From evolutionary ecosystem simulations to computational models of human behavior

We have a wide breadth of computational tools available today that enable a more ethical approach to the study of human cognition and behavior. We argue that the use of computer models to study evolving ecosystems provides a rich source of inspiration, as they enable the study of complex systems that change over time. Often employing a combination of genetic algorithms and agent-based models, these methods span theoretical approaches from games to complexification, nature-inspired methods from studies of self-replication to the evolution of eyes, and evolutionary ecosystems of humans, from entire economies to the effects of personalities in teamwork. The review of works provided here illustrates the power of evolutionary ecosystem simulations and how they enable new insights for researchers. They also demonstrate a novel methodology of hypothesis exploration: building a computational model that encapsulates a hypothesis of human cognition enables it to be tested under different conditions, with its predictions compared to real data to enable corroboration. Such computational models of human behavior provide us with virtual test labs in which unlimited experiments can be performed. This article is categorized under: Computer Science and Robotics > Artificial Intelligence

Using a Variational Autoencoder to Learn Valid Search Spaces of Safely Monitored Autonomous Robots for Last-Mile Delivery

The use of autonomous robots for delivery of goods to customers is an exciting new way to provide a reliable and sustainable service. However, in the real world, autonomous robots still require human supervision for safety reasons. We tackle the real-world problem of optimizing autonomous robot timings to maximize deliveries, while ensuring that there are never too many robots running simultaneously so that they can be monitored safely. We assess the use of a recent hybrid machine-learning-optimization approach COIL (constrained optimization in learned latent space) and compare it with a baseline genetic algorithm for the purposes of exploring variations of this problem. We also investigate new methods for improving the speed and efficiency of COIL. We show that only COIL can find valid solutions where appropriate numbers of robots run simultaneously for all problem variations tested. We also show that when COIL has learned its latent representation, it can optimize 10% faster than the GA, making it a good choice for daily re-optimization of robots where delivery requests for each day are allocated to robots while maintaining safe numbers of robots running at once

COIL: Constrained optimization in learned latent space: learning representations for valid solutions

Constrained optimization problems can be difficult because their search spaces have properties not conducive to search, e.g., multimodality, discontinuities, or deception. To address such difficulties, considerable research has been performed on creating novel evolutionary algorithms or specialized genetic operators. However, if the representation that defined the search space could be altered such that it only permitted valid solutions that satisfied the constraints, the task of finding the optimal would be made more feasible without any need for specialized optimization algorithms. We propose Constrained Optimization in Latent Space (COIL), which uses a VAE to generate a learned latent representation from a dataset comprising samples from the valid region of the search space according to a constraint, thus enabling the optimizer to find the objective in the new space defined by the learned representation. Preliminary experiments show promise: compared to an identical GA using a standard representation that cannot meet the constraints or find fit solutions, COIL with its learned latent representation can perfectly satisfy different types of constraints while finding high-fitness solutions

Prior Cancer Is Associated with Lower Atherosclerotic Cardiovascular Disease Risk at First Acute Myocardial Infarction

BACKGROUND: Patients with cancer are at increased risk of acute myocardial infarction (AMI). It is unclear if the Atherosclerotic Cardiovascular Disease (ASCVD) risk score at incident AMI is reflective of this higher risk in patients with prior cancer than those without. METHODS: We linked nationwide AMI and cancer registries from 2008 to 2019. A total of 18,200 eligible patients with ASCVD risk score calculated at incident AMI were identified (1086 prior cancer; 17,114 no cancer). RESULTS: At incident AMI, age-standardized mean ASCVD risk was lower in the prior cancer group (18.6%) than no cancer group (20.9%) (p < 0.001). Prior to incident AMI, smoking, hypertension, hyperlipidemia and diabetes mellitus were better controlled in the prior cancer group. However post-AMI, prior cancer was associated with lower guideline-directed medical therapy usage and higher all-cause mortality (adjusted hazard ratio 1.85, 95% confidence interval 1.66-2.07). CONCLUSIONS: AMI occurred despite better control of cardiovascular risk factors and lower age-standardized estimated mean 10-year ASCVD risk among patients with prior cancer than no cancer. Prior cancer was associated with lower guideline-directed medical therapy post-AMI and higher mortality

Linking the effects of helminth infection, diet and the gut microbiota with human whole-blood signatures

Helminth infection and dietary intake can affect the intestinal microbiota, as well as the immune system. Here we analyzed the relationship between fecal microbiota and blood profiles of indigenous Malaysians, referred to locally as Orang Asli, in comparison to urban participants from the capital city of Malaysia, Kuala Lumpur. We found that helminth infections had a larger effect on gut microbial composition than did dietary intake or blood profiles. Trichuris trichiura infection intensity also had the strongest association with blood transcriptional profiles. By characterizing paired longitudinal samples collected before and after deworming treatment, we determined that changes in serum zinc and iron levels among the Orang Asli were driven by changes in helminth infection status, independent of dietary metal intake. Serum zinc and iron levels were associated with changes in the abundance of several microbial taxa. Hence, there is considerable interplay between helminths, micronutrients and the microbiota on the regulation of immune responses in humans

Systems of systems engineering: A research imperative

Systems of Systems Engineering constitutes a major challenge for the 21st Century and research into this topic has become an imperative. The Support Action, T-AREA-SoS has been initiated by the European Commission to develop a research agenda in Systems of Systems (SoS) that will inform future investment in this area. Through an extensive consultation and review, a number of SoS capability gaps have been identified. Through structuring and subsequent consultation, these have been developed into twelve research themes the detailed areas of which are mapped to the three SoS characteristics of control, evolution, and emergent behaviour. A framework is presented through which researchers can develop a research campaign in SoS. © 2013 IEEE

Cudraflavone C induces tumor-specific apoptosis in colorectal cancer cells through inhibition of the phosphoinositide 3-kinase (PI3K)-AKT pathway

Cudraflavone C (Cud C) is a naturally-occurring flavonol with reported anti-proliferative activities. However, the mechanisms by which Cud C induced cytotoxicity have yet to be fully elucidated. Here, we investigated the effects of Cud C on cell proliferation, caspase activation andapoptosis induction in colorectal cancer cells (CRC). We show that Cud C inhibits cell proliferation in KM12, Caco-2, HT29, HCC2998, HCT116 and SW48 CRC but not in the non-transformed colorectal epithelial cells, CCD CoN 841. Cud C induces tumorselective apoptosis via mitochondrial depolarization and activation of the intrinsic caspase pathway. Gene expression profiling by microarray analyses revealed that tumor suppressor genes EGR1, HUWE1 and SMG1 were significantly up-regulated while oncogenes such as MYB1, CCNB1 and GPX2 were down-regulated following treatment with Cud C. Further analyses using Connectivity Map revealed that Cud C induced a gene signature highly similar to that of protein synthesis inhibitors and phosphoinositide 3-kinase (PI3K)-AKT inhibitors, suggesting that Cud C might inhibit PI3K-AKT signaling. A luminescent cell free PI3K lipid kinase assay revealed that Cud C significantly inhibited p110?/p85? PI3K activity, followed by p120?, p110?/p85?, and p110?/p85? PI3K activities. The inhibition by Cud C on p110?/p85? PI3K activity was comparable to LY-294002, a known PI3K inhibitor. Cud C also inhibited phosphorylation of AKT independent of NF?B activity in CRC cells, while ectopic expression of myristoylated AKT completely abrogated the anti-proliferative effects, and apoptosis induced by Cud C in CRC. These findings demonstrate that Cud C induces tumor-selective cytotoxicity by targeting the PI3K-AKT pathway. These findings provide novel insights into the mechanism of action of Cud C, and indicate that Cud C further development of Cud C derivatives as potential therapeutic agents is warranted

Establishment of Wolbachia strain wAlbB in Malaysian populations of Aedes aegypti for dengue control

Dengue has enormous health impacts globally. A novel approach to decrease dengue incidence involves the introduction of Wolbachia endosymbionts that block dengue virus transmission into populations of the primary vector mosquito, Aedes aegypti. The wMel Wolbachia strain has previously been trialed in open releases of Ae. aegypti; however, the wAlbB strain has been shown to maintain higher density than wMel at high larval rearing temperatures. Releases of Ae. aegypti mosquitoes carrying wAlbB were carried out in 6 diverse sites in greater Kuala Lumpur, Malaysia, with high endemic dengue transmission. The strain was successfully established and maintained at very high population frequency at some sites or persisted with additional releases following fluctuations at other sites. Based on passive case monitoring, reduced human dengue incidence was observed in the release sites when compared to control sites. The wAlbB strain of Wolbachia provides a promising option as a tool for dengue control, particularly in very hot climates

Glucuronidation by UGT1A1 Is the Dominant Pathway of the Metabolic Disposition of Belinostat in Liver Cancer Patients

10.1371/journal.pone.0054522PLoS ONE81