Absorption cross section in Lifshitz black hole

We derive the absorption cross section of a minimally coupled scalar in the Lifshitz black hole obtained from the new massive gravity. The absorption cross section reduces to the horizon area in the low energy and massless limit of s-wave mode propagation, indicating that the Lifshitz black hole also satisfies the universality of low energy absorption cross section for black holes.Comment: 13 pages, 1 figure, version to appear in EPJ

Ultra-large library docking for discovering new chemotypes

Despite intense interest in expanding chemical space, libraries containing hundreds-of-millions to billions of diverse molecules have remained inaccessible. Here we investigate structure-based docking of 170 million make-on-demand compounds from 130 well-characterized reactions. The resulting library is diverse, representing over 10.7 million scaffolds that are otherwise unavailable. For each compound in the library, docking against AmpC β-lactamase (AmpC) and the D 4 dopamine receptor were simulated. From the top-ranking molecules, 44 and 549 compounds were synthesized and tested for interactions with AmpC and the D 4 dopamine receptor, respectively. We found a phenolate inhibitor of AmpC, which revealed a group of inhibitors without known precedent. This molecule was optimized to 77 nM, which places it among the most potent non-covalent AmpC inhibitors known. Crystal structures of this and other AmpC inhibitors confirmed the docking predictions. Against the D 4 dopamine receptor, hit rates fell almost monotonically with docking score, and a hit-rate versus score curve predicted that the library contained 453,000 ligands for the D 4 dopamine receptor. Of 81 new chemotypes discovered, 30 showed submicromolar activity, including a 180-pM subtype-selective agonist of the D 4 dopamine receptor

Virtual discovery of melatonin receptor ligands to modulate circadian rhythms

The neuromodulator melatonin synchronizes circadian rhythms and related physiological functions through the actions of two G-protein-coupled receptors: MT1 and MT2. Circadian release of melatonin at night from the pineal gland activates melatonin receptors in the suprachiasmatic nucleus of the hypothalamus, synchronizing the physiology and behaviour of animals to the light–dark cycle1–4. The two receptors are established drug targets for aligning circadian phase to this cycle in disorders of sleep5,6 and depression1–4,7–9. Despite their importance, few in vivo active MT1-selective ligands have been reported2,8,10–12, hampering both the understanding of circadian biology and the development of targeted therapeutics. Here we docked more than 150 million virtual molecules to an MT1 crystal structure, prioritizing structural fit and chemical novelty. Of these compounds, 38 high-ranking molecules were synthesized and tested, revealing ligands with potencies ranging from 470 picomolar to 6 micromolar. Structure-based optimization led to two selective MT1 inverse agonists—which were topologically unrelated to previously explored chemotypes—that acted as inverse agonists in a mouse model of circadian re-entrainment. Notably, we found that these MT1-selective inverse agonists advanced the phase of the mouse circadian clock by 1.3–1.5 h when given at subjective dusk, an agonist-like effect that was eliminated in MT1- but not in MT2-knockout mice. This study illustrates the opportunities for modulating melatonin receptor biology through MT1-selective ligands and for the discovery of previously undescribed, in vivo active chemotypes from structure-based screens of diverse, ultralarge libraries. © 2020, The Author(s), under exclusive licence to Springer Nature Limited

Photonic band gaps in materials with triply periodic surfaces and related tubular structures

We calculate the photonic band gap of triply periodic bicontinuous cubic structures and of tubular structures constructed from the skeletal graphs of triply periodic minimal surfaces. The effect of the symmetry and topology of the periodic dielectric structures on the existence and the characteristics of the gaps is discussed. We find that the C(I2-Y**) structure with Ia3d symmetry, a symmetry which is often seen in experimentally realized bicontinuous structures, has a photonic band gap with interesting characteristics. For a dielectric contrast of 11.9 the largest gap is approximately 20% for a volume fraction of the high dielectric material of 25%. The midgap frequency is a factor of 1.5 higher than the one for the (tubular) D and G structures

CMS physics technical design report: Addendum on high density QCD with heavy ions

This report presents the capabilities of the CMS experiment to explore the rich heavy-ion physics programme offered by the CERN Large Hadron Collider (LHC). The collisions of lead nuclei at energies ,will probe quark and gluon matter at unprecedented values of energy density. The prime goal of this research is to study the fundamental theory of the strong interaction - Quantum Chromodynamics (QCD) - in extreme conditions of temperature, density and parton momentum fraction (low-x). This report covers in detail the potential of CMS to carry out a series of representative Pb-Pb measurements. These include "bulk" observables, (charged hadron multiplicity, low pT inclusive hadron identified spectra and elliptic flow) which provide information on the collective properties of the system, as well as perturbative probes such as quarkonia, heavy-quarks, jets and high pT hadrons which yield "tomographic" information of the hottest and densest phases of the reaction.0info:eu-repo/semantics/publishe