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Modelling water quality for water distribution systems
This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Maintaining water quality in distribution systems has become a prominent issue in the study of water networks. This thesis concentrates on disinfectant and particle counts as two important indicators of water quality. The models discussed in this work are based on data collected by the author. The experimental set-up and procedure are described and observations of particle counts, particle counter size distributions, monochloramine as disinfectant, temperature, heterotrophic plate counts and epifluorescence microscopy counts are reported. A model of the response of particle counts to an increase in flow is developed. This model is obtained from specification derived from the data and assumptions, and is validated by its interpretability and its fit to data. A local shear-off density and an initial biofilm shedding profile were introduced and thus a linear model for this part of the water quality dynamics could be obtained. A procedure for the identification of the parameters of the local shear-off function and for the determination of the biofilm shedding profile is presented. This profile can be used to provide information about the status of the distribution system in terms of shear-off from the biofilm on the pipe walls. Monochloramine decay dynamics are investigated. The chlorine meter data is preprocessed with the help of titration data to correct meter drift. The data is then used in calibrating two different possible chlorine models: a model with a single decay coefficient and a model with bulk decay coefficient and wall demand (as used in Epanet). Important difficulties in identifying these parameters that come about because of the structure of the models are highlighted. Identified decay coefficients are compared and tested for flow, inlet chlorine and temperature dependence. The merits and limits of the approach to modelling taken in this work and a possible generalisation are discussed. The water industry perspective and an outlook are provided
NLO QCD corrections to W+ W- b anti-b production with leptonic decays in the light of top quark mass and asymmetry measurements
We present the NLO QCD corrections to the processes p p and p anti-p to W+ W-
b anti-b including leptonic decays of the W bosons. Non-resonant contributions
as well as diagrams with doubly resonant and singly resonant top quark
propagators are fully taken into account. We employ the narrow width
approximation to perform the decays of the W bosons; spin correlations are
however preserved. We also calculate observables relevant for top quark mass
measurements, and study the impact of kinematical requirements and different
scale choices on t anti-t asymmetries.Comment: 29 pages, 14 figures, version submitted to and accepted by JHE
Global DNA hypomethylation prevents consolidation of differentiation programs and allows reversion to the embryonic stem cell state.
DNA methylation patterns change dynamically during mammalian development and lineage specification, yet scarce information is available about how DNA methylation affects gene expression profiles upon differentiation. Here we determine genome-wide transcription profiles during undirected differentiation of severely hypomethylated (Dnmt1⁻/⁻) embryonic stem cells (ESCs) as well as ESCs completely devoid of DNA methylation (Dnmt1⁻/⁻;Dnmt3a⁻/⁻;Dnmt3b⁻/⁻ or TKO) and assay their potential to transit in and out of the ESC state. We find that the expression of only few genes mainly associated with germ line function and the X chromosome is affected in undifferentiated TKO ESCs. Upon initial differentiation as embryoid bodies (EBs) wild type, Dnmt1⁻/⁻ and TKO cells downregulate pluripotency associated genes and upregulate lineage specific genes, but their transcription profiles progressively diverge upon prolonged EB culture. While Oct4 protein levels are completely and homogeneously suppressed, transcription of Oct4 and Nanog is not completely silenced even at late stages in both Dnmt1⁻/⁻ and TKO EBs. Despite late wild type and Dnmt1⁻/⁻ EBs showing a much higher degree of concordant expression, after EB dissociation and replating under pluripotency promoting conditions both Dnmt1⁻/⁻ and TKO cells, but not wild type cells rapidly revert to expression profiles typical of undifferentiated ESCs. Thus, while DNA methylation seems not to be critical for initial activation of differentiation programs, it is crucial for permanent restriction of developmental fate during differentiation
NLO and off-shell effects in top quark mass determinations
We study the impact of different theoretical descriptions of top quark pair production on top quark mass measurements in the di-lepton channel. To this aim, the full NLO corrections to pp→W+W−bb¯¯→(e+νe)(μ−ν¯¯¯μ)bb¯¯ production are compared to calculations in the narrow width approximation, where the production of a top quark pair is calculated at NLO and combined with three different descriptions of the top quark decay: leading order, next-to-leading order and via a parton shower. The different theory predictions then enter the calibration of template fit functions, which are used for a fit to pseudo-data. The offsets in the top quark mass resulting from the fits based on the various theoretical descriptions are determined
A Difference Version of Nori's Theorem
We consider (Frobenius) difference equations over (F_q(s,t), phi) where phi
fixes t and acts on F_q(s) as the Frobenius endomorphism. We prove that every
semisimple, simply-connected linear algebraic group G defined over F_q can be
realized as a difference Galois group over F_{q^i}(s,t) for some i in N. The
proof uses upper and lower bounds on the Galois group scheme of a Frobenius
difference equation that are developed in this paper. The result can be seen as
a difference analogue of Nori's Theorem which states that G(F_q) occurs as
(finite) Galois group over F_q(s).Comment: 29 page
5-Lipoxygenase contributes to PPAR [gamma] activation in macrophages in response to apoptotic cells
Background: One hallmark contributing to immune suppression during the late phase of sepsis is macrophage polarization to an anti-inflammatory phenotype upon contact with apoptotic cells (AC). Taking the important role of the nuclear receptor PPARγ for this phenotype switch into consideration, it remains elusive how AC activate PPARγ in macrophages. Therefore, we were interested to characterize the underlying principle.
Methods: Apoptosis was induced by treatment of Jurkat T cells for 3 hours with 0.5 μg/ml staurosporine. Necrotic cells (NC) were prepared by heating cells for 20 minutes to 65°C. PPARγ activation was followed by stably transducing RAW264.7 macrophages with a vector encoding the red fluorescent protein mRuby after PPARγ binding to 4 × PPRE sites downstream of the reporter gene sequence. This readout was established by treatment with the PPARγ agonist rosiglitazone (1 μM) and AC (5:1). Twenty-four hours after stimulation, mRuby expression was analysed by fluorescence microscopy. Lipid rafts of AC, NC, as well as living cells (LC) were enriched by sucrose gradient centrifugation. Fractions were analysed for lipid raft-associated marker proteins. Lipid rafts were incubated with transduced RAW264.7 macrophages as described above. 5-Lipoxygenase (5-LO) involvement was verified by pharmacological inhibition (MK-866, 1 μM) and overexpression.
Results: Assuming that the molecule responsible for PPARγ activation in macrophages is localized in the cell membrane of AC, most probably associated to lipid rafts, we isolated lipid rafts from AC, NC and LC. Mass spectrometric analysis of lipid rafts of AC showed the expression of 5-LO, whereas lipid rafts of LC did not. Moreover, incubating macrophages with lipid rafts of AC induced mRuby expression. In contrast, lipid rafts of NC and LC did not. To verify the involvement of 5-LO in activating PPARγ in macrophages, Jurkat T cells were incubated for 30 minutes with the 5-LO inhibitor MK-866 (1 μM) before apoptosis induction. In line with our hypothesis, these AC did not induce mRuby expression. Finally, although living Jurkat T cells overexpressing 5-LO did not activate PPARγ in macrophages, mRuby expression was significantly increased when AC were generated from 5-LO overexpressing compared with wild-type Jurkat cells.
Conclusion: Our results suggest that induction of apoptosis activates 5-LO, localizing to lipid rafts, necessary for PPARγ activation in macrophages. Therefore, it will be challenging to determine whether 5-LO activity in AC, generated from other cell types, correlates with PPARγ activation, contributing to an immune-suppressed phenotype in macrophages
Tuning the Mechanical Properties in Model Nanocomposites: Influence of the Polymer-Filler Interfacial Interactions
This paper presents a study of the polymer-filler interfacial effects on
filler dispersion and mechanical reinforcement in Polystyrene (PS) / silica
nanocomposites by direct comparison of two model systems: un-grafted and
PS-grafted silica dispersed in PS matrix. The structure of nanoparticles has
been investigated by combining Small Angle Neutron Scattering (SANS)
measurements and Transmission Electronic Microscopic (TEM) images. The
mechanical properties were studied over a wide range of deformation by
plate/plate rheology and uni-axial stretching. At low silica volume fraction,
the particles arrange, for both systems, in small finite size non-connected
aggregates and the materials exhibit a solid-like behavior independent of the
local polymer/fillers interactions suggesting that reinforcement is dominated
by additional long range effects. At high silica volume fraction, a continuous
connected network is created leading to a fast increase of reinforcement whose
amplitude is then directly dependent on the strength of the local
particle/particle interactions and lower with grafting likely due to
deformation of grafted polymer.Comment: Journal Polymer Science (2011
Binding cooperativity of membrane adhesion receptors
The adhesion of cells is mediated by receptors and ligands anchored in
apposing membranes. A central question is how to characterize the binding
affinity of these membrane-anchored molecules. For soluble molecules, the
binding affinity is typically quantified by the binding equilibrium constant
K3D in the linear relation [RL] = K3D [R][L] between the volume concentration
[RL] of bound complexes and the volume concentrations [R] and [L] of unbound
molecules. For membrane-anchored molecules, it is often assumed by analogy that
the area concentration of bound complexes [RL] is proportional to the product
[R][L] of the area concentrations for the unbound receptor and ligand
molecules. We show here (i) that this analogy is only valid for two planar
membranes immobilized on rigid surfaces, and (ii) that the thermal roughness of
flexible membranes leads to cooperative binding of receptors and ligands. In
the case of flexible membranes, the area concentration [RL] of receptor-ligand
bonds is proportional to the square of [R][L] for typical lengths and
concentrations of receptors and ligands in cell adhesion zones. The cooperative
binding helps to understand why different experimental methods for measuring
the binding affinity of membrane-anchored molecules have led to values
differing by several orders of magnitude.Comment: 9 pages, 4 figures; to appear in Soft Matte
Neighbourhood greenness and income of occupants in four German areas: GINIplus and LISAplus
Objective We investigated whether families with lower individual-level socioeconomic status (SES) reside in less green neighbourhoods in four areas in Germany. Methods Data were collected within two German birth cohorts – GINIplus and LISAplus. Net equivalent household income was categorized into study area-specific tertiles and used as a proxy for individual-level SES. Neighbourhood greenness was calculated in 500-m buffers around home addresses as: 1) the mean normalized difference vegetation index (NDVI); 2) percent tree cover. Associations between income and neighbourhood greenness were assessed per study area using adjusted linear regression models. Results In the Munich and Leipzig areas, families in the low and medium income tertiles resided in neighbourhoods with lower NDVI compared to those in the high income tertile (mean percent change in NDVI: −4.0 (95% confidence interval = −6.7 to −1.3) and −5.5 (−10.9 to −0.2), respectively). In contrast, in the Wesel area, families in the low income tertile resided in neighbourhoods with higher NDVI (2.9 (0.5–5.3)). Only the association in the Munich area was replicated when using tree cover instead of the NDVI. Conclusions This study provides suggestive evidence that the presence and direction of associations between greenness and SES is region-specific in Germany. The degree of urbanization did not clarify this heterogeneity completely
Rapid identification of Burkholderia mallei and Burkholderia pseudomallei by intact cell Matrix-assisted Laser Desorption/Ionisation mass spectrometric typing
BACKGROUND: Burkholderia (B.) pseudomallei and B. mallei are genetically closely related species. B. pseudomallei causes melioidosis in humans and animals, whereas B. mallei is the causative agent of glanders in equines and rarely also in humans. Both agents have been classified by the CDC as priority category B biological agents. Rapid identification is crucial, because both agents are intrinsically resistant to many antibiotics. Matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-TOF MS) has the potential of rapid and reliable identification of pathogens, but is limited by the availability of a database containing validated reference spectra. The aim of this study was to evaluate the use of MALDI-TOF MS for the rapid and reliable identification and differentiation of B. pseudomallei and B. mallei and to build up a reliable reference database for both organisms. RESULTS: A collection of ten B. pseudomallei and seventeen B. mallei strains was used to generate a library of reference spectra. Samples of both species could be identified by MALDI-TOF MS, if a dedicated subset of the reference spectra library was used. In comparison with samples representing B. mallei, higher genetic diversity among B. pseudomallei was reflected in the higher average Eucledian distances between the mass spectra and a broader range of identification score values obtained with commercial software for the identification of microorganisms. The type strain of B. pseudomallei (ATCC 23343) was isolated decades ago and is outstanding in the spectrum-based dendrograms probably due to massive methylations as indicated by two intensive series of mass increments of 14 Da specifically and reproducibly found in the spectra of this strain. CONCLUSIONS: Handling of pathogens under BSL 3 conditions is dangerous and cumbersome but can be minimized by inactivation of bacteria with ethanol, subsequent protein extraction under BSL 1 conditions and MALDI-TOF MS analysis being faster than nucleic amplification methods. Our spectra demonstrated a higher homogeneity in B. mallei than in B. pseudomallei isolates. As expected for closely related species, the identification process with MALDI Biotyper software (Bruker Daltonik GmbH, Bremen, Germany) requires the careful selection of spectra from reference strains. When a dedicated reference set is used and spectra of high quality are acquired, it is possible to distinguish both species unambiguously. The need for a careful curation of reference spectra databases is stressed
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