Exon-intron architecture is one of the major features directing the splicing machinery to the short exons that are located within long flanking introns. However, the evolutionary dynamics of exon-intron architecture and its impact on splicing is largely unknown. Using a comparative genomic approach, we analyzed 17 vertebrate genomes and reconstructed the ancestral motifs of both 39 and 59 splice sites, as also the ancestral length of exons and introns. Our analyses suggest that vertebrate introns increased in length from the shortest ancestral introns to the longest primate introns. An evolutionary analysis of splice sites revealed that weak splice sites act as a restrictive force keeping introns short. In contrast, strong splice sites allow recognition of exons flanked by long introns. Reconstruction of the ancestral state suggests these phenomena were not prevalent in the vertebrate ancestor, but appeared during vertebrate evolution. By calculating evolutionary rate shifts in exons, we identified cis-acting regulatory sequences that became fixed during the transition from early vertebrates to mammals. Experimental validations performed on a selection of these hexamers confirmed their regulatory function. We additionally revealed many features of exons that can discriminate alternative from constitutive exons. These features were integrated into a machine-learning approach to predict whether an exon is alternative. Our algorithm obtains very high predictive power (AUC of 0.91), and using these predictions we have identified and successfully validated novel alternatively spliced exons. Overall, we provide novel insights regarding the evolutionary constraints acting upon exons and their recognition by the splicing machinery.[Supplemental material is available for this article.]In the process of splicing, introns are removed from an mRNA precursor (pre-mRNA), and exons are ligated to form a mature mRNA (Black 2003). Exons and introns are recognized in the splicing process by many different signals and interactions along the exonintron structure. Several signals along the pre-mRNA help the splicing machinery to recognize exon-intron junctions: The 39 and 59 splice sites (39ss and 59ss) located on both exon-intron junctions, and the branch site and polypyrimidine tract (PPT) located upstream of the 39ss (Black 2003). In alternative splicing, the splicing mechanism produces more than one mRNA from a single premRNA (Graveley 2001). This is done by the splicing of different sets of exons from a single pre-mRNA, resulting in an increased number of protein isoforms that can be synthesized from one gene. Previous studies revealed that the percentage of exons undergoing alternative splicing is higher in vertebrates compared with invertebrates, and in human compared with other vertebrates ). This suggests that alternative splicing has a major role in the production of higher levels of biological complexity.Exon-intron structure plays a major role in the recognition of exons by the splicing machinery. It was previously demon...

The attitude of a satellite is often controlled by reactive forces requiring some additional energy. But it can also be stabilized by means of some subsystem of the satellite moving in a nonideal fluid as an oscillator with damping. This does not require additional energy and is called ''passive stabilization.'' Moreover the relative motion tends asymptotically to zero together with the satellite finding the desired position. Here we consider passive stabilization for hamiltonian systems from a mathematical point of view and show that stabilization can sometimes be obtained by nonlinear terms. As an example, we consider passive stabilization of a simple pendulum. ᮊ 2000 Academic Press

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The paper discusses forced combined angular-radial oscillations of rotor centrifugal pump model under the influence of random forcings. System reliability is evaluated using the theory of random functions runs: the probability of finding a random vector of quality system “rotor-annular seals” in the range of admissible values of its parameters is determined. Evaluation of the influence of erosive wear of sealing surfaces in the process of pump operating on reliability system is made.

Digitalization is the general trend in the development of higher education in the world, which requires researching into the international and Russian experience of incorporating digital media in the educational processes to provide their digital transformation. The conducted research presents an attempt to integrate British and Russian scientific pedagogical thought, aimed at studying digital educational media technologies based on the systematization and analysis of their functional effectiveness in the educational process. The research aims to define the didactic possibilities of digital educational media technologies in foreign language teaching at university.The methodology of the paper is based on the analytical classification of educational media proposed by the British scientist Pr. Diana Laurillard. The methods of research exploited by the