Data generated by genome-wide association studies (GWAS) are growing fast with the linkage of biobank samples to health records, and expanding capture of high-dimensional molecular phenotypes. However the utility of these efforts can only be fully realised if their complete results are collected from their heterogeneous sources and formats, harmonised and made programmatically accessible. Here we present the OpenGWAS database, an open source, open access, scalable and high-performance cloud-based data infrastructure that imports and publishes complete GWAS summary datasets and metadata for the scientific community. Our import pipeline harmonises these datasets against dbSNP and the human genome reference sequence, generates summary reports and standardises the format of results and metadata. Users can access the data via a website, an application programming interface, R and Python packages, and also as downloadable files that can be rapidly queried in high performance computing environments. OpenGWAS currently contains 126 billion genetic associations from 14,582 complete GWAS datasets representing a range of different human phenotypes and disease outcomes across different populations. We developed R and Python packages to serve as conduits between these GWAS data sources and a range of available analytical tools, enabling Mendelian randomization, genetic colocalisation analysis, fine mapping, genetic correlation and locus visualisation. OpenGWAS is freely accessible at https://gwas.mrcieu.ac.uk, and has been designed to facilitate integration with third party analytical tools.

The life of a class of submarines can be measured in decades. As such the operational demands and expectations change both strategically and tactically over its lifetime. Coupling this adaptability with the length of time submarines take to design, build, and maintain, no two “as built” submarines in a class will ever be the same even when constructed/maintained to the same “build to” design. Traditionally this has been accepted as the case and in most cases the full information set has been managed via the configuration management team at a class or batch level but not at an individual submarine level. The configuration of an individual submarine has been managed in terms of agreed changes against the class or batch baseline. Advances in technology (hardware performance, software tools and standards) now give us the opportunity to not only manage the full information set related to individual submarine system configuration baselines as they change over time but also undertake rigorous model based trade‐off studies to plan the manner in which a class, a batch, an individual submarine (variant), or any combination thereof can be modified over time. This paper will explore the use of Model‐Based Systems Engineering (MBSE) coupled with recent developments of Product Line Engineering (PLE) / Orthogonal Variability Modelling (OVM) to provide a means to plan, track, manage and evaluate an individual submarine's configuration over time in the context of the class, whilst simultaneously highlighting the wider application in the submarine enterprise and beyond.

This paper presents a method with which we can generate update messages for use with Smalltalk's dependency mechanism. The basic idea is that any messages which cause an object to change are forwarded to the object's dependants. The method is perfectly general and future-proofs objects against changes in their dependants.

One can measure the life of a class of submarines in decades. As such, the operational demands and expectations change both strategically and tactically over its lifetime. Coupling this adaptability with the length of time submarines take to design, build, and maintain, no two as‐built submarines in a class will ever be the same, even when constructed/maintained to the same build‐to design. Traditionally, we have accepted this as the standard, and in most cases the configuration management team managed the full information set at a class or batch level, but not at an individual submarine level. The team managed the configuration of an individual submarine in terms of agreed changes against the class or batch baseline. Advances in technology (hardware performance, software tools, and standards) now give us the opportunity to not only manage the full information set related to individual submarine system configuration baselines as they change over time, but also undertake rigorous model‐based trade‐off studies to plan the manner in which we can modify a class, a batch, an individual submarine (variant), or any combination thereof over time. This paper will explore the use of model‐based systems engineering (MBSE) coupled with recent developments of product line engineering (PLE)/orthogonal variability modelling (OVM) to provide a means to plan, track, manage, and evaluate an individual submarine's configuration over time in the context of the class, whilst simultaneously highlighting the wider application in the submarine enterprise and beyond.