Generating stable molecules using imitation and reinforcement learning

Chemical space is routinely explored by machine learning methods to discover interesting molecules, before time-consuming experimental synthesizing is attempted. However, these methods often rely on a graph representation, ignoring 3D information necessary for determining the stability of the molecules. We propose a reinforcement learning (RL) approach for generating molecules in Cartesian coordinates allowing for quantum chemical prediction of the stability. To improve sample-efficiency we learn basic chemical rules from imitation learning (IL) on the GDB-11 database to create an initial model applicable for all stoichiometries. We then deploy multiple copies of the model conditioned on a specific stoichiometry in a RL setting. The models correctly identify low energy molecules in the database and produce novel isomers not found in the training set. Finally, we apply the model to larger molecules to show how RL further refines the IL model in domains far from the training data

Practice patterns in diagnostics, staging, and management strategies of gallbladder cancer among Nordic tertiary centers

Background and objective: Gallbladder cancer (GBC) is a rare malignancy in the Nordic countries and no common Nordic treatment guidelines exist. This study aimed to characterize the current diagnostic and treatment strategies in the Nordic countries and disclose differences in these strategies. Methods: This was a survey study with a cross-sectional questionnaire of all 19 university hospitals providing curative-intent surgery for GBC in Sweden, Norway, Denmark, and Finland. Results: In all Nordic countries except Sweden, neoadjuvant/downstaging chemotherapy was used in GBC patients. In T1b and T2, majority of the centers (15–18/19) performed extended cholecystectomy. In T3, majority of the centers (13/19) performed cholecystectomy with resection of segments 4b and 5. In T4, majority of the centers (12–14/19) chose palliative/oncological care. The centers in Sweden extended lymphadenectomy beyond the hepatoduodenal ligament, whereas all other Nordic centers usually limited lymphadenectomy to the hepatoduodenal ligament. All Nordic centers except those in Norway used adjuvant chemotherapy routinely for GBC. There were no major differences between the Nordic centers in diagnostics and follow-up. Conclusions: The surgical and oncological treatment strategies of GBC vary considerably between the Nordic centers and countries.publishedVersio

Probing nonlocal effects in metals with graphene plasmons

In this paper we analyze the effects of nonlocality on the optical properties of a system consisting of a thin metallic film separated from a graphene sheet by a hexagonal boron nitride (hBN) layer. We show that nonlocal effects in the metal have a strong impact on the spectrum of the surface plasmon-polaritons on graphene. If the graphene sheet is shaped into a grating, we show that the extinction curves can be used to shed light on the importance of nonlocal effects in metals. Therefore, graphene surface plasmons emerge as a tool for probing nonlocal effects in metallic nanostructures, including thin metallic films. As a byproduct of our study, we show that nonlocal effects lead to smaller losses for the graphene plasmons than what is predicted by a local calculation. We show that these effects can be very well mimicked using a local theory with an effective spacer thickness larger than its actual value.The authors thank Sébastien Nanot and Itai Epstein for valuable discussions and comments. E.J.C.D., Yu.V.B. and N.M.R.P. acknowledge support from the European Commission through the project GrapheneDriven Revolutions in ICT and Beyond (Ref. No. 785219), and from the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Financing UID/FIS/04650/2013. E.J.C.D. acknowledges FCT for the grant CFUM-BI-14/2016. D.A.I. acknowledges the FPI grant BES-2014-068504. F.H.L.K. acknowledges financial support from the Government of Catalonia trough the SGR grant (2014-SGR-1535), and from the Spanish Ministry of Economy and Competitiveness, through the Severo Ochoa Programme for Centres of Excellence in R&D (SEV-2015-0522), support by Fundacio Cellex Barcelona, CERCA Programme / Generalitat de Catalunya and the Mineco grants Ramn y Cajal (RYC-2012-12281) and Plan Nacional (FIS201347161-P and FIS2014-59639-JIN). Furthermore, the research leading to these results has received funding from the European Union Seventh Framework Programme under grant agreement no.696656 Graphene Flagship, the ERC starting grant (307806, CarbonLight), and project GRASP (FP7-ICT-2013-613024-GRASP). N. A. M. is a VILLUM Investigator supported by VILLUM FONDEN (grant No. 16498). Center for Nano Optics is financially supported by the University of Southern Denmark (SDU 2020 funding). Center for Nanostructured Graphene is supported by the Danish National Research Foundation (DNRF103).info:eu-repo/semantics/publishedVersio

Moment Closure - A Brief Review

Moment closure methods appear in myriad scientific disciplines in the modelling of complex systems. The goal is to achieve a closed form of a large, usually even infinite, set of coupled differential (or difference) equations. Each equation describes the evolution of one "moment", a suitable coarse-grained quantity computable from the full state space. If the system is too large for analytical and/or numerical methods, then one aims to reduce it by finding a moment closure relation expressing "higher-order moments" in terms of "lower-order moments". In this brief review, we focus on highlighting how moment closure methods occur in different contexts. We also conjecture via a geometric explanation why it has been difficult to rigorously justify many moment closure approximations although they work very well in practice.Comment: short survey paper (max 20 pages) for a broad audience in mathematics, physics, chemistry and quantitative biolog

Multi-decadal changes in tundra environments and ecosystems: Synthesis of the International Polar Year-Back to the Future Project (IPY-BTF).

Understanding the responses of tundra systems to global change has global implications. Most tundra regions lack sustained environmental monitoring and one of the only ways to document multi-decadal change is to resample historic research sites. The International Polar Year (IPY) provided a unique opportunity for such research through the Back to the Future (BTF) project (IPY project #512). This article synthesizes the results from 13 papers within this Ambio Special Issue. Abiotic changes include glacial recession in the Altai Mountains, Russia; increased snow depth and hardness, permafrost warming, and increased growing season length in sub-arctic Sweden; drying of ponds in Greenland; increased nutrient availability in Alaskan tundra ponds, and warming at most locations studied. Biotic changes ranged from relatively minor plant community change at two sites in Greenland to moderate change in the Yukon, and to dramatic increases in shrub and tree density on Herschel Island, and in sub-arctic Sweden. The population of geese tripled at one site in northeast Greenland where biomass in non-grazed plots doubled. A model parameterized using results from a BTF study forecasts substantial declines in all snowbeds and increases in shrub tundra on Niwot Ridge, Colorado over the next century. In general, results support and provide improved capacities for validating experimental manipulation, remote sensing, and modeling studies

Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration

The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P= 3.96 x 10(-14)). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.Peer reviewe