Source: https://www.sthildas.ox.ac.uk/content/dr-lorna-j-smith
Timestamp: 2019-04-20 11:18:35+00:00

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Dr Lorna Smith holds the Peacock Tutorial Fellowship in Chemistry at St Hilda's and is an Associate Professor in the Department of Chemistry. She teaches Inorganic Chemistry to all the St Hilda's undergraduates. In addition she supervises fourth year undergraduate Part II projects in the Inorganic Chemistry Laboratory. Dr Smith is also the Disability Fellow at St. Hilda’s and is available to help and advise any student with a disability.
Dr Smith's research uses a combination of experimental and theoretical approaches to study the structure and dynamical properties of proteins. Much of her current work concentrates on characterising denatured, partially folded and misfolded proteins. This work has relevance with regard to our understanding of a range of disease states resulting from protein misfolding or aggregation, such as Alzheimer's disease and the spongiform encephalophies (CJD, BSE), as well as contributing to our understanding of food allergies.
(1) L.J. Smith, M.J. Sutcliffe, C. Redfield & C.M. Dobson. ‘Analysis of φ and χ1 Torsion Angles for Hen Lysozyme in Solution from 1H NMR Spin-Spin Coupling Constants.’ (1991) Biochemistry 30, 986-996.
(2) C. Redfield, L.J. Smith, J. Boyd, G.M.P. Lawrence, R.G. Edwards, R.A.G. Smith & C.M. Dobson. ‘Secondary Structure and Topology of Human Interleukin-4 in Solution.’ (1991) Biochemistry 30, 11029-11035.
(3) L.J. Smith, C. Redfield, J. Boyd, G.M.P. Lawrence, R.G. Edwards, R.A.G. Smith & C.M. Dobson. ‘Human Interleukin-4: The Solution Structure of a Four-Helix-Bundle.’ (1992) J. Mol. Biol. 224, 899-904.
(4) C. Redfield, J. Boyd, L.J. Smith, R.A.G. Smith, & C.M. Dobson. ‘Loop Mobility in a Four-Helix-Bundle Protein: 15N Relaxation Measurements on Human Interleukin-4.’ (1992) Biochemistry 31, 10431-10437.
(5) L.J. Smith, M.J. Sutcliffe, C. Redfield & C.M. Dobson. ‘The Structure of Hen Lysozyme in Solution.’ (1993) J. Mol. Biol. 229, 930-944.
(6) C. Redfield, L.J. Smith, J. Boyd, G.M.P. Lawrence, R.G. Edwards, R.A.G. Smith & C.M. Dobson. ‘Analysis of the Solution Structure of Human Interleukin-4 determined by Heteronuclear NMR Techniques.’ (1994) J. Mol. Biol. 238, 23-41.
(7) L.J. Smith, C. Redfield, R.A.G. Smith, C.M. Dobson, G.M. Clore, A.M. Gronenborn, M.R. Walter, T.L. Nagabushan & A. Wlodawer. ‘Comparison of Four Independently Determined Structures of Human Recombinant Interleukin-4.’ (1994) Nature Structural Biology 1, 301-310.
(8) L.J. Smith, A.T. Alexandrescu, M. Pitkeathly & C.M. Dobson. ‘Solution Structure of a Peptide Fragment of Human α-lactalbumin in Trifluoroethanol: a Model for Local Structure in the Molten Globule.’ (1994) Structure 2, 703-712.
(9) L.J. Smith & C.M. Dobson. ‘Protein Structures in Solution Viewed by NMR.’ (1995) In Making the Most of Your Model (ed. W.N. Hunter, J.M. Thornton & S. Bailey) CCL Daresbury pp. 53-62.
(10) L.J. Smith, A.E. Mark, C.M. Dobson & W.F. van Gunsteren. ‘Comparison of MD Simulations and NMR Experiments for Hen Lysozyme. Analysis of Local Fluctuations, Cooperative Motions and Global Changes.’ (1995) Biochemistry 34, 10918-10931.
(11) L.J. Smith, K.A. Bolin, H. Schwalbe, M.W. MacArthur, J.M. Thornton & C.M. Dobson. ‘Analysis of Main Chain Torsion Angles in Proteins. Prediction of NMR Coupling Constants for Native and Denatured Conformations.’ (1996) J. Mol. Biol. 255, 494-506.
(12) K.M. Fiebig, H. Schwalbe, M. Buck, L.J. Smith & C.M. Dobson. ‘Towards a Description of the Conformations of Denatured States of Proteins. Comparison of a Random Coil Model with NMR Measurements.’ (1996) J. Phys. Chem. 100, 2661-2666.
(13) K.A. Bolin, M. Pitkeathly, A. Miranker, L.J. Smith & C.M. Dobson. ‘Insight into a Random Coil Conformation and an Isolated Helix: Structural and Dynamical Characterisation of the C-Helix Peptide from Hen Lysozyme.’ (1996) J. Mol. Biol. 261, 443-453.
(14) L.J. Smith & C.M. Dobson. ‘NMR and Protein Dynamics.’ (1996) Int. J. Quantum Chem. 59, 315-332.
(15) L.J. Smith, K.M. Fiebig, H. Schwalbe & C.M. Dobson. ‘The Concept of a Random Coil. Residual Structure in Peptides and Denatured Proteins.’ (1996) Folding and Design 1, R95-R106.
(16) J.J. Yang, B. van der Berg, M. Pitkeathly, L.J. Smith, K.A. Bolin, T.A. Keiderling, C. Redfield, C.M. Dobson & S.E. Radford. ‘Native-like Secondary Structure in a Peptide from the α-domain of Hen Lysozyme.’ (1996) Folding and Design 1, 473-484.
(17) L.J. Smith & C.M. Dobson. ‘Insight into Protein Dynamics by NMR Techniques.’ (1996) In Dynamics and the problem of recognition in biological macromolecules (ed. O. Jardetzky & J. F. Lefevre) Plenum, New York pp. 127-138.
(18) H. Schwalbe, K.M. Fiebig, M. Buck, J.A. Jones, S.B. Grimshaw, A. Spencer, S. Glaser, L.J. Smith & C.M. Dobson. ‘Structural and Dynamical Properties of a Denatured Protein. Heteronuclear 3D NMR Experiments and Theoretical Simulations of Lysozyme in 8M Urea.’ (1997) Biochemistry 36, 8977-8991.
(19) C.J. Penkett, C. Redfield, I. Dodd, J. Hubbard, D.L. McBay, D.E. Mossakowska, R.A.G. Smith, C.M. Dobson & L.J. Smith. ‘NMR Analysis of Main-chain Conformational Preferences in an Unfolded Fibronectin-Binding Protein.’ (1997) J. Mol. Biol. 274, 152-159.
(20) J.A. Jones, D.K. Wilkins, L.J. Smith & C.M. Dobson. ‘Characterisation of Protein Unfolding by NMR Diffusion Measurements.’ (1997) J. Biomol. NMR 10, 199-209.
(21) L.J. Smith, A.E. Mark, C.M. Dobson & W.F. van Gunsteren. ‘Molecular Dynamics Simulations of Peptide Fragments from Hen Lysozyme. Insight into Non-Native Protein Conformations.’ (1998) J. Mol. Biol. 280, 703-719.
(22) N.J. West & L.J. Smith. ‘Side chains in Native and Random Coil Protein Conformations. An Analysis of NMR Coupling Constants and χ1 Torsion Angle Preferences.’ (1998) J. Mol. Biol. 280, 867-877.
(23) C.J. Penkett, C. Redfield, J.A. Jones, J. Hubbard, R.A.G. Smith, L.J. Smith & C.M. Dobson. ‘Structural and Dynamical Characterisation of an Unfolded Fibronectin-binding Protein from Staphylococcus aureus.’ Biochemistry 37, 17054-17067 (1998).
(24) S.I. Mathieson, C.J. Penkett & L.J. Smith. ‘Characterisation of Side Chain Conformational Preferences in a Biologically Active but Unfolded Protein.’ Pacific Symposium on Biocomputing 4, 542-553 (1999).
(25) W.F. van Gunsteren, A.M.J.J. Bovin, X. Daura & L.J. Smith. ‘Aspects of Modelling Biomolecular Structure on the Basis of Spectroscopic or Diffraction Data.’ (1999) In Biological Magnetic Resonance, Volume 17: Structure Computation and Dynamics in Protein NMR (ed. N.R. Krishna & L.J. Berliner) Plenum , New York pp. 3-35.
(26) D. K. Wilkins, S. B. Grimshaw, V. Receveur, C. M. Dobson, J. A. Jones & L. J. Smith. 'Hydrodynamic Radii of Native and Denatured Proteins Measured using Pulse Field Gradient NMR Techniques.' Biochemistry 38, 16424-16431 (1999).
(27) L.J. Smith, C.M. Dobson & W.F. van Gunsteren. ‘Side Chain Conformational Disorder in a Molten Globule: Molecular Dynamics Simulations of Human α-lactalbumin.’ J. Mol. Biol. 286, 1567-1580 (1999).
(28) L.J. Smith, C.M. Dobson & W.F. van Gunsteren. ‘Molecular Dynamics Simulations of Human α-lactalbumin. Changes to the Structural and Dynamical Properties of the Protein at Low pH.’ Proteins: Structure, Function and Genetics 36, 77-86 (1999).
(29) M. Hennig, W. Bermel, C.M. Dobson, L.J. Smith & H. Schwalbe. ‘Side-chain Conformations in an Unfolded Protein: Distributions in Denatured Hen Lysozyme Determined by Heteronuclear 13C,15N NMR Spectroscopy.’ J. Mol. Biol. 288, 705-723 (1999).
(30) C.J. Penkett, C.M. Dobson, L.J. Smith, J.R. Bright, A.R. Pickford, I.D. Campbell & J.R. Potts. 'Identification of Residues Involved in the Interaction of Staphylococcus aureus Fibronectin Binding Protein with the 4F15F1 Module Pair of Human Fibronectin Using Heteronuclear NMR Spectroscopy.' Biochemistry 39, 2887-2893 (2000).
(31) C.J. Morgan, D.K. Wilkins, L.J. Smith, Y. Kawata & C.M. Dobson. 'A Compact Monomeric Intermediate Identified by NMR in the Denaturation of Dimeric Triose Phosphate Isomerase.' J. Mol. Biol. 300, 11-16 (2000).
(32) A.R. Dinner, A. Sali, L.J. Smith, C.M. Dobson & M. Karplus. ‘Understanding Protein Folding via Free-Energy Surfaces From Theory and Experiment.’ Trends in Biochem. Sci. 25, 331-339 (2000).
(33) T.A. Pertinhez, D. Hamada, L J. Smith, F. Chiti, N. Taddei, M. Stefani & C.M. Dobson. ‘Initial Denaturing Conditions Influence the Slow folding Phase of Acylphosphatase associated with Proline Isomerization.’ Protein Science 9, 1466-1473 (2000).
(34) W. Peti, M. Hennig, L.J. Smith & H. Schwalbe. ‘NMR Spectroscopic Investigation of ψ Torsion angle Distributions in Unfolded Ubiquitin from Analysis of 3J(Cα,Cα) Coupling constants and Cross Correlated ΓHN,N,Cα,Hα Relaxation Rates.’ J. Am. Chem. Soc. 122, 12017-12018 (2000).
(35) W. Peti, L.J. Smith, C. Redfield & H. Schwalbe 'Chemical Shifts in Denatured Proteins: Resonance Assignments for Denatured Ubiquitin and Comparisons with other Denatured Proteins.' J. Biomol. NMR 19, 153-165 (2001).
(36) E. Paci, L.J. Smith, C.M. Dobson & M. Karplus 'Exploration of Partially Unfolded States of Human α-lactalbumin by Molecular Dynamics Simulation.' J. Mol. Biol. 306, 329-347 (2001).
(37) H. Schwalbe, S.B. Grimshaw, M. Buck, A. Spencer, J. Boyd, C.M. Dobson, C, Redfield, & L.J. Smith 'A Refined Solution Structure of Hen Lysozyme determined using Residual Dipolar Coupling Data.' Protein Science 10, 677-688 (2001).
(38) Y.O. Kamatari, H. Yamada, K. Akasaka, J.A. Jones, C.M. Dobson & L.J. Smith. 'Pressure Response of Native and Denatured Hen Lysozyme studied by 15N/1H NMR Spectroscopy.' Eur. J. Biochem. 268,1782-1793 (2001).
(39) T. A. Pertinhez , M. L. Bouchard, E. J. Tomlinson, R. Wain, S. J. Ferguson , C. M. Dobson & L. J. Smith. ‘Amyloid Fibril Formation by a Helical Cytochrome.’ FEBS Lett. 495, 184-186 (2001).
(40) R. Wain, T. A. Pertinhez, E. J. Tomlinson, L. Hong, C. M. Dobson, S. J. Ferguson & L. J. Smith ‘The Cytochrome c Fold can be attained from a Compact Apo State by occupancy of a Nascent Heme Binding Site.’ J. Biol. Chem. 276, 45813-45817 (2001).
(41) H. Schäfer, L.J. Smith, A.E. Mark & W.F. van Gunsteren. ‘Entropy Calculations of the Molten Globule State of a Protein: Side-chain Entropies of α-lactalbumin.’ Proteins: Structure, Function and Genetics 46, 215-224 (2002).
(42) J. Klein-Seetharaman, M. Oikawa, S. B. Grimshaw, J. Wirmer, E. Duchardt, T. Ueda, T. Imoto L. J.Smith, C. M. Dobson & H. Schwalbe. ‘Long-range Interactions within a Nonnative Protein.’ Science 295, 1719-1722 (2002).
(43) L.J. Smith, X. Daura & W.F. van Gunsteren. ‘Assessing Equilibration and Convergence in Biomolecular Simulations.’ Proteins: Structure, Function and Genetics 48, 487-496 (2002).
(44) T.A. Pertinhez, M. Bouchard, R.A.G. Smith, C.M. Dobson & L.J. Smith ‘Stimulation and Inhibition of Fibril Formation by a Peptide in the Presence of Different Concentrations of SDS.’ FEBS letters 529, 193-197 (2002).
(45) T.A, Pertinhez, A.K. Sherwood, L.F. Fraceto, M. Bouchard, M. Pitkeathly and L.J. Smith ‘α and β Conformational Preferences in Fibril Forming Peptides Characterised using NMR and CD Techniques.’ Spectroscopy - Int. J. 18, 1-11 (2004).
(46) L.J. Smith, H.J.C. Berendsen and W.F. van Gunsteren ‘Computer Simulation of Urea-Water Mixtures: A Test of Force Field Parameters for Use in Biomolecular Simulation.’ J. Phys. Chem. B 108, 1065-1071 (2004).
(47) R. Wain, C. Redfield, S.J. Ferguson and L.J. Smith ‘NMR Analysis shows that a b-Type Variant of Hydrogenobacter thermophilus Cytochrome c552 retains its Native Structure.’ J. Biol. Chem. 279, 15177-15182 (2004).
(48) L.J. Smith ‘Computational Methods for Generating Models of Denatured and Partially Folded Proteins’ Methods 34, 144-150 (2004).
(50) T.A. Soares, X. Daura, C. Oostenbrink, L.J. Smith, W.F. van Gunsteren ‘Validation of the GROMOS Force-Field Parameter Set 45A3 against Nuclear Magnetic Resonance data of Hen Egg Lysozyme.’ J. Biomol. NMR 30, 407-422 (2004).
(51) L.J. Smith, R.M. Jones and W.F. van Gunsteren ‘Characterization of the Denaturation of Human α-lactalbumin in Urea by Molecular Dynamics Simulations.’ Proteins: Structure, Function and Bioinformatics 58, 439-449 (2005).
(52) R. Wain, L.J. Smith and C.M. Dobson ‘Oxidative refolding of amyloidogenic variants of human lysozyme.’ J. Mol. Biol. 351, 662-671 (2005).
(53) I.J. Day, R. Wain, K. Tozawa, L.J. Smith and P.J. Hore ‘Photo-CIDNP NMR spectroscopy of a heme-containing protein.’ J. Magn. Reson. 175, 330-335 (2005).
(54) E. Paci, L.H. Greene, R.M. Jones and L.J. Smith ‘Characterization of the molten globule state of retinol-binding protein using a molecular dynamics simulation approach.’ FEBS J. 272, 4826-4838 (2005).
(55) L.J. Smith, R.J. Davies and W.F. van Gunsteren ‘Molecular dynamics simulations of Hydrogenobacter thermophilus cytochrome c552: Comparisons of the wild-type protein, a b-type variant, and the apo state.’ Proteins: Structure, Function and Bioinformatics 65, 702-711 (2006).
(56) R. Wijesinha-Bettoni, C. Gao, J.A. Jenkins, A. Mackie, P.J. Wilde, E.N.C. Mills and L.J. Smith ‘Heat treatment of bovine α-lactalbumin results in partially-folded, disulfide bond shuffled states with enhanced surface activity’. Biochemistry, 46, 9774-9784 (2007).
(57) R. Wijesinha-Bettoni, C. Gao, J.A. Jenkins, A. Mackie, P.J. Wilde, E.N.C. Mills and L.J. Smith ‘Post-translational modification of barley LTP1b: the lipid adduct lies in the hydrophobic cavity and alters the protein dynamics’. FEBS Letters, 581, 4557-4561 (2007).
(58) C. Gao, R. Wijesinha-Bettoni, P.J. Wilde, E.N.C. Mills, L.J. Smith and A.R.Mackie. ‘Surface properties are highly sensitive to small pH induced changes in the 3-D structure of α-lactalbumin’ Biochemistry, 47, 1659-1666 (2008).
(59) N. Schmid, C. Bolliger, L.J. Smith and W.F. van Gunsteren ‘Disulfide Bond Shuffling in Bovine alpha-Lactalbumin: MD Simulation Confirms Experiment’ Biochemistry, 47, 12104-12107 (2008).
(60) V. A. Higman, H. I. Rösner, R. Ugolini, L. H. Greene, C. Redfield and L. J. Smith ‘Probing the urea dependence of residual structure in denatured human α-lactalbumin’ J. Biomol. NMR 45, 121-131 (2009).
(61) E. N. C. Mills, C. Gao, P. J. Wilde, N. M. Rigby, R. Wijesinha-Bettoni, V. E. Johnson, L. J. Smith and A. R. Mackie ‘Partially folded forms of barley lipid transfer protein are more surface active.’ Biochemistry 48, 12081-12088 (2009).
(62) T. A. Pertinhez, E. Ferrari, E. Casali, J. A. Patel, A. Spisni and L. J. Smith ‘The binding cavity of mouse major urinary protein is optimised for a variety of ligand binding modes.’ Biochem. Biophys. Res. Comm. 390, 1266-1271 (2009).
(63) R. Wijesinha-Bettoni, Y. Alexeev, P. Johnson, J. Marsh, A. I. Sancho, S. U. Abdullah, A. R. Mackie, P. R. Shewry, L. J. Smith and E. N. C. Mills ‘The structural characteristics of non-specific lipid transfer protein explain their resistance to gastroduodenal proteolysis.’ Biochemistry 49, 2130-2139 (2010).
(65) E, Abraham, C. W. Bailey, T. D. W. Claridge, S. G. Davies, K. B. Ling, B. Odell, T. L. Rees, P. M. Roberts, A. J. Russell, A. D. Smith, L. J. Smith, H. R. Storr, M. J. Sweet, A. L. Thompson, J. E. Thomson, G. E. Tranter and D. J. Watkins. ‘A systematic study of the solid state and solution phase conformational preferences of beta-peptides derived from transpentacin.’ Tetrahedron – Asymmetry 21, 1797-1815 (2010).
(66) V. A. Higman, J. Boyd, L. J. Smith and C. Redfield. ‘Residual dipolar couplings: are multiple independent alignments always possible?’ J. Biomol. NMR 49, 53-60 (2011).
(67) Y. O. Kamatari, L. J. Smith, C. M. Dobson and K. Akasaka ‘Cavity hydration as a gateway to unfolding: An NMR study of hen lysozyme at high pressure and low temperature.’ Biophys. Chem. 156, 24-30 (2011).
(68) E. Abraham, T. D. W. Claridge, S. G. Davies, B. Odell, P. M. Roberts, A. J. Russell, A. D. Smith, L. J. Smith, H. R. Storr, M. J. Sweet, A. L. Thompson, J. E. Thomson, G. E. Tranter and D. J. Watkin. ‘A systematic study of the solid state and solution phase conformational preferences of beta-peptides derived from C(3)-alkyl substituted transpentacin derivatives.’ Tetrahedron – Asymmetry 22, 69-100 (2011).
(69) A. P. Eichenberger, L. J. Smith and W. F. van Gunsteren. ‘Ester-linked hen egg white lysozyme shows a compact fold in a molecular dynamics simulation - possible causes and sensitivity of experimentally observable quantities to structural changes maintaining this compact fold.’ FEBS J. 279, 299-315 (2012).
(70) Z. Hall, A. Politis, M. F. Bush, L. J. Smith and C. V. Robinson. ‘Charge-State Dependent Compaction and Dissociation of Protein Complexes: Insights from Ion Mobility and Molecular Dynamics.’ J. Amer. Chem. Soc. 134, 3429-3438 (2012).
(71) S. Lewney and L. J. Smith. ‘Characterization of an alternative low energy fold for bovine a-lactalbumin formed by disulfide bond shuffling.’ Proteins: Structure, Function and Bioinformatics 80, 913-919 (2012).
(72) J. R. Allison, S. Hertig, J. H. Missimer, L. J. Smith, M. O. Steinmetz and J. Dolenc. Probing the Structure and Dynamics of Proteins by Combining Molecular Dynamics Simulations and Experimental NMR Data.’ J. Chem. Theory and Computation 8, 3430-3444 (2012).
(73) L. J. Smith, W. F. van Gunsteren and J. R. Allison. ‘Multiple binding modes for palmitate to barley lipid transfer protein facilitated by the presence of proline 12.’ Protein Sci. 22, 56-64 (2013).
(74) A. P. Eichenberger, W. F. van Gunsteren and L. J. Smith. ‘Structure of hen egg-white lysozyme solvated in TFE/water: a molecular dynamics simulation study based on NMR data.’ J. Biomol. NMR 55, 339-353 (2013).
(75) L. J. Smith, A. M. Bowen, A. Di Paolo, A. Matagne and C. Redfield ‘The Dynamics of Lysozyme from Bacteriophage Lambda in Solution Probed by NMR and MD Simulations.’ ChemBioChem. 14, 1780-1788 (2013).
(76) L.J. Smith, W. F. van Gunsteren and N. Hansen ‘Characterisation of the flexible lip regions in bacteriophage lambda lysozyme using MD simulations.’ Eur. Biophysics J. 44, 235-247 (2015).
(77) K. Tozawa, S. J. Ferguson, C. Redfield and L. J. Smith ‘Comparison of the backbone dynamics of wild-type Hydrogenobacter thermophilus cytochrome c552 and its b-type variant.’ J. Biomol. NMR 62, 221-231 (2015).
(78) Y. F. Zhao, G.B. Chen, T. Bian, C. Zhou, G. I. N. Waterhouse, L. Z. Wu, C. H. Tung, L. J. Smith, D. O’Hare and T. R. Zhang ‘Defect-rich ultrathin ZnAl-layered double hydroxide nanosheets for efficient photoreduction of CO2 to CO with water.’ Ad. Materials 27, 7824-7831 (2015).
(79) L.J.Smith, G.Rought Whitta, J.Dolenc, D.Q.Wang, W.F. van Gunsteren 'A molecular dynamics simulation investigation of the relative stability of the cyclic peptide octreotide and its deprotonated and its (CF3)-Trp substituted analogs in different solvents' Bioorganic and Medicinal Chemistry 24, 4936-4948 (2016).
(80) W. F. van Gunsteren, J. R. Allison, X. Daura, J. Dolenc, N. Hansen, A. E. Mark, C. Oostenbrink, V. H. Rusu, and L. J. Smith ‘Deriving structural information from experimentally measured data on biomolecules.’ Angewandte Chemie – Int. Ed. 55, 15990-16010 (2016).
(81) L.J. Smith, W. F. van Gunsteren and N. Hansen ‘On the use of time-averaging restraints when deriving biomolecular structure from 3J-coupling values obtained from NMR experiments’ J. Biomol NMR 66, 69-83 (2016).
(82) L. J. Smith, R. Athill, W. F. van Gunsteren and N. Hansen ‘Interpretation of Seemingly Contradictory Data: Low NMR S2 Order Parameters Observed in Helices and High NMR S2 Order Parameters in Disordered Loops of the Protein hGH at Low pH’ Chem. Eur. J. 23, 9585-9591 (2017).
(83) L.J. Smith, W. F. van Gunsteren and N. Hansen ‘Using Complementary NMR Data Sets To Detect Inconsistencies and Model Flaws in the Structure Determination of Human Interleukin-4’ J. Phys. Chem. B 121, 7055-7063 (2017).

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