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This paper presents a multiobjective evolutionary algorithm to optimize radial basis function neural networks (RBFNNs) in order to approach target functions from a set of input-output pairs. The procedure allows the application of heuristics to improve the solution of the problem at hand by including some new genetic operators in the evolutionary process.(More)
Penicillium chrysogenum npe6 lacking isopenicillin N acyltransferase activity is an excellent host for production of different beta-lactam antibiotics. We have constructed P. chrysogenum strains expressing cefD1, cefD2, cefEF, and cefG genes cloned from Acremonium chrysogenum. Northern analysis revealed that the four genes were expressed in P. chrysogenum.(More)
The conversion of deacetylcephalosporin C to cephalosporin C is inefficient in most Acremonium chrysogenum strains. The cefG gene, which encodes deacetylcephalosporin C acetyltransferase, is expressed very poorly in A. chrysogenum as compared to other genes of the cephalosporin pathway. Introduction of additional copies of the cefG gene with its native(More)
Glucose repressed transcription of the penicillin biosynthesis genes pcbAB, pcbC and penDE when added at inoculation time to cultures of Penicillium chrysogenum AS-P-78 but it had little repressive effect when added at 12 h and no effect when added at 24 or 36 h. A slight increase in the expression of pcbC and penDE (and to a smaller extent of pcbAB) was(More)
The design of a new versatile control system that will underlie future releases of the automated model-building package ARP/wARP is presented. A sophisticated expert system is under development that will transform ARP/wARP from a very useful model-building aid to a truly automated package capable of delivering complete, well refined and validated models(More)
The penicillin biosynthetic genes (pcbAB, pcbC, penDE) of Penicillium chrysogenum AS-P-78 were located in a 106.5-kb DNA region that is amplified in tandem repeats (five or six copies) linked by conserved TTTACA sequences. The wild-type strains P. chrysogenum NRRL 1951 and Penicillium notatum ATCC 9478 (Fleming's isolate) contain a single copy of the(More)
PURPOSE This study aimed to evaluate the presence of abnormalities in the retinal nerve fibre layer (RNFL) in multiple sclerosis (MS) patients with normal ophthalmic examination, and to compare the ability of optical coherence tomography (OCT) and scanning laser polarimetry (GDx) to detect axonal loss. METHODS Patients with MS and disease-free controls(More)
The epimerization step that converts isopenicillin N into penicillin N during cephalosporin biosynthesis has remained uncharacterized despite its industrial relevance. A transcriptional analysis of a 9-kb region located downstream of the pcbC gene revealed the presence of two transcripts that correspond to the genes named cefD1 and cefD2 encoding proteins(More)
PURPOSE To quantify changes in the retinal nerve fiber layer (RNFL) of patients with multiple sclerosis (MS) over 3 years and to evaluate whether treatment protects against RNFL degeneration. METHODS Ninety-four MS patients and 50 healthy subjects were followed-up over 3 years. All subjects underwent a complete ophthalmic examination, which included(More)