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Showing papers by "University of Freiburg published in 2005"


Journal ArticleDOI
07 Jul 2005-Nature
TL;DR: It is reported that ACE2 and the angiotensin II type 2 receptor (AT2) protect mice from severe acute lung injury induced by acid aspiration or sepsis, pointing to a possible therapy for a syndrome affecting millions of people worldwide every year.
Abstract: Acute respiratory distress syndrome (ARDS), the most severe form of acute lung injury, is a devastating clinical syndrome with a high mortality rate (30-60%) (refs 1-3). Predisposing factors for ARDS are diverse and include sepsis, aspiration, pneumonias and infections with the severe acute respiratory syndrome (SARS) coronavirus. At present, there are no effective drugs for improving the clinical outcome of ARDS. Angiotensin-converting enzyme (ACE) and ACE2 are homologues with different key functions in the renin-angiotensin system. ACE cleaves angiotensin I to generate angiotensin II, whereas ACE2 inactivates angiotensin II and is a negative regulator of the system. ACE2 has also recently been identified as a potential SARS virus receptor and is expressed in lungs. Here we report that ACE2 and the angiotensin II type 2 receptor (AT2) protect mice from severe acute lung injury induced by acid aspiration or sepsis. However, other components of the renin-angiotensin system, including ACE, angiotensin II and the angiotensin II type 1a receptor (AT1a), promote disease pathogenesis, induce lung oedemas and impair lung function. We show that mice deficient for Ace show markedly improved disease, and also that recombinant ACE2 can protect mice from severe acute lung injury. Our data identify a critical function for ACE2 in acute lung injury, pointing to a possible therapy for a syndrome affecting millions of people worldwide every year.

2,183 citations


Proceedings ArticleDOI
10 May 2005
TL;DR: This work presents topic diversification, a novel method designed to balance and diversify personalized recommendation lists in order to reflect the user's complete spectrum of interests, and introduces the intra-list similarity metric to assess the topical diversity of recommendation lists.
Abstract: In this work we present topic diversification, a novel method designed to balance and diversify personalized recommendation lists in order to reflect the user's complete spectrum of interests. Though being detrimental to average accuracy, we show that our method improves user satisfaction with recommendation lists, in particular for lists generated using the common item-based collaborative filtering algorithm.Our work builds upon prior research on recommender systems, looking at properties of recommendation lists as entities in their own right rather than specifically focusing on the accuracy of individual recommendations. We introduce the intra-list similarity metric to assess the topical diversity of recommendation lists and the topic diversification approach for decreasing the intra-list similarity. We evaluate our method using book recommendation data, including offline analysis on 361, !, 349 ratings and an online study involving more than 2, !, 100 subjects.

1,813 citations


Journal ArticleDOI
06 Jan 2005-Nature
TL;DR: This work shows that five PIN genes collectively control auxin distribution to regulate cell division and cell expansion in the primary root and reveals an interaction network of auxin transport facilitators and root fate determinants that control patterning and growth of the root primordium.
Abstract: Local accumulation of the plant growth regulator auxin mediates pattern formation in Arabidopsis roots and influences outgrowth and development of lateral root- and shoot-derived primordia. However, it has remained unclear how auxin can simultaneously regulate patterning and organ outgrowth and how its distribution is stabilized in a primordium-specific manner. Here we show that five PIN genes collectively control auxin distribution to regulate cell division and cell expansion in the primary root. Furthermore, the joint action of these genes has an important role in pattern formation by focusing the auxin maximum and restricting the expression domain of PLETHORA (PLT) genes, major determinants for root stem cell specification. In turn, PLT genes are required for PIN gene transcription to stabilize the auxin maximum at the distal root tip. Our data reveal an interaction network of auxin transport facilitators and root fate determinants that control patterning and growth of the root primordium.

1,794 citations


Journal ArticleDOI
15 Sep 2005-Nature
TL;DR: It is shown that lysine-specific demethylase 1 co-localizes with the androgen receptor in normal human prostate and prostate tumour and pargyline is identified as an inhibitor of LSD1, providing a mechanism by which demethylases control specific gene expression.
Abstract: Gene regulation in eukaryotes requires the coordinate interaction of chromatin-modulating proteins with specific transcription factors such as the androgen receptor. Gene activation and repression is specifically regulated by histone methylation status at distinct lysine residues. Here we show that lysine-specific demethylase 1 (LSD1; also known as BHC110) co-localizes with the androgen receptor in normal human prostate and prostate tumour. LSD1 interacts with androgen receptor in vitro and in vivo, and stimulates androgen-receptor-dependent transcription. Conversely, knockdown of LSD1 protein levels abrogates androgen-induced transcriptional activation and cell proliferation. Chromatin immunoprecipitation analyses demonstrate that androgen receptor and LSD1 form chromatin-associated complexes in a ligand-dependent manner. LSD1 relieves repressive histone marks by demethylation of histone H3 at lysine 9 (H3-K9), thereby leading to de-repression of androgen receptor target genes. Furthermore, we identify pargyline as an inhibitor of LSD1. Pargyline blocks demethylation of H3-K9 by LSD1 and consequently androgen-receptor-dependent transcription. Thus, modulation of LSD1 activity offers a new strategy to regulate androgen receptor functions. Here, we link demethylation of a repressive histone mark with androgen-receptor-dependent gene activation, thus providing a mechanism by which demethylases control specific gene expression.

1,666 citations


Journal ArticleDOI
TL;DR: The concept of mental illness stigma is clarified and consequences for individuals with mental illness are discussed, focussing on self-stigma/empowerment and fear of stigma as a barrier to using health services.

1,309 citations


Journal ArticleDOI
TL;DR: This paper uses a stagewise fitting process to construct the logistic regression models that can select relevant attributes in the data in a natural way, and shows how this approach can be used to build the logistics regression models at the leaves by incrementally refining those constructed at higher levels in the tree.
Abstract: Tree induction methods and linear models are popular techniques for supervised learning tasks, both for the prediction of nominal classes and numeric values. For predicting numeric quantities, there has been work on combining these two schemes into `model trees', i.e. trees that contain linear regression functions at the leaves. In this paper, we present an algorithm that adapts this idea for classification problems, using logistic regression instead of linear regression. We use a stagewise fitting process to construct the logistic regression models that can select relevant attributes in the data in a natural way, and show how this approach can be used to build the logistic regression models at the leaves by incrementally refining those constructed at higher levels in the tree. We compare the performance of our algorithm to several other state-of-the-art learning schemes on 36 benchmark UCI datasets, and show that it produces accurate and compact classifiers.

1,200 citations


Journal ArticleDOI
TL;DR: This paper presents an approach for the coordination of multiple robots, which simultaneously takes into account the cost of reaching a target point and its utility and describes how this algorithm can be extended to situations in which the communication range of the robots is limited.
Abstract: In this paper, we consider the problem of exploring an unknown environment with a team of robots. As in single-robot exploration the goal is to minimize the overall exploration time. The key problem to be solved in the context of multiple robots is to choose appropriate target points for the individual robots so that they simultaneously explore different regions of the environment. We present an approach for the coordination of multiple robots, which simultaneously takes into account the cost of reaching a target point and its utility. Whenever a target point is assigned to a specific robot, the utility of the unexplored area visible from this target position is reduced. In this way, different target locations are assigned to the individual robots. We furthermore describe how our algorithm can be extended to situations in which the communication range of the robots is limited. Our technique has been implemented and tested extensively in real-world experiments and simulation runs. The results demonstrate that our technique effectively distributes the robots over the environment and allows them to quickly accomplish their mission.

1,107 citations


Journal ArticleDOI
TL;DR: This review focuses mainly on eudicot seeds, and on the interactions between abscisic acid (ABA), gibberellins (GA), ethylene, brassinosteroids, auxin and cytokinins in regulating the interconnected molecular processes that control dormancy release and germination.
Abstract: This review focuses mainly on eudicot seeds, and on the interactions between abscisic acid (ABA), gibberellins (GA), ethylene, brassinosteroids (BR), auxin and cytokinins in regulating the interconnected molecular processes that control dormancy release and germination. Signal transduction pathways, mediated by environmental and hormonal signals, regulate gene expression in seeds. Seed dormancy release and germination of species with coat dormancy is determined by the balance of forces between the growth potential of the embryo and the constraint exerted by the covering layers, e.g. testa and endosperm. Recent progress in the field of seed biology has been greatly aided by molecular approaches utilizing mutant and transgenic seeds of Arabidopsis thaliana and the Solanaceae model systems, tomato and tobacco, which are altered in hormone biology. ABA is a positive regulator of dormancy induction and most likely also maintenance, while it is a negative regulator of germination. GA releases dormancy, promotes germination and counteracts ABA effects. Ethylene and BR promote seed germination and also counteract ABA effects. We present an integrated view of the molecular genetics, physiology and biochemistry used to unravel how hormones control seed dormancy release and germination.

1,006 citations


Journal ArticleDOI
TL;DR: A new identification system for a trimer using three Arabic numerals, based on the alpha, beta and gamma chain numbers is introduced, which is introduced for laminin trimers.

836 citations


Journal ArticleDOI
TL;DR: Cardiovascular risks because of periprocedural aspirin withdrawal and bleeding risks with the continuation of aspirin are reviewed and quantified.
Abstract: . Objectives. Low-dose aspirin given for secondary prevention of cardiovascular disease is frequently withdrawn prior to surgical or diagnostic procedures to reduce bleeding complications. This may expose patients to increased cardiovascular morbidity and mortality. Aim of the study was to review and quantify cardiovascular risks because of periprocedural aspirin withdrawal and bleeding risks with the continuation of aspirin. Methods. We screened MEDLINE (January 1970–October 2004) with additional manual cross-referencing for clinical studies, surveys on the opinions of doctors and guidelines. Results. Studies reporting the relative risk of acute cardiovascular events after aspirin withdrawal when compared with its continuation were not found. However, retrospective investigations revealed that aspirin withdrawal precedes up to 10.2% of acute cardiovascular syndromes. The time interval between discontinuation and acute cerebral events was 14.3 ± 11.3 days, 8.5 ± 3.6 days for acute coronary syndromes, and 25.8 ± 18.1 days for acute peripheral arterial syndromes (P < 0.02 versus acute coronary syndromes). On aspirin-related bleeding risks, we obtained 41 (12 observational retrospective, 19 observational prospective, 10 randomized) studies, reporting on 49 590 patients (14 981 on aspirin). Baseline frequency of bleeding complications varied between 0 (skin lesion excision, cataract surgery) and 75% (transrectal prostate biopsy). Whilst aspirin increased the rate of bleeding complications by factor 1.5 (median, interquartile range: 1.0–2.5), it did not lead to a higher level of the severity of bleeding complications (exception: intracranial surgery, and possibly transurethral prostatectomy). Surveys amongst doctors on the management of this problem demonstrate wide variations. Available guidelines are scarce and in part contradictory. Conclusions. Only if low-dose aspirin may cause bleeding risks with increased mortality or sequels comparable with the observed cardiovascular risks after aspirin withdrawal, it should be discontinued prior to an intended operation or procedure. Controlled clinical studies are urgently needed.

814 citations


Journal ArticleDOI
TL;DR: A critical overview of the peripheral interfaces available and trace their use from research to clinical application in controlling artificial and robotic prostheses is provided.
Abstract: Considerable scientific and technological efforts have been devoted to develop neuroprostheses and hybrid bionic systems that link the human nervous system with electronic or robotic prostheses, with the main aim of restoring motor and sensory functions in disabled patients. A number of neuroprostheses use interfaces with peripheral nerves or muscles for neuromuscular stimulation and signal recording. Herein, we provide a critical overview of the peripheral interfaces available and trace their use from research to clinical application in controlling artificial and robotic prostheses. The first section reviews the different types of non-invasive and invasive electrodes, which include surface and muscular electrodes that can record EMG signals from and stimulate the underlying or implanted muscles. Extraneural electrodes, such as cuff and epineurial electrodes, provide simultaneous interface with many axons in the nerve, whereas intrafascicular, penetrating, and regenerative electrodes may contact small groups of axons within a nerve fascicle. Biological, technological, and material science issues are also reviewed relative to the problems of electrode design and tissue injury. The last section reviews different strate- gies for the use of information recorded from peripheral interfaces and the current state of control neuroprostheses and hybrid bionic systems.

Proceedings ArticleDOI
18 Apr 2005
TL;DR: Adapt techniques to reduce the number of particles in a Rao-Blackwellized particle filter for learning grid maps are presented and an approach to selectively carry out re-sampling operations which seriously reduces the problem of particle depletion is presented.
Abstract: Recently Rao-Blackwellized particle filters have been introduced as effective means to solve the simultaneous localization and mapping (SLAM) problem. This approach uses a particle filter in which each particle carries an individual map of the environment. Accordingly, a key question is how to reduce the number of particles. In this paper we present adaptive techniques to reduce the number of particles in a Rao-Blackwellized particle filter for learning grid maps. We propose an approach to compute an accurate proposal distribution taking into account not only the movement of the robot but also the most recent observation. This drastically decrease the uncertainty about the robot's pose in the prediction step of the filter. Furthermore, we present an approach to selectively carry out re-sampling operations which seriously reduces the problem of particle depletion. Experimental results carried out with mobile robots in large-scale indoor as well as in outdoor environments illustrate the advantages of our methods over previous approaches.

Journal ArticleDOI
TL;DR: Fuid flow increases inversin levels in ciliated tubular epithelial cells and seems to regulate this crucial switch between Wnt signaling pathways during renal development, implying that an inhibition of canonical Wnt behavior is required for normal renal development.
Abstract: Cystic renal diseases are caused by mutations of proteins that share a unique subcellular localization: the primary cilium of tubular epithelial cells1. Mutations of the ciliary protein inversin cause nephronophthisis type II, an autosomal recessive cystic kidney disease characterized by extensive renal cysts, situs inversus and renal failure2. Here we report that inversin acts as a molecular switch between different Wnt signaling cascades. Inversin inhibits the canonical Wnt pathway by targeting cytoplasmic dishevelled (Dsh or Dvl1) for degradation; concomitantly, it is required for convergent extension movements in gastrulating Xenopus laevis embryos and elongation of animal cap explants, both regulated by noncanonical Wnt signaling. In zebrafish, the structurally related switch molecule diversin ameliorates renal cysts caused by the depletion of inversin, implying that an inhibition of canonical Wnt signaling is required for normal renal development. Fluid flow increases inversin levels in ciliated tubular epithelial cells and seems to regulate this crucial switch between Wnt signaling pathways during renal development.

Journal ArticleDOI
TL;DR: In this article, a review of the literature concerning forest and woodland structure at the scale of an individual stand is presented, where stand structure is defined in terms of structural attributes and stand structural complexity.

Journal ArticleDOI
TL;DR: The recessive mutation 'Heedless' (hdl) was detected in third-generation N-ethyl-N-nitrosourea–mutated mice that showed defective responses to microbial inducers, and the data suggest that the TLR4–MD-2 complex distinguishes LPS chemotypes, but CD14 nullifies this distinction.
Abstract: The recessive mutation 'Heedless' (hdl) was detected in third-generation N-ethyl-N-nitrosourea-mutated mice that showed defective responses to microbial inducers. Macrophages from Heedless homozygotes signaled by the MyD88-dependent pathway in response to rough lipopolysaccharide (LPS) and lipid A, but not in response to smooth LPS. In addition, the Heedless mutation prevented TRAM-TRIF-dependent signaling in response to all LPS chemotypes. Heedless also abolished macrophage responses to vesicular stomatitis virus and substantially inhibited responses to specific ligands for the Toll-like receptor 2 (TLR2)-TLR6 heterodimer. The Heedless phenotype was positionally ascribed to a premature stop codon in Cd14. Our data suggest that the TLR4-MD-2 complex distinguishes LPS chemotypes, but CD14 nullifies this distinction. Thus, the TLR4-MD-2 complex receptor can function in two separate modes: one in which full signaling occurs and one limited to MyD88-dependent signaling.

Journal ArticleDOI
TL;DR: Heterozygosity with respect to mutations causing the amino acid substitutions S144X and C104R abrogated APRIL binding and resulted in loss of TACI function, as evidenced by impaired proliferative response to IgM-APRIL costimulation and defective class switch recombination induced by IL-10 and APRIL or BAFF.
Abstract: The functional interaction of BAFF and APRIL with TNF receptor superfamily members BAFFR, TACI and BCMA is crucial for development and maintenance of humoral immunity in mice and humans. Using a candidate gene approach, we identified homozygous and heterozygous mutations in TNFRSF13B, encoding TACI, in 13 individuals with common variable immunodeficiency. Homozygosity with respect to mutations causing the amino acid substitutions S144X and C104R abrogated APRIL binding and resulted in loss of TACI function, as evidenced by impaired proliferative response to IgM-APRIL costimulation and defective class switch recombination induced by IL-10 and APRIL or BAFF. Family members heterozygous with respect to the C104R mutation and individuals with sporadic common variable immunodeficiency who were heterozygous with respect to the amino acid substitutions A181E, S194X and R202H had humoral immunodeficiency. Although signs of autoimmunity and lymphoproliferation are evident, the human phenotype differs from that of the Tnfrsf13b-/- mouse model.

Journal ArticleDOI
TL;DR: In this paper, various approaches based on bounding volume hierarchies, distance fields and spatial partitioning are discussed for collision detection of deformable objects in interactive environments for surgery simulation and entertainment technology.
Abstract: Interactive environments for dynamically deforming objects play an important role in surgery simulation and entertainment technology. These environments require fast deformable models and very efficient collision handling techniques. While collision detection for rigid bodies is well investigated, collision detection for deformable objects introduces additional challenging problems. This paper focuses on these aspects and summarizes recent research in the area of deformable collision detection. Various approaches based on bounding volume hierarchies, distance fields and spatial partitioning are discussed. In addition, image-space techniques and stochastic methods are considered. Applications in cloth modeling and surgical simulation are presented.

Journal ArticleDOI
TL;DR: In this article, the development and demonstration of a highly efficient warm-white all-nitride phosphor-converted light emitting diode (pc-LED) is presented utilizing a GaN based quantum well blue LED and two novel nitrogen containing luminescent materials doped with Eu2+.
Abstract: In the Editor's Choice [1] the development and demonstration of a highly efficient warm-white all-nitride phosphor-converted light emitting diode (pc-LED) is presented utilizing a GaN based quantum well blue LED and two novel nitrogen containing luminescent materials doped with Eu2+. These novel LEDs are superior to both incandescent and fluorescent lamps and may therefore become the next generation of general lighting sources. The cover picture is an artist's view of the 2-pc-LED: On a copper slug and underneath a plastic lens a ‘flip-chip’ is soldered to metal contacts; ‘flip-chip’ meaning the substrate on which the stack of GaN and InGaN layers has been deposited is used as light exit, the (bottom) p-contacts being highly reflective. The color converting phosphors are placed on top of the chip, embedded in silicone. Primary blue as well as color-converted red and green photons are emitted. The first author, Regina Mueller-Mach, manages the Charac-terization Laboratory at Lumileds which runs R&D work on phosphor converted LEDs in close cooperation with Philips Research Laboratories and the Department of Chemistry and Biochemistry of the University of Munich.

Journal ArticleDOI
01 Jul 2005
TL;DR: The main idea of the deformable model is to replace energies by geometric constraints and forces by distances of current positions to goal positions, determined via a generalized shape matching of an undeformed rest state with the current deformed state of the point cloud.
Abstract: We present a new approach for simulating deformable objects. The underlying model is geometrically motivated. It handles pointbased objects and does not need connectivity information. The approach does not require any pre-processing, is simple to compute, and provides unconditionally stable dynamic simulations.The main idea of our deformable model is to replace energies by geometric constraints and forces by distances of current positions to goal positions. These goal positions are determined via a generalized shape matching of an undeformed rest state with the current deformed state of the point cloud. Since points are always drawn towards well-defined locations, the overshooting problem of explicit integration schemes is eliminated. The versatility of the approach in terms of object representations that can be handled, the efficiency in terms of memory and computational complexity, and the unconditional stability of the dynamic simulation make the approach particularly interesting for games.

Journal ArticleDOI
TL;DR: A comprehensive review of the literature to summarize the pharmacological and clinical effects of this popular plant material found ginger exerts in vitro antioxidative, antitumorigenic and immunomodulatory effects and is an effective antimicrobial and antiviral agent.

Journal ArticleDOI
TL;DR: It is shown that cholecystokinin (CCK)-expressing interneurons in rat dentate gyrus release GABA in a highly asynchronous manner, in contrast to parvalbumin (PV) interneurs, thus generating long-lasting inhibition in the brain.
Abstract: Hippocampal GABAergic interneurons show diverse molecular and morphological properties. The functional significance of this diversity for information processing is poorly understood. Here we show that cholecystokinin (CCK)-expressing interneurons in rat dentate gyrus release GABA in a highly asynchronous manner, in contrast to parvalbumin (PV) interneurons. With a gamma-frequency burst of ten action potentials, the ratio of asynchronous to synchronous release is 3:1 in CCK interneurons but is 1:5 in parvalbumin interneurons. N-type channels trigger synchronous and asynchronous release in CCK interneuron synapses, whereas P/Q-type Ca(2+) channels mediate release at PV interneuron synapses. Effects of Ca(2+) chelators suggest that both a long-lasting presynaptic Ca(2+) transient and a large distance between Ca(2+) source and sensor of exocytosis contribute to the higher ratio of asynchronous to synchronous release in CCK interneuron synapses. Asynchronous release occurs at physiological temperature and with behaviorally relevant stimulation patterns, thus generating long-lasting inhibition in the brain.

Journal ArticleDOI
TL;DR: Nutritional support, addressing the specific needs of this patient group, is required to help improve prognosis, and reduce the consequences of cancer-associated nutritional decline.

Journal ArticleDOI
TL;DR: In this article, the authors describe the genomes of eight newly sequenced isolates and combine them with the first four genomes for a comprehensive analysis of the core (shared by all isolates) and flexible genes of the Prochlorococcus group, and the patterns of loss and gain of the flexible genes over the course of evolution.
Abstract: Prochlorococcus is a marine cyanobacterium that numerically dominates the mid-latitude oceans and is the smallest known oxygenic phototroph. Numerous isolates from diverse areas of the world’s oceans have been studied and shown to be physiologically and genetically distinct. All isolates described thus far can be assigned to either a tightly clustered high-light (HL)-adapted clade, or a more divergent low-light (LL)-adapted group. The 16S rRNA sequences of the entire Prochlorococcus group differ by at most 3%, and the four initially published genomes revealed patterns of genetic differentiation that help explain physiological differences among the isolates. Here we describe the genomes of eight newly sequenced isolates and combine them with the first four genomes for a comprehensive analysis of the core (shared by all isolates) and flexible genes of the Prochlorococcus group, and the patterns of loss and gain of the flexible genes over the course of evolution. There are 1,273 genes that represent the core shared by all 12 genomes. They are apparently sufficient, according to metabolic reconstruction, to encode a functional cell. We describe a phylogeny for all 12 isolates by subjecting their complete proteomes to three different phylogenetic analyses. For each non-core gene, we used a maximum parsimony method to estimate which ancestor likely first acquired or lost each gene. Many of the genetic differences among isolates, especially for genes involved in outer membrane synthesis and nutrient transport, are found within the same clade. Nevertheless, we identified some genes defining HL and LL ecotypes, and clades within these broad ecotypes, helping to demonstrate the basis of HL and LL adaptations in Prochlorococcus. Furthermore, our estimates of gene gain events allow us to identify highly variable genomic islands that are not apparent through simple pairwise comparisons. These results emphasize the functional roles, especially those connected to outer membrane synthesis and transport that dominate the flexible genome and set it apart from the core. Besides identifying islands and demonstrating their role throughout the history of Prochlorococcus, reconstruction of past gene gains and losses shows that much of the variability exists at the ‘‘leaves of the tree,’’ between the most closely related strains. Finally, the identification of core and flexible genes from this 12-genome comparison is largely consistent with the relative frequency of Prochlorococcus genes found in global ocean metagenomic databases, further closing the gap between our understanding of these organisms in the lab and the wild.

Journal ArticleDOI
TL;DR: A literature analysis on trends regarding changes in the incidence, geographic distribution, and etiologic factors of non-Hodgkin’s lymphoma finds that a male predominance throughout all age groups is apparent, and increases in high-grade NHL and extranodal disease are predominant.
Abstract: While for most cancers incidence and mortality are decreasing, those of non-Hodgkin's lymphoma (NHL) are steadily increasing. Research to define reasons for this increase is extensive, but has not yet resolved them. We have conducted a literature analysis on trends regarding changes in the incidence, geographic distribution, and etiologic factors of NHL. From our own and previous analyses, an increasing NHL incidence at a rate of 3-4% per year was observed for the 1970s and 1980s. This stabilized in the 1990s, nevertheless still with an annual rise of 1-2%, resulting in almost a doubling of the NHL incidence. This rise has been noted worldwide, particularly in elderly persons >55 years. Concerning gender subgroups, a male predominance throughout all age groups is apparent. Although the NHL incidence has historically been higher in whites than blacks, disproportional increases have recently been observed in the latter group. Increases in high-grade NHL and extranodal disease are predominant. Differences in geographic distribution are striking for follicular lymphoma, which is more common in Western countries than elsewhere. Asians have higher rates of aggressive NHL, T-cell lymphomas, and extranodal disease. In the Middle East, high rates of intestinal extranodal disease are observed, whereas in Africa, endemic Burkitt's lymphoma accounts for a substantial proportion. Risks for developing NHL include immunosuppression and a causal link between infectious agents, and lymphomagenesis has also been determined, particularly for human T-cell leukemia/lymphoma virus type 1 (HTLV-1), Epstein-Barr virus (EBV), and Helicobacter pylori infections. Exposure to environmental agents and occupational risks have been studied; however, their significance is as yet uncertain.

Journal ArticleDOI
18 Aug 2005-Neuron
TL;DR: It is shown that Apoer2 is present in the postsynaptic densities of excitatory synapses where it forms a functional complex with NMDA receptors, a novel component of the NMDA receptor complex.

Journal ArticleDOI
TL;DR: The area of micropumps is definitely one of those “long runners” as discussed by the authors, and the potential applications especially the combination of biochemical sensing and microfluidics has provided a substantial stimulus for micropump research and development in the past and will do so in the future.
Abstract: If a high and on-going research dynamics is taken as a rejuvenating factor microfluidics can still be regarded as a truly young discipline, although some microfluidic devices definitely can not be considered as “youngsters” any more. In a time of 30 years of ISFETOLOGY it may be worth to take a look at these devices in order to examine, whether they had—and still have—the potential to stimulate the imagination and creativity of researchers in a similar way as the Ion Sensitive Fieldeffect Transistor did since its invention in 1970. The area of micropumps is definitely one of those “long runners”. Starting in the mid 1970s a steadily growing and astonishing diversity of micropump principles, technical concepts and applications has emerged in this area. Until today MEMS science is delivering a constant flow of novel modelling approaches, microstructured materials, actuation principles, fabrication technologies and applications, that are readily taken and transferred into micropump research. Among the potential applications especially the combination of biochemical sensing and microfluidics has provided a substantial stimulus for micropump research and development in the past and will do so in the future.

Journal ArticleDOI
TL;DR: A structure-based clustering approach that is capable of extracting putative RNA classes from genome-wide surveys for structured RNAs and suggests several novel classes of ncRNAs for which to date no representative has been experimentally characterized.
Abstract: The RFAM database defines families of ncRNAs by means of sequence similarities that are sufficient to establish homology. In some cases, such as microRNAs and box H/ACA snoRNAs, functional commonalities define classes of RNAs that are characterized by structural similarities, and typically consist of multiple RNA families. Recent advances in high-throughput transcriptomics and comparative genomics have produced very large sets of putative noncoding RNAs and regulatory RNA signals. For many of them, evidence for stabilizing selection acting on their secondary structures has been derived, and at least approximate models of their structures have been computed. The overwhelming majority of these hypothetical RNAs cannot be assigned to established families or classes. We present here a structure-based clustering approach that is capable of extracting putative RNA classes from genome-wide surveys for structured RNAs. The LocARNA (local alignment of RNA) tool implements a novel variant of the Sankoff algorithm that is sufficiently fast to deal with several thousand candidate sequences. The method is also robust against false positive predictions, i.e., a contamination of the input data with unstructured or nonconserved sequences. We have successfully tested the LocARNA-based clustering approach on the sequences of the RFAM-seed alignments. Furthermore, we have applied it to a previously published set of 3,332 predicted structured elements in the Ciona intestinalis genome (Missal K, Rose D, Stadler PF (2005) Noncoding RNAs in Ciona intestinalis. Bioinformatics 21 (Supplement 2): i77–i78). In addition to recovering, e.g., tRNAs as a structure-based class, the method identifies several RNA families, including microRNA and snoRNA candidates, and suggests several novel classes of ncRNAs for which to date no representative has been experimentally characterized.

Journal ArticleDOI
TL;DR: A systematic three-stage SNP scan of 16.4 Mb on chromosome 6p21 in as many as 947 independent cases of familial and sporadic sarcoidosis and found that a 15-kb segment of the gene butyrophilin-like 2 (BTNL2) was associated with the disease.
Abstract: Sarcoidosis is a polygenic immune disorder with predominant manifestation in the lung. Genome-wide linkage analysis previously indicated that the extended major histocompatibility locus on chromosome 6p was linked to susceptibility to sarcoidosis. Here, we carried out a systematic three-stage SNP scan of 16.4 Mb on chromosome 6p21 in as many as 947 independent cases of familial and sporadic sarcoidosis and found that a 15-kb segment of the gene butyrophilin-like 2 (BTNL2) was associated with the disease. The primary disease-associated variant (rs2076530; P(TDT) = 3 x 10(-6), P(case-control) = 1.1 x 10(-8); replication P(TDT) = 0.0018, P(case-control) = 1.8 x 10(-6)) represents a risk factor that is independent of variation in HLA-DRB1. BTNL2 is a member of the immunoglobulin superfamily and has been implicated as a costimulatory molecule involved in T-cell activation on the basis of its homology to B7-1. The G --> A transition constituting rs2076530 leads to the use of a cryptic splice site located 4 bp upstream of the affected wild-type donor site. Transcripts of the risk-associated allele have a premature stop in the spliced mRNA. The resulting protein lacks the C-terminal IgC domain and transmembrane helix, thereby disrupting the membrane localization of the protein, as shown in experiments using green fluorescent protein and V5 fusion proteins.

Journal ArticleDOI
TL;DR: A technique for learning collections of trajectories that characterize typical motion patterns of persons and how to incorporate the probabilistic belief about the potential trajectories of persons into the path planning process of a mobile robot is proposed.
Abstract: Whenever people move through their environments they do not move randomly. Instead, they usually follow specific trajectories or motion patterns corresponding to their intentions. Knowledge about such patterns enables a mobile robot to robustly keep track of persons in its environment and to improve its behavior. In this paper we propose a technique for learning collections of trajectories that characterize typical motion patterns of persons. Data recorded with laser-range finders are clustered using the expectation maximization algorithm. Based on the result of the clustering process, we derive a hidden Markov model that is applied to estimate the current and future positions of persons based on sensory input. We also describe how to incorporate the probabilistic belief about the potential trajectories of persons into the path planning process of a mobile robot. We present several experiments carried out in different environments with a mobile robot equipped with a laser-range scanner and a camera system. The results demonstrate that our approach can reliably learn motion patterns of persons, can robustly estimate and predict positions of persons, and can be used to improve the navigation behavior of a mobile robot.

Journal ArticleDOI
TL;DR: In this article, a review of geometric partial differential equations (PDEs) involving curvature has been presented, including the methods of analysis, discretization and numerical analysis of mean curvature flow.
Abstract: This review concerns the computation of curvature-dependent interface motion governed by geometric partial differential equations. The canonical problem of mean curvature flow is that of finding a surface which evolves so that, at every point on the surface, the normal velocity is given by the mean curvature. In recent years the interest in geometric PDEs involving curvature has burgeoned. Examples of applications are, amongst others, the motion of grain boundaries in alloys, phase transitions and image processing. The methods of analysis, discretization and numerical analysis depend on how the surface is represented. The simplest approach is when the surface is a graph over a base domain. This is an example of a sharp interface approach which, in the general parametric approach, involves seeking a parametrization of the surface over a base surface, such as a sphere. On the other hand an interface can be represented implicitly as a level surface of a function, and this idea gives rise to the so-called level set method. Another implicit approach is the phase field method, which approximates the interface by a zero level set of a phase field satisfying a PDE depending on a new parameter. Each approach has its own advantages and disadvantages. In the article we describe the mathematical formulations of these approaches and their discretizations. Algorithms are set out for each approach, convergence results are given and are supported by computational results and numerous graphical figures. Besides mean curvature flow, the topics of anisotropy and the higher order geometric PDEs for Willmore flow and surface diffusion are covered.