Dehydration and ionic conductance quantization in nanopores

There has been tremendous experimental progress in the last decade in identifying the structure and function of biological pores (ion channels) and fabricating synthetic pores. Despite this progress, many questions still remain about the mechanisms and universal features of ionic transport in these systems. In this paper, we examine the use of nanopores to probe ion transport and to construct functional nanoscale devices. Specifically, we focus on the newly predicted phenomenon of quantized ionic conductance in nanopores as a function of the effective pore radius - a prediction that yields a particularly transparent way to probe the contribution of dehydration to ionic transport. We study the role of ionic species in the formation of hydration layers inside and outside of pores. We find that the ion type plays only a minor role in the radial positions of the predicted steps in the ion conductance. However, ions with higher valency form stronger hydration shells, and thus, provide even more pronounced, and therefore, more easily detected, drops in the ionic current. Measuring this phenomenon directly, or from the resulting noise, with synthetic nanopores would provide evidence of the deviation from macroscopic (continuum) dielectric behavior due to microscopic features at the nanoscale and may shed light on the behavior of ions in more complex biological channels.Comment: 13 pages, 10 figure

Structural characteristics of positionally-disordered lattices: relation to the first sharp diffraction peak in glasses

Positional disorder has been introduced into the atomic structure of certain crystalline lattices, and the orientationally-averaged structure factor S(k) and pair-correlation function g(r) of these disordered lattices have been studied. Analytical expressions for S(k) and g(r) for Gaussian positional disorder in 2D and 3D are confirmed with precise numerical simulations. These analytic results also have a bearing on the unsolved Gauss circle problem in mathematics. As the positional disorder increases, high-k peaks in S(k) are destroyed first, eventually leaving a single peak, that with the lowest-k value. The pair-correlation function for lattices with such high levels of positional disorder exhibits damped oscillations, with a period equal to the separation between the furthest-separated (lowest-k) lattice planes. The last surviving peak in S(k) is, for example for silicon and silica, at a wavevector nearly identical to that of the experimentally-observed first sharp diffraction peak (FSDP) in the amorphous phases of those materials. Thus, for these amorphous materials at least, the FSDP can be regarded as arising from scattering from atomic configurations equivalent to the single family of positionally-disordered local Bragg planes having the furthest separation.Comment: v2: changes in response to referees' comments: Figure 2 made more readable, improved discussion of height of peaks in S(k), other minor changes 4 pages, 3 figures, submitted to Physical Review

Observation of sub-Bragg diffraction of waves in crystals

We investigate the diffraction conditions and associated formation of stopgaps for waves in crystals with different Bravais lattices. We identify a prominent stopgap in high-symmetry directions that occurs at a frequency below the ubiquitous first-order Bragg condition. This sub-Bragg diffraction condition is demonstrated by reflectance spectroscopy on two-dimensional photonic crystals with a centred rectangular lattice, revealing prominent diffraction peaks for both the sub-Bragg and first-order Bragg condition. These results have implications for wave propagation in 2 of the 5 two-dimensional Bravais lattices and 7 out of 14 three-dimensional Bravais lattices, such as centred rectangular, triangular, hexagonal and body-centred cubic

Glyburide inhibits the Cryopyrin/Nalp3 inflammasome

Inflammasomes activate caspase-1 for processing and secretion of the cytokines interleukin-1 beta (IL-1 beta) and IL-18. Cryopyrin/NALP3/NLRP3 is an essential component of inflammasomes triggered by microbial ligands, danger-associated molecular patterns (DAMPs), and crystals. Inappropriate Cryopyrin activity has been incriminated in the pathogenesis of gouty arthritis, Alzheimer's, and silicosis. Therefore, inhibitors of the Nalp3 inflammasome offer considerable therapeutic promise. In this study, we show that the type 2 diabetes drug glyburide prevented activation of the Cryopyrin inflammasome. Glyburide's cyclohexylurea group, which binds to adenosine triphosphatase (ATP)-sensitive K+ (K-ATP) channels for insulin secretion, is dispensable for inflammasome inhibition. Macrophages lacking K-ATP subunits or ATP-binding cassette transporters also activate the Cryopyrin inflammasome normally. Glyburide analogues inhibit ATP- but not hypothermia-induced IL-1 beta secretion from human monocytes expressing familial cold-associated autoinflammatory syndrome associated Cryopyrin mutations, thus suggesting that inhibition occurs upstream of Cryopyrin. Concurrent with the role of Cryopyrin in endotoxemia, glyburide significantly delays lipopolysaccharide-induced lethality in mice. Therefore, glyburide is the first identified compound to prevent Cryopyrin activation and microbial ligand-, DAMP-, and crystal-induced IL-1 beta secretion

Analysis of musculoskeletal and breast tumours by fast field-cycling MRI

Peer reviewedPublisher PD

Describing interruptions, multi-tasking and task-switching in the community pharmacy: A qualitative study in England

Background: There is growing evidence base around interruptions and distractions in the community pharmacy setting. There is also evidence to suggest these practices may be associated with dispensing errors. Up to date, qualitative research on this subject is limited. Objective: To explore interruptions and distractions in the community setting; utilising an ethnographic approach to be able to provide a detailed description of the circumstances surrounding such practices. Setting: Community pharmacies in England, July to October 2011. Method: An ethnographic approach was taken. Non participant, unstructured observations were utilised to make records of pharmacists’ every activities. Case studies were formed by combining field notes with detailed information on pharmacists and their respective pharmacy businesses. Content analysis was undertaken both manually and electronically, utilising NVivo 10. Results: Response rate was 12% (n=11). Over fifteen days, a total of 123 hours and 58 minutes of observations were recorded in 11 separate pharmacies of 11 individual pharmacists. The sample was evenly split by gender (female n=6; male n=5) and pharmacy ownership (independent n=5; multiple n=6). Employment statuses included employee pharmacists (n=6), owners (n=4) and a locum (n=1). Average period of registration as a pharmacist was 19 years (range 5-39 years). Average prescriptions busyness of pharmacies ranged from 2,600 – 24,000 items dispensed per month. Two key themes were: “Interruptions and task-switching” and “distractions and multi-tasking.” All observed pharmacists’ work was dominated by interruptions, task-switches, distractions and multi-tasking, often to manage a barrage of conflicting demands. These practices were observed to be part of a deep-rooted culture in the community setting. Directional work maps illustrated the extent and direction of task switching employed by pharmacists. Conclusions: In this study pharmacists’ working practices were permeated by interruptions and multi-tasking. These practices are inefficient and potentially reduce patient safety in terms of dispensing accuracy

Becoming-Bertha: virtual difference and repetition in postcolonial 'writing back', a Deleuzian reading of Jean Rhys’s Wide Sargasso Sea

Critical responses to Wide Sargasso Sea have seized upon Rhys’s novel as an exemplary model of writing back. Looking beyond the actual repetitions which recall Brontë’s text, I explore Rhys’s novel as an expression of virtual difference and becomings that exemplify Deleuze’s three syntheses of time. Elaborating the processes of becoming that Deleuze’s third synthesis depicts, Antoinette’s fate emerges not as a violence against an original identity. Rather, what the reader witnesses is a series of becomings or masks, some of which are validated, some of which are not, and it is in the rejection of certain masks, forcing Antoinette to become-Bertha, that the greatest violence lies

Energy Relaxation at a Hot-Electron Vortex Instability

At high dissipation levels, vortex motion in a superconducting film has been observed to become unstable at a certain critical vortex velocity v*. At substrate temperatures substantially below Tc, the observed behavior can be accounted for by a model in which the electrons reach an elevated temperature relative to the phonons and the substrate. Here we examine the underlying assumptions concerning energy flow and relaxation times in this model. A calculation of the rate of energy transfer from the electron gas to the lattice finds that at the instability, the electronic temperature reaches a very high value close to the critical temperature. Our calculated energy relaxation times are consistent with those deduced from the experiments. We also estimate the phonon mean free path and assess its effect on the flow of energy in the film.Comment: 8 pages, 7 figure

Cubulating CAT(0) groups and Property (T) in random groups

This thesis considers two properties important to many areas of mathematics: those of cubulation and Property (T). Cubulation played a central role in Agol’s proof of the virtual Haken conjecture, while Property (T) has had an impact on areas such as group theory, ergodic theory, and expander graphs. The aim is to cubulate some examples of groups known in the literature, and prove that many ‘generic’ groups have Property (T). Graphs will be central objects of study throughout this text, and so in Chapter 2 we provide some definitions and note some results. In Chapter 3, we provide a condition on the links of polygonal complexes that allows us to cubulate groups acting properly discontinuously and cocompactly on such complexes. If the group is hyperbolic then this action is also cocompact, hence by Agol’s Theorem the group is virtually special (in the sense of Haglund–Wise); in particular it is linear over Z. We consider some applications of this work. Firstly, we consider the groups classified by [KV10] and [CKV12], which act simply transitively on CAT(0) triangular complexes with the minimal generalized quadrangle as their links, proving that these groups are virtually special. We further apply this theorem by considering generalized triangle groups, in particular a subset of those considered by [CCKW20]. To analyse Property (T) in generic groups, we first need to understand the eigenvalues of some random graphs: this is the content of Chapter 4, in which we analyse the eigenvalues of Erdös–Rényi random bipartite graphs. In particular, we consider p satisfying m1p = (log m2), and let G ~ G(m1, m2, p). We show that with probability tending to 1 as m1 tends to infinity: μ2(A(G)) <=O(sqrt{m2p}). In Chapter 5 we study Property (T) in the (n, k, d) model of random groups: as k tends to infinity this gives the Gromov density model, introduced in [Gro93]. We provide bounds for Property (T) in the k-angular model of random groups, i.e. the (n, k, d) model where k is fixed and n tends to infinity. We also prove that for d > 1/3, a random group in the (n, k, d) model has Property (T) with probability tending to 1 as k tends to infinity, strengthening the results of Zuk and Kotowski–Kotowski, who consider only groups in the (n, 3k, d) model.EPSRC studentshi

Photoswitchable diacylglycerols enable optical control of protein kinase C.

Increased levels of the second messenger lipid diacylglycerol (DAG) induce downstream signaling events including the translocation of C1-domain-containing proteins toward the plasma membrane. Here, we introduce three light-sensitive DAGs, termed PhoDAGs, which feature a photoswitchable acyl chain. The PhoDAGs are inactive in the dark and promote the translocation of proteins that feature C1 domains toward the plasma membrane upon a flash of UV-A light. This effect is quickly reversed after the termination of photostimulation or by irradiation with blue light, permitting the generation of oscillation patterns. Both protein kinase C and Munc13 can thus be put under optical control. PhoDAGs control vesicle release in excitable cells, such as mouse pancreatic islets and hippocampal neurons, and modulate synaptic transmission in Caenorhabditis elegans. As such, the PhoDAGs afford an unprecedented degree of spatiotemporal control and are broadly applicable tools to study DAG signaling