1,798 research outputs found
Effects of chemical composition on the lung cell response to coal particles: Implications for coal workers' pneumoconiosis
Background and objectiveCoal mine dust has a complex and heterogeneous chemical composition. It has been suggested that coal particle chemistry plays a critical role in determining the pathogenesis of coal workers' pneumoconiosis (CWP). In this study, we aimed to establish the association between the detrimental cellular response and the chemical composition of coal particles. MethodsWe sourced 19 real-world coal samples. Samples were crushed prior to use to minimize the impact of particle size on the response and to ensure the particles were respirable. Key chemical components and inorganic compounds were quantified in the coal samples. The cytotoxic, inflammatory and pro-fibrotic responses in epithelial cells, macrophages and fibroblasts were assessed following 24 h of exposure to coal particles. Principal component analysis (PCA) and stepwise regression were used to determine which chemical components of the coal particles were associated with the cell response. ResultsThe cytotoxic, inflammatory and pro-fibrotic response varied considerably between coal samples. There was a high level of collinearity in the cell responses and between the chemical compounds within the coal samples. PCA identified three factors that explained 75% of the variance in the cell response. Stepwise multiple regression analysis identified K2O (p 2O3 (p = 0.011) as significant predictors of cytotoxicity and cytokine production, respectively. ConclusionOur data clearly demonstrate that the detrimental cellular effects of exposure to coal mine dusts are highly dependent on particle chemistry. This has implications for understanding the pathogenesis of CWP
An elementary stringy estimate of transport coefficients of large temperature QCD
Modeling QCD at large temperature with a simple holographic five dimensional
theory encoding minimal breaking of conformality, allows for the calculation of
all the transport coefficients, up to second order, in terms of a single
parameter. In particular, the shear and bulk relaxation times are provided. The
result follows by deforming the AdS background with a scalar dual to a
marginally relevant operator, at leading order in the deformation parameter.Comment: 11 pages; v2: comments and references adde
The long noncoding RNA MALAT1 promotes tumor-driven angiogenesis by up-regulating pro-angiogenic gene expression
Neuroblastoma is the most common solid tumor during early childhood. One of the key features of neuroblastoma is extensive tumor-driven angiogenesis due to hypoxia. However, the mechanism through which neuroblastoma cells drive angiogenesis is poorly understood. Here we show that the long noncoding RNA MALAT1 was upregulated in human neuroblastoma cell lines under hypoxic conditions. Conditioned media from neuroblastoma cells transfected with small interfering RNAs (siRNA) targeting MALAT1, compared with conditioned media from neuroblastoma cells transfected with control siRNAs, induced significantly less endothelial cell migration, invasion and vasculature formation. Microarray-based differential gene expression analysis showed that one of the genes most significantly downregulated following MALAT1 suppression in human neuroblastoma cells under hypoxic conditions was fibroblast growth factor 2 (FGF2). RT-PCR and immunoblot analyses confirmed that MALAT1 suppression reduced FGF2 expression, and Enzyme-Linked Immunosorbent Assays revealed that transfection with MALAT1 siRNAs reduced FGF2 protein secretion from neuroblastoma cells. Importantly, addition of recombinant FGF2 protein to the cell culture media reversed the effects of MALAT1 siRNA on vasculature formation. Taken together, our data suggest that up-regulation of MALAT1 expression in human neuroblastoma cells under hypoxic conditions increases FGF2 expression and promotes vasculature formation, and therefore plays an important role in tumor-driven angiogenesis
The Bulk Channel in Thermal Gauge Theories
We investigate the thermal correlator of the trace of the energy-momentum
tensor in the SU(3) Yang-Mills theory. Our goal is to constrain the spectral
function in that channel, whose low-frequency part determines the bulk
viscosity. We focus on the thermal modification of the spectral function,
. Using the operator-product expansion we give
the high-frequency behavior of this difference in terms of thermodynamic
potentials. We take into account the presence of an exact delta function
located at the origin, which had been missed in previous analyses. We then
combine the bulk sum rule and a Monte-Carlo evaluation of the Euclidean
correlator to determine the intervals of frequency where the spectral density
is enhanced or depleted by thermal effects. We find evidence that the thermal
spectral density is non-zero for frequencies below the scalar glueball mass
and is significantly depleted for .Comment: (1+25) pages, 6 figure
Bridging Time Scales in Cellular Decision Making with a Stochastic Bistable Switch
Cellular transformations which involve a significant phenotypical change of
the cell's state use bistable biochemical switches as underlying decision
systems. In this work, we aim at linking cellular decisions taking place on a
time scale of years to decades with the biochemical dynamics in signal
transduction and gene regulation, occuring on a time scale of minutes to hours.
We show that a stochastic bistable switch forms a viable biochemical mechanism
to implement decision processes on long time scales. As a case study, the
mechanism is applied to model the initiation of follicle growth in mammalian
ovaries, where the physiological time scale of follicle pool depletion is on
the order of the organism's lifespan. We construct a simple mathematical model
for this process based on experimental evidence for the involved genetic
mechanisms. Despite the underlying stochasticity, the proposed mechanism turns
out to yield reliable behavior in large populations of cells subject to the
considered decision process. Our model explains how the physiological time
constant may emerge from the intrinsic stochasticity of the underlying gene
regulatory network. Apart from ovarian follicles, the proposed mechanism may
also be of relevance for other physiological systems where cells take binary
decisions over a long time scale.Comment: 14 pages, 4 figure
Thermal photons in QGP and non-ideal effects
We investigate the thermal photon production-rates using one dimensional
boost-invariant second order relativistic hydrodynamics to find proper time
evolution of the energy density and the temperature. The effect of
bulk-viscosity and non-ideal equation of state are taken into account in a
manner consistent with recent lattice QCD estimates. It is shown that the
\textit{non-ideal} gas equation of state i.e behaviour
of the expanding plasma, which is important near the phase-transition point,
can significantly slow down the hydrodynamic expansion and thereby increase the
photon production-rates. Inclusion of the bulk viscosity may also have similar
effect on the hydrodynamic evolution. However the effect of bulk viscosity is
shown to be significantly lower than the \textit{non-ideal} gas equation of
state. We also analyze the interesting phenomenon of bulk viscosity induced
cavitation making the hydrodynamical description invalid. We include the
viscous corrections to the distribution functions while calculating the photon
spectra. It is shown that ignoring the cavitation phenomenon can lead to
erroneous estimation of the photon flux.Comment: 11 pages, 13 figures; accepted for publication in JHE
The use of thermographic imaging to evaluate therapeutic response in human tumour xenograft models
YesNon-invasive methods to monitor tumour growth are an important goal in cancer drug development. Thermographic imaging systems offer potential in this area, since a change in temperature is known to be induced due to changes within the tumour microenvironment. This study demonstrates that this imaging modality can be applied to a broad range of tumour xenografts and also, for the first time, the methodology’s suitability to assess anti-cancer agent efficacy. Mice bearing subcutaneously implanted H460 lung cancer xenografts were treated with a novel vascular disrupting agent, ICT-2552, and the cytotoxin doxorubicin. The effects on tumour temperature were assessed using thermographic imaging over the first 6 hours post-administration and subsequently a further 7 days. For ICT-2552 a significant initial temperature drop was observed, whilst for both agents a significant temperature drop was seen compared to controls over the longer time period. Thus thermographic imaging can detect functional differences (manifesting as temperature reductions) in the tumour response to these anti-cancer agents compared to controls. Importantly, these effects can be detected in the first few hours following treatment and therefore the tumour is observable non-invasively. As discussed, this technique will have considerable 3Rs benefits in terms of reduction and refinement of animal use.University of Bradfor
Hierarchical information clustering by means of topologically embedded graphs
We introduce a graph-theoretic approach to extract clusters and hierarchies
in complex data-sets in an unsupervised and deterministic manner, without the
use of any prior information. This is achieved by building topologically
embedded networks containing the subset of most significant links and analyzing
the network structure. For a planar embedding, this method provides both the
intra-cluster hierarchy, which describes the way clusters are composed, and the
inter-cluster hierarchy which describes how clusters gather together. We
discuss performance, robustness and reliability of this method by first
investigating several artificial data-sets, finding that it can outperform
significantly other established approaches. Then we show that our method can
successfully differentiate meaningful clusters and hierarchies in a variety of
real data-sets. In particular, we find that the application to gene expression
patterns of lymphoma samples uncovers biologically significant groups of genes
which play key-roles in diagnosis, prognosis and treatment of some of the most
relevant human lymphoid malignancies.Comment: 33 Pages, 18 Figures, 5 Table
Thermodynamics of deformed AdS model with a positive/negative quadratic correction in graviton-dilaton system
By solving the Einstein equations of the graviton coupling with a real scalar
dilaton field, we establish a general framework to self-consistently solve the
geometric background with black-hole for any given phenomenological holographic
models. In this framwork, we solve the black-hole background, the corresponding
dilaon field and the dilaton potential for the deformed AdS model with a
positive/negative quadratic correction. We systematically investigate the
thermodynamical properties of the deformed AdS model with a positive and
negative quadratic correction, respectively, and compare with lattice QCD on
the results of the equation of state, the heavy quark potential, the Polyakov
loop and the spatial Wilson loop. We find that the bulk thermodynamical
properties are not sensitive to the sign of the quadratic correction, and the
results of both deformed holographic QCD models agree well with lattice QCD
result for pure SU(3) gauge theory. However, the results from loop operators
favor a positive quadratic correction, which agree well with lattice QCD
result. Especially, the result from the Polyakov loop excludes the model with a
negative quadratic correction in the warp factor of .Comment: 26 figures,36 pages,V.3: an appendix,more equations and references
added,figures corrected,published versio
Multiple ITS Copies Reveal Extensive Hybridization within Rheum (Polygonaceae), a Genus That Has Undergone Rapid Radiation
During adaptive radiation events, characters can arise multiple times due to parallel evolution, but transfer of traits through hybridization provides an alternative explanation for the same character appearing in apparently non-sister lineages. The signature of hybridization can be detected in incongruence between phylogenies derived from different markers, or from the presence of two divergent versions of a nuclear marker such as ITS within one individual.In this study, we cloned and sequenced ITS regions for 30 species of the genus Rheum, and compared them with a cpDNA phylogeny. Seven species contained two divergent copies of ITS that resolved in different clades from one another in each case, indicating hybridization events too recent for concerted evolution to have homogenised the ITS sequences. Hybridization was also indicated in at least two further species via incongruence in their position between ITS and cpDNA phylogenies. None of the ITS sequences present in these nine species matched those detected in any other species, which provides tentative evidence against recent introgression as an explanation. Rheum globulosum, previously indicated by cpDNA to represent an independent origin of decumbent habit, is indicated by ITS to be part of clade of decumbent species, which acquired cpDNA of another clade via hybridization. However decumbent and glasshouse morphology are confirmed to have arisen three and two times, respectively.These findings suggested that hybridization among QTP species of Rheum has been extensive, and that a role of hybridization in diversification of Rheum requires investigation
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