983 resultados para 418
Resumo:
Background
G protein-coupled receptors (GPCRs) constitute one of the largest groupings of eukaryotic proteins, and represent a particularly lucrative set of pharmaceutical targets. They play an important role in eukaryotic signal transduction and physiology, mediating cellular responses to a diverse range of extracellular stimuli. The phylum Platyhelminthes is of considerable medical and biological importance, housing major pathogens as well as established model organisms. The recent availability of genomic data for the human blood fluke Schistosoma mansoni and the model planarian Schmidtea mediterranea paves the way for the first comprehensive effort to identify and analyze GPCRs in this important phylum.
Results
Application of a novel transmembrane-oriented approach to receptor mining led to the discovery of 117 S. mansoni GPCRs, representing all of the major families; 105 Rhodopsin, 2 Glutamate, 3 Adhesion, 2 Secretin and 5 Frizzled. Similarly, 418 Rhodopsin, 9 Glutamate, 21 Adhesion, 1 Secretin and 11 Frizzled S. mediterranea receptors were identified. Among these, we report the identification of novel receptor groupings, including a large and highly-diverged Platyhelminth-specific Rhodopsin subfamily, a planarian-specific Adhesion-like family, and atypical Glutamate-like receptors. Phylogenetic analysis was carried out following extensive gene curation. Support vector machines (SVMs) were trained and used for ligand-based classification of full-length Rhodopsin GPCRs, complementing phylogenetic and homology-based classification.
Conclusions
Genome-wide investigation of GPCRs in two platyhelminth genomes reveals an extensive and complex receptor signaling repertoire with many unique features. This work provides important sequence and functional leads for understanding basic flatworm receptor biology, and sheds light on a lucrative set of anthelmintic drug targets.
Resumo:
A vaginally-worn temperature telemeter may be used by women to chart their basal body temperature for ovulation detection. The telemeter uses a temperature to pulse width converter to key a Colpitts oscillator which is controlled in frequency by a 418 MHz SAW resonator. The circuit’s tank inductor acts as a compact, multi-turn loop antenna with a radiated power in isolation of around 1 uW. The transmission characteristics of the system are affected by the proximity of the human body, which acts as an electrically-large lossy dielectric. The RF link-budget must allow for the reduction in total emitted power, directional body-induced fading, and polarization effects. The polar power patterns of the telemeter were measured for both isolated and in-situ cases, using horizontal and vertical polarization. The power patterns were numerically integrated to determine relative emitted power, and a reference dipole used to determine the emitted power for the isolated device. In isolation the telemeter radiation is vertically polarized and isotropic in nature. With the telemeter in-situ, total body absorption was found to be over 20 dB, with directional fades of up to 40 dB; there was extensive cross-polarization, with up to 60% of radiated power horizontally polarized. With limited radiated power and directional fading, the operating range for the telemeter is limited to single room operation (less than 10m). The majority of RF radiation is absorbed by the body, but the radiation hazard is negligible due to the low power level of the device. The high level of cross-polarization suggests that either horizontal or vertically polarized base-station antennas may be used.
Resumo:
We investigate the spatial coincidence of ultraluminous X-ray sources (ULXs) with young massive stellar clusters. In particular, we perform astrometry on Chandra and Hubble Space Telescope (HST) data of two ULXs that are possibly associated with such clusters.
Resumo:
We report the genome sequence of Klebsiella pneumoniae subsp. pneumoniae Ecl8, a spontaneous streptomycin-resistant mutant of strain ECL4, derived from NCIB 418. K. pneumoniae Ecl8 has been shown to be genetically tractable for targeted gene deletion strategies and so provides a platform for in-depth analyses of this species.
Resumo:
The development of conceptual frameworks for the analysis of social exclusion has somewhat out-stripped related methodological developments. This paper seeks to contribute to filling this gap through the application of self-organising maps (SOMs) to the analysis of a detailed set of material deprivation indicators relating to the Irish case. The SOM approach allows us to offer a differentiated and interpretable picture of the structure of multiple deprivation in contemporary Ireland. Employing this approach, we identify 16 clusters characterised by distinct profiles across 42 deprivation indicators. Exploratory analyses demonstrate that, controlling for equivalised household income, SOM cluster membership adds substantially to our ability to predict subjective economic stress. Moreover, in comparison with an analogous latent class approach, the SOM analysis offers considerable additional discriminatory power in relation to individuals' experience of their economic circumstances. The results suggest that the SOM approach could prove a valuable addition to a 'methodological platform' for analysing the shape and form of social exclusion. (c) 2009 Elsevier Inc. All rights reserved.
Resumo:
The interpretation of supernova (SN) spectra is essential for deriving SN ejecta properties such as density and composition, which in turn can tell us about their progenitors and the explosion mechanism. A very large number of atomic processes are important for spectrum formation. Several tools for calculating SN spectra exist, but they mainly focus on the very early or late epochs. The intermediate phase, which requires a non-local thermodynamic equilibrium (NLTE) treatment of radiation transport has rarely been studied. In this paper, we present a new SN radiation transport code, nero, which can look at those epochs. All the atomic processes are treated in full NLTE, under a steady-state assumption. This is a valid approach between roughly 50 and 500days after the explosion depending on SN type. This covers the post-maximum photospheric and the early and the intermediate nebular phase. As a test, we compare nero to the radiation transport code of Jerkstrand, Fransson & Kozma and to the nebular code of Mazzali et al. All three codes have been developed independently and a comparison provides a valuable opportunity to investigate their reliability. Currently, nero is one-dimensional and can be used for predicting spectra of synthetic explosion models or for deriving SN properties by spectral modelling. To demonstrate this, we study the spectra of the 'normal' Type Ia supernova (SN Ia) 2005cf between 50 and 350 days after the explosion and identify most of the common SN Ia line features at post-maximum epochs. © 2011 The Authors Monthly Notices of the Royal Astronomical Society © 2011 RAS.
Resumo:
This paper queries the soundness of the view that wrongful possession (eg a thief’s possession of goods he has stolen) should be protected by the standard actions for interference with goods. It uses close historical analysis of the development of the relevant concepts through the cases to argue that this is not a proposition that is compelled on the authorities, nor one demanded as a matter of principle. It then abstracts to consider the implications of this argument at a theoretical level, exposing great need for development in the common law’s basic principles of possessory protection. It argues innovatively that the objects of the law might be better served by the creation of a more limited form of possessory protection, achieved through the possessor’s acquisition of a personal right, and correlatively that the values that underpin and justify our basic rules of possessory protection entail a more nuanced response to matters of property acquisition.
Resumo:
We show that the diffusion approximation breaks down for particle acceleration at oblique shocks with velocities typical of young supernova remnants. Higher order anisotropies flatten the spectral index at quasi-parallel shocks and steepen the spectral index at quasi-perpendicular shocks. We compare the theory with observed spectral indices.
Resumo:
Risk factors for the microvascular complications (nephropathy and retinopathy) of Type 1 and Type 2 diabetes mellitus and the associated accelerated atherosclerosis include: age, diabetes duration, genetic factors, hyperglycaemia, hypertension, smoking, inflammation, glycation and oxidative stress and dyslipoproteinaemia. Hypertriglyceridaemia, low HDL and small dense LDL are common features of Type 2 diabetes and Type 1 diabetes with poor glycaemic control or renal complications. With the expansion of knowledge and of clinical and research laboratory tools, a broader definition of 'lipid' abnormalities in diabetes is appropriate. Dyslipoproteinaemia encompasses alterations in lipid levels, lipoprotein subclass distribution, composition (including modifications such as non-enzymatic glycation and oxidative damage), lipoprotein-related enzymes, and receptor interactions and subsequent cell signaling. Alterations occur in all lipoprotein classes; chylomicrons, VLDL, LDL, HDL, and Lp(a). There is also emerging evidence implicating lipoprotein related genotypes in the development of diabetic nephropathy and retinopathy. Lipoprotein related mechanisms associated with damage to the cardiovascular system may also be relevant to damage to the renal and ocular microvasculature. Adverse tissue effects are mediated by both alterations in lipoprotein function and adverse cellular responses. Recognition and treatment of lipoprotein-related risk factors, supported by an increasing array of assays and therapeutic agents, may facilitate early recognition and treatment of high complication risk diabetic patients. Further clinical and basic research, including intervention trials, is warranted to guide clinical practice. Optimal lipoprotein management, as part of a multi-faceted approach to diabetes care, may reduce the excessive personal and economic burden of microvascular complications and the related accelerated atherosclerosis.
Resumo:
Employee voice has been an enduring theme within the employment relations literature.This article profiles the incidence of a range of direct and indirect employee voice mechanisms within multinational companies (MNCs) and, using an analytical framework, identifies a number of different approaches to employee voice. Drawing from a highly representative sample of MNCs in Ireland, we point to quite a significant level of engagement with all types of employee voice, both direct and indirect. Using the analytical framework, we find that the most common approach to employee voice was an indirect voice approach (i.e. the use of trade unions and/or non-union structures of collective employee representation). The regression analysis identifies factors such as country of origin, sector, the European Union Directive on Information and Consultation and date of establishment as having varying impacts on the approaches adopted by MNCs to employee voice. © The Author(s) 2010.