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Multifactorial diseases arise from complex patterns of interaction between a set of genetic traits and the environment. To fully capture the genetic biomarkers that jointly explain the heritability component of a disease, thus, all SNPs from a genome-wide association study should be analyzed simultaneously.
In this paper, we present Bag of Naïve Bayes (BoNB), an algorithm for genetic biomarker selection and subjects classification from the simultaneous analysis of genome-wide SNP data. BoNB is based on the Naïve Bayes classification framework, enriched by three main features: bootstrap aggregating of an ensemble of Naïve Bayes classifiers, a novel strategy for ranking and selecting the attributes used by each classifier in the ensemble and a permutation-based procedure for selecting significant biomarkers, based on their marginal utility in the classification process. BoNB is tested on the Wellcome Trust Case-Control study on Type 1 Diabetes and its performance is compared with the ones of both a standard Naïve Bayes algorithm and HyperLASSO, a penalized logistic regression algorithm from the state-of-the-art in simultaneous genome-wide data analysis.
The significantly higher classification accuracy obtained by BoNB, together with the significance of the biomarkers identified from the Type 1 Diabetes dataset, prove the effectiveness of BoNB as an algorithm for both classification and biomarker selection from genome-wide SNP data.
Source code of the BoNB algorithm is released under the GNU General Public Licence and is available at http://www.dei.unipd.it/~sambofra/bonb.html webcite.
In the past few years, the hereditary component of complex multifactorial diseases has started to be explored through the novel paradigm of Genome-Wide Association Studies (GWASs). A GWAS searches for patterns of genetic variation, in the form of Single Nucleotide Polymorphisms (SNPs), between a population of affected individuals (cases) and a healthy population (controls). The objective of a GWAS is twofold: on the one hand, one searches for the set of SNPs that best explains the hereditary component of the disease (genetic biomarkers); on the other hand, one tries to learn a rule for classifying unknown subjects as cases or controls, given their genetic profile and possibly other environmental covariates [1].
Further applications of GWASs include searching for the genetic predisposition to complex traits, such as height [2] or Body Mass Index [3], or to the responsiveness to a treatment in a randomized trial [4]. The application of GWAS is not limited to human: successful results have been obtained by applying the GWAS framework to animal [5] and plant research [6].
The extremely large numbers involved in a GWAS (millions of SNPs measured for thousands of individuals) have led the vast majority of studies to rely upon single, univariate SNP association tests [7-9]. Multifactorial diseases, however, have an heterogeneous nature, arising from complex patterns of interaction between a set of genetic traits and the environment: to fully capture the optimal set of genetic biomarkers, thus, all SNPs in a GWAS should be analyzed simultaneously in a multivariate framework [10].
In the literature, the few approaches to multivariate SNP analysis on a genome-wide scale mainly rely on two methodological frameworks: penalized logistic regression [10-12] and Bayesian analysis [13]. In the first case, SNPs are modelled as discrete variables from the finite domain {0,1,2} (where 0 usually encodes the homozygous pair of minor alleles, 1 the heterozygous pair and 2 the homozygous pair of major alleles) and a log-additive model of genetic effect on the disease is assumed. In the second case, SNPs are modelled as ternary categorical variables and no assumptions are usually made on pre-specified genetic models.
All methods for the simultaneous analysis of the whole SNP set have to cope with genetic linkage, i.e. the non random association between portions of the genome close to each other, which acts as a confounding factor: in the proximity of a true causal genetic biomarker, several SNPs highly correlated with the biomarker but mildly associated to the disease are often observed [14].
In this work, we present Bag of Naïve Bayes (BoNB), an algorithm for classification and genetic biomarker selection from the simultaneous analysis of genome-wide SNP data. Our algorithm is based on Naïve Bayes (NB) classification [15], thus it relies on contingency table analysis and it does not assume a pre-specified model of genetic effect.
Three strategies are exploited in BoNB to tailor the Naïve Bayes framework to genome-wide SNP data analysis: (a) a bagging of Naïve Bayes classifiers, to improve the robustness of the predictions, (b) a novel strategy for ranking and selecting the attributes used by each bagged classifier, to enforce attribute independence, and (c) a permutation-based procedure for selecting significant biomarkers, based on their marginal utility in the classification process.
BoNB is tested on the WTCCC case-control study on Type 1 Diabetes [7]. In terms of classification performance, assessed through repeated random sub-sampling cross validation and measured with the Matthews Correlation Coefficient [16], BoNB outperforms both a standard Naïve Bayes classifier, trained on the SNPs that reached genome-wide significance in a univariate test, and HyperLASSO, a state-of-the-art penalized logistic regression technique specifically designed for the simultaneous analysis of genome-wide data [10].
Given a dataset X, consisting of n observations (subjects) of p attributes (SNPs), and a set Y of class labels, one for each observation (case/control), a Naïve Bayes Classifier (NBC, [15]) estimates from the dataset a classification rule in the form:
where Y is the random variable representing the class label and X1 . . . Xp are the random variables representing the p attributes.
The classification rule of Equation (1) states that the probability of a subject being in class yk, given a combination of values for the attributes X1 . . . Xp, is equal to the a priori probability of class yk, Pr(Y = yk), times the probability of each attribute given class yk, Pr(Xi|Y = yk): the implicit assumption below this classification rule is that attributes X1 . . . Xp are all conditionally independent given Y.
For categorical attributes, such as SNPs, probability distributions Pr(Y = yk) and Pr(Xi|Y = yk) are represented with conditional probability tables, which are estimated from the data by counting the occurrences of each combination of genotypes and class labels (see Methods for more details).
Our algorithm, Bag of Naïve Bayes (BoNB), consists in an ensemble of Naïve Bayes Classifiers, trained on GWAS data with the procedure known as Bootstrap Aggregating or Bagging [17].
Given a training dataset X, the Bagging procedure starts by computing a set of B Bootstrap replicates of X, i.e. a set {X(1) . . . X(B)} of datasets, each one obtained by sampling n observations with replacement from the training set X [18]. A Naïve Bayes Classifier NBC(b) is then trained on each Bootstrap sample X(b). Class probabilities of unseen subjects, drawn from an independent test set, are then obtained by averaging the output class probabilities computed by each NBC(b) (Figure 1). Such an approach is known to increase the robustness of the predictions [17].
Figure 1. Schematics of the BoNB algorithm: B Bootstrap samples {X(1) . . . X(B)} are drawn from a GWAS training dataset X; B Naïve Bayes Classifiers (NBC) are trained on the Bootstrap samples, with the novel procedure for attribute ranking and selection; predictions of unseen subjects from a GWAS test dataset are carried out independently by each NBC and class probabilities are then averaged; biomarker selection is carried out with the novel permutation-based procedure, exploiting Out-of-Bag (OOB) samples.
Given the binary nature of the case/control classification problem and the frequent unbalance between the number of cases and controls in a GWAS, we decided to rely on the Matthews Correlation Coefficient (MCC, [16]) for assessing classification performance. The MCC is defined as:
where tp, tn, fp and fn stand for true positives, true negatives, false positives and false negatives, respectively.
The MCC is often preferred to standard classification accuracy, i.e. to the proportion of correctly classified examples, because it is not sensitive to class unbalance: the MCC, in fact, ranges from -1 (all examples incorrectly classified) to 1 (all correctly classified) and equals 0 in case of majority classification, i.e. when all labels are assigned to the most represented class.
The conditional independence assumption below the Naïve Bayes classification rule (Equation (1)) is unlikely to hold if all the SNPs of a GWAS are exploited as attributes, because of genetic linkage. Moreover, computing Equation (1) for the whole SNP set can be computationally cumbersome and can lead to numerical and overfitting problems.
We thus developed a procedure for selecting a good set of independent SNPs for each NBC(b): the procedure consists of a ranking step followed by an attribute selection step. In the ranking step, each SNP is given a score, according to its ability in discriminating the subjects in the bootstrap sample X(b). The score is thus defined as the MCC of a Naïve Bayes Classifier, trained and tested on the same set X(b), with the SNP as a single attribute (a precise mathematical description of the Naïve Bayes attribute score is given in Methods). SNPs are then ranked in decreasing order of score.
In the attribute selection step, SNPs are iteratively extracted from the top of the ranked list and added as attributes of NBC(b). Each time a SNP is included as an attribute, the procedure removes from the ranked list all the SNPs that are both close to the SNP on the genome (distance < 1 Mb) and correlated with it (r2 >θ, where r2 is the squared correlation between the two SNPs and θ is a user defined threshold, default = 0.1). Such an approach enforces attribute independence, thus coping with the problems arising from genetic linkage.
Rather than including one SNP at a time, uncorrelated SNPs are added in groups of exponentially increasing size, starting from one SNP and doubling the size at each new addition. New SNPs are added as long as the generalization ability of NBC(b) increases: to estimate the generalization ability, we test each NBC(b) on the corresponding Out-of-Bag sample OOB(b), consisting of all the observations left out from X when sampling X(b), and measure the MCC of the prediction. The exponential increase in the number of added attributes allows BoNB to reach the adequate size for the attribute set of each NBC in a logarithmic number of steps.
The attribute selection procedure, iterated for the B bootstrap samples, results in an ensemble of B Naïve Bayes Classifiers, each with a possibly different set of attributes. Classification of unseen subjects, the first objective of GWASs, is then obtained by averaging the output class probabilities across all NBCs. Classification performance of the ensemble of NBCs can then be assessed on an independent GWAS test set, by measuring the MCC of the predictions.
For the second objective of GWASs, biomarker selection, we adapted for BoNB a procedure originally designed for the Random Forests bagged classifier [19]: for each of the SNPs included as attributes by at least 5% of the NBCs, we randomly permute the genotype of the SNP in the OOB sets, test each NBC(b) on its corresponding OOB(b) and record the relative decrease in MCC due to the permutation. Such a measure, which we define marginal utility (MU), can be used as an indicator of the importance of each selected attribute, given all other selected attributes.
For each SNP, the permutation procedure returns a list of values of MU, one value for each NBC that included the SNP: we test for MUs significantly greater than zero with a one-tailed Wilcoxon signed rank test, selecting as biomarkers the SNPs for which the p-value of the test is lower than 0.05.
The following pseudocode summarizes the training phase and the biomarker selection phase of the BoNB algorithm:
BoNB(X, Y, B, θ)
// Training
1 for b = 1 to B
2 [X(b), OOB(b)] = bootstrap replicate from X
3 for s = 1 to p
4 Compute the contingency table for SNP s from X(b)
5 Compute the Naïve Bayes attribute score of s
6 L(b) = list of SNPs in decreasing order of score
7 Initialize NBC(b) as a Naïve Bayes Classifier with no attributes
8 Extract M = 1 new attributes for NBC(b) from the top of L(b), excluding from future additions all SNPs at distance > 1 Mb and with r2 <θ
9 while MCC of NBC(b), tested on OOB(b) with the new attributes, increases
10 Add the new attributes to NBC(b)
11 Update M = 2 * M
12 Extract M new attributes from the top of L, excluding each time from future additions all SNPs at distance > 1 Mb and with r2 <θ
// Biomarker selection
13 for s in all SNPs selected by at least 5% of the NBCs
14 for b in all NBCs that selected s
15 Permute the genotype of s in OOB(b)
16 Record the Marginal Utility (MU) of s
17 Select as biomarkers the SNPs with MU significantly larger than zero.
For analyzing the computational complexity of BoNB, one can start by noting that, for each b in B, the attribute ranking step (lines 3-6) has complexity O(np) for computing the contingency tables and the scores (where n is the number of subjects and p is the number of SNPs in the dataset) plus O(p log p) for sorting the score list, thus has a total complexity of O[Bpn + Bp log p)].
The attribute selection step (lines 7-12), executed for each b in B, has a computational complexity dominated by two operations: computation of the squared correlation coefficient r2 between SNPs and test of NBC(b) on OOB(b). If we define the average number of attributes included by each NBC (which is problem dependent) and the average number of SNPs in a 1 Mb section of the DNA (which is dataset dependent, but is a roughly linear function of p), we can note that the first operation costs O(n) for each SNP pair and is executed times, having thus a total computational complexity of . The second operation, on the other hand, is executed log times, each time with a doubling number of features for NBC(b), and its computational complexity is thus expressed by the following summation:
where is the average number of subjects in an OOB set, tending to (1 - 1/e) · n for large n [18]; the total complexity of the second operation is thus , asymptotically negligible with respect to the cost of computing the squared correlation coefficients. The total computational complexity of the training phase of the BoNB algorithm is thus .
For the complexity of the biomarker selection phase of BoNB, we define the number of SNPs selected by at least 5% of NBCs (which is problem dependent) and note that the inner loop of lines 15-16 is executed at most times; since the cost of the two operations in the loop is linear in n, the biomarker selection phase has a total computational complexity of .
BoNB was tested on the WTCCC case-control study on Type 1 Diabetes [7]: the study examined approximately 2000 T1D cases and 3000 healthy controls. Each subject was genotyped on the Affymetrix GeneChip 500K Mapping Array Set.
We excluded a small number of subjects according to the sample exclusion lists provided by the WTCCC. In addition, we excluded a SNP if (i) it is on the SNP exclusion list provided by the WTCCC; (ii) it has a poor cluster plot as defined by the WTCCC. The resulting dataset consists of 458376 SNPs, measured for 1963 cases and 2938 controls.
The number B of Bootstrap replicates used by BoNB was set to 200 and the threshold θ on r2 for uncorrelated SNPs was set to 0.1. Please see Methods for an analysis of how performance is affected by variations of the parameters B and θ.
Independent train-test set pairs for assessing the classification performance of BoNB were obtained by repeatedly sub-sampling at random 90% of the dataset for training and 10% for testing. The procedure was iterated 10 times and classification performance was assessed with the MCC of the predictions on the test sets. The list of selected biomarkers, on the other hand, was computed on the whole dataset.
Classification performance was compared with the ones obtained by a standard Naïve Bayes Classifier, trained on all the SNPs that reached the significance threshold of 5 × 10-7 (as in [7]) in a single 2df χ2 test of association with a general genetic model, and by HyperLASSO, a logistic regression method for the simultaneous analysis of all SNPs in a genome-wide association study [10]. The former algorithm was chosen to assess the improvement of BoNB both in terms of biomarker selection, with respect to a standard univariate test, and in terms of classification performance, with respect to the algorithm on which BoNB is based. The latter algorithm was chosen because of its best performance among classification and biomarker selection methods for genome-wide data, as reported in [10] and [20], and because of the complete availability of the source code (see Methods for further details on the Naïve Bayes and HyperLASSO algorithms).
On the experimental dataset, BoNB reached an MCC of 0.55 ± 0.03 (mean ± standard deviation), significantly higher than the ones reached by both the standard Naïve Bayes Classifier (0.31 ± 0.05, Wilcoxon signed-rank p-value 0.002) and by HyperLASSO (0.46 ± 0.03, p-value 0.002). Figure 2 (left panel) shows the boxplots of the MCC obtained by the three algorithms on the ten iterations of the sub-sampling procedure. For the sake of completeness, Figure 2 (right panel) shows also the boxplots of classification accuracy. The dashed lines in the two plots represent the classification performance of a majority classifier.
Figure 2. Box plots of MCC (left panel) and classification accuracy (right panel) of the standard Naïve Bayes classifier, HyperLASSO and BoNB on ten random subsamplings of the WTCCC T1D dataset. The dashed lines represent the classification performance of a majority classifier.
To further analyze the behaviour of the three methods at different levels of the output function (i.e. of the output class probability for BoNB and the standard Naïve Bayes classifier and of the logistic regression value for HyperLASSO) we report in Figure 3 the Precision vs Recall curve and the Receiver Operating Characteristic, or True Positive Rate vs True Negative Rate curve, of the three algorithms on one of the ten random subsamplings (the behaviour on the other subsamplings is similar). As it is clear from the figure, the performance of the standard Naïve Bayes classifier is completely dominated by the performance of both BoNB and HyperLASSO. Concerning the two latter algorithms, one can observe that HyperLASSO has a better performance at the two extremities of the curves, i.e. for subjects whose logistic regression value is closer to the maximum or the minimum; moving from the extremities to the middle scores, BoNB outperforms HyperLASSO, being indeed able to reach overall higher MCC and classification accuracy.
Figure 3. Precision vs Recall curve (left panel) and Receiver Operating Characteristic (right panel) of the standard Naïve Bayes classifier, HyperLASSO and BoNB on a random subsampling of the WTCCC T1D dataset.
For biomarker selection, we run BoNB on the whole dataset and compared its results with the biomarkers identified by HyperLASSO and by the general 2df test. The average number of attributes included by BoNB in each NBC was 3.24, 75 SNPs were included by at least one NBC and 9 SNPs by at least 5% of the NBCs (see Table 1). Among the 9 SNPs, only 7 SNPs reached the significance level on the permutation test and were chosen as genetic biomarkers (marked in bold in Table 1). All the 7 selected SNPs fall into regions of interest for Type 1 Diabetes according to the on-line database T1DBase [21] (cytobands p13.2 on chromosome 1 and p21.32 on chromosome 6, also known as the MHC region) and their association with the disease was confirmed in a larger meta-analysis, subsequent to the WTCCC study [9]. The squared correlation coefficients between all pairs of selected SNPs are all lower than 0.155, indicating low redundancy in the information coded by the set of 7 SNPs.
Table 1. SNPs selected as attributes for at least 5% of the Naïve Bayes Classifiers by BoNB on the WTCCC T1D dataset, with B = 200 Bootstrap samples and classifiers.
Compared to the 394 SNPs that reached the significance level on the 2df general test, both the list of 75 SNPs used for classification and the list of 7 biomarkers selected by BoNB are more compact, but this does not prevent BoNB to reach significantly higher classification performance.
HyperLASSO selected 8 SNPs, all in the MHC region of chromosome 6: 4 of the SNPs are among the biomarkers selected by BoNB, thus suggesting a certain coherence between the two algorithms and providing further confidence on the identified biomarkers.
BoNB is implemented in C++ and relies only on standard libraries, thus being fully portable across operating systems. On the WTCCC case-control study on Type 1 Diabetes, BoNB takes approximately 50 minutes for training 200 NBCs and selecting the biomarkers on a 3.00 GHz Intel Xeon Processor E5450. A careful allocation strategy makes BoNB occupy around 600 MB of RAM for the WTCCC dataset, allowing it to be easily run on a desktop computer.
In this paper, we presented a novel algorithm for classification and biomarker selection from genome-wide SNP data. The algorithm, Bag of Naïve Bayes (BoNB), is based on the Naïve Bayes classification framework, enriched by three main features: bootstrap aggregating of an ensemble of Naïve Bayes classifiers, a novel strategy for ranking and selecting the attributes used by each classifier and a permutation-based procedure for selecting significant biomarkers, based on their marginal utility in the classification process.
The effectiveness of BoNB was demonstrated by applying it to the WTCCC case-control study on Type 1 Diabetes: BoNB indeed outperforms two algorithms from the state of the art, namely a Naïve Bayes Classifier and HyperLASSO, in terms of classification performance and all the genetic biomarkers identified by BoNB are meaningful for Type 1 Diabetes.
Learning an ensemble of classifiers from a bootstrap sample of the original dataset provides BoNB with two main advantages: on the one hand, it guarantees a higher generalization ability by increasing the stability of the learning process [17]; on the other hand, it allows to define a measure of the marginal utility of each SNP, given all the other SNPs exploited for classification, and to select significant biomarkers among these SNPs in a sound and statistically principled way.
Two features of the Naïve Bayes Classifier, chosen as building block of the BoNB algorithm, make it rather appealing for genome-wide data analysis: on the one hand, conditional probability table analysis does not assume a pre-specified model of genetic effect, on the other hand, missing values are seamlessly handled by both the learning and the classification procedure.
The idea of bagging Naïve Bayes classifiers has already been proposed in the Random Naïve Bayes algorithm of Prinzie and Van der Poel [22]. The authors suggest, as a means for enforcing independence between the attributes of each NBC, to sample the attributes at random from the whole attribute set. Such an approach, however, is unfit to genome-wide data analysis: the number of informative attributes is largely lower than the total number of attributes and the probability of capturing them by random sampling is thus extremely low.
Our approach to attribute selection, consisting in a univariate ranking step followed by a multivariate selection step, has the advantage of favouring informative attributes, but without the need of pre-selecting fixed sets of attributes or of defining cut-offs on the strength of the association with the disease: attributes, in fact, are added to the classifiers as long as their combined effect on the generalization ability increases.
To provide the reader with further insight on the Naïve Bayes attribute score, exploited in BoNB for univariate attribute ranking, we studied it against the 2df χ2 statistic of association for all the SNPs in the Wellcome Trust Case-Control Study on Type 1 Diabetes (Figure 4).
Figure 4. Naïve Bayes attribute score vs χ2 statistic for all SNPs in the WTCCC T1D dataset.
As it can be seen from the figure, the two measures are in a strong monotonic relation for the majority of SNPs; when used as ranking criteria, thus, they are deemed to return similar ranked lists.
Major exceptions are the points plotted along the two axes of Figure 4. Along the vertical axis lie the SNPs for which the χ2 test can not be run, because at least one of the entries in the SNP contingency table has less than 5 elements. Along the horizontal axis, on the other hand, lie the SNPs that, when used to train a Naïve Bayes Classifier, lead to a majority classifier, i.e. a classifier that always returns the most frequent of the two classes as output: this happens when one of the classes is the most represented for all the three genotypes of a SNP.
Analyzing the extreme behaviours of the two scoring measures provides the key for understanding the main difference between them: while χ2 is designed to capture a difference in SNP frequencies from the frequencies expected under no association between the SNP and the disease, the Naïve Bayes attribute score is meant to select good predictors of the disease, under the Naïve Bayes classification model.
For this reason, the Naïve Bayes attribute score is not much sensitive to small variations of contingency table entries with few or zero elements and thus it does not require a minimum number of elements per entry. On the other hand, it does not reward SNPs with even large differences in frequencies from the case of no association, if one of the two classes is consistently over represented, since such SNPs can not be effective as univariate predictors in the dataset under analysis.
The analysis of genome-wide SNP data for multifactorial diseases mainly suffers from two, intertwined problems: on the one hand, multifactorial diseases are caused by complex patterns of interaction between multiple genetic traits and the environment, on the other hand, genetic linkage confounds the search for genetic biomarkers, because of the non-random association between the true genetic causes and the SNPs in genomic regions close to them. The algorithm we proposed, Bag of Naïve Bayes, proved effective in tackling both of these problems: the simultaneous analysis of all SNPs on a genome-wide scale can capture the sets of SNPs with the strongest joint effect on the disease; the novel procedure for attribute ranking and selection enforces attributes independence, thus discriminating causal SNPs from nearby weaker signals.
Apart from genome-wide association studies, BoNB can also be applied, with minor modifications, to the analysis of SNP data from case/control exome sequencing experiments [23,24]: in this scenario, given the lower average distance between SNPs on the same genes and the consequently stronger effect of genetic linkage, the ability of BoNB to enforce attribute independence would prove even more useful.
Naïve Bayes Algorithm
The Naïve Bayes Algorithm [15] for discrete-valued inputs and binary classification learns the probability distributions of Equation 1 estimating two sets of parameters. The first is:
for each input attribute Xi, each of its possible values xij (J = 3 in case of SNPs) and each of the two possible values yk of Y. The #D {x} operator returns the number of elements in the training set D that satisfy property x.
In addition, the algorithm must estimate the parameters of the prior probability over Y:
where |D| denotes the number of elements in the training set D.
The only tunable parameter of the Naïve Bayes Algorithm is the l term, known in the Bayesian literature as Equivalent Sample Size or Dirichlet Weight. Both for the ensemble of classifiers exploited by the BoNB algorithm and for the standard Naïve Bayes algorithm used in the comparison l was fixed to 1, implementing what is called a Laplace smoothing [15].
Naïve Bayes attribute score
In the BoNB algorithm, SNPs are ranked as candidate attributes of the b-th Naïve Bayes Classifier according to their ability in discriminating the subjects in the Bootstrap replicate X(b); this is estimated for each SNP as the MCC of a Naïve Bayes Classifier, trained and tested on X(b), with the SNP as the single attribute. The rationale for such a measure is to give a higher rank to SNPs that guarantee a lower training error on X(b) when used as attributes.
For a more formal definition of the score, we start by defining the elements of the contingency table for the SNP as in Table 2. Considering that the parameters of a Naïve Bayes Classifier are estimated according to Equations (3) and (4) (presented in the previous section) and that we set the Dirichlet Weight l to 1, we can define the three following inequalities:
and the three corresponding indicator functions I0, I1 and I2, returning 1 if the inequality holds and 0 otherwise. The three inequalities determine the behaviour of the Naïve Bayes Classifier in classifying unseen subjects according to their genotype, by comparing the posterior probabilities of the two classes.
When the same set X(b) is used both for training and for testing, the Naïve Bayes attribute score S can be computed as the MCC of the prediction from Equation (2):
where XOR (·,·) is the boolean operator returning 1 if exactly one of the operands is equal to 1, and 0 otherwise.
Table 2. Contingency table of a SNP, with the genotype codes 0 for the homozygous pair of minor alleles, 1 for the heterozygous pair and 2 for the homozygous pair of major alleles.
HyperLASSO algorithm
The HyperLASSO algorithm [10] is a Bayesian-inspired penalized logistic regression approach exploiting a NEG prior for the attribute weights. The NEG prior is a continuous prior distribution with a sharp mode at zero, which has the effect of shrinking the regression weights heavily when they are near zero. The NEG prior has a shape parameter, which we set to the default value 0.1.
Like all other penalized logistic regression approaches, the HyperLASSO algorithm has a tunable parameter λ controlling the relative weight of the model complexity (i.e. of the number of SNPs included in the classifier) versus the model likelihood. We tested several values of λ, namely 50, 100, 250 and 500, and chose the one leading to the best classification performance on the WTCCC T1D dataset (λ = 250).
The HyperLASSO algorithm has an element of stochasticity, namely in the order with which model parameters are updated in the model selection procedure, and is designed to carry out multiple runs with different orderings and report the best scoring model. For our analysis, we set the number of runs to 10, resulting in approximately 60 hours for processing the entire WTCCC T1D dataset on a 3.00 GHz Intel Xeon Processor E5450.
Effect of parameters variation on the performance of BoNB
The BoNB algorithm exposes two parameters to the user: the number of Bootstrap replicates and Naïve Bayes Classifiers, B, and the threshold on the squared correlation coefficient above which two SNPs are considered correlated, θ.
Figure 5, left panel, represents the MCC obtained by BoNB on ten random subsamplings of the WTCCC T1D dataset, for B = 200 and θ ranging from 0.02 to 0.5. As it is clear from the figure, θ = 0.1 is optimal and results in a significantly higher classification performance (Kruskal-Wallis test p-value 3.7 × 10-4).
Figure 5. Box plots of the MCC obtained by BoNB on ten random subsamplings of the WTCCC T1D dataset, for B = 200 and θ ranging from 0.02 to 0.5 (left panel) and for θ = 0.1 and B ranging from 50 to 500 (right panel).
Concerning the number of Bootstrap replicates B, on the other hand, one can observe from Figure 5, right panel, that classification performance is not much sensitive to variations of B (Kruskal-Wallis test p-value 0.98), though it is slightly higher for B = 50 and 200. Analyzing the list of selected biomarkers, BoNB returns the same seven biomarkers reported in Table 1 for B = 200 and 500, adds SNP rs2856688 to the list for B = 100 and misses SNPs rs6679677 and rs492899 for B = 50.
Given the consistency among the results for higher values of B, suggested values for BoNB parameters are thus θ = 0.1 and B = 200.
List of abbreviations
SNP: Single Nucleotide Polymorphism; GWAS: Genome-Wide Association Study; NBC: Naïve Bayes Classifier; OOB: Out-of-Bag; MCC: Matthews Correlation Coefficient; MU: Marginal Utility.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
FS designed and implemented the BoNB algorithm, carried out its performance analysis and drafted the manuscript. ET carried out the performance analysis of the algorithms for the comparison. BDC participated in the design of both the algorithm and the performance analysis and helped to draft the manuscript. GMT helped to design the performance analysis and to draft the manuscript. CC coordinated the study and helped to draft the manuscript. All authors read and approved the final manuscript.
The research was supported by the European Union's Seventh Framework Programme (FP7/2007-2013) for the Innovative Medicine Initiative under grant agreement n. IMI/115006 (the SUMMIT consortium).
This study makes use of data generated by the Wellcome Trust Case-Control Consortium. A full list of the investigators who contributed to the generation of the data is available from http://www.wtccc.org.uk. Funding for the project was provided by the Wellcome Trust under award 076113 and 085475.
This article has been published as part of BMC Bioinformatics Volume 13 Supplement 14, 2012: Selected articles from Research from the Eleventh International Workshop on Network Tools and Applications in Biology (NETTAB 2011). The full contents of the supplement are available online at http://www.biomedcentral.com/bmcbioinformatics/supplements/13/S14
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Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, Erlich HA, Julier C, Morahan G, Nerup J, Nierras C, Plagnol V, Pociot F, Schuilenburg H, Smyth DJ, Stevens H, Todd JA, Walker NM, Rich SS: Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes.
Nature Genetics 2009, 41(6):703-707. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Hoggart CJ, Whittaker JC, De Iorio M, Balding DJ: Simultaneous Analysis of All SNPs in Genome-Wide and Re-Sequencing Association Studies.
PLoS Genet 2008, 4(7):e1000130. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
He Q, Lin DY: A variable selection method for genome-wide association studies.
Bioinformatics 2011, 27:1-8. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Wu TT, Chen YF, Hastie T, Sobel E, Lange K: Genome-wide association analysis by lasso penalized logistic regression.
Bioinformatics 2009, 25(6):714-721. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Sebastiani P, Solovieff N, Puca A, Hartley SW, Melista E, Andersen S, Dworkis DA, Wilk JB, Myers RH, Steinberg MH, Montano M, Baldwin CT, Perls TT: Genetic Signatures of Exceptional Longevity in Humans.
Science 2010.
Moore JH, Asselbergs FW, Williams SM: Bioinformatics challenges for genome-wide association studies.
Bioinformatics 2010, 26(4):445-455. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Baldi P, Brunak S, Chauvin Y, Andersen CAF, Nielsen H: Assessing the accuracy of prediction algorithms for classification: an overview.
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Breiman L: Bagging Predictors.
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Eichler EE, Flint J, Gibson G, Kong A, Leal SM, Moore JH, Nadeau JH: Missing heritability and strategies for finding the underlying causes of complex disease.
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text:
The ACLU has filed a lawsuit challenging the constitutionality of the National Security Agency's mass collection of Americans' phone records. The complaint argues that the dragnet, justified by the Patriot Act's Section 215, violates the right of privacy protected by the Fourth Amendment as well as the First Amendment rights of free speech and association. The complaint also charges that the program exceeds the authority that Congress provided through the Patriot Act. The lawsuit seeks to end the mass domestic spying and have all of the collected data deleted. In December 2013, a federal judge denied the ACLU's motion for a preliminary injunction and granted the government's motion to dismiss, and we appealed. On May 7, 2015, the Court of Appeals for the Second Circuit ruled that the call-records program violates Section 215 of the Patriot Act.
On June 5, 2013, The Guardian revealed details of the NSA's domestic spying activities, including a secret order from the Foreign Intelligence Surveillance Court (FISC) to Verizon Business Network Services. The order required the company to turn over on "an ongoing daily basis" phone call details including whom calls are placed to and from, when those calls are made, and how long they last. This information, known as metadata, can reveal intimate details about our private lives. The order is part of an ongoing program that continues today. On June 11, the ACLU and NYCLU, both of which are current or recent Verizon Business customers, filed the lawsuit.
Because the NSA's aggregation of metadata constitutes an invasion of privacy and an unreasonable search, it is unconstitutional under the Fourth Amendment. The call-tracking program also violates the First Amendment, because it vacuums up sensitive information about associational and expressive activity.
The Patriot Act's Section 215 – also known as the "business records" provision – allows the FBI to obtain secret court orders from the FISC compelling third parties to produce "any tangible thing" that is "relevant" to foreign intelligence or terrorism investigations. In addition to the constitutional claims above, the lawsuit charges that the executive branch's use of Section 215 goes far beyond what the statute permits. Whatever Section 215's "relevance" requirement might allow, it does not permit the government to cast a seven-year dragnet sweeping up every phone call made or received by Americans.
The ACLU is also currently litigating a Freedom of Information Act lawsuit seeking documents on the government's legal interpretation and use of Section 215, and has also filed a motion with the FISC asking it to release its secret opinions authorizing the NSA program.
The ACLU's 2008 lawsuit challenging the constitutionality of the FISA Amendments Act, which authorized the so-called "warrantless wiretapping program," was dismissed 5–4 by the Supreme Court in February 2013 on the grounds that the plaintiffs could not prove that they had been monitored. The ACLU does not believe the issue of standing to be a problem in ACLU v. Clapper because of the FISC order showing that the NSA is collecting the telephone records of all Verizon Business customers – including the ACLU.
View all of the documents filed in the case
More on NSA surveillance, reform legislation, and other ACLU cases
Case Updates
Appeals court rules call-tracking program unlawful.May 7, 2015
On May 7, 2015, the Court of Appeals for the Second Circuit ruled that the call-records program violates Section 215 of the Patriot Act.
Judge grants government's motion to dismissDecember 27, 2013
A district court judge rules that the government's bulk collection of phone records is lawful under Section 215 of the Patriot Act and under the Fourth Amendment.
Oral argument in challenge to NSA phone spying programNovember 22, 2013
The ACLU argues the case before the U.S. District Court for the Southern District of New York.
Challenge to call-tracking program filed.June 11, 2013
On June 11, 2013, the ACLU and NYCLU file suit challenging the constitutionality of the NSA's phone records program.
Follow The Case
Legal Documents
ACLU v. Clapper - Appeals Court Cuncurring Opinion
ACLU v. Clapper - Appeals Court Ruling
ACLU v. Clapper - ACLU Appeal Reply Brief
ACLU v. Clapper - Government Appeal Brief
ACLU v. Clapper – Amicus Brief of Rutherford Institute in Support of Plaintiffs–Appellants
ACLU v. Clapper – Amicus Brief of Experts in Computer & Data Science in Support of Plaintiffs–Appellants

subset: commoncrawl


text:
White House lifts ban on photos during tours — see the first pics!
Excellent! Presidential candidate Ted Cruz auditions for 'The Simpsons'
Girl Scouts make history by camping out on White House lawn
Chris Christie: Why I'm the most qualified for the White House
What we can learn from Joe Riley, mayor of Charleston for 40 years
Charleston church shooting renews confederate flag debate
Susan Rice: 'No deal' is better than a bad nuclear deal with Iran
Royally sweet! Michelle Obama brought gifts for Prince George and baby Charlotte
Governor Pitbull? See Jeb Bush slow jam the news with Fallon on 'Tonight'
Barbara Bush on 90th birthday: 'I've been the luckiest woman in the world'
'This is a painful time': See what Bristol Palin said about canceled wedding
Bill Clinton as first lady? Obama learns to tweet, teases former president
Bristol Palin's wedding called off, her mom Sarah Palin announces
Karl Rove on Jeb Bush's Iraq comments: He won't make the mistake again
Carly Fiorina jokingly buys SethMeyers.org after criticism
Carly Fiorina, husband talk 2016 with Kathie Lee, Hoda
'The timing couldn't be worse': Chuck Todd on Bridgegate and Chris Christie
Michelle Obama proposes a post-White House plan with David Letterman
Watch this sixth-grade interviewer nudge the leader of the free world 'to get on'
'Clinton Cash' author: Foundation donors got favors
Chris Christie talks presidential prospects, ice cream endorsement on 'Tonight'
Little girl to Michelle Obama: You're too young for 51!
Which woman should be the face of the $20 bill?
From Hillary Clinton to Chris Christie: The week's big politics news on TODAY
CEO who said females shouldn't be president: 'I am a strong woman'
Whoops! Sen. Pat Roberts' 'Let it Go' ringtone interrupts meeting
Chris Christie on 2016: My wife and I 'have not made this decision yet'
CEO on Hillary Clinton: 'A female shouldn't be president'
Chuck Todd grades 2016 presidential campaigners
Hillary Clinton's campaign website error page might just quack you up
Rubio sees differences between himself, Obama in '08, 'friend' Jeb Bush
Kelley Paul on Rand's Savannah Guthrie interview: He has a good relationship with women
Chuck Todd discusses Hillary Clinton rebranding for 2016 bid
What role will Chelsea Clinton play in mom's presidential campaign?
Hillary Clinton: Granddaughter led me 'to speed up' political plans
Rainbow ruler: President Obama delivers a colorful farewell as he leaves Jamaica
Yes, Vice President Joe Biden stole a baby's pacifier
Rand Paul on Iran nuclear deal: 'I'm going to keep an open mind'
President Obama offers campaign advice to Hillary Clinton: She's 'going to do great'
Obama: Climate change may fuel spread of diseases
White House staffers reveal secrets of famous first families in new book
Politics Video


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Childbirth Education Class--Health Central Hospital Location
- 10000 W Colonial Dr, Ocoee, FL
Boot Camp for New Dads @ Seminole County Health Department
Healthy Start Coalition of Orange County
Multiple Dates
Sanford, FL
This is a free guys only class for both new and expecting fathers as well as "veteran" fathers. The one-time, three-hour class provides hands-on experience, and participants learn how to calm a crying baby, how to change a diaper, and more. This relaxed "locker room meets nursery" setting allows participants the opportunity to get answers to all of their questions. Participants receive a Crashcourse for New Dads book and get entered to win a $30 gift card.
The Healthy Start Coalition of Orange County's mission is to improve maternal and child health in Orange County through community partnerships. Our vision is to be the leader in maternal and child health to ensure that all babies have a "healthy start." For more information about Healthy Start and other programs and classes offered, visit us on our website www.healthystartorange.org.
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text:
Mad Bastards on Bulldozers - South Is NZ
View Single Post
Trans-Global Chook Chaser
Joined: May 2004
Location: Rotoiti, New Zealand
Oddometer: 3,584
Cheers guys.
The next morning I went for a spin down the remaining 6km of track to the North-East while Mccardigan relaxed at the hut. It was rougher again & had only seen bike & quad traffic for a while, no 4wds. I crossed Dubious Creek (yes I walked that one 1st
) & got to Stony Flat, the end of the line.
I admired the mighty Mt Tapuae-O-Uenuku (Tappy to his friends) for a bit then buzzed back to Goose Flat.
We got on the track back out the way we had come. After cruising ahead a bit I realised I had lost Chris. The further I went back the more worried I got so I turned up the pace a bit only to have my long suffering panniers finally break a strap. After ziptieing them back on I carried on back & was relieved to find an upright McCardigan. The R80 wasn't in such a happy position though.
A bit of a wobble & a badly placed rut had shot it over the side & into a thorny briar bush. We removed some weight then after much pushing & pulling & sweating & revving got it upright & back on the track.
We followed a slightly different route up the first part of the Heron stream & I popped in to the historic Black Spur Hut for a look.
Then it was up & up around the bluffs & switchbacks to Blind Saddle again.
Looking at the showers moving into the valley below we decided we had timed our exit about right. Some of the steep clay sections of track we had done would be all but impassable in the wet.
After signing out at the road end we rode southwest on the delightfully twisty inland Kaikoura rd to Waiau. After a beer at the pub we installed ourselves in a cabin at the campground. The
Waiau Motor Camp
gets a special mention for the really friendly owners, priority motorcycle parking, great value, & nicely looked after facilities. Then it was back to the pub for a very tasty dinner & a few more ales.
More tomorrow
'03 KTM 640 LC4 Enduro
The wilderness, the desert - why are they not crowded
.................................................. .....
with pilgrims?
View Public Profile
Find More Posts by clintnz


text:
Screen Junkies Breaking News
Relive Iron Man, the adventure that kicked off the Marvel Cinematic Universe, and the film that…we kinda had to do since we've already done the sequels.
About 12 hours ago by Jared Jones
'Hunger Games: Mockingjay – Part 2′ Cast Get Regrettable Face Tattoos
About 9 hours ago by Wookie Johnson
I'd expect this from Woody Harrelson but not from you, Peeta.
Neil Casey Cast As 'Ghostbusters' Villain
About 10 hours ago by Wookie Johnson
No Peter Dinklage?
'Alvin And The Chipmunks: The Road Chip' Will Uptown Munk You Up
About 11 hours ago by Wookie Johnson
I want you to punch me in the face as hard as you can.
Find Out What Happens When You Run 'Fear And Loathing' Through Google's Deep Dream
About 11 hours ago by Wookie Johnson
Ok, So Now Harry Shearer WILL Be Returning To The Simpsons
About 12 hours ago by Penn Collins
But I was just mastering my Montgomery burns audition tape!
Now 'Cosby' Reruns Are Getting Pulled By Networks
About 12 hours ago by Penn Collins
He's officially as popular as the Confederate Flag.
Ruh-Roh: 'Cujo' Remake To Be Titled 'C.U.J.O.'
About 12 hours ago by Wookie Johnson
It's your ass, Mr. Postman!
If You Want To See Jeremy Clarkson Do A Car Show In Britain, You'll Likely Have to Wait Until 2017
About 13 hours ago by Penn Collins
Damn those non-compete clauses!
'Hannibal' Gets No Love From Amazon Or Netflix, May be Dead
About 14 hours ago by Penn Collins
You don't want to say no to Hannibal. He'll do terrible things to you.
Someone ONCE AGAIN Wrote To An Advice Column Pretending To Be A Character From 'The Room'
About 14 hours ago by Penn Collins
That's terrible and awesome.
Andy Garcia And Omar Comin' To 'Ghostbusters' Cast
About 14 hours ago by Wookie Johnson
Neither are set to play ghosts.
Dustin Hoffman Thinks Movies Are Bad Nowadays
Monday, July 6 by Wookie Johnson
We've built an entire website around this belief.
The Director Of 'Selma' Passed On Marvel's 'Black Panther'
Monday, July 6 by Wookie Johnson
Believe it or not.
'Sharknado 3: Oh Hell No' Might Be The One We Can't Contain With Chainsaws
Monday, July 6 by Wookie Johnson
If you see only one Frankie Muniz vs Sharks movie, make it this one.
'The Fresh Prince' GTA V Intro Wins
Monday, July 6 by Wookie Johnson
You get in one little fight (involving a hatchet) and your mom gets scared…
The 5 Greatest Man Caves In Movies And TV
When a man has witnessed a man cave with everything a man could ever want, chances are, he has seen one of these hidden treasures. "They go in, but they...
5 Things Your DVD Collection Says About You
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6 Movie Props Worth More Than Your House
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The 4 Lamest Superhero Cars In Movies
Batman has his trademark
Great MMA Movies Like Never Back Down
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6 Closeted Gay Characters Who Never Came Out Of The Closet
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text:
I'm not an educator either, although I have taught some college courses and a graduate seminar. But that lack of professional activity does not make me hesitate about pontificating concerning the state of education in New York City.After all, I am a native New Yorker and a product of the New York City public school system, as well as the public college system. And while my current educational contacts are limited to those who teach science and environmental education, I think I have a fairly good idea of what is going on, at least from an interested layman's point of view.I have no quarrel with efforts to teach children to read and write well. Nor do I have a problem with efforts to teach them mathematics. And certainly, science education needs a large boost in this country; we are falling behind other industrialized nations.But, these emphases tend to leave out other areas of education which are important, if we are to have citizens who are what used to be called "well-rounded" in their knowledge. I mean the study of art and music.When I was growing up in Elmhurst, I attended PS 102 on Van Horn Street in Elmhurst and then Junior High School 73 in Maspeth, before moving on to Newtown High School. I was in school when the financial situation in the nation and in the city was not one of great prosperity.Nevertheless, there was always art class and there was always music class. It was a given. Such classes were part of the education we received.(An interesting coincidence: In sorting through some old papers recently, I found one of the small monthly "newspapers" published at JHS 73. It mentioned that the principal was not only a pianist, but had played a program of Liszt, Beethoven and Chopin for the students during the music program the previous month. That's how much music was thought of in those "poor" days.)So what happened?Why is it different today, especially in schools in poorer neighborhoods, where children do not have the access to the wonderful art and music venues of our city that are enjoyed by those from more affluent homes? Why can't the education system afford music and art classes throughout the school system on a regular basis?These should not be "fringe" subjects, easily disposable when times get tough. They are part of the basis of a proper education in a democracy and should be available to all.It is especially disheartening to see the lack of universal art and music studies in a city which many of us consider the center of the universe when it comes to so many things. Certainly we are the "culture capital" of the nation - and perhaps of the world. But not all our children benefit from their proximity to these resources. How many of them are made aware and take advantages of our marvelous museums and the many places where music is played?In Elmhurst and in Maspeth, in times of financial problems, art and music were there for me when I grew up. Why should it be different for today's children, when economic times are so much better?We can and must improve this situation. The soul of a city and a nation is not based on tests of English and math alone. We must find a way to bring back art and music for all the students of our great city - and keep it back.There are some hopeful signs: A coalition of parents from three school districts in Brooklyn, calling itself the Brooklyn Education Collaborative, has joined with community groups and two labor unions to push for more music and art classes. It has pointed out that in 29 schools in the three districts with middle grades, 15 have no music classes. Isn't it time for Queens parents to start some action along these lines?(Looking ahead: National Trails Day will be celebrated throughout New York City on Saturday, June 4. To find out about what is going on in Queens, call 311 or visit www.nyc.gov/parks. On Saturday, Sept. 24, from 10 a.m. to 3 p.m., the Alley Pond Environmental Center will hold the "Little Neck Bay Festival," as part of National Estuary Day. To find out about it, call 718-229-4000. I plan to write a column about the day and its local observance at APEC sometime in late summer.)
©2005 Community News Group
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text:
Vince Licata
Vince lost 68 lbs!
Vince lost 68 lbs!
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It was now or never I had to make a change! Which road would I follow?
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So far, I have lost 53 pounds and I have not had this much energy in years. The program is so easy and I am learning healthy habits that will stay with me for the rest of my life. Best of all I did not have to do this alone. I had the caring support of my Health Coach... more
Featuring real Health Coaches, this Discover Take Shape For Life video encapsulates what it means to transform your life and the lives of others by embracing the mission and vision of Take Shape For Life and adopting the Habits of Health.
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text:
22 Free Crochet Patterns: Afghan Patterns, Crochet Hats, and More
Bonus: Get our newsletter & special offers for free. We will not share or sell your email address. View our Privacy Policy
19 Free Baby Afghan Patterns For Knitters
By: Blair Chavis, editor for FaveCrafts.com
We are adding the craft to your Craft Projects.
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Before heading out to your next baby shower, check out these free knit afghan patterns. These 19 Free Baby Afghan Patterns For Knitters can be given as holiday gifts or make especially meaningful presents for new arrivals. These easy afghan patterns don't fit a specific mold - there are free baby blanket knitting patterns for everyone from beginners to experts. Save these ideas for later - you never know when you'll need a baby shower or new mommy gift. Best of all, these items will surely become keepsakes and comfort items for little ones.
There are so many free baby blanket knitting patterns, you might not know where to start. If you're new to knitting, consider working on a solid afghan. Once you've had some practice, move on to more intricate free knit baby blanket patterns. While you're at it, test your skills and try something new - you won't regret it. Show off your work and give your baby blanket knit pattern as a gift or save it and use it for yourself - no one will know that it's actually meant for little ones!
19 Free Baby Afghan Patterns For Knitters
Table of Contents
Solid Free Knitting Afghan Patterns
Multi-Colored Free Knitting Afghan Patterns
Free Knitting Afghan Patterns with Designs
Square-Design Free Knitting Afghan Patterns
Knitters and crocheters alike will fall in love with these 66 Fantastic Free Afghan Patterns + 5 New Crochet Afghan Patterns. There are so many great ideas in this collection, so prepare to spend time working on some quality free baby blanket knitting patterns. The colors and designs make these projects one-of-a-kind and unexpected. Start working on one of these free baby afghan patterns today.
Solid-Colored Free Knitting Afghan Patterns
Don't assume that solid-colored free baby blanket knitting patterns are boring. These projects are pretty and eye-catching but still easy enough for beginners. Follow these free knit baby blanket patterns and discover how fun it is to create your own gifts for baby showers and birthdays. With these projects, you'll learn a bunch of new techniques and tricks.
Multi-Colored Free Knitting Afghan Patterns
Once you've mastered free baby blanket knitting patterns that one use one color of yarn, it's time to move on to more complicated projects. These free knitting afghan patterns aren't too complicated to create, making them ideal for anyone with a little experience. Choose your favorite colors and add a fun persona touch to your work.
Free Knitting Afghan Patterns with Designs
Now it's time to get down to business and really challenge yourself. These free baby blanket knitting patterns aren't just for newborns - the designs and motifs will make them a hit with small children, too. Don't be afraid to step outside the box and try something new. These free knit baby blanket patterns allow you to use the techniques you have while building new skills.
Blue and Yellow Nursery Blanket
Square-Design Free Knitting Afghan Patterns
Get back to basics with these easy afghan patterns. If think squares aren't an exciting look, think again. These free knit baby blanket patterns prove that you don't have to have years of knitting experience to create a beautiful design.
Radiating Squares Baby Blanket
If you like easy afghan patterns then you'll Baby Love, a free eBook from FaveCrafts and Red Heart Yarn. You'll find both crochet projects and free knit baby blanket patterns. Download a copy and get to work on your next fantastic creation.
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text:
Narrow your search
These Bluetooth headphones sold out fast last time, and may do so again now that they're even cheaper. Plus: three bonus deals!
How do you know that the larger-screen phone trend is here in a big way? When you back it up with cold, hard numbers -- like the new Apple iPhones' mega-sales.
A doll-sized humanoid robot has learned how to use a cockpit simulator to fly a light aircraft designed for humans.
"The New World," a digital novel by Chris Adrian and Eli Horowitz, tackles topics like love, grief, memory, and immortality. Special e-book design elements add to the immersive experience.
Twitter has unveiled a new account for a quadcopter drone taking snapshots at the Cannes Lions festival.
Superhero humor, comic book style, and Beth Riesgraf (but not just her). Crave contributor Kelsey Adams explains how a few streamed Web episodes made her a "Caper" crusader.
Everywhere you look, games are going free-to-play, which sounds like a good thing. But sometimes the ways developers try to part you from your money are anything but fun.
Samsung boss JK Shin has taken to calling the Galaxy Note series 'fonblets' instead of phablets, or you know, just big phones.
A German electronics manufacturer has built a giant, fire-breathing robotic dragon that has been awarded the Guinness world record for the world's largest walking robot.
A new 3D printer does away with SLS layering, and is able to print gravity-defying cables in three dimensions.


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Texas A&M Corpus Christi Islanders at Oklahoma Sooners Basketball
Mon, Dec 31, 2012 2:00 pm
Lloyd Noble Center, Norman, OK
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Job Description
KENVOX is experiencing great growth and we have multiple postions available. We are looking for quality Sales Manager, Sales Representative, Business and Marketing Consultant to join our team immediately in our Salt Lake City office. Pls reach us by: email@example.com or call: 650-888 4128; We are OEM manufacturing group owning three state-of-the-art factories in China, specializing in plastic, silicone and metal tooling and their finished products. We offer one-stop turnkey service. We help our customers in all aspects of product development, from the initial idea through to desired finished products. Our products can be found in consumer electronics retailers, automobiles, medical devices, outdoors and sporting goods retailers, hardware stores, home improvement centers and big box retailers. To gain more information, please visit us at: http://www.youtube.com/watch?v=CERDzwda2oQ www.kenvox.com & www.siliconekenvox.com SUMMARY: This is really an excellent opportunity for the right people who want to join us and get plugged into the Chinese manufacturing industry. The right candidates will be Responsible for the development, marketing, and growth of tooling and OEM products through existing B2B client relationships and new growth channels. COMPENSATION: ??? Base Salary of $30k-$45k to start. Great earning potential (up to $300k or more per year) for motivated and energetic individuals. If you can perform you will earn a lot of money. If you can't you'll be terminated. ??? Average commission is 3% on sales orders. ??? Travel allowance. ??? Full business developing training will be provided. EDUCATION REQUIREMENTS: ??? Bachelor???s Degree in Business or Technical Field is preferred. ??? Previous sales,consultant, and marketing experience is preferred. Keywords: sales manager / director, business management,customer support,operation, manufacturing,manufacturer
This is a contract position.
Relocation costs may be covered.
JOB PREREQUISITES: ??? Initiate, develop and foster new and existing B2B client relationships. ??? Identify, prospect and develop new accounts, and business relationships. ??? Aggressively manage and generate sales revenue by developing new business accounts and increasing current account volume levels. ??? Responsible for monitoring the performance of the sales team by establishing a system of reports and communications involving sales reports, cyclical sales meetings, sales newsletters and electronic bulletins. ??? Manage the sales administration function, operational performance reporting, streamlining processes and systems wherever possible, and advising senior management on maximizing business relationships and creating an environment where customer service can flourish. ??? Must have good analytical, statistical and problem solving skills. ??? No Chinese language needed. But must be fluent in English. ??? Good interpersonal/customer relation skills and communications skills. ??? Ability to travel, attend trade show and visit customers at any given time. Keywords: sales manager / director, business management,customer support,operation, manufacturing,manufacturer
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We are conducting interviews.So, please submit your resume immediately at: email@example.com
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I respect Rabbi Yosef's erudition and his brave and sometimes iconoclastic halakhic (Jewish legal) writings.
Anderson carries his erudition lightly, but there's enough scholarship there to make an academic proud.
Our 57 writers otherwise showed an astonishing breadth of interest and erudition, from Babar to The New Larousse Gastronomique.
c.1400, "instruction, education," from Latin eruditionem (nominative eruditio) "an instructing," noun of action from past participle stem of erudire (see erudite). Meaning "learning, scholarship" is from 1520s.


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I am just wondering what influence, if any, the PS4 will have on sales of the Vita. I know there is rumours about a $500 bundle, but it is just that, a rumour.
It seems to me that this is really Sony's last chance to push a "companionship" angle for the Vita and the PS4. Tie those two device in and show how they compliment each other.
It would also be great if you could somehow install Vita games to your PS4 and stream them to your Vita. I have read a few articles suggesting most people play their mobile devices/gaming devices at home, specifically in bed, anyway. This could negate the expensive memory card issue which I think has had a huge negative effect on the Vita.
Thoughts? Ideas? Fears? Hate?
No, please, no hate.


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Pennsylvania Zip Codes
Recent environmental features
Damming Dissent: Community leaders behind bars in Guatemala after opposing hydro projects
(07/02/2015) The Guatemalan government has granted concessions for several hydroelectric dams in the department of Huehuetenango without consulting the local Mayan population or obtaining their consent, activists charge. Communities resisting the dam projects have been experiencing a multi-pronged crackdown, including arrests and at least three murders.
Chinese turtle heist sends rare Philippine species to brink of extinction, international rescue underway
(06/29/2015) On Friday, June 19, Philippine authorities raided a warehouse on the island of Palawan and confiscated more than 4,000 live, illegally harvested rare turtles, only days before they were to be shipped to foreign food and pet markets. The massive haul included over 3,800 critically endangered Philippine forest turtles – animals in very poor health and showing signs of severe neglect from long captivity.
Do we need to move 'beyond certification' to save forests?
(06/25/2015) Over the past two years dozens of companies have established 'zero-deforestation' or 'deforestation-free' policies for the commodities they source, trade, and produce. The pace of adoption has been staggeringly fast for a business that have been historically slow-moving relative to other industries. Some sectors, like the Indonesian palm oil industry and the Brazilian soy industry, even appear to be nearing a critical mass where the majority of international buyers and traders are now bound by such agreements.
Amazon tribe creates 500-page traditional medicine encyclopedia
(06/24/2015) In one of the great tragedies of our age, indigenous traditions, stories, cultures and knowledge are winking out across the world. Whole languages and mythologies are vanishing, and in some cases even entire indigenous groups are falling into extinction. This is what makes the news that a tribe in the Amazon have created a 500-page encyclopedia of their traditional medicine all the more remarkable.
Video: Vet describes emotional toll of responding to brutal rhino poaching
(06/24/2015) In March 2012 poachers struck a South African game reserve. They drugged three rhinos and hacked off their horns, inflicting massive facial trauma to the immobile but unanesthetized animals. Wildlife veterinarian Will Fowlds attended to the victims.
Social-media firestorm defends popular man-eating tiger in India, raising conservation questions
(06/23/2015) On May 8, 56-year-old forest guard Rampal Saini was attacked and killed by a tiger named Ustad with a bite to the neck. Ustad was hugely popular with tourists and had gained a massive online following. But Saini was Ustad's fourth victim in a span of five years, and his death unleashed a heated debate — especially online — about whether the ensuing decision to banish him to captivity was the right one.
New solidarity in struggle to protect Turkey's 'life spaces'
(06/19/2015) Emerging regional and national networks seek to build connections between local communities and provide support to their fights against dams, mines, and other environmental threats.
Can we save the Sumatran rhino? Indonesia holds out hope
(06/19/2015) 'One percent of the world's population,' veterinarian Zulfi Arsan says as he nods towards Bina, a 714-kilogram, 30-year-old female Sumatran rhinoceros leisurely crunching branches whole. A gentle and easygoing rhino, pink-hued Bina doesn't seem to mind the two-legged hominids snapping pictures and awing at her every move at the Sumatran Rhino Sanctuary.
It can be done! – Building better dams in the Andean Amazon
(06/18/2015) More than 150 dams are currently planned for five of the six major Andean tributaries of the Amazon River. Damming those large, free-flowing streams would provide hydropower to half a dozen South American countries – meeting their energy needs for decades to come, but with unknown, potentially calamitous environmental and social impacts.
151 dams could be catastrophic to Amazon ecological connectivity
(06/10/2015) As South American countries begin to move beyond fossil fuels, many are looking to hydropower. The rivers flowing from the Andes Mountains down into the Amazon basin could provide a wealth of liquid potential to meet the energy demands of expanding populations, economies, and development.
Saving the greater sage grouse, the most hotly-debated bird since the spotted owl (PHOTOS)
(06/09/2015) The greater sage grouse -- also known as the sage chicken, sage hen and sage cock -- is North America's largest grouse and an icon of both sagebrush country and the untamed West. But it is rapidly disappearing from the 11 Western U.S. states and two Canadian provinces it calls home.
Bolivia's aggressive agricultural development plans threaten forests
(06/08/2015) Bolivia's government, supported by some small and most large producers, pushes to expand agricultural lands at the expense of the nation's environment. In April 2015, small-scale Bolivian farmers gathered for a summit with stakeholders from a very different part of the agricultural sector: commercial farmers who oversee vast farms and watch international exchange markets just as closely as the weather.
Amid rhinoceros poaching frenzy, dark days for South African society
(06/05/2015) South Africa is in the eye of a global rhino-poaching cyclone, with highly organized and elusive international syndicates running a brisk black-market trade in rhino horn. Public trust is faltering: 'Rhino money buys many people at all levels,' a senior antipoaching official said.
Cajamarca: Let them Eat Gold
(06/03/2015) Mega-dam projects on the main stem of the Marañón River would drown Peru's Breadbasket. The Marañón River is one of the mighty Amazon's most important tributaries. It runs through a region of northern Peru where two of South America's most important bioregions merge: the mountainous highlands of the Andes joining the dense tropical rainforest of the Amazon. It is one of the most biologically rich, rapidly changing and threatened areas of the world.
Photo essay: Polluted, overfished, and choked by weeds, world's second-largest lake is 'on its knees'
(06/02/2015) Lake Victoria is choking with pollution from industrial, agricultural, and human waste. Its problems are compounded by illegal fishing, catching of juvenile fish, and infestations of water hyacinth and the carnivorous Nile perch, which has wiped out many native fish species. Activists say lax law enforcement and a lack of political will are failing the lake, whose fisheries help feed nearly 22 million people.
Have the 'Bandit 6' poached their last toothfish in the Southern Ocean?
(06/01/2015) Last month the Songhua and the Yongding were boarded by authorities in Cape Verde. They were the last of six vessels notorious for poaching toothfish in the waters around Antarctica to be put out of commission in recent months, in large part due to a confrontational campaign by the ocean conservation group Sea Shepherd.
Vaquita porpoises down to 'way less than 100,' Mexican agents shoot fisherman while enforcing new protected area
(05/29/2015) With fewer than 100 individuals alive and dropping fast, the vaquita porpoise is just a swish of the tail away from extinction. In April, alerted by scientists that the vaquita population had recently suffered its biggest decline ever, the Mexican government announced an emergency two-year ban on gillnet fishing across the porpoise's main habitat in the upper Gulf of California. A frenzied race to fish for another critically endangered species, the totoaba, is behind the plummeting porpoise numbers.
GAR, Wilmar punish palm oil supplier for clearing rainforest in New Guinea
(05/28/2015) Palm oil trader Golden Agri-Resources announced today that it would suspend purchases of crude palm oil from plantation developer Austindo Nusantara Jaya Agri, which was outed in an NGO report last week for the third time in the past year for clearing forest in Indonesia's West Papua province, in violation of Golden Agri's no-deforestation commitment. Wilmar has also frozen its dealings with the company, though Asian Agri and Musim Mas, which also buy from it, have given no indication they will do the same.
Drone Herders: Tanzanian rangers and researchers use UAVs to protect elephants and crops
(05/27/2015) HEC, otherwise known as human elephant conflict, is a centuries-old problem responsible for the deaths of untold numbers of elephants. This ongoing battle between African farmers trying to grow crops and hungry elephants foraging for a meal, has motivated conservationists to find solutions for protecting the largest and one of the most intelligent land animals on the planet. Scientists' most recent effort -- Unmanned Aerial Vehicles (UAVs), frisbee-sized remote controlled quad-helicopters -- may provide the answer that researchers have been looking for.
Can improved oil palm productivity and Indonesia's forestry moratorium go hand in hand?
(05/27/2015) An op-ed from Mongabay-Indonesia chief editor Ridzki R. Sigit, who calls for renewed efforts to boost smallholder productivity on Indonesia's oil palm plantations in the wake of the renewal of the country's moratorium on new concessions in primary forests and on peat.
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The Dreams of Grandeur Paperwallet is a triple threat that combines recyclable materials, hot art, and simple functionality. This playful, tear- and water-resistant wallet is made from fully recyclable Tyvek, which makes it one of the most eco-friendly wallets out there. The durable, paper-thin design expands to fit your needs, slips right into your back pocket, and prevents butt bulge. The enticing design effortlessly fuses street art and fantasy, decked with a sexy siren with a penetrating gaze.
Includes 2 credit card slots, 2 business card flaps, 2 easy access pockets, and 1 cash compartment. Fits 12+ credit cards. Paper-thin, tear-resistant, and water-resistant. Made from Tyvek, a recyclable material.
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Open: H 3.15" W 7.88" D 0.125"
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DUI Checkpoints
DUI checkpoints are a common tool used to apprehend drunk drivers in Los Angeles, Orange County, Riverside, San Diego and throughout California. Law enforcement agencies modeled this approach on the success of roadside safety checks and license/registration inspections. In this process the police agency will set up a DUI checkpoint on a highway and if the selected driver's speech sounds slurred or his breath smells of alcohol, he will be asked to leave the car and perform a field sobriety tests at the scene.
In 1990, the United States Supreme Court reversed a state supreme court decision that declared DUI sobriety checkpoints unconstitutional. In Michigan Department of State Police v. Sitz, 496 U.S. 444 (1990), the Court held that the DUI checkpoint operation in question did not violate the Fourth Amendment's prohibition against unreasonable searches and seizures.
The Court's 6-3 decision authored by Chief Justice Rehnquest was not an unexpected result. The ruling recognized that DUI checkpoints do constitute a "seizure" within the bounds of the Fourth Amendment, but the Chief Justice reasoned that the intrusion on individual liberties must be weighed against the need and effectiveness of the DUI roadblock. In the end, the interests in reducing alcohol-related fatalities outweighed the intrusion on human privacy rights and sobriety checkpoints were deemed constitutionally acceptable.
Confronted with a case involving a DUI checkpoint, DUI lawyers must consider the adequacy of the procedures employed: Was the sobriety checkpoint conducted in a constitutionally permissible manner? Even Chief Justice Rehnquist implicitly acknowledged that there must exist "guidelines" concerning such matters as location, publicity, and roadblock operation. Note that in Sitz the DUI roadblock was set up only after a "Sobriety Checkpoint Advisory Committee" had been appointed to establish guidelines; this committee consisted of representatives of the state police, local police, prosecutors, and the University of Michigan Transportation Research Institute.
But what are the "guidelines" for a DUI checkpoint? Rehnquist's opinion in Sitz leaves the question of minimal adequacy of such standards unanswered, presumably to be determined on a case-by-case basis. Counsel may find some guidance in the decisions of sister states. In one of the most influential of these pre-Sitz cases, the California Supreme Court set forth what it felt to be the procedural safe-guards required for a DUI sobriety checkpoint to comply with the Constitution. Ingersoll v. Palmer, 743 P.2d 1299 (Cal. 1987).
For information on where DUI checkpoints are being scheduled near you, review the following resources:
California DUI Checkpoints: Recent Alerts
A general but abbreviated listing of sobriety checkpoints planned for locations throughout the State of California. Note: for more detailed listings, refer to the Recent Alerts for the specific counties listed below.
Current California DUI Checkpoint Locations
A very partial list of alerts on Facebook for some sobriety checkpoints scheduled in California primarily in Central and Southern California.
Los Angeles DUI Checkpoints: Recent Alerts
A current and much more comprehensive list of roadblocks scheduled in Los Angeles County. The site, duiblock.com, also offers monthly subscriptions for DUI checkpoint alerts via yet and email.
Orange County DUI Checkpoints: Recent Alerts
Another extensive list of planned sobriety checkpoints, this one for the Orange County area.
Riverside DUI Checkpoints: Recent Alerts
A similar listing of future and recent checkpoints for Riverside County from duiblock.com.
San Bernardino DUI Checkpoints: Recent Alerts
Current list of DUI sobriety checkpoints planned for San Bernardino County.
San Diego DUI Checkpoints: Recent Alerts
Another set of fairly complete schedules from duiblock.com for sobriety checkpoints, these planned for San Diego County.
Latest DUI Checkpoint Locations
This Twitter site provides Tweets for scheduled checkpoint locations, with an emphasis on California, Ohio and Florida.
Latest Orange County DUI Checkpoints
A similar Twitter site but focusing on Orange County, California.
What is the Purpose of DUI Checkpoints?
Are DUI sobriety checkpoints effective at detecting and arresting drunk drivers or are they used primarily as a deterrence and to raise revenue? See also, Police Department Explains Real Purpose of DUI Roadblocks.
Sobriety Checkpoint Issues
A discussion of the constitutionality and merits of sobriety roadblocks from alcohol abuse expert Dr. David J. Hanson, Ph.D.
Sobriety Checkpoints
An extensive coverage on Wikipedia of the factual and legal issues concerning drunk driving roadblocks: overview, legality, procedures and effectiveness.
US Supreme Court Decision on Sobriety Checkpoints
Summary of the landmark case of Michigan vs, Sitz, upholding the legality of DUI checkpoints, from the largest DUI information website on the internet, DUICenter.com.
National Sobriety Checkpoint Laws
A summary chart from the Governors Highway Safety Association of the sobriety checkpoint laws of 38 states: use of checkpoints, frequency and legality.
The simple fact is that DUI checkpoints are largely wastes of police resources and taxpayer money not to mention unjustified invasions of privacy. In fact, in the United States Supreme Court decision upholding their constitutionality, a dissenting justice pointed out the the findings of the trial court, based on an extensive record and affirmed by the Michigan Court of Appeals, indicate that the net effect of sobriety checkpoints on traffic safety is infinitesimal and possibly negative.
This is confirmed by the federal governments National Highway Traffic Safety Administration studies, which conclude that the number of DWI arrests made by the roving patrol program was nearly three times the average number of DWI arrests made by the DWI checkpoint programs.


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The Rogue And The Wolf are the two tale heroes your parents never read you about. They'll growl their way into your heart to steal what you have sealed inside only to return it round your neck or in your pocket
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