The landscape of viral associations in human cancers

Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, for which whole-genome and—for a subset—whole-transcriptome sequencing data from 2,658 cancers across 38 tumor types was aggregated, we systematically investigated potential viral pathogens using a consensus approach that integrated three independent pipelines. Viruses were detected in 382 genome and 68 transcriptome datasets. We found a high prevalence of known tumor-associated viruses such as Epstein–Barr virus (EBV), hepatitis B virus (HBV) and human papilloma virus (HPV; for example, HPV16 or HPV18). The study revealed significant exclusivity of HPV and driver mutations in head-and-neck cancer and the association of HPV with APOBEC mutational signatures, which suggests that impaired antiviral defense is a driving force in cervical, bladder and head-and-neck carcinoma. For HBV, HPV16, HPV18 and adeno-associated virus-2 (AAV2), viral integration was associated with local variations in genomic copy numbers. Integrations at the TERT promoter were associated with high telomerase expression evidently activating this tumor-driving process. High levels of endogenous retrovirus (ERV1) expression were linked to a worse survival outcome in patients with kidney cancer

Artificial Immune Systems for Combinatorial Optimisation: A Theoretical Investigation

We focus on the clonal selection inspired computational models of the immune system developed for general-purpose optimisation. Our aim is to highlight when these artificial immune systems (AIS) are more efficient than evolutionary algorithms (EAs). Compared to traditional EAs, AIS use considerably higher mutation rates (hypermutations) for variation, give higher selection probabilities to more recent solutions and lower selection probabilities to older ones (ageing). We consider the standard Opt-IA that includes both of the AIS distinguishing features and argue why it is of greater applicability than other popular AIS. Our first result is the proof that the stop at first constructive mutation version of its hypermutation operator is essential. Without it, the hypermutations cannot optimise any function with an arbitrary polynomial number of optima. Afterwards we show that the hypermutations are exponentially faster than the standard bit mutation operator used in traditional EAs at escaping from local optima of standard benchmark function classes and of the NP-hard Partition problem. If the basin of attraction of the local optima is not too large, then ageing allows even greater speed-ups. For the Cliff benchmark function this can make the difference between exponential and quasi-linear expected time. If the basin of attraction is too large, then ageing can implicitly detect the local optimum and escape it by automatically restarting the search process. The described power of hypermutations and ageing allows us to prove that they guarantee (1+epsilon) approximations for Partition in expected polynomial time for any constant epsilon. These features come at the expense of the hypermutations being a linear factor slower than EAs for standard unimodal benchmark functions and of eliminating the power of ageing at escaping local optima in the complete Opt-IA. We show that hypermutating with inversely proportional rates mitigates such drawbacks at the expense of losing the explorative advantages of the standard operator. We conclude the thesis by designing fast hypermutation operators that are provably a linear factor faster than the traditional ones for the unimodal benchmark functions and Partition, while maintaining explorative power and working in harmony together with ageing

The future of Cybersecurity in Italy: Strategic focus area

This volume has been created as a continuation of the previous one, with the aim of outlining a set of focus areas and actions that the Italian Nation research community considers essential. The book touches many aspects of cyber security, ranging from the definition of the infrastructure and controls needed to organize cyberdefence to the actions and technologies to be developed to be better protected, from the identification of the main technologies to be defended to the proposal of a set of horizontal actions for training, awareness raising, and risk management

On Easiest Functions for Mutation Operators in Bio-Inspired Optimisation

Understanding which function classes are easy and which are hard for a given algorithm is a fundamental question for the analysis and design of bio-inspired search heuristics. A natural starting point is to consider the easiest and hardest functions for an algorithm. For the (1+1) EA using standard bit mutation (SBM) it is well known that OneMax is an easiest function with unique optimum while Trap is a hardest. In this paper we extend the analysis of easiest function classes to the contiguous somatic hypermutation (CHM) operator used in artificial immune systems. We define a function MinBlocks and prove that it is an easiest function for the (1+1) EA using CHM, presenting both a runtime and a fixed budget analysis. Since MinBlocks is, up to a factor of 2, a hardest function for standard bit mutations, we consider the effects of combining both operators into a hybrid algorithm. We rigorously prove that by combining the advantages of k operators, several hybrid algorithmic schemes have optimal asymptotic performance on the easiest functions for each individual operator. In particular, the hybrid algorithms using CHM and SBM have optimal asymptotic performance on both OneMax and MinBlocks. We then investigate easiest functions for hybrid schemes and show that an easiest function for an hybrid algorithm is not just a trivial weighted combination of the respective easiest functions for each operator.publishersversionPeer reviewe

Evolution of Control Programs for a Swarm of Autonomous Unmanned Aerial Vehicles

Unmanned aerial vehicles (UAVs) are rapidly becoming a critical military asset. In the future, advances in miniaturization are going to drive the development of insect size UAVs. New approaches to controlling these swarms are required. The goal of this research is to develop a controller to direct a swarm of UAVs in accomplishing a given mission. While previous efforts have largely been limited to a two-dimensional model, a three-dimensional model has been developed for this project. Models of UAV capabilities including sensors, actuators and communications are presented. Genetic programming uses the principles of Darwinian evolution to generate computer programs to solve problems. A genetic programming approach is used to evolve control programs for UAV swarms. Evolved controllers are compared with a hand-crafted solution using quantitative and qualitative methods. Visualization and statistical methods are used to analyze solutions. Results indicate that genetic programming is capable of producing effective solutions to multi-objective control problems