The exceptional set for the number of primes in short intervals

We give upper bounds for the number of x up to X such that the interval (x, x+h) does not contain the expected quantity of primes. Here h is small with respect to x

Optimization of Gene Prediction via More Accurate Phylogenetic Substitution Models

Determining the beginning and end positions of each exon in each protein coding gene within a genome can be difficult because the DNA patterns that signal a gene’s presence have multiple weakly related alternate forms and the DNA fragments that comprise a gene are generally small in comparison to the size of the genome. In response to this challenge, automated gene predictors were created to generate putative gene structures. N SCAN identifies gene structures in a target DNA sequence and can use conservation patterns learned from alignments between a target and one or more informant DNA sequences. N SCAN uses a Bayesian network, generated from a phylogenetic tree, to probabilistically relate the target sequence to the aligned sequence(s). Phylogenetic substitution models are used to estimate substitution likelihood along the branches of the tree. Although N SCAN’s predictive accuracy is already a benchmark for de novo HMM based gene predictors, optimizing its use of substitution models will allow for improved conservation pattern estimates leading to even better accuracy. Selecting optimal substitution models requires avoiding overfitting as more detailed models require more free parameters; unfortunately, the number of parameters is limited by the number of known genes available for parameter estimation (training). In order to optimize substitution model selection, we tested eight models on the entire genome including General, Reversible, HKY, Jukes-Cantor, and Kimura. In addition to testing models on the entire genome, genome feature based model selection strategies were investigated by assessing the ability of each model to accurately reflex the unique conservation patterns present in each genome region. Context dependency was examined using zeroth, first, and second order models. All models were tested on the human and D. melanogaster genomes. Analysis of the data suggests that the nucleotide equilibrium frequency assumption (denoted as πi) is the strongest predictor of a model’s accuracy, followed by reversibility and transition/transversion inequality. Furthermore, second order models are shown to give an average of 0.6% improvement over first order models, which give an 18% improvement over zeroth order models. Finally, by limiting parameter usage by the number of training examples available for each feature, genome feature based model selection better estimates substitution likelihood leading to a significant improvement in N SCAN’s gene annotation accuracy

A Comparison of High School Graduation Predictors Between Two Ontario Student Cohorts

While a number of factors have already been shown to impact variations in graduation rates among students in Canada, there is little research examining the changing impact of these factors on Ontario students’ secondary education completion over time. This research draws on data from two Grade 9 cohorts (2006 and 2011) from the Toronto District School Board in order to unpack how predictors of high school graduation change over time. In particular, we use multivariate analysis to examine whether predictors (including gender, race, parental education, household income, suspension, academic achievement, special education needs, and Grade 9 absenteeism) are significant by cohort of students and if there are gaps in secondary school success between subgroups. Findings demonstrate that high school completion is increasing over time and that there is a diminishing importance of parental education and neighbourhood household income as a predictor of high school graduation. However, we do find evidence of persistent under-achievement among students of certain racial backgrounds, lower academic streams, and those with high rates of absenteeism. We argue that additional data infrastructure in Ontario and beyond are necessary to identify how our findings generalize to the province as a whole.Bien qu’il ait déjà été démontré qu’un certain nombre de facteurs influencent les variations des taux d’obtention de diplôme chez les élèves au Canada, peu de recherches se sont penchées sur les conséquences de ces facteurs sur l’achèvement des études secondaires des élèves ontariens au fil du temps. La présente recherche repose sur des données recueillies auprès de la Commission scolaire du district de Toronto concernant deux promotions de 9e année (2006 et 2011) et vise à déterminer comment les indicateurs relatifs à l’obtention des diplômes d’études secondaires évoluent au fil du temps. Plus particulièrement, nous recourons à une analyse multivariée pour déterminer si les indicateurs (notamment le sexe, la race, le niveau d’éducation des parents, le revenu du ménage, la suspension, le rendement scolaire, les besoins en matière d’éducation spécialisée et l’absentéisme en 9e année) sont significatifs par groupe d’élèves et s’il y a des écarts en matière de réussite au secondaire entre les sous-groupes. Les résultats obtenus prouvent que le taux d’achèvement des études secondaires augmente au fil du temps et que l’importance de l’éducation des parents et du revenu moyen des ménages du quartier en tant que facteurs prédictifs de l’obtention du diplôme d’études secondaires diminue. Cependant, nous observons la persistance de mauvais résultats chez les élèves de certaines minorités raciales, dans les classes inférieures et chez ceux qui ont un taux d’absentéisme élevé. Nous estimons que des infrastructures de données supplémentaires sont nécessaires en Ontario et ailleurs pour savoir si les résultats que nous avons obtenus s’appliquent à l’ensemble de la province

Magnetic Reversal in Nanoscopic Ferromagnetic Rings

We present a theory of magnetization reversal due to thermal fluctuations in thin submicron-scale rings composed of soft magnetic materials. The magnetization in such geometries is more stable against reversal than that in thin needles and other geometries, where sharp ends or edges can initiate nucleation of a reversed state. The 2D ring geometry also allows us to evaluate the effects of nonlocal magnetostatic forces. We find a `phase transition', which should be experimentally observable, between an Arrhenius and a non-Arrhenius activation regime as magnetic field is varied in a ring of fixed size.Comment: RevTeX, 23 pages, 7 figures, to appear in Phys. Rev.

A revision of the Larainae (Coleoptera, Elmidae) of Venezuela, with description of nine new species

The species of the riffle beetle subfamily Larainae occurring in Venezuela are revised. Examination of 756 specimens yielded 22 species in nine genera occurring throughout the country. Seven species are newly recorded from the country: Phanoceroides sp. 1, Phanocerus clavicornis Sharp, 1882, Phanocerus congener Grouvelle, 1898, Pharceonus volcanus Spangler & Santiago-Fragoso, 1992, Disersus dasycolus Spangler & Santiago-Fragoso, 1992, Disersus chibcha Spangler & Santiago-Fragoso, 1987, and Disersus inca Spangler & Santiago-Fragoso, 1992. Nine species are found to be new to science, which are here described: Hexanchorus dentitibialis sp. n., H. falconensis sp. n., H. flintorum sp. n., H. homaeotarsoides sp. n., H. inflatus sp. n., Phanocerus rufus sp. n., Pharceonus grandis sp. n., Pharceonus ariasi sp. n., Potamophilops bostrychophallus sp. n. Additionally, a key to species, distribution maps, and photographs and genitalia illustrations are provided for all species

Exercise training reverses myocardial dysfunction induced by CaMKIIδC overexpression by restoring Ca2+-homeostasis

Several conditions of heart disease, including heart failure and diabetic cardiomyopathy, are associated with upregulation of cytosolic Ca2+/calmodulin-dependent protein kinase II (CaMKIIδC) activity. In the heart, CaMKIIδC isoform targets several proteins involved in intracellular Ca2+ homeostasis. We hypothesized that high-intensity endurance training activates mechanisms that enable a rescue of dysfunctional cardiomyocyte Ca2+ handling and thereby ameliorate cardiac dysfunction despite continuous and chronic elevated levels of CaMKIIδC. CaMKIIδC transgenic (TG) and wild-type (WT) mice performed aerobic interval exercise training over 6 wk. Cardiac function was measured by echocardiography in vivo, and cardiomyocyte shortening and intracellular Ca2+ handling were measured in vitro. TG mice had reduced global cardiac function, cardiomyocyte shortening (47% reduced compared with WT, P < 0.01), and impaired Ca2+ homeostasis. Despite no change in the chronic elevated levels of CaMKIIδC, exercise improved global cardiac function, restored cardiomyocyte shortening, and reestablished Ca2+ homeostasis to values not different from WT. The key features to explain restored Ca2+ homeostasis after exercise training were increased L-type Ca2+ current density and flux by 79 and 85%, respectively (P < 0.01), increased sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) function by 50% (P < 0.01), and reduced diastolic SR Ca2+ leak by 73% (P < 0.01), compared with sedentary TG mice. In conclusion, exercise training improves global cardiac function as well as cardiomyocyte function in the presence of a maintained high CaMKII activity. The main mechanisms of exercise-induced improvements in TG CaMKIIδC mice are mediated via increased L-type Ca2+ channel currents and improved SR Ca2+ handling by restoration of SERCA2a function in addition to reduced diastolic SR Ca2+ leak

C-terminal phosphorylation of NaV1.5 impairs FGF13-dependent regulation of channel inactivation

International audienceVoltage-gated Na(+) (NaV) channels are key regulators of myocardial excitability, and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)-dependent alterations in NaV1.5 channel inactivation are emerging as a critical determinant of arrhythmias in heart failure. However, the global native phosphorylation pattern of NaV1.5 subunits associated with these arrhythmogenic disorders and the associated channel regulatory defects remain unknown. Here, we undertook phosphoproteomic analyses to identify and quantify in situ the phosphorylation sites in the NaV1.5 proteins purified from adult WT and failing CaMKIIδc-overexpressing (CaMKIIδc-Tg) mouse ventricles. Of 19 native NaV1.5 phosphorylation sites identified, two C-terminal phosphoserines at positions 1938 and 1989 showed increased phosphorylation in the CaMKIIδc-Tg compared with the WT ventricles. We then tested the hypothesis that phosphorylation at these two sites impairs fibroblast growth factor 13 (FGF13)-dependent regulation of NaV1.5 channel inactivation. Whole-cell voltage-clamp analyses in HEK293 cells demonstrated that FGF13 increases NaV1.5 channel availability and decreases late Na(+) current, two effects that were abrogated with NaV1.5 mutants mimicking phosphorylation at both sites. Additional co-immunoprecipitation experiments revealed that FGF13 potentiates the binding of calmodulin to NaV1.5 and that phosphomimetic mutations at both sites decrease the interaction of FGF13 and, consequently, of calmodulin with NaV1.5. Together, we have identified two novel native phosphorylation sites in the C terminus of NaV1.5 that impair FGF13-dependent regulation of channel inactivation and may contribute to CaMKIIδc-dependent arrhythmogenic disorders in failing hearts

Predicting Successful Introduction of Novel Fruit to Preschool Children

Background: Few children eat sufficient fruits and vegetables despite their established health benefits. The feeding practices used by parents when introducing novel foods to their children, and their efficacy, require further investigation. Objective: We aimed to establish which feeding strategies parents commonly use when introducing a novel fruit to their preschool-aged children and assess the effectiveness of these feeding strategies on children’s willingness to try a novel fruit. Design Correlational design. Participants/setting Twenty-five parents and their children aged 2 to 4 years attended our laboratory and consumed a standardized lunch, including a novel fruit. Interactions between parent and child were recorded and coded. Statistical analyses performed Pearson’s correlations and multiple linear regression analyses. Results: The frequency with which children swallowed and enjoyed the novel fruit, and the frequency of taste exposures to the novel fruit during the meal, were positively correlated with parental use of physical prompting and rewarding/bargaining. Earlier introduction of solids was related to higher frequency of child acceptance behaviors. The child’s age at introduction of solids and the number of physical prompts displayed by parents significantly predicted the frequency of swallowing and enjoying the novel fruit. Age of introduction to solids and parental use of rewards/bargaining significantly pre- dicted the frequency of taste exposures. Conclusions: Prompting a child to eat and using rewards or bargains during a positive mealtime interaction can help to overcome barriers to novel fruit consumption. Early introduction of solids is also associated with greater willingness to consume a novel fruit.Peer reviewedFinal Accepted Versio

1,2-Dimethyl-4,5-diphenyl­benzene determined on a Bruker SMART X2S benchtop crystallographic system

The title compound, C20H18, has two crystallographically independent mol­ecules in the asymmetric unit. The phenyl substituents of mol­ecule A are twisted away from the plane defined by the central benzene ring by 131.8 (2) and −52.7 (3)°. The phenyl substituents of mol­ecule B are twisted by −133.3 (2) and 50.9 (3)°. Each mol­ecule is stabilized by a pair of intra­molecular C(aryl, sp 2)—H⋯π inter­actions, as well as by several inter­molecular C(methyl, sp 3)—H⋯π inter­actions

Mapping functional transcription factor networks from gene expression data

A critical step in understanding how a genome functions is determining which transcription factors (TFs) regulate each gene. Accordingly, extensive effort has been devoted to mapping TF networks. In Saccharomyces cerevisiae, protein–DNA interactions have been identified for most TFs by ChIP-chip, and expression profiling has been done on strains deleted for most TFs. These studies revealed that there is little overlap between the genes whose promoters are bound by a TF and those whose expression changes when the TF is deleted, leaving us without a definitive TF network for any eukaryote and without an efficient method for mapping functional TF networks. This paper describes NetProphet, a novel algorithm that improves the efficiency of network mapping from gene expression data. NetProphet exploits a fundamental observation about the nature of TF networks: The response to disrupting or overexpressing a TF is strongest on its direct targets and dissipates rapidly as it propagates through the network. Using S. cerevisiae data, we show that NetProphet can predict thousands of direct, functional regulatory interactions, using only gene expression data. The targets that NetProphet predicts for a TF are at least as likely to have sites matching the TF's binding specificity as the targets implicated by ChIP. Unlike most ChIP targets, the NetProphet targets also show evidence of functional regulation. This suggests a surprising conclusion: The best way to begin mapping direct, functional TF-promoter interactions may not be by measuring binding. We also show that NetProphet yields new insights into the functions of several yeast TFs, including a well-studied TF, Cbf1, and a completely unstudied TF, Eds1