Developmental regulation of p70 S6 kinase by a G protein-coupled receptor dynamically modelized in primary cells

The mechanisms whereby G protein-coupled receptors (GPCR) activate signalling pathways involved in mRNA translation are ill-defined, in contrast to tyrosine kinase receptors (TKR). We compared a GPCR and a TKR, both endogenously expressed, for their ability to mediate phosphorylation of 70-kDa ribosomal S6 kinase p70S6K in primary rat Sertoli cells at two developmental stages. In proliferating cells stimulated with follicle-stimulating hormone (FSH), active p70S6K was phosphorylated on T389 and T421/S424, through cAMP-dependent kinase (PKA) and phosphatidyl-inositide-3 kinase (PI3K) antagonizing actions. In FSH-stimulated differentiating cells, active p70S6K was phosphorylated solely on T389, PKA and PI3K independently enhancing its activity. At both developmental stages, insulin-induced p70S6K regulation was consistent with reported data. Therefore, TKR and GPCR trigger distinct p70S6K active conformations. p70S6K developmental regulation was formalized in a dynamic mathematical model fitting the data, which led to experimentally inaccessible predictions on p70S6K phosphorylation rate.     

The correspondence between James Hutton (1726–1797) and James Watt (1736–1819) with two letters from Hutton to George Clerk-Maxwell (1715–1784): Part I

In the collection of Watt's papers at Doldowlod, home of Lord Gibson-Watt, there are seven previously unpublished letters from James Hutton to James Watt, and four letters from Watt to Hutton, also unpublished. The letters were written between 1774 and 1795. Very little of Hutton's other correspondence survives, so these letters add significantly to our knowledge. The earliest letters, together with two letters to George Clerk-Maxwell (in the Scottish Record Office), describe geological tours that Hutton made through Wales, the Midlands, and the south-west of England in 1774. The correspondence after 1774, which will appear in a later edition of Annals of Science, reveals Watt's expertise in geology, and also discusses meteorology, varnish making, Symington's steam engines, the first experiments with steam navigation, pneumatic medicine, and other topics.     

The subfamily Anomiopsyllinae (Hystrichopsyllidae: Siphonaptera). I. a revision of the genus Anomiopsyllus Baker

Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} In this taxonomic revision of the Nearctic flea genus Anomiopsyllus Baker morphological characters, phylogeny, affinities with other genera in the subfamily Anomiopsyllinae, evolutionary adaptations, geographic distribution, ecological parameters, and host preferences are discussed. Characters primarily associated with the male genitalia, in particular the number and placement of spiniforms on the movable process (finger) of the clasper, are used for species discrimination. A key to the males of the 15 species and subspecies is provided, including illustrations of both males and females.        

Newtonian Emanation, Spinozism, Measurement and the Baconian Origins of the Laws of Nature

The first two sections of this paper investigate what Newton could have meant in a now famous passage from “De Graviatione” (hereafter “DeGrav”) that “space is as it were an emanative effect of God.” First it offers a careful examination of the four key passages within DeGrav that bear on this. The paper shows that the internal logic of Newton’s argument permits several interpretations. In doing so, the paper calls attention to a Spinozistic strain in Newton’s thought. Second it sketches four interpretive options: (i) one approach is generic neo-Platonic; (ii) another approach is associated with the Cambridge Platonist, Henry More; a variant on this (ii*) emphasizes that Newton mixes Platonist and Epicurean themes; (iii) a necessitarian approach; (iv) an approach connected with Bacon’s efforts to reformulate a useful notion of form and laws of nature. Hitherto only the second and third options have received scholarly attention in scholarship on DeGrav. The paper offers new arguments to treat Newtonian emanation as a species of Baconian formal causation as articulated, especially, in the first few aphorisms of part two of Bacon’s New Organon. If we treat Newtonian emanation as a species of formal causation then the necessitarian reading can be combined with most of the Platonist elements that others have discerned in DeGrav, especially Newton’s commitment to doctrines of different degrees of reality as well as the manner in which the first existing being ‘transfers’ its qualities to space (as a kind of causa-sui). This can clarify the conceptual relationship between space and its formal cause in Newton as well as Newton’s commitment to the spatial extended-ness of all existing beings. While the first two sections of this paper engage with existing scholarly controversies, in the final section the paper argues that the recent focus on emanation has obscured the importance of Newton’s very interesting claims about existence and measurement in “DeGrav”. The paper argues that according to Newton God and other entities have the same kind of quantities of existence; Newton is concerned with how measurement clarifies the way of being of entities. Newton is not claiming that measurement reveals all aspects of an entity. But if we measure something then it exists as a magnitude in space and as a magnitude in time. This is why in DeGrav Newton’s conception of existence really helps to “lay truer foundations of the mechanical sciences.”     

THE PERIODIC CAPACITATED ARC ROUTING PROBLEM LINEAR PROGRAMMING MODEL, METAHEURISTIC AND LOWER BOUNDS

1. Introduction The Capacitated Arc Routing Problem(CARP) is defined on an undirected network inwhich a fleet of identical vehicles with limitedcapacity is based at a depot node. Each edge hasa non-negative traversal cost and can betraversed any number…     

Purity and Danger of an Information Infrastructure

We critically assess deep-seated assumptions and images of an information infrastructure, namely, that it needs to be uniform, tidy, and nonfragmented. This is necessary because our perception of order is socially constructed and, more importantly, because it has implications. Based on an historical reconstruction of the establishment of a Lotus Notes-based infrastructure in an internationally oriented oil company with 17,000 employees, we describe and analyze the productive role that appeals to an orderly infrastructure play. We trace its sources and describe how it operates. We also identify the implications in terms of choice of technological solution, delegation of organizational roles, and making organizational actors (in)visible.     

Probability distributions,trading strategies and leverage: an application of Gaussian mixture models

The purpose of this paper is twofold. Firstly, to assess the merit of estimating probability density functions rather than level or classification estimations on a one‐day‐ahead forecasting task of the EUR/USD time series. This is implemented using a Gaussian mixture model neural network, benchmarking the results against standard forecasting models, namely a naïve model, a moving average convergence divergence technical model (MACD), an autoregressive moving average model (ARMA), a logistic regression model (LOGIT) and a multi‐layer perceptron network (MLP). Secondly, to examine the possibilities of improving the trading performance of those models with confirmation filters and leverage. While the benchmark models perform best without confirmation filters and leverage, the Gaussian mixture model outperforms all of the benchmarks when taking advantage of the possibilities offered by a combination of more sophisticated trading strategies and leverage. This might be due to the ability of the Gaussian mixture model to identify successfully trades with a high Sharpe ratio. Copyright © 2004 John Wiley & Sons, Ltd.     

Beyond heuristics and biases: A contingency model of judgemental forecasting

The conflicting viewpoints about the quality of judgemental forecasts are examined and a model is proposed that attempts to resolve the conflict. The model sees forecasts as contingent upon the repertory of forecasting strategies that the forecaster brings to the forecasting task, the strategy that he or she selects as a function of the characteristics of the task, and the rigour with which he or she applies the strategy as a function of the motivating characteristics of the environment in which the task is encountered. The implications of differences in subjects' and experimenters' assumptions about which strategies are appropriate in experimental studies are examined, as are the implications of the differences between the motivating aspects of experimental and applied settings on both performance and on the generatizability of the results of experiments to applied judgemental forecasting.