Showing papers by "Ludwig Maximilian University of Munich published in 2004"
TL;DR: UNLABELLED Analysis of Phylogenetics and Evolution (APE) is a package written in the R language for use in molecular evolution and phylogenetics that provides both utility functions for reading and writing data and manipulating phylogenetic trees.
Abstract: Summary: Analysis of Phylogenetics and Evolution (APE) is a package written in the R language for use in molecular evolution and phylogenetics. APE provides both utility functions for reading and writing data and manipulating phylogenetic trees, as well as several advanced methods for phylogenetic and evolutionary analysis (e.g. comparative and population genetic methods). APE takes advantage of the many R functions for statistics and graphics, and also provides a flexible framework for developing and implementing further statistical methods for the analysis of evolutionary processes.
Availability: The program is free and available from the official R package archive at http://cran.r-project.org/src/contrib/PACKAGES.html#ape. APE is licensed under the GNU General Public License.
10,818 citations
TL;DR: This poster presents a selection of photographs from around the world taken in the period of May 21 to 29, 1997, as well as some of the more recent photographs taken in China and the United States.
Abstract: Pieter Baas – Leiden, The Netherlands Nadezhda Blokhina – Vladivostok, Russia Tomoyuki Fujii – Ibaraki, Japan Peter Gasson – Kew, UK Dietger Grosser – Munich, Germany Immo Heinz – Munich, Germany Jugo Ilic – South Clayton, Australia Jiang Xiaomei – Beijing, China Regis Miller – Madison, WI, USA Lee Ann Newsom – University Park, PA, USA Shuichi Noshiro – Ibaraki, Japan Hans Georg Richter – Hamburg, Germany Mitsuo Suzuki – Sendai, Japan Teresa Terrazas – Montecillo, Mexico Elisabeth Wheeler – Raleigh, NC, USA Alex Wiedenhoeft – Madison, WI, USA
1,308 citations
TL;DR: Systematic review and meta-analysis of published epidemiological studies comparing early feeding-mode and adjusting for potential confounding factors showed that breast-feeding reduced the risk of obesity in childhood significantly.
Abstract: OBJECTIVE: To investigate the relationship between breast-feeding and obesity in childhood. DESIGN: Systematic review and meta-analysis of published epidemiological studies (cohort, case–control or cross-sectional studies) comparing early feeding-mode and adjusting for potential confounding factors. Electronic databases were searched and reference lists of relevant articles were checked. Calculations of pooled estimates were conducted in fixed- and random-effects models. Heterogeneity was tested by Q-test. Publication bias was assessed from funnel plots and by a linear regression method. OUTCOME MEASURES: Odds ratio (OR) for obesity in childhood defined as body mass index (BMI) percentiles. RESULTS: Nine studies with more than 69 000 participants met the inclusion criteria. The meta-analysis showed that breast-feeding reduced the risk of obesity in childhood significantly. The adjusted odds ratio was 0.78, 95% CI (0.71, 0.85) in the fixed model. The assumption of homogeneity of results of the included studies could not be refuted (Q-test for heterogeneity, P>0.3), stratified analyses showed no differences regarding different study types, age groups, definition of breast-feeding or obesity and number of confounding factors adjusted for. A dose-dependent effect of breast-feeding duration on the prevalence of obesity was reported in four studies. Funnel plot regression gave no indication of publication bias. CONCLUSION: Breast-feeding seems to have a small but consistent protective effect against obesity in children.
1,241 citations
TL;DR: Investigating ‘chronotypes' observed an abrupt change in the timing of sleep at around the age of 20 and propose this change as the first biological marker of the end of adolescence.
1,218 citations
TL;DR: TREEFINDER is a versatile framework for analyzing phylogenetic data across different platforms that is suited both for exploratory as well as advanced studies.
Abstract: Most analysis programs for inferring molecular phylogenies are difficult to use, in particular for researchers with little programming experience
1,141 citations
TL;DR: In this article, a general strategy is described which allows for transferring hydrophobically capped nanocrystals from organic to aqueous solution by wrapping an amphiphilic polymer around the particles.
Abstract: A general strategy is described which allows for transferring hydrophobically capped nanocrystals from organic to aqueous solution by wrapping an amphiphilic polymer around the particles. In particular, high quality CoPt3, Au, CdSe/ZnS, and Fe2O3 nanocrystals have been water-solubilized in this way. Analysis with transmission electron microscopy, gel electrophoresis, and fluorescence correlation spectroscopy demonstrates that monodispersity of the particles is conserved upon phase transfer to aqueous solution.
1,042 citations
TL;DR: The potential cellular and enzymatic sources of ROS in platelets, their molecular mechanisms of action in platelet activation, and in vitro and in vivo evidence for their physiological and potential therapeutic relevance are discussed.
Abstract: Platelets participate not only in thrombus formation but also in the regulation of vessel tone, the development of atherosclerosis, angiogenesis, and in neointima formation after vessel wall injury. It is not surprising, therefore, that the platelet activation cascade (including receptor-mediated tethering to the endothelium, rolling, firm adhesion, aggregation, and thrombus formation) is tightly regulated. In addition to already well-defined platelet regulatory factors, such as nitric oxide (NO), prostacyclin (PGI2), and adenosine, reactive oxygen species (ROS) participate in the regulation of platelet activation. Although exogenously derived ROS are known to affect the regulation of platelet activation, recent data suggest that the platelets themselves generate ROS. Intracellular ROS signaling in activated platelets could be of significant relevance after transient platelet contact with the vessel wall, during the recruitment of additional platelets, and in thrombus formation. This review discusses the potential cellular and enzymatic sources of ROS in platelets, their molecular mechanisms of action in platelet activation, and summarizes in vitro and in vivo evidence for their physiological and potential therapeutic relevance.
1,040 citations
Vita-Salute San Raffaele University1, National University of Singapore2, University of Buenos Aires3, University of California, San Francisco4, University of Miami5, Wake Forest Institute for Regenerative Medicine6, University of Western Ontario7, Mayo Clinic8, Johns Hopkins University9, Duke University10, Karolinska University Hospital11, Aristotle University of Thessaloniki12, Tulane University13, Erasmus University Rotterdam14, London Bridge Hospital15, Istanbul University16, Rush University Medical Center17, Georgia Regents University18, University of Florence19, Deakin University20, Cleveland Clinic21, University of Milan22, Memorial Sloan Kettering Cancer Center23, Concordia University Wisconsin24, Valparaiso University25, University of Medicine and Dentistry of New Jersey26, Maimonides Medical Center27, Ludwig Maximilian University of Munich28, Rambam Health Care Campus29, Emory University30
TL;DR: Specific evaluation, treatment guidelines, and algorithms were developed for every sexual dysfunction in men, including erectile dysfunction; disorders of libido, orgasm, and ejaculation; Peyronie's disease; and priapism.
993 citations
TL;DR: In this article, the Omega-3 Index was proposed as a new risk factor for death from coronary heart disease (CHD) and the relationship between this putative marker and risk for CHD death, especially sudden cardiac death (SCD), was evaluated in several published primary and secondary prevention studies.
966 citations
TL;DR: It is proposed that the FKBP5 variant–dependent alterations in HPA-axis regulation could be related to the faster response to antidepressant drug treatment and the increased recurrence of depressive episodes observed in this subgroup of depressed individuals.
Abstract: The stress hormone-regulating hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the causality as well as the treatment of depression. To investigate a possible association between genes regulating the HPA axis and response to antidepressants and susceptibility for depression, we genotyped single-nucleotide polymorphisms in eight of these genes in depressed individuals and matched controls. We found significant associations of response to antidepressants and the recurrence of depressive episodes with single-nucleotide polymorphisms in FKBP5, a glucocorticoid receptor-regulating cochaperone of hsp-90, in two independent samples. These single-nucleotide polymorphisms were also associated with increased intracellular FKBP5 protein expression, which triggers adaptive changes in glucocorticoid receptor and, thereby, HPA-axis regulation. Individuals carrying the associated genotypes had less HPA-axis hyperactivity during the depressive episode. We propose that the FKBP5 variant-dependent alterations in HPA-axis regulation could be related to the faster response to antidepressant drug treatment and the increased recurrence of depressive episodes observed in this subgroup of depressed individuals. These findings support a central role of genes regulating the HPA axis in the causality of depression and the mechanism of action of antidepressant drugs.
903 citations
TL;DR: Advances in understanding nuclear structure have revealed insights into the process of malignant transformation and provide a basis for the development of new diagnostic tools and therapeutics.
Abstract: Nuclear architecture — the spatial arrangement of chromosomes and other nuclear components — provides a framework for organizing and regulating the diverse functional processes within the nucleus. There are characteristic differences in the nuclear architectures of cancer cells, compared with normal cells, and some anticancer treatments restore normal nuclear structure and function. Advances in understanding nuclear structure have revealed insights into the process of malignant transformation and provide a basis for the development of new diagnostic tools and therapeutics.
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TL;DR: In this article, a Bayesian version of P-spline is proposed for modeling nonlinear smooth effects of covariates within the additive and varying coefficient models framework, which is particularly useful in situations with changing curvature of the underlying smooth function or with highly oscillating functions.
Abstract: P-splines are an attractive approach for modeling nonlinear smooth effects of covariates within the additive and varying coefficient models framework. In this article, we first develop a Bayesian version for P-splines and generalize in a second step the approach in various ways. First, the assumption of constant smoothing parameters can be replaced by allowing the smoothing parameters to be locally adaptive. This is particularly useful in situations with changing curvature of the underlying smooth function or with highly oscillating functions. In a second extension, one-dimensional P-splines are generalized to two-dimensional surface fitting for modeling interactions between metrical covariates. In a last step, the approach is extended to situations with spatially correlated responses allowing the estimation of geoadditive models. Inference is fully Bayesian and uses recent MCMC techniques for drawing random samples from the posterior. In a couple of simulation studies the performance of Bayesian P-spline...
TL;DR: In this article, the authors translate the TEBD algorithm into the language of matrix product states in order to both highlight and exploit its resemblances to the widely used density-matrix renormalization-group (DMRG) algorithms.
Abstract: An algorithm for the simulation of the evolution of slightly entangled quantum states has been recently proposed as a tool to study time-dependent phenomena in one-dimensional quantum systems. Its key feature is a time-evolving block-decimation (TEBD) procedure to identify and dynamically update the relevant, conveniently small, subregion of the otherwise exponentially large Hilbert space. Potential applications of the TEBD algorithm are the simulation of time-dependent Hamiltonians, transport in quantum systems far from equilibrium and dissipative quantum mechanics. In this paper we translate the TEBD algorithm into the language of matrix product states in order to both highlight and exploit its resemblances to the widely used density-matrix renormalization-group (DMRG) algorithms. The TEBD algorithm, being based on updating a matrix product state in time, is very accessible to the DMRG community and it can be enhanced by using well-known DMRG techniques, for instance in the event of good quantum numbers. More importantly, we show how it can be simply incorporated into existing DMRG implementations to produce a remarkably effective and versatile 'adaptive time-dependent DMRG' variant, that we also test and compare to previous proposals.
TL;DR: This work characterize and quantify the genuine multiparticle entanglement of such graph states in terms of the Schmidt measure, to which it provides upper and lower bounds in graph theoretical terms.
Abstract: Graph states are multiparticle entangled states that correspond to mathematical graphs, where the vertices of the graph take the role of quantum spin systems and edges represent Ising interactions. They are many-body spin states of distributed quantum systems that play a significant role in quantum error correction, multiparty quantum communication, and quantum computation within the framework of the one-way quantum computer. We characterize and quantify the genuine multiparticle entanglement of such graph states in terms of the Schmidt measure, to which we provide upper and lower bounds in graph theoretical terms. Several examples and classes of graphs will be discussed, where these bounds coincide. These examples include trees, cluster states of different dimensions, graphs that occur in quantum error correction, such as the concatenated [7,1,3]-CSS code, and a graph associated with the quantum Fourier transform in the one-way computer. We also present general transformation rules for graphs when local Pauli measurements are applied, and give criteria for the equivalence of two graphs up to local unitary transformations, employing the stabilizer formalism. For graphs of up to seven vertices we provide complete characterization modulo local unitary transformations and graph isomorphisms.
TL;DR: Galectin-3, a macrophage-derived mediator, induces cardiac fibroblast proliferation, collagen deposition, and ventricular dysfunction, which implies that HF therapy aimed at inflammatory responses may need to be targeted at the early stages of HF and probably needs to antagonize multiple inflammatory mediators, including galectIn-3.
Abstract: Background— Inflammatory mechanisms have been proposed to be important in heart failure (HF), and cytokines have been implicated to add to the progression of HF. However, it is unclear whether such mechanisms are already activated when hypertrophied hearts still appear well-compensated and whether such early mechanisms contribute to the development of HF. Methods and Results— In a comprehensive microarray study, galectin-3 emerged as the most robustly overexpressed gene in failing versus functionally compensated hearts from homozygous transgenic TGRmRen2-27 (Ren-2) rats. Myocardial biopsies obtained at an early stage of hypertrophy before apparent HF showed that expression of galectin-3 was increased specifically in the rats that later rapidly developed HF. Galectin-3 colocalized with activated myocardial macrophages. We found galectin-3-binding sites in rat cardiac fibroblasts and the extracellular matrix. Recombinant galectin-3 induced cardiac fibroblast proliferation, collagen production, and cyclin D1...
Iowa State University1, University of Georgia2, Stanford University3, Ludwig Institute for Cancer Research4, University of California, Berkeley5, Duke University6, University of California, San Diego7, University of Notre Dame8, University of Tokyo9, Max Planck Society10, University of Colorado Boulder11, Harvard University12, Colorado State University13, Indiana University14, Ludwig Maximilian University of Munich15, University of California, Davis16, University of California, San Francisco17, University of Washington18
TL;DR: A standardized kinesin nomenclature based on 14 family designations is set forth, which unifies all previous phylogenies and nomenClature proposals, while allowing individual sequence names to remain the same, and for expansion to occur as new sequences are discovered.
Abstract: In recent years the kinesin superfamily has become so large that several different naming schemes have emerged, leading to confusion and miscommunication. Here, we set forth a standardized kinesin nomenclature based on 14 family designations. The scheme unifies all previous phylogenies and nomenclature proposals, while allowing individual sequence names to remain the same, and for expansion to occur as new sequences are discovered.
Journal Article•
TL;DR: Dental literature, predominantly since 1990, was reviewed for longitudinal, controlled clinical studies and retrospective cross-sectional studies of posterior restorations and principal reasons for failure were secondary caries, fracture, marginal deficiencies, wear and postoperative sensitivity.
Abstract: This review provides a survey on the longevity of restorations in stress-bearing posterior cavities and assesses possible reasons for clinical failure. The dental literature, predominantly since 1990, was reviewed for longitudinal, controlled clinical studies and retrospective cross-sectional studies of posterior restorations. Only studies investigating the clinical performance of restorations in permanent teeth were included. Longevity and annual failure rates of amalgam, direct composite restorations, compomers, glass ionomers and derivative products, composite and ceramic inlays and cast gold restorations were determined for Class I and II cavities. Mean (SD) annual failure rates in posterior stress-bearing cavities are: 3.0% (1.9) for amalgam restorations, 2.2% (2.0) for direct composites, 3.6% (4.2) for direct composites with inserts, 1.1% (1.2) for compomer restorations, 7.2% (5.6) for regular glass ionomer restorations, 7.1% (2.8) for tunnel glass ionomers, 6.0% (4.6) for ART glass ionomers, 2.9% (2.6) for composite inlays, 1.9% (1.8) for ceramic restorations, 1.7% (1.6) for CAD/CAM ceramic restorations and 1.4% (1.4) for cast gold inlays and onlays. Publications from 1990 forward showed better results. Indirect restorations exhibited a significantly lower mean annual failure rate than direct techniques (p=0.0031). Longevity of dental restorations is dependent upon many different factors, including material, patient- and dentist-related. Principal reasons for failure were secondary caries, fracture, marginal deficiencies, wear and postoperative sensitivity. We need to learn to distinguish between reasons that cause early failures and those that are responsible for restoration loss after several years of service.
TL;DR: This study demonstrates that, in the case of diagnostic image quality, contrast-enhanced MDCT permits an accurate identification of coronary plaques and that computed tomography density values measured within plaques reflect echogenity and plaque composition.
TL;DR: This critical review describes recent developments in the field of supramolecular chemistry of terpyridine-metal complexes and places a special emphasis upon the properties of functional systems.
Abstract: This critical review describes recent developments in the field of supramolecular chemistry of terpyridine–metal complexes. The synthesis and characteristics of single as well as multiple homo- and heterometallic complexes is discussed. Furthermore, complexes containing fullerenes, biological building blocks, extended aggregates of different architectures as well as rings are presented. A special emphasis is placed upon the properties (e.g. redox properties, luminescence etc.) of functional systems. Potential applications in optical nano-devices, molecular storage units, molecular switches and solar cells are discussed.
TL;DR: It is shown that alternative macrophages are essential during schistosomiasis for protection against organ injury through downregulation of egg-induced inflammation.
TL;DR: Direct experimental evidence for passive (or intrinsic) optical cooling of a micromechanical resonator is reported and cavity-induced photothermal pressure is exploited to quench the brownian vibrational fluctuations of a gold-coated silicon microlever from room temperature down to an effective temperature of 18 K.
Abstract: The prospect of realizing entangled quantum states between macroscopic objects and photons1 has recently stimulated interest in new laser-cooling schemes2,3. For example, laser-cooling of the vibrational modes of a mirror can be achieved by subjecting it to a radiation2 or photothermal4 pressure, actively controlled through a servo loop adjusted to oppose its brownian thermal motion within a preset frequency window. In contrast, atoms can be laser-cooled passively without such active feedback, because their random motion is intrinsically damped through their interaction with radiation5,6,7,8. Here we report direct experimental evidence for passive (or intrinsic) optical cooling of a micromechanical resonator. We exploit cavity-induced photothermal pressure to quench the brownian vibrational fluctuations of a gold-coated silicon microlever from room temperature down to an effective temperature of 18 K. Extending this method to optical-cavity-induced radiation pressure might enable the quantum limit to be attained, opening the way for experimental investigations of macroscopic quantum superposition states1 involving numbers of atoms of the order of 1014.
TL;DR: In this paper, the authors discuss the processes involved in pentacene film growth, emphasizing differences with respect to inorganic films and the influence of growth parameters such as substrate nature and temperature, the deposition rate, and the kinetic energy of the molecular beam on the structure and morphology of Pentacene films.
Abstract: Pentacene stands out as a model molecule among organic semiconductors due to its ability to form well-ordered films that show a high field effect mobility. We discuss the processes involved in pentacene film growth, emphasizing differences with respect to inorganic films. The influence of growth parameters such as the substrate nature and temperature, the deposition rate, and the kinetic energy of the molecular beam on the structure and morphology of pentacene films are discussed. Finally, we overview recent attempts to model pentacene film nucleation and growth, and draw attention to the role of dislocations.
TL;DR: The results suggest that the combination of EEG and fMRI permits an improved understanding of the spatiotemporal dynamics of brain activity.
TL;DR: In this article, a prospective randomized study in patients with relapsed disease showed that the addition of rituximab to FCM chemotherapy significantly improves the outcome of relapsed or refractory FL and mantle cell lymphoma (MCL).
TL;DR: Intracellular 1,25‐dihydroxyvitamin D receptor (VDR) is expressed in human skeletal muscle tissue, but it is unknown whether VDR expression in vivo is related to age or vitamin D status, or whether V DR expression differs between skeletal muscle groups.
Abstract: Intracellular 1,25-dihydroxyvitamin D receptor (VDR) is expressed in human skeletal muscle tissue. However, it is unknown whether VDR expression in vivo is related to age or vitamin D status, or whether VDR expression differs between skeletal muscle groups. Introduction: We investigated these factors and their relation to 1,25-dihydroxyvitamin D receptor (VDR) expres- sion in freshly removed human muscle tissue. Materials and Methods: We investigated biopsy specimens of the gluteus medius taken at surgery from 20 female patients undergoing total hip arthroplasty (mean age, 71.6 14.5; 72% 65 years) and biopsy specimens of the transversospinalis muscle taken at surgery from 12 female patients with spinal operations (mean age, 55.2 19.6; 28% 65 years). The specimens were obtained by immunohistological staining of the VDR using a monoclonal rat antibody to the VDR (Clone no. 9A7). Quantitative VDR expression (number of VDR positive nuclei) was assessed by counting 500 nuclei per specimen and person. Serum concentrations of 25-hydroxyvitamin D and 1,25- dihydroxyvitamin D were assessed at day of admission to surgery. Results: All muscle biopsy specimens stained positive for VDR. In the univariate analyses, increased age was associated with decreased VDR expression (r 0.5: p 0.004), whereas there were no significant correlations between VDR expression and 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D levels. VDR expression did not differ between patients with hip and spinal surgery. In the multivariate analysis, older age was a significant predictor of decreased VDR expression after controlling biopsy location (gluteus medius or the transversospinalis muscle), and 25-hydroxyvitamin D levels (linear regression analysis: -estimate 2.56; p 0.047). Conclusions: Intranuclear immunostaining of the VDR was present in muscle biopsy specimens of all orthopedic patients. Older age was significantly associated with decreased VDR expression, independent of biopsy location and serum 25-hydroxyvitamin D levels. J Bone Miner Res 2004;19:265-269.
TL;DR: It now appears that one needs to Take Five genes to produce a deadly peptide by a proteolytic mechanism, which paradoxically is otherwise of pivotal importance for development and cell fate decisions.
Abstract: In 1959, Dave Brubeck and Paul Desmond revolutionized modern jazz music by composing their unforgettable Take Five in 5/4, one of the most defiant time signatures in all music. Of similar revolutionary importance for biomedical and basic biochemical research is the identification of the minimal set of genes required to obtain a deadly time bomb ticking in all of us: Alzheimer's disease. It now appears that one needs to Take Five genes to produce a deadly peptide by a proteolytic mechanism, which paradoxically is otherwise of pivotal importance for development and cell fate decisions.
TL;DR: Early consolidation by myeloablative radiochemotherapy followed by ASCT is feasible and results in a significant prolongation of PFS in advanced-stage MCL, and longer follow-up is needed to determine the effect on OS.
TL;DR: Preliminary ICF Core Sets are preliminary and need to be tested in the coming years based on a standardized protocol in close cooperation with the ICF research branch of the WHO FIC CC (DIMDI) in Munich and the CAS team at WHO.
Abstract: Objective: The objective of the ICF Core Sets project is the development of internationally agreed Brief ICF Core Sets and Comprehensive ICF Core Sets. Methods: The methods to develop both ICF Core Sets, the Comprehensive ICF Core Set and the Brief ICF Core Set, involved a formal decision-making and consensus process integrating evidence gathered from preliminary studies and expert opinion. Results: The results regarding the development of the ICF Core Sets for 12 health conditions (chronic widespread pain, low back pain, osteoarthritis, osteoporosis, rheumatoid arthritis, chronic ischemic heart disease, diabetes mellitus, obesity, obstructive pulmonary diseases, breast cancer, depression, and stroke) are presented in this supplement. Conclusion: Both, the Brief ICF Core Sets and the Comprehensive ICF Core Sets are preliminary and need to be tested in the coming years based on a standardized protocol in close cooperation with the ICF research branch of the WHO FIC CC (DIMDI) in Munich and the CAS team at WHO. The final goals are valid and globally agreed tools to be used in clinical practice, research and health statistics.
TL;DR: The results suggest that genetic variation in TLR2 is a major determinant of the susceptibility to asthma and allergies in children of farmers.
Abstract: Background The finding that the prevalence of asthma and allergies is less frequent in children raised on animal farms has led to the conjecture that exposure to microbial products modifies immune responses. The toll-like receptors (TLRs) represent an evolutionarily conserved family of innate immunity receptors with microbial molecules as ligands. Objectives We reasoned that polymorphisms in genes encoding TLRs might modulate the protective effects observed in farming populations. Methods Farmers' and nonfarmers' children living in rural areas in Austria and Germany and who were enrolled in the cross-sectional ALEX study were genotyped for single nucleotide polymorphisms in the TLR2 and TLR4 genes. The frequencies of asthma, allergic rhinitis, and atopic sensitization were compared between the genotypes in relation to exposure to farming and endotoxin. Results Among farmers' children, those carrying a T allele in TLR2/−16934 compared with children with genotype AA were significantly less likely to have a diagnosis of asthma (3% vs 13%, P = .012), current asthma symptoms (3% vs 16%, P = .004), atopic sensitization (14% vs 27%, P = .023), and current hay fever symptoms (3% vs 14%, P = .01). The association between TLR2/−16934 and asthma among children of farmers was independent of atopy. No such association was found among children from the same rural communities but not living on farms. Conclusion Our results suggest that genetic variation in TLR2 is a major determinant of the susceptibility to asthma and allergies in children of farmers.