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| 2. |
- Sundberg, Johan, et al.
(författare)
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Professional male singers ’ formant tuning strategies for the vowel /a
- 2011
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Ingår i: Logopedics Phoniatrics Vocology. - : Informa UK Limited. - 1651-2022 .- 1401-5439. ; 36:4, s. 156-167
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Tidskriftsartikel (refereegranskat)abstract
- Certain spectrum characteristics have been identified as important for register equalization around the male passaggio, an effect ascribed to formant tuning although descriptions of formant tuning diverge. Eight professional singers sang scales including their passaggio range on different vowels, applying two formant tuning strategies as found in (1) classical and (2) non-classical singing. Formant frequencies were measured using inverse filtering. Results revealed differences between the two strategies. For the classical formant tuning, systematic changes of formant frequencies with pitch were observed. For the highest note sung on /a/, F1 was below the second partial and F2 in the vicinity of the third. Similar spectrum characteristics were achieved by different F1 and F2 values between singers.
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| 3. |
- Brolen, Gabriella, et al.
(författare)
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Hepatocyte-like cells derived from human embryonic stem cells specifically via definitive endoderm and a progenitor stage
- 2010
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Ingår i: Journal of Biotechnology. - : Elsevier BV. - 1873-4863 .- 0168-1656. ; 145:3, s. 284-294
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Tidskriftsartikel (refereegranskat)abstract
- Human embryonic stem cells offer a potential unlimited supply for functional hepatocytes, since they can differentiate into hepatocyte-like cells displaying a characteristic hepatic morphology and expressing various hepatic markers. These cells could be used in various applications such as studies of drug metabolism and hepatotoxicity, which however, would require a significant expression of drug metabolizing enzymes. To derive these cells we use a stepwise differentiation protocol where growth- and maturation factors are added. The first phase involves the formation of definitive endoderm. Next, these cells are treated with factors known to promote the induction and proliferation towards hepatic progenitor cell types. In the last phase the cells are terminally differentiated and maturated into functional hepatocyte-like cells. The cultures were characterized by analysis of endodermal or hepatic markers and compared to cultures derived without induction via definitive endoderm. Hepatic functions such as urea secretion, glycogen storage, indocyanine green uptake and secretion, and cytochrome P450-expression and activity were evaluated. The DE-Hep showed a hepatocyte morphology with sub-organized cells and exhibited many liver-functions including transporter activity and capacity to metabolize drugs specific for important cytochrome P450 sub-families. This represents an importantstep in differentiation of hESC into functional hepatocytes. (C) 2009 Elsevier B.V. All rights reserved.
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| 4. |
- Dahlgren, Hanna, et al.
(författare)
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Solar flares detected by the new narrowband VLF receiver at SANAE IV
- 2011
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Ingår i: South African Journal of Science. - : Academy of Science of South Africa. - 0038-2353 .- 1996-7489. ; 107:9-10, s. 39-46
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Tidskriftsartikel (refereegranskat)abstract
- A narrowband receiver was installed at the SANAE IV base in Antarctica to monitor specific very low frequency (VLF) radio signals from transmitters around the world. VLF waves propagating through the Earth-Ionosphere Waveguide are excellent probes of the varying properties of the lower region of the ionosphere. This paper describes the set-up of the narrowband system and demonstrates its capabilities with data from a set of solar flares on 08 February and 12 February 2010.
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| 7. |
- Haslemo, T, et al.
(författare)
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UGT1A4*3 encodes significantly increased glucuronidation of olanzapine in patients on maintenance treatment and in recombinant systems
- 2012
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Ingår i: Clinical Pharmacology and Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 92:2, s. 221-227
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Tidskriftsartikel (refereegranskat)abstract
- Olanzapine, a world leader in antipsychotic drugs, is used in the treatment of schizophrenia and bipolar disorder. There is considerable interpatient variability in its hepatic clearance. Polymorphic glucuronidation of olanzapine by uridine diphosphate glucuronosyltransferase 1A4 (UGT1A4) was investigated retrospectively in patient samples taken for routine therapeutic drug monitoring (TDM) and in recombinant metabolic systems in vitro. Multivariate analyses revealed that patients who were heterozygous as well as those who were homozygous for the UGT1A4*3 allelic variant had significantly higher concentrations of the major metabolite olanzapine 10-N-glucuronide in serum (+38% (P = 0.011) and +246% (P < 0.001), respectively). This finding was in line with the significant increases in glucuronidation activity of olanzapine observed with recombinant UGT1A4.3 (Val-48) as compared with UGT1A4.1 (Leu-48) (1.3-fold difference, P < 0.001). By contrast, serum concentrations of the parent drug were not significantly influenced by UGT1A4 genotype. Our findings therefore indicate that UGT1A4-mediated metabolism is not a major contributor to interpatient variability in olanzapine levels. However, with respect to other drugs for which UGT1A4 has a dominant role in clearance, increased glucuronidation encoded by UGT1A4*3 might impact the risk for subtherapeutic drug exposure.
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| 8. |
- Holmgren, Gustav, et al.
(författare)
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Long-Term Chronic Toxicity Testing Using Human Pluripotent Stem Cell-Derived Hepatocytes
- 2014
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Ingår i: Drug Metabolism and Disposition. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0090-9556 .- 1521-009X. ; 42:9, s. 1401-1406
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Tidskriftsartikel (refereegranskat)abstract
- Human pluripotent stem cells (hPSC) have the potential to become important tools for the establishment of new models for in vitro drug testing of, for example, toxicity and pharmacological effects. Late-stage attrition in the pharmaceutical industry is to a large extent caused by selection of drug candidates using nonpredictive preclinical models that are not clinically relevant. The current hepatic in vivo and in vitro models show clear limitations, especially for studies of chronic hepatotoxicity. For these reasons, we evaluated the potential of using hPSC-derived hepatocytes for long-term exposure to toxic drugs. The differentiated hepatocytes were incubated with hepatotoxic compounds for up to 14 days, using a repeated-dose approach. The hPSC-derived hepatocytes became more sensitive to the toxic compounds after extended exposures and, in addition to conventional cytotoxicity, evidence of phospholipidosis and steatosis was also observed in the cells. This is, to the best of our knowledge, the first report of a long-term toxicity study using hPSC-derived hepatocytes, and the observations support further development and validation of hPSC-based toxicity models for evaluating novel drugs, chemicals, and cosmetics.
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| 9. |
- La, Filipa M. B., et al.
(författare)
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Effects of the Menstrual Cycle and Oral Contraception on Singers' Pitch Control
- 2012
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Ingår i: Journal of Speech, Language and Hearing Research. - : American Speech Language Hearing Association. - 1092-4388 .- 1558-9102. ; 55:1, s. 247-261
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Difficulties with intonation and vibrato control during the menstrual cycle have been reported by singers; however, this phenomenon has not yet been systematically investigated. Method: A double-blind randomized placebo-controlled trial assessing effects of the menstrual cycle and use of a combined oral contraceptive pill (OCP) on pitch control in singing is presented. Audio-electrolaryngograph recordings were made and blood samples were taken from 9 singers in each of the 3 phases of the menstrual cycle both under the placebo and the OCP conditions for a total of 6 months. Participants sang an exercise consisting of an ascending octave followed by a descending major triad, starting on pitches F4 and B4. Pitch control was assessed in terms of the octave's deviations from pure intonation and of the vibrato rate and extent. Results: Significant differences were found between the 3 phases of the cycle regarding octave size only for pitch F5 during OCP use. Significant vibrato rate differences between placebo and OCP conditions were found only for pitch F5. Conclusion: OCP use may have an effect on pitch control in singers. Possible explanations point to a complex interaction between hormonal milieu and pitch control, enhancing the need for longitudinal studies.
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