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Jens Timmer

Publications and source records attributed to Jens Timmer.

32 records · Page 2Linked to original sources
PubMed2005

Estimating rate constants from single ion channel currents when the initial distribution is known.

Single ion channel currents can be analysed by hidden or aggregated Markov models. A classical result from Fredkin et al. (Proceedings of the Berkeley conference in honor of Jerzy Neyman and Jack Kiefer, vol I, pp 269-289, 1985) states that the maximum number of identifiable parameters is bounded by 2n(o)n(c), where n(o) and n(c) denote the number of open and closed states, respectively. We show that this bound can be overcome when the probabilities of the initial distribution are known and the data consist of several sweeps.

Biophysics↗
PubMed2005

Capillary physiology and drug delivery in central nervous system lymphomas.

To evaluate whether the chemosensitivity of primary central nervous system lymphomas to water-soluble drugs could result from improved drug delivery, we quantitatively assessed pharmacokinetic factors in seven patients. The capillary permeability surface product was found to be significantly increased in central nervous system lymphomas compared with glioblastoma multiforme, medulloblastomas, and metastases. Tumoral blood flow was significantly greater than in normal white matter. Our results suggest favorable pharmacokinetics to water- and lipid-soluble drugs in primary central nervous system lymphomas.

Adult↗
PubMed2005

Gene expression profiling in polycythaemia vera: overexpression of transcription factor NF-E2.

Summary The molecular aetiology of polycythaemia vera (PV) remains unknown and the differential diagnosis between PV and secondary erythrocytosis (SE) can be challenging. Gene expression profiling can identify candidates involved in the pathophysiology of PV and generate a molecular signature to aid in diagnosis. We thus performed cDNA microarray analysis on 40 PV and 12 SE patients. Two independent data sets were obtained: using a two-step training/validation design, a set of 64 genes (class predictors) was determined, which correctly discriminated PV from SE patients. Separately 253 genes were identified to be upregulated and 391 downregulated more than 1.5-fold in PV compared with healthy controls (P < 0.01). Of the genes overexpressed in PV, 27 contained Sp1 sites: we therefore propose that altered activity of Sp1-like transcription factors may contribute to the molecular aetiology of PV. One Sp1 target, the transcription factor NF-E2 [nuclear factor (erythroid-derived 2)], is overexpressed 2- to 40-fold in PV patients. In PV bone marrow, NF-E2 is overexpressed in megakaryocytes, erythroid and granulocytic precursors. It has been shown that overexpression of NF-E2 leads to the development of erythropoietin-independent erythroid colonies and that ectopic NF-E2 expression can reprogram monocytic cells towards erythroid and megakaryocytic differentiation. Transcription factor concentration may thus control lineage commitment. We therefore propose that elevated concentrations of NF-E2 in PV patients lead to an overproduction of erythroid and, in some patients, megakaryocytic cells/platelets. In this model, the level of NF-E2 overexpression determines both the severity of erythrocytosis and the concurrent presence or absence of thrombocytosis.

Blotting, Northern↗
PubMed2005

Computational processing and error reduction strategies for standardized quantitative data in biological networks.

High-quality quantitative data generated under standardized conditions is critical for understanding dynamic cellular processes. We report strategies for error reduction, and algorithms for automated data processing and for establishing the widely used techniques of immunoprecipitation and immunoblotting as highly precise methods for the quantification of protein levels and modifications. To determine the stoichiometry of cellular components and to ensure comparability of experiments, relative signals are converted to absolute values. A major source for errors in blotting techniques are inhomogeneities of the gel and the transfer procedure leading to correlated errors. These correlations are prevented by randomized gel loading, which significantly reduces standard deviations. Further error reduction is achieved by using housekeeping proteins as normalizers or by adding purified proteins in immunoprecipitations as calibrators in combination with criteria-based normalization. Additionally, we developed a computational tool for automated normalization, validation and integration of data derived from multiple immunoblots. In this way, large sets of quantitative data for dynamic pathway modeling can be generated, enabling the identification of systems properties and the prediction of targets for efficient intervention.

Algorithms↗
PubMed2004

Is the rhythm of physiological tremor involved in cortico-cortical interactions?

The function of low-frequency oscillations as correlates of physiological tremor in supplementary motor area (SMA) and M1 remains unclear. In epicortical recordings from M1 and SMA and surface electromyographic (EMG) recordings in an epileptic patient we found reproducibly significant coherence between all three recording sites in the 6- to 15-Hz band. The partial coherence between SMA and muscle, however, was not significant. There was a constant phase shift between SMA and M1 indicating synchronized activity. We conclude that the cortical correlates of physiological tremor may be involved in linking different cortical motor centers and might therefore play a role in cortical motor planning.

Adult↗
PubMed2003

Expression profiling on chronically rejected transplant kidneys.

BACKGROUND: Chronic transplant nephropathy remains a poorly defined inflammatory process that limits the survival rate of most renal transplants. We analyzed the gene profile of chronically rejected kidney transplants to identify candidate genes that characterize chronic transplant nephropathy. METHODS: To distinguish genes present in normal renal tissue or specific for end-stage renal failure, we compared the gene profiles of 13 chronically rejected kidney transplants with 16 normal kidneys and 12 end-stage polycystic kidneys using a 7K human cDNA microarray. After elimination of genes with signals close to background, 2190 genes were available for statistical analysis. RESULTS: More than 20% of the examined genes were significantly regulated when compared with the expression level of normal renal tissue (P<0.0003). Hierarchic clustering based on 571 genes differentiated normal and transplant tissue, and transplant and polycystic kidney tissue. Most of these genes encoded proteins involved in cellular metabolism, transport, signaling, transcriptional activation, adhesion, and the immune response. Notably, comprehensive gene profiling of chronically rejected kidneys revealed two distinct subsets of chronically rejected transplants. Neither clinical data nor histology could explain this genetic heterogeneity. CONCLUSIONS: Microarray analysis of rejected kidneys may help to define different entities of transplant nephropathy, reflecting the multifactorial cause of chronic rejection.

Adult↗
PubMed2002

Quantitative analyses of anaerobic wastewater treatment processes: identifiability and parameter estimation.

We investigated the problem of identifying the parameters of a nonlinear fifth order model describing the population dynamics of two main bacterial groups in an anaerobic wastewater treatment process. In addition to addressing problems concerning structural and practical identifiability, we also analyzed how mathematical descriptions of bacterial population dynamics can model real data. Using three data sets recorded under different experimental conditions, we estimated important biochemical parameters and demonstrated that our model could describe the data successfully. Parameters, which are simultaneously determined using information from all three experiments, have more reliable estimates. We conclude that, after appropriate estimation, this model can be used for optimization and the control of continuous processes.

Anaerobiosis↗
PubMed2002

Diagnosis of sleep apnea by automatic analysis of nasal pressure and forced oscillation impedance.

Detecting and differentiating central and obstructive respiratory events is an important aspect of the diagnosis of sleep-related breathing disorders with respect to the choice of an appropriate treatment. The purpose of this study was to evaluate the performance of a new algorithm for automated detection and classification of apneas and hypopneas, compared with visual analysis of standard polysomnographic signals. The algorithm is based on time series analysis of nasal mask pressure and a forced oscillation signal related to mechanical respiratory input impedance, measured at a frequency of 20 Hz throughout the night. The method was applied to all-night measurements on 19 subjects. Two experts in sleep medicine independently scored the corresponding simultaneously recorded polysomnographic signals. Evaluating the agreement between two scorers by a weighted kappa statistic on a second-by-second basis, we found that inter-expert variability and the discrepancy between automatic analysis and visual analysis performed by an expert were not significantly different. Implementation of this algorithm in a device for home monitoring of breathing during sleep might aid in the differential diagnosis of sleep-related breathing disorders and/or as a means for follow-up and treatment control.

Airway Resistance↗
PubMed2002

Effects of attention and precision of exerted force on beta range EEG-EMG synchronization during a maintained motor contraction task.

OBJECTIVE: The present study was aimed at investigating the effect of attention and precision level of exerted force on beta range EEG-EMG synchronization. METHODS: We simultaneously recorded cortical electrical activity (EEG) in a bipolar manner from the contralateral sensorimotor areas and surface electromyographic (EMG) activity from the flexor digitorum superficialis muscle in 10 healthy subjects during a maintained motor contraction task at 8% of the maximal voluntary contraction (MVC) force level. The coherence between oscillatory processes in the EEG and EMG was calculated. Three different conditions were investigated: (i) performing the task with high precision (HP); (ii) performing the task with high precision and simultaneously performing a mental arithmetic task (HPAT), i.e. attention was divided between the motor task and the mental arithmetic task; and (iii) performing the task with low precision (LP). RESULTS: We have found that the amount of beta range EEG-EMG synchronization decreases below the 95% confidence level when attention is divided between the motor task and the mental arithmetic task. The results also show that the frequency of beta range synchronization is higher with a higher level of precision but still lies within the beta frequency range (15-30 Hz). CONCLUSIONS: The data indicate that beta range synchronization represents a state of the cortico-muscular network when attention is directed towards the motor task. The frequency of synchronization of this network is associated with, and possibly encodes, precision in force production.

Adult↗
PubMed2001

Corticomuscular coherence in the 6-15 Hz band: is the cortex involved in the generation of physiologic tremor?

Physiologic tremor (PT) consists of a peripheral mechanical oscillation at the limbs' resonance frequency and an independent central component in the 6-15 Hz band. This central component has mainly been attributed to spinal interneuronal systems or subcortical oscillators but more recently also to cortical rhythms. We recorded PT electromyographically and accelerometrically from different parts of the arm in parallel to epicortical recordings from grid electrodes covering the primary sensorimotor areas of the contralateral cortex in six epileptic patients. Previous bipolar electrical stimulation of the cortical electrodes resulted in a somatotopic map of the primary cortex underlying the grid. Spectral and cross-spectral analysis including coherence spectra between epicortical electrodes and EMG and the corresponding phase spectra were performed off-line. We found significant corticomuscular coherence in the 6-15 Hz range in four out of the six patients. This coherence was focal on the cortex and it was distributed somatotopically mainly within the primary motor area. The frequency band of the coherence mostly corresponding to the EMG frequency remained stable with added inertia, while the main accelerometric frequency was clearly reduced following the resonance frequency. The phase spectra between electrocorticogram (ECoG) and EMG showed a clear delay between cortex and muscle in two of the patients, which was compatible with conduction in fast pyramidal pathways. These findings indicate that the 6-15 Hz coherence between cortex and EMG reflects a corticomuscular transmission of the oscillation rather than peripheral feedback to the cortex. We conclude that cortical networks are involved in the generation of physiologic tremor.

Adolescent↗
PubMed1995

Tremor classification and tremor time series analysis.

The separation between physiologic tremor (PT) in normal subjects and the pathological tremors of essential tremor (ET) or Parkinson's disease (PD) was investigated on the basis of monoaxial accelerometric recordings of 35 s hand tremor epochs. Frequency and amplitude were insufficient to separate between these conditions, except for the trivial distinction between normal and pathologic tremors that is already defined on the basis of amplitude. We found that waveform analysis revealed highly significant differences between normal and pathologic tremors, and, more importantly, among different forms of pathologic tremors. We found in our group of 25 patients with PT and 15 with ET a reasonable distinction with the third momentum and the time reversal invariance. A nearly complete distinction between these two conditions on the basis of the asymmetric decay of the autocorrelation function. We conclude that time series analysis can probably be developed into a powerful tool for the objective analysis of tremors. (c) 1995 American Institute of Physics.

Journal Article↗
PubMedDate not supplied

An open source protein gel documentation system for proteome analyses.

Data organization and data mining represents one of the main challenges for modern high throughput technologies in pharmaceutical chemistry and medical chemistry. The presented open source documentation and analysis system provides an integrated solution (tutorial, setup protocol, sources, executables) aimed at substituting the traditionally used lab-book. The data management solution provided incorporates detailed information about the processing of the gels and the experimental conditions used and includes basic data analysis facilities which can be easily extended. The sample database and User-Interface are available free of charge under the GNU license from http://webber.physik.uni-freiburg.de/~fallerd/tutorial.htm.

Documentation↗
PubMedDate not supplied

Incomplete forced expiration - estimating vital capacity by a mathematical method.

BACKGROUND: Vital capacity is a key parameter in the determination of lung function, usually assessed by means of a forced expiration maneuver. This maneuver can be exhausting, and patients often cannot complete it. OBJECTIVES: This study evaluates a method to estimate forced vital capacity (FVC) based on the extrapolation of volume-time curves from forced expiration. METHODS: The algorithm was applied to 2,363 volume-time curves from patients with and without respiratory disease. 416 of these spirograms originated from incomplete maneuvers. For each spirogram, estimated (FVC(est)) and measured FVC were compared with inspiratory vital capacity. RESULTS: Reliable FVC(est) were obtained for 82% of all and for 76% of the incomplete maneuvers. Regardless of the category of respiratory disease and acceptability of forced expiration, FVC(est) were close to inspiratory vital capacities. CONCLUSIONS: When assessing the lung function of patients who cannot complete forced expiration, this method could help to reduce the duration of maneuvers required to provide a reliable estimate for vital capacity.

Algorithms↗