Staff Publications

Staff Publications

  • external user (warningwarning)
  • Log in as
  • language uk
  • About

    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

    We have a manual that explains all the features 

    Current refinement(s):

    Records 1 - 14 / 14

    • help
    • print

      Print search results

    • export

      Export search results

    Check title to add to marked list
    Genome-Wide Mapping of Structural Variations Reveals a Copy Number Variant That Determines Reproductive Morphology in Cucumber
    Zhang, Z. ; Mao, L. ; Chen, Junshi ; Bu, F. ; Li, G. ; Sun, J. ; Li, S. ; Sun, H. ; Jiao, C. ; Blakely, R. ; Pan, J. ; Cai, R. ; Luo, R. ; Peer, Y. Van de; Jacobsen, E. ; Fei, Z. ; Huang, S. - \ 2015
    The Plant Cell 27 (2015)6. - ISSN 1040-4651 - p. 1595 - 1604.
    indel-associated mutation - tuberculate fruit gene - false discovery rate - arabidopsis-thaliana - population-scale - functional impact - sequencing data - synthase gene - paired-end - sativus l.
    Structural variations (SVs) represent a major source of genetic diversity. However, the functional impact and formation mechanisms of SVs in plant genomes remain largely unexplored. Here, we report a nucleotide-resolution SV map of cucumber (Cucumis sativas) that comprises 26,788 SVs based on deep resequencing of 115 diverse accessions. The largest proportion of cucumber SVs was formed through nonhomologous end-joining rearrangements, and the occurrence of SVs is closely associated with regions of high nucleotide diversity. These SVs affect the coding regions of 1676 genes, some of which are associated with cucumber domestication. Based on the map, we discovered a copy number variation (CNV) involving four genes that defines the Female (F) locus and gives rise to gynoecious cucumber plants, which bear only female flowers and set fruit at almost every node. The CNV arose from a recent 30.2-kb duplication at a meiotically unstable region, likely via microhomology-mediated break-induced replication. The SV set provides a snapshot of structural variations in plants and will serve as an important resource for exploring genes underlying key traits and for facilitating practical breeding in cucumber.
    Do field margins enrich the diet of the Eurasian Skylark Alauda arvensis on intensive farmland?
    Ottens, H.J. ; Kuiper, M.W. ; Flinks, H. ; Ruijven, J. van; Siepel, H. ; Koks, B.J. ; Berendse, F. ; Snoo, G.R. de - \ 2014
    Ardea 102 (2014)2. - ISSN 0373-2266 - p. 161 - 174.
    false discovery rate - sown weed strips - food resources - nestling diet - agricultural intensification - bird populations - breeding-season - adjacent fields - perdix-perdix - prey quality
    To help restore food availability for birds, arable field margins (extensively managed strips of land sown with grasses and forbs) have been established on European farmland. In this study we describe the effect of field margins on the diet of Eurasian Skylark nestlings and adults living on intensively managed Dutch farmland. We tested the hypotheses that field margins offer a higher diversity of invertebrate prey than intensively managed crops, and that the diet of nestlings receiving food from field margins will therefore be more diverse than that of other nestlings. Field margins had a greater variety of invertebrate prey groups to offer than the intensively managed crops. Coleoptera were the most frequently and most abundantly eaten prey group by both adults and nestlings. Together, Coleoptera, Diptera, Lepidoptera, Hymenoptera and Araneae accounted for 91% of the nestling diet. Nestlings ate larger prey items and a larger proportion of larvae than adults. Almost 75% of both adults and nestlings consumed plant material, perhaps indicating a scarcity of invertebrate resources. When provided with food from field margins, the mean number of invertebrate orders in the nestling diet increased significantly from 4.7 to 5.5 and the number of families from 4.2 to 5.8 per sample. Thus, birds that used field margins for foraging could indeed provide their young with more invertebrate prey groups than birds only foraging in crops and grassland.
    Within and between population variation in inbreeding depression in the locally threatened perennial Scabiosa columbaria
    Angeloni, F. ; Vergeer, P. ; Wagemaker, C.A.M. ; Ouborg, N.J. - \ 2014
    Conservation Genetics 15 (2014)2. - ISSN 1566-0621 - p. 331 - 342.
    among-family variation - false discovery rate - self-fertilization - life-history - genetic differentiation - grassland plant - mating systems - size - extinction - conservation
    Inbreeding depression plays a central role within the conservation genetics paradigm. Until now inbreeding depression is incorporated into models of population viability as a mean value (e.g. number of lethal equivalents) for all traits in a population. In this study of the locally threatened perennial plant species Scabiosa columbaria we investigated both the mean and the variance among families of inbreeding depression in eight life history traits for five natural populations varying in size from 300 to more than 120,000 individuals. Significant inbreeding depression was found in all populations and all traits. The mean inbreeding depression value per trait was never correlated to population size. Within each population, highly significant variation in inbreeding depression between families (VIFLID) was found. Per trait, families with inbreeding depression next to families with outbreeding depression were often found within the same population. Inbreeding depression at the family level was in many cases not correlated among traits and independent of correlations between traits themselves. VIFLID was negatively correlated with population size: in two traits these correlations were significant. The results underline that inbreeding depression is a complex, highly dynamic phenomenon. Models of viability should incorporate inbreeding depression distributions, with a trait specific mean and variance. Moreover, models of metapopulation dynamics should incorporate genotype quality as factor in colonization success.
    Genome-wide analysis of coordinated transcript abundance during seed development in different Brassica rapa morphotypes
    Basnet, R.K. ; Moreno Pachón, N.M. ; Lin, K. ; Bucher, J. ; Visser, R.G.F. ; Maliepaard, C.A. ; Bonnema, A.B. - \ 2013
    BMC Genomics 14 (2013). - ISSN 1471-2164
    gene-expression profiles - false discovery rate - arabidopsis-thaliana - network analysis - prolamin-box - napus - germination - embryo - maize - plant
    Brassica seeds are important as basic units of plant growth and sources of vegetable oil. Seed development is regulated by many dynamic metabolic processes controlled by complex networks of spatially and temporally expressed genes. We conducted a global microarray gene co-expression analysis by measuring transcript abundance of developing seeds from two diverse B. rapa morphotypes: a pak choi (leafy-type) and a yellow sarson (oil-type), and two of their doubled haploid (DH) progenies, (1) to study the timing of metabolic processes in developing seeds, (2) to explore the major transcriptional differences in developing seeds of the two morphotypes, and (3) to identify the optimum stage for a genetical genomics study in B. rapa seed.
    The first taste is always with the eyes: A meta-analysis on the neural correlates of processing visual food cues
    Laan, L.N. van der; Ridder, D.T.D. de; Viergever, M.A. ; Smeets, P.A.M. - \ 2011
    NeuroImage 55 (2011)1. - ISSN 1053-8119 - p. 296 - 303.
    high-calorie foods - prader-willi-syndrome - false discovery rate - brain activation - functional mri - orbitofrontal cortex - ale metaanalysis - appetizing foods - human amygdala - reward
    Food selection is primarily guided by the visual system. Multiple functional neuro-imaging studies have examined the brain responses to visual food stimuli. However, the results of these studies are heterogeneous and there still is uncertainty about the core brain regions involved in the neural processing of viewing food pictures. The aims of the present study were to determine the concurrence in the brain regions activated in response to viewing pictures of food and to assess the modulating effects of hunger state and the food's energy content. We performed three Activation Likelihood Estimation (ALE) meta-analyses on data from healthy normal weight subjects in which we examined: 1) the contrast between viewing food and nonfood pictures (17 studies. 189 foci), 2) the modulation by hunger state (five studies, 48 foci) and 3) the modulation by energy content (seven studies, 86 foci). The most concurrent brain regions activated in response to viewing food pictures, both in terms of ALE values and the number of contributing experiments, were the bilateral posterior fusiform gyrus, the left lateral orbitofrontal cortex (OFC) and the left middle insula. Hunger modulated the response to food pictures in the right amygdala and left lateral OFC, and energy content modulated the response in the hypothalamus/ventral striatum. Overall, the concurrence between studies was moderate: at best 41% of the experiments contributed to the clusters for the contrast between food and nonfood. Therefore, future research should further elucidate the separate effects of methodological and physiological factors on between-study variations.
    Regulatory control of high levels of carotenoid accumulation in potato tubers
    Zhou, X. ; McQuinn, R. ; Fei, Z. ; Wolters, A.M.A. ; Eck, J. van; Brown, C. ; Giovannoni, J.J. ; Li, L. - \ 2011
    Plant, Cell & Environment 34 (2011)6. - ISSN 0140-7791 - p. 1020 - 1030.
    lycopene epsilon-cyclase - false discovery rate - beta-carotene - transcription factor - phytoene synthase - genetic-variation - hydroxylase gene - microarray data - tomato - fruit
    Potato (Solanum tuberosum L.) tubers contain a wide range of carotenoid contents. To decipher the key factors controlling carotenoid levels in tubers, four potato lines (Atlantic, Désirée, 91E22 and POR03) were examined by a combination of biochemical, molecular and genomics approaches. These lines contained incremental levels of carotenoids, which were found to be associated with enhanced capacity of carotenoid biosynthesis as evident from norflurazon treatment. Microarray analysis of high and low carotenoid lines (POR03 versus Atlantic) revealed 381 genes that showed significantly differential expression. The carotenoid metabolic pathway genes ß-carotene hydroxylase 2 (BCH2) and ß-carotene hydroxylase 1 (BCH1), along with zeaxanthin epoxidase (ZEP), and carotenoid cleavage dioxygenase 1A (CCD1A) were among the most highly differentially expressed genes. The transcript levels of BCH2 and BCH1 were lowest in Atlantic and highest in POR03, whereas those of ZEP and CCD1A were high in low carotenoid lines and low in high carotenoid lines. The high expression of BCH2 in POR03 line was associated with enhanced response to sugars. Our results indicate that high levels of carotenoid accumulation in potato tubers were due to an increased metabolic flux into carotenoid biosynthetic pathway, as well as the differential expression of carotenoid metabolic genes.
    Comparison of nutrient acquisition in exotic plant species and congeneric natives
    Meisner, A. ; Boer, W. de; Verhoeven, K.J.F. ; Boschker, H.T.S. ; Putten, W.H. van der - \ 2011
    Journal of Ecology 99 (2011)6. - ISSN 0022-0477 - p. 1308 - 1315.
    false discovery rate - mycorrhizal fungi - invasive plant - microbial communities - solidago-gigantea - enemy release - fatty-acids - soil - nitrogen - bacteria
    1. The ability of exotic plant species to establish and expand in new areas may be enhanced by a relatively high ability to acquire soil nutrients. To test this hypothesis, we predicted that the capacity for nutrient acquisition would be higher in seedlings of exotic species than in seedlings of native congeners. 2. We selected the five exotic species that had recently increased in abundance in a riverine habitat in the Netherlands and that had a native congener that was common in the same habitat. We grew seedlings of each of these ten species singly in pots of soil from this habitat in a glasshouse. After two months, we measured the final dry mass and N and P content of each plant and components of microbial biomass and nutrient mineralization in the soil. We also measured these soil characteristics in pots that had been left unplanted. 3. Exotic and native congeners did not differ consistently in the uptake of N or P or in effects on components of soil mineralization. Within a genus, values of these measurements were sometimes higher, sometimes lower and sometimes similar to the exotic when compared with the native species. 4. Depending upon the statistical analysis used, biomarker-based biomass of arbuscular mycorrhizal fungi was generally higher in soil planted with exotic than with native species. Most measures of microbial biomass and soil mineralization were higher in pots that had been planted with plants than in pots with no plant. 5. Synthesis. Our results do not suggest that invasive, exotic plant species generally possess greater capacity for nutrient acquisition during the early establishment than native species do
    Identification of human gustatory cortex by activation likelihood estimation
    Veldhuizen, M.G. ; Albrecht, J. ; Zelano, C. ; Boesveldt, S. ; Breslin, P. ; Lundstrom, J.N. - \ 2011
    Human Brain Mapping 32 (2011)12. - ISSN 1065-9471 - p. 2256 - 2266.
    caudolateral orbitofrontal cortex - medial prefrontal cortex - anterior temporal-lobe - taste cortical areas - false discovery rate - human brain - rhesus-monkey - intensity perception - macaque monkeys - ale metaanalysis
    Over the last two decades, neuroimaging methods have identified a variety of taste-responsive brain regions. Their precise location, however, remains in dispute. For example, taste stimulation activates areas throughout the insula and overlying operculum, but identification of subregions has been inconsistent. Furthermore, literature reviews and summaries of gustatory brain activations tend to reiterate rather than resolve this ambiguity. Here, we used a new meta-analytic method [activation likelihood estimation (ALE)] to obtain a probability map of the location of gustatory brain activation across 15 studies. The map of activation likelihood values can also serve as a source of independent coordinates for future region-of-interest analyses. We observed significant cortical activation probabilities in: bilateral anterior insula and overlying frontal operculum, bilateral mid dorsal insula and overlying Rolandic operculum, and bilateral posterior insula/parietal operculum/postcentral gyrus, left lateral orbitofrontal cortex (OFC), right medial OFC, pregenual anterior cingulate cortex (prACC) and right mediodorsal thalamus. This analysis confirms the involvement of multiple cortical areas within insula and overlying operculum in gustatory processing and provides a functional "taste map" which can be used as an inclusive mask in the data analyses of future studies. In light of this new analysis, we discuss human central processing of gustatory stimuli and identify topics where increased research effort is warranted
    An eQTL analysis of partial resistance to Puccinia hordei in barley
    Chen, Xinwei ; Hackett, C.A. ; Niks, R.E. ; Hedley, P.E. ; Booth, C. ; Druka, A. ; Marcel, T.C. ; Vels, S.A. ; Bayer, M. ; Milne, I. ; Morris, J. ; Ramsay, L. ; Marshall, D. ; Cardle, L. ; Waugh, R. - \ 2010
    PLoS ONE 5 (2010)1. - ISSN 1932-6203 - 15 p.
    quantitative trait locus - density consensus map - false discovery rate - gene-expression - powdery mildew - leaf rust - flowering-time - stem rust - basal defense - arabidopsis
    Background - Genetic resistance to barley leaf rust caused by Puccinia hordei involves both R genes and quantitative trait loci. The R genes provide higher but less durable resistance than the quantitative trait loci. Consequently, exploring quantitative or partial resistance has become a favorable alternative for controlling disease. Four quantitative trait loci for partial resistance to leaf rust have been identified in the doubled haploid Steptoe (St)/Morex (Mx) mapping population. Further investigations are required to study the molecular mechanisms underpinning partial resistance and ultimately identify the causal genes.Methodology/Principal Findings - We explored partial resistance to barley leaf rust using a genetical genomics approach. We recorded RNA transcript abundance corresponding to each probe on a 15K Agilent custom barley microarray in seedlings from St and Mx and 144 doubled haploid lines of the St/Mx population. A total of 1154 and 1037 genes were, respectively, identified as being P. hordei-responsive among the St and Mx and differentially expressed between P. hordei-infected St and Mx. Normalized ratios from 72 distant-pair hybridisations were used to map the genetic determinants of variation in transcript abundance by expression quantitative trait locus (eQTL) mapping generating 15685 eQTL from 9557 genes. Correlation analysis identified 128 genes that were correlated with resistance, of which 89 had eQTL co-locating with the phenotypic quantitative trait loci (pQTL). Transcript abundance in the parents and conservation of synteny with rice allowed us to prioritise six genes as candidates for Rphq11, the pQTL of largest effect, and highlight one, a phospholipid hydroperoxide glutathione peroxidase (HvPHGPx) for detailed analysis.Conclusions/Significance - The eQTL approach yielded information that led to the identification of strong candidate genes underlying pQTL for resistance to leaf rust in barley and on the general pathogen response pathway. The dataset will facilitate a systems appraisal of this host-pathogen interaction and, potentially, for other traits measured in this population
    A multiple testing approach to high-dimensional association studies with an application to the detection of associations between risk factors of heart disease and genetic polymorphisms
    Ferreira, J.A. ; Berkhof, J. ; Souverein, O.W. ; Zwinderman, K. - \ 2009
    Statistical Applications in Genetics and Molecular Biology 8 (2009)1. - ISSN 1544-6115
    false discovery rate - coronary-artery-disease - myocardial-infarction - cholesterol levels - protein - variant
    We present an approach to association studies involving a dozen or so 'response' variables and a few hundred 'explanatory' variables which emphasizes transparency, simplicity, and protection against spurious results. The methods proposed are largely non-parametric, and they are systematically rounded-off by the Benjamini-Hochberg method of multiple testing. An application to the detection of associations between risk factors of heart disease and genetic polymorphisms using the REGRESS dataset provides ample illustration of our approach. Special attention is paid to book-keeping and information-management aspects of data analysis, which allow the creation of an informative and reasonably digestible 'map of relationships'-the end-product of an association study as far as statistics is concerned.
    Relative power and sample size analysis on gene expression profiling data
    Iterson, M. van; Hoen, P.A.C. 't; Pedotti, P. ; Hooiveld, G.J.E.J. ; Dunnen, J.T. den; Ommen, G.J.B. van; Boer, J.M. ; Menezes, R.X. - \ 2009
    BMC Genomics 10 (2009). - ISSN 1471-2164
    false discovery rate - control maqc project - microarray data - dna microarray
    Background - With the increasing number of expression profiling technologies, researchers today are confronted with choosing the technology that has sufficient power with minimal sample size, in order to reduce cost and time. These depend on data variability, partly determined by sample type, preparation and processing. Objective measures that help experimental design, given own pilot data, are thus fundamental. Results - Relative power and sample size analysis were performed on two distinct data sets. The first set consisted of Affymetrix array data derived from a nutrigenomics experiment in which weak, intermediate and strong PPARa agonists were administered to wild-type and PPARa-null mice. Our analysis confirms the hierarchy of PPARa-activating compounds previously reported and the general idea that larger effect sizes positively contribute to the average power of the experiment. A simulation experiment was performed that mimicked the effect sizes seen in the first data set. The relative power was predicted but the estimates were slightly conservative. The second, more challenging, data set describes a microarray platform comparison study using hippocampal dC-doublecortin-like kinase transgenic mice that were compared to wild-type mice, which was combined with results from Solexa/Illumina deep sequencing runs. As expected, the choice of technology greatly influences the performance of the experiment. Solexa/Illumina deep sequencing has the highest overall power followed by the microarray platforms Agilent and Affymetrix. Interestingly, Solexa/Illumina deep sequencing displays comparable power across all intensity ranges, in contrast with microarray platforms that have decreased power in the low intensity range due to background noise. This means that deep sequencing technology is especially more powerful in detecting differences in the low intensity range, compared to microarray platforms. Conclusion - Power and sample size analysis based on pilot data give valuable information on the performance of the experiment and can thereby guide further decisions on experimental design. Solexa/Illumina deep sequencing is the technology of choice if interest lies in genes expressed in the low-intensity range. Researchers can get guidance on experimental design using our approach on their own pilot data implemented as a BioConductor package, SSPA
    Changes in allele frequencies in landraces, old and modern barley cultivars of marker loci close to QTL for grain yield under high and low input conditions
    Pswarayi, A. ; Eeuwijk, F.A. van; Ceccarelli, S. ; Grando, S. ; Comadran, J. ; Russell, J.R. ; Pecchioni, N. ; Alessandro, T. ; Akar, T. ; Al-Yassin, A. ; Benbelkacem, A. ; Ouabbou, H. ; Thomas, W.T.B. ; Romagosa, I. - \ 2008
    Euphytica 163 (2008)3. - ISSN 0014-2336 - p. 435 - 447.
    quantitative trait loci - false discovery rate - field-grown barley - environmental covariables - stress tolerance - adaptation - genotype - genome - maize - dart
    Changes in alleles frequencies of marker loci linked to yield quantitative trait loci (QTL) were studied in 188 barley entries (landraces, old and modern cultivars) grown in six trials representing low and high yielding conditions in Spain (2004) and Syria (2004, 2005). A genome wise association analysis was performed per trial, using 811 DArT® markers of known map position. At the first stage of analysis, spatially adjusted genotypic means were created per trial by fitting mixed models. At the second stage, single QTL models were fitted with correction for population substructure, using regression models. Finally, multiple QTL models were constructed by backward selection from a regression model containing all significant markers from the single QTL analyses. In addition to the association analyses per trial, genotype by environment interaction was investigated across the six trials. Landraces seemed best adapted to low yielding environments, while old and modern entries adapted better to high yielding environments. The number of QTL and the magnitude of their effects were comparable for low and high input conditions. However, none of the QTL were found within a given bin at any chromosome in more than two of the six trials. Changes in allele frequencies of marker loci close to QTL for grain yield in landraces, old and modern barley cultivars could be attributed to selection exercised in breeding, suggesting that modern breeding may have increased frequencies of marker alleles close to QTL that favour production particularly under high yield potential environments. Moreover, these results also indicate that there may be scope for improving yield under low input systems, as breeding so far has hardly changed allele frequencies at marker loci close to QTL for low yielding conditions.
    Toxicity of reduced nitrogen in eelgrass (Zostera marina) is highly dependent on shoot density and pH
    Heide, Tj. van; Smolders, A.J.P. ; Rijkens, B. ; Nes, E.H. van; Katwijk, M.M. van; Roelofs, J.G.M. - \ 2008
    Oecologia 158 (2008)3. - ISSN 0029-8549 - p. 411 - 419.
    free amino-acids - water-column nitrate - false discovery rate - ammonium toxicity - submersed macrophyte - seagrass ecosystems - nutritional-status - sediment sulfide - nh4+ toxicity - pine needles
    In sheltered, eutrophicated estuaries, reduced nitrogen (NH x ), and pH levels in the water layer can be greatly enhanced. In laboratory experiments, we studied the interactive effects of NH x , pH, and shoot density on the physiology and survival of eelgrass (Zostera marina). We tested long-term tolerance to NH x at pH 8 in a 5-week experiment. Short-term tolerance was tested for two shoot densities at both pH 8 and 9 in a 5-day experiment. At pH 8, eelgrass accumulated nitrogen as free amino acids when exposed to high loads of NH x , but showed no signs of necrosis. Low shoot density treatments became necrotic within days when exposed to NH x at pH 9. Increased NH3 intrusion and carbon limitation seemed to be the cause of this, as intracellular NH x could no longer be assimilated. Remarkably, experiments with high shoot densities at pH 9 showed hardly any necrosis, as the plants seemed to be able to alleviate the toxic effects of high NH x loads through joint NH x uptake. Our results suggest that NH x toxicity can be important in worldwide observed seagrass mass mortalities. We argue that the mitigating effect of high seagrass biomass on NH x toxicity is a positive feedback mechanism, potentially leading to alternative stable states in field conditions.
    Whole Genome Scan to Detect Chromosomal Regions Affecting Multiple Traits in Dairy Cattle
    Schrooten, C. ; Bink, M.C.A.M. ; Bovenhuis, H. - \ 2004
    Journal of Dairy Science 87 (2004)10. - ISSN 0022-0302 - p. 3550 - 3560.
    marker-assisted selection - false discovery rate - milk-production - holstein population - daughter design - loci - linkage - yield - efficiency - complexes
    Chromosomal regions affecting multiple traits ( multiple trait quantitative trait regions or MQR) in dairy cattle were detected using a method based on results from single trait analyses to detect quantitative trait loci (QTL). The covariance between contrasts for different traits in single trait regression analysis was computed. A chromosomal region was considered an MQR when the observed covariance between contrasts deviated from the expected covariance under the null hypothesis of no pleiotropy or close linkage. The expected covariance and the confidence interval for the expected covariance were determined by permutation of the data. Four categories of traits were analyzed: production ( 5 traits), udder conformation ( 6 traits), udder health ( 2 traits), and fertility ( 2 traits). The analysis of a granddaughter design involving 833 sons of 20 grandsires resulted in 59 MQR(alpha = 0.01, chromosomewise). Fifteen MQR were found on Bos taurus autosome (BTA) 14. Four or more MQR were found on BTA 6, 13, 19, 22, 23, and 25. Eight MQR involving udder conformation and udder health and 4 MQR involving production traits and udder health were found. Five MQR were identified for combinations of fertility and udder conformation traits, and another 5 MQR were identified for combinations of fertility and production traits. For 22 MQR, the difference between the correlation attributable to the MQR and the overall genetic correlation was > 0.60. Although the false discovery rate was relatively high (0.52), it was considered important to present these results to assess potential consequences of using these MQR for marker-assisted selection.
    Check title to add to marked list

    Show 20 50 100 records per page

    Please log in to use this service. Login as Wageningen University & Research user or guest user in upper right hand corner of this page.