Портал «Единое окно» как платформа для репозитория учебно-методических материалов, размещаемых со свободными лицензиями

The paper provides information on a pilot project aimed at setting up a Russian-language repository of Open Educational Resources (OER) developed for higher education institutions. The resources will be available under open licenses (Creative Commons family or other free licenses). This is a joint project of the State Institute of Information Technology and Telecommunications INFORMIKA and the UNESCO Institute for Information Technologies in Education (IITE).В докладе рассматривается проект создания хранилища учебно-методических материалов, создаваемых в вузах и размещаемых в открытом доступе со свободными лицензиями. Данный проект реализуется как совместная инициатива Государственного научно-исследовательского института информационных технологий и телекоммуникаций "Информика" и Института ЮНЕСКО по информационным технологиям в образовании

Abelian and nonabelian vector field effective actions from string field theory

The leading terms in the tree-level effective action for the massless fields of the bosonic open string are calculated by integrating out all massive fields in Witten's cubic string field theory. In both the abelian and nonabelian theories, field redefinitions make it possible to express the effective action in terms of the conventional field strength. The resulting actions reproduce the leading terms in the abelian and nonabelian Born-Infeld theories, and include (covariant) derivative corrections.Comment: 49 pages, 1 eps figur

Polycation-π Interactions Are a Driving Force for Molecular Recognition by an Intrinsically Disordered Oncoprotein Family

Molecular recognition by intrinsically disordered proteins (IDPs) commonly involves specific localized contacts and target-induced disorder to order transitions. However, some IDPs remain disordered in the bound state, a phenomenon coined "fuzziness", often characterized by IDP polyvalency, sequence-insensitivity and a dynamic ensemble of disordered bound-state conformations. Besides the above general features, specific biophysical models for fuzzy interactions are mostly lacking. The transcriptional activation domain of the Ewing's Sarcoma oncoprotein family (EAD) is an IDP that exhibits many features of fuzziness, with multiple EAD aromatic side chains driving molecular recognition. Considering the prevalent role of cation-π interactions at various protein-protein interfaces, we hypothesized that EAD-target binding involves polycation- π contacts between a disordered EAD and basic residues on the target. Herein we evaluated the polycation-π hypothesis via functional and theoretical interrogation of EAD variants. The experimental effects of a range of EAD sequence variations, including aromatic number, aromatic density and charge perturbations, all support the cation-π model. Moreover, the activity trends observed are well captured by a coarse-grained EAD chain model and a corresponding analytical model based on interaction between EAD aromatics and surface cations of a generic globular target. EAD-target binding, in the context of pathological Ewing's Sarcoma oncoproteins, is thus seen to be driven by a balance between EAD conformational entropy and favorable EAD-target cation-π contacts. Such a highly versatile mode of molecular recognition offers a general conceptual framework for promiscuous target recognition by polyvalent IDPs. © 2013 Song et al

Analyzing the forces binding a restriction endonuclease to DNA using a synthetic nanopore

Restriction endonucleases are used prevalently in recombinant DNA technology because they bind so stably to a specific target sequence and, in the presence of cofactors, cleave double-helical DNA specifically at a target sequence at a high rate. Using synthetic nanopores along with molecular dynamics (MD), we have analyzed with atomic resolution how a prototypical restriction endonuclease, EcoRI, binds to the DNA target sequence—GAATTC—in the absence of a Mg2+ ion cofactor. We have previously shown that there is a voltage threshold for permeation of DNA bound to restriction enzymes through a nanopore that is associated with a nanonewton force required to rupture the complex. By introducing mutations in the DNA, we now show that this threshold depends on the recognition sequence and scales linearly with the dissociation energy, independent of the pore geometry. To predict the effect of mutation in a base pair on the free energy of dissociation, MD is used to qualitatively rank the stability of bonds in the EcoRI–DNA complex. We find that the second base in the target sequence exhibits the strongest binding to the protein, followed by the third and first bases, with even the flanking sequence affecting the binding, corroborating our experiments

Targeted Energy Transfer and Modal Energy Redistribution in Automotive Drivetrains

The new generations of compact high output power-to-weight ratio internal combustion engines generate broadband torsional oscillations, transmitted to lightly damped drivetrain systems. A novel approach to mitigate these untoward vibrations can be the use of nonlinear absorbers. These act as Nonlinear Energy Sinks (NESs). The NES is coupled to the primary (drivetrain) structure, inducing passive irreversible targeted energy transfer (TET) from the drivetrain system to the NES. During this process, the vibration energy is directed from the lower-frequency modes of the structure to the higher ones. Thereafter, vibrations can be either dissipated through structural damping or consumed by the NES. This paper uses a lumped parameter model of an automotive driveline to simulate the effect of TET and the assumed modal energy redistribution. Significant redistribution of vibratory energy is observed through TET. Furthermore, the integrated optimization process highlights the most effective configuration and parametric evaluation for use of NES

Beta-gamma systems and the deformations of the BRST operator

We describe the relation between simple logarithmic CFTs associated with closed and open strings, and their "infinite metric" limits, corresponding to the beta-gamma systems. This relation is studied on the level of the BRST complex: we show that the consideration of metric as a perturbation leads to a certain deformation of the algebraic operations of the Lian-Zuckerman type on the vertex algebra, associated with the beta-gamma systems. The Maurer-Cartan equations corresponding to this deformed structure in the quasiclassical approximation lead to the nonlinear field equations. As an explicit example, we demonstrate, that using this construction, Yang-Mills equations can be derived. This gives rise to a nontrivial relation between the Courant-Dorfman algebroid and homotopy algebras emerging from the gauge theory. We also discuss possible algebraic approach to the study of beta-functions in sigma-models.Comment: LaTeX2e, 15 pages; minor revision, typos corrected, Journal of Physics A, in pres

The Impact of Small Molecule Binding on the Energy Landscape of the Intrinsically Disordered Protein C-Myc

Intrinsically disordered proteins are attractive therapeutic targets owing to their prevalence in several diseases. Yet their lack of well-defined structure renders ligand discovery a challenging task. An intriguing example is provided by the oncoprotein c-Myc, a transcription factor that is over expressed in a broad range of cancers. Transcriptional activity of c-Myc is dependent on heterodimerization with partner protein Max. This protein-protein interaction is disrupted by the small molecule 10058-F4 (1), that binds to monomeric and disordered c-Myc. To rationalize the mechanism of inhibition, structural ensembles for the segment of the c-Myc domain that binds to 1 were computed in the absence and presence of the ligand using classical force fields and explicit solvent metadynamics molecular simulations. The accuracy of the computed structural ensembles was assessed by comparison of predicted and measured NMR chemical shifts. The small molecule 1 was found to perturb the composition of the apo equilibrium ensemble and to bind weakly to multiple distinct c-Myc conformations. Comparison of the apo and holo equilibrium ensembles reveals that the c-Myc conformations binding 1 are already partially formed in the apo ensemble, suggesting that 1 binds to c-Myc through an extended conformational selection mechanism. The present results have important implications for rational ligand design efforts targeting intrinsically disordered proteins

The Potential and Challenges of Nanopore Sequencing

A nanopore-based device provides single-molecule detection and analytical capabilities that are achieved by electrophoretically driving molecules in solution through a nano-scale pore. The nanopore provides a highly confined space within which single nucleic acid polymers can be analyzed at high throughput by one of a variety of means, and the perfect processivity that can be enforced in a narrow pore ensures that the native order of the nucleobases in a polynucleotide is reflected in the sequence of signals that is detected. Kilobase length polymers (single-stranded genomic DNA or RNA) or small molecules (e.g., nucleosides) can be identified and characterized without amplification or labeling, a unique analytical capability that makes inexpensive, rapid DNA sequencing a possibility. Further research and development to overcome current challenges to nanopore identification of each successive nucleotide in a DNA strand offers the prospect of ‘third generation’ instruments that will sequence a diploid mammalian genome for ~$1,000 in ~24 h.Molecular and Cellular BiologyPhysic