Mean first-passage time of surface-mediated diffusion in spherical domains

We present an exact calculation of the mean first-passage time to a target on the surface of a 2D or 3D spherical domain, for a molecule alternating phases of surface diffusion on the domain boundary and phases of bulk diffusion. The presented approach is based on an integral equation which can be solved analytically. Numerically validated approximation schemes, which provide more tractable expressions of the mean first-passage time are also proposed. In the framework of this minimal model of surface-mediated reactions, we show analytically that the mean reaction time can be minimized as a function of the desorption rate from the surface.Comment: to appear in J. Stat. Phy

Kinetics of active surface-mediated diffusion in spherically symmetric domains

We present an exact calculation of the mean first-passage time to a target on the surface of a 2D or 3D spherical domain, for a molecule alternating phases of surface diffusion on the domain boundary and phases of bulk diffusion. We generalize the results of [J. Stat. Phys. {\bf 142}, 657 (2011)] and consider a biased diffusion in a general annulus with an arbitrary number of regularly spaced targets on a partially reflecting surface. The presented approach is based on an integral equation which can be solved analytically. Numerically validated approximation schemes, which provide more tractable expressions of the mean first-passage time are also proposed. In the framework of this minimal model of surface-mediated reactions, we show analytically that the mean reaction time can be minimized as a function of the desorption rate from the surface.Comment: Published online in J. Stat. Phy

Aging dynamics in a colloidal glass of Laponite

The aging dynamics of colloidal suspensions of Laponite, a synthetic clay, is investigated using dynamic light stattering (DLS) and viscometry after a quench into the glassy phase. DLS allows to follow the diffusion of Laponite particles and reveals that there are two modes of relaxation. The fast mode corresponds to a rapid diffusion of particles within "cages" formed by the neighboring particles. The slow mode corresponds to escape from the cages: its average relaxation time increases exponentially fast with the age of the glass. In addition, the slow mode has a broad distribution of relaxation times, its distribution becoming larger as the system ages. Measuring the concomitant increase of viscosity as the system ages, we can relate the slowing down of the particle dynamics to the viscosity.Comment: 9 pages, 8 Postscript figures, submitted to Phys. Rev.

Transfer RNA-derived small RNAs in the cancer transcriptome

The cellular lifetime includes stages such as differentiation, proliferation, division, senescence and apoptosis.These stages are driven by a strictly ordered process of transcription dynamics. Molecular disruption to RNA polymerase assembly, chromatin remodelling and transcription factor binding through to RNA editing, splicing, post-transcriptional regulation and ribosome scanning can result in significant costs arising from genome instability. Cancer development is one example of when such disruption takes place. RNA silencing is a term used to describe the effects of post-transcriptional gene silencing mediated by a diverse set of small RNA molecules. Small RNAs are crucial for regulating gene expression and microguarding genome integrity.RNA silencing studies predominantly focus on small RNAs such as microRNAs, short-interfering RNAs and piwi-interacting RNAs. We describe an emerging renewal of inter-est in a‘larger’small RNA, the transfer RNA (tRNA).Precisely generated tRNA-derived small RNAs, named tRNA halves (tiRNAs) and tRNA fragments (tRFs), have been reported to be abundant with dysregulation associated with cancer. Transfection of tiRNAs inhibits protein translation by displacing eukaryotic initiation factors from messenger RNA (mRNA) and inaugurating stress granule formation.Knockdown of an overexpressed tRF inhibits cancer cell proliferation. Recovery of lacking tRFs prevents cancer metastasis. The dual oncogenic and tumour-suppressive role is typical of functional small RNAs. We review recent reports on tiRNA and tRF discovery and biogenesis, identification and analysis from next-generation sequencing data and a mechanistic animal study to demonstrate their physiological role in cancer biology. We propose tRNA-derived small RNA-mediated RNA silencing is an innate defence mechanism to prevent oncogenic translation. We expect that cancer cells are percipient to their ablated control of transcription and attempt to prevent loss of genome control through RNA silencing

Chord distribution functions of three-dimensional random media: Approximate first-passage times of Gaussian processes

The main result of this paper is a semi-analytic approximation for the chord distribution functions of three-dimensional models of microstructure derived from Gaussian random fields. In the simplest case the chord functions are equivalent to a standard first-passage time problem, i.e., the probability density governing the time taken by a Gaussian random process to first exceed a threshold. We obtain an approximation based on the assumption that successive chords are independent. The result is a generalization of the independent interval approximation recently used to determine the exponent of persistence time decay in coarsening. The approximation is easily extended to more general models based on the intersection and union sets of models generated from the iso-surfaces of random fields. The chord distribution functions play an important role in the characterization of random composite and porous materials. Our results are compared with experimental data obtained from a three-dimensional image of a porous Fontainebleau sandstone and a two-dimensional image of a tungsten-silver composite alloy.Comment: 12 pages, 11 figures. Submitted to Phys. Rev.

Diffusion on random site percolation clusters. Theory and NMR microscopy experiments with model objects

Quasi two-dimensional random site percolation model objects were fabricate based on computer generated templates. Samples consisting of two compartments, a reservoir of H$_2$O gel attached to a percolation model object which was initially filled with D$_2$O, were examined with NMR (nuclear magnetic resonance) microscopy for rendering proton spin density maps. The propagating proton/deuteron inter-diffusion profiles were recorded and evaluated with respect to anomalous diffusion parameters. The deviation of the concentration profiles from those expected for unobstructed diffusion directly reflects the anomaly of the propagator for diffusion on a percolation cluster. The fractal dimension of the random walk, $d_w$, evaluated from the diffusion measurements on the one hand and the fractal dimension, $d_f$, deduced from the spin density map of the percolation object on the other permits one to experimentally compare dynamical and static exponents. Approximate calculations of the propagator are given on the basis of the fractional diffusion equation. Furthermore, the ordinary diffusion equation was solved numerically for the corresponding initial and boundary conditions for comparison. The anomalous diffusion constant was evaluated and is compared to the Brownian case. Some ad hoc correction of the propagator is shown to pay tribute to the finiteness of the system. In this way, anomalous solutions of the fractional diffusion equation could experimentally be verified for the first time.Comment: REVTeX, 12 figures in GIF forma

The Human Fungal Pathogen Cryptococcus neoformans Escapes Macrophages by a Phagosome Emptying Mechanism That Is Inhibited by Arp2/3 Complex-Mediated Actin Polymerisation

The lysis of infected cells by disease-causing microorganisms is an efficient but risky strategy for disseminated infection, as it exposes the pathogen to the full repertoire of the host's immune system. Cryptococcus neoformans is a widespread fungal pathogen that causes a fatal meningitis in HIV and other immunocompromised patients. Following intracellular growth, cryptococci are able to escape their host cells by a non-lytic expulsive mechanism that may contribute to the invasion of the central nervous system. Non-lytic escape is also exhibited by some bacterial pathogens and is likely to facilitate long-term avoidance of the host immune system during latency. Here we show that phagosomes containing intracellular cryptococci undergo repeated cycles of actin polymerisation. These actin ‘flashes’ occur in both murine and human macrophages and are dependent on classical WASP-Arp2/3 complex mediated actin filament nucleation. Three dimensional confocal imaging time lapse revealed that such flashes are highly dynamic actin cages that form around the phagosome. Using fluorescent dextran as a phagosome membrane integrity probe, we find that the non-lytic expulsion of Cryptococcus occurs through fusion of the phagosome and plasma membranes and that, prior to expulsion, 95% of phagosomes become permeabilised, an event that is immediately followed by an actin flash. By using pharmacological agents to modulate both actin dynamics and upstream signalling events, we show that flash occurrence is inversely related to cryptococcal expulsion, suggesting that flashes may act to temporarily inhibit expulsion from infected phagocytes. In conclusion, our data reveal the existence of a novel actin-dependent process on phagosomes containing cryptococci that acts as a potential block to expulsion of Cryptococcus and may have significant implications for the dissemination of, and CNS invasion by, this organism.\ud \u

Automated Analysis of Cryptococcal Macrophage Parasitism Using GFP-Tagged Cryptococci

The human fungal pathogens Cryptococcus neoformans and C. gattii cause life-threatening infections of the central nervous system. One of the major characteristics of cryptococcal disease is the ability of the pathogen to parasitise upon phagocytic immune effector cells, a phenomenon that correlates strongly with virulence in rodent models of infection. Despite the importance of phagocyte/Cryptococcus interactions to disease progression, current methods for assaying virulence in the acrophage system are both time consuming and low throughput. Here, we introduce the first stable and fully characterised GFP–expressing derivatives of two widely used cryptococcal strains: C. neoformans serotype A type strain H99 and C. gattii serotype B type strain R265. Both strains show unaltered responses to environmental and host stress conditions and no deficiency in virulence in the macrophage model system. In addition, we report the development of a method to effectively and rapidly investigate macrophage parasitism by flow cytometry, a technique that preserves the accuracy of current approaches but offers a four-fold improvement in speed

Accentuating institutional brands: A multimodal analysis of the homepages of selected South African universities

In seeking to disentangle themselves from the constraints of apartheid, South African universities have immersed themselves in an identity modification process in which they not only seek to redress the past, but also to reposition their identities as equal opportunity and non-racial institutions. In this paper, we investigate how the University of the Western Cape, the University of Cape Town and Stellenbosch University have used visual and verbal semiotics to re-design their identities on their homepages to appeal to diverse national and international clients. Using Multimodal Discourse Analysis (MDA), we show how the multi-semiotic choices work together on the homepages to give the universities differentiated, competitive, powerful and attractive brands. We conclude that the homepages blended cultural semiotic artefacts, historical, global and transformational discourses, and architectural landscapes to construct different brand identities that, in turn, rebrand the universities from edifices of apartheid education to equal opportunity institutions

The Latest Evidence with Regards to Femtosecond Laser-Assisted Cataract Surgery and Its Use Post 2020.

Femtosecond laser-assisted cataract surgery (FLACS) was introduced with the hope of making cataract surgery safer and making the refractive result more predictable. It is only in the last four years that level 1 prospective randomised controlled trials (RCT) using current technology have been published. These, along with a meta-analysis of recent studies have shown that there seems to be little long-term visual benefit when using FLACS with monofocal lenses. The promised decrease in ultrasound energy required to remove a cataract has not been consistently demonstrated. There is level one evidence that the rate of posterior capsular rupture is less with FLACS using modern software. The round capsulotomy may be of increasing importance with the uptake of toric, multifocal and extended depth of focus lenses where a predictable capsulotomy size and precise placement of the lens becomes more important