Closures of exponential families

The variation distance closure of an exponential family with a convex set of canonical parameters is described, assuming no regularity conditions. The tools are the concepts of convex core of a measure and extension of an exponential family, introduced previously by the authors, and a new concept of accessible faces of a convex set. Two other closures related to the information divergence are also characterized.Comment: Published at http://dx.doi.org/10.1214/009117904000000766 in the Annals of Probability (http://www.imstat.org/aop/) by the Institute of Mathematical Statistics (http://www.imstat.org

Characterisation of Dof, an essential adaptor molecule in fibroblast growth factor signalling in Drosophila melanogaster

The FGF signal transducer molecule Dof has been shown to act upstream of the Ras-MAPK pathway. It is unknown how Dof transmits the signal from the activated FGF receptor to the MAPK cascade. Several approaches were taken to analyse this mechanism. 1. One way to resolve this question is to analyse Dof mediated interactions. In this work interaction of Dof with selected candidates of a yeast two hybrid screen was analysed biochemically. Most but not all of the tested candidates were able to form a complex with Dof in Drosophila S2 cells. The predicted capability of Dof for self-association was validated by showing that the molecule was able to form dimers/oligomers in S2 cells. Co-immunoprecipitation studies of Dof with the FGF receptor Heartless showed that the DBB domain - an essential region of the molecule needed for dimerisation and shared with BCAP and BANK - is required for efficient receptor binding. A consensus sumoylation site is located within the DBB domain of Dof. Mutation of this site impaired binding to the FGF receptor Heartless. Dof interacted with the SUMO conjugating enzyme Ubc9 and was sumoylated in Drosophila S2 cells suggesting that SUMO modification of the molecule might regulate interaction with the FGF receptor. 2. As a second approach phosphorylation of Dof was analysed that might influence the activity of the protein in signal transmission. Dof becomes phosphorylated in the presence of an activated FGF receptor at the conserved tyrosine motifs for PI3K and Csw binding. In addition, we identified a novel tyrosine motif as a phosphorylation target which appears four times in Dof. Strikingly, it is also present in BANK and some other signalling molecules. The C-terminal part of Dof is also phosphorylated and might be involved in conformational regulation of the protein, since the removal of the last 200 amino acids improved the binding affinity of Dof to Heartless. 3. Dof is cleaved in Drosophila S2 cells, which might give an additional level in the regulation of signalling. This cleavage is caspase dependent, regulated by Dronc and requires an intact caspase cleavage site in Dof. However, a Dof transgene mutant for the caspase cleavage site rescued efficiently dof mutant phenotypes indicating that this site is not essential for Dof functions assayed in this work. Mutant Dof constructs with C-terminal truncations of different lengths that removed the caspase cleavage site varied in their expression levels despite their similar stability in S2 cells. These differences were not seen in mRNA abundance but only in protein levels and higher expression levels correlated with the presence of a region in Dof identified as a binding site for the ribosomal protein S10. Full length Dof showed expression levels comparable to that of the mutant construct lacking the ribosomal protein binding site. Thus, this is the first indication that Dof cleavage products might have additional roles in the regulation of Dof function. 4. One essential function of Dof is to activate the Ras-MAPK pathway in vivo. To find out if only the MAPK signalling panel is utilised by Ras activity the role of the three Ras effectors Raf, RalGDS and PI3K were determined in FGF signalling during Drosophila embryogenesis. This analysis showed that both the Raf and RalGDS effector pathways might have a function in FGF signalling but that additional Ras activity is required either to regulate these cascades or to turn on other effector pathways. Our results indicate that PI3K is not needed for FGF signal transduction. In addition to Ras, Rap1 might be also involved in FGF signalling downstream or in parallel to Dof. How Rap1 is activated and to what extent the two closely related Ras family GTPases share downstream effectors is not understood at present

The Paradox of Deception: Lawyers, Negotiation, and an Appeal for Regulation

The use of deception in negotiations has spurred much debate in the legal ethics arena. Ethics are concerned with upholding principles of honesty, fairness and good faith. A lawyer’s use of deceptive negotiation tactics would therefore seem to violate the principles of legal ethics. However, certain deceptive tactics in legal negotiations are viewed as not only acceptable, but even expected as part of the negotiation process. This presents a paradox: how can a lawyer act deceptively but also ethically? This paper explores the degree of deception in negotiations that legal professionals are willing to permit on both an ethical and strategic basis. This paper draws on the rules of legal ethics from different jurisdictions as well as the literature on lying and negotiation, to help demonstrate why reform is needed. Reform of the law society rules would not only to improve the public perception of the legal profession, but better serve individuals who rely on negotiation as a primary means of access to justice

Seriality and the Search for Order: Scientific Print and its Problems During the Late Nineteenth Century

History of Scienc

Continuity bounds on the quantum relative entropy

The quantum relative entropy is frequently used as a distance, or distinguishability measure between two quantum states. In this paper we study the relation between this measure and a number of other measures used for that purpose, including the trace norm distance. More precisely, we derive lower and upper bounds on the relative entropy in terms of various distance measures for the difference of the states based on unitarily invariant norms. The upper bounds can be considered as statements of continuity of the relative entropy distance in the sense of Fannes. We employ methods from optimisation theory to obtain bounds that are as sharp as possible.Comment: 13 pages (ReVTeX), 3 figures, replaced with published versio

Is the area postrema resistant to the anesthetic effects of MS-222?

MS-222 is a common fish anesthetic that dampens neural activity by inhibiting neuronal voltage-gated sodium channels (Nav) required for action potentials. Previous experiments conducted by our lab’s primary investigator using fluorescence calcium imaging in zebrafish neurons resulted in the observation that neurons in the area postrema (AP), a circumventricular organ located in the dorsal hindbrain, displayed prominent fluorescence intensity during MS-222 induced sedation. I used the genetically encoded calcium indicator GCaMP6s to conduct fluorescence calcium imaging with the goal of recording neural activity in the larval zebrafish area postrema and optic tectum to compare the anesthetic effects of MS-222 across brain regions. A 2 x 2 analysis of variance (ANOVA) was used to calculate the differences in fluorescence intensity before and after MS-222 in both brain regions. Contrary to our hypothesis, the results of the experiment indicate that MS-222 had an insignificant effect on the change in fluorescence intensity in each brain region and although insignificant, appears to slightly increase area postrema and optic tectum mean standard deviations. These results are theoretically inconsistent with the literary understanding of how voltage-gated sodium channel antagonism affects cellular behavior. A small sample size with high variance is the most likely explanation for these results

CPS Platform Approach to Industrial Robots: State of the Practice, Potentials, Future Research Directions

Approaches, such as Cloud Robotics, Robot-as-a-Service, merged Internet of Things and robotics, and Cyber-Physical Systems (CPS) in production, show that the industrial robotics domain experiences a paradigm shift that increasingly links robots in real-life factories with virtual reality. However, despite the growing body of research to date, though insightful, the paradigm shift to CPS in industrial robotics remains an under-researched area. Findings from the present paper make several contributions to the current state of research: We provide a potentially reusable framework of analysis and apply this framework in order to reveal whether and to what extent the industrial robotics branch implements abilities and characteristics of CPS. We examine the top five industrial robot manufacturers ABB, Fanuc, Kawasaki, Kuka, and Yaskawa and identify considerable, current implementations. However, concerning one of three perspectives—the perspective on CPS as industry platform constructs, takes the industrial robotics branch only certain small steps towards CPS platforms. We discuss them and outline a set of business model patterns that can transform product innovations, enabled by abilities and characteristics of CPS, into business model innovations in the industrial robot domain. In order to enable the industry to exploit the full potential of industrial robots understood as CPS, we question the right degree of openness in the context of industry platform constructs. Our methodological approach combines conceptual with empirical research