Can we always sweep the details of RNA-processing under the carpet?

RNA molecules follow a succession of enzyme-mediated processing steps from transcription until maturation. The participating enzymes, for example the spliceosome for mRNAs and Drosha and Dicer for microRNAs, are also produced in the cell and their copy-numbers fluctuate over time. Enzyme copy-number changes affect the processing rate of the substrate molecules; high enzyme numbers increase the processing probability, low enzyme numbers decrease it. We study different RNA processing cascades where enzyme copy-numbers are either fixed or fluctuate. We find that for fixed enzyme-copy numbers the substrates at steady-state are Poisson-distributed, and the whole RNA cascade dynamics can be understood as a single birth-death process of the mature RNA product. In this case, solely fluctuations in the timing of RNA processing lead to variation in the number of RNA molecules. However, we show analytically and numerically that when enzyme copy-numbers fluctuate, the strength of RNA fluctuations increases linearly with the RNA transcription rate. This linear effect becomes stronger as the speed of enzyme dynamics decreases relative to the speed of RNA dynamics. Interestingly, we find that under certain conditions, the RNA cascade can reduce the strength of fluctuations in the expression level of the mature RNA product. Finally, by investigating the effects of processing polymorphisms we show that it is possible for the effects of transcriptional polymorphisms to be enhanced, reduced, or even reversed. Our results provide a framework to understand the dynamics of RNA processing

Addressing the Higher Level Language Skills for the Common Core State Standards in Kindergarten

Kindergarten is a critical year, providing a foundation for children’s success in school. With a common set of standards, the Common Core State Standards (CCSS), finalized and made available to states for adoption critical skills in numeracy and literacy will be uniformed from kindergarten through high school. Some children enter school with a sufficient foundation to support success in kindergarten and subsequent years. However, some children either because of lack of exposure during preschool years (e.g., Aikens & Barbarin, 2008; Hart & Risley, 1995; Schacter, 1979; Snow, Burns & Griffin, 1998) or because of language delays associated with developmental disabilities or delays (e.g., Catts, Adolf & Weismer, 2006; Gough & Tunmer, 1986; Kuhn & Stahl, 2003; Nation & Snowling, 1998; Yuill & Oakhill, 1991) are already far behind their peers upon entrance into kindergarten. The current study investigated the effects of presenting a multilevel approach to storybook reading on a broad range of language skills over 32 weeks of intervention for children at-risk for reading. Specifically, growth in overall language, semantics, syntax, letter awareness, and phonology was explored. Thirty-six at-risk kindergarten students comprised a group that either received intervention utilizing scaffolded talk across a continuum of increasingly more decentered meanings or represented a comparison group. The results of the study revealed that the intervention group made statistically significant gains in overall language, semantic, and syntax skills. A visual inspection of gain composite scores revealed that majority of the intervention groups increased near or at least one standard deviation of change from pre- to posttest; these gains were not evident in the comparison group. The result of the study indicated that utilizing scaffolded talk across a continuum of increasing more decentered meanings in kindergarten hold potential to address the language goals of the CCSS

Calculation of multivariate Chebyshev-type inequalities

AbstractA general multivariate Chebyshev inequality has been obtained by Whittle and Olkin and Pratt. Application of their inequality is made difficult because of the presence of a certain intractable matrix equation. Dharmadhikari and Joag-Dev have obtained a bivariate Gauss inequality. In this paper, we extend the bivariat Gauss inequality to the general multivariate case, encountering the same intractable matrix equation. We develop a general method for the solution of this equation, applying recent results in the solution of systems of nonlinear equations

Influence of mutation rate on estimators of genetic differentiation - lessons from Arabidopsis thaliana

It has been brought to our attention that our paper (Kronholm et al. BMC Genetics 2010, 11: 33) may have caused some confusion for readers interested in the correct quantification of population differentiation. We feel that this issue is of some importance and wish to clarify any confusion that might have resulted

Co-expression of neighbouring genes in Arabidopsis: separating chromatin effects from direct interactions

<p>Abstract</p> <p>Background</p> <p>In all eukaryotic species examined, genes that are chromosomal neighbours are more similar in their expression than random gene pairs. Currently, it is still unclear how much of this local co-expression is caused by direct transcriptional interactions, and how much is due to shared chromatin environments.</p> <p>Results</p> <p>We analysed neighbouring genes in <it>Arabidopsis thaliana</it>. At large intergenic distances (>400 bp), divergently and convergently transcribed gene pairs show very similar levels of co-expression, mediated most likely by shared chromatin environments. At gene distances below 400 bp, co-expression is strongly enhanced only for divergently transcribed gene pairs, indicating bi-directional transcription from a single promoter. Conversely, co-expression is suppressed for short convergently or uni-directionally transcribed pairs. This suppression points to transcriptional interference concentrated at the 3' end, e.g., in the context of transcription termination.</p> <p>Conclusions</p> <p>Classifying linked gene pairs by their orientation, we are able to partially tease apart the different levels of regional expression modulation. (i) Regional chromatin characteristics modulate the accessibility for regulation and transcription, regardless of gene orientation; the strength of this chromatin effect can be assessed from divergently or convergently transcribed distant neighbours. (ii) Shared promoter regions up to 400 bp in length enhance the co-expression of close bi-directional neighbours. (iii) Transcriptional interference of close neighbours is concentrated at the 3' ends of genes, and reduces co-expression on average by 40%.</p

On the algebraic immunity of direct sum constructions

In this paper, we study sufficient conditions to improve the lower bound on the algebraic immunity of a direct sum of Boolean functions. We exhibit three properties on the component functions such that satisfying one of them is sufficient to ensure that the algebraic immunity of their direct sum exceeds the maximum of their algebraic immunities. These properties can be checked while computing the algebraic immunity and they allow to determine better the security provided by functions central in different cryptographic constructions such as stream ciphers, pseudorandom generators, and weak pseudorandom functions. We provide examples for each property and determine the exact algebraic immunity of candidate constructions

Independence Distribution Preserving Covariance Structures for the Multivariate Linear Model

AbstractConsider the multivariate linear model for the random matrixYn×p∼MN(XB,V⊗Σ), whereBis the parameter matrix,Xis a model matrix, not necessarily of full rank, andV⊗Σ is annp×nppositive-definite dispersion matrix. This paper presents sufficient conditions on the positive-definite matrixVsuch that the statistics for testingH0:CB=0vsHa:CB≠0have the same distribution as under the i.i.d. covariance structureI⊗Σ