Synthesis, Kinetic Evaluation and Utilization of a Biotinylated Dipeptide Proline Diphenyl Phosphonate for the Disclosure of Dipeptidyl Peptidase IV-like Serine Proteases

In this study, we report on the synthesis, kinetic characterisation, and application of a novel biotinylated and active site-directed inactivator of dipeptidyl peptidase IV (DPP-IV). Thus, the dipeptide-derived proline diphenyl phosphonate NH(2)-Glu(biotinyl-PEG)-Pro(P)(OPh)(2) has been prepared by a combination of classical solution- and solid-phase methodologies and has been shown to be an irreversible inhibitor of porcine DPP-IV, exhibiting an over all second-order rate constant (k(i)/K(i)) for inhibition of 1.57 x 10(3) M(-1) min(-1). This value compares favourably with previously reported rates of inactivation of DPP-IV by dipeptides containing a P(1) proline diphenyl phosphonate grouping [B. Boduszek, J. Oleksyszyn, C.M. Kam, J. Selzler, R.E. Smith, J.C. Powers, Dipeptide phophonates as inhibitors of dipeptidyl peptidase IV, J. Med. Chem. 37 (1994) 3969-3976; B.F. Gilmore, J.F. Lynas, C.J. Scott, C. McGoohan, L. Martin, B. Walker, Dipeptide proline diphenyl phosphonates are potent, irreversible inhibitors of seprase (FAPalpha), Biochem, Biophys. Res. Commun. 346 (2006) 436-446.], thus demonstrating that the incorporation of the side-chain modified (N-biotinyl-3-(2-(2-(3-aminopropyloxy)-ethoxy)-ethoxy)-propyl) glutamic acid residue at the P(2) position is compatible with inhibitor efficacy. The utilisation of this probe for the detection of both purified dipeptidyl peptidase IV and the disclosure of a dipeptidyl peptidase IV-like activity from a clinical isolate of Porphyromonas gingivalis, using established electrophoretic and Western blotting techniques previously developed by our group, is also demonstrated.

Making 'party identification' more versatile: operationalising the concept for the multiparty setting

The conventional operationalisation of the concept of party identification is not appropriate for the multiparty setting. I offer new measures that facilitate multiple, and negative as well as positive, identities. Using survey evidence from Northern Ireland, these new measures are validated in a number of ways and their role in a comprehensive model of voting is illustrated.

A non-LTE analysis of the spectra of two narrow lined main sequence stars in the SMC

An analysis of high-resolution VLT/UVES spectra of two B-type main sequence stars, NGC 346-11 and AV 304, in the Small Magellanic Cloud (SMC), has been undertaken, using the non-LTE tlusty model atmospheres to derive the stellar parameters and chemical compositions of each star. The chemical compositions of the two stars are in reasonable agreement. Moreover, our stellar analysis agrees well with earlier analyses of H II regions. The results derived here should be representative of the current base-line chemical composition of the SMC interstellar medium as derived from B-type stars.

A search for star formation around the Galactic halo B-type star PHL 346 with the 2dF spectrograph

A preliminary search for stars that may have formed coevally with the apparently young halo B-type star PHL 346 has been performed with the 2dF multifibre spectrograph on the Anglo- Australian Telescope (AAT). Candidates were selected for spectroscopy from APM scans of B and R Schmidt plates centred on PHL 346. A total of 476 stars of spectral type A or F were found; radial velocity estimates and more accurate spectral type assignments narrowed the number of possible coeval candidates to 6 A-type and 14 F-type stars. A statistical analysis of these results using a comparison with a control field suggests that the number of A-type or F-type candidate stars around PHL 346 is not unexpected, and that they need not be associated with PHL 346. A number of ways to improve the project are suggested.

Idealised operation of zero-voltage-switching series-L/parallel-tuned Class-E power amplifier

An analysis of a modified series-L/parallel-tuned Class-E power amplifier is presented, which includes the effects that a shunt capacitance placed across the switching device will have on Class-E behaviour. In the original series L/parallel-tuned topology in which the output transistor capacitance is not inherently included in the circuit, zero-current switching (ZCS) and zero-current derivative switching (ZCDS) conditions should be applied to obtain optimum Class-E operation. On the other hand, when the output transistor capacitance is incorporated in the circuit, i.e. in the modified series-L/parallel-tuned topology, the ZCS and ZCDS would not give optimum operation and therefore zero-voltage-switching (ZVS) and zero-voltage-derivative switching (ZVDS) conditions should be applied instead. In the modified series-L/parallel-tuned Class-E configuration, the output-device inductance and the output-device output capacitance, both of which can significantly affect the amplifier's performance at microwave frequencies, furnish part, if not all, of the series inductance L and the shunt capacitance COUT, respectively. Further, when compared with the classic shunt-C/series-tuned topology, the proposed Class-E configuration offers some advantages in terms of 44% higher maximum operating frequency (fMAX) and 4% higher power-output capability (PMAX). As in the classic topology, the fMAX of the proposed amplifier circuit is reached when the output-device output capacitance furnishes all of the capacitance COUT, for a given combination of frequency, output power and DC supply voltage. It is also shown that numerical simulations agree well with theoretical predictions.

Transition region velocity oscillations observed by EUNIS-06

Spectroscopic measurements of NOAA AR 10871, obtained with the Extreme Ultraviolet Normal Incidence Spectrograph (EUNIS) sounding rocket instrument on 2006 April 12, reveal velocity oscillations in the He II 303.8 angstrom emission line formed at T approximate to 5; 10(4) K. The oscillations appear to arise in a bright active region loop arcade about 25 '' wide which crosses the EUNIS slit. The period of these transition region oscillations is 26 +/- 4 s, coupled with a velocity amplitude of +/- 10 km s(-1), detected over four complete cycles. Similar oscillations are observed in lines formed at temperatures up to T approximate to 4; 10(5) K, but we find no evidence for the coupling of these velocity oscillations with corresponding phenomena in the corona. We interpret the detected oscillations as originating from an almost purely adiabatic plasma, and infer that they are generated by the resonant transmission of MHD waves through the lower active region atmospheres. Through the use of seismological techniques, we establish that the observed velocity oscillations display wave properties most characteristic of fast body global sausage modes.

SGK1 activity in Na+ absorbing airway epithelial cells monitored by assaying NDRG1-Thr(346/356/366) phosphorylation

Studies of HeLa cells and serum- and glucocorticoid-regulated kinase 1 (SGK1) knockout mice identified threonine residues in the n-myc downstream-regulated gene 1 protein (NDRG1-Thr(346/356/366)) that are phosphorylated by SGK1 but not by related kinases (Murray et al., Biochem J 385:1-12, 2005). We have, therefore, monitored the phosphorylation of NDRG1-Thr(346/356/366) in order to explore the changes in SGK1 activity associated with the induction and regulation of the glucocorticoid-dependent Na+ conductance (G (Na)) in human airway epithelial cells. Transient expression of active (SGK1-S422D) and inactive (SGK1-K127A) SGK1 mutants confirmed that activating SGK1 stimulates NDRG1-Thr(346/356/366) phosphorylation. Although G (Na) is negligible in hormone-deprived cells, these cells displayed basal SGK1 activity that was sensitive to LY294002, an inhibitor of 3-phosphatidylinositol phosphate kinase (PI3K). Dexamethasone (0.2 mu M) acutely activated SGK1 and the peak of this response (2-3 h) coincided with the induction of G (Na), and both responses were PI3K-dependent. While these data suggest that SGK1 might mediate the rise in G (Na), transient expression of the inactive SGK1-K127A mutant did not affect the hormonal induction of G (Na) but did suppress the activation of SGK1. Dexamethasone-treated cells grown on permeable supports formed confluent epithelial sheets that generated short circuit current due to electrogenic Na+ absorption. Forskolin and insulin both stimulated this current and the response to insulin, but not forskolin, was LY294002-sensitive and associated with the activation of SGK1. While these data suggest that SGK1 is involved in the control of G (Na), its role may be minor, which could explain why sgk1 knockout has different effects upon different tissues.

The VLT-FLAMES survey of massive stars: observations centered on the Magellanic Cloud clusters NGC 330, NGC 346, NGC 2004, and the N11 region

We present new observations of 470 stars using the Fibre Large Array Multi-Element Spectrograph ( FLAMES) instrument in fields centered on the clusters NGC330 and NGC346 in the Small Magellanic Cloud (SMC), and NGC2004 and the N11 region in the Large Magellanic Cloud (LMC). A further 14 stars were observed in the N11 and NGC330 fields using the Ultraviolet and Visual Echelle Spectrograph (UVES) for a separate programme. Spectral classifications and stellar radial velocities are given for each target, with careful attention to checks for binarity. In particular, we have investigated previously unexplored regions around the central LH9/LH10 complex of N11, finding similar to 25 new O-type stars from our spectroscopy. We have observed a relatively large number of Be-type stars that display permitted Fe II emission lines. These are primarily not in the cluster cores and appear to be associated with classical Be-type stars, rather than pre main-sequence objects. The presence of the Fe II emission, as compared to the equivalent width of Ha, is not obviously dependent on metallicity. We have also explored the relative fraction of Be- to normal B-type stars in the field-regions near to NGC330 and NGC2004, finding no strong evidence of a trend with metallicity when compared to Galactic results. A consequence of service observations is that we have reasonable time-sampling in three of our FLAMES fields. We find lower limits to the binary fraction of O- and early B-type stars of 23 to 36%. One of our targets (NGC346-013) is especially interesting with a massive, apparently hotter, less luminous secondary component.

The VLT-FLAMES survey of massive stars: NGC 346-013 as a test case for massive close binary evolution

Context. NGC 346-013 is a peculiar double-lined eclipsing binary in the Small Magellanic Cloud (SMC) discovered by the VLT-FLAMES survey of massive stars.

MO-FG-BRA-06: Material Optimisation for Nanoparticle-Sensitized Radiotherapy

Ophthalmology. 2011 Dec;118(12):2343-50. doi: 10.1016/j.ophtha.2011.06.016. Epub 2011 Sep 1. Randomized, controlled trial of an educational intervention to promote spectacle use in rural China: the see well to learn well study.

OBJECTIVE: To test an educational intervention promoting the purchase of spectacles among Chinese children. DESIGN: Randomized, controlled trial. PARTICIPANTS: Children in years 1 and 2 of all 20 junior and senior high schools (ages 12-17 years) in 3 rural townships in Guangdong, China. METHODS: Children underwent visual acuity (VA) testing, and parents of participants with presenting VA worse than 6/12 in either eye improving by more than 2 lines with cycloplegic refraction were recommended to purchase glasses. Children at 10 randomly selected schools received a lecture, video, and classroom demonstration promoting spectacle purchase. MAIN OUTCOME MEASURES: Self-reported purchase of spectacles (primary outcome) and observed wear or possession of newly purchased glasses (secondary outcome) at follow-up examinations (mean, 219 ± 87 days after the baseline visit). RESULTS: Among 15 404 eligible children, examinations were completed for 6379 (74.6%) at intervention schools and 5044 (73.6%) at control schools. Spectacles were recommended for 2236 (35.1%) children at intervention schools and for 2212 (43.9%) at control schools. Of these, 417 (25.7%) intervention schools children and 537 (34.0%, P = 0.45) control schools children reported buying glasses. Predictors of purchase in regression models included female gender (P = 0.02), worse uncorrected VA (P < 0.001), and higher absolute value of refractive error (P = 0.001). Neither the rate of self-reported purchase of glasses or observed wear or possession of newly purchased glasses differed between control schools and intervention schools in mixed-effect logistic regression models. Among children not purchasing glasses, 21.7% had better-eye VA of worse than 6/18. CONCLUSIONS: An intervention based on extensive pilot testing and focus groups in the area failed to promote spectacle purchase or wear. The high burden of remaining uncorrected poor vision underscores the need to develop better interventions. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.