• Vibrational spectroscopic study of salbutamol hemisulphate

      Ali, H.R.H.; Edwards, Howell G.M.; Kendrick, John; Scowen, Ian J. (Elsevier, 01/01/2009)
      Salbutamol hemisulphate is a relatively selective ß2-adrenergic agonist and is used as a bronchodilator. In this work, we present a detailed vibrational spectroscopic investigation of salbutamol hemisulphate using mid-infrared and near-infrared Fourier-transform (NIR-FT) Raman spectroscopies. These data are supported by quantum chemical calculations, which allow us to characterise the vibrational spectra of this compound reasonably. As such, this study could be viable for examining the way in which this drug interacts with its target molecules.
    • Significant progress in predicting the crystal structures of small organic molecules ¿ a report on the fourth blind test.

      Day, G.M.; Cooper, T.G.; Cruz-Cabeza, A.; Hejczyk, K.E.; Ammon, H.L.; Boerrigter, S.X.M.; Tan, J.S.; Della Valle, R.G.; Venuti, E.; Jose, J.; Gadre, S.R.; Desiraju, G.R.; Thakur, T.S.; van Eijck, B.P.; Facelli, J.C.; Bazterra, V.E.; Ferraro, M.B.; Hofmann, D.W.M.; Neumann, M.A.; Leusen, Frank J.J.; Kendrick, John; Price, S.L.; Misquitta, A.J.; Karamertzanis, P.G.; Welch, G.W.A.; Scheraga, H.A.; Arnautova, Y.A.; Schmidt, M.U.; van de Streek, J.; Wolf, A.K.; Schweizer, B. (International Union of Crystallography, 01/04/2009)
      We report on the organization and outcome of the fourth blind test of crystal structure prediction, an international collaborative project organized to evaluate the present state in computational methods of predicting the crystal structures of small organic molecules. There were 14 research groups which took part, using a variety of methods to generate and rank the most likely crystal structures for four target systems: three single-component crystal structures and a 1:1 cocrystal. Participants were challenged to predict the crystal structures of the four systems, given only their molecular diagrams, while the recently determined but as-yet unpublished crystal structures were withheld by an independent referee. Three predictions were allowed for each system. The results demonstrate a dramatic improvement in rates of success over previous blind tests; in total, there were 13 successful predictions and, for each of the four targets, at least two groups correctly predicted the observed crystal structure. The successes include one participating group who correctly predicted all four crystal structures as their first ranked choice, albeit at a considerable computational expense. The results reflect important improvements in modelling methods and suggest that, at least for the small and fairly rigid types of molecules included in this blind test, such calculations can be constructively applied to help understand crystallization and polymorphism of organic molecules.
    • Vibrational spectroscopic study of terbutaline hemisulphate

      Ali, H.R.H.; Edwards, Howell G.M.; Kendrick, John; Scowen, Ian J. (01/05/2009)
      The Raman spectrum of terbutaline hemisulphate is reported for the first time, and molecular assignments are proposed on the basis of ab initio BLYP DFT calculations with a 6-31G* basis set and vibrational frequencies predicted within the quasi-harmonic approximation; these predictions compare favourably with the observed vibrational spectra. Comparison with previously published infrared data explains several spectral features. The results from this study provide data that can be used for the preparative process monitoring of terbutaline hemisulphate, an important ß2 agonist drug in various dosage forms and its interaction with excipients and other components.
    • An evaluation of the Amblyopia and Strabismus Questionnaire using Rasch analysis

      Vianya-Estopa, Marta; Elliott, David B.; Barrett, Brendan T. (Association for Research in Vision and Ophthalmology, 01/05/2010)
      PURPOSE. To evaluate whether the Amblyopia and Strabismus Questionnaire (A&SQ) is a suitable instrument for the assessment of vision-related quality-of life (VR-QoL) in individuals with strabismus and/or amblyopia. METHODS. The A&SQ was completed by 102 individuals, all of whom had amblyopia, strabismus, or both. Rasch analysis was used to evaluate the usefulness of individual questionnaire items (i.e., questions); the response-scale performance; how well the items targeted VR-QoL; whether individual items showed response bias, depending on factors such as whether strabismus was present; and dimensionality. RESULTS. Items relating to concerns about the appearance of the eyes were applicable only to those with strabismus, and many items showed large ceiling effects. The response scale showed disordered responses and underused response options, which improved after the number of response options was reduced from five to three. This change improved the discriminative ability of the questionnaire (person separation index increased from 1.98 to 2.11). Significant bias was found between strabismic and nonstrabismic respondents. Separate Rasch analyses conducted for subjects with and without strabismus indicated that all A&SQ items seemed appropriate for individuals with strabismus (Rasch infit values between 0.60 and 1.40), but several items fitted the model poorly in amblyopes without strabismus. The AS&Q was not found to be unidimensional. CONCLUSIONS. The findings highlight the limitations of the A&SQ instrument in the assessment of VR-QoL in subjects with strabismus and especially in those with amblyopia alone. The results suggest that separate instruments are needed to quantify VR-QoL in amblyopes with and without strabismus.
    • Revisiting the Blind Tests in Crystal Structure Prediction: Accurate Energy Ranking of Molecular Crystals.

      Asmadi, Aldi; Neumann, M.A.; Kendrick, John; Girard, P.; Perrin, M-A.; Leusen, Frank J.J. (American Chemical Society, 01/12/2009)
      In the 2007 blind test of crystal structure prediction hosted by the Cambridge Crystallographic Data Centre (CCDC), a hybrid DFT/MM method correctly ranked each of the four experimental structures as having the lowest lattice energy of all the crystal structures predicted for each molecule. The work presented here further validates this hybrid method by optimizing the crystal structures (experimental and submitted) of the first three CCDC blind tests held in 1999, 2001, and 2004. Except for the crystal structures of compound IX, all structures were reminimized and ranked according to their lattice energies. The hybrid method computes the lattice energy of a crystal structure as the sum of the DFT total energy and a van der Waals (dispersion) energy correction. Considering all four blind tests, the crystal structure with the lowest lattice energy corresponds to the experimentally observed structure for 12 out of 14 molecules. Moreover, good geometrical agreement is observed between the structures determined by the hybrid method and those measured experimentally. In comparison with the correct submissions made by the blind test participants, all hybrid optimized crystal structures (apart from compound II) have the smallest calculated root mean squared deviations from the experimentally observed structures. It is predicted that a new polymorph of compound V exists under pressure.
    • Induced deficits in speed perception by transcranial magnetic stimulation of human cortical areas V5/MT+ and V3A

      McKeefry, Declan J.; Burton, Mark P.; Vakrou, Chara; Barrett, Brendan T.; Morland, A.B. (Society for Neuroscience, 02/07/2008)
      In this report, we evaluate the role of visual areas responsive to motion in the human brain in the perception of stimulus speed. We first identified and localized V1, V3A, and V5/MT+ in individual participants on the basis of blood oxygenation level-dependent responses obtained in retinotopic mapping experiments and responses to moving gratings. Repetitive transcranial magnetic stimulation (rTMS) was then used to disrupt the normal functioning of the previously localized visual areas in each participant. During the rTMS application, participants were required to perform delayed discrimination of the speed of drifting or spatial frequency of static gratings. The application of rTMS to areas V5/MT and V3A induced a subjective slowing of visual stimuli and ( often) caused increases in speed discrimination thresholds. Deficits in spatial frequency discrimination were not observed for applications of rTMS to V3A or V5/MT+. The induced deficits in speed perception were also specific to the cortical site of TMS delivery. The application of TMS to regions of the cortex adjacent to V5/MT and V3A, as well as to area V1, produced no deficits in speed perception. These results suggest that, in addition to area V5/MT+, V3A plays an important role in a cortical network that underpins the perception of stimulus speed in the human brain.
    • A Hydrocortisone Nanoparticle Dosage Form.

      Zghebi, Salwa S.; de Matas, Marcel; Denyer, Morgan C.T.; Blagden, Nicholas (09/03/2011)
      Of particular importance in recent years has been the development of techniques for producing nanoparticles (NPs) of poorly-water soluble drugs with dimensions less than 1000 nm for which their high surface area can lead to improvements in bioavailability. Furthermore, the small size of these particles can also enable cellular uptake, particularly for positively charged systems. Therefore, an overall objective of this part of the project was to produce nanoparticles with different levels of positive surface charge using the bottom-up method.
    • An optimized force field for crystalline phases of resorcinol.

      Chatchawalsaisin, Jittima; Kendrick, John; Tuble, S.C.; Anwar, Jamshed (Royal Society of Chemistry, 10/03/2008)
      The two known crystalline phases of resorcinol and their phase transitions are of considerable interest. The crystals exhibit pyro- and piezo-electricity and, remarkably, the higher temperature phase is the denser phase. Furthermore, crystals of the phase, by virtue of having a polar axis, have played a crucial role in investigating fundamental issues of crystal growth. We report an optimized force field for the molecular simulation of crystalline phases of resorcinol. The hydroxyl groups of the resorcinol molecule have a torsional degree of freedom and the molecule adopts a different conformation in each of the two phases of resorcinol. The torsional barrier, therefore, was considered to be critical and has been characterized using ab initio methods. Although the atomic partial charges showed some dependence on the molecular conformation, a single set of partial charges was found to be sufficient in describing the electrostatic potential for all conformations. The parameters for the van der Waals interactions were optimized using sensitivity analysis. The proposed force field reproduces not only the static structures but also the stability of the crystalline phases in extended molecular dynamics simulations.
    • Olive oil or lard? Distinguishing plant oils from animal fats in the archaeological record of the eastern Mediterranean using gas chromatography/combustion/isotope ratio mass spectrometry.

      Steele, Valerie J.; Stern, Ben; Stott, A.W. (15/12/2010)
      Distinguishing animal fats from plant oils in archaeological residues is not straightforward. Characteristic plant sterols, such as ¿-sitosterol, are often missing in archaeological samples and specific biomarkers do not exist for most plant fats. Identification is usually based on a range of characteristics such as fatty acid ratios, all of which indicate that a plant oil may be present, none of which uniquely distinguish plant oils from other fats. Degradation and dissolution during burial alter fatty acid ratios and remove short chain fatty acids, resulting in degraded plant oils with similar fatty acid profiles to other degraded fats. Compound specific stable isotope analysis of ¿13C18:0 and ¿13C16:0, carried out by gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS), has provided a means of distinguishing fish oils, dairy fats, ruminant and non-ruminant adipose fats but plant oils are rarely included in these analyses. For modern plant oils where C18:1 is abundant, ¿13C18:1 and ¿13C16:0 are usually measured. These results cannot be compared with archaeological data or other modern reference fats where ¿13C18:0 and ¿13C16:0 are measured, as C18:0 and C18:1 are formed by different processes resulting in different isotopic values. Eight samples of six modern plant oils were saponified releasing sufficient C18:0 to measure the isotopic values, which were plotted against ¿13C16:0. The isotopic values for these oils, with one exception, formed a tight cluster between ruminant and non-ruminant animal fats. This result complicates the interpretation of mixed fatty residues in geographical areas where both animal fats and plant oils were in use.
    • The Canny edge detector revisited

      McIlhagga, William H. (16/10/2010)
      Canny (IEEE Trans. Pattern Anal. Image Proc. 8(6):679-698, 1986) suggested that an optimal edge detector should maximize both signal-to-noise ratio and localization, and he derived mathematical expressions for these criteria. Based on these criteria, he claimed that the optimal step edge detector was similar to a derivative of a gaussian. However, Canny's work suffers from two problems. First, his derivation of localization criterion is incorrect. Here we provide a more accurate localization criterion and derive the optimal detector from it. Second, and more seriously, the Canny criteria yield an infinitely wide optimal edge detector. The width of the optimal detector can however be limited by considering the effect of the neighbouring edges in the image. If we do so, we find that the optimal step edge detector, according to the Canny criteria, is the derivative of an ISEF filter, proposed by Shen and Castan (Graph. Models Image Proc. 54:112-133, 1992). In addition, if we also consider detecting blurred (or non-sharp) gaussian edges of different widths, we find that the optimal blurred-edge detector is the above optimal step edge detector convolved with a gaussian. This implies that edge detection must be performed at multiple scales to cover all the blur widths in the image. We derive a simple scale selection procedure for edge detection, and demonstrate it in one and two dimensions.
    • Guaianolide sesquiterpenes from Pulicaria crispa (Forssk.) Oliv.

      Stavri, M.; Matthew, K.T.; Gordon, Andrew; Shnyder, Steven D.; Falconer, Robert A.; Gibbons, S. (17/03/2008)
      A phytochemical study of the asteraceous herb Pulicaria crispa (Forssk.) Oliv. resulted in the characterisation of three guaianolide sesquiterpenes, 2¿,4¿-dihydroxy-7¿H,8¿H,10¿H-guaia-1(5),11(13)-dien-8ß,12-olide (1), 1¿,2¿-epoxy-4ß-hydroxy-5¿H,7¿H,8¿H,10¿H-guaia-11(13)-en-8ß,12-olide (2) and 5,10-epi-2,3-dihydroaromatin (3). The structures were assigned on the basis of extensive 1 and 2D NMR experiments. Compound 3 exhibited weak antimycobacterial activity against Mycobacterium phlei with a minimum inhibitory concentration of 0.52 mM and cytotoxicity (IC50 of 5.8 ± 0.2 ¿M) in a human bladder carcinoma cell line, EJ-138.
    • Genetics of type 5 M protein of Streptococcus pyogenes

      Kehoe, M.A.; Miller, L.; Poirier, T.P.; Beachey, E.H.; Lee, M.; Harrington, Dean J. (1987)
    • The management of vegetation change on Ilkley Moor

      Hale, William H.G.; Cotton, David E. (1988)
    • Vegetation Changes on Ilkley Moor 1964-1984

      Cotton, David E.; Hale, William H.G. (1989)
      In 1970 a set of maps was published which summarized the results of an extensive survey of the vegetation of Ilkley Moor. This paper presents new maps showing the distribution of selected vegetation communities based on a detailed survey undertaken in 1983-84, and examines the changes which have occurred in the period 1964--1984. Comparison of the maps reveals that Calluna vulgaris and Pteridium aquilinum have increased their occupancy of the moor, whilst there has been a marked reduction in the abundance of Empetrum nigrum and Eriophorum spp. These changes indicate that the degradation of the moor which was recorded during the 1960s was reversed, at least partially, between 1964 and 1984.
    • The mutagenic activity of ethylmethanesulphonate, benzidine and benzo[a]pyrene at the hprt locus of wild-type L5178Y mouse lymphoma cells

      Kennelly, J.C.; Clare, C.B.; Campbell, J.; Lane, M.P.; Harrington, Dean J.; Cole, H.; Garner, R.C. (1990)
      Ethylmethanesulphonate (EMS), benzidine (BZD) and benzo[a]pyrene (B[a]P) were assayed for ability to induce mutation at the hprt locus of wild-type L5178Y mouse lymphoma cells. EMS was assayed in the absence of metabolic activation, B[a]P in the presence of metabolic activation (S-9 mix) and BZD both in the absence and presence of S-9. Treatment with EMS minus S-9 and B[a]P plus S-9, especially when the S-9 content of the incubation was 2% (v/v), produced strong dose-related increases in mutant frequency. BZD failed to induce mutation at the hprt locus, either in the absence or presence of S-9.
    • Vegetation Changes on Ilkley Moor between 1964 and 1984, and Possible Environmental Causes

      Hale, William H.G.; Cotton, David E. (1993)
      In recent years there has been concern about the decrease in the quality and quantity of Britain's heaths and moorlands. This concern has prompted attempts to monitor change in moorland vegetation, and programmes of action designed to halt the decline, both nationally and locally (Bunce, 1989; Hudson & Newborn, 1989a). In northern England the decline has been brought about partly by a reduction in the areal extent of the moors but mainly by changes in their species composition, with Calluna vulgaris (L.) Hull (heather) declining and grasses, Empetrum nigrum L. (crowberry) and other species increasing. These changes have been attributed to changed management practices, such as less effective burning regimes and increased sheep grazing (Bunce, 1989). However, there are few detailed quantitative studies of long-term vegetation change. This paper draws upon historical records to determine the nature and extent of change in the vegetation of Ilkley Moor over a twenty-year interval.
    • Multiple changes in cell wall antigens of isogenic mutants of Streptococcus mutans

      Harrington, Dean J.; Russell, R.R.B. (1993-09)
      Isogenic mutants of Streptococcus mutans LT11, deficient in the production of the wall-associated protein antigens A and B, were generated by recombinant DNA technology. The hydrophobicity, adherence, and aggregation of the mutants were compared with those of the parent strain. These studies indicated that hydrophobicity, adherence, and saliva- or sucrose-induced aggregation were unaltered in the A- mutant but that hydrophobicity and adherence to saliva-coated hydroxylapatite were greatly reduced in the B- mutant whilst sucrose-dependent adherence and aggregation were increased. To determine whether these changes correlated with changes in the mutated gene product alone, the levels of a number of cell wall antigens were determined in each of the mutants. The loss of antigen A resulted in significantly reduced levels of wall-associated lipoteichoic acid, and loss of antigen B resulted in reductions in both antigen A and lipoteichoic acid. Data presented here thus suggest that changes in the expression of one wall antigen can have a dramatic effect on the levels of others.