51 resultados para Organizational Probes


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The conventional wisdom regarding party system fragmentation assumes that the effects of electoral systems and social cleavages are linear. However, recent work applying organizational ecology theories to the study of party systems has challenged the degree to which electoral system effects are linear. This paper applies such concepts to the study of social cleavages. Drawing from theories of organizational ecology and the experience of many ethnically diverse African party systems, I argue that the effects of ethnic diversity are nonlinear, with party system fragmentation increasing until reaching moderate levels of diversity before declining as diversity reaches extreme values. Examining this argument cross-nationally, the results show that accounting for nonlinearity in ethnic diversity effects significantly improves model fit.

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Cystic Fibrosis (CF) is a genetic disease featuring a chronic cycle of inflammation and infection in the airways of sufferers. Mutations lead to altered ion transport, which in turn causes dehydrated airways and reduced mucociliary clearance which predisposes the patient to infection, resulting in a severe immune response and tissue destruction (1). Airway dehydration is primarily caused by the hyperabsorption of sodium by the epithelial sodium channel (ENaC) (2). ENaC is activated by the action of a number of predominantly trypsin-like Channel Activating Proteases (CAPs) including prostasin, matriptase and furin (3). Additional proteases known to activate ENaC include human airway trypsin (3), plasmin, neutrophil elastase and chymotrypsin (4).

Activity profiling is a valuable technique which involves the use of small inhibitory molecules called Activity-Based Probes (ABPs) which can be used to covalently label the active site of proteases and provide a range of information regarding its structure, catalytic mechanism, location and function within biological systems. The development of novel ABPs for CAPs, would enhance understanding of the role of these proteases in CF airways disease and in particular their role in ENaC activation and airway dehydration. This project investigates the application of a range of novel broad-spectrum ABPs targeting the various subclasses of serine proteases, to include those proteases involved in ENaC activation. Additionally, the application of more selective ABPs in detecting specific serine proteases is investigated.

Compounds were synthesised by Solid-Phase Peptide Synthesis (SPPS) using a standard Fmoc/tBu strategy. Kinetic evaluation of synthesised ABPs against various serine proteases was determined by fluorogenic steady-state enzyme assays. Furthermore, application of ABPs and confirmation of irreversible nature of the compounds was carried out through SDS-PAGE and electroblotting techniques.

Synthesised compounds showed potent irreversible inhibition of serine proteases within their respective targeting class (NAP855 vs Trypsin k3/Ki = 2.60 x 106 M-1 min-1, NFP849 vs Chymotrypsin k3/Ki = 1.28 x 106 M-1 min-1 and NVP800 vs Neutrophil Elastase k3/Ki = 6.41 x 104 M-1 min-1). Furthermore ABPs showed little to no cross-reactivity between classes and so display selectivity between classes. The irreversible nature of compounds was further demonstrated through labelling of proteases, followed by separation and detection via SDS-PAGE and electroblotting techniques. Targeted labelling of active proteases only, was demonstrated by failure of ABPs to detect previously inactivated proteases. Extension of the substrate recognition site within probes resulted in an increased potency and selectivity in the detection of the target proteases. Successful detection of neutrophil elastase from CF sputum samples by NVP800, demonstrated the application of compounds within biological samples and their potential use in identifying further proteases involved in ENaC activation and airway dehydration in CF patients.

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Electrical conductivity of the supercooled ionic liquid [C8MIM][NTf2], determined as a function of temperature and pressure, highlights strong differences in its ionic transport behavior between low and high temperature regions. To date, the crossover effect which is very well known for low molecular van der Waals liquids has been rarely described for classical ionic liquids. This finding highlights that the thermal fluctuations could be dominant mechanisms driving the dramatic slowing down of ion motions near Tg. An alternative way to analyze separately low and high temperature dc-conductivity data using a density scaling approach was then proposed. Based on which a common value of the scaling exponent [gamma] = 2.4 was obtained, indicating that the applied density scaling is insensitive to the crossover effect. By comparing the scaling exponent [gamma] reported herein along with literature data for other ionic liquids, it appears that [gamma] decreases by increasing the alkyl chain length on the 1-alkyl-3-methylimidazolium-based ionic liquids. This observation may be related to changes in the interaction between ions in solution driven by an increase in the van der Waals type interaction by increasing the alkyl chain length on the cation. This effect may be related to changes in the ionic liquid nanostructural organization with the alkyl chain length on the cation as previously reported in the literature based on molecular dynamic simulations. In other words, the calculated scaling exponent [gamma] may be then used as a key parameter to probe the interaction and/or self-organizational changes in solution with respect to the ionic liquid structure.

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We investigate the use of type Ic superluminous supernovae (SLSN Ic) as standardizable candles and distance indicators. Their appeal as cosmological probes stems from their remarkable peak luminosities, hot blackbody temperatures, and bright rest-frame ultraviolet emission. We present a sample of 16 published SLSN, from redshifts 0.1 to 1.2, and calculate accurate K corrections to determine uniform magnitudes in 2 synthetic rest-frame filter bandpasses with central wavelengths at 400 nm and 520 nm. At 400 nm, we find an encouragingly low scatter in their uncorrected, raw mean magnitudes with M(400) = -21.86 ± 0.35 mag for the full sample of 16 objects. We investigate the correlation between their decline rates and peak magnitude and find that the brighter events appear to decline more slowly. In a manner similar to the Phillips relation for type Ia SNe (SNe Ia), we define a ΔM 20 decline relation. This correlates peak magnitude and decline over 20 days and can reduce the scatter in standardized peak magnitudes to ±0.22 mag. We further show that M(400) appears to have a strong color dependence. Redder objects are fainter and also become redder faster. Using this peak magnitudecolor evolution relation, a surprisingly low scatter of between ±0.08 mag and ±0.13 mag can be found in peak magnitudes, depending on sample selection. However, we caution that only 8 to 10 objects currently have enough data to test this peak magnitudecolor evolution relation. We conclude that SLSN Ic are promising distance indicators in the high-redshift universe in regimes beyond those possible with SNe Ia. Although the empirical relationships are encouraging, the unknown progenitor systems, how they may evolve with redshift, and the uncertain explosion physics are of some concern. The two major measurement uncertainties are the limited numbers of low-redshift, well-studied objects available to test these relationships and internal dust extinction in the host galaxies.

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A novel microwave high-resolution near-field imaging technique is proposed and experimentally evaluated in reflectometry imaging scenarios involving planar metal-dielectric structures. Two types of resonance near field probes-a small helix antenna and a loaded subwavelength slot aperture are studied in this paper. These probes enable very tight spatial field localization with the full width at half maximum around one tenth of a wavelength, λ, at λ/100-λ/10 standoff distance. Importantly, the proposed probes permit resonance electromagnetic coupling to dielectric or printed conductive patterns, which leads to the possibility of very high raw image resolution with imaged feature-to-background contrast greater than 10-dB amplitude and 50° phase. In addition, high-resolution characterization of target geometries based on the cross correlation image processing technique is proposed and assessed using experimental data. It is shown that printed elements features with subwavelength size ~λ/15 or smaller can be characterized with at least 10-dB resolution contrast.