Cyclin K goes with Cdk12 and Cdk13

The cyclin-dependent kinases (Cdks) regulate many cellular processes, including the cell cycle, neuronal development, transcription, and posttranscriptional processing. To perform their functions, Cdks bind to specific cyclin subunits to form a functional and active cyclin/Cdk complex. This review is focused on Cyclin K, which was originally considered an alternative subunit of Cdk9, and on its newly identified partners, Cdk12 and Cdk13. We briefly summarize research devoted to each of these proteins. We also discuss the proteins' functions in the regulation of gene expression via the phosphorylation of serine 2 in the C-terminal domain of RNA polymerase II, contributions to the maintenance of genome stability, and roles in the onset of human disease and embryo development

Characteristic-based formulation of boundary conditions for preconditioned or non-preconditioned flow equations

A numerical implementation of characteristic boundary conditions for Euler and Navier-Stokes equations is presented. The method combines the specified boundary conditions and the outgoing characteristic variables according to the wave propagation directions. In the general case, the proposed boundary conditions update the primitive variables by solving a small system of linear equations (4×4 in 2D, 5×5 in 3D) at each boundary point/cell. The method can be used for both preconditioned and non-preconditioned equations. For a perfect gas without preconditioning, a closed analytical solution is provided. Two possible methods of extrapolating the outgoing characteristic variables are discussed. Finally, the numerical approach is validated for the 2D internal flow in a channel with a bump

Nová fáze regionálního rozvoje v ČR?

The article aims to identify the development phases in the process of the regional differentiation in the Czech Republic after 1989, & examines whether this differentiation trend is currently changing. The assumption the article's hypothesis is based on is that during recent development the basic 'parameters' of the principal features of the country's regional structure have been stabilized amidst the conditions of parliamentary democracy & a market economy. Unlike the first phases of socio- economic transition, when differentiating trends prevailed, a certain degree of stabilization can now be assumed, alongside the emergence of new trends. The development of regional differences was analyzed using indicators of GDP, the unemployment rate, entrepreneurial activity, & tax revenue from self- employed physical persons. The findings show that over the course of the 1990s regional differences intensified at both the mezo- regional (regional) level & the micro- regional level. It was also confirmed that at the turn of the millennium the phase of divergent regional development ended, & since that time regional differences have hovered around the same level

A Study of Modified Characteristics of Hadronic Interactions

We have implemented ad-hoc modifications to the CORSIKA Monte-Carlo generator which allow us to simultaneously adjust the multiplicity, elasticity and cross-section of hadronic interactions with respect to the predictions of the Sibyll 2.3d interaction model, in order to assess whether a reasonable combination of changes (that is not excluded by current experimental data) could alleviate the observed tension between the model predictions and observed features of extensive air showers induced by ultra-high energy cosmic rays (UHECR). Previously, we have studied the effects of such changes on proton-initiated showers. Because a multitude of experimental data suggest that the primary composition of the UHECR is mixed, we have expanded the modification procedure to include nuclear projectiles in a consistent way based on the superposition model, in a similar manner as was used in the previous studies carried out using one-dimensional simulation methods. As we are using a fully three-dimensional approach, we can quantify the effects of the changes on both longitudinal and lateral features of the showers. With the inclusion of nuclear projectiles, we can study the impact of the changes on observable quantities for realistic primary beams as well as on the determination of the primary composition from data under the assumption of the modified hadronic interactions.Comment: 6 pages, 9 figures, a conference proceeding for UHECR202

Oligomerization of HEXIM1 via 7SK snRNA and coiled-coil region directs the inhibition of P-TEFb

Transcriptional elongation of most eukaryotic genes by RNA polymerase II requires the kinase activity of the positive transcription elongation factor b (P-TEFb). The catalytically active P-TEFb complex becomes inactive when sequestered into the large complex by the cooperative actions of 7SK snRNA and HEXIM1. In this study, we report that HEXIM1 forms oligomers in cells. This oligomerization is mediated by its predicted coiled-coil region in the C-terminal domain and 7SK snRNA that binds a basic region within the central part of HEXIM1. Alanine-mutagenesis of evolutionary conserved leucines in the coiled-coil region and the digestion of 7SK snRNA by RNase A treatment prevent this oligomerization. Importantly, mutations of the N-terminal part of the coiled-coil region abrogate the ability of HEXIM1 to bind and inhibit P-TEFb. Finally, the formation of HEXIM1 oligomers via the C-terminal part of the coiled-coil or basic regions is critical for the inhibition of transcription. Our results suggest that two independent regions in HEXIM1 form oligomers to incorporate P-TEFb into the large complex and determine the inhibition of transcriptional elongation

Underpinning effective strategy design: reflection paper

The debate around the smart specialisation concept and its applicability to regional development policy has so far concentrated on the design phase of policies, most notably on the question of definition of specialisation domains through an entrepreneurial discovery process involving a wide range of stakeholders. This question of prioritisation is indeed a central piece of the strategy for regions willing to upgrade their economic transformation potential

Regions with less developed research and innovation systems

The aim of this working paper is to contribute to the debate on how to identify regions with less developed research and innovation systems. We look at both conceptual and empirical approaches that figure prominently in scholarly work on regional innovation systems. Based on a critical review and discussion of the literature we shed light on a large number and variety of barriers and weaknesses that may hamper regional innovation and industrial change. It is shown in this paper that the regional innovation system concept can essentially inform the current debate on the design and implementation of smart specialisation strategies. It offers rich insights into various dimensions of regional innovation systems that may be weakly developed and allows for the development of typologies that capture the heterogeneity of these systems. We also demonstrate that empirical approaches to identify regions with less-developed research and innovation systems fall short of taking account of the conceptual advances made in the recent past