Biology‐Oriented Synthesis of a Withanolide‐Inspired Compound Collection Reveals Novel Modulators of Hedgehog Signaling

Biology‐oriented synthesis employs the structural information encoded in complex natural products to guide the synthesis of compound collections enriched in bioactivity. The trans‐hydrindane dehydro‐δ‐lactone motif defines the characteristic scaffold of the steroid‐like withanolides, a plant‐derived natural product class with a diverse pattern of bioactivity. A withanolide‐inspired compound collection was synthesized by making use of three key intermediates that contain this characteristic framework derivatized with different reactive functional groups. Biological evaluation of the compound collection in cell‐based assays that monitored biological signal‐transduction processes revealed a novel class of Hedgehog signaling inhibitors that target the protein Smoothened.     

Enantiomeric separation of 1,3‐dimethylamylamine by capillary electrophoresis with indirect UV detection using a dual‐selector system

The CE method employing an indirect UV detection for the enantioseparation of 1,3‐dimethylamylamine (DMAA), widely used in various preworkout and dietary supplements labeled as a constituent of geranium extract has been developed. The dual‐selector system consisting of negatively charged sulfated α‐CD (1.1% w/v) and sulfated β‐CD (0.2% w/v) in 5 mM phosphate/Tris buffer (pH 3.0) containing the addition of 10 mM benzyltriethylammonium chloride (BTEAC) as the chromophoric additive was used for the enantiomeric separation of DMAA stereoisomers with the LODs in the range of 7.82–9.24 μg/mL. The method was partly validated and applied for the determination of the stereoisomeric composition of DMAA in commercial dietary supplements to verify the potential natural origin of DMAA.     

On the Wiener–Hopf Method for Surface Plasmons: Diffraction from Semiinfinite Metamaterial Sheet

By formally invoking the Wiener–Hopf method, we explicitly solve a one‐dimensional, singular integral equation for the excitation of a slowly decaying electromagnetic wave, called surface plasmon‐polariton (SPP), of small wavelength on a semiinfinite, flat conducting sheet irradiated by a plane wave in two spatial dimensions. This setting is germane to wave diffraction by edges of large sheets of single‐layer graphene. Our analytical approach includes (i) formulation of a functional equation in the Fourier domain; (ii) evaluation of a split function, which is expressed by a contour integral and is a key ingredient of the Wiener–Hopf factorization; and (iii) extraction of the SPP as a simple‐pole residue of a Fourier integral. Our analytical solution is in good agreement with a finite‐element numerical computation.     

Static shakedown theorems in piecewise linearized poroplasticity

Summary A fully saturated two-phase solid or structure subjected to variable, in particular cyclic, external actions is described as a nonhardening poroelastoplastic material with piecewise linearized yield loci. With reference to a multifield finite element model, sufficient and necessary conditions for shakedown are established by the static Melan's approach. Shakedown analysis by linear programming is briefly discussed. Received 29 December 1997, accepted for publications 25 June 1998     

Quadratic programming and theory of elastic-perfectly plastic structures

Summary For elastic perfectly plastic discretized structures acted upon by given loads and dislocations, it is shown, under holonomic constitutive laws or no local unloading hypothesis, that the formulation of the analysis problem in terms of finite (not incremental) stresses, is amenable to the Kuhn-Tucker conditions of a quadratic program. Then it is readily derived a generalized form of the principle of Haar and Kármán, together with an extremum theorem for displacements and plastic strains, which is the dual of the preceding one. As special cases of this theorems known variational principles follow, which thus turn out to be related in pairs by the duality notion as understood in programming theory. Also the statical and kinematical theorems of limit analysis are proved by means of the unitary conceptual framework supplied by quadratic programming.

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Sommario Con riferimento a strutture discretizzate idealmente elastoplastiche, soggette a dati carichi e distorsioni, si mostra che nell'ipotesi di olonomia dei legami costitutivi o di assenza di ritorni elastici, la formulazione del problema strutturale negli sforzi finiti (non incrementali) è riducibile alle condizioni di Kuhn e Tucker di un programma quadratico. Se ne deducono direttamente una forma generalizzata del principio di Haar e Kármán ed un teorema di estremo negli spostamenti e nelle deformazioni plastiche, duale al precedente. Dai due teoremi discendono come casi speciali noti principi variazionali, che cosi risultano collegati in coppie dalla nozione di dualitá propria della teoria delle ottimizzazioni.Si mostra come anche i teoremi statico e cinematico del calcolo a rottura trovano una nuova dimostrazione nell'inquadramento teorico unitario fondato sulla programmazione quadratica.

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The results presented here form part of a series of studies supported by the C.N.R. (National Research Council).     

Exciplexes in highly excited triplet states

A mechanism of energy transfer from highly excited triplet aromatic molecules has been developed, which involves a stage of formation of an exciplex between a highly excited energy-donor molecule and an unexcited energy-acceptor molecule. Interpretation of the experimental data on the shape and the intensity of triplet-triplet absorption bands and the energy transfer probability is presented. In this interpretation, the results of quantum-chemical calculations of the energies of highly excited triplet states of toluene and benzene molecules are used.