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DNA methylation is an inheritable chemical modification of cytosine, and represents one of the most important epigenetic events. Computational prediction of the DNA methylation status can be employed to speed up the genome-wide methylation profiling, and to identify the key features that are correlated with various methylation patterns. Here, we develop CpGIMethPred, the support vector machine-based models to predict the methylation status of the CpG islands in the human genome under normal conditions. The features for prediction include those that have been previously demonstrated effective (CpG island specific attributes, DNA sequence composition patterns, DNA structure patterns, distribution patterns of conserved transcription factor binding sites and conserved elements, and histone methylation status) as well as those that have not been extensively explored but are likely to contribute additional information from a biological point of view (nucleosome positioning propensities, gene functions, and histone acetylation status). Statistical tests are performed to identify the features that are significantly correlated with the methylation status of the CpG islands, and principal component analysis is then performed to decorrelate the selected features. Data from the Human Epigenome Project (HEP) are used to train, validate and test the predictive models. Specifically, the models are trained and validated by using the DNA methylation data obtained in the CD4 lymphocytes, and are then tested for generalizability using the DNA methylation data obtained in the other 11 normal tissues and cell types. Our experiments have shown that (1) an eight-dimensional feature space that is selected via the principal component analysis and that combines all categories of information is effective for predicting the CpG island methylation status, (2) by incorporating the information regarding the nucleosome positioning, gene functions, and histone acetylation, the models can achieve higher specificity and accuracy than the existing models while maintaining a comparable sensitivity measure, (3) the histone modification (methylation and acetylation) information contributes significantly to the prediction, without which the performance of the models deteriorate, and, (4) the predictive models generalize well to different tissues and cell types. The developed program CpGIMethPred is freely available at http://users.ece.gatech.edu/~hzheng7/CGIMetPred.zip webcite.
Epigenetics refers to structural adaptation of chromosomal regions to register, signal or perpetuate altered activity states [1]. A major type of epigenetic event is DNA methylation, which involves the addition of a methyl group to the number 5 carbon of the cytosine pyrimidine ring [2]. In the human genome, is DNA methylation mostly restricted to the cytosines of CpG dinucleotides. Though the human genome generally shows a great deficit of CpG dinucleotides (the genome-wide observed-to-expected CpG ratio is ~0.2), and most of these CpG dinucleotides are methylated in somatic cells [3], the CpG dinucleotides are enriched around gene promoters and form CpG islands, and tend to be protected from DNA methylation [4]. It has been shown that DNA methylation plays an instrumental roles during normal cell development and cell differentiation, and is also involved in a number of key processes including genetic imprinting, X-chromosome inactivation, suppression of retroviral elements, and carcinogenesis [5,6].
A variety of techniques, based on biochemical experiments and computational analysis, have been devised for DNA methylation profiling. The biochemical experiment-based approaches are mainly based on methylation-sensitive restriction, immunoprecipitation, or bisulfite conversion, combined with the next-generation sequencing technologies [7]. Whereas, computational predictive models have been developed to identify CpG dinucleotides methylated or unmethylated [8,9], CpG islands (or CpG-rich regions) methylated or unmethylated [3,10-13], and CpG islands (or CpG-rich regions) differentially methylated in different tissue/cell types or phenotypes [4,14]. These computational approaches can effectively complement the biochemical-experiment based approaches to speed up genome-wide DNA methylation profiling and to identify critical factors or pathways controlling DNA methylation patterns.
A key step for building computational predictive models is to select features. Here we provide a brief review of the existing computational models based on their features for prediction. For the prediction of DNA methylation, the features can be roughly grouped into two broad categories: genetic and epigenetic. Given a region of interest (ROI, e.g., a CpG island or a genomic region centered around a particular CpG dinucleotide), the genetic features include (1) general attributes of the ROI (e.g., length of the ROI, and distribution of the CpG dinucleotides in the ROI), (2) patterns of the DNA sequence composition of the ROI, (3) patterns of conserved transcription factor binding sites (TFBSs) or conserved elements within or near the ROI, (4) structural and physicochemical properties of the ROI, (5) functions of the genes within or near the ROI, (6) the extent of the diversity of the ROI within the population, and (7) the extent of the conservation of the ROI among species. And, the epigenetic features mainly regard the methylation and acetylation status of the histones.
Bhasin et al. used DNA composition features to predict the methylation of single cytosines. A 39-nucleotide long DNA fragment centered around the cytosine of interest was considered as the ROI, and each nucleotide in the ROI was coded by using a 5-bit binary sparse code. In this way, each ROI was represented by a series of codes, and the difference between ROIs was able to be quantified. A ~75% accuracy was reported using a support vector machine-based classifier [8]. Lu et al. also used DNA composition features for predicting whether a CpG dinucleotide is methylated or not. A 1,000 nucleotide long DNA fragment centered around the CpG dinucleotide was used as the ROI, and the frequencies of all pentamer oligonucleotides formed the features. A ~77% accuracy was reported for the CD4 lymphocytes data set using a nearest neighbor-based classifier [9]. Feltus et al. used frequencies of seven DNA patterns, TCCCCCNC, TTTCCTNC, TCCNCCNCCC, GGAGNAAG, GAGANAAG, GCCACCCC, and GAGGAGGNNG with N representing any base, and achieved an ~82% accuracy on the human fibroblast data set when distinguishing between methylation-prone and methylation-resistant CpG islands using a linear programming-based classifier [4].
In addition to DNA composition features, Fang et al. also used the distribution of the repetitive element AluY as well as the distribution of TFBSs for predicting the methylation status of CpG rich segments, and reported an ~84% specificity and ~84% sensitivity on the human brain data set using a support vector machine-based classifier [3]. Bock et al. used DNA composition features, predicted DNA helix structure, attributes of repeat elements and TFBSs, evolutionary conservation of PhastCons elements [15] and the number of single nucleotide polymorphisms (SNPs) for the prediction of CpG island methylation [10,11], and their method achieved a high specificity (~98%) but a relatively low sensitivity (~67%) on human lymphocytes using a support vector machine-based classifier [13]. Ali et al. also used the DNA composition information, predicted DNA structure, and SNP features, and reported a ~72% accuracy on the human lymphocytes data set using a K nearest neighbor-based classifier [12]. To predict tissue-specific differentially methylated regions (DMRs), Previti et al. used CpG island specific attributes, attributes of repetitive elements, number and frequency of PhastCons elements, as well as structural and physicochemical properties. When classifying CpG islands into four categories: constitutively methylated, constitutively unmethylated, tissue-specific DMR, and lack of methylation exclusively in sperm, they reported an ~89% accuracy using a decision tree-based classifier [14].
Computational prediction models that are solely based on genetic features can hardly fully characterize DNA methylation status. This is because DNA methylation, as an epigenetic phenomenon, is affected by some other epigenetic factors, such as histone methylation and histone acetylation. In light of the reported interaction between histone modification enzymes and DNA methylases [16,17], Fan et al. found four histone methylation marks that are highly correlated with the DNA methylation status of CpG islands, and then incorporated these histone methylation marks into the prediction of the methylation status of CpG islands. Compared to those methods without histone methylation information [13,11], the augmented features indeed led to improved performance: a ~94% specificity and ~74% sensitivity on the CD4 T cell data set using a support vector machine-based classifier [13].
In this study, we consider various attributes that are possibly related to the CpG island methylation. These attributes include those that have been previously investigated (CpG island specific attributes, DNA sequence composition patterns, DNA structure patterns, distribution patterns of conserved TFBS's and conserved elements, and histone methylation status), and those that have not been extensively investigated but are potentially related to DNA methylation from biochemical perspectives (nucleosome positioning propensities, gene functions, and histone acetylation status). The contribution of each individual feature is evaluated by statistical tests; and the correlation between features is reduced by principal component analysis (PCA). These DNA methylation-relevant yet non-intercorrelated features are then used to build support vector machine (SVM)-based models to predict the methylation status of CpG islands. The predictive models are evaluated by using the HEP data set. Specifically, the CpG island methylation profiles in the CD4 lymphocytes are used to train and validate the models, while the CpG island methylation profiles in the other 11 tissues/cell types are used to test the generalizability of the models. Through these experiments, we assess the individual and combinational influence of the newly added features and the impact of histone modification information.
The rest of the paper is organized as follows. In Section 2, we describe the data collection used to train, validate and test the computational models. In Section 3, we discuss the methods for feature extraction, feature selection, and building the predictive models. The experimental results are reported in Section 4. And finally in Section 5 we draw conclusions.
Data sets
We obtain the methylation profiles of the human genome from HEP. bisulfite DNA sequencing technique, and provides high-resolution data of the genome-wide DNA methylation patterns in various tissues and cell lines [18]. It currently covers chromosomes 6, 20 and 22, and contains ~1.9 million CpG methylation values of 2,524 amplicons from 12 different tissues and 43 different samples. The methylation values of the CpGs range from 0 to 100 inclusive, where 0 corresponds to the lowest and 100 to the highest methylation intensity.
We define the CpG island as a DNA stretch that is not a repetitive element but satisfies the Gardiner-Garden criteria, i.e., with length of ≥ 200 bps, GC content ≥ 50%, and observed to expected CpG ratio ≥ 0.6 [19]. We construct our training data set based on the CpG islands extracted from the UCSC genome browser and the DNA methylation profiles specified by HEP. Specifically, we only consider those CpG islands more than 10% of whose CpG dinucleotides are annotated with methylation intensities. For each tissue or cell type, the methylation intensity of a CpG dinucleotide is calculated as the average in different samples [20]; and the methylation intensity of a CpG island is calculated as the average of all the CpG dinucleotides within it. The CpG islands with methylation intensity ≥ 50 are regarded as the methylated (positive), while those with methylation intensity ≤ 10 are regarded as the unmethylated (negative) [13]. The number of so-obtained methylated and unmethylated CpG islands are summarized in Table 1. In particular, there are 101 methylated and 368 unmethylated CpG islands for the CD4 lymphocytes, which are used for training and validating the predictive models, while the CpG islands in the other tissues or cell types are used for generalizability testing.
Table 1. Number of methylated and unmethylated CpG islands in the twelve different tissue and cell types based on the DNA methylation profiles of HEP.
The core of our establishment of the computational predictive models consists of three parts, feature extraction, feature selection and model training and testing, as depicted in Figure 1. We here describe these three steps in detail.
Figure 1. Workflow used for the prediction of the methylation status of CpG island in human genome. The CpG island map is obtained by applying the traditional Gardiner-Garden sequence criteria on non-repetitive sequences of the human genome. The core steps of our model development consist of three parts - feature extraction, feature selection and predictive modeling.
Feature extraction
A key step for building computational predictive models is to select features. It has been shown that the CpG island methylation status is correlated with the following features: CpG island specific attributes (e.g. length, GC content, GC observed/expected ratio) [14,21,3], patterns of DNA sequence composition [4,21,10], patterns of predicted DNA structure [14,10], patterns of conserved TFBS's and conserved elements [14], as well as the methylation status of nearby histones [13]. Computational prediction of CpG island methylation status based on the statistical properties of these features could render fairly reasonable accuracy (e.g., ~89% [4,13]). In this study we incorporate three more sets of attributes that have not been extensively explored, including (i) the nucleosome positioning propensities of the CpG island, (ii) the acetylation status of nearby histones, and (iii) the functional roles of nearby genes. In the following paragraphs, we describe how these features are extracted.
General attributes
Three attributes, including the GC content, length and observed/expected CpG ratio, are directly obtained from UCSC human genome browser for each CpG island [22].
DNA sequence composition
We use the tetramer frequencies and their corresponding z-scores to characterize the DNA composition patterns of the CpG island. The z-score of a tetramer, Z(N1N2N3N4), depicts how much the observed frequency of the tetramer N1N2N3N4, O(N1N2N3N4), deviates from its expected frequency E(N1N2N3N4).
where E(N1N2N3N4) is approximated by using a maximal-order Markov model [23]:
and the standard deviation σ(N1N2N3N4) is calculated based on the observed frequencies of dimers and trimers:
Altogether, we extract 512 features about DNA sequence composition, including 256 for tetramer frequencies and 256 for their z-scores.
Conserved TFBS's and conserved elements
The distribution patterns of the conserved TFBS's and conserved elements in the CpG island and the flanking regions are also taken into account. Here a conserved TFBS refers to one that is conserved in human, mouse and rat genomes [24]; and there are 258 such TFBS's that can roughly be grouped into 115 groups according to their function similarity [10]. Also, a conserved element refers to a genomic segment (other than TFBS) that is conserved across vertebrate, insect, worm and yeast genomes [15]. Each conserved TFBS or conserved element is characterized by a score quantifying its degree of conservativeness. We consider both the short- and long-range associations between these elements and CpG islands, and therefore select the flanking regions of various lengths (ranging from 100 bps to 2,000 bps with an increment of 100 bps) upstream and downstream of each CpG island. Given a CpG island (and its flanking region of a particular length), for each TFBS group (or conserved element), we count the number of TFBS's (or conserved elements) that overlap with this CpG island (and its flanking region) and the average score of these TFBS's (or conserved elements). Therefore, in terms of conserved TFBS's and conserved elements, each CpG island is characterized by 210 (115 × 2, for conserved TFBS's) plus two features (for conserved elements).
Structural properties
We focus on those basic characteristics that capture the DNA 3-D conformation and newly added nucleosome positioning propensities. The DNA conformation related features measure the twist, tilt, roll, shift, slide and rise propensities of dinucleotides [25]. For each of these six features, the average value over all dinucleotides in the CpG island is used.
Due to an accumulating body of evidence showing that DNA methylation is influenced by nucleosome positioning propensities [26], we also investigate these features. Nucleosome positioning propensities of the CpG islands are estimated based on the genome-wide prediction of the nucleosome organization map [27]. There are two types of predictions, one at the nucleotide level, and the other at the DNA fragment level. The nucleotide level prediction regards the probability of each nucleotide being covered by any nucleosome, based on which we calculate the mean and standard deviation over the entire CpG island. The fragment level prediction regards the nucleosome positioning potential of each 147 bp (typical length of a nucleosome) DNA fragment, based on which we calculate the mean and standard deviation over all fragments overlapping with the CpG island. Altogether, we extract four features regarding nucleosome positioning propensities.
Functional roles of nearby genes
Since DNA methylation is heavily involved in biological processes such as tumor suppressor gene silencing [28,29], we examine whether a CpG island's nearby genes are involved in any cancer-related biological processes. A CpG island's nearby genes refer to those whose promoter region (from the 1,000 bps upstream to the 200 bps downstream of the transcription start site) overlaps with the CpG island. 37 biological processes (30 oncogene related, 11 tumor suppressor related, and 4 common) are determined through gene ontology enrichment analysis of the genes retrieved from the Cancer Gene Census [30]. If the gene ontology annotations of a gene include one or more of these processes, the corresponding gene function feature is 1 and 0 otherwise. We have two features for functional roles of nearby genes, one for oncogene related and the other for tumor suppressor gene related biological processes.
Histone methylation and acetylation
We consider the methylation status of each CpG island's nearby histones. The histone methylation information is obtained from Barkski et al's data set, which characterizes the genome wide distribution of 20 histone methylations as well as histone variant H2A.Z, RNA polymerase II, and the insulator binding protein CTCF in CD4 lymphocytes [31].
Since DNA methylation has also been observed to be associated with histone acetylation [32], we further include the histone acetylation features in the feature set. The histone acetylation information is obtained from Wang et al.'s data set [33], which characterizes the genome-wide patterns of 18 histone acetylations in CD4 lymphocytes.
In both data sets, a nucleotide is tagged if its nearby histone undertakes a methylation or acetylation modification; hence, the number of tags at each nucleotide can be interpreted as being proportional to the modification level of nearby histones. We use the average and standard deviation of the number of tags over all nucleotides of a CpG island to represent the methylation (or acetylation) level of the CpG island's nearby histones. Altogether, we have 46 features for histone methylation and 36 features for histone acetylation.
Feature selection
Altogether, we generate 841 features using the above procedure as summarized in Table 2. Compared to the size of our training data set (see Table 1), this dimension of the feature space is prohibitively high, which will potentially lead to classifier designs that are too expensive to implement or that cannot well generalize to unseen data. Therefore, we perform a two-step feature selection procedure, where the statistical test is used to select those features that are highly correlated with the methylation status of CpG islands, and PCA is used to minimize the redundancy in the features.
Table 2. Number of features in each category and information resource for the feature extraction.
Statistical test
Three statistical tests, Fisher's exact [34], Chi-squared [35] and Kolmogorov-Smirnov (KS) tests [36], are used to identify those features whose statistical patterns are significantly different between the positive and negative datasets. Specifically, the Fisher's exact tests are used for functional roles of nearby genes, for which the feature variable is categorical and some expected values in the contingency tables are extremely small (< 5). The Chi-squared tests are applied to categorical features, including the number of conserved TFBS's and conserved elements. And, the KS tests are applied to the numeric features, including CpG island general attributes, DNA sequence composition features (frequencies and z-scores), average scores of conserved TFBS's and conserved elements, structural properties, histone methylation and histone acetylation. A feature is selected if the p-value rendered by the statistical test is less than 0.05.
Although statistical tests may identify those features showing correlation with the CpG island methylation, the identified features might be inter-correlated themselves. For example, DNA sequence and structure properties are likely to be correlated, because most DNA structures are predicted based on DNA sequences. The histone methylation and acetylation status are likely to be correlated, because some acetylation and methylation (e.g. histone H3 at lysine 9) play opposite roles in gene activity [37]. The correlation between features makes the feature space unnecessarily high-dimensional. To minimize the redundancy in the features, we perform the PCA on those methylation-related features that are selected via the above statistical tests. The PCA uses an orthogonal transformation to convert a set of values of possibly correlated dimensions into a set of values of uncorrelated dimensions called principal components [38]. After PCA transformation, the feature components are completely decorrelated, and the information contained in the original feature space before the transformation is maximally retained in the first several number of components of the new feature space. Therefore, by keeping only the first several components of the new feature space, most of the information can still be retained while the redundancy in the feature collection is greatly removed and the dimensionality of the feature space is greatly reduced.
Model training, validation and testing
After feature selection through statistical tests and PCA, each CpG island is represented by a multi-dimensional feature vector that corresponds to the retained principal components. The feature is then fed to the models to predict the methylation status of the CpG island. To examine the contribution of the newly added features as well as the impact of the inhibitive-to-acquire histone modification information, we establish 16 models, (1) M1: with all information being incorporated, (2) M2: with all but the histone modification information being incorporated, (3) M3-M9: models with individual or combinations of the newly added features being excluded, and (4) M10-M16: models with individual or combinations of the newly added features as well as the histone methylation information being excluded. Each model is based on the SVM, and outputs binary results indicating whether the CpG islands are methylated or unmethylated and continuous results ranging from 0 (minimum) to 100 (maximum) indicating the methylation intensities of the CpG islands. Given the binary predictions provided by a model and the true methylation status as specified in the HEP data set for a group of CpG islands, we can estimate the specificity, sensitivity and accuracy of the model as in Eqns. (4)-(6):
where SP, SE, ACC stand for specificity, sensitivity and accuracy, respectively. And, given the continuous predictions and the true methylation intensities of the CpG islands, we can calculate their correlation coefficient as:
where CC stand for correlation coefficient, cov(·) denotes the covariance, and σ denotes the standard deviation. Note that the specificity reflects the model's capabilities in dealing with the negative (unmethylated) data - a high specificity measure implies that a predicted unmethylated CpG island is highly likely truly unmethylated. And the sensitivity reflects the models's capabilities in dealing with the positive (methylated) data - a high sensitivity measure implies that a predicted methylated CpG island is highly likely truly methylated. Whereas, the accuracy and correlation coefficient reflect the model's overall capabilities in dealing with all types of CpG islands - high accuracy and high (close to one) correlation coefficient implies that the predictions are highly likely true.
All these models are trained and validated by using the CD4 lymphocyte data with a 10-fold cross validation scheme. The 469 CpG islands are randomly partitioned into 10 approximately equally-sized folds. Each fold is used in turn for validation while the remaining folds are used for training. The performance of the model is assessed based on the data in the validation fold. This partition-training-and-validation procedure is repeated for 20 times, and the performance of the model (in terms of specificity, sensitivity, accuracy and correlation coefficient) is averaged over the 200 validation folds (10 validation folds per partition ×20 partitions).
Generalizability test
Two predictive models built on the CD4 lymphocyte data, M1 (using all information) and M2 (using all but histone modification information), are also tested for generalizability using the data of the other 11 tissues and cell types. For generalizability testing on M1, we apply the histone modification information of the CD4 lymphocyte to the other 11 tissues and cell types because correlation analysis by ourselves and others has indicated that histone modifications exhibit modest to strong correlations for different cell lines [39,13]. The generalizability performance of the model is also measured in terms of specificity, sensitivity, accuracy and correlation coefficient, which are averaged over all the models constructed from all the above training/validation partitions.
Results and discussions
Statistical tests and PCA
Out of a total number of 841 features, 342 features are retained whose p-values in the statistical tests are less than 0.05. These features include two of the CpG island specific attributes, 217 DNA sequence compositional features, and eight DNA structural features, 35 features regarding the conserved TFBSs, two features regarding the conserved elements, two features regarding the functional roles of the neighboring genes, and 76 features related to the modification status of nearby histones. Particularly, among the newly added features, two out of the four nucleosome positioning features, all of the 36 histone acetylation features, and both of the features regarding the functional roles of the neighboring genes are retained after statistical tests.
PCA is performed on these 342 selected features to minimize their correlations. Table 3 summarizes the number of principal components that must be retained to keep a certain percentage of the variance of the original feature space. Observe that the first eight principal components together can account for the ~99.90% of the total variance and are therefore used to build the predictive models. Figure 2 depicts the contribution of each of the 342 original feature dimensions to the eight principal components. Observe from Figure 2 that each of the following categories of features, (i) the CpG island general attributes, (ii) DNA sequence composition, (iii) distribution of the conserved TFBS's and conserved elements, (iv) DNA structure patterns, (v) gene functions, (vi) histone methylation and acetylation status, makes substantial contributions to one or more principal components, suggesting that these categories of information, though correlated, are complementary to a certain extent for predicting the CpG island methylation.
Table 3. Number of principal components (PCs) required to retain a certain percentage (Pcnt) of the variance of the original feature space of the 342 features selected through statistical tests.
Figure 2. Contribution of the 342 features to the eight principal components. Each column corresponds to a principal component, and each row corresponds to an original feature dimension. All feature categories make substantial contributions to one or more principal components, suggesting that these categories of information, though correlated, are complementary to a certain extent for predicting the CpG island methylation.
Performance of the predictive models based on the CD4 lymphocyte data
The specificity, sensitivity, accuracy and correlation coefficient measures of our predictive model M1 that incorporates all information are summarized in Table 4. The performance of our classifier is compared to that of Fan et al.'s method (which is based on a similar set of features and represents the state of the art [13]). Note that both models have incorporated the histone modification information. Observe that our model shows an improved specificity and accuracy while maintaining a comparable sensitivity.
Table 4. Performance of our classifiers M1 on CD4 lymphocytes with comparison to the existing method.
We could argue that the improvement of our model M1 over the existing model is partly due to the incorporation of the three new types of features - nucleosome positioning propensities, gene functions, and histone acetylation status. The performance of our models M3 through M9, each with an individual or a combination of the new types of features being excluded, are summarized in Table 5. Observe that the performance of the predictive model deteriorate to different extents when individual or combinations of the newly added features are excluded. Specifically, the models without histone acetylation information (M3, M6, M7, and M9) deteriorate more than those models with histone acetylation information but without the other two types of newly added features (M4, M5, and M8). Therefore, histone acetylation appears to be the most influential feature to the performance of the predictive model among the newly added features.
Table 5. Performance of the predictive models (M3 through M16), each with an individual or a combination of the newly added categories of features being excluded.
We suspect that the information carried by the histone methylation features is too dominant to fairly assess the influence of these newly added features; and therefore exclude the histone methylation features and repeat the above experiments excluding individual or combinations of the newly added features. The resultant models are M10 through M16, and their performance is summarized in Table 5. Similarly, the models without an individual or a combination of the newly added features deteriorate. It is noteworthy that (1) the histone methylation and acetylation information greatly affect the sensitivity of the models, and (2) the loss of histone methylation information could largely be made up by including the histone acetylation information. This is not surprising, given that these two forms of histone modifications are closely related as repeatedly observed in various tissues and cell types [37].
Classifier generalizability
The two predictive models, one with the histone modification information (M1) and the other without (M2), that are both built on the human CD4 lymphocyte data are then tested on the data of the other 11 tissue and cell types for their generalizability. The sensitivity, specificity, accuracy and correlation coefficient of M1 and M2 during these testing experiments are summarized in Tables 6 and 7.
Table 6. Performance of the classifier model and the influence of newly added features on the data of 11 different tissues and cell types: with histone modification.
Table 7. Performances of the classifier model and the influence of newly added features on the data of 11 different tissues and cell types: without histone modification.
When the histone modification information is incorporated, the classifier model built on the CD4 lymphocyte data can be applied to most of the other tissues and cell types (except for sperm) with little or no performance deterioration. When the histone modification information is not used, the performance of the predictive model on the data of the other tissues and cell types deteriorate substantially, especially in terms of the sensitivity. However, if compared to the validation results where the histone modification information is not used (see Table 3), the performance on the testing data is not unexpected. Therefore, with or without the histone modification information, the predictive model established on the CD4 lymphocyte data can well generalize to the other tissue or cell type data.
Considering that DNA methylation is heavily involved in cellular differentiation, our results in Tables 6 and 7 may look suspicious. We therefore count the number of differentially methylated CpG islands (Table 8) and calculate the correlation of the CpG island methylation levels between any two different tissue and cell types (Figure 3). Observe that between somatic/placenta cells, the number of differentially methylated CpG islands is small and the correlation coefficients are very high, whereas between the somatic/placenta and sperm cells, the number of differentially correlated CpG islands is relatively larger and the correlation coefficients is relatively lower. This suggests that the methylation status of CpG islands are highly correlated in various somatic/placenta cells, and therefore do not represent tissue-specific differentially methylated regions. Our observations are consistent with recent studies [17,40] that there are few variance in methylation levels of autosomal CpG island promoters, and there is only a relatively small fraction of CpG islands with tissue-specific methylation. The difference between the somatic/placenta and sperm cells, as reflected by their moderate cross-correlations and the performance deteriorations of our prediction models being applied to the sperm cell data, suggests that gametes are epigenetically more deviated from somatic cells than somatic cells themselves. This difference is likely related to the meiotic process, the special conditions and gene expression required for gamete production [41].
Table 8. The number of CpG islands that are differentially methylated in any two tissues among 321 common CpG islands for all the 12 tissues.
Figure 3. Correlation coefficients of the CpG island methylation levels across different tissues and cell types. The methylation status of CpG islands are highly correlated among the somatic and placenta cells. The methylation status of CpG island in sperm exhibits much difference in comparison with other tissue and cell types.
Conclusions and future works
The establishment of DNA methylation pattern is a crucial part of cell differentiation and organ development, suppression of viral genes and deleterious elements, and carcinogenesis. Computational prediction of DNA methylation levels provides an effective, fast and cheap alternative approach for studying the DNA methylation patterns. In this study, we perform the computational prediction of the CpG island methylation by incorporating additional features and effectively selecting and decorrelating the features. We incorporate the information regarding the nucleosome positioning propensity, acetylation status of nearby histones, and the functional roles of nearby genes. These features are first screened through statistical tests and PCA. The most DNA methylation-relevant yet non-intercorrelated features are subsequently used to build computational models to predict the methylation status of CpG islands. Our experiments on the HEP data set demonstrated that (1) an eight-dimensional feature space, which combines all the eight categories of information, is effective in predicting the methylation status of CpG islands; (2) by incorporating the information regarding the nucleosome positioning propensities, gene functions, and histone acetylation, our predictive model achieves a higher specificity and accuracy than the existing model while maintaining a comparable sensitivity; (3) the histone modification attributes carry a weight of information for the prediction, without which the performance of the predictive model deteriorates substantially in terms of sensitivity; (4) with or without the histone modification information, the performance of the predictive models are consistent on the validation and testing data.
Though it is known that DNA methylation is heavily involved in the normal development and differentiation, as well as in the onset and progression of diseases, the exact mechanisms are yet to be discovered. It will certainly help to accelerate biomedical investigations if we can, through computational predictions, comparative analyses, and evolutionary studies, identify those DNA regions whose methylation variation patterns are correlated with, indicative of, and underlying of the variations in gene expressions, histone modifications and chromatin structures that are related to normal development, cell differentiation, genome imprinting, X-chromosome inactivation, and phenotypic changes, respectively. This computational model, with its evidently high specificity and sensitivity, provides an effective tool for identification of new methylation targets and therefore lays foundation for our future endeavors in the regulation mechanisms of DNA methylation.
An standalone program for the CpGIMethPred is freely available for download at http://users.ece.gatech.edu/~hzheng7/CGIMetPred.zip webcite. Given the chromosome location (hg18) of a CpG islands, CpGIMethPred is able to predict the methylation status of it.
Competing interests
The authors declare that they have no competing interests.
This study is partially supported by Georgia Cancer Coalition Award RC672 "Establishing the Computational Model to Detect Cancer-Specific Differentially Methylated CpG Islands in Human Genome."
This article has been published as part of BMC Medical Genomics Volume 6 Supplement 1, 2013: Proceedings of the 2011 International Conference on Bioinformatics and Computational Biology (BIOCOMP'11). The full contents of the supplement are available online at http://www.biomedcentral.com/bmcmedgenomics/supplements/6/S1. Publication of this supplement has been supported by the International Society of Intelligent Biological Medicine.
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Fan S, Zhang M, Zhang X: Histone methylation marks play important roles in predicting the methylation status of CpG islands.
Biochemical and Biophysical Research Communications 2008, 374:559-564. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Previti C, Harari O, Zwir I, del Val C: Profile analysis and prediction of tissue-specific CpG island methylation classes.
BMC Bioinformatics 2009, 10:116. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text
Siepel A, Bejerano G, Pedersen J, Hinrichs A, Hou M, Rosenbloom K, Clawson H, Spieth J, Hillier L, Richards S, Weinstock G, Wilson R, Gibbs R, Kent W, Miller W, Haussler D: Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes.
Genome Research 2005, 15:1034-1050. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Bernstein B, Mikkelsen T, Xie X, Kamal M, Huebert D, Cu J, Fry B, Meissner A, Wernig M, Plath K, Jaenisch R, Wagscha A, Feil R, Schreiber S, Lander E: A bivalent chromatin structure marks key developmental genes in embryonic stem cells.
Cell 2006, 125:315-326. PubMed Abstract | Publisher Full Text
Weber M, Hellmann I, Stadler M, Ramos L, Paabo S, Rebhan M, Schubeler D: Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome.
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Eckhardt F, Lewin J, Cortese R, Rakyan V, Attwood J, Burger M, Burton J, Cox T, Davies R, Down T, Haefliger C, Horton R, Howe K, Jackson D, Kunde J, Koenig C, Liddle J, Niblett D, Otto T, Pettett R, Seemann S, Thompson C, West T, Rogers J, Olek A, Berlin K, Beck S: DNA methylation profiling of human chromosomes 6, 20 and 22.
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Das R, Dimitrova N, Xuan Z, Rollins R, Haghighi F, Edwards J, Ju J, Bestor T, Zhang M: Computational prediction of methylation status in human genomic sequences.
Fujita P, Rhead B, Zweig A, Hinrichs A, Karolchik D, Cline M, Goldman M, Barber G, Clawson H, Coelho A, Diekhans M, Dreszer T, Giardine B, Harte R, Hillman-Jackson J, Hsu F, Kirkup V, Kuhn R, Learned K, Li C, Meyer L, Pohl A, Raney B, Rosenbloom K, Smith K, Haussler D, Kent W: The UCSC Genome Browser database: update 2011.
Nucleic Acids Res 2011, 39(Database):D876-82. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Schbath S, Prum B, Turckheim E: Exceptional motifs in different Markov chain models for a statistical analysis of DNA sequences.
Journal of Computational Biology 1995, 2:417-437. PubMed Abstract | Publisher Full Text
Karolchik D, Baertsch R, Diekhans M, Furey T, Hinrichs A, Lu Y, Roskin K, Schwartz M, Sugnet C, Thomas D, Weber R, Haussler D, Kent W: The UCSC Genome Browser Database.
Nucleic Acids Res 2003, 31:51-54. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Goñi J, Pérez A, Torrents D, Orozco M: Determining promoter location based on DNA structure frst-principles calculations.
Genome Biology 2007, 8:R263. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text
Chodavarapu R, Feng S, Bernatavichute Y, Chen P, Stroud H, Yu Y, Hetzel J, Kuo F, Kim J, Cokus S, Casero D, Bernal M, Huijser P, Clark A, Kramer U, Merchant S, Zhang X, Jacobsen S, Pellegrini M: Relationship between nucleosome positioning and DNA methylation.
Nature Letter 2010, 466:388-392. Publisher Full Text
Kaplan N, Moore I, Fondufe-Mittendorf Y, Gossett A, Tillo D, Field Y, LeProust E, Hughes T, Lieb J, Widom J, Segal E: The DNA-encoded nucleosome organization of a eukaryotic genome.
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University of Mississippi
Archives & Special Collections
Open Doors
Civil Rights, Mississippi, and the Novelist's Craft
Civil Rights Events
Emmett Till
Medgar Evers
Freedom Summer
John Armistead
Bebe Moore Campbell
Ellen Douglas
Ronald L. Fair
James D. Forman
John Grisham
William Mahoney
Jay Milner
Lewis Nordan
P.J. Parish
Leroy L. Ramsey
Shepard Rifkin
Patrick Smith
Eudora Welty
Joan Williams
Book Production
Author's Notes
Uncorrected Galleys
Author's Notes
Ellen Douglas
Ellen Douglas is the pseudonym of Mississippi author Josephine Haxton. She received a grant from the National Endowment Association to complete
The Rock Cried Out
(1979), which won a literature award from the Mississippi Institute of Arts and Letters. In this novel, a young man returns home to Mississippi where he seeks to understand the tragic death of a beautiful cousin seven years earlier in the midst of the 1964 Freedom Summer.
On display from the Ellen Douglas Collection is a timeline of events created by the author, as well as a typed manuscript from one of her drafts.
a copy of Ellen Douglas's notes for
The Rock Cried Out
a copy of Ellen Douglas's typed manuscript for
The Rock Cried Out

subset: commoncrawl


text:
Nichole's Diary
MY BIRTHDAY!!December 25th 2006 5:45 pm[ Leave A Comment ] I GOT A NEW COLLIER FOR MY BIRTHDAY ITS BLACK WITH FLAIMS AND IT IS SOFT!!! I LOVE IT, IM STILL WATING FOR MY CHRISTMAS PRESENT CUZ ITS NOT REDDY, I THINK SARA IS MAKING A NEW DOGGIE HOUSE FOR ME!! THAT WOULD BE AWSOME!! I FOUND AWAY TO GET OUT TO THE FRUNT FROM THE BACK YARD AND SARA AND EVERY ONE KEEPS GETTING MAD AT ME WEN I DO THAT SO MAYBE I SHOULD STOP, BUT THEY NEVER COME GET ME FROM OUT SIDE WEN I WANT TO, I THIK THERE SHOULD BE A PUPPIE BELL FOR ME TO RING FOR WEN I WANT IN!! It's SaraDecember 12th 2006 8:25 am[ Leave A Comment ] heyzz it's Sara, Nikki's ouner...Nikki's birthday is coming up and i have an idea what to give her, she does not have her dog door any more and someone alse took our last house and she had a little dog house but my mom threw it out wen we moved so now i'm thinking to buld her a house and put it in the back yard, i mean start from scrach like go buy wood and build it, i think i mite get my dad to help me, he is good with things like that! getting thereNovember 16th 2006 2:17 pm[ Leave A Comment ] well i saw my two best friends and i'm going to agen in a few weeks, i cant w8!! i'm getting used to the place now, i still miss my dog door, i have to hold it till Sara gets home from school. she lets me out the frunt the second she gets in! i like the new town, more people to bark at and there was this wierd night once, people keped coming to our door and they wer deresst in verry odd clothing, one person had to heads, and so did my family. Most said "trick or treat" is that somesort of code? cuz wen ever they said that Sara or someone alse would give them candy! Sara tryed putting a somthing on me but i keps kikking it off. OOO A SQURILE GOT TO GO!! Diary#2October 1st 2006 12:02 pm[ Leave A Comment ] well i gotten used to the place, i still miss my dog door, i have to w8 till Sara gets home from school every day to go to the bathroom...well im having fun hear, sara olways has this girl i have groun to like over her name is Shannah she is cool, sh sleped over last night. i grown to like it, i got more room to run around the house, my bed is in Sara's room but i never use it though. i hav'nt make any doggie friends yet. but Sara and i are going for a walk soon so you never know. what happend?July 12th 2006 3:18 pm[ Leave A Comment ] somthing wierd is going on, iam in a tottaly diffrent place, I'm not home any more....WERE IS MY DOG DOOR?!?! i want to go out side, iam in a diffrent house and have bin here for about a week in a half now so its kinda diffrenti went for a walk the other day and noticed that iam in a diffrent town aswell, were in the world i'm i? did we move? aww i miss the dogs up the street and i want to go play with them, iam so sad...maybe i will make more puppie frends...that wood be cool, hey my oner told me about a germen shepperd up the street a little ways, mybe i will meet him one day. There is the big box thing in frunt of our house and people keep coming to pick up evelopes, just to make sure they know iam in the house reddy to attack if they brake in i bark at them...every one shuts me up thoughbut wen i feel i have to bark i do. Early early this morning it was raining and i sleep with my ouner Sara and she has a sky light in her room and i got skared because it was raining and it was verry loud so i jumped up on her bed and liyed right beside her and woke her up and she huged me and we both fell asleep, it was scarry. OOO DINNER BYE! |
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7 years ago by Linda Bustos Comments Off
Bloggers Digest 1/25/08
Thought we'd kick this week off with a hilarious video I came across via GrokDotCom:
I linked to this yesterday, but it deserves another nod. Justin Palmer shares 3 creative ways online retailers handle product stock-outs. We incorporated his ...


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General Question
Students: What do you use to organize your schedule and notes?
Asked by dpworkin (26965
July 28th, 2009
Is there any software that you have come to like that manages classroom-related stuff for you such as schedules and assignments?
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How Would You Like to Have a Song Named After You?
LAGUNA BEACH, Calif., April 22 /PRNewswire/ — For the perfect Mother's Day Gift or the unique hard to find present for that special someone, Laguna Beach Modern Gypsy/Flamenco guitarist and composer Emilio is offering to create and name a song for that individual. The musician has built a loyal following of fans on TV and through his concerts in Orange County having sold more than 35,000 albums and is now planning his next venture: working on an International Documentary about Flamenco and the culture and beauty of Spain. The film is just part of a project that is coinciding with Emilio working with a Grammy award winning producer on a recording scheduled for May.
As an invitation for a patron of Nuevo Flamenco to financially back this project, Emilio is offering to name a song after them for all posterity. The opportunity will also include a private performance at their residence and other perks as well. As Emilio explains, "this is a unique experience and special opportunity for the individual to be remembered and leave behind a lasting legacy with a song that will be written especially for them."
Emilio and his family have made Laguna Beach their home. He has performed for years at the St. Regis Hotel in Dana Point, Disneyland, QVC television, the OC Pavillion and the El Cid among others.
Check out the following links.
Emilio was featured on a YouTube video with a musical compilation of Modern Gypsy Shows:
He sold out the Barclay Theater at UCI in 2007:
Thousands of his CDs were sold in 9 minutes:
Contact: - Emilio (949) 510-5328 email@example.com www.emiliotv.com www.moderngypsyllc.com
Available Topic Expert(s): For information on the listed expert(s), click appropriate link.
Emilio Castillo
SOURCE O'Connor Creative, Inc.


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Rocky Comfort Plantation RV Park
Phone: (706) 830-4177
Visit Campground Website
Sites: 16
Recent Rate: $25 3/2015
Latitude: 33.317541
Longitude: -82.647495
These reviews are the opinion of an RVParkReviews' member and not the views of RVParkReviews.com
Date of Stay: March, 2015 - $25.00
We stayed here 2 nights in a pull through site #3 right across from the owner and the pond/lake. Very peaceful setting. Owner extremely friendly and accommodating. Campground is off the beaten path about 13 miles from I-20 but very quiet and peaceful. Some of the trees could be trimmed back for higher rigs and we had to have one board on our door side to make the rig level. At highway 278 after you exit there is diesel fuel, a true value hardware and Piggly Wiggly (we had a need for all 3). We would stay here again if in the area. We camped at Rocky Comfort Plantation RV Park in a Fifth Wheel.
Date of Stay: November, 2010 - $22.00
Drove thru this park with the notion of spending a couple of nights here. Honor system for payment. Gravel sites and driveways. No office on site. Very rural, but clean and nice appearing. Not much rhyme or reason to the layout. Suggest you do not pull in here after dark with a big rig for the first time. Don't miss the turn off the paved road, small sign. Right on Rocky Comfort Creek. We declined to return with our 5er this time, but would return. We camped at Rocky Comfort Plantation RV Park in a Fifth Wheel.
Date of Stay: March, 2008 - $16.00
This is a new campground. It is very pretty and clean. However, you must be self-contained as there are no facilities. The owners came by to check on us as we were the only ones camping that night. The campground is located on a small fishing lake. We camped at Rocky Comfort Plantation RV Park in a Fifth Wheel.
UndoPre-Register below to access free and enhanced features coming in the near future.
Access to marketing tools, ability respond to reviews and monitor performance as well as expanded listings.
More Information about our Campground Owner Management and its enhancements are coming very soon. Features subject to change.


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Welcome! You are browsing as a guest
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© Evelyn A. Clark
Sweet Pea Baby Shawl
Sweet Pea is pictured on page 48 of the 2nd Edition, and the sample is approximately 32" (81.5 cm) square. It is designed with Solid Pattern, Pod Insert, and Garter Eyelet Edging.
An outline of the stitch patterns for this design is included in the book, and the stitch patterns are written for use with any gauge of yarn. A chart in the book's Appendix lists yarn requirements and dimensions for twelve sizes in 4 weights of yarn.


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Internet of Things
IEEE standards enabling products with real-world applications.
Recognizing the value of IoT to industry and the benefits this technology innovation brings to the public, the IEEE Standards Association (IEEE-SA) has a number of standards, projects and events that are directly related to creating the environment needed for a vibrant IoT. This area provides a reference point for all things in SA related to IoT.
IEEE-SA IoT Ecosystem Study
IEEE-SA engaged stakeholders in key regions of the world to create an
IoT Ecosystem Study. The study comprises three principal areas: Market, Technology, and Standards, along with an examination of the role of academia and research and the importance of user acceptance. An
executive summary of the study is available.
IEEE P2413, Draft Standard for an Architectural Framework for the
Internet of Things Working Group
This draft standard defines an architectural framework for the Internet of
Things (IoT), including descriptions of various IoT domains, definitions of
IoT domain abstractions, and identification of commonalities between
different IoT domains. To participate in the
development of this standard, visit the IEEE P2413 Working Group page.
Check out some photos of our recent IoT Startup Soiree event at the Consumer Electronics Show (CES) in Las Vegas, NV this past January: IEEE-SA IoT Startup Soiree Photo Album
Chuck Adams IEEE on Internet of Things
Why the internet of things should be designed with efficiency in mind
Open Standards Will Enable the IoT's Growth
Your Questions Answered: The Internet of Things
The IEEE Internet of Things Initiative is a single resource for "IoT"
information, articles, conferences, training and much, much more. Join
this technical community today!


text:
Air Ranger: Rescue Helicopter
An exciting challenge for all budding aviators, Air Ranger Rescue Helicopter puts you in the role of Kane, a dedicated rescue pilot. Four enormous stages and eight types of rescue are on offer as you - and your brave colleagues, Bob, Matilda and Ivan - try to avert disaster and save the day. From evacuating runaway trains to extinguishing an inferno from the air, you will be stretched to your limit in this exciting helicopter sim.
If you're stuck in Air Ranger: Rescue Helicopter, ask your fellow GameFAQs members for help.
Game List Statistics
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New Arrivals
These are an excellent supplement for lactating bitches.
Calcium is needed in our bodies no matter what kind of "animal" we are. Kati loves the Pet Tabs. We never have a problem with her taking them. We also have never had a problem with Entirely Pets. We receive our shipments in a timely matter & they are always correct the FIRST TIME!!!!!
This product has met all of the stringent quality and safety standards set by the NASC.
The NASC (National Animal Supplement Council) is a non-profit self regulatory group that set specific guidelines to which manufactures must strictly adhere.
This seal is meant to minimize risk by providing an easy way of communicating to consumers that a product and its manufacturer meet particular standards of quality, customer safety and service.
Those products that have the seal for NASC Quality and Safety standards have been strictly audited and were determined as meeting the following criteria:
Sign into your EntirelyPets Account for the best experience!


text:
Go on your way I'm fine then. Yesterday was too late. I'll be missing you,. I paint a picture with a glass heart. Humanoid is my one true art. Aren't they beautifully made. You walk In and through the doors that are shut. Walk away, passing him. On the street. Observing life watch time at the edge of the barbershop. People they act like your not even there. They just don't care, but I do. Ive been here with you the tears that fall from your face. I will wash them all away. Hear the melody amazing grace. Forgiven but not forgotten dead but now is coming to life. Sometimes but always I was there for you then. Im more than brother more than a friend. Have you ever known anyone who'll stick till the end. I'm kinda like them. But still more than even that. You are the picture that I painted with my father. And even if you can't hear me. I will be listening wrote all that you've said. Counting all strands on your head. More than a friend.
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Book your room at 5000 Motel
Room, 1 Queen Bed, Kitchen
Max Occupancy: 2 guests (up to 1 child, 1 infant)Room, 2 Queen Beds, Refrigerator & Microwave
Max Occupancy: 4 guests (up to 3 children, 2 infants)Suite, 1 Bedroom, Kitchen
Max Occupancy: 4 guests (up to 3 children, 2 infants)Suite, 2 Bedrooms, Kitchen
Max Occupancy: 5 guests (up to 4 children, 3 infants)Motel in Penticton with outdoor pool
Collect 200 points
Simply enter your Nectar card number when prompted. Your points will be credited 30 days after you return from your trip.*Offers may apply
Situated in Penticton, this motel is within 2 mi (3 km) of Penticton Museum and Archives, Penticton and Wine Country Visitor Center, and Penticton Art Gallery. Rotary Park and South Okanagan Events Centre are also within 2 mi (3 km).
Property Features
An outdoor pool, laundry facilities, and tour/ticket assistance are available at this motel. WiFi in public areas is free. Other amenities include barbecue grills and a picnic area.
Room Amenities
Rooms provide conveniences like refrigerators and coffee makers, plus free WiFi and flat-screen TVs with cable channels.
Information missing or incorrect? Tell us!Hotel Amenities
Hotel Amenities
5000 Motel features an outdoor pool, tour/ticket assistance, and barbecue grills. Public areas are equipped with complimentary high-speed wireless Internet access. This Penticton motel also offers a picnic area, laundry facilities, and beach/pool umbrellas.
- Barbecue grill(s)
- Beach/pool umbrellas
- Tours/ticket assistance
- Free WiFi
- Laundry facilities
- Picnic area
- Pool sun loungers
- Outdoor pool
Available in all rooms: Free WiFi
Available in some public areas: Free WiFi
Room Amenities
- Air conditioning
- Free local calls
- Refrigerator
- Coffee/tea maker
- Cable TV service
- Flat-panel TV
- Free WiFi
Hotel Policies
Pets allowed, Maximum number of pets per room 1, Pet maximum weight in lb is 10
You need to know
Extra-person charges may apply and vary depending on hotel policy.
Government-issued photo identification and a credit card or cash deposit are required at check-in for incidental charges.
Special requests are subject to availability upon check-in and may incur additional charges. Special requests cannot be guaranteed.
- Pet fee: CAD 10 per pet, per night


text:
Scholarships 101: The Real-World Guide to Getting Cash for College
You're the parent of a teenager who's ready to apply for college and you're concerned that she might not be able to afford it. She's bright, talented, and hardworking, but she's not the captain of the volleyball team or the valedictorian. You know your child deserves the very best education, but how do you ensure that she gets the money she needs to attend the school of her dreams, even if she's not a straight-A student? Author Kimberly Stezala passionately believes that every student should have access to a quality education. Now, she enables you to approach the scholarship process like a pro. Filled with inspiring advice from successful students and scholarship providers, this book shows kids how to: Apply for those scholarships that are the best match for their profile and skills, Create a scholarship application that will stand apart from the rest, Find the buried treasure of scholarships that aren't available on common websites. Straightforward and savvy, this book will ensure that your kids get the best start in life.
Additional information
Place of publication:
- New York
- 2008


text:
When I saw pictures of the young rioters in Tunisia and Algeria, I thought I was looking at pictures of young rioters in England or France. The Tunisian and Algerian rioters made the same gestures as their Western European counterpartsperhaps there are not all that many ways to riotand dressed in precisely the same fashion, that is to say, in international slum-youth costume. Its nice to know that the world is drawing closer together.
Different as the societies of the Maghreb and Western Europe might at first appear to be, they share at least some important featuresfor example, high rates of youth unemploymentand for the same reasons. In fact, when one considers that about half of the population of Tunisia and Algeria is under 25, it is possible that they do better than European countries such as Spain, France, and Britain in absorbing young people into the labor market.
Societies on both sides of the Mediterranean suffer from what one might call diplomatosis. This dangerous disease is caused by the assumption that, since a modern economy requires educated people, the more educated people it can call uponas measured by the average number of years in schoolthe more productive that economy will be. On this view, education is in itself the motor of growth, and the demand for educated labor will automatically keep up with, if not outstrip, the supply.
The story of the young Tunisian Mohammed Bouazizi, whose suicidal self-immolation was the spark that set Tunisia aflame, is instructive. He was 26 and had a degree in computer science. Like 200,000 other university graduates in Tunisia (in a population of 10 million), he could not find a job. He then tried selling fruits and vegetables from a stall. However, he did not have bureaucratic permission to do thissuch permission being bestowed by other university graduates, lucky or well-connected enough to have found jobs in the public-sector bureaucracy. The police constantly harassed him because he didnt have the requisite licenses. It is said that he set fire to himself when a policeman spat in his face.
No policy could be more dangerous, more certain ultimately to produce a social explosion, than to educate young people for many years and deny them first the opportunity to earn a living that they believe is commensurate with their education, and then the opportunity to earn a living at all. But this is the policy that many countries persist in following on both sides of the Mediterranean.
From one point of view, it is heartening that the current riots in Tunisia and Algeria appear devoid of religious motivation. But the Salafists must surely regard them with glee, for the young indignant easily turn to false messiahs. For the moment, the rioters are demanding that the government find work for the unemployed (the president of Tunisia has promised a job to Mohammed Bouazizis mother, whose other children, likewise educated, are also unemployed). The penny is not likely to drop soon regarding the fact that governments dont create jobs; at best, they create the conditions in which jobs can be created. The future of Europe, I fear, can be discerned in Tunis and Algiers.
Theodore Dalrymple, a physician, is a contributing editor of City Journal and the Dietrich Weismann Fellow at the Manhattan Institute.


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Republic of South Africa
The Republic of South Africa is one of the largest countries on the African continent. With coastlines on the Indian and Atlantic Oceans, it borders Namibia, Zimbabwe, Botswana, Mozambique and Swaziland. The Kingdom of Lesotho lies entirely within its borders.
Although the republic has become a wealthy industrialized country over the past few decades, the rural areas of the former homelands resemble developing countries.
The country has been divided into nine provinces since the end of Apartheid in 1994: KwaZulu-Natal, Eastern Cape, Western Cape, Northern Cape, North West, Gauteng, Mpumalanga, Free State and Limpopo. SolarWorld AG will install a total of 29 Sun-TV stations in South Africa. For detailed information on the stations that have already been installed, see our press area.
Stations in KwaZulu-Natal | |||
Edenvale | Lemontville | Durban | Inkandla |
Ulundi | Bhekabantu High School | Ntabane High School | Himeville |
Stations in Western Cape | |||
Ashbury | Gansbaai | Kayelitsha | Living Waters Farm |
Oasis Business Park, Philippi |
Stations in Eastern Cape | |||
Ithembelhile Comprehensive School | Tafelhashi Arts Center | Tafelhashi Church hall | |
Mndwaka | Bulungula School | Willowmore |
Stations in Northern Cape | |||
Van der Waltspoort Primary | Dombietersfontein | Pampoen Poort Primary |
Station in North West Province | |||
Chaneng Community Center |
Stations in the province Gauteng | |||
John Wesley Community Center in Etwatwa | Stinkwater | Soweto |
Station in the province Mpumalanga | ||||
Kildare B |
South Africa 29 Stations |
Botswana 1 Station |
Namibia 4 Stations |
Lesotho 1 Station |
Swaziland 1 Station |


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Fax: 401.874.7872
URI professor helps disadvantaged speak for themselves
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New Bedford, Mass. program grants up to six college credits free of charge
KINGSTON, R.I.—May 1, 2009 –-Kathleen Torrens of Providence, an associate professor of communication studies at the University of Rhode Island, has taught public speaking to hundreds--if not thousands--of college students during the past 14 years. Two years ago she began teaching that skill to an untraditional class of economically disadvantaged individuals for whom college seemed out of reach, both financially and academically.
"Knowing how to make a cogent, persuasive argument is important because this population should be able to stand up for themselves -- whether in the courts, the school systems, or in other public forums where public advocacy is necessary to protect themselves and their families," explains Torrens.
The URI professor is part of a team of instructors who follow the Bard College Clemente Course in the Humanities, which gives low-income students the chance to study literature, art history, philosophy, and American history and earn up to six college credits. Students attend classes for 28 weeks free of charge.
Bard College, a liberal arts college located in New York's Hudson Valley, initiated the course in 1995. The course is now taught in at least 14 different sites around the country.
"Most, if not all, Clemente programs feature writing instruction, but our program may be unique with our addition of public communication," says Torrens who informally introduced public speaking two years ago and integrated it into the curriculum this year.
The class meets Monday and Wednesday evenings from September through May in the PACE facility on Smith Street in New Bedford. Mass. Class population varies from year to year. Students vary in age, diversity, and backgrounds. One student came from China, another was a Hurricane Katrina evacuee, and one couple had a few college credits. Some students are in recovery programs. Most students have children.
Torrens, a URI John Hazen White Center for Ethics and Public Service Fellow, feels strongly about empowering people who too often are voiceless. "People who are disadvantaged educationally and economically are easily made invisible to our "mainstream" culture," she says. "They often struggle with language issues, have had legal trouble, and can be readily marginalized because they don't have money.
"Basically, I would argue that the skills of public advocacy (which include critical thinking and listening, as well as the production of arguments) are necessary to an informed citizenry. Part of Clemente, with its focus on the humanities, is to move all citizens to public participation," she says. "In addition, many Clemente graduates enter community colleges or universities and continue their education."
Torrens adds that the program not only enriches students, but gives confidence to those students who continue in college.
"I think Rhode Island is ripe for a Clemente program if we can get enough financial support," the URI professor says, noting she was part of a group that tried to initiate one for the 2008-09 year, but fell $15,000 short of its goal.
"The program, in comparison to some public initiatives directed toward poverty eradication and education, is cheap," she says. The New Bedford Clemente Program runs on $50,000 a year."
Anyone who would like to know more about the program or help in the establishment of a program in Rhode Island should contact Torrens at firstname.lastname@example.com or 401.874.4809.
John Hazen White Sr. Center for Ethics and Public Service Faculty Fellows
Kathleen Torrens is one of eight Faculty Fellows appointed by the University of Rhode Island's John Hazen White Sr. Center for Ethics and Public Service this year. She received a $2,000 stipend for her work to help teach public speaking to people with low incomes.
These teachers and scholars, whose fields of expertise include a wide range of disciplines, participate in program development, seminar workshops and research and writing on issues related to ethics and public service.
The other Faculty Fellows appointed for a one-year term are:
• Bridget Buxton, assistant professor of history and William Krieger, assistant professor of philosophy. Project: The ethics of handling human remains in the context of deep submergence archaeology.
• Kathryn Jervis, assistant professor of accounting. Project: Investigating disparities in municipal disclosure policies.
• Roger LeBrun, professor of plant sciences. Project: The use of DDT in combating malaria in developing countries.
• Zahra Meghani, assistant professor of philosophy. Project: Public participation in ethical questions of new technology risk assessment in deliberative and participatory democracies.
• John Pantalone, journalism lecturer. Project: Internal reactions to recent ethics violations in major U.S. newspapers and the role of ombudsmen in preventing similar infractions.
• George Tsiatas, civil and environmental engineering. Project: Gathering, organizing, and disseminating engineering ethics case studies.


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Title: | [Letter] 1818 Nov. 19, Cherokee Agency, [to] Daniel Graham / Jos[eph] McMinn: a machine-readable transcription of an image |
Author: | McMinn, Joseph |
Availability: |
This work is the property of the Tennessee State Library and Archives, Nashville, Tennessee. It may be used freely by individuals for research, teaching, and personal use as long as this statement of availability is included in the text. |
Date: | November 19, 1818 |
Extent: | 4p |
Summary: | This document was written by Governor Joseph McMinn (1815-1821) to Secretary of State Daniel Graham on November 19, 1818. Governor McMinn writes that he will soon have taken the land east of the Mississippi River from the Cherokee and that if they want compensation, they must relinquish their possessions and claims to the United States within a certain number of years. He adds that the Cherokee look up to him for guidance, and he has been witness to vast amounts of monies and supplies trading hands for the trip west. |
Collection: | Governor McMinn Letters |
Box: | 10 |
Folder: | 59 |
Document: | tl011 |
Keywords: |
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29 June to 3 July 2009
Isaac Newton Institute for Mathematical Sciences, Cambridge, UK
Peter Clarkson (Kent), Rod Halburd (University College London), Masatoshi Noumi (Kobe, Japan) and Adri Olde Daalhuis (Edinburgh)
in association with the Newton Institute programme Discrete Integrable Systems (19 January to 3 July 2009)
Workshop Home Page | Programme | Participants | Accommodation and Cost
The deadline for receipt of applications has now passed. However, if you wish to apply to attend this event, please contact Tracey Andrew.
Please note that due to space restrictions we cannot guarantee that your application will be accepted.
Information for Conference Participants | Local Information | Newton Institute Map | Discrete Integrable System | Workshops | Newton Institute Home Page


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If the game freezes, just click inside it (games can get unresponsive if you click elsewhere on the page).
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Have you ever dreamed of owning your own Fomula 1 team? Now your dream is reality! In this game you will mount your own Formula 1 team making decisions that will cater for defining your team success or failure!
This game is played with mouse only.


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- 3.5-hour Grand Cayman dinner cruise
- Relax aboard a luxury catamaran as you coast past Seven Mile Beach at sunset
- Sip a cocktail from the cash bar aboard the boat
- Be awed by breathtaking views of the Cayman Islands as you sail in the Caribbean
- Enjoy a three-course gourmet dinner and delicious coffee
What You Can Expect
Tuesday - Curry Night
Chicken Curry or Fish Curry with mango chutney
Coconut Rice
Roasted Vegetables
Green Salad with assorted dressings
Chocolate Cake with Raspberry Coulis
Thursday - Local Night
Roasted Red Pepper and Scotch Bonnet Soup
Jerk Chicken or Seared Red Snapper with Herb Butter
Saffron Rice
Roasted Vegetables
Green Salad with assorted dressings
Chocolate Cake with Raspberry Coulis
Saturday - Island Night
Tomato basil soup
BBQ pork ribs or Mahi Mahi with Cayman sauce
Herb roasted vegetables
Island rice and beans
Local green salad
Chocolate cake with raspberry coulis
*All Meals come with bread & butter
Customer Reviews
June 2014
Highly recommended! The crew were very nice and made it a great expierence. Have some amazing photos, all 4 of us absolutely loved it.
June 2014
Dinner was okay but the crew was fabulous and meet some great people !


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Welcome to the Oklahoma Public School Resource Center (OPSRC). The OPSRC was created to provide educational support services and technical assistance to all of Oklahoma's public schools in the areas of school finance, law, technology, communications and teaching and learning. The OPSRC also provides networking and training opportunities for member schools and serves as an advocate for public education as a whole. The center offers all stakeholders accurate, current information about best practices and educational policy.
Mission & Whom We Serve
The Oklahoma Public School Resource Center provides public schools across the state the resources they need to unburden administrators, support teachers, and most importantly, engage students. Membership in the OPSRC is open to all public schools in Oklahoma. While all public schools are welcomed, we are particularly focused on meeting the needs of small schools. These schools typically lack a large central/administrative office typically found in larger schools and the technical services offered by the Center are tailored to help address the administrative challenges facing such schools.
The Oklahoma Public School Resource Center is here to help your district succeed in every way. So what are you waiting for? Click on the button below and schedule a meeting with us today!
Member Services
The OPSRC Finance staff provides assistance in school improvement planning, federal and state categorical spending, school financial policy development, overtime, purchasing, inventory management, fiscal distress trends and issues, salary schedules, school audit, and issues in Teacher Retirement. The Finance team offers targeted workshops and trainings in many of these areas.
Teaching & Learning
The OPSRC Teaching & Learning team is committed to ensuring our partner schools are competitive in academic achievement. We do so by providing access to resources and information, technical assistance, and targeted professional development. The Teaching & Learning team designs and implements a wide variety of professional development units and provides training to member districts.
The OPSRC Communications team works with schools and districts on their own communication and public relations by sending school press releases, creating district brochures, developing district or school publicity or public relations plans, conducting an analysis of the school or district website, and addressing any other community stakeholder communication needs.
The Legal staff is available to member schools as an in-house general counsel and will provide services including but not limited to the following: legal document creation and review, including those pertaining to personnel, students, grant applications, standards monitoring, and state/federal program compliance, and other professional services; consultations by phone, e-mail, or in-person at the school site or the OPSRC office(s); innovative and updated sharing of legal news and case briefs affecting member schools.
The OPSRC Technology team provides assistance to schools with technical issues and also provides training and workshops on pressing technology topics. The technology is available to assist with continuity plans, eRate applications, and other school and district technology decisions. Technology workshops focus on topics of interest including iPads in the classroom, Web 2.0, The Flipped Classroom model, District Websites, and iBooks Author.
Join OPSRC
Here at the Oklahoma Public School Resource Center, all schools are important. Regardless of the size of your district or the challenges you're facing we're here to help! Our focus is on making your school successful and helping you excel. So what are you waiting for? Schedule a meeting with us today!
OPSRC has teamed up with NWEA to give educators the data and resources they need to place the child at the center of the educational experience. OPSRC members are now eligible for reduced rates through NWEA.
NWEA provides research-based educational growth measures, professional training and consulting services to improve teaching and learning.
Additionally, its Growth Research Database, the most extensive collection of student growth data in the country, provides a rich source for the study of academic achievement.
Reports are available at individual, classroom, school, program and district levels. Students see their scores immediately, and teachers see detailed reports within 24 hours. Within 72 hours, principals and other administrators can access reports of aggregated data that show student growth, proficiency and norms.
NWEA Pricing is a 3-year-tiered system
Professional Development is a requirement when purchasing MAP and MPG. Your district pays $1000 for the "Getting Started with MAP" online training.
NWEA and OPSRC will host regional training workshops representatives from your district can attend. Please contact us to set up and meeting and learn more about this subsidy.
Online Supplemental Learning
In partnership with the Arkansas Public School Resource Center (APSRC), OPSRC is now offering to member and non-member schools alike access to a robust online supplemental learning portal. This resource provides middle and high school students with a wide range of teacher-led and facilitated courses to complement their traditional classwork. In addition to general education courses, students can select from a variety of Advanced Placement, honors, credit recovery and remediation, and various electives, including foreign languages. If you have students who need advanced or specialized coursework, students who want to improve their skills in specific subjects, advanced students who need expanded educational offerings, or homebound students needing access to credit recovery options, this portal may be the answer! For instructions on how to sign up, click here. To go to the Online Supplemental Learning Portal, click on the button below!
Take a minute to watch our video and find out more about OPSRC.
The Oklahoma Public School Resource Center has teamed up with DonorsChoose.org to help add additional funding for teacher projects within our member schools! We will match dollar for dollar any project that gets funded by supporters, up to $1,500.00. This means if a teacher creates a project totaling $500.00, the teacher only needs to raise $250.00, and we will cover the rest!
If you are a teacher at a member school, all you need to do to register is go to the DonorsChoose.com website and create a project as you normally would--there are no special steps you have to take. Once the project is created, DonorsChoose will match it up with our grant. Don't miss out on this fantastic opportunity to get additional funds for your classroom and students!


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Chicago Riverwalk
State Street Bridge To Close For Riverwalk Work
The Chicago Department of Transportation said the bridge will be closed to all traffic from 6 a.m. Wednesday through the afternoon of Aug. 23.
Construction Barge Sinks In Chicago River
The small equipment barge, which was being used as part of the project to expand the Chicago Riverwalk, sunk near the LaSalle Street bridge early Thursday.
City Awards First Contract For Riverwalk Renovation
Walsh bid $43 million to build the riverwalk from State Street to LaSalle Street. The project is set to be completed by the end of 2014.
Man Slashed With Knife After Attacking Pair On Riverwalk
A man who tried to attack two people near the Chicago Riverwalk got more than he bargained for Monday night, when one of his targets fended off his attack by slashing him with a knife.
Emanuel Proposes Big Hikes In City Fees For River Tour Boats
The decade-long agreement that Emanuel introduced at Wednesday's City Council meeting includes dramatically higher fees expected to generate $42.5 million over the life of the contract.
Teen Kayaker Helps Rescue Man Who Fell In Chicago River
A 17-year-old boy, who was kayaking for the first time, helped rescue a man who fell into the Chicago River on Wednesday.
Sanctuaries in the City: Eight Places to Unwind in Chicago
Even the most urbane of city dwellers needs the occasional respite from the psychic pressure of the concrete jungle. For those without a go-to chill spot, here's a selection of relaxation stations to consider.


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PHOTOS: New Exhibit Highlights Diversity of LGBT Families
BY Alex J Davidson
November 12 2013 6:00 AM ET
Above: Emily Hunt and Sarah Snyder
"At the end of the day, it's really all about love and having a safe place to live and support your loved ones," Christensen says. "This was the central idea and heart of this exhibit, as what matters is 'love, care, and support,' and that this exhibit helps promote and showcase that we are all really the same and need the same things as humans in this life."
Christensen and the center partnered with the Family Equality Council to put on the exhibit. The goal is to expand upon the existing photos in 2014, focusing on gay pride and the celebrations in June.
Tags: Families
most popular


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About This Game
- Summary
- Features
- Game Editions
ATV Quad Kings immerses the player in the world of ATV motocross racing where aggressive driving skills are needed to become the number one ATV rider. There is nowhere to hide -- its dirty, fast, and furious racing! Travel across the globe from the USA to Australia to compete in 18 incredible high adrenaline races in 9 breathtaking locations and that's not all ... perform daring tricks and catch big air to increase your skills and earn extra money!
Storm City Games
- 14 different vehicles to unlock including ATV's and Dune Buggies
- Full 3D racing with 3 modes to compete in
- Win races to earn money to unlock new tracks and vehicles
- Over 35 races to take on, start at 90cc and work your way to 700cc


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Hot answers tagged zoroastrianism
There are only approximately 20,000 Zoroastrians in Iran, which is about 0.026% of the total population. I would not say Zoroastrianism is strong in Iran in terms of the total population. The only way Zoroastrianism can be said to be strong in Iran is because it has the second-largest Zoroastrian population after India (~69,000). See List of countries by ...
Not exactly an expert but I don't think the two religions can be more dis-similar.
Zoroastria is a revealed religion, it has a distinct founder and prophet who historically existed (although whether really a prophet is another question). It's a monotheistic religion - arguably the first.
Hinduism is a collection of much older (potentially several millenia ...
Only top voted, non community-wiki answers of a minimum length are eligible


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Knut Paul Ourom & daughter
A photo of Knut Paul Ourom and his daughter skiing at the newcoming road passing by Våler i Solør before the opening in the seventies. About Knut Paul Ourom: Married to Ragnhild 1950. ... show more
- Album: All photos
- Heart Unheart
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Fresh freeze-dried Bilberry POW-der Description from ECLECTIC INSTITUTE 100% Fresh Freeze-Dried-The classic eye health herb.-130 mg of Anthocyanins per serving. Equal to 520mg of 25% anthocyanin standardized extract (typically 6 capules).-A serving of bilberry pow-der contains all the anthocyanins of a standardized extract plus the complete array of naturally occuring vitamins, minerals & other nutrients.-Numerous studies have shown that bilberry improves visual acuity.-One of nature's top antioxidant fruits, bilberry is also high in fiber and Vitamin C.-Bilberry protects the brain and other organs from oxidative stress.-Freeze-drying is the best method for preserving the complex chemistry, active enzymes and entire matrix of a berry in it's fresh form.-We start and end with whole, raw food.
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Villa for sale in Marbella West, Marbella
Built 1,000m² • 7 Beds • 7 Baths • Terraces 130m² • Plot 2000m² • reference: 606124AE839
Enquire about this propertyProperty Description
This charming luxury villa offers fantastic views over the Marbella area towards the sea. Built to the highest standards on two levels plus a basement with staff quarters, office and home cinema.
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If you've decided to buy a home on the Costa del Sol, but you're not quite sure where, our brief and independently written area guides are a great place to start. But between us we know the region inside out, so whatever you'd like to know, just ask. It's what we're here for!
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Can it be that Fashion Month is almost over? It seems like it flashed past in the wink of an eye, leaving us exhausted shells of our former selves, clutching to little more than dreams of new ways to reinvent our style for the season ahead. Oh, okay, fine. That might be a tad dramatic. But we're thinking Valentino might be thinking along those same lines, as they have given their Paris store on the Avenue Montaigne a makeover.
The space, which boasts the only complete view of the Eiffel Tower from its entrance, is an ocean of calm interior space, sparkly lighting and muted color ways. Think terrazzo marble floors and gray leather in the changing rooms — and that's just the beginning. We're certain that the store cultivates just the right atmosphere to tempt a person to snap up a dramatic red gown or two. How can we resist, after all?
Photo: Courtesy of Valentino