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A polymorphic CAG repeat was identified in the human alpha 1A voltage-dependent calcium channel subunit. To test the hypothesis that expansion of this CAG repeat could be the cause of an inherited progressive ataxia, we genotyped a large number of unrelated controls and ataxia patients. Eight unrelated patients with late onset ataxia had alleles with larger(More)
The glycosylation pattern of chCE7, an antineuroblastoma chimeric IgG1, was engineered in Chinese hamster ovary cells with tetracycline-regulated expression of beta(1,4)-N-acetylglucosaminyltransferase III (GnTIII), a glycosyltransferase catalyzing formation of bisected oligosaccharides that have been implicated in antibody-dependent cellular cytotoxicity(More)
The intracellular carbon flux distribution in wild-type and pyruvate kinase-deficient Escherichia coli was estimated using biosynthetically directed fractional 13C labeling experiments with [U-13C6]glucose in glucose- or ammonia-limited chemostats, two-dimensional nuclear magnetic resonance (NMR) spectroscopy of cellular amino acids, and a comprehensive(More)
Biosynthetically directed fractional 13C labeling of the proteinogenic amino acids is achieved by feeding a mixture of uniformly 13C-labeled and unlabeled carbon source compounds into a bioreaction network. Analysis of the resulting labeling pattern enables both a comprehensive characterization of the network topology and the determination of metabolic flux(More)
A mathematical model of regulation of the G1-S transition of the mammalian cell cycle has been formulated to organize available experimental molecular-level information in a systematic quantitative framework and to evaluate the ability of this manifestation of current knowledge to calculate correctly experimentally observed phenotypes. This model includes(More)
The classical method of metabolic engineering, identifying a rate-determining step in a pathway and alleviating the bottleneck by enzyme overexpression, has motivated much research but has enjoyed only limited practical success. Intervention of other limiting steps, of counter-balancing regulation, and of unknown coupled pathways often confounds this direct(More)
Aerobic and anaerobic central metabolism of Saccharomyces cerevisiae cells was explored in batch cultures on a minimal medium containing glucose as the sole carbon source, using biosynthetic fractional (13)C labeling of proteinogenic amino acids. This allowed, firstly, unravelling of the network of active central pathways in cytosol and mitochondria,(More)
Caspases (cysteine-containing aspartate-specific proteases) are at the core of the cell's suicide machinery. These enzymes, once activated, dismantle the cell by selectively cleaving key proteins after aspartate residues. The events culminating in caspase activation are the subject of intense study because of their role in cancer, and neurodegenerative and(More)
A mathematical model based on known molecular interactions has been formulated to describe quantitatively regulation of expression of the lactose (lac) operon in the Escherichia coli chromosome and in multicopy plasmids. This model is genetically structured such that a nucleotide sequence change affecting transcription initiation at the lac(More)