A hydrogen tethered inhibitor of matrix metalloproteinases

During wound repair, the balance between matrix metalloproteinases (MMPs) and their natural inhibitors (the TIMPs) is crucial for the normal extra cellular matrix turnover. However, the over expression of several MMPs including MMP-1, 2, 3, 8, 9 and MMP-10, combined with abnormally high levels of activation or low expression of TIMPs, may contribute to excessive degradation of connective tissue and formation of chronic ulcers. There are many groups exploring strategies for promoting wound healing involving delivery of growth factors, cells, ECM components and small molecules. Our approach for improving the balance of MMPs is not to add anything more to the wound, but instead to neutralise the over-expressed MMPs using inhibitors tethered to a bandage-like hydrogel. Our in vitro experiments using designed synthetic pseudo peptide inhibitors have been demonstrated to inhibit MMP activity in standard solutions. These inhibitors have also been tethered to polyethylene glycol hydrogels using a facile reaction between the linker unit on the inhibitor and the gel. After tethering the inhibition of MMPs diminishes to some extent and we postulate that this arises due to poor diffusion of the MMPs into the gels. When the tethered inhibitors were tested against chronic wound fluid obtained against patients we observed over 40% inhibition in proteolytic activity suggesting our approach may prove useful in rebalancing MMPs within chronic wounds.

Exponential asymptotics with multiple stokes lines

When asymptotic series methods are applied in order to solve problems that arise in applied mathematics in the limit that some parameter becomes small, they are unable to demonstrate behaviour that occurs on a scale that is exponentially small compared to the algebraic terms of the asymptotic series. There are many examples of physical systems where behaviour on this scale has important effects and, as such, a range of techniques known as exponential asymptotic techniques were developed that may be used to examinine behaviour on this exponentially small scale. Many problems in applied mathematics may be represented by behaviour within the complex plane, which may subsequently be examined using asymptotic methods. These problems frequently demonstrate behaviour known as Stokes phenomenon, which involves the rapid switches of behaviour on an exponentially small scale in the neighbourhood of some curve known as a Stokes line. Exponential asymptotic techniques have been applied in order to obtain an expression for this exponentially small switching behaviour in the solutions to orginary and partial differential equations. The problem of potential flow over a submerged obstacle has been previously considered in this manner by Chapman & Vanden-Broeck (2006). By representing the problem in the complex plane and applying an exponential asymptotic technique, they were able to detect the switching, and subsequent behaviour, of exponentially small waves on the free surface of the flow in the limit of small Froude number, specifically considering the case of flow over a step with one Stokes line present in the complex plane. We consider an extension of this work to flow configurations with multiple Stokes lines, such as flow over an inclined step, or flow over a bump or trench. The resultant expressions are analysed, and demonstrate interesting implications, such as the presence of exponentially sub-subdominant intermediate waves and the possibility of trapped surface waves for flow over a bump or trench. We then consider the effect of multiple Stokes lines in higher order equations, particu- larly investigating the behaviour of higher-order Stokes lines in the solutions to partial differential equations. These higher-order Stokes lines switch off the ordinary Stokes lines themselves, adding a layer of complexity to the overall Stokes structure of the solution. Specifically, we consider the different approaches taken by Howls et al. (2004) and Chap- man & Mortimer (2005) in applying exponential asymptotic techniques to determine the higher-order Stokes phenomenon behaviour in the solution to a particular partial differ- ential equation.

Spectroscopy of selected copper group minerals : chalcophyllite and chenevixite-implications for hydrogen bonding

NIR and IR spectroscopy has been applied for detection of chemical species and the nature of hydrogen bonding in arsenate complexes. The structure and spectral properties of copper(II) arsenate minerals chalcophyllite and chenevixite are compared with copper(II) sulphate minerals devilline, chalcoalumite and caledonite. Split NIR bands in the electronic spectrum of two ranges 11700-8500 cm-1 and 8500-7200 cm-1 confirm distortion of octahedral symmetry for Cu(II) in the arsenate complexes. The observed bands with maxima at 9860 and 7750 cm-1 are assigned to Cu(II) transitions 2B1g ® 2B2g and 2B1g ® 2A1g. Overlapping bands in the NIR region 4500-4000 cm-1 is the effect of multi anions OH-, (AsO4)3- and (SO4)2-. The observation of broad and diffuse bands in the range 3700-2900 cm-1 confirms strong hydrogen bonding in chalcophyllite relative to chenevixite. The position of the water bending vibrations indicates the water is strongly hydrogen bonded in the mineral structure. The strong absorption feature centred at 1644 cm-1 in chalcophyllite indicates water is strongly hydrogen bonded in the mineral structure. The H2O-bending vibrations shift to low wavenumbers in chenevixite and an additional band observed at 1390 cm-1 is related to carbonate impurity. The characterisation of IR spectra by ν3 antisymmetric stretching vibrations of (SO4)2- and (AsO4)3 ions near 1100 and 800 cm-1 respectively is the result of isomorphic substitution for arsenate by sulphate in both the minerals of chalcophyllite and chenevixite.

Signalling layout for fixed-block railway lines with real-coded genetic algorithms.

Signalling layout design is one of the keys to railway operations with fixed-block signalling system and it also carries direct effect on overall train efficiency and safety. Based on an analysis to system objectives, this paper presents an optimization model with two objectives in order to devise an efficient signalling layout scheme. Taking into account the present railway line design practices in China, the paper describes steps of the computer-based signalling layout optimisation with real-coded genetic algorithms. A computer-aided system, based on train movement simulator, has also been employed to assist the optimisation process. A case study on a practical railway line has been conducted to make comparisons between the proposed GA-based approach and the current practices. The results illustrate the improved performance of the proposed approach in reducing signal block joints and shortening minimum train service headway.

Three-dimensional hydrogen-bonded structures in the guanidinium salts of the monocyclic dicarboxylic acids rac-trans-cyclohexane-1,2-dicarboxylic acid (2:1, anhydrous), isophthalic acid (1:1, monohydrate) and terephthalic acid (2:1, trihydrate).

The structures of bis(guanidinium)rac-trans-cyclohexane-1,2-dicarboxylate, 2(CH6N3+) C8H10O4- (I), guanidinium 3-carboxybenzoate monohydrate CH6N3+ C8H5O4- . H2O (II) and bis(guanidinium) benzene-1,4-dicarboxylate trihydrate, 2(CH6N3+) C8H4O4^2- . 3H2O (III) have been determined and the hydrogen bonding in each examined. All three compounds form three-dimensional hydrogen-bonded framework structures. In anhydrous (I), both guanidinium cations give classic cyclic R2/2(8) N--H...O,O'(carboxyl) and asymmetric cyclic R1/2(6) hydrogen-bonding interactions while one cation gives an unusual enlarged cyclic interaction with O acceptors of separate ortho-related carboxyl groups [graph set R2/2(11)]. Cations and anions also associate across inversion centres giving cyclic R2/4(8) motifs. In the 1:1 guanidinium salt (II), the cation gives two separate cyclic R1/2(6) interactions, one with a carboxyl O-acceptor, the other with the water molecule of solvation. The structure is unusual in that both carboxyl groups give short inter-anion O...H...O contacts, one across a crystallographic inversion centre [2.483(2)\%A], the other about a two-fold axis of rotation [2.462(2)\%A] with a half-occupancy hydrogen delocalized on the symmetry element in each. The water molecule links the cation--anion ribbon structures into a three-dimensional framework. In (III), the repeating molecular unit comprises a benzene-1,4-dicarboxylate dianion which lies across a crystallographic inversion centre, two guanidinium cations and two water molecules of solvation (each set related by two-fold rotational symmetry), and a single water molecule which lies on a two-fold axis. Each guanidinium cation gives three types of cyclic interactions with the dianions: one R^1^~2~(6), the others R2/3(8) and R3/3(10) (both of these involving the water molecules), giving a three-dimensional structure through bridges down the b cell direction. The water molecule at the general site also forms an unusual cyclic R2/2(4) homodimeric association across an inversion centre [O--H...O, 2.875(2)\%A]. The work described here provides further examples of the common cyclic guanidinium cation...carboxylate anion hydrogen-bonding associations as well as featuring other less common cyclic motifs.

Hydrogen bonding in the anhydrous 1:1 proton-transfer compounds of isonipecotamide with nitro-substituted benzoic acids: the salts of the three isomeric mononitrobenzoic acids and of 3,5-dinitrobenzoic acid

The structures of the anhydrous 1:1 proton-transfer compounds of isonipecotamide (piperidine-4-carboxamide) with the three isomeric mononitro-substituted benzoic acids and 3,5-dinitrobenzoic acid, namely 4-carbamoylpiperidinium 2-nitrobenzoate (I), 4-carbamoylpiperidinium 3-nitrobenzoate (II), 4-carbamoylpiperidinium 4-nitrobenzoate (III), (C6H13N2O+ C7H4NO4-) and 4-carbamoylpiperidinium 3,5-dinitrobenzoate (IV) (C6H13N2O+ C7H5N2O6-)respectively, have been determined at 200 K. All salts form hydrogen-bonded structures: three-dimensional in (I), two-dimensional in (II) and (III) and one-dimensional in (IV). Featured in the hydrogen bonding of three of these [(I), (II) and (IV)] is the cyclic head-to-head amide--amide homodimer motif [graph set R2/2~(8)] through a duplex N---H...O association, the dimer then giving structure extension via either piperidinium or amide H-donors and carboxylate-O and in some examples [(II) and (IV)], nitro-O atom acceptors. In (I), the centrosymmetric amide-amide homodimers are expanded laterally through N-H...O hydrogen bonds via cyclic R2/4(8) interactions forming ribbons which extend along the c cell direction. These ribbons incorporate the 2-nitrobenzoate cations through centrosymmetric cyclic piperidine N-H...O(carboxyl) associations [graph set R4/4(12)], giving inter-connected sheets in the three-dimensional structure. In (II) in which no amide-amide homodimer is present, duplex piperidinium N-H...O(amide) hydrogen-bonding homomolecular associations [graph set R2/2(14)] give centrosymmetric head-to-tail dimers. Structure extension occurs through hydrogen-bonding associations between both the amide H-donors and carboxyl and nitro O-acceptors as well as a three-centre piperidinium N-H...O,O'(carboxyl) cyclic R2/1(4) association giving the two-dimensional network structure. In (III), the centrosymmetric amide-amide dimers are linked through the two carboxyl O-atom acceptors of the anions via bridging piperidinium and amide N-H...O,O'...H-N(amide) hydrogen bonds giving the two-dimensional sheet structure which features centrosymmetric cyclic R4/4(12) associations. In (IV), the amide-amide dimer is also centrosymmetric with the dimers linked to the anions through amide N-H...O(nitro) interactions. The piperidinium groups extend the structure into one-dimensional ribbons via N-H...O(carboxyl) hydrogen bonds. The structures reported here further demonstrate the utility of the isonipecotamide cation in molecular assembly and highlight the efficacy of the cyclic R2/2(8) amide-amide hydrogen-bonding homodimer motif in this process and provide an additional homodimer motif type in the head-to-tail R2/2(14) association.

Darkening the lines

A collaborative process reviewed from the inside: David megarrity and Clare carmody examine what it's like to make a 'real play' with 8-12 year olds.

Directional earth fault relay operation in mutually coupled multiple circuit distribution lines

Many of the power utilities around the world experienced spurious tripping of directional earth fault relays in their mesh distribution networks due to induced circulating currents. This circulating current is zero sequence and induced in the healthy circuit due to the zero sequence current flow resulting from a ground fault of a parallel circuit. This paper quantitatively discusses the effects of mutual coupling on earth fault protection of distribution systems. An actual spurious tripping event is analyzed to support the theory and to present options for improved resilience to spurious tripping.

Hydrogen bonding in proton-transfer compounds of 5-sulfosalicylic acid with a series of aliphatic nitrogen Lewis bases

The crystal structures of the proton-transfer compounds of 5-sulfosalicylic acid (3-carboxy-4-hydroxybenzenesulfonic acid) with the aliphatic nitrogen Lewis bases, hydroxylamine, triethylamine, pyrrolidine, morpholine, N-methylmorpholine and piperazine, viz. hydroxyammonium 3-carboxy-4-hydroxybenzenesulfonate (1), triethylaminium 3-carboxy-4-hydroxybenzenesulfonate (2), pyrrolidinium 3-carboxy-4-hydroxybenzenesulfonate monohydrate (3), morpholinium 3-carboxy-4-hydroxybenzenesulfonate monohydrate (4), N-methylmorpholinium 3-carboxy-4-hydroxybenzenesulfonate monohydrate (5) and piperazine-1,4-diium bis(3-carboxy-4-hydroxybenzenesulfonate) hexahydrate (6) have been determined and their comparative structural features and hydrogen-bonding patterns described. Crystals of 4 are triclinic, space group P-1 while the remainder are monoclinic with space group either P21/c (1 - 3) or P21/n (5, 6). Unit cell dimensions and contents are: for 1, a = 5.0156(3), b = 10.5738(6), c = 18.4785(9) Å, β = 96.412(5)o, Z = 4; for 2, a = 8.4998(4), b = 12.3832(6), c = 15.4875(9) Å, β = 102.411(5)o, Z = 4; for 3, a = 6.8755(2), b = 15.5217(4), c = 12.8335(3) Å, β = 92.074(2)o, Z = 4; for 4, a = 6.8397(2), b = 12.9756(5), c = 15.8216(6) Å, α = 90.833(3), β = 95.949(3), γ = 92.505(3)o, Z = 4; for 5, a = 7.0529(3), b = 13.8487(7), c = 15.6448(6) Å, β = 90.190(6)o, Z = 4; for 6, a = 7.0561(2), b = 15.9311(4), c = 12.2102(3) Å, β = 100.858(3)o, Z = 2. The hydrogen bonding generates structures which are either two-dimensional (2 and 5) or three-dimensional (1, 3, 4 and 6). Compound 6 represents the third reported structure of a salt of 5-sulfosalicylic acid having a dicationic piperazine species.

Structure of selected basic zinc/copper (II) phosphate minerals based upon near-infrared spectroscopy : implications for hydrogen bonding

The NIR spectra of reichenbachite, scholzite and parascholzite have been studied at 298 K. The spectra of the minerals are different, in line with composition and crystal structural variations. Cation substitution effects are significant in their electronic spectra and three distinctly different electronic transition bands are observed in the near-infrared spectra at high wavenumbers in the 12000-7600 cm-1 spectral region. Reichenbachite electronic spectrum is characterised by Cu(II) transition bands at 9755 and 7520 cm-1. A broad spectral feature observed for ferrous ion in the 12000-9000 cm-1 region both in scholzite and parascholzite. Some what similarities in the vibrational spectra of the three phosphate minerals are observed particularly in the OH stretching region. The observation of strong band at 5090 cm-1 indicates strong hydrogen bonding in the structure of the dimorphs, scholzite and parascholzite. The three phosphates exhibit overlapping bands in the 4800-4000 cm-1 region resulting from the combinations of vibrational modes of (PO4)3- units.

Altering heavy vehicle air suspension dynamic forces by modifying air lines

An experimental programme in 2007 used three air suspended heavy vehicles travelling over typical urban roads to determine whether dynamic axle-to-chassis forces could be reduced by using larger-than-standard diameter longitudinal air lines. This paper presents methodology, interim analysis and partial results from that programme. Alterations to dynamic measures derived from axle-to-chassis forces for the case of standard-sized longitudinal air lines vs. the test case where larger longitudinal air lines were fitted are presented and discussed. This leads to conclusions regarding the possibility that dynamic loadings between heavy vehicle suspensions and chassis may be reduced by fitting larger longitudinal air lines to air-suspended heavy vehicles. Reductions in the shock and vibration loads to heavy vehicle suspension components could lead to lighter and more economical chassis and suspensions. This could therefore lead to reduced tare and increased payloads without an increase in gross vehicle mass.

Raman spectroscopy of hydrogen arsenate group (AsO3OH)2− in solid-state compounds: cobalt-containing zinc arsenate mineral, koritnigite (Zn,Co)(AsO3OH)·H2O

Raman spectra of two well-defined types of koritnigite crystals from the Jáchymov ore district, Czech Republic, were recorded and interpreted. No substantial differences were observed between both crystal types. Observed Raman bands were attributed to the (AsO3OH)2- stretching and bending vibrations, stretching and bending vibrations of water molecules and hydroxyl ions. Non-interpreted Raman spectra of koritnigite from the RRUFF database, and published infrared spectra of cobaltkoritnigite were used for comparison. The O-H...O hydrogen bond lengths in the crystal structure of koritnigite were inferred from the Raman spectra and compared with those derived from the X-ray single crystal refinement. The presence of (AsO3OH)2- units in the crystal structure of koritnigite was proved from the Raman spectra which supports the conclusions of the X-ray structure analysis.

The hydrogen-bonded coordination polymer tetracesium bis(5-nitroisophthalate) heptahydrate

The coordination polymer complex tetracesium bis(5-nitroisophthalate) heptahydrate [Cs4(C8H3NO6)2 (H2O)7]n has been synthesized and characterized using single-crystal X-ray diffraction. Crystals are monoclinic, space group P21/c, with Z = 4 in a cell with dimensions a = 12.3213(3), b =6.7557(2) c = 36.2020(9) Å, β = 90.548(2)o. The complex is based on a repeating unit comprising four independent and different Cs coordination centres, two 6-coordinate, and two 8-coordinate [Cs-O, range 2.959(5)-3.386(5)Å], and seven water molecules, two of which are monodentate and the other five bridging, while all other oxygen atoms in the structure, including those of the nitro groups form inter-Cs bridges. Extensive water O-H…O hydrogen-bonding interactions give a three-dimensional framework. This structure represents the first of an alkali metal compound of 5-nitroisophthalic acid that has been reported.