2,816 research outputs found
Antimicrobial efficacy against Pseudomonas aeruginosa biofilm formation in a three-dimensional lung epithelial model and the influence of fetal bovine serum
In vitro models that mimic in vivo host-pathogen interactions are needed to evaluate candidate drugs that inhibit bacterial virulence traits. We established a new approach to study Pseudomonas aeruginosa biofilm susceptibility on biotic surfaces, using a three-dimensional (3-D) lung epithelial cell model. P. aeruginosa formed antibiotic resistant biofilms on 3-D cells without affecting cell viability. The biofilm-inhibitory activity of antibiotics and/or the anti-biofilm peptide DJK-5 were evaluated on 3-D cells compared to a plastic surface, in medium with and without fetal bovine serum (FBS). In both media, aminoglycosides were more efficacious in the 3-D cell model. In serum-free medium, most antibiotics (except polymyxins) showed enhanced efficacy when 3-D cells were present. In medium with FBS, colistin was less efficacious in the 3-D cell model. DJK-5 exerted potent inhibition of P. aeruginosa association with both substrates, only in serum-free medium. DJK-5 showed stronger inhibitory activity against P. aeruginosa associated with plastic compared to 3-D cells. The combined addition of tobramycin and DJK-5 exhibited more potent ability to inhibit P. aeruginosa association with both substrates. In conclusion, lung epithelial cells influence the efficacy of most antimicrobials against P. aeruginosa biofilm formation, which in turn depends on the presence or absence of FBS
Degenerate Rotating Black Holes, Chiral CFTs and Fermi Surfaces I - Analytic Results for Quasinormal Modes
In this work we discuss charged rotating black holes in
that degenerate to extremal black holes with zero entropy. These black holes
have scaling properties between charge and angular momentum similar to those of
Fermi surface operators in a subsector of SYM. We add a
massless uncharged scalar to the five dimensional supergravity theory, such
that it still forms a consistent truncation of the type IIB ten dimensional
supergravity and analyze its quasinormal modes. Separating the equation of
motion to a radial and angular part, we proceed to solve the radial equation
using the asymptotic matching expansion method applied to a Heun equation with
two nearby singularities. We use the continued fraction method for the angular
Heun equation and obtain numerical results for the quasinormal modes. In the
case of the supersymmetric black hole we present some analytic results for the
decay rates of the scalar perturbations. The spectrum of quasinormal modes
obtained is similar to that of a chiral 1+1 CFT, which is consistent with the
conjectured field-theoretic dual. In addition, some of the modes can be found
analytically.Comment: 41 pages, 1 figure, LaTeX; v2: typos corrected, references adde
Students' attitudes towards the introduction of a Personal and Professional Development portfolio: potential barriers and facilitators
Peer reviewedPublisher PD
Breakdown of the adiabatic limit in low dimensional gapless systems
It is generally believed that a generic system can be reversibly transformed
from one state into another by sufficiently slow change of parameters. A
standard argument favoring this assertion is based on a possibility to expand
the energy or the entropy of the system into the Taylor series in the ramp
speed. Here we show that this argumentation is only valid in high enough
dimensions and can break down in low-dimensional gapless systems. We identify
three generic regimes of a system response to a slow ramp: (A) mean-field, (B)
non-analytic, and (C) non-adiabatic. In the last regime the limits of the ramp
speed going to zero and the system size going to infinity do not commute and
the adiabatic process does not exist in the thermodynamic limit. We support our
results by numerical simulations. Our findings can be relevant to
condensed-matter, atomic physics, quantum computing, quantum optics, cosmology
and others.Comment: 11 pages, 5 figures, to appear in Nature Physics (originally
submitted version
Troubling "understanding mathematics-in-depth": Its role in the identity work of student-teachers in England
Copyright @ The Author(s) 2013. This article is published with open access at Springerlink.comThis article has been made available through the Brunel Open Access Publishing Fund.In this paper, we focus on an initiative in England devised to prepare non-mathematics graduates to train as secondary mathematics teachers through a 6-month Mathematics Enhancement Course (MEC) to boost their subject knowledge. The course documentation focuses on the need to develop “understanding mathematics in-depth” in students in order for them to become successful mathematics teachers. We take a poststructural approach, so we are not interested in asking what such an understanding is, about the value of this approach or about the effectiveness of the MECs in developing this understanding in their participants. Instead we explore what positions this discourse of “understanding mathematics in-depth” makes available to MEC students. We do this by looking in detail at the “identity work” of two students, analysing how they use and are used by this discourse to position themselves as future mathematics teachers. In doing so, we show how even benign-looking social practices such as “understanding mathematics in-depth” are implicated in practices of inclusion and exclusion. We show this through detailed readings of interviews with two participants, one of whom fits with the dominant discourses in the MEC and the other who, despite passing the MEC, experiences tensions between her national identity work and MEC discourses. We argue that it is vital to explore “identity work” within teacher education contexts to ensure that becoming a successful mathematics teacher is equally available to all.King’s College Londo
A Simple Iterative Model Accurately Captures Complex Trapline Formation by Bumblebees Across Spatial Scales and Flower Arrangements
PMCID: PMC3591286This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Delivery of sTRAIL variants by MSCs in combination with cytotoxic drug treatment leads to p53-independent enhanced antitumor effects
Mesenchymal stem cells (MSCs) are able to infiltrate tumor tissues and thereby effectively deliver gene therapeutic payloads. Here, we engineered murine MSCs (mMSCs) to express a secreted form of the TNF-related apoptosis-inducing ligand (TRAIL), which is a potent inducer of apoptosis in tumor cells, and tested these MSCs, termed MSC.sTRAIL, in combination with conventional chemotherapeutic drug treatment in colon cancer models. When we pretreated human colorectal cancer HCT116 cells with low doses of 5-fluorouracil (5-FU) and added MSC.sTRAIL, we found significantly increased apoptosis as compared with single-agent treatment. Moreover, HCT116 xenografts, which were cotreated with 5-FU and systemically delivered MSC.sTRAIL, went into remission. Noteworthy, this effect was protein 53 (p53) independent and was mediated by TRAIL-receptor 2 (TRAIL-R2) upregulation, demonstrating the applicability of this approach in p53-defective tumors. Consequently, when we generated MSCs that secreted TRAIL-R2-specific variants of soluble TRAIL (sTRAIL), we found that such engineered MSCs, labeled MSC.sTRAIL DR5, had enhanced antitumor activity in combination with 5-FU when compared with MSC.sTRAIL. In contrast, TRAIL-resistant pancreatic carcinoma PancTu1 cells responded better to MSC.sTRAIL DR4 when the antiapoptotic protein XIAP (X-linked inhibitor of apoptosis protein) was silenced concomitantly. Taken together, our results demonstrate that TRAIL-receptor selective variants can potentially enhance the therapeutic efficacy of MSC-delivered TRAIL as part of individualized and tumor-specific combination treatments. © 2013 Macmillan Publishers Limited All rights reserved
Regional Genetic Structure in the Aquatic Macrophyte Ruppia cirrhosa Suggests Dispersal by Waterbirds
The evolutionary history of the genus Ruppia has been shaped by hybridization, polyploidisation and vicariance that have resulted in a problematic taxonomy. Recent studies provided insight into species circumscription, organelle takeover by hybridization, and revealed the importance of verifying species identification to avoid distorting effects of mixing different species, when estimating population connectivity. In the present study, we use microsatellite markers to determine population diversity and connectivity patterns in Ruppia cirrhosa including two spatial scales: (1) from the Atlantic Iberian coastline in Portugal to the Siculo-Tunisian Strait in Sicily and (2) within the Iberian Peninsula comprising the Atlantic-Mediterranean transition. The higher diversity in the Mediterranean Sea suggests that populations have had longer persistence there, suggesting a possible origin and/or refugial area for the species. The high genotypic diversities highlight the importance of sexual reproduction for survival and maintenance of populations. Results revealed a regional population structure matching a continent-island model, with strong genetic isolation and low gene flow between populations. This population structure could be maintained by waterbirds, acting as occasional dispersal vectors. This information elucidates ecological strategies of brackish plant species in coastal lagoons, suggesting mechanisms used by this species to colonize new isolated habitats and dominate brackish aquatic macrophyte systems, yet maintaining strong genetic structure suggestive of very low dispersal.Fundacao para a Cincia e Tecnologia (FCT, Portugal) [PTDC/MAR/119363/2010, BIODIVERSA/0004/2015, UID/Multi/04326/2013]Pew FoundationSENECA FoundationMurcia Government, Spain [11881/PI/09]FCT Investigator Programme-Career Development [IF/00998/2014]Spanish Ministry of Education [AP2008-01209]European Community [00399/2012]info:eu-repo/semantics/publishedVersio
Evolutionary relationships between Rhynchosporium lolii sp. nov. and other Rhynchosporium species on grass.
Copyright: 2013 King et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedThe fungal genus Rhynchosporium (causative agent of leaf blotch) contains several host-specialised species, including R. commune (colonising barley and brome-grass), R. agropyri (couch-grass), R. secalis (rye and triticale) and the more distantly related R. orthosporum (cocksfoot). This study used molecular fingerprinting, multilocus DNA sequence data, conidial morphology, host range tests and scanning electron microscopy to investigate the relationship between Rhynchosporium species on ryegrasses, both economically important forage grasses and common wild grasses in many cereal growing areas, and other plant species. Two different types of Rhynchosporium were found on ryegrasses in the UK. Firstly, there were isolates of R. commune that were pathogenic to both barley and Italian ryegrass. Secondly, there were isolates of a new species, here named R. lolii, that were pathogenic only to ryegrass species. R. lolii was most closely related to R. orthosporum, but exhibited clear molecular, morphological and host range differences. The species was estimated to have diverged from R. orthosporum ca. 5735 years before the present. The colonisation strategy of all of the different Rhynchosporium species involved extensive hyphal growth in the sub-cuticular regions of the leaves. Finally, new species-specific PCR diagnostic tests were developed that could distinguish between these five closely related Rhynchosporium species.Peer reviewedFinal Published versio
A verified generational garbage collector for CakeML
This paper presents the verification of a generational copying garbage collector for the CakeML runtime system. The proof is split into an algorithm proof and an implementation proof. The algorithm proof follows the structure of the informal intuition for the generational collector’s correctness, namely, a partial collection cycle in a generational collector is the same as running a full collection on part of the heap, if one views pointers to old data as non-pointers. We present a pragmatic way of dealing with ML-style mutable state, such as references and arrays, in the proofs. The development has been fully integrated into the in-logic bootstrapped CakeML compiler, which now includes command-line arguments that allow configuration of the generational collector. All proofs were carried out in the HOL4 theorem prover
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