Engineering linear F(ab')2 fragments for efficient production in Escherichia coli and enhanced antiproliferative activity

We developed a novel bivalent antibody fragment, the linear(L-) F(ab')₂, comprising tandem repeats of a heavy chain fragmentV_H–C_H1–V_H–C_H1 cosecreted with a light chain.Functional humanized L-F(ab')₂ directed against p185^HER2 wassecreted from Escherichia coli at high titer (100 mg/l) andpurified to homogeneity. The L-F(ab')₂ binds two equivalentsof antigen with an apparent affinity (K_d = 0.46 nM) that iswithin 3-fold of the corresponding thioether-linked F(ab')₂fragment The N-terminal site binds antigen with an affinity(K_d = 1.2 nM) that is 4-fold greater than that for the C-terminalsite, as shown by the comparison of L-F(ab')₂ variants containinga single functional binding site. L-F(ab')₂ has greater antiproliferativeactivity than the thioether-linked F(ab')₂ against the p185^HER2-overexpressingtumor cell line BT474. Linear and thioether-linked F(ab')₂ havevery similar pharmacokinetic properties in normal mice, andtheir serum permanence times are respectively 7- and 8-foldlonger than the corresponding Fab fragment L-F(ab')₂ offersa facile route to bivalent antibody fragments that are potentiallysuitable for clinical applications, and that may have improvedbiological activity compared with thioether-linked F(ab')₂ fragments.     

Hybrid learning for interval type-2 fuzzy logic systems based on orthogonal least-squares and back-propagation methods

This paper presents a novel learning methodology based on a hybrid algorithm for interval type-2 fuzzy logic systems. Since only the back-propagation method has been proposed in the literature for the tuning of both the antecedent and the consequent parameters of type-2 fuzzy logic systems, a hybrid learning algorithm has been developed. The hybrid method uses a recursive orthogonal least-squares method for tuning the consequent parameters and the back-propagation method for tuning the antecedent parameters. Systems were tested for three types of inputs: (a) interval singleton, (b) interval type-1 non-singleton, and (c) interval type-2 non-singleton. Experiments were carried out on the application of hybrid interval type-2 fuzzy logic systems for prediction of the scale breaker entry temperature in a real hot strip mill for three different types of coil. The results proved the feasibility of the systems developed here for scale breaker entry temperature prediction. Comparison with type-1 fuzzy logic systems shows that hybrid learning interval type-2 fuzzy logic systems provide improved performance under the conditions tested.     

A distributed control scheme for multiple robotic vehicles to make group formations

This paper presents a novel distributed control scheme of multiple robotic vehicles. Each robotic vehicle in this scheme has its own coordinate system, and it senses its relative position and orientation to others, in order to make group formations. Although there exists no supervisor and each robotic vehicle has only relative position feedback from the others in the local area around itself, all the robotic vehicles are stabilized, which we have succeeded in proving mathematically only in the cases where the attractions between the robots are symmetrical. Each robotic vehicle especially has a two-dimensional control input referred to as a “formation vector” and the formation is controllable by the vectors. The validity of this scheme is supported by computer simulations.     

The checkered puffer (Spheroides testudineus) and its helminths as bioindicators of chemical pollution in Yucatan coastal lagoons

The suitability of using helminth communities as bioindicators of environmental quality of the Yucatan coastal lagoons status was tested on the checkered puffer (Spheroides testudineus) in four coastal lagoons along the Yucatan coast. The concentration of chemical pollutants in sediments, water quality parameters, helminth infracommunity characteristics, as well as fish physiological biomarkers, including EROD (7-ethoxyresorufin-O-deethylase) and catalase activities, were measured. Results from sediment analyses demonstrated the presence of hydrocarbons, organochlorine pesticides and polychlorinated biphenyls at varying concentrations, some of which exceeded the Probability Effect Level (PEL). Significant negative associations among organochlorine pesticides, infracommunity characteristics and fish physiological responses were observed in most of the lagoons. Results suggest that EROD activity and parasite infracommunity characteristics could be useful tools to evaluate the effects of chemical pollutants on the fish host and in the environment. Importantly, certain parasites appear to influence biomarker measurements, indicating that parasites should be considered in ecotoxicological studies.     

Urban Imaginaries: Locating the Modern City

In this article, we review three microcomputer programs for assessing regional economic impacts. The programs are ADOTMATR, GRIMP, and REMI, which we discuss in terms of their suitability for policy analysis and planning practice. We assess the programs in terms of range of applicability, flexibility and ease of use in conducting impact analyses, quality of output, and cost. ADOTMATR and GRIMP are similar; however, GRIMP is easier to use but less flexible and more limited than ADOTMATR. Although REMI is more sophisticated than the other two programs, it is more expensive and more limited in application.