Supported Membranes on Chemically Structured and Rough Surfaces

We present a general linear response description of membrane adhesion at rough or chemically structured surfaces. Our method accounts for non-local Van der Waals effects and contains the more approximate (and local) Deryagin approach in a simple limit. Specializing to supported membranes we consider the effects of substrate structure on the membrane adhesion energy and configuration. Adhesion is usually less favorable for rough substrates and the membrane shape tends to follow that of the surface contours. Chemical patterning, however, favors adhesion with the membrane configuration being out of phase with the surface structure. Finally, considering a surface indented with `V'-shaped trenches, we show that our approach is in fair agreement with an exact numerical solution.Comment: 21 pages, 7 ps figures, submitted to PR

Ultrasensitivity in phosphorylation-dephosphorylation cycles with little substrate

Cellular decision-making is driven by dynamic behaviours, such as the preparations for sunrise enabled by circadian rhythms and the choice of cell fates enabled by positive feedback. Such behaviours are often built upon ultrasensitive responses where a linear change in input generates a sigmoidal change in output. Phosphorylation-dephosphorylation cycles are one means to generate ultrasensitivity. Using bioinformatics, we show that in vivo levels of kinases and phosphatases frequently exceed the levels of their corresponding substrates in budding yeast. This result is in contrast to the conditions often required by zero-order ultrasensitivity, perhaps the most well known means for how such cycles become ultrasensitive. We therefore introduce a mechanism to generate ultrasensitivity when numbers of enzymes are higher than numbers of substrates. Our model combines distributive and non-distributive actions of the enzymes with two-stage binding and concerted allosteric transitions of the substrate. We use analytical and numerical methods to calculate the Hill number of the response. For a substrate with [Formula: see text] phosphosites, we find an upper bound of the Hill number of [Formula: see text], and so even systems with a single phosphosite can be ultrasensitive. Two-stage binding, where an enzyme must first bind to a binding site on the substrate before it can access the substrate's phosphosites, allows the enzymes to sequester the substrate. Such sequestration combined with competition for each phosphosite provides an intuitive explanation for the sigmoidal shifts in levels of phosphorylated substrate. Additionally, we find cases for which the response is not monotonic, but shows instead a peak at intermediate levels of input. Given its generality, we expect the mechanism described by our model to often underlay decision-making circuits in eukaryotic cells

Using accelerometer, high sample rate GPS and magnetometer data to develop a cattle movement and behaviour model

The study described in this paper developed a model of animal movement, which explicitly recognised each individual as the central unit of measure. The model was developed by learning from a real dataset that measured and calculated, for individual cows in a herd, their linear and angular positions and directional and angular speeds. Two learning algorithms were implemented: a Hidden Markov model (HMM) and a long-term prediction algorithm. It is shown that a HMM can be used to describe the animal's movement and state transition behaviour within several “stay” areas where cows remained for long periods. Model parameters were estimated for hidden behaviour states such as relocating, foraging and bedding. For cows’ movement between the “stay” areas a long-term prediction algorithm was implemented. By combining these two algorithms it was possible to develop a successful model, which achieved similar results to the animal behaviour data collected. This modelling methodology could easily be applied to interactions of other animal specie

Tracing the Sources of Cellular Variation

As the adage says, variety is the spice of life, and despite our best attempts, cells, even those with the same genome, never seem to behave the same. By combining mathematical and experimental analyses, Colman-Lerner and colleagues propose, in a recent issue of Nature, a method to delicately unravel the sources of this variation (Colman-Lerner et al., 2005). Applying their technique to the pheromone response in budding yeast, they show that much of the observed variation originates from cell cycle effects and is dependent on levels of pathway input

Accurate prediction of gene feedback circuit behavior from component properties

A basic assumption underlying synthetic biology is that analysis of genetic circuit elements, such as regulatory proteins and promoters, can be used to understand and predict the behavior of circuits containing those elements. To test this assumption, we used time‐lapse fluorescence microscopy to quantitatively analyze two autoregulatory negative feedback circuits. By measuring the gene regulation functions of the corresponding repressor–promoter interactions, we accurately predicted the expression level of the autoregulatory feedback loops, in molecular units. This demonstration that quantitative characterization of regulatory elements can predict the behavior of genetic circuits supports a fundamental requirement of synthetic biology

Influence of noise intensity on the spectrum of an oscillator

This paper investigates the influence of high-intensity noise on the correlation spectrum of a two-dimensional (2-D) nonlinear oscillator. An exact analytical solution for the correlation spectrum of this 2-D oscillator is provided. The analytical derivations are well suited for oscillators with white noise of any intensity, but computational constraints on the solution of the partial differential equation may make it impractical for cases where the number of state variables exceeds three. The spectral results predicted by our analytical method are verified by numerical simulations of the noisy oscillator in the time domain. We find that the peak of the oscillator spectrum shifts toward higher frequencies as the noise intensity is increased, as opposed to the fixed oscillation frequency predicted in the existing literature. This phenomenon does not appear to have been reported previously in the context of phase noise in oscillators

Keck Interferometer: from development phase to facility-class instrument

The Keck Interferometer is entering a regular limited observational phase. A restricted number of observers are expected to use the instrument over the course of the next few years in a shared-risk capacity. To facilitate this, the W. M. Keck Observatory and the Jet Propulsion Laboratory are following a Handover procedure consisting of a number of stages related to the science modes of the instrument as they reach completion. The first of these is the Visibility Science mode that involves only the two Keck telescopes. Other modes to follow are Nulling, Differential Phase, Astrometry, and Imaging. The process includes defining a reasonable level of functionality of each mode, training observatory staff to maintain and schedule tasks related to the upkeep of each mode, and defining and documenting each of the subsystems related to each mode. Here we discuss the outline of the Handover plan and report on its progress to date

Outline for a discussion forum on citizens' action: how bridging the accountability gap leads to water and sanitation service provision

Outline for a discussion forum on citizens' action: how bridging the accountability gap leads to water and sanitation service provisio