Molecular Basis of Prostate Cancer Diagnostics and Therapeutics

Prostate Cancer is now the second biggest cause of cancer mortality in the UK. Media coverage has been rising, with some attributing to a rise in the cases diagnosed and treated in the NHS down to the “Fry and Turnbull effect”. Our understanding of prostate cancer has increased tremendously in the past decades, with advances in molecular biology and genomics driving the way to new treatments and diagnostics. This Special Edition of Translational Andrology and Urology 2019: Prostate Cancer Biology and Genomics aims to review the current state of prostate cancer genomics, proteomics, diagnostics and treatment

Hydrodynamic induced deformation and orientation of a microscopic elastic filament

We describe simulations of a microscopic elastic filament immersed in a fluid and subject to a uniform external force. Our method accounts for the hydrodynamic coupling between the flow generated by the filament and the friction force it experiences. While models that neglect this coupling predict a drift in a straight configuration, our findings are very different. Notably, a force with a component perpendicular to the filament axis induces bending and perpendicular alignment. Moreover, with increasing force we observe four shape regimes, ranging from slight distortion to a state of tumbling motion that lacks a steady state. We also identify the appearance of marginally stable structures. Both the instability of these shapes and the observed alignment can be explained by the combined action of induced bending and non-local hydrodynamic interactions. Most of these effects should be experimentally relevant for stiff micro-filaments, such as microtubules.Comment: three figures. To appear in Phys Rev Let

Observations of mesoscale and boundary-layer circulations affecting dust uplift and transport in the Saharan boundary layer

International audienceObservations of the Saharan boundary layer, made during the GERBILS field campaign, show that mesoscale land surface temperature variations (which were related to albedo variations) induced mesoscale circulations, and that mesoscale and boundary-layer circulations affected dust uplift and transport. These processes are unrepresented in many climate models, but may have significant impacts on the vertical transport and uplift of desert dust. Mesoscale effects in particular tend to be difficult to parameterise. With weak winds along the aircraft track, land surface temperature anomalies with scales of greater than 10 km are shown to significantly affect boundary-layer temperatures and winds. Such anomalies are expected to affect the vertical mixing of the dusty and weakly stratified Saharan Air Layer (SAL). Mesoscale variations in winds are also shown to affect dust loadings in the boundary-layer. In a region of local uplift, with strong along-track winds, boundary-layer rolls are shown to lead to warm moist dusty updraughts in the boundary layer. Large eddy model (LEM) simulations suggest that these rolls increased uplift by approximately 30%. The modelled effects of boundary-layer convection on uplift is shown to be larger when the boundary-layer wind is decreased, and most significant when the mean wind is below the threshold for dust uplift and the boundary-layer convection leads to uplift which would not otherwise occur

Survival of near-critical branching Brownian motion

Consider a system of particles performing branching Brownian motion with negative drift $\mu = \sqrt{2 - \epsilon}$ and killed upon hitting zero. Initially there is one particle at $x>0$. Kesten showed that the process survives with positive probability if and only if $\epsilon>0$. Here we are interested in the asymptotics as \eps\to 0 of the survival probability $Q_\mu(x)$. It is proved that if $L= \pi/\sqrt{\epsilon}$ then for all $x \in \R$, $\lim_{\epsilon \to 0} Q_\mu(L+x) = \theta(x) \in (0,1)$ exists and is a travelling wave solution of the Fisher-KPP equation. Furthermore, we obtain sharp asymptotics of the survival probability when $x<L$ and $L-x \to \infty$. The proofs rely on probabilistic methods developed by the authors in a previous work. This completes earlier work by Harris, Harris and Kyprianou and confirms predictions made by Derrida and Simon, which were obtained using nonrigorous PDE methods

Lattice simulation method to model diffusion and NMR spectra in porous materials.

A coarse-grained simulation method to predict nuclear magnetic resonance (NMR) spectra of ions diffusing in porous carbons is proposed. The coarse-grained model uses input from molecular dynamics simulations such as the free-energy profile for ionic adsorption, and density-functional theory calculations are used to predict the NMR chemical shift of the diffusing ions. The approach is used to compute NMR spectra of ions in slit pores with pore widths ranging from 2 to 10 nm. As diffusion inside pores is fast, the NMR spectrum of an ion trapped in a single mesopore will be a sharp peak with a pore size dependent chemical shift. To account for the experimentally observed NMR line shapes, our simulations must model the relatively slow exchange between different pores. We show that the computed NMR line shapes depend on both the pore size distribution and the spatial arrangement of the pores. The technique presented in this work provides a tool to extract information about the spatial distribution of pore sizes from NMR spectra. Such information is difficult to obtain from other characterisation techniques.C.M. acknowledges the School of the Physical Sciences of the University of Cambridge for funding through an Oppenheimer Research Fellowship. C.M., A.C.F., J.M.G., and C.P.G. acknowledge the Sims Scholarship (A.C.F.), EPSRC (via the Supergen consortium, J.M.G.), and the EU ERC (via an Advanced Fellowship to C.P.G.) for funding. A.C.F. and J.M.G. thank the NanoDTC Cambridge for travel funding. D.F. acknowledges EPSRC Grant No. EP/I000844/1.This is the final published version. It first appeared at http://scitation.aip.org/content/aip/journal/jcp/142/9/10.1063/1.4913368

Observations of mesoscale and boundary-layer scale circulations affecting dust transport and uplift over the Sahara

Observations of the Saharan boundary layer, made during the GERBILS field campaign, show that mesoscale land surface temperature variations (which were related to albedo variations) induced mesoscale circulations. With weak winds along the aircraft track, land surface temperature anomalies with scales of greater than 10 km are shown to significantly affect boundary-layer temperatures and winds. Such anomalies are expected to affect the vertical mixing of the dusty and weakly stratified Saharan Residual Layer (SRL). Mesoscale variations in winds are also shown to affect dust loadings in the boundary layer. &lt;br&gt;&lt;br&gt; Using the aircraft observations and data from the COSMO model, a region of local dust uplift, with strong along-track winds, was identified in one low-level flight. Large eddy model (LEM) simulations based on this location showed linearly organised boundary-layer convection. Calculating dust uplift rates from the LEM wind field showed that the boundary-layer convection increased uplift by approximately 30%, compared with the uplift rate calculated neglecting the convection. The modelled effects of boundary-layer convection on uplift are shown to be larger when the boundary-layer wind is decreased, and most significant when the mean wind is below the threshold for dust uplift and the boundary-layer convection leads to uplift which would not otherwise occur. &lt;br&gt;&lt;br&gt; Both the coupling of albedo features to the atmosphere on the mesoscale, and the enhancement of dust uplift by boundary-layer convection are unrepresented in many climate models, but may have significant impacts on the vertical transport and uplift of desert dust. Mesoscale effects in particular tend to be difficult to parametrise

Ag on Ge(111): 2D X-ray structure analysis of the (Wurzel)3 x (Wurzel)3 superstructure

We have studied the Ag/Ge(111)(Wurzel)3 x (Wurzel)3 superstructure by grazing-incidence X-ray diffraction. In our structural analysis we find striking similarities to the geometry of Au on Si(111). The Ag atoms form trimer clusters with an Ag-Ag distance of 2.94+-0.04°A with the centers of the trimers being located at the origins of the (Wurzel)3 x (Wurzel)3 lattice. The Ag layer is incomplete and at least one substrate layer is distorted

Mapping the inhomogeneous electrochemical reaction through porous LiFePO&lt;inf&gt;4&lt;/inf&gt;-electrodes in a standard coin cell battery

[Image - see article] Nanosized, carbon-coated LiFePO4 (LFP) is a promising cathode for Li-ion batteries. However, nano-particles are problematic for electrode design, optimized electrodes requiring high tap densities, good electronic wiring, and a low tortuosity for efficient Li diffusion in the electrolyte in between the solid particles, conditions that are difficult to achieve simultaneously. Using in situ energy-dispersive X-ray diffraction, we map the evolution of the inhomogeneous electrochemical reaction in LFP-electrodes. On the first cycle, the dynamics are limited by Li diffusion in the electrolyte at a cycle rate of C/7. On the second cycle, there appear to be two rate-limiting processes: Li diffusion in the electrolyte and electronic conductivity through the electrode. Three-dimensional modeling based on porous electrode theory shows that this change in dynamics can be reproduced by reducing the electronic conductivity of the composite electrode by a factor of 8 compared to the first cycle. The poorer electronic wiring could result from the expansion and contraction of the particles upon cycling and/or the formation of a solid-electrolyte interphase layer. A lag was also observed perpendicular to the direction of the current: the LFP particles at the edges of the cathode reacted preferentially to those in the middle, owing to the closer proximity to the electrolyte source. Simulations show that, at low charge rates, the reaction becomes more uniformly distributed across the electrode as the porosity or the width of the particle-size distribution is increased. However, at higher rates, the reaction becomes less uniform and independent of the particle-size distribution.We acknowledge the Engineering Physical Science Research Council (EPSRC) for a Doctoral Training Account Award (for FCS) and the US Department of Energy (DOE) for support via the NECCES, an Energy Frontier Research Center (DE-SC0001294 and DE-SC0012583). FCS acknowledges the Science and Technology Facilities Council for travel funding through the Global Challenge Network in Batteries and Electrochemical Energy Devices. Synchrotron X-ray beamtime was provided by Diamond Light Source, under experiment number EE8385. We also thank Zlatko Saracevic at the Department of Chemical Engineering at the University of Cambridge for help with the BET experiments and Jon Rickard at the Department of Physics at the University of Cambridge for help with the SEM. Lastly; we thank Charles Monroe and Paul Shearing for discussions on this project.This is the final version of the article. It first appeared from ACS Publications via http://dx.doi.org/10.1021/cm504317