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Showing papers by "University of Bonn published in 2006"


Journal ArticleDOI
E.-C. Oerke1
TL;DR: Despite a clear increase in pesticide use, crop losses have not significantly decreased during the last 40 years, however, pesticide use has enabled farmers to modify production systems and to increase crop productivity without sustaining the higher losses likely to occur from an increased susceptibility to the damaging effect of pests.
Abstract: Productivity of crops grown for human consumption is at risk due to the incidence of pests, especially weeds, pathogens and animal pests. Crop losses due to these harmful organisms can be substantial and may be prevented, or reduced, by crop protection measures. An overview is given on different types of crop losses as well as on various methods of pest control developed during the last century.Estimates on potential and actual losses despite the current crop protection practices are given for wheat, rice, maize, potatoes, soybeans, and cotton for the period 2001–03 on a regional basis (19 regions) as well as for the global total. Among crops, the total global potential loss due to pests varied from about 50% in wheat to more than 80% in cotton production. The responses are estimated as losses of 26–29% for soybean, wheat and cotton, and 31, 37 and 40% for maize, rice and potatoes, respectively. Overall, weeds produced the highest potential loss (34%), with animal pests and pathogens being less important (losses of 18 and 16%). The efficacy of crop protection was higher in cash crops than in food crops. Weed control can be managed mechanically or chemically, therefore worldwide efficacy was considerably higher than for the control of animal pests or diseases, which rely heavily on synthetic chemicals. Regional differences in efficacy are outlined. Despite a clear increase in pesticide use, crop losses have not significantly decreased during the last 40 years. However, pesticide use has enabled farmers to modify production systems and to increase crop productivity without sustaining the higher losses likely to occur from an increased susceptibility to the damaging effect of pests.The concept of integrated pest/crop management includes a threshold concept for the application of pest control measures and reduction in the amount/frequency of pesticides applied to an economically and ecologically acceptable level. Often minor crop losses are economically acceptable; however, an increase in crop productivity without adequate crop protection does not make sense, because an increase in attainable yields is often associated with an increased vulnerability to damage inflicted by pests.

3,821 citations


Journal ArticleDOI
10 Nov 2006-Science
TL;DR: It is demonstrated that the 5′-triphosphate end of RNA generated by viral polymerases is responsible for retinoic acid–inducible protein I (RIG-I)–mediated detection of RNA molecules in viruses known to be detected by MDA-5 such as the picornaviruses.
Abstract: The structural basis for the distinction of viral RNA from abundant self RNA in the cytoplasm of virally infected cells is largely unknown. We demonstrated that the 5'-triphosphate end of RNA generated by viral polymerases is responsible for retinoic acid-inducible protein I (RIG-I)-mediated detection of RNA molecules. Detection of 5'-triphosphate RNA is abrogated by capping of the 5'-triphosphate end or by nucleoside modification of RNA, both occurring during posttranscriptional RNA processing in eukaryotes. Genomic RNA prepared from a negative-strand RNA virus and RNA prepared from virus-infected cells (but not from noninfected cells) triggered a potent interferon-alpha response in a phosphatase-sensitive manner. 5'-triphosphate RNA directly binds to RIG-I. Thus, uncapped 5'-triphosphate RNA (now termed 3pRNA) present in viruses known to be recognized by RIG-I, but absent in viruses known to be detected by MDA-5 such as the picornaviruses, serves as the molecular signature for the detection of viral infection by RIG-I.

2,353 citations


Journal ArticleDOI
TL;DR: In this paper, the authors present a formal theory of reciprocity, which takes into account that people evaluate the kindness of an action not only by its consequences but also by its underlying intention.

1,912 citations


Journal ArticleDOI
TL;DR: The Scale for the Assessment and Rating of Ataxia is a reliable and valid measure of ataxia, making it an appropriate primary outcome measure for clinical trials.
Abstract: OBJECTIVE: To develop a reliable and valid clinical scale measuring the severity of ataxia. METHODS: The authors devised the Scale for the Assessment and Rating of Ataxia (SARA) and tested it in two trials of 167 and 119 patients with spinocerebellar ataxia. RESULTS: The mean time to administer SARA in patients was 14.2 +/- 7.5 minutes (range 5 to 40). Interrater reliability was high, with an intraclass coefficient (ICC) of 0.98. Test-retest reliability was high with an ICC of 0.90. Internal consistency was high as indicated by Cronbach's alpha of 0.94. Factorial analysis revealed that the rating results were determined by a single factor. SARA ratings showed a linear relation to global assessments using a visual analogue scale, suggesting linearity of the scale (p < 0.0001, r(2) = 0.98). SARA score increased with the disease stage (p < 0.001) and was closely correlated with the Barthel Index (r = -0.80, p < 0.001) and part IV (functional assessment) of the Unified Huntington's Disease Rating Scale (UHDRS-IV) (r = -0.89, p < 0.0001), whereas it had only a weak correlation with disease duration (r = 0.34, p < 0.0002). CONCLUSIONS: The Scale for the Assessment and Rating of Ataxia is a reliable and valid measure of ataxia, making it an appropriate primary outcome measure for clinical trials.

1,392 citations


Journal ArticleDOI
TL;DR: In this article, a curvature-dimension condition CD(K, N) for metric measure spaces is introduced, which is more restrictive than the curvature bound for Riemannian manifolds.
Abstract: We introduce a curvature-dimension condition CD (K, N) for metric measure spaces. It is more restrictive than the curvature bound $\underline{{{\text{Curv}}}} {\left( {M,{\text{d}},m} \right)} > K$ (introduced in [Sturm K-T (2006) On the geometry of metric measure spaces. I. Acta Math 196:65–131]) which is recovered as the borderline case CD(K, ∞). The additional real parameter N plays the role of a generalized upper bound for the dimension. For Riemannian manifolds, CD(K, N) is equivalent to $${\text{Ric}}_{M} {\left( {\xi ,\xi } \right)} > K{\left| \xi \right|}^{2} $$ and dim(M) ⩽ N. The curvature-dimension condition CD(K, N) is stable under convergence. For any triple of real numbers K, N, L the family of normalized metric measure spaces (M, d, m) with CD(K, N) and diameter ⩽ L is compact. Condition CD(K, N) implies sharp version of the Brunn–Minkowski inequality, of the Bishop–Gromov volume comparison theorem and of the Bonnet–Myers theorem. Moreover, it implies the doubling property and local, scale-invariant Poincare inequalities on balls. In particular, it allows to construct canonical Dirichlet forms with Gaussian upper and lower bounds for the corresponding heat kernels.

1,382 citations


Journal ArticleDOI
TL;DR: Loss-of-function mutations in a previously uncharacterized, predominantly neuronal P-type ATPase gene, ATP13A2, underlying an autosomal recessive form of early-onset parkinsonism with pyramidal degeneration and dementia are described.
Abstract: Neurodegenerative disorders such as Parkinson and Alzheimer disease cause motor and cognitive dysfunction and belong to a heterogeneous group of common and disabling disorders. Although the complex molecular pathophysiology of neurodegeneration is largely unknown, major advances have been achieved by elucidating the genetic defects underlying mendelian forms of these diseases. This has led to the discovery of common pathophysiological pathways such as enhanced oxidative stress, protein misfolding and aggregation and dysfunction of the ubiquitin-proteasome system. Here, we describe loss-of-function mutations in a previously uncharacterized, predominantly neuronal P-type ATPase gene, ATP13A2, underlying an autosomal recessive form of early-onset parkinsonism with pyramidal degeneration and dementia (PARK9, Kufor-Rakeb syndrome). Whereas the wild-type protein was located in the lysosome of transiently transfected cells, the unstable truncated mutants were retained in the endoplasmic reticulum and degraded by the proteasome. Our findings link a class of proteins with unknown function and substrate specificity to the protein networks implicated in neurodegeneration and parkinsonism.

1,112 citations


Journal ArticleDOI
TL;DR: This review summarizes new developments of the last five years and deals with "small molecules", proteins, and nucleic acids which can either be irreversibly activated with light (these compounds are referred to as "caged compounds") or reversibly switched between an active and an inactive state.
Abstract: Biologically active compounds which are light-responsive offer experimental possibilities which are otherwise very difficult to achieve. Since light can be manipulated very precisely, for example, with lasers and microscopes rapid jumps in concentration of the active form of molecules are possible with exact control of the area, time, and dosage. The development of such strategies started in the 1970s. This review summarizes new developments of the last five years and deals with "small molecules", proteins, and nucleic acids which can either be irreversibly activated with light (these compounds are referred to as "caged compounds") or reversibly switched between an active and an inactive state.

1,034 citations


Journal ArticleDOI
TL;DR: In this paper, a thorough treatment of universality for the system of three identical bosons is presented, and the universal information that is currently available for other 3-body systems is summarized.

968 citations


Journal ArticleDOI
TL;DR: It is proposed that CAMPs and CAMP-resistance mechanisms have co-evolved, leading to a transient host–pathogen balance that has shaped the existing CAMP repertoire.
Abstract: Endogenous cationic antimicrobial peptides (CAMPs) are among the most ancient and efficient components of host defence. It is somewhat of an enigma that bacteria have not developed highly effective CAMP-resistance mechanisms, such as those that inhibit many therapeutic antibiotics. Here, we propose that CAMPs and CAMP-resistance mechanisms have co-evolved, leading to a transient host-pathogen balance that has shaped the existing CAMP repertoire. Elucidating the underlying principles of this process could help in the development of more sustainable antibiotics.

955 citations


Journal ArticleDOI
TL;DR: Vitamin D(3) reduces the inflammatory milieu in CHF patients and might serve as a new antiinflammatory agent for the future treatment of the disease.

890 citations


Journal ArticleDOI
TL;DR: The largely complementary palaeobotanical and genetic data indicate that beech survived the last glacial period in multiple refuge areas and the modern genetic diversity was shaped over multiple glacial-interglacial cycles.
Abstract: Summary • Here, palaeobotanical and genetic data for common beech (Fagus sylvatica) in Europe are used to evaluate the genetic consequences of long-term survival in refuge areas and postglacial spread. • Four large datasets are presented, including over 400 fossil-pollen sites, 80 plant-macrofossil sites, and 450 and 600 modern beech populations for chloroplast and nuclear markers, respectively. • The largely complementary palaeobotanical and genetic data indicate that: (i) beech survived the last glacial period in multiple refuge areas; (ii) the central European refugia were separated from the Mediterranean refugia; (iii) the Mediterranean refuges did not contribute to the colonization of central and northern Europe; (iv) some populations expanded considerably during the postglacial period, while others experienced only a limited expansion; (v) the mountain chains were not geographical barriers for beech but rather facilitated its diffusion; and (vi) the modern genetic diversity was shaped over multiple glacial–interglacial cycles. • This scenario differs from many recent treatments of tree phylogeography in Europe that largely focus on the last ice age and the postglacial period to interpret genetic structure and argue that the southern peninsulas (Iberian, Italian and Balkan) were the main source areas for trees in central and northern Europe.

Reference BookDOI
23 Jun 2006
TL;DR: In this paper, a simple to multiple-to-multipleure correlation analysis approach is proposed to measure the degree of participation of women in the labor force by using a subset of an indicator matrix.
Abstract: CORRESPONDENCE ANALYSIS AND RELATED METHODS IN PRACTICE, Jorg Blasius and Michael Greenacre A simple example Basic method Concepts of correspondence analysis Stacked tables Multiple correspondence analysis Categorical principal components analysis Active and supplementary variables Multiway data Content of the book FROM SIMPLE TO MULTIPLE CORRESPONDENCE ANALYSIS, Michael Greenacre Canonical correlation analysis Geometric approach Supplementary points Discussion and conclusions DIVIDED BY A COMMON LANGUAGE: ANALYZING AND VISUALIZING TWO-WAY ARRAYS, John C. Gower Introduction: two-way tables and data matrices Quantitative variables Categorical variables Fit and scaling Discussion and conclusion NONLINEAR PRINCIPAL COMPONENTS ANALYSIS AND RELATED TECHNIQUES, Jan de Leeuw Linear PCA Least-squares nonlinear PCA Logistic NLPCA Discussion and conclusions Software Notes THE GEOMETRIC ANALYSIS OF STRUCTURED INDIVIDUALS o VARIABLES TABLES, Henry Rouanet PCA and MCA as geometric methods Structured data analysis The basketball study The EPGY study Concluding comments CORRELATIONAL STRUCTURE OF MULTIPLE-CHOICE DATA AS VIEWED FROM DUAL SCALING, Shizuhiko Nishisato Permutations of categories and scaling Principal components analysis and dual scaling Statistics for correlational structure of data Forced classification Correlation between categorical variables Properties of squared item-total correlation Structure of nonlinear correlation Concluding remarks VALIDATION TECHNIQUES IN MULTIPLE CORRESPONDENCE ANALYSIS, Ludovic Lebart External validation Internal validation (resampling techniques) Example of MCA validation Conclusion MULTIPLE CORRESPONDENCE ANALYSIS OF SUBSETS OF RESPONSE CATEGORIES, Michael Greenacre and Rafael Pardo Correspondence analysis of a subset of an indicator matrix Application to women's participation in labor force Subset MCA applied to the Burt matrix Discussion and conclusions SCALING UNIDIMENSIONAL MODELS WITH MULTIPLE CORRESPONDENCE ANALYSIS, Matthijs J. Warrens and Willem J. Heiser The dichotomous Guttman scale The Rasch model The polytomous Guttman scale The graded response model Unimodal models Conclusion THE UNFOLDING FALLACY UNVEILED: VISUALIZING STRUCTURES OF DICHOTOMOUS UNIDIMENSIONAL ITEM-RESPONSE-THEORY DATA BY MULTIPLE CORRESPONDENCE ANALYSIS, Wijbrandt van Schuur and Jorg Blasius Item response models for dominance data Visualizing dominance data Item response models for proximity data Visualizing unfolding data Every two cumulative scales can be represented as a single unfolding scale Consequences for unfolding analysis Discussion REGULARIZED MULTIPLE CORRESPONDENCE ANALYSIS, Yoshio Takane and Heungsun Hwang The method Examples Concluding remarks THE EVALUATION OF "DON'T KNOW" RESPONSES BY GENERALIZED CANONICAL ANALYSIS, Herbert Matschinger and Matthias C. Angermeyer Method Results Discussion MULTIPLE FACTOR ANALYSIS FOR CONTINGENCY TABLES, Jerome Pages and Monica Becue-Bertaut Tabular conventions Internal correspondence analysis Balancing the influence of the different tables Multiple factor analysis for contingency tables (MFACT) MFACT properties Rules for studying the suitability of MFACT for a data set Conclusion SIMULTANEOUS ANALYSIS: A JOINT STUDY OF SEVERAL CONTINGENCY TABLES WITH DIFFERENT MARGINS, Amaya Zarraga and Beatriz Goitisolo Simultaneous analysis Interpretation rules for simultaneous analysis Comments on the appropriateness of the method Application: study of levels of employment and unemployment according to autonomous community, gender, and training level Conclusions MULTIPLE FACTOR ANALYSIS OF MIXED TABLES OF METRIC AND CATEGORICAL DATA, Elena Abascal, Ignacio Garcia Lautre, and M. Isabel Landaluce Multiple factor analysis MFA of a mixed table: an alternative to PCA and MCA Analysis of voting patterns across provinces in Spain's 2004 general election Conclusions CORRESPONDENCE ANALYSIS AND CLASSIFICATION, Gilbert Saporta and Ndeye Niang Linear methods for classification The "Disqual" methodology Alternative methods A case study Conclusion MULTIBLOCK CANONICAL CORRELATION ANALYSIS FOR CATEGORICAL VARIABLES: APPLICATION TO EPIDEMIOLOGICAL DATA, Stephanie Bougeard, Mohamed Hanafi, Hicham Nocairi, and El-Mostafa Qannari Multiblock canonical correlation analysis Application Discussion and perspectives PROJECTION-PURSUIT APPROACH FOR CATEGORICAL DATA, Henri Caussinus and Anne Ruiz-Gazen Continuous variables Categorical variables Conclusion CORRESPONDENCE ANALYSIS AND CATEGORICAL CONJOINT MEASUREMENT, Anna Torres-Lacomba Categorical conjoint measurement Correspondence analysis and canonical correlation analysis Correspondence analysis and categorical conjoint analysis Incorporating interactions Discussion and conclusions A THREE-STEP APPROACH TO ASSESSING THE BEHAVIOR OF SURVEY ITEMS IN CROSS-NATIONAL RESEARCH, Jorg Blasius and Victor Thiessen Data Method Solutions Discussion ADDITIVE AND MULTIPLICATIVE MODELS FOR THREE-WAY CONTINGENCY TABLES: DARROCH (1974) REVISITED, Pieter M. Kroonenberg and Carolyn J. Anderson Data and design issues Multiplicative and additive modeling Multiplicative models Additive models: three-way correspondence analysis Categorical principal components analysis Discussion and conclusions A NEW MODEL FOR VISUALIZING INTERACTIONS IN ANALYSIS OF VARIANCE, Patrick J.F. Groenen and Alex J. Koning Holiday-spending data Decomposing interactions Interaction decomposition of holiday spending Conclusions LOGISTIC BIPLOTS. Jose L. Vicente-Villardon, M. Purificacion Galindo-Villardon, and Antonio Blazquez-Zaballos Classical biplots Logistic biplot Application: microarray gene expression data Final remarks References Appendix Index

Journal ArticleDOI
01 Jul 2006-Allergy
TL;DR: The consensus report is endorsed by both academies and aims to serve as a guideline for clinical practice in Europe as well as in North America.
Abstract: There are remarkable differences in the diagnostic and therapeutic management of atopic dermatitis practiced by dermatologists and pediatricians in different countries. Therefore, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams who were given the task of finding a consensus to serve as a guideline for clinical practice in Europe as well as in North America. The consensus report is part of the PRACTALL initiative, which is endorsed by both academies.

Journal ArticleDOI
TL;DR: An improved understanding of astrocyte biology and heterogeneity and the involvement of these cells in pathogenesis offers the potential for developing novel strategies to treat neurological disorders.
Abstract: Recent work on glial cell physiology has revealed that glial cells, and astrocytes in particular, are much more actively involved in brain information processing than previously thought. This finding has stimulated the view that the active brain should no longer be regarded solely as a network of neuronal contacts, but instead as a circuit of integrated, interactive neurons and glial cells. Consequently, glial cells could also have as yet unexpected roles in the diseased brain. An improved understanding of astrocyte biology and heterogeneity and the involvement of these cells in pathogenesis offers the potential for developing novel strategies to treat neurological disorders.

Journal ArticleDOI
TL;DR: This revised nomenclature accommodates functional genes and pseudogenes, and although designed specifically for the full complement of human keratins, it offers the flexibility needed to incorporate additional keratin proteins from other mammalian species.
Abstract: Keratins are intermediate filament–forming proteins that provide mechanical support and fulfill a variety of additional functions in epithelial cells. In 1982, a nomenclature was devised to name the keratin proteins that were known at that point. The systematic sequencing of the human genome in recent years uncovered the existence of several novel keratin genes and their encoded proteins. Their naming could not be adequately handled in the context of the original system. We propose a new consensus nomenclature for keratin genes and proteins that relies upon and extends the 1982 system and adheres to the guidelines issued by the Human and Mouse Genome Nomenclature Committees. This revised nomenclature accommodates functional genes and pseudogenes, and although designed specifically for the full complement of human keratins, it offers the flexibility needed to incorporate additional keratins from other mammalian species.

Journal ArticleDOI
TL;DR: In this article, a simple test for causality in the frequency domain is proposed to investigate the predictive content of the yield spread for future output growth, which can also be applied to cointegrated systems.

Journal ArticleDOI
TL;DR: The ‘acid mantle’ of the stratum corneum seems to be important for both permeability barrier formation and cutaneous antimicrobial defense, however, the origin of the acidic pH, measurable on the skin surface, remains conjectural.
Abstract: The ‘acid mantle’ of the stratum corneum seems to be important for both permeability barrier formation and cutaneous antimicrobial defense. However, the origin of the acidic pH, measurable on the skin

Journal ArticleDOI
TL;DR: Higher age, malignant disease and major comorbidity were found to be the main contributors to malnutrition and adequate nutritional support should be initiated in order to optimize the clinical outcome of patients.

Journal ArticleDOI
TL;DR: It is shown here that densely sampled taxon trees built with multiple genes provide an indispensable test of taxon-sparse trees inferred from genome sequences.
Abstract: Phylogenetic relationships among the four major lineages of land plants (liverworts, mosses, hornworts, and vascular plants) remain vigorously contested; their resolution is essential to our understanding of the origin and early evolution of land plants. We analyzed three different complementary data sets: a multigene supermatrix, a genomic structural character matrix, and a chloroplast genome sequence matrix, using maximum likelihood, maximum parsimony, and compatibility methods. Analyses of all three data sets strongly supported liverworts as the sister to all other land plants, and analyses of the multigene and chloroplast genome matrices provided moderate to strong support for hornworts as the sister to vascular plants. These results highlight the important roles of liverworts and hornworts in two major events of plant evolution: the water-to-land transition and the change from a haploid gametophyte generation-dominant life cycle in bryophytes to a diploid sporophyte generation-dominant life cycle in vascular plants. This study also demonstrates the importance of using a multifaceted approach to resolve difficult nodes in the tree of life. In particular, it is shown here that densely sampled taxon trees built with multiple genes provide an indispensable test of taxon-sparse trees inferred from genome sequences.

Journal ArticleDOI
27 Apr 2006-Nature
TL;DR: An annually resolved oxygen isotope record from tree-rings is presented, providing a millennial-scale reconstruction of precipitation variability in the high mountains of northern Pakistan, where the climatic signal originates mainly from winter precipitation, and is robust over ecologically different sites.
Abstract: A warming climate could significantly alter the global rate and distribution of rainfall, and arguably it is changing rainfall, rather than temperature, that would have the greater direct impact on human well-being and on ecosystems. An annually resolved oxygen isotope record from tree-rings has been used to produce a millennial-scale reconstruction of precipitation variability in the mountains of northern Pakistan. The data reveal an increase in precipitation during the late nineteenth and the twentieth centuries, producing the wettest conditions seen in the past thousand years. A comparison with other climate reconstructions points to large-scale intensification of the hydrological cycle coincident with the onset of industrialization and global warming. Its unprecedented amplitude argues for a human contribution to the change. Long-term precipitation reconstructions indicate a large-scale intensification of the hydrological cycle coincident with the onset of industrialization and global warming — such unprecedented amplitude argues for a human role. Twentieth-century warming could lead to increases in the moisture-holding capacity of the atmosphere, altering the hydrological cycle and the characteristics of precipitation1. Such changes in the global rate and distribution of precipitation may have a greater direct effect on human well-being and ecosystem dynamics than changes in temperature itself2,3. Despite the co-variability of both of these climate variables3, attention in long-term climate reconstruction has mainly concentrated on temperature changes4,5,6,7,8. Here we present an annually resolved oxygen isotope record from tree-rings, providing a millennial-scale reconstruction of precipitation variability in the high mountains of northern Pakistan. The climatic signal originates mainly from winter precipitation, and is robust over ecologically different sites. Centennial-scale variations reveal dry conditions at the beginning of the past millennium and through the eighteenth and early nineteenth centuries, with precipitation increasing during the late nineteenth and the twentieth centuries to yield the wettest conditions of the past 1,000 years. Comparison with other long-term precipitation reconstructions indicates a large-scale intensification of the hydrological cycle coincident with the onset of industrialization and global warming, and the unprecedented amplitude argues for a human role.

Journal ArticleDOI
TL;DR: In this article, a family-based approach revealed prominent associations between the 2 loss-of-function FLG mutations and AD, as previously observed in a traditional Mendelian linkage analysis and case-control cohort analysis approach.
Abstract: Background Atopic dermatitis (AD) is a chronic inflammatory skin disease with a strong genetic background. One of the characteristic features of AD and causative factor for the disease is an impaired epidermal skin barrier based on a primary defect of epidermal differentiation. Objectives Recently, 2 loss-of-function mutations (R501X and 2282derl4) in the filaggrin gene (FLG) that cause ichthyosis vulgaris, one of the most common inherited skin disorders of keratinization, have been reported to be strong predisposing factors for AD. Methods We evaluated the association of the loss-of-function mutations R501X and 2282del4 within the FLG gene in a large collection of 476 well-characterized white German families with AD by using the transmission-disequilibrium test. Results Our family-based approach revealed prominent associations between the 2 loss-of-function FLG mutations and AD, as previously observed in a traditional Mendelian linkage analysis and case-control cohort analysis approach. In addition, we observed associations of the FLG mutations in particular with the extrinsic subtype of AD, which is characterized by high total serum IgE levels and concomitant allergic sensitizations. Furthermore, FLG mutations are significantly associated with palmar hyperlinearity in patients with AD, which represents a shared feature of AD and ichthyosis vulgaris. Conclusion Together these data implicate that FLG is the first really strong genetic factor identified in a common complex disease. Clinical implications These findings underline the crucial role of the skin barrier in preventing allergic sensitization.

Journal ArticleDOI
20 Mar 2006
TL;DR: In this article, the authors presented an IRAM PdBI interferometry of eight sub-millimeter galaxies at z 2-3.4, where they detect continuum at 1 mm and/or CO lines at 3 and 1 mm.
Abstract: We present ~06 resolution IRAM PdBI interferometry of eight submillimeter galaxies at z ~ 2-3.4, where we detect continuum at 1 mm and/or CO lines at 3 and 1 mm. The CO 3-2/4-3 line profiles in five of the sources are double-peaked, indicative of orbital motion either in a single rotating disk or of a merger of two galaxies. The millimeter line and continuum emission is compact; we marginally resolve the sources or obtain tight upper limits to their intrinsic sizes in all cases. The median FWHM diameter for these sources and the previously resolved sources, SMM J023952-0136 and SMM J140104+0252, is ≤05 (4 kpc). The compactness of the sources does not support a scenario in which the far-IR/submillimeter emission comes from a cold (T < 30 K), very extended dust distribution. These measurements clearly show that the submillimeter galaxies (SMGs) we have observed resemble scaled-up and more gas-rich versions of the local universe, ultraluminous galaxy population. Their central densities and potential well depths are much greater than those in other z ~ 2-3 galaxy samples studied so far. They are comparable to those of elliptical galaxies or massive bulges. The SMG properties fulfill the criteria of "maximal" starbursts, in which most of the available initial gas reservoir of 1010-1011 M☉ is converted to stars on a timescale ~3-10tdyn ~ a few times 108 yr.

Journal ArticleDOI
TL;DR: It is demonstrated that astrocytic gap junctions accelerate potassium clearance, limit potassium accumulation during synchronized neuronal firing, and aid in radial potassium relocation in the stratum lacunosum moleculare, and it is suggested that the perpendicular array of individualAstrocytes in thestratum radiatum makes these cells ideally suited for spatial buffering of potassium released by pyramidal cells, independent of gap junctional coupling.
Abstract: Astrocytic gap junctions have been suggested to contribute to spatial buffering of potassium in the brain. Direct evidence has been difficult to gather because of the lack of astrocyte-specific gap junction blockers. We obtained mice with coupling-deficient astrocytes by crossing conditional connexin43-deficient mice with connexin30−/− mice. Similar to wild-type astrocytes, genetically uncoupled hippocampal astrocytes displayed negative resting membrane potentials, time- and voltage-independent whole-cell currents, and typical astrocyte morphologies. Astrocyte densities were also unchanged. Using potassium-selective microelectrodes, we assessed changes in potassium buffering in hippocampal slices of mice with coupling-deficient astrocytes. We demonstrate that astrocytic gap junctions accelerate potassium clearance, limit potassium accumulation during synchronized neuronal firing, and aid in radial potassium relocation in the stratum lacunosum moleculare. Furthermore, slices of mice with coupling-deficient astrocytes displayed a reduced threshold for the generation of epileptiform events. However, it was evident that radial relocation of potassium in the stratum radiatum was not dependent on gap junctional coupling. We suggest that the perpendicular array of individual astrocytes in the stratum radiatum makes these cells ideally suited for spatial buffering of potassium released by pyramidal cells, independent of gap junctions. In general, a surprisingly large capacity for K+ clearance was conserved in mice with coupling-deficient astrocytes, indicating that gap junction-dependent processes only partially account for K+ buffering in the hippocampus.

Journal ArticleDOI
TL;DR: The Shear Testing Programme (STEP) is a collaborative project to improve the accuracy and reliability of all weak lensing measurements in preparation for the next generation of wide-field surveys as discussed by the authors.
Abstract: The Shear Testing Programme (STEP) is a collaborative project to improve the accuracy and reliability of all weak lensing measurements in preparation for the next generation of wide-field surveys. In this first STEP paper, we present the results of a blind analysis of simulated ground-based observations of relatively simple galaxy morphologies. The most successful methods are shown to achieve percent level accuracy. From the cosmic shear pipelines that have been used to constrain cosmology, we find weak lensing shear measured to an accuracy that is within the statistical errors of current weak lensing analyses, with shear measurements accurate to better than 7 per cent. The dominant source of measurement error is shown to arise from calibration uncertainties where the measured shear is over or underestimated by a constant multiplicative factor. This is of concern as calibration errors cannot be detected through standard diagnostic tests. The measured calibration errors appear to result from stellar contamination, false object detection, the shear measurement method itself, selection bias and/or the use of biased weights. Additive systematics (false detections of shear) resulting from residual point-spread function anisotropy are, in most cases, reduced to below an equivalent shear of 0.001, an order of magnitude below cosmic shear distortions on the scales probed by current surveys. Our results provide a snapshot view of the accuracy of current ground-based weak lensing methods and a benchmark upon which we can improve. To this end we provide descriptions of each method tested and include details of the eight different implementations of the commonly used Kaiser, Squires & Broadhurst method (KSB+) to aid the improvement of future KSB+ analyses.

Journal ArticleDOI
TL;DR: Membrane-bound P2-receptors mediate the actions of extracellular nucleotides in cell-to-cell signalling and have a crucial role in platelet aggregation as well as in inhibition of neuronal cells.

Journal ArticleDOI
TL;DR: In this article, the authors investigate possible sources of bias in the log-likelihood function and its subsequent analysis, focusing on estimators of the inverse covariance matrix, and show that the inverse of the maximum likelihood estimator of the covariance is biased, the amount of bias depending on the ratio of the number of bins (data vector variables), P, to the size of data sets, N.
Abstract: AIMS. The maximum-likelihood method is the standard approach to obtain model fits to observational data and the corresponding confidence regions. We investigate possible sources of bias in the log-likelihood function and its subsequent analysis, focusing on estimators of the inverse covariance matrix. Furthermore, we study under which circumstances the estimated covariance matrix is invertible. METHODS. We perform Monte-Carlo simulations to investigate the behaviour of estimators for the inverse covariance matrix, depending on the number of independent data sets and the number of variables of the data vectors. RESULTS. We find that the inverse of the maximum-likelihood estimator of the covariance is biased, the amount of bias depending on the ratio of the number of bins (data vector variables), P, to the number of data sets, N. This bias inevitably leads to an -- in extreme cases catastrophic -- underestimation of the size of confidence regions. We report on a method to remove this bias for the idealised case of Gaussian noise and statistically independent data vectors. Moreover, we demonstrate that marginalisation over parameters introduces a bias into the marginalised log-likelihood function. Measures of the sizes of confidence regions suffer from the same problem. Furthermore, we give an analytic proof for the fact that the estimated covariance matrix is singular if P>N.

Journal ArticleDOI
TL;DR: Multivariate models involving feature assessment have a diagnostic accuracy superior to that of qualitative characterization of the dynamic enhancement pattern and architectural and dynamic features are important in breast MR imaging interpretation.
Abstract: Purpose: To prospectively determine the prevalence and predictive value of three-dimensional (3D) and dynamic breast magnetic resonance (MR) imaging and contrast material kinetic features alone and as part of predictive diagnostic models. Materials and Methods: The study protocol was approved by the institutional review board or ethics committees of all participating institutions, and informed consent was obtained from all participants. Although study data collection was performed before HIPAA went into effect, standards that would be compliant with HIPAA were adhered to. Data from the International Breast MR Consortium trial 6883 were used in the analysis. Women underwent 3D (minimum spatial resolution, 0.7 × 1.4 × 3 mm; minimal temporal resolution, 4 minutes) and dynamic two-dimensional (temporal resolution, 15 seconds) MR imaging examinations. Readers rated enhancement shape, enhancement distribution, border architecture, enhancement intensity, presence of rim enhancement or internal septations, and th...

Journal ArticleDOI
S. Schael1, R. Barate, R. Bruneliere, I. De Bonis  +1279 moreInstitutions (141)
TL;DR: In this paper, four LEP collaborations, ALEPH, DELPHI, L3 and OPAL, have searched for the neutral Higgs bosons which are predicted by the minimal supersymmetric standard model (MSSM).
Abstract: The four LEP collaborations, ALEPH, DELPHI, L3 and OPAL, have searched for the neutral Higgs bosons which are predicted by the Minimal Supersymmetric standard model (MSSM). The data of the four collaborations are statistically combined and examined for their consistency with the background hypothesis and with a possible Higgs boson signal. The combined LEP data show no significant excess of events which would indicate the production of Higgs bosons. The search results are used to set upper bounds on the cross-sections of various Higgs-like event topologies. The results are interpreted within the MSSM in a number of “benchmark” models, including CP-conserving and CP-violating scenarios. These interpretations lead in all cases to large exclusions in the MSSM parameter space. Absolute limits are set on the parameter cosβ and, in some scenarios, on the masses of neutral Higgs bosons.

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TL;DR: In this article, the role of neuronal synchronization in different frequency domains for the subsequent stages of memory formation was investigated, and it was shown that gamma synchronization between hippocampal and parahippocampal regions may induce LTP in the CA3 region of the hippocampus.

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TL;DR: In this paper, the structure of the nuclear force in the framework of chiral effective field theory of QCD and its applications to processes involving few nucleons are discussed. But they do not consider the nuclear forces in terms of the number of nucleons.