Numerical simulations of black-hole binaries and gravitational wave emission

We review recent progress in numerical relativity simulations of black-hole (BH) spacetimes. Following a brief summary of the methods employed in the modeling, we summarize the key results in three major areas of BH physics: (i) BHs as sources of gravitational waves (GWs), (ii) astrophysical systems involving BHs, and (iii) BHs in high-energy physics. We conclude with a list of the most urgent tasks for numerical relativity in these three areas.Comment: Updated version, references added; 47 pages, 3 figure

Treating Cancer by Spindle Assembly Checkpoint Abrogation: Discovery of Two Clinical Candidates, BAY 1161909 and BAY 1217389, Targeting MPS1 Kinase

Inhibition of monopolar spindle 1 MPS1 kinase represents a novel approach to cancer treatment instead of arresting the cell cycle in tumor cells, cells are driven into mitosis irrespective of DNA damage and unattached misattached chromosomes, resulting in aneuploidy and cell death. Starting points for our optimization efforts with the goal to identify MPS1 inhibitors were two HTS hits from the distinct chemical series triazolopyridines and imidazopyrazines . The major initial issue of the triazolopyridine series was the moderate potency of the HTS hits. The imidazopyrazine series displayed more than 10 fold higher potencies; however, in the early project phase, this series suffered from poor metabolic stability. Here, we outline the evolution of the two hit series to clinical candidates BAY 1161909 and BAY 1217389 and reveal how both clinical candidates bind to the ATP site of MPS1 kinase, while addressing different pockets utilizing different binding interactions, along with their synthesis and preclinical characterization in selected in vivo efficacy model

Structure and Dynamics of Helix-0 of the N-BAR Domain in Lipid Micelles and Bilayers

Bin/Amphiphysin/Rvs-homology (BAR) domains generate and sense membrane curvature by binding the negatively charged membrane to their positively charged concave surfaces. N-BAR domains contain an N-terminal extension (helix-0) predicted to form an amphipathic helix upon membrane binding. We determined the NMR structure and nano-to-picosecond dynamics of helix-0 of the human Bin1/Amphiphysin II BAR domain in sodium dodecyl sulfate and dodecylphosphocholine micelles. Molecular dynamics simulations of this 34-amino acid peptide revealed electrostatic and hydrophobic interactions with the detergent molecules that induce helical structure formation from residues 8–10 toward the C-terminus. The orientation in the micelles was experimentally confirmed by backbone amide proton exchange. The simulation and the experiment indicated that the N-terminal region is disordered, and the peptide curves to adopted the micelle shape. Deletion of helix-0 reduced tubulation of liposomes by the BAR domain, whereas the helix-0 peptide itself was fusogenic. These findings support models for membrane curving by BAR domains in which helix-0 increases the binding affinity to the membrane and enhances curvature generation

The Einstein Toolkit

The Einstein Toolkit is a&nbsp;community-driven software platform of core computational tools to advance and support research in relativistic astrophysics and gravitational physics. </span

The H1 detector at HERA

General aspects of the H1 detector at the electron-proton storage ring HERA as well as technical descriptions of the magnet, luminosity system, trigger, slow-control, data acquisition and off-line data handling are given. The three major components of the detector, the tracking, calorimeter and muon detectors, will be described in a forthcoming article. The present paper describes the detector that was used from 1992 to the end of 1994. After this a major upgrade of some components was undertaken. Some performance figures from luminosity runs at HERA during 1993 and 1994 are given.0SCOPUS: ar.jinfo:eu-repo/semantics/publishe