Automated protein structure calculation from NMR data

Current software is almost at the stage to permit completely automatic structure determination of small proteins of < 15 kDa, from NMR spectra to structure validation with minimal user interaction. This goal is welcome, as it makes structure calculation more objective and therefore more easily validated, without any loss in the quality of the structures generated. Moreover, it releases expert spectroscopists to carry out research that cannot be automated. It should not take much further effort to extend automation to ca 20 kDa. However, there are technological barriers to further automation, of which the biggest are identified as: routines for peak picking; adoption and sharing of a common framework for structure calculation, including the assembly of an automated and trusted package for structure validation; and sample preparation, particularly for larger proteins. These barriers should be the main target for development of methodology for protein structure determination, particularly by structural genomics consortia

The nature and formation of cristobalite at the Soufrière Hills volcano, Montserrat: implications for the petrology and stability of silicic lava domes

Cristobalite is commonly found in the dome lava of silicic volcanoes but is not a primary magmatic phase; its presence indicates that the composition and micro-structure of dome lavas evolve during, and after, emplacement. Nine temporally and mineralogically diverse dome samples from the Soufrière Hills volcano (SHV), Montserrat, are analysed to provide the first detailed assessment of the nature and mode of cristobalite formation in a volcanic dome. The dome rocks contain up to 11 wt.% cristobalite, as defined by X-ray diffraction. Prismatic and platy forms of cristobalite, identified by scanning electron microscopy (SEM), are commonly found in pores and fractures, suggesting that they have precipitated from a vapour phase. Feathery crystallites and micro-crystals of cristobalite and quartz associated with volcanic glass, identified using SEM-Raman, are interpreted to have formed by varying amounts of devitrification. We discuss mechanisms of silica transport and cristobalite formation, and their implications for petrological interpretations and dome stability. We conclude: (1) that silica may be transported in the vapour phase locally, or from one part of the magmatic system to another; (2) that the potential for transport of silica into the dome should not be neglected in petrological and geochemical studies because the addition of non-magmatic phases may affect whole rock composition; and (3) that the extent of cristobalite mineralisation in the dome at SHV is sufficient to reduce porosity—hence, permeability—and may impact on the mechanical strength of the dome rock, thereby potentially affecting dome stability

Optimization of inhomogeneous electron correlation factors in periodic solids

A method is presented for the optimization of one-body and inhomogeneous two-body terms in correlated electronic wave functions of Jastrow-Slater type. The most general form of inhomogeneous correlation term which is compatible with crystal symmetry is used and the energy is minimized with respect to all parameters using a rapidly convergent iterative approach, based on Monte Carlo sampling of the energy and fitting energy fluctuations. The energy minimization is performed exactly within statistical sampling error for the energy derivatives and the resulting one- and two-body terms of the wave function are found to be well-determined. The largest calculations performed require the optimization of over 3000 parameters. The inhomogeneous two-electron correlation terms are calculated for diamond and rhombohedral graphite. The optimal terms in diamond are found to be approximately homogeneous and isotropic over all ranges of electron separation, but exhibit some inhomogeneity at short- and intermediate-range, whereas those in graphite are found to be homogeneous at short-range, but inhomogeneous and anisotropic at intermediate- and long-range electron separation.Comment: 23 pages, 15 figures, 1 table, REVTeX4, submitted to PR

Variability in the area, energy and time costs of wintering waders responding to disturbance

Birds’ responses to human disturbance are interesting due to their similarities to anti-predator behaviour, and understanding this behaviour has practical applications for conservation management by informing measures such as buffer zones to protect priority species. To understand better the costs of disturbance and whether it will impact on population size, studies should quantify time-related responses as well as the more commonly reported flight initiation distance (FID). Using waders wintering on an estuarine area, we experimentally disturbed foraging birds on the Wash Embayment, UK, by walking towards them and recording their responses (FID, alert time, time spent in flight, time taken to resume feeding, and total feeding time lost). We present data for 10 species of conservation concern: Curlew Numenius arquata, Oystercatcher Haematopus ostralegus, Bar-tailed Godwit Limosa lapponica, Grey Plover Pluvialis squatarola, Redshank Tringa totanus, Knot Calidris canutus, Turnstone Arenaria interpres, Ringed Plover Charadrius hiaticula, Sanderling Calidris alba and Dunlin Calidris alpina. Larger species responded more strongly, response magnitude was greater under milder environmental conditions, and responses varied over both small and large spatial scales. The energetic costs of individual responses, however, were low relative to daily requirements and disturbance events were unlikely to be frequent enough to seriously limit foraging time. We suggest, therefore, that wintering wader populations on the Wash are not currently significantly negatively impacted by human disturbance during the intertidal foraging period. This is also likely to be the case at other estuarine sites with comparable access levels, visitor patterns, invertebrate food availability and environmental conditions

Dispelling the Myth of Passivated Codoping in TiO2

Modification of TiO2 to increase its visible light activity and promote higher performance photocatalytic ability has become a key research goal for materials scientists in the past 2 decades. One of the most popular approaches proposed this as “passivated codoping”, whereby an equal number of donor and acceptor dopants are introduced into the lattice, producing a charge neutral system with a reduced band gap. Using the archetypal codoping pairs of [Nb + N]- and [Ta + N]-doped anatase, we demonstrate using hybrid density functional theory that passivated codoping is not achievable in TiO2. Our results indicate that the natural defect chemistry of the host system (in this case n-type anatase TiO2) is dominant, and so concentration parity of dopant types is not achievable under any thermodynamic growth conditions. The implications of passivated codoping for band gap manipulation in general are discussed

Predicting the young’s modulus of defect free radiata pine shooks in finger-jointing using resonance frequency

In this paper, dynamic MOE and static MOE of short-length radiata pine specimens produced for finger jointing were measured using non-destructive technique and correlated to each other. In order to obtain reliable static MOE data, 36 mm thickness shooks as well as the matched samples of reduced thickness (15mm) were tested, and the effect of annual growth rings on dynamic and static MOE is also addressed. Mathematical correlations were fitted between the dynamic MOE for the 36 mm thick shooks and the static MOE of the 15 mm thick samples. The coefficient of determination for dynamic MOE group 4,00-7,99 GPa was the strongest (R2 = 0,82) and the correlation strength was further improved for sorted quarter sawn samples (R2 = 0,92). Finally, the correlation between static modulus of rupture (MOR) and dynamic MOE is discussed

Resonant Ta Doping for Enhanced Mobility in Transparent Conducting SnO2

Transparent conducting oxides (TCOs) are ubiquitous in modern consumer electronics. SnO2 is an earth abundant, cheaper alternative to In2O3 as a TCO. However, its performance in terms of mobilities and conductivities lags behind that of In2O3. On the basis of the recent discovery of mobility and conductivity enhancements in In2O3 from resonant dopants, we use a combination of state-of-the-art hybrid density functional theory calculations, high resolution photoelectron spectroscopy, and semiconductor statistics modeling to understand what is the optimal dopant to maximize performance of SnO2-based TCOs. We demonstrate that Ta is the optimal dopant for high performance SnO2, as it is a resonant dopant which is readily incorporated into SnO2 with the Ta 5d states sitting ∼1.4 eV above the conduction band minimum. Experimentally, the band edge electron effective mass of Ta doped SnO2 was shown to be 0.23m0, compared to 0.29m0 seen with conventional Sb doping, explaining its ability to yield higher mobilities and conductivities

Characterization and sequence mapping of large RNA and mRNA therapeutics using mass spectrometry

Large RNA including mRNA (mRNA) has emerged as an important new class of therapeutics. Recently, this has been demonstrated by two highly efficacious vaccines based on mRNA sequences encoding for a modified version of the SARS-CoV-2 spike protein. There is currently significant demand for the development of new and improved analytical methods for the characterization of large RNA including mRNA therapeutics. In this study, we have developed an automated, high-throughput workflow for the rapid characterization and direct sequence mapping of large RNA and mRNA therapeutics. Partial RNase digestions using RNase T1 immobilized on magnetic particles were performed in conjunction with high-resolution liquid chromatography–mass spectrometry analysis. Sequence mapping was performed using automated oligoribonucleotide annotation and identifications based on MS/MS spectra. Using this approach, a >80% sequence of coverage of a range of large RNAs and mRNA therapeutics including the SARS-CoV-2 spike protein was obtained in a single analysis. The analytical workflow, including automated sample preparation, can be completed within 90 min. The ability to rapidly identify, characterize, and sequence map large mRNA therapeutics with high sequence coverage provides important information for identity testing, sequence validation, and impurity analysis

Carbon clusters near the crossover to fullerene stability

The thermodynamic stability of structural isomers of $\mathrm{C}_{24}$, $\mathrm{C}_{26}$, $\mathrm{C}_{28}$ and $\mathrm{C}_{32}$, including fullerenes, is studied using density functional and quantum Monte Carlo methods. The energetic ordering of the different isomers depends sensitively on the treatment of electron correlation. Fixed-node diffusion quantum Monte Carlo calculations predict that a $\mathrm{C}_{24}$ isomer is the smallest stable graphitic fragment and that the smallest stable fullerenes are the $\mathrm{C}_{26}$ and $\mathrm{C}_{28}$ clusters with $\mathrm{C}_{2v}$ and $\mathrm{T}_{d}$ symmetry, respectively. These results support proposals that a $\mathrm{C}_{28}$ solid could be synthesized by cluster deposition.Comment: 4 pages, includes 4 figures. For additional graphics, online paper and related information see http://www.tcm.phy.cam.ac.uk/~prck