Production planning of a flexible manufacturing system in a material requirements planning environment

Early flexible manufacturing system (FMS) production planning models exhibited a variety of planning objectives; typically, these objectives were independent of the overall production environment. More recently, some researchers have proposed hierarchical production planning and scheduling models for FMS. In this article, we examine production planning of FMS in a material requirements planning (MRP) environment. We propose a hierarchical structure that integrates FMS production planning into a closed-loop MRP system. This structure gives rise to the FMS/MRP rough-cut capacity planning (FMRCP) problem, the FMS/MRP grouping and loading (FMGL) problem, and the FMS/MRP detailed scheduling problem. We examine the FMRCP and FMGL problems in detail and present mathematical programming models for each of these problems. In particular, the FMRCP problem is modeled as a generalized assignment problem (GAP), and a GAP-based heuristic procedure is defined for the problem. We define a two-phase heuristic for the FMGL problem and present computational experience with both heuristics. The FMRCP heuristic is shown to solve problems that exhibit a dependent-demand relation within the FMS and with FMS capacity utilization as high as 99 percent. The FMGL heuristic requires very little CPU time and obtains solutions to the test problems that are on average within 1.5 percent of a theoretical lower bound. This FMS/MRP production planning framework, together with the resulting models, constitutes an important step in the integration of FMS technology with MRP production planning. The hierarchical planning mechanism directly provides for system-level MRP planning priorities to induce appropriate production planning and control objectives on the FMS while simultaneously allowing for necessary feedback from the FMS. Moreover, by demonstrating the tractability of the FMRCP and FMGL problems, this research establishes the necessary groundwork upon which to explore systemwide issues pertaining to the coordination of the hierarchical structure.     

Oxidant inhibition of epithelial active sodium transport

The purpose of this study was to quantify the effects of extracellularly generated partially reduced oxygen species on active sodium (NA⁺) transport across the ventral toad skin, a well-studied epithelium. Sections of skin from decapitated toads were mounted in an Ussing chamber, bathed on both sides with electrolyte solution containing 500 μM xanthine and bubbled continuously with room air. The tissues were short-circuited, and short circuit current (Isc) and tissue resistance (R_t were monitored continuously with an automatic voltage clamp apparatus. Fifteen mU/ml of xanthine oxidase (XO), either purchased from Calbiochem or purified from cream, were instilled in either the apical (mucosal) or basolateral (serosal) baths at t = 0 and T = 10 min. Hydrogen peroxide (H₂O₂) concentrations increased to 200 μM within the first 20 min and then decreased, reaching a value of 40 μM by 60 min. Mean [H₂O₂] was 90 μM. Instillation of XO in the apical bath resulted in a large decrease in Isc and an increase in R_t, their values being 43% and 160% of their corresponding controls 85 min after the first instillation. Addition of superoxide dismutase and catalase completely prevented these changes. Instillation of XO in the basolateral bath had no effect. Similar physiological responses were obtained using the Calbiochem XO or the purified XO, which contained no measurable protease activity. It was concluded that extracellularly generated partially reduced oxygen species may interfere with active Na⁺ transport by possibly damaging apical Na⁺ channel proteins.     

Molecular evolution of enzyme structure: Construction of a hybrid hamster/Escherichia coli aspartate transcarbamoylase

Summary Aspartate transcarbamoylase (ATCase, EC 2.1.3.2) is the first unique enzyme common to de novo pyrimidine biosynthesis and is involved in a variety of structural patterns in different organisms. InEscherichia coli, ATCase is a functionally independent, oligomeric enzyme; in hamster, it is part of a trifunctional protein complex, designated CAD, that includes the preceding and subsequent enzymes of the biosynthetic pathway (carbamoyl phosphate synthetase and dihydroorotase). The complete complementary DNA (cDNA) nucleotide sequence of the ATCase-encoding portion of the hamster CAD gene is reported here. A comparison of the deduced amino acid sequences of the hamster andE. coli catalytic peptides revealed an overall 44% amino acid similarity, substantial conservation of predicted secondary structure, and complete conservation of all the amino acids implicated in the active site of theE. coli enzyme. These observations led to the construction of a functional hybrid ATCase formed by intragenic fusion based on the known tertiary structure of the bacterial enzyme. In this fusion, the amino terminal half (the “polar domain”) of the fusion protein was provided by a hamster ATCase cDNA subclone, and the carboxyl terminal portion (the “equatorial domain”) was derived from a clonedpyrBI operon ofE. coli K-12. The recombinant plasmid bearing the hybrid ATCase was shown to satisfy growth requirements of transformedE. coli pyrB ⁻ cells. The functionality of thisE. coli-hamster hybrid enzyme confirms conservation of essential structure-function relationships between evolutionarily distant and structurally divergent ATCases.     

Androgen receptor locus on the human X chromosome: regional localization to Xq11-12 and description of a DNA polymorphism

The gene for the androgen receptor, mutations at which cause the X-linked androgen insensitivity syndrome, has been localized to the q11----q12 region of the human X chromosome by analysis, using a cloned cDNA for the androgen receptor, of somatic cell hybrid panels segregating portions of the X chromosome. A moderate-frequency HindIII RFLP has been found which should be useful in genetic linkage analysis of the various inherited forms of androgen insensitivity.     

Structure/activity relationships in the arginine taste pathway of the channel catfish

To characterize the molecular/structural requirements for activationor antagonism of the arginine taste pathways in catfish, Ictaluruspunctatus, structure/activity studies were performed using integratedmultiunit responses and cross-adaptation. Of all the guanidinium-containingcompounds tested, only L-arginine, L--amino-ß-guanidinopropionic acid (L-AGPA) and L-arginine methyl and ethyl esterswere strong stimuli. Results of functional group substitutionsand modification of the L-arginine parent molecule indicatedthat: (i) stereospecificity was observed with D-arginine beinga much less effective stimulus than L-arginine; (ii) an L-aminogroup must be present and unblocked (-chloro-guanidino-N-valericacid and N-acetyl L-arginine were weak or inactive stimuli);(iii) a free carboxylic acid group was not necessary for activity;(iv) the distance between the anomeric carbon and the guanidiniumgroup was not critical (L-AGPA, having two methylene groupsless than L-arginine was a moderately strong stimulus as wasL-canavanine) and (v) modification or substitution of the guanidinumgroup by other basic groups including amine, methyl or dimethylamineor by an isosterc (ureido) resulted in loss of stimulatory ability.In general, those stimuli and analogs that were good cross-adaptersof L-arginine stimulation were also good competitors for L-[³H]argininebinding to a partial membrane fraction (P2) from catfish tasteepithelium. On the other hand, compounds that were poor cross-adaptingstimuli were also poor binding competitors. While D-argininewas a poor stimulus, it did cross-adapt L-arginine and competedwell with L-[³H]arginine for binding to fraction P2.     

Anticoagulant activity of synthetic hirudin peptides

Synthetic peptides based on the COOH-terminal 21 residues of hirudin were prepared in order to 1) evaluate the role of this segment in hirudin action toward thrombin, 2) define the shortest peptide derivative with anticoagulant activity, and 3) investigate the role of tyrosine sulfation in the peptides' inhibitory activities. A hirudin derivative of 20 amino acids, Hir45-64 (derived from residues 45-64 of the hirudin polypeptide), was found to effect a dose-dependent increase in the activated partial thromboplastin time (APTT) of normal human plasma but to have no measurable inhibitory activity toward thrombin cleavage of a tripeptidyl p-nitroanilide substrate. Anticoagulant activity in hirudin derivatives was comparable in peptides of 20, 16, and 12 residues truncated from the NH2 terminus. Additional truncated peptides prepared by synthesis and carboxypeptidase treatment reveal that the minimal sequence of a hirudin peptide fragment with maximal anticoagulant activity is contained within the sequence: NH2-Asn-Gly-Asp-Phe-Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-COOH. The 12-residue derivative thus identified was reacted with dicyclohexylcarbodiimide in the presence of sulfuric acid to yield a Tyr-sulfated peptide, S-Hir53-64. By comparison to unsulfated peptide, S-Hir53-64 was found to contain a specific inhibitory activity enhanced by one order of magnitude toward increase in APTT and to effect a dose-dependent increase in thrombin time of normal human plasma to yield a 4-fold increase in thrombin time with 2.5 micrograms/ml peptide using 0.8 units/ml alpha-thrombin. Comparison of S-Hir53-64 to hirudin in thrombin time and APTT assays reveals a 50-fold difference in molar specific activities toward inhibition of thrombin. Comparison of antithrombin activities of S-Hir53-64 using a variety of animal thrombins demonstrates greatest inhibitory activity toward murine, rat, and human enzymes and a 10-fold reduced activity toward bovine thrombin.     

Reduction of 3-methoxytyramine concentrations in the caudate nucleus of rats after exposure to high-energy iron particles: evidence for deficits in dopaminergic neurons

Exposure to low doses of high-energy iron particles can alter motor behavior. The ability of rats to hang from a wire has been reported to be significantly degraded after exposure to doses as low as 0.5 Gy. In addition, deficits in the ability of acetylcholine to regulate dopamine release in the caudate nucleus (an area in the brain important for motor function) have been found. The concentrations of 3-methoxytyramine (3-MT), a metabolite of dopamine whose concentrations reflect dopamine release in vivo, were measured after rats were exposed to different doses of high-energy iron particles to gain further information about the effect of radiation on the dopaminergic system. Concentrations of 3-MT were significantly reduced 3 days after exposure to 5 Gy but returned to control values by 8 days. After 6 months, concentrations were again less than control values. Exposure to 5 Gy of high-energy electrons or gamma photons had no effect 3 days after exposure. Very high doses of electrons were needed to alter 3-MT concentrations. One hundred grays of electrons decreased 3-MT 30 min after irradiation but levels returned to control values by 60 min. Gamma photons had no effect after doses up to 200 Gy. These results provide further evidence that exposure to heavy particles can degrade motor behavior through an action on dopaminergic mechanisms and that this can occur after doses much lower than those needed for low-LET radiation.     

Ganglioside Composition of Normal and Mutant Mouse Embryos

The enrichment of gangliosides in neuronal membranes suggests that they play an important role in CNS development. We recently found a marked tetrasialoganglioside deficiency in twl/twl mutant mouse embryos at embryonic day (E)-11. The recessive twl/twl mutants die at embryonic ages E-9 to E-18 from failed neural differentiation in the ventral portion of the neural tube. In the present study, we examined the composition and distribution of gangliosides in twl/twl mutant mouse embryos at E-12. The total ganglioside sialic acid concentration was significantly lower in the mutants than in normal (+/-) embryos. The mutants also expressed significant deficiencies of gangliosides in the "b" metabolic pathway (GD3, GD1b, GT1b, and GQ1b) and elevations in levels of gangliosides in the "a" metabolic pathway (GM3, GM2, GM1, and GD1a). These findings suggest that the mutants have a partial deficiency in the activity of a specific sialyltransferase in the b pathway. Regional ganglioside distribution was also studied in E-12 normal mouse embryos. The ganglioside composition in heads and bodies was similar to each other and to whole embryos. Total ganglioside concentration and the distribution of b pathway gangliosides were significantly higher in neural tube regions than in nonneural tube regions. These findings suggest that b pathway gangliosides accumulate in differentiating neural cells and that the deficiency of these gangliosides in the twl/twl mutants is closely associated with failed neural differentiation.