Structure and absolute stereochemistry of phormidolide,a new toxic metabolite from the marine cyanobacterium Phormidium sp

The extract from a laboratory culture of an Indonesian isolate of the cyanobacterium Phormidium sp. displayed inhibitory activity in a Ras-Raf protein interaction assay. Assay-guided fractionation led to the isolation of both active and inactive materials of novel structure. The major inactive metabolite, phormidolide, was nevertheless highly toxic to brine shrimp (LC(50) = 1.5 microM), and hence, its structure was elucidated using various spectroscopic methods, primarily NMR. A series of partial structures were developed from standard experiments and then assembled using GHMBC, 2D INADEQUATE, and ACCORD-ADEQUATE data obtained on a (13)C-enriched sample. The relative stereochemistry at phormidolide's 11 chiral centers was established using the J-based configuration analysis method in concert with the G-BIRD(R)-HSQMBC NMR experiment. Absolute stereochemistry was determined on a bis-acetonide derivative using the variable temperature Mosher ester method. The robust number of NMR restraints provided from determination of most homonuclear and heteronuclear coupling constants in phormidolide, along with an abundance of NOE information, allowed construction of a refined lowest energy three-dimensional structure in Macromodel. Phormidolide is one of only a few macrolide-type natural products to be reported from marine cyanobacteria.     

Gradient nanoscale polycrystalline elasticity: Intergrain interactions and triple-junction conditions

Using the principle of virtual power, we develop general balance equations, interface conditions, triple-junction conditions, and boundary conditions for second-grade nanocrystalline elastic materials undergoing infinitesimal deformations. We further develop thermodynamically consistent constitutive equations and provide a weak formulation of resulting boundary-value problems that automatically yields internal conditions such those that hold across interfaces and at triple junctions.     

Identities in Finite Strain

First of all the deformation is considered of two infinitesimal material line elements lying along vectors M,N emanating from a particle at X in a body. For all M,N lying in a given plane, an identity is derived relating the stretches along M,N and the angles of the pair of infinitesimal material line elements before and after deformation. Then, the deformation is considered of three non-coplanar infinitesimal material line elements lying along vectors M,N,P emanating from a particle at X in a body. An identity is derived relating the stretches along M,N,P and the angles between the three pairs of infinitesimal material line elements before and after deformation. The identity is factored leading to easy interpretation. The special case of infinitesimal strain is considered.      

Théorie des effets rhéo-optiques dans un continu polarisable et magnétisable

Summary The total momentum-energy tensor describing the interaction of a polarizable and magnetizable continuum with an electromagnetic field is constructed on the basis ofLorentz invariance. The equations of balance of energy and momentum are deduced and applied to the study of the magnetooptical, electrooptical and photoelastic behavior of an elastic polarizable and magnetizable isotropic continuum. This model exhibits theCotton-Mouton andKerr effects but thePockels andFaraday rotations don't appear.     

Bestimmung kleiner Bleimengen in Silber

Ohne Zusammenfassung     

Methodology for the validation of analytical methods involved in uniformity of dosage units tests

Validation of analytical methods is required prior to their routine use. In addition, the current implementation of the Quality by Design (QbD) framework in the pharmaceutical industries aims at improving the quality of the end products starting from its early design stage. However, no regulatory guideline or none of the published methodologies to assess method validation propose decision methodologies that effectively take into account the final purpose of developed analytical methods. In this work a solution is proposed for the specific case of validating analytical methods involved in the assessment of the content uniformity or uniformity of dosage units of a batch of pharmaceutical drug products as proposed in the European or US pharmacopoeias. This methodology uses statistical tolerance intervals as decision tools. Moreover it adequately defines the Analytical Target Profile of analytical methods in order to obtain analytical methods that allow to make correct decisions about Content uniformity or uniformity of dosage units with high probability. The applicability of the proposed methodology is further illustrated using an HPLC-UV assay as well as a near infra-red spectrophotometric method.     

New advances in method validation and measurement uncertainty aimed at improving the quality of chemical data

The implementation of quality systems in analytical laboratories has now, in general, been achieved. While this requirement significantly modified the way that the laboratories were run, it has also improved the quality of the results. The key idea is to use analytical procedures which produce results that fulfil the users needs and actually help when making decisions. This paper presents the implications of quality systems on the conception and development of an analytical procedure. It introduces the concept of the lifecycle of a method as a model that can be used to organize the selection, development, validation and routine application of a method. It underlines the importance of method validation, and presents a recent approach based on the accuracy profile to illustrate how validation must be fully integrated into the basic design of the method. Thanks to the -expectation tolerance interval introduced by Mee (Technometrics (1984) 26(3):251–253), it is possible to unambiguously demonstrate the fitness for purpose of a new method. Remembering that it is also a requirement for accredited laboratories to express the measurement uncertainty, the authors show that uncertainty can be easily related to the trueness and precision of the data collected when building the method accuracy profile.     

Interaction between a disclination and a uniaxial-isotropic phase interface in a nematic liquid crystal

We consider the interaction between a disclination line of strength +/-1/2 and an interface between the uniaxial and isotropic phases of a nematic liquid crystal. We apply a recently developed set of interface conditions including a configurational force balance which generalizes the Gibbs-Thomson equation to account for the curvature elasticity of the uniaxial phase and the orientation dependence of the interfacial free-energy density. We consider a rectangular vessel containing both phases and a disclination. We formulate a relevant free-boundary problem and use numerical methods to determine equilibrium shapes of the interface. When the interfacial free-energy is constant, the shape of the interface is insensitive to whether the strength of the defect is +1/2 or -1/2 and to rotations of the director field consistent with the boundary conditions. Accounting for the dependence of the interfacial free-energy density on the angle between the interfacial unit normal field and the director field eliminates these degeneracies. In particular, when such dependence is taken into account, different solution branches are found, indicating the presence of a bifurcation. We find also that, depending on the magnitude of the anisotropic contribution to the interfacial free-energy density, the interaction between the disclination and the interface may be repulsive or attractive. When the interaction is repulsive, the disclination line positions itself at an energetically optimal distance adjacent to the interface. Otherwise, the uniaxial phase expels the disclination to the interface where a cusp forms.     

Tensor Gauge Fields in Arbitrary Representations of GL( D, $${\mathbb{R})}$$ : II. Quadratic Actions

Quadratic, second-order, non-local actions for tensor gauge fields transforming in arbitrary irreducible representations of the general linear group in D-dimensional Minkowski space are explicitly written in a compact form by making use of Levi–Civita tensors. The field equations derived from these actions ensure the propagation of the correct massless physical degrees of freedom and are shown to be equivalent to non-Lagrangian local field equations proposed previously. Moreover, these actions allow a frame-like reformulation à la MacDowell–Mansouri, without any trace constraint in the tangent indices. Chargé de Recherches FNRS, Belgium