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21.
M. Wagner S. Michalek J. Timmer 《Proceedings. Biological sciences / The Royal Society》1999,266(1431):1919
A typical task in the application of aggregated Markov models to ion channel data is the estimation of the transition rates between the states. Realistic models for ion channel data often have one or more loops. We show that the transition rates of a model with loops are not identifiable if the model has either equal open or closed dwell times. This non-identifiability of the transition rates also has an effect on the estimation of the transition rates for models which are not subject to the constraint of either equal open or closed dwell times. If a model with loops has nearly equal dwell times, the Hessian matrix of its likelihood function will be ill-conditioned and the standard deviations of the estimated transition rates become extraordinarily large for a number of data points which are typically recorded in experiments. 相似文献
22.
T Timmer P Terpstra A van den Berg P M Veldhuis A Ter Elst A Y van der Veen K Kok S L Naylor C H Buys 《Genomics》1999,60(2):238-240
In searching for a tumor suppressor gene in the 3p21.3 region, we isolated two genes, RBM5 and RBM6. Sequence analysis indicated that these genes share similarity. RBM5 and-to a lesser extent-RBM6 also have similarity to DXS8237E at Xp11.3-11.23, which maps less than 20 kb upstream of UBE1. A homologue of UBE1, UBE1L, is located at 3p21. 3. FISH analysis showed that the distance between UBE1L and RBM5 in 3p21.3 is about 265 kb. DXS8237E and UBE1 on the X chromosome have the same orientation, whereas on chromosome 3 the orientation of RBM5 and that of RBM6 are opposite to the orientation of UBE1L. Presumably, part of the Xp11.3-11.23 region has duplicated to chromosome 3. Part of this region on chromosome 3 may subsequently have duplicated again within the same chromosomal region. Inversion at some stage of the evolution of the human genome would explain the change in orientation of the genes on chromosome 3 compared with that of the genes on the X chromosome. 相似文献
23.
Bouyer D Geier F Kragler F Schnittger A Pesch M Wester K Balkunde R Timmer J Fleck C Hülskamp M 《PLoS biology》2008,6(6):e141
Trichome patterning in Arabidopsis serves as a model system to study how single cells are selected within a field of initially equivalent cells. Current models explain this pattern by an activator–inhibitor feedback loop. Here, we report that also a newly discovered mechanism is involved by which patterning is governed by the removal of the trichome-promoting factor TRANSPARENT TESTA GLABRA1 (TTG1) from non-trichome cells. We demonstrate by clonal analysis and misexpression studies that Arabidopsis TTG1 can act non-cell-autonomously and by microinjection experiments that TTG1 protein moves between cells. While TTG1 is expressed ubiquitously, TTG1–YFP protein accumulates in trichomes and is depleted in the surrounding cells. TTG1–YFP depletion depends on GLABRA3 (GL3), suggesting that the depletion is governed by a trapping mechanism. To study the potential of the observed trapping/depletion mechanism, we formulated a mathematical model enabling us to evaluate the relevance of each parameter and to identify parameters explaining the paradoxical genetic finding that strong ttg1 alleles are glabrous, while weak alleles exhibit trichome clusters. 相似文献
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26.
Nicole Philippi Dorothee Walter Rebekka Schlatter Karine Ferreira Michael Ederer Oliver Sawodny Jens Timmer Christoph Borner Thomas Dandekar 《BMC systems biology》2009,3(1):97-11
Background
The decision pro- or contra apoptosis is complex, involves a number of different inputs, and is central for the homeostasis of an individual cell as well as for the maintenance and regeneration of the complete organism. 相似文献27.
The apical protease of the human intrinsic apoptotic pathway, caspase-9, is activated in a polymeric activation platform known as the apoptosome. The mechanism has been debated, and two contrasting hypotheses have been suggested. One of these postulates an allosteric activation of monomeric caspase-9; the other postulates a dimer-driven assembly at the surface of the apoptosome--the "induced proximity" model. We show that both Hofmeister salts and a reconstituted mini-apoptosome activate caspase-9 by a second-order process, compatible with a conserved dimer-driven process. Significantly, replacement of the recruitment domain of the apical caspase of the extrinsic apoptotic pathway, caspase-8, by that of caspase-9 allows activation of this hybrid caspase by the apoptosome. Consequently, apical caspases can be activated simply by directing their zymogens to the apoptosome, ruling out the requirement for allosteric activation and supporting an induced proximity dimerization model for apical caspase activation in vivo. 相似文献
28.
W. J. Groot H. S. Soedjak P. B. Donck R. G. J. M. van der Lans K. Ch. A. M. Luyben J. M. K. Timmer 《Bioprocess and biosystems engineering》1990,5(5):203-216
Extraction can successfully be used for in-situ alcohol recovery in butanol fermentations to increase the substrate conversion. An advantage of extraction over other recovery methods may be the high capacity of the solvent and the high selectivity of the alcohol/water separation. Extraction, however, is a comprehensive operation, and the design of an extraction apparatus can be complex. The aim of this study is to assess the practical applicability of liquid-liquid extraction and membrane solvent extraction in butanol fermentations. In this view various aspects of extraction processes were investigated.Thirty-six chemicals were tested for the distribution coefficient for butanol, the selectivity of alcohol/water separation and the toxicity towards Clostridia. Convenient extractants were found in the group of esters with high molar mass.Liquid-liquid extraction was carried out in a stirred fermenter and a spray column. The formation of emulsions and the fouling of the solvent in a fermentation broth causes problems with the operation of this type of equipment. With membrane solvent extraction, in which the solvent is separated from the broth by a membrane, a dispersion-free extraction is possible, leading to an easy operation of the equipment. In this case the mass transfer in the membrane becomes important.With membrane solvent extraction the development of a process is emphasized in which the extraction characteristics of the solvent are combined with the property of silicone rubber membranes to separate butanol from water. In the case of apolar solvents with a high molar mass, the characteristics of the membrane process are determined completely by the solvent. In the case of polar solvents (e.g. ethylene glycol), the permselectivity of the membrane can profitably be used. This concept leads to a novel type of extraction process in which alcohol is extracted with a water-soluble solvent via a hydrophobic semipermeable membrane. This extraction process has been investigated for the recovery of butanol and ethanol from water. A major drawback in all processes with membrane solvent extraction was the permeation of part of the solvent to the aqueous phase.The extraction processes were coupled to batch, fed batch and continuous butanol fermentations to affirm the applicability of the recovery techniques in the actual process. In the batch and fed batch fermentations a three-fold increase in the substrate consumption could be achieved, in the continuous fermentation about 30% increase. 相似文献
29.
The effect of calcium on the nodulation of lucerne was studied using EGTA, a specific calcium-chelator. First, the effects
of the chelator were tested on hydroponically grown plants at pH 7.0. Optimal numbers of nodules were obtained in nutrient
solution containing 0.2 mM CaCl2. When 0.4 mM EGTA was given additionally, nodulation was completely inhibited. Nodulation was restored specifically with CaCl2, but not with MgCl2.
For studies in an acid soil (pH-H2O 5.2), lucerne seedlings were grown in rhizotrons. 67% of the seedlings became nodulated when the soil around the seed was
neutralized locally with 1.0 μmol of K2CO3 in drops of 12 μL volume. When native calcium was removed with 2 μmol of EGTA, nodulation was reduced to 12%. However, addition of EGTA to soil resulted in a drop of pH from 6.1 to 5.2. A
phosphate buffer could also not keep soil-pH sufficiently stable. Such pH-decreases could be avoided by placing agar blocks
containing 6 μmol of EGTA for three hours on freshly developed roots. This treatment reduced nodulation from 87% to 32%, with soil-pH lowering
only from 6.2 to 6.0. Nodulation could be restored by adding 2 μmol of CaCl2. The depletion of soil-calcium could depress nodule formation only during the first day after inoculation. 相似文献
30.
S.?Yokota J.?P.?OttervangerEmail author M.?Mouden M.?J.?de?Boer P.?L.?Jager J.?R.?Timmer 《Netherlands heart journal》2018,26(4):192-202