Synthesis of novel simplified eleutheside analogues with potent microtubule-stabilizing activity, using ring-closing metathesis as the key-step

The synthesis of a number of novel simplified eleutheside analogues with potent tubulin-assembling and microtubule-stabilizing properties is described, using ring-closing metathesis as the key-step for obtaining the 6-10 fused bicyclic ring system.     

Introduction to session 4

Applied Biochemistry and Biotechnology -     

Kraichnan Flow in a Square: An Example of Integrable Chaos

The Kraichnan flow provides an example of a random dynamical system accessible to an exact analysis. We study the evolution of the infinitesimal separation between two Lagrangian trajectories of the flow. Its long-time asymptotics is reflected in the large deviation regime of the statistics of stretching exponents. Whereas in the flow that is isotropic at small scales the distribution of such multiplicative large deviations is Gaussian, this does not have to be the case in the presence of an anisotropy. We analyze in detail the flow in a two-dimensional periodic square where the anisotropy generally persists at small scales. The calculation of the large deviation rate function of the stretching exponents reduces in this case to the study of the ground state energy of an integrable periodic Schrödinger operator of the Lamé type. The underlying integrability permits to explicitly exhibit the non-Gaussianity of the multiplicative large deviations and to analyze the time-scales at which the large deviation regime sets in. In particular, we indicate how the divergence of some of those time scales when the two Lyapunov exponents become close allows a discontinuity of the large deviation rate function in the parameters of the flow. The analysis of the two-dimensional anisotropic flow permits to identify the general scenario for the appearance of multiplicative large deviations together with the restrictions on its applicability.     

The effect of relative humidity of inhaled air onacoustic parameters of voice in normal subjects

The hypothesis that relative humidity (RH) of air exerts an effect on voice has been widely accepted. The aim of this study has been to assess whether this can be demonstrated. Eight healthy subjects inhaled during ten minutes three different air conditions: dry, standard room, and humidified air. After inhalation, the subjects produced repeatedly a sustained /a/ of controlled pitch and loudness, which was analyzed for perturbation and noise-to-harmonic parameters. Perturbation measures increased after inhalation of dry air. No significant differences existed between standard and humidified air. No significant difference in the noise-to-harmonic ratio was found among the three conditions. We conclude that the human voice is very sensitive to decreases in RH of inhaled air, because even after a short provocation with dry air, a significant increase in perturbation measures was found.     

A procedure for “iodolactamization”

Treatment of an unsaturated amide with TMS-OTf, then iodine in THF gives the iodolactam.     

Synthesis of (±)-8,9-deoxyalliacol B

The first elaboration of the novel framework of the alliacane group of sesquiterpene lactones is exemplified by the synthesis of (±)-8,9-deoxyalliacol B (13).     

Box-spline–based approach to the formulation of numerical methods for partial differential equations

A multivariate box spline framework for the formulation of numerical methods for partial differential equations has been constructed. In particular, a fourth-order Galerkin method and a second-order collocation method were derived and applied to a test problem (classical Poisson equation on a square). The examples indicate that accuracy compares favorably with standard methods and the success of iterative schemes suggests an underlying stabilizing effect.     

An improved route to steganone

A new route, readily applicable on a large scale, is described to the phenanthrene ($\text{8}$) the key intermediate in the synthesis of steganone ($\text{1}$).     

Uniqueness of Gibbs states for generalP(ϕ)2-weak coupling models by cluster expansion

We consider quantum fields with weak coupling in two space-time dimensions. We prove that the set of their ultraregular Gibbs states consists of only one point and this point is an extremal Gibbs state.     

Localizing Antifungal Drugs to the Correct Organelle Can Markedly Enhance their Efficacy

A critical aspect of drug design is optimal target inhibition by specifically delivering the drug molecule not only to the target tissue or cell but also to its therapeutically active site within the cell. This study demonstrates, as a proof of principle, that drug efficacy can be increased considerably by a structural modification that targets it to the relevant organelle. Specifically, by varying the fluorescent dye segment an antifungal azole was directed from the fungal cell mitochondria to the endoplasmic reticulum (ER), the organelle that harbors the drug target. The ER‐localized azole displayed up to two orders of magnitude improved antifungal activity and also dramatically reduced the growth of drug‐tolerant fungal subpopulations in a panel of Candida species, which are the most prevalent causes of serious human fungal infections. The principle underlying the “target organelle localization” approach provides a new paradigm to improve drug potency and replenish the limited pipeline of antifungal drugs.