Quasi-infra-red fixed points and renormalisation group invariant trajectories for non-holomorphic soft supersymmetry breaking

In the MSSM the quasi-infra-red fixed point for the top-quark Yukawa coupling gives rise to specific predictions for the soft-breaking parameters. We discuss the extent to which these predictions are modified by the introduction of additional ``non-holomorphic'' soft-breaking terms. We also show that in a specific class of theories there exists an RG-invariant trajectory for the ``non-holomorphic'' terms, which can be understood using a holomorphic spurion term.Comment: 24 pages, TeX, two figures. Uses Harvmac (big) and epsf. Minor errors corrected, and the RG trajectory explained in terms of a holomorphic spurion ter

Publisher Correction: Structural basis of ligand recognition at the human MT1 melatonin receptor (Nature, (2019), 569, 7755, (284-288), 10.1038/s41586-019-1141-3)

Change history: In this Letter, the rotation signs around 90°, 135° and 15° were missing and in the HTML, Extended Data Tables 2 and 3 were the wrong tables; these errors have been corrected online. © 2019, The Author(s), under exclusive licence to Springer Nature Limited

Structural basis of ligand recognition at the human MT1 melatonin receptor

Melatonin (N-acetyl-5-methoxytryptamine) is a neurohormone that maintains circadian rhythms1 by synchronization to environmental cues and is involved in diverse physiological processes2 such as the regulation of blood pressure and core body temperature, oncogenesis, and immune function3. Melatonin is formed in the pineal gland in a light-regulated manner4 by enzymatic conversion from 5-hydroxytryptamine (5-HT or serotonin), and modulates sleep and wakefulness5 by activating two high-affinity G-protein-coupled receptors, type 1A (MT1) and type 1B (MT2)3,6. Shift work, travel, and ubiquitous artificial lighting can disrupt natural circadian rhythms; as a result, sleep disorders affect a substantial population in modern society and pose a considerable economic burden7. Over-the-counter melatonin is widely used to alleviate jet lag and as a safer alternative to benzodiazepines and other sleeping aids8,9, and is one of the most popular supplements in the United States10. Here, we present high-resolution room-temperature X-ray free electron laser (XFEL) structures of MT1 in complex with four agonists: the insomnia drug ramelteon11, two melatonin analogues, and the mixed melatonin–serotonin antidepressant agomelatine12,13. The structure of MT2 is described in an accompanying paper14. Although the MT1 and 5-HT receptors have similar endogenous ligands, and agomelatine acts on both receptors, the receptors differ markedly in the structure and composition of their ligand pockets; in MT1, access to the ligand pocket is tightly sealed from solvent by extracellular loop 2, leaving only a narrow channel between transmembrane helices IV and V that connects it to the lipid bilayer. The binding site is extremely compact, and ligands interact with MT1 mainly by strong aromatic stacking with Phe179 and auxiliary hydrogen bonds with Asn162 and Gln181. Our structures provide an unexpected example of atypical ligand entry for a non-lipid receptor, lay the molecular foundation of ligand recognition by melatonin receptors, and will facilitate the design of future tool compounds and therapeutic agents, while their comparison to 5-HT receptors yields insights into the evolution and polypharmacology of G-protein-coupled receptors

Posible pendiente anular cerrado, deformado - Salv_AR_1_0030

Proyectos del Plan Nacional I+D+I con referencias PB94-0129, PB97-1132, BHA 2002-00138, HUM 2006-06250/HISTProyectos de la CAM con referencias 06/0020/1997, 06/0094/1998, 06/0090/2000, 06/0043/2001Programa Consolider-Ingenio 2010 con sigla CSD2007-00058NoMuseo Arqueológico Nacional (Madrid)Salvacañete (Cuenca)Posible pendiente anular cerrado, deformad

Algorithmic aspects of proportional symbol maps

Proportional symbol maps visualize numerical data associated with point locations by placing a scaled symbol—typically opaque disks or squares—at the corresponding point on a map. Overlapping symbols need to be drawn in such a way that the user can still judge their relative sizes accurately. We identify two types of suitable drawings: physically realizable drawings and stacking drawings. For these we study the following two problems: Max-Min—maximize the minimum visible boundary length of each symbol—and Max-Total—maximize the total visible boundary length over all symbols. We show that both problems are NP-hard for physically realizable drawings. Max-Min can be solved in O(n2 log n) time for stacking drawings, which can be improved to O(n log n) or O(n log2 n) time when the input has certain properties. We also experimented with four methods to compute stacking drawings: our solution to the Max-Min problem performs best on the data sets considered