4,635 research outputs found
Isolation, cDNA cloning, and overexpression of a 33-kD cell surface glycoprotein that binds to the globular 'heads' of C1q
This work describes the functional characterization, cDNA cloning, and expression of a novel cell surface protein. This protein designated gC1q-R, was first isolated from Raji cells and was found to bind to the globular 'heads' of C1q molecules, at physiological ionic strength, and also to inhibit complement-mediated lysis of sheep erythrocytes by human serum. The NH 2-terminal amino acid sequence of the first 24 residues of the C1q- binding protein was determined and this information allowed the synthesis of two degenerate polymerase chain reaction primers for use in the preparation of a probe in the screening of a B cell cDNA library. The cDNA isolated, using this probe, was found to encode a pre-pro protein of 282 residues. The NH 2 terminus of the protein isolated from Raji cells started at residue 74 of the predicted pre-pro sequence. The cDNA sequence shows that the purified protein has three potential N-glycosylation residues and is a highly charged, acidic molecule. Hence, its binding to C1q may be primarily but not exclusively due to ionic interactions. The 'mature' protein, corresponding to amino acid residues 74-282 of the predicted pre-pro sequence, was overexpressed in Escherichia coli and was purified to homogeneity. This recombinant protein was also able to inhibit the complement-mediated lysis of sheep erythrocytes by human serum and was shown to be a tetramer by gel filtration in nondissociating conditions. Northern blot and RT-PCR studies showed that the C1q-binding protein is expressed at high levels in Raji and Daudi cell lines, at moderate levels in U937, Molt-4, and HepG2 cell lines, and at a very low level in the HL60 cell line. However, it is not expressed in the K562 cell line. Comparison of gC1q-R NH 2-terminal sequence with that of the receptor for the collagen-like domain of C1q (cC1q-R) showed no similarity. Furthermore, antibodies to gC1q-R or an 18-amino acid residue- long NH 2-terminal synthetic gC1q-R peptide did not cross-react with antibodies to cC1q-R. Anti-gC1q-R immunoblotted a 33-kD Raji cell membrane protein, whereas anti cC1q-R recognized a molecule of ~60 kD. The NH 2- terminal sequence of gC1g-R appears to be displayed extracellularly since anti-gC1g-R peptide reacted with surface molecules on lymphocytes, polymorphonuclear leukocytes, and platelets, as assessed by flow cytometric and confocal laser scanning microscopic analyses. In addition, all or part of the gC1q binding domain may reside within the 24 amino acid stretch of the NH 2-terminal sequence of gC1q-R since the 18 amino acid residue long- synthetic peptide corresponding to this region inhibited serum C1q hemolytic activity. The data presented in this report suggest that there are at least two types of C1q-R which appear to be expressed on the same type of cells and these receptors individually or in concert may contribute to the diversity of C1q-mediated responses.published_or_final_versio
Forecasting and Granger Modelling with Non-linear Dynamical Dependencies
Traditional linear methods for forecasting multivariate time series are not
able to satisfactorily model the non-linear dependencies that may exist in
non-Gaussian series. We build on the theory of learning vector-valued functions
in the reproducing kernel Hilbert space and develop a method for learning
prediction functions that accommodate such non-linearities. The method not only
learns the predictive function but also the matrix-valued kernel underlying the
function search space directly from the data. Our approach is based on learning
multiple matrix-valued kernels, each of those composed of a set of input
kernels and a set of output kernels learned in the cone of positive
semi-definite matrices. In addition to superior predictive performance in the
presence of strong non-linearities, our method also recovers the hidden dynamic
relationships between the series and thus is a new alternative to existing
graphical Granger techniques.Comment: Accepted for ECML-PKDD 201
A comparative map viewer integrating genetic maps for Brassica and Arabidopsis
Background: Molecular genetic maps provide a means to link heritable traits with underlying genome sequence variation. Several genetic maps have been constructed for Brassica species, yet to date, there has been no simple means to compare this information or to associate mapped traits with the genome sequence of the related model plant, Arabidopsis. Description: We have developed a comparative genetic map database for the viewing, comparison and analysis of Brassica and Arabidopsis genetic, physical and trait map information. This web- based tool allows users to view and compare genetic and physical maps, search for traits and markers, and compare genetic linkage groups within and between the amphidiploid and diploid Brassica genomes. The inclusion of Arabidopsis data enables comparison between Brassica maps that share no common markers. Analysis of conserved syntenic blocks between Arabidopsis and collated Brassica genetic maps validates the application of this system. This tool is freely available over the internet on http://bioinformatics.pbcbasc.latrobe.edu.au/cmap. Conclusion: This database enables users to interrogate the relationship between Brassica genetic maps and the sequenced genome of A. thaliana, permitting the comparison of genetic linkage groups and mapped traits and the rapid identification of candidate genes
Efimov physics beyond three particles
Efimov physics originally refers to a system of three particles. Here we
review recent theoretical progress seeking for manifestations of Efimov physics
in systems composed of more than three particles. Clusters of more than three
bosons are tied to each Efimov trimer, but no independent Efimov physics exists
there beyond three bosons. The case of a few heavy fermions interacting with a
lighter atom is also considered, where the mass ratio of the constituent
particles plays a significant role. Following Efimov's study of the (2+1)
system, the (3+1) system was shown to have its own critical mass ratio to
become Efimovian. We show that the (4+1) system becomes Efimovian at a mass
ratio which is smaller than its sub-systems thresholds, giving a pure five-body
Efimov effect. The (5+1) and (6+1) systems are also discussed, and we show the
absence of 6- and 7-body Efimov physics there
Clinicians' attitude towards a placebo-controlled randomised clinical trial investigating the effect of neuraminidase inhibitors in adults hospitalised with influenza
Background: The value of neuraminidase inhibitors (NAIs) in reducing severe clinical outcomes from influenza is debated. A clinical trial to generate better evidence is desirable. However, it is unknown whether UK clinicians would support a placebo controlled trial. A survey was conducted to determine the attitude of clinicians towards a clinical trial and their current practice in managing adults admitted to hospital with suspected influenza.
Methods: Senior clinicians (n=50) across the UK actively involved in the care of patients hospitalised with severe respiratory infections and/or respiratory infection research were invited to participate in an on-line survey. Participants were asked their opinion on the evidence for benefit of NAIs in influenza, their current practice in relation to: a) testing for influenza; b) treating empirically with NAIs; and c) when influenza infection is virolologically confirmed, prescribing NAIs.
Results: Thirty-five (70%) of 50 clinicians completed the survey. Respondents were drawn mainly from infectious diseases, intensive care and respiratory medicine. Only 11 (31%) of 35 respondents agreed that NAIs are effective at reducing influenza mortality;14(40%)disagreed, 10 (28.6%) neither agreed nor disagreed. When managing adults admitted to non-ICU wards with a respiratory infection during an influenza season, 15 (51.7%) clinicians indicated they would usually perform a test for influenza in greater than 60% of patients but only 9 (31%) would treat empirically with NAIs in greater than 60% of patients. Few clinicians would either test or empirically treat patients presenting with other (non-respiratory infection related) diagnoses. If influenza infection is confirmed, 17 (64.5%) clinicians would prescribe NAIs in greater than 80% of patients with a respiratory infection treated on non-ICU wards Thirty-one (89%) clinicians agreed that a placebo-controlled clinical trial should be conducted and 29 (85%) would participate in such a trial.
Conclusions: There is strong support from UK clinicians for a placebo-controlled trial of NAI treatment in adults hospitalised with suspected influenza. Current variation in medical opinion and clinical practice demonstrates collective equipoise, supporting ethical justification for a trial. Low use of NAIs in the UK suggests randomisation of treatment would not substantially divert patients towards placebo
Paving the way for research findings: writers' rhetorical choices in education and applied linguistics
Notwithstanding the existence of previous investigations into how research results are presented in different academic disciplines, fewer studies have looked into how authors pave the way for their results, the interdisciplinary differences in ‘result pavements’, and the interconnections between their communicative functions and linguistic choices. Using the techniques of genre analysis, I have analyzed two corpora of research reports in applied linguistics and education in order to identify the possible ways in which experienced writers schematically pave the way for their findings. Using evidence based on authentic research articles, this study demonstrates how writers set the stage for their research results by (i) demonstrating their control of the structure and flow of result-related information, (ii) connecting past research with a current finding while furnishing pertinent background elements that lead the readership progressively to specific findings, (iii) regenerating readers’ interest in their initial research purposes, and (iv) deploying locatives to embed results in a ‘space-saving strategy’ aimed at presenting an abridged Results section. I have also analyzed interdisciplinary differences in the frequencies of these rhetorical steps and the range of intricate linguistic mechanisms employed by authors as communicative resources in each step to establish a smooth rhetorical transition that sets the stage for their research results
Revisiting Date and Party Hubs: Novel Approaches to Role Assignment in Protein Interaction Networks
The idea of 'date' and 'party' hubs has been influential in the study of
protein-protein interaction networks. Date hubs display low co-expression with
their partners, whilst party hubs have high co-expression. It was proposed that
party hubs are local coordinators whereas date hubs are global connectors. Here
we show that the reported importance of date hubs to network connectivity can
in fact be attributed to a tiny subset of them. Crucially, these few, extremely
central, hubs do not display particularly low expression correlation,
undermining the idea of a link between this quantity and hub function. The
date/party distinction was originally motivated by an approximately bimodal
distribution of hub co-expression; we show that this feature is not always
robust to methodological changes. Additionally, topological properties of hubs
do not in general correlate with co-expression. Thus, we suggest that a
date/party dichotomy is not meaningful and it might be more useful to conceive
of roles for protein-protein interactions rather than individual proteins. We
find significant correlations between interaction centrality and the functional
similarity of the interacting proteins.Comment: 27 pages, 5 main figures, 4 supplementary figure
Evaluation of Phage Display Discovered Peptides as Ligands for Prostate-Specific Membrane Antigen (PSMA)
The aim of this study was to identify potential ligands of PSMA suitable for further development as novel PSMA-targeted peptides using phage display technology. The human PSMA protein was immobilized as a target followed by incubation with a 15-mer phage display random peptide library. After one round of prescreening and two rounds of screening, high-stringency screening at the third round of panning was performed to identify the highest affinity binders. Phages which had a specific binding activity to PSMA in human prostate cancer cells were isolated and the DNA corresponding to the 15-mers were sequenced to provide three consensus sequences: GDHSPFT, SHFSVGS and EVPRLSLLAVFL as well as other sequences that did not display consensus. Two of the peptide sequences deduced from DNA sequencing of binding phages, SHSFSVGSGDHSPFT and GRFLTGGTGRLLRIS were labeled with 5-carboxyfluorescein and shown to bind and co-internalize with PSMA on human prostate cancer cells by fluorescence microscopy. The high stringency requirements yielded peptides with affinities KD∼1 μM or greater which are suitable starting points for affinity maturation. While these values were less than anticipated, the high stringency did yield peptide sequences that apparently bound to different surfaces on PSMA. These peptide sequences could be the basis for further development of peptides for prostate cancer tumor imaging and therapy. © 2013 Shen et al
Long term time variability of cosmic rays and possible relevance to the development of life on Earth
An analysis is made of the manner in which the cosmic ray intensity at Earth
has varied over its existence and its possible relevance to both the origin and
the evolution of life. Much of the analysis relates to the 'high energy' cosmic
rays () and their variability due to the changing
proximity of the solar system to supernova remnants which are generally
believed to be responsible for most cosmic rays up to PeV energies. It is
pointed out that, on a statistical basis, there will have been considerable
variations in the likely 100 My between the Earth's biosphere reaching
reasonable stability and the onset of very elementary life. Interestingly,
there is the increasingly strong possibility that PeV cosmic rays are
responsible for the initiation of terrestrial lightning strokes and the
possibility arises of considerable increases in the frequency of lightnings and
thereby the formation of some of the complex molecules which are the 'building
blocks of life'. Attention is also given to the well known generation of the
oxides of nitrogen by lightning strokes which are poisonous to animal life but
helpful to plant growth; here, too, the violent swings of cosmic ray
intensities may have had relevance to evolutionary changes. A particular
variant of the cosmic ray acceleration model, put forward by us, predicts an
increase in lightning rate in the past and this has been sought in Korean
historical records. Finally, the time dependence of the overall cosmic ray
intensity, which manifests itself mainly at sub-10 GeV energies, has been
examined. The relevance of cosmic rays to the 'global electrical circuit'
points to the importance of this concept.Comment: 18 pages, 5 figures, accepted by 'Surveys in Geophysics
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