Application of regulatory sequence analysis and metabolic network analysis to the interpretation of gene expression data

We present two complementary approaches for the interpretation of clusters of co-regulated genes, such as those obtained from DNA chips and related methods. Starting from a cluster of genes with similar expression profiles, two basic questions can be asked: 1. Which mechanism is responsible for the coordinated transcriptional response of the genes? This question is approached by extracting motifs that are shared between the upstream sequences of these genes. The motifs extracted are putative cis-acting regulatory elements. 2. What is the physiological meaning for the cell to express together these genes? One way to answer the question is to search for potential metabolic pathways that could be catalyzed by the products of the genes. This can be done by selecting the genes from the cluster that code for enzymes, and trying to assemble the catalyzed reactions to form metabolic pathways. We present tools to answer these two questions, and we illustrate their use with selected examples in the yeast Saccharomyces cerevisiae. The tools are available on the web (http://ucmb.ulb.ac.be/bioinformatics/rsa-tools/; http://www.ebi.ac.uk/research/pfbp/; http://www.soi.city.ac.uk/~msch/)

Use and non-use of accounting information: The case of controversial projects in public and non-profit settings

This paper investigates whether and how accounting information is used in debates and decision-making processes about controversial projects in public sector and non-profit settings in the Netherlands and Italy. The research is based on two case studies and relies on multiple methods of qualitative data collection, including documents, interviews with key actors and media reports. The research finds a more limited extent of accounting information use than expected given the controversiality of the projects. It raises various types of explanations for this limited accounting information use, especially that ruling groups of actors supporting the project do not give room to the opposing minority for putting forward their concerns and preferences. The power position of the ruling majority thus matters in mitigating opportunities for a dialogic use of accounting information leading to the decision-making about the projects. So, controversiality is a determining factor, but insufficient as an explanation for the extent to which accounting information is used. In addition, the type of accounting information use is depending on the actors’ appreciation of the project. Advocates and opponents concerning both projects were in general inclined to an ammunition type of accounting information use, whereas actors holding a neutral position used available accounting information in a more rational way.This paper investigates whether and how accounting information is used in debates and decision-making processes about controversial projects in public sector and non-profit settings in the Netherlands and Italy. The research is based on two case studies and relies on multiple methods of qualitative data collection, including documents, interviews with key actors and media reports. The research finds a more limited extent of accounting information use than expected given the controversiality of the projects. It raises various types of explanations for this limited accounting information use, especially that ruling groups of actors supporting the project do not give room to the opposing minority for putting forward their concerns and preferences. The power position of the ruling majority thus matters in mitigating opportunities for a dialogic use of accounting information leading to the decision-making about the projects. So, controversiality is a determining factor, but insufficient as an explanation for the extent to which accounting information is used. In addition, the type of accounting information use is depending on the actors’ appreciation of the project. Advocates and opponents concerning both projects were in general inclined to an ammunition type of accounting information use, whereas actors holding a neutral position used available accounting information in a more rational way

Vertrouwen Versus Control

Wat is de effectiviteit van risicomanagement en wat is de functie van vertrouwen in een relatie waarbij operationele processen grotendeels geautomatiseerd zijn? Vanuit het gehouden literatuuronderzoek is naar voren gekomen dat op het gebied van relationeel en performance risico, governance en vertrouwen veel literatuur is te vinden, maar weinig met betrekking tot relaties waarbij sprake is van een hoge mate van automatisering. In de literatuur wordt behoorlijk wat aandacht besteed aan de relatie tussen de wijze waarop een samenwerkingsverband bestuurd wordt en het beheersen van risico's. In het oog springt hierbij het onderzoek van De Man & Roijakkers (2009). In het veldonderzoek is allereerst het replicatieonderzoek gehouden waarbij de stappen van De Man & Roijakkers zoveel mogelijk zijn gevolgd. Vervolgens zijn in het vergelijkingsonderzoek twee samenwerkingsrelaties met het verificatieonderzoek vergeleken. Op de meeste punten komen het model van De Man & Roijakkers en de gevonden resultaten overeen. Dat betekent dat het model bruikbaar is. In beide relaties wordt er op basis van vertrouwen gewerkt. Er wordt door beide partijen aangegeven dat er wel een contract aan ten grondslag moet liggen: desgewenst kan het contract als redmiddel dienen

New development: The ethics of accounting information manipulation in the political arena

ABSTRACT This article explores ethical issues of accounting information manipulation (AIM) in the political arena. After conceptualizing AIM, including its drivers, techniques, contextualities and impacts, the authors discuss underlying tensions between various types of values that emerge as a trigger for applying AIM. In that respect a distinction is made between values at the societal, organizational and individual level, such as, respectively, sustainability, transparency and honesty, and additionally between private values related to personal gain and public values

Cavity ring down spectroscopy on solid C₆₀

The light absorption of a solid sample in the 8.5 μm region is measured via cavity ring down (CRD) absorption spectroscopy, using a free electron laser (FEL) as a source of widely tunable infrared (IR) radiation. A 3 mm thick zinc-selenide (ZnSe) window is used as a substrate for a 20–30 nm thick C60 film. On top of the structureless absorption due to ZnSe (60 is measured with monolayer sensitivity

Downregulation of Fzd6 and Cthrc1 and upregulation of olfactory receptors and protocadherins by dietary beta-carotene in lungs of Bcmo1-/- mice.

An ongoing controversy exists on beneficial versus harmful effects of high beta-carotene (BC) intake, especially for the lung. To elucidate potential mechanisms, we studied effects of BC on lung gene expression. We used a beta-carotene 15,15'-monooxygenase 1 (Bcmo1) knockout mouse (Bcmo1-/-) model, unable to convert BC to retinoids, and wild-type mice (Bcmo1+/+) mice to dissect the effects of intact BC from effects of BC metabolites. As expected, BC supplementation resulted in a higher BC accumulation in lungs of Bcmo1-/- mice than in lungs of Bcmo1+/+ mice. Whole mouse genome transcriptome analysis on lung tissue revealed that more genes were regulated in Bcmo1-/- mice than Bcmo1+/+ mice upon BC supplementation. Frizzled homolog 6 (Fzd6) and collagen triple helix repeat containing 1 (Cthrc1) were significantly downregulated (fold changes -2.99 and -2.60, respectively, false discovery rate <0.05) by BC in Bcmo1-/-. Moreover, many olfactory receptors and many members of the protocadherin family were upregulated. Since both olfactory receptors and protocadherins have an important function in sensory nerves and Fzd6 and Cthrc1 are important in stem cell development, we hypothesize that BC might have an effect on the highly innervated pulmonary neuroendocrine cell (PNEC) cluster. PNECs are highly associated with sensory nerves and are important cells in the control of stem cells. A role for BC in the innervated PNEC cluster might be of particular importance in smoke-induced carcinogenesis since PNEC-derived lung cancer is highly associated with tobacco smoke

Altered fractalkine cleavage potentially promotes local inflammation in NOD salivary gland

Introduction: In the nonobese diabetic (NOD) mouse model of Sjögren's syndrome, lymphocytic infiltration is preceded by an accumulation of dendritic cells in the submandibular glands (SMGs). NOD mice also exhibit an increased frequency of mature, fractalkine receptor (CX3C chemokine receptor [CX3CR]1) expressing monocytes, which are considered to be precursors for tissue dendritic cells. To unravel further the role played by fractalkine-CX3CR1 interactions in the salivary gland inflammation, we studied the expression of fractalkine in NOD SMGs. Methods: We studied protein expression using Western blot analysis of whole tissue lysates. Protease activity was measured in salivary gland tissue lysates using fluorimetric substrates. Digestive capacity of enzymes was determined by in vitro incubation of recombinant enzyme and fractalkine, followed by protein staining and Western blot. Results: Fractalkine was detected in salivary glands of both NOD and control mice at all ages. Western blot analysis showed fractalkine cleavage with increasing age, which was more pronounced in NOD mice. This cleavage resulted in a decrease in the 31 kDa form of the protein, and the generation of an approximately 19 kDa band. Furthermore, in NOD animals older than 15

Generalized Newton-Cartan geometries for particles and strings

We discuss the generalized Newton-Cartan geometries that can serve as gravitational background fields for particles and strings. In order to enable us to define affine connections that are invariant under all the symmetries of the structure group, we describe torsionful geometries with independent torsion tensors. A characteristic feature of the non-Lorentzian geometries we consider is that some of the torsion tensors are so-called ‘intrinsic torsion’ tensors. Setting some components of these intrinsic torsion tensors to zero leads to constraints on the geometry. For both particles and strings, we discuss various such constraints that can be imposed consistently with the structure group symmetries. In this way, we reproduce several results in the literature.</p