Retail price dynamics and retailer heterogeneity: UK evidence

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.We examine retailer heterogeneity in price adjustment in UK supermarkets. Considerable variation in the price change frequency of identically bar-coded products among retail chains is found. Decomposition analysis suggests that price adjustment is evenly split between sales and reference prices with substantive variation across retailers.We acknowledge funding under the European Commission’s Seventh Framework Programme, Project name: TRANSFOP Project no.: KBBE-265601-

Inhibition of D-Ala:D-Ala ligase through a phosphorylated form of the antibiotic D-cycloserine

D-cycloserine is an antibiotic which targets sequential bacterial cell wall peptidoglycan biosynthesis enzymes: alanine racemase and D-alanine:D-alanine ligase. By a combination of structural, chemical and mechanistic studies here we show that the inhibition of D-alanine:D-alanine ligase by the antibiotic D-cycloserine proceeds via a distinct phosphorylated form of the drug. This mechanistic insight reveals a bimodal mechanism of action for a single antibiotic on different enzyme targets and has significance for the design of future inhibitor molecules based on this chemical structure

Mathematical and Statistical Techniques for Systems Medicine: The Wnt Signaling Pathway as a Case Study

The last decade has seen an explosion in models that describe phenomena in systems medicine. Such models are especially useful for studying signaling pathways, such as the Wnt pathway. In this chapter we use the Wnt pathway to showcase current mathematical and statistical techniques that enable modelers to gain insight into (models of) gene regulation, and generate testable predictions. We introduce a range of modeling frameworks, but focus on ordinary differential equation (ODE) models since they remain the most widely used approach in systems biology and medicine and continue to offer great potential. We present methods for the analysis of a single model, comprising applications of standard dynamical systems approaches such as nondimensionalization, steady state, asymptotic and sensitivity analysis, and more recent statistical and algebraic approaches to compare models with data. We present parameter estimation and model comparison techniques, focusing on Bayesian analysis and coplanarity via algebraic geometry. Our intention is that this (non exhaustive) review may serve as a useful starting point for the analysis of models in systems medicine.Comment: Submitted to 'Systems Medicine' as a book chapte

Nonlocal observables and lightcone-averaging in relativistic thermodynamics

The unification of relativity and thermodynamics has been a subject of considerable debate over the last 100 years. The reasons for this are twofold: (i) Thermodynamic variables are nonlocal quantities and, thus, single out a preferred class of hyperplanes in spacetime. (ii) There exist different, seemingly equally plausible ways of defining heat and work in relativistic systems. These ambiguities led, for example, to various proposals for the Lorentz transformation law of temperature. Traditional 'isochronous' formulations of relativistic thermodynamics are neither theoretically satisfactory nor experimentally feasible. Here, we demonstrate how these deficiencies can be resolved by defining thermodynamic quantities with respect to the backward-lightcone of an observation event. This approach yields novel, testable predictions and allows for a straightforward-extension of thermodynamics to General Relativity. Our theoretical considerations are illustrated through three-dimensional relativistic many-body simulations.Comment: typos in Eqs. (12) and (14) corrected, minor additions in the tex

Entanglement of spin waves among four quantum memories

Quantum networks are composed of quantum nodes that interact coherently by way of quantum channels and open a broad frontier of scientific opportunities. For example, a quantum network can serve as a `web' for connecting quantum processors for computation and communication, as well as a `simulator' for enabling investigations of quantum critical phenomena arising from interactions among the nodes mediated by the channels. The physical realization of quantum networks generically requires dynamical systems capable of generating and storing entangled states among multiple quantum memories, and of efficiently transferring stored entanglement into quantum channels for distribution across the network. While such capabilities have been demonstrated for diverse bipartite systems (i.e., N=2 quantum systems), entangled states with N > 2 have heretofore not been achieved for quantum interconnects that coherently `clock' multipartite entanglement stored in quantum memories to quantum channels. Here, we demonstrate high-fidelity measurement-induced entanglement stored in four atomic memories; user-controlled, coherent transfer of atomic entanglement to four photonic quantum channels; and the characterization of the full quadripartite entanglement by way of quantum uncertainty relations. Our work thereby provides an important tool for the distribution of multipartite entanglement across quantum networks.Comment: 4 figure

Protein disulfide-isomerase interacts with a substrate protein at all stages along its folding pathway

In contrast to molecular chaperones that couple protein folding to ATP hydrolysis, protein disulfide-isomerase (PDI) catalyzes protein folding coupled to formation of disulfide bonds (oxidative folding). However, we do not know how PDI distinguishes folded, partly-folded and unfolded protein substrates. As a model intermediate in an oxidative folding pathway, we prepared a two-disulfide mutant of basic pancreatic trypsin inhibitor (BPTI) and showed by NMR that it is partly-folded and highly dynamic. NMR studies show that it binds to PDI at the same site that binds peptide ligands, with rapid binding and dissociation kinetics; surface plasmon resonance shows its interaction with PDI has a Kd of ca. 10−5 M. For comparison, we characterized the interactions of PDI with native BPTI and fully-unfolded BPTI. Interestingly, PDI does bind native BPTI, but binding is quantitatively weaker than with partly-folded and unfolded BPTI. Hence PDI recognizes and binds substrates via permanently or transiently unfolded regions. This is the first study of PDI's interaction with a partly-folded protein, and the first to analyze this folding catalyst's changing interactions with substrates along an oxidative folding pathway. We have identified key features that make PDI an effective catalyst of oxidative protein folding – differential affinity, rapid ligand exchange and conformational flexibility

Dynamics of dental evolution in ornithopod dinosaurs.

Ornithopods were key herbivorous dinosaurs in Mesozoic terrestrial ecosystems, with a variety of tooth morphologies. Several clades, especially the 'duck-billed' hadrosaurids, became hugely diverse and abundant almost worldwide. Yet their evolutionary dynamics have been disputed, particularly whether they diversified in response to events in plant evolution. Here we focus on their remarkable dietary adaptations, using tooth and jaw characters to examine changes in dental disparity and evolutionary rate. Ornithopods explored different areas of dental morphospace throughout their evolution, showing a long-term expansion. There were four major evolutionary rate increases, the first among basal iguanodontians in the Middle-Late Jurassic, and the three others among the Hadrosauridae, above and below the split of their two major clades, in the middle of the Late Cretaceous. These evolutionary bursts do not correspond to times of plant diversification, including the radiation of the flowering plants, and suggest that dental innovation rather than coevolution with major plant clades was a major driver in ornithopod evolution

Predator Mimicry: Metalmark Moths Mimic Their Jumping Spider Predators

Cases of mimicry provide many of the nature's most convincing examples of natural selection. Here we report evidence for a case of predator mimicry in which metalmark moths in the genus Brenthia mimic jumping spiders, one of their predators. In controlled trials, Brenthia had higher survival rates than other similarly sized moths in the presence of jumping spiders and jumping spiders responded to Brenthia with territorial displays, indicating that Brenthia were sometimes mistaken for jumping spiders, and not recognized as prey. Our experimental results and a review of wing patterns of other insects indicate that jumping spider mimicry is more widespread than heretofore appreciated, and that jumping spiders are probably an important selective pressure shaping the evolution of diurnal insects that perch on vegetation

Culture-independent molecular analysis of bacterial diversity in uranium-ore/-mine waste-contaminated and non-contaminated sites from uranium mines

Soil, water and sediment samples collected from in and around Jaduguda, Bagjata and Turamdih mines were analyzed for physicochemical parameters and cultured, and yet to be cultured microbial diversity. Culturable fraction of microbial community measured as Colony Forming Unit (CFU) on R2A medium revealed microbes between 104 and 109 CFU/g sample. Community DNA was extracted from all the samples; 16S rRNA gene amplified, cloned and subject to Amplified Ribosomal DNA Restriction Analysis. Clones representing each OTU were selected and sequenced. Sequence analyses revealed that non-contaminated samples were mostly represented by Acidobacteria, Bacteroidetes, Firmicutes and Proteobacteria (β-, γ-, and/or δ-subdivisions) along with less frequent phyla Nitrospira, Deferribacteres, Chloroflexi. In contrast, samples obtained from highly contaminated samples showed distinct abundance of β-,γ- and α-Proteobacteria along with Acidobacteria,Bacteroidetes and members of Firmicutes, Chloroflexi, Candidate division, Planctomycete, Cyanobacteria and Actinobacteria as minor groups. Our data represented the baseline information on bacterial community composition within non-contaminated samples which could potentially be useful for assessing the impact of metal and radionuclides contamination due to uranium mine activities