962 research outputs found
Learning to Detect and Track Cells for Quantitative Analysis of Time-Lapse Microscopic Image Sequences
© 2015 IEEE.Studying the behaviour of cells using time-lapse microscopic imaging requires automated processing pipelines that enable quantitative analysis of a large number of cells. We propose a pipeline based on state-of-the-art methods for background motion compensation, cell detection, and tracking which are integrated into a novel semi-automated, learning based analysis tool. Motion compensation is performed by employing an efficient nonlinear registration method based on powerful discrete graph optimisation. Robust detection and tracking of cells is based on classifier learning which only requires a small number of manual annotations. Cell motion trajectories are generated using a recent global data association method and linear programming. Our approach is robust to the presence of significant motion and imaging artifacts. Promising results are presented on different sets of in-vivo fluorescent microscopic image sequences
NK cells augment oncolytic adenovirus cytotoxicity in ovarian cancer
Oncolytic viruses (OVs) can trigger profound innate and adaptive immune responses, which have the potential both to potentiate and reduce the activity of OVs. Natural killer (NK) cells can mediate potent anti-viral and anti-tumoral responses, but there are no data on the role of NK cells in oncolytic adenovirus activity. Here, we have used two different oncolytic adenoviruses—the Ad5 E1A CR2-deletion mutant dl922-947 (group C) and the chimeric Ad3/Ad11p mutant enadenotucirev (group B)—to investigate the effect of NK cells on overall anti-cancer efficacy in ovarian cancer. Because human adenoviruses do not replicate in murine cells, we utilized primary human NK cells from peripheral blood and ovarian cancer ascites. Our results show that dl922-947 and enadenotucirev do not infect NK cells, but induce contact-dependent activation and anti-cancer cytotoxicity against adenovirus-infected ovarian cancer cells. Moreover, manipulation of NK receptors DNAM-1 (DNAX accessory molecule-1) and TIGIT (T cell immunoreceptor with Ig and ITIM domains) significantly influences NK cytotoxicity against adenovirus-infected cells. Together, these results indicate that NK cells act to increase the activity of oncolytic adenovirus in ovarian cancer and suggest that strategies to augment NK activity further via the blockade of inhibitory NK receptor TIGIT could enhance therapeutic potential of OVs
Bridging topological and functional information in protein interaction networks by short loops profiling
Protein-protein interaction networks (PPINs) have been employed to identify potential novel interconnections between proteins as well as crucial cellular functions. In this study we identify fundamental principles of PPIN topologies by analysing network motifs of short loops, which are small cyclic interactions of between 3 and 6 proteins. We compared 30 PPINs with corresponding randomised null models and examined the occurrence of common biological functions in loops extracted from a cross-validated high-confidence dataset of 622 human protein complexes. We demonstrate that loops are an intrinsic feature of PPINs and that specific cell functions are predominantly performed by loops of different lengths. Topologically, we find that loops are strongly related to the accuracy of PPINs and define a core of interactions with high resilience. The identification of this core and the analysis of loop composition are promising tools to assess PPIN quality and to uncover possible biases from experimental detection methods. More than 96% of loops share at least one biological function, with enrichment of cellular functions related to mRNA metabolic processing and the cell cycle. Our analyses suggest that these motifs can be used in the design of targeted experiments for functional phenotype detection.This research was supported by the Biotechnology and Biological Sciences Research Council (BB/H018409/1 to AP, ACCC and FF, and BB/J016284/1 to NSBT) and by the Leukaemia & Lymphoma Research (to NSBT and FF). SSC is funded by a Leukaemia & Lymphoma Research Gordon Piller PhD Studentship
Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human Natural Killer cells
It has been suggested that receptor-ligand complexes segregate or co-localise within immune synapses according to their size, and this is important for receptor signaling. Here, we set out to test the importance of receptor-ligand complex dimensions for immune surveillance of target cells by human Natural Killer (NK) cells. NK cell activation is regulated by integrating signals from activating receptors, such as NKG2D, and inhibitory receptors, such as KIR2DL1. Elongating the NKG2D ligand MICA reduced its ability to trigger NK cell activation. Conversely, elongation of KIR2DL1 ligand HLA-C reduced its ability to inhibit NK cells. Whereas normal-sized HLA-C was most effective at inhibiting activation by normal-length MICA, only elongated HLA-C could inhibit activation by elongated MICA. Moreover, HLA-C and MICA that were matched in size co-localised, whereas HLA-C and MICA that were different in size were segregated. These results demonstrate that receptor-ligand dimensions are important in NK cell recognition, and suggest that optimal integration of activating and inhibitory receptor signals requires the receptor-ligand complexes to have similar dimensions
The dependence of dijet production on photon virtuality in ep collisions at HERA
The dependence of dijet production on the virtuality of the exchanged photon,
Q^2, has been studied by measuring dijet cross sections in the range 0 < Q^2 <
2000 GeV^2 with the ZEUS detector at HERA using an integrated luminosity of
38.6 pb^-1.
Dijet cross sections were measured for jets with transverse energy E_T^jet >
7.5 and 6.5 GeV and pseudorapidities in the photon-proton centre-of-mass frame
in the range -3 < eta^jet <0. The variable xg^obs, a measure of the photon
momentum entering the hard process, was used to enhance the sensitivity of the
measurement to the photon structure. The Q^2 dependence of the ratio of low- to
high-xg^obs events was measured.
Next-to-leading-order QCD predictions were found to generally underestimate
the low-xg^obs contribution relative to that at high xg^obs. Monte Carlo models
based on leading-logarithmic parton-showers, using a partonic structure for the
photon which falls smoothly with increasing Q^2, provide a qualitative
description of the data.Comment: 35 pages, 6 eps figures, submitted to Eur.Phys.J.
Beauty photoproduction measured using decays into muons in dijet events in ep collisions at =318 GeV
The photoproduction of beauty quarks in events with two jets and a muon has
been measured with the ZEUS detector at HERA using an integrated luminosity of
110 pb. The fraction of jets containing b quarks was extracted from the
transverse momentum distribution of the muon relative to the closest jet.
Differential cross sections for beauty production as a function of the
transverse momentum and pseudorapidity of the muon, of the associated jet and
of , the fraction of the photon's momentum participating in
the hard process, are compared with MC models and QCD predictions made at
next-to-leading order. The latter give a good description of the data.Comment: 32 pages, 6 tables, 7 figures Table 6 and Figure 7 revised September
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Search for a narrow charmed baryonic state decaying to D^*+/- p^-/+ in ep collisions at HERA
A resonance search has been made in the D^*+/- p^-/+ invariant-mass spectrum
with the ZEUS detector at HERA using an integrated luminosity of 126 pb^-1. The
decay channels D^*+ -> D^0 pi^+_s -> (K^- pi^+) pi^+_s and D^*+ -> D^0 pi^+_s
-> (K^- pi^+ pi^+ pi^-) pi^+_s (and the corresponding antiparticle decays) were
used to identify D^*+/- mesons. No resonance structure was observed in the
D^*+/- p^-/+ mass spectrum from more than 60000 reconstructed D^*+/- mesons.
The results are not compatible with a report of the H1 Collaboration of a
charmed pentaquark, Theta^0_c.Comment: 22 pages, 7 figures, 1 table; minor text revisions; 2 references
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Angular and Current-Target Correlations in Deep Inelastic Scattering at HERA
Correlations between charged particles in deep inelastic ep scattering have
been studied in the Breit frame with the ZEUS detector at HERA using an
integrated luminosity of 6.4 pb-1. Short-range correlations are analysed in
terms of the angular separation between current-region particles within a cone
centred around the virtual photon axis. Long-range correlations between the
current and target regions have also been measured. The data support
predictions for the scaling behaviour of the angular correlations at high Q2
and for anti-correlations between the current and target regions over a large
range in Q2 and in the Bjorken scaling variable x. Analytic QCD calculations
and Monte Carlo models correctly describe the trends of the data at high Q2,
but show quantitative discrepancies. The data show differences between the
correlations in deep inelastic scattering and e+e- annihilation.Comment: 26 pages including 10 figures (submitted to Eur. J. Phys. C
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