Asymmetric total synthesis of the indole alkaloid cyclopiazonic acid and first structure-activity data

The indole alkaloid α-cyclopiazonic acid (CPA) is one of the few known inhibitors of sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA) besides the terpenoids thapsigargin and artemisinin. We report here the first asymmetric total synthesis of cyclopiazonic acid by a modification of the Knight synthesis, currently the most efficient route to CPA. First structure-activity data of CPA derivatives and stereoisomers are presented and will be discussed in connection with the published crystal structures of CPA-SERCA complexes.     

The converse of a theorem of W. Gaschütz on Frattini subgroups

Dedicated to W. Gaschütz on the occasion of his 75th birthday Received 26 January 1995; in final form 2 May 1995     

Direct fluorometric analysis of a newly synthesised fluorescein-labelled marker for glomerular filtration rate

There is an obvious and growing medical need for an accurate determination of kidney function in the diagnosis and management of renal diseases. The glomerular filtration rate (GFR) is the accepted gold standard measurement of kidney function. Several approaches to estimate the GFR are available, but most of them are inconvenient and, therefore, of limited acceptance. A new method of quantification with fluorescein-isothiocyanate (FITC) sinistrin (FS), a novel GFR marker, has been evaluated. The method is based on the fluorescence label of FS and can be performed with a standard fluorometer. To control the interference of protein with the fluorescence signal, a calibration function was developed. The accuracy of the fluorometric method established is comparable to the so-called gold standard of enzymatic determination of polyfructosan. Moreover, FS is easy to handle and requires low-cost instruments. Our results demonstrate the potential of the direct fluorometric analysis of the new FITC-labelled marker of being a precise, simple, rapid and cost-effective method for diagnosing disturbed kidney function and monitoring its treatment efficacy. The dramatic decrease in analytical effort will result in a significantly higher acceptability of GFR determination.     

CoLab: A hybrid knowledge representation and compilation laboratory

Knowledge bases for real-world domains such as mechanical engineering require expressive and efficient representation and processing tools. We pursue a declarative-compilative approach to knowledge engineering.While Horn logic (as implemented in PROLOG) is well-suited for representing relational clauses, other kinds of declarative knowledge call for hybrid extensions: functional dependencies and higher-order knowledge should be modeled directly. Forward (bottom-up) reasoning should be integrated with backward (top-down) reasoning. Constraint propagation should be used wherever possible instead of search-intensive resolution. Taxonomic knowledge should be classified into an intuitive subsumption hierarchy.Our LISP-based tools provide directtranslators of these declarative representations into abstract machines such as an extended Warren Abstract Machine (WAM) and specialized inference engines that are interfaced to each other. More importantly, we provide source-to-sourcetransformers between various knowledge types, both for user convenience and machine efficiency.These formalisms with their translators and transformers have been developed as part of CoLab, acompilationlaboratory for studying what we call, respectively, vertical and horizontal compilation of knowledge, as well as for exploring the synergeticcolaboration of the knowledge representation formalisms.A case study in the realm of mechanical engineering has been an important driving force behind the development of CoLab. It will be used as the source of examples throughout the paper when discussing the enhanced formalisms, the hybrid representation architecture, and the compilers.Supported by BMFT Research Project ARC-TEC (grant ITW 8902 C4)     

Infrared behaviour of metallic systems in one, two and three dimensions

A simple approximate expression for the electron lifetime() in metals is rederived and discussed for different dimensions. In the 3D-case we get the well known Drude behaviour, i.e. a constant. In one dimension() is strongly frequency-dependent in the IR. The 2D-case is intermediate to the preceding ones. These results are essentially due to the different form of the Fermi surface for an electron gas in one, two and three dimensions.     

Phase behavior of colloidal hard tetragonal parallelepipeds (cuboids): a Monte Carlo simulation study

The impact of particle geometry on the phase behavior of hard colloidal tetragonal parallelepipeds (TPs) was studied by using Monte Carlo simulations in continuum space. TPs or "cuboids" of aspect ratios varying from 0.25 to 8 were simulated by approximating their shapes with multisite objects, i.e., via rigid clusters of hard spheres. Using equation of state curves, order parameters, radial distribution functions, particle distribution functions along three directions, and visual analysis of configurations, an approximate phase diagram for the TPs was mapped out as a function of aspect ratio (r) and volume fraction. For r > 3 and intermediate concentrations, the behavior of the TPs was similar to that of spherocylinders, exhibiting similar liquid crystalline mesophases (e.g., nematic and smectic phases). For r = 1, a cubatic phase occurs with orientational order along the three axes but with little translational order. For 1 < r < 4, the TPs exhibit a cubatic-like mesophase with a high degree of order along three axes where the major axes of the particles are not all aligned in the same direction. For r < 1, the TPs exhibit a smectic-like phase where the particles have rotational freedom in each layer but form stacks with tetratic order. The equation of state for perfect hard cubes (r = 1) was also simulated and found to be consistent with that of the rounded-edge r = 1 TPs, except for its lack of discontinuity at the cubatic-solid transition.     

Facile synthesis of @-tide beta-strand peptidomimetics: improved assembly in solution and on solid phase

The synthesis of @-tide beta-strand peptidomimetics has been improved such that oligomers now can be obtained from solution- and solid-phase synthesis protocols approaching the efficiency and flexibility of peptide chemistry. These methods enable the synthesis of @-tide oligomers with a variety of amino acids and with lengths up to 13 units. [reaction: see text]     

The quickest flow problem

Consider a network =(G, c, ) whereG=(N, A) is a directed graph andc _ij and _ij , respectively, denote the capacity and the transmission time of arc (i, j) A. The quickest flow problem is then to determine for a given value the minimum numberT() of time units that are necessary to transmit (send) units of flow in from a given sources to a given sinks.In this paper we show that the quickest flow problem is closely related to the maximum dynamic flow problem and to linear fractional programming problems. Based on these relationships we develop several polynomial algorithms and a strongly polynomial algorithm for the quickest flow problem.Finally we report computational results on the practical behaviour of our metholds. It turns out that some of them are practically very efficient and well-suited for solving large problem instances.Partial financial support by the Air Force Office of Scientific Research under grants AFOSR-89-0512 and AFOSR-90-0008 is gratefully acknowledged by the first author.