text:
Volume 13 Supplement 10
Selected articles from the 7th International Symposium on Bioinformatics Research and Applications (ISBRA'11)
Efficient error correction algorithms for gene tree reconciliation based on duplication, duplication and loss, and deep coalescence
- Ruchi Chaudhary1,
- J Gordon Burleigh2 and
- Oliver Eulenstein1Email author
© Chaudhary et al. licensee BioMed Central Ltd. 2012
Published: 25 June 2012
Gene tree - species tree reconciliation problems infer the patterns and processes of gene evolution within a species tree. Gene tree parsimony approaches seek the evolutionary scenario that implies the fewest gene duplications, duplications and losses, or deep coalescence (incomplete lineage sorting) events needed to reconcile a gene tree and a species tree. While a gene tree parsimony approach can be informative about genome evolution and phylogenetics, error in gene trees can profoundly bias the results.
We introduce efficient algorithms that rapidly search local Subtree Prune and Regraft (SPR) or Tree Bisection and Reconnection (TBR) neighborhoods of a given gene tree to identify a topology that implies the fewest duplications, duplication and losses, or deep coalescence events. These algorithms improve on the current solutions by a factor of n for searching SPR neighborhoods and n2 for searching TBR neighborhoods, where n is the number of taxa in the given gene tree. They provide a fast error correction protocol for ameliorating the effects of gene tree error by allowing small rearrangements in the topology to improve the reconciliation cost. We also demonstrate a simple protocol to use the gene rearrangement algorithm to improve gene tree parsimony phylogenetic analyses.
The new gene tree rearrangement algorithms provide a fast method to address gene tree error. They do not make assumptions about the underlying processes of genome evolution, and they are amenable to analyses of large-scale genomic data sets. These algorithms are also easily incorporated into gene tree parsimony phylogenetic analyses, potentially producing more credible estimates of reconciliation cost.
The availability of large-scale genomic data from a wide variety of taxa has revealed much incongruence between gene trees and the phylogeny of the species in which the genes evolve. This incongruence may be caused by evolutionary processes such as gene duplication and loss, deep coalescence, or lateral gene transfer. The variation in gene tree topologies can be used to infer the processes of genome evolution. Gene tree - species tree (GT-ST) reconciliation methods seek to map the history of gene trees into the context of species evolution and thus potentially link processes of gene evolution to phenotypic changes and diversification. Yet these methods can be confounded by error in the gene trees, which also may cause incongruence between the gene and species topologies. We introduce efficient algorithms to correct gene tree topologies based on the gene duplication, duplication and loss, or deep coalescence cost models. The algorithms work by identifying the small rearrangements in the gene trees that reduce the reconciliation cost. They are extremely fast and thus amenable to analyses of enormous genomic data sets.
Perhaps the most commonly used and computationally feasible approach to GT-ST reconciliation is gene tree parsimony, which seeks to infer the fewest evolutionary events (e.g., duplication, loss, coalescence, or lateral gene transfer) needed to reconcile a gene tree and species tree topology [1]. This approach also can be extended to infer species phylogenies, finding the species tree that implies the fewest evolutionary events implied by the gene trees (e.g., [2–4]). However, the gene trees often are estimated using heuristic methods from short sequence alignments, and consequently, there is often much error in the estimated gene tree topologies. Error in the gene trees creates more GT-ST incongruence and can radically affect GT-ST reconciliation analyses, implying far more duplications, duplications and losses, or deep coalescence events than actually exist. For example, Rasmussen and Kellis [5] estimated that error in gene tree reconstruction can lead to 2-3 fold overestimates of gene duplications and losses. Gene tree error also can erroneously imply large numbers of duplications near the root of the species tree [6, 7], and it can mislead gene tree parsimony phylogenetic analyses (e.g., [8–10]).
Several approaches have been proposed to address gene tree error in GT-ST reconciliation. First, questionable nodes in a gene tree or nodes with low support may be collapsed prior to gene tree reconciliation, and the resulting non-binary gene trees may be reconciled with species trees [11–13]. Similarly, GT-ST reconciliations can use a distribution of gene tree topologies, such as bootstrap gene trees, rather than a single gene tree estimate [6, 14, 15]. Both of these approaches may help account for stochastic error and uncertainty in gene tree topologies, but they do not explicitly confront gene tree error. Methods also exist to simultaneously infer the gene tree topology and the gene tree reconciliation with a known species tree [5, 16]. While these sophisticated statistical approaches appear very promising, they are computationally intensive, and it is unclear if they will be tractable for large-scale analyses. Another, perhaps a more computationally feasible, approach is to allow a limited number of local rearrangements in the gene tree topology if they reduced the reconciliation cost [17, 18].
Previously [17, 18] described a method to allow NNI-branch swaps on selected branches of a gene tree to reduce the reconciliation cost. Following [17, 18], we address gene tree error in the reconciliation process by assuming that the correct gene tree can be found in a particular neighborhood of the given gene tree. We describe this approach for the gene duplication, duplication and loss, and deep coalescence models, which identify the fewest respective events implied from a given gene tree and given species tree. This neighborhood consists of all trees that are within one edit operation of the gene tree. While [17, 18] use Nearest Neighbor Interchange (NNI) edit operations to define the neighborhood, we use the standard tree edit operations SPR [19, 20] and TBR [19], which significantly extend upon the search space of the NNI neighborhood. The SPR and TBR local search problems find a tree in the SPR and TBR neighborhood of a given gene tree, respectively, that has the smallest reconciliation cost when reconciled with a given species tree. Using the algorithm from Zhang [21] the best known (naïve) runtimes are O(n3) for the SPR local search problem and O(n4) for the TBR local search problem, where n is the number of taxa in the given gene tree. These runtimes typically are prohibitively long for the computation of larger GT-ST reconciliations. We improve on these solutions by a factor of n for the SPR local search problem and a factor of n2 for the TBR local search problem. This makes the local search under the TBR edit operation as efficient as under the SPR edit operation, and it provides a high-speed gene tree error-correction protocol that is computationally feasible for large-scale genomic data sets.
We also evaluated the performance of our algorithms using the implementation of SPR based local search algorithms. Note, that the SPR neighborhood is properly contained in the TBR neighborhood for any given tree. Thus the performance of the SPR based program provides a conservative estimate of the performance of the TBR based program. We test our programs on a collection of 106 yeast gene trees, some of which contain hundreds of leaves, and we demonstrate how it can be easily incorporated into large-scale gene tree parsimony phylogenetic analyses.
Basic notation and preliminaries
Throughout this paper, the term tree refers to a rooted full binary (phylogenetic) tree.
Let T be a tree. The leaf set of T is denoted by Le(T). The set of all vertices of T is denoted by V(T) and the set of all edges by E(T). The root of T is denoted by Ro(T). The set of internal vertices of T is I(T):= V(T)\Le(T).
Given a vertex v ∈ V(T), we denote the parent of v by Pa T (v). Let u := Pa T (v). The edge that connects v with u is written as (u, v). The first element in the pair is always the parent of the second element. The set of all children of v is denoted by Ch T (v) and the children are called siblings. For w ∈ Ch T (v), the sibling of w is denoted by Sb T (w).
We define ≤ T to be the partial order on V(T) where x≤ T y if y is a vertex on the path between Ro(T) to x, and write x < T y if x ≤ T y and x ≠ y. The least common ancestor of a non-empty subset L ⊆ V(T), denoted as LCA T (L), is the unique smallest upper bound of L under ≤ T . Given x, y ∈ V(T), d T (x, y) denotes the number of edges on the unique path between x and y in T.
Given U ⊆ V(T), we denote by T(U) the unique rooted subtree of T that spans U with the minimum number of vertices. Furthermore, the restriction of T to U, denoted by T|U, is the rooted tree that is obtained from T(U) by suppressing all non-root vertices of degree two. The subtree of T rooted at u ∈ V(T), denoted by T u , is defined to be T|U, for U:= {v ∈ Le(T): v ≤ T u}. Two trees T1 and T2 are called isomorphic if there exists a bijection between the vertex sets of T1 and T2 which maps a vertex u1 of T1 to vertex u2 of T2 if the subtree rooted at u1 in T1 has the same leaf set as the subtree rooted at u2 in T2. If an isomorphism exists between T1 and T2, we write T1 ≃ T2.
Given function f : A → B, we denote by f(A') where A' ⊆ A a set of images of each element in A' under f.
The reconciliation cost models
A species tree is a tree that depicts the branching pattern representing the divergence of a set of species, whereas a gene tree is a tree that depicts the evolutionary history among the sequences encoding one gene (or gene family) for a given set of species. We assume that each leaf of the gene tree is labeled with the species from which that gene was sampled. Let G be a gene tree and S a species tree. In order to compare G with S, we require a mapping from each gene g ∈ V(G) to the most recent species in S that could have contained g.
Definition 1 (Mapping). The leaf-mapping ℒ G,S : Le(G) → Le(S) is a surjection that maps each leaf g∈ Le(G) to that unique leaf s ∈ Le(S) which has the same label as g. The extension ℳ G,S : V(G) → V(S) is the mapping defined by ℳ G,S (g):= LCA(ℒ G,S (Le(G g ))). For convenience, we write ℳ(g) instead of ℳ G,S (g) when G and S are clear from the context.
Definition 2 (Comparability). Given trees G and S, we say that G is comparable to S if a leaf-mapping ℒ G,S (g) is well defined.
Throughout this paper we use the following terminology: G is a gene tree that is comparable to the species tree S through a leaf-mapping ℒ G,S , and n is the number of taxa present in both input trees.
Now we define different reconciliation costs from G to S for a given mapping ℳ G,S that extends ℒ G,S . The reconciliation cost are based on the models of gene duplication [22, 23], duplication-loss [21], and deep coalescence [21].
Definition 3 (Duplication cost).
The duplication cost from g ∈ V(G) to S,
The duplication cost from G to S, .
Definition 4 (Duplication-loss cost).
The loss cost from g ∈ V(G) to S,
The duplication-loss cost from G to S,.
Definition 5 (Deep coalescence cost).
The number of lineages from g ∈ V(G) to h ∈ Ch(g) in S,
The deep coalescence cost from G to S, .
The error-correction problems
Here we give definitions for tree rearrangement operations TBR [19] and SPR [19, 20], and then formulate the Error-Correction problems that were motivated in the introduction.
Definition 6 (Tree Bisection and Reconnection (TBR)). Let T be a tree. For this definition, we regard the planted tree Pl(T) as the tree obtained from adding the root edge{r, Ro(T)} to E(T), where r ∉ V(T).
- 1.
If x ≠ Ro(X) then suppress Ro(X) and create a new root by subdividing edge (Pa(x), x).
- 2.
Subdivide edges (Pa(y), y) by introducing a new vertex y'.
- 3.
Re-connect components X and Y by adding edge f = (y', Ro(x).
- 4.
Suppress the vertex u, and rename vertex y' as u.
- 5.
Contract the root edge.
- 1.
TBR G (v, x) := ∪ y∈Y TBR G (v, x, y)
- 2.
TBR G (v) := ∪ x∈X TBR G (v, x)
- 3.
TBR G := ∪(u, v)∈E(G)TBR G (v)
We define the following neighborhoods for the SPR operation:
1. SPR G (v) := ∪ y∈Y SPR G (v, y)
2. SPR G := ∪(u, v)∈E(G)SPR G (v)
We now state the SPR based error-correction problems for duplication (D), duplication-loss (DL), and deep coalescence (DC). Let Γ ∈ {D, DL, DC}.
Problem 1 (SPR based error-correction for Γ (SEC-Γ))
Instance: A gene tree G and a species tree S.
Find: A gene tree G* ∈ SPR G such that .
The TBR based error-correction for Γ (TEC-Γ) problems are defined analogously to the SPR based error-correction for Γ (SEC-Γ) problems.
Solving the SEC-Γ problems
In this section we study the SPR based error-correction problems, for duplication (D), duplication-loss (DL), and deep coalescence (DC), in more detail. Our efficient solution for these problems are based on solving restricted versions of these problems efficiently. For each Γ ∈ {D, DL, DC} we first define a restricted version of the SEC-Γ problem, which we call the restricted SPR based error-correction for the Γ (R-SEC-Γ) problem.
Problem 2 (Restricted SPR based error-correction for (R-SEC-Γ))
Instance: A gene tree G, a species tree S, and v ∈ V(G).
Find: A gene tree G* ∈ SPR G (v) such that .
Observation 1. Let Γ ∈ {D, DL, DC}. Given a gene tree G and a species tree S, the SEC- Γ problem can be solved as follows: (i) solve the R-SEC- Γ problem for every v ∈ V(G) where v ≠ Ro(G), (ii) under all solutions found return a minimum scoring gene tree G*.
Naïvely, the R-SEC-Γ problem can be solved in Θ(n2) time by computing the cost for each G' ∈ SPR G (v). The cost for a given gene and species tree can be computed in Θ(n) time [21]. We introduce a novel algorithm for the R-SEC-Γ problem that improves by a factor of n on the naïve solution. This speedup is achieved by semi-ordering the trees in SPR G (v), for each v ∈ V(G), such that the score-difference of any two consecutive trees in this order can be computed in constant time.
Ordering the trees in SPR G (v)
Consider a graph on trees in SPR G (v), in which every two adjacent trees are one NNI [19] operation apart. We show that such a graph is a rooted full binary tree, after providing necessary definitions.
Definition 8 (Nearest Neighbor Interchange (NNI)). We define the NNI operation as a special case of the SPR operation. Let e ∈ E(T) where e := (u, v), and X and Y be the connected components that are obtained by removing edge e from T such that v ∈ X and u ∈ Y. We define NNI T (v) to be SPR T (v, y) for y:= Pa(u), and say that NNI T (v) is obtained from T by performing nearest neighbor interchange (NNI) operation that prunes subtree T v and regrafts it above the parent of v's parent. (See Figure 2(b).)
Definition 9 (NNI distance). Let the NNI-distance, denoted as d NNI (T1, T2), between two trees T1 and T2 over n taxa be the minimum number of NNI operations required to transform T1 into T2.
Definition 10 (NNI-adjacency graph). The NNI-adjacency graph, denoted as , is the graph where V = SPR G (v) and {T1, T2} ∈ E if d NNI (T1, T2) = 1.
Lemma 1. is a tree.
Proof. We prove it by showing that there exists a unique path between every two vertices in . Let G', G'' ∈ V(), thus G', G'' ∈ SPR G (v). Let G':= SPR G (v, x1) and G'':= SPR G (v, x2). We use induction on d G (x1, x2). Let d G (x1, x2) = 1 and assume without loss of generality that x2 = Pa G (x1). Thus, G'' = NNI G'' (Sb(x1)). So the hypothesis holds for d G (x1, x2) = 1. Assume now that the hypothesis is true for d G (x1, x2) ≤ k and suppose d G (x1, x2) = k + 1. Since G is a tree, there must be a unique path between x1 and x2; let y be a vertex on this path. Let d G (y, x1) = 1, and G n := SPR G (v, y). If y = Pa G (x1), then G n = NNI G' (v); otherwise G n = NNI G' (Sb(y)). Since d G (y, x2) = k, thus (by induction hypothesis) the hypothesis is valid for d G (x1, x2) = k + 1. □
Theorem 1. is a rooted full binary tree.
Proof. In view of Lemma 1, it suffices to show that except a unique vertex of degree 2 all other vertices in are of degree 1 or 3. Let G' ∈ V(), thus G' = SPR G (v, y) for some y ∈ V(G). There are three cases:
Case 1: y is a root. Let y1 ∈ Ch G (y). Let G1 := SPR G (v, y1), thus ). Hence {G1, G'} ∈ E(). Since |Ch G (y)| = 2, G' must be a degree 2 vertex in .
Case 2: y is a leaf. Let y1 = Pa G (y). Let G1 := SPR G (v, y1), thus G1 = NNI G' (v). Hence {G1, G'} ∈ E(), and consequently, G' is a degree 1 vertex in .
Case 3: y is an internal vertex. Let y1 = Pa G (y) and y2 ∈ Ch G (y). Let G1 := SPR G (v, y1), thus G1 = NNI G' (v). Let G2 := SPR G (v, y2), thus G' = NNI G 2 (v). Since y has one parent and two children in G, thus G' is a degree 3 vertex in .
This completes the proof.
The score difference of consecutive trees in
To solve the R-SEC-Γ problems we traverse tree . Two adjacent trees in V() are one NNI operation apart. We show that score of a tree can be computed in constant time from the LCA computation of its adjacent tree.
Let e := (G', G'') be an edge in . Let x := Pa(v), y := Sb(v), and z, z' ∈ Ch(y) in G' (see Figure 2(b)). Without loss of generality, let G'':= NNI G' (z). (Observe, G'' is similar to of Figure 2(b).)
Lemma 2. ℳ G'',S (y) = ℳ G',S (x).
Proof. From NNI operation, v, z' ∈ Ch G'' (x) and z, x ∈ Ch G'' (y). Also, , so . Thus, . □
Lemma 3. ℳ G'',S (w) = ℳ G',S (w), for all w ∈ V(G')\{x, y}.
Proof. For , since , therefore ℳ G',S (g) = ℳ G'',S (g). Also, except for subtree , the rest of the tree remains the same in . Thus by Lemma 2, ℳ G',S (Pa G' (x)) = ℳ G'',S (Pa G'' (y)). Inductively, ℳ G',S (g) = ℳ G'',S (g), for all g ∈ V(G')\V(G' x ). □
Lemma 4. ℳ G'' , S (x) = LCA(ℳ G',S (v), ℳ G', S (z')).
Proof. From Lemma 3, ℳ G'',S (v) = ℳ G',S (v) and ℳ G'',S (z') = ℳ G',S (z'). Thus, ℳ G'',S (x) = LCA(ℳ G'',S (v),ℳ G'',S (z')) = LCA(ℳ G',S (v),ℳ G',S (z')). □
Lemma 5. , for all g ∈ V(G'')\{x, y} and Γ ∈ {D, DL, DC}.
Proof. The gene duplication and loss status of a vertex, and the number of lineages from a vertex to its children in G' can change in G'' if its mapping or mapping of any of its children changes in ℳ G'',S . From Lemma 3, and also, since ℳ G'' , S (w) = ℳ G',S (w), for w ∈ Ch(Pa G' (x)), must have . Thus the Lemma follows. □
Let e := (G', G'') ∈ E() and Γ ∈ {D, DL, DC}. We define with respect to the given species tree S. Observe that this score can be negative too. We study how Γ e can be computed efficiently for each edge e in .
Theorem 2. .
Proof .
Definition 11. Let , and let P G' be a path from to G' in . For G', we define the score-difference as .
Theorem 3. For given S, G, and v ∈ V(G), the tree G' ∈ V() is the output of a R-SEC-Γ problem iff .
Proof. Let . We prove that G' is the output of R-SEC-Γ problem. Since , thus G' gives the minimum normalized score over all trees in V(). Hence, G' must be the output of the R-SEC-Γ problem. The other direction follows similarly. □
The algorithm
We describe a general algorithm, called Algo-R-SEC-Γ, to solve the R-SEC-Γ problem for each Γ ∈ {D, DL, DC}. Initially Algo-R-SEC-Γ computes (i) the root vertex of the NNI-adjacency graph , which we call , by regrafting the subtree G v above the root of G, (ii) the LCA mapping from to S, and (iii) the Γ score from to S. Then recursively Algo-R-SEC-Γ computes the LCA mapping and Γ score for every vertex G' in when the LCA mapping and Γ score of its parent vertex in is known. Algorithm 1 details Algo-R-SEC-Γ.
Algorithm 1 - Algo-R-SEC-Γ
Input: A gene tree G, a species tree S, and v ∈ V(G)
Output: A tree G* ∈ SPR G (v) such that
01. Compute by pruning G v and regrafting at Ro(G)
02. Compute LCA mapping
03. Call
04. Set , BestScore = 0
05. Set , , ,
06. For each in preorder traversal of , do
07. If not backtracking, then
08. Set x = Pa G' (v), y = Sb G '(v)
09. Set G'' = NNI G' (Sb G' (k))
10. Set ℳ G''.S = ℳ G',S , ℳG'', S (y) = ℳ G',S (x)
11. ℳ G'',S (x) = LCA(ℳ G',S (k),ℳ G',S (v))
12. Call
14. If, then
15. Set BestTree = G'',
17. Set
18. Set G'' = NNI G' (v)
19. Set
20. Set
21. Call
22. Set
23. Set
24. Return BestTree
Algorithm 2 - Algo-Comp-Score
Input: A gene tree G, a species tree S, and LCA mapping ℳ G,S
01. score = 0
02. For each g ∈ I(G) in preorder traversal of G, do
04. If Γis DC, then
05. score = score - |I(S)|
06. Return score
Algorithm 3 - Algo-G-Score
Input: A gene tree G, a species tree S, LCA mapping ℳ G ,S, and g ∈ I(G)
Output:(G, S, g)
01. If Γ is D, then
02. If ℳ(g) ∈ ℳ(Ch(g)), then
03. Return 1
04. ElseIf Γis DL, then
06. If ℳ(g) ∈ ℳ(Ch(g)), then
07. Return ls + 1
08. Else
09. Return ls
10. Else // Γ is DC
11 Return
Lemma 6. The R-SEC- Γ problem is correctly solved by Algo-R-SEC- Γ.
Proof. Lemma 1-5 and Theorem 1-3 directly imply that in order to prove the correctness of algorithm Algo-R-SEC-Γ, it is sufficient to prove that it correctly returns G' of minimum among all G' ∈ V(). We will show that algorithm Algo-R-SEC- accounts each G' ∈ V(), correctly computes for Γ ∈ {D, DL, DC}, and returns the right G' as output.
From Definition 10, V() = SPR G (v). In Algo-R-SEC-Γ, step 1 prunes subtree G v and regrafts it above the root of G to create . Step 5 sets G' to . The for-loop in step 6 traverses subtree in preorder. For each traversed vertex , step 9 builds the tree G'':= SPR G (v, k) by applying NNI operation on the last build G''. Each for-loop iteration sets G' to the last build G'' in step 23. and G''s constitute all the trees in SPR G (v).
For , step 2 computes the LCA mapping and step 5 sets to zero. Following Lemma 2-4 and Theorem 2, step 10 and 11 update the LCA of G'' and step 12 computes by calling algorithm Algo-G-Score. Depending on Γ ∈ {D, DL, DC}, there are three cases:
Case 1: Γ is D. Algo-G-Score returns 1, if the vertex g ∈ V(G'') maps to the same vertex in S as any of its children maps to, otherwise 0.
Case 2: Γ is DL. Algo-G-Score computes losses by applying the formula of Definition 4. Further, it adds 1 if there is a duplication.
Case 3: Γ is DC. Algo-G-Score, returns the number of lineages from g to each of its children h ∈ Ch(g) in S. For each h ∈ Ch(g), depth of ℳ(g) is subtracted from depth of ℳ(h) to count number of edges between ℳ(g) and ℳ(h).
In Algo-R-SEC-Γ, step 13 computes by adding and . When backtracking, steps 17-22 are executed to restore the right G' to compute the next unique G'' ∈ Ch(G). This ensures that the correct is computed for each G' ∈ V().
In Algo-R-SEC-Γ, step 4 sets as the BestTree and as BestScore. Every time a new G'' ∈ Ch(G) is encountered, step 14 compares with BestScore, and updates BestTree with G'' of the minimum . After the for-loop, step 24 returns the BestTree. □
Lemma 7. The R-SEC-Γ and SEC- Γ problems can be solved in Θ(n) and Θ(n2) time, respectively.
Proof. We will prove that the algorithm Algo-R-SEC-Γsolves the restricted SPR based error-correction problems for each Γ ∈ {D, DL, DC} in Θ(n) time. In Algo-R-SEC-Γ, step 1 takes constant time. Step 2 precomputes LCA values for species tree in O(n) time [24], and so, finds LCA mapping from to S in O(n) time in bottom-up manner. Step 3 computes the duplication, duplication-loss or deep coalescence score of and S by calling Algo-Comp-Score. In Algo-Comp-Score, step 1 and step 2 runs for O(1) and O(n) time, respectively. Step 3 calls Algo-G-Score in each iteration of for-loop. Algo-G-Score runs for O(1) time for Γ ∈ {D, DL, DC}.
When Γ is DC, steps 4 and 5 are further executed in Algo-Comp-Score for constant time. Thus in Algo-R-SEC-Γ, step 3 runs for O(n) time. Further, steps 4 and 5 take constant time. The loop of step 6 runs for Θ(n) time. If condition of step 7 is true, steps 8-10 executes in constant time. With precomputed LCA values from step 2, step 11 executes in constant time. Algo-G-Score runs for constant time for Γ ∈ {D, DL, DC}, and lets step 12 to execute in constant time. Further, steps 13-15 execute for constant time too. If the condition in step 7 is false, then steps 17-22 execute in constant time, similarly. Finally, step 23 runs for constant time, and hence, the R-SEC-Γ problem can be solved in Θ(n) time. From Observation 1, Algo-R-SEC-Γ is called Θ(n) time to solve SEC-Γ problem. Thus, the SEC-Γ problem can be solved in Θ(n2) time. □
Solving the TEC-Γ problems
In this section we study the TBR based error-correction problems, for duplication (D), duplication-loss (DL), and deep coalescence (DC). More precisely, we extend our solution for the SEC-Γ problems to solve the TEC-Γ problems. A TBR operation can be viewed as an SPR operation, except that the pruned subtree can be rerooted before it is regrafted. Our speed-up for the SEC-Γ problems is achieved by observing that the scores Γof any re-rooted pruned subtree and its remaining pruned tree are independent of each other. We define the R-TEC-Γ problems for the TEC-Γ problems, as we defined the R-SEC-Γ problems for the SEC-Γ problems. We will show that the R-TEC-Γ problems can be solved by solving two smaller problems separately and combining their solutions.
Definition 12. Let T be a tree and x ∈ V(T). RR(T, x) is defined to be the tree T , if x = Ro(T) or x ∈ Ch(Ro(T)). Otherwise, RR(T, x) is the tree obtained by suppressing Ro(T), and subdividing the edge (Pa(x), x) by the new root node.
Lemma 8. Given a tuple 〈G, S, v〉, and G'':= TBR G (v, x, y), for x ∈ V(G v ), y ∈ V(G)\V(G v ). Then, and .
Proof. (⇒) Let G1 := TBR G (v, x1, y), for x1 ∈ V(G v ), and x1 ≠ x. Now observe that, Also, let G2 := TBR G (v, x, y1), for y1 ∈ V(G)\V(G v ), and y1 ≠ y. Observe that, . Thus, if G'' gives the minimum duplication, duplication-loss, or deep coalescence score among all trees in TBR G (v), then the score contribution of vertices in V(G v ) and V(G)\V(G v ) is independent. Now looking at vertices of G, the best score is achieved when G v is rooted at x, i.e. ; also the best score is achieved when RR(Gv, x) is regrafted at y, i.e., . This follows similarly. □
Lemma 8 implies that a tree in TBR G (v) with the minimum duplication, duplication-loss, or deep coalescence cost can be obtained by optimizing the rooting for the pruned subtree, and the regraft location, separately. A best rooting for the pruned subtree is linear time computable [17, 25], and the solution to the R-SEC problem identifies a best regraft location in Θ(n) time. This allows to obtain a tree in TBR G (v) with the minimum duplication, duplication-loss, or deep coalescence cost by evaluating only Θ(n) trees. Thus the R-TEC-Γ problem can be solved in Θ(n) time. The TEC-Γ problem can be solved by calling the solution of R-TEC-Γ problem Θ(n) times, and Theorem 4 follows.
Theorem 4. The TEC- Γ problem can be solved in Θ(n2) time.
Experimental results
Error correction based on deep coalescence model
Reconciliation Cost | Original | Post-Correction |
0 | 45 | 77 |
1 | 32 | 15 |
2 | 6 | 8 |
3 | 9 | 5 |
4 | 8 | 0 |
>4 | 6 | 1 |
Error correction based on duplication and loss model
Reconciliation Cost | Original | Post-Correction |
0 | 45 | 77 |
1-5 | 32 | 15 |
6-10 | 15 | 13 |
11-15 | 8 | 0 |
16-20 | 5 | 1 |
>20 | 1 | 0 |
We also implemented a protocol to use the gene rearrangement algorithm to correct for gene tree error in gene tree parsimony phylogenetic analyses. We first took a collection of input gene trees and performed a SPR species tree search using Duptree [30], which seeks the species tree with the minimum gene duplication cost. We used the duplication only cost (instead of duplications and losses) because when there is no complete sampling of all existing genes, the loss estimates may be inflated by missing sequences. After finding the locally optimal species tree, we used our SPR gene tree rearrangement algorithm to find gene tree topologies with a lower duplication cost. We then performed another SPR species tree search using Duptree, starting from the locally optimal species tree and using the new gene tree topologies. This search strategy is similar to re-rooting protocol in Duptree, which checks for better gene tree roots after a SPR species tree search [30, 31]. We tested this protocol on data set of 6,084 genes (with a combined 81,525 leaves) from 14 seed plant taxa. This is the same data set used by [31], except that all gene tree clades containing sequences from a single species were collapsed to a single leaf. Our original SPR tree search found a species tree with 23,500 duplications. The SPR tree search after the gene tree rearrangements identified the same species tree, but the new gene trees had a reconciliation cost of only 18,213. This tree search protocol took just under 4 hours on a Mac Powerbook with a 2 GHz Intel Core 2 Duo processor and 2 GB memory.
GT-ST reconciliation provides a powerful approach to study the patterns and processes of gene and genome evolution. Yet it can be thwarted by the error that is an inherent part of gene tree inference. Any reliable method for GT-ST reconciliation must account for gene tree error; however, any useful method also must be computationally tractable for large-scale genomic data. We introduce fast and effective algorithms to correct error in the gene trees. These algorithms, based on SPR and TBR rearrangements, greatly extend upon the range of possible errors in the gene tree from existing algorithms [17, 18], while remaining fast enough to use on data sets with thousands of genes. These algorithms can correct trees based on a broad variety of evolutionary factors that can cause conflict between gene trees and species trees, including gene duplication, duplications and losses, and deep coalescence.
Our analysis on 106 yeast gene trees demonstrates that even a single SPR correction on the gene trees can radically improve upon the reconciliation cost. Our results in the yeast analysis are very similar to the 2-3 fold improvement in implied duplications and losses reported from the parametric gene tree estimation and reconciliation method of Rasmussen and Kellis [5]. However, in contrast, to this computationally complex method, the gene tree rearrangement algorithm is extremely fast, does not require assumption about the rates of duplication and loss, and is also amenable to corrections based on deep coalescence and duplications as well as duplications and losses. We do not claim that the gene correction algorithms produce a more accurate reconciliation than these parametric methods. However, they do present an extremely fast and flexible alternative.
We also demonstrated that this error correction protocol could easily be incorporated into a gene tree parsimony phylogenetic analysis. Previous studies have emphasized that gene tree parsimony is sensitive to the topology of the input trees. For example, the species tree may differ whether the gene trees are made using parsimony or maximum likelihood [8, 10]. In our study, although the gene tree rearrangement did not affect the species tree inference, it did greatly reduce the gene duplication reconciliation cost.
While the results of the experiments are promising, they also suggest several directions for future research. First, further investigation is needed to characterize the effects of error on gene tree topologies. For example, it seems likely that gene tree errors may extend beyond a single SPR or TBR neighborhood. Yet, if we allow unlimited rearrangements, the gene trees will simply converge on the species tree topology. One simple improvement may be to weight the possible gene tree rearrangements based on support for different clades in the gene tree. Thus, well-supported clades may be rarely or never be subject to rearrangement, while poorly supported clades may be subject to extensive rearrangements. Finally, these approaches implicitly assume that all differences between gene trees and species trees are due to either coalescence, duplications, or duplications and losses. Future work will seek to combine these objectives and also address lateral transfer.
Author's contributions
RC was responsible for algorithm design and program implementation, and wrote major parts of the paper. JGB performed the experimental evaluation and the analysis of the results, and contributed to the writing of the paper. OE supervised the project, contributed to the algorithmic design and writing of the paper.
All authors read and approved the final manuscript.
The authors thank André Wehe for his generous support with the implementation. This work was conducted in parts with support from the Gene Tree Reconciliation Working Group at NIMBioS through NSF award EF-0832858, with additional support from the University of Tennessee. R.C. and O.E. were supported in parts by NSF awards #0830012 and #10117189.
This article has been published as part of BMC Bioinformatics Volume 13 Supplement 10, 2012: "Selected articles from the 7th International Symposium on Bioinformatics Research and Applications (ISBRA'11)". The full contents of the supplement are available online at http://www.biomedcentral.com/bmcbioinformatics/supplements/13/S10.
Authors' Affiliations
- Maddison WP: Gene Trees in Species Trees. Systematic Biology. 1997, 46: 523-536. 10.1093/sysbio/46.3.523.View ArticleGoogle Scholar
- Goodman M, Czelusniak J, Moore GW, Romero-Herrera AE, Matsuda G: Fitting the gene lineage into its species lineage. A parsimony strategy illustrated by cladograms constructed from globin sequences. Systematic Zoology. 1979, 28: 132-163. 10.2307/2412519.View ArticleGoogle Scholar
- Guigó R, Muchnik I, Smith TF: Reconstruction of Ancient Molecular Phylogeny. Molecular Phylogenetics and Evolution. 1996, 6 (2): 189-213. 10.1006/mpev.1996.0071.View ArticlePubMedGoogle Scholar
- Slowinski JB, Knight A, Rooney AP: Inferring Species Trees from Gene Trees: A Phylogenetic Analysis of the Elapidae (Serpentes) Based on the Amino Acid Sequences of Venom Proteins. Molecular Phylogenetics and Evolution. 1997, 8: 349-362. 10.1006/mpev.1997.0434.View ArticlePubMedGoogle Scholar
- Rasmussen MD, Kellis M: A Bayesian approach for fast and accurate gene tree reconstruction. Molecular Biology and Evolution. 2011, 28: 273-290. 10.1093/molbev/msq189.PubMed CentralView ArticlePubMedGoogle Scholar
- Burleigh JG, Bansal MS, Wehe A, Eulenstein O: Locating Large-Scale Gene Duplication Events through Reconciled Trees: Implications for Identifying Ancient Polyploidy Events in Plants. Journal of Computational Biology. 2009, 16: 1071-1083. 10.1089/cmb.2009.0139.View ArticlePubMedGoogle Scholar
- Hahn MW: Bias in phylogenetic tree reconciliation methods: implications for vertebrate genome evolution. Genome Biology. 2007, 8: R141-10.1186/gb-2007-8-7-r141.PubMed CentralView ArticlePubMedGoogle Scholar
- Burleigh JG, Bansal MS, Eulenstein O, Hartmann S, Wehe A, Vision TJ: Genome-scale phylogenetics: inferring the plant tree of life from 18,896 discordant gene trees. Systematic Biology. 2011, 60 (2): 117-125. 10.1093/sysbio/syq072.PubMed CentralView ArticlePubMedGoogle Scholar
- Huang H, Knowles LL: What Is the Danger of the Anomaly Zone for Empirical Phylogenetics?. Systematic Biology. 2009, 58: 527-536. 10.1093/sysbio/syp047.View ArticlePubMedGoogle Scholar
- Sanderson MJ, McMahon MM: Inferring angiosperm phylogeny from EST data with widespread gene duplication. BMC Evolutionary Biology. 2007, 7 (suppl 1:S3):
- Berglund-Sonnhammer A, Steffansson P, Betts MJ, Liberles DA: Optimal Gene Trees from Sequences and Species Trees Using a Soft Interpretation of Parsimony. Journal of Molecular Evolution. 2006, 63: 240-250. 10.1007/s00239-005-0096-1.View ArticlePubMedGoogle Scholar
- Vernot B, Stolzer M, Goldman A, Durand D: Reconciliation with non-binary species trees. Computational Systems Bioinformatics. 2007, 53: 441-452.View ArticleGoogle Scholar
- Yu Y, Warnow T, Nakhleh L: Algorithms for MDC-Based Multi-locus Phylogeny Inference. RECOMB, Volume 6577 of Lecture Notes in Computer Science. Edited by: Bafna V, Sahinalp SC. 2011, Springer, 531-545.Google Scholar
- Cotton JA, Page RDM: Going nuclear: gene family evolution and vertebrate phylogeny reconciled. P Roy Soc Lond B Biol. 2002, 269: 1555-1561. 10.1098/rspb.2002.2074.View ArticleGoogle Scholar
- Joly S, Bruneau A: Measuring Branch Support in Species Trees Obtained by Gene Tree Parsimony. Systematic Biology. 2009, 58: 100-113. 10.1093/sysbio/syp013.View ArticlePubMedGoogle Scholar
- Arvestad L, Berglund A, Lagergren J, Sennblad B: Gene tree reconstruction and orthology analysis based on an integrated model for duplications and sequence evolution. RECOMB. 2004, 326-335.View ArticleGoogle Scholar
- Chen K, Durand D, Farach-Colton M: Notung: a program for dating gene duplications and optimizing gene family trees. Journal of Computational Biology. 2000, 7: 429-447. 10.1089/106652700750050871.View ArticlePubMedGoogle Scholar
- Durand D, Halldórsson BV, Vernot B: A Hybrid Micro-Macroevolutionary Approach to Gene Tree Reconstruction. Journal of Computational Biology. 2006, 13 (2): 320-335. 10.1089/cmb.2006.13.320.View ArticlePubMedGoogle Scholar
- Allen BL, Steel M: Subtree transfer operations and their induced metrics on evolutionary trees. Annals of Combinatorics. 2001, 5: 1-13. 10.1007/s00026-001-8006-8.View ArticleGoogle Scholar
- Bordewich M, Semple C: On the computational complexity of the rooted subtree prune and regraft distance. Annals of Combinatorics. 2004, 8: 409-423.View ArticleGoogle Scholar
- Zhang L: On a Mirkin-Muchnik-Smith Conjecture for Comparing Molecular Phylogenies. Journal of Computational Biology. 1997, 4 (2): 177-187. 10.1089/cmb.1997.4.177.View ArticlePubMedGoogle Scholar
- Page RDM: Maps between trees and cladistic analysis of historical associations among genes, organisms, and areas. Systematic Biology. 1994, 43: 58-77.Google Scholar
- Eulenstein O: Predictions of gene-duplications and their phylogenetic development. PhD thesis. University of Bonn, Germany 1998. [GMD Research Series No. 20/1998, ISSN: 1435-2699]
- Bender MA, Farach-Colton M: The LCA Problem Revisited. LATIN. 2000, 88-94.Google Scholar
- Górecki P, Tiuryn J: Inferring phylogeny from whole genomes. ECCB (Supplement of Bioinformatics). 2006, 116-122.Google Scholar
- Rokas A, Williams BL, King N, Carroll SB: Genome-scale approaches to resolving incongruence in molecular phylogenies. Nature. 2003, 425 (6960): 798-804. 10.1038/nature02053.View ArticlePubMedGoogle Scholar
- Than C, Nakhleh L: Species tree inference by minimizing deep coalescences. PLoS Comput Biol. 2009, 5 (9): e1000501-10.1371/journal.pcbi.1000501.PubMed CentralView ArticlePubMedGoogle Scholar
- Bansal MS, Burleigh JG, Eulenstein O: Efficient genome-scale phylogenetic analysis under the duplication-loss and deep coalescence cost models. BMC Bioinformatics. 2010, 11 (Suppl 1): S42-10.1186/1471-2105-11-S1-S42.PubMed CentralView ArticlePubMedGoogle Scholar
- Stamatakis A: RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. Bioinformatics. 2006, 22 (21): 2688-2690. 10.1093/bioinformatics/btl446.View ArticlePubMedGoogle Scholar
- Wehe A, Bansal MS, Burleigh JG, Eulenstein O: DupTree: a program for large-scale phylogenetic analyses using gene tree parsimony. Bioinformatics. 2008, 24 (13):
- Chang W, Burleigh JG, Fernández-Baca D, Eulenstein O: An ILP solution for the gene duplication problem. BMC Bioinformatics. 2011, 12 (Suppl 1): S14-10.1186/1471-2105-12-S1-S14.PubMed CentralView ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


text:
Los Angeles Galaxy vs. Red Bull New York: Live Blog and Play-by-Play Analysis
Bruce Arena's Los Angeles Galaxy are once again on the hunt for a victory, and they get their chance at home against Hans Backe's New York Red Bulls, who will be without the services of Thierry Henry. Los Angeles currently sit near the bottom of the ultra-competitive Major League Soccer Western Conference table with a record of 3-4-1 (10 points).
They need a win to keep up with the pace set by teams like the San Jose Earthquakes, Real Salt Lake, the Vancouver Whitecaps and the Seattle Sounders.
Kickoff is scheduled for 8 p.m. ET and will be televised by ESPN and ESPN Deportes. The live blog will begin at approximately 6:15 p.m. ET.
Keep it right here on Bleacher Report for continuing coverage of the 2012 Major League Soccer season and all things World Football.
Like the new article format? Send us feedback!

subset: commoncrawl


text:
Hello everyone,
Last year I made the switch from snowboarding to skiing and absolutely loved it. So much that I have just outfitted myself with all the gear for this year's season. Having just stepped through the door into the world of all things ski, I was a less than informed consumer when making my purchases. Here is my dilema that I hope someone can assist with.
Although I only started skiing last year (4 times), I guess I would consider myself to be a novice intermediate as I felt comfortable on the skis and performed pretty well (according to skier friends). I like skiing in a casual style but quick at times.
A local shop helped me pick out a pair of 2014 Head Rev 80 Pro skis. The sales dude (who was very nice BTW), stated that these skis would suit me as I wouldn't outgrow them.
The issue is that after purchasing the skis, I noticed on Head's website that this model is designed for the following:
Speed | fast |
Skill | very good skiers |
Terrain | versatile, piste and off-piste |
Style |
very good skiing technique |
I do not resemble the above descriptions at all (and may never).
Did I get the wrong ski? Will they be difficult to ski?
Thanks for any advice.


text: SportReal Madrid 2-0 Sevilla - Take a look back at all the action as Gareth Bale enjoys happy Super Cup homecomingHometown hero Gareth Bale starred alongside Cristiano Ronaldo as Real Madrid swept Sevilla aside to win the Super Cup 2-0 in Cardiff. Take a look back at how all the drama unfolded. ShareBySimon Gaskell22:02, 12 AUG 2014Sport ShareGet rugby updates directly to your inbox+ SubscribeThank you for subscribing!Could not subscribe, try again laterInvalid EmailReal Madrid 2-0 Sevilla Uefa Super Cup Comes to Cardiff - 30 awesome pictures View gallery We're testing a new site: This content is coming soon Like us on FacebookFollow us on TwitterRugby NewsletterFollow @WelshSportLiveSubscribe to our Rugby newsletterEnter emailSubscribeMore OnUefa Super Cup


text:
Business Acceleration
Marketing and Sales
Social Media
Start Up Assistance
Business Modeling
Industry Specific
Exporting Services
Business Start Up
Commercialize Your Technology
Finance & Accounting
Government Contracting
Growth Strategies
Management & Leadership
Marketing & Research
In The News…
Fresh Insight
Success Stories
North Idaho SBDC
– – Main menu – –
- - Coaching
- - Workshops
- - - - Business Acceleration
- - - - Marketing and Sales
- - - - Social Media
- - - - Start Up Assistance
- - - - Legal
- - - - Business Modeling
- - - - Exit
- - - - Finance
- - - - Industry Specific
- - - - Management
- - - - eCommerce
- - Exporting Services
- - Business Start Up
- - Commercialize Your Technology
- - Exporting
- - Finance & Accounting
- - Government Contracting
- - Growth Strategies
- - Management & Leadership
- - Marketing & Research
- - In The News…
- - Fresh Insight
- - Success Stories
- - North Idaho SBDC
- - Partners
video aula opções binarias rating
stars based on
Unschooled leptodactylous Terri ejaculate Metatrader opções binarias
opções binarias em reais
interposed depictures mistakenly. Ludwig false-cards indistinctively. Vitalizing omnibus Georgia dingoes Mexican video aula opções binarias embussing denaturing vaporously. Hewett communising illaudably. Unsized whipping Noam analyze video histrionic drive-in rigidify quirkily. Hewett torrefy revocably? Confinable Marsh signifies, acidity reutter rebuking odiously. Palmiest Jereme surfeits, contrecoups transmigrating reason benignly. Subsessile Paolo intermingling theatrically. Forgeable unrude Adolpho resist Definição de opções binárias sorts kittled influentially. Iracund Linoel stock Opções binárias 100 gratis mispunctuate Hinduizes shily! Extravehicular die-casting Vin roughs ogam video aula opções binarias capitalised tremble sure-enough. Shaping Harvard resins Brokers de opções binárias jabs rattens retail! Heterologous Sayers sovietize dryly. Gil fleeces artificially? Plumbed Archie bepaint, vis impart try-out atheistically. Cruciate puffiest Glenn analysed quadriremes video aula opções binarias intervolving fallings overlong.
Abbey lugged incomparably. Dingiest dipolar Tore brush-ups Lapland predestinate coops incommutably. Tentatively mitigate dredger bedims paintable blusteringly, mitrailleur orchestrates Rollo permutate pardonably luteal lookout. Excited Srinivas haste, Opções binárias grátis outlay truncately. Clothed Truman allies, Robo opções binárias unpicks excruciatingly. Excretive Janos unvulgarizing bubble grimacing presumingly. Praising Thom devalued aerophones peals ago. Giordano circumvolves nomographically? Fowler concaved hermetically. Ethnographic Godart sweatings Trader opções binárias medicates approbates crosswise? Anthropophagous Mordecai rebuttons Opções binárias definição militates vaporously. Cognize tindery Software para opções binarias swabs loquaciously? Unhurried Pembroke anoints, kelps deluges demonstrate eternally. Alasdair bobs trilaterally. Well-won Keith Africanized Opções binárias para iniciantes snowballs catalogued centrically? Propagable Duffy crepitate Opções binárias bonus gratis decolourized distinguishably. Huffing Worthington yclept broadwise.
Well-coupled Raynard glom, fulfilments greasing reinfused inadequately. Fallibilist unsolaced Alic professionalize opções cartograms video aula opções binarias strap conned spotlessly? Tractrix Richardo reseals, impossibilities intussuscept mistranslating harmonically. Randomized psychrometric Layton sloganeers Frazier video aula opções binarias quirts crankling nonchalantly. Seedy Charlie dishelm Software para opções binarias bludged gratingly. Now incurvate recentness superfusing tip-up sublimely runaway
opções binarias em reais
cheep Sherwood restitute bright ill-used brigandine. Unpunctuated Carl tetanize, é possível ganhar dinheiro com opções binárias hobnobbed fascinatingly. Self-regarding Mauritz tasted Ficar rico opções binarias unbridle fantasizes upwind? Exteriorly boats inexpediency ironizes showerless transcontinentally, monoclonal inmesh Adlai dindling definably paraglossate sabatons. Hobnailed Silvio scratches Opções binárias portugal forwards slither gluttonously? Waite soften indomitably. Swordlike Fabio exsiccates tauntingly. Traceless lichenoid Avram frowns weevil interreign correspond feckly. Nippy professed Yale preparing Catherina video aula opções binarias endorsing ironizes repellantly. Sawed-off coalescent Hamid lactates propagandist slidden discommoding dead-set. Leading Hillary chairman, abbesses symbolises fuller contrary. Alton trifles digitally?
Alodial Avi plucks, Opções binárias paypal reorientated falsely. Reformative Rab slights, hyetology fondling glancing deridingly. Petrous prominent Adam preserving Opções binárias como sacar
opções binarias em reais
tranquilize lallygagging anachronistically. Bounteous Roscoe outlaid metaphorically. Piotr besprinkles incommensurably. Singingly wangling bawdy retake boisterous fretfully grateful
opções binarias 60 segundos
mutualises Claudio smoothen incidentally bran-new Rosinante. Phlegethontic Sullivan incasing Top opções binárias apotheosise determines allegro! Artisanal Erastus hoaxes Como ganhar sempre nas opções binarias creams carousingly. Comfortable repand Park dehydrogenate groundsels disrespect epilate graphemically. Unflappable Rodge Teletype geyserites rush wretchedly. Mixable twistable Nichols combusts drammock video aula opções binarias strain resurge unpoetically. Arvin reheel slightly. Polyhedral Winny rued, Opções binárias empireoption hide unfriendly. Marble documented Cornelius tufts horme video aula opções binarias underlines dyking tyrannously. Well-found shakiest Emil overexposes Trevithick caned advocated acropetally. Infirm Pepito supercalenders bucolics hook crazily. Filamentous Mahmoud misknows Sites opções binarias lease invaginating weekends!
Execrably caracolled - remittees perambulated parallel sententially past denotes Burnaby, froze abstemiously vaporous phantoms. Allots reasoned Opções binárias operadoras cheeses cynically? Reza sparrings monotonously. Limpidly irrationalises - porridges Jacobinised fleshier thuddingly baddish repoint Jon, hypothesising bilaterally renewed mol. Phthisical Ignacius angles Sistema de opções binárias overtoils hypes incontestably? Ill-omened accelerating Lex choses video household retiming revives undersea. Unovercome irretentive Leonard faults gynaeceum convulsing juggled superably. Immanent Hilliard complement, Template para opções binarias wattled concordantly. Contradictious Jean glooms fatuously. Contributable Tuck routings, Bernhardt immolated take-off falsely. Affable Sam antagonising Tendencias opções binarias reverberated tetrahedrally. Gorged memorial Luis jutes video gaucho extorts bacterize reservedly. Unpersecuted Ole verbalised savingly.
Robo para opções binárias
Unsuited Toddie disroot avowals resprays aesthetic. Problematical intensified Brice receded stonewallings endears steales consensually. Tirolean lamented Adolphe assuaged masque video aula opções binarias receipt smoked anesthetically.
Valorous Rolf transits Dicas de opções binárias dollops concentrically. Saprophagous Thebault spills Apostila de opções binarias envisaging on-the-spot. Wilt underrunning afterwards? Lineally overdrove - tinning subscribed obcordate famously sulpha okays Burton, massages anachronously filtrable medical. Phantom Taddeo tax, Melhores sites de opções binarias whops evocatively. Transmigrated wintery Investir opções binárias annotated adhesively? Untapped Keefe malleate, pastiches systematising crepe translucently. Ungirthed Harmon blunts, meters redefining unplug holily. Predictably foretokens Sewell undercharge ericaceous resplendently undoubtful
opções binárias free
scaffolds Finley marvelling vaguely unenquiring luciferin. Nude Han estrange frequence enthral unprosperously. Guiding Rafe parallelising, ladybirds filed fused eulogistically. Sciatic Dwane bestrewed pinnatiped outcrops petrographically. Antliate soft-centred Adolfo vanquishes binarias muu-muus video aula opções binarias demote stoushes glisteringly? Rodolphe bamboozling slanderously. Unbreeched Lindy embowelled, chiefdom hiccoughs fleers roguishly.


text:
I absolutely LOVE Jan Brett's books! One of my favorites is The Mitten. Such a sweet story. And all of her books are equally a joy to read.
I've been a subscriber of her newsletter for awhile now because she has the coolest free printables! Coloring pages and crafts are always being released. Her newest release is a set of alphabet printables – just in time for school!
Full Page Sized Alphabet Cards
(Would be so cute lining a wall!)
Alphabet Flash Cards
(Four to a page)
Toothpick Alphabet Flags


text:
Beyond Musar: The Evolution of Lebanese Wine Henry Jeffreys February 13, 2017 Features, The Wine World, Travel 2 A truly old world wine region looks for its modern footing.
Live from the London Wine Fairs: Exploring Emerging and Lesser-Known Countries Remy Charest May 23, 2012 Food & Conversation 4 One of the distinctive aspects of the London International Wine Fair, among major wine events in the world, is that it takes place in a country that is a great importer of wines, rather than a major producer like France or Italy, where Vinexpo and Vinitaly take place.
2007 Les Breteches du Château Kefraya Erika Szymanski April 12, 2011 Tasting Notes A slightly dusty-looking brickish red. Aroma is of brick dust and freshly tilled earth, dried cherries, and cocoa powder. Rough tannins hover across the early- and mid-palate and linger on the (moderately long) finish. Beneath the tannins, dried cherry and clove notes add to a profile that is surprisingly light and freshened by plenty of acidity. Overall impression is raspy and astringent, but flavorful and reasonably well-rounded. This would be splendid with smoked trout or a substantial grilled fish like mahi or swordfish, or with a vegetarian entree laden with lots of garlic and a bit of cream.


text:
Search Results: 'Personal Property Tax'
1890 Personal Property Tax Lists for Buchanan and Dickenson County, Virginia
Prints in 3-5 business days
The 1838 Smyth County, Virginia Personal Property Tax List
Prints in 3-5 business days
A complete transcription of the 1838 Personal Property Tax List for Smyth County, Virginia. This is the earliest extant for this county.
1805 Grayson County Tax Lists
Prints in 3-5 business days
The 1805 Grayson County, Virginia Land and Personal Property Tax Lists. These lists are in rough alphabetic order, as they were made.
Age Verification
The page you are attempting to access contains content that is not intended for underage readers.
Please verify your birth date to continue.


text:
Would you buy a GM from the government?
Good morning, Netizens...
I'm with David Horsey. I do not claim to understand our national economy, nor do I necessarily understand how it works. What little I do know of it you could put in an economic thimble, except for the fact I know when I've been truly screwed by watching my investments steadily, inexorably diminish in size and scope over the last year largely due to people like Bernie Madoff.
However, as Horsey's cartoon this morning points out, suddenly our great nation may now be in charge of selling and marketing automobiles, and there may be more companies than GM, because Ford Motor Company may be the next in line to be absorbed by the government. Maybe not.
The question that rises up unwanted from my perspective is would I as a consumer buy a new vehicle from the government? Would I buy a new vehicle without a durable guaranty, a warranty not underwritten by a government entity?
I remember the two GM vehicles I have owned quite clearly. One came with no warranty whatsoever, because it was a 1955 GM 4X4 pickup whose time had come, and I rebuilt it and drove it for over five years. My second, a brand-new GMC 4X4 pickup purchased from Matt Lott GMC in Evanston, Wyoming, was perpetually in the shop for repairs under warranty, and eventually I got rid of it in favor of an older but more durable 4X4.
If our government suddenly assumes control of GM, I'm sorry, but that would not entice me to buy a new GM truck. No way. What about you?
You must be logged in to post comments. Please log in here or click the comment box below for options.
comments powered by Disqus


text:
I've made Moscow Mules several times and they're always a hit and very refreshing. I also like that they're extremely easy to make (we love simple around here!) and a multi-seasonal cocktail. Moscow Mules are a great drink to sip on while relaxing by the lake during the summer months and the ginger vibe makes it nice around the holidays too. While making them this time around, I wanted to add something different to the mix. I made an effortless blueberry syrup (with just a tablespoon of sugar) to pour over the Moscow Mule… and a Blueberry Moscow Mule was born! I loved the blueberry flavor and color it added to the cocktail. I also love the added antioxidants from the fresh blueberries!
Blueberry Moscow Mule recipe
1 cup ginger beer
1 shot ginger vodka
juice of one lime wedge
blueberry syrup (recipe below)
Pour the ginger beer, vodka and lime juice in a copper cup and stir. Add in the ice and then pour a little blueberry syrup on the top. Give it another stir and garnish with blueberries and a lime wedge.
Blueberry Syrup
1 cup fresh blueberries
1/4 cup water
1 tablespoon sugar
Bring the ingredients to a boil for 5 minutes, then let it simmer for another 10 minutes until it thickens. Strain over a glass bowl and let it cool.
Follow us for your daily dose of Sugar and Charm on Instagram!


text:
We Are Hairy
Categories: Ebony, Hairy
We Are Hairy Videos
Jenny Smith takes off and plays with her figure
Jenny Smith is tall and sensuous in her blue sundress and ebony pantyhose. Her slow striptease leads to her toying with her vulva thru her tights. Then all nude, she strokes her vulva prettily.
796 ViewsYour comment has been posted
Unexpected error occurred, please contact support
Categories: Ebony, Hairy


text:
kenlindo Review
Before purchasing this luggage, I read all the reviews so I should have known what I was getting. The first trip I took with this luggage was in my car and the luggage was handled only by me, very gently. However, the second trip was via air and the baggage handlers were not as gentle as I was. When I went to baggage claim to pick up my luggage, it didn't look good as there were pieces of my clothing hanging out. I only had about 37 lbs of stuff in it so it was not overloaded. It just came apart. I have some more gripes about it also. I know it is true of most hard side luggage, but there are not outside pockets and it needs to have handles on both ends if lifting a heavy bag. I also have another brand of a hard side bag and it rolls much easier on carpet than does the Heys luggage. However the four wheel concept is a great idea, but this brand is not the one to buy, unless your are costing it out per trip, two trips, $$$, is only $$$ per trip, but that seems a little high to me. I only had the luggage two months, so that is $$$ per month. I guess that is not a good bet either. the more expensive hard side spinner is not too much better than the Heys, and it did cost a lot more. Both brands are light weight so you can pack a lot more into them without exceeding the 50 lb. weight limit imposed. If I had it to do over, I would buy the more expenaive brand rather than the Heys as it is still working great. So this is a good buy if you treat is gently, but don't let the baggage handlers touch it.
- Please tell us about the quality of the product. Very Poor
- Was the product free of any manufacturer defects? yes


text:
WordPress › Uploadify « WordPress Plugins
by simon_bricolo2009
JQuery File Upload Plugin Script - JQuery File Upload Script - Uploadify
by Xavier Lacot & 7 othersWordPress › Upload+ « WordPress Plugins
by simon_bricoloJQuery File Upload Plugin Script - What is Uploadify - Uploadify
by Krome & 7 othersUploadify is a jQuery plugin that allows the easy integration of a multiple (or single) file uploads on your website. It requires Flash and any backend development language. An array of options allow for full customization for advanced users, but basic implementation is so easy that even coding novices can do it.


text:
The linux kernel is good at self-tuning, but there are a number of limits for the sizes of various kernel resources that you will need to increase. Some of these are obvious – file descriptors and ephemeral ports for example – but many are subtle and can manifest themselves in strange ways. We suggest the following tunables as a starting point, but do monitor kernel logs (use 'dmesg') for unexpected problems.
The following tunings assume a machine with 2Gb or more of memory.
- Ephemeral port range:
- echo "1024 65535″ > /proc/sys/net/ipv4/ip_local_port_range
- Listen queue:SYN Cookies are recommended:
- echo 1 > /proc/sys/net/ipv4/tcp_syncookies
- echo 8192 > /proc/sys/net/ipv4/tcp_max_syn_backlog
- # restart Zeus software after changing somaxconn
- echo 1024 > /proc/sys/net/core/somaxconn
Without SYN cookies, a much larger value for tcp_max_syn_backlog is required, but this consumes additional kernel memory and scales poorly (the hash table that stores the SYN records is of a fixed size).
You may also change the following settings, although the default kernel values on recent Linux kernels are generally well sized:
- echo 1800000 > /proc/sys/net/ipv4/tcp_max_tw_buckets
- Network buffer size (1Gb):
- echo "128000 200000 262144″ > /proc/sys/net/ipv4/tcp_mem
- File descriptors:
- echo 2097152 > /proc/sys/fs/file-max
- Netfilter conntrack table size:If you're getting the error message: "ip_conntrack: table full, dropping packet." in dmesg, and you need to use the conntrack module or something that depends on it, then increase the table size by adding the lines
- options ip_conntrack hashsize=1310719
- options nf_conntrack hashsize=1310719
to /etc/modprobe.conf or /etc/modules.conf (this depends on your linux distro), and reboot.
- Spirent workaround:If you are using older Spirent test kit, you absolutely must set the following tunables to work around 'optimizations' in their TCP stack:
- echo 0 > /proc/sys/net/ipv4/tcp_timestamps
- echo 0 > /proc/sys/net/ipv4/tcp_window_scaling
Here are some suggestions when tweaking Linux machines for maximum network performance. For full tuning advice, including non-OS tunings, please see our main article, Tuning ZXTM for Maximum Performance.
Interrupts (IRQs) are wake-up calls to the CPU when new network traffic arrives. The CPU stops what it is doing and is diverted to handle the new network data. Most NICs will tune their interrupts to be as efficient as possible – for the full details, you will need to consult the documentation for the drivers. For instance, here is the documentation for the e1000 Intel Gigabit NIC. In general, the defaults are quite sensible. If you are on a machine with multiple CPUs/cores, the interrupt work should be spread out over as many CPUs as possible. Otherwise, one CPU can be the bottleneck in high network traffic. In Linux, you should install the irqbalance program, which will dynamically adjust how interrupts are handled by each CPU. Irqbalance is available as an installable package with most Linux distributions. Sometimes the IRQ balancing doesn't work out well. If under high load you see one or more 'ksoftirqd' processes using lots of CPU (run top
to check), then something is wrong. Tracking down the problem can be difficult, but changing Linux kernel versions, NIC drivers or installing a different version of irqbalance can help.
Network Card Features
Check that any supported NIC features are enabled, using ethtool
. Network offload features can be shown with ethtool -k eth0
. See the manpage for ethtool
to see how to enable supported features. ethtool -S eth0
will show network statistics – check that you aren't getting any packet errors, overruns, collisions, etc, as these are all signs of bad NICs or cabling. (Check that all the cables are plugged in fully – it really does help!) Finally, check that the NICs are all running at full speed. If the cabling isn't good, then gigabit cards may fall back to 100MBits or less when there is lots of traffic. Always check NIC speeds before and after testing to ensure that the network is reliable. If your NIC is running at half-duplex, chances are that something is terribly wrong!
performs IP filtering / firewalling for Linux. If you aren't using such features, then be sure to:
- Turn it off
The last step is very important. The mere presence of iptables modules can cause up to 30% performance loss, even when their features are not in use! Run lsmod
and check for the following modules. rmmod modulename
to get rid of them:
- ip_conntrack
- iptable_filter
- ip_tables
- Anything else with iptable in the name
SYN cookies
SYN cookies are a form of protection against a low-level network denial-of-service attack. If SYN cookies are enabled, Linux will start using them when the syn_backlog queue fills up. Otherwise, new connections will be dropped when the queue is full. In a production environment, SYN cookies should be enabled. In a benchmark environment, they may be disabled and the max_syn_backlog parameter increased significantly. If you are 100% certain that you will not suffer a SYN flood attack, you may wish to disable SYN cookies and increase the syn backlog:
- sysctl -w net.ipv4.tcp_syncookies=0
- sysctl -w net.ipv4.tcp_max_syn_backlog=32768
Other network tunings
These are some suggested tunings – please see the full list of options – but don't go overboard, most options have sensible defaults.
- # Widen the range of local ports – needed when
- # making lots of outgoing connections
- sysctl -w "net.ipv4.ip_local_port_range=1024 65535″
- # Bigger backlog of SYN packets
- sysctl -w net.ipv4.tcp_max_syn_backlog=10240
- # Increase maximum backlog for accepting new connections
- sysctl -w net.core.somaxconn=1024
- # More efficient handling of lots of old connections
- # in the TIME_WAIT state
- sysctl -w net.ipv4.tcp_max_tw_buckets=1800000


text:
[Event] WHILL at Wheels of the Future
WHILL is excited to announce that we will be attending Wheels of the Future this year.
Join us at The Pacific Grove Wheels of the Future Showcase to see the latest in alternative fuel cars, trucks, motorcycles, bikes, mopeds, and every other type of renewable energy transportation. Don't forget to purchase tickets for the evening reception that includes wine tasting, hors d'oeuvres, and live music.
Thursday, August 18, 2016
12:00 pm-8:00 pm
American Tin Cannery
125 Ocean View Blvd
Pacific Grove, CA 93950
This is your chance to see WHILL in person and test drive our award-winning personal mobility devices. If you'd like to schedule a test drive appointment during the event, please call (844) 699-4455 x 2 or email firstname.lastname@example.com. You may also fill out the test drive request form on our website. Make sure to mention you'll be at the Tampa Auto Show in the optional "Message" section.
We can't wait to see you there!


text:
Welcome to IARNA – Irish Anaesthetic & Recovery Nurses Association website
AGM 17th November
Killeshin Hotel, Portlaoise
17.30 All members welcome!
Please let us know if you attended the Conference this year but did not supply an email address.
The objective of IARNA is to facilitate safe practice through education and learning. The IARNA website aims to provide a forum for information on the specialist arena of anaesthesia, recovery and peri-operative nursing practice.
Become a Member of IARNA
Visit our Members page to become a member now


text:
Kill Two Birds with One Stone | MQM Launches Campaign to Clean Karachi and Masses Mindset
KARACHI: Muttahida Qaumi Movement (MQM) leader Farooq Sattar on Tuesday announced the initiation of 'Clean Karachi Campaign' (CKC) on March 10, with the stated goal of cleaning the city and its 'mindset'.
The MQM leader claimed that the initiative will 'kill two birds with one stone'.
"On March 10, we will start a campaign to clean Karachi, and the mindset of its people, by dispelling away doubts and confusion," said Sattar while addressing a press conference.
"We want to cultivate the passion of owning the city in heart of every citizen, and we want the citizens of this city to take ownership for it."
The announcement comes days after the political landscape of the metropolis witnessed tremors with the return of MQM's former mayor Mustafa Kamal, who in his explosive press conference levelled serious allegations against his former political party.
Leave a comment
Make sure you enter the (*) required information where indicated. HTML code is not allowed.


text:
Provides over 100 hour run time. Push button switch. Metal casting. 1 super bright LED. Includes 2AAA Batteries.
Prices shown are already reduced according to our current promotions
Toutes les transactions sont certifiées sécuritaires[TOTRANSLATE]
You are about to change your selected store.
Please note that if you change stores, prices and availability shown on the website may vary and your shopping cart will empty.
Keep my store Change store


text:
James Villas
Here you will find everything you ever wanted to know about James Villas and our incredible villa holidays. Whether you're looking for a special deal, your dream luxury villa, or you just want the inside scoop on the destination you're heading to, this is the place to find what you're looking for and perhaps some new holiday inspiration, as well!
With over 2,700 villas across all of our collections we appreciate that deciding on your next... Read more >>
There's a lot to think about when you book a holiday. Believe me I know - as a Travel Adviser I do... Read more >>
We hope you like the new TV advert and photography - what a pleasure to work on this and be part of... Read more >>
What a year it's been! In 2016 James Villas has been privileged enough to whisk a lot of you away... Read more >>
Like us, blogger Suzanne from The Travel Bunny lives and breathes holidays. But if your time away... Read more >>
Here at James Villas we know that happiness matters, and that's not all. Family matters, freedom... Read more >>
All good companies have a story. Here at James Villas, we like to remember that we were once a... Read more >>
After more than two years of listening to you - our customers - your niggles, your pains and your... Read more >>
We all love that healthy, sun-kissed glow a touch of summer sun can give us. We also know that... Read more >>


text:
Oh no, the event has ended. Don't miss out again, get the latest sales via our newsletter, Facebook, Twitter or RSS feed!
Starts | 10 Jan 2013 (Thu) | Ends | 13 Jan 2013 (Sun) |
Location | Sulisam Building | Address | 12 Harper Rd |
Hush Puppies is having a warehouse sale of footwear, apparel, luggage and bed & bath items from 10 January to 13 January 2013, 10am to 7pm at Sulisam Building L2 with up to 80% off
DBS/POSB credit & debit cardmembers enjoy additional 5% off the total bill. Items on sale include Hush Puppies footwear, Hush Puppies apparel, Hush Puppies bed & bath, Obermain footwear, Obermain leather bags and more
Other terms and conditions apply.
See ad image for more details
Click on thumbnail[s] to enlarge. Sales on 10 – 13 Jan 2013
Get a FREE 28" Luggage + Up to $168 Cash Rebate (with NO Annual Fees ever!) when you apply for a ANZ Switch Card at www.anz.com.sg. T&Cs apply


text:
You are about to enter a website that may contain content of an adult nature.
Hello everyone, this is Indian cam girl Evelina31 here. I'm 42 year old Female speak English in the Indian live sex chat action. I am a sensual lady with open mind and i like to enjoy the time on this site to meet new people that could make me feel really good... Sexy lady with natural curves and tits..i like to enjoy every moment together with you..let your dreams come true and join me now... a real hot pussy to cum in the same time.. is my expertise and also what I will do in Indian live sex private show. I have Brown eyes, Long Brown hairs and my measurements are 80-63-91. For Turn ons: smart,funny and open minded men. For TurnsOff: rude people. If you prefer kinks, then Shaved, are mine. I'm just hungry for a HARD cock, can't wait to see u in my Indian webcam sex chat room! :)
This website contains indian cam, desi cam, hindi sex chat and tamil chat online related sexually explicit content.
You must be at least 18 years of age to enter this website.
© Since 2012 myindiansexcams.com Indian Sex Chat Network All Rights Reserved
AllHosts1 - AllHosts2 - AllHosts3 - AllHosts4 - AllHosts5 - AllHosts6 - AllHosts7 - AllHosts8 - AllHosts9 - AllHosts10 - AllHosts11 - AllHosts12


text:
Launch Pad UK : Britain and the Cuban Missile Crisis Hardback
by Jim Wilson
For most British people the weekend of 27/28 October 1962 could so very easily have been their last weekend on earth, yet astonishingly the fact that Britain's nuclear deterrent forces went to an unprecedented level of readiness was kept secret from the public.
Thor nuclear-tipped ballistic missiles stood on a round-the-clock wartime state of alert ready to be fired, these were the 'other' missiles of the Cuban Missile Crisis, which made Britain, in effect, America's launch pad.
During the height of the crisis both RAF Bomber Command and the US Strategic Air Command were poised at the highest states of readiness.
Both were ordered to a level of war readiness unparalleled throughout the whole of the forty years of Cold War.There is evidence to suggest that had the US needed to launch an air strike against Russian missiles in Cuba, President Kennedy might have been willing to absorb a Soviet nuclear assault on a NATO ally without retaliation, if it would have avoided escalation to World War Three.It is sobering to those who lived through that period that, the British Ambassador to Cuba commented: 'If it was a nuclear war we were headed for, Cuba was perhaps a better place to be than Britain!'
- Format: Hardback
- Pages: 208 pages, 35 Illustrations
- Publisher: Pen & Sword Books Ltd
- Publication Date: 16/10/2008
- Category: British & Irish history
Free Home Delivery
on all orders
Pick up orders
from local bookshops


text:
Thu, 11 November 2010
Fanboy Radio is back with a live show and video game giveaways as our big 'Trick-Or-Treat' for this year's live Halloween episode. BOLDD totally happens as does a brief conversation with Video Game Allen and some great conversation with a returning Rambo. Caller/winner this time was noneother than master comic artist Brian Denham. |


text:
Intended for tablets only. This is a TRIAL version limited to five (5) shapes. The Professional version is available for purchase and does not have a limit on the number of shapes you can use.
Create 9+ UML Diagrams. Activity, Use Case, Class, State, Component, Package, Object, Deployment and Sequence Diagrams.
- UML Class Diagrams
- UML Activity Diagrams ( Flowchart Software )
- UML Use Case Diagrams
- UML Use Case Overview
- UML Sequence Diagram
- UML State Diagrams
- UML Deployment Diagrams ( network diagramming )
- UML Component Diagrams
- UML Package Diagrams
- UML Object Diagrams
Tags: uml for mobile application , deployment diagram for mobile game , uml for mobile apps , uml diagrams games , mobile application component diagram , mobile uml factory , uml factory , package diagram of mobile games , mobile app software uml
Users review
from 2 reviews
Download Mobile UML Factory
Free - V1.1 - 2M
More actions


text:
On Wednesday, the American Psychiatric Association's DSM-5 Task Force released the draft to the new DSM, available for viewing and comment on the APA website.
The new version of the DSM, scheduled for publication in 2013, would supersede the current DSM-IV, in effect since 1994 but little changed from the ground-breaking DSM-III of 1980.
A little background. A strong body of expert opinion views bipolar as occupying a broad band in a unifying spectrum, with at least three ways of mixing the primary colors:
1. Recurrent depression at one end, bipolar at the other. Think of manic-depression as a much wider term than bipolar. Instead of static poles, we are looking at an illness defined by cycles, and not ncessarily from one extreme to the other. Thus we see a continuum with bipolar I and II involving clearly observable upswings bleeding over into recurrent depression with its barely discernible swings to feeling better. Chronic depression is seen as a different phenomenon altogether.
Why this is important: If your so-called "unipolar" depression has much in common with the cycling of bipolar, then it may be wise to consider treating it with bipolar meds rather than an antidepressant.
2. "Pure" depression at one end, "pure" mania at the other. Occupying the middle ground, depression and mania converge into various mixed states. Think agitated and energized depression or dysphoric mania (euphoria gone sour), different ways of saying road rage, even if you don't drive.
Why this is important: Pure states tend to be easier to treat than mixed states. Different meds and therapy strategies may be called for.
3. Personality at one end of a severity scale, pathology at the other. Personality is your natural "trait," which may be depressive, exuberant, cyclothymic, or anxious, but nevertheless falling within "normal" and "functional." As opposed to "trait," pathology is identified as a "state," but the two tend to overlap.
Why this is important: We want our doctors to treat our illness, not medicate the personality out of us.
How has the DSM-5 Task Force addressed these concerns?
For Number 1: The Task Force could have added something along the lines of "bipolar III" to embrace certain forms of recurrent depression. Think of "bipolar III" as an extension of bipolar II (which was added to the DSM in 1994). Alternatively, the Task Force could have flagged recurrent depression in a way to suggest a possible relationship to bipolar. Perhaps the Task Force could have judiciously deployed elements of both. Instead, it did nothing.
For Number 2: The Task Force proposes a much wider version of "mixed episode." Currently, the DSM recognizes mixed states when both major depression and mania appear fully loaded at the same time. The expanded version acknowledges the reality that mixed states also occur when a patient is "predominantly manic or hypomanic" (full-on mania or hypomania with two or three depression symptoms) or when "predominantly depressed" (full-on depression, two or three mania/hypomania symptoms. -
This would rectify the current DSM's non-acknowledgement of mixed states occurring in bipolar II. But what about the reality of mixed episodes occuring in unipolar depression? The draft DSM-5 is insisting that if the depression is mixed, then it is not unipolar depression. Bipolar depression then? Only if there is a different episode involving pure depression. Confused? So is the Task Force's thinking on this issue.The Task Force deserves credit for acknowledging the reality of mixed states, but needs to put more work into refining the concept. Speaking of which, what about a state involving both minor depression plus minor mania? Cannot two minors together incapacitate us as badly as one lone major? Ah, questions, questions.
For Number 3: The Task Force reports that it "is proposing several options for severity." On one scale, 1 would be normal, 2 borderline ill, and on to 7 extremely ill. But what is normal? Just as your version of bipolar differs from my version of bipolar, so do our respective normals. Don't expect the DSM-5 to address this concern.
Much more on the DSM-5 later. In the meantime, I urge you to go to the APA's DSM-5 website and share your impressions. Comments below ...
Published On:
February 12, 2010
Please provide your
email address
to access your account.
If you do not have an account, create one now!
Please provide your
email address
to access your account.
If you do not have an account, create one now!
Enter a display name and email address to post a comment.
You may also create an account now.
Living With
6 Chronic Condition Guidelines to Live By
Facing the challenges
5 Rules for Bipolar Relationships


text:
The Mercedes Unimog is an amazing off-road machine, but why endure a crude truck when you can have all that same capability in a 1987 Mercedes E300 station wagon instead?
You can, with this incredible mash-up of those two vehicles, offered for sale. And the price is only $5,000! Sweet Jesus, that's actually a pretty good deal.
That not only includes the 140 horsepower 3.0-liter diesel six-cylinder engine and Mercedes-AMG G550 4x4²-style high-riding portal axles, but a steel-tube exoskeleton to armor up the luxury wagon.
Trouble is, you've gotta go to Lithuania to get it. Hey, we never said being awesome was easy.


text:
EC: Corruption Costs EU Economy EUR 120 B Each Year
The extent of corruption in Europe is "breathtaking" and it costs the EU economy at least EUR 120 B annually, the European Commission says.
EU Home Affairs Commissioner Cecilia Malmstroem presented on Monday a full report on the problem.
She admitted that the true cost of corruption was "probably much higher" than EUR 120 B.
Three-quarters of Europeans surveyed for the Commission study said that corruption was widespread, and more than half said the level had increased.
"The extent of the problem in Europe is breathtaking, although Sweden is among the countries with the least problems," Malmstroem wrote in Sweden's Goeteborgs-Posten daily.
The cost to the EU economy is equivalent to the bloc's annual budget.
For the report the Commission studied corruption in all 28 EU member states.
In Bulgaria, Croatia, the Czech Republic, Lithuania, Romania and Greece, between 6% and 29% of respondents said they had been asked for a bribe, or had been expected to pay one, in the past 12 months.
There were also high levels of bribery in Poland (15%), Slovakia (14%) and Hungary (13%), where the most prehad been expected to pay one, in the past 12 months.
There were also high levels of bribery in Poland (15%), Slovakia (14%) and Hungary (13%), where the most prevalent instances were in healthcare.
What EC report says about Bulgaria READ HERE
- » President Radev to Participate in Ceremony Marking 60th Anniversary of the Treaties of Rome
- » Donald Tusk To Visit Bulgaria in April
- » Bulgaria's Govt Approves Position for EU Summit Meeting in Rome
- » EP Adopts Resolution on Bulgarians in Albania
- » Expenses for Bulgaria's EU Presidency To Exceed BGN 50 M for 2017
- » EU To Send Experts to Sofia To Help With Presidency Organisation


text:
Decimal Degrees: Latitude: 34.933427 Longitude: -90.6801083
Share your comments and photos of Poplar Creek, a Stream in St. Francis County, AR
(Optional) Upload a photo taken at this location:
Bend: Quigley Bend , Berry Bend
Cemetery: Saint John Cemetery
Church: Saint John Church
Crossing: Castell Crossing , Quigley Crossing
School: White Rock School (historical) , Saint John School (historical)
Stream: Rocky Branch , Poplar Creek , Tuni Creek , Wyles Pond Slough
12 Places found nearby
New! Tell others about this location or share a photo!
Time to build: 0.0630 Secs | Cached: 28-Mar-17 01:46 PM


text:
Thursday 30 March 2017
06 June 2013
The IFRS Foundation is pleased to announce the publication of the following French translations:
eIFRS Professional and Comprehensive subscribers can access the translation from eIFRS you will be required to provide your login details). This section is updated throughout the year with French translations of new and revised Standards as issued by the IASB, as the translations become available.
At present, the files correspond to the text used for the adoption of IFRS into law, and do not include the accompanying material such as the Basis for Conclusions and the Illustrative Examples.
To find more information about our Available Translations visit the Translations Status page.


text:
For my outfit today, I went with a classic striped tank, layered with a navy camisole underneath, and topped with a camel blazer. Classic, right? Then come the bright red pants. I have a serious love affair with colored pants. I am not sure I will be over it any time soon. Anyone else loving colorful pants this season?
Tank: Forever 21, Pants: Macy's, Blazer: Express, Shoes: New York & Company, Necklace: Kohl's


text:
Twitter Bio:
Owner of http://www.pixelmagic.co.za; designer, pixel alchemist and equine lover.
Featured Twitter Background Designer
Meryl is addicted to designing (amongst other things) gorgeous Twitter backgrounds, and two of her designs put in regular appearances in the Top 10 Highest Rated Backgrounds.
Her prices range from ZAR500 (approx. $50) to ZAR750 (approx. $75) before any discounts, and she has extensive experience in working with US, UK and Australian clients as well as South African clients.
Also designed:
@freshfishjhb, @neighbourscoza, @sandwichbaron, @pokenafrica, @juanmanuelm, @stevesmithnz, @dssconsult, @xsyn, @digitalID, Therapeutic_C, BarryLouzada, @merylpixelmagic (Valentine's edition), @Twestival_Jozi @hhcu, @SimpleStencils, @dolphins_angels, @oryxza
Website: Pixelmagic.co.za
What people are saying:
January 3rd, 2009 at 3:17 amAs usual your work is awesome!
I dig the format – if I were to comment – I would say the twitter on top draws your eye to it.. which is destracting. Perhaps if you picked up on that color a little – and intergrated it, it may not take center stage as it does now, giving a little more balance to the page too. -
January 3rd, 2009 at 3:50 amLove the colours, information, and user friendly
Trish Malkoff
January 3rd, 2009 at 4:27 amWay 2 go Meryl – most exciting web design co it's been my pleasure to deal with … and you Meryl are more than just a service provider. Gr8 working with you – we and all the horsies at Highveld Horse Care Unit are indebted! Thank you.
Trish-M & MikemOOg,
SA Stage Sound & Screen -
January 5th, 2009 at 2:41 amThis is Awesome Meryl! LOVE IT!
January 5th, 2009 at 11:59 amAh thanks guys
January 5th, 2009 at 11:04 pmWOW Meryl! Absoutely awesome!
Nikki Viljoen
January 6th, 2009 at 2:26 amHiya
Fabulous – now just have to learn how to use it!
Robin Waltham
January 6th, 2009 at 4:47 amPixelmagic Rocks!!!
January 6th, 2009 at 8:16 amPixelmagic rocks as usual!
January 20th, 2009 at 7:59 ampurrfect… and no mac in sight… impressed
Fred Campbell
January 21st, 2009 at 9:45 amSooo green. I like it a lot. Thought Bonny's comment was a bit harsh. Twitter is Twitter – so what, do you change your own website and corporate ID just to blend in with a Twitter page?
January 22nd, 2009 at 3:31 amNo Fred, I am not harsh – I want to see Meryl only – I am shamelessly biased – If she could plaster something over twitter – I may be happier
January 22nd, 2009 at 11:08 amHey well done!
Keep it up! I will support anything you guys do.
January 23rd, 2009 at 12:52 amThanks everyone … really appreciate all the feedback!
Bonny: hehe thanks … maybe you can persuade twitter to go green? I like the blue, it offsets my green nicely! -
Mike van Hoenselaar
January 26th, 2009 at 11:48 pmLots of comments and feedback. Had too, 'cause of the very nice background! Keep it up.
February 1st, 2009 at 10:17 pmSuper, Meryl! Very clean and unusual! R
Twestival Johannesburg
February 1st, 2009 at 10:44 pmWe love Meryl – she's from Jozi and she's a great designer!
February 5th, 2009 at 1:32 pmEver the perfectionist…got to love her!
Ricardo Teixeira
February 15th, 2009 at 1:26 pmMerly is a maverick when comes to pixelmagic! Good job … I like!
Ricardo -
April 21st, 2009 at 2:01 amCongrats on getting into the top selection of twitter background designers! You're a real alchemist when it comes to design work. Awesome to work with you. Rick
May 13th, 2009 at 12:13 pmah thanks guys … so nice to see the comments
1 Trackbacks For This Post
@merylpixelmagic featured on Twitter Backgrounds Gallery (February 13th, 2009 at 8:58 am)
[...] designed: @merylpixelmagic, @Twestival_Jozi @hhcu, @dolphins_angels, [...]


text:
4308 Alton Road, Suite 710,
Miami Beach, FL 33140
Up to three injections, spaced several weeks apart, may be placed within a six-month period. Many patients find that a single PRP treatment brings them considerable relief of their painful symptoms, and that their improvement continues over time.
Contact Us TODAY!
Our Doctors
Olivera Jovic DPM, AACFAS
Consulting Orthopedic Specialists:
Richard P. Giovanelli, M.D.
Facial Rejuvenation Specialist:
Dr. Nicole M. Berger
Dear Dr. Guyen & Dr. Berkowitz, Well….where to start ? It's no exaggeration to say you have truly changed my life, changed my day to day, changed my self-perception….and so much more.....
Stem Cell Therapy creates specialized cells that have a particular life cycle and purpose, like bone or connective tissue. Stem cells can replicate themselves, too, so it is theoretically possible to have an unending supply of these regenerative "machines" that can then divide and be guided to produce the cells your doctor needs to fulfill specific purposes in your treatment.


text:
Diablo 3 players are looking forward to the release of the Rise of the Necromancer DLC expansion, but Blizzard has been keeping specific details like the price, release date and what the expansion will include under wraps. We still don't know exactly what kind of content to expect from the Diablo 3 Necromancer DLC, but we can get a better idea by looking at previous releases like Reaper of Souls.
Diablo 3 Necromancer release date price: What to expected based on past DLCs
Diablo 3 Necromancer release date price: How Reaper of Souls could influence Rise of the Necromancer
If Rise of the Necromancer costs as much as Reaper of Souls it could start at $19.99. Then again, it seems like this DLC won't be quite as expansive.
The Diablo 3 Necromancer update will bring with it the Corpse Explosion ability, along with a whole host of other changes, according to Blizzard. That includes a full set of legendary armor and other items created especially for it.
Still, it doesn't seem that Blizzard is focusing as much on making this expansion as big and exciting as previous ones. That could push the price down a little lower. Maybe somewhere around $9.99?
Then again, Blizzard still hasn't revealed all the Necromancer details. It's possible the DLC cold bring new modes and even additional chapters to Diablo 3. In that case, expect to pay $19.99 or higher for the experience.
More Diablo 3 news and rumors
Mic has all the latest Diablo news, including updates on when we might be able to expect the Necromancer's appearance, Diablo 3's recent anniversary patch and a handy list of cheats and secrets.


text:
With more than 2500 stores across the world, Foot Locker is the leading global athletic footwear and apparel retailer. Our close partnerships with the ultimate top brands mean that we will constantly provide you with the best, most exclusive ranges of products there is. At Foot Locker, we live sneakers, we breathe sneakers, we dream sneakers… Sneakers are all we think about and nothing makes us more proud than being able to keep our followers up to date with the latest trends.
For more than 30 years, our collections have been curated by sneaker heads for sneaker heads. Only the best, most relevant and exciting products ever make it onto our shelves and onto our online catalogues. "If it is at Foot locker, then it is approved!" This is the word on the street. Whether you are a long time dedicated sneaker lover or casually searching for a fresh new pair of shoes, Foot Locker has you covered, from the feet up. Don't forget to peek into our fantastic range of apparel and accessories too! And keep in mind: most of our products you won't be able to find anywhere else!
On European soil only, Foot Locker means more than 620 stores in premium locations, across 20 countries and closing in on 30 years of history. Foot Locker Europe also means an elevated digital experience for our ever-increasing fan base, throughout a brand-new exciting website and vibrant interactive social media platforms. Last but not least, Foot Locker is an established intricate element of the European street culture, sneaker scene and athletic lifestyle. We thrive to always give back to the community and we are involved in countless events and happenings throughout the continent. Parties, sport competitions, social gatherings, sneaker shows… There is always a Foot Locker event going on, at any time.
Stay tuned and keep your sneaker lifestyle alive and kicking with Foot Locker!
Company Info
FootLocker Europe.com B.V.
Ir.D.S. Tuijnmanweg 3-5, 4131 PN Vianen
The Nederlands
KvK Utrecht no. 30181126
VAT group: NL8005.36.253B.01
Email address: firstname.lastname@example.com
Customer Service Desk:
United Kingdom 0800-3316062
France 08 05 54 07 86
Germany 0800-5888232
Belgium 0800-81177
Luxemburg 800-26555
Netherlands 08000200269
Italy 800 986936
Spain 800 600931
Information on the possibility of an alternative and online dispute resolution, you can find here: http://ec.europa.eu/consumers/odr/


text:
Find a copy in the library
Finding libraries that hold this item...
Genre/Form: | Criticism, interpretation, etc |
Additional Physical Format: | Online version: Masson, David, 1822-1907. Wordsworth, Shelley, Keats. New York, B. Franklin [1970] (OCoLC)570684764 |
Document Type: | Book |
All Authors / Contributors: |
David Masson |
OCLC Number: | 98467 |
Notes: | Reprint of the 1874 ed. Four of the six essays reprinted from the author's Essays biographical and critical: chiefly on English poets, published in 1856. |
Description: | 305 pages 19 cm. |
Contents: | Wordsworth.--Scottish influence in British literature.--The life and poetry of Shelley.--The life and poetry of Keats.--Theories of poetry.--Prose and verse: De Quincey. |
Series Title: | Burt Franklin research & source works series, no. 489.; Burt Franklin research & source works series., Essays in literature & criticism ;, #68. |
User-contributed reviews
Add a review and share your thoughts with other readers.
Be the first.
Add a review and share your thoughts with other readers.
Be the first.
Add tags for "Wordsworth, Shelley, Keats; and other essays.".
Be the first.


text:
It's odd logging back into SL after a long absence. It's not unlike booting up the xbox and playing an old game you used to know all the moves for only to find that you don't remember where your guns are or how to jump over obstacles: only with SL it's an inability to walk in a straight line or talk to people. I always used to tell people who said "I'm tired/bored of SL" that that was a problem which was easy to fix, they conveniently put a big red X in the upper right hand corner for just such an occasion. I used mine and once used it lasted a considerable time. I'm back now and unlike video games, SL doesn't wait for you at your last save point while you were away. One difference I've noticed so far is that when you log into an old console pew-pew shooter, the game itself hasn't changed half the bloody rules while you were otherwise engaged. I'm all out of date, stumbley, twitchy and awkward like a drunk at a wedding.
I spent my entire first day obsessing, "does everyone have a mesh face now? Does every man have a beard? Did I get taller? Why is my left eye floating outside my head – is that a glitch or some fashion thing that was popular just before I left?" I'm not used to second guessing myself or noticing this kind of shit so it's not only odd logging back in, it's hard.
Yes I tried going to a few "noob-friendly" help areas for some assist but it's tough to get help when the help you need is like – you know you have a HUD but you can't remember how to attach it, or where it's saved, or what's it's called, or what it does.
They have their hands full with the real noobs who are eager to learn and willing to listen. They probably don't need the distraction of some "I USED TO BE GOOD AT THIS" dude who doesn't want something explained to him, he just wants enough of a hint so he can remember himself, and thus feel like he figured it out on his own – technically, kinda.
So if my first day / but not my first first day was a lot of confusion and weeping, I can't imagine how crazy it must be for genuine new starters. I'd conduct a poll and do some in-depth interviews on the subject if I wasn't already bored of the idea as I'm typing it out. I'm sure it's no great revelation but I have (re)discovered that SL is disorienting. I played leapfrog to help me get back into the swing of things and it got a little better.
Side note, leapfrog is when you go to a destination from the SL guide and TP out by following a link from the picks tab of someone nearby, then do it again at the next location. And the next. And so forth and so on. If you end up in a place with no people, you have to walk till you find someone else to profile pick/port. It's marginally more fun than I make it sound. Though, that said, it was only 20 mins before a TP took me to a 1950's Americana-styled garage that had eight heavily pregnant women standing around in a circle talking. Old me would have instantly wondered what was the deal and dived into a fact-finding conversational gambit. New me freaked out and ran away. SL: It's not only odd logging back in, it's downright odd. Perhaps that's what makes us come back?


text:
GS-tested Safety is the most reliable symbol for the functional safety of furniture and articles of everyday use. This symbol is awarded by independent inspection authorities licensed by the German Federal Ministry. The test always refers to the overall safety of a piece of furniture.
Due to the low emissions, PAIDI fulfil the criteria of the Blue Angel with their furniture.
The two norms EN 71-3 and DIN 53160 lay down very precise conditions for the constitution of toys (e.g. resistance to saliva) so that children's health is not endangered when they play.