Solution bias in ant colony optimisation: Lessons for selecting pheromone models

Ant colony optimisation is a constructive metaheuristic in which solutions are built probabilistically influenced by the parameters of a pheromone model—an analogue of the trail pheromones used by real ants when foraging for food. Recent studies have uncovered the presence of biases in the solution construction process, the existence and nature of which depend on the characteristics of the problem being solved. The presence of these solution construction biases induces biases in the pheromone model used, so selecting an appropriate model is highly important. The first part of this paper presents new findings bridging biases due to construction with biases in pheromone models. Novel approaches to the prediction of this bias are developed and used with the knapsack and generalised assignment problems. The second part of the paper deals with the selection of appropriate pheromone models when detailed knowledge of their biases is not available. Pheromone models may be derived either from characteristics of the way solutions are represented by the algorithm or characteristics of the solutions represented, which are often quite different. Recently it has been suggested that the latter is more appropriate. The relative performance of a number of alternative pheromone models for six well-known combinatorial optimisation problems is examined to test this hypothesis. Results suggest that, in general, modelling characteristics of solutions (rather than their representations) does lead to the best performance in ACO algorithms. Consequently, this principle may be used to guide the selection of appropriate pheromone models in problems to which ACO has not yet been applied.     

Capillary Assembly of Liquid Particles

Capillary assembly is a versatile method for depositing colloidal particles within templates, resulting in nano/microarrays and colloidal superstructures for optical, plasmonic, and sensory applications. Liquid particles (LPs), comprised of oligomerized 3‐(trimethoxysilyl)propyl methacrylate, are herein shown to deposit into patterned cavities via capillary assembly. In contrast to solid colloids, LPs coalesce upon solvent evaporation and assume the geometry of the template. Incorporating small molecules such as dyes followed by LP solidification generates fluorescent polymer microarrays of any geometry. The LP size is inversely proportional to the quantity of deposited material and the convexity of the final polymer array. Cavity filling can be tuned by increasing the assembly temperature. Extraction of the polymerized regions produces solidified particles with faceted shapes including square prisms, trapezoids, and ellipsoids with sizes up to 14 µm that retain the shape of the cavity in which they are initially held. LP deposition thus presents a highly controllable fabrication scheme for geometrically diverse polymer microarrays and anisotropic colloids of any conceivable polygonal shape due to space filling of the template. The extension of capillary assembly to LPs that can be doped with small molecule dyes and analytes invaluably expands the synthetic toolbox for top‐down, scalable, hierarchically engineered materials.     

Modulare Verfahrenstechnik: Apparateentwicklung für wandlungsfähige Produktionssysteme

The process industry faces the challenges of intensified, global competition with increasing market dynamics. Modular, transformable production concepts promise a better adaption to these in the dimensions of throughput, product mix and production location. In order to unfold the full potential, modularization and transformability have to be applied not only on plant and logistics level but also on apparatus level. Characteristics like setup and scaling concepts are discussed. Examples for modular apparatuses concerning the process engineering tasks of mixing, heat exchange, reaction and separation are presented and further research needs are derived.     

Computer system implementation, batch standards and validation

Today's market requirements drive companies in all industries to find ways to become more competitive, reduce project time lines and keep costs low. We at Genzyme Corporation's new Allston Landing Biopharmaceutical Manufacturing Facility have used standards — such as Instrument Society of America (ISA) draft standards for Batch Control Systems Models and Technology (ISA dSP88.01) — to save engineering time, money and help us meet our Food and Drug Administration (FDA) regulatory objectives with respect to implementation of a process management system.     

Process automation toward ultra-high-throughput screening of combinatorial one-bead-one-compound (OBOC) peptide libraries

With an aim to develop peptide-based protein capture agents that can replace antibodies for in vitro diagnosis, an ultra-high-throughput screening strategy has been investigated by automating labor-intensive, time-consuming processes that are the construction of peptide libraries, sorting of positive beads, and peptide sequencing through analysis of tandem mass spectrometry data. Although instruments for automation, such as peptide synthesizers and automatic bead sorters, have been used in some groups, the overall process has not been well optimized to minimize time, cost, and efforts, as well as to maximize product quality and performance. Herein we suggest and explore several solutions to the existing problems with the automation of the key processes. The overall process optimization has been done successfully in orchestration with the technologies such as rapid cleavage of peptides from beads and semiautomatic peptide sequencing that we have developed previously. This optimization allowed one-round screening, from peptide library construction to peptide sequencing, to be completed within 4 to 5 days. We also successfully identified a 6-mer ligand for carcinoembryonic antigen-cell adhesion molecule 5 (CEACAM 5) through three-round screenings, including one-round screening of a focused library.     

Effects of the Tumor‐Vasculature‐Disrupting Agent Verubulin and Two Heteroaryl Analogues on Cancer Cells,Endothelial Cells,and Blood Vessels

Two analogues of the discontinued tumor vascular‐disrupting agent verubulin (Azixa®, MPC‐6827, 1 ) featuring benzo‐1,4‐dioxan‐6‐yl (compound 5 a ) and N‐methylindol‐5‐yl (compound 10 ) residues instead of the para‐anisyl group on the 4‐(methylamino)‐2‐methylquinazoline pharmacophore, were prepared and found to exceed the antitumor efficacy of the lead compound. They were antiproliferative with single‐digit nanomolar IC₅₀ values against a panel of nine tumor cell lines, while not affecting nonmalignant fibroblasts. Indole 10 surpassed verubulin in seven tumor cell lines including colon, breast, ovarian, and germ cell cancer cell lines. In line with docking studies indicating that compound 10 may bind the colchicine binding site of tubulin more tightly (E_bind=?9.8 kcal mol^?1) than verubulin (E_bind=?8.3 kcal mol^?1), 10 suppressed the formation of vessel‐like tubes in endothelial cells and destroyed the blood vessels in the chorioallantoic membrane of fertilized chicken eggs at nanomolar concentrations. When applied to nude mice bearing a highly vascularized 1411HP germ cell xenograft tumor, compound 10 displayed pronounced vascular‐disrupting effects that led to hemorrhages and extensive central necrosis in the tumor.