Bayesian Learning and Predictability in a Stochastic Nonlinear Dynamical Model

Bayesian inference methods are applied within a Bayesian hierarchical modelling framework to the problems of joint state and parameter estimation, and of state forecasting. We explore and demonstrate the ideas in the context of a simple nonlinear marine biogeochemical model. A novel approach is proposed to the formulation of the stochastic process model, in which ecophysiological properties of plankton communities are represented by autoregressive stochastic processes. This approach captures the effects of changes in plankton communities over time, and it allows the incorporation of literature metadata on individual species into prior distributions for process model parameters. The approach is applied to a case study at Ocean Station Papa, using Particle Markov chain Monte Carlo computational techniques. The results suggest that, by drawing on objective prior information, it is possible to extract useful information about model state and a subset of parameters, and even to make useful long-term forecasts, based on sparse and noisy observations

Hierarchical Emulation & Data Assimilation into the Sediment Transport Model

AbstractSynthetic observations of the suspended sediment concentration in an idealised macro-tidal estuary are assimilated into the 3d sediment transport model. The assimilation scheme relies on fast and cheap surrogates of the complex model (called emulators) to update the model's state variables and its 2 parameters. A scenario with a hierarchically structured emulator is contrasted to the scenario with a more conventional non-hierarchical emulator. Numerical experiments indicate that for a given size of the ensemble an emulator which replicates a hierarchical structure of the model tends to provide a better approximation of that model. Improving the quality of the emulator translates into the improved quality of the assimilation products

Simplified Algorithms for Determining Cycle Shift between qPCR Fluorescence Curves

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.The polymerase chain reaction is a central component of current molecular biology. It is a cyclic process, in each early cycle of which the template DNA approximately doubles. An indicator which fluoresces when bound to DNA quantifies the DNA present at the end of each cycle, giving rise to a fluorescence curve which is characteristically sigmoid in shape. The fluorescence curve quantifies the amount of DNA initially present; the more the initial DNA, the earlier the rise in the fluorescence. Accordingly the amount of DNA initially present in two samples can be compared: the sample with the less DNA gives rise to a relatively delayed fluorescence curve and the ratio of the DNAs can be deduced from the separation of the curves. There is, however, a second determinant of this separation, the fold increase in DNA per cycle: ideally a twofold increase but frequently less. Current guidelines recommend that this be determined experimentally by carrying out PCR on a series of dilutions. If the value of the fold increase is known, then the algorithm for determining the separation can be reduced to a relatively simple computation, rather than employing a multidimensional nonlinear optimization such as the Marquardt-Levenberg as currently employed

A fixed-point algorithm for estimating amplification efficiency from a polymerase chain reaction dilution series

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background The polymerase chain reaction amplifies and quantifies small amounts of DNA. It is a cyclic process, during each cycle of which each strand of template DNA is copied with probability approaching one: the amount of DNA approximately doubles and this amount can be estimated fluorimetrically each cycle, producing a set of fluorescence values hereafter referred to as the amplification curve. Commonly the biological question of relevance is one of the ratio of DNA concentrations in two samples: a ratio that is deduced by comparing the two amplification curves, usually by way of a plot of fluorescence against cycle number. Central to this analysis is measuring the extent to which one amplification curve is shifted relative to the other, a measurement often accomplished by defining a threshold or quantification cycle, Cq, for each curve: the fractional cycle number at which fluorescence reaches some threshold or at which some other criterion (maximum slope, maximum rate of change of slope) is satisfied. We propose an alternative where position is measured relative to a reference curve; position equates to the cycle shift which maximizes the correlation between the reference and the observed fluorescence sequence. A key parameter of the reference curve is obtained by fixed-point convergence. Results We consider the analysis of dilution series constructed for the estimation of qPCR amplification efficiency. The estimate of amplification efficiency is based on the slope of the regression line when the Cq is plotted against the logarithm of dilution. We compare the approach to three commonly used methods for determining Cq; each is applied to publicly accessible calibration data sets, and to ten from our own laboratory. As in the established literature we judge their relative merits both from the standard deviation of the slope of the calibration curve, and from the variance in Cq for replicate fluorescence curves. Conclusions The approach does not require modification of experimental protocols, and can be applied retrospectively to existing data. We recommend that it be added to the methodological toolkit with which laboratories interpret their real-time PCR data. Keywords: qPCR; Fixed-point; Amplification efficienc

Use of remote-sensing reflectance to constrain a data assimilating marine biogeochemical model of the Great Barrier Reef

Skillful marine biogeochemical (BGC) models are required to understand a range of coastal and global phenomena such as changes in nitrogen and carbon cycles. The refinement of BGC models through the assimilation of variables calculated from observed in-water inherent optical properties (IOPs), such as phytoplankton absorption, is problematic. Empirically derived relationships between IOPs and variables such as chlorophyll-a concentration (Chl a), total suspended solids (TSS) and coloured dissolved organic matter (CDOM) have been shown to have errors that can exceed 100% of the observed quantity. These errors are greatest in shallow coastal regions, such as the Great Barrier Reef (GBR), due to the additional signal from bottom reflectance. Rather than assimilate quantities calculated using IOP algorithms, this study demonstrates the advantages of assimilating quantities calculated directly from the less error-prone satellite remote-sensing reflectance (RSR). To assimilate the observed RSR, we use an in-water optical model to produce an equivalent simulated RSR and calculate the mismatch between the observed and simulated quantities to constrain the BGC model with a deterministic ensemble Kalman filter (DEnKF). The traditional assumption that simulated surface Chl a is equivalent to the remotely sensed OC3M estimate of Chl a resulted in a forecast error of approximately 75 %. We show this error can be halved by instead using simulated RSR to constrain the model via the assimilation system. When the analysis and forecast fields from the RSR-based assimilation system are compared with the non-assimilating model, a comparison against independent in situ observations of Chl a, TSS and dissolved inorganic nutrients (NO3, NH4 and DIP) showed that errors are reduced by up to 90 %. In all cases, the assimilation system improves the simulation compared to the non-assimilating model. Our approach allows for the incorporation of vast quantities of remote-sensing observations that have in the past been discarded due to shallow water and/or artefacts introduced by terrestrially derived TSS and CDOM or the lack of a calibrated regional IOP algorithm

On misunderstanding Heraclitus: The justice of organisation structure

Writers on organisational change often refer to the cosmology of Heraclitus in their work. Some use these references to support arguments for the constancy and universality of organisational change and the consignment to history of organisational continuity and stability. These writers misunderstand the scope of what Heraclitus said. Other writers focus exclusively on the idea that originated with Heraclitus that the universe is composed of processes and not of things. This idea, which has been particularly associated with Heraclitus’s thought from the time of Plato, does indeed provide a rich source of insights into organisational analysis, not least the current trends towards giving proper attention to processual studies of organisational change. Yet there is some uncertainty as to whether Heraclitus actually said that the universe was composed exclusively of processes rather than things, and even if that was what he thought, he intended his ideas on flux to be understood not in isolation but in the context of other aspects of his cosmology. Writers on organisational change seldom make reference to this wider context. Heraclitus was a rational but also a religious thinker. A central element in his thought was the notion of divine Justice, which to a Greek of his era meant the order of the universe. Remote as his Olympian theology may seem today, it sets a crucial and entirely rational context for understanding his ideas about flux. It means that ideas about continuity and stability were quite as important in Heraclitus’s cosmology as his more commonly quoted ideas about change. This paper sets out an overview of Heraclitus’s philosophy, insofar as it appears to have potential relevance to organisational analysis, and discusses how far it supports or contradicts the ideas that organisational change scholars have drawn from it

Initial characteristics of RbcX proteins from Arabidopsis thaliana

Form I of Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase) is composed of eight large (RbcL) and eight small (RbcS) subunits. Assembly of these subunits into a functional holoenzyme requires the assistance of additional assembly factors. One such factor is RbcX, which has been demonstrated to act as a chaperone in the assembly of most cyanobacterial Rubisco complexes expressed in heterologous system established in Escherichia coli cells. Analysis of Arabidopsis thaliana genomic sequence revealed the presence of two genes encoding putative homologues of cyanobacterial RbcX protein: AtRbcX1 (At4G04330) and AtRbcX2 (At5G19855). In general, both RbcX homologues seem to have the same function which is chaperone activity during Rubisco biogenesis. However, detailed analysis revealed slight differences between them. AtRbcX2 is localized in the stromal fraction of chloroplasts whereas AtRbcX1 was found in the insoluble fraction corresponding with thylakoid membranes. Search for putative “partners” using mass spectrometry analysis suggested that apart from binding to RbcL, AtRbcX1 may also interact with β subunit of chloroplast ATP synthase. Quantitative RT-PCR analysis of AtRbcX1 and AtRbcX2 expression under various stress conditions indicated that AtRbcX2 is transcribed at a relatively stable level, while the transcription level of AtRbcX1 varies significantly. In addition, we present the attempts to elucidate the secondary structure of AtRbcX proteins using CD spectroscopy. Presented results are the first known approach to elucidate the role of RbcX proteins in Rubisco assembly in higher plants

An Association of Cancer Physicians' strategy for improving services and outcomes for cancer patients.

The Association of Cancer Physicians in the United Kingdom has developed a strategy to improve outcomes for cancer patients and identified the goals and commitments of the Association and its members.The ACP is very grateful to all of its members who have expressed views on the development of the strategy and to the sponsors of our workshops and publications, especially Cancer Research UK and Macmillan Cancer SupportThis is the final version of the article. It was first available from Cancer Intelligence via http://dx.doi.org/10.3332/ecancer.2016.60

Directing the evolution of Rubisco and Rubisco activase: first impressions of a new tool for photosynthesis research

During the last decade the practice of laboratory-directed protein evolution has become firmly established as a versatile tool in biochemical research by enabling molecular evolution toward desirable phenotypes or detection of novel structure–function interactions. Applications of this technique in the field of photosynthesis research are still in their infancy, but recently first steps have been reported in the directed evolution of the CO2-fixing enzyme Rubisco and its helper protein Rubisco activase. Here we summarize directed protein evolution strategies and review the progressive advances that have been made to develop and apply suitable selection systems for screening mutant forms of these enzymes that improve the fitness of the host organism. The goal of increasing photosynthetic efficiency of plants by improving the kinetics of Rubisco has been a long-term goal scoring modest successes. We discuss how directed evolution methodologies may one day be able to circumvent the problems encountered during this venture