Showing papers by "University of Bonn published in 1999"

Monte Carlo localization for mobile robots

Abstract: To navigate reliably in indoor environments, a mobile robot must know where it is. Thus, reliable position estimation is a key problem in mobile robotics. We believe that probabilistic approaches are among the most promising candidates to providing a comprehensive and real-time solution to the robot localization problem. However, current methods still face considerable hurdles. In particular the problems encountered are closely related to the type of representation used to represent probability densities over the robot's state space. Earlier work on Bayesian filtering with particle-based density representations opened up a new approach for mobile robot localization based on these principles. We introduce the Monte Carlo localization method, where we represent the probability density involved by maintaining a set of samples that are randomly drawn from it. By using a sampling-based representation we obtain a localization method that can represent arbitrary distributions. We show experimentally that the resulting method is able to efficiently localize a mobile robot without knowledge of its starting location. It is faster, more accurate and less memory-intensive than earlier grid-based methods,.

Scaling and criticality in a stochastic multi-agent model of a financial market

Abstract: Financial prices have been found to exhibit some universal characteristics1,2,3,4,5,6 that resemble the scaling laws characterizing physical systems in which large numbers of units interact. This raises the question of whether scaling in finance emerges in a similar way — from the interactions of a large ensemble of market participants. However, such an explanation is in contradiction to the prevalent ‘efficient market hypothesis’7 in economics, which assumes that the movements of financial prices are an immediate and unbiased reflection of incoming news about future earning prospects. Within this hypothesis, scaling in price changes would simply reflect similar scaling in the ‘input’ signals that influence them. Here we describe a multi-agent model of financial markets which supports the idea that scaling arises from mutual interactions of participants. Although the ‘news arrival process’ in our model lacks both power-law scaling and any temporal dependence in volatility, we find that it generates such behaviour as a result of interactions between agents.

A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy

Abstract: SMN1 and SMN2 (survival motor neuron) encode identical proteins. A critical question is why only the homozygous loss of SMN1, and not SMN2, results in spinal muscular atrophy (SMA). Analysis of transcripts from SMN1/SMN2 hybrid genes and a new SMN1 mutation showed a direct relationship between presence of disease and exon 7 skipping. We have reported previously that the exon-skipped product SMNΔ7 is partially defective for self-association and SMN self-oligomerization correlated with clinical severity. To evaluate systematically which of the five nucleotides that differ between SMN1 and SMN2 effect alternative splicing of exon 7, a series of SMN minigenes was engineered and transfected into cultured cells, and their transcripts were characterized. Of these nucleotide differences, the exon 7 C-to-T transition at codon 280, a translationally silent variance, was necessary and sufficient to dictate exon 7 alternative splicing. Thus, the failure of SMN2 to fully compensate for SMN1 and protect from SMA is due to a nucleotide exchange (C/T) that attenuates activity of an exonic enhancer. These findings demonstrate the molecular genetic basis for the nature and pathogenesis of SMA and illustrate a novel disease mechanism. Because individuals with SMA retain the SMN2 allele, therapy targeted at preventing exon 7 skipping could modify clinical outcome.

Dynamic breast MR imaging: are signal intensity time course data useful for differential diagnosis of enhancing lesions?

Abstract: PURPOSE: To assess the relevance of the signal intensity time course for the differential diagnosis of enhancing lesions in dynamic magnetic resonance (MR) imaging of the breast. MATERIALS AND METHODS: Two hundred sixty-six breast lesions were examined with a two-dimensional dynamic MR imaging series and subtraction postprocessing. Time–signal intensity curves of the lesions were obtained and classified according to their shapes as type I, which was steady enhancement; type II, plateau of signal intensity; or type III, washout of signal intensity. Enhancement rates and curve types of benign and malignant lesions were compared. RESULTS: There were 101 malignant and 165 benign lesions. The distribution of curve types for breast cancers was type I, 8.9%; type II, 33.6%; and type III, 57.4%. The distribution of curve types for benign lesions was type I, 83.0%; type II, 11.5%; and type III, 5.5%. The distributions proved significantly different (χ2 = 139.6; P < .001). The diagnostic indices for signal intensit...

Embryonic Stem Cell-Derived Glial Precursors: A Source of Myelinating Transplants

Abstract: Self-renewing, totipotent embryonic stem (ES) cells may provide a virtually unlimited donor source for transplantation. A protocol that permits the in vitro generation of precursors for oligodendrocytes and astrocytes from ES cells was devised. Transplantation in a rat model of a human myelin disease shows that these ES cell-derived precursors interact with host neurons and efficiently myelinate axons in brain and spinal cord. Thus, ES cells can serve as a valuable source of cell type-specific somatic precursors for neural transplantation.

Use of the cell wall precursor lipid II by a pore-forming peptide antibiotic

Abstract: Resistance to antibiotics is increasing in some groups of clinically important pathogens. For instance, high vancomycin resistance has emerged in enterococci. Promising alternative antibiotics are the peptide antibiotics, abundant in host defense systems, which kill their targets by permeabilizing the plasma membrane. These peptides generally do not act via specific receptors and are active in the micromolar range. Here it is shown that vancomycin and the antibacterial peptide nisin Z use the same target: the membrane-anchored cell wall precursor Lipid II. Nisin combines high affinity for Lipid II with its pore-forming ability, thus causing the peptide to be highly active (in the nanomolar range).

MINERVA: a second-generation museum tour-guide robot

Abstract: This paper describes an interactive tour-guide robot, which was successfully exhibited in a Smithsonian museum. During its two weeks of operation, the robot interacted with thousands of people, traversing more than 44 km at speeds of up to 163 cm/sec. Our approach specifically addresses issues such as safe navigation in unmodified and dynamic environments, and short-term human-robot interaction. It uses learning pervasively at all levels of the software architecture.

Dendrimers: From Design to Application-A Progress Report.

Abstract: A unique combination of a clearly defined particle structure and a very highly functionalized surface is offered by the topical dendrimers. Many groups work on this unusual molecular architecture to develop new applications. The most advanced progress in this respect is an MRI contrast agent based on dendrimers (see schematic representation) that facilitate the visualization of bloodstreams.

Polymorphisms in the dopamine D2 receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers.

Abstract: The density of striatal dopamine D2 receptors has been shown to vary considerably among healthy subjects. This variability might be due to genetic or environmental factors. In the present analysis we searched for relationships between dopamine D2 receptor gene (DRD2) polymorphisms and striatal dopamine D2 receptor density in vivo, as measured by positron emission tomography and [11C]raclopride in 56 healthy subjects. There was a significant association between presence of a putative functional DRD2 promoter allele (-141C Del) and high striatal dopamine receptor density (t= 2.32, P= 0.02). In agreement with some previous studies the presence of the DRD2 TaqIA1 allele was associated with measures of low dopamine receptor density (t=2.58, P=0.01). Also the DRD2 TaqIB1 allele was associated with low dopamine receptor density (t= 2.58, P= 0.01) wheras there was no significant relationship between another common silent intronic DRD2 short tandem repeat polymorphism (STRP) and striatal dopamine D2 receptor density. The results suggest that DRD2 genotypes may participate differentially in the regulation of striatal dopamine D2 receptor density in healthy human subjects. The results should be interpreted with caution because of the limited sample size.

Excess of High Activity Monoamine Oxidase A Gene Promoter Alleles in Female Patients with Panic Disorder

Abstract: A genetic contribution to the pathogenesis of panic disorder has been demonstrated by clinical genetic studies. Molecular genetic studies have focused on candidate genes suggested by the molecular mechanisms implied in the action of drugs utilized for therapy or in challenge tests. One class of drugs effective in the treatment of panic disorder is represented by monoamine oxidase A inhibitors. Therefore, the monoamine oxidase A gene on chromosome X is a prime candidate gene. In the present study we investigated a novel repeat polymorphism in the promoter of the monoamine oxidase A gene for association with panic disorder in two independent samples (German sample, n = 80; Italian sample, n = 129). Two alleles (3 and 4 repeats) were most common and constituted >97% of the observed alleles. Functional characterization in a luciferase assay demonstrated that the longer alleles (3a, 4 and 5) were more active than allele 3. Among females of both the German and the Italian samples of panic disorder patients (combined, n = 209) the longer alleles (3a, 4 and 5) were significantly more frequent than among females of the corresponding control samples (combined, n = 190, chi2 = 10.27, df = 1, P = 0.001). Together with the observation that inhibition of monoamine oxidase A is clinically effective in the treatment of panic disorder these findings suggest that increased monoamine oxidase A activity is a risk factor for panic disorder in female patients.

Empirical evaluation of dissimilarity measures for color and texture

Abstract: This paper empirically compares nine image dissimilarity measures that are based on distributions of color and texture features summarizing over 1,000 CPU hours of computational experiments. Ground truth is collected via a novel random sampling scheme for color and via an image partitioning method for texture. Quantitative performance evaluations are given for classification, image retrieval, and segmentation tasks, and for a wide variety of dissimilarity measures. It is demonstrated how the selection of a measure, based on large scale evaluation, substantially improves the quality of classification, retrieval, and unsupervised segmentation of color and texture images.

Latent class models for collaborative filtering

Abstract: This paper presents a statistical approach to collaborative filtering and investigates the use of latent class models for predicting individual choices and preferences based on observed preference behavior. Two models are discussed and compared: the aspect model, a probabilistic latent space model which models individual preferences as a convex combination of preference factors, and the two-sided clustering model, which simultaneously partitions persons and objects into clusters. We present EM algorithms for different variants of the aspect model and derive an approximate EM algorithm based on a variational principle for the two-sided clustering model. The benefits of the different models are experimentally investigated on a large movie data set.

Childhood hepatoblastomas frequently carry a mutated degradation targeting box of the beta-catenin gene.

Abstract: Hepatoblastomas (HBs) are embryonal tumors affecting young children and representing the most frequent malignant liver tumors in childhood. The molecular pathogenesis of HB is poorly understood. Although most cases are sporadic, the incidence is highly elevated in patients with familial adenomatous polyposis coli. These patients carry germline mutations of the APC tumor suppressor gene. APC controls the degradation of the oncogene product beta-catenin after its NH2-terminal phosphorylation on serine/threonine residues. APC, as well as beta-catenin, has been found to be a central effector of the growth promoting wingless signaling pathway in development. To find out if this pathway is involved in the pathogenesis of sporadic HBs, we examined 52 biopsies and three cell lines from sporadic HBs for mutations in the APC and beta-catenin genes. Using single-strand conformational polymorphism analysis, deletion screening by PCR, and direct sequencing, we found a high frequency of beta-catenin mutations in sporadic HBs (48%). The mutations affected exon 3 encoding the degradation targeting box of beta-catenin leading to accumulation of intracytoplasmic and nuclear beta-catenin protein. The high frequency of activating mutations in the beta-catenin gene indicates an important role in the pathogenesis of HB.

Spontaneous breathing during ventilatory support improves ventilation-perfusion distributions in patients with acute respiratory distress syndrome.

Abstract: Ventilation–perfusion (V˙ a/Q˙) distributions were evaluated in 24 patients with acute respiratory distress syndrome (ARDS), during airway pressure release ventilation (APRV) with and without spontaneous breathing, or during pressure support ventilation (PSV). Whereas PSV provides mechanical assistance of each inspiration, APRV allows unrestricted spontaneous breathing throughout the mechanical ventilation. Patients were randomly assigned to receive APRV and PSV with equal airway pressure limits (Paw) (n = 12) or minute ventilation (V˙ e) (n = 12). In both groups spontaneous breathing during APRV was associated with increases (p < 0.05) in right ventricular end-diastolic volume, stroke volume, cardiac index (CI), PaO2 , oxygen delivery, and mixed venous oxygen tension (PvO2 ) and with reductions (p < 0.05) in pulmonary vascular resistance and oxygen extraction. PSV did not consistently improve CI and PaO2 when compared with APRV without spontaneous breathing. Improved V˙ a/Q˙ matching during spontaneous b...

Issues in Using Function Approximation for Reinforcement Learning

Abstract: Reinforcement learning techniques address the problem of learning to select actions in unknown, dynamic environments. It is widely acknowledged that to be of use in complex domains, reinforcement learning techniques must be combined with generalizing function approximation methods such as artificial neural networks. Little, however, is understood about the theoretical properties of such combinations, and many researchers have encountered failures in practice. In this paper we identify a prime source of such failures—namely, a systematic overestimation of utility values. Using Watkins’ Q-Learning [18] as an example, we give a theoretical account of the phenomenon, deriving conditions under which one may expected it to cause learning to fail. Employing some of the most popular function approximators, we present experimental results which support the theoretical findings.

Sphingolipids-Their Metabolic Pathways and the Pathobiochemistry of Neurodegenerative Diseases.

Abstract: Glycolipids such as ganglioside GM1 are involved in the building of carbohydrate layers on the surface of living cells. The investigation of the metabolism of this class of compounds gives insight into human diseases, novel signal transduction processes, and the epidermal water permeability barrier.

Quantitative analysis of survival motor neuron copies: identification of subtle SMN1 mutations in patients with spinal muscular atrophy, genotype-phenotype correlation, and implications for genetic counseling.

Abstract: Summary Problems with diagnosis and genetic counseling occur for patients with autosomal recessive proximal spinal muscular atrophy (SMA) who do not show the most common mutation: homozygous absence of at least exon 7 of the telomeric survival motor neuron gene ( SMN1 ). Here we present molecular genetic data for 42 independent nondeleted SMA patients. A nonradioactive quantitative PCR test showed one SMN1 copy in 19 patients (45%). By sequencing cloned reverse-transcription (RT) PCR products or genomic fragments of SMN1, we identified nine different mutations in 18 of the 19 patients, six described for the first time: three missense mutations (Y272C, T274I, S262I), three frameshift mutations in exons 2a, 2b, and 4 (124insT, 241-242ins4, 591delA), one nonsense mutation in exon 1 (Q15X), one Alu-mediated deletion from intron 4 to intron 6, and one donor splice site mutation in intron 7 (c.922+6T→G). The most frequent mutation, Y272C, was found in 6 (33%) of 18 patients. Each intragenic mutation found in at least two patients occurred on the same haplotype background, indicating founder mutations. Genotype-phenotype correlation allowed inference of the effect of each mutation on the function of the SMN1 protein and the role of the SMN2 copy number in modulating the SMA phenotype. In 14 of 23 SMA patients with two SMN1 copies, at least one intact SMN1 copy was sequenced, which excludes a 5q-SMA and suggests the existence of further gene(s) responsible for ∼4%–5% of phenotypes indistinguishable from SMA. We determined the validity of the test, and we discuss its practical implications and limitations.

Fluorine-18 fluorodeoxyglucose positron emission tomography in thyroid cancer: results of a multicentre study.

Abstract: =222) and the group with negative radioiodine scan (n=166), respectively. Specificity was 90% in the whole patient group. Sensitivity and specificity of WBS were 50% and 99%, respectively. When the results of FDG-PET and WBS were considered in combination, tumour tissue was missed in only 7%. Sensitivity and specificity of MIBI/Tl were 53% and 92%, respectively (n=117). We conclude that FDG-PET is a sensitive method in the follow-up of thyroid cancer which should be considered in all patients suffering from differentiated thyroid cancer with suspected recurrence and/or metastases, and particularly in those with elevated thyroglobulin values and negative WBS.

Precision Mass Spectroscopy of the Antiproton and Proton Using Simultaneously Trapped Particles

Abstract: This last of a series of three measurements improves the comparison of antiproton $(\overline{p})$ and proton $(p)$ by almost a factor of ${10}^{6}$ over earlier exotic atom measurements, and is the most precise $\mathrm{CPT}$ test with baryons by a similar large factor. Measuring the cyclotron frequencies of a simultaneously trapped $\overline{p}$ and ${H}^{\ensuremath{-}}$ ion establishes that the ratio of $q/m$ for $\overline{p}$ and $p$ is $\ensuremath{-}0.99999999991\ifmmode\pm\else\textpm\fi{}0.00000000009$, more than 10 times the accuracy over our previous measurement. This $9\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}11}$ comparison makes the first use of simultaneously trapped particles for sub-ppb spectroscopy.

Permeability prediction based on fractal pore‐space geometry

Abstract: Estimating permeability from grain-size distributions or from well logs is attractive but difficult. In this paper we present a new, generally applicable, and relatively inexpensive approach which yields permeability information on the scale of core samples and boreholes. The approach is theoretically based on a fractal model for the internal structure of a porous medium. It yields a general and petrophysically justified relation linking porosity to permeability, which may be calculated either from porosity or from the pore-radius distribution. This general relation can be tuned to the entire spectrum of sandstones, ranging from clean to shaly. The resulting expressions for the different rock types are calibrated to a comprehensive data set of petrophysical and petrographical rock properties measured on 640 sandstone core samples of the Rotliegend Series (Lower Permian) in northeastern Germany. With few modifications, this new straight-forward and petrophysically motivated approach can also be applied to metamorphic and igneous rocks. Permeability calculated with this procedure from industry porosity logs compares very well with permeability measured on sedimentary and metamorphic rock samples.

Real-Time Tracking of Memory Formation in the Human Rhinal Cortex and Hippocampus

Abstract: A fundamental question about human memory is which brain structures are involved, and when, in transforming experiences into memories. This experiment sought to identify neural correlates of memory formation with the use of intracerebral electrodes implanted in the brains of patients with temporal lobe epilepsy. Event-related potentials (ERPs) were recorded directly from the medial temporal lobe (MTL) as the patients studied single words. ERPs elicited by words subsequently recalled in a memory test were contrasted with ERPs elicited by unrecalled words. Memory formation was associated with distinct but interrelated ERP differences within the rhinal cortex and the hippocampus, which arose after about 300 and 500 milliseconds, respectively. These findings suggest that declarative memory formation is dissociable into subprocesses and sequentially organized within the MTL.

Conduction Disturbances and Increased Atrial Vulnerability in Connexin40-Deficient Mice Analyzed by Transesophageal Stimulation

Abstract: Background—Recently, it has been reported that connexin40 (Cx40) deficiency in targeted mouse mutants is associated with a prolongation of P-wave and QRS complex duration on surface electrograms. The specific effects of Cx40 deficiency on sinus node function, sinoatrial, and atrioventricular conduction properties as well as on atrial vulnerability have not yet been investigated systematically by electrophysiological analysis. Methods and Results—Fifty-two mice (18 Cx40+/+, 15 Cx40+/−, and 19 Cx40−/− mice) were subjected to rapid atrial transesophageal stimulation after anesthesia with avertin. A significant prolongation of sinus node recovery time was noticed in Cx40−/− mice compared with Cx40+/− and Cx40+/+ mice (287.8±109.0 vs 211.1±61.8 vs 204.4±60.9 ms; P<0.05). In addition, Wenckebach periodicity occurred at significantly longer atrial pacing cycle lengths in Cx40−/− mice than in Cx40+/− or Cx40+/+ mice (93.3±11.8 vs 83.9±9.7 vs 82.8±8.0 ms, P<0.05). Analysis of 27 Cx40−/− mice showed a significant i...

Bidirectional reaction steps in metabolic networks: III. Explicit solution and analysis of isotopomer labeling systems.

Abstract: The last few years have brought tremendous progress in experimental methods for metabolic flux determination by carbon-labeling experiments. A significant enlargement of the available measurement data set has been achieved, especially when isotopomer fractions within intracellular metabolite pools are quantitated. This information can be used to improve the statistical quality of flux estimates. Furthermore, several assumptions on bidirectional intracellular reaction steps that were hitherto indispensable may now become obsolete. To make full use of the complete measurement information a general mathematical model for isotopomer systems is established in this contribution. Then, by introducing the important new concept of cumomers and cumomer fractions, it is shown that the arising nonlinear isotopomer balance equations can be solved analytically in all cases. In particular, the solution of the metabolite flux balances and the positional carbon-labeling balances presented in part I of this series turn out to be just the first two steps of the general solution procedure for isotopomer balances. A detailed analysis of the isotopomer network structure then opens up new insights into the intrinsic structure of isotopomer systems. In particular, it turns out that isotopomer systems are not as complex as they appear at first glance. This enables some far-reaching conclusions to be drawn on the information potential of isotopomer experiments with respect to flux identification. Finally, some illustrative examples are examined to show that an information increase is not guaranteed when isotopomer measurements are used in addition to positional enrichment data.