Resolving social dilemmas with minimal reward transfer

Multi-agent cooperation is an important topic, and is particularly challenging in mixed-motive situations where it does not pay to be nice to others. Consequently, self-interested agents often avoid collective behaviour, resulting in suboptimal outcomes for the group. In response, in this paper we introduce a metric to quantify the disparity between what is rational for individual agents and what is rational for the group, which we call the general self-interest level. This metric represents the maximum proportion of individual rewards that all agents can retain while ensuring that achieving social welfare optimum becomes a dominant strategy. By aligning the individual and group incentives, rational agents acting to maximise their own reward will simultaneously maximise the collective reward. As agents transfer their rewards to motivate others to consider their welfare, we diverge from traditional concepts of altruism or prosocial behaviours. The general self-interest level is a property of a game that is useful for assessing the propensity of players to cooperate and understanding how features of a game impact this. We illustrate the effectiveness of our method on several novel games representations of social dilemmas with arbitrary numbers of players.Comment: 34 pages, 13 tables, submitted to the Journal of Autonomous Agents and Multi-Agent Systems: Special Issue on Citizen-Centric AI System

Variations of Particle Size Distribution, Black Carbon, and Brown Carbon during a Severe Winter Pollution Event over Xi'an, China

Real-time particulate matter (PM) size distributions, 4-hour time resolution, PM2.5, carbonaceous materials, and their optical properties were measured during a severe pollution event in Xi'an, China High PM2.5 /PM10 ratios were observed on both pollution (0.83) and non-pollution (0.73) days, emphasizing the abundance of fine particles during sampling days. The particle number (PN) first peaked with a wide size range (30-100 nm) before morning rush hours (approximately 01:00-05:00) on pollution and non-pollution days, demonstrating that PN was governed by the accumulation of freshly emitted diesel particles and characterized by distinct aerosol condensation growth. By contrast, the second peak time and size range differed between pollution and non-pollution days because of different formation mechanisms The light-absorbing coefficients of both black carbon (BC, b(abs-880nm,BC)) and brown carbon (BrC, b(abs-370nm, BrC)) were high on pollution days and decreased to approximately half of those values on non-pollution days, indicating that the degree of light absorption is reduced by rain. The diurnal variation in b(abs-880nm, BC) pollution peaked with traffic on January 1 and 2. By contrast, it remained in relatively stable and high ranges (120-160 Mm(-1)) in the second period (January 3-5) without traffic peaks, illustrating that the dominant sources changed even during the same pollution period. High values of both b(abs-370nm, BrC) and b(abs-880nm,) (BC )coincided in the afternoon and evening due to emissions from primary sources, and abundant aqueous secondary organic carbon, respectively. A highly variable mass absorption coefficient of BrC also indicated the variety of fuel combustion sources of primary BrC in Xi'an

Melhoramento genético de citros por meio de mutações espontâneas de gemas.

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Discovery of first-in-class inhibitors of ASH1L histone methyltransferase with anti-leukemic activity

ASH1L histone methyltransferase plays a crucial role in the pathogenesis of different diseases, including acute leukemia. While ASH1L represents an attractive drug target, developing ASH1L inhibitors is challenging, as the catalytic SET domain adapts an inactive conformation with autoinhibitory loop blocking the access to the active site. Here, by applying fragment-based screening followed by medicinal chemistry and a structure-based design, we developed first-in-class small molecule inhibitors of the ASH1L SET domain. The crystal structures of ASH1L-inhibitor complexes reveal compound binding to the autoinhibitory loop region in the SET domain. When tested in MLL leukemia models, our lead compound, AS-99, blocks cell proliferation, induces apoptosis and differentiation, downregulates MLL fusion target genes, and reduces the leukemia burden in vivo. This work validates the ASH1L SET domain as a druggable target and provides a chemical probe to further study the biological functions of ASH1L as well as to develop therapeutic agents

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms