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- van Kuilenburg, André B P, et al.
(författare)
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Novel disease-causing mutations in the dihydropyrimidine dehydrogenase gene interpreted by analysis of the three-dimensional protein structure
- 2002
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Ingår i: Biochemical Journal. - : Portland Press Ltd.. - 0264-6021 .- 1470-8728. ; 364:Pt 1, s. 157-163
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Tidskriftsartikel (refereegranskat)abstract
- Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disease characterized by thymine-uraciluria in homozygous deficient patients. Cancer patients with a partial deficiency of DPD are at risk of developing severe life-threatening toxicities after the administration of 5-fluorouracil. Thus, identification of novel disease-causing mutations is of the utmost importance to allow screening of patients at risk. In eight patients presenting with a complete DPD deficiency, a considerable variation in the clinical presentation was noted. Whereas motor retardation was observed in all patients, no patients presented with convulsive disorders. In this group of patients, nine novel mutations were identified including one deletion of two nucleotides [1039-1042delTG] and eight missense mutations. Analysis of the crystal structure of pig DPD suggested that five out of eight amino acid exchanges present in these patients with a complete DPD deficiency, Pro86Leu, Ser201Arg, Ser492Leu, Asp949Val and His978Arg, interfered directly or indirectly with cofactor binding or electron transport. Furthermore, the mutations Ile560Ser and Tyr211Cys most likely affected the structural integrity of the DPD protein. Only the effect of the Ile370Val and a previously identified Cys29Arg mutation could not be readily explained by analysis of the three-dimensional structure of the DPD enzyme, suggesting that at least the latter might be a common polymorphism. Our data demonstrate for the first time the possible consequences of missense mutations in the DPD gene on the function and stability of the DPD enzyme.
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- Karlsson, Fredrik, et al.
(författare)
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Development of a Gender Difference in Voice Onset Time
- 2004
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Ingår i: Proceedings of the 10th Australian International Conference on Speech Science & Technology.
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Konferensbidrag (refereegranskat)abstract
- This paper investigates the effect of gender on voice onset time distribution at three stages of speech development. Two subject groups consisting of children, aged approximately 3 and 9 years, were compared to adult speakers regarding voice onset time of initial plosives. The results showed significant gender effects in the aspirated plosives in the young subjects that were not present in the plosives produced by adults. It is hypothesised that the effect of gender at the earlier stages of develpment may be due to the differences in airflow intensity and variability.
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- Karlsson, Fredrik, et al.
(författare)
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Då or Tå, Pår or Bår - Seeing is believing!
- 2003
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Ingår i: Proceeding of the 15th International Congress of Phonetic Sciences.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Several acoustic properties of plosives have been established as correlates of voicing contrast, including voice onset time (VOT), F1 cut-back, aspiration duration and initial F1 and F2 transition. Therefore, acquisition of the voicing contrast for plosives could be viewed as gaining the ability to combine interacting acoustic cues in an adult-like manner, resulting in a large number of possible developmental routes. The presented investigation examined initial plosives produced by one child from ages 18¿31 months that had been judged as voiced in an auditory analysis. The results show that some perceptually voiced and unaspirated plosives (elicited using voiceless targets) were produced with VOT values within the range of voiceless plosives for adult speakers of Swedish, and also had increased duration of high frequency, aperiodic friction after plosive release. It was conjectured that the child was attempting a voicing contrast by using increased VOT and increased duration of aperiodic friction that were not perceptible to adult listeners.
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