Development of combinatorial chemistry methods for coatings: high-throughput adhesion evaluation and scale-up of combinatorial leads

Coupling of combinatorial chemistry methods with high-throughput (HT) performance testing and measurements of resulting properties has provided a powerful set of tools for the 10-fold accelerated discovery of new high-performance coating materials for automotive applications. Our approach replaces labor-intensive steps with automated systems for evaluation of adhesion of 8 x 6 arrays of coating elements that are discretely deposited on a single 9 x 12 cm plastic substrate. Performance of coatings is evaluated with respect to their resistance to adhesion loss, because this parameter is one of the primary considerations in end-use automotive applications. Our HT adhesion evaluation provides previously unavailable capabilities of high speed and reproducibility of testing by using a robotic automation, an expanded range of types of tested coatings by using the coating tagging strategy, and an improved quantitation by using high signal-to-noise automatic imaging. Upon testing, the coatings undergo changes that are impossible to quantitatively predict using existing knowledge. Using our HT methodology, we have developed several coatings leads. These HT screening results for the best coating compositions have been validated on the traditional scales of coating formulation and adhesion loss testing. These validation results have confirmed the superb performance of combinatorially developed coatings over conventional coatings on the traditional scale.     

Symplectic curvature tensors

In the paper, one establishes the decomposition of the space of tensors which have the symmetries of the curvature of a torsionless symplectic connection into Sp (n)-irreducible components. This leads to three interesting classes of symplectic connections: flat, Ricci flat, and similar to the Levi-Civita connections of Kähler manifolds with constant holomorphic sectional curvature (we call them connections with reducible curvature). A symplectic manifold with two transversal polarizations has a canonical symplectic connection, and we study properties that are encountered if this canonical connection belongs to the classes mentioned above. For instance, in the reducible case we can compute the Pontrjagin classes, and these will be zero if the polarizations are real, etc. If the polarizations are real and there exist points where they are either singular or nontransversal, one has residues in the sense ofLehmann [L], which should be expected to play an interesting role in symplectic geometry.     

Screening for protease substrate by polyvalent phage display

Proteases are key regulators of many physiological and pathological processes [1,2], and are recognized as important and tractable drug candidates. Consequently, knowledge of protease substrate recognition and specificity promotes identification of biologically relevant substrates, helps elucidating a protease's biological function, and the design of specific inhibitors. Traditional methods for establishing substrate recognition profiles involve the identification of the scissile bond within a given protein substrate by proteomic methods such as Edman degradation. Then, synthetic peptide variants of this sequence can be screened in an iterative fashion to arrive at more optimized substrates. Even though it can be fruitful, this iterative strategy is biased toward the original substrate sequence and it is also tremendously cumbersome. Furthermore, it is not amenable to high throughput analysis. In 1993, Matthew & Wells presented a method for the use of monovalent "substrate phage" libraries for discovering peptide substrates for proteases, in which more than 10(7) potential substrates can be tested concurrently [3]. A library of fusion proteins was constructed containing randomized substrate sequences placed between a binding domain and the gene III coat protein of the filamentous phage, M13, which displays the fusion protein and packages the gene coding for it inside. Each fusion protein was displayed as a single copy on filamentous phagemid particles (substrate phage). This method allows one to rapidly survey the substrate recognition and specificity of individual or closely related members of proteases. Over the past decade, substrate phage screening has shown terrific utility in rapidly determining protease specificity and characterization of substrate recognition profile of proteases. In some cases, the structural insights of the catalytic domain were obtained from comparison of substrate specificity among closely related family of proteases [4-6]. The number of proteases (from various classes) characterized by this approach testifies to its power. Since the initial development of substrate phage library, different versions of the substrate phage cloning vectors have been constructed to further improve the utility of substrate phage display. This review will provide an overview of the construction of substrate phage display libraries, screening of substrate phage libraries, examples of application, summary and future directions.     

Foliate partial holomorphic structures on principal bundles

Thefoliate partial holomorphic (f.p.h.) pseudogroup is the pseudogroup of the local diffeomorphisms of ^m which preserve a distribution of the form span , wherey ^a are real coordinates,z are complex coordinates, and ^m may have also some other real coordinates. The f.p.h. structures on manifolds are described geometrically by the Nirenberg-Frobenius theorem [N], and occur in many interesting situations [R], [FW], [DK1], [V3], etc. The present paper discusses f.p.h. structures on principal bundles, and associates with such structures adapted connections, and forms with values in an associated bundle of Lie algebras.     

Riemannian manifolds with a parallel field of complex planes

The purpose of this paper is to discuss Riemannian manifolds which admit a parallel field of complex planes, consisting of vectors of the form , where a,b are real orthogonal vectors of equal length. Using the Nirenberg Frobenius Theorem [12], it follows that these are reducible Riemannian manifolds, whose metric is locally a sum of a Kähler and of a Riemann metric, and we are calling thempartially Kähler manifolds.After a general presentation of these manifolds (including a general presentation of the complex integrable plane fields) we are discussing harmonic forms, Betti numbers, and Dolbeault cohomology. This discussion is based on a theorem of Chern [4], and it provides generalizations of the results of Goldberg [9], as well as some other new results.To Prof. R. Artzy on his 70th Birthday     

On locally conformal almost Kähler manifolds

In the first section of this note, we discuss locally conformal symplectic manifolds, which are differentiable manifoldsV ²ⁿ endowed with a nondegenerate 2-form Ω such thatdΩ=θ ∧ Ω for some closed form θ. Examples and several geometric properties are obtained, especially for the case whendΩ ≠ 0 at every point. In the second section, we discuss the case when Ω above is the fundamental form of an (almost) Hermitian manifold, i.e. the case of the locally conformal (almost) Kähler manifolds. Characterizations of such manifolds are given. Particularly, the locally conformal Kähler manifolds are almost Hermitian manifolds for which some canonically associated connection (called the Weyl connection) is almost complex. Examples of locally conformal (almost) Kähler manifolds which are not globally conformal (almost) Kähler are given. One such example is provided by the well-known Hopf manifolds.     

Exotic characteristic classes of quaternionic bundles

For aC ^∞ quaternionic vector bundle, the odd-dimensional real Chern classes vanish, and this allows for a construction of secondary (exotic) characteristic classes associated with a pair of quaternionic structures of a given complex vector bundle. This construction is then applied to obtain exotic characteristic classes associated with an automorphismβ of the holomorphic tangent bundle of a Kähler manifold. These results are the complex analoga of those given for the higher order Maslov classes in [V2].