Stability analysis of non-autonomous reaction-diffusion systems: the effects of growing domains

By using asymptotic theory, we generalise the Turing diffusively-driven instability conditions for reaction-diffusion systems with slow, isotropic domain growth. There are two fundamental biological differences between the Turing conditions on fixed and growing domains, namely: (i) we need not enforce cross nor pure kinetic conditions and (ii) the restriction to activator-inhibitor kinetics to induce pattern formation on a growing biological system is no longer a requirement. Our theoretical findings are confirmed and reinforced by numerical simulations for the special cases of isotropic linear, exponential and logistic growth profiles. In particular we illustrate an example of a reaction-diffusion system which cannot exhibit a diffusively-driven instability on a fixed domain but is unstable in the presence of slow growth

Cell-scale degradation of peritumoural extracellular matrix fibre network and its role within tissue-scale cancer invasion

Local cancer invasion of tissue is a complex, multiscale process which plays an essential role in tumour progression. Occurring over many different temporal and spatial scales, the first stage of invasion is the secretion of matrix degrading enzymes (MDEs) by the cancer cells that consequently degrade the surrounding extracellular matrix (ECM). This process is vital for creating space in which the cancer cells can progress and it is driven by the activities of specific matrix metalloproteinases (MMPs). In this paper, we consider the key role of two MMPs by developing further the novel two-part multiscale model introduced in [33] to better relate at micro-scale the two micro-scale activities that were considered there, namely, the micro-dynamics concerning the continuous rearrangement of the naturally oriented ECM fibres within the bulk of the tumour and MDEs proteolytic micro-dynamics that take place in an appropriate cell-scale neighbourhood of the tumour boundary. Focussing primarily on the activities of the membrane-tethered MT1-MMP and the soluble MMP-2 with the fibrous ECM phase, in this work we investigate the MT1-MMP/MMP-2 cascade and its overall effect on tumour progression. To that end, we will propose a new multiscale modelling framework by considering the degradation of the ECM fibres not only to take place at macro-scale in the bulk of the tumour but also explicitly in the micro-scale neighbourhood of the tumour interface as a consequence of the interactions with molecular fluxes of MDEs that exercise their spatial dynamics at the invasive edge of the tumour

Multiscale models for movement in oriented environments and their application to hilltopping in butterflies

Hilltopping butterflies direct their movement in response to topography, facilitating mating encounters via accumulation at summits. In this paper, we take hilltopping as a case study to explore the impact of complex orienteering cues on population dynamics. The modelling employs a standard multiscale framework, in which an individual's movement path is described as a stochastic 'velocity-jump' process and scaling applied to generate a macroscopic model capable of simulating large populations in landscapes. In this manner, the terms and parameters of the macroscopic model directly relate to statistical inputs of the individual-level model (mean speeds, turning rates and turning distributions). Applied to hilltopping in butterflies, we demonstrate how hilltopping acts to aggregate populations at summits, optimising mating for low-density species. However, for abundant populations, hilltopping is not only less effective but also possibly disadvantageous, with hilltopping males recording a lower mating rate than their non-hilltopping competitors. © 2013 Springer Science+Business Media Dordrecht

The structure of the PapD-PapGII pilin complex reveals an open and flexible P5 pocket

P pili are hairlike polymeric structures that mediate binding of uropathogenic Escherichia coli to the surface of the kidney via the PapG adhesin at their tips. PapG is composed of two domains: a lectin domain at the tip of the pilus followed by a pilin domain that comprises the initial polymerizing subunit of the 1,000-plus-subunit heteropolymeric pilus fiber. Prior to assembly, periplasmic pilin domains bind to a chaperone, PapD. PapD mediates donor strand complementation, in which a beta strand of PapD temporarily completes the pilin domain's fold, preventing premature, nonproductive interactions with other pilin subunits and facilitating subunit folding. Chaperone-subunit complexes are delivered to the outer membrane usher where donor strand exchange (DSE) replaces PapD's donated beta strand with an amino-terminal extension on the next incoming pilin subunit. This occurs via a zip-in-zip-out mechanism that initiates at a relatively accessible hydrophobic space termed the P5 pocket on the terminally incorporated pilus subunit. Here, we solve the structure of PapD in complex with the pilin domain of isoform II of PapG (PapGIIp). Our data revealed that PapGIIp adopts an immunoglobulin fold with a missing seventh strand, complemented in parallel by the G1 PapD strand, typical of pilin subunits. Comparisons with other chaperone-pilin complexes indicated that the interactive surfaces are highly conserved. Interestingly, the PapGIIp P5 pocket was in an open conformation, which, as molecular dynamics simulations revealed, switches between an open and a closed conformation due to the flexibility of the surrounding loops. Our study reveals the structural details of the DSE mechanism

Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort

Data from epidemiological and animal model studies suggest that nutrition during pregnancy may affect the health status of subsequent generations. These transgenerational effects are now being explained by disruptions at the level of the epigenetic machinery. Besides in vitro environmental exposures, the possible impact on the reprogramming of methylation profiles at imprinted genes at a much earlier time point, such as during spermatogenesis or oogenesis, has not previously been considered. In this study, our aim was to determine associations between preconceptional obesity and DNA methylation profiles in the offspring, particularly at the differentially methylated regions (DMRs) of the imprinted Insulin-like Growth Factor 2 (IGF2) gene

A simulation study comparing aberration detection algorithms for syndromic surveillance

BACKGROUND: The usefulness of syndromic surveillance for early outbreak detection depends in part on effective statistical aberration detection. However, few published studies have compared different detection algorithms on identical data. In the largest simulation study conducted to date, we compared the performance of six aberration detection algorithms on simulated outbreaks superimposed on authentic syndromic surveillance data. METHODS: We compared three control-chart-based statistics, two exponential weighted moving averages, and a generalized linear model. We simulated 310 unique outbreak signals, and added these to actual daily counts of four syndromes monitored by Public Health – Seattle and King County's syndromic surveillance system. We compared the sensitivity of the six algorithms at detecting these simulated outbreaks at a fixed alert rate of 0.01. RESULTS: Stratified by baseline or by outbreak distribution, duration, or size, the generalized linear model was more sensitive than the other algorithms and detected 54% (95% CI = 52%–56%) of the simulated epidemics when run at an alert rate of 0.01. However, all of the algorithms had poor sensitivity, particularly for outbreaks that did not begin with a surge of cases. CONCLUSION: When tested on county-level data aggregated across age groups, these algorithms often did not perform well in detecting signals other than large, rapid increases in case counts relative to baseline levels

Modeling Diffusion Directions of Corpus Callosum

Diffusion Tensor Imaging (DTI) has been used to study the characteristics of Multiple Sclerosis (MS) in the brain. The von Mises- Fisher distribution (vmf) is a probability distribution for modeling directional data on the unit hypersphere. In this paper we modeled the diffusion directions of the Corpus Callosum (CC) as a mixture of vmf distributions for both MS subjects and healthy controls. Higher diffusion concentration around the mean directions and smaller sum of angles between the mean directions are observed on the normal-appearing CC of the MS subjects as compared to the healthy controls

Single Mode Lasing from Hybrid Hemispherical Microresonators

Enormous attention has been paid to optical microresonators which hold a great promise for microlasers as well as fundamental studies in cavity quantum electrodynamics. Here we demonstrate a three-dimensional (3D) hybrid microresonator combining self-assembled hemispherical structure with a planar reflector. By incorporating dye molecules into the hemisphere, optically pumped lasing phenomenon is observed at room temperature. We have studied the lasing behaviors with different cavity sizes, and particularly single longitudinal mode lasing from hemispheres with diameter ∼15 μm is achieved. Detailed characterizations indicate that the lasing modes shift under varying pump densities, which can be well-explained by frequency shift and mode hopping. This work provides a versatile approach for 3D confined microresonators and opens an opportunity to realize tunable single mode microlasers

Laser oscillation in a strongly coupled single quantum dot-nanocavity system

Strong coupling of photons and materials in semiconductor nanocavity systems has been investigated because of its potentials in quantum information processing and related applications, and has been testbeds for cavity quantum electrodynamics (QED). Interesting phenomena such as coherent exchange of a single quantum between a single quantum dot and an optical cavity, called vacuum Rabi oscillation, and highly efficient cavity QED lasers have been reported thus far. The coexistence of vacuum Rabi oscillation and laser oscillation appears to be contradictory in nature, because the fragile reversible process may not survive in laser oscillation. However, recently, it has been theoretically predicted that the strong-coupling effect could be sustained in laser oscillation in properly designed semiconductor systems. Nevertheless, the experimental realization of this phenomenon has remained difficult since the first demonstration of the strong-coupling, because an extremely high cavity quality factor and strong light-matter coupling are both required for this purpose. Here, we demonstrate the onset of laser oscillation in the strong-coupling regime in a single quantum dot (SQD)-cavity system. A high-quality semiconductor optical nanocavity and strong SQD-field coupling enabled to the onset of lasing while maintaining the fragile coherent exchange of quanta between the SQD and the cavity. In addition to the interesting physical features, this device is seen as a prototype of an ultimate solid state light source with an SQD gain, which operates at ultra-low power, with expected applications in future nanophotonic integrated systems and monolithic quantum information devices.Comment: 12 pages, 4 figure

A Comparative Approach Linking Molecular Dynamics of Altered Peptide Ligands and MHC with In Vivo Immune Responses

The recognition of peptide in the context of MHC by T lymphocytes is a critical step in the initiation of an adaptive immune response. However, the molecular nature of the interaction between peptide and MHC and how it influences T cell responsiveness is not fully understood.We analyzed the immunological consequences of the interaction of MHC class II (I-Au) restricted 11-mer peptides of myelin basic protein with amino acid substitutions at position 4. These mutant peptides differ in MHC binding affinity, CD4+ T cell priming, and alter the severity of peptide-induced experimental allergic encephalomyelitis. Using molecular dynamics, a computational method of quantifying intrinsic movements of proteins at high resolution, we investigated conformational changes in MHC upon peptide binding. We found that irrespective of peptide binding affinity, MHC deformation appears to influence costimulation, which then leads to effective T cell priming and disease induction. Although this study compares in vivo and molecular dynamics results for three altered peptide ligands, further investigation with similar complexes is essential to determine whether spatial rearrangement of peptide-MHC and costimulatory complexes is an additional level of T cell regulation