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C Knudsen

Publications and source records attributed to C Knudsen.

10 recordsLinked to original sources

Improved parameter estimation for systems with an experimentally located Hopf bifurcation.

When performing system identification, we have two sources of information: experimental data and prior knowledge. Many cell-biological systems are oscillating, and sometimes we know an input where the system reaches a Hopf bifurcation. This is the case, for example, for glycolysis in yeast cells and for the Belousov-Zhabotinsky reaction, and for both of these systems there exist significant numbers of quenching data, ideal for system identification. We present a method that includes prior knowledge of the location of a Hopf bifurcation in estimation based on time-series. The main contribution is a reformulation of the prior knowledge into the standard formulation of a constrained optimisation problem. This formulation allows for any of the standard methods to be applied, including all the theories regarding the method's properties. The reformulation is carried out through an over-parametrisation of the original problem. The over-parametrisation allows for extra constraints to be formed, and the net effect is a reduction of the search space. A method that can solve the new formulation of the problem is presented, and the advantage of adding the prior knowledge is demonstrated on the Brusselator.

Algorithms↗

The importance of structural transitions of the switch II region for the functions of elongation factor Tu on the ribosome.

Elongation factor Tu (EF-Tu) undergoes a large conformational transition when switching from the GTP to GDP forms. Structural changes in the switch I and II regions in the G domain are particularly important for this rearrangement. In the switch II region, helix alpha2 is flanked by two glycine residues: Gly(83) in the consensus element DXXG at the N terminus and Gly(94) at the C terminus. The role of helix alpha2 was studied by pre-steady-state kinetic experiments using Escherichia coli EF-Tu mutants where either Gly(83), Gly(94), or both were replaced with alanine. The G83A mutation slows down the association of the ternary complex EF-Tu.GTP.aminoacyl-tRNA with the ribosome and abolishes the ribosome-induced GTPase activity of EF-Tu. The G94A mutation strongly impairs the conformational change of EF-Tu from the GTP- to the GDP-bound form and decelerates the dissociation of EF-Tu.GDP from the ribosome. The behavior of the double mutant is dominated by the G83A mutation. The results directly relate structural transitions in the switch II region to specific functions of EF-Tu on the ribosome.

Codon↗

A phase II study of crisnatol mesylate in patients with ovarian carcinoma.

Fourteen patients with advanced ovarian cancer received a 72 hour infusion of a new DNA intercalator, crisnatol mesylate, administered intravenously. There was no evidence of antitumor efficacy. A syndrome of nausea and vomiting associated with vertigo, dizziness and ataxia was observed in nearly all patients. Two of the patients developed severe CNS toxicity manifested in one by a grand-mal seizure and in the other by peripheral neuropathy. Further explorations into the potential efficacy of crisnatol mesylate administered intraperitoneally are underway.

Aged↗

Effects of extra- and intracellular calcium concentration on DNA replication, lateral growth, and differentiation of human epidermal cells in culture.

Variation in the extra- and intra-cellular concentration of calcium ([Ca]e and [Ca]i) affected the 3H-thymidine labeling pattern of sorted S-phase cells in human epidermal cultures. A lowering of [Ca]e resulted in retarded lateral growth but, unless [Ca]e was extremely low, caused an increase in the proportion of strongly labelled (rapidly cycling) S-phase cells. An increased desquamation of superficial cells due to a reduced cellular cohesiveness was also observed in low calcium medium. Thus, a lowering of [Ca]e might stimulate the proliferation of a pool of cycling cells destined for rapid terminal differentiation and tissue regeneration, whereas proliferation destined for lateral growth is inhibited. Attempts to decrease the [Ca]i with the calcium chelator quin-2 at low [Ca]e seemed to elevate the proportion of strongly labelled S-phase cells, whereas an increased [Ca]i obtained with the ionophore A23187 caused a dramatic decrease in the proportion of S-phase cells that showed strong 3H-thymidine incorporation. This implies that variation in both [Ca]i and [Ca]e may play a role in the regulation of proliferation and differentiation, in keratinocytes.

Aminoquinolines↗

An abnormal growth mutant in maize has a defective mitochondrial cytochrome oxidase gene.

We describe a new maternally inherited maize mutation, nonchromosomal stripe 5 (NCS5), that adversely affects plant growth and yield. Mutant plants are characterized by reduced height, defective yellow striping on leaves, and aborted kernels on ears. NCS5 striped plants carry both normal and partially deleted versions of the mitochondrial cytochrome oxidase subunit 2 gene and exhibit greatly reduced levels of cox2 transcripts when compared with nonstriped control plants. Other mitochondrial genes and their mRNAs are not affected. Thus, the defective plant phenotype is correlated with a reduction in the number of functional cytochrome oxidase subunit 2 genes. The NCS5 mutant mitochondrial genome appears to have arisen by amplification of a rare homologous recombination product.

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A partially deleted mitochondrial cytochrome oxidase gene in the NCS6 abnormal growth mutant of maize.

The nonchromosomal stripe (NCS) mutations of maize are a set of maternally inherited mutations that result in reduced plant growth and lowered reproductive capacity. NCS6 mutants are characterized by stunted growth, yellow stripes on leaves, and sectors of aborted kernels on ears. The heteroplasmic NCS6 striped plants carry both partially deleted and normal versions of the mitochondrial cytochrome oxidase subunit 2 (cox2) gene and have low levels of cox2 transcripts when compared with nonstriped control plants. Other tested mitochondrial genes and their transcripts appear to be unaltered in NCS6 plants. The level of COXII protein is also specifically reduced in the striped plants relative to that of control plants. In the NCS6 mutant mitochondrial genome, a portion of the first exon of the cox2 gene is deleted along with the 5' flanking region. The formation of the defective cox2 gene appears to have involved a recombination event between 31-bp repeats.

Base Sequence↗