There are only few major key functions that lie beneath the fundamental architecture of metabolism and life. These are multiplication, variation and heredity. Only if these factors interact ...synergistically can Darwinian selection power the evolution of biodiversity. Transposable elements have always played a major role in this process. The genomes of all organisms consist of chromosomes that are built up of double-stranded nucleic acid chains on whose stability and integrity the existence of cells depend. While DNA repair warrants the chemical integrity of DNA and protects it from metabolic and environmental mutagens, meiotic recombination and transposable element activity appear to counteract the molecular guardians of genome stability. Transposable elements and their kind often make up the bulk of genomic DNA, often approaching 50% of the genome. By contrast, the classic genes represent as little as 1.8% of genomic DNA, in case of the human genome. This volume gives an overview on mobile DNA and how such contradiction to the obligatory stability of genomes can be understood. Obviously, an understanding can only be achieved by cutting deeply into the evolutionary history of life along with the evolution of transposable elements and dynamic genomes. This book therefore also celebrates Charles Darwin’s 200th birthday. The reader is challenged to view the role of movable DNA along historical roots from the levels of cells to populations to biological species integrating the accompanying molecular evolution of host, cell and genome interaction. One will witness even the reactivation of a long since dead, fossil transposable element and the infection of germline cells by the first established, mobile and endogenous insect retrovirus.
Unfitted finite element techniques are valuable tools in different applications where the generation of body-fitted meshes is difficult. However, these techniques are prone to severe ill conditioning ...problems that obstruct the efficient use of iterative Krylov methods and, in consequence, hindersthe practical usage of unfitted methods for realistic large scale applications. In this work, we present a technique that addresses such conditioning problems by constructing enhanced finite element spaces based on a cell aggregation technique. The presented method, called aggregated unfitted finite element method, is easy to implement, and can be used, in contrast to previous works, in Galerkin approximations of coercive problems with conforming Lagrangian finite element spaces. The mathematical analysis of the method states that the condition number of the resulting linear system matrix scales as in standard finite elements for body-fitted meshes, without being affected by small cut cells, and that the method leads to the optimal finite element convergence order. These theoretical results are confirmed with 2D and 3D numerical experiments.
AMPK has emerged as a critical mechanism for salutary effects of polyphenols on lipid metabolic disorders in type 1 and type 2 diabetes. Here we demonstrate that AMPK interacts with and directly ...phosphorylates sterol regulatory element binding proteins (SREBP-1c and -2). Ser372 phosphorylation of SREBP-1c by AMPK is necessary for inhibition of proteolytic processing and transcriptional activity of SREBP-1c in response to polyphenols and metformin. AMPK stimulates Ser372 phosphorylation, suppresses SREBP-1c cleavage and nuclear translocation, and represses SREBP-1c target gene expression in hepatocytes exposed to high glucose, leading to reduced lipogenesis and lipid accumulation. Hepatic activation of AMPK by the synthetic polyphenol S17834 protects against hepatic steatosis, hyperlipidemia, and accelerated atherosclerosis in diet-induced insulin-resistant LDL receptor-deficient mice in part through phosphorylation of SREBP-1c Ser372 and suppression of SREBP-1c- and -2-dependent lipogenesis. AMPK-dependent phosphorylation of SREBP may offer therapeutic strategies to combat insulin resistance, dyslipidemia, and atherosclerosis.
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▴ AMPKα subunit interacts with and directly phosphorylates SREBP-1c and SREBP-2 ▴ Phosphorylation of SREBP-1c by AMPK represses de novo lipogenesis in hepatocytes ▴ AMPK inhibits SREBP cleavage and gene transcription in insulin-resistant mice ▴ SREBP suppression by polyphenols attenuates hepatic steatosis and atherosclerosis
A joint IUPAC/IUPAP Working Party (JWP) has confirmed the discovery of the elements with atomic numbers (
) 113, 115, 117 and 118. In accordance with the 2016 IUPAC guideline for naming new elements, ...the discoverers were invited to propose names and symbols for the elements. Claims have been assigned to them and the following are proposed: (a) nihonium and symbol Nh, for the element with
=113, (b) moscovium with the symbol Mc, for the element with
=115, (c) tennessine with the symbol Ts, for the element with
=117, and oganesson with the symbol Og, for the element with
=118. After careful deliberation on these names and symbols, considering the 2016 rules and a public review period, the Inorganic Chemistry Division recommended these proposals for acceptance by the IUPAC Council.
A numerical model is presented for the ground-borne vibration produced by trains running in tunnels. The model makes use of the assumption that the geometry and material properties are invariant in ...the axial direction. It is based on the so-called two-and-a-half dimensional (2.5D) coupled Finite Element and Boundary Element methodology, in which a two-dimensional cross-section is discretised into finite elements and boundary elements and the third dimension is represented by a Fourier transform over wavenumbers. The model is applied to a particular case of a metro line built with a cast-iron tunnel lining. An equivalent continuous model of the tunnel is developed to allow it to be readily implemented in the 2.5D framework. The tunnel structure and the track are modelled using solid and beam finite elements while the ground is modelled using boundary elements. The 2.5D track-tunnel-ground model is coupled with a train consisting of several vehicles, which are represented by multi-body models. The response caused by the passage of a train is calculated as the sum of the dynamic component, excited by the combined rail and wheel roughness, and the quasi-static component, induced by the constant moving axle loads. Field measurements have been carried out to provide experimental validation of the model. These include measurements of the vibration of the rail, the tunnel invert and the tunnel wall. In addition, simultaneous measurements were made on the ground surface above the tunnel. Rail roughness and track characterisation measurements were also made. The prediction results are compared with measured vibration obtained during train passages, with good agreement.
A new hybrid finite element method-boundary element method (FEM-BEM) scheme is proposed for the solution of the nonlinear 2-D Laplace problem. The novelty is an original approach of the BEM where the ...domain integrals are eliminated at the discrete level by using the FEM approximation of the fundamental solution at every node of the related mesh in the linear regions. The implementation of this FEM-Green approach requires less computational burden than the standard BEM. The coupling with FEM is straightforward and appears to be more natural. The validity of the method is examined through numerical examples.
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