversion of the substrates of this enolising enzyme.     

Instruments of Music,Instruments of Science: Hermann von Helmholtz's Musical Practices,his Classicism,and his Beethoven Sonata

The young Hermann Helmholtz, in an 1838 letter home, declared that he always appreciated music much more when he played it for himself. Though a frequent concert-goer, and celebrated for his highly influential 1863 work on the physiological basis of music theory, Die Lehre von den Tonempfindungen, it is likely that Helmholtz's enduring engagement with music began with his initial, personal experience of playing music for himself. I develop this idea, shifting the discussion of Helmholtz's work on sound sensation back to its origins, and examine the role of his material interaction with musical instruments and music itself. In his sound sensation studies, Helmholtz understood sound as an external, physical object. But Helmholtz also conceived of sound in musical terms. Further, Helmholtz's particular musical tastes as well as his deeply personal interaction with musical instruments allowed him to reconcile his conception of sound as physical object with his conception of sound as music. Helmholtz's physiological theory of sound sensation was both the product of and constitutive of how he heard and created sound. I argue that Helmholtz himself was the embodied reconciliation of his physiological theory of sound sensation and his belief that musical aesthetics were historically and culturally contingent.     

Chemistry and meteorology, 1700–1825

In 1639–1640 Benedetto Castelli (1577–1643) wrote a treatise on the loadstone which is quite unlike any of its contemporaries. In it are the origins of the notion of elementary magnets sharing a common alignment, the idea that all materials are magnetic in different ways, and the first intimation of the conception of magnetic domains. Castelli did not publish his treatise. Nevertheless his work was noted during his life-time, and may have exerted an influence on the development of magnetic theory in the 17th century. The treatise was published in 1883. Since then, however, it has either been neglected or not appreciated. It deserves being rescued from the neglect of more than three centuries.     

The American Philosophical Society and the rise of astronomy in the United States in the middle of the nineteenth century

Early geological investigations in the St David's area (Pembrokeshire) are described, particularly the work of Murchison. In a reconnaissance survey in 1835, he regarded a ridge of rocks at St David's as intrusive in unfossiliferous Cambrian; and the early Survey mapping (chiefly the work of Aveline and Ramsay) was conducted on that assumption, leading to the publication of maps in 1845 and 1857. The latter represented the margins of the St David's ridge as ‘Altered Cambrian’. So the supposedly intrusive ‘syenite’ was regarded as younger, and there was no Precambrian. These views were challenged by a local doctor, Henry Hicks, who developed an idea of the ex-Survey palaeontologist John Salter that the rocks of the ridge were stratified and had formed a Precambrian island, round which Cambrian sediments (now confirmed by fossil discoveries) had been deposited. Hicks subsequently proposed subdivision of his Precambrian into ‘Dimetian’, ‘Pebidian’, and (later) ‘Arvonian’, and he attempted correlations with rocks in Shropshire, North Wales, and even North America, seeking to develop the neo-Neptunist ideas of Sterry Hunt. The challenge to the Survey's work was countered in the 1880s by the Director General, Geikie, who showed that Hicks's idea of stratification in the Dimetian was mistaken. A heated controversy developed, several amateur geologists, supported by a group of Cambridge Sedgwickians, forming a coalition of ‘Archaeans’ against the Survey. Geikie was supported by Lloyd Morgan. Attention focused particularly on Ogof Lle-sugn Cave and St Non's Arch, with theory/controversy-ladenness of observations evident on both sides. Evidence from an eyewitness student record of a Geological Society meeting reveals the ‘sanit`ized’ nature of the official summary of the debate in QJGS. Field mapping early in the twentieth century by J. F. N. Green allowed a compromise consensus to be achieved, but Green's evidence for unconformity between the Cambrian and the Dimetian, obtained by excavation, can no longer be verified, and his consensual history of the area may need revision. Unconformity between the Cambrian and the Pebidian tuffs is not in doubt, however, and Precambrian at St David's is accepted. The study exhibits features of geological controversy and the British geological community in the nineteenth century. It also furnishes a further instance of the great influence of Murchison in nineteenth-century British geology and the side-effects of his controversy with Sedgwick.     

On the Difficulty of Measuring Forecasting Skill in Financial Markets

The use of correlation between forecasts and actual returns is commonplace in the literature, often used as a measurement of investors' skill. A prominent application of this is the concept of the information coefficient (IC). Not only can the IC be used as a tool to rate analysts and fund managers but it also represents an important parameter in the asset allocation and portfolio construction process. Nevertheless, a theoretical understanding of it has typically been limited to the partial equilibrium context where the investing activities of each agent have no effect on other market participants. In this paper we show that this can be an undesirable oversimplification and we demonstrate plausible circumstances in which conventional empirical measurements of IC can be highly misleading. We suggest that improved understanding of IC in a general equilibrium setting can lead to refined portfolio decision making ex ante and more informative analysis of performance ex post. Copyright © 2015 John Wiley & Sons, Ltd.     

Multiple paths to aquatic specialisation in four species of Central American Anolis lizards

Aquatic anoles present an interesting ecomorphological puzzle. On the one hand, the link between habitat use and morphology is well established as convergent within the Caribbean anole radiation. On the other hand, aquatic anoles do not appear to form an ecomorphological group – rather, it appears that there may be several ways to adapt to aquatic habitats. We explore this issue by examining the ecology, morphology and performance of four species of Central American aquatic anoles belonging to two different lineages. Overall, we find that aquatic anoles overlap in multiple ecological and morphological dimensions. However, we do find some differences in substrate use, claw and limb morphology, and bite force that distinguish Anolis aquaticus from the other three species (A. lionotus, A. oxylophus and A. poecilopus). Our results suggest that A. aquaticus is adapted to climb on boulders, whereas the other species utilise vegetation in streamside habitats.     

Forecasting VaR models under Different Volatility Processes and Distributions of Return Innovations

This paper provides clear‐cut evidence that the out‐of‐sample VaR (value‐at‐risk) forecasting performance of alternative parametric volatility models, like EGARCH (exponential general autoregressive conditional heteroskedasticity) or GARCH, and Markov regime‐switching models, can be considerably improved if they are combined with skewed distributions of asset return innovations. The performance of these models is found to be similar to that of the EVT (extreme value theory) approach. The performance of the latter approach can also be improved if asset return innovations are assumed to be skewed distributed. The performance of the Markov regime‐switching model is considerably improved if this model allows for EGARCH effects, for all different volatility regimes considered. Copyright © 2014 John Wiley & Sons, Ltd.