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| 383. |
- Leibiger, B, et al.
(författare)
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Short-term regulation of insulin gene transcription by glucose
- 1998
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 95:16, s. 9307-9312
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Tidskriftsartikel (refereegranskat)abstract
- Whereas short-term regulation of insulin biosynthesis at the level of translation is well accepted, glucose-dependent transcriptional control is still believed to be a long-term effect occurring after more than 2 hr of glucose stimulation. Because pancreatic β cells are exposed to elevated glucose levels for minutes rather than hours after food uptake, we hypothesized the existence of a short-term transcriptional control. By studying the dynamics of newly synthesized (prepro)insulin RNA and by employing on-line monitoring of gene expression in single, insulin-producing cells, we were able to provide convincing evidence that insulin gene transcription indeed is affected by glucose within minutes. Exposure of insulinoma cells and isolated pancreatic islets to elevated glucose for only 15 min resulted in a 2- to 5-fold elevation in (prepro)insulin mRNA levels within 60–90 min. Similarly, insulin promoter-driven green fluorescent protein expression in single insulin-producing cells was significantly enhanced after transient glucose stimulation. Thus, short-term signaling, such as that involved in insulin secretion, also may regulate insulin gene transcription.
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| 384. |
- Lemmens, Raf, et al.
(författare)
-
Ca2+-induced Ca2+ release from the endoplasmic reticulum amplifies the Ca2+ signal mediated by activation of voltage-gated L-type Ca2+ channels in pancreatic beta-cells
- 2001
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 276:13, s. 9971-9977
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Tidskriftsartikel (refereegranskat)abstract
- Stimulus-secretion coupling in pancreatic beta-cells involves membrane depolarization and Ca(2+) entry through voltage-gated L-type Ca(2+) channels, which is one determinant of increases in the cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)). We investigated how the endoplasmic reticulum (ER)-associated Ca(2+) apparatus further modifies this Ca(2+) signal. When fura-2-loaded mouse beta-cells were depolarized by KCl in the presence of 3 mm glucose, [Ca(2+)](i) increased to a peak in two phases. The second phase of the [Ca(2+)](i) increase was abolished when ER Ca(2+) stores were depleted by thapsigargin. The steady-state [Ca(2+)](i) measured at 300 s of depolarization was higher in control cells compared with cells in which the ER Ca(2+) pools were depleted. The amount of Ca(2+) presented to the cytoplasm during depolarization as estimated from the integral of the increment in [Ca(2+)](i) over time (integralDelta[Ca(2+)](i).dt) was approximately 30% higher compared with that in the Ca(2+) pool-depleted cells. neo-thapsigargin, an inactive analog, did not affect [Ca(2+)](i) response. Using Sr(2+) in the extracellular medium and exploiting the differences in the fluorescence properties of Ca(2+)- and Sr(2+)-bound fluo-3, we found that the incoming Sr(2+) triggered Ca(2+) release from the ER. Depolarization-induced [Ca(2+)](i) response was not altered by, an inhibitor of phosphatidylinositol-specific phospholipase C, suggesting that stimulation of the enzyme by Ca(2+) is not essential for amplification of Ca(2+) signaling. [Ca(2+)](i) response was enhanced when cells were depolarized in the presence of 3 mm glucose, forskolin, and caffeine, suggesting involvement of ryanodine receptors in the amplification process. Pretreatment with ryanodine (100 microm) diminished the second phase of the depolarization-induced increase in [Ca(2+)](i). We conclude that Ca(2+) entry through L-type voltage-gated Ca(2+) channels triggers Ca(2+) release from the ER and that such a process amplifies depolarization-induced Ca(2+) signaling in beta-cells.
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| 385. |
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| 386. |
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| 387. |
- Li, M. X. D., et al.
(författare)
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Assessing track geometry quality based on wavelength spectra and track-vehicle dynamic interaction
- 2008
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Ingår i: Vehicle System Dynamics. - : Informa UK Limited. - 0042-3114 .- 1744-5159. ; 46:Suppl. S, s. 261-276
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a study of assessing track geometry quality (longitudinal level and alignment) by the use of dynamic track-vehicle simulations and wavelength spectra analysis. Two simulation models are developed: one is based on the software package GENSYS, which provides realistic simulations of the nonlinear dynamic behaviour of a vehicle running on real track. and (he other one is based on a newly developed linear track-vehicle model. which is Suitable for effectively calculating wheel-rail forces for very long track sections. The linear model. first proposed in 11,21 to assess vertical track geometry quality (longitudinal level), is extended in the present paper to simulate lateral track-vehicle dynamic interaction and, thus, to assess lateral track geometry quality (alignment) as well. Numerical results are presented to compare the simulation results with online measurement and to demonstrate the possibilities of enhancing track quality assessment and maintenance by simulations of track-vehicle interaction.
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| 388. |
- Li, M. X. D., et al.
(författare)
-
Assessment of vertical track geometry quality based on simulations of dynamic track-vehicle interaction
- 2009
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Ingår i: Proceedings of the Institution of mechanical engineers. Part F, journal of rail and rapid transit. - 0954-4097 .- 2041-3017. ; 223:2, s. 131-139
-
Tidskriftsartikel (refereegranskat)abstract
- A study assessing vertical track geometry quality based on simulations of dynamic track-vehicle interaction is presented in this article. The dynamic model is composed of track, vehicle, and wheel-rail contact with moving irregularities and is solved in the frequency domain by fast Fourier transform or in the time domain by constructing a filter function based on system identification. Frequency-dependent stiffness and loss factor of railpads are used in this study. Numerical simulations are carried out for a 120 km long track to demonstrate the potential benefits of enhancing track quality assessment by calculating wheel-rail forces.
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| 389. |
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| 390. |
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