An expedient synthesis of diversified pyrrolizines and indolizines

A general and rapid synthesis of new families of pyrrolizines and indolizines in good overall yields via an intramolecular [3+2] cycloaddition reaction is described. Diversity of substitutions can be achieved by the appropriate choice of readily available starting materials. The experimental procedures are straightforward and are performed under neutral conditions. New syntheses are also described for the preparation of N-propargylic 2-amino-benzaldehydes and S-propargylic 2-thiobenzaldehydes.     

Phylogenetic Diversity Over an Abelian Group

There is a natural way to associate to any tree T with leaf set X, and with edges weighted by elements from an abelian group G, a map from the power set of X into G—simply add the elements on the edges that connect the leaves in that subset. This map has been well-studied in the case where G has no elements of order 2 (particularly when G is the additive group of real numbers) and, for this setting, subsets of leaves of size two play a crucial role. However, the existence and uniqueness results in that setting do not extend to arbitrary abelian groups. We study this more general problem here, and by working instead with both, pairs and triples of leaves, we obtain analogous existence and uniqueness results. Some particular results for elementary abelian 2-groups are also described. Received July 13, 2005     

Ensuring population diversity in genetic algorithms: A technical note with application to the cell formation problem

The entropy-based measure has been used in previous works to compute the population diversity in solving the cell formation problem with the genetic algorithm. Population diversity is crucial to the genetic algorithm’s ability to continue fruitful exploration as it may be used in choosing an initial population, in defining a stopping criterion, in evaluating the population convergence, and in making the search more efficient throughout the selection of crossover operators or the adjustment of various control parameters (e.g., crossover or mutation rate, population size). We show in this note that, when a non-ordinal chromosome representation corresponding to the allocation of machines to cells is used, the current way of measuring the population diversity is inaccurate. Consequently, it leads to wrong conclusions when, at various iterations, carrying out fruitful exploration or an efficient search of the solution space is guided by the perceived population diversity degree. An alternative approach based on computing the distance and the similarity between chromosomes is discussed.     

Affinity genetic algorithm

Based on some phenomena from human society and nature, we propose a binary affinity genetic algorithm (aGA) by adopting the following strategies: the population is adaptively updated to avoid stagnation; the newly generated individuals will be ensured to survive for some generations in order for them to have time to show their good genes; new individuals and the old ones are balanced to have the advantages of both. In order to quantitatively analyze the selective pressure, the concept of selection degree and a simple linear control equation are introduced. We can maintain the diversity of the evolutionary population by controlling the value of the selection degree. Performance of aGA is further enhanced by incorporating local search strategies. Partially supported by a National Key Basic Research Project of China and by a USA NSF grant CCR-0201253.     

基于免疫原理的蚁群系统及其应用

针对蚁群算法在寻优过程中容易出现停滞现象,同意在该算法中引入免疫机制,将待求解问题看成抗原,而问题的解看成抗体,通过基于浓度的选择机制和多样性保持策略来提高蚁群算法的全局搜索能力和避免停滞现象.对TSP问题的仿真实验结果表明,该算法极大地提高了搜索能力和避免了停滞现象.     

Morphological similarity: A 3D molecular similarity method correlated with protein-ligand recognition

Recognition of small molecules by proteins depends on three-dimensional molecular surface complementarity. However, the dominant techniques for analyzing the similarity of small molecules are based on two-dimensional chemical structure, with such techniques often outperforming three-dimensional techniques in side-by-side comparisons of correlation to biological activity. This paper introduces a new molecular similarity method, termed morphological similarity (MS), that addresses the apparent paradox. Two sets of molecule pairs are identified from a set of ligands whose protein-bound states are known crystallographically. Pairs that bind the same protein sites form the first set, and pairs that bind different sites form the second. MS is shown to separate the two sets significantly better than a benchmark 2D similarity technique. Further, MS agrees with crystallographic observation of bound ligand states, independent of information about bound states. MS is efficient to compute and can be practically applied to large libraries of compounds.     

Synthesis of structurally diverse biflavonoids

Synthetic biflavonoids are associated with interesting biological activities, yet they remain poorly explored within drug discovery. Recent years have witnessed a growing interest in synthetic approaches that can provide access to structurally novel biflavonoids so that the biological usefulness of this compound class can be more fully investigated. Herein, we report upon the exploration of strategies based around Suzuki-Miyaura cross-coupling and alcohol methylenation for the synthesis of two classes of biflavonoids: (i) rare ‘hybrid’ derivatives containing flavonoid monomers belonging to different subclasses, and (ii) homodimeric compounds in which the two flavonoid monomers are linked by a methylenedioxy group. Application of these strategies enabled the preparation of a structurally diverse collection of novel biflavonoids from readily-available starting materials, thereby facilitating the probing of uncharted regions of biologically interesting chemical space.     

Anderson Localization, Non-linearity and Stable Genetic Diversity

In many models of genotypic evolution, the vector of genotype populations satisfies a system of linear ordinary differential equations. This system of equations models a competition between differential replication rates (fitness) and mutation. Mutation operates as a generalized diffusion process on genotype space. In the large time asymptotics, the replication term tends to produce a single dominant quasi-species, unless the mutation rate is too high, in which case the asymptotic population becomes de-localized. We introduce a more macroscopic picture of genotypic evolution wherein a random fitness term in the linear model produces features analogous to Anderson localization. When coupled with density dependent non-linearities, which limit the population of any given genotype, we obtain a model whose large time asymptotics display stable genotypic diversity.Research partially supported by DARPA under the FUNBIO program and the Francis J. Carey Term Chair.