University of Warwick

About: University of Warwick is a education organization based out in Coventry, Warwickshire, United Kingdom. It is known for research contribution in the topics: Population & Context (language use). The organization has 26212 authors who have published 77127 publications receiving 2666552 citations. The organization is also known as: Warwick University & The University of Warwick.

Association between C reactive protein and coronary heart disease: mendelian randomisation analysis based on individual participant data

Abstract: Objective To use genetic variants as unconfounded proxies of C reactive protein concentration to study its causal role in coronary heart disease. Design Mendelian randomisation meta-analysis of ind ...

Relationships among Ionic Lattice Energies, Molecular (Formula Unit) Volumes, and Thermochemical Radii.

Abstract: The linear generalized equation described in this paper provides a further dimension to the prediction of lattice potential energies/enthalpies of ionic solids. First, it offers an alternative (and often more direct) approach to the well-established Kapustinskii equation (whose capabilities have also recently been extended by our recent provision of an extended set of thermochemical radii). Second, it makes possible the acquisition of lattice energy estimates for salts which, up until now, except for simple 1:1 salts, could not be considered because of lack of crystal structure data. We have generalized Bartlett's correlation for MX (1:1) salts, between the lattice enthalpy and the inverse cube root of the molecular (formula unit) volume, such as to render it applicable across an extended range of ionic salts for the estimation of lattice potential energies. When new salts are synthesized, acquisition of full crystal structure data is not always possible and powder data provides only minimal structural in...

The Top 10 oomycete pathogens in molecular plant pathology

Abstract: Oomycetes form a deep lineage of eukaryotic organisms that includes a large number of plant pathogens which threaten natural and managed ecosystems. We undertook a survey to query the community for their ranking of plant-pathogenic oomycete species based on scientific and economic importance. In total, we received 263 votes from 62 scientists in 15 countries for a total of 33 species. The Top 10 species and their ranking are: (1) Phytophthora infestans; (2, tied) Hyaloperonospora arabidopsidis; (2, tied) Phytophthora ramorum; (4) Phytophthora sojae; (5) Phytophthora capsici; (6) Plasmopara viticola; (7) Phytophthora cinnamomi; (8, tied) Phytophthora parasitica; (8, tied) Pythium ultimum; and (10) Albugo candida. This article provides an introduction to these 10 taxa and a snapshot of current research. We hope that the list will serve as a benchmark for future trends in oomycete research.

Metal Complexes as DNA Intercalators

Abstract: DNA has a strong affinity for many heterocyclic aromatic dyes, such as acridine and its derivatives. Lerman in 1961 first proposed intercalation as the source of this affinity, and this mode of DNA binding has since attracted considerable research scrutiny. Organic intercalators can inhibit nucleic acid synthesis in vivo, and they are now common anticancer drugs in clinical therapy. The covalent attachment of organic intercalators to transition metal coordination complexes, yielding metallointercalators, can lead to novel DNA interactions that influence biological activity. Metal complexes with σ-bonded aromatic side arms can act as dual-function complexes: they bind to DNA both by metal coordination and through intercalation of the attached aromatic ligand. These aromatic side arms introduce new modes of DNA binding, involving mutual interactions of functional groups held in close proximity. The biological activity of both cis- and trans-diamine Pt(II) complexes is dramatically enhanced by the addition of σ-bonded intercalators. We have explored a new class of organometallic "piano-stool" Ru(II) and Os(II) arene anticancer complexes of the type [(η(6)-arene)Ru/Os(XY)Cl](+). Here XY is, for example, ethylenediamine (en), and the arene ligand can take many forms, including tetrahydroanthracene, biphenyl, or p-cymene. Arene-nucleobase stacking interactions can have a significant influence on both the kinetics and thermodynamics of DNA binding. In particular, the cytotoxic activity, conformational distortions, recognition by DNA-binding proteins, and repair mechanisms are dependent on the arene. A major difficulty in developing anticancer drugs is cross-resistance, a phenomenon whereby a cell that is resistant to one drug is also resistant to another drug in the same class. These new complexes are non-cross-resistant with cisplatin towards cancer cells: they constitute a new class of anticancer agents, with a mechanism of action that differs from the anticancer drug cisplatin and its analogs. The Ru-arene complexes with dual functions are more potent towards cancer cells than their nonintercalating analogs. In this Account, we focus on recent studies of dual-function organometallic Ru(II)- and Os(II)-arene complexes and the methods used to detect arene-DNA intercalation. We relate these interactions to the mechanism of anticancer activity and to structure-activity relationships. The interactions between these complexes and DNA show close similarities to those of covalent polycyclic aromatic carcinogens, especially to N7-alkylating intercalation compounds. However, Ru-arene complexes exhibit some new features. Classical intercalation and base extrusion next to the metallated base is observed for {(η(6)-biphenyl)Ru(ethylenediamine)}(2+) adducts of a 14-mer duplex, while penetrating arene intercalation occurs for adducts of the nonaromatic bulky intercalator {(η(6)-tetrahydroanthracene)Ru(ethylenediamine)}(2+) with a 6-mer duplex. The introduction of dual-function Ru-arene complexes introduces new mechanisms of antitumor activity, novel mechanisms for attack on DNA, and new concepts for developing structure- activity relationships. We hope this discussion will stimulate thoughtful and focused research on the design of anticancer chemotherapeutic agents using these unique approaches.

A theory of regularity structures

Abstract: We introduce a new notion of "regularity structure" that provides an algebraic framework allowing to describe functions and / or distributions via a kind of "jet" or local Taylor expansion around each point. The main novel idea is to replace the classical polynomial model which is suitable for describing smooth functions by arbitrary models that are purpose-built for the problem at hand. In particular, this allows to describe the local behaviour not only of functions but also of large classes of distributions. We then build a calculus allowing to perform the various operations (multiplication, composition with smooth functions, integration against singular kernels) necessary to formulate fixed point equations for a very large class of semilinear PDEs driven by some very singular (typically random) input. This allows, for the first time, to give a mathematically rigorous meaning to many interesting stochastic PDEs arising in physics. The theory comes with convergence results that allow to interpret the solutions obtained in this way as limits of classical solutions to regularised problems, possibly modified by the addition of diverging counterterms. These counterterms arise naturally through the action of a "renormalisation group" which is defined canonically in terms of the regularity structure associated to the given class of PDEs. As an example of a novel application, we solve the long-standing problem of building a natural Markov process that is symmetric with respect to the (finite volume) measure describing the $\Phi^4_3$ Euclidean quantum field theory. It is natural to conjecture that the Markov process built in this way describes the Glauber dynamic of 3-dimensional ferromagnets near their critical temperature.