A demonstration of melt rate control during VAR of “Cracked” electrodes

A particularly challenging problem associated with vacuum arc remelting occurs when trying to maintain accurate control of electrode melt rate as the melt zone passes through a transverse crack in the electrode. As the melt zone approaches the crack, poor heat conduction across the crack drives the local temperature in the electrode tip above its steady-state value, causing the controller to cut back on melting current in response to an increase in melting efficiency. The difficulty arises when the melt zone passes through the crack and encounters the relatively cold metal on the other side, giving rise to an abrupt drop in melt rate. This extremely dynamic melting situation is very difficult to handle using standard load-cell based melt rate control, resulting in large melt rate excursions. We have designed and tested a new generation melt rate controller that is capable of controlling melt rate through crack events. The controller is designed around an accurate dynamic melting model that uses four process variables: electrode tip thermal boundary layer, electrode gap, electrode mass and melting efficiency. Tests, jointly sponsored by the Specialty Metals Processing Consortium and Sandia National Laboratories, were performed at Carpenter Technology Corporation wherein two 0.43 m diameter Pyromet® 718 electrodes were melted into 0.51 m diameter ingots. Each electrode was cut approximately halfway through its diameter with an abrasive saw to simulate an electrode crack. Relatively accurate melt rate control through the cuts was demonstrated despite the observation of severe arc disturbances and loss of electrode gap control. Subsequent to remelting, one ingot was sectioned in the “as cast” condition, whereas the other was forged to 0.20 m diameter billet. Macrostructural characterization showed solidification white spots in regions affected by the cut in the electrode.     

General acid/base catalysis in the active site of Escherichia coli thioredoxin

Enzymic catalysts of thiol:disulfide oxidoreduction contain two cysteine residues in their active sites. Another common residue is an aspartate (or glutamate), the role of which has been unclear. Escherichia coli thioredoxin (Trx) is the best characterized thiol:disulfide oxidoreductase, and in Trx these three active-site residues are Cys32, Cys35, and Asp26. Structural analyses had indicated that the carboxylate of Asp26 is positioned properly for the deprotonation of the thiol of Cys35, which would facilitate its attack on Cys32 in enzyme-substrate mixed disulfides. Here, Asp26 of Trx was replaced with isologous asparagine and leucine residues. D26N Trx and D26L Trx are reduced and oxidized more slowly than is wild-type Trx during catalysis by E.coli thioredoxin reductase. Stopped-flow spectroscopy demonstrated that the cleavage of the mixed disulfide between Trx and a substrate is slower in the D26N and D26L enzymes. Buffers increase the rate of mixed disulfide cleavage in these variants but not in wild-type Trx. These results indicate that Asp26 serves as an acid/base in the oxidation/reduction reactions catalyzed by Trx. Specifically, Asp26 protonates (during substrate oxidation) or deprotonates (during substrate reduction) the thiol of Cys35. A similar role is likely filled by the analogous aspartate (or glutamate) residue in protein disulfide isomerase, DsbA, and other thiol:disulfide oxidoreductases. Moreover, these results provide the first evidence for general acid/base catalysis in a thiol:disulfide interchange reaction.     

Metastatic parathyroid carcinoma in the MEN2A syndrome

We report a patient with a metastatic parathyroid carcinoma and medullary carcinoma of the thyroid. This patient represents a variation of the multiple endocrine neoplasia syndrome (MEN) type 2A. There was no evidence of a phaeochromocytoma. The case illustrates the difficulties that may be encountered in localising the source of PTH secretion; the patient underwent four unsuccessful exploratory operations of the neck and mediastinum before further investigations revealed a single metastatic deposit of parathyroid carcinoma involving the first thoracic vertebra. PCR amplification and sequencing of the RET oncogene from the metastatic parathyroid carcinoma and genomic DNA revealed a heterozygous mutation (Cys634Tyr) in exon 11, as has previously been described to occur in MEN 2A. In addition, loss of tumour heterozygosity was demonstrated at loci from chromosomes 1, 2, 3p, 13q and 16p. This represents the first report of a parathyroid carcinoma in a MEN2A patient, in which the multiple allelic deletions are consistent with the generalised losses observed in aggressive tumours.     

Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q

The epilepsies are a group of disorders characterised by recurrent seizures caused by episodes of abnormal neuronal hyperexcitability involving the brain. Up to 60 million people are affected worldwide and genetic factors may contribute to the aetiology in up to 40% of patients. The most common human genetic epilepsies display a complex pattern of inheritance. These are categorised as idiopathic in the absence of detectable structural or metabolic abnormalities. Juvenile myoclonic epilepsy (JME) is a distinctive and common variety of familial idiopathic generalised epilepsy (IGE) with a prevalence of 0.5-1.0 per 1000 and a ratio of sibling risk to population prevalence (lambda(s)) of 42. The molecular genetic basis of these familial idiopathic epilepsies is entirely unknown, but a mutation in the gene CHRNA4, encoding the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (nAChR), was recently identified in a rare Mendelian variety of idiopathic epilepsy. Chromosomal regions harbouring genes for nAChR subunits were therefore tested for linkage to the JME trait in 34 pedigrees. Significant evidence for linkage with heterogeneity was found to polymorphic loci encompassing the region in which the gene encoding the alpha7 subunit of nAChR (CHRNA7) maps on chromosome 15q14 (HLOD = 4.4 at alpha = 0.65; Z(all) = 2.94, P = 0.0005). This major locus contributes to genetic susceptibility to JME in a majority of the families studied.     

Neural networks,rational functions,and realization theory

The problem of parametrizing single hidden layer scalar neural networks with continuous activation functions is investigated. A connection is drawn between realization theory for linear dynamical systems, rational functions, and neural networks that appears to be new. A result of this connection is a general parametrization of such neural networks in terms of strictly proper rational functions. Some existence and uniqueness results are derived. Jordan decompositions are developed, which show how the general form can be expressed in terms of a sum of canonical second order sections. The parametrization may be useful for studying learning algorithms.This work was supported by the Australian Research Council, the Australian Telecommunications and Electronics Research Board, and the Boeing Commencai Aircraft Company (thanks to John Moore).     

Expression of a human homeobox-containing gene is regulated by 1,25(OH)2D3 in bone cells

The seasonal variation in the nutrient composition of Enhydra fluctuans and Marsilea quadrifolia, two edible semi-aquatic plants, was studied in order to promote their consumption as green leafy vegetables. Both plants had a high crude protein content throughout all harvesting seasons. Enhydra fluctuans had a low ash content and was a good source of beta-carotene (3.7 to 4.2 mg/100 g on a fresh weight basis). Marsilea quadrifolia exhibited wide fluctuations between seasons and was not very promising in nutrient composition when compared to other commonly used green leafy vegetables.