A stereospecific approach to diterpene alkaloids with a bridge across ring B

Zusammenfassung Die Herstellung eines Schlüsselprodukts für die Synthese von Alkaloiden des Songorin- und Delphinin-Typs wird beschrieben.

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We wish to thank the Hoffmann La Roche Company Inc., Nutley, New Jersey, and specifically Dr.A. Brossi, not only for financial support but also for collaboration and help. Financial support by the National Research Council of Canada is gratefully acknowledged.     

The chemistry of certain imines related to the diterpene alkaloids

Zusammenfassung Aconitum- und Delphinium-Alkaloide gehen teilweise ungewöhnliche chemische Reaktionen ein, deren Ursache in der polycyclischen Struktur, im besonderen in deren hohem Grad von Brückenbildungen zu suchen ist.Einige dieser Reaktionen, speziell solche der Imine und Imminiumsalze der Diterpenalkaloide Atisin und Veatchin werden diskutiert.

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Parts of this paper were presented before the Symposium on Enamine Chemistry at the American Chemical Society meeting in Chicago, September 6 (1961), and at the International Phytochemistry Symposium held during the Golden Jubilee Congress of the University of Hong Kong on September 12 (1961).     

A facile approach to dihydrojasmone

Résumé La dihydrojasmone a été synthétisée en trois étapes à partir du pentanedione-2,4.

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This research was supported by NRCC, Ottawa.     

A comparative approach to fish respiration

Zusammenfassung Es wird ein Überblick über neuere Forschungen gegeben, die das weite Arbeitsgebiet des Mechanismus der Fischatmung betreffen. Nachdruck wird auf den vergleichenden Standpunkt einer solchen Forschungsarbeit gelegt, wobei gezeigt wird, dass die Wahl besonderer Spezies ein förderndes Licht auf allgemein wichtige Probleme werfen kann, die bei Kiemenuntersuchungen sowohl auf der Makrostrukturstufe wie auf der Ultrastrukturstufe auftreten. Vom physiologischen Standpunkt aus gesehen, erweisen sich einige Arten auf Grund ihrer Lebensweise für experimentelle Untersuchungen ihres Sauerstoffverbrauchs besonders geeignet. Die strukturelle Anordnung des Pumpenmechanismus anderer Arten erleichert wiederum äusserst günstig die Direktmessung des Ventilationsvolumens und anderer mit dem Gasaustausch zusammenhängender Parameter.

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Based on lectures given in Spring 1969 at Duke University (N. Carolina, USA), Universities of Goteborg, Umca and Uppsala (Sweden).     

A mathematical approach to cognitive processes

Summary A mathematical formalization of cognitive processes based on concepts previously given in Experientia¹ is presented. Cognitive processes are described as a set of exponentially decaying interaction probabilities determined by previous interactions between different elements and an association parameter, the inverse of the cognitive stability. The interactions occur in a cognitive string surrounded by a cognitive plasma which carries the contextual information. The complexity of a cognitive process is proportional to time.     

A choice-semantical approach to theoretical truth

A central topic in the logic of science concerns the proper semantic analysis of theoretical sentences, that is sentences containing theoretical terms. In this paper, we present a novel choice-semantical account of theoretical truth based on the epsilon-term definition of theoretical terms. Specifically, we develop two ways of specifying the truth conditions of theoretical statements in a choice functional semantics, each giving rise to a corresponding logic of such statements. In order to investigate the inferential strength of these logical systems, we provide a translation of each truth definition into a modal definition of theoretical truth. Based on this, we show that the stronger notion of choice-semantical truth captures more adequately our informal semantic understanding of scientific statements.     

A mathematical approach to cognitive processes

A mathematical formalization of cognitive processes based on concepts previously given in Experientia is presented. Cognitive processes are described as a set of exponentially decaying interaction probabilities determined by previous interactions between different elements and an association parameter, the inverse of the cognitive stability. The interactions occur in a 'cognitive string' surrounded by a 'cognitive plasma' which carries the contextual information. The 'complexity' of a cognitive process is proportional to time.     

A Helmholtzian approach to space and time

A slight modification of Helmholtz’s metrical approach to the foundations of geometry leads to the locally Euclidian character of space without restriction of the curvature. A bolder generalization involving time measurement leads to the locally Minkowskian character of spacetime. Some philosophical consequences of these results are drawn.     

A mid-level approach to modeling scientific communities

This paper provides an account of mid-level models which calibrate highly theoretical agent-based models of scientific communities by incorporating empirical information from real-world systems. As a result, these models more closely correspond with real-world communities, and are better suited for informing policy decisions than extant how-possibly models. I provide an exemplar of a mid-level model of science funding allocation that incorporates bibliometric data from scientific publications and data generated from empirical studies of peer review into an epistemic landscape model. The results of my model show that on a dynamic epistemic landscape, allocating funding by modified and pure lottery strategies performs comparably to a perfect selection funding allocation strategy. These results support the idea that introducing randomness into a funding allocation process may be a tractable policy worth exploring further through pilot studies. My exemplar shows that agent-based models need not be restricted to the abstract and the apriori; they can also be informed by empirical data.     

A bayesian approach to modelling stochastic cycles

This article deals with a fully Bayesian approach to describe the cyclical behaviour of a univariate time series. A damped sine wave where both the period and the damping factor are time varying is assumed as the underlying mathematical model for the cyclical component. The model is applied to two real data sets; the annual rainfall observations in Fortaleza, Brazil, and the annual Wolf sunspot numbers.     

When and how to use scenario planning: A heuristic approach with illustration

This paper offers a step-by-step analysis of a heuristic approach to scenario planning, taking a managerial perspective. The scenario method is contrasted in general with more traditional planning techniques, which tend to perform less well when faced with high uncertainty and complexity. An actual case involving a manufacturing company is used to illustrate the main steps of the proposed heuristic. Its essence is to identify relevant trends and uncertainties, and blend them into scenarios that are internally consistent. In addition, the scenarios should bound the range of plausible uncertainties and challenge managerial thinking. Links to decision making are examined next, including administrative policies as well as integrative techniques. At the strategic level, a key-success-factor matrix is proposed for integrating scenarios, competitor analysis and strategic vision. At the operational level, Monte Carlo simulation is suggested and illustrated as one useful technique for combining scenario thinking with formal project evaluation (after appropriate translations). The paper concludes with a general discussion of scenario planning, to place it in a broader perspective.     

A new approach to analysis of human sweating

In human skin transplanted to the back of 3 strains of immuno-deficient mice the functin of the eccrine sweat glands of the human transplant was tested by topical intradermal application of pilocarine, adrenaline and atropine+pilocarpine. Sweat responses were observed in pre-selected fields of observation by means of video macroscope. The iodine strarch reaction served as an indicator for the appearance of seat sport and permitted the evaluation of areas wetted by sweat in the field of observation. Among 9 animals tested, the hybrids between the CB-17-scid mouse and the BALB/cA-nu mouse (BALB/cA-nu,scid) seemed to exhibit the most consistent seweating response to local pharmacological stimulation. According to histological examination, eccrine sweat glands were preserved in human skin trasplanted into the back skin of the BALB/cA-nu,scid mouse strain. the heterologous, human skin graft provides a novel model permitting, independent of the normal sweat gland innervation, the analysis of moecular receptors of sweat gland cells by which the actions of natural transmitters and pharmacological agents are transduced.     

A bayesian decision approach to model monitoring and cusums

Cumulative Sum techniques are widely used in quality control and model monitoring. A single-sided cusum may be regarded essentially as a sequence of sequential tests which, in many cases, such as those for the Exponential Family, is equivalent to a Sequence of Sequential Probability Ratio Tests. The relationship between cusums and Bayesian decisions is difficult to establish using conventional methods. An alternative approach is proposed which not only reveals a relation but also offers a very simple formulation of the decision process involved in model monitoring. This is first illustrated for a Normal mean and then extended to other important practical cases including Dynamic Models. For V-mask cusum graphs a particular feature is the interpretation of the distance of the V vertex from the latest plotted point in terms of the prior precision as measured in ‘equivalent’ observations.     

Taxuspine D,a new taxane diterpene fromTaxus cuspidata with potent inhibitory activity against Ca2+-induced depolymerization of microtubules

A new taxane diterpenoid, taxuspine D (1), possessing an enolacetate moiety, has been isolated from stems of the Japanese yewTaxus cuspidata Sieb. et Zucc., and the structure elucidated on the basis of spectroscopic data. Taxuspine D (1) markedly inhibited Ca²⁺-induced depolymerization of microtubules.     

Host-plant pyrrolizidine alkaloids inNyctemera annulata Boisduval: Their persistence through the life-cycle and transfer to a parasite

Summary Larvae ofNyctemera annulata Boisduval ingest pyrrolizidine alkaloids fromSenecio spathulatus A. Rich. which subsequently appear in the adult months and their eggs; the acquisition of the alkaloids by a parasite of theN. annulata larvae provides a further illustration of their ability to persist in insects.Acknowledgments. We thank Dr R. Yamdagni of the Chemistry Department, University of Calgary, Canada, and Dr O. Madsen of the Organic Chemistry Department, The Technical University of Denmark, Lyngby, Denmark, for much help with the MS data collection. We are also very grateful to Dr C.C.J. Culvenor, CSIRO Animal Health Lab., Parkville, Victoria, Australia, who most generously provided us with authentic reference specimens of pyrrolizidine alkaloids.     

Selective killing of smooth muscle cells in culture by the ricin A-chain conjugated with monoclonal antibodies to a cell surface antigen via a dextran bridge

Monoclonal antibodies to a surface antigen of the modulated smooth muscle cells originally isolated from the rat aorta media were conjugated with ricin A-chain via an oxidized dextran bridge. The interaction of cultured cells with the conjugates obtained and with control substances was monitored following incorporation of 14C-leucine radioactivity. It was found that 14C-leucine incorporation was suppressed by 80-90% at a conjugate concentration of 10(-6)-10(-7) M. Antigen-negative cells (line IAR; rat hepatocytes) were insensitive to the conjugate at any concentration used. Control use of purified ricin A-chain, native or oxidized dextran, specific and nonspecific IgG did not affect normal 14C-leucine incorporation. The data obtained may be useful for designing targeted drug transport systems and for selective screening of modulated smooth cells in vascular pathology models in vivo.     

Selective killing of smooth muscle cells in culture by the ricin A-chain conjugated with monoclonal antibodies to a cell surface antigen via a dextran bridge

Summary Monoclonal antibodies to a surface antigen of the modulated smooth muscle cells originally isolated from the rat aorta media were conjugated with ricin A-chain via an oxidized dextran bridge. The interaction of cultured cells with the conjugates obtained and with control substances was monitored following incorporation of¹⁴C-leucine radioactivity. It was found that¹⁴C-leucine incorporation was suppressed by 80–90% at a conjugate concentration of 10^–6–10^–7 M. Antigen-negative cells (line IAR; rat hepatocytes) were insensitive to the conjugate at any concentration used. Control use of purified ricin A-chain, native or oxidized dextran, specific and nonspecific IgG did not affect normal¹⁴C-leucine incorporation. The data obtained may be useful for designing targeted drug transport systems and for selective screening of modulated smooth cells in vascular pathology models in vivo.     

A state space approach to forecasting the final vintage of revised data with an application to the index of industrial production

There is considerable interest in the index of industrial production (IIP) as an indicator of the state of the UK's industrial base and, more generally, as a leading economic indicator. However, this index, in common with a number of key macroeconomic time series, is subject to revision as more information becomes available. This raises the problem of forecasting the final vintage of data on IIP. We construct a state space model to solve this problem which incorporates bias adjustments, a model of the measurement error process, and a dynamic model for the final vintage of IIP. Application of the Kalman filter produces an optimal forecast of the final vintage of data.