Steady State Analysis of Flexible Nets

The modeling and analysis of complex dynamic systems, such as those in manufacturing, logistics and biology, require powerful analysis methods for their study and optimization. A significant modeling and analysis challenge posed by both, artificial and natural systems, is the existence of uncertain parameters. Flexible Nets is a novel modeling formalism, inspired by Petri nets, that can handle different types of uncertain parameters in a natural way. This paper develops an efficient method to analyse the evolution of a system modeled by a Flexible Net in the long run. More precisely, the method focuses on the computation of steady state bounds for an objective function of interest. The method makes use of a set of constraints, expressed as linear inequalities, that the state variables must satisfy in the steady state. In order to account for systems that do not reach a constant steady state, the developed constraints allow the system state to switch among different values, i.e. the steady state variables are not forced to be constant.European Commission: FormalBio Contract No: 623995, Call reference: FP7-PEOPLE-2013-IE

Modeling, analyzing and controlling hybrid systems by Guarded Flexible Nets

A number of artificial and natural systems can be modeled as hybrid models in which continuous and discrete variables interact. Such hybrid models are usually challenging to analyze and control due to the computational complexity associated with existing methods. In this paper, the novel modeling formalism of Guarded Flexible Nets (GFNs) is proposed for the modeling, analysis and control of hybrid system. A GFN consists of an event net that determines how the state changes as processes execute, and an intensity net that determines the speeds of the processes. In a GFN, the continuous state is given by the value of its state variables, and the discrete state is given by the region within which such variables lie. GFNs are shown to possess a high modeling power while offering appealing analysis and control possibilities.European Commission through a 7th Framework Program BIOLEDGE Contract No: 289126 to SGO Marie Curie Intra European Fellowship to JJ (FormalBio Contract No: 623995, Call reference: FP7-PEOPLE-2013-IEF). Biotechnology & Biological Sciences Research Council (UK) grant no. BB/N02348X/1 as part of the IBiotech Program, and by the Indus- trial Biotechnology Catalyst (Innovate UK, BBSRC, EPSRC) to support the translation, development and commercialisation of innovative Industrial Biotechnology processes

Comparative analysis of the core proteomes among the Pseudomonas major evolutionary groups reveals species-specific adaptations for Pseudomonas aeruginosa and Pseudomonas chlororaphis

The Pseudomonas genus includes many species living in diverse environments and hosts. It is important to understand which are the major evolutionary groups and what are the genomic/proteomic components they have in common or are unique. Towards this goal, we analyzed 494 complete Pseudomonas proteomes and identified 297 core-orthologues. The subsequent phylogenomic analysis revealed two well-defined species (Pseudomonas aeruginosa and Pseudomonas chlororaphis) and four wider phylogenetic groups (Pseudomonas fluorescens, Pseudomonas stutzeri, Pseudomonas syringae, Pseudomonas putida) with a sufficient number of proteomes. As expected, the genus-level core proteome was highly enriched for proteins involved in metabolism, translation, and transcription. In addition, between 39–70% of the core proteins in each group had a significant presence in each of all the other groups. Group-specific core proteins were also identified, with P. aeruginosa having the highest number of these and P. fluorescens having none. We identified several P. aeruginosa-specific core proteins (such as CntL, CntM, PlcB, Acp1, MucE, SrfA, Tse1, Tsi2, Tse3, and EsrC) that are known to play an important role in its pathogenicity. Finally, a holin family bacteriocin and a mitomycin-like biosynthetic protein were found to be core-specific for P. cholororaphis and we hypothesize that these proteins may confer a competitive advantage against other root-colonizers.</jats:p

Developing a logical model of yeast metabolism

With the completion of the sequencing of genomes of increasing numbers of organisms, the focus of biology is moving to determining the role of these genes (functional genomics). To this end it is useful to view the cell as a biochemical machine: it consumes simple molecules to manufacture more complex ones by chaining together biochemical reactions into long sequences referred to as em metabolic pathways. Such metabolic pathways are not linear but often interesect to form complex networks. Genes play a fundamental role in these networks by providing the information to synthesise the enzymes that catalyse biochemical reactions. Although developing a complete model of metabolism is of fundamental importance to biology and medicine, the size and complexity of the network has proven beyond the capacity of human reasoning. This paper presents the first results of the Robot Scientist research programme that aims to automatically discover the function of genes in the metabolism of the yeast em Saccharomyces cerevisiae. Results include: (1) the first logical model of metabolism;(2) a method to predict phenotype by deductive inference; and (3) a method to infer reactions and gene function by aductive inference. We describe the em in vivo experimental set-up which will allow these em in silico predictions to be automatically tested by a laboratory robot

Combining inductive logic programming, active learning and robotics to discover the function of genes

The paper is addressed to AI workers with an interest in biomolecular genetics and also to biomolecular geneticists interested in what AI tools may do for them. The authors are engaged in a collaborative enterprise aimed at partially automating some aspects of scientific work. These aspects include the processes of forming hypotheses, devising trials to discriminate between these competing hypotheses, physically performing these trials and then using the results of these trials to converge upon an accurate hypothesis. As a potential component of the reasoning carried out by an "artificial scientist" this paper describes ASE-Progol, an Active Learning system which uses Inductive Logic Programming to construct hypothesised first-order theories and uses a CART-like algorithm to select trials for eliminating ILP derived hypotheses. In simulated yeast growth tests ASE-Progol was used to rediscover how genes participate in the aromatic amino acid pathway of Saccharomyces cerevisiae. The cost of the chemicals consumed in converging upon a hypothesis with an accuracy of around 88% was reduced by five orders of magnitude when trials were selected by ASE-Progol rather than being sampled at random. While the naive strategy of always choosing the cheapest trial from the set of candidate trials led to lower cumulative costs than ASE-Progol, both the naive strategy and the random strategy took significantly longer to converge upon a final hypothesis than ASE-Progol. For example to reach an accuracy of 80%, ASE-Progol required 4 days while random sampling required 6 days and the naive strategy required 10 days

Chronological Lifespan in Yeast Is Dependent on the Accumulation of Storage Carbohydrates Mediated by Yak1, Mck1 and Rim15 Kinases

Upon starvation for glucose or any other macronutrient, yeast cells exit from the mitotic cell cycle and acquire a set of characteristics that are specific to quiescent cells to ensure longevity. Little is known about the molecular determinants that orchestrate quiescence entry and lifespan extension. Using starvation-specific gene reporters, we screened a subset of the yeast deletion library representing the genes encoding 'signaling' proteins. Apart from the previously characterised Rim15, Mck1 and Yak1 kinases, the SNF1/AMPK complex, the cell wall integrity pathway and a number of cell cycle regulators were shown to be necessary for proper quiescence establishment and for extension of chronological lifespan (CLS), suggesting that entry into quiescence requires the integration of starvation signals transmitted via multiple signaling pathways. The CLS of these signaling mutants, and those of the single, double and triple mutants of $\textit{RIM15}$, $\textit{YAK1}$ and $\textit{MCK1}$ correlates well with the amount of storage carbohydrates but poorly with transition-phase cell cycle status. Combined removal of the glycogen and trehalose biosynthetic genes, especially $\textit{GSY2}$ and $\textit{TPS1}$, nearly abolishes the accumulation of storage carbohydrates and severely reduces CLS. Concurrent overexpression of $\textit{GSY2}$ and $\textit{TSL1}$ or supplementation of trehalose to the growth medium ameliorates the severe CLS defects displayed by the signaling mutants ($\textit{rim15Δyak1Δ}$ or $\textit{rim15Δmck1Δ}$). Furthermore, we reveal that the levels of intracellular reactive oxygen species are cooperatively controlled by Yak1, Rim15 and Mck1, and the three kinases mediate the $\textit{TOR1}$-regulated accumulation of storage carbohydrates and CLS extension. Our data support the hypothesis that metabolic reprogramming to accumulate energy stores and the activation of anti-oxidant defence systems are coordinated by Yak1, Rim15 and Mck1 kinases to ensure quiescence entry and lifespan extension in yeast.This work was sponsored by a scholarship awarded by National University of Defense Technology of China (to LC) and a scholarship from Lucy Cavendish College, Cambridge (to ZQ). Reagents and tools were supported by the UNICELLSYS Collaborative Project (No. 201142) of the European Commission (awarded to SGO). NZ is grateful to the Wellcome Trust and the University of Cambridge for support and facilities

The European Large Area ISO Survey: ELAIS

I describe a European collaborative project to survey \sim 20 square degrees of the sky at 15\micron and 90\micron with ISO. This is the largest open time project being undertaken by ISO. The depth and areal coverage were designed to complement the various Guaranteed Time surveys. The main science thrust is to explore star formation in galaxies to a much higher redshift than was probed by IRAS. We expect to detect around 8000 extra-galactic objects and a similar number of Galactic sources. The maps and source catalogues will represent a major legacy from ISO, inspiring follow up work for many years to come.Comment: Also at ELAIS home-page http://artemis.ph.ic.ac.uk/ ; "Cold Gas at High Redshift" Eds: Malcolm Bremer et al Pubs: Kluwe

Assessing Dysplasia of a Bronchial Biopsy with FTIR Spectroscopic Imaging

An FTIR image of an 8 µm section of de-paraffinised bronchial biopsy that shows a histological transition from normal to severe dysplasia/squamous cell carcinoma (SCC) insitu was obtained in transmission by stitching together images of 256 x 256 µm recorded using a 96 x 96 element FPA detector. Each pixel spectrum was calculated from 128 co-added interferograms at 4 cm−1 resolution. In order to improve the signal to noise ratio, blocks of 4x4 adjacent pixels were subsequently averaged. Analyses of this spectral image, after conversion of the spectra to their second derivatives, show that the epithelium and the lamina propria tissue types can be distinguished using the area of troughs at either 1591, 1334, 1275 or 1215 cm−1 or, more effectively, by separation into two groups by hierarchical clustering (HCA) of the 1614-1465 region. Due to an insufficient signal to noise ratio, disease stages within the image could not be distinguished with this extent of pixel averaging. However, after separation of the cell types, disease stages within either the epithelium or the lamina propria could be distinguished if spectra were averaged from larger, manually selected areas of the tissue. Both cell types reveal spectral differences that follow a transition from normal to cancerous histology. For example, spectral changes that occurred in the epithelium over the transition from normal to carcinoma insitu could be seen in the 1200-1000 cm−1 region, particularly as a decrease in the second derivative troughs at 1074 and 1036 cm−1 , consistent with changes in some form of carbohydrate. Spectral differences that indicate a disease transition from normal to carcinoma in the lamina propria could be seen in the 1350-1175 cm−1 and 1125-1030 cm−1 regions. Thus demonstrating that a progression from healthy to severe dysplasia/squamous cell carcinoma (SCC) insitu can be seen using FTIR spectroscopic imaging and multivariate analysis

Fission stories: using PomBase to understand Schizosaccharomyces pombe biology

PomBase (www.pombase.org), the model organism database (MOD) for the fission yeast Schizosaccharomyces pombe, supports research within and beyond the S. pombe community by integrating and presenting genetic, molecular, and cell biological knowledge into intuitive displays and comprehensive data collections. With new content, novel query capabilities, and biologist-friendly data summaries and visualization, PomBase also drives innovation in the MOD community

Color changes upon cooling of Lepidoptera scales containing photonic nanoarchitectures, and a method for identifying the changes

The effects produced by the condensation of water vapor from the environment in the various intricate nanoarchitectures occurring in the wing scales of several Lepidoptera species were investigated by controlled cooling (from 23° C, room temperature to -5 to -10° C) combined with in situ measurements of changes in the reflectance spectra. It was determined that all photonic nanoarchitectures giving a reflectance maximum in the visible range and having an open nanostructure exhibited alteration of the position of the reflectance maximum associated with the photonic nanoarchitectures. The photonic nanoarchitectures with a closed structure exhibited little to no alteration in color. Similarly, control specimens colored by pigments did not exhibit a color change under the same conditions. Hence, this method can be used to identify species with open photonic nanoarchitectures in their scales. For certain species, an almost complete disappearance of the reflectance maximum was found. All specimens recovered their original colors following warming and drying. Cooling experiments using thin copper wires demonstrated that color alterations could be limited to a width of a millimeter or less. Dried museum specimens did not exhibit color changes when cooled in the absence of a heat sink due to the low heat capacity of the wings