The log2 of the number of sequences in the population of all DNA 7-mers that are below or equal to the relative binding energy indicated on the x-axis.

<p>The “log2 of cutoff” is a DNA-protein binding energy based on the affinity values listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0006736#pone-0006736-g001" target="_blank">Figure 1B</a>.</p

Performance of the position weight matrix models with Boltzmann sampling.

<p>A–C. Alignments containing 20 sites. D–F. Alignments containing 50 sites. G–I. Alignments containing 200 sites. The log-odds, Match, and quadratic programming results are denoted by the red open-square, yellow open-diamond, and blue filled-oval markers respectively. Each data point is the mean of five replicates. Error bars denote the standard deviation of the mean.</p

Receiver operator characteristic curves of the position weight matrix models with step-function sampling.

<p>The log-odds, Match, and quadratic programming results are denoted by red, yellow, and blue markers respectively. Each data point is the mean of five replicates and points are allowed to overlap. Error as standard deviation of the mean extends from each curve by the size of a single marker. A. Alignments containing 20 sites; cutoff = 4. The log-odds, Match, and quadratic programming curves attain TP = 1 at FP = 0.013, 0.099, and 0.019, respectively. B. Alignments containing 20 sites; cutoff = 7. The log-odds, Match, and quadratic programming curves attain TP = 1 at FP = 0.329, 0.495, and 0.200, respectively. C. Alignments containing 50 sites; cutoff = 4. The log-odds, Match, and quadratic programming curves attain TP = 1 at FP = 0.014, 0.057, and 0.011, respectively. D. Alignments containing 50 sites; cutoff = 7. The log-odds, Match, and quadratic programming curves attain TP = 1 at FP = 0.151, 0.437, and 0.070, respectively. E. Alignments containing 200 sites; cutoff = 4. The log-odds, Match, and quadratic programming curves attain TP = 1 at FP = 0.009, 0.038, and 0.006, respectively. F. Alignments containing 200 sites; cutoff = 7. The log-odds, Match, and quadratic programming curves attain TP = 1 at FP = 0.061, 0.253, and 0.013, respectively.</p

Creating a ROC curve.

<p>This figure shows a portion of a typical spreadsheet used to construct a ROC curve. In this example the PWM model is a log-odds model based on 50 sites. The cutoff is 4 and the sampling mode is Boltzmann. There are 77 sites whose true energy is below or equal to the cutoff (i.e. K = 77). In the original spreadsheet the index <i>i</i> runs from 1 to 16,384.</p

Performance of the position weight matrix models with step-function sampling.

<p>A–C. Alignments containing 20 sites. D–F. Alignments containing 50 sites. G–I. Alignments containing 200 sites. The log-odds, Match, and quadratic programming results are denoted by the red open-square, yellow open-diamond, and blue filled-oval markers respectively. Each data point is the mean of five replicates. Error bars denote the standard deviation of the mean.</p

Mnt binding matrices.

<p>A. The experimentally observed relative frequency of each type of DNA base at each position in the 7-long Mnt protein half-site. The highest affinity site is: 5′-GTGGACC-3′. B. The negative log2 of the values shown in A. Each entry represents the binding energy contributed by a particular base at that position in the site to the total binding energy. This matrix represents the “true” binding model.</p

Histologic evaluation of intestinal tissue.

<p>(A) Snapshot image of an entire digital slide. (B) Intestinal lesions identified on the slide depicted in (A) Upper left: representative hyperplasia of mucosal epithelium that could be miscounted as adenoma on visual gross exam. Upper right: small adenoma that could be easily missed at visual gross exam. Lower left: adenoma adjacent to Peyer’s patch on the first serial section from slide shown in (A) Lower right: the same adenoma from lower left image appearing on the next serial section cut approximately 350μm deeper into the paraffin block. (C) Average lesions per age group. For tissue counted histologically, lesion number includes hyperplasias and adenomas. Columns represent the average lesion count. Bars = standard deviation. n = 4 mice per age group, except 6.6 weeks old, where n = 3. * p < 0.01 comparing total lesions, ** p <0.05 comparing adenomas only, p < 0.001 comparing total lesions using Student’s t-test.</p

Adenoma Counts Before and After Pathologist Review.

<p>Adenoma Counts Before and After Pathologist Review.</p

Lesion counting is inconsistent between observers.

<p>(A) Adenomas were counted by two observers, blind to the mouse group as well as the lesion count of the other observer. Columns represent the average count. n = 3 per group, except Group 1 where n = 1, Bars = Stdev. (B) Percent difference between observers by animal, using the same animals as in (A) Each column represents a single animal.</p

A comparative computational study on molecular structure, NBO analysis, multiple interactions, chemical reactivity and first hyperpolarisability of imatinib mesylate polymorphs using DFT and QTAIM approach

<div><p>Imatinib, a phenylaminopyrimidine compound is a therapeutic drug for treatment of chronic myelogeneous leukaemia and gastrointestinal stromal tumours. It is well known that imatinib mesylate (ImM) exists in two polymorphic forms α and β. In this work, a computational study on molecular properties of ImM polymorphs is presented using density functional theory, B3LYP functional and 6-311G(d,p) as basis set. Natural bond orbital analysis is carried out to investigate the various conjugative and hyperconjugative interactions within the molecule and their second-order stabilisation energy (<i>E</i>⁽²⁾). The local nucleophilic reactivity descriptors such as Fukui functions (), local softness () and electrophilicity indices () analyses are carried out to determine the reactive sites within the molecule. To determine strength and nature of intra- and intermolecular interactions, topological parameters as electron density (ED) (ρ_BCP), Laplacian of ED (▽²ρ_BCP) and total electron energy density (<i>H</i>_BCP) at bond critical points have been analysed by ‘quantum theory of atoms in molecules’ in detail. The computed first hyperpolarisability (β₀) for both forms of ImM molecule (10.927 and 10.354 × 10^− 30 esu) suggests that the investigated molecule is an attractive object in future for non-linear optical properties. Molecular electrostatic potential surface of ImM has been mapped to predict the inhibitory activity and binding affinity with a panel of protein tyrosine kinases.</p></div