Rapid antimicrobial sensitivity testing by single cell nanoscale optical interference

Growing antimicrobial resistance (AMR) is a serious global threat to human health, with estimates of AMR leading to 10 million deaths per year and costing the global economy $100tn by 20501,2. Current methods to detect resistance include phenotypic antibiotic sensitivity testing (AST) which measures bacterial growth and is therefore hampered by slow time to result (~12-24 hours). Therefore new rapid phenotypic methods for AST are urgently needed3. Here we describe a novel method for detecting phenotypic antibiotic resistance in ~45 minutes, capable of detecting single bacteria. The method uses a sensitive laser and detector system to measure nanoscale optical interference of single bacterial cells present in media, with simple sample preparation. This provides a read out of bacterial antibiotic resistance by detecting growth (resistant) or death (sensitive), much faster than current methods. We demonstrate the potential of this technique by determining resistance in both lab and clinical strains of E. coli, a key species for clinically burdensome urinary tract infections. This work provides the basis for a simple and fast diagnostic tool to detect antibiotic resistance in bacteria, reducing the health and economic burdens of AMR

Second Order Perturbations of Flat Dust FLRW Universes with a Cosmological Constant

We summarize recent results concerning the evolution of second order perturbations in flat dust irrotational FLRW models with $\Lambda\ne 0$. We show that asymptotically these perturbations tend to constants in time, in agreement with the cosmic no-hair conjecture. We solve numerically the second order scalar perturbation equation, and very briefly discuss its all time behaviour and some possible implications for the structure formation.Comment: 6 pages, 1 figure. to be published in "Proceedings of the 5th Alexander Friedmann Seminar on Gravitation and Cosmology", Int. Journ. Mod. Phys. A (2002). Macros: ws-ijmpa.cls, ws-p9-75x6-50.cl

Nonlinear Effects in the Cosmic Microwave Background

Major advances in the observation and theory of cosmic microwave background anisotropies have opened up a new era in cosmology. This has encouraged the hope that the fundamental parameters of cosmology will be determined to high accuracy in the near future. However, this optimism should not obscure the ongoing need for theoretical developments that go beyond the highly successful but simplified standard model. Such developments include improvements in observational modelling (e.g. foregrounds, non-Gaussian features), extensions and alternatives to the simplest inflationary paradigm (e.g. non-adiabatic effects, defects), and investigation of nonlinear effects. In addition to well known nonlinear effects such as the Rees-Sciama and Ostriker-Vishniac effects, further nonlinear effects have recently been identified. These include a Rees-Sciama-type tensor effect, time-delay effects of scalar and tensor lensing, nonlinear Thomson scattering effects and a nonlinear shear effect. Some of the nonlinear effects and their potential implications are discussed.Comment: Invited contribution to Relativistic Cosmology Symposium (celebrating the 60th year of GFR Ellis); to appear Gen. Rel. Gra

Skewness in the Cosmic Microwave Background Anisotropy from Inflationary Gravity Wave Background

In the context of inflationary scenarios, the observed large angle anisotropy of the Cosmic Microwave Background (CMB) temperature is believed to probe the primordial metric perturbations from inflation. Although the perturbations from inflation are expected to be gaussian random fields, there remains the possibility that nonlinear processes at later epochs induce ``secondary'' non-gaussian features in the corresponding CMB anisotropy maps. The non-gaussianity induced by nonlinear gravitational instability of scalar (density) perturbations has been investigated in existing literature. In this paper, we highlight another source of non-gaussianity arising out of higher order scattering of CMB photons off the metric perturbations. We provide a simple and elegant formalism for deriving the CMB temperature fluctuations arising due to the Sachs-Wolfe effect beyond the linear order. In particular, we derive the expression for the second order CMB temperature fluctuations. The multiple scattering effect pointed out in this paper leads to the possibility that tensor metric perturbation, i.e., gravity waves (GW) which do not exhibit gravitational instability can still contribute to the skewness in the CMB anisotropy maps. We find that in a flat $\Omega =1$ universe, the skewness in CMB contributed by gravity waves via multiple scattering effect is comparable to that from the gravitational instability of scalar perturbations for equal contribution of the gravity waves and scalar perturbations to the total rms CMB anisotropy. The secondary skewness is found to be smaller than the cosmic variance leading to the conclusion that inflationary scenarios do predict that the observed CMB anisotropy should be statistically consistent with a gaussian random distribution.Comment: 10 pages, Latex (uses revtex), 1 postscript figure included. Accepted for publication in Physical Review

A Texture Bestiary

Textures are topologically nontrivial field configurations which can exist in a field theory in which a global symmetry group $G$ is broken to a subgroup $H$, if the third homotopy group \p3 of $G/H$ is nontrivial. We compute this group for a variety of choices of $G$ and $H$, revealing what symmetry breaking patterns can lead to texture. We also comment on the construction of texture configurations in the different models.Comment: 34 pages, plain Tex. (Minor corrections to an old paper.

Cosmic Microwave Background anisotropies from second order gravitational perturbations

This paper presents a complete analysis of the effects of second order gravitational perturbations on Cosmic Microwave Background anisotropies, taking explicitly into account scalar, vector and tensor modes. We also consider the second order perturbations of the metric itself obtaining them, for a universe dominated by a collision-less fluid, in the Poisson gauge, by transforming the known results in the synchronous gauge. We discuss the resulting second order anisotropies in the Poisson gauge, and analyse the possible relevance of the different terms. We expect that, in the simplest scenarios for structure formation, the main effect comes from the gravitational lensing by scalar perturbations, that is known to give a few percent contribution to the anisotropies at small angular scales.Comment: 15 pages, revtex, no figures. Version to be published in Phys. Rev.

The development of intermodal freight transport in Poland from 2007 to 2016: Barriers and opportunities to its further development

International transport has grown dynamically in Poland since it becomes a European Union (EU) member. This being the case, it is now, more than ever, important to identify the approaches that are most suitable for delivering sustainable freight transport to the nation. Intermodal options appear to be the most appropriate for this task. This study examines the development of intermodal freight transport in Poland from 2007 to 2016. It considers the barriers overcome and that remain to be overcome as well as identifying opportunities for further development. Initially, secondary data sourced from the Główny Urząd Statystyczny, Urząd Transportu Kolejowego and Eurostat databases, was utilised to explore the situation. This was then reinforced by primary data collection, in the form of a survey, the aim of which being to validate the reviewed literature and the findings of the derived from the database data with the subjective perspective of the respondents. It was found that although the prevalence of intermodal transport has an upward trend in Poland its uptake remains significantly lower than in other EU member states. The major issue inhibiting the development of intermodal transport in Poland is the condition of the nation’s infrastructure. This is accompanied by an element of concern for the external costs generated by intermodal carriers. However, Poland’s participation in a range of EU funded projects that support the modernisation of its ageing infrastructure has been, and remains, a major driving force behind the ongoing development of the intermodal transportation of freight within the country

Regulation of cell survival by sphingosine-1-phosphate receptor S1P1 via reciprocal ERK-dependent suppression of bim and PI-3-kinase/protein kinase C-mediated upregulation of Mcl-1

Although the ability of bioactive lipid sphingosine-1-phosphate (S1P) to positively regulate anti-apoptotic/pro-survival responses by binding to S1P1 is well known, the molecular mechanisms remain unclear. Here we demonstrate that expression of S1P1 renders CCL39 lung fibroblasts resistant to apoptosis following growth factor withdrawal. Resistance to apoptosis was associated with attenuated accumulation of pro-apoptotic BH3-only protein Bim. However, although blockade of extracellular signal-regulated kinase (ERK) activation could reverse S1P1-mediated suppression of Bim accumulation, inhibition of caspase-3 cleavage was unaffected. Instead S1P1-mediated inhibition of caspase-3 cleavage was reversed by inhibition of phosphatidylinositol-3-kinase (PI3K) and protein kinase C (PKC), which had no effect on S1P1 regulation of Bim. However, S1P1 suppression of caspase-3 was associated with increased expression of anti-apoptotic protein Mcl-1, the expression of which was also reduced by inhibition of PI3K and PKC. A role for the induction of Mcl-1 in regulating endogenous S1P receptor-dependent pro-survival responses in human umbilical vein endothelial cells was confirmed using S1P receptor agonist FTY720-phosphate (FTY720P). FTY720P induced a transient accumulation of Mcl-1 that was associated with a delayed onset of caspase-3 cleavage following growth factor withdrawal, whereas Mcl-1 knockdown was sufficient to enhance caspase-3 cleavage even in the presence of FTY720P. Consistent with a pro-survival role of S1P1 in disease, analysis of tissue microarrays from ER+ breast cancer patients revealed a significant correlation between S1P1 expression and tumour cell survival. In these tumours, S1P1 expression and cancer cell survival were correlated with increased activation of ERK, but not the PI3K/PKB pathway. In summary, pro-survival/anti-apoptotic signalling from S1P1 is intimately linked to its ability to promote the accumulation of pro-survival protein Mcl-1 and downregulation of pro-apoptotic BH3-only protein Bim via distinct signalling pathways. However, the functional importance of each pathway is dependent on the specific cellular context