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Concurrent exposure to a wide variety of xenobiotics and their combined toxic effects can play a pivotal role in health and disease, yet are largely unexplored. Investigating the totality of these exposures, i.e., the "exposome", and their specific biological effects constitutes a new paradigm for environmental health but still lacks high-throughput, user-friendly technology. We demonstrate the utility of mass spectrometry-based global exposure metabolomics combined with tailored database queries and cognitive computing for comprehensive exposure assessment and the straightforward elucidation of biological effects. The METLIN Exposome database has been redesigned to help identify environmental toxicants, food contaminants and supplements, drugs, and antibiotics as well as their biotransformation products, through its expansion with over 700 000 chemical structures to now include more than 950 000 unique small molecules. More importantly, we demonstrate how the XCMS/METLIN platform now allows for the readout of the biological effect of a toxicant through metabolomic-derived pathway analysis, and further, artificial intelligence provides a means of assessing the role of a potential toxicant. The presented workflow addresses many of the methodological challenges current exposomics research is facing and will serve to gain a deeper understanding of the impact of environmental exposures and combinatory toxic effects on human health.

We present ab initio calculations of the internal C-C bond dissociation curve for single molecules of (cis-1,4) polyisoprene and polybutadiene. We define "bond rupture" as that point on the reaction coordinate where the unrestricted Kohn-Sham, or diradical, solution falls below the restricted, or closed-shell, solution. Using this definition, we find that rupture occurs at a tensile force of 6.8 nN for polyisoprene and 7.2 nN for polybutadiene. Their respective rupture strains are 45% and 42%. Our calculations show that the energy density versus extension is not sensitive to the number of isoprene units contained in the molecule, i.e., it is essentially independent of the chain length. These relatively large rupture strains have important implications for understanding the failure mechanism in rubber, and imply that purely enthalpic chain stretching must commence well before tensile failure occurs.

The design process used to produce an innovative computer system is presented. The computer system that resulted from the process uses a circular motif both for the user interface and the input device. The input device is a dial and the user interface is visually organized around the concept of a circle. The design process itself proceeded in the presence of a great many constraints and we discuss these constraints and how an innovative design was achieved in spite of the constraints.

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We investigate the thermodynamic consequences of the distribution of rotational conformations of polyisoprene on the elastic response of a network chain. In contrast to the classical theory of rubber elasticity, which associates the elastic force with the distribution of end-to-end distances, we find that the distribution of chain contour lengths provides a simple mechanism for an elastic force. Entropic force constants were determined for small contour length extensions of chains constructed as a series of localized kinks, with each kink containing between one and five cis-1,4-isoprene units. The probability distributions for the kink end-to-end distances were computed by two methods: (1) by constructing a Boltzmann distribution from the lengths corresponding to the minimum energy dihedral rotational conformations, obtained by optimizing isoprene using first principles density functional theory, and (2) by sampling the trajectories of molecular dynamics simulations of an isolated molecule composed of five isoprene units. Analogous to the well-known tube model of elasticity, we make the assumption that, for small strains, the chain is constrained by its surrounding tube, and can only move, by a process of reptation, along the primitive path of the contour. Assuming that the chain entropy is Boltzmann's constant times the logarithm of the contour length distribution, we compute the tensile force constants for chain contour length extension as the change in entropy times the temperature. For a chain length typical of moderately crosslinked rubber networks (78 isoprene units), the force constants range between 0.004 and 0.033 N/m, depending on the kink size. For a cross-linked network, these force constants predict an initial tensile modulus of between 3 and 8 MPa, which is comparable to the experimental value of 1 MPa. This mechanism is also consistent with other thermodynamic phenomenology.

The study investigated the association between two dependent variables, and 58 other variables, in 33 Sheffield secondary schools. The dependent variables were persistent absenteeism and exclusion for disciplinary reasons. Of the other variables, 22 described the schools' catchment area, with the remainder describing structural and organisational aspects of the schools themselves. There was no significant relationship between the two dependent variables. Results suggested that poor school attendance is strongly associated with socio-economic disadvantage, but not to the same extent with structural or organisational aspects of the school. In contrast no model was found which could satisfactorily account for exclusion rates. This was taken as evidence that policy on exclusion is largely idiosyncratic to each school.