Army-NASA aircrew/aircraft integration program (A3I) software detailed design document, phase 3

The capabilities and design approach of the MIDAS (Man-machine Integration Design and Analysis System) computer-aided engineering (CAE) workstation under development by the Army-NASA Aircrew/Aircraft Integration Program is detailed. This workstation uses graphic, symbolic, and numeric prototyping tools and human performance models as part of an integrated design/analysis environment for crewstation human engineering. Developed incrementally, the requirements and design for Phase 3 (Dec. 1987 to Jun. 1989) are described. Software tools/models developed or significantly modified during this phase included: an interactive 3-D graphic cockpit design editor; multiple-perspective graphic views to observe simulation scenarios; symbolic methods to model the mission decomposition, equipment functions, pilot tasking and loading, as well as control the simulation; a 3-D dynamic anthropometric model; an intermachine communications package; and a training assessment component. These components were successfully used during Phase 3 to demonstrate the complex interactions and human engineering findings involved with a proposed cockpit communications design change in a simulated AH-64A Apache helicopter/mission that maps to empirical data from a similar study and AH-1 Cobra flight test

Transformations of High-Level Synthesis Codes for High-Performance Computing

Specialized hardware architectures promise a major step in performance and energy efficiency over the traditional load/store devices currently employed in large scale computing systems. The adoption of high-level synthesis (HLS) from languages such as C/C++ and OpenCL has greatly increased programmer productivity when designing for such platforms. While this has enabled a wider audience to target specialized hardware, the optimization principles known from traditional software design are no longer sufficient to implement high-performance codes. Fast and efficient codes for reconfigurable platforms are thus still challenging to design. To alleviate this, we present a set of optimizing transformations for HLS, targeting scalable and efficient architectures for high-performance computing (HPC) applications. Our work provides a toolbox for developers, where we systematically identify classes of transformations, the characteristics of their effect on the HLS code and the resulting hardware (e.g., increases data reuse or resource consumption), and the objectives that each transformation can target (e.g., resolve interface contention, or increase parallelism). We show how these can be used to efficiently exploit pipelining, on-chip distributed fast memory, and on-chip streaming dataflow, allowing for massively parallel architectures. To quantify the effect of our transformations, we use them to optimize a set of throughput-oriented FPGA kernels, demonstrating that our enhancements are sufficient to scale up parallelism within the hardware constraints. With the transformations covered, we hope to establish a common framework for performance engineers, compiler developers, and hardware developers, to tap into the performance potential offered by specialized hardware architectures using HLS

A Hybrid Multi-Robot Control Architecture

Multi-robot systems provide system redundancy and enhanced capability versus single robot systems. Implementations of these systems are varied, each with specific design approaches geared towards an application domain. Some traditional single robot control architectures have been expanded for multi-robot systems, but these expansions predominantly focus on the addition of communication capabilities. Both design approaches are application specific and limit the generalizability of the system. This work presents a redesign of a common single robot architecture in order to provide a more sophisticated multi-robot system. The single robot architecture chosen for application is the Three Layer Architecture (TLA). The primary strength of TLA is in the ability to perform both reactive and deliberative decision making, enabling the robot to be both sophisticated and perform well in stochastic environments. The redesign of this architecture includes incorporation of the Unified Behavior Framework (UBF) into the controller layer and an addition of a sequencer-like layer (called a Coordinator) to accommodate the multi-robot system. These combine to provide a robust, independent, and taskable individual architecture along with improved cooperation and collaboration capabilities, in turn reducing communication overhead versus many traditional approaches. This multi-robot systems architecture is demonstrated on the RoboCup Soccer Simulator showing its ability to perform well in a dynamic environment where communication constraints are high

Advanced Methods for Real-time Metagenomic Analysis of Nanopore Sequencing Data

Whole shotgun metagenomics sequencing allows researchers to retrieve information about all organisms in a complex sample. This method enables microbiologists to detect pathogens in clinical samples, study the microbial diversity in various environments, and detect abundance differences of certain microbes under different living conditions. The emergence of nanopore sequencing has offered many new possibilities for clinical and environmental microbiologists. In particular, the portability of the small nanopore sequencing devices and the ability to selectively sequence only DNA from interesting organisms are expected to make a significant contribution to the field. However, both options require memory-efficient methods that perform real-time data analysis on commodity hardware like usual laptops. In this thesis, I present new methods for real-time analysis of nanopore sequencing data in a metagenomic context. These methods are based on optimized algorithmic approaches querying the sequenced data against large sets of reference sequences. The main goal of those contributions is to improve the sequencing and analysis of underrepresented organisms in complex metagenomic samples and enable this analysis in low-resource settings in the field. First, I introduce ReadBouncer as a new tool for nanopore adaptive sampling, which can reject uninteresting DNA molecules during the sequencing process. ReadBouncer improves read classification compared to other adaptive sampling tools and has fewer memory requirements. These improvements enable a higher enrichment of underrepresented sequences while performing adaptive sampling in the field. I further show that, besides host sequence removal and enrichment of low-abundant microbes, adaptive sampling can enrich underrepresented plasmid sequences in bacterial samples. These plasmids play a crucial role in the dissemination of antibiotic resistance genes. However, their characterization requires expensive and time-consuming lab protocols. I describe how adaptive sampling can be used as a cheap method for the enrichment of plasmids, which can make a significant contribution to the point-of-care sequencing of bacterial pathogens. Finally, I introduce a novel memory- and space-efficient algorithm for real-time taxonomic profiling of nanopore reads that was implemented in Taxor. It improves the taxonomic classification of nanopore reads compared to other taxonomic profiling tools and tremendously reduces the memory footprint. The resulting database index for thousands of microbial species is small enough to fit into the memory of a small laptop, enabling real-time metagenomics analysis of nanopore sequencing data with large reference databases in the field

Bioinformatics for personal genomics: development and application of bioinformatic procedures for the analysis of genomic data

In the last decade, the huge decreasing of sequencing cost due to the development of high-throughput technologies completely changed the way for approaching the genetic problems. In particular, whole exome and whole genome sequencing are contributing to the extraordinary progress in the study of human variants opening up new perspectives in personalized medicine. Being a relatively new and fast developing field, appropriate tools and specialized knowledge are required for an efficient data production and analysis. In line with the times, in 2014, the University of Padua funded the BioInfoGen Strategic Project with the goal of developing technology and expertise in bioinformatics and molecular biology applied to personal genomics. The aim of my PhD was to contribute to this challenge by implementing a series of innovative tools and by applying them for investigating and possibly solving the case studies included into the project. I firstly developed an automated pipeline for dealing with Illumina data, able to sequentially perform each step necessary for passing from raw reads to somatic or germline variant detection. The system performance has been tested by means of internal controls and by its application on a cohort of patients affected by gastric cancer, obtaining interesting results. Once variants are called, they have to be annotated in order to define their properties such as the position at transcript and protein level, the impact on protein sequence, the pathogenicity and more. As most of the publicly available annotators were affected by systematic errors causing a low consistency in the final annotation, I implemented VarPred, a new tool for variant annotation, which guarantees the best accuracy (>99%) compared to the state-of-the-art programs, showing also good processing times. To make easy the use of VarPred, I equipped it with an intuitive web interface, that allows not only a graphical result evaluation, but also a simple filtration strategy. Furthermore, for a valuable user-driven prioritization of human genetic variations, I developed QueryOR, a web platform suitable for searching among known candidate genes as well as for finding novel gene-disease associations. QueryOR combines several innovative features that make it comprehensive, flexible and easy to use. The prioritization is achieved by a global positive selection process that promotes the emergence of the most reliable variants, rather than filtering out those not satisfying the applied criteria. QueryOR has been used to analyze the two case studies framed within the BioInfoGen project. In particular, it allowed to detect causative variants in patients affected by lysosomal storage diseases, highlighting also the efficacy of the designed sequencing panel. On the other hand, QueryOR simplified the recognition of LRP2 gene as possible candidate to explain such subjects with a Dent disease-like phenotype, but with no mutation in the previously identified disease-associated genes, CLCN5 and OCRL. As final corollary, an extensive analysis over recurrent exome variants was performed, showing that their origin can be mainly explained by inaccuracies in the reference genome, including misassembled regions and uncorrected bases, rather than by platform specific errors